A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018

Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030

Development and psychometric evaluation of the sex fantasy questionnaire

Includes bibliographical references (pages [96]-104)Several theories regarding the etiology and maintenance of paraphilic behavior implicate deviant fantasizing as a primary factor. In addition, several treatment techniques incorporate fantasy alternation and alteration. Yet standardized measures of deviant (i.e., paraphilic) sexual fantasy are few, and those which exist appear inadequate regarding different aspects of their reliability and validity as measures of paraphilic fantasy material. The present study attempted to address this inadequacy. The purpose of this study was to develop a sexual fantasy questionnaire (the SFQ) which specifically targets paraphilic as well as non-paraphilic fantasies. A second goal of this study was to examine some of the psychometric properties of this sex fantasy questionnaire. Specifically, test-retest reliability, internal consistency, and construct, content, and convergent validities will be assessed. These goals were accomplished by administering the sex fantasy questionnaire to male sex offenders (inmates and out-patients) as well as a convenient comparison group of male college students. Subjects were administered the sex fantasy questionnaire on two occasions, in order to allow for estimation of the SFQ’s reliability. Additionally, comparisons were made between and within the different subject groups in order to estimate different types of the SFQ’s validity. Results indicated good internal consistency (mean alpha = .82) and good test-retest reliability (mean coefficient = .84). Evidence for the criterion validity of this measure was supported by the finding that child molesters scored significantly higher than normal controls on the child fantasy scale. Inmate offenders scored significantly higher than outpatient offenders or controls. Additionally, several hypotheses were generated regarding the relative scores of the three different groups based on sexual fantasy literature. Child molesters did not report more fantasies of sexual dysfunction and did report a similar number of normal fantasies as the normal controls. Inconsistent with some recent findings, convicted pedophiles did not report multiple-paraphilic fantasies.M.A. (Master of Arts