Dengue fever is the most important mosquito-borne viral disease of humans with more than 50 million cases estimated annually in more than 100 countries. Disturbingly, the geographic range of dengue ...is currently expanding and the severity of outbreaks is increasing. Control options for dengue are very limited and currently focus on reducing population abundance of the major mosquito vector, Aedes aegypti. These strategies are failing to reduce dengue incidence in tropical communities and there is an urgent need for effective alternatives. It has been proposed that endosymbiotic bacterial Wolbachia infections of insects might be used in novel strategies for dengue control. For example, the wMelPop-CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in stably transinfected lines. This life-shortening phenotype was predicted to reduce the potential for dengue transmission. The recent discovery that several Wolbachia infections, including wMelPop-CLA, can also directly influence the susceptibility of insects to infection with a range of insect and human pathogens has markedly changed the potential for Wolbachia infections to control human diseases. Here we describe the successful transinfection of A. aegypti with the avirulent wMel strain of Wolbachia, which induces the reproductive phenotype cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, providing optimal phenotypic effects for invasion. Under semi-field conditions, the wMel strain increased from an initial starting frequency of 0.65 to near fixation within a few generations, invading A. aegypti populations at an accelerated rate relative to trials with the wMelPop-CLA strain. We also show that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV-2) in A. aegypti, forming the basis of a practical approach to dengue suppression.
How extinct, non-avian theropod dinosaurs moved is a subject of considerable interest and controversy. A better understanding of non-avian theropod locomotion can be achieved by better understanding ...terrestrial locomotor biomechanics in their modern descendants, birds. Despite much research on the subject, avian terrestrial locomotion remains little explored in regards to how kinematic and kinetic factors vary together with speed and body size. Here, terrestrial locomotion was investigated in twelve species of ground-dwelling bird, spanning a 1,780-fold range in body mass, across almost their entire speed range. Particular attention was devoted to the ground reaction force (GRF), the force that the feet exert upon the ground. Comparable data for the only other extant obligate, striding biped, humans, were also collected and studied. In birds, all kinematic and kinetic parameters examined changed continuously with increasing speed, while in humans all but one of those same parameters changed abruptly at the walk-run transition. This result supports previous studies that show birds to have a highly continuous locomotor repertoire compared to humans, where discrete 'walking' and 'running' gaits are not easily distinguished based on kinematic patterns alone. The influences of speed and body size on kinematic and kinetic factors in birds are developed into a set of predictive relationships that may be applied to extinct, non-avian theropods. The resulting predictive model is able to explain 79-93% of the observed variation in kinematics and 69-83% of the observed variation in GRFs, and also performs well in extrapolation tests. However, this study also found that the location of the whole-body centre of mass may exert an important influence on the nature of the GRF, and hence some caution is warranted, in lieu of further investigation.
Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical ...hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10
) and thalamus (d=-0.148; P=4.27 × 10
) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10
) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.
The international Inherited Neuropathy Consortium (INC) was created with the goal of obtaining much needed natural history data for patients with Charcot-Marie-Tooth (CMT) disease. We analysed ...clinical and genetic data from patients in the INC to determine the distribution of CMT subtypes and the clinical impairment associated with them.
We analysed data from 1652 patients evaluated at 13 INC centres. The distribution of CMT subtypes and pathogenic genetic mutations were determined. The disease burden of all the mutations was assessed by the CMT Neuropathy Score (CMTNS) and CMT Examination Score (CMTES).
997 of the 1652 patients (60.4%) received a genetic diagnosis. The most common CMT subtypes were CMT1A/PMP22 duplication, CMT1X/GJB1 mutation, CMT2A/MFN2 mutation, CMT1B/MPZ mutation, and hereditary neuropathy with liability to pressure palsy/PMP22 deletion. These five subtypes of CMT accounted for 89.2% of all genetically confirmed mutations. Mean CMTNS for some but not all subtypes were similar to those previously reported.
Our findings confirm that large numbers of patients with a representative variety of CMT subtypes have been enrolled and that the frequency of achieving a molecular diagnosis and distribution of the CMT subtypes reflects those previously reported. Measures of severity are similar, though not identical, to results from smaller series. This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials. These data will provide a representative baseline for longitudinal studies of CMT.
ID number NCT01193075.
It is well known that the trapezoidal rule converges geometrically when applied to analytic functions on periodic intervals or the real line. The mathematics and history of this phenomenon axe ...reviewed, and it is shown that far from being a curiosity, it is linked with computational methods all across scientific computing, including algorithms related to inverse Laplace transforms, special functions, complex analysis, rational approximation, integral equations, and the computation of functions and eigenvalues of matrices and operators.
The Amazon basin hosts half the planet's remaining moist tropical forests, but they may be threatened in a warming world. Nevertheless, climate model predictions vary from rapid drying to modest ...wetting. Here we report that the catchment of the world's largest river is experiencing a substantial wetting trend since approximately 1990. This intensification of the hydrological cycle is concentrated overwhelmingly in the wet season driving progressively greater differences in Amazon peak and minimum flows. The onset of the trend coincides with the onset of an upward trend in tropical Atlantic sea surface temperatures (SST). This positive longer‐term correlation contrasts with the short‐term, negative response of basin‐wide precipitation to positive anomalies in tropical North Atlantic SST, which are driven by temporary shifts in the intertropical convergence zone position. We propose that the Amazon precipitation changes since 1990 are instead related to increasing atmospheric water vapor import from the warming tropical Atlantic.
Key Points
Intensification of Amazon Hydrological Cycle since 1990
Revealed by both river discharge and precipitation records
In parallel onset of tropical Atlantic warming offering explanation
The release of uranium and other transuranics into the environment, and their subsequent mobility, are subjects of intense public concern. Uranium dominates the inventory of most medium- and ...low-level radioactive waste sites and under oxic conditions is highly mobile as U(VI), the soluble uranyl dioxocation {UO2}2+. Specialist anaerobic bacteria are, however, able to reduce U(VI) to insoluble U(IV), offering a strategy for the bioremediation of uranium-contaminated groundwater and a potential mechanism for the biodeposition of uranium ores. Despite the environmental importance of U(VI) bioreduction, there is little information on the mechanism of this transformation. In the course of this study we used X-ray absorption spectroscopy (XAS) to show that the subsurface metal-reducing bacterium Geobacter sulfurreducens reduces U(VI) by a one-electron reduction, forming an unstable {UO2}+ species. The final, insoluble U(IV) product could be formed either through further reduction of U(V) or through its disproportionation. When G. sulfurreducens was challenged with the chemically analogous {NpO2}+, which is stable with respect to disproportionation, it was not reduced, suggesting that it is disproportionation of U(V) which leads to the U(IV) product. This surprising discrimination between U and Np illustrates the need for mechanistic understanding and care in devising in situ bioremediation strategies for complex wastes containing other redox-active actinides, including plutonium.
Microwave spectroscopy experiments have been performed on two quantum levels of a macroscopic superconducting loop with three Josephson junctions. Level repulsion of the ground state and first ...excited state is found where two classical persistent-current states with opposite polarity are degenerate, indicating symmetric and antisymmetric quantum superpositions of macroscopic states. The two classical states have persistent currents of 0.5 microampere and correspond to the center-of-mass motion of millions of Cooper pairs.
Carbon and other volatiles are transported from Earth’s surface into the mantle at subduction margins. The efficiency of this transfer has profound implications for the nature and scale of ...geochemical heterogeneities in Earth’s deep (mantle) and shallow (crustal) reservoirs, as well as Earth’s oxidation state. However, the proportion of volatiles released in the forearc and backarc are not well constrained compared to fluxes from the volcanic front. Here, we use helium and carbon isotope data from deeply sourced springs along two cross-arc transects to show that ~91% of carbon released from the slab/mantle beneath the Costa Rica forearc is sequestered within the crust by calcite deposition, and an additional ~3% is incorporated into biomass through microbial chemolithoautotrophy. We estimate that ~1.2 × 10(exp 8) to 1.3 × 10(exp 10) mol CO2/yr are released from the slab beneath the forearc, resulting in up to ~19% less carbon being transferred to Earth’s deep mantle than previously estimated.
Ejection fraction (EF) and end-systolic volume index (ESVI) are established predictors of outcomes following ST-segment elevation myocardial infarction (STEMI). We sought to assess the relative ...impact of infarct size, EF and ESVI on clinical outcomes and left ventricular (LV) remodelling.
Prospective cohort study.
Academic hospital in Chicago, USA.
122 patients with STEMI following acute percutaneous reperfusion.
Death, recurrent myocardial infarction (MI) and heart failure.
Cardiac magnetic resonance imaging was obtained within 1 week following STEMI in 122 subjects. ESVI, EF and infarct size were tested for the association with outcomes over 2 years in 113 subjects, and a repeat study was obtained 4 months later to assess LV remodelling in 91 subjects.
Acute infarct size correlated linearly with the initial ESVI (r = 0.69, p<0.001), end-diastolic volume index (EDVI) (r = 0.42, p<0.001) and EF (r = -0.75, p<0.001). All were independently associated with outcomes (one death, one recurrent MI and 16 heart failure admissions). However, infarct size was the only significant predictor of adverse outcomes (p<0.05) by multivariate analysis. The smallest infarct size tertile had an increased EF (49% (SD 8%) to 53% (6%); p = 0.002) and unchanged EDVI (p = 0.7). In contrast, subjects with the largest infarct tertile also had improved EF (32% (9%) to 36% (11%); p = 0.002) at the expense of a dramatic increase in EDVI (86 (19) to 95 (21) ml/m(2); p = 0.005).
Infarct size, EF and ESVI can predict the development of future cardiac events. Acute infarct size, which is independent of LV stunning and loading, directly relates to LV remodelling and is a stronger predictor of future events than measures of LV systolic performance.
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