HIV transmission networks among transgender women in Los Angeles County, CA, USA: a phylogenetic analysis of surveillance data.

BackgroundTransgender women are among the groups at highest risk for HIV infection, with a prevalence of 27·7% in the USA; and despite this known high risk, undiagnosed infection is common in this population. We set out to identify transgender women and their partners in a molecular transmission network to prioritise public health activities.MethodsSince 2006, HIV protease and reverse transcriptase gene (pol) sequences from drug resistance testing have been reported to the Los Angeles County Department of Public Health and linked to demographic data, gender, and HIV transmission risk factor data for each case in the enhanced HIV/AIDS Reporting System. We reconstructed a molecular transmission network by use of HIV-TRAnsmission Cluster Engine (with a pairwise genetic distance threshold of 0·015 substitutions per site) from the earliest pol sequences from 22 398 unique individuals, including 412 (2%) self-identified transgender women. We examined the possible predictors of clustering with multivariate logistic regression. We characterised the genetically linked partners of transgender women and calculated assortativity (the tendency for people to link to other people with the same attributes) for each transmission risk group.Findings8133 (36·3%) of 22 398 individuals clustered in the network across 1722 molecular transmission clusters. Transgender women who indicated a sexual risk factor clustered at the highest frequency in the network, with 147 (43%) of 345 being linked to at least one other person (adjusted odds ratio [aOR] 2·0, p=0·0002). Transgender women were assortative in the network (assortativity 0·06, p<0·001), indicating that they tended to link to other transgender women. Transgender women were more likely than expected to link to other transgender women (OR 4·65, p<0·001) and cisgender men who did not identify as men who have sex with men (MSM; OR 1·53, p<0·001). Transgender women were less likely than expected to link to MSM (OR 0·75, p<0·001), despite the high prevalence of HIV among MSM. Transgender women were distributed across 126 clusters, and cisgender individuals linked to one transgender woman were 9·2 times more likely to link to a second transgender woman than other individuals in the surveillance database. Reconstruction of the transmission network is limited by sample availability, but sequences were available for more than 40% of diagnoses.InterpretationClustering of transgender women and the observed tendency for linkage with cisgender men who did not identify as MSM, shows the potential to use molecular epidemiology both to identify clusters that are likely to include undiagnosed transgender women with HIV and to improve the targeting of public health prevention and treatment services to transgender women.FundingCalifornia HIV and AIDS Research Program and National Institutes of Health-National Institute of Allergy and Infectious Diseases

Motivation, Comportements Organisationnels Discrétionnaires et Bien-être en Milieu Africain : Quand le Devoir Oblige

This study tested with Gabonese employees (N = 146) an organizational citizenship behavior (OCB) model based on the motivational model of job burnout (MMJB). It was hypothesized that the more supervisors will satisfy employee's needs for self-determination, competence, and relatedness, the more employee work motivations will be self-determined. Supervisory style and motivation will then predict job satisfaction which then influences life satisfaction. Work motivation and job satisfaction should also determine OCB and the latter should then influence life satisfaction. Structural equation modeling analyses mostly confirmed the model. One unexpected link was that altruism OCB was negatively predicted by self-determined motivations which then negatively predicted life satisfaction. Results support SDT showing, as such, that a behavior regulated by non-self-determined motivations will negatively affect well-being. Cette étude vérifie auprès d'employés gabonais (N = 146) un modèle de comportements organisationnels discrétionnaires (COD) basé sur le modèle motivationnel de l'épuisement professionnel. Il postule que plus le style de mobilisation du supérieur satisfait les besoins d'autodétermination, de compétence et d'attachement, plus la motivation sera autodéterminée et meilleure sera la satisfaction au travail; en retour, ces variables influenceront positivement l'adoption de COD altruistes et consciencieux, lesquels auront finalement des répercussions positives sur la satisfaction de vie. Des analyses de modélisation confirment dans l'ensemble ce modèle. La motivation autodéterminée était toutefois négativement reliée aux comportements altruistes, lesquels prédisaient d'ailleurs négativement la satisfaction de vie. Ces résultats appuient également la théorie de l'autodétermination selon laquelle les comportements issus d'une motivation non autodéterminée affectent négativement le bien-être.Organizational citizenship behavior, Work motivation, Supervisory style, Well-being, Africa, Self-Determination Theory, Comportements Organisationnels Discrétionnaires, Motivation au travail, Style de supervision, Bien-être, Afrique, Théorie de l'autodétermination

Elucidating the cellular dynamics of the brain with single-cell RNA sequencing

Single-cell RNA-sequencing (scRNA-seq) has emerged in recent years as a breakthrough technology to understand RNA metabolism at cellular resolution. In addition to allowing new cell types and states to be identified, scRNA-seq can permit cell-type specific differential gene expression changes, pre-mRNA processing events, gene regulatory networks and single-cell developmental trajectories to be uncovered. More recently, a new wave of multi-omic adaptations and complementary spatial transcriptomics workflows have been developed that facilitate the collection of even more holistic information from individual cells. These developments have unprecedented potential to provide penetrating new insights into the basic neural cell dynamics and molecular mechanisms relevant to the nervous system in both health and disease. In this review we discuss this maturation of single-cell RNA-sequencing over the past decade, and review the different adaptations of the technology that can now be applied both at different scales and for different purposes. We conclude by highlighting how these methods have already led to many exciting discoveries across neuroscience that have furthered our cellular understanding of the neurological disease

Initiatives on early detection and intervention to proactively identify health and social problems in older people:Experiences from the Netherlands

Background Over the last years, several initiatives on early detection and intervention have been put in place to proactively identify health and social problems in (frail) older people. An overview of the initiatives currently available in the Netherlands is lacking, and it is unknown whether they meet the preferences and needs of older people. Therefore, the objectives of this study were threefold: 1. To identify initiatives on early detection and intervention for older people in the Netherlands and compare their characteristics; 2. To explore the experiences of professionals with these initiatives; and 3. To explore to what extent existing initiatives meet the preferences and needs of older people. Methods We performed a qualitative descriptive study in which we conducted semi-structured interviews with seventeen experts in preventive elderly care and three group interviews with volunteer elderly advisors. Data were analysed using the framework analysis method. Results We identified eight categories of initiatives based on the setting (e.g. general practitioner practice, hospital, municipality) in which they were offered. Initiatives differed in their aims and target groups. The utilization of peers to identify problems and risks, as was done by some initiatives, was seen as a strength. Difficulties were experienced with identifying the target group that would benefit from proactive delivery of care and support most, and with addressing prevalent issues among older people (e.g. psychosocial issues, self-reliance issues). Conclusion Although there is a broad array of initiatives available, there is a discrepancy between supply and demand. Current initiatives insufficiently address needs of (frail) older people. More insight is needed in “what should be done by whom, for which target group and at what moment”, in order to improve current practice in preventive elderly care. Keywords: Early detection, Preventive home visit, Health and social problems, Older people, Frailty, Qualitative researc

A review of published analyses of case-cohort studies and recommendations for future reporting.

The case-cohort study design combines the advantages of a cohort study with the efficiency of a nested case-control study. However, unlike more standard observational study designs, there are currently no guidelines for reporting results from case-cohort studies. Our aim was to review recent practice in reporting these studies, and develop recommendations for the future. By searching papers published in 24 major medical and epidemiological journals between January 2010 and March 2013 using PubMed, Scopus and Web of Knowledge, we identified 32 papers reporting case-cohort studies. The median subcohort sampling fraction was 4.1% (interquartile range 3.7% to 9.1%). The papers varied in their approaches to describing the numbers of individuals in the original cohort and the subcohort, presenting descriptive data, and in the level of detail provided about the statistical methods used, so it was not always possible to be sure that appropriate analyses had been conducted. Based on the findings of our review, we make recommendations about reporting of the study design, subcohort definition, numbers of participants, descriptive information and statistical methods, which could be used alongside existing STROBE guidelines for reporting observational studies.SJS was supported by the Medical Research Council www.mrc.ac.uk [Unit Programme number MC_UU_12015/1]. IRW was supported by the Medical Research Council www.mrc.ac.uk [Unit Programme number U105260558]. MP, SGT and AMW were supported by the British Heart Foundation www.bhf.org.uk [grant number CH/12/2/29428].This is the final published version distributed under a Creative Commons Attribution License 2.0, which can also be viewed on the publisher's website at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.010117

Does social support at home moderate the association between social support at work and work functioning among cancer patients?

PURPOSE: The aims of this study were to examine (1) the longitudinal associations of supervisor and colleague social support with work functioning in cancer patients who have returned to work and (2) the moderating role of social support at home.METHODS: Data from the longitudinal Work Life after Cancer study were used (n = 384). Work functioning (low versus moderate to high work functioning) was measured with the validated Work Role Functioning Questionnaire 2.0. Social support at work was measured from both supervisor and colleagues with the Copenhagen Psychosocial Questionnaire. Social support at home was measured with the Social Support List-Discrepancies. Logistic generalized estimating equations were used to analyse associations between supervisor and colleague social support and work functioning, and to examine the possible moderating effect of social support at home.RESULTS: More supervisor (OR: 1.21; 95% CI: 1.10, 1.32) and colleague (1.13; 1.03, 1.24) social support were significantly associated with moderate to high work functioning. The association between colleague social support and work functioning was attenuated for those who did not experience enough social support at home but remained almost significant for supervisor social support (1.17; 1.00, 1.37).CONCLUSIONS: Supervisor social support is associated with better work functioning regardless of social support at home, while colleague social support is only associated with better work functioning when cancer patients experience enough social support at home.IMPLICATIONS FOR CANCER SURVIVORS: Occupational physicians may play a key role in creating awareness that social support at work and at home are beneficial for cancer patients' work functioning.</p

Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7

Background: Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease process at the molecular level. Results: We have localized the genetic cause of the dwarfism phenotype by a genome wide approach to a 3 Mb region on the p-arm of equine chromosome 14. The DNA of two dwarfs and one control Friesian horse was sequenced completely and we identified the missense mutation ECA14:g.4535550C> T that cosegregated with the phenotype in all Friesians analyzed. The mutation leads to the amino acid substitution p.(Arg17Lys) of xylosylprotein beta 1,4-galactosyltransferase 7 encoded by B4GALT7. The protein is one of the enzymes that synthesize the tetrasaccharide linker between protein and glycosaminoglycan moieties of proteoglycans of the extracellular matrix. The mutation not only affects a conserved arginine codon but also the last nucleotide of the first exon of the gene and we show that it impedes splicing of the primary transcript in cultured fibroblasts from a heterozygous horse. As a result, the level of B4GALT7 mRNA in fibroblasts from a dwarf is only 2 % compared to normal levels. Mutations in B4GALT7 in humans are associated with Ehlers-Danlos syndrome progeroid type 1 and Larsen of Reunion Island syndrome. Growth retardation and ligamentous laxity are common manifestations of these syndromes. Conclusions: We suggest that the identified mutation of equine B4GALT7 leads to the typical dwarfism phenotype in Friesian horses due to deficient splicing of transcripts of the gene. The mutated gene implicates the extracellular matrix in the regular organization of chrondrocyte columns of the growth plate. Conservation of individual amino acids may not be necessary at the protein level but instead may reflect underlying conservation of nucleotide sequence that are required for efficient splicing

