bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of routinely collected data in a UK cohort of publicly funded randomised clinical trials
Authors: McKay Andrew J. , Jones Ashley P. , Gamble Carrol L. , Farmer Andrew J. , Williamson Paula R. 
Published: June 2020

Routinely collected data about health in medical records, registries and hospital activity statistics is now routinely collected in an electronic form. The extent to which such sources of data are now being routinely accessed to deliver efficient clinical trials, is unclear. The aim of this study was to ascertain current practice amongst a United Kingdom (UK) cohort of recently funded and ongoing randomised controlled trials (RCTs) in relation to sources and use of routinely collected outcome data. Recently funded and ongoing RCTs were identified for inclusion by searching the National Institute for Health Research journals library. Trials that have a protocol available were assessed for inclusion and those that use or plan to use routinely collected health data (RCHD) for at least one outcome were included. RCHD sources and outcome information were extracted. Of 216 RCTs, 102 (47%) planned to use RCHD. A RCHD source was the sole source of outcome data for at least one outcome in 46 (45%) of those 102 trials. The most frequent sources are Hospital Episode Statistics (HES) and Office for National Statistics (ONS), with the most common outcome data to be extracted being on mortality, hospital admission, and health service resource use. Our study has found that around half of publicly funded trials in a UK cohort (NIHR HTA funded trials that had a protocol available) plan to collect outcome data from routinely collected data sources. This is much higher than the figure of 8% found in a cohort of 189 RCTs published since 2000, the majority of which were carried out in North America (McCord et al., 2019).
Identifying and understanding factors that affect the translation of therapies from the laboratory to patients: a study protocol
Authors: Lalu Manoj M. , Montroy Joshua , Begley C. Glenn , Bubela Tania , Hunniford Victoria , Ripsman David , Wesch Neil , Kimmelman Jonathan , Macleod Malcolm , Moher David , Tieu Alvin , Sikora Lindsey , Fergusson Dean A. 
Published: June 2020

Background: The process of translating preclinical findings into a clinical setting takes decades. Previous studies have suggested that only 5-10% of the most promising preclinical studies are successfully translated into viable clinical applications. The underlying determinants of this low success rate (e.g. poor experimental design, suboptimal animal models, poor reporting) have not been examined in an empirical manner. Our study aims to determine the contemporary success rate of preclinical-to-clinical translation, and subsequently determine if an association between preclinical study design and translational success/failure exists. Methods: Established systematic review methodology will be used with regards to the literature search, article screening and study selection process. Preclinical, basic science studies published in high impact basic science journals between 1995 and 2015 will be included. Included studies will focus on publicly available interventions with potential clinical promise. The primary outcome will be successful clinical translation of promising therapies - defined as the conduct of at least one Phase II trial (or greater) with a positive finding. A case-control study will then be performed to evaluate the association between elements of preclinical study design and reporting and the likelihood of successful translation. Discussion: This study will provide a comprehensive analysis of the therapeutic translation from the laboratory bench to the bedside. Importantly, any association between factors of study design and the success of translation will be identified. These findings may inform future research teams attempting preclinical-to-clinical translation. Results will be disseminated to identified knowledge users that fund/support preclinical research.
Application of the intervention Complexity Assessment Tool for Systematic Reviews within a Cochrane review: an illustrative case study
Authors: Cadogan Cathal A. , Rankin Audrey , Lewin Simon , Hughes Carmel M. 
Published: June 2020

Background: The intervention Complexity Assessment Tool for Systematic Reviews (iCAT_SR) has been developed to facilitate detailed assessments of intervention complexity in systematic reviews. Worked examples of the tool’s application are needed to promote its use and refinement. The aim of this case study was to apply the iCAT_SR to a subset of 20 studies included in a Cochrane review of interventions aimed at improving appropriate polypharmacy in older people. Methods: Interventions were assessed independently by two authors using the six core iCAT_SR dimensions: (1) ‘Target organisational levels/categories’; (2) ‘Target behaviour/actions’; (3) ‘Active intervention components’; (4) ‘Degree of tailoring’; (5) ‘Level of skill required by intervention deliverers’; (6) ‘Level of skill required by intervention recipients’. Attempts were made to apply four optional dimensions: ‘Interaction between intervention components’; ‘Context/setting’; ‘Recipient/provider factors’; ‘Nature of causal pathway’. Inter-rater reliability was assessed using Cohen’s Kappa coefficient. Disagreements were resolved by consensus discussion. The findings are presented narratively. Results: Assessments involving the core iCAT_SR dimensions showed limited consistency in intervention complexity across included studies, even when categorised according to clinical setting. Interventions were delivered across various organisational levels and categories (i.e. healthcare professionals and patients) and typically comprised multiple components. Intermediate skill levels were required by those delivering and receiving the interventions across all studies. A lack of detail in study reports precluded application of the iCAT_SR’s optional dimensions. The inter-rater reliability was substantial (Cohen's Kappa = 0.75) Conclusions: This study describes the application of the iCAT_SR to studies included in a Cochrane systematic review. Future intervention studies need to ensure more detailed reporting of interventions, context and the causal pathways underlying intervention effects to allow a more holistic understanding of intervention complexity and facilitate replication in other settings. The experience gained has helped to refine the original guidance document relating to the application of iCAT_SR.
ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network): a pilot protocol for case based antimicrobial resistance surveillance
Authors: Turner Paul , Ashley Elizabeth A. , Celhay Olivier J. , Douangnouvong Anousone , Hamers Raph L. , Ling Clare L. , Lubell Yoel , Miliya Thyl , Roberts Tamalee , Soputhy Chansovannara , Ngoc Thach Pham , Vongsouvath Manivanh , Waithira Naomi , Wannapinij Prapass , van Doorn H. Rogier 
Published: June 2020

Background: Antimicrobial resistance (AMR) / drug resistant infections (DRIs) are a major global health priority. Surveillance data is critical to inform infection treatment guidelines, monitor trends, and to assess interventions. However, most existing AMR / DRI surveillance systems are passive and pathogen-based with many potential biases. Addition of clinical and patient outcome data would provide considerable added value to pathogen-based surveillance. Methods: The aim of the ACORN project is to develop an efficient clinically-oriented AMR surveillance system, implemented alongside routine clinical care in hospitals in low- and middle-income country settings. In an initial pilot phase, clinical and microbiology data will be collected from patients presenting with clinically suspected meningitis, pneumonia, or sepsis. Community-acquired infections will be identified by daily review of new admissions, and hospital-acquired infections will be enrolled during weekly point prevalence surveys, on surveillance wards. Clinical variables will be collected at enrolment, hospital discharge, and at day 28 post-enrolment using an electronic questionnaire on a mobile device. These data will be merged with laboratory data onsite using a flexible automated computer script. Specific target pathogens will be Streptococcus pneumoniae, Staphylococcus aureus, Salmonella spp., Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. A bespoke browser-based app will provide sites with fully interactive data visualisation, analysis, and reporting tools. Discussion: ACORN will generate data on the burden of DRI which can be used to inform local treatment guidelines / national policy and serve as indicators to measure the impact of interventions. Following development, testing and iteration of the surveillance tools during an initial six-month pilot phase, a wider rollout is planned.
Estimating the burden of antimicrobial resistance in Malawi: protocol for a prospective observational study of the morbidity, mortality and economic cost of third-generation cephalosporin resistant bloodstream infection
Authors: Lester Rebecca , Maheswaran Hendran , Jewell Christopher P. , Lalloo David G. , Feasey Nicholas A. 
Published: June 2020

