Relative levels of natural and anthropogenic lead in recent Antarctic snow

Concentrations of lead have been measured by ultraclean isotope dilution mass spectrometry in large blocks of surface snow collected along a 433-km coast-interior axis in East Antarctica and near the geographic south pole. Slight contamination existed on the outside of the blocks, but concentration profiles from their exteriors to their interiors indicate that lead concentrations in the innermost parts of the blocks do represent the original concentrations in present-day Antarctic snow. Geographical variations of lead concentrations appear to be mainly due to local emissions from Dumont d'Urville and Amundsen Scott stations. The globally significant lead concentration in present-day Antarctic snow is found to be about 2 pg Pb/g. The corresponding value in Antarctic air is estimated to be about 7 pg Pb/m^3 STP, which is approximately fivefold larger than total natural lead contributed by soil dusts, volcanoes and sea salts. A tentative temporal curve of globally significant lead concentrations in Antarctic ice and snow for the last 13,000 years is given. It shows concentrations of about 0.4 pg Pb/g throughout most of the Holocene, with recent fivefold increases to about 2 pg Pb/g today. The general picture is then that four-fifths of total lead in the Antarctic troposphere today is anthropogenic

Detection of Trace Amounts of Toxic Metals in Environmental Samples by Laser-excited Atomic Fluorescence Spectrometry

Results for the direct determination of trace amounts of Pb and Cd in Antarctic and Greenland ancient ice and recent snow by laser-excited atomic fluorescence spectrometry (LEAFS) are presented. The whole procedure starting from field sampling, mechanical decontamination of the samples in an ultra-clean laboratory and final analysis of the decontaminated samples is described. The measured concentrations varied in the ranges 0.1–3 pg ml^(–1) for Cd and 0.3–30 pg ml^(–1) for Pb. The results for direct analysis by LEAFS agree favourable with those obtained by isotope dilution mass spectrometry and electrothermal atomic absorption spectrometry, which require time-consuming pre-treatment and pre-concentration stages

Exercise therapy, manual therapy, or both, for osteoarthritis of the hip or knee: a factorial randomised controlled trial protocol

<p>Abstract</p> <p>Background</p> <p>Non-pharmacological, non-surgical interventions are recommended as the first line of treatment for osteoarthritis (OA) of the hip and knee. There is evidence that exercise therapy is effective for reducing pain and improving function in patients with knee OA, some evidence that exercise therapy is effective for hip OA, and early indications that manual therapy may be efficacious for hip and knee OA. There is little evidence as to which approach is more effective, if benefits endure, or if providing these therapies is cost-effective for the management of this disorder. The MOA Trial (Management of OsteoArthritis) aims to test the effectiveness of two physiotherapy interventions for improving disability and pain in adults with hip or knee OA in New Zealand. Specifically, our primary objectives are to investigate whether:</p> <p>1. Exercise therapy versus no exercise therapy improves disability at 12 months;</p> <p>2. Manual physiotherapy versus no manual therapy improves disability at 12 months;</p> <p>3. Providing physiotherapy programmes in addition to usual care is more cost-effective than usual care alone in the management of osteoarthritis at 24 months.</p> <p>Methods</p> <p>This is a 2 × 2 factorial randomised controlled trial. We plan to recruit 224 participants with hip or knee OA. Eligible participants will be randomly allocated to receive either: (a) a supervised multi-modal exercise therapy programme; (b) an individualised manual therapy programme; (c) both exercise therapy and manual therapy; or, (d) no trial physiotherapy. All participants will continue to receive usual medical care. The outcome assessors, orthopaedic surgeons, general medical practitioners, and statistician will be blind to group allocation until the statistical analysis is completed. The trial is funded by Health Research Council of New Zealand Project Grants (Project numbers 07/199, 07/200).</p> <p>Discussion</p> <p>The MOA Trial will be the first to investigate the effectiveness and cost-effectiveness of providing physiotherapy programmes of this kind, for the management of pain and disability in adults with hip or knee OA.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry ref: ACTRN12608000130369.</p

Novel Common Genetic Susceptibility Loci for Colorectal Cancer

BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screenin

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour

Geochemical composition of snow samples from Antarctica, Greenland and northeast Canada

In this paper, we present new detailed data on the trace metal content of more than 200 shallow polar snow samples collected at various depths in numerous locations mainly in Antarctica and Greenland. The samples were collected in ultraclean plexiglass or teflon tubes from the walls of hand dug pits, using stringent contamination free techniques controlled by severe blank tests. They were then analysed for Na, Mg, K, Ca, Fe, Al, Mn, Pb, Cd, Cu, Zn and Ag in clean room conditions by flameless atomic absorption, after a preconcentration step (by non boiling evaporation in teflon bulbs) which includes dissolving any solid particles by concentrated nitric and hydrofluoric acids. The overall precision on the measured concentrations is of the order of 10 % for all the metals except Pb (20 %) and Cd (35 %), using 95 % confidence limits. The data obtained are compared with those published previously in the literature. Part of these previous data are shown to be erroneously too high, probably because of con-tamination problems both during field collection and analysis