Pontocerebellar hypoplasia type 2: a neuropathological update

Pontocerebellar hypoplasia type 2 (PCH-2; MIM 277470), an autosomal recessive neurodegeneration with fetal onset, was studied in six autopsies with ages at death ranging between 1 and 22 years. Three patients were distantly related. A case of olivopontocerebellar hypoplasia (OPCH; MIM 225753) was studied for comparison. Typical findings are: short cerebellar folia with poor branching (“hypoplasia”), relative sparing of the vermis, sharply demarcated areas of full thickness loss of cerebellar cortex probably resulting from regression at an early stage of development, segmental loss of dentate nuclei with preserved islands and reactive changes, segmental loss in the inferior olivary nucleus with reactive changes, loss of ventral pontine nuclei with near absence of transverse pontine fibers and sparing of spinal anterior horn cells. Variable findings are: cystic cerebellar degeneration, found in two, with vascular changes limited to the cerebellum in one. Comparison to olivopontocerebellar hypoplasia (OPCH) strongly suggests a continuum of pathology between this disorder and PCH-2. Immunohistochemical evaluation of the endoplasmic reticulum stress response is negative. We conclude that the neuropathological findings in PCH-2 are sufficiently specific to enable an unequivocal diagnosis based on neuropathology

Vision and Foraging in Cormorants: More like Herons than Hawks?

Background Great cormorants (Phalacrocorax carbo L.) show the highest known foraging yield for a marine predator and they are often perceived to be in conflict with human economic interests. They are generally regarded as visually-guided, pursuit-dive foragers, so it would be expected that cormorants have excellent vision much like aerial predators, such as hawks which detect and pursue prey from a distance. Indeed cormorant eyes appear to show some specific adaptations to the amphibious life style. They are reported to have a highly pliable lens and powerful intraocular muscles which are thought to accommodate for the loss of corneal refractive power that accompanies immersion and ensures a well focussed image on the retina. However, nothing is known of the visual performance of these birds and how this might influence their prey capture technique. Methodology/Principal Findings We measured the aquatic visual acuity of great cormorants under a range of viewing conditions (illuminance, target contrast, viewing distance) and found it to be unexpectedly poor. Cormorant visual acuity under a range of viewing conditions is in fact comparable to unaided humans under water, and very inferior to that of aerial predators. We present a prey detectability model based upon the known acuity of cormorants at different illuminances, target contrasts and viewing distances. This shows that cormorants are able to detect individual prey only at close range (less than 1 m). Conclusions/Significance We conclude that cormorants are not the aquatic equivalent of hawks. Their efficient hunting involves the use of specialised foraging techniques which employ brief short-distance pursuit and/or rapid neck extension to capture prey that is visually detected or flushed only at short range. This technique appears to be driven proximately by the cormorant's limited visual capacities, and is analogous to the foraging techniques employed by herons

Limitations of student-driven formative assessment in a clinical clerkship. A randomised controlled trial

Background Teachers strive to motivate their students to be self-directed learners. One of the methods used is to provide online formative assessment material. The concept of formative assessment and use of these processes is heavily promoted, despite limited evidence as to their efficacy.Methods Fourth year medical students, in their first year of clinical work were divided into four groups. In addition to the usual clinical material, three of the groups were provided with some form of supplementary learning material. For two groups, this was provided as online formative assessment. The amount of time students spent on the supplementary material was measured, their opinion on learning methods was surveyed, and their performance in summative exams at the end of their surgical attachments was measured.Results The performance of students was independent of any educational intervention imposed by this study. Despite its ready availability and promotion, student use of the online formative tools was poor.Conclusion Formative learning is an ideal not necessarily embraced by students. If formative assessment is to work students need to be encouraged to participate, probably by implementing some form of summative assessment.Edward J Palmer and Peter G Devit

Estimating the burden of disease attributable to four selected environmental risk factors in South Africa

The first South African National Burden of Disease study quantified the underlying causes of premature mortality and morbidity experienced in South Africa in the year 2000. This was followed by a Comparative Risk Assessment to estimate the contributions of 17 selected risk factors to burden of disease in South Africa. This paper describes the health impact of exposure to four selected environmental risk factors: unsafe water, sanitation and hygiene; indoor air pollution from household use of solid fuels; urban outdoor air pollution and lead exposure.The study followed World Health Organization comparative risk assessment methodology. Population-attributable fractions were calculated and applied to revised burden of disease estimates (deaths and disability adjusted life years, [DALYs]) from the South African Burden of Disease study to obtain the attributable burden for each selected risk factor. The burden attributable to the joint effect of the four environmental risk factors was also estimated taking into account competing risks and common pathways. Monte Carlo simulation-modeling techniques were used to quantify sampling, uncertainty.Almost 24 000 deaths were attributable to the joint effect of these four environmental risk factors, accounting for 4.6% (95% uncertainty interval 3.8-5.3%) of all deaths in South Africa in 2000. Overall the burden due to these environmental risks was equivalent to 3.7% (95% uncertainty interval 3.4-4.0%) of the total disease burden for South Africa, with unsafe water sanitation and hygiene the main contributor to joint burden. The joint attributable burden was especially high in children under 5 years of age, accounting for 10.8% of total deaths in this age group and 9.7% of burden of disease.This study highlights the public health impact of exposure to environmental risks and the significant burden of preventable disease attributable to exposure to these four major environmental risk factors in South Africa. Evidence-based policies and programs must be developed and implemented to address these risk factors at individual, household, and community levels

Circular RNAs Are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types

Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence. By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order. Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs. Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells

The G-308A variant of the Tumor Necrosis Factor-α (TNF-α) gene is not associated with obesity, insulin resistance and body fat distribution

BACKGROUND: Tumor Necrosis Factor-α (TNF-α) has been implicated in the pathogenesis of insulin resistance and obesity. The increased expression of TNF-α in adipose tissue has been shown to induce insulin resistance, and a polymorphism at position -308 in the promoter region ofTNF-α has been shown to increase transcription of the gene in adipocytes. Aim of this study is to investigate the role of the G-308A TNFα variant in obesity and to study the possible influence of this mutation on body fat distribution and on measures of obesity (including Fat Free Mass, Fat Mass, basal metabolic rate), insulin resistance (measured as HOMA(IR)), and lipid abnormalities. The G-308A TNFα polymorphism has been studied in 115 patients with obesity (mean BMI 33.9 ± 0.5) and in 79 normal lean subjects (mean BMI 24.3 ± 0.3). METHODS: The G-308A variant, detected by PCR amplification and Nco-1 digestion, determines the loss of a restriction site resulting in a single band of 107 bp [the (A) allele]. RESULTS: The (A) allele frequencies of the G-308A TNFα polymorphism were 13.1% in the obese group and 14.6% in the lean subjects, with no significant difference between the two groups. Furthermore, no association was found with BMI classes, body fat distribution, HOMA(IR), and metabolic abnormalities. CONCLUSIONS: Our study did not detect any significant association of the G-308A TNFα polymorphism with obesity or with its clinical and metabolic abnormalities in this population. Our data suggests that, in our population, the G-308A TNFα polymorphism is unlikely to play a major role in the pathogenesis of these conditions

Different Patterns of Evolution in the Centromeric and Telomeric Regions of Group A and B Haplotypes of the Human Killer Cell Ig-Like Receptor Locus

The fast evolving human KIR gene family encodes variable lymphocyte receptors specific for polymorphic HLA class I determinants. Nucleotide sequences for 24 representative human KIR haplotypes were determined. With three previously defined haplotypes, this gave a set of 12 group A and 15 group B haplotypes for assessment of KIR variation. The seven gene-content haplotypes are all combinations of four centromeric and two telomeric motifs. 2DL5, 2DS5 and 2DS3 can be present in centromeric and telomeric locations. With one exception, haplotypes having identical gene content differed in their combinations of KIR alleles. Sequence diversity varied between haplotype groups and between centromeric and telomeric halves of the KIR locus. The most variable A haplotype genes are in the telomeric half, whereas the most variable genes characterizing B haplotypes are in the centromeric half. Of the highly polymorphic genes, only the 3DL3 framework gene exhibits a similar diversity when carried by A and B haplotypes. Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ∼6 million years ago, contemporaneously with the separation of human and chimpanzee ancestors. In contrast, the telomeric motifs that distinguish A and B haplotypes emerged more recently, ∼1.7 million years ago, before the emergence of Homo sapiens. Thus the centromeric and telomeric motifs that typify A and B haplotypes have likely been present throughout human evolution. The results suggest the common ancestor of A and B haplotypes combined a B-like centromeric region with an A-like telomeric region

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

The effect of leisure-time physical activity on the risk of acute myocardial infarction depending on Body Mass Index: a population-based case-control study

BACKGROUND: High body mass index (BMI) and lack of physical activity have been recognized as important risk factors for coronary heart disease. The aim of the present study was to evaluate whether leisure-time physical activity compensates for the increased risk of acute myocardial infarction associated with overweight and obesity. METHODS: Data from the SHEEP (Stockholm Heart Epidemiology Program) study were used. The SHEEP study is a large Swedish population-based case-control study, comprising 1204 male and 550 female cases, and 1538 male and 777 female controls, conducted in Stockholm County, Sweden, during the period 1992–1994. Odds ratios (OR), together with 95 % confidence intervals (95% CI), were calculated using unconditional logistic regression, as estimates of the relative risks. RESULTS: Regular leisure-time physical activity was associated with a decreased risk of myocardial infarction among lean, normal-weight and overweight subjects, but not among obese subjects. Obese (BMI ≥ 30) and physically active persons had an almost twofold risk of myocardial infarction, compared with normal-weight and sedentary persons (OR 1.85, 95% CI 1.07–3.18). The results were similar for men and women. CONCLUSION: While regular leisure-time physical activity seems to provide protection against myocardial infarction among lean, normal-weight and overweight subjects, this does not appear to be the case in obese subjects

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns