A multi-institutional study of outcomes in stage I–III uterine carcinosarcoma

To evaluate the use of adjuvant therapy after primary surgery for stage I–III uterine carcinosarcoma (CS)

Countries with delayed COVID-19 introduction - characteristics, drivers, gaps, and opportunities.

BACKGROUND: Three months after the first reported cases, COVID-19 had spread to nearly 90% of World Health Organization (WHO) member states and only 24 countries had not reported cases as of 30 March 2020. This analysis aimed to 1) assess characteristics, capability to detect and monitor COVID-19, and disease control measures in these 24 countries, 2) understand potential factors for the reported delayed COVID-19 introduction, and 3) identify gaps and opportunities for outbreak preparedness, particularly in low and middle-income countries (LMICs). We collected and analyzed publicly available information on country characteristics, COVID-19 testing, influenza surveillance, border measures, and preparedness activities in these countries. We also assessed the association between the temporal spread of COVID-19 in all countries with reported cases with globalization indicator and geographic location. RESULTS: Temporal spreading of COVID-19 was strongly associated with countries' globalization indicator and geographic location. Most of the 24 countries with delayed COVID-19 introduction were LMICs; 88% were small island or landlocked developing countries. As of 30 March 2020, only 38% of these countries reported in-country COVID-19 testing capability, and 71% reported conducting influenza surveillance during the past year. All had implemented two or more border measures, (e.g., travel restrictions and border closures) and multiple preparedness activities (e.g., national preparedness plans and school closing). CONCLUSIONS: Limited testing capacity suggests that most of the 24 delayed countries may have lacked the capability to detect and identify cases early through sentinel and case-based surveillance. Low global connectedness, geographic isolation, and border measures were common among these countries and may have contributed to the delayed introduction of COVID-19 into these countries. This paper contributes to identifying opportunities for pandemic preparedness, such as increasing disease detection, surveillance, and international collaborations. As the global situation continues to evolve, it is essential for countries to improve and prioritize their capacities to rapidly prevent, detect, and respond, not only for COVID-19, but also for future outbreaks

Application of Homozygosity Haplotype Analysis to Genetic Mapping with High-Density SNP Genotype Data

BACKGROUND: In families segregating a monogenic genetic disorder with a single disease gene introduction, patients share a mutation-carrying chromosomal interval with identity-by-descent (IBD). Such a shared chromosomal interval or haplotype, surrounding the actual pathogenic mutation, is typically detected and defined by multipoint linkage and phased haplotype analysis using microsatellite or SNP genotype data. High-density SNP genotype data presents a computational challenge for conventional genetic analyses. A novel non-parametric method termed Homozygosity Haplotype (HH) was recently proposed for the genome-wide search of the autosomal segments shared among patients using high density SNP genotype data. METHODOLOGY/PRINCIPAL FINDINGS: The applicability and the effectiveness of HH in identifying the potential linkage of disease causative gene with high-density SNP genotype data were studied with a series of monogenic disorders ascertained in eastern Canadian populations. The HH approach was validated using the genotypes of patients from a family affected with a rare autosomal dominant disease Schnyder crystalline corneal dystrophy. HH accurately detected the approximately 1 Mb genomic interval encompassing the causative gene UBIAD1 using the genotypes of only four affected subjects. The successful application of HH to identify the potential linkage for a family with pericentral retinal disorder indicates that HH can be applied to perform family-based association analysis by treating affected and unaffected family members as cases and controls respectively. A new strategy for the genome-wide screening of known causative genes or loci with HH was proposed, as shown the applications to a myoclonus dystonia and a renal failure cohort. CONCLUSIONS/SIGNIFICANCE: Our study of the HH approach demonstrates that HH is very efficient and effective in identifying potential disease linked region. HH has the potential to be used as an efficient alternative approach to sequencing or microsatellite-based fine mapping for screening the known causative genes in genetic disease study

Media Reporting of Health Interventions: Signs of Improvement, but Major Problems Persist

Background: Studies have persistently shown deficiencies in medical reporting by the mainstream media. We have been monitoring the accuracy and comprehensiveness of medical news reporting in Australia since mid 2004. This analysis of more than 1200 stories in the Australian media compares different types of media outlets and examines reporting trends over time. Methods and Findings: Between March 2004 and June 2008 1230 news stories were rated on a national medical news monitoring web site, Media Doctor Australia. These covered a variety of health interventions ranging from drugs, diagnostic tests and surgery to dietary and complementary therapies. Each story was independently assessed by two reviewers using ten criteria. Scores were expressed as percentages of total assessable items deemed satisfactory according to a coding guide. Analysis of variance was used to compare mean scores and Fishers exact test to compare proportions. Trends over time were analysed using un-weighted linear regression analysis. Broadsheet newspapers had the highest average satisfactory scores: 58% (95% CI 56–60%), compared with tabloid newspapers and online news outlets, 48% (95% CI 44–52) and 48% (95% CI 46–50) respectively. The lowest scores were assigned to stories broadcast by human interest/current affairs television programmes (average score 33% (95% CI 28–38)). While there was a non- significant increase in average scores for all outlets, a significant improvement was seen in the online news media: a rise of 5.1% (95%CI 1.32, 8.97; P 0.009). Statistically significant improvements were seen in coverage of the potential harms of interventions, the availability of treatment or diagnostic options, and accurate quantification of benefits. Conclusion: Although the overall quality of medical reporting in the general media remains poor, this study showed modest improvements in some areas. However, the most striking finding was the continuing very poor coverage of health news by commercial current affairs television programs

A global biodiversity observing system to unite monitoring and guide action

The rate and extent of global biodiversity change is surpassing our ability to measure, monitor and forecast trends. We propose an interconnected worldwide system of observation networks — a global biodiversity observing system (GBiOS) — to coordinate monitoring worldwide and inform action to reach international biodiversity targets.acceptedVersio

WISE x SuperCOSMOS photometric redshift catalog: 20 million galaxies over 3pi steradians

We cross-match the two currently largest all-sky photometric catalogs, mid-infrared WISE and SuperCOSMOS scans of UKST/POSS-II photographic plates, to obtain a new galaxy sample that covers 3pi steradians. In order to characterize and purify the extragalactic dataset, we use external GAMA and SDSS spectroscopic information to define quasar and star loci in multicolor space, aiding the removal of contamination from our extended-source catalog. After appropriate data cleaning we obtain a deep wide-angle galaxy sample that is approximately 95% pure and 90% complete at high Galactic latitudes. The catalog contains close to 20 million galaxies over almost 70% of the sky, outside the Zone of Avoidance and other confused regions, with a mean surface density of over 650 sources per square degree. Using multiwavelength information from two optical and two mid-IR photometric bands, we derive photometric redshifts for all the galaxies in the catalog, using the ANNz framework trained on the final GAMA-II spectroscopic data. Our sample has a median redshift of z_{med} = 0.2 but with a broad dN/dz reaching up to z>0.4. The photometric redshifts have a mean bias of |delta_z|~10^{-3}, normalized scatter of sigma_z = 0.033 and less than 3% outliers beyond 3sigma_z. Comparison with external datasets shows no significant variation of photo-z quality with sky position. Together with the overall statistics, we also provide a more detailed analysis of photometric redshift accuracy as a function of magnitudes and colors. The final catalog is appropriate for `all-sky' 3D cosmology to unprecedented depths, in particular through cross-correlations with other large-area surveys. It should also be useful for source pre-selection and identification in forthcoming surveys such as TAIPAN or WALLABY

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.The Fenland Study is funded by the Medical Research Council (MC_U106179471) and Wellcome Trust