A cross-sectional survey on the early impact of COVID-19 on the uptake of decentralised trial methods in the conduct of clinical trials

BACKGROUND: The COVID-19 pandemic significantly impacted the conduct of clinical trials through delay, interruption or cancellation. Decentralised methods in clinical trials could help to continue trials during a pandemic. This paper presents the results of an exploratory study conducted early in the pandemic to gain insight into and describe the experiences of organisations involved in clinical trials, with regard to the impact of COVID-19 on the conduct of trials, and the adoption of decentralised methods prior to, and as mitigation for the impact, of COVID-19. METHODS: A survey with 11 open-ended and four multiple choice questions was conducted in June 2020 among member organisations of the public-private “Trials@Home” consortium. The survey investigated (1) the impact and challenges of COVID-19 on the continuation of ongoing clinical trials, (2) the adoption of decentralised methods in clinical trials prior to and as a mitigation strategy for COVID-19, (3) the challenges of conducting clinical trials during COVID-19, (4) the expected permanency of COVID-19-driven changes to the adoption of decentralised methods in clinical trials, and (5) lessons learned from conducting clinical trials during the COVID-19 pandemic. A thematic, inductive analysis of open survey questions was performed, complemented with descriptive statistics (frequencies and distributions). RESULTS: The survey had a response rate of 81%. All organisations included in the analysis (n = 18) implemented (some) decentralised methods in their clinical trials prior to COVID-19, and 15 (83%) implemented decentralised methods as mitigation for COVID-19. Decentralised methods for IMP supply, patient-health care provider interaction and communication, clinic visits and source document verification were used more often as mitigation strategies than they were used prior to COVID-19. Many respondents expect to maintain those decentralised methods they implemented during COVID-19 in ongoing trials, as well as implement them in future trials. CONCLUSIONS: Decentralised methods are a widely implemented mitigation strategy for trial conduct in the face of the COVID-19 pandemic. The results of this survey show that there is an interest to continue the use of decentralised methods in future trials, but important points of attention have been identified that need solutions to help guide the transition from the traditional trial model to a more decentralised trial model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06706-x

Knot Theory: from Fox 3-colorings of links to Yang-Baxter homology and Khovanov homology

This paper is an extended account of my "Introductory Plenary talk at Knots in Hellas 2016" conference We start from the short introduction to Knot Theory from the historical perspective, starting from Heraclas text (the first century AD), mentioning R.Llull (1232-1315), A.Kircher (1602-1680), Leibniz idea of Geometria Situs (1679), and J.B.Listing (student of Gauss) work of 1847. We spend some space on Ralph H. Fox (1913-1973) elementary introduction to diagram colorings (1956). In the second section we describe how Fox work was generalized to distributive colorings (racks and quandles) and eventually in the work of Jones and Turaev to link invariants via Yang-Baxter operators, here the importance of statistical mechanics to topology will be mentioned. Finally we describe recent developments which started with Mikhail Khovanov work on categorification of the Jones polynomial. By analogy to Khovanov homology we build homology of distributive structures (including homology of Fox colorings) and generalize it to homology of Yang-Baxter operators. We speculate, with supporting evidence, on co-cycle invariants of knots coming from Yang-Baxter homology. Here the work of Fenn-Rourke-Sanderson (geometric realization of pre-cubic sets of link diagrams) and Carter-Kamada-Saito (co-cycle invariants of links) will be discussed and expanded. Dedicated to Lou Kauffman for his 70th birthday.Comment: 35 pages, 31 figures, for Knots in Hellas II Proceedings, Springer, part of the series Proceedings in Mathematics & Statistics (PROMS

Beyond handover: supporting awareness for continuous coverage

Abstract Hospitals are required to operate as a continuous system because patient care cannot be temporarily suspended and handover is seen as a key method for enabling this. This paper reports a study of handover in a medical admissions unit. We draw on the notion of awareness as conceptualised within the Computer Supported Cooperative Work literature to explore the role played by a variety of cognitive artifacts in supporting continuous coverage. While such awareness is typically characterised as being ‘effortless’, our study reveals that maintaining awareness in a context such as the medical admissions unit is effortful due to invisible work. We suggest that the notion of awareness is beneficial for exploring the practices of continuous coverage because it moves attention away from the moment of handover, instead encouraging consideration of the variety of practices through which clinicians display their work to, and monitor the work of, colleagues on different shifts. We argue that efforts to support continuous coverage should focus on improving awareness by increasing the visibility of information

Age and Ethnicity among Hospitalized Alcoholics: A Nationwide Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65651/1/j.1530-0277.1992.tb00694.x.pd

Are adolescents with high socioeconomic status more likely to engage in alcohol and illicit drug use in early adulthood?

<p>Abstract</p> <p>Background</p> <p>Previous literature has shown a divergence by age in the relationship between socioeconomic status (SES) and substance use: adolescents with low SES are more likely to engage in substance use, as are adults with high SES. However, there is growing evidence that adolescents with high SES are also at high risk for substance abuse. The objective of this study is to examine this relationship longitudinally, that is, whether wealthier adolescents are more likely than those with lower SES to engage in substance use in early adulthood.</p> <p>Methods</p> <p>The study analyzed data from the National Longitudinal Survey of Adolescent Health (AddHealth), a longitudinal, nationally-representative survey of secondary school students in the United States. Logistic regression models were analyzed examining the relationship between adolescent SES (measured by parental education and income) and substance use in adulthood, controlling for substance use in adolescence and other covariates.</p> <p>Results</p> <p>Higher parental education is associated with higher rates of binge drinking, marijuana and cocaine use in early adulthood. Higher parental income is associated with higher rates of binge drinking and marijuana use. No statistically significant results are found for crystal methamphetamine or other drug use. Results are not sensitive to the inclusion of college attendance by young adulthood as a sensitivity analysis. However, when stratifying by race, results are consistent for white non-Hispanics, but no statistically significant results are found for non-whites. This may be a reflection of the smaller sample size of non-whites, but may also reflect that these trends are driven primarily by white non-Hispanics.</p> <p>Conclusions</p> <p>Previous research shows numerous problems associated with substance use in young adults, including problems in school, decreased employment, increases in convictions of driving under the influence (DUI) and accidental deaths. Much of the previous literature is focused on lower SES populations. Therefore, it is possible that teachers, parents and school administrators in wealthier schools may not perceive as great to address substance abuse treatment in their schools. This study can inform teachers, parents, school administrators and program officials of the need for addressing drug abuse prevention activities to this population of students.</p

An Oral Recombinant Vaccine in Dogs against Echinococcus granulosus, the Causative Agent of Human Hydatid Disease: A Pilot Study

Dogs are the main source of human cystic echinococcosis. An oral vaccine would be an important contribution to control programs in endemic countries. We conducted two parallel experimental trials in Morocco and Tunisia of a new oral vaccine candidate against Echinococcus granulosus in 28 dogs. The vaccine was prepared using two recombinant proteins from adult worms, a tropomyosin (EgTrp) and a fibrillar protein similar to paramyosin (EgA31), cloned and expressed in a live attenuated strain of Salmonella enterica serovar typhimurium

A gene frequency model for QTL mapping using Bayesian inference

<p>Abstract</p> <p>Background</p> <p>Information for mapping of quantitative trait loci (QTL) comes from two sources: linkage disequilibrium (non-random association of allele states) and cosegregation (non-random association of allele origin). Information from LD can be captured by modeling conditional means and variances at the QTL given marker information. Similarly, information from cosegregation can be captured by modeling conditional covariances. Here, we consider a Bayesian model based on gene frequency (BGF) where both conditional means and variances are modeled as a function of the conditional gene frequencies at the QTL. The parameters in this model include these gene frequencies, additive effect of the QTL, its location, and the residual variance. Bayesian methodology was used to estimate these parameters. The priors used were: logit-normal for gene frequencies, normal for the additive effect, uniform for location, and inverse chi-square for the residual variance. Computer simulation was used to compare the power to detect and accuracy to map QTL by this method with those from least squares analysis using a regression model (LSR).</p> <p>Results</p> <p>To simplify the analysis, data from unrelated individuals in a purebred population were simulated, where only LD information contributes to map the QTL. LD was simulated in a chromosomal segment of 1 cM with one QTL by random mating in a population of size 500 for 1000 generations and in a population of size 100 for 50 generations. The comparison was studied under a range of conditions, which included SNP density of 0.1, 0.05 or 0.02 cM, sample size of 500 or 1000, and phenotypic variance explained by QTL of 2 or 5%. Both 1 and 2-SNP models were considered. Power to detect the QTL for the BGF, ranged from 0.4 to 0.99, and close or equal to the power of the regression using least squares (LSR). Precision to map QTL position of BGF, quantified by the mean absolute error, ranged from 0.11 to 0.21 cM for BGF, and was better than the precision of LSR, which ranged from 0.12 to 0.25 cM.</p> <p>Conclusions</p> <p>In conclusion given a high SNP density, the gene frequency model can be used to map QTL with considerable accuracy even within a 1 cM region.</p

QTL linkage analysis of connected populations using ancestral marker and pedigree information

The common assumption in quantitative trait locus (QTL) linkage mapping studies that parents of multiple connected populations are unrelated is unrealistic for many plant breeding programs. We remove this assumption and propose a Bayesian approach that clusters the alleles of the parents of the current mapping populations from locus-specific identity by descent (IBD) matrices that capture ancestral marker and pedigree information. Moreover, we demonstrate how the parental IBD data can be incorporated into a QTL linkage analysis framework by using two approaches: a Threshold IBD model (TIBD) and a Latent Ancestral Allele Model (LAAM). The TIBD and LAAM models are empirically tested via numerical simulation based on the structure of a commercial maize breeding program. The simulations included a pilot dataset with closely linked QTL on a single linkage group and 100 replicated datasets with five linkage groups harboring four unlinked QTL. The simulation results show that including parental IBD data (similarly for TIBD and LAAM) significantly improves the power and particularly accuracy of QTL mapping, e.g., position, effect size and individuals’ genotype probability without significantly increasing computational demand

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Embedding physical activity in the heart of the NHS: the need for a whole-system approach

Solutions to the global challenge of physical inactivity have tended to focus on interventions at an individual level, when evidence shows that wider factors, including the social and physical environment, play a major part in influencing health-related behaviour. A multidisciplinary perspective is needed to rewrite the research agenda on physical activity if population-level public health benefits are to be demonstrated. This article explores the questions that this raises regarding the particular role that the UK National Health Service (NHS) plays in the system. The National Centre for Sport and Exercise Medicine in Sheffield is put forward as a case study to discuss some of the ways in which health systems can work in collaboration with other partners to develop environments and systems that promote active lives for patients and staff