The Physiological Changes That Occur Post Endovascular Renal Denervation in Dialysis Patients

Sympathetic neural activation is markedly increased in end-stage kidney disease (ESKD). Catheter-based renal denervation (RDN) reduces sympathetic over-activity and blood pressure in resistant hypertension. The effect of renal denervation on sympathetic neural activation and left ventricular mass was investigated in patients with ESKD. Nine ESKD (six haemodialysis and three peritoneal dialysis) patients with a dialysis vintage of ≥11 months were treated with RDN (EnligHTN system). Data were obtained on a non-dialysis day; at baseline, one (1M), three (3M) and twelve months (12M) post-RDN. At baseline, sympathetic neural activation measured by muscle sympathetic nervous activity (MSNA) and plasma norepinephrine concentrations were markedly elevated. Left ventricular hypertrophy (LVH) was evident in eight of the nine patients. At 12M post-RDN, blind analysis revealed that MSNA frequency (-12.2 bursts·min-1, 95% CI [-13.6, -10.7]) and LV mass (-27 g·m-2, 95% CI [-47, -8]) were reduced. Mean ambulatory BP (systolic: -24 mmHg, 95% CI [-42, -5] and diastolic: -13 mmHg, 95% CI [-22, -4]) was also reduced at 12M. Office BP was reduced as early as 1M (systolic: -25 mmHg, 95% CI [-45, -5] and diastolic: -13 mmHg, 95% CI [-24, - 1]). Both ambulatory and office BP had clinically significant reductions in at least 50% of patients out to 12M. Catheter-based RDN significantly reduced MSNA and LV mass as well as systemic BP in this group of patients with ESKD

Enhanced performance in fluorene-free organometal halide perovskite light-emitting diodes using tunable, low electron affinity oxide electron injectors.

Fluorene-free perovskite light-emitting diodes (LEDs) with low turn-on voltages, higher luminance and sharp, color-pure electroluminescence are obtained by replacing the F8 electron injector with ZnO, which is directly deposited onto the CH3NH3PbBr3 perovskite using spatial atmospheric atomic layer deposition. The electron injection barrier can also be reduced by decreasing the ZnO electron affinity through Mg incorporation, leading to lower turn-on voltages.The authors would like to acknowledge funding from the Cambridge Commonwealth, European and International Trusts, Rutherford Foundation of New Zealand, A*STAR National Science Scholarship, Girton College Cambridge, Gates Cambridge Scholarship, EPSRC (Reference: EP/G060738/1), the ERC Advanced Investigator Grant, Novox, ERC-2009-adG 247276 and Cambridge Display Technology.This is the final version of the article. It was first published by Wiley at http://onlinelibrary.wiley.com/doi/10.1002/adma.201405044/abstract

Differential cellular and humoral immune responses in immunocompromised individuals following multiple SARS-CoV-2 vaccinations

Introduction: The heterogeneity of the immunocompromised population means some individuals may exhibit variable, weak or reduced vaccine-induced immune responses, leaving them poorly protected from COVID-19 disease despite receiving multiple SARS-CoV-2 vaccinations. There is conflicting data on the immunogenicity elicited by multiple vaccinations in immunocompromised groups. The aim of this study was to measure both humoral and cellular vaccine-induced immunity in several immunocompromised cohorts and to compare them to immunocompetent controls. Methods: Cytokine release in peptide-stimulated whole blood, and neutralising antibody and baseline SARS-CoV-2 spike-specific IgG levels in plasma were measured in rheumatology patients (n=29), renal transplant recipients (n=46), people living with HIV (PLWH) (n=27) and immunocompetent participants (n=64) post third or fourth vaccination from just one blood sample. Cytokines were measured by ELISA and multiplex array. Neutralising antibody levels in plasma were determined by a 50% neutralising antibody titre assay and SARS-CoV-2 spike specific IgG levels were quantified by ELISA. Results: In infection negative donors, IFN-γ, IL-2 and neutralising antibody levels were significantly reduced in rheumatology patients (p=0.0014, p=0.0415, p=0.0319, respectively) and renal transplant recipients (p<0.0001, p=0.0005, p<0.0001, respectively) compared to immunocompetent controls, with IgG antibody responses similarly affected. Conversely, cellular and humoral immune responses were not impaired in PLWH, or between individuals from all groups with previous SARS-CoV-2 infections. Discussion: These results suggest that specific subgroups within immunocompromised cohorts could benefit from distinct, personalised immunisation or treatment strategies. Identification of vaccine non-responders could be critical to protect those most at risk

Understanding the Role of Grain Boundaries on Charge‐Carrier and Ion Transport in Cs 2 AgBiBr 6 Thin Films

Funder: Cambridge Trust and Chinese ScholarshipFunder: Royal Academy of Engineering; Id: http://dx.doi.org/10.13039/501100000287Abstract: Halide double perovskites have gained significant attention, owing to their composition of low‐toxicity elements, stability in air, and recent demonstrations of long charge‐carrier lifetimes that can exceed 1 µs. In particular, Cs2AgBiBr6 is the subject of many investigations in photovoltaic devices. However, the efficiencies of solar cells based on this double perovskite are still far from the theoretical efficiency limit of the material. Here, the role of grain size on the optoelectronic properties of Cs2AgBiBr6 thin films is investigated. It is shown through cathodoluminescence measurements that grain boundaries are the dominant nonradiative recombination sites. It also demonstrates through field‐effect transistor and temperature‐dependent transient current measurements that grain boundaries act as the main channels for ion transport. Interestingly, a positive correlation between carrier mobility and temperature is found, which resembles the hopping mechanism often seen in organic semiconductors. These findings explain the discrepancy between the long diffusion lengths >1 µm found in Cs2AgBiBr6 single crystals versus the limited performance achieved in their thin film counterparts. This work shows that mitigating the impact of grain boundaries will be critical for these double perovskite thin films to reach the performance achievable based on their intrinsic single‐crystal properties

International Perspectives on the Legal Environment for Selection

Perspectives from 22 countries on aspects of the legal environment for selection are presented in this article. Issues addressed include (a) whether there are racial/ethnic/religious subgroups viewed as "disadvantaged,” (b) whether research documents mean differences between groups on individual difference measures relevant to job performance, (c) whether there are laws prohibiting discrimination against specific groups, (d) the evidence required to make and refute a claim of discrimination, (e) the consequences of violation of the laws, (f) whether particular selection methods are limited or banned, (g) whether preferential treatment of members of disadvantaged groups is permitted, and (h) whether the practice of industrial and organizational psychology has been affected by the legal environmen

Early ultrasound surveillance of newly-created haemodialysis arteriovenous fistula

IntroductionWe assess if ultrasound surveillance of newly-created arteriovenous fistulas (AVFs) can predict nonmaturation sufficiently reliably to justify randomized controlled trial (RCT) evaluation of ultrasound-directed salvage intervention.MethodsConsenting adults underwent blinded fortnightly ultrasound scanning of their AVF after creation, with scan characteristics that predicted AVF nonmaturation identified by logistic regression modeling.ResultsOf 333 AVFs created, 65.8% matured by 10 weeks. Serial scanning revealed that maturation occurred rapidly, whereas consistently lower fistula flow rates and venous diameters were observed in those that did not mature. Wrist and elbow AVF nonmaturation could be optimally modeled from week 4 ultrasound parameters alone, but with only moderate positive predictive values (PPVs) (wrist, 60.6% [95% confidence interval, CI: 43.9–77.3]; elbow, 66.7% [48.9–84.4]). Moreover, 40 (70.2%) of the 57 AVFs that thrombosed by week 10 had already failed by the week 4 scan, thus limiting the potential of salvage procedures initiated by that scan’s findings to alter overall maturation rates. Modeling of the early ultrasound characteristics could also predict primary patency failure at 6 months; however, that model performed poorly at predicting assisted primary failure (those AVFs that failed despite a salvage attempt), partly because patency of at-risk AVFs was maintained by successful salvage performed without recourse to the early scan data.ConclusionEarly ultrasound surveillance may predict fistula maturation, but is likely, at best, to result in only very modest improvements in fistula patency. Power calculations suggest that an impractically large number of participants (>1700) would be required for formal RCT evaluation

Endovascular Renal Denervation in End-Stage Kidney Disease Patients: Cardiovascular Protection—A Proof-of-Concept Study

Sympathetic neural activation is markedly increased in end-stage kidney disease (ESKD). Catheter-based renal denervation (RDN) reduces sympathetic overactivity and blood pressure in resistant hypertension. We investigated the effect of RDN on sympathetic neural activation and left ventricular mass in patients with ESKD. Methods: Nine ESKD (6 hemodialysis and 3 peritoneal dialysis) patients with dialysis vintage of ≥11 months were treated with RDN (EnligHTN system). Data were obtained on a nondialysis day; at baseline, 1, 3, and 12 months post-RDN. Results: At baseline sympathetic neural activation measured by muscle sympathetic nervous activity (MSNA) and plasma norepinephrine concentrations were markedly elevated. Left ventricular hypertrophy (LVH) was evident in 8 of the 9 patients. At 12 months post-RDN, blind analysis revealed that MSNAfrequency (–12.2 bursts/min1, 95% CI [–13.6, –10.7]) and LV mass (–27 g/m2, 95% CI [–47, –8]) were reduced. Mean ambulatory BP (systolic: –24 mm Hg, 95% CI [–42, –5] and diastolic: –13 mm Hg, 95% CI [–22, –4]) was also reduced at 12 months. Office BP was reduced as early as 1 month (systolic: –25 mm Hg, 95% CI [–45, –5] and diastolic: –13 mm Hg, 95% CI [–24, –1]). Both ambulatory and office BP had clinically significant reductions in at least 50% of patients out to 12 months. Discussion: Catheter-based RDN significantly reduced MSNA and LV mass as well as systemic BP in this group of patients with ESKD