Guide_Concerning_Legislative_Issues
Feng Zhang实验室CRISPR设计工具在iPSCs基因组编辑中的应用说明说明书
Genome editing in iPSCsCrispr designWe used the Feng Zhang lab CRISPR Design tool () to design the guide RNA. The guide RNA should bind as closely as possible to the target nucleotide (ideally between 2-10 bp).To correct a mutation, the mutated DNA sequence should be used for the gRNA design.To introduce a mutation, the wild-type DNA sequence should be used for the gRNA design.For each selected gRNA, order two oligonucleotides - the sense and antisense of the guide sequence. The BbsI restriction site overhangs (depends on the plasmid) are as follows:Fw oligo: 5’-CACC[G]”guide_sense_sequence”-3’Rv oligo: 5’-AAAC”guide_antisense_sequence”[C]-3’Resuspend each oligo in distilled water to 100µM.Note: only add the G and the C in square brackets if the guide doesn't start with a G. This is necessary for optimal transcription initiation from the U6 promoter.Typically, we design two gRNAs and test the cutting efficiency before the HDR experiment.Design of ssDNA Oligo HDR donor templateWe use a mix of up to 4 HDR donor ssDNA Oligos (100nt long) depending on the targeted mutation, the gRNA binding site and the PAM sequence.We will design the donor OligosCloning of guide RNA in the pSpCas9(BB)-2A-GFP vector (Addgene: px458)Step1. Oligo phosphorylation and annealing:To phosphorylate and anneal each pair of oligos, combine the following in a 0.2ml tube:1 µl oligo Fw (100µM in water)1 µl oligo Rv (100µM in water)1 µl 10X T4 Ligation Buffer (NEB)6.5 µl ddH2 O0.5 µl T4 PNK (NEB)Total volume = 10 µl totalIncubate37°C 30 min95°C 5 minRamp down to 25°C at 5°C/minStep 2. Digestion and ligation:1 µl pX330 or other backbone vector pSpCas9(BB)-2A-GFP (100ng/ul)2 µl of diluted oligo duplex from step 1 (diluted 1:250 in water)2 µl 10X FastDigest Buffer1 µl DTT (10mM)1 µl ATP (10mM)1 µl FastDigest BbsI (ThermoFisher)0.5 µl T7 DNA ligase (NEB)11.5 µl ddH2OTotal volume = 20 µlIncubate:37°C 5 min23°C 5 minCycle 6 times (total run time ~1h)Step 3. Transformation:•Add 5µl of ligation mix to 50 µl E.coli strain e.g One Shot competent cells•Incubate on ice for 20 minutes•Heat-shock the cells at 42°C for 45 seconds•Cool on ice for 2 minutes•Add 500µl of SOC media and incubate at 37°C with shaking for 30 minutes•Plate 100µl of the transformed bacteria on LB-agar + 100µg/ml ampicillin plates.•Incubate at 37°C overnight.Step 4. E coli colony screening for gRNAThe next morning, pick 5 colonies and incubate overnight in 5ml LB + 100µg/ml ampicilline at 37°C with shaking. After 8 hours, isolate the DNA with a DNA miniprep kit and send for Sanger sequencing with the hU6_Fw primer (5’-ACTATCATATGCTTACCGTAAC-3’).iPSC cultureReagents:•Essential 8 (Life Technologies, A14666SA)•Matrigel™ hESC-Qualified Matrix (Corning, cat. no. 354277)•Gentle Dissociation Solution (Stem Cell Technologies 07174)•Y-27632-HCl (Biorbyt, cat. no. orb154626)Thawing hiPSC:•hiPSC should be either generated in-house or can be obtained from available depositories e.g Wicell, Coriell or the Stanford CVI iPSC Biobank.•Remove vial from liquid nitrogen, place in 37 °C water bath until only a sliver of ice remains.Transfer the vial content dropwise (~1 mL) to a 15 mL conical tube filled with 4 ml of pre-warmed E8 supplemented with 2.5µM Y-27632 (E8 + iRock)•Centrifuge at 200 g for 4 min. Carefully aspirate the supernatant. Re-suspend the cell pellet in 2 mL of E8 + iRock and transfer to 1 well of a Matrigel-coated 6-well plate •Change media every 24 h with fresh E8. Cells should be 70-80% confluent in 3-4 days Passage of hiPSC:•Ideally cells should have reached 70-80% confluence in 3-4 days (adjust split ratio accordingly, typically 1/6-1/12).•Aspirate the E8 culture medium.•Add 2 mL per well of Gentle Dissociation Solution, incubate for 6-8 min at RT (in hood) •Whilst waiting, aspirate medium from Matrigel-coated plates and replace with 1 mL of E8Y.•Aspirate Gentle Dissociation Solution from each well.•Add 1 mL of E8 + iRock medium to the well. Gently detach the colonies by scraping with a serological pipette or a cell scraper. Add 6 mL of E8 + iRock for a 1:6 split.•Mix gently and transfer 1 mL in each well of the 6-well plate (2ml per well total volume). NOTE: We aim to keep the pluripotent cells in the logarithmic growth phase. Cells should not be allowed to become more than 90% confluent.TransfectionThe day before transfection, split the cells 1:2/1:3. Cell should be 50-60% confluent the next day: •Remove the medium•Wash once with PBS•Add 2.0ml Gentle Dissociation Solution•Incubate 5 min 37°C•Gently pipette up and down to dissociate the cells•Plate in a previously coated new well in E8 + iRock.On the day of transfection:•Replace media with fresh E8 media (1.0 mL/well).•For each well of a 6-well plate, prepare 4 separate reactions•Prepare the reactions by adding the reagents in the order shown:(i)Set up the CRISPR-Cas9-gRNA rxn:Mix A:o200 µL of Opti-MEMo10 µL of Lipofectamine Stem reagentMix B:o200 µL of Opti-MEMo1µg of CRISPR/Cas9 vector (pSpCas9(BB)-2A-GFP)Combine mix A & B – mix well and incubate for 15min @ RT(ii) A separate reaction is set up for the ssDNA donor oligos:Mix C:o200 µL of Opti-MEMo7.5 µL of RNAi max reagentMix D:o200 µL of Opti-MEMo 4 µg of ssDNA donor mix (if using 4 oligos, use 1µg each)Combine mix C & D – mix well and incubate for 15min @ RT•Add 400µl transfection mix of A+B and 400µl transfection mix of C+D to one well•Place the cells back in the incubator•After 4 hours, aspirate the transfection media from each well and replace with 2ml of fresh E8 supplemented with E8 + iRock•16-24h later, check the transfected cells under a fluorescent microscope for GFP+. Typically, the transfection efficiency is 5%-30% depending on the iPSC line. We FACs sort the cells 24-36h post transfection.FACS GFP+ cells•Aspirate the media•Wash once with PBS•Add 2.0 ml TrypLE express•Incubate 5-6 min 37°C until cells have detached – mix gently with a P1000 pipette to break down the cells to single cells•Add 4ml E8 + iRock•Transfer to a 15ml tube•Centrifuge 5 min @200g room temperature•Discard the supernatant and re-suspend the cells in 0.4 ml E8 + iRock•Filter the suspension through a 35-µm mesh Corning™ Falcon™ Test Tube with Cell Strainer Snap Cap•Prepare a 15ml collection tube containing 6ml E8 + iRock•Sort GFP-expressing cells using FACS sorter with a 100-µm nozzle – typically we sort 12,000 cells•Plate sorted cells in 6-well plates at a density of 2000 cells/well in E8 + 2.5µM iRcokIsolation of iPSC ClonesUsually 8-10 days after sorting, single iPSC colonies are large enough to be picked. We usually pick 30-40 clones that are clearly isolated from 3-6 wells of a 6-well plate.•Aspirate media and add 3ml of fresh E8 + iROCK media per well at least 2h before picking.•Manually pick individual iPSC clones (we use a P200 pipette set at 100µl) using a stereo-microscope located inside a cell culture hood, and transfer each clone to a 1.5ml tube.•Pipet up and down 2-3 times to partially dissociate the clone and transfer 90 µl of cell suspension into a separate well of a 24-well plate (Matrigel-coated) containing 500µL of E8+iRock. Savethe remaining 10µl of cells suspension for HDR screening by direct PCR (the samples can bestored at -20o C).•Allow the cells to attach for 24–48 h and then add 500µl E8 media. Feed the cells with fresh E8 media every other day.Genomic DNA isolationProtocol adapted from Phire Animal Tissue Direct PCR Kit (Thermo Fisher; Cat#: F140WH).•For each clone, dilute 0.5µl of DNA Release Additive in 19.5µl Dilution Buffer. We make a master mix for all the clones. Add 20µl of the master mix to each tube containing the ~10 µl of residual cell suspension from the clone picking step.•Mix well and incubate at room temperature for 10 minutes.•Then heat the samples at 98°C for 2 minutes.•Add 25µl of molecular grade water and centrifuge at top speed for 1 min at room temperature to allow for cell debris sedimentation. Use 3µl of the resulting solution as a template in the PCRreaction.Direct PCRPerform PCR using PrimeSTAR GXL DNA Polymerase (Clontech) and primers that amplify a region of 500nt around the target nucleotide. For each sample combine the following:13.5µl ddH2O (for 3µl template DNA)5µl PrimeSTAR GXL Buffer 5X2µl dNTP (2.5mM each)0.5 µl 10µM Fw Primer0.5 µl 10µM Rv Primer0.5 µl PrimeSTAR GXL DNA Polymerase3.0 µl of cell sampleTotal volume = 25 µlSet up the following program on the thermocycler:2 min 98°C10 sec 98°C15 sec 62°C20 sec 68°C(repeat X40)2 min 68°Chold 4°CSanger SequencingFirst, run 5µl of the PCR reaction on a 1% agarose gel to verify genomic DNA amplification.Once verified, the unpurified PCR samples (~20 µl) are sent out for sequencing using either the forward or the reverse primer.。
2016强制执行的LVD 新指令 (英文原文)A ON THE TRANSPOSITION OF LVD 2014 35 EU.doc (1)
EUROPEAN COMMISSIONRef. Ares(2015)4308055 - 15/10/2015 Directorate-General for Internal Market, Industry, Entrepreneurship and SMEsIndustrial Transformation and Advanced Value ChainsAdvanced Engineering and Manufacturing SystemsDRAFT G UIDANCE D OCUMENTON THE L OW V OLTAGE D IRECTIVE TRANSITIONFROM 2006/95/EC TO 2014/35/EUThe new Low Voltage Directive 2014/35/EU1 is the result of the alignment of the previousLow Voltage Directive 2006/95/EC to the "New Legislative Framework" (NLF)2, inparticular to Decision No 768/2008/EC3, as well as to the provisions of the Treaty on the Functioning of the European Union (TFEU) after the Treaty of Lisbon.Being the result of an alignment and a recast, the main changes in the new Directive2014/35/EU with respect to the previous Directive 2006/95/EC are quite limited, and do not concern the most substantial characteristics of the act that remain the same: scope, safety objectives, conformity assessment procedure. The main changes are the following:▪Reference number: according to the model YYYY / No / UE▪Definitions: horizontal additions from the NLF▪Economic operators (manufacturers, authorised representatives, importers, distributors) and their obligations: more detailed descriptions from the NLF▪Harmonised standards and presumption of conformity: reference to Regulation (EU) No 1025/2012 on European Standardisation4▪CE marking: reference to Regulation (EC) No 765/200851 Directive 2014/35/EU of the European Parliament and of the Council of 26 February 2014 on theharmonisation of the laws of the Member States relating on the harmonisation of the laws of the MemberStates relating to the making available on the market of electrical equipment designed for use within certainvoltage limits (OJ L 96, 29.3.2014, p. 357–374)2 See http://ec.europa.eu/growth/single-market/goods/new-legislative-framework/index_en.htm3 Decision No 768/2008/EC of the European Parliament and of the Council of 9 July 2008 on a commonframework for the marketing of products, and repealing Council Decision 93/465/EEC (OJ L 218, 13.8.2008,p. 82)4 Regulation (EU) No 1025/2012 of the European Parliament and of the Council of 25 October 2012 onEuropean standardisation, amending Council Directives 89/686/EEC and 93/15/EEC and Directives 94/9/EC,94/25/EC, 95/16/EC, 97/23/EC, 98/34/EC, 2004/22/EC, 2007/23/EC, 2009/23/EC and 2009/105/EC of theEuropean Parliament and of the Council and repealing Council Decision 87/95/EEC and Decision No1673/2006/EC of the European Parliament and of the Council (OJ L 316, 14.11.2012, p. 12)5 Regulation (EC) No 765/2008 of the European Parliament and of the Council of 9 July 2008 setting out the requirements for accreditation and market surveillance relating to the marketing of products and repealingRegulation (EEC) No 339/93 (OJ L 218, 13.8.2008, p. 30)▪Market surveillance and safeguard procedure: reinforced activities and new simplified procedures (also related to the "Product safety and market surveillance package"6)▪Electrical Equipment Committee and implementing acts: reference to Regulation (EU) No 182/20117 ("Comitology") concerning Commission Implementing Decisions onformal objections against harmonised standards and safeguard clauses against products ▪EU declaration of conformity: more detailed contents, and a model, from the NLFThe new Low Voltage Directive 2014/35/EU is applicable from 20 April 2016.This document includes a list of "Frequently Asked Questions and Answers" on the transition to the Low Voltage Directive 2014/35/EU, which covers both "horizontal" and "sectorial" questions, this is to say, those common to all the EU legislation aligned to the "New Legislative Framework"8 and those specifically related to Directive 2014/35/EU. It reflects the result of ongoing discussions, notably at the workshop on the transition to the new LVD 2014/35/EU held on 27October 2014.It should be noted that this document is preliminary, pending the revision of the Blue Guide and the LVD Guidelines. Upon finalisation of the revised Blue Guide (planned for end of 2015) and the LVD Guidelines (planned for mid-2016) the latter documents have to be considered as the main references for the interpretation of horizontal issues related to the New Legislative Framework and the LVD respectively.6 See http://ec.europa.eu/growth/single-market/goods/building-blocks/market-surveillance/organisation/index_en.htm7 Regulation (EU) No 182/2011 of the European Parliament and of the Council of 16 February 2011 laying down the rules and general principles concerning mechanisms for control by Member States of the Commission’s exercise of implementing powers (OJ L 55, 28.2.2011, p. 13)8Pyrotechnic Articles Directive 2013/29/EU (applicable 1 July 2015); Civil Explosives Directive 2014/28/EU, Simple Pressure Vessels Directive 2014/29/EU, Electromagnetic Compatibility Directive 2014/30/EU, Non-automatic Weighing Instruments Directive 2014/31/EU, Measuring Instruments Directive 2014/32/EU, Lifts Directive 2014/33/EU, ATEX Directive 2014/34/EU, Low Voltage Directive 2014/35/EU (applicable 20 April 2016); Radio Equipment Directive 2014/53/EU (applicable 13 June 2016); Pressure Equipment Directive 2014/68/EU (applicable 19 July 2016) and Marine Equipment Directive 2014/90/EU (applicable 18 September 2016). See http://ec.europa.eu/growth/single-market/goods/new-legislative-framework/index_en.htmFREQUENTLY ASKED QUESTIONS ON LVD 2014/35/EUTOPIC QUESTION REPLYPlace on themarketArticles 4, 6, 7, 8Difference between “placing on the market” and“making available on the market” in the frame of2014/35/EU (e.g. in Art. 4 making available is mentioned,but for the same activity when the responsibilities ofeconomic operators are covered – e.g. Art. 6, 7, 8 –placing on the market is mentioned)?'Making available' is the overall concept. Any transfer between economicoperators of a product is considered as making available. 'Placing on themarket' is a specific case of making available, namely it is the first time thatthe product is introduced on the market. It is important because at thatmoment the EU legislation applies. Any subsequent transfer is makingavailable.The operation is reserved either for a manufacturer or an importer, i.e. themanufacturer and the importer are the only economic operators who placeproducts on the market. When a manufacturer or an importer supplies aproduct to a distributor or an end-user for the first time, that operation islabelled in legal terms as placing on the market. Any subsequent operation,for instance, form a distributor to another or to an end-user is defined asmaking available.See also § 2.2. "Making available" and § 2.3. "Placing on the market" ofthe "Blue Guide"3In many cases products can be marketed through internet or other means but the product is not physically in the EU. Placing on the market requires the products to be physically in the EU territory? Union harmonisation legislation applies to all forms of selling. A product offered in a catalogue or by means of electronic commerce has to comply with Union harmonisation legislation when the catalogue or website directs its offer to the Union market and includes an ordering and shipping system. Products offered for sale online by sellers based outside the EU are considered to be placed on the Union market if sales are specifically targeted at EU consumers or businesses.See also § 2.1. "Product coverage" of the "Blue Guide"ManufacturerArticle 6.5 Type, batch or serial number:Does this Article mean that a product specification isrequired, but not necessarily a serial number? Wouldthere be a way to specify the sequential serial numberusing a barcode?The important point is that the numbering must allow making a clear link tothe relevant documentation that demonstrates the conformity of the specifictype of product, in particular the declaration of conformity.A barcode can also be used if this can reasonably be considered by amanufacturer as an appropriate way to identify and trace his products and tomake the link to the relevant documentation. Depending on the product, itis up to the manufacturer to decide whether the identification elementshould allow the identification of each single product or just the relevantbatch or type. But manufacturers should be aware that when publicauthorities recall products and it is not possible to distinguish betweenbatches or serial numbers, all products of that brand must be removed fromthe market.The Directive allows placing the information on the packaging or in adocument accompanying the electrical equipment if the size or nature ofthe electrical equipment does not allow it. Of course if the information is4not visible at a first sight, it must be easily and safely accessible. See also § 4.2.2.3. "Identification element" of the "Blue Guide"Article 6.6Name and address on the productIf lack of space, would be possible to indicate the nameand address within the product?The manufacturer must indicate his (1) name, (2) registered trademark and(3) a single contact postal address on the product or, when not possiblebecause of the size or physical characteristics of the product, on itspackaging and/or on the accompanying documentation.If the information is put inside the product, it must be easily accessible bythe Market Surveillance Authorities, without damaging the product or theneed for disassembling it with specific tools.See also §3.1. "Manufacturer" and §4.2.2.1. "The requirement to indicatename and address of the manufacturer" of the "Blue Guide"Must the information refer to the local distributor or theeconomic operator placing the product on the EU market?The information is related to the economic operator that places the producton the market i.e. the manufacturer or importer, not the distributor.In the case that a company is based in a third country andin an EU country, is necessary to put the information ofboth places as manufacturer and importer?If both, manufacturer and importer belong to the same group or companyand if the company based in the EU takes the full manufacturer'sresponsibility, the indication of the branch based in the EU will suffice tocomply with the requirements.5The postal address in which the manufacturer can be contacted, must be the one of the manufacturer? Not necessarily. The postal address must be "at which [the manufacturer] can be contacted": this is not necessarily the address where the manufacturer is actually established. This address can for example be the one of the authorised representative or of the customer services.See also § 4.2.2.1. "The requirement to indicate name and address for manufacturers" of the "Blue Guide"How to implement the requirement that the contact details shall be in a language easily understood? This provision refers to the use of alphabets. The address details do not have to be translated. The characters of the language must allow identifying the origin and the name of the company. This is not possible with certain alphabets.Article 6.7Instructions and safety informationWhat does mean ‘manufacturer’s documentation’ withinthe Low Voltage Directive?As Low Voltage Directive covers safety matters only,may any mandatory documentation relate to safety only? Instructions and safety information need to be provided, whether the product is intended for consumers or other end-users. The Low Voltage Directive does not make a distinction on who is the user of the product. The documentation should include all the necessary information for the safe use of the product, to enable the consumer to assemble, install, operate, store, maintain, repair, and dispose of the product.It is for the manufacturer to determine the relevant information which should be included in the instructions and safety information for a particular product.One single document can include both safety info and instructions.6Should each product sold in a bulk contain the instructions and safety information?May documents for products to be used most likely by professionals remain only in English? In principle, every individual product must be accompanied by the safety instructions but it does not mean that the full instructions must be given in paper. In some specific cases, where several identical products are bundled in a packaging for use in one application (e.g. installation equipment), it is sufficient to accompany the shipping unit with one set of instructions. If another economic operator along the distribution chain dismantles the bundle and sells the products individually, he should ensure that each product individually sold is accompanied by the necessary instructions and safety information.It is the national law that must indicate the languages required and if the use of English is allowed for specific uses.This item will also be clarified in the Blue Guide.See also § 3.1. "Manufacturer" of the "Blue Guide"Article 6.8The Directive requires that where the electrical equipmentpresents a risk, manufacturers shall immediately informthe competent national authorities.Which is the threshold of unacceptable risk above whichauthorities have to be informed? The acceptable level of risk for a product is determined by the compliance with the essential requirements. The essential requirements of the LVD have not been changed and therefore the previous thresholds for assessing the risks would continue to apply.7Importer Article 8.2“Before placing electrical equipment on the marketimporters shall ensure that the appropriate conformityassessment procedure has been carried out by themanufacturer. They shall ensure that the manufacturer hasdrawn up the technical documentation, that the electricalequipment bears the CE marking and is accompanied bythe required documents, and that the manufacturer hascomplied with the requirements set out in Article 6(5) and(6)”How do we interpret “the market importers shallensure”? Does it mean that the importers must have acopy of the declaration of conformity and the TechnicalDocumentation?The importer needs to have a copy of the declaration of conformity and hasto keep it for 10 years after a product has been placed on the market.The importer does not have to have a copy of the technical documentationbut has to ensure that the technical documentation can be made available tothe competent national authority upon request.Even if there is no explicit obligation, the importer is advised to requireformal assurance in writing from the manufacturer that the documents willbe made available when requested by the surveillance authority. But thetechnical documentation can be given directly by the manufacturer to thesurveillance authorities. What is important is that the authorities receive thedocumentation and that at importer's request the manufacturer provides theinformation to Member States.The importer also has to check the CE marking, labelling of the product,the identification number of the product, the contact details and that thecorrect conformity assessment procedure has been carried out.See also § 3.3 of the Blue Guide on the obligations of importersShould be the product accompanied not only by theinstructions for usage and safety but also by the CEdeclaration of conformity and/or technicaldocumentation?In the LVD context, the only document that has to accompany the productis the instructions and safety information.8Article 8.4“Importers shall ensure that the electrical equipment is accompanied by instructions and safety information in a language which can be easily understood by consumers and other end-users, as determined by the Member State concerned.”Can the product be imported with instructions only in English created by the manufacturer, and can the importer himself create a translation of the instructions that will accompany the product when is placed on the Union market? The Directive does not specify which economic operator has to translate the instructions and safety information. Manufacturers, importers and distributors have the obligation to ensure that the product is accompanied by instructions in a language which can be easily understood by consumers and other end-users, as determined by the Member State concerned.It is for each economic operator which makes available the product in a Member State, to ensure that all the languages are available. Nothing prevents economic operators from reaching contractual agreements on the manner in which they are translated.What happens if the product is placed on a market for which the manufacturer has not foreseen a translation? A manufacturer has a certain set of languages where he intends to ship the product but if it goes somewhere else, importer and distributor must ensure that instructions are translated in the relevant language. It depends on how economic operators are organised by contractual arrangements.What happens with bad translations? According to Article 6.7, instructions and safety information, as well as any labelling, shall be clear, understandable and intelligible and therefore bad translations will be considered as non-compliance.9Distributor Article 9.2“Before making electrical equipment available on themarket, distributors shall verify that the electricalequipment bears the CE marking, that it is accompaniedby the required documents and by instructions and safetyinformation in a language which can be easily understoodby consumers and other end-users in the Member State inwhich the electrical equipment is to be made available onthe market, and that the manufacturer and the importerhave complied with the requirements set out in Article6(5) and (6) and Article 8(3) respectively.”What exactly are the “required documents” that arementioned in this paragraph?The "required documents” that the distributor needs to make sure that arepresent are the ones which have to accompany the product, as described ineach aligned Directive.In LVD, besides the CE marking which the product needs to bear, therequired documents are only the instructions and safety information. Thedistributor does not have to have a copy of the Declaration of conformityor the Technical Documentation.See also § 3.4 of the Blue Guide.How do the distributors check if the requirements weremet except for the CE marking and the instructions ofusage and safety?The distributor must check that the manufacturer and importer haveindicated their name, registered trade name or trademark and the address atwhich they can be contacted on the product or when not possible becauseof the size or physical characteristics of the products, on its packagingand/or accompanying documentation and that the product bears a type,batch or serial number or other element allowing the identification of theproduct.10The distributor must be able to identify the manufacturer, his authorisedrepresentative, the importer or the person who has provided him with theproduct in order to assist the market surveillance authority in its efforts toobtain the EU declaration of conformity and the necessary parts of thetechnical documentation. Market surveillance authorities have thepossibility to address their request for the technical documentation directlyto the distributor. The latter, is however not expected to be in possession ofthe relevant documentation.Regarding the declaration of conformity, few electrical products fall onlyunder the LVD, normally they are covered by other Directives too. Whenseveral Directives regulate a product, the DoC should refer to all of themand the essential requirements. For this reason, when one product iscovered by several Directives for which the DoC must accompany theproduct, if the LVD applies as well, its reference should be included in the'global' DoC. This should be checked by the importer or distributor.In this regard, when some Directives apply, such as lifts, machinery orR&TTE, the LVD ceases to apply.Article 9.5“Distributors shall, further to a reasoned request from acompetent national authority, provide it with all theinformation and documentation in paper or electronicform necessary to demonstrate the conformity of electrical equipment. They shall cooperate with that authority, at its request, on any action taken to eliminate the risks posed by electrical equipment which they have made available on the market.” There is not specific time limit in the Directive for a "reasonable period". This period has to be assessed by the authorities on a case-by-case basis, taking into account the level of urgency/seriousness of risk and the efforts for the economic operator to follow-up the request. A default period could be e.g. 10 working days, but giving the possibility to shorten it or extend depending of the case. Member States are free to fix a default period inWhat is a reasonable period for the distributors to provide the necessary documents, taking in account the fact that even the smallest distributor should provide the information? their national laws, but there should always be a possibility to shorten or prolong that period.Harmonised standards Article 12List of harmonised standardsWhat would happen with the list of LVD harmonisedstandards if in the date of applicability of the newDirective new standards are not published?The LVD mandate requests CENELEC to provide the list of harmonisedstandards two months before the date of applicability of the new Directive.If the list of harmonised standards referring to the new Directive is notpublished in time, the mandate and Article 27 of the new LVD state that thereferences to the repealed Directive shall be construed as references to thenew Directive. Therefore, references to the existing LVD would givepresumption of conformity with the safety objectives of the new Directive2014/35/EU, because they remain the same.Are LVD harmonized standards going to content anAnnex ZA indicating the safety objectives covered by thestandard?The LVD mandate request CENELEC to include the Annex ZA only innew or revised standards, 12 months after the date of application of the newDirective.The annex ZA template will be unified for all New Legislative FrameworkDirectives and ESOs taking into consideration the Directives particularities.Declaration of conformityArticle 15.2Article 15.1 Article 15.2 TranslationIs the translation of the EU declaration of conformitymanufacturer's responsibility when he markets theequipment under his name or trade mark?Can the importer translate the declaration before heplaces the product on the market or can the distributortranslate it before making it available on the market andprovide the translation together with the EU declarationof conformity of the manufacturer which is for examplein English?Union harmonisation legislation does not necessarily specify who has theobligation to translate.It must be considered that, in the LVD, just the manufacturer or theimporter has to have a copy of the DoC. There can be a contractualarrangement between the manufacturer and the importer about who doesthe translation. It should be noted that there is a compulsory template of theDoC in Annex IV, which is translated in the OJEU in all EU languages.Must the translations of the declaration of conformity besigned by the manufacturer?The EU declaration of conformity must be signed by the manufacturer (byan individual working for the manufacturer) or his authorisedrepresentative, and the employee's function shall also be indicated.If a translation of the EU declaration of conformity is not signed by themanufacturer, a copy of the original EU declaration of conformity signedby the manufacturer must be provided together with the translated version. Information to be includedWhich information must be included in the declaration ofconformity?If a manufacturer produces a declaration of conformity that follows strictlythe template set out in Annex IV, he will completely fulfil the requirementsof the declaration of conformity. The reference in Annex III does not addany additional requirement. Additional information can be included.Article 15.3Reference to the new LVDFrom what date a manufacturer has to mention the newdirectives for his EU declaration of conformity (DoC)? Before 20 April 2016 all the EC declarations of conformity for LVD products placed on the EU market must be in line with Directive2006/95/EC. According to Article 25, products that are already in the distribution chain before 20 April 2016 (including stockpiles: see Recital 36) can continue to be made available on the EU market with this EC declaration of conformity referring to Directive 2006/95/EC as they have already been lawfully placed on the market. Declarations of conformity (EC or EU) remain valid according to the legislation in force when the product is placed on the market (= made available on the EU market for the first time). There is no need to change legislative references in documents accompanying the product.For LVD products placed on the EU market as of 20 April 2016 the EU declaration of conformity must be in accordance to the new LVD2014/35/EU by that date.Although in the LVD case, the DoC does not have to accompany the product, electrical equipment must comply with other EU legislation and the DoC accompanies often the product. In order to facilitate the transition to the new Directive 2014/35/EU, the EU declaration of conformity can indicate the following: “The object of the declaration described above is in conformity with the relevant Union harmonisation legislation: Directive 2006/95/EC (until April 19th, 2016) and Directive 2014/35/EU (from April 20th, 2016).”Equipment presenting arisk Article 19What is the purpose of Article 19 which describes theprocedure to deal with electrical equipment presenting arisk at national level?Article 19 describes the procedure for products presenting a risk.If upon request of the market surveillance authority (MSA), the economicoperator agrees to take the necessary corrective action (voluntary measuresby the operator), the procedure ends here. In this case, if the MSA considerthat the risk goes beyond the national territory, they will inform theCommission and other Member States (MS) of the results of the evaluationand the actions the economic operator intends to take.However, if the economic operator does not take corrective action asrequested by the MSA, the MSA shall take appropriate measures againstthe product (compulsory measures). In this case, the national authoritiesnotify the measure to the Commission and other MS, who have thepossibility to object to it during a 3-month period. If no objection is raised,the measure is deemed to be justified. In this case all Member States areobliged to take appropriate action against the product on their territories.If objections are raised, the Commission needs to take a decision todetermine whether the measure should be considered as justified or not(Union safeguard procedure in Article 20).The purpose is that restrictive measures against the product are not anunjustified restriction of the free movement of goods. Additionally, is aninformation-sharing tool between MSAs. This exchange of information,although non-compulsory in the phase of voluntary corrective actions, isalso expected to be submitted by the MSA to other MS.The safeguard clause procedure has not changed and must be applied in。
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1、1）Supply illustrations at the size they are to be printed, usually 76 mm wide (single column of text) or for especially large figures 161 mm (two columns of text). The intermediate width of 100 mm is also available should neither of these suffice.2）Do not put a box around graphs, diagrams or other artwork.3）Ensure that lettering is appropriately sized – should correspond to 8 or 9 pt when... amp;tpg=2&age=02、Conflicts of interestWe ask authors to state all possible conflicts of interest, including financial and other relationships. If you are sure that there is no conflict of interest, please state this. You might like to look at an editorial in the British Medical Journal on Beyond conflict of interest (cgi/content/short/317/7154/291). Remember that sources of funding should be acknowledged in your paper.... amp;tpg=2&age=03、Submission items include a cover letter (Authors are highly encouraged to include a list of 5-6 potential reviewers for their manuscript, with complete contact information), the manuscript (including title page, abstract, manuscript text, references, and table/figure legends), tables, and figures.The manuscript must be accompanied by a covering letter detailing what you are submitting (type of contribution, title, authors' names and affiliation, etc.).... amp;tpg=3&age=04、1）.Authors can submit their articles electronically via the “Author Gateway” page of this journal ( system automatically converts source files to a single Adobe Acrobat PDF version of the article, which is used in the peer-review process. Please note that even though manuscript source files are converted to PDF at submission for the review process, these source files are needed for further processing after acceptance.2）.Alternatively authors can submit by sending three hard copies of the manuscript and matching disk or e-mail directly to an editor who is an expert in the field of work being submitted.3）.The Publisher welcomes the receipt of an electronic version of your accepted manuscript (preferably encoded in LATEX). If there is not already a copy of this (on diskette) with the journal Editor at the time the manuscript is being refereed, you will be asked to send a file with the text of the accepted manuscript directly to the Publisher by e-mail or on diskette to the address given the electronic file is suitable for processing by the Publisher, the article will be published without rekeying the full text. The article should be encoded in LATEX, preferably using the Elsevier document class ‘elsart’, or alternatively the standar d document class ‘article’ or the document style ‘re-vtex’. ... amp;tpg=3&age=05、1）Manuscripts should be written in clear, concise form and sent to the Director，Three copies of the manuscripts must be written in English and double-spaced throughout.2） Each table should be titled, appropriately numbered and typed on a separate sheet.Units of measurement should be indicated and all abbreviations defined. 3） All the illustrations (graphs, drawings and photographs) should be referred to in the text as Figures. These should be good quality glossy photographs (or original India-ink drawings).4） Since graphs are generally reduced in size to cm, numbers, letters and symbols are to be originally large enough so that, when reduced, they will remain at least 2 mm high to maintain legibility. To avoid reduction, photographs' width should generally not exceed cm. When necessary, photographs can be arranged to form a plate of the maximum size of 17 cm (width) x 18 cm (height). Legends to figures should be typed on a separate sheet.5） Reprints should be ordered when returning the revised proofs and will be charged to the Authors.... amp;tpg=3&age=06、The Title page should include (1) a short and informative full articletitle (series titles are not accepted); (2) names of all authors (with one forename in full for each author), followed by their affiliations (department, institution, city with postcode, country); (3) the mailing address, fax and phone number and e-mail address of the corresponding author; (4) a running title of 50 characters or less.... amp;tpg=4&age=07、Entering a Comment is Required for Submission.You must include below an ethical statement that the manuscript has not and will not be submitted for publication elsewhere, while it is in review for MRB.Please suggest 3 suitable reviewers for your manuscript. Please provide the full name and e-mail address, and if possible, telephone number and postal address of each suggested reviewer.Please enter any additional comments that you would like to send to the editorial office. These comments do not appear in your manuscript. ... amp;tpg=4&age=08、running title，teaching cases... amp;tpg=5&age=09、Two complete sets of ullitrations must be submitted with legends typed on the same sheet... amp;tpg=6&age=010、All illustrations should accompany the typescript, but not be inserted in the textphotographs....should have the author's name, bthe figure number and an indication as to which is the top of the picture.Script should be typed doulbe-spaced on one side of the paper only", "doulbe-spaced“... amp;tpg=6&age=011、“The name of the author and the number of the figure (in Arabic numbers) should be written in the margin in blue pencil.”The legends of the figures should be typed on a separate sheet headed "Figure legends".）（figure legend）... amp;tpg=7&age=012、Submit the text (including any Tables) as a single file, in a standard disk inch, not high density; 100 and 250 MB Zip disk and CD are also accepted), together with two hard copies of the manuscript and two sets of figures (not photocopies). Not photocopies... amp;tpg=7&age=013、reviewer suggestions... amp;tpg=8&age=014、The manuscript must be accompanied by copies of all relevant papers published elsewhere by the authors and by copies of relevant manuscripts that are in press or under editorial consideration. If any tables or illustrations have been published elsewhere the editorial office must be informed so that permission to reproduce can be obtained from the original publishers.Papers must be arranged in the following order of presentation: title of paper; names of the authors; address of the place at which the work was carried out; a self-contained synopsis of the paper (100-200 words in length); tables; an abbreviated title for use as a running headline; captions to figures (on a separate page). Submissions not conforming to these guidelines may be returned to the authors.a self-contained synopsis of the paper (100-200 words in length); tables; an abbreviated title for use as a running headline; captions to figures (on a separate page)Figure captions should be submitted on a separate sheet of manuscript paper, clearly labeled. A total of 25 reprints of each paper will be provided free of charge to the author... amp;tpg=1&age=015、cover letter和reviewer suggestions... mp;tpg=17&age=016、In my experience, most overseas English journals with IF 1-5 don't require any review fees and publication fees. Moreover, you may receive up to 50 reprints for free when the paper is published.However, some (not all) journals with higher IF, you may need such fees. You have to check if before or when you submit (normally online) your paper.... mp;tpg=19&age=017、The authors should submit all the following files:official letter (paper with the heading of the institute, laboratory or company submitting the manuscript) signed by one of the authors, scanned as an image or pdf file.... mp;tpg=21&age=018、cover letter 和comment... mp;tpg=25&age=019、Running Title... mp;tpg=30&age=0【投稿状态】1、awaiting AE assignment... amp;tpg=3&age=02、with mini-hanging committee... amp;tpg=4&age=03、Current Status：Required Reviews Completed... amp;tpg=4&age=04、Awaiting Chief Editor Decision... amp;tpg=4&age=05、with referees Awaiting ED Recommendation... amp;tpg=5&age=0... amp;tpg=6&age=06、under review... amp;tpg=5&age=07、Required reviews completed... amp;tpg=5&age=08、with editor... amp;tpg=6&age=09、status date... amp;tpg=6&age=0awaiting reviwer assignment... amp;tpg=7&age=010、in press ；Corrected Proof；Available online 16 September 2005 ... amp;tpg=8&age=011、awaiting scores awaiting AE decision AE... mp;tpg=13&age=012、in review... mp;tpg=17&age=013、with editor for decision... mp;tpg=23&age=0【图表要求】1、Submit original figures with the final manuscript. Figures are normally glossy prints of photographs or crisp black and white reproductions (photostats) of line drawings. To submit figures as computer files follow the instructions below. Image resolution must be 300 ppi at final printed image size. If the final printed image size is unknown, size the image at a larger than final print size, maintaining at least 300 ppi resolution, and we will downsample the image to fit the final print dimensions (we cannot enlarge a digitized image). Image sizes as follows: 2175 pixels wide for a 2-column image; 975 pixels wide fora 1-column image.... amp;tpg=1&age=02、line artwork, halftone artwork, combination artwork(line/tone) ... amp;tpg=1&age=0... mp;tpg=13&age=03、“ Authors should NOT in addition then post a hard copy submission to the editorial office, unless you are supplying artwork, letters or files that cannot be submitted electronically, or have been instructed to do so by the editorial office.”“References to figures and tables should be made in order of appearance in the text and should be in Arabic numerals in parentheses, . (Fig. 2). Most file formats are accepted, but TIFF and EPS files, with fonts embedded, are preferred. If scanned, line art should be at a resolution of 800 dpi, and halftones and colour at 300 dpi. All colour values should be CMYK. ”... amp;tpg=2&age=04、Figures (photographs, diagrams and graphs)All illustrations should be provided in camera-ready form, suitable for reproduction (which may include reduction) without retouching. In addition, illustrations should be sent in electronic form wherever possible, with each illustration included as an individual TIFF or EPS file.Figures should be numbered consecutively in the order which they are referred to. They should not be included in the manuscript pages. The following standard symbols should be used as they are readily available to the typesetter: [] ע. Figure captions should be typed on a single sheet and placed at the end of the manuscript. The amount of lettering on a drawing should be reduced as far as possible by transferring it to the legend.... amp;tpg=3&age=05、Tables should be typed on separate pages and be numbered consecutively using Arabic numerals.... amp;tpg=4&age=06、For each item you wish to submit, scroll down and:Select the appropriate Item from the drop-down list. Mandatory Items are marked with an asterisk *.Enter a Description in the text box. Click Browse. In the open a window, select the file on your computer (original source file, not a PDF) and click Open. 'File Name' is filled now. Click Attach This File.Repeat steps 1-5 to attach the next submission Item When all Items have been attached, click Next at the bottom of the page.Note 1: Figures, graphics, photos should not be embedded in the manuscript text file. Please upload separate figure files, preferred formats are EPS, TIFF, JPEG.Note 2: If a Figure or Table is uploaded as a separate file, then please exclude this from the manuscript textfile, otherwise it will be shown in the PDF twice.... mp;tpg=15&age=07、Line graphs and bar charts should be sent in bitmap TIFF files witha minimum resolution of 1200 dpi, or as EPS files, with a preferred line width of 1 pt (minimum line width of pt). Bitmap images should be sent as TIFF files and not placed within EPS files .... mp;tpg=23&age=0。
欧洲药品管理局的科学准则和欧洲药典专论和监管框架的章节适用于医药产品的状态
European Medicines Agency7 Westferry Circus, Canary Wharf, London, E14 4HB, UKTel. (44-20) 74 18 84 00 Fax (44-20) 74 18 86 13E-mail: mail@emea.europa.eu http://www.emea.europa.eu 11 September 2008 - corrEMEA/42371/2008STATUS OF EMEA SCIENTIFIC GUIDELINES AND EUROPEAN PHARMACOPOEIA MONOGRAPHS AND CHAPTERS IN THE REGULATORY FRAMEWORK APPLICABLETO MEDICINAL PRODUCTSExecutive summaryThe present guideline clarifies the status of EMEA guidelines and European Pharmacopoeia monographs and chapters in the context of the regulatory framework applicable to medicinal products in the European Union.1. Rules governing Medicinal Products in the European UnionThe ‘Introduction and general principles’ of Annex I of Directive 2001/83/EC1, as amended, defines the principles governing the assurance of quality of medicinal products:∙(4) In assembling the dossier for application for marketing authorisation, applicants shall also take into account the scientific guidelines relating to the quality, safety and efficacy of medicinal products for human use as adopted by the [Committee for Medicinal Products for Human Use (CHMP)2] and published by the European Medicine Evaluation Agency (EMEA) and the other pharmaceutical Community guidelines published by the Commission in the different volumes of The rules governing medicinal products in the European Community.∙(5) With respect to the quality part (chemical, pharmaceutical and biological) of the dossier, all monographs including general monographs and general chapters of the European Pharmacopoeia are applicable.∙(6) The manufacturing process shall comply with the requirements of Commission Directive 91/356/EEC laying down the principles and guidelines of Good Manufacturing Practice (GMP) for medicinal products for human use (2) and with the principles and guidelines on GMP, published by the Commission in The rules governing medicinal products in the European Community, Volume 4.Since Annex I of Directive 2001/83/EC, as amended, defines the detailed scientific and technical requirements for the marketing authorisation of medicinal products, these principles only apply to the evaluation of marketing authorisation applications and to authorised medicinal products.These principles are also defined in the legislation governing veterinary medicinal products.2. Role of EMEA scientific guidelines and European Pharmacopoeia monographs andchaptersEMEA scientific guidelinesA guideline is a Community document, which is either referred to in the legislative framework as intended to fulfil a legal obligation laid down in the Community pharmaceutical legislation or 1 Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (Official Journal L 311, 28/11/2001 p. 67 - 128), as amended.2 Previously called ‘Committee for Proprietary Medicinal Products’ (CPMP)considered to provide advice to applicants or marketing authorisation holders, competent authorities and/or other interested parties on the best or most appropriate way to fulfil an obligation laid down in the community pharmaceutical legislation. In the case of scientific guidelines, these may relate to specific scientific issues reflecting a harmonised EU approach and based on the most up-to-date scientific knowledge.Within the framework of the pharmaceutical legislation, scientific guidelines do not have legal force and the definitive legal requirements are those outlined in the relevant Community legislative framework (Directives, Regulations, Decisions etc.) as well as appropriate national rules. However, scientific guidelines are to be considered as a harmonised Community position, which if they are followed by relevant parties such as the applicants, marketing authorisation holders, sponsors, manufacturers and regulators will facilitate assessment, approval and control of medicinal products in the European Union. Nevertheless, alternative approaches may be taken, provided that these are appropriately justified3.European Pharmacopoeia monographs and chaptersThe European Pharmacopoeia is a collection of standardised specifications on the quality of pharmaceutical preparations, their constituents or their containers. The European Pharmacopoeia covers but is not limited to: Synthetic chemical active substances; Natural products (e.g. herbal drugs, herbal preparations, herbal teas, essential oils, extracts); Biological products and biotechnology-derived products; Vaccines for human use; Veterinary vaccines; Mineral products; Radiopharmaceutical products; Excipients; Containers; Dosage forms; Homoeopathic preparations; Standard Terms on dosage forms, routes of administration and containers.Some requirements may apply simultaneously to classes of substances and preparations and therefore are covered by general monographs and some requirements may be specific to a monograph dedicated to the substance/preparation in question.Within the framework of the pharmaceutical legislation, monographs including general monographs and general chapters have legal force (see section 1 above) with regard to the quality part of the dossier supporting marketing authorisations unless the scope of the particular monograph or general chapter makes it clear that the text is not mandatory. The mandatory status of European Pharmacopoeia texts is explained in the General Notices of the European Pharmacopoeia.4 Furthermore, within the regulatory framework, reference to either the European Pharmacopoeia, the Pharmacopoeia of an EU Member State, the United States Pharmacopoeia or the Japanese Pharmacopoeia is acceptable for products under development, for instance products undergoing clinical trials. For active substances, the suitability of the referenced monograph to adequately control the quality (impurity profile) will have to be demonstrated by the applicant/sponsor. Nevertheless, the need for later compliance with the European Pharmacopoeia to obtain a marketing authorisation should be taken into account during development to avoid difficulties during evaluation of the application for authorisation. Further information on this aspect is provided in the Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials (CHMP/QWP/185401/2004).3 An exception to this general rule is the “Note for guidance on minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products” which is published in the Official Journal by the European Commission and updated regularly.In accordance with Directives 2001/82/EC and 2001/83/EC, this Note for Guidance has to be explicitly complied with. The mandatory requirement has been translated by the Ph. Eur. into the general monograph Products with risk of transmitting agents of animal spongiform encephalopathies (1483), which refers to the Note for guidance verbatim.4 The General Notices (1.1) of the Ph. Eur. state: “Unless otherwise indicated in the General Notices or in the monographs, statements in monographs constitute mandatory requirements. General chapters become mandatory when referred to in a monograph, unless such referenceis made in a way that indicates that it is not the intention to make the text referred to mandatory but rather to cite it for information. (...) General monographs and individual monographs are complementary. If the provisions of a general monograph do not apply to a particular product, this is expressly stated in the individual monograph.” Furthermore, “Statements containing the word ‘should’ are informative or advisory” and the General Notices (1.4) specify those sections of a Monograph that constitute mandatory requirements and those that do not.3. Complementary roles of EMEA scientific guidelines and European Pharmacopoeiamonographs and chaptersHence, EMEA scientific guidelines and European Pharmacopoeia monographs and chapters are complementary instruments to ensure the quality of medicinal products:∙guidelines provide advice on the best or most appropriate way to fulfil legal obligations∙the European Pharmacopoeia sets standardised specifications for pharmaceutical preparations, their constituents and containers.For areas already covered by existing EMEA scientific guidelines, cross-references in European Pharmacopoeia texts to guidelines avoid repeating such guidance to facilitate updating. This is particularly important for new and rapidly evolving technologies for which guidelines may have to be amended frequently5.5 The General Notices (1.2) of the Ph. Eur. state:”References to regulatory documents. Monographs and general chapters may contain references to documents issued by regulatory authorities for medicines, for example directives and notes for guidance of the European Union. These references are provided for information for users for the Pharmacopoeia. Inclusion of such a reference does not modify the status of the documents referred to, which may be mandatory or for guidance.”。
苏格兰 围术期预防的抗菌药物使用
KEY TO EVIDENCE STATEMENTS AND GRADES OF RECOMMENDATIONS
LEVELS OF EVIDENCE 1++ 1+ 12++ 2+ 23 4 High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias Well conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias Meta-analyses, systematic reviews, or RCTs with a high risk of bias High quality systematic reviews of case control or cohort studies High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal Non-analytic studies, eg case reports, case series Expert opinion
(EU) No 995-2010 - Final Guidance document FOR THE EU TIMBER REGULATION
GUIDANCE DOCUMENTFOR THE EU TIMBER REGULATIONINTRODUCTIONRegulation (EU) No 995/2010 laying down the obligations of operators who place timber and timber products on the market1 (the EU Timber Regulation; EUTR) provides for adoption of non-legislative measures by the Commission aiming at uniform implementation. The Commission adopted a delegated Regulation laying down detailed requirements and a procedure for recognition and withdrawal of recognition to monitoring organisations2 and an implementing Regulation laying down detailed rules regarding the due diligence system and the frequency and nature of the checks to be carried out by Member States' competent authorities on monitoring organisations3.Following consultations with stakeholders, experts from Member States and members of the FLEGT Committee a common view emerged that certain aspects of the EU Timber Regulation need clarification. It was agreed that a guidance document was necessary, in which issues related to the EU Timber Regulation and its non-legislative acts to be addressed. The guidance document was discussed and elaborated with the assistance of the FLEGT Committee.The guidance document will not have a binding legal effect; its sole purpose is to provide explanations on certain aspects of the EU Timber Regulation and the two Commission non-legislative acts. It does not replace, add or amend anything to the provisions of the Regulation (EU) No 995/2010, the Commission Regulation (EU) No 363/2012, and the Commission Regulation (EU) No 607/2012, which constitute the legal basis to be applied. The issues addressed in the guidance document should not be considered in isolation; they must be used in conjunction with the legislation, and not as a “stand-alone” reference.Our belief however is that the guidance document will be a useful reference material for everyone who will have to comply with the EU TR as it provides important elucidation on parts of the legislative text that are difficult to understand. The guidance document will serve also to guide national competent authorities and enforcement bodies in the process of implementation and enforcement of this legislative package.During the consultation process for elaborating the two Commission non-legislative acts and after holding numerous bilateral meetings with stakeholders a number of issues were outlined and to be included in a guidance document. After gathering some experience in application of the EUTR and if need be the list of issues could be further expanded and the document supplemented accordingly.1 OJ L 295, 12.11.2010, p. 23.2 OJ L 115, 27.4.2012, p. 12.3 OJ L 177, 7.7.12, p. 16.1. The definition of "placing on the market"Relevant legislation:EU Timber RegulationArticle 2 Definitions[···](b) 'placing on the market ' means the supply by any means, irrespective of the selling technique used, of timber or timber products for the first time on the internal market for distribution or use in the course of a commercial activity, whether in return for payment or free of charge. It also includes the supply by means of distance communication as defined in Directive 97/7/EC of the European Parliament and of the Council of 20 May 1997 on the protection of consumers in respect of distance contracts (3). The supply on the internal market of timber products derived from timber or timber products already placed on the internal market shall not constitute 'placing on the market '[···]This definition clearly states that the "supply" must be:•on the internal market - so the timber must be physically present in the EU, either harvested here or imported and cleared by customs for free circulation as products do notacquire the status of "European Union goods" before they have entered the territory of thecustoms union. Goods under special customs procedures (e.g. temporary importation; inwardprocessing; processing under customs control; customs warehouses; free zones) as well astransits and reexportation are not considered to be placed on the market.•for the first time - timber products already placed on the EU market will not be covered nor will products derived from timber products already placed on the market. Making a productavailable for the first time further refers to each individual product placed on the marketafter the date of entry into application of the EU Timber Regulation (3rd March 2013), andnot to the launch of a new product or product line. Moreover the concept of placing on themarket refers to each individual product, not to a type of product, irrespective of whether itwas manufactured as an individual unit or a series• in the course of a commercial activity - so the Regulation does not impose requirements on non-commercial consumersAll the above elements must be present simultaneously. 'Placing on the market' should therefore, be understood as occurring when an operator first makes timber or timber products available on the EU market for distribution or for use in the course of his commercial activity.The provisions of the Regulation concerning "operators" therefore apply to:•companies or individuals which harvest timber within the EU, for the purpose of processing or for distribution to commercial or non-commercial consumers•companies or individuals which bring timber or timber products into the EU, for the purpose of processing or for distribution to commercial or non-commercial consumers, and •companies or individuals which harvest timber within the EU or bring timber or timber products into the EU exclusively for use in their own business.Under this interpretation, a business which harvests timber within the EU or which brings into the EU timber or timber products for use in its own organisation needs to implement a due diligence system. This interpretation does not require the timber to be sold or physically transferred to a specific person: the timber is covered by the Regulation as soon as a supplier made it available for distribution or use in the EU4.The position under the Regulation of 'agents' who act as middle men, sourcing products for others and not merely acting as shipping agents, will need to be determined by reference to the particular facts of each case and the applicable contractual arrangements. An 'agent' who purchases and brings stock into the EU to meet anticipated orders from buyers will be an "operator" in his own right, unlike a true agent who acts only on behalf of another party and at no point takes actual ownership of products himself.For timber harvested outside the EU:•Where an EU based company buys timber or timber products in a third country and imports them into the EU, the EU based company becomes an operator when the timber or timber products enter the EU•Where an EU based company buys timber or timber products in a third country and then has an agent imports them into the EU, the EU based company becomes an operator when the timber or timber products enter the EU•Where an EU based company orders timber or timber products in a third country from a non-EU based supplier who imports them into the EU, the EU company becomes an operator when the timber enters the EU (even if ownership does not formally transfer until the timber is delivered to the EU based company)•Where a non-EU based company imports timber or timber products into the EU, obtains the4This interpretation broadly accords with the approach taken in the Guide to the Implementation of Directives based on the New Approach and the Global Approach ("the Blue Guide"), which could be seen on: http://ec.europa.eu/enterprise/policies/single-market-goods/files/blue-guide/guidepublic_en.pdf. However, the definition in the EU Timber Regulation differs from the one used in the single market directives.release for free circulation and then seeks a buyer, the non-EU based company becomes an operator when the timber or timber products enter the EU (because the non-EU company has made the timber products available on the EU market)•Where a non-EU based company sells timber or timber products from a third country directly to non-commercial end-users in the EU, the non-EU company becomes an operator when the timber or timber products enter the EUAll operators, whether EU or non-EU based, must comply with the prohibition on placing illegally harvested timber on the market and the obligation to exercise due diligenceScenarios outlining how the interpretation of placing on the market would work in practice are given in Annex I.The EU Timber Regulation does not have retroactive effect. This means that the prohibition will not apply to timber and timber products placed on the marked before its entry into application on 3rd March 2013. However operators will need to show, when checked by the competent authorities, that they have established a due diligence system which is operational as of 3rd March 2013. Therefore it is important that operators are able to identify their supply before and after that date. The obligation for traceability for traders also applies from that date.2. Definition of negligible riskRelevant legislation:EU Timber RegulationArticle 6Due diligence systems[…](c) except where the risk identified in course of the risk assessment procedures referred to in point (b) is negligible, risk mitigation procedures which consist of a set of measures and procedures that are adequate and proportionate to minimise effectively that risk and which may include requiring additional information or documents and/or requiring third party verification.Due diligence requires an operator to gather information about timber and timber products and their suppliers in order to conduct a full risk assessment. The information required to be assessed under Article 6 can be divided into two categories.•Article 6(1)(a) - specific information related to the timber or timber product itself: a description, its country of harvest (and, where applicable the sub-national region and concession), the supplier and trader, and documentation indicating compliance with applicable legislation.•Article 6(1)(b) general information providing the context for assessing the product- specific information, about the prevalence of illegal harvesting of specific tree species and prevalence of illegal harvesting practices in the place of harvest, and on the complexity of the supply chain, While the general information provides operators with the context in which to evaluate the level of risk, the product specific information is necessary to determine the risk linked to the timber product itself. It means that if the general information points to potential risks, special attention needs to be given to the gathering of the product specific-information. If the product is derived from several timber sources it will be necessary to assess the risk for each component or species.The level of risk can only be assessed on a case-by-case basis as it depends upon a number of factors. Although there is not a single accepted system for risk assessment, as a general rule however, the operator will have to address the following questions:•Where was the timber harvested?Is illegal logging prevalent in the country, or sub-region, or concession from where the timber originates? Is the specific tree species involved particularly at risk of illegal logging? Are there sanctions imposed by the UN Security Council or the Council of the European Union on timber imports and exports?•Is the level of governance of concern?The level of governance might undermine the reliability of some documents indicating compliance with applicable legislation. Thus the country's corruption level, business risk indices, or other governance indicators should be considered.•Are all documents indicating compliance with applicable legislation made available by the supplier, and are verifiable?If all possible documents are readily available, there is a stronger likelihood that the product's supply chain has been established. There should be well founded confidence that the documents are genuine and reliable.•Are there indications of involvement of any company in the supply chain in practices related to illegal logging?There is a greater risk that timber purchased from a company that has been involved in practices related to illegal logging will have been illegally harvested.•Is the supply chain complex?5The more complex the supply chain the harder it may be to trace the origins of the wood in a product back to the logging source. Failure to establish necessary information at any point in the supply chain may increase the possibility of illegally harvested timber entering the chain.Negligible risk should be understood to apply to a supply when, following full assessment of both the product-specific and the general information no cause for concern can be discerned.The list of risk assessment criteria is not exhaustive; operators may choose to add further criteria if they help determine the likelihood that timber in a product had been illegally harvested, or alternatively, demonstrate legal harvesting.5 For clarification of "complexity of supply chain" see section 3.3. Clarification of "complexity of the supply chain"Relevant legislation:EU Timber RegulationArticle 6Due diligence systems[···](b) risk assessment procedures enabling the operator to analyse and evaluate the risk of illegally harvested timber or timber products derived from such timber being placed on the market.Such procedures shall take into account the information set out in point (a) as well as relevant risk assessment criteria, including:[···]— complexity of the supply chain of timber and timber products.Complexity of the supply chain is explicitly listed amongst the risk assessment criteria in Article 6 of the Regulation and therefore is relevant to the risk assessment and risk mitigation part of the due diligence exercise.The rationale underpinning this criterion is that tracing timber back to its place of harvest (country of harvest and, where applicable, the sub-national region and the concession of harvest) may be more difficult if the supply chain is complex. Failure to establish necessary information at any point in the supply chain can increase the possibility of illegally harvested timber entering the chain. However it is not the length of the supply chain which should be regarded as the factor that elevates risk. What matters is the ability to trace the timber in a product back to its place of harvest. The level of risk will increase if the complexity of the supply chain makes it difficult to identify the information required by Article 6(1)(a) and (b) of the EU Timber Regulation. The existence of unidentified steps in the supply chain can lead to the conclusion that the risk is non-negligible.The complexity of the supply chain increases with the number of processors and middlemen between the place of harvest and the operator. Complexity may also increases when more than one species or timber sources are used in the product.In order to assess the complexity of the supply chain operators might use the following questions, which are neither obligatory nor exclusive:9Are there several processors and steps in the supply chain before the placing of a particular timber product on the EU market?9Have timber and timber products been traded in more than one country before placing on the EU market?9Does the timber in the product to be placed on the market consist of more than one tree species?9Does the timber in the product to be placed on the market come from different sources?4. Clarification of the requirement for documents indicating compliance oftimber with applicable legislationRelevant legislation:EU Timber RegulationArticle 2[···](f) 'legally harvested' means harvested in accordance with the applicable legislation in the country of harvest;(g) 'illegally harvested' means harvested in contravention of the applicable legislation in the country of harvest;(h) 'applicable legislation' means the legislation in force in the country of harvest covering the following matters:- rights to harvest timber within legally gazetted boundaries,- payments for harvest rights and timber including duties related to timber harvesting,- timber harvesting, including environmental and forest legislation including forest management and biodiversity conservation, where directly related to timber harvesting,- third parties ' legal rights concerning use and tenure that are affected by timber harvesting, and- trade and customs, in so far as the forest sector is concerned.Article 6Due diligence systems(1) [···](a) measures and procedures providing access to the following information concerning the operator 's supply of timber or timber products placed on the market:[···]documents or other information indicating compliance of those timber and timber products with the applicable legislationThe rationale behind this obligation is that in the absence of an internationally agreed definition of legally harvested timber the basis for defining what constitutes illegal logging should be the legislation of the country where the timber was harvested.The EUTR provides in Art. 6(1)(a) last indent that documents or other information indicating compliance with applicable legislation in the country of harvest must be collected as part of the due diligence obligation. It should be stressed from the outset that collecting documentation must be done for the purposes of the risk assessment and should not be viewed as a self-standing requirement.The EUTR takes a flexible approach by listing a number of legislative areas without specifying particular laws, which are differ from country to country and may be subject to amendments. In order to obtain documents or other information indicating compliance with the applicable legislation in the country of harvest operators must in the first place be aware of what legislation exists in a particular country of harvest. In this effort they may be supported by the Member States' Competent Authorities in collaboration with the European Commission 6. They may also make use of the services of monitoring organisations (MO). In cases where operators are not using services of a MO they may seek assistance from organisations with specialist knowledge of the forest sector in specific countries where timber and timber products are harvested.The obligation to obtain documents or other information should be interpreted broadly as different regulatory regimes exist in different countries, and not all of them require issuing of specific documentation. Therefore it should be read as including official documents issued by competent authorities; documents demonstrating contractual obligations; documents showing company policies; codes of conducts; certificates issued by third party verified schemes, etc.The following table gives some concrete examples, which are for illustration purposes and cannot be considered compulsory or exhaustive:6 The EU has concluded a number of Voluntary Partnership Agreements (VPA) with third countries, which contain a detailed description of legislation applicable in those countries. They can guide operators regarding the applicable law in relation to products, which are not included in the Annex to a particular VPA as the case might be.1. Documentation for rights to harvest timber within legally gazetted boundaries Generally available documents in paper or electronic form e.g. documentation ofownership/rights to land use or contract orconcession agreements2. Payments for harvest rights and timber including duties related to timber harvesting Generally available documents in paper or electronically e.g. contracts, bank notes, VATdocumentation, official receipts, etc.3. Timber harvesting, including environmental and forest legislation including forest management and biodiversity conservation, where directly related to timber harvesting. Official audit reports; environmental clearance certificates; approved harvest plans; coupe closure reports, ISO certificates; codes of conducts;publicly available information demonstratingrigorous legislative supervision and timber trackingand control procedures; official documents issuedby competent authorities in a country of harvest etc.4. Third parties' legal rights concerning use and tenure that are affected by timber harvesting Environnemental impact sassements,environnemental management plans,environnemental audit reports, socialresponsibility agreements, specific reports on tenureand rights claims and conflicts.5. Trade and customs, in so far as the forest sector isconcernedGenerally available documents in paper or electronic format e.g. contracts, bank notes, trade notes, import licenses, export licenses, officialreceipts for export duties, export ban lists, exportquota awards, etc.5a. Clarification of the product scope - packaging materialsRelevant legislation:EU Timber RegulationArticle 2(a) "Timber and timber products means the timber and timber products as set out in the Annex, with the exception of timber and timber products or components of such products manufactured from timber and timber products that have completed their lifecycle and would otherwise be disposed of as waste as defined in Article 3(1) of Directive 2008/98/EC of the European Parliament and of the Council of 19 November 2008 on waste"The Annex to the EU Timber Regulation[···]4415 Packing cases, boxes, crates, drums and similar packing, of wood; cable-drums of wood; pallets, box pallets and other load boards, of wood; pallet collars of wood(Not packing material used exclusively as packing material to support, protect or carry another product placed on the market.) "[···]Pulp and paper of Chapters 47 and 48 of the Combined Nomenclature, with the exception of bamboo-based and recovered (waste and scrap) products[···]The Annex sets out the "Timber and timber products as classified in the Combined Nomenclature7 set out in Annex I to Council Regulation (EEC) No 2658/87, to which this Regulation applies"HS Code 4819 covers : "Cartons, boxes, cases, bags and other packing containers, of paper, paperboard, cellulose wadding or webs of cellulose fibres; box files, letter trays, and similar articles, of paper or paperboard, of a kind used in offices, shops or the like ".•When any of the above articles are placed on the market as products in their own right, rather than simply being used as packaging for another product, they will be covered by the Regulation and therefore due diligence must be applied.•If packaging, as classified under HS code 4415 or 4819, is used to 'support, protect or carry' another product it will not be covered by the Regulation.This means that the above cited restriction in brackets to HS Code 4415 within the Annex of the EUTR is used by analogy also to HS Code 4819.7The current version of the Combined Nomenclature is available at: http://eur- lex .europa.eu/Result.do?direct=yes&lang=en&where=EUROVOC :005751 &whereihm=EUR OVOC:Combined%20NomenclatureWithin these categories there is a further distinction between packaging that is considered to give a product its 'essential character' and packaging which is shaped and fitted to a specific product, but not an integral part of the product itself. General rule 5 for the interpretation of the Combined Nomenclature8 clarifies these differences and examples are contained below. However, these additional distinctions are only like to be relevant to a small proportion of goods subject to the Regulation.In summary,Covered by the Regulation•Packaging material of HS codes 4415 or 4819 placed on the market as a product in itself.•Containers which fall within HS codes 4415 or 4819 which give a product its essential character:e.g. decorative gift boxes,Exempt from the Regulation:•Packing material presented with the goods therein and used exclusively to support, protect or carry another product (which may or may not be a wood-based product).8 http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1999:278:0011:0012:EN:PDF5b. Clarification of the product scope - "waste*'/"recovered" products Relevant legislation:EU Timber RegulationRecital (11)Bearing in mind that the use of recycled timber and timber products should be encouraged, and that including such products in the scope of this Regulation would place a disproportionate burden on operators, used timber and timber products that have completed their life cycle, and would otherwise be disposed of as waste, should be excluded from the scope of this Regulation.Article 2(a) 'timber and timber products ' means timber and timber products set out in the Annex, with the exception of timber products or components of such products manufactured from timber or timber products that have completed their lifecycle and would otherwise be disposed of as waste, as defined in Article 3(1) of Directive 2008/98/EC of the European Parliament and of the Council of 19 November on waste9.'Directive 2008/98/EC Article 3(1)' 'waste ' means any substance or object which the holder discards or intends or is required to discard' This exemption applies to:timber products of a kind covered by the Annex, which are produced from material that hascompleted its lifecycle and would otherwise have been discarded as waste (e.g. timberretrieved from dismantled buildings, or products made from waste wood),This exemption does not apply to:• by-products from a manufacturing process involving material which had not completed its lifecycle and would otherwise have been discarded as waste.ScenariosWill wood chips and sawdust produced as a by-product of sawmilling be subject to the Regulation? Yes.However, wood chips or other timber products produced from material which has previously been placed on the internal market will not be subject to the requirements of the Regulation which relate to 'placing on the market' (Article 2(b) EUTR, final sentence).Will furniture made from timber recovered from demolition of houses be subject to the Regulation?No, the material in these products has completed its lifecycle and would otherwise have been discarded as waste.9OJ L 312, 22.11.2008, p. 3.6. The role of third parties verified schemes in the process of riskassessment and risk mitigation10Relevant legislation:The EU Timber RegulationRecital (19)In order to recognize good practice in the forestry sectors, certification or other third party verified schemes that include verification of compliance with applicable legislation may be used in the risk assessment procedure.Article 6Due diligence system[...]"[...] Risk assessment procedures shall take into account [...] relevant risk assessment criteria including: Assurance of compliance with applicable legislation, which may include certification or third-party-verified schemes which cover compliance with applicable legislation [...]"and under risk mitigation:"[...] risk mitigation procedures [...] may include requiring additional information or documents and/or third party verification".Commission implementing Regulation (EU) No 607/2012Art. 4Risk assessment and mitigationCertification or other third party verified schemes referred to in the first indent of the second paragraph of Article 6(1)(b) and in Article 6(1)(c) may be taken into account in the risk assessment and risk mitigation procedures where they meet the following criteria:they have established and made available for third party use a publicly available system of requirements, which system shall at the least include all relevant requirements of the applicable legislation;they specify that appropriate checks, including field-visits, are made by a third party at regular intervals no longer than 12 months to verify that the applicable legislation is complied with;they include means, verified by a third party, to trace timber harvested in accordance with applicable legislation, and timber products derived from such timber, at any point in the supply chain before such timber or timber products are placed on the market;they include controls, verified by a third party, to ensure that timber or timber products of unknown origin, or timber or timber products which have not been harvested in accordance with applicable legislation, do not enter the supply chain.10Note that certification is not granted the same status as FLEGT licences and CITES permits (section 10 below).。
类风湿性关节炎欧洲指南中文
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学术英语写作-东南大学中国大学mooc课后章节答案期末考试题库2023年
学术英语写作_东南大学中国大学mooc课后章节答案期末考试题库2023年1.Sequence markersin English are a certain group of items that link sentencestogether into a larger unit of _______.参考答案:discourse2.When the author uses “Methodology” as the title of this section, he/she needsto provide the_______for how the experiment was designed and conducted for the current study.参考答案:rationales3.“Shopping malls are wonderful places.” is a weak thesis statemen t in that itrestates conventional wisdom.参考答案:错误4.One way is to examine one thing thoroughly and then examine the other. Thismethod is called _____ comparison or contrast.参考答案:block5. A strong thesis statement makes a claim that offers some point about thesignificance ofour evidence that requires further argumentation.参考答案:正确6.Strictly speaking, the purpose of _______ is to show similarities while contrastis used to show differences.参考答案:comparison7.In the elements of the Method Section, ______ refer to the precautions taken tomake sure that the data are valid.参考答案:Restrictions8.Paraphrasing is to explain the original ideas of a passage, chapter, article orbook in fewer words.参考答案:错误9.To avoid plagiarism and conform to academic ethics, you need to providereference to every citation and check for plagiarism before submitting your paper.参考答案:正确10.Which of the following tenses could be used to discuss previously publishedworks which is generally considered to be established knowledge?参考答案:The present simple11.Which of the following tenses could be used when the year of publication isstated within the main sentence.参考答案:The past tense12.Which of the following reporting verbs could be categorized as strong?参考答案:reject13.Reporting verbs can indicate either参考答案:All of the options.14.What is included in a complex model of literature review but NOT included ina simple one?参考答案:Research question15.You can choose any information or data from the graphwhen you describeagraph.参考答案:错误16.Redundancy, raising a totally new point, understatement, anticlimax are thetypical issues in structuring the Conclusion.参考答案:错误17.Unlike the Abstract and Introduction，the Conclusions section does providebackground details.参考答案:错误18. 1. The register of the following discourse is____.I, James Bond, take you, JudithKroll, to be my wife, to have and to hold from this day forward, for better, for worse, for richer, for poorer, in sickness and in health, to love and to cherish, till death us do part, according to God's holy law, in the presence of God Imake thisvow.参考答案:static19.What should you do when you write a literature review?参考答案:Include a critical analysis of various opinions from credible sources.20.To end the Discussion section which also has a Conclusion, the author mayadmit what she/he has not been able to do and as a consequence cannotprovide conclusions on.参考答案:正确21.If the authors are to announce the results of their study, they can just statethe results without saying “we think that…”参考答案:正确22.You can use “he or she” to avoid gender discrimination every time when youmean “everyone”.参考答案:错误23.When writing an academic paper, you should nominalize as many words aspossible.参考答案:错误24.Beginning the Discussion section an author would possibly refer back topapers he/she cited in the Review of the Literature.参考答案:正确25.“The U.S. constitution” is not a good title for an essay, because it is toogeneral.参考答案:正确26.“What implications are revealed in my results?” is a question to considerafter drafting the Discussion section.参考答案:错误27.The process paragraphs are usually developed step by step in a chronologicalor logical sequence.参考答案:正确28.The Results Section can only be presented both in diagrams or graphs.参考答案:错误29.The Method Section can be called Materials and Methods in naturalsciences.参考答案:正确30.The Method Section is considered the most important section becauseitappears in the middle of a research paper.参考答案:错误31.Nominalization is the process of converting simple nouns within a sentenceto complex nouns.参考答案:错误32.If you can discuss a cause without having to discuss any other causes thenvery likely it is an indirect cause.参考答案:错误33.Oversimplification should be avoided because many problems have complexcauses and complex effects.参考答案:正确34.First personal pronouns can never be used in academic paper.参考答案:错误35. A weak thesis statement either makes no claim or makes a claim that doesnot need proving.参考答案:正确36.One of the key elements of the Conclusion section is a final judgment on theimportance and significance of the findings in terms of their implications and impact, along with possible applications to other areas.参考答案:正确37.Effects are the consequences of an event and they respond to the question“Why did that event happen?”参考答案:错误。
指南中推荐意见的形成英文
指南中推荐意见的形成英文The Formulation of Recommendations in GuidelinesThe development of clinical practice guidelines is a critical process in the field of healthcare, as these guidelines serve as a valuable tool to guide healthcare professionals in delivering evidence-based and high-quality care. One of the key components of this process is the formulation of recommendations, which are the core of any guideline. The recommendations provide healthcare professionals with clear and concise guidance on the most appropriate course of action for specific clinical scenarios.The formulation of recommendations in guidelines is a complex and multifaceted process that involves a careful consideration of various factors. These factors include the quality and strength of the available evidence, the potential benefits and harms of the proposed interventions, the preferences and values of patients, and the feasibility and cost-effectiveness of the recommendations.One of the primary considerations in the formulation of recommendations is the quality and strength of the available evidence. Guideline developers must carefully evaluate the existingresearch on the topic at hand, assessing the methodological rigor, study design, and overall quality of the evidence. This assessment is crucial in determining the confidence that can be placed in the recommendations.In cases where the available evidence is strong and of high quality, the recommendations can be made with a greater degree of confidence. However, in situations where the evidence is limited or of lower quality, guideline developers must exercise caution and consider the potential uncertainties and limitations of the available data. In such instances, the recommendations may be qualified or presented with a lower level of certainty.Another important factor in the formulation of recommendations is the consideration of the potential benefits and harms of the proposed interventions. Guideline developers must weigh the potential positive outcomes, such as improved patient outcomes, reduced morbidity, or decreased healthcare costs, against the potential negative consequences, such as adverse effects, increased resource utilization, or patient burden.This careful balancing act is essential in ensuring that the recommendations strike the right balance between promoting optimal patient care and minimizing potential harm. Guideline developers may also consider the preferences and values of patients,as these can play a significant role in the acceptability and uptake of the recommendations.The feasibility and cost-effectiveness of the recommendations are also crucial considerations in the formulation process. Guideline developers must assess whether the proposed interventions are practical to implement within the healthcare system, taking into account factors such as resource availability, infrastructure, and provider expertise. Additionally, the cost-effectiveness of the recommendations must be evaluated to ensure that they represent a wise use of healthcare resources.The process of formulating recommendations in guidelines is further complicated by the need to account for contextual factors, such as local healthcare systems, cultural norms, and resource constraints. Guideline developers must carefully consider how these factors may impact the applicability and implementation of the recommendations in different settings.To address this challenge, many guideline development organizations have adopted the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The GRADE system provides a structured framework for evaluating the quality of evidence and the strength of recommendations, taking into account factors such as the risk of bias, the consistency ofresults, the directness of the evidence, and the precision of the estimates.By using the GRADE approach, guideline developers can provide healthcare professionals with clear and transparent information about the level of confidence they can have in the recommendations, as well as the rationale behind the formulation of those recommendations.In conclusion, the formulation of recommendations in clinical practice guidelines is a complex and multifaceted process that requires careful consideration of a range of factors. Guideline developers must balance the quality and strength of the available evidence, the potential benefits and harms of the proposed interventions, the preferences and values of patients, and the feasibility and cost-effectiveness of the recommendations. By adopting a structured and transparent approach, such as the GRADE system, guideline developers can ensure that the recommendations they provide are evidence-based, patient-centered, and ultimately effective in improving the quality of healthcare delivery.。
gpt润色ssci命令 -回复
gpt润色ssci命令-回复SSCI命令是一种常用于社会科学研究中的命令结构，它由主题、选择、比较和影响四个要素构成。
在本文中，我将详细解释SSCI命令并对其中涉及的每个要素一一进行回答。
SSCI命令中的第一个要素是主题。
主题是研究问题的核心内容，它定义了研究的范围和目标。
在本文中，我们以"社交媒体对青少年心理健康的影响"作为主题进行讨论。
第二个要素是选择。
选择指的是我们在研究中选择要考察的独立变量和依赖变量。
在这个主题中，我们可以选择独立变量为社交媒体使用频率和内容，依赖变量为青少年的心理健康水平。
接下来是比较。
比较是指我们在研究中进行的不同组别或条件之间的对比。
在本文中，我们可以比较社交媒体使用频率高和低的青少年群体之间的心理健康水平是否存在差异。
最后一个要素是影响。
影响指的是我们要探究的因果关系或者相关性。
在这个主题中，我们想要了解社交媒体对青少年心理健康的影响，我们可以研究社交媒体使用频率的增加是否与青少年心理健康问题的增加相关。
基于以上的SSCI命令要素，下面我将一步一步回答这些问题：1. 主题：社交媒体对青少年心理健康的影响社交媒体已经成为现代社会中青少年日常生活中不可或缺的一部分。
然而，越来越多的研究表明，社交媒体的使用可能会对青少年的心理健康产生负面影响。
2. 选择：我们选择了独立变量为社交媒体使用频率和内容。
通过调查问卷或者数据收集工具，我们可以了解青少年在社交媒体上花费的时间以及他们主要参与的活动和互动方式。
我们将青少年的心理健康水平作为依赖变量。
在研究中，可以使用心理健康评估工具或者症状量表来测量青少年的心理健康水平。
3. 比较：我们将比较社交媒体使用频率高和低的群体之间的青少年心理健康水平是否存在差异。
通过对两个不同群体的心理健康评估结果进行统计分析，我们可以比较两组之间的差异，并判断是否存在相关性或因果关系。
4. 影响：通过分析社交媒体使用频率的增加是否与青少年心理健康问题的增加相关，我们可以确定社交媒体对青少年心理健康的影响。
Microsoft Dynamics NAV 国际化与本地化指南说明书
Product Availability, Localization & Translation Guide for Microsoft Dynamics NAV*) Use of the word country is for convenience only and is not intended to imply sovereignty for any disputed territory that may be mentioned hereinKey Benefits:Country LocalizationsLocalization is the process of adapting software to meet country-specific laws or regulations.Microsoft localizes Microsoft Dynamics NAV to include features and functionality designed to address specific tax, counting or financial reporting requirements for various countries. Features or functionalities that are available in a particular country may not be available in all countries.Please consult your channel partner for details about product features and capabilities. Also consult them and/or your professional advisers to determine whether this software is appropriate for your business needs in a given country.LanguagesTranslation is the process of adapting software or documentation to meet language requirements for a particular country. For a given language, Microsoft may translate some, all or none of the user interface (UI) and documentation for Microsoft Dynamics NAV . Contact your channel partner or the local Microsoft office for more information.Microsoft Dynamics NAV is localized, translated and supported by Microsoft and made generally available in the countries *) andlanguages listed below. To learn more about supported versions of Microsoft Dynamics NAV localized and/or translated by Microsoft, please refer to the product availability table below. In addition to country-specific localizations and/or translations that Microsoft creates, our channel partners may make partner created localizations and/or translations of Microsoft Dynamics NAV available incountries where Microsoft does not provide a localized or translated version. See the Microsoft Dynamics Localization and Translation Overview below for more information on partner-created solutions.1) Details regarding availability of Microsoft Dynamics NAV 2013 will be provided in a future update of this guideMicrosoft Dynamics Localization and Translation OverviewOrganizations doing business in a particular country must comply with country-specific laws, regulations and common business practices to handle their daily business transactions and operations and meet their legal obligations for activities conducted in the country. Microsoft recognizes that non-adherence to these laws and regulations can lead to severe consequences for an organization doing business in that country. As an enterprise resource planning (ERP) solution, Microsoft Dynamics NAV software helps organizations manage their various business processes through its extensible architecture. Microsoft extends the business process functionalityof its Microsoft Dynamics NAV software by developing specific commercial requirements, language, and non-vertical, nationalor international functionality to address specific tax, accountingor financial reporting requirements for countries where Microsoft makes this software generally available. The process of adapting software to meet local laws or requirements is called localization. The process of adapting software to meet language requirements is called translation. Since laws and regulations that affect businesses vary in each country, Microsoft Dynamics NAV software is not supported in terms of localizations, translations, or technical support in all countries. While Microsoft Dynamics NAV software “out-of-the-box” is localized and/or translated to address specific laws and/ or regulations for particular countries, it is not supported in termsof localizations, translations, or technical support in all countries. Features or functionalities that are available in a particular country may not be available in all countries. Rather, we look to our channel partners, who are an important part of our global strategy, to deliver Microsoft Dynamics NAV solutions that help customers meet their compliance obligations. Channel partners may adapt the Microsoft Dynamics NAV software to: • Supplement the base Microsoft Dynamics NAV application by developing functionality to meet specific laws or regulations that are not covered by features provided ”out-of-the-box” (e.g., regulations that are unique to states, provinces, cities, or municipalities in a particular country); or • Create their own localizations and/or translations in countries where Microsoft does not offer a localized and/or translated version of Microsoft Dynamics NAV software. Partner-created solutions are owned, implemented, maintained, and serviced by, or on behalf of, the originating channel partner.Channel Partner-Created Solutions:For additional information about partner-created solutions inyour country, please contact your Microsoft channel partner or local Microsoft office, or utilize the Microsoft Dynamics Marketplace (http://dynamicserp.pinpoint. ) to identify channel partner solutions that might be available in your country.Notice and DisclaimerThis content is provided for information purposes only and is subject to change without notice. It is provided “as is” and is not warranted to be error-free. This information is not intended to constitute tax, accounting, legal or other professional advice or to be used as a substitute for specific advice from your channel partner or a licensed professional. You should not act (or refrain from acting) based on information in this document without obtaining professional advice about your particular facts and circumstances. Microsoft does not make any representation, warranty (express, implied or otherwise) or assurance about the performance or suitability of any localized and/ or translated version of Microsoft Dynamics NAV used outside the country in which Microsoft makes that software generally available, including implied warranties and conditions of merchantability or fitness for a particular purpose. Although Microsoft may refer to its channel partners as “partners”, they are independent entities. There is no partnership, joint venture, agency or franchise relationship or fiduciary duty between Microsoft and its channel partners. Channel partners are solely responsible for any configurations, customizations, localizations and/or translations they create or implement on behalf of customers, including any support or other service they provide to customers for such solutions. Microsoft does not warrant or guarantee partner-created solutions and disclaims any and all liability arising out of any partner-created solution and/or service.。
RECSIT1.1中英文对照全文
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)新版实体瘤疗效评价标准：修订的RECIST指南（1.1版本）Abstract摘要Background背景介绍Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews.临床上评价肿瘤治疗效果最重要的一点就是对肿瘤负荷变化的评估：瘤体皱缩（目标疗效）和病情恶化在临床试验中都是有意义的判断终点。
Biosafety Level 3 (BSL-3) 实验室设计标准说明书
Biosafety Level 3 (BSL-3) LaboratoryDesign StandardsJanuary 2020CC Noncommercial LicenseThis manual is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. When reusing the content under this license,please provide (1) attribution to “Environment, Health & Safety at the University of California, Office of the President”; (2) the following copyright notice: © The Regents of the University of California; and (3) if feasible, a hyperlink to where the original source material appears.IntroductionThe University of California (UC) is home to some of the world’s most advanced and pioneering biomedical science and clinical research. Consistently ranked among the leaders in the field of Infectious Disease research, the UC is often called upon to provide critical expertise in response to worldwide public health crises. Infectious Disease research involving highly pathogenic and primarily aerosol transmissible agents (i.e., Risk Group 3 agents) has the potential to present significant risk to individuals, the community, and the environment. The ability to safely conduct these research activities is largely dependent upon the highly engineered Biosafety Level 3 (BSL-3) laboratory, the highest-level containment facilities currently operated by the UC. The primary objective of these laboratories is to provide the best possible physical containment of Risk Group 3 agents. Hence, the design and engineering of these laboratories must be maintained at the highest attainable standards.Several authorities have published standards for the design of BSL-3 laboratories. Development of the UC Biosafety Level 3 Design Standards has incorporated input from several of these sources, including the following:• CDC Biosafety in Microbiological and Biomedical Laboratories (BMBL), 5th Edition, 2009 • NIH Design Requirements Manual for Biomedical Laboratories and Animal Research Facilities (DRM), 2019• NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), 2016• National Institutes of Health Biosafety Level 3 Laboratory Certification Requirements, 2006• Industry Standards and Best PracticesThe information presented in these Standards addresses facility design and engineering systems for BSL-3 containment laboratories and incorporates additional design elements to assist campuses in conducting facility risk assessments. It is important to note that an effective BSL-3 program is not only reliant upon the facility and engineering, but also operation and maintenance (O&M) protocols, robust training programs, administrative controls, and standard operating procedures (SOPs).ApplicationThe BSL-3 Laboratory Design Standards represent the UC requirements for constructing BSL-3 laboratories. These Standards need to be referenced and used by UC design teams includingresearchers, architects and engineers, as well as outside contractors. They provide necessary tools and information for BSL-3 planning, construction, and commissioning on UC campuses. While incorporating all applicable regulatory requirements, the standards identify UC requirements, provide explanations of those standards, and document best practices for consideration during the facility risk assessment. This range of acceptable parameters will allow campuses to build each laboratory with a level of features commensurate with the facility risk assessment. These Standards pertain to new facility builds and/or major renovations or retrofits of existing BSL-3 laboratory space. It is not the intent of these Standards to require upgrades to existing BSL-3 spaces, but to provide design standards and guidance when embarking on a new construction or major renovation project.For the purposes of these Design Standards, major renovations/retrofits are defined as any of the following: 1. Changes to fixed primary containment equipment (e.g. ducted BSCs or any other devices connected to the BSL-3 exhaust system); 2. Changes to major HVAC systems/components (e.g. exhaust fans, air handling units, airflow control valves, isolation dampers, Building Management Systems / Building Automation Systems (BMS/BAS), ductwork, etc.); 3. Changes to floorplans or structural components of the secondary containment boundaries (e.g. walls, ceilings, or attached fixtures); 4. Any other changes to the facility that could impact overall safety, operations, or ventilation system performance. This Standard is applicable to the specific retrofit and not meant to apply to the entire facility. As plans to renovate specific features of an existing facility evolve, it is important to address any identified issues that may affect the safe operations of a BSL-3 laboratory, potentially presenting a risk to the UC community or the environment. These Standards have been approved by the UC systemwide High Containment Laboratory Oversight Committee (HCLOC), and shall be incorporated or referenced in Campus Building Standards.Note: Facilities required to comply with the Federal Select Agent Program and/or Dual Use Research of Concern may have additional biosafety or biosecurity design features beyond these UC Standards. In addition to the UC Standards, campuses must reference and comply with the applicable Federal regulatory standards when designing Federal Select Agent or Dual Use Research high-containment facilities.Campus InvolvementAt the onset of a new BSL-3 laboratory or existing laboratory renovation design project, it is important to consider the involvement of specific campus experts. Consultation with these key campus members may provide insight into critical design flaws that may affect specific aspects of the laboratory’s functionality. These contributions could prove to be exceptionally cost-effective interms of both time and resources. Involvement from the following campus members is recommended:• PI (researcher)/Department Chair• EH&S Biosafety• High Containment Laboratory Director• Campus Design Management Group• Capital Programs• UC Building Officials• Campus ADA Reviewer• Campus Security or Campus Police Department• Campus Emergency Response• Campus Fire Marshal• Campus Facilities Operations & Management GroupDeviationsCampuses must comply with the UC Biosafety Level 3 Design Standards and Best Practices should be considered when appropriate. When justified by a documented risk assessment, a deviation may be considered. A campus seeking a deviation approval must first complete the UC BSL3 Design Standards Deviation Request Form, Appendix I. The completed form and requested documentation shall be presented to the campus High Containment Laboratory Oversight Group (HCLOG) for approval. With campus HCLOG approval, the deviation request will be presented to the UC systemwide HCLOC, for final approval.Revisions to the StandardsA full review and revision of the UC BSL3 Design Standards shall be conducted every two years, on even years. Between full revisions, the Design Standards may be revised on an as needed basis via continual evaluation and application. Through the use of these Design Standards, any identified gaps, errors, or sections requiring further clarification will be noted and highlighted by local EH&S and Design professionals. Corrections, clarifications and all identified issues shall be presented to the UC systemwide HCLOC for confirmation and approval. Once approved by the HCLOC, updates will be completed and distributed to each location. Revised versions of the Standards must receive approval by the UC systemwide HCLOC prior to implementation.Table of ContentsList of Codes, Standards and Guidelines (1)BSL-3 Architectural (2)General (2)Containment Barrier (3)Anterooms (4)Doors (5)Windows (6)Floors (7)Base (7)Walls (7)Ceilings (8)Access Panels (9)Finishes (9)Furniture (10)Sealing (11)BSL-3 Architectural References (13)Heating, Ventilation & Air Conditioning (19)HVAC References (24)Electrical (27)Electrical References (34)Plumbing (38)Water Distribution (39)Vacuum Line (39)Sinks (40)Shower (41)Drains (41)Traps (42)Waste Pipe Cleanout (43)Plumbing References (44)Telecom, Security & Documentation (47)Telecom (47)Security (47)Signage (49)Enhanced Facilities (50)Verification & Documentation (50)Seismic (51)Telecom, Security & Documentation References (52)Safety and Decontamination (53)Safety (53)Decontamination (55)Safety and Decontamination References (57)BSL-3 Standard Equipment (59)Autoclaves (59)Biosafety Cabinets (60)Flow Cytometry (61)Centrifuge (61)BSL-3 Standard Equipment References (62)CC Noncommercial LicenseThis manual is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. When reusing the content under this license,please provide (1) attribution to “Environment, Health & Safety at the University of California, Office of the President”; (2) the following copyright notice: © The Regents of the University of California; and (3) if feasible, a hyperlink to where the original source material appears.List of Codes, Standards and Guidelines• Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition, 2009 https:///labs/pdf/CDC-BiosafetyMicrobiologicalBiomedicalLaboratories-2009-P.PDFThe BMBL is published jointly by the U.S. Department of Health and Human Services, the Centers for Disease Control and the National Institutes of Health. The document describes Biological risk assessment, lab practices, safety equipment, and facilities requirements required for designing and operating laboratories at Biosafety Levels (BSL) 1 through 4. Although not a code, certification of BSL facilities is dependent on following the recommendations in thisdocument.• NIH Design Requirements Manual (DRM) 2019 Rev 1.4: 4/24/19https:///TechnicalResources/Documents/DRM/DRM1.4042419.pdf• National Institutes of Health Biosafety Level 3 Laboratory Certification Requirements,July 2006 https:///PoliciesAndGuidelines/Bioenvironmental/Documents/BSL-3CertificationGuidelinesFINAL_508.pdf• ANSI/ASSE Z9.14-2014 Testing and Performance-Verification Methodologies for Ventilation Systems for Biosafety Level 3 (BSL-3) and Animal Biosafety Level 3 (ABSL-3) Facilities -This document can be purchased at: https:///PersonifyEbusiness/Store/Product-Details/productId/11562952• NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines), 2016• University of California Environment, Health & Safety (EH&S) Laboratory Safety Design Guide, Second Edition, September 2007。
英语作文-如何在互联网上获取权威的健康知识认证
英语作文-如何在互联网上获取权威的健康知识认证With the rapid development of the internet, accessing reliable health information has become increasingly important. However, the vast amount of information available online can be overwhelming and it is crucial to be able to distinguish between trustworthy and misleading sources. In this article, we will explore how to obtain authoritative health knowledge certification on the internet.First and foremost, one should prioritize reputable sources when seeking health information online. Government websites, such as those run by health departments or national institutes of health, are generally reliable and provide evidence-based information. These websites often have a .gov domain, ensuring their credibility. Additionally, academic institutions and medical journals are excellent sources of reliable health knowledge. Websites ending with .edu or .org are more likely to provide accurate and up-to-date information.Another effective way to obtain authoritative health knowledge certification is by consulting healthcare professionals and experts. Online forums and communities dedicated to health topics can be valuable resources. However, it is important to verify the credentials and expertise of the individuals providing information. Look for professionals with relevant qualifications, such as doctors, nurses, or registered dietitians. Their expertise and experience can help ensure the accuracy and reliability of the information they provide.Furthermore, it is essential to critically evaluate the information found online. This involves checking for references, citations, and sources of the information presented. Reliable sources will often provide references to scientific studies or other reputable sources. Assessing the quality and relevance of these sources can help determine the credibility of the information. Additionally, cross-referencing information from multiple sources can help verify its accuracy.In recent years, many organizations and websites have emerged that evaluate the reliability of health information online. These organizations, such as Health On the Net Foundation (HON) and the National Institute for Health and Care Excellence (NICE), aim to promote trustworthy health information on the internet. They provide certifications or seals of approval to websites that meet certain criteria, such as transparency, accuracy, and ethical standards. Seeking information from websites with these certifications can enhance the credibility of the obtained health knowledge.Moreover, it is important to be cautious of potential biases or conflicts of interest when accessing health information online. Some websites or individuals may have financial or commercial interests that could influence the information they provide. Being aware of these potential biases can help users make more informed decisions about the reliability of the information.In conclusion, obtaining authoritative health knowledge certification on the internet requires careful consideration and evaluation of the sources. Prioritizing reputable sources, consulting healthcare professionals, critically evaluating information, and being cautious of biases are all essential steps in ensuring the reliability of health information. By following these guidelines, individuals can make informed decisions about their health and well-being in the digital age.。
EN 50128铁路应用—通信、信号和处理系统—铁路控制和防护系统软件
EN 50128 : 2001铁路应用——通信、信号和处理系统——铁路控制和防护系统软件2007.6序言本欧洲标准是SC 9XA,即通信，信号传输和处理系统技术委员会（CENELEC TC 9X）制订，铁路电气和电子应用的标准。
草案文本作为EN 50128正式提交投票并于2000-11-01获得CENELEC 批准。
修改了下列日期--欧盟各国必须通过认可或发布相同的国家标准来执行本欧洲标准的截止日期2001 -1 1-01--与本欧洲标准冲突的国家标准必须被废止的截止日期2003-1 1-01本欧洲标准必须与EN50126铁路应用——可靠性，可用性，可维护性和安全性（RAMS）；EN50129铁路应用——信号领域的安全相关电子系统同时阅读。
附件中指定的“规范性的”是本项标准主体的一部分。
附件中指定的“参考性的”只用于获得的信息。
本项标准中，附件A是规范性的而附件B是参考性的。
目录引言1.范围2.参考文献3.定义4.目标和符合5.软件安全完整性等级5．1目标5．2需求6.人员及职责6．1目标6．2需求7.生命周期和文档7．1目标7．2需求8.软件需求规格说明8．1目标8．2输入文档8．3输出文档8．4需求9.软件体系结构9．1目标9．2输入文档9．3输出文档9．4需求10.软件设计和实现10．1目标10．2输入文档10．3输出文档10．4需求11.软件验证和测试11．1目标11．2输入文档11．3输出文档11．4需求12.软件/硬件集成12．1目标12．2输入文档12．3输出文档12．4需求13.软件确认13．1目标13．2输入文档13．3输出文档13．4需求14.软件评估14．1目标14．2输入文档14．3输出文档14．4需求15.软件质量保障15．1目标15．2输入文档15．3输出文档15．4需求16.软件维护16．1目标16．2输入文档16．3输出文档16．4需求17.根据应用数据配置的系统17．1目标17．2输入文档17．3输出文档17．4需求17．4．1数据准备生命周期17．4．2数据准备程序和工具17．4．3软件开发附件A：技术和措施的选择准则附件B：技术参考书目附图图1——安全相关系统的完整性等级图2——软件安全性路径图图3——开发生命周期1图4——开发生命周期2图5——独立性与软件完整性等级图6——通用系统开发和应用开发之间的关系引言本标准是相关标准系列中的一部分。
Guidanceconcerni...
EUROPEAN COMMISSIONENTERPRISE AND INDUSTRY DIRECTORATE-GENERALConsumer goodsPharmaceuticals2006 MayGuidance concerning consultations with target patient groups for the package leafletArticle 59(3) and 61(1) of Directive 2001/83/EC as amended by Directive2004/27/EC1. INTRODUCTIONAccording to Articles 59(3) and 61(1) of Directive 2001/83/EC as amended by Directive 2004/27/EC new requirements apply to the package leaflet. Article 59(3) as amended requires that consultation with target patient groups (‘user consultation’) be carried out to demonstrate the readability and usefulness of the package leaflet to patients.Article 59(3) reads:“The package leaflet shall reflect the results of consultations with targetpatient groups to ensure that it is legible, clear and easy to use.”Article 61(1) states that“The results of assessments carried out in cooperation with target patientgroups shall also be provided to the competent authority."Article 63(2) states that:“The package leaflet must be written and designed to be clear andunderstandable, enabling the user to act appropriately”In addition Article 28(2) and (3) of Directive 2001/83/EC requires that products authorised through the mutual recognition and decentralised procedures will result in a harmonised package leaflet between Member States.2. SCOPEFor all marketing authorisations granted after 30 October 2005, all the requirements set out in Directive 2001/83/EC as amended apply. Therefore all package leaflets included in Community or national marketing authorisations have to be checked accordingly and the information about the patient consultation must be included in the application dossier. Further guidance is given in section 8 of this guideline.For changes to existing marketing authorisations, the need for user consultation covers in principle situations where significant changes are made to the package leaflet, either through a variation or a procedure according to Article 61(3) of Directive 2001/83/EC.3. FORMS OF PATIENTS CONSULTATIONArticles 59(3) and 61(1) of Directive 2001/83 require that the package leaflet shall reflect the results of consultations with target patient groups to ensure that it is legible, clear and easy to use and that these results of assessments carried out in cooperation with target patient groups shall also be provided to the competent authority.They do not define the precise method to be used. As a consequence, these provisions permit user testing as well as other appropriate forms of consultation.Testing3.1 UserOne of the possible ways of complying with the new legal requirement is by performing a ‘user testing’ of the package leaflet.User testing means to test the readability of a specimen with a group of selected test subjects. It is a development tool which is flexible and aims to identify whether or not the information as presented, conveys the correct messages to those who read it. Testing itself does not improve the quality of the information but it will indicate where there are problem areaswhich should be rectified. The user testing should be part of Module 1 of the application dossier.methods3.2 OtherOther methods than user testing may be acceptable provided that the outcome ensures that the information is legible, clear and easy to use so that patients can locate important information within the package leaflet, understand it and enables the user to act appropriately. Such alternative methodology will have to be justified by the applicant/marketing authorisation holder and will be considered on a case-by-case basis.4. DEMONSTRATION OF PATIENTS CONSULTATIONIn general, performing the user testing or another justified consultation method will be essential prior to granting or varying any marketing authorisation under either the centralised, mutual recognition, decentralised or national procedures.Member States and the European Medicines Agency agreed on harmonised Quality Review of Documents (QRD) templates for the package leaflet to ensure that the statutory information appears as intended by the Directive 2001/83/EC as amended. Compliance with the QRD templates does not exempt from the obligation to undertake a user test or other form of user consultation.a) New consultation for a medicinal productIn the following situations a user consultation is always required: First authorisation of a medicinal product with a new active substance,•Medicinal products which have undergone a change in legal status,•Medicinal products with a new presentation,•Medicinal products with particular critical safety issues.b)Reference to already approved package leaflets according to Article 59(3) and Article 61(1) of Directive 2001/83/ECThe evidence from tests on similar package leaflets may be used where appropriate. Examples of when this may be considered acceptable based on a sound justification by theapplicant/marketing authorisation holder are:•extensions for the same route of administration e.g. intravenous/intramuscular or oropharyngeal/laryngopharyngea,•same safety issues identified,•same class of medicinal product.It may be appropriate for an applicant/marketing authorisation holder to refer to a representative sample of package leaflets for medicinal products which comply with the new legislative requirements. The types of package leaflets should be chosen carefully to be representative of one or more of the following considerations:•recently approved package leaflets for a corresponding medicinal product,•reflect complex issues of risk communication which may need careful handling,•medical terminology which requires detailed explanation .However, certain package leaflets may require further user consultation to provide reassurance that patients will benefit from the information provided. This is e.g. the case where user consultation concentrates on one particular aspect of a leaflet which may need particular patient attention, e.g. expression of risk of side effects or complex instructions how to administer the medicinal product.5. TESTING OF MULTIPLE LANGUAGE VERSIONSThe package leaflet should be legible, clear and easy to read in all EEA languages. As a matter of principle it is normally sufficient to undertake patient consultation in one EEA language. Results of such consultation should be presented in English for the centralised, decentralised and mutual recognition procedure, or in the national language for national procedures to permit the assessment of the test to be undertaken by competent authority responsible for granting the marketing authorisation.In the centralised, decentralised and mutual recognition procedure, only the English language version of the package leaflet will be agreed during the scientific assessment.The quality of translation should be the focus of a thorough review by the applicant/marketing authorisation holder once the original package leaflet has been properly tested and modified. During the drafting of the original package leaflet every effort should be made to ensure that the package leaflet can be translated from the original to the various national languages in a clear and understandable way. It is important that the outcome of the user consultation is then correctly translated into the other languages. Strict literal translations from the original language may lead to package leaflets which contain unnatural phrases resulting in a package leaflet which is difficult for patients to understand. Therefore, different language versions of the same package leaflet should be ‘faithful’ translations allowing for regional translation flexibility, whilst maintaining the same core meaning.Following the grant of the marketing authorisation, the responsibility for the production of faithful translations will rest with the marketing authorisation holder in consultation with the Member States/European Medicines Agency.If user consultation has been performed on a package leaflet in the old QRD template, there is no need to be retested when updating according to the new QRD template.6. PRESENTATION OF RESULTSThe presentation of results should be shortened to a summary explaining how the consultation was executed and how the resulting package leaflet accommodated any need for change. The summary should be in Module 1.3.4 of the application and should have the following structure:1.Product description2.Consultation or test details, such as:·Method used·Explanation on the choice of population consulted·Language(s) tested3.Questionnaire (including instructions and observation forms)4.Original and revised package leaflets5.Summary and discussion of results (subjects’ answers, problems identified and revisionsmade to relevant package leaflet section)6.ConclusionAll other details should be available on demand.The report and the results of the consultation should be presented in English for the centralised, decentralised and mutual recognition procedure or in the national language for national procedures.7. APPROVAL BY THE COMPETENT AUTHORITYIn approving package leaflets the competent authorities will look for evidence that people who are likely to rely on the package leaflet can understand it and act appropriately. Any consultation submitted in support of a package leaflet will need to cover the following: •Data gathered from users under defined conditions•The people who are likely to rely on the package leaflet for a particular medicine will depend upon a number of factors and may include carers (e.g. parents, partners, friends, as well as nursing assistants) rather than patients if the medicine is generally intended for administration by someone other than the patient.•In order to ensure that those involved can understand and apply the information, the evidence presented must demonstrate that they can pick out the relevant information,interpret this and describe the action they would take as a result.•The key information will need to be defined prior to the consultation by the marketing authorisation holder and is likely to include significant side effects, warnings, what the medicine is for and how to take/use the product.8. OTHER ISSUES FOR CONSIDERATIONThe Member States or the European Medicines Agency will have considered other aspects in relation to consultation or user testing and usability of package leaflets and additional guidance is available or under development concerning:•Timing of user consultation, submission and assessment within the evaluation procedure;•Guidance in relation to usability and presentation of information;•Guidance on how user testing should be carried out and what alternative methods are acceptable.。
请用中英文简述敏捷模型的12个敏捷原则。
请用中英文简述敏捷模型的12个敏捷原则。
Agile principles are the guiding values and beliefs that underpin the agile methodology. They provide a foundation for creating successful and efficient software development processes, and are a fundamental part of the agile manifesto. There are 12 agile principles that encapsulate the core ideas and philosophies of the agile approach to software development.1. Our highest priority is to satisfy the customer through early and continuous delivery of valuable software.This principle emphasizes the importance of delivering working software to the customer as early and as frequently as possible. It ensures that the development team stays focused on meeting the needs of the customer and delivering value, which is essential for project success.2. Welcome changing requirements, even late in development. Agile processes harness change for thecustomer's competitive advantage.Embracing change is a key aspect of agile development. Instead of viewing changing requirements as a hindrance,agile teams understand that they contribute to delivering a better product. By being flexible and adaptable, teams can respond to evolving customer needs and market demands.3. Deliver working software frequently, from a couple of weeks to a couple of months, with a preference to the shorter timescale.The principle of frequent software delivery encourages teams to produce working software in short, iterative cycles. By delivering software more regularly, teams can get feedback from customers sooner, identify and address issues faster, and adapt to changing requirements more effectively.4. Business people and developers must work togetherdaily throughout the project.Effective collaboration between business stakeholders and development teams is crucial for the success of agile projects. This principle emphasizes the need for constant communication, shared understanding, and alignment of goals between the business and development teams.5. Build projects around motivated individuals. Give them the environment and support they need, and trust them to get the job done.Agile teams thrive when individuals are given autonomy, trust, and support to do their best work. By fostering an environment that empowers and motivates team members, organizations can cultivate high-performing teams thatdeliver exceptional results.6. The most efficient and effective method of conveying information to and within a development team is face-to-face conversation.Face-to-face communication is highly valued in agile development. It allows for better understanding, quicker decision-making, and the ability to address issues in real-time. While face-to-face communication may not always be feasible, agile teams strive to maximize opportunities for direct interaction.7. Working software is the primary measure of progress.Agile teams gauge their progress based on the working software they deliver. This approach ensures that the focus remains on producing tangible results and delivering value to the customer, rather than getting caught up in abstract metrics or documentation.8. Agile processes promote sustainable development. The sponsors, developers, and users should be able to maintain a constant pace indefinitely.Sustainable development is essential for the long-term success of a project. Agile teams prioritize maintaining a consistent and manageable pace of work, preventing burnout and ensuring the sustainability of the development process over time.9. Continuous attention to technical excellence and good design enhances agility.Emphasizing technical excellence and good design practices is vital for building software that is adaptable, maintainable, and scalable. By prioritizing quality and craftsmanship, agile teams can respond more effectively to changes and evolving requirements.10. Simplicity--the art of maximizing the amount of work not done--is essential.Simplicity is a core principle of agile development. By focusing on delivering the most valuable features and minimizing unnecessary complexity, teams can avoid waste and ensure that their efforts are directed towards creating meaningful outcomes.11. The best architectures, requirements, and designs emerge from self-organizing teams.Agile teams are empowered to self-organize and make decisions collaboratively. This principle recognizes that the most effective solutions and designs often arise from the collective knowledge, creativity, and expertise of the team members.12. At regular intervals, the team reflects on how to become more effective, then tunes and adjusts its behavior accordingly.Continuous improvement is an integral part of agile development. Teams regularly reflect on their practices,processes, and interactions, seeking opportunities to enhance their effectiveness and make adjustments as necessary. This principle ensures that teams remain adaptable, responsive, and continually evolve in their pursuit of excellence.In conclusion, the 12 agile principles encapsulate the core values and beliefs that guide the agile methodology. By adhering to these principles, teams can foster a culture of collaboration, delivery, responsiveness, and continuous improvement, ultimately leading to more successful and efficient software development processes.。
DS-K3G501LX系列翻转扶手快速启动指南说明书
DS-K3G501LX Series Tripod TurnstileQuick Start GuideUD30298B©2022Hangzhou Hikvision Digital Technology Co.,Ltd.All rights reserved.About this ManualThe Manual includes instructions for using and managing the Product.Pictures,charts, images and all other information hereinafter are for description and explanation only. The information contained in the Manual is subject to change,without notice,due to firmware updates or other reasons.Please find the latest version of this Manual at the Hikvision website(https:///).Please use this Manual with the guidance and assistance of professionals trained in supporting the Product.Trademarksand other Hikvision’s trademarks and logos are the properties of Hikvision in various jurisdictions.Other trademarks and logos mentioned are the properties of their respective owners. DisclaimerTO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW,THIS MANUAL AND THE PRODUCT DESCRIBED,WITH ITS HARDWARE,SOFTWARE AND FIRMWARE,ARE PROVIDED “AS IS”AND“WITH ALL FAULTS AND ERRORS”.HIKVISION MAKES NO WARRANTIES, EXPRESS OR IMPLIED,INCLUDING WITHOUT LIMITATION,MERCHANTABILITY, SATISFACTORY QUALITY,OR FITNESS FOR A PARTICULAR PURPOSE.THE USE OF THE PRODUCT BY YOU IS AT YOUR OWN RISK.IN NO EVENT WILL HIKVISION BE LIABLE TO YOU FOR ANY SPECIAL,CONSEQUENTIAL,INCIDENTAL,OR INDIRECT DAMAGES,INCLUDING, AMONG OTHERS,DAMAGES FOR LOSS OF BUSINESS PROFITS,BUSINESS INTERRUPTION, OR LOSS OF DATA,CORRUPTION OF SYSTEMS,OR LOSS OF DOCUMENTATION,WHETHER BASED ON BREACH OF CONTRACT,TORT(INCLUDING NEGLIGENCE),PRODUCT LIABILITY, OR OTHERWISE,IN CONNECTION WITH THE USE OF THE PRODUCT,EVEN IF HIKVISION HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES OR LOSS.YOU ACKNOWLEDGE THAT THE NATURE OF THE INTERNET PROVIDES FOR INHERENT SECURITY RISKS,AND HIKVISION SHALL NOT TAKE ANY RESPONSIBILITIES FOR ABNORMAL OPERATION,PRIVACY LEAKAGE OR OTHER DAMAGES RESULTING FROM CYBER-ATTACK, HACKER ATTACK,VIRUS INFECTION,OR OTHER INTERNET SECURITY RISKS;HOWEVER, HIKVISION WILL PROVIDE TIMELY TECHNICAL SUPPORT IF REQUIRED.YOU AGREE TO USE THIS PRODUCT IN COMPLIANCE WITH ALL APPLICABLE LAWS,AND YOU ARE SOLELY RESPONSIBLE FOR ENSURING THAT YOUR USE CONFORMS TO THE APPLICABLE LAW.ESPECIALLY,YOU ARE RESPONSIBLE,FOR USING THIS PRODUCT IN A MANNER THAT DOES NOT INFRINGE ON THE RIGHTS OF THIRD PARTIES,INCLUDING WITHOUT LIMITATION,RIGHTS OF PUBLICITY,INTELLECTUAL PROPERTY RIGHTS,OR DATA PROTECTION AND OTHER PRIVACY RIGHTS.YOU SHALL NOT USE THIS PRODUCT FOR ANY PROHIBITED END-USES,INCLUDING THE DEVELOPMENT OR PRODUCTION OF WEAPONS OF MASS DESTRUCTION,THE DEVELOPMENT OR PRODUCTION OF CHEMICAL OR BIOLOGICAL WEAPONS,ANY ACTIVITIES IN THE CONTEXT RELATED TO ANY NUCLEAR EXPLOSIVE OR UNSAFE NUCLEAR FUEL-CYCLE,OR IN SUPPORT OF HUMAN RIGHTS ABUSES.IN THE EVENT OF ANY CONFLICTS BETWEEN THIS MANUAL AND THE APPLICABLE LAW, THE LATTER PREVAILS.Data ProtectionDuring the use of device,personal data will be collected,stored and processed.To protect data,the development of Hikvision devices incorporates privacy by design principles.For example,for device with facial recognition features,biometrics data is stored in your device with encryption method;for fingerprint device,only fingerprint template will be saved,which is impossible to reconstruct a fingerprint image.As data controller,you are advised to collect,store,process and transfer data in accordance with the applicable data protection laws and regulations,including without limitation,conducting security controls to safeguard personal data,such as, implementing reasonable administrative and physical security controls,conduct periodic reviews and assessments of the effectiveness of your security controls.pedestals.L+282SlotHighThelargerIf the installationbetweenWe recommendRegulatory Information FCC InformationPlease take attention that changes or modification not expressly approved by the party responsible for compliance could void the user’s authority to operate the equipment.FCC compliance:This equipment has been tested and found to comply with the limits for a Class B digital device,pursuant to part 15of the FCC Rules.These limits are designed to provide reasonable protection against harmful interference in a residential installation.This equipment generates,uses and can radiate radio frequency energy and,if notinstalled and used in accordance with the instructions,may cause harmful interference to radio communications.However,there is no guarantee that interference will not occur in a particular installation.If this equipment does cause harmful interference to radio or television reception,which can be determined by turning the equipment off and on,the user is encouraged to try to correct the interference by one or more of the following measures:—Reorient or relocate the receiving antenna.—Increase the separation between the equipment and receiver.—Connect the equipment into an outlet on a circuit different from that to which the receiver is connected.—Consult the dealer or an experienced radio/TV technician for help.This equipment should be installed and operated with a minimum distance 20cm between the radiator and your body.FCC ConditionsThis device complies with part 15of the FCC Rules.Operation is subject to the following two conditions:1.This device may not cause harmful interference.2.This device must accept any interference received,including interference that may cause undesired operation.This product and -if applicable -the supplied accessories too are marked with "CE"and comply therefore with the applicable harmonized European standards listed under the RE Directive 2014/53/EU,the EMC Directive 2014/30/EU,the RoHS Directive 2011/65/EU.2006/66/EC (battery directive):This product contains a battery that cannot be disposed of as unsorted municipal waste in the European Union.See the product documentation for specificbattery information.The battery is marked with this symbol,which may include lettering to indicate cadmium (Cd),lead (Pb),or mercury (Hg).For proper recycling,return the battery to your supplier or to a designated collection point.For more information see:2012/19/EU (WEEE directive):Products marked with this symbol cannot be disposed of as unsorted municipal waste in theEuropean Union.For proper recycling,return this product to your local supplier upon the purchase of equivalent new equipment,or dispose of it at designated collection points.For more information see:Press Press Hold leval Press menuPress Press Press paramter level-1•You •The Refer Scan the QR code to view the user manual.。
legislative contact point at primary level
legislative contact point at
primary level
立法联系点作为基层民主立法实践的新探索，是地方立法工作的重要创新。
它不仅在促进立法民主化、科学化方面发挥了重要作用，而且为基层群众参与立法过程提供了有效渠道。
立法联系点通常设立在乡镇（街道）或基层单位，这些联系点作为立法机关与基层群众之间的桥梁，负责收集、整理和反馈基层群众对立法工作的意见和建议。
通过这种方式，立法机关能够更直接地了解基层群众的需求和关切，使立法工作更加贴近实际、贴近民生。
立法联系点的设立有助于推动基层民主立法实践。
它使得基层群众能够参与到立法过程中，表达自己的观点和利益诉求。
这种参与不仅增强了立法的民主性，也提高了群众对法律的认同感和遵守意愿。
同时，立法联系点还能够及时发现和解决基层群众在法律法规实施过程中遇到的问题，为法律法规的完善提供了有力支持。
然而，立法联系点在运行过程中也面临一些挑战。
例如，如何确保收集到的意见和建议真实、有效；如何平衡不同群体的利益诉求；如何提高基层群众参与立法的能力等。
为了解决这些问题，需要不断完善立法联系点的工作机制，加强培训和指导，提高基层群众参与立法的能力和水平。
总之，立法联系点在基层民主立法实践中发挥着重要作用。
它促进了立法民主化、科学化，为基层群众参与立法过程提供了有效渠道。
未来，应继续加强立法联系点的建设和管理，推动基层民主立法实践不断深入发展。
用药助手里的指南引用
用药助手里的指南引用英文回答：Using the medication assistant guide, I can provide information and guidance on various medications. The medication assistant guide is a valuable tool that helps individuals understand the usage, dosage, and potential side effects of different medications. It provides comprehensive information on various drugs, including prescription medications, over-the-counter drugs, and herbal supplements.The medication assistant guide can be accessed through a mobile application or a website. It is designed to be user-friendly and easily accessible to anyone seeking information about medications. The guide allows users to search for specific medications or browse through different categories to find the desired information.One of the key features of the medication assistantguide is that it provides detailed information about each medication, including its indications, contraindications, dosage instructions, and potential drug interactions. This helps individuals make informed decisions about their medications and ensures their safety and effectiveness. Moreover, the guide also highlights the potential side effects of each medication, allowing users to be aware of any adverse reactions that may occur.In addition to providing information on medications, the medication assistant guide also offers guidance on how to properly use and store medications. It provides instructions on how to take medications, whether with or without food, and at what time of the day. It also advises on the proper storage conditions for medications, such as storing them in a cool and dry place, away from direct sunlight or moisture.Furthermore, the medication assistant guide includes a section on common drug interactions. It alerts users about potential interactions between different medications, as well as interactions between medications and certain foods,beverages, or other substances. This information is crucial in preventing harmful drug interactions that could affect the efficacy of the medications or cause adverse effects.The medication assistant guide is a reliable source of information for healthcare professionals, patients, and caregivers. It helps individuals understand their medications better, empowers them to ask informed questions to their healthcare providers, and promotes medication safety and adherence.中文回答：使用药物助手指南，我可以提供有关各种药物的信息和指导。
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A Guide Concerning
Legislative Issues
Volume V
P.O. Box 2016
Edmonds, WA 98020-9516
(425) 967-0045 • (425) 771-9588 fax
info@
© March 2007 by The National Federation of Paralegal Associations, Inc.
State Legislative Websites
State URL /legislative
New /government/state.html New
New
New York (General Assembly)
New York (Senate)
North
North
Rhode
South
South
West
Sample Written Testimony
WRITTEN TESTIMONY OF
THE NATIONAL FEDERATION OF PARALEGAL ASSOCIATIONS, INC.
[NAME OF] COMMITTEE
THE HONORABLE [NAME], CHAIR
[CAPITOL CITY, STATE]
Honorable [Name of Committee Chair], Members of the [Name of Committee] Committee:
The National Federation of Paralegal Associations, Inc. (“NFPA”) presents this testimony on [insert legislative body and number of bill]. NFPA respectfully requests the amendment of [insert legislative body and number of bill] to contain a provision…
[Continue with text by (1) making general overall comments pertaining to bill,
and, further, (2) by discussing the particulars of the bill. Make each point in
favor of or opposition to the bill, in order of consecutive bill sections. Conclude
with information describing the background of the individual or entity offering
the testimony and a closing paragraph which summarizes the position in the
testimony.]
NFPA was founded in 1974 and is a grassroots non-profit professional association of paralegals representing over 11,000 paralegals nationwide. NFPA affirms the paralegal profession as an independent, self-directed profession which supports increased quality, efficiency and accessibility in the delivery of legal services. In addition, it promotes the growth, development and recognition of the profession as an integral partner in the delivery of legal services.
For the foregoing reasons, NFPA respectfully urges the amendment of [legislative body and number of bill] to include a provision [e.g., for awarding attorney fees for paralegal services]. Please feel free to contact NFPA if you have any questions or require further information. Thank you for the opportunity to offer these comments.
Respectfully submitted,
[Author's name]
[Author's title if association representative]
Page 17。