Active site manipulation in MoS2 cluster electrocatalysts by transition metal doping

The development of non-platinum group metal catalysts for the hydrogen evolution reaction (HER) in water electrolyser devices is essential for their widespread and sustainable deployment. In recent years, molybdenum disulfide (MoS2) catalysts have received significant attention as they not only exhibit good electrocatalytic HER activity but also, crucially, acid-stability. However, further performance enhancement is required for these materials to be competitive with Pt and to that end transition metal doping of MoS2 has been explored as a route to further increasing its catalytic activity. In this work, cluster beam deposition was employed to produce controlled cobalt-doped MoS2 clusters (MoS2–Co). We demonstrate that, in contrast to previous observations of performance enhancement in MoS2 resulting from nickel doping (MoS2–Ni), the introduction of Co has a detrimental effect on HER activity. The contrasting behaviours of Ni and Co doping are rationalized by density functional theory (DFT) calculations, which suggest that HER-active surface vacancies are deactivated by combination with Co dopant atoms, whilst their activity is retained, or even partially enhanced, by combination with Ni dopant atoms. Furthermore, the adatom dopant–vacancy combination kinetics appear to be more than three orders of magnitude faster in MoS2–Co than for MoS2–Ni. These findings highlight a fundamental difference in the influence of transition metal dopants on the HER performance of MoS2 electrocatalysts and stress the importance of considering surface atomic defects when predicting their behaviour

Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom

Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations

Preliminary evaluation of a rapid lateral flow calprotectin test for the diagnosis of prosthetic joint infection

Aims This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients. Methods A convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards. Results According to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)). Conclusion This study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required

Screening history of women with cervical cancer: a 6-year study in Aarhus, Denmark

To identify possible weaknesses in cervical screening in Aarhus County, 10 years after the programme was introduced, screening histories were examined. A major problem for the screening programme was that 31% of women were never screened and 61% under-screened, the latter group being significantly dominated by older women and high-stage tumours

The effects of surface mixers on stratification, dissolved oxygen, and cyanobacteria in a shallow eutrophic reservoir

Top-down surface mixers are increasingly used in drinking water reservoirs to prevent the development of stratification, control cyanobacteria, and limit sediment release of soluble manganese. A targeted field investigation enabled the discrimination of artificial mixing by surface mixers from wind and convection in a shallow (6.6 m), eutrophic drinking water reservoir. Top-down surface mixers were effective at reducing vertical temperature and dissolved oxygen gradients over a 20 m radius, within which turbulent kinetic energy (TKE) input from the mixers exceeded the maximum TKE contribution from wind and convection. Meteorological conditions appeared to have a stronger influence beyond a 60 m radius from the mixers. Near-bed velocities measured using an Acoustic Doppler Velocimeter (ADV) ∼ 30 m north of the mixers were significantly lower when the mixers were not operating; when operating, ADV signal amplitude showed localized sediment resuspension. Cyanobacteria cell counts were high throughout the reservoir but counts of low-light adapted Planktothrix sp. were highest near the mixers, indicating mixer operation may improve growing conditions for Planktothrix. While the destratification goal of mixers was accomplished locally, the limited range of influence left >90% of the reservoir subject to diurnal stratification, anoxia, and potential internal loading of inorganic nutrients and soluble metals, restricting mixer effectiveness as an in-reservoir management technique to improve raw water quality in shallow systems

Representations of the family in postwar British amateur film: family histories in the Lane and Scrutton collection at the East Anglian Film Archive

This article examines the construction of the postwar British family in amateur film with reference to the Sidney Lane and Cecil Scrutton collection held at the East Anglian Film Archive (EAFA), particularly the films covering 1948 – 1961. Heather Norris Nicholson argues that home movies contribute to 'an understanding of leisure and visual-related practices of consumption as well as the social processes by which people came to give themselves, and others, identities' in the mid-twentieth century (Nicholson, 2004, p. 323). By considering the social and historical contexts in which these home movies were produced, and using accompanying notes by one of the filmmaker’s sons, the leisure time films of Lane and Scrutton can be analysed in order to understand how the amateur cine hobby ideologically constructed family, community and national identity in postwar Britain. The images of Christmas parties, daytrips and holidays in these films reveal much about this particular family, and are therefore very illuminating to the social historian and film scholar of today

The 7th National Audit Project (NAP7) baseline survey of individual anaesthetists: preparedness for and experiences of peri-operative cardiac arrest

