The British Army\u27s African Recruitment Policy, 1790-1807

The article is drawn from a presentation to the Five College Black Studies Seminar Series, University of Massachusetts Amherst, 25 February 1982. It argues that delays in the British abolition of the slave trade was related to military policies and imperial interests

Satisfaction of Older Patients With Emergency Department Care: Psychometric Properties and Construct Validity of the Consumer Emergency Care Satisfaction Scale.

BACKGROUND: Patient satisfaction is an important indicator of quality of care, but its measurement remains challenging. The Consumer Emergency Care Satisfaction Scale (CECSS) was developed to measure patient satisfaction in the emergency department (ED). Although this is a valid and reliable tool, several aspects of the CECSS need to be improved, including the definition, dimension, and scoring of scales. PURPOSE: The purpose of this study was to examine the construct validity of the CECSS and make suggestions on how to improve the tool to measure overall satisfaction with ED care. METHODS: We administered 2 surveys to older adults who presented with a fall to the ED and used electronic health record data to examine construct validity of the CECSS and ceiling effects. RESULTS: Using several criteria, we improved construct validity of the CECSS, reduced ceiling effects, and standardized scoring. CONCLUSION: We addressed several methodological issues with the CECSS and provided recommendations for improvement

Reviewing research priorities in weed ecology, evolution and management: A horizon scan

Weedy plants pose a major threat to food security, biodiversity, ecosystem services and consequently to human health and wellbeing. However, many currently used weed management approaches are increasingly unsustainable. To address this knowledge and practice gap, in June 2014, 35 weed and invasion ecologists, weed scientists, evolutionary biologists and social scientists convened a workshop to explore current and future perspectives and approaches in weed ecology and management. A horizon scanning exercise ranked a list of 124 pre-submitted questions to identify a priority list of 30 questions. These questions are discussed under seven themed headings that represent areas for renewed and emerging focus for the disciplines of weed research and practice. The themed areas considered the need for transdisciplinarity, increased adoption of integrated weed management and agroecological approaches, better understanding of weed evolution, climate change, weed invasiveness and finally, disciplinary challenges for weed science. Almost all the challenges identified rested on the need for continued efforts to diversify and integrate agroecological, socio-economic and technological approaches in weed management. These challenges are not newly conceived, though their continued prominence as research priorities highlights an ongoing intransigence that must be addressed through a more system-oriented and transdisciplinary research agenda that seeks an embedded integration of public and private research approaches. This horizon scanning exercise thus set out the building blocks needed for future weed management research and practice; however, the challenge ahead is to identify effective ways in which sufficient research and implementation efforts can be directed towards these needs

The low frequency radio emission and spectrum of the extended SNR W44: new VLA observations at 74 and 324 MHz

We present new Very Large Array (VLA) radio images at 74 and 324 MHz of the SNR W44. The VLA images, obtained with unprecedented angular resolution and sensitivity for such low frequencies have been used in combination with existing 1442 MHz radio data, Spitzer IR data, and ROSAT and Chandra X-ray data to investigate morphological and spectral properties of this SNR. The spatially resolved spectral index study revealed that the bright filaments, both around and across the SNR, have a straight spectrum between 74 and 1442 MHz, with alpha ~ -0.5, with two clear exceptions: a short portion of the SNR limb to the southeast, with alpha varying between 0 and +0.4 and a bright arc to the west where the spectrum breaks around 300 MHz and looks concave down. We conclude that at the shell and along the internal filaments, the electrons responsible for the synchrotron emission were accelerated at the shock according to a simple diffusive shock model; the positive spectrum corresponds to a location where the SN shock is running into a molecular cloud and where the line of sight intersects the photo dissociation region of an HII region and a young stellar object is present. The curved spectrum on the westernmost bright arc is explained as the consequence of strong post-shock densities and enhanced magnetic fields after the interaction of the SN shock with a collindant molecular cloud.Comment: After language edited, 16 pages, 12 figures (3 in color). Figures degraded to reduce file size. Accepted 01/03/2007 for publicaion in A&

Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant. Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049). Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role. Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interes

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe