What factors predict who will have a strong social network following a stroke?

Purpose: Measures of social networks assess the number and nature of a person's social contacts, and strongly predict health outcomes. We explored how social networks change following a stroke and analysed concurrent and baseline predictors of social networks six months post stroke. Method: Prospective longitudinal observational study. Participants were assessed two weeks (baseline), three months and six months post stroke. Measures included: Stroke Social Network Scale; MOS Social Support Survey; NIH Stroke Scale; Frenchay Aphasia Screening Test; Frenchay Activities Index; and the Barthel Index. ANOVA and standard multiple regression were used to analyse change and identify predictors. Results: 87 participants (37% with aphasia) were recruited; 71 (16% with aphasia) were followed up at six months. Social network scores declined post stroke (p = .001). While the Children and Relatives factors remained stable, the Friends factor significantly weakened (p <.001). Concurrent predictors of social network at six months were: perceived social support, ethnicity, aphasia and extended ADL (adjusted R 2 = .42). There were two baseline predictors: pre-morbid social network and aphasia (adjusted R 2 = .60). Conclusions: Social networks declined post stroke. Aphasia was the only stroke-related factor measured at the time of the stroke that predicted social network six months later

Sex differences in perceived risk and testing experience of HIV in an urban fishing setting in Ghana

The concept of neighborhood remains important in criminology but there is an increasing academic interest in the potential impact of the Modifiable Areal Unit Problem (MAUP) on neighborhood based studies. In the present study data over arson from the Swedish rescue services 2007-2012 have been employed to analyze MAUP in the city of Malmö, Sweden. The city has been divided into 50*50 meter pixels as micro-places (n=64540) which have been assigned a value for arson from frequency of arson within the pixel. The analysis is based on a comparison of two types of administrative geographical units alongside 40 randomly generated sets of thiessen polygon geographical units. Empty two-level hierarchical regression models with the micro-places as level 1 unit have been used to calculate Intra-Class Correlations (ICC) separately with each of the 42 different geographical units of analysis as level 2 units. The analysis is repeated with two alternative methods, kernel density and euclidian distance, to calculate a value for each micro-place. Results show that administrative geographical units of analysis in some cases just are marginally better than geographical units with random boundaries if the basic urban structure is taken into account

Combined loss of the BH3-only proteins Bim and Bmf restores B-cell development and function in TACI-Ig transgenic mice.

Terminal differentiation of B cells depends on two interconnected survival pathways, elicited by the B-cell receptor (BCR) and the BAFF receptor (BAFF-R), respectively. Loss of either signaling pathway arrests B-cell development. Although BCR-dependent survival depends mainly on the activation of the v-AKT murine thymoma viral oncogene homolog 1 (AKT)/PI3-kinase network, BAFF/BAFF-R-mediated survival engages non-canonical NF-κB signaling as well as MAPK/extracellular-signal regulated kinase and AKT/PI3-kinase modules to allow proper B-cell development. Plasma cell survival, however, is independent of BAFF-R and regulated by APRIL that signals NF-κB activation via alternative receptors, that is, transmembrane activator and CAML interactor (TACI) or B-cell maturation (BCMA). All these complex signaling events are believed to secure survival by increased expression of anti-apoptotic B-cell lymphoma 2 (Bcl2) family proteins in developing and mature B cells. Curiously, how lack of BAFF- or APRIL-mediated signaling triggers B-cell apoptosis remains largely unexplored. Here, we show that two pro-apoptotic members of the 'Bcl2 homology domain 3-only' subgroup of the Bcl2 family, Bcl2 interacting mediator of cell death (Bim) and Bcl2 modifying factor (Bmf), mediate apoptosis in the context of TACI-Ig overexpression that effectively neutralizes BAFF as well as APRIL. Surprisingly, although Bcl2 overexpression triggers B-cell hyperplasia exceeding the one observed in Bim(-/-)Bmf(-/-) mice, Bcl2 transgenic B cells remain susceptible to the effects of TACI-Ig expression in vivo, leading to ameliorated pathology in Vav-Bcl2 transgenic mice. Together, our findings shed new light on the molecular machinery restricting B-cell survival during development, normal homeostasis and under pathological conditions. Our data further suggest that Bcl2 antagonists might improve the potency of BAFF/APRIL-depletion strategies in B-cell-driven pathologies

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells

Upon activation by antigen, B cells form germinal centers where they clonally expand and introduce affinity-enhancing mutations into their B cell receptor genes. Somatic mutagenesis and class switch recombination in germinal center B cells are initiated by the activation-induced cytidine deaminase (AID). Upon germinal center exit, B cells differentiate into antibody-secreting plasma cells. Germinal center maintenance and terminal fate choice require transcriptional reprogramming that associates with a substantial reconfiguration of DNA methylation patterns. Here we examine the role of TET proteins, enzymes that facilitate DNA demethylation and promote a permissive chromatin state by oxidizing 5-methylcytosine, in antibody-mediated immunity. Using a conditional gene ablation strategy, we show that TET2 and TET3 guide the transition of germinal center B cells to antibody-secreting plasma cells. Optimal AID expression requires TET function, and TET2 and TET3 double-deficient germinal center B cells show defects in class switch recombination. However, TET2/TET3 double-deficiency does not prevent the generation and selection of high-affinity germinal center B cells. Rather, combined TET2 and TET3 loss-of-function in germinal center B cells favors C-to-T and G-to-A transition mutagenesis, a finding that may be of significance for understanding the etiology of B cell lymphomas evolving in conditions of reduced TET function

Canonical NF-κB signaling is uniquely required for the long-term persistence of functional mature B cells

Although canonical NF-κB signaling is crucial to generate a normal mature B-cell compartment, its role in the persistence of resting mature B cells is controversial. To resolve this conflict, we ablated NF-κB essential modulator (NEMO) and I{kappa}B kinase 2 (IKK2), two essential mediators of the canonical pathway, either early on in B-cell development or specifically in mature B cells. Early ablation severely inhibited the generation of all mature B-cell subsets, but follicular B-cell numbers could be largely rescued by ectopic expression of B-cell lymphoma 2 (Bcl2), despite a persisting block at the transitional stage. Marginal zone (MZ) B and B1 cells were not rescued, indicating a possible role of canonical NF-κB signals beyond the control of cell survival in these subsets. When canonical NF-κB signaling was ablated specifically in mature B cells, the differentiation and/or persistence of MZ B cells was still abrogated, but follicular B-cell numbers were only mildly affected. However, the mutant cells exhibited increased turnover as well as functional deficiencies upon activation, suggesting that canonical NF-κB signals contribute to their long-term persistence and functional fitness

Hydrofoil Configurations for Sailing Superyachts: Hydrodynamics, Stability and Performance

Hydrofoil-assisted racing monohulls have undergone significant development phases in the past decade, yet very little scientific data has reached the public domain: an increasingly critical issue as the superyacht industry is now looking at the implementation of foils onto leisure vessels. Consequently, three contemporary configurations, namely a Dynamic Stability System, a Dali-Moustache and a Chistera have been towing tank tested to present the first complete characterisation of the hydrodynamic efficiency, quantification of the added dynamic stability and eventually the resulting impact on sailing performance. Furthermore, the considerations inherent to the design and installation of hydrofoils onto superyachts will be detailed. Building on extensive experimental work, this paper provides a comprehensive assessment of current design options with both technical and practical guidelines and recommendations to improve performance