Toxicity of dietary methylmercury to fish: Derivation of ecologically meaningful threshold concentrations

Threshold concentrations associated with adverse effects of dietary exposure to methylmercury (MeHg) were derived from published results of laboratory studies on a variety of fish species. Adverse effects related to mortality were uncommon, whereas adverse effects related to growth occurred only at dietary MeHg concentrations exceeding 2.5 µg g −1 wet weight. Adverse effects on behavior of fish had a wide range of effective dietary concentrations, but generally occurred above 0.5 µg g −1 wet weight. In contrast, effects on reproduction and other subclinical endpoints occurred at dietary concentrations that were much lower (<0.2 µg g −1 wet wt). Field studies generally lack information on dietary MeHg exposure, yet available data indicate that comparable adverse effects have been observed in wild fish in environments corresponding to high and low MeHg contamination of food webs and are in agreement with the threshold concentrations derived here from laboratory studies. These thresholds indicate that while differences in species sensitivity to MeHg exposure appear considerable, chronic dietary exposure to low concentrations of MeHg may have significant adverse effects on wild fish populations but remain little studied compared to concentrations in mammals or birds. Environ. Toxicol. Chem. 2012; 31: 1536–1547. © 2012 SETACPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92130/1/etc_1859_sm_SupplReferences.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/92130/2/1859_ftp.pd

Enhanced activation of the left inferior frontal gyrus in deaf and dyslexic adults during rhyming

Hearing developmental dyslexics and profoundly deaf individuals both have difficulties processing the internal structure of words (phonological processing) and learning to read. In hearing non-impaired readers, the development of phonological representations depends on audition. In hearing dyslexics, many argue, auditory processes may be impaired. In congenitally profoundly deaf individuals, auditory speech processing is essentially absent. Two separate literatures have previously reported enhanced activation in the left inferior frontal gyrus in both deaf and dyslexic adults when contrasted with hearing non-dyslexics during reading or phonological tasks. Here, we used a rhyme judgement task to compare adults from these two special populations to a hearing non-dyslexic control group. All groups were matched on non-verbal intelligence quotient, reading age and rhyme performance. Picture stimuli were used since this requires participants to generate their own phonological representations, rather than have them partially provided via text. By testing well-matched groups of participants on the same task, we aimed to establish whether previous literatures reporting differences between individuals with and without phonological processing difficulties have identified the same regions of differential activation in these two distinct populations. The data indicate greater activation in the deaf and dyslexic groups than in the hearing non-dyslexic group across a large portion of the left inferior frontal gyrus. This includes the pars triangularis, extending superiorly into the middle frontal gyrus and posteriorly to include the pars opercularis, and the junction with the ventral precentral gyrus. Within the left inferior frontal gyrus, there was variability between the two groups with phonological processing difficulties. The superior posterior tip of the left pars opercularis, extending into the precentral gyrus, was activated to a greater extent by deaf than dyslexic participants, whereas the superior posterior portion of the pars triangularis extending into the ventral pars opercularis, was activated to a greater extent by dyslexic than deaf participants. Whether these regions play differing roles in compensating for poor phonological processing is not clear. However, we argue that our main finding of greater inferior frontal gyrus activation in both groups with phonological processing difficulties in contrast to controls suggests greater reliance on the articulatory component of speech during phonological processing when auditory processes are absent (deaf group) or impaired (dyslexic group). Thus, the brain appears to develop a similar solution to a processing problem that has different antecedents in these two populations

CCAT-prime: a novel telescope for submillimeter astronomy

The CCAT-prime telescope is a 6-meter aperture, crossed-Dragone telescope, designed for millimeter and sub-millimeter wavelength observations. It will be located at an altitude of 5600 meters, just below the summit of Cerro Chajnantor in the high Atacama region of Chile. The telescope's unobscured optics deliver a field of view of almost 8 degrees over a large, flat focal plane, enabling it to accommodate current and future instrumentation fielding >100k diffraction-limited beams for wavelengths less than a millimeter. The mount is a novel design with the aluminum-tiled mirrors nested inside the telescope structure. The elevation housing has an integrated shutter that can enclose the mirrors, protecting them from inclement weather. The telescope is designed to co-host multiple instruments over its nominal 15 year lifetime. It will be operated remotely, requiring minimum maintenance and on-site activities due to the harsh working conditions on the mountain. The design utilizes nickel-iron alloy (Invar) and carbon-fiber-reinforced polymer (CFRP) materials in the mirror support structure, achieving a relatively temperature-insensitive mount. We discuss requirements, specifications, critical design elements, and the expected performance of the CCAT-prime telescope. The telescope is being built by CCAT Observatory, Inc., a corporation formed by an international partnership of universities. More information about CCAT and the CCAT-prime telescope can be found at www.ccatobservatory.org.Comment: Event: SPIE Astronomical Telescope + Instrumentation, 2018, Austin, Texas, USA; Proceedings Volume 10700, Ground-based and Airborne Telescopes VII; 107005X (2018

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

The Potential for Enhancing the Power of Genetic Association Studies in African Americans through the Reuse of Existing Genotype Data

We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African-American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study

Durvalumab (MEDI 4736) in combination with extended neoadjuvant regimens in rectal cancer : a study protocol of a randomised phase II trial (PRIME-RT)

Acknowledgements We are grateful to Mr George Davidson and Ms Monica Jeffers for their input with writing the PRIME-RT protocol and patient information sheet. This study is co-sponsored by the University of Glasgow and NHS Greater Glasgow and Clyde. Funding PRIME-RT is funded by Astrazeneca and receives core funding from CRUK Clinical Trials Unit Glasgow for the purposes of trial set-up and data collection. The trial is co-sponsored by the University Of Glasgow and NHS Greater Glasgow and Clyde.Peer reviewedPublisher PD

A core outcome set for studies evaluating interventions to prevent and/or treat delirium for adults requiring an acute care hospital admission : an international key stakeholder informed consensus study

Abstract Background Trials of interventions to prevent or treat delirium in adults in an acute hospital setting report heterogeneous outcomes. Our objective was to develop international consensus among key stakeholders for a core outcome set (COS) for future trials of interventions to prevent and/or treat delirium in adults with an acute care hospital admission and not admitted to an intensive care unit. Methods A rigorous COS development process was used including a systematic review, qualitative interviews, modified Delphi consensus process, and in-person consensus using nominal group technique (registration http://www.comet - initiative.org/studies/details/796 ). Participants in qualitative interviews were delirium survivors or family members. Participants in consensus methods comprised international representatives from three stakeholder groups: researchers, clinicians, and delirium survivors and family members. Results Item generation identified 8 delirium-specific outcomes and 71 other outcomes from 183 studies, and 30 outcomes from 18 qualitative interviews, including 2 that were not extracted from the systematic review. De-duplication of outcomes and formal consensus processes involving 110 experts including researchers (N = 32), clinicians (N = 63), and delirium survivors and family members (N = 15) resulted in a COS comprising 6 outcomes: delirium occurrence and reoccurrence, delirium severity, delirium duration, cognition, emotional distress, and health-related quality of life. Study limitations included exclusion of non-English studies and stakeholders and small representation of delirium survivors/family at the in-person consensus meeting. Conclusions This COS, endorsed by the American and Australian Delirium Societies and European Delirium Association, is recommended for future clinical trials evaluating delirium prevention or treatment interventions in adults presenting to an acute care hospital and not admitted to an intensive care unit

Measurement of the lepton charge asymmetry in W-boson decays produced in p-pbar collisions

We describe a measurement of the charge asymmetry of leptons from W boson decays in the rapidity range 0 enu, munu events from 110+/-7 pb^{-1}of data collected by the CDF detector during 1992-95. The asymmetry data constrain the ratio of d and u quark momentum distributions in the proton over the x range of 0.006 to 0.34 at Q2 \approx M_W^2. The asymmetry predictions that use parton distribution functions obtained from previously published CDF data in the central rapidity region (0.0<|y_l|<1.1) do not agree with the new data in the large rapidity region (|y_l|>1.1).Comment: 13 pages, 3 tables, 1 figur

Population Substructure and Control Selection in Genome-Wide Association Studies

Determination of the relevance of both demanding classical epidemiologic criteria for control selection and robust handling of population stratification (PS) represents a major challenge in the design and analysis of genome-wide association studies (GWAS). Empirical data from two GWAS in European Americans of the Cancer Genetic Markers of Susceptibility (CGEMS) project were used to evaluate the impact of PS in studies with different control selection strategies. In each of the two original case-control studies nested in corresponding prospective cohorts, a minor confounding effect due to PS (inflation factor λ of 1.025 and 1.005) was observed. In contrast, when the control groups were exchanged to mimic a cost-effective but theoretically less desirable control selection strategy, the confounding effects were larger (λ of 1.090 and 1.062). A panel of 12,898 autosomal SNPs common to both the Illumina and Affymetrix commercial platforms and with low local background linkage disequilibrium (pair-wise r2<0.004) was selected to infer population substructure with principal component analysis. A novel permutation procedure was developed for the correction of PS that identified a smaller set of principal components and achieved a better control of type I error (to λ of 1.032 and 1.006, respectively) than currently used methods. The overlap between sets of SNPs in the bottom 5% of p-values based on the new test and the test without PS correction was about 80%, with the majority of discordant SNPs having both ranks close to the threshold. Thus, for the CGEMS GWAS of prostate and breast cancer conducted in European Americans, PS does not appear to be a major problem in well-designed studies. A study using suboptimal controls can have acceptable type I error when an effective strategy for the correction of PS is employed