Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar

More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself

Cardiac Alterations in Human African Trypanosomiasis (T.b. gambiense) with Respect to the Disease Stage and Antiparasitic Treatment

In Human African Trypanosomiasis (HAT), neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The electrocardiogram (ECG) is a tool to evaluate cardiac involvement and the risk of arrythmias. We analysed the ECG of 465 HAT patients and compared them with the ECG of 61 healthy volunteers. In HAT patients the QTc interval was prolonged. This comprises a risk of fatal arrhythmias if new drugs with antiarrhythmic potential will be used. Further, repolarization changes and low voltage were more frequent than in healthy controls. This could be explained by an inflammation of the heart. Treatment of HAT was associated with appearance of repolarization changes but not with a QTc prolongation. These changes appear to be associated with the disease, but not with a specific drug. The main conclusion of this study is that heart involvement is frequent in HAT and mostly well tolerated. However, it can become relevant, if new compounds with antiarrhythmic potential will be used

Results of the MAJORANA DEMONSTRATOR's Search for Double-Beta Decay of 76Ge to Excited States of 76Se

The MAJORANA DEMONSTRATOR is searching for double-beta decay of 76Ge to excited states (E.S.) in 76Se using a modular array of high purity Germanium detectors. 76Ge can decay into three E.S.s of 76Se. The E.S. decays have a clear event signature consisting of a ββ-decay with the prompt emission of one or two γ-rays, resulting in with high probability in a multi-site event. The granularity of the DEMONSTRATOR detector array enables powerful discrimination of this event signature from backgrounds. Using 21.3 kg-y of isotopic exposure, the DEMONSTRATOR has set world leading limits for each E.S. decay, with 90% CL lower half-life limits in the range of (0.56 2.1) ⋅ 1024 y. In particular, for the 2v transition to the first 0+ E.S. of 76Se, a lower half-life limit of 0.68 ⋅ 1024 at 90% CL was achieved

Molecular motors robustly drive active gels to a critically connected state

Living systems often exhibit internal driving: active, molecular processes drive nonequilibrium phenomena such as metabolism or migration. Active gels constitute a fascinating class of internally driven matter, where molecular motors exert localized stresses inside polymer networks. There is evidence that network crosslinking is required to allow motors to induce macroscopic contraction. Yet a quantitative understanding of how network connectivity enables contraction is lacking. Here we show experimentally that myosin motors contract crosslinked actin polymer networks to clusters with a scale-free size distribution. This critical behavior occurs over an unexpectedly broad range of crosslink concentrations. To understand this robustness, we develop a quantitative model of contractile networks that takes into account network restructuring: motors reduce connectivity by forcing crosslinks to unbind. Paradoxically, to coordinate global contractions, motor activity should be low. Otherwise, motors drive initially well-connected networks to a critical state where ruptures form across the entire network.Comment: Main text: 21 pages, 5 figures. Supplementary Information: 13 pages, 8 figure

ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value

Methicillin-resistant Staphylococcus aureus (MRSA) in rehabilitation and chronic-care-facilities: what is the best strategy?

BACKGROUND: The risk associated with methicillin-resistant Staphylococcus aureus (MRSA) has been decreasing for several years in intensive care departments, but is now increasing in rehabilitation and chronic-care-facilities (R-CCF). The aim of this study was to use published data and our own experience to discuss the roles of screening for MRSA carriers, the type of isolation to be implemented and the efficiency of chemical decolonization. DISCUSSION: Screening identifies over 90% of patients colonised with MRSA upon admission to R-CCF versus only 50% for intensive care units. Only totally dependent patients acquire MRSA. Thus, strict geographical isolation, as opposed to "social reinsertion", is clearly of no value. However, this should not lead to the abandoning of isolation, which remains essential during the administration of care. The use of chemicals to decolonize the nose and healthy skin appeared to be of some value and the application of this procedure could make technical isolation unnecessary in a non-negligible proportion of cases. SUMMARY: Given the increase in morbidity associated with MRSA observed in numerous hospitals, the emergence of a community-acquired disease associated with these strains and the evolution of glycopeptide-resistant strains, the voluntary application of a strategy combining screening, technical isolation and chemical decolonization in R-CCF appears to be an urgent matter of priority

Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi) from Ghana and Gabon

<p>Abstract</p> <p>Background</p> <p>Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials.</p> <p>Methods</p> <p>Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests.</p> <p>Results</p> <p>Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort.</p> <p>Conclusion</p> <p>The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low.</p> <p>Trial registration</p> <p>Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial) and NCT ID # 00167843 (Lambaréné Trial), <url>http://www.clinicaltrials.gov</url>.</p

Cost-effectiveness of intermittent preventive treatment of malaria in infants (IPTi) for averting anaemia in Gabon: a comparison between intention to treat and according to protocol analyses

ABSTRACT: BACKGROUND: In Gabon, the impact of intermittent preventive treatment of malaria in infants (IPTi) was not statistically significant on malaria reduction, but the impact on moderate anaemia was, with some differences between the intention to treat (ITT) and the according to protocol (ATP) trial analyses. Specifically, ATP was statistically significant, while ITT analysis was borderline. The main reason for the difference between ITT and ATP populations was migration. METHODS: This study estimates the cost-effectiveness of IPTi on the reduction of anaemia in Gabon, comparing results of the ITT and the ATP clinical trial analyses. Threshold analysis was conducted to identify when the intervention costs and protective efficacy of IPTi for the ATP cohort equalled the ITT cost-effectiveness ratio. RESULTS: Based on IPTi intervention costs, the cost per episode of moderate anaemia averted was US$12.88 (CI 95$11.30 (CI 95% 4.56, 26.66) using the ATP analysis. In order for the ATP results to equal the cost-effectiveness of ITT, total ATP intervention costs should rise from US$118.38 to US$134 or the protective efficacy should fall from 27% to 18.1%. The uncertainty surrounding the cost-effectiveness ratio using ITT trial results was higher than using the ATP results. CONCLUSIONS: Migration implies great challenges in the organization of health interventions that require repeat visits in Gabon. This was apparent in the study as the cost-effectiveness of IPTp-SP worsened when drop out from the prevention was taken into account. Despite such challenges, IPTi was both inexpensive and efficacious in averting cases of moderate anaemia in infant

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

<p>Abstract</p> <p>Background</p> <p>In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence.</p> <p>Method</p> <p>The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at <url>http://www.seleblat.org.</url> Patients are randomly assigned to selenium yeast (200 μg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study.</p> <p>Design</p> <p>The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial.</p> <p>Discussion</p> <p>This is the first report on a selenium randomized trial in bladder cancer patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00729287">NCT00729287</a></p

Patterns of GPS Tracks Suggest Nocturnal Foraging by Incubating Peruvian Pelicans (Pelecanus thagus)

Most seabirds are diurnal foragers, but some species may also feed at night. In Peruvian pelicans (Pelecanus thagus), the evidence for nocturnal foraging is sparse and anecdotal. We used GPS-dataloggers on five incubating Peruvian pelicans from Isla Lobos de Tierra, Perú, to examine their nocturnality, foraging movements and activities patterns at sea. All instrumented pelicans undertook nocturnal trips during a 5–7 day tracking period. Eighty-seven percent of these trips (n = 13) were strictly nocturnal, whereas the remaining occurred during the day and night. Most birds departed from the island after sunset and returned a few hours after sunrise. Birds traveled south of the island for single-day trips at a maximum range of 82.8 km. Overall, 22% of the tracking period was spent at sea, whereas the remaining time was spent on the island. In the intermediate section of the trip (between inbound and outbound commutes), birds spent 77% of the trip time in floating bouts interspersed by short flying bouts, the former being on average three times longer than the latter. Taken together, the high sinuosity of the bird's tracks during floating bouts, the exclusively nocturnal trips of most individuals, and the fact that all birds returned to the island within a few hours after sunrise suggest that pelicans were actively feeding at night. The nocturnal foraging strategy of Peruvian pelicans may reduce food competition with the sympatric and strictly diurnal Guanay cormorants (Phalacrocorax bougainvillii), Peruvian boobies (Sula variegata) and Blue-footed boobies (S. nebouxii), which were present on the island in large numbers. Likewise, plankton bioluminescence might be used by pelicans as indirect cues to locate anchovies during their upward migration at night. The foraging success of pelicans at night may be enhanced by seizing prey close to the sea surface using a sit-and-wait strategy