The effect of a home-based, gamified stability skills intervention on 4-5-year-old children's physical and cognitive outcomes: A pilot study.

BACKGROUND: Stability skills (e.g., static/dynamic balance) are a precursor for other movement skill development (e.g., jumping, catching). However, young children consistently demonstrate low stability and movement skill ability. There is therefore a need to develop effective strategies to improve stability skills in early childhood. AIM: To pilot the effect of a home-based gamified stability skills intervention on 4-5-year-old children's physical skills, self-perceptions and cognitions. METHODS: One-hundred-and-eleven 4-5-year-old children participated from three schools. Two schools were allocated into the intervention group (n = 66 children, 33 boys) and one to the control group (n = 45 children, 25 boys). Stability, fundamental movement skills, perceived motor competence, and cognition were assessed at baseline and at post-intervention. The intervention group was given a booklet detailing the 12-week gamified stability skill intervention. The control group participated in their usual weekly activities. RESULTS: A series of ANCOVAs controlling for baseline values demonstrated significantly higher stability skills (F(1,93) = 24.79, p < 0.001, partial η2 = 0.212), fundamental movement skills (F(1,94) = 15.5, p = < 0.001, partial η2 = 0.139), perceived motor competence (F(1,96) = 5.48, p = 0.021, partial η2 = 0.054) and cognition (F(1,96) = 15.5, p = < 0.001, partial η2 = 0.139) at post-test for the intervention versus control groups. DISCUSSION: This study demonstrates that a home-based, gamified, stability skills intervention enhances stability skills, fundamental movement skills, perceived motor competence and cognition in children aged 4-5-years old.

Post mortem blood bromazolam concentrations and co-findings in 96 coronial cases within England and Wales.

Bromazolam is a newly emerging benzodiazepine drug which is not licensed for medicinal use. It may be sourced as a New Psychoactive Substance (NPS) for its desired effects or be consumed unknowingly via counterfeit Xanax® or Valium® preparations. As part of our Coronial workload, we observed an increase in the detection of bromazolam from September 2021 to November 2022. We report a series of 96 cases in which bromazolam was quantitated by high resolution accurate mass - mass spectrometry (HRAM - MS) in post-mortem blood. The mean (SD) post-mortem blood bromazolam concentration from our case series was 64.6 ( ± 79.4) µg/L (range <1-425 µg/L). Routine toxicological screening results have also been reported; the most commonly encountered drugs taken in combination with bromazolam were cocaine, gabapentinoids and diazepam. In 48% of cases at least one further designer benzodiazepine drug was also present (etizolam, flualprazolam, flubromazolam, flubromazepam). It is essential that laboratories providing toxicological investigations are aware of the limitations of their assays; and inclusion of bromazolam within targeted screening panels using LC-MS/MS is encouraged. Bromazolam has not been associated with death in isolation from resulting toxic concentrations; however, it is likely to enhance adverse clinical effects when taken in combination with stimulant and/or centrally-acting depressant drugs (poly-drug deaths). Bromazolam, similar to other benzodiazepines, may also impair cognition and decision making skills.

Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep.

Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline-treated group. The results show that cortisol overexposure before birth programmes pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.

Interpopulation differences and temporal synchrony in rates of adult survival between two seabird colonies that differ in population size and distance to foraging grounds.

Understanding the processes that drive interpopulation differences in demography and population dynamics is central to metapopulation ecology. In colonial species, populations are limited by local resource availability. However, individuals from larger colonies will travel greater distances to overcome density-dependent competition. Consequently, these individuals may also experience greater carry-over effects and interpopulation differences in demography. To test this prediction, we use mark-recapture data collected over four decades from two breeding colonies of a seabird, the Manx shearwater (Puffinus puffinus), that exhibit strong spatial overlap throughout the annual cycle but differ in population size and maximum foraging distances. We quantify interpopulation differences and synchrony in rates of survival and assess whether local mean wind speeds act to strengthen or disrupt synchrony. In addition, we examine whether the imputed interpopulation differences in survival can generate population-level consequences. The colony where individuals travel further during the breeding season had slightly lower and more variable rates of survival, indicative of individuals experiencing greater carry-over effects. Fluctuations in survival were highly synchronous between the colonies, but neither synchronous, nor asynchronous, variation could be strongly attributed to fluctuations in local mean wind speeds. Finally, we demonstrate that the imputed interpopulation differences in rates of survival could lead to considerable differences in population growth. We hypothesise that the observed interpopulation differences in rates of adult survival reflect carry-over effects associated with foraging distances during the breeding season. More broadly, our results highlight that breeding season processes can be important for understanding interpopulation differences in the demographic rates and population dynamics of long-lived species, such as seabirds.

Dental referrals for patients with diabetes: survey of barriers and enablers for medical and health professionals.

BACKGROUND: Oral health care improves diabetes management; however, medical and other health practitioners do not commonly refer their patients with diabetes for oral health care. This study aimed to understand barriers to and enablers of dental referrals for patients with diabetes. METHODS: Quantitative data were collected from a cross-sectional survey of health care providers attending a virtual Grand Rounds on the relationship between oral health and diabetes. Attendees were invited to complete and share a Forms survey. Barriers to and enablers of dental referrals were compared for 18 health professionals working in inpatient/ward settings to 23 working in community/primary care settings using the chi-square test. RESULTS: Across both work settings, only 12% of respondents often or always discussed the importance of oral health and only 8% often or always referred their patients with diabetes for dental care. Time barriers, awareness and knowledge of how/where to send dental referrals were significant barriers, while online referral pathways, more education and availability of brochures for the patient to take home were identified as key enablers for dental referrals. CONCLUSIONS: Online referral pathways, targeted oral health education and resources for medical and health professionals caring for patients with diabetes may increase the number of patients being referred for dental care as part of their diabetes managements. © 2023 Australian Dental Association.

Ethnic differences in complement system biomarkers and their association with metabolic health in men of Black African and White European ethnicity.

Inflammation plays a fundamental role in the development of several metabolic diseases, including obesity and type 2 diabetes (T2D); the complement system has been implicated in their development. People of Black African (BA) ethnicity are disproportionately affected by T2D and other metabolic diseases but the impact of ethnicity on the complement system has not been explored. We investigated ethnic differences in complement biomarkers and activation status between men of BA and White European (WE) ethnicity and explored their association with parameters of metabolic health. We measured a panel of 15 complement components, regulators, and activation products in fasting plasma from 89 BA and 96 WE men. Ethnic differences were statistically validated. Association of complement biomarkers with metabolic health indices (BMI, waist circumference, insulin resistance, and HbA1c) were assessed in the groups. Plasma levels of the key complement components C3 and C4, the regulators clusterin and properdin and the activation marker iC3b were significantly higher in BA compared to WE men after age adjustment, while FD levels were significantly lower. C3 and C4 levels positively correlated with some or all markers of metabolic dysfunction in both ethnic groups while FD was inversely associated with HbA1c in both groups, and clusterin and properdin were inversely associated with some markers of metabolic dysfunction only in the WE group. Our findings of increased levels of complement components and activation products in BA compared to WE men suggest differences in complement regulation that may impact susceptibility to poor metabolic health.

Assessment of Dietary Intake in Three Cohorts of Advanced Age in Two Countries: Methodology Challenges.

OBJECTIVES: Dietary intake information is key to understanding nutrition-related outcomes. Intake changes with age and some older people are at increased risk of malnutrition. Application, difficulties, and advantages of the 24-hour multiple pass recall (24hr-MPR) dietary assessment method in three cohorts of advanced age in the United Kingdom (UK) and New Zealand (NZ) is described. PARTICIPANTS: The Newcastle 85+ study (UK) recruited a single year birth cohort of people aged 85 years during 2006-7. LiLACS NZ recruited a 10-year birth cohort of Maori (indigenous New Zealanders) aged 80-90 years and a single year birth cohort of non-Maori aged 85 years in 2010. MEASUREMENTS: Two 24hr-MPR were conducted on non-consecutive days by trained assessors. Pictorial resources and language were adapted for the New Zealand and Maori contexts. Detailed methods are described. RESULTS: In the Newcastle 85+ study, 805 (93%) participants consented to the 24-MPR, 95% of whom completed two 24hr-MPR; in LiLACS NZ, 218 (82%) consented and 203 (76%) Maori and 353 (90%) non-Maori completed two 24hr-MPR. Mean time to complete each 24hr-MPR was 22 minutes in the Newcastle 85+ study, and 45 minutes for Maori and 39 minutes for non-Maori in LiLACS NZ. Dietary assessment of participants residing in residential care and those requiring proxy respondents were successfully included in both studies. Most participants (83-94%) felt that data captured by the 24hr-MPR reflected their usual dietary intake. CONCLUSIONS: Dietary assessment using 24hr-MPR was successful in capturing detailed dietary data including information on portion size and time of eating for over 1300 octogenarians in the UK and New Zealand (Maori and non- Maori). The 24hr-MPR is an acceptable method of dietary assessment in this age group.

Lateral cystic neck masses in adults: a ten-year series and comparative analysis of diagnostic modalities.

BACKGROUND: In adults, the solitary lateral cystic neck mass remains a diagnostic challenge with little solid material to target for cytology and few clues on imaging modalities to suggest underlying malignancy. METHOD: This study was a retrospective review of patients presenting with a lateral cystic neck mass to a tertiary academic head and neck centre over a 10-year period. RESULTS: A total of 25 of 157 cystic lesions were subsequently malignant on paraffin section histopathology, with the youngest patient being 42 years. In the age cohort over 40 years, 30 per cent of males and 10 per cent of females were diagnosed with malignancy. The ipsilateral palatine tonsil was the most common primary site (50 per cent). A total of 85 per cent of cases demonstrated integrated human papillomavirus infection. Age, male sex and alcohol were significant risk factors on univariate analysis. Ultrasound-guided fine needle aspiration cytology and magnetic resonance imaging represented the most accurate pre-open biopsy tests. CONCLUSION: The authors of this study advocate for a risk-stratified, evidence-based workup in patients with solitary lateral cystic neck mass in order to optimise timely diagnosis.

European survey on the current surveillance practices, management guidelines, treatment pathways and heterogeneity of testing of Clostridioides difficile, 2018-2019: results from The Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI).

BACKGROUND: Awareness and compliance with international guidelines for diagnosis and clinical management of Clostridioides difficile infection (CDI) are unknown. AIM: To compare the awareness and compliance with the recommended strategies for diagnosis and clinical management of CDI across Europe in 2018-2019. METHODS: Hospital sites and their associated community practices across 12 European countries completed an online survey in 2018-2019, to report on their practices in terms of surveillance, prevention, diagnosis, and treatment of CDI. Responses were collected from 105 hospitals and 39 community general practitioners (GPs). FINDINGS: Hospital sites of 11 countries reported participation in national surveillance schemes compared with six countries for international schemes. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID)-recommended CDI testing methodologies were used by 82% (86/105) of hospitals, however countries reporting the highest incidence of CDI used non-recommended tests. Over 75% (80/105) of hospitals were aware of the most recent European CDI treatment guidelines at the time of this survey compared with only 26% (10/39) of surveyed GPs. However, up to 15% (16/105) of hospitals reported using the non-recommended metronidazole for recurrent CDI cases, sites in countries with lower awareness of CDI treatment guidelines. Only 37% (39/105) of hospitals adopted contact isolation precautions in case of suspected CDI. CONCLUSION: Good awareness of guidelines for the management of CDI was observed across the surveyed European hospital sites. However, low compliance with diagnostic testing guidelines, infection control measures for suspected CDI, and insufficient awareness of treatment guidelines continued to be reported in some countries.

Advancing our understanding of skeletal muscle across the lifecourse: Protocol for the MASS_Lifecourse study and characteristics of the first 80 participants.

INTRODUCTION: Sarcopenia, the age-related loss of skeletal muscle strength and mass, carries a significant burden for affected individuals. There has been little investigation of sarcopenia using experimental medicine techniques to study human muscle tissue in detail. The aim of the Muscle Ageing Sarcopenia Studies Lifecourse (MASS_Lifecourse) study is to recruit up to 160 participants, equally divided between females and males between ages 45 and 85 years for detailed phenotyping of skeletal muscle health. Here we describe the protocol for the study and the characteristics of the first 80 participants. METHODS: We are recruiting participants from three sources in the north-east of England. Study fieldwork comprises a home visit (or videocall) for consent and assessment of health, cognition, lifestyle, and wellbeing. This is followed by a visit to a clinical research facility for assessment of sarcopenia status and collection of samples including a vastus lateralis muscle biopsy. We produced descriptive statistics for the first 80 participants, including expressing their grip strength relative to normative data in the form of Z-scores. RESULTS: The first 80 participants (53.8 % female) covered the target ages, ranging from 48 to 84 years. They were regularly physically active, reported good physical function and had a prevalence of sarcopenia (including probable sarcopenia) of 11.3 % based on the revised European consensus. Their grip strength was similar to that in the general population, with a mean Z-score of 0.09 standard deviations (95 % CI: -1.64, 1.83) above that expected. CONCLUSIONS: The MASS_Lifecourse study combines comprehensive health and lifestyle data with a range of biological samples including skeletal muscle. The findings from planned analyses should contribute to improvements in the diagnosis, treatment, and prevention of sarcopenia.

The assessment of sarcopenia and the frailty phenotype in the outpatient care of older people: implementation and typical values obtained from the Newcastle SarcScreen project.

PURPOSE: Sarcopenia and the frailty phenotype both indicate older adults at risk of adverse health outcomes and yet are not widely assessed in practice. We developed the Newcastle SarcScreen to enable assessment of these two ageing syndromes during clinical care. In the setting of our Older People's Medicine Day Unit, our aims were to describe the implementation of the SarcScreen and to examine the typical values obtained. METHODS: The SarcScreen comprised height, weight, questions (three on the Fried frailty phenotype and five on the SARC-F questionnaire), grip strength and gait speed. We analysed data from 552 patients completing the SarcScreen. We expressed grip strength as Z-scores (number of standard deviations above the mean expected for a patient's age and sex). RESULTS: It was possible to implement the SarcScreen. In 552 patients (65.9% females) with mean age 80.1 (7.7) years, grip strength was feasible in 98.2% and gait speed in 82.1%. Gait speed was typically not assessed due to mobility impairment. Most patients had weak grip strength (present in 83.8%), slow gait speed (88.8%) and the frailty phenotype (66.2%). We found a high prevalence of probable sarcopenia and the frailty phenotype across all age groups studied. This was reflected by low grip strength Z-scores, especially at younger ages: those aged 60-69 had grip strength 2.7 standard deviations (95% CI 2.5-2.9) below that expected. CONCLUSION: It is possible to implement an assessment of sarcopenia and the frailty phenotype as part of the routine outpatient care of older people.

Transcriptomic and cellular decoding of functional brain connectivity changes reveal regional brain vulnerability to pro- and anti-inflammatory therapies.

BACKGROUND: Systemic inflammation induces acute changes in mood, motivation and cognition that closely resemble those observed in depressed individuals. However, the mechanistic pathways linking peripheral inflammation to depression-like psychopathology via intermediate effects on brain function remain incompletely understood. METHODS: We combined data from 30 patients initiating interferon-α treatment for Hepatitis-C and 20 anti-tumour necrosis factor (TNF) therapy for inflammatory arthritis and used resting-state functional magnetic resonance imaging to investigate acute effects of each treatment on regional global brain connectivity (GBC). We leveraged transcriptomic data from the Allen Human Brain Atlas to uncover potential biological and cellular pathways underpinning regional vulnerability to GBC changes induced by each treatment. RESULTS: Interferon-α and anti-TNF therapies both produced differential small-to-medium sized decreases in regional GBC. However, these were observed within distinct brain regions and the regional patterns of GBC changes induced by each treatment did not correlate suggesting independent underlying processes. Further, the spatial distribution of these differential GBC decreases could be captured by multivariate patterns of constitutive regional expression of genes respectively related to: i) neuroinflammation and glial cells; and ii) glutamatergic neurotransmission and neurons. The extent to which each participant expressed patterns of GBC changes aligning with these patterns of transcriptomic vulnerability also correlated with both acute treatment-induced changes in interleukin-6 (IL-6) and, for Interferon-α, longer-term treatment-associated changes in depressive symptoms. CONCLUSIONS: Together, we present two transcriptomic models separately linking regional vulnerability to the acute effects of interferon-α and anti-TNF treatments on brain function to glial neuroinflammation and glutamatergic neurotransmission. These findings generate hypotheses about two potential brain mechanisms through which bidirectional changes in peripheral inflammation may contribute to the development/resolution of psychopathology.

Evolution of MET and NRAS gene amplification as acquired resistance mechanisms in EGFR mutant NSCLC.

EGFR mutant non-small cell lung cancer patients' disease demonstrates remarkable responses to EGFR-targeted therapy, but inevitably they succumb to acquired resistance, which can be complex and difficult to treat. Analyzing acquired resistance through broad molecular testing is crucial to understanding the resistance mechanisms and developing new treatment options. We performed diverse clinical testing on a patient with successive stages of acquired resistance, first to an EGFR inhibitor with MET gene amplification and then subsequently to a combination EGFR and MET targeted therapies. A patient-derived cell line obtained at the time of disease progression was used to identify NRAS gene amplification as an additional driver of drug resistance to combination EGFR/MET therapies. Analysis of downstream signaling revealed extracellular signal-related kinase activation that could only be eliminated by trametinib treatment, while Akt activation could be modulated by various combinations of MET, EGFR, and PI3K inhibitors. The combination of an EGFR inhibitor with a MEK inhibitor was identified as a possible treatment option to overcome drug resistance related to NRAS gene amplification.

Glucocorticoid maturation of mitochondrial respiratory capacity in skeletal muscle before birth.

In adults, glucocorticoids act to match the supply and demand for energy during physiological challenges, partly through actions on tissue mitochondrial oxidative phosphorylation (OXPHOS) capacity. However, little is known about the role of the natural prepartum rise in fetal glucocorticoid concentrations in preparing tissues for the increased postnatal energy demands. This study examined the effect of manipulating cortisol concentrations in fetal sheep during late gestation on mitochondrial OXPHOS capacity of two skeletal muscles with different postnatal locomotive functions. Mitochondrial content, biogenesis markers, respiratory rates and expression of proteins and genes involved in the electron transfer system (ETS) and OXPHOS efficiency were measured in the biceps femoris (BF) and superficial digital flexor (SDF) of fetuses either infused with cortisol before the prepartum rise or adrenalectomised to prevent this increment. Cortisol infusion increased mitochondrial content, biogenesis markers, substrate-specific respiration rates and abundance of ETS complex I and adenine nucleotide translocator (ANT1) in a muscle-specific manner that was more pronounced in the SDF than BF. Adrenalectomy reduced mitochondrial content and expression of PGC1α and ANT1 in both muscles, and ETS complex IV abundance in the SDF near term. Uncoupling protein gene expression was unaffected by cortisol manipulations in both muscles. Gene expression of the myosin heavy chain isoform, MHCIIx, was increased by cortisol infusion and reduced by adrenalectomy in the BF alone. These findings show that cortisol has a muscle-specific role in prepartum maturation of mitochondrial OXPHOS capacity with important implications for the health of neonates born pre-term or after intrauterine glucocorticoid overexposure.

Ancient DNA, lipid biomarkers and palaeoecological evidence reveals construction and life on early medieval lake settlements.

Direct evidence of ancient human occupation is typically established through archaeological excavation. Excavations are costly and destructive, and practically impossible in some lake and wetland environments. We present here an alternative approach, providing direct evidence from lake sediments using DNA metabarcoding, steroid lipid biomarkers (bile acids) and from traditional environmental analyses. Applied to an early Medieval Celtic settlement in Ireland (a crannog) this approach provides a site chronology and direct evidence of human occupation, crops, animal farming and on-site slaughtering. This is the first independently-dated, continuous molecular archive of human activity from an archeological site, demonstrating a link between animal husbandry, food resources, island use. These sites are under threat but are impossible to preserve in-situ so this approach can be used, with or without excavation, to produce a robust and full site chronology and provide direct evidence of occupation, the use of plants and animals, and activities such as butchery.

The effect of intestinal microbiota dysbiosis on growth and detection of carbapenemase-producing Enterobacterales within an in vitro gut model.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) can colonize the gut and are of major clinical concern. Identification of CPE colonization is problematic; there is no gold-standard detection method, and the effects of antibiotic exposure and microbiota dysbiosis on detection are unknown. AIM: Based on a national survey we selected four CPE screening assays in common use. We used a clinically reflective in vitro model of human gut microbiota to investigate the performance of each test to detect three different CPE strains under different, clinically relevant antibiotic exposures. METHODS: Twelve gut models were seeded with a pooled faecal slurry and exposed to CPE either before, after, concomitant with, or in the absence of piperacillin-tazobactam (358 mg/L, 3 × daily, seven days). Total Enterobacterales and CPE populations were enumerated daily. Regular screening for CPE was performed using Cepheid Xpert® Carba-R molecular test, and with Brilliance™ CRE, Colorex™ mSuperCARBA and CHROMID® CARBA SMART agars. FINDINGS: Detection of CPE when the microbiota are intact is problematic. Antibiotic exposure disrupts microbiota populations and allows CPE proliferation, increasing detection. The performances of assays varied, particularly with respect to different CPE strains. The Cepheid assay performed better than the three agar methods for detecting a low level of CPE within an intact microbiota, although performance of all screening methods was comparable when CPE populations increased in a disrupted microbiota. CONCLUSION: CPE strains differed in their dynamics of colonization in an in vitro gut model and in their subsequent response to antibiotic exposure. This affected detection by molecular and screening methods, which has implications for the sensitivity of CPE screening in healthcare settings.

Pilot of the Patient Concerns Inventory - Ward Discharge in Patients following major reconstructive surgery for head and neck cancer.

Planning discharge from hospital following microvascular free-tissue surgery can be complex and challenging. Planning involves the patient, carers, and multiple health professionals. Poor communication and expectations can delay discharge or give a suboptimal discharge process. It was hypothesised that prompt-list modelled along the principals of the Patient Concerns Inventory (PