238 research outputs found
A Multi-Criteria Methodology for Measuring the Resilience of Transportation Assets and Prioritizing Security Investments
Transportation project prioritization uses performance measures that are related to the transportation asset, its operations, and its environment. However, in the state of practice, evaluation does not consider directly the likelihood of natural or man-made threats, the infrastructure resilience, or the consequences of the infrastructure damage in the event that the threat occurs. Thus, during the prioritization of investments, assets of low security do not receive the due attention they deserve. In defining security as the lack of risk of damage from threats due to inherent structure or functional resilience, this paper is based on the premise that the inclusion of security considerations in prioritization introduces a much needed element of robustness in investment prioritization However, the inclusion of investment security impacts leads to an increase in the number of performance measures for the investment evaluation. This paper presents a methodology to quantify the overall security level for an asset in terms of the environmental threats it faces, its resilience or vulnerability to damage, and the consequences of the infrastructure damage. The overall framework consists of the traditional steps in risk management, and this paper\u27s specific contribution is in the part of the framework that measures the risk. This paper applies the methodology to a given set of assets by measuring the risk (security) of each asset and prioritizing security investments across multiple assets using multiple criteria analysis
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
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A systematic review of the impact of stroke on social support and social networks: associated factors and patterns of change
Objective: Identify what factors are associated with functional social support and social network post stroke; explore stroke survivors’ perspectives on what changes occur and how they are perceived.
Data sources: The following electronic databases were systematically searched up to May 2015: Academic Search Complete; CINAHL Plus; E-journals; Health Policy Reference Centre; MEDLINE; PsycARTICLES; PsycINFO; and SocINDEX.
Review methods: PRISMA guidelines were followed in the conduct and reporting of this review. All included studies were critically appraised using the Critical Appraisal Skills Program tools. Meta-ethnographic techniques were used to integrate findings from the qualitative studies. Given the heterogeneous nature of the quantitative studies, data synthesis was narrative.
Results: 70 research reports met the eligibility criteria: 22 qualitative and 48 quantitative reporting on 4,816 stroke survivors. The qualitative studies described a contraction of the social network, with non-kin contact being vulnerable. Although family were more robust network members, significant strain was observed within the family unit. In the quantitative studies, poor functional social support was associated with depression (13/14 studies), reduced quality of life (6/6 studies) and worse physical recovery (2/2 studies). Reduced social network was associated with depression (7/8 studies), severity of disability (2/2 studies) and aphasia (2/2 studies). Although most indicators of social network reduced post stroke (for example, contact with friends, 5/5 studies), the perception of feeling supported remained relatively stable (4/4 studies).
Conclusion: Following a stroke non-kin contact is vulnerable, strain is observed within the family unit, and poor social support is associated with depressive symptoms
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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
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