Patterns of progressive atrophy vary with age in Alzheimer's disease patients

Age is not only the greatest risk factor for Alzheimer's disease (AD) but also a key modifier of disease presentation and progression. Here, we investigate how longitudinal atrophy patterns vary with age in mild cognitive impairment (MCI) and AD. Data comprised serial longitudinal 1.5-T magnetic resonance imaging scans from 153 AD, 339 MCI, and 191 control subjects. Voxel-wise maps of longitudinal volume change were obtained and aligned across subjects. Local volume change was then modeled in terms of diagnostic group and an interaction between group and age, adjusted for total intracranial volume, white-matter hyperintensity volume, and apolipoprotein E genotype. Results were significant at p < 0.05 with family-wise error correction for multiple comparisons. An age-by-group interaction revealed that younger AD patients had significantly faster atrophy rates in the bilateral precuneus, parietal, and superior temporal lobes. These results suggest younger AD patients have predominantly posterior progressive atrophy, unexplained by white-matter hyperintensity, apolipoprotein E, or total intracranial volume. Clinical trials may benefit from adapting outcome measures for patient groups with lower average ages, to capture progressive atrophy in posterior cortices

Breast clinic and life style study BLLISS

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Subcortical brain atrophy persists even in HAART-regulated HIV disease

The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy

Anthropometric factors and breast cancer risk among urban and rural women in South India: a multicentric case–control study

Breast cancer (BC) incidence in India is approximately twice as high in urban women than in rural women, among whom we investigated the role of anthropometric factors and body size. The study was conducted at the Regional Cancer Centre, Trivandrum, and in three cancer hospitals in Chennai during 2002–2005. Histologically confirmed cases (n=1866) and age-matched controls (n=1873) were selected. Anthropometric factors were measured in standard ways. Information on body size at different periods of life was obtained using pictograms. Odds ratios (OR) of BC were estimated through logistic regression modelling. Proportion of women with body mass index (BMI)>25.0 kg/m2, waist size >85 cm and hip size >100 cm was significantly higher among urban than rural women. Risk was increased for waist size >85 cm (pre-menopausal: OR=1.24, 95% CI: 0.96–1.62; post-menopausal: 1.61, 95% CI: 1.22–2.12) and hip size >100 cm (pre-menopausal: OR=1.47, 95% CI: 1.05–2.06; post-menopausal 2.42, 95% CI: 1.72–3.41). Large body size at age 10 (OR=1.75, 95% CI: 1.01–3.03) and increased BMI (OR=1.33, 95% CI: 1.05–1.69 for 25.0–29.9 kg/m2 and OR=1.56, 95% CI: 1.03–2.35 for 30+ kg/m2) were associated with pre-menopausal BC risk. Our data support the hypotheses that increased anthropometric factors are risk factors of BC in India

The importance of sample size in marine megafauna tagging studies

Telemetry is a key, widely used tool to understand marine megafauna distribution, habitat use, behavior, and physiology; however, a critical question remains: “How many animals should be tracked to acquire meaningful data sets?” This question has wide-ranging implications including considerations of statistical power, animal ethics, logistics, and cost. While power analyses can inform sample sizes needed for statistical significance, they require some initial data inputs that are often unavailable. To inform the planning of telemetry and biologging studies of marine megafauna where few or no data are available or where resources are limited, we reviewed the types of information that have been obtained in previously published studies using different sample sizes. We considered sample sizes from one to >100 individuals and synthesized empirical findings, detailing the information that can be gathered with increasing sample sizes. We complement this review with simulations, using real data, to show the impact of sample size when trying to address various research questions in movement ecology of marine megafauna. We also highlight the value of collaborative, synthetic studies to enhance sample sizes and broaden the range, scale, and scope of questions that can be answered

Laparoscopic Sleeve Gastrectomy is a Safe and Effective Bariatric Procedure for the Lower BMI (35.0–43.0 kg/m2) Population

# The Author(s) 2010. This article is published with open access at Springerlink.com Background The laparoscopic vertical sleeve gastrectomy (LSG) is derived from the biliopancreatic diversion with duodenal switch operation (Marceau et al., Obes Surg 3:29

QTLs for height: results of a full genome scan in Dutch sibling pairs.

Height is a highly heritable, complex trait. At present, the genes responsible for the variation in height have not yet been identified. This paper summarizes the results of previous linkage studies and presents results of an additional linkage analysis. Using data from the Netherlands Twin Register, a sib-pair-based linkage analysis for adult height was conducted. For 513 sib-pairs from 174 families complete genome scans and adult height were available. The strongest evidence for linkage was found for a region on chromosome 6, near markers D6S1053 and D6S1031 (LOD = 2.32). This replicated previous findings in other data sets. LOD scores ranging from 1.53 to 2.04 were found for regions on chromosomes 1, 5, 8, 10, and 18. The region on chromosome 18 (LOD = 1.83) also corresponded with the results of previous studies. Several chromosomal regions are now implied in the variance in height, but further study is needed to draw definite conclusions with regard to the significance of these regions for adult heigh

Molecular diagnoses in the congenital malformations caused by ciliopathies cohort of the 100,000 Genomes Project

Background Primary ciliopathies represent a group of inherited disorders due to defects in the primary cilium, the ‘cell’s antenna’. The 100,000 Genomes Project was launched in 2012 by Genomics England (GEL), recruiting National Health Service (NHS) patients with eligible rare diseases and cancer. Sequence data were linked to Human Phenotype Ontology (HPO) terms entered by recruiting clinicians. Methods Eighty-three prescreened probands were recruited to the 100,000 Genomes Project suspected to have congenital malformations caused by ciliopathies in the following disease categories: Bardet-Biedl syndrome (n=45), Joubert syndrome (n=14) and ‘Rare Multisystem Ciliopathy Disorders’ (n=24). We implemented a bespoke variant filtering and analysis strategy to improve molecular diagnostic rates for these participants. Results We determined a research molecular diagnosis for n=43/83 (51.8%) probands. This is 19.3% higher than previously reported by GEL (n=27/83 (32.5%)). A high proportion of diagnoses are due to variants in non-ciliopathy disease genes (n=19/43, 44.2%) which may reflect difficulties in clinical recognition of ciliopathies. n=11/83 probands (13.3%) had at least one causative variant outside the tiers 1 and 2 variant prioritisation categories (GEL’s automated triaging procedure), which would not be reviewed in standard 100,000 Genomes Project diagnostic strategies. These include four structural variants and three predicted to cause non-canonical splicing defects. Two unrelated participants have biallelic likely pathogenic variants in LRRC45, a putative novel ciliopathy disease gene. Conclusion These data illustrate the power of linking large-scale genome sequence to phenotype information. They demonstrate the value of research collaborations in order to maximise interpretation of genomic data