Variable sediment oxygen uptake in response to dynamic forcing

Seiche-induced turbulence and the vertical distribution of dissolved oxygen above and within the sediment were analyzed to evaluate the sediment oxygen uptake rate (JO2), diffusive boundary layer thickness (δDBL), and sediment oxic zone depth (zmax) in situ. High temporal-resolution microprofiles across the sediment-water interface and current velocity data within the bottom boundary layer in a medium-sized mesotrophic lake were obtained during a 12-h field study. We resolved the dynamic forcing of a full 8-h seiche cycle and evaluated JO2 from both sides of the sediment-water interface. Turbulence (characterized by the energy dissipation rate, ε), the vertical distribution of dissolved oxygen across the sediment-water interface (characterized by δDBL and zmax), JO2, and the sediment oxygen consumption rate (RO2) are all strongly correlated in our freshwater system. Seiche-induced turbulence shifted from relatively active (ε = 1.2 × 10-8 W kg-1) to inactive (ε = 7.8 × 10-12 W kg-1). In response to this dynamic forcing, δDBL increased from 1.0 mm to the point of becoming undefined, zmax decreased from 2.2 to 0.3 mm as oxygen was depleted from the sediment, and JO2 decreased from 7.0 to 1.1 mmol m-2 d-1 over a time span of hours. JO2 and oxygen consumption were found to be almost equivalent (within ~ 5% and thus close to steady state), with RO2 adjusting rapidly to changes in JO2. Our results reveal the transient nature of sediment oxygen uptake and the importance of accurately characterizing turbulence when estimating JO2

Mixed-ethnicity face shape and attractiveness in humans

Many studies show agreement within and between populations and cultures for general judgments of facial attractiveness. Studies that have examined the attractiveness of specific traits have also highlighted cross-cultural differences for factors such as symmetry, averageness, and masculinity. One trait that should be preferred across cultures is heterozygosity. Indeed, several studies suggest that mixed ethnicity, in terms of appearing to possess a mixture of traits from different human population groups, may be found attractive, which could reflect preferences for heterozygosity. We examined preferences for manipulated face shape associated with different populations in both Europeans (Britain) and Africans (Guinea-Bissau). We found that mixed-ethnicity face shapes were more attractive than enhanced single-ethnicity face shape across both populations. These results are consistent with evolutionary theories suggesting individuals should prefer heterozygosity in partners because facial cues to mixed-ethnicity are likely to indicate diverse genes compared to cues that indicate a face belongs to a single particular culture or population

Probabilistic 21st and 22nd Century Sea-Level Projections at a Global Network of Tide-Gauge Sites

Sea-level rise due to both climate change and non-climatic factors threatens coastal settlements, infrastructure, and ecosystems. Projections of mean global sea-level (GSL) rise provide insufficient information to plan adaptive responses; local decisions require local projections that accommodate different risk tolerances and time frames and that can be linked to storm surge projections. Here we present a global set of local sea-level (LSL) projections to inform decisions on timescales ranging from the coming decades through the 22nd century. We provide complete probability distributions, informed by a combination of expert community assessment, expert elicitation, and process modeling. Between the years 2000 and 2100, we project a very likely (90% probability) GSL rise of 0.51.2m under representative concentration pathway (RCP) 8.5, 0.40.9m under RCP 4.5, and 0.30.8m under RCP 2.6. Site-to-site differences in LSL projections are due to varying non-climatic background uplift or subsidence, oceanographic effects, and spatially variable responses of the geoid and the lithosphere to shrinking land ice. The Antarctic ice sheet (AIS) constitutes a growing share of variance in GSL and LSL projections. In the global average and at many locations, it is the dominant source of variance in late 21st century projections, though at some sites oceanographic processes contribute the largest share throughout the century. LSL rise dramatically reshapes flood risk, greatly increasing the expected number of 1-in-10 and 1-in-100 year events

Prevalence of Transmitted Drug Resistance and Impact of Transmitted Resistance on Treatment Success in the German HIV-1 Seroconverter Cohort

BACKGROUND: The aim of this study is to analyse the prevalence of transmitted drug resistance, TDR, and the impact of TDR on treatment success in the German HIV-1 Seroconverter Cohort. METHODS: Genotypic resistance analysis was performed in treatment-naïve study patients whose sample was available 1,312/1,564 (83.9% October 2008). A genotypic resistance result was obtained for 1,276/1,312 (97.3%). The resistance associated mutations were identified according to the surveillance drug resistance mutations list recommended for drug-naïve patients. Treatment success was determined as viral suppression below 500 copies/ml. RESULTS: Prevalence of TDR was stable at a high level between 1996 and 2007 in the German HIV-1 Seroconverter Cohort (N = 158/1,276; 12.4%; CI(wilson) 10.7-14.3; p(for trend) = 0.25). NRTI resistance was predominant (7.5%) but decreased significantly over time (CI(Wilson): 6.2-9.1, p(for trend) = 0.02). NNRTI resistance tended to increase over time (NNRTI: 3.5%; CI(Wilson): 2.6-4.6; p(for trend)= 0.07), whereas PI resistance remained stable (PI: 3.0%; CI(Wilson): 2.1-4.0; p(for trend) = 0.24). Resistance to all drug classes was frequently caused by singleton resistance mutations (NRTI 55.6%, PI 68.4%, NNRTI 99.1%). The majority of NRTI-resistant strains (79.8%) carried resistance-associated mutations selected by the thymidine analogues zidovudine and stavudine. Preferably 2NRTI/1PIr combinations were prescribed as first line regimen in patients with resistant HIV as well as in patients with susceptible strains (susceptible 45.3%; 173/382 vs. resistant 65.5%; 40/61). The majority of patients in both groups were treated successfully within the first year after ART-initiation (susceptible: 89.9%; 62/69; resistant: 7/9; 77.8%). CONCLUSION: Overall prevalence of TDR remained stable at a high level but trends of resistance against drug classes differed over time. The significant decrease of NRTI-resistance in patients newly infected with HIV might be related to the introduction of novel antiretroviral drugs and a wider use of genotypic resistance analysis prior to treatment initiation

Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom

Background: The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial. Methods and Results: We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death. Conclusions: A TRV≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531

Haplotype Reconstruction Error as a Classical Misclassification Problem: Introducing Sensitivity and Specificity as Error Measures

BACKGROUND: Statistically reconstructing haplotypes from single nucleotide polymorphism (SNP) genotypes, can lead to falsely classified haplotypes. This can be an issue when interpreting haplotype association results or when selecting subjects with certain haplotypes for subsequent functional studies. It was our aim to quantify haplotype reconstruction error and to provide tools for it. METHODS AND RESULTS: By numerous simulation scenarios, we systematically investigated several error measures, including discrepancy, error rate, and R(2), and introduced the sensitivity and specificity to this context. We exemplified several measures in the KORA study, a large population-based study from Southern Germany. We find that the specificity is slightly reduced only for common haplotypes, while the sensitivity was decreased for some, but not all rare haplotypes. The overall error rate was generally increasing with increasing number of loci, increasing minor allele frequency of SNPs, decreasing correlation between the alleles and increasing ambiguity. CONCLUSIONS: We conclude that, with the analytical approach presented here, haplotype-specific error measures can be computed to gain insight into the haplotype uncertainty. This method provides the information, if a specific risk haplotype can be expected to be reconstructed with rather no or high misclassification and thus on the magnitude of expected bias in association estimates. We also illustrate that sensitivity and specificity separate two dimensions of the haplotype reconstruction error, which completely describe the misclassification matrix and thus provide the prerequisite for methods accounting for misclassification

Characterization of the patterns of drug-resistance mutations in newly diagnosed HIV-1 infected patients naïve to the antiretroviral drugs

<p>Abstract</p> <p>Background</p> <p>The transmission of HIV-1 drug-resistant strains in drug naive patients may seriously compromise the efficacy of a first-line antiretroviral treatment. To better define this problem, a study in a cohort of newly diagnosed HIV-1 infected individuals has been conducted. This study is aimed to assess the prevalence and the patterns of the mutations recently associated with transmitted drug resistance in the reverse transcriptase (RT) and in protease (PR) of HIV-1.</p> <p>Methods</p> <p>Prevalence of transmitted drug resistant strains is determined in 255 newly diagnosed HIV-1 infected patients enrolled in different counselling and testing (CT) centres in Central Italy; the Avidity Index (AI) on the first available serum sample is also used to estimate time since infection. Logistic regression models are used to determine factors associated with infection by drug resistant HIV-1 strains.</p> <p>Results</p> <p>The prevalence of HIV-1 strains with at least one major drug resistance mutation is 5.9% (15/255); moreover, 3.9% (10/255) of patients is infected with HIV nucleoside reverse transcriptase inhibitor (NRTI)-resistant viruses, 3.5% (9/255) with HIV non-NRTI-resistant viruses and 0.4% (1/255) with HIV protease inhibitor (PI)-resistant viruses. Most importantly, almost half (60.0%) of patients carries HIV-1 resistant strains with more than one major drug resistance mutation. In addition, patients who had acquired HIV through homosexual intercourses are more likely to harbour a virus with at least one primary resistance mutation (OR 7.7; 95% CI: 1.7–35.0, P = 0.008).</p> <p>Conclusion</p> <p>The prevalence of drug resistant HIV-1 strains among newly diagnosed individuals in Central Italy is consistent with the data from other European countries. Nevertheless, the presence of drug-resistance HIV-1 mutations in complex patterns highlights an additional potential risk for public health and strongly supports the extension of wide genotyping to newly diagnosed HIV-1 infected patients.</p

Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods. Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer dev

Single Collateral Reconstructions Reveal Distinct Phases of Corticospinal Remodeling after Spinal Cord Injury

Injuries to the spinal cord often result in severe functional deficits that, in case of incomplete injuries, can be partially compensated by axonal remodeling. The corticospinal tract (CST), for example, responds to a thoracic transection with the formation of an intraspinal detour circuit. The key step for the formation of the detour circuit is the sprouting of new CST collaterals in the cervical spinal cord that contact local interneurons. How individual collaterals are formed and refined over time is incompletely understood