The Royal College of Anaesthetists' 7th National Audit Project baseline survey assessed knowledge, attitudes, practices and experiences of peri-operative cardiac arrests among UK anaesthetists and Anaesthesia Associates. We received 10,746 responses, representing a 71% response rate. In-date training in adult and paediatric advanced life support was reported by 9646 (90%) and 7125 (66%) anaesthetists, respectively. There were 8994 (84%) respondents who were confident in leading a peri-operative cardiac arrest, with males more confident than females, but only 5985 (56%) were confident in leading a debrief and 7340 (68%) communicating with next of kin. In the previous two years, 4806 (46%) respondents had managed at least one peri-operative cardiac arrest, of which 321 (7%) and 189 (4%) of these events involved a child or an obstetric patient, respectively. Respondents estimated the most common causes of peri-operative cardiac arrest to be hypovolaemia, hypoxaemia and cardiac ischaemia, with haemorrhage coming fifth. However, the most common reported causes for the most recently attended peri-operative cardiac arrest were haemorrhage; (927, 20%); anaphylaxis (474, 10%); and cardiac ischaemia (397, 9%). Operating lists or shifts were paused or stopped after 1330 (39%) cardiac arrests and 1693 (38%) respondents attended a debrief, with ‘hot’ debriefs most common. Informal wellbeing support was relatively common (2458, 56%) and formal support was uncommon (472, 11%). An impact on future care delivery was reported by 196 (4%) anaesthetists, most commonly a negative psychological impact. Management of a peri-operative cardiac arrest during their career was reported by 8654 (85%) respondents. The overall impact on professional life was more often judged positive (2630, 30%) than negative (1961, 23%), but impact on personal life was more often negative

Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia.

Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide-induced hyponatremia (TIH), a clinically significant adverse effect, is poorly understood. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with TIH. In a cohort of 109 TIH patients, those with severe TIH displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin E2 excretion, and reduced excretion of serum chloride, magnesium, zinc, and antidiuretic hormone. GWAS in a separate cohort of 48 TIH patients and 2,922 controls from the 1958 British birth cohort identified an additional 14 regions associated with TIH. We identified a suggestive association with a variant in SLCO2A1, which encodes a prostaglandin transporter in the distal nephron. Resequencing of SLCO2A1 revealed a nonsynonymous variant, rs34550074 (p.A396T), and association with this SNP was replicated in a second cohort of TIH cases. TIH patients with the p.A396T variant demonstrated increased urinary excretion of prostaglandin E2 and metabolites. Moreover, the SLCO2A1 phospho-mimic p.A396E showed loss of transporter function in vitro. These findings indicate that the phenotype of TIH involves a more extensive metabolic derangement than previously recognized. We propose one mechanism underlying TIH development in a subgroup of patients in which SLCO2A1 regulation is altered.This work was supported by an Academy of Medical Sciences grant for clinical lecturers (to JSW and MG), British Heart Foundation grant PG/09/089 (to KMO), the National Institute for Health Research (NIHR) Royal Brompton Cardiovascular Biomedical Research Unit (to JSW and SC), the Fondation Leducq (to JSW and SC), and the British Heart Foundation (to JSW and SC). MDT holds a Medical Research Council Senior Clinical Fellowship (G0902313). This work was supported by the Medical Research Council (grant numbers G510364 and G1000861). This research used the ALICE and SPECTRE High Performance Computing Facilities at the University of Leicester

Ultra-Fast and Sensitive Detection of Non-Typhoidal Salmonella Using Microwave-Accelerated Metal-Enhanced Fluorescence (“MAMEF”)

Certain serovars of Salmonella enterica subsp. enterica cause invasive disease (e.g., enteric fever, bacteremia, septicemia, meningitis, etc.) in humans and constitute a global public health problem. A rapid, sensitive diagnostic test is needed to allow prompt initiation of therapy in individual patients and for measuring disease burden at the population level. An innovative and promising new rapid diagnostic technique is microwave-accelerated metal-enhanced fluorescence (MAMEF). We have adapted this assay platform to detect the chromosomal oriC locus common to all Salmonella enterica subsp. enterica serovars. We have shown efficient lysis of biologically relevant concentrations of Salmonella spp. suspended in bacteriological media using microwave-induced lysis. Following lysis and DNA release, as little as 1 CFU of Salmonella in 1 ml of medium can be detected in <30 seconds. Furthermore the assay is sensitive and specific: it can detect oriC from Salmonella serovars Typhi, Paratyphi A, Paratyphi B, Paratyphi C, Typhimurium, Enteritidis and Choleraesuis but does not detect Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae or Acinetobacter baumanii. We have also performed preliminary experiments using a synthetic Salmonella oriC oligonucleotide suspended in whole human blood and observed rapid detection when the sample was diluted 1∶1 with PBS. These pre-clinical data encourage progress to the next step to detect Salmonella in blood (and other ordinarily sterile, clinically relevant body fluids)