HIV prevalence and undiagnosed infection among a community sample of gay and bisexual men in Scotland, 2005-2011: implications for HIV testing policy and prevention

<b>Objective</b><p></p> To examine HIV prevalence, HIV testing behaviour, undiagnosed infection and risk factors for HIV positivity among a community sample of gay men in Scotland.<p></p> <b>Methods</b><p></p> Cross-sectional survey of gay and bisexual men attending commercial gay venues in Glasgow and Edinburgh, Scotland with voluntary anonymous HIV testing of oral fluid samples in 2011. A response rate of 65.2% was achieved (1515 participants).<p></p> <b>Results</b><p></p> HIV prevalence (4.8%, 95% confidence interval, CI 3.8% to 6.2%) remained stable compared to previous survey years (2005 and 2008) and the proportion of undiagnosed infection among HIV-positive men (25.4%) remained similar to that recorded in 2008. Half of the participants who provided an oral fluid sample stated that they had had an HIV test in the previous 12 months; this proportion is significantly higher when compared to previous study years (50.7% versus 33.8% in 2005, p<0.001). Older age (>25 years) was associated with HIV positivity (1.8% in those <25 versus 6.4% in older ages group) as was a sexually transmitted infection (STI) diagnosis within the previous 12 months (adjusted odds ratio 2.13, 95% CI 1.09–4.14). There was no significant association between age and having an STI or age and any of the sexual behaviours recorded.<p></p> <b>Conclusion</b><p></p> HIV transmission continues to occur among gay and bisexual men in Scotland. Despite evidence of recent testing within the previous six months, suggesting a willingness to test, the current opt-out policy may have reached its limit with regards to maximising HIV test uptake. Novel strategies are required to improve regular testing opportunities and more frequent testing as there are implications for the use of other biomedical HIV interventions.<p></p&gt

Clades of huge phages from across Earth's ecosystems.

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation

Analysing NSW state policy for child obesity prevention: strategic policy versus practical action

There is increasing worldwide recognition of the need for government policies to address the recent increases in the incidence and prevalence of childhood obesity. The complexity and inter-relatedness of the determinants of obesity pose a genuine policy challenge, both scientifically and politically. This study examines the characteristics of one of the early policy responses, the NSW Government\u27s Prevention of Obesity in Children and Young People: NSW Government Action Plan 2003-2007 (GAP), as a case study, assessing it in terms of its content and capacity for implementation. This policy was designed as an initial set of practical actions spanning five government sectors. Most of the policy actions fitted with existing implementation systems within NSW government, and reflected an incremental approach to policy formulation and implementation. As a case study, the NSW Government Action Plan illustrates that childhood obesity policy development and implementation are at an early stage. This policy, while limited, may have built sufficient commitment and support to create momentum for more strategic policy in the future. A more sophisticated, comprehensive and strategic policy which can also be widely implemented and evaluated should now be built on this base

CoastColour Round Robin datasets: A data base to evaluate the performance of algorithms for the retrieval of water quality parameters in coastal waters

The use of in situ measurements is essential in the validation and evaluation of the algorithms that provide coastal water quality data products from ocean colour satellite remote sensing. Over the past decade, various types of ocean colour algorithms have been developed to deal with the optical complexity of coastal waters. Yet there is a lack of a comprehensive intercomparison due to the availability of quality checked in situ databases. The CoastColour Round Robin (CCRR) project, funded by the European Space Agency (ESA), was designed to bring together three reference data sets using these to test algorithms and to assess their accuracy for retrieving water quality parameters. This paper provides a detailed description of these reference data sets, which include the Medium Resolution Imaging Spectrometer (MERIS) level 2 match-ups, in situ reflectance measurements, and synthetic data generated by a radiative transfer model (HydroLight). These data sets, representing mainly coastal waters, are available from doi:10.1594/PANGAEA.841950. The data sets mainly consist of 6484 marine reflectance (either multispectral or hyperspectral) associated with various geometrical (sensor viewing and solar angles) and sky conditions and water constituents: total suspended matter (TSM) and chlorophyll a (CHL) concentrations, and the absorption of coloured dissolved organic matter (CDOM). Inherent optical properties are also provided in the simulated data sets (5000 simulations) and from 3054 match-up locations. The distributions of reflectance at selected MERIS bands and band ratios, CHL and TSM as a function of reflectance, from the three data sets are compared. Match-up and in situ sites where deviations occur are identified. The distributions of the three reflectance data sets are also compared to the simulated and in situ reflectances used previously by the International Ocean Colour Coordinating Group (IOCCG, 2006) for algorithm testing, showing a clear extension of the CCRR data which covers more turbid waters.JRC.H.1-Water Resource

Structural Analysis of Papain-Like NlpC/P60 Superfamily Enzymes with a Circularly Permuted Topology Reveals Potential Lipid Binding Sites

NlpC/P60 superfamily papain-like enzymes play important roles in all kingdoms of life. Two members of this superfamily, LRAT-like and YaeF/YiiX-like families, were predicted to contain a catalytic domain that is circularly permuted such that the catalytic cysteine is located near the C-terminus, instead of at the N-terminus. These permuted enzymes are widespread in virus, pathogenic bacteria, and eukaryotes. We determined the crystal structure of a member of the YaeF/YiiX-like family from Bacillus cereus in complex with lysine. The structure, which adopts a ligand-induced, “closed” conformation, confirms the circular permutation of catalytic residues. A comparative analysis of other related protein structures within the NlpC/P60 superfamily is presented. Permutated NlpC/P60 enzymes contain a similar conserved core and arrangement of catalytic residues, including a Cys/His-containing triad and an additional conserved tyrosine. More surprisingly, permuted enzymes have a hydrophobic S1 binding pocket that is distinct from previously characterized enzymes in the family, indicative of novel substrate specificity. Further analysis of a structural homolog, YiiX (PDB 2if6) identified a fatty acid in the conserved hydrophobic pocket, thus providing additional insights into possible function of these novel enzymes

Structural and Sequence Analysis of Imelysin-Like Proteins Implicated in Bacterial Iron Uptake

Imelysin-like proteins define a superfamily of bacterial proteins that are likely involved in iron uptake. Members of this superfamily were previously thought to be peptidases and were included in the MEROPS family M75. We determined the first crystal structures of two remotely related, imelysin-like proteins. The Psychrobacter arcticus structure was determined at 2.15 Å resolution and contains the canonical imelysin fold, while higher resolution structures from the gut bacteria Bacteroides ovatus, in two crystal forms (at 1.25 Å and 1.44 Å resolution), have a circularly permuted topology. Both structures are highly similar to each other despite low sequence similarity and circular permutation. The all-helical structure can be divided into two similar four-helix bundle domains. The overall structure and the GxHxxE motif region differ from known HxxE metallopeptidases, suggesting that imelysin-like proteins are not peptidases. A putative functional site is located at the domain interface. We have now organized the known homologous proteins into a superfamily, which can be separated into four families. These families share a similar functional site, but each has family-specific structural and sequence features. These results indicate that imelysin-like proteins have evolved from a common ancestor, and likely have a conserved function

Utilization of a population health survey in policy and practice: a case study

BackgroundThere is growing interest by funding bodies and researchers in assessing the impact of research on real world policy and practice. Population health monitoring surveys provide an important source of data on the prevalence and patterns of health problems, but few empirical studies have explored if and how such data is used to influence policy or practice decisions. Here we provide a case study analysis of how the findings from an Australian population monitoring survey series of children&rsquo;s weight and weight-related behaviors (Schools Physical Activity and Nutrition Survey (SPANS)) have been used, and the key facilitators and barriers to their utilization.MethodsData collection included semi-structured interviews with the chief investigators (n = 3) and end-users (n = 9) of SPANS data to explore if, how and under what circumstances the survey findings had been used, bibliometric analysis and verification using documentary evidence. Data analysis involved thematic coding of interview data and triangulation with other data sources to produce case summaries of policy and practice impacts for each of the three survey years (1997, 2004, 2010). Case summaries were then reviewed and discussed by the authors to distil key themes on if, how and why the SPANS findings had been used to guide policy and practice.ResultsWe found that the survey findings were used for agenda setting (raising awareness of issues), identifying areas and target groups for interventions, informing new policies, and supporting and justifying existing policies and programs across a range of sectors. Reported factors influencing use of the findings were: i) the perceived credibility of survey findings; ii) dissemination strategies used; and, iii) a range of contextual factors.ConclusionsUsing a novel approach, our case study provides important new insights into how and under what circumstances population health monitoring data can be used to influence real world policy and practice. The findings highlight the importance of population monitoring programs being conducted by independent credible agencies, researchers engaging end-users from the inception of survey programs and utilizing existing policy networks and structures, and using a range of strategies to disseminate the findings that go beyond traditional peer review publications.<br /

Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice

The ability to genetically manipulate mice has led to rapid progress in our understanding of the roles of different gene products in human disease. Transgenic mice have often been created in the FVB/NJ (FVB) strain due to its high fecundity, while gene-targeted mice have been developed in the 129/SvJ-C57Bl/6J strains due to the capacity of 129/SvJ embryonic stem cells to facilitate germline transmission. Gene-targeted mice are commonly backcrossed into the C57Bl/6J (B6) background for comparison with existing data. Genetic modifiers have been shown to modulate mammary tumor latency in mouse models of breast cancer and it is commonly known that the FVB strain is susceptible to mammary tumors while the B6 strain is more resistant. Since gene-targeted mice in the B6 background are frequently bred into the polyomavirus middle T (PyMT) mouse model of breast cancer in the FVB strain, we have sought to understand the impact of the different genetic backgrounds on the resulting phenotype. We bred mice deficient in the inducible nitric oxide synthase (iNOS) until they were congenic in the PyMT model in the FVB and B6 strains. Our results reveal that the large difference in mean tumor latencies in the two backgrounds of 53 and 92 days respectively affect the ability to discern smaller differences in latency due to the Nos2 genetic mutation. Furthermore, the longer latency in the B6 strain enables a more detailed analysis of tumor formation indicating that individual tumor development is not stoichastic, but is initiated in the #1 glands and proceeds in early and late phases. NO production affects tumors that develop early suggesting an association of iNOS-induced NO with a more aggressive tumor phenotype, consistent with human clinical data positively correlating iNOS expression with breast cancer progression. An examination of lung metastases, which are significantly reduced in PyMT/iNOS(−/−) mice compared with PyMT/iNOS(+/+) mice only in the B6 background, is concordant with these findings. Our data suggest that PyMT in the B6 background provides a useful model for the study of inflammation-induced breast cancer