Introduction: Antimicrobial resistance (AMR) is a global public health concern, but the problems are context specific, with each county or setting facing differing challenges. In sub-Saharan Africa, third-generation cephalosporin resistant Enterobacterales (3GCR-E) are of particular concern, given the widespread reliance on ceftriaxone for treatment of severe infection in this setting. In Malawi, despite rising prevalence of 3GCR-E, the health-impact of these infections has not been described. This study is designed to estimate attributable mortality, morbidity and economic cost of 3GCR-E bloodstream infection (BSI) in a large, urban hospital. Methods: This study will investigate the burden of AMR by recruiting a a prospective longitudinal cohort of patients who have bloodstream infection with 3GCR-E, at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients whose blood culture is positive for either third-generation cephalosporin susceptible (3GC-S) or third-generation resistant (3GC-R) Enterobacterales will be enrolled and provide clinical and healthcare economic data. Patients will be followed throughout their hospital stay and to 6-months post discharge. The primary outcomes for the study are mortality and morbidity from 3GCR-E. Healthcare economic outcomes will be assessed by comparing healthcare provider costs, indirect patient costs and health-related quality of life outcomes in patients with 3GC-S and 3GC-R BSI. Based on our observation that some patients with clinical suspicion of sepsis and 3GC-R BSI are surviving without an effective antibiotic, we review each patient prospectively and classify what role the isolated bacteria is playing in the patient’s clinical presentation. Each BSI episode will be classified into the following categories: definite Gram-negative sepsis, probable Gram-negative sepsis, transient or occult bacteraemia, or contaminated blood culture. These classifications will be incorporated into our analysis. Ethics and dissemination: The study protocol has been approved by the Malawi College of Medicine Research Ethics Committee and by the Liverpool School of Tropical Medicine Research Ethics committee.
Variants associated with HHIP expression have sex-differential effects on lung function
Authors: Fawcett Katherine A. , Obeidat Ma'en , Melbourne Carl A. , Shrine Nick , Guyatt Anna L. , John Catherine , Luan Jian'an , Richmond Anne , Moksnes Marta R. , Granell Raquel , Weiss Stefan , Imboden Medea , May-Wilson Sebastian , Hysi Pirro , Boutin Thibaud S. , Portas Laura , Flexeder Claudia , Harris Sarah E. , Wang Carol A. , Lyytikäinen Leo-Pekka , Palviainen Teemu , Foong Rachel E. , Keidel Dirk , Minelli Cosetta , Langenberg Claudia , Bossé Yohan , Van den Berge Maarten , Sin Don D. , Hao Ke , Campbell Archie , Porteous David , Padmanabhan Sandosh , Smith Blair H. , Evans David M. , Ring Sue , Langhammer Arnulf , Hveem Kristian , Willer Cristen , Ewert Ralf , Stubbe Beate , Pirastu Nicola , Klaric Lucija , Joshi Peter K. , Patasova Karina , Massimo Mangino , Polasek Ozren , Starr John M. , Karrasch Stefan , Strauch Konstantin , Meitinger Thomas , Rudan Igor , Rantanen Taina , Pietiläinen Kirsi , Kähönen Mika , Raitakari Olli T. , Hall Graham L. , Sly Peter D. , Pennell Craig E. , Kaprio Jaakko , Lehtimäki Terho , Vitart Veronique , Deary Ian J. , Jarvis Debbie , Wilson James F. , Spector Tim , Probst-Hensch Nicole , Wareham Nicholas J. , Völzke Henry , Henderson John , Strachan David P. , Brumpton Ben M. , Hayward Caroline , Hall Ian P. , Tobin Martin D. , Wain Louise V. 
Published: June 2020

Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10-8) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10-6). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV1) (P=3.15x10-15), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV1 more in males (untransformed FEV1 β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein (HHIP) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10-6), but we could not detect sex differential effects of rs7697189 on expression. Conclusions: We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
Estimating the time-varying reproduction number of SARS-CoV-2 using national and subnational case counts
Authors: Abbott Sam , Hellewell Joel , Thompson Robin N. , Sherratt Katharine , Gibbs Hamish P. , Bosse Nikos I. , Munday James D. , Meakin Sophie , Doughty Emma L. , Chun June Young , Chan Yung-Wai Desmond , Finger Flavio , Campbell Paul , Endo Akira , Pearson Carl A. B. , Gimma Amy , Russell Tim ,   CMMID COVID modelling group, Flasche Stefan , Kucharski Adam J. , Eggo Rosalind M. , Funk Sebastian 
Published: June 2020

Background: Interventions are now in place worldwide to reduce transmission of the novel coronavirus. Assessing temporal variations in transmission in different countries is essential for evaluating the effectiveness of public health interventions and the impact of changes in policy. Methods: We use case notification data to generate daily estimates of the time-dependent reproduction number in different regions and countries. Our modelling framework, based on open source tooling, accounts for reporting delays, so that temporal variations in reproduction number estimates can be compared directly with the times at which interventions are implemented. Results: We provide three example uses of our framework. First, we demonstrate how the toolset displays temporal changes in the reproduction number. Second, we show how the framework can be used to reconstruct case counts by date of infection from case counts by date of notification, as well as to estimate the reproduction number. Third, we show how maps can be generated to clearly show if case numbers are likely to decrease or increase in different regions. Results are shown for regions and countries worldwide on our website (https://epiforecasts.io/covid/) and are updated daily. Our tooling is provided as an open-source R package to allow replication by others. Conclusions: This decision-support tool can be used to assess changes in virus transmission in different regions and countries worldwide. This allows policymakers to assess the effectiveness of current interventions, and will be useful for inferring whether or not transmission will increase when interventions are lifted. As well as providing daily updates on our website, we also provide adaptable computing code so that our approach can be used directly by researchers and policymakers on confidential datasets. We hope that our tool will be used to support decisions in countries worldwide throughout the ongoing COVID-19 pandemic.
The Effects of Tip Recommendations on Customer Tipping, Satisfaction, Repatronage, and Spending
Authors: Alexander Damon , Boone Christopher , Lynn Michael 
Published: June 2020

A field experiment involving 94,571 orders from 24,637 customers of an app-based laundry pick-up, cleaning, and delivery service examined the effects of various randomly assigned tip recommendations on consumers’ tip amounts, satisfaction ratings, frequency of return, and bill size. We find that tip recommendations affect tip amounts, but not customer satisfaction, patronage frequency, or bill size, which implies that neither the processes underlying the tip-recommendation effects on tipping nor consumer tipping itself affect these other consumer outcomes. From a practical perspective, these results and conclusions inform efforts to increase or decrease tipping. Recommending larger tip amounts, at least within the $2–$10 or 5%–25% ranges studied here, appears to be a safe means of increasing the amounts customers leave. More generally, altering customers’ tipping behavior will not itself adversely affect those customers’ subsequent satisfaction, repatronage, or spending, as long as the means used to alter tipping do not directly affect these other outcomes. This paper was accepted by John List, behavioral economics.
Tendency towards operative treatment is increasing in children’s fractures: results obtained from patient databases, causes, impact of evidence-based medicine
Authors: Ömeroğlu Hakan , Cassiano Neves Manuel 
Published: June 2020

Results of numerous studies assessing the national or the local patient databases in several countries have indicated that the overall rate of operative treatment in fractures, as well as the rate in certain upper and lower limb fractures, has significantly increased in children. The most prominent increase in the rate of operative treatment was observed in forearm shaft fractures. Results of several survey studies have revealed that there was not a high level of agreement among paediatric orthopaedic surgeons concerning treatment preferences for several children’s fractures. The reasons for the increasing tendency towards operative treatment are multifactorial and patient-, parent- and surgeon-dependent factors as well as technological, economic, social, environmental and legal factors seem to have an impact on this trend. It is obvious that evidence-based medicine is not the only factor that leads to this tendency. A high level of scientific evidence is currently lacking to support the statement that operative treatment really leads to better long-term outcomes in children’s fractures. Properly designed multicentre clinical trials are needed to determine the best treatment options in many fractures in children.Cite this article: EFORT Open Rev 2020;5:347-353. DOI: 10.1302/2058-5241.5.200012
Development of a photoelectric phase-locked loop model to better synchronize frequency combs and microwaves
Authors: Zhang Wanpeng , Zhou Weifeng , Chen Xing , Zhao Yingxin , Lin Wei , Meng Sensen , Liu Bo , Wu Hong 
Published: June 2020

The high phase coherence between ultralow-noise microwaves and ultrahigh-stable optical frequency combs (OFCs) is of both scientific and technological relevance for telecommunication, timekeeping, astronomy, and metrology. Here, a photoelectric phase-locked loop (PLL) model with ultralow phase noise based on the optical-microwave phase detector technique has been proposed and experimentally demonstrated. A detailed mathematical model for tight, real-time phase synchronization of OFCs and microwaves is developed to investigate the feasibility and analyze the characteristics of the phase-coherent system. We fabricate a compact PLL circuit with a proportional-integral-derivative regulator for the synchronization of an OFC to a microwave reference. Once synchronized, the long-term stability of the OFC agrees to

2.4

×

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14

at a 1000 s averaging time, which is enhanced by more than 4 orders of magnitude. Besides, the OFC almost acquires the same frequency stability as the microwave source. The ability to better phase synchronize OFCs and microwaves enables a wide range of applications beyond the laboratory.
Stimulated emission tomography for entangled photon pairs with different detection spectral ranges
Authors: Yang Yiquan , Zhang Peiyu , Ma Xiao-Song 
Published: June 2020

Frequency nondegenerate entangled photon pairs have been employed in quantum communication, imaging, and sensing. To characterize quantum entangled states with long-wavelength [infrared (IR) or even terahertz (THz)] photons, one needs to either develop the single-photon detectors at the corresponding wavelengths or use a novel tomography technique that does not rely on single-photon detections, such as stimulated emission tomography (SET). We use standard quantum state tomography and SET to measure the density matrix of entangled photon pairs, with one photon at 1550 nm and the other one at 810 nm, and obtain highly consistent results, showing the reliability of SET. Our work paves the way for efficient measurement of entangled photons with highly dissimilar frequencies, even to the frequencies where single-photon detections are not available.