A scoping review to ascertain the parameters for an evidence synthesis of psychological interventions to improve work and wellbeing outcomes among employees with chronic pain

Background: Psychological interventions have mixed effects on improving employee outcomes, partly due to significant variability across studies and a lack of focus on mechanisms of action. This scoping review reports on the parameters of these interventions and examines intervention content to bring clarity to this heterogeneous topic area and direct future systematic review work. Method: Six databases were searched (Cinahl, Cochrane, Embase, Medline, PsychINFO and Web of Science) from April 2010 to August 2020, and a grey literature search was undertaken. Screening was undertaken independently by two authors. The results summarised country, participant and employment characteristics, psychological interventions and work, health and wellbeing outcomes. 10% of the papers were analysed to determine the feasibility of coding intervention descriptions for theory and behaviour change technique (BCT) components. Results: Database searches yielded 9341 titles, of which 91 studies were included. Most studies were conducted in Europe (78%) and included males and females (95%) ranging in age from 31-56.6 years although other demographic, and employment information was lacking. Musculoskeletal pain was common (87%). Psychological interventions commonly included cognitive behavioural therapy (30%) and education (28%). Most studies employed a randomised control trial design (64%). Over half contained a control group (54%). Interventions were delivered in mostly healthcare settings (72%) by health professionals. Multiple outcomes were often reported, many of which involved measuring sickness absence and return-to-work (62%) and pain and general health (53%). Within the feasibility analysis, most papers met the minimum criteria of containing one paragraph of intervention description, but none explicitly mentioned theory or BCTs. Conclusion: Psychological interventions for employees with chronic pain vary in their nature and implementation. We have shown scoping reviews can be used to assess the feasibility of applying tools from health psychology to identify the content of these interventions in future systematic review work to improve intervention development

Evaluation of Kentucky\u27s Graduated Driver Licensing System

Kentucky\u27s current GDL program, which applies to drivers up to age 18, was enacted in 1996. The program includes a six-month instruction permit for drivers under age 18 (minimum age 16), a restriction on driving between midnight and 6am and a requirement for adult-supervised driving for permit drivers. In addition, there is a six-point limit on traffic violations with a penalty of license suspension for drivers under age 18, a requirement for a four-hour driving safety education class (or driver education course) and a 0.02 ml/dl limit on blood alcohol concentration (continues up to age 21 ). Objectives: The objectives of this program evaluation were: (a) to examine teen driver motor vehicle crashes, crash-related injuries, and crash-related costs before and after the implementation of the GDL program; (b) to examine the implementation of the program at the local level ; and (c) to recommend actions to enhance the program\u27s effectiveness in addressing the teen crash problem. Methods: Crash and licensing data before ( 1993-1995) and after GDL ( 1997-2000) were analyzed. Data on miles driven were obtained from driving logs of over I ,000 high school students. Estimation of the cost of crashes was derived from analysis of crash data using the Crash Cost computer software program. Information on local implementation of GDL was obtained through interviews and through a questionnaire survey of 700 law enforcement officers and over 40 district judges. Results: Results indicate a 31 percent reduction in crashes for 16 year-old drivers after the GDL program, and a similar reduction in fatal crashes (31 percent) and injury crashes (33 percent), crashes between midnight and 6am (36 percent), and alcohol-related crashes (32 percent). Cost analysis indicates an estimated reduction of $36 million per year in 16 year-old teen driver crash-related expenses. Results indicate that this is due to the 83% reduction in the number of 16 to 16 1/2 year-old drivers involved in crashes. However, the number of crashes has not been reduced for drivers over age 16 1/2, i.e. drivers who may be past the permit level. In addition, the six-point limit on traffic violations and the non-cumulative penalties on 0.02 blood alcohol limit violations have not reduced the number of traffic violations or alcohol-related crashes for teen drivers over age 16 1/2. Recommendations: The six-month permit level has been successful in substantially reducing crash-related injuries and fatalities and should be retained. Additional measures, such as upgrading to an expanded GDL program, are needed to reduce crash-related injuries and fatalities for 16 1/2 to 18 year-old drivers. Specific recommendation are made to increase parental awareness and enforcement of program provisions

Conscientious Objection: Understanding When and Why Primary Care Physicians Object to Providing Health Care to Transgender and Gender-Diverse Patients in an Appalachian Medical Center

Introduction: Transgender and gender-diverse (TGD) individuals face barriers to accessing primary and gender-affirming care, especially in rural regions where a national shortage of medical providers with skills in caring for TGD people is further magnified. This care may also be impacted by individual providers’ strongly held personal or faith beliefs and associated conscientious objection to care. Purpose: This study assesses the prevalence of conscientious objection to providing care and gender-affirming hormone (GAH) therapy to TGD individuals among physicians in an Appalachian academic medical center. Methods: An anonymous, online, cross-sectional survey of physicians was distributed to resident and faculty physicians in an Appalachian medical center. Survey domains included demographics, personal religious affiliations and practices, and assessments of willingness to provide specific types of care. Results: Surveyed physicians (n = 115) had no objection to caring for TGD patients but notable objection to prescribing GAH therapy to adults (23.5%) and minors (33.0%). Self-identified “very religious” physicians were more likely to object. Implications: Physician objection may present a barrier to care for TGD individuals in Appalachia. Provider and system-level interventions should be considered to ensure access to these necessary medical services

LINE-1 Retrotransposition Activity in Human Genomes

SummaryHighly active (i.e., “hot”) long interspersed element-1 (LINE-1 or L1) sequences comprise the bulk of retrotransposition activity in the human genome; however, the abundance of hot L1s in the human population remains largely unexplored. Here, we used a fosmid-based, paired-end DNA sequencing strategy to identify 68 full-length L1s that are differentially present among individuals but are absent from the human genome reference sequence. The majority of these L1s were highly active in a cultured cell retrotransposition assay. Genotyping 26 elements revealed that two L1s are only found in Africa and that two more are absent from the H952 subset of the Human Genome Diversity Panel. Therefore, these results suggest that hot L1s are more abundant in the human population than previously appreciated, and that ongoing L1 retrotransposition continues to be a major source of interindividual genetic variation

Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach

Therapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia

The khmer software package: enabling efficient nucleotide sequence analysis

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

The khmer software package: enabling efficient nucleotide sequence analysis [version 1; referees: 2 approved, 1 approved with reservations]

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR