Postsynthetic treatment of nickel–iron layered double hydroxides for the optimum catalysis of the oxygen evolution reaction

D.T., S.J., J.C., and V.N. wish to thank the support of the ERC CoG, 3D2DPring (GA 681544) and PoC Powering_eTextiles (GA 861673) and SFI AMBER (12/RC/2278_P2). The authors would like to thank the Advanced Microscopy Lab and CRANN Trinity College Dublin for providing STEM-EDX measurements. This publication has emanated from research supported in part by a grant from Science Foundation Ireland under Grant number 12/RC/2278_P2. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. Publisher Copyright: © 2021, The Author(s).Nickel–iron-layered double hydroxide (NiFe LDH) platelets with high morphological regularity and submicrometre lateral dimensions were synthesized using a homogeneous precipitation technique for highly efficient catalysis of the oxygen evolution reaction (OER). Considering edge sites are the point of activity, efforts were made to control platelet size within the synthesized dispersions. The goal is to controllably isolate and characterize size-reduced NiFe LDH particles. Synthetic approaches for size control of NiFe LDH platelets have not been transferable based on published work with other LDH materials and for that reason, we instead use postsynthetic treatment techniques to improve edge-site density. In the end, size-reduced NiFe LDH/single-wall carbon nanotube (SWCNT) composites allowed to further reduce the OER overpotential to 237 ± 7 mV ( = 0.16 ± 0.01 μm, 20 wt% SWCNT), which is one of the best values reported to date. This approach as well improved the long-term activity of the catalyst in operating conditions.publishersversionpublishe

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Does Pain Predict Frailty in Older Men and Women? Findings From the English Longitudinal Study of Ageing (ELSA)

Background: Pain has been suggested to act as a stressor during aging, potentially accelerating declines in health and functioning. Our objective was to examine the longitudinal association between self-reported pain and the development, or worsening, of frailty among older men and women. Methods: The study population consisted of 5,316 men and women living in private households in England, mean age 64.5 years, participating in the English Longitudinal Study of Ageing (ELSA). Data from Waves 2 and 6 of ELSA were used in this study with 8 years of follow-up. At Wave 2, participants were asked whether they were “often troubled with pain” and for those who reported yes, further information regarding the intensity of their pain (mild, moderate, or severe) was collected. Socioeconomic status (SES) was assessed using information about the current/most recent occupation and also net wealth. A frailty index (FI) was generated, with the presence of frailty defined as an FI >0.35. Among those without frailty at Wave 2, the association between pain at Wave 2 and frailty at Wave 6 was examined using logistic regression. We investigated whether pain predicted change in FI between Waves 2 and 6 using a negative binomial regression model. For both models adjustments were made for age, gender, lifestyle factors, depressive symptoms, and socioeconomic factors. Results: At Wave 2, 455 (19.7%) men and 856 (28.7%) women reported they often experienced moderate or severe pain. Of the 5,159 participants who were nonfrail at Wave 2, 328 (6.4%) were frail by Wave 6. The mean FI was 0.11 (standard deviation [SD] = 0.1) at Wave 2 and 0.15 (SD = 0.1) at Wave 6. After adjustment for age, gender, body mass index, lifestyle factors, and depressive symptoms, compared to participants reporting no pain at Wave 2 those reporting moderate (odds ratio [OR] = 3.08, 95% confidence interval [CI] = 2.28, 4.16) or severe pain (OR = 3.78, 95% CI = 2.51, 5.71) were significantly more likely to be frail at Wave 6. This association persisted after further adjustment for either occupational class and/or net wealth level. Compared to those without pain, those with mild, moderate, or severe pain were also more likely to develop worsening frailty, as assessed using the FI, and this association persisted after adjustment for SES. There was no evidence that the association between pain and frailty was influenced by gender. Conclusion: Pain is associated with an increased risk and intensity of frailty in older men and women. Socioeconomic factors contribute to the occurrence of frailty; though in our study do not explain the relationship between pain and frailty

Genome-wide characterization of mitochondrial DNA methylation in human brain

BackgroundThere is growing interest in the role of DNA methylation in regulating the transcription of mitochondrial genes, particularly in brain disorders characterized by mitochondrial dysfunction. Here, we present a novel approach to interrogate the mitochondrial DNA methylome at single base resolution using targeted bisulfite sequencing. We applied this method to investigate mitochondrial DNA methylation patterns in post-mortem superior temporal gyrus and cerebellum brain tissue from seven human donors.ResultsWe show that mitochondrial DNA methylation patterns are relatively low but conserved, with peaks in DNA methylation at several sites, such as within the D-LOOP and the genes MT-ND2, MT-ATP6, MT-ND4, MT-ND5 and MT-ND6, predominantly in a non-CpG context. The elevated DNA methylation we observe in the D-LOOP we validate using pyrosequencing. We identify loci that show differential DNA methylation patterns associated with age, sex and brain region. Finally, we replicate previously reported differentially methylated regions between brain regions from a methylated DNA immunoprecipitation sequencing study.ConclusionsWe have annotated patterns of DNA methylation at single base resolution across the mitochondrial genome in human brain samples. Looking to the future this approach could be utilized to investigate the role of mitochondrial epigenetic mechanisms in disorders that display mitochondrial dysfunction

Imidazol-1-ylethylindazole Voltage-Gated Sodium Channel Ligands Are Neuroprotective during Optic Neuritis in a Mouse Model of Multiple Sclerosis

[Image: see text] A series of imidazol-1-ylethylindazole sodium channel ligands were developed and optimized for sodium channel inhibition and in vitro neuroprotective activity. The molecules exhibited displacement of a radiolabeled sodium channel ligand and selectivity for blockade of the inactivated state of cloned neuronal Na(v) channels. Metabolically stable analogue 6 was able to protect retinal ganglion cells during optic neuritis in a mouse model of multiple sclerosis

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar