Population prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae in the Netherlands. should asymptomatic persons be tested during Population-based chlamydia Screening also for gonorrhoea or only if chlamydial infection is found?

BACKGROUND: Screening and active case finding for Chlamydia trachomatis (CT) is recommended to prevent reproductive morbidity. However insight in community prevalence of gonococcal infections and co-infections with Neisseria gonorrhoea (NG) is lacking. METHODS: Nested study within a large population-based Chlamydia Screening Pilot among 21.000 persons 15–29 year. All CT-positive (166) and a random sample of 605 CT-negative specimens were as well tested for gonococcal infection. RESULTS: Overall Chlamydia prevalence in the Pilot was 2.0% (95% CI: 1.7–2.3), highest in very urban settings (3.2%; 95% CI: 2.4–4.0) and dependent of several risk factors. Four gonococcal infections were found among 166 participants with CT infection (4/166 = 2.4%; 95% CI: 0.1%–4.7%). All four had several risk factors and reported symptoms. Among 605 CT-negative persons, no infection with NG could be confirmed. CONCLUSION: A low rate of co-infections and a very low community prevalence of gonococcal infections were found in this population based screening programme among young adults in the Netherlands. Population screening for asymptomatic gonococcal infections is not indicated in the Netherlands. Although co-infection with gonorrhoea among CT-positives is dependent on symptoms and well-known algorithms for elevated risks, we advise to test all CT-positives also for NG, whether symptomatic or asymptomatic

Impact of model improvements on 80 m wind speeds during the second Wind Forecast Improvement Project (WFIP2)

During the second Wind Forecast Improvement Project (WFIP2; October 2015&ndash;March 2017, held in the Columbia River Gorge and Basin area of eastern Washington and Oregon states), several improvements to the parameterizations used in the High Resolution Rapid Refresh (HRRR &ndash; 3&thinsp;km horizontal grid spacing) and the High Resolution Rapid Refresh Nest (HRRRNEST &ndash; 750&thinsp;m horizontal grid spacing) numerical weather prediction (NWP) models were tested during four 6-week reforecast periods (one for each season). For these tests the models were run in control (CNT) and experimental (EXP) configurations, with the EXP configuration including all the improved parameterizations. The impacts of the experimental parameterizations on the forecast of 80&thinsp;m wind speeds (wind turbine hub height) from the HRRR and HRRRNEST models are assessed, using observations collected by 19 sodars and three profiling lidars for comparison. Improvements due to the experimental physics (EXP vs. CNT runs) and those due to finer horizontal grid spacing (HRRRNEST vs. HRRR) and the combination of the two are compared, using standard bulk statistics such as mean absolute error (MAE) and mean bias error (bias). On average, the HRRR 80&thinsp;m wind speed MAE is reduced by 3&thinsp;%&ndash;4&thinsp;% due to the experimental physics. The impact of the finer horizontal grid spacing in the CNT runs also shows a positive improvement of 5&thinsp;% on MAE, which is particularly large at nighttime and during the morning transition. Lastly, the combined impact of the experimental physics and finer horizontal grid spacing produces larger improvements in the 80&thinsp;m wind speed MAE, up to 7&thinsp;%&ndash;8&thinsp;%. The improvements are evaluated as a function of the model's initialization time, forecast horizon, time of the day, season of the year, site elevation, and meteorological phenomena. Causes of model weaknesses are identified. Finally, bias correction methods are applied to the 80&thinsp;m wind speed model outputs to measure their impact on the improvements due to the removal of the systematic component of the errors. </div

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Structure, function and diversity of the healthy human microbiome

Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead