HIV seroconversion among factory workers in Harare: who is getting newly infected?

A clinical report on the impact of HIV/AIDS among factory workers in Zimbabwe's industrial areas of Harare.It was estimated that by the of 1996 more than 8.4 million AIDS cases had occurred worldwide.1 Because of the long and variable duration between infection with the human immunodeficiency virus (HIV) and the ultimate development of AIDS, a more useful indication of current trends in the epidemic is the number of new infections with HIV. Twenty eight million people from 190 countries across the world were HIV positive by mid 1996.Composed of distinct epidemics, each with its own features, degree and extent, the pandemic has had a disproportionately severe impact on the developing world. Despite wide information on HIV prevention, 3.1 million new infections occurred during 1996. Up to 93% of the HIV infections recorded in 1996 were from developing countries with 68% from sub-Saharan Africa.2 Developing countries, who have weaker economic structures, continue to bear the greatest burden of HIV infections. HIV infection appears be spreading much faster in Southern Africa than anywhere else

Constraining the primordial spectrum of metric perturbations from gravitino and moduli production

We consider the production of gravitinos and moduli fields from quantum vacuum fluctuations induced by the presence of scalar metric perturbations at the end of inflation. We obtain the corresponding occupation numbers, up to first order in perturbation theory, in terms of the power spectrum of the metric perturbations. We compute the limits imposed by nucleosynthesis on the spectral index $n_s$ for different models with constant $n_s$. The results show that, in certain cases, such limits can be as strong as $n_s<1.12$, which is more stringent than those coming from primordial black hole production.Comment: 16 pages, LaTeX, 5 figures. Corrected figures, new references included. Final version to appear in Phys. Rev.

Preferred Healthy Food Nudges, Food Store Environments, and Customer Dietary Practices in 2 Low-Income Southern Communities

Objective To examine how food store environments can promote healthful eating, including (1) preferences for a variety of behavioral economics strategies to promote healthful food purchases, and (2) the cross-sectional association between the primary food store where participants reported shopping, dietary behaviors, and body mass index. Methods Intercept survey participants (n = 342) from 2 midsized eastern North Carolina communities completed questionnaires regarding preferred behavioral economics strategies, the primary food store at which they shopped, and consumption of fruits, vegetables, and sugary beverages. Results Frequently selected behavioral economic strategies included: (1) a token and reward system for fruit and vegetable purchases; and (2) price discounts on healthful foods and beverages. There was a significant association between the primary food store and consumption of fruits and vegetables (P = .005) and sugary beverages (P = .02). Conclusions and Implications Future studies should examine associations between elements of the in-store food environment, purchases, and consumption

Zebrafish models of collagen VI-related myopathies

Collagen VI is an integral part of the skeletal muscle extracellular matrix, providing mechanical stability and facilitating matrix-dependent cell signaling. Mutations in collagen VI result in either Ullrich congenital muscular dystrophy (UCMD) or Bethlem myopathy (BM), with UCMD being clinically more severe. Recent studies demonstrating increased apoptosis and abnormal mitochondrial function in Col6a1 knockout mice and in human myoblasts have provided the first mechanistic insights into the pathophysiology of these diseases. However, how loss of collagen VI causes mitochondrial dysfunction remains to be understood. Progress is hindered in part by the lack of an adequate animal model for UCMD, as knockout mice have a mild motor phenotype. To further the understanding of these disorders, we have generated zebrafish models of the collagen VI myopathies. Morpholinos designed to exon 9 of col6a1 produced a severe muscle disease reminiscent of UCMD, while ones to exon 13 produced a milder phenotype similar to BM. UCMD-like zebrafish have increased cell death and abnormal mitochondria, which can be attenuated by treatment with the proton pump modifier cyclosporin A (CsA). CsA improved the motor deficits in UCMD-like zebrafish, but failed to reverse the sarcolemmal membrane damage. In all, we have successfully generated the first vertebrate model matching the clinical severity of UCMD and demonstrated that CsA provides phenotypic improvement, thus corroborating data from knockout mice supporting the use of mitochondrial permeability transition pore modifiers as therapeutics in patients, and providing proof of principle for the utility of the zebrafish as a powerful preclinical model

Rare tandem repeat expansions associate with genes involved in synaptic and neuronal signaling functions in schizophrenia

Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex disorders such as cancer and autism spectrum disorder. The role of TREs in schizophrenia is now emerging. In this study, we have performed a genome-wide investigation of TREs in schizophrenia. Using genome sequence data from 1154 Swedish schizophrenia cases and 934 ancestry-matched population controls, we have detected genome-wide rare (<0.1% population frequency) TREs that have motifs with a length of 2–20 base pairs. We find that the proportion of individuals carrying rare TREs is significantly higher in the schizophrenia group. There is a significantly higher burden of rare TREs in schizophrenia cases than in controls in genic regions, particularly in postsynaptic genes, in genes overlapping brain expression quantitative trait loci, and in brain-expressed genes that are differentially expressed between schizophrenia cases and controls. We demonstrate that TRE-associated genes are more constrained and primarily impact synaptic and neuronal signaling functions. These results have been replicated in an independent Canadian sample that consisted of 252 schizophrenia cases of European ancestry and 222 ancestry-matched controls. Our results support the involvement of rare TREs in schizophrenia etiology

Modern temporal network theory: A colloquium

The power of any kind of network approach lies in the ability to simplify a complex system so that one can better understand its function as a whole. Sometimes it is beneficial, however, to include more information than in a simple graph of only nodes and links. Adding information about times of interactions can make predictions and mechanistic understanding more accurate. The drawback, however, is that there are not so many methods available, partly because temporal networks is a relatively young field, partly because it more difficult to develop such methods compared to for static networks. In this colloquium, we review the methods to analyze and model temporal networks and processes taking place on them, focusing mainly on the last three years. This includes the spreading of infectious disease, opinions, rumors, in social networks; information packets in computer networks; various types of signaling in biology, and more. We also discuss future directions.Comment: Final accepted versio

Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

Congenital Heart Disease (CHD) affects approximately 7-9 children per 1000 live births. Numerous genetic studies have established a role for rare genomic variants at the copy number variation (CNV) and single nucleotide variant level. In particular, the role of de novo mutations (DNM) has been highlighted in syndromic and non-syndromic CHD. To identify novel haploinsufficient CHD disease genes we performed an integrative analysis of CNVs and DNMs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm (TAA). We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed mutation rate testing for DNMs identified in 2,489 parent-offspring trios. Our combined analysis revealed 21 genes which were significantly affected by rare genomic deletions and/or constrained non-synonymous de novo mutations in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in singletons and small cases series, or show new associations with CHD. In addition, a systems level analysis revealed shared contribution of CNV deletions and DNMs in CHD probands, affecting protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes