Binding of Lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan.

The arenavirus Lassa virus (LASV) causes a severe haemorrhagic fever with high mortality in man. The cellular receptor for LASV is dystroglycan (DG). DG is a ubiquitous receptor for extracellular matrix (ECM) proteins, which cooperates with β1 integrins to control cell-matrix interactions. Here, we investigated whether LASV binding to DG triggers signal transduction, mimicking the natural ligands. Engagement of DG by LASV resulted in the recruitment of the adaptor protein Grb2 and the protein kinase MEK1 by the cytoplasmic domain of DG without activating the MEK/ERK pathway, indicating assembly of an inactive signalling complex. LASV binding to cells however affected the activation of the MEK/ERK pathway via α6β1 integrins. The virus-induced perturbation of α6β1 integrin signalling critically depended on high-affinity LASV binding to DG and DG's cytoplasmic domain, indicating that LASV-receptor binding perturbed signalling cross-talk between DG and β1 integrins.

The Brazilian policy for reduction of accidents and violence aligns with international perspectives?

The study analyzed The Brazilian Policy for Reduction of Morbidity and Mortality from Accidents and Violence, in the socio-political perspective. We used as a base the chapter “Violence: a global public health problem” from the World Report on Violence and Health. The analysis revealed convergent and divergent elements of the Brazilian Policy in comparison with the international perspectives. We verified that the Brazilian Policy tried to converge to the international policies, however: it emphasizes the health promotion actions, but are limited to the context and behavior of individuals and individual communities; the performance of health professionals is expected without providing more structural investments, as the improvement in work conditions, the increase of financial and material resources; there are few clear definitions of the government and economical sector responsibilities.

Disinfection with sodium hypochlorite in hospital environmental surfaces in the reduction of contamination and infection prevention: a systematic review

OBJECTIVETo search for evidence of the efficiency of sodium hypochlorite on environmental surfaces in reducing contamination and prevention of healthcare-associated infection HAIs.METHODSystematic review in accordance with the Cochrane Collaboration.RESULTSWe analyzed 14 studies, all controlled trials, published between 1989-2013. Most studies resulted in inhibition of microorganism growth. Some decreased infection, microorganism resistance and colonization, loss of efficiency in the presence of dirty and surface-dried viruses.CONCLUSIONThe hypochlorite is an effective disinfectant, however, the issue of the direct relation with the reduction of HAIs remains. The absence of control for confounding variables in the analyzed studies made the meta-analysis performance inadequate. The evaluation of internal validity using CONSORT and TREND was not possible because its contents were not appropriate to laboratory and microbiological studies. As a result, there is an urgent need for developing specific protocol for evaluating such studies.

Performance comparison of an active matrix flat panel imager, computed radiography system, and a screen-film system at four standard radiation qualities.

Four standard radiation qualities (from RQA 3 to RQA 9) were used to compare the imaging performance of a computed radiography (CR) system (general purpose and high resolution phosphor plates of a Kodak CR 9000 system), a selenium-based direct flat panel detector (Kodak Direct View DR 9000), and a conventional screen-film system (Kodak T-MAT L/RA film with a 3M Trimax Regular screen of speed 400) in conventional radiography. Reference exposure levels were chosen according to the manufacturer's recommendations to be representative of clinical practice (exposure index of 1700 for digital systems and a film optical density of 1.4). With the exception of the RQA 3 beam quality, the exposure levels needed to produce a mean digital signal of 1700 were higher than those needed to obtain a mean film optical density of 1.4. In spite of intense developments in the field of digital detectors, screen-film systems are still very efficient detectors for most of the beam qualities used in radiology. An important outcome of this study is the behavior of the detective quantum efficiency of the digital radiography (DR) system as a function of beam energy. The practice of users to increase beam energy when switching from a screen-film system to a CR system, in order to improve the compromise between patient dose and image quality, might not be appropriate when switching from screen-film to selenium-based DR systems.

Reduction of connexin36 content by ICER-1 contributes to insulin-secreting cells apoptosis induced by oxidized LDL particles.

Connexin36 (Cx36), a trans-membrane protein that forms gap junctions between insulin-secreting beta-cells in the Langerhans islets, contributes to the proper control of insulin secretion and beta-cell survival. Hypercholesterolemia and pro-atherogenic low density lipoproteins (LDL) contribute to beta-cell dysfunction and apoptosis in the context of Type 2 diabetes. We investigated the impact of LDL-cholesterol on Cx36 levels in beta-cells. As compared to WT mice, the Cx36 content was reduced in islets from hypercholesterolemic ApoE-/- mice. Prolonged exposure to human native (nLDL) or oxidized LDL (oxLDL) particles decreased the expression of Cx36 in insulin secreting cell-lines and isolated rodent islets. Cx36 down-regulation was associated with overexpression of the inducible cAMP early repressor (ICER-1) and the selective disruption of ICER-1 prevented the effects of oxLDL on Cx36 expression. Oil red O staining and Plin1 expression levels suggested that oxLDL were less stored as neutral lipid droplets than nLDL in INS-1E cells. The lipid beta-oxidation inhibitor etomoxir enhanced oxLDL-induced apoptosis whereas the ceramide synthesis inhibitor myriocin partially protected INS-1E cells, suggesting that oxLDL toxicity was due to impaired metabolism of the lipids. ICER-1 and Cx36 expressions were closely correlated with oxLDL toxicity. Cx36 knock-down in INS-1E cells or knock-out in primary islets sensitized beta-cells to oxLDL-induced apoptosis. In contrast, overexpression of Cx36 partially protected INS-1E cells against apoptosis. These data demonstrate that the reduction of Cx36 content in beta-cells by oxLDL particles is mediated by ICER-1 and contributes to oxLDL-induced beta-cell apoptosis.

Risk reduction practices in men who have sex with men in Switzerland: serosorting, strategic positioning, and withdrawal before ejaculation.

The aim of this study was to identify predictors of intentional use of the HIV risk reduction practices of serosorting, strategic positioning, and withdrawal before ejaculation during unprotected anal intercourse (UAI) with casual partners. A cross-sectional survey pertaining to the Swiss HIV behavioral surveillance system, using an anonymous self-administered questionnaire, was conducted in 2007 in a self-selected sample of men having sex with other men (MSM). Analysis was restricted to participants with UAI with casual partner(s) (N = 410). Logistic regression was used to estimate factors associated with intentional use of serosorting, strategic positioning, and withdrawal before ejaculation. In the previous 12 months, 71% of participants reported having UAI with a casual partner of different or unknown HIV-status. Of these, 47% reported practicing withdrawal, 38% serosorting, and 25% strategic positioning. In the 319 participants with known HIV-status, serosorting was associated with frequent Internet use to find partners (OR = 2.32), STI (OR = 2.07), and HIV testing in the past 12 months (OR = 1.81). Strategic positioning was associated with HIV-status (OR = 0.13) and having UAI with a partner of different or unknown HIV-status (OR = 3.57). Withdrawal was more frequently practiced by HIV-negative participants or participants reporting high numbers of sexual partners (OR = 2.48) and having UAI with a partner of unknown or different serostatus (OR = 2.08). Risk reduction practices are widely used by MSM, each practice having its own specificities. Further research is needed to determine the contextual factors surrounding harm reduction practices, particularly the strategic or opportunistic nature of their use.

The algebraic equality of two asymptotic tests for the hypothesis that a normal distribution has a specified correlation matrix

It is proved the algebraic equality between Jennrich's (1970) asymptotic$X^2$ test for equality of correlation matrices, and a Wald test statisticderived from Neudecker and Wesselman's (1990) expression of theasymptoticvariance matrix of the sample correlation matrix.

Compact matrix expressions for generalized Wald tests of equality of moment vectors

Asymptotic chi-squared test statistics for testing the equality ofmoment vectors are developed. The test statistics proposed aregeneralizedWald test statistics that specialize for different settings by inserting andappropriate asymptotic variance matrix of sample moments. Scaled teststatisticsare also considered for dealing with situations of non-iid sampling. Thespecializationwill be carried out for testing the equality of multinomial populations, andtheequality of variance and correlation matrices for both normal andnon-normaldata. When testing the equality of correlation matrices, a scaled versionofthe normal theory chi-squared statistic is proven to be an asymptoticallyexactchi-squared statistic in the case of elliptical data.

Reduction of Helicobacter infection in IL-10-/- mice is dependent on CD4+ T cells but not on mast cells.

BACKGROUND: In contrast to wild type, interleukin-10-deficient (IL-10(-/-)) mice are able to clear Helicobacter infection. In this study, we investigated the immune response of IL-10(-/-) mice leading to the reduction of Helicobacter infection. MATERIALS AND METHODS: We characterized the immune responses of Helicobacter felis-infected IL-10(-/-) mice by studying the systemic antibody and cellular responses toward Helicobacter. We investigated the role of CD4(+) T cells in the Helicobacter clearance by injecting H. felis-infected IL-10(-/-) mice with anti-CD4 depleting antibodies. To examine the role of mast cells in Helicobacter clearance, we constructed and infected mast cells and IL-10 double-deficient mice. RESULTS: Reduction of Helicobacter infection in IL-10(-/-) mice is associated with strong humoral (fivefold higher serum antiurease antibody titers were measured in IL-10(-/-) in comparison to wild-type mice, p < .008) and cellular (urease-stimulated splenic CD4(+) T cells isolated from infected IL-10(-/-) mice produce 150-fold more interferon-gamma in comparison to wild-type counterparts, p < .008) immune responses directed toward Helicobacter. Depletion of CD4(+) cells from Helicobacter-infected IL-10(-/-) mice lead to the loss of bacterial clearance (rapid urease tests are threefold higher in CD4(+) depleted IL-10(-/-) in comparison to nondepleted IL-10(-/-) mice, p < .02). Mast cell IL-10(-/-) double-deficient mice clear H. felis infection, indicating that mast cells are unnecessary for the bacterial eradication in IL-10(-/-) mice. CONCLUSION: Taken together, these results suggest that CD4(+) cells are required for Helicobacter clearance in IL-10(-/-) mice. This reduction of Helicobacter infection is, however, not dependent on the mast cell population.

Improving Transition Outcomes: Resource Mapping Workshop: Service Matrix

Resource Mapping tool from the Improving Transition Outcomes Resource Mapping Workshops

Some hypothesis tests for the covariance matrix when the dimension is large compared to the sample size

This paper analyzes whether standard covariance matrix tests work whendimensionality is large, and in particular larger than sample size. Inthe latter case, the singularity of the sample covariance matrix makeslikelihood ratio tests degenerate, but other tests based on quadraticforms of sample covariance matrix eigenvalues remain well-defined. Westudy the consistency property and limiting distribution of these testsas dimensionality and sample size go to infinity together, with theirratio converging to a finite non-zero limit. We find that the existingtest for sphericity is robust against high dimensionality, but not thetest for equality of the covariance matrix to a given matrix. For thelatter test, we develop a new correction to the existing test statisticthat makes it robust against high dimensionality.

Honey, I shrunk the sample covariance matrix

The central message of this paper is that nobody should be using the samplecovariance matrix for the purpose of portfolio optimization. It containsestimation error of the kind most likely to perturb a mean-varianceoptimizer. In its place, we suggest using the matrix obtained from thesample covariance matrix through a transformation called shrinkage. Thistends to pull the most extreme coefficients towards more central values,thereby systematically reducing estimation error where it matters most.Statistically, the challenge is to know the optimal shrinkage intensity,and we give the formula for that. Without changing any other step in theportfolio optimization process, we show on actual stock market data thatshrinkage reduces tracking error relative to a benchmark index, andsubstantially increases the realized information ratio of the activeportfolio manager.

Microfabrics in carbonate mylonites along a large-scale shear zone (Helvetic Alps)

Carbonate mylonites with varying proportions of second-phase minerals were collected at positions of increasing metamorphic grade along the basal thrust of the Morcles nappe (Helvetic nappes, Switzerland). Variations of temperature, stress, and strain rate, changes in chemistry of solid and fluid phases, and differing degrees of strain localization and annealing were tracked by measuring the shapes, mean sizes, and size distributions of both matrix and second-phase grains, as well as crystal preferred orientation (CPO) of the matrix. Field structures suggest that strain rate was constant along the fault. The mean and distribution of the calcite grain sizes were affected most profoundly by temperature: Increased temperature, presumably accompanied by decreased stress, correlated with larger mean sizes and wider size distributions. At a given location, the matrix grains in mylonites with more second-phase particles are, on average, smaller, have narrower size distributions, and have more elongate shapes. For example, mylonites with 50 vol.% of second phases have matrix grain sizes half that of pure mylonites. Changes in calcite chemistry and the presence of synkinematic fluids seemed to influence microfabric only weakly. Temporal variations in conditions, such as exhumation-induced cooling, apparently provoke changes in temperature, stress, and strain rate along the nappe. These changes result in further strain localization during retrograde conditions and cause the grain size to be reduced by an additional 50%. The matrix CPO strengthens with increasing temperature or strain, but weakens and rotates with increasing second-phase content, These fabric changes suggest differing rates of grain growth, grain size reduction, and development of CPO owing to variations in the deformation conditions and, perhaps, mechanisms. To interpret natural mylonite structures or to extrapolate mechanical data to natural situations requires careful characterization of the microfabric, and, in particular, second-phase minerals. (c) 2007 Elsevier B.V, All rights reserved.