Étude démographique et généalogique de deux maladies héréditaires au Saguenay

La population du Saguenay est depuis longtemps reconnue pour l’ampleur des problèmes génétiques auxquels elle fait face. S’agissant en particulier de maladies récessives comme la tyrosinémie, l’ataxie de Friedreich (forme Charlevoix-Saguenay), le rachitisme ou l’agénésie du corps calleux, on a imputé les fortes incidences observées à divers facteurs comme les nombreux mariages consanguins, la stabilité de la population, un effet fondateur particulièrement accentué, un modèle particulier d’immigration, etc. Cependant, les analyses que nous avons commencé à réaliser à l’aide du fichier de population construit par SOREP obligent à réviser ces énoncés. La construction des généalogies par ordinateur et l’étude des comportements démographiques à l’aide de la reconstitution automatique des familles permettent en effet des analyses rétrospectives très approfondies et livrent des aperçus qui étaient hors de portée jusqu’à ce jour. L’enquête que nous rapportons ici revêt un caractère expérimental ; c'était la première fois que nous tentions une utilisation rigoureuse du fichier de population dans cette direction. Les résultats obtenus ont d’ores et déjà des retombées sur le conseil génétique et, en outre, ils modifient substantiellement notre perception de la dynamique démographique au Saguenay.The population of the Saguenay has long been known for the magnitude of the genetic problems it faces. In particular, since the problem is one of recessive illnesses such as tyrosinemia, Friedreich's ataxia (Charlevoix-Saguenay type), rickets or agenesis of corpus callosum, the strong observed effects have been ascribed to several factors such as the numerous mariages between blood relatives, the stability of the population, a particularly strong founder effect, a specific model of immigration, etc. However, the analysis we have begun to carry out with the aid of SOREP's population data base, forces us to revise these statements. The computer construction of genealogies and the study of demographic behaviour using automatic family reconstruction allow, indeed, for very thorough retrospective analyses, and deliver insights that, to this day, were out of reach. The survey on which we report is of an experimental nature; it was the first time we attempted a rigorous use of the population data base, for such purposes. The results obtained have already had an impact on underlying assumptions in the field of genetics, and moreover, they have substantially changed our perception of the demographic dynamics of the Saguenay.Hace tiempo que la población saguenayense es reputada por la envergadura de los problemas genéticos que enfrenta. Se trata particularmente de las enfermedades recesivas como la tirosinemia, la ataxia de Friedreich (tipo Charlevoix-Saguenay), el raquitismo o la agenesia del cuerpo calloso, cuya alta frecuencia se ha atribuido a diversos factores tales como el alto numero de uniones consanguíneas, la estabilidad de la población, un efecto "fundador" especialmente acentuado, un patrón particular de migración, etc. No obstante, los análisis que hemos comenzado a realizar gracias al archivo de población elaborado por SOREP (Sociedad de Investigaciones acerca de las Poblaciones), compelen a examinar de nuevo estos enunciados. La creación de genealogías por medio del computador y el estudio de los coiportamientos demográficos a través de la reconstitución automática de las familias, permiten elaborar análisis retrospectivos refinados que ofrecen una visión que antes estaba fuera de nuestro alcance. La investigación, de la cual damos cuenta en este articulo, es de carácter experimental; por primera ocasión intentamos el uso minucioso del archivo de población en este sentido. Los resultados obtenidos tienen ya su resonancia en la orientación que prodigan los genetistas, además de que modifican substancialmente nuestra percepción acerca de la dinámica demográfica del Saguenay

Reliability, minimal detectable change and responsiveness to change: indicators to select the best method to measure sedentary behaviour in older adults in different study designs

Introduction : Prolonged sedentary behaviour (SB) is associated with poor health. It is unclear which SB measure is most appropriate for interventions and population surveillance to measure and interpret change in behaviour in older adults. The aims of this study: to examine the relative and absolute reliability, Minimal Detectable Change (MDC) and responsiveness to change of subjective and objective methods of measuring SB in older adults and give recommendations of use for different study designs. Methods : SB of 18 older adults (aged 71 (IQR 7) years) was assessed using a systematic set of six subjective tools, derived from the TAxonomy of Self report Sedentary behaviour Tools (TASST), and one objective tool (activPAL3c), over 14 days. Relative reliability (Intra Class Correlation coefficients-ICC), absolute reliability (SEM), MDC, and the relative responsiveness (Cohen's d effect size (ES) and Guyatt's Responsiveness coefficient (GR)) were calculated for each of the different tools and ranked for different study designs. Results : ICC ranged from 0.414 to 0.946, SEM from 36.03 to 137.01 min, MDC from 1.66 to 8.42 hours, ES from 0.017 to 0.259 and GR from 0.024 to 0.485. Objective average day per week measurement ranked as most responsive in a clinical practice setting, whereas a one day measurement ranked highest in quasi-experimental, longitudinal and controlled trial study designs. TV viewing Previous Week Recall (PWR) ranked as most responsive subjective measure in all study designs. Conclusions : The reliability, Minimal Detectable Change and responsiveness to change of subjective and objective methods of measuring SB is context dependent. Although TV viewing-PWR is the more reliable and responsive subjective method in most situations, it may have limitations as a reliable measure of total SB. Results of this study can be used to guide choice of tools for detecting change in sedentary behaviour in older adults in the contexts of population surveillance, intervention evaluation and individual care