Chemical weathering outputs from the flood plain of the Ganga

Transport of sediment across riverine flood plains contributes a significant but poorly constrained fraction of the total chemical weathering fluxes from rapidly eroding mountain belts which has impor- tant implications for chemical fluxes to the oceans and the impact of orogens on long term climate. We report water and bedload chemical analyses from the Ganges flood-plain, a major transit reservoir of sediment from the Himalayan orogen. Our data comprise six major southern tributaries to the Ganga, 31 additional analyses of major rivers from the Himalayan front in Nepal, 79 samples of the Ganga collected close to the mouth below the Farakka barrage every two weeks over three years and 67 water and 8 bedload samples from tributaries confined to the Ganga flood plain,. The flood plain tributaries are characterised by a shallow d 18 O - dD array, compared to the meteoric water line, with a low dD excess from evaporative loss from the flood plain which is mirrored in the higher dD excess of the mountain rivers in Nepal. The stable-isotope data confirms that the waters in the flood plain tributaries are domi- nantly derived from flood plain rainfall and not by redistribution of waters from the mountains. The flood plain tributaries are chemically distinct from the major Himalayan rivers. They can be divided into two groups. Tributaries from a small area around the Kosi river have 87 Sr/ 86 Sr ratios > 0.75 and molar Na/Ca ratios as high as 6. Tributaries from the rest of the flood plain have 87 Sr/ 86 Sr ratios <0.74 and most have Na/Ca ratios <1. One sample of the Gomti river and seven small adjacent tributaries have elevated Na concentrations likely caused by dissolution of Na carbonate salts. The compositions of the carbonate and silicate components of the sediments were determined from sequential leaches of floodplain bedloads and these were used to partition the dissolved cation load between silicate and car- bonate sources. The 87 Sr/ 86 Sr and Sr/Ca ratios of the carbonate inputs were derived from the ace- tic-acid leach compositions and silicate Na/Ca and 87 Sr/ 86 Sr ratios derived from silicate residues from leaching. Modelling based on the 87 Sr/ 86 Sr and Sr/Ca ratios of the carbonate inputs and 87 Sr/ 86 Sr ratios of the silicates indicates that the flood plain waters have lost up to 70% of their Ca (average ~ 50%) to precipitation of secondary calcite which is abundant as a diagenetic cement in the flood plain sedi- ments. 31% of the Sr, 8% of the Ca and 45% of the Mg are calculated to be derived from silicate miner- als. Because of significant evaporative loss of water across the flood plain, and in the absence of hy- drological data for flood plain tributaries, chemical weathering fluxes from the flood plain are best calculated by mass balance of the Na, K, Ca, Mg, Sr, SO 4 and 87 Sr/ 86 Sr compositions of the inputs, comprising the flood plain tributaries, Himalayan rivers and southern rivers, with the chemical dis- charge in the Ganga at Farakka. The calculated fluxes from the flood plain for Na, K, Ca and Mg are within error of those estimated from changes in sediment chemistry across the flood plain (Lupker et al., 2012, Geochemica Cosmochimica Acta). Flood plain weathering supplies between 33 and 48% of the major cation and Sr fluxes and 58% of the alkalinity flux carried by the Ganga at Farakka which compares with 24% supplied by Himalayan rivers and 18% by the southern tributaries

Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants.

To evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL) in very low birth weight (VLBW) infants. Exposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age &lt; 32 weeks and/or with a birthweight &lt; 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth. We identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78). The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6-13.2) and the control group (median 7.9 mg/kg, Q1-Q3 0-12.8, p = 0.47). The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58). Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls. The impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment

High natural erosion rates are the backdrop for enhanced anthropogenic soil erosion in the Middle Hills of Nepal

Although agriculturally accelerated soil erosion is implicated in the unsustainable environmental degradation of mountain environments, such as in the Himalaya, the effects of land use can be challenging to quantify in many mountain settings because of the high and variable natural background rates of erosion. In this study, we present new long-term denudation rates, derived from cosmogenic 10Be analysis of quartz in river sediment from the Likhu Khola, a small agricultural river basin in the Middle Hills of central Nepal. Calculated long-term denudation rates, which reflect background natural erosion processes over 1000+ years prior to agricultural intensification, are similar to present-day sediment yields and to soil loss rates from terraces that are well maintained. Similarity in short- and long-term catchment-wide erosion rates for the Likhu is consistent with data from elsewhere in the Nepal Middle Hills but contrasts with the very large increases in short-term erosion rates seen in agricultural catchments in other steep mountain settings. Our results suggest that the large sediment fluxes exported from the Likhu and other Middle Hills rivers in the Himalaya are derived in large part from natural processes, rather than from soil erosion as a result of agricultural activity. Catchment-scale erosional fluxes may be similar over short and long timescales if both are dominated by mass wasting sources such as gullies, landslides, and debris flows (e.g., as is evident in the landslide-dominated Khudi Khola of the Nepal High Himalaya, based on compiled data). As a consequence, simple comparison of catchment-scale fluxes will not necessarily pinpoint land use effects on soils where these are only a small part of the total erosion budget, unless rates of mass wasting are also considered. Estimates of the mass wasting contribution to erosion in the Likhu imply catchment-averaged soil production rates on the order of ~ 0.25–0.35 mm yr−1, though rates of mass wasting are poorly constrained. The deficit between our best estimates for soil production rates and measurements of soil loss rates supports conclusions from previous studies that terraced agriculture in the Likhu may not be associated with a large systematic soil deficit, at least when terraces are well maintained, but that poorly managed terraces, forest, and scrubland may lead to rapid depletion of soil resources

Long-Term Potentiation: One Kind or Many?

Do neurobiologists aim to discover natural kinds? I address this question in this chapter via a critical analysis of classification practices operative across the 43-year history of research on long-term potentiation (LTP). I argue that this 43-year history supports the idea that the structure of scientific practice surrounding LTP research has remained an obstacle to the discovery of natural kinds

Orally active antischistosomal early leads identified from the open access malaria box.

BACKGROUND: Worldwide hundreds of millions of schistosomiasis patients rely on treatment with a single drug, praziquantel. Therapeutic limitations and the threat of praziquantel resistance underline the need to discover and develop next generation drugs. METHODOLOGY: We studied the antischistosomal properties of the Medicines for Malaria Venture (MMV) malaria box containing 200 diverse drug-like and 200 probe-like compounds with confirmed in vitro activity against Plasmodium falciparum. Compounds were tested against schistosomula and adult Schistosoma mansoni in vitro. Based on in vitro performance, available pharmacokinetic profiles and toxicity data, selected compounds were investigated in vivo. PRINCIPAL FINDINGS: Promising antischistosomal activity (IC50: 1.4-9.5 µM) was observed for 34 compounds against schistosomula. Three compounds presented IC50 values between 0.8 and 1.3 µM against adult S. mansoni. Two promising early leads were identified, namely a N,N'-diarylurea and a 2,3-dianilinoquinoxaline. Treatment of S. mansoni infected mice with a single oral 400 mg/kg dose of these drugs resulted in significant worm burden reductions of 52.5% and 40.8%, respectively. CONCLUSIONS/SIGNIFICANCE: The two candidates identified by investigating the MMV malaria box are characterized by good pharmacokinetic profiles, low cytotoxic potential and easy chemistry and therefore offer an excellent starting point for antischistosomal drug discovery and development

Dissolved noble gases and stable isotopes as tracers of preferential fluid flow along faults in the Lower Rhine Embayment, Germany

Groundwater in shallow unconsolidated sedimentary aquifers close to the Bornheim fault in the Lower Rhine Embayment (LRE), Germany, has relatively low δ2H and δ18O values in comparison to regional modern groundwater recharge, and 4He concentrations up to 1.7 × 10−4 cm3 (STP) g–1 ± 2.2 % which is approximately four orders of magnitude higher than expected due to solubility equilibrium with the atmosphere. Groundwater age dating based on estimated in situ production and terrigenic flux of helium provides a groundwater residence time of ∼107 years. Although fluid exchange between the deep basal aquifer system and the upper aquifer layers is generally impeded by confining clay layers and lignite, this study’s geochemical data suggest, for the first time, that deep circulating fluids penetrate shallow aquifers in the locality of fault zones, implying  that sub-vertical fluid flow occurs along faults in the LRE. However, large hydraulic-head gradients observed across many faults suggest that they act as barriers to lateral groundwater flow. Therefore, the geochemical data reported here also substantiate a conduit-barrier model of fault-zone hydrogeology in unconsolidated sedimentary deposits, as well as corroborating the concept that faults in unconsolidated aquifer systems can act as loci for hydraulic connectivity between deep and shallow aquifers. The implications of fluid flow along faults in sedimentary basins worldwide are far reaching and of particular concern for carbon capture and storage (CCS) programmes, impacts of deep shale gas recovery for shallow groundwater aquifers, and nuclear waste storage sites where fault zones could act as potential leakage pathways for hazardous fluids

Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance

Confusion and dependence in uses of history

Many people argue that history makes a special difference to the subjects of biology and psychology, and that history does not make this special difference to other parts of the world. This paper will show that historical properties make no more or less of a difference to biology or psychology than to chemistry, physics, or other sciences. Although historical properties indeed make a certain kind of difference to biology and psychology, this paper will show that historical properties make the same kind of difference to geology, sociology, astronomy, and other sciences. Similarly, many people argue that nonhistorical properties make a special difference to the nonbiological and the nonpsychological world. This paper will show that nonhistorical properties make the same difference to all things in the world when it comes to their causal behavior and that historical properties make the same difference to all things in the world when it comes to their distributions. Although history is special, it is special in the same way to all parts of the worl

An investigation of the structural requirements for ATP hydrolysis and DNA cleavage by the EcoKI Type I DNA restriction and modification enzyme

Type I DNA restriction and modification enzym

A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes

A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different Type II enzymes now identified and provides a system for naming the putative genes found by sequence analysis of microbial genomes