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

Feel My Pain: Design and Evaluation of Painpad, a Tangible Device for Supporting Inpatient Self-Logging of Pain

Monitoring patients' pain is a critical issue for clinical caregivers, particularly among staff responsible for providing analgesic relief. However, collecting regularly scheduled pain readings from patients can be difficult and time-consuming for clinicians. In this paper we present Painpad, a tangible device that was developed to allow patients to engage in self-logging of their pain. We report findings from two hospital-based field studies in which Painpad was deployed to a total of 78 inpatients recovering from ambulatory surgery. We find that Painpad results in improved frequency and compliance with pain logging, and that self-logged scores may be more faithful to patients' experienced pain than corresponding scores reported to nurses. We also show that older adults may prefer tangible interfaces over tablet-based alternatives for reporting their pain, and we contribute design lessons for pain logging devices intended for use in hospital settings

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

Dynamique Motivationnelle de l'Épuisement et du Bien-être chez des Enseignants Africains

This study examines the links between antecedents and consequences of Gabonese teachers' work motivation (N= 152). The theoretical underpinnings are based on the Motivational Model of Job Burnout (MMJB) and Self- Determination Theory (SDT) which states that the more supervisors will satisfy employee's needs for self-determination, competence, and relatedness, the more their work motivations will be self-determined. The latter will then have an impact on job satisfaction that will then determine life satisfaction. Higher levels of Self-determined motivations will also generate lower emotional exhaustion and psychological distress. The model was confirmed via structural equation modeling and provides support for the validity and generalizability for the MMJB and SDT. Cette étude examine la nature des liens entre des antécédents et conséquences de la motivation au travail d'enseignants gabonais (N = 152). Elle s'appuie sur le modèle motivationnel de l'épuisement professionnel qui soutient que plus le style de mobilisation du supérieur satisfait les besoins d'autodétermination, de compétence et d'attachement, plus la motivation des employés sera autodéterminée. Plus la motivation sera autodéterminée, meilleure sera la satisfaction au travail et, par la suite, la satisfaction de vie; en outre, moins élevé sera l'épuisement professionnel et, par la suite, la détresse psychologique. Le modèle a été confirmé à l'aide d'analyses par équations structurales et présente également un appui à la théorie de l'autodétermination.African teachers, Work motivation, Stress, Burnout, Sup style, Well-being, Self-Determination Theory, Enseignants africains, Motivation, Stress, Épuisement, Style de supervision, Bien-être, Travail, Théorie de l'autodétermination

A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses

Background: Hydrocephalus in Friesian horses is a developmental disorder that often results in stillbirth of affected foals and dystocia in dams. The occurrence is probably related to a founder effect and inbreeding in the population. The aim of our study was to find genomic associations, to investigate the mode of inheritance, to allow a DNA test for hydrocephalus in Friesian horses to be developed. In case of a monogenic inheritance we aimed to identify the causal mutation. Results: A genome-wide association study of hydrocephalus in 13 cases and 69 controls using 29,720 SNPs indicated the involvement of a region on ECA1 (P T corresponding to XP_001491595 p.Gln475* was identical to a B3GALNT2 mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All 16 available cases and none of the controls were homozygous for the mutation, and all 17 obligate carriers (= dams of cases) were heterozygous. A random sample of the Friesian horse population (n = 865) was tested for the mutation in a commercial laboratory. One-hundred and forty-seven horses were carrier and 718 horses were homozygous for the normal allele; the estimated allele frequency in the Friesian horse population is 0.085. Conclusions: Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* in B3GALNT2 (1: 75,859,296-75,909,376) is concordant with hydrocephalus in Friesian horses. Application of a DNA test in the breeding programme will reduce the losses caused by hydrocephalus in the Friesian horse population

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

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

A new view of electrochemistry at highly oriented pyrolytic graphite

Major new insights on electrochemical processes at graphite electrodes are reported, following extensive investigations of two of the most studied redox couples, Fe(CN)64–/3– and Ru(NH3)63+/2+. Experiments have been carried out on five different grades of highly oriented pyrolytic graphite (HOPG) that vary in step-edge height and surface coverage. Significantly, the same electrochemical characteristic is observed on all surfaces, independent of surface quality: initial cyclic voltammetry (CV) is close to reversible on freshly cleaved surfaces (>400 measurements for Fe(CN)64–/3– and >100 for Ru(NH3)63+/2+), in marked contrast to previous studies that have found very slow electron transfer (ET) kinetics, with an interpretation that ET only occurs at step edges. Significantly, high spatial resolution electrochemical imaging with scanning electrochemical cell microscopy, on the highest quality mechanically cleaved HOPG, demonstrates definitively that the pristine basal surface supports fast ET, and that ET is not confined to step edges. However, the history of the HOPG surface strongly influences the electrochemical behavior. Thus, Fe(CN)64–/3– shows markedly diminished ET kinetics with either extended exposure of the HOPG surface to the ambient environment or repeated CV measurements. In situ atomic force microscopy (AFM) reveals that the deterioration in apparent ET kinetics is coupled with the deposition of material on the HOPG electrode, while conducting-AFM highlights that, after cleaving, the local surface conductivity of HOPG deteriorates significantly with time. These observations and new insights are not only important for graphite, but have significant implications for electrochemistry at related carbon materials such as graphene and carbon nanotubes