PCB uptake and transfer to humans by lake trout

A mathematical model for contaminant uptake from food and water by fishes is combined with a model for yield as a function of fishing mortality in order to examine both the contaminant concentration in fishes and the amount of contaminant transferred to humans from fishes as functions of fishing mortality. The models are fitted to lake trout Salvelinus namaycush data from Lake Michigan, where there has been a persistent problem of PCB contamination. Transfer of contaminants from fishes to humans can be regulated through control of fishing. The concentration of contaminant decreases exponentially as fishing mortality increases because fishing reduces the number of older individuals in the population and concentration is a function of age. The amount of contaminant transferred from a fish population to humans increases to a maximum and then begins to decrease as fishing effort increases. The maximum rate of transfer occurs at a relatively low level of fishing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24956/1/0000383.pd

On the Reliability of Meta-Analytic Reviews

The article addresses the issue of intercoder reliability in meta-analyses. The current practice of reporting a single, mean intercoder agreement score in meta-analytic research leads to systematic bias and overestimates the true reliability. An alternative approach is recommended in which average intercoder agreement scores or other reliability statistics are calculated within clusters of coded variables. These clusters form a hierarchy in which the correctness of coding decisions at a given level of the hierarchy is contingent on decisions made at higher levels. Two separate studies of intercoder agreement in meta-analysis are presented to assess the validity of the model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67840/2/10.1177_0193841X9301700303.pd

A stochastic model for heart rate fluctuations

Normal human heart rate shows complex fluctuations in time, which is natural, since heart rate is controlled by a large number of different feedback control loops. These unpredictable fluctuations have been shown to display fractal dynamics, long-term correlations, and 1/f noise. These characterizations are statistical and they have been widely studied and used, but much less is known about the detailed time evolution (dynamics) of the heart rate control mechanism. Here we show that a simple one-dimensional Langevin-type stochastic difference equation can accurately model the heart rate fluctuations in a time scale from minutes to hours. The model consists of a deterministic nonlinear part and a stochastic part typical to Gaussian noise, and both parts can be directly determined from the measured heart rate data. Studies of 27 healthy subjects reveal that in most cases the deterministic part has a form typically seen in bistable systems: there are two stable fixed points and one unstable one.Comment: 8 pages in PDF, Revtex style. Added more dat

A dynamical model of lipoprotein metabolism

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Important marine areas for the conservation of northern rockhopper penguins within the Tristan da Cunha Exclusive Economic Zone

The designation of Marine Protected Areas has become an important approach to conserving marine ecosystems that relies on robust information on the spatial distribution of biodiversity. We used GPS tracking data to identify marine Important Bird and Biodiversity Areas (IBAs) for the endangered northern rockhopper penguin Eudyptes moseleyi within the Exclusive Economic Zone (EEZ) of Tristan da Cunha in the South Atlantic. Penguins were tracked throughout their breeding season from 3 of the 4 main islands in the Tristan da Cunha group. Foraging trips remained largely within the EEZ, with the exception of those from Gough Island during the incubation stage. We found substantial variability in trip duration and foraging range among breeding stages and islands, consistent use of areas among years and spatial segregation of the areas used by neighbouring islands. For colonies with no or insufficient tracking data, we defined marine IBAs based on the mean maximum foraging range and merged the areas identified to propose IBAs around the Tristan da Cunha archipelago and Gough Island. The 2 proposed marine IBAs encompass 2% of Tristan da Cunha’s EEZ, and are used by all northern rockhopper penguins breeding in the Tristan da Cunha group, representing ~90% of the global population. Currently, the main threat to northern rockhopper penguins within the Tristan da Cunha EEZ is marine pollution from shipping, and the risk of this would be reduced by declaring waters within 50 nautical miles of the coast as ‘Areas To Be Avoided

Phase 1–2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS

BACKGROUND Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations. METHODS We conducted a phase 1–2 ascending-dose trial evaluating tofersen in adults with ALS due to SOD1 mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned in a 3:1 ratio to receive five doses of tofersen or placebo, administered intrathecally for 12 weeks. The primary outcomes were safety and pharmacokinetics. The secondary outcome was the change from baseline in the cerebrospinal fluid (CSF) SOD1 concentration at day 85. Clinical function and vital capacity were measured. RESULTS A total of 50 participants underwent randomization and were included in the analyses; 48 participants received all five planned doses. Lumbar puncture–related adverse events were observed in most participants. Elevations in CSF white-cell count and protein were reported as adverse events in 4 and 5 participants, respectively, who received tofersen. Among participants who received tofersen, one died from pulmonary embolus on day 137, and one from respiratory failure on day 152; one participant in the placebo group died from respiratory failure on day 52. The difference at day 85 in the change from baseline in the CSF SOD1 concentration between the tofersen groups and the placebo group was 2 percentage points (95% confidence interval [CI], −18 to 27) for the 20-mg dose, −25 percentage points (95% CI, −40 to −5) for the 40-mg dose, −19 percentage points (95% CI, −35 to 2) for the 60-mg dose, and −33 percentage points (95% CI, −47 to −16) for the 100-mg dose. CONCLUSIONS In adults with ALS due to SOD1 mutations, CSF SOD1 concentrations decreased at the highest concentration of tofersen administered intrathecally over a period of 12 weeks. CSF pleocytosis occurred in some participants receiving tofersen. Lumbar puncture–related adverse events were observed in most participants. (Funded by Biogen; ClinicalTrials.gov number, NCT02623699. opens in new tab; EudraCT number, 2015-004098-33. opens in new tab.

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe