De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder

Genetics of disease, diagnosis and treatmen

Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980�2015: the Global Burden of Disease Study 2015

Background Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. Methods For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification. Findings Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95 uncertainty interval UI 3·1�3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5�2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6�40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7�1·9 million) in 2005, to 1·2 million deaths (1·1�1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. Interpretation Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. Funding Bill & Melinda Gates Foundation, and National Institute of Mental Health and National Institute on Aging, National Institutes of Health. © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licens

Stand-alone performance of a computer-assisted detection prototype for detection of acute pulmonary embolism: a multi-institutional comparison

OBJECTIVE: To assess whether the performance of a computer-assisted detection (CAD) algorithm for acute pulmonary embolism (PE) differs in pulmonary CT angiographies acquired at various institutions. METHODS: In this retrospective study, we included 40 consecutive scans with and 40 without PE from 3 institutions (n = 240) using 64-slice scanners made by different manufacturers (General Electric; Philips; Siemens). CAD markers were classified as true or false positive (FP) using independent evaluation by two readers and consultation of a third chest radiologist in discordant cases. Image quality parameters were subjectively scored using 4/5-point scales. Image noise and vascular enhancement were measured. Statistical analysis was done to correlate image quality of the three institutions with CAD stand-alone performance. RESULTS: Patient groups were comparable with respect to age (p = 0.22), accompanying lung disease (p = 0.12) and inpatient/outpatient ratio (p = 0.67). The sensitivity was 100% (34/34), 97% (37/38) and 92% (33/36), and the specificity was 18% (8/44), 15% (6/41) and 13% (5/39). Neither significantly differed between the institutions (p = 0.21 and p = 0.820, respectively). The mean number of FP findings (4.5, 6.2 and 3.7) significantly varied (p = 0.02 and p = 0.03), but median numbers (2, 3 and 3) were comparable. Image quality parameters were significantly associated with the number of FP findings (p<0.05) but not with sensitivity. After correcting for noise and vascular enhancement, the number of FPs did not significantly differ between the three institutions (p = 0.43). CONCLUSIONS: CAD stand-alone performance is independent of scanner type but strongly related to image quality and thus scanning protocols

Abdominal stent-graft collapse due to progression of a Stanford type B dissection.

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Pulmonary ground-glass nodules: Increase in mass as an early indicator of growth

Purpose: To compare manual measurements of diameter, volume, and mass of pulmonary ground-glass nodules (GGNs) to establish which method is best for identifying malignant GGNs by determining change across time. Materials and Methods: In this ethics committee - approved retrospective study, baseline and follow-up CT examinations of 52 GGNs detected in a lung cancer screening trial were included, resulting in 127 GGN data sets for evaluation. Two observers measured GGN diameter with electronic calipers, manually outlined GGNs to obtain volume and mass, and scored whether a solid component was present. Observer 1 repeated all measurements after 2 months. Coefficients of variation and limits of agreement were calculated by using Bland-Altman methods. In a subgroup of GGNs containing all resected malignant lesions, the ratio between intraobserver variability and growth (growth-to-variability ratio) was calculated for each measurement technique. In this subgroup, the mean time for growth to exceed the upper limit of agreement of each measurement technique was determined. Results: The κ values for intra- and interobserver agreement for identifying a solid component were 0.55 and 0.38, respectively. Intra- and interobserver coefficients of variation were smallest for GGN mass ( P<.001). Thirteen malignant GGNs were resected. Mean growth-to-variability ratios were 11, 28, and 35 for diameter, volume, and mass, respectively ( P = .03); mean times required for growth to exceed the upper limit of agreement were 715, 673, and 425 days, respectively ( P = .02). Conclusion: Mass measurements can enable detection of growth of GGNs earlier and are subject to less variability than are volume or diameter measurements