The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implem...The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implementations,but provide guidance for improving Findability,Accessibility,Interoperability and Reusability of digital resources.This has likely contributed to the broad adoption of the FAIR principles,because individual stakeholder communities can implement their own FAIR solutions.However,it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible implementations.Thus,while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways,for true interoperability we need to support convergence in implementation choices that are widely accessible and(re)-usable.We introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible,robust,widespread and consistent FAIR implementations.Any self-identified stakeholder community may either choose to reuse solutions from existing implementations,or when they spot a gap,accept the challenge to create the needed solution,which,ideally,can be used again by other communities in the future.Here,we provide interpretations and implementation considerations(choices and challenges)for each FAIR principle.展开更多
Since 2014,"Bring Your Own Data"workshops(BYODs)have been organised to inform people about the process and benefits of making resources Findable,Accessible,Interoperable,and Reusable(FAIR,and the FAIRificati...Since 2014,"Bring Your Own Data"workshops(BYODs)have been organised to inform people about the process and benefits of making resources Findable,Accessible,Interoperable,and Reusable(FAIR,and the FAIRification process).The BYOD workshops'content and format differ depending on their goal,context,and the background and needs of participants.Data-focused BYODs educate domain experts on how to make their data FAIR to find new answers to research questions.Management-focused BYODs promote the benefits of making data FAIR and instruct project managers and policy-makers on the characteristics of FAIRification projects.Software-focused BYODs gather software developers and experts on FAIR to implement or improve software resources that are used to support FAIRification.Overall,these BYODs intend to foster collaboration between different types of stakeholders involved in data management,curation,and reuse(e.g.domain experts,trainers,developers,data owners,data analysts,FAIR experts).The BYODs also serve as an opportunity to learn what kind of support for FAIRification is needed from different communities and to develop teaching materials based on practical examples and experience.In this paper,we detail the three different structures of the BYODs and describe examples of early BYODs related to plant breeding data,and rare disease registries and biobanks,which have shaped the structure of the workshops.We discuss the latest insights into making BYODs more productive by leveraging our almost ten years of training experience in these workshops,including successes and encountered challenges.Finally,we examine how the participants'feedback has motivated the research on FAIR,including the development of workflows and software.展开更多
The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at differe...The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at different wavelengths.In the UK,academia,industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications.This historical review looks at the contribution the UK has made to the advancement of the technology,the development of systems and components and their exploitation over the last 60 years.展开更多
Prediction of the potentially devastating impact of landfalling tropical cyclones(TCs)relies substantially on numerical prediction systems.Due to the limited predictability of TCs and the need to express forecast conf...Prediction of the potentially devastating impact of landfalling tropical cyclones(TCs)relies substantially on numerical prediction systems.Due to the limited predictability of TCs and the need to express forecast confidence and possible scenarios,it is vital to exploit the benefits of dynamic ensemble forecasts in operational TC forecasts and warnings.RSMCs,TCWCs,and other forecast centers value probabilistic guidance for TCs,but the International Workshop on Tropical Cyclones(IWTC-9)found that the“pull-through”of probabilistic information to operational warnings using those forecasts is slow.IWTC-9 recommendations led to the formation of the WMO/WWRP Tropical Cyclone-Probabilistic Forecast Products(TC-PFP)project,which is also endorsed as a WMO Seamless GDPFS Pilot Project.The main goal of TC-PFP is to coordinate across forecast centers to help identify best practice guidance for probabilistic TC forecasts.TC-PFP is being implemented in 3 phases:Phase 1(TC formation and position);Phase 2(TC intensity and structure);and Phase 3(TC related rainfall and storm surge).This article provides a summary of Phase 1 and reviews the current state of the science of probabilistic forecasting of TC formation and position.There is considerable variability in the nature and interpretation of forecast products based on ensemble information,making it challenging to transfer knowledge of best practices across forecast centers.Communication among forecast centers regarding the effectiveness of different approaches would be helpful for conveying best practices.Close collaboration with experts experienced in communicating complex probabilistic TC information and sharing of best practices between centers would help to ensure effective decisions can be made based on TC forecasts.Finally,forecast centers need timely access to ensemble information that has consistent,user-friendly ensemble information.Greater consistency across forecast centers in data accessibility,probabilistic forecast products,and warnings and their communication 展开更多
We sought to determine the characteristics of viral specimens associated with fatal cases,asymptomatic cases and non-fatal symptomatic cases of COVID-19.This included the analysis of 1264 specimens found reactive for ...We sought to determine the characteristics of viral specimens associated with fatal cases,asymptomatic cases and non-fatal symptomatic cases of COVID-19.This included the analysis of 1264 specimens found reactive for at least two SARS-CoV-2 specific loci from people screened for infection in Northern Nevada in March-May of 2020.Of these,30 were specimens from fatal cases,while 23 were from positive,asymptomatic cases.We assessed the relative amounts of SARS-CoV-2 RNA from sample swabs by real-time PCR and use of the threshold crossing value(Ct).Moreover,we compared the amount of human RNase P found on the same swabs.A considerably higher viral load was found to be associated with swabs from cases involving fatality and the difference was found to be strongly statistically significant.Noting this difference,we sought to assess whether any genetic correlation could be found in association with virus from fatal cases using whole genome sequencing.While no common genetic elements were discerned,one branch of epidemiologically linked fatal cases did have two point mutations,which no other of 156 sequenced cases from northern Nevada had.The mutations caused amino acid changes in the 3′-5′exonuclease protein,and the product of the gene,orf8.展开更多
We have developed a novel dual enzyme chemistry called rhAmp®SNP genotyping based on RNase H2-dependent PCR (rhPCR) that provides high signal and specificity for SNP analysis. rhAmp SNP genotyping combines a u...We have developed a novel dual enzyme chemistry called rhAmp®SNP genotyping based on RNase H2-dependent PCR (rhPCR) that provides high signal and specificity for SNP analysis. rhAmp SNP genotyping combines a unique two-enzyme system with 3’ end blocked DNA-RNA hybrid primers to interrogate SNP loci. Activation of the blocked primers occurs upon hybridization to its perfectly matched target, which eliminates or greatly reduces primer dimers. A thermostable hot-start RNase H2 cleaves the primer immediately 5’ of the ribose sugar, releasing the blocking group and allowing primer extension. PCR specificity is further improved with the use of a mutant Taq DNA polymerase, resulting in improved allelic discrimination. Signal generation is obtained using a universal reporter system which requires only two reporter probes for any bi-allelic SNP. 1000 randomly selected SNPs were chosen to validate the 95% design rate of the design pipeline. A subsampling of 130 human SNP targets was tested and achieved a 98% call rate, and 99% call accuracy. rhAmp SNP genotyping assays are compatible with various qPCR instruments including QuantStudioTM 7 Flex, CFX384TM, IntelliQube®, and Biomark HDTM. In comparison to TaqMan®, rhAmp SNP genotyping assays show higher signal (Rn) and greater cluster separation, resulting in more reliable SNP genotyping performance. The rhAmp SNP genotyping solution is suited for high-throughput SNP genotyping applications in humans and plants.展开更多
Why is it that ABO3 perovskites generally do not exhibit negative thermal expansion(NTE)over a wide temperature range,whereas layered perovskites of the same chemical family often do?It is generally accepted that ther...Why is it that ABO3 perovskites generally do not exhibit negative thermal expansion(NTE)over a wide temperature range,whereas layered perovskites of the same chemical family often do?It is generally accepted that there are two key ingredients that determine the extent of NTE:the presence of soft phonon modes that drive contraction(have negative Grüneisen parameters);and anisotropic elastic compliance that predisposes the material to the deformations required for NTE along a specific axis.This difference in thermal expansion properties is surprising since both ABO3 and layered perovskites often possess these ingredients in equal measure in their high-symmetry phases.Using first principles calculations and symmetry analysis,we show that in layered perovskites there is a significant enhancement of elastic anisotropy due to symmetry breaking that results from the combined effect of layering and condensed rotations of oxygen octahedra.This feature,unique to layered perovskites of certain symmetry,is what allows uniaxial NTE to persist over a large temperature range.This fundamental insight means that symmetry and the elastic tensor can be used as descriptors in high-throughput screening and to direct materials design.展开更多
Background:Young children are at high risk for developing complications of influenza,as well as severe clinical presentation of disease.Vaccination provides direct protection and reduces symptom severity in breakthrou...Background:Young children are at high risk for developing complications of influenza,as well as severe clinical presentation of disease.Vaccination provides direct protection and reduces symptom severity in breakthrough in-fections.We assessed whether adjuvanted trivalent seasonal influenza vaccine is associated with symptom severity in children who developed laboratory-confirmed influenza,as compared to children who received quadrivalent inactivated influenza.Methods:A cluster randomized controlled trial of influenza vaccines in Canadian Hutterite colonies was conducted from the 2016-2017 to the 2018-2019 influenza season.Children were vaccinated with either quadrivalent inactivated influenza vaccine(QIV),or the MF59 adjuvanted trivalent influenza vaccine(aTIV).We assessed children who developed PCR-confirmed influenza infection for symptom severity outcomes using multivariable generalized negative binomial regression.Results:Among vaccinated children,49 infections were observed across 1779 person-days.Vaccine formulation(aTIV vs QIV)was not significantly associated with composite symptom outcomes,including total number of symptoms or total duration of symptom presentation(p>0.05 for all outcomes).Receipt of aTIV vaccination was significantly associated with attenuation of fever,with an estimated 74%reduction in fever severity.In influenza A type infections,adjuvanted vaccination was significantly associated with reduced systemic symptoms(incidence rate ratios:0.16,95%confidence intervals:0.03,0.64,p=0.01).No associations were observed between vaccine formulation and symptom severity in influenza B infections.Conclusions:In vaccinated children who develop an influenza infection,vaccine formulation was associated with attenuated fever severity,leading to reduced systemic symptoms.In influenza A infections,adjuvanted vaccination was significantly associated with reduced systemic symptoms.展开更多
AIM: To investigate the patient characteristics, relationship between the Logistic EuroSCORE (LES) and the observed outcomes in octogenarians who underwent surgical aortic valve replacement (AVR). METHODS: Two hundred...AIM: To investigate the patient characteristics, relationship between the Logistic EuroSCORE (LES) and the observed outcomes in octogenarians who underwent surgical aortic valve replacement (AVR). METHODS: Two hundred and seventy three octogenarians underwent AVR between 1996 and 2008 at Bristol Royal Inf irmary. Demographics, acute outcomes,length of hospital stay and mortality were obtained. The LES was calculated to characterize the predicted operative risk. Two groups were def ined: LES ≥ 15 (n = 80) and LES < 15 (n = 193). RESULTS: In patients with LES ≥ 15, 30 d mortality was 14% (95% CI: 7%-23%) compared with 4% (95% CI: 2%-8%) in the LES < 15 group (P < 0.007). Despite the increase in number of operations from 1996 to 2008, the average LES did not change. Only 5% of patients had prior bypass surgery. The LES identifi ed a low risk quartile of patients with a very low mortality (4%, n = 8, P < 0.007) at 30 d. The overall surgical results for octogenarians were excellent. The low risk group had an excellent outcome and the high risk group had a poor outcome after surgical AVR. CONCLUSION: It may be better treated with transcatheter aortic valve implantation.展开更多
Objective and Impact Statement.There is a need to develop platforms delineating inflammatory biology of the distal human lung.We describe a platform technology approach to detect in situ enzyme activity and observe dr...Objective and Impact Statement.There is a need to develop platforms delineating inflammatory biology of the distal human lung.We describe a platform technology approach to detect in situ enzyme activity and observe drug inhibition in the distal human lung using a combination of matrix metalloproteinase(MMP)optical reporters,fibered confocal fluorescence microscopy(FCFM),and a bespoke delivery device.Introduction.The development of new therapeutic agents is hindered by the lack of in vivo in situ experimental methodologies that can rapidly evaluate the biological activity or drug-target engagement in patients.Methods.We optimised a novel highly quenched optical molecular reporter of enzyme activity(FIB One)and developed a translational pathway for in-human assessment.Results.We demonstrate the specificity for matrix metalloproteases(MMPs)2,9,and 13 and probe dequenching within physiological levels of MMPs and feasibility of imaging within whole lung models in preclinical settings.Subsequently,in a first-in-human exploratory experimental medicine study of patients with fibroproliferative lung disease,we demonstrate,through FCFM,the MMP activity in the alveolar space measured through FIB One fluorescence increase(with pharmacological inhibition).Conclusion.This translational in situ approach enables a new methodology to demonstrate active drug target effects of the distal lung and consequently may inform therapeutic drug development pathways.展开更多
Background:Lateral ankle sprain is the most common musculoskeletal injury.Although clinical research in this field is growing,there is a broader concern that clinical trial outcomes are often false and fail to transla...Background:Lateral ankle sprain is the most common musculoskeletal injury.Although clinical research in this field is growing,there is a broader concern that clinical trial outcomes are often false and fail to translate into patient benefits.Methods:We audited 30 years of experimental research related to lateral ankle sprain management(n=74 randomized controlled trials)to determine if reports of treatment effectiveness could be validated beyond statistical certainty.Results:A total of 77%of trials reported positive treatment effects,but there was a high risk of false discovery.Most trials were unregistered and relied solely on statistical significance,or lack of statistical significance,rather than on interpreting key measures of minimum clinical importance(e.g.,minimal detectable change,minimal clinically important difference).Conclusion:Future clinical trials must adopt higher standards of reporting and data interpretation.This includes consideration of the ethical responsibility to preregister their research and interpretation of clinical outcomes beyond statistical significance.展开更多
Many states rely upon the Pennsylvania 1957 Gas Well Pillar Study to evaluate the coal barrier surrounding gas wells.The study included 77 gas well failure cases that occurred in the Pittsburgh and Freeport coal seams...Many states rely upon the Pennsylvania 1957 Gas Well Pillar Study to evaluate the coal barrier surrounding gas wells.The study included 77 gas well failure cases that occurred in the Pittsburgh and Freeport coal seams over a 25-year span.At the time,coal was mined using the room-and-pillar mining method with full or partial pillar recovery,and square or rectangle pillars surrounding the gas wells were left to protect the wells.The study provided guidelines for pillar sizes under different overburden depths up to 213 m(700 ft).The 1957 study has also been used to determine gas well pillar sizes in longwall mines since longwall mining began in the 1970 s.The original study was developed for room-and-pillar mining and could be applied to gas wells in longwall chain pillars under shallow cover.However,under deep cover,severe deformations in gas wells have occurred in longwall chain pillars.Presently,with a better understanding of coal pillar mechanics,new insight into subsidence movements induced by retreat mining,and advances in numerical modeling,it has become both critically important and feasible to evaluate the adequacy of the 1957 study for longwall gas well pillars.In this paper,the data from the 1957 study is analyzed from a new perspective by considering various factors,including overburden depth,failure location,failure time,pillar safety factor(SF),and floor pressure.The pillar SF and floor pressure are calculated by considering abutment pressure induced by full pillar recovery.A statistical analysis is performed to find correlations between various factors and helps identify the most significant factors for the stability of gas wells influenced by retreat mining.Through analyzing the data from the 1957 study,the guidelines for gas well pillars in the 1957 study are evaluated for their adequacy for roomand-pillar mining and their applicability to longwall mining.Numerical modeling is used to model the stability of gas wells by quantifying the mining-induced stresses in gas well casings.Results of this stud展开更多
Introduction: Our aim was to determine what patient volume, if any, in-laboratory testing provides results faster than Point-of-Care-Testing (POCT). Methods: To evaluate POCT effectiveness during high volume situation...Introduction: Our aim was to determine what patient volume, if any, in-laboratory testing provides results faster than Point-of-Care-Testing (POCT). Methods: To evaluate POCT effectiveness during high volume situations, POCT was compared to in-laboratory testing during busy periods with large numbers of patients. Our setting was an urban level 1 trauma center with an academic emergency medicine department (ED) and annual patient volume of 70,000. Patients seen requiring laboratory testing during peak volume between 11 a.m. and 7 p.m. were enrolled over a five-week period. One tube of blood was sent to the laboratory and the other tube was run in the ED using POCT. Turnaround time was recorded as time from when the tube was received to when the result was available. We also completed a time-motion study to assess the number of POCT machines that would be needed to process the entire average hourly hospital laboratory volume. Results: We collected 539 hematology and chemistry specimens. The POCT group was significantly faster than in-laboratory testing, with mean POCT [complete blood count (CBC) and chemistry] 3.5 minutes compared to in-laboratory CBC test time of 30.9 minutes and chemistry test time of 55 minutes. As the volume of samples peaked, there was a slight but insignificant decrease in POCT turnaround time. If POCT was used to process the entire average hospital laboratory volume which approached 54 samples an hour, 3 POCT machines would be necessary to maintain turnaround times. Conclusion: Even during ED high volume situations, POCT provided results significantly faster than in-laboratory testing.展开更多
Executive Summary There seema to be a common expectation among radio frequency identification(RFID) newcomers that putting an inexpensive,passive smart label on a box will create an accounting nirvana.
In the research article“Optical Detection of Distal Lung Enzyme Activity in Human Inflammatory Lung Disease”[1],the data availability statement was inadvertently omitted by the publisher.This has now been corrected ...In the research article“Optical Detection of Distal Lung Enzyme Activity in Human Inflammatory Lung Disease”[1],the data availability statement was inadvertently omitted by the publisher.This has now been corrected in the PDF and HTML(full text).展开更多
基金The work of A.Jacobsen,C.Evelo,M.Thompson,R.Cornet,R.Kaliyaperuma and M.Roos is supported by funding from the European Union’s Horizon 2020 research and innovation program under the EJP RD COFUND-EJP N°825575.The work of A.Jacobsen,C.Evelo,C.Goble,M.Thompson,N.Juty,R.Hooft,M.Roos,S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista is supported by funding from ELIXIR EXCELERATE,H2020 grant agreement number 676559.R.Hooft was further funded by NL NWO NRGWI.obrug.2018.009.N.Juty and C.Goble were funded by CORBEL(H2020 grant agreement 654248)N.Juty,C.Goble,S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista were funded by FAIRplus(IMI grant agreement 802750)+12 种基金N.Juty,C.Goble,M.Thompson,M.Roos,S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista were funded by EOSClife H2020-EU(grant agreement number 824087)C.Goble was funded by DMMCore(BBSRC BB/M013189/)M.Thompson,M.Roos received funding from NWO(VWData 400.17.605)S-A.Sansone,P.McQuilton,P.Rocca-Serra and D.Batista have been funded by grants awarded to S-A.Sansone from the UK BBSRC and Research Councils(BB/L024101/1,BB/L005069/1)EU(H2020-EU 634107H2020-EU 654241,IMI(IMPRiND 116060)NIH Data Common Fund,and from the Wellcome Trust(ISA-InterMine 212930/Z/18/ZFAIRsharing 208381/A/17/Z)The work of A.Waagmeester has been funded by grant award number GM089820 from the National Institutes of Health.M.Kersloot was funded by the European Regional Development Fund(KVW-00163).The work of N.Meyers was funded by the National Science Foundation(OAC 1839030)The work of M.D.Wilkinson is funded by Isaac Peral/Marie Curie cofund with the Universidad Politecnica de Madrid and the Ministerio de Economia y Competitividad grant number TIN2014-55993-RMThe work of B.Magagna,E.Schultes,L.da Silva Santos and K.Jeffery is funded by the H2020-EU 824068The work of B.Magagna,E.Schultes and L.da Silva Santos is funded by the GO FAIR ISCO grant of the Dutch Ministry of Science and CultureThe work of G.Guizzardi is supported by the OCEAN Project(FUB).M.Courtot received funding from the I
文摘The FAIR principles have been widely cited,endorsed and adopted by a broad range of stakeholders since their publication in 2016.By intention,the 15 FAIR guiding principles do not dictate specific technological implementations,but provide guidance for improving Findability,Accessibility,Interoperability and Reusability of digital resources.This has likely contributed to the broad adoption of the FAIR principles,because individual stakeholder communities can implement their own FAIR solutions.However,it has also resulted in inconsistent interpretations that carry the risk of leading to incompatible implementations.Thus,while the FAIR principles are formulated on a high level and may be interpreted and implemented in different ways,for true interoperability we need to support convergence in implementation choices that are widely accessible and(re)-usable.We introduce the concept of FAIR implementation considerations to assist accelerated global participation and convergence towards accessible,robust,widespread and consistent FAIR implementations.Any self-identified stakeholder community may either choose to reuse solutions from existing implementations,or when they spot a gap,accept the challenge to create the needed solution,which,ideally,can be used again by other communities in the future.Here,we provide interpretations and implementation considerations(choices and challenges)for each FAIR principle.
基金support from the RD-Connect project(funded from the European Community's Seventh Framework Program under grant agreement n°305444"RD-CONNECT")ELIXIR and ELIXIR-EXCELERATE(Grant number EU H2020#676559)+1 种基金the Istituto Superiore di Sanita(ISS),the Leiden University Medical Center(LUMC)the University Medical Center Groningen,and the Dutch Techcentre for Life Sciences(DTL)between 2014 and 2018.From 2019 to 2023,the RD-BYOD has been funded by the European Joint Programme Rare Diseases(EJP RD)and its partners(European Union Horizon 2020 Research and Innovation Programme under Grant Agreement n°825575),and we are grateful for their continued support.
文摘Since 2014,"Bring Your Own Data"workshops(BYODs)have been organised to inform people about the process and benefits of making resources Findable,Accessible,Interoperable,and Reusable(FAIR,and the FAIRification process).The BYOD workshops'content and format differ depending on their goal,context,and the background and needs of participants.Data-focused BYODs educate domain experts on how to make their data FAIR to find new answers to research questions.Management-focused BYODs promote the benefits of making data FAIR and instruct project managers and policy-makers on the characteristics of FAIRification projects.Software-focused BYODs gather software developers and experts on FAIR to implement or improve software resources that are used to support FAIRification.Overall,these BYODs intend to foster collaboration between different types of stakeholders involved in data management,curation,and reuse(e.g.domain experts,trainers,developers,data owners,data analysts,FAIR experts).The BYODs also serve as an opportunity to learn what kind of support for FAIRification is needed from different communities and to develop teaching materials based on practical examples and experience.In this paper,we detail the three different structures of the BYODs and describe examples of early BYODs related to plant breeding data,and rare disease registries and biobanks,which have shaped the structure of the workshops.We discuss the latest insights into making BYODs more productive by leveraging our almost ten years of training experience in these workshops,including successes and encountered challenges.Finally,we examine how the participants'feedback has motivated the research on FAIR,including the development of workflows and software.
文摘The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at different wavelengths.In the UK,academia,industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications.This historical review looks at the contribution the UK has made to the advancement of the technology,the development of systems and components and their exploitation over the last 60 years.
文摘Prediction of the potentially devastating impact of landfalling tropical cyclones(TCs)relies substantially on numerical prediction systems.Due to the limited predictability of TCs and the need to express forecast confidence and possible scenarios,it is vital to exploit the benefits of dynamic ensemble forecasts in operational TC forecasts and warnings.RSMCs,TCWCs,and other forecast centers value probabilistic guidance for TCs,but the International Workshop on Tropical Cyclones(IWTC-9)found that the“pull-through”of probabilistic information to operational warnings using those forecasts is slow.IWTC-9 recommendations led to the formation of the WMO/WWRP Tropical Cyclone-Probabilistic Forecast Products(TC-PFP)project,which is also endorsed as a WMO Seamless GDPFS Pilot Project.The main goal of TC-PFP is to coordinate across forecast centers to help identify best practice guidance for probabilistic TC forecasts.TC-PFP is being implemented in 3 phases:Phase 1(TC formation and position);Phase 2(TC intensity and structure);and Phase 3(TC related rainfall and storm surge).This article provides a summary of Phase 1 and reviews the current state of the science of probabilistic forecasting of TC formation and position.There is considerable variability in the nature and interpretation of forecast products based on ensemble information,making it challenging to transfer knowledge of best practices across forecast centers.Communication among forecast centers regarding the effectiveness of different approaches would be helpful for conveying best practices.Close collaboration with experts experienced in communicating complex probabilistic TC information and sharing of best practices between centers would help to ensure effective decisions can be made based on TC forecasts.Finally,forecast centers need timely access to ensemble information that has consistent,user-friendly ensemble information.Greater consistency across forecast centers in data accessibility,probabilistic forecast products,and warnings and their communication
文摘We sought to determine the characteristics of viral specimens associated with fatal cases,asymptomatic cases and non-fatal symptomatic cases of COVID-19.This included the analysis of 1264 specimens found reactive for at least two SARS-CoV-2 specific loci from people screened for infection in Northern Nevada in March-May of 2020.Of these,30 were specimens from fatal cases,while 23 were from positive,asymptomatic cases.We assessed the relative amounts of SARS-CoV-2 RNA from sample swabs by real-time PCR and use of the threshold crossing value(Ct).Moreover,we compared the amount of human RNase P found on the same swabs.A considerably higher viral load was found to be associated with swabs from cases involving fatality and the difference was found to be strongly statistically significant.Noting this difference,we sought to assess whether any genetic correlation could be found in association with virus from fatal cases using whole genome sequencing.While no common genetic elements were discerned,one branch of epidemiologically linked fatal cases did have two point mutations,which no other of 156 sequenced cases from northern Nevada had.The mutations caused amino acid changes in the 3′-5′exonuclease protein,and the product of the gene,orf8.
文摘We have developed a novel dual enzyme chemistry called rhAmp®SNP genotyping based on RNase H2-dependent PCR (rhPCR) that provides high signal and specificity for SNP analysis. rhAmp SNP genotyping combines a unique two-enzyme system with 3’ end blocked DNA-RNA hybrid primers to interrogate SNP loci. Activation of the blocked primers occurs upon hybridization to its perfectly matched target, which eliminates or greatly reduces primer dimers. A thermostable hot-start RNase H2 cleaves the primer immediately 5’ of the ribose sugar, releasing the blocking group and allowing primer extension. PCR specificity is further improved with the use of a mutant Taq DNA polymerase, resulting in improved allelic discrimination. Signal generation is obtained using a universal reporter system which requires only two reporter probes for any bi-allelic SNP. 1000 randomly selected SNPs were chosen to validate the 95% design rate of the design pipeline. A subsampling of 130 human SNP targets was tested and achieved a 98% call rate, and 99% call accuracy. rhAmp SNP genotyping assays are compatible with various qPCR instruments including QuantStudioTM 7 Flex, CFX384TM, IntelliQube®, and Biomark HDTM. In comparison to TaqMan®, rhAmp SNP genotyping assays show higher signal (Rn) and greater cluster separation, resulting in more reliable SNP genotyping performance. The rhAmp SNP genotyping solution is suited for high-throughput SNP genotyping applications in humans and plants.
基金supported by an Imperial College Research Fellowship and a Royal Society Research Grantthe John Fell Fund,Oxford(DPD09750)for funding to support this project+2 种基金supported by a studentship in the Centre for Doctoral Training on Theory and Simulation of Materials at Imperial College London funded by the EPSRC(EP/L015579/1)supported by the Thomas Young Centre under grant TYC-101partially funded by EPSRC(EP/P020194/1).
文摘Why is it that ABO3 perovskites generally do not exhibit negative thermal expansion(NTE)over a wide temperature range,whereas layered perovskites of the same chemical family often do?It is generally accepted that there are two key ingredients that determine the extent of NTE:the presence of soft phonon modes that drive contraction(have negative Grüneisen parameters);and anisotropic elastic compliance that predisposes the material to the deformations required for NTE along a specific axis.This difference in thermal expansion properties is surprising since both ABO3 and layered perovskites often possess these ingredients in equal measure in their high-symmetry phases.Using first principles calculations and symmetry analysis,we show that in layered perovskites there is a significant enhancement of elastic anisotropy due to symmetry breaking that results from the combined effect of layering and condensed rotations of oxygen octahedra.This feature,unique to layered perovskites of certain symmetry,is what allows uniaxial NTE to persist over a large temperature range.This fundamental insight means that symmetry and the elastic tensor can be used as descriptors in high-throughput screening and to direct materials design.
文摘Background:Young children are at high risk for developing complications of influenza,as well as severe clinical presentation of disease.Vaccination provides direct protection and reduces symptom severity in breakthrough in-fections.We assessed whether adjuvanted trivalent seasonal influenza vaccine is associated with symptom severity in children who developed laboratory-confirmed influenza,as compared to children who received quadrivalent inactivated influenza.Methods:A cluster randomized controlled trial of influenza vaccines in Canadian Hutterite colonies was conducted from the 2016-2017 to the 2018-2019 influenza season.Children were vaccinated with either quadrivalent inactivated influenza vaccine(QIV),or the MF59 adjuvanted trivalent influenza vaccine(aTIV).We assessed children who developed PCR-confirmed influenza infection for symptom severity outcomes using multivariable generalized negative binomial regression.Results:Among vaccinated children,49 infections were observed across 1779 person-days.Vaccine formulation(aTIV vs QIV)was not significantly associated with composite symptom outcomes,including total number of symptoms or total duration of symptom presentation(p>0.05 for all outcomes).Receipt of aTIV vaccination was significantly associated with attenuation of fever,with an estimated 74%reduction in fever severity.In influenza A type infections,adjuvanted vaccination was significantly associated with reduced systemic symptoms(incidence rate ratios:0.16,95%confidence intervals:0.03,0.64,p=0.01).No associations were observed between vaccine formulation and symptom severity in influenza B infections.Conclusions:In vaccinated children who develop an influenza infection,vaccine formulation was associated with attenuated fever severity,leading to reduced systemic symptoms.In influenza A infections,adjuvanted vaccination was significantly associated with reduced systemic symptoms.
文摘AIM: To investigate the patient characteristics, relationship between the Logistic EuroSCORE (LES) and the observed outcomes in octogenarians who underwent surgical aortic valve replacement (AVR). METHODS: Two hundred and seventy three octogenarians underwent AVR between 1996 and 2008 at Bristol Royal Inf irmary. Demographics, acute outcomes,length of hospital stay and mortality were obtained. The LES was calculated to characterize the predicted operative risk. Two groups were def ined: LES ≥ 15 (n = 80) and LES < 15 (n = 193). RESULTS: In patients with LES ≥ 15, 30 d mortality was 14% (95% CI: 7%-23%) compared with 4% (95% CI: 2%-8%) in the LES < 15 group (P < 0.007). Despite the increase in number of operations from 1996 to 2008, the average LES did not change. Only 5% of patients had prior bypass surgery. The LES identifi ed a low risk quartile of patients with a very low mortality (4%, n = 8, P < 0.007) at 30 d. The overall surgical results for octogenarians were excellent. The low risk group had an excellent outcome and the high risk group had a poor outcome after surgical AVR. CONCLUSION: It may be better treated with transcatheter aortic valve implantation.
基金supported by the Medical Research Council(under the Developmental Pathway Funding Scheme grant number MR/J014702)the Engineering and Physical Sciences Research Council(EP/K03197X/1,EP/R005257/1,and NS/A000049/1)+3 种基金the Wellcome Trust(203148/Z/16/Z)AA is supported by a Cancer Research UK Clinician Scientist Fellowship(A24867)TV is supported by a Medtronic/Royal Academy of Engineering Research Chair(RCSRF1819\7\34)The research leading to these results has received funding from the European Union Seventh Framework Programme FP72012 under grant agreement No.326465(AMF).
文摘Objective and Impact Statement.There is a need to develop platforms delineating inflammatory biology of the distal human lung.We describe a platform technology approach to detect in situ enzyme activity and observe drug inhibition in the distal human lung using a combination of matrix metalloproteinase(MMP)optical reporters,fibered confocal fluorescence microscopy(FCFM),and a bespoke delivery device.Introduction.The development of new therapeutic agents is hindered by the lack of in vivo in situ experimental methodologies that can rapidly evaluate the biological activity or drug-target engagement in patients.Methods.We optimised a novel highly quenched optical molecular reporter of enzyme activity(FIB One)and developed a translational pathway for in-human assessment.Results.We demonstrate the specificity for matrix metalloproteases(MMPs)2,9,and 13 and probe dequenching within physiological levels of MMPs and feasibility of imaging within whole lung models in preclinical settings.Subsequently,in a first-in-human exploratory experimental medicine study of patients with fibroproliferative lung disease,we demonstrate,through FCFM,the MMP activity in the alveolar space measured through FIB One fluorescence increase(with pharmacological inhibition).Conclusion.This translational in situ approach enables a new methodology to demonstrate active drug target effects of the distal lung and consequently may inform therapeutic drug development pathways.
文摘Background:Lateral ankle sprain is the most common musculoskeletal injury.Although clinical research in this field is growing,there is a broader concern that clinical trial outcomes are often false and fail to translate into patient benefits.Methods:We audited 30 years of experimental research related to lateral ankle sprain management(n=74 randomized controlled trials)to determine if reports of treatment effectiveness could be validated beyond statistical certainty.Results:A total of 77%of trials reported positive treatment effects,but there was a high risk of false discovery.Most trials were unregistered and relied solely on statistical significance,or lack of statistical significance,rather than on interpreting key measures of minimum clinical importance(e.g.,minimal detectable change,minimal clinically important difference).Conclusion:Future clinical trials must adopt higher standards of reporting and data interpretation.This includes consideration of the ethical responsibility to preregister their research and interpretation of clinical outcomes beyond statistical significance.
文摘Many states rely upon the Pennsylvania 1957 Gas Well Pillar Study to evaluate the coal barrier surrounding gas wells.The study included 77 gas well failure cases that occurred in the Pittsburgh and Freeport coal seams over a 25-year span.At the time,coal was mined using the room-and-pillar mining method with full or partial pillar recovery,and square or rectangle pillars surrounding the gas wells were left to protect the wells.The study provided guidelines for pillar sizes under different overburden depths up to 213 m(700 ft).The 1957 study has also been used to determine gas well pillar sizes in longwall mines since longwall mining began in the 1970 s.The original study was developed for room-and-pillar mining and could be applied to gas wells in longwall chain pillars under shallow cover.However,under deep cover,severe deformations in gas wells have occurred in longwall chain pillars.Presently,with a better understanding of coal pillar mechanics,new insight into subsidence movements induced by retreat mining,and advances in numerical modeling,it has become both critically important and feasible to evaluate the adequacy of the 1957 study for longwall gas well pillars.In this paper,the data from the 1957 study is analyzed from a new perspective by considering various factors,including overburden depth,failure location,failure time,pillar safety factor(SF),and floor pressure.The pillar SF and floor pressure are calculated by considering abutment pressure induced by full pillar recovery.A statistical analysis is performed to find correlations between various factors and helps identify the most significant factors for the stability of gas wells influenced by retreat mining.Through analyzing the data from the 1957 study,the guidelines for gas well pillars in the 1957 study are evaluated for their adequacy for roomand-pillar mining and their applicability to longwall mining.Numerical modeling is used to model the stability of gas wells by quantifying the mining-induced stresses in gas well casings.Results of this stud
文摘Introduction: Our aim was to determine what patient volume, if any, in-laboratory testing provides results faster than Point-of-Care-Testing (POCT). Methods: To evaluate POCT effectiveness during high volume situations, POCT was compared to in-laboratory testing during busy periods with large numbers of patients. Our setting was an urban level 1 trauma center with an academic emergency medicine department (ED) and annual patient volume of 70,000. Patients seen requiring laboratory testing during peak volume between 11 a.m. and 7 p.m. were enrolled over a five-week period. One tube of blood was sent to the laboratory and the other tube was run in the ED using POCT. Turnaround time was recorded as time from when the tube was received to when the result was available. We also completed a time-motion study to assess the number of POCT machines that would be needed to process the entire average hourly hospital laboratory volume. Results: We collected 539 hematology and chemistry specimens. The POCT group was significantly faster than in-laboratory testing, with mean POCT [complete blood count (CBC) and chemistry] 3.5 minutes compared to in-laboratory CBC test time of 30.9 minutes and chemistry test time of 55 minutes. As the volume of samples peaked, there was a slight but insignificant decrease in POCT turnaround time. If POCT was used to process the entire average hospital laboratory volume which approached 54 samples an hour, 3 POCT machines would be necessary to maintain turnaround times. Conclusion: Even during ED high volume situations, POCT provided results significantly faster than in-laboratory testing.
文摘Executive Summary There seema to be a common expectation among radio frequency identification(RFID) newcomers that putting an inexpensive,passive smart label on a box will create an accounting nirvana.
文摘In the research article“Optical Detection of Distal Lung Enzyme Activity in Human Inflammatory Lung Disease”[1],the data availability statement was inadvertently omitted by the publisher.This has now been corrected in the PDF and HTML(full text).
