Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

Background: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods: We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D ,75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results: Clinical characteristics of 26 patients were: age 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616 to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to 3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Trial Registration: ClinicalTrials.gov NCT0200571

Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit

OBJECTIVES: Faecal serine proteases (FSPs) may play a role in irritable bowel syndrome with diarrhoea (IBS-D), but their origin is unclear. We aimed to structurally characterise them and define the impact of colonic cleansing and transit time. DESIGN: Faecal samples were obtained from 30 healthy volunteers (HV) and 79 patients with IBS-D participating in a trial of ondansetron versus placebo. Colonic transit was measured using radio-opaque markers. Samples were also obtained from 24 HV before and after colonic cleansing with the osmotic laxative MoviPrep. FSPs were purified from faecal extracts using benzamidine-Sepharose affinity chromatography. SDS-PAGE profiled components were identified using trypsinolysis and tandem mass spectrometry. Functional protease activity in faecal extracts was measured using a colorimetric assay based on the proteolysis of azo-casein. RESULTS: Protein analysis identified the most abundant FSPs as being of human origin and probably derived from pancreatic juice. Functional assays showed increased faecal protease (FP) and amylase in patients with IBS-D compared with HV. Those with higher amylase had significantly higher FP and greater anxiety. FP activity correlated negatively with whole gut transit in patients with IBS-D (Spearman r=−0.32, p=0.005) and HV (r=−0.55, p=0.014). Colon cleansing caused a significant rise in FP activity in HV from a baseline of median (IQR) 253 (140–426) to 1031 (435–2296), levels similar to those seen in patients with IBS-D. FSP activity correlated positively with days/week with urgency. CONCLUSIONS: The most abundant FSPs are of human origin. Rapid transit through the colon and/or decreased (possibly bacterial) proteolytic degradation increases their faecal concentration and could contribute to visceral hypersensitivity in patients with IBS-D. CLINICALTRIALS.GOV: NCT00745004

Quantifying and contextualising cyclone-driven, extreme flood magnitudes in bedrock-influenced dryland rivers

In many drylands worldwide, rivers are subjected to episodic, extreme flood events and associated sediment stripping. These events may trigger transformations from mixed bedrock-alluvial channels characterised by high geomorphic and ecological diversity towards more dominantly bedrock channels with lower diversity. To date, hydrological and hydraulic data has tended to be limited for these bedrock-influenced dryland rivers, but recent advances in high-resolution data capture are enabling greater integration of different investigative approaches, which is helping to inform assessment of river response to changing hydroclimatic extremes. Here, we use field and remotely sensed data along with a novel 2D hydrodynamic modelling approach to estimate, for the first time, peak discharges that occurred during cyclone-driven floods in the Kruger National Park, eastern South Africa, in January 2012. We estimate peak discharges in the range of 4470 to 5630 m3s-1 for the Sabie River (upstream catchment area 5715 km2) and 14 407 to 16 772 m3s-1 for the Olifants River (upstream catchment area 53 820 km2). These estimates place both floods in the extreme category for each river, with the Olifants peak discharge ranking among the largest recorded or estimated for any southern African river in the last couple of hundred years. On both rivers, the floods resulted in significant changes to dryland river morphology, sediment flux and vegetation communities. Our modelling approach may be transferable to other sparsely gauged or ungauged rivers, and to sites where palaeoflood evidence is preserved. Against a backdrop of mounting evidence for global increases in hydroclimatic extremes, additional studies will help to refine our understanding of the relative and synergistic impacts of high-magnitude flood events on dryland river development

Morphodynamic simulation of sediment deposition patterns on a recently stripped bedrock anastomosed channel

Some mixed bedrock-alluvial dryland rivers are known to undergo cycles of alluvial building during low flow periods, punctuated by stripping events during rare high magnitude flows. We focus on the Olifants River, Kruger National Park, South Africa, and present 2-D morphodynamic simulations of hydraulics and sed-iment deposition patterns over an exposed bedrock anastomosed pavement. We examine the assumptions un-derlying a previous conceptual model, namely that sedimentation occurs preferentially on bedrock highs. Our modelling results and local field observations in fact show that sediment thicknesses are greater over bedrock lows, suggesting these are the key loci for deposition, barform initiation and island building. During peak flows, velocities in the topographic lows tend to be lower than in intermediate topographic areas. It is likely that inter-mediate topographic areas supply sediment to the topographic lows at this flow stage, which is then deposited in the lows on the falling limb of the hydrograph as velocities reduce. Subsequent vegetation establishment on de-posits in the topographic lows is likely to play a key role in additional sedimentation and vegetation succession, both through increasing the cohesive strength of alluvial units and by capturing new sediments and propagules

Morphodynamics of bedrock-influenced dryland rivers during extreme floods: insights from the Kruger National Park, South Africa

High-magnitude flood events are among the world’s most widespread and significant natural hazards and play a key role in shaping river channel–floodplain morphology and riparian ecology. Development of conceptual and quantitative models for the response of bedrock-influenced dryland rivers to such floods is of growing scientific and practical importance, but in many instances, modeling efforts are hampered by a paucity of relevant field data. Here, we combined extensive aerial and field data with hydraulic modeling to document erosion, deposition, and vegetation changes that have occurred during two successive, cyclonedriven, extreme floods along a 50-km-long reach of the bedrock-influenced Sabie River in the Kruger National Park, eastern South Africa.  Aerial light detection and ranging (LiDAR) data and photography obtained after extreme floods in 2000 and 2012 (discharges >4000 m3 s–1) were used to generate digital elevation models (DEMs) and provide the boundary conditions for hydraulic modeling (flow shear stresses for three discharges up to 5000 m3 s–1). For the Sabie River study reach as a whole, DEM differencing revealed that the 2012 floods resulted in net erosion of ~1,219,000 m3 (~53 mm m–2). At the subreach scale, however, more complex spatial patterns of erosion, deposition, and vegetation change occurred, as largely controlled by differences in channel type (e.g., degree of bedrock and alluvial exposure) and changing hydraulic conditions (shear stresses widely >1000 N m–2 across the river around peak flow). The impact of flood sequencing and relative flood magnitude is also evident; in some subreaches, remnant islands and vegetation that survived the 2000 floods were removed during the smaller 2012 floods owing to their wider exposure to flow. These findings were synthesized to refine and extend a conceptual model of bedrock-influenced dryland river response that incorporates flood sequencing, channel type, and sediment supply influences. In particular, with some climate change projections indicating the potential for future increases in the frequency of cyclone-generated extreme floods in eastern southern Africa, the Sabie and other Kruger National Park rivers may experience additional sediment stripping and vegetation removal. Over time, such rivers may transition to a more bedrock-dominated state, with significant implications for ecological structure and function and associated ecosystem services. These findings contribute to an improved analysis of the Kruger National Park rivers in particular, but also to growing appreciation of the global diversity of dryland rivers and the relative and synergistic impacts of extreme floods

Anastomosing reach control on hydraulics and sediment distribution on the Sabie River, South Africa

Many of the large rivers in southern Africa exhibit a strong bedrock influence, being characterised by a channel incised 10–20 m into ancient planation surfaces. Under alluviated conditions, these channels display downstream sequences of channel types, including alluvial single thread, braided, bedrock anastomosed, mixed anastomosed, and pool-rapid. This sequence of channel types has been reviewed using aerial imagery for the Sabie River, which drains a 6320km2 catchment and flows across the Lowveld of South Africa. Prior to 2000, the river exhibited a downstream sequence of channel types that broadly alternated from alluvial single thread or braided to bedrock anstomosed or mixed anastomosed, with pool-rapid types also present locally. Unconsolidated (predominantly sandy) alluvial sediments were significantly eroded by cyclone-driven extreme floods both in 2000 and 2012, exposing the underlying bedrock template along considerable lengths of the river. This bedrock-dominated state was surveyed using aerial LIDAR following the 2012 flood. Long profile data revealed the strong gradient control exerted by the bedrock anastomosed and mixed anastomosed channel types, which creates hydraulic conditions suitable for deposition in the upstream alluvial reaches. The role of these bedrock-influenced channel types on hydraulic character is also revealed in the results of 2D hydraulic modelling of moderate flood (3500 m3s-1) as the bedrock or mixed anastomosed channel type is drowned out, resulting in dramatically increased velocities along the entire river and a general stripping of unconsolidated and consolidated sediments regardless of initial channel type or location

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of pp collision data at s√ = 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a W boson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be 0.96+0.26−0.30 at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about the s−s¯¯¯ quark asymmetry

Search for dark matter in events with heavy quarks and missing transverse momentum in pp collisions with the ATLAS detector

This article reports on a search for dark matterpair production in association with bottom or top quarks in20.3fb−1ofppcollisions collected at√s=8TeVbytheATLAS detector at the LHC. Events with large missing trans-verse momentum are selected when produced in associationwith high-momentum jets of which one or more are identifiedas jets containingb-quarks. Final states with top quarks areselected by requiring a high jet multiplicity and in some casesa single lepton. The data are found to be consistent with theStandard Model expectations and limits are set on the massscale of effective field theories that describe scalar and tensorinteractions between dark matter and Standard Model par-ticles. Limits on the dark-matter–nucleon cross-section forspin-independent and spin-dependent interactions are alsoprovided. These limits are particularly strong for low-massdark matter. Using a simplified model, constraints are set onthe mass of dark matter and of a coloured mediator suitableto explain a possible signal of annihilating dark matter

A pilot study of alterations in oxidized angiotensinogen and antioxidants in pre-eclamptic pregnancy

© 2020, The Author(s). The oxidation status of angiotensinogen (AGT) may have a critical role in pre-eclampsia. We used a validated, quantitative, mass spectrometry-based method to measure the oxidized and total AGT levels in plasma of pre-eclamptic women (n = 17), normotensive-matched controls (n = 17), and healthy non-pregnant women (n = 10). Measurements of plasma glutathione peroxidase (GPx) activity and serum selenium concentrations were performed as markers of circulating antioxidant capacity. Higher proportions of oxidized AGT in plasma from pre-eclamptic women compared to matched normotensive pregnant controls (P = 0.006), whilst maintaining a similar total plasma AGT concentration were found. In the pre-eclamptic group, blood pressure were correlated with the proportion of oxidized AGT; no such correlation was seen in the normotensive pregnant women. Plasma GPx was inversely correlated with oxidized AGT, and there was an inverse association between serum selenium concentration and the proportion of oxidized AGT. This is the first time that oxidized AGT in human plasma has been linked directly to antioxidant status, providing a mechanism for the enhanced oxidative stress in pre-eclampsia. We now provide pathophysiological evidence that the conversion of the reduced form of AGT to its more active oxidized form is associated with inadequate antioxidant status and could indeed contribute to the hypertension of pre-eclampsia