Suitability of simple human immunodeficiency virus rapid tests in clinical trials in community-based clinic settings

The suitability and accuracy of using simple human immunodeficiency virus (HIV) rapid (SR) tests in community-based clinics in northwest Tanzania were determined to assess eligibility for participation in clinical trials. The HIV rapid and ELISA test results for 789 women aged 16 to 54 who were screened for two clinical trials of HIV prevention were compared. Women were offered voluntary HIV counseling and testing (VCT) at screening; those who accepted were tested with the Abbott Determine and Trinity Biotech Capillus SR tests in parallel. The results were confirmed by two parallel HIV enzyme-linked immunosorbent assay (ELISA) tests (Abbott Murex HIV Ag/Ab combination and Vironostika Uniform II HIV Ag/Ab) to determine eligibility. Positive samples for any of the four assays were confirmed by a line immunoassay and p24 testing. The parallel SR tests had high concordance (96.2%) with the parallel ELISA algorithm. The sensitivities of the SR tests were 98.6% for Capillus (95% confidence interval [CI], 95.1 to 99.8%), 99.3% for Determine (95% CI, 96.2 to 100%), and 98.6% for the parallel SR (95% CI, 95.1 to 99.8%). The specificities were 99.7% for Capillus (95% CI, 98.9 to 100%), 99.7% for Determine (95% CI, 98.9 to 100%), and 100% for the parallel SR (95% CI, 99.4 to 100%). SR tests are suitable for use in community-based clinical research settings to assess eligibility both for trial participation and for the provision of on-site VCT services. Copyrigh

Physical safety and security: policies, spending and outcomes 2015-2020

This paper sets out to evaluate the development of policy in relation to physical safety and security in the period since the Conservative Government took office in 2015. Whilst people’s physical safety and security depend on a wide range of social policies as discussed below, the remit of this paper is primarily social policies, spending and outcomes related to the criminal justice system. Other related policy areas, such as health and education, are discussed briefly here as far as the scope of the paper allows and are analysed more fully in their own right as separate papers in the SPDO research programme

Pharamcological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in LDLR-/- mouse model of atherosclerosis

The authors wish to thank Professor Nicholas Tonks for providing the PTP1B inhibitor trodusquemine; Linda Robertson for her help with the aorta histology; Dr Fiona Grieg for tuition into aortic dissection and Dr James Hislop for critical reading of this manuscript. We also wish to thank the British Heart Foundation (PG/14/43/30889) for supporting this researchPeer reviewedPublisher PD

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Can a warm and supportive adult protect against mental health problems amongst children with experience of adversity? A twin-difference study

Background Adverse childhood experiences (ACEs) are associated with mental health problems, but many children who experience ACEs do not develop such difficulties. A warm and supportive adult presence in childhood is associated with a lower likelihood of developing mental health problems after exposure to ACEs. However, it is unclear whether this association is causal, as previous research has not accounted for genetic and environmental confounding. Methods We used the twin-difference design to strengthen causal inference about whether a warm and supportive adult presence protects children exposed to ACEs from mental health problems. Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative birth cohort of 2,232 same-sex twins. ACEs were measured prospectively from ages 5 to 12. Maternal warmth was assessed at ages 5 and 10 through maternal speech samples. Adult support was assessed through child reports at age 12. Mental health problems were assessed through interviews at age 12 with parents and teachers and participants at age 18. Results Among children exposed to ACEs, those who experienced greater maternal warmth and adult support had lower levels of mental health problems at ages 12 and 18. In monozygotic twin-difference analyses, the protective effects of maternal warmth and adult support on mental health were attenuated by 70% for maternal warmth and 81% for adult support, compared to phenotypic analyses. Twins who experienced greater maternal warmth and adult support had minimal or no difference in mental health compared to their co-twins, concordant for ACE exposure. Conclusions The apparent protective effect of a warm, supportive adult against mental health problems following ACEs is largely explained by genetic and environmental confounding. This suggests that interventions which boost maternal warmth and adult support should be supplemented by components addressing wider family environments and heritable vulnerabilities in children exposed to adversity, to improve mental health

Long term effects of management intensity and bioclimatic variables on leatherjacket (Tipula paludosa Meigen) populations at farm-scale.

Leatherjackets (Tipula spp.) are soil-dwelling pests associated with agriculture. Land management decisions made at farm scale can have subsequent effects on their populations. Between 1980 and 2020, surveys were conducted across Scotland to collect field histories and larval population data from grassland farms. To assess the impact of management and bioclimatic factors on leatherjacket occurrence over time, this study investigated data from fields continuously sampled between 2009 and 2018. We utilized a Generalized Linear Mixed-Effect Model on a dataset of 61 fields on 19 farms. Results indicated three significant factors affecting larval populations; field size, grazing type and application of insecticides or herbicides (referred to collectively as pesticides). Larval populations were significantly lower in fields that were larger in size and under sheep grazing, compared to no grazing. Pesticide application also caused a significant reduction in larval populations. Management variables were amalgamated to create a Management Intensity Index, revealing significantly increased larval populations under low-management systems. These results, coupled with significant effects of bioclimatic variables, pinpoint predictive signals for high infestations and potential routes for control strategies

Can a warm and supportive adult protect against mental health problems amongst children with experience of adversity? A twin-differences study

Background: Adverse childhood experiences (ACEs) are associated with mental health problems, but many children who experience ACEs do not develop such difficulties. A warm and supportive adult presence in childhood is associated with a lower likelihood of developing mental health problems after exposure to ACEs. However, it is unclear whether this association is causal, as previous research has not accounted for genetic and environmental confounding.Methods: We used the twin-difference design to strengthen causal inference about whether a warm and supportive adult presence protects children exposed to ACEs from mental health problems. Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative birth cohort of 2,232 same-sex twins. ACEs were measured prospectively from ages 5-12. Maternal warmth was assessed at ages 5 and 10 through maternal speech samples. Adult support was assessed through child reports at age 12. Mental health problems were assessed through interviews at age 12 with parents and teachers, and participants at age 18. Results: Among children exposed to ACEs, those who experienced greater maternal warmth and adult support had lower levels of mental health problems at ages 12 and 18. In monozygotic twin-difference analyses, the protective effects of maternal warmth and adult support on mental health were attenuated by 70% for maternal warmth, and 81% for adult support, compared to phenotypic analyses. Twins who experienced greater maternal warmth and adult support had minimal or no difference in mental health compared to their co-twins, concordant for ACE exposure.Conclusions: The apparent protective effect of a warm, supportive adult against mental health problems following ACEs is largely explained by genetic and environmental confounding. This suggests that interventions which boost maternal warmth and adult support should be supplemented by components addressing wider family environments and heritable vulnerabilities in children exposed to adversity, to improve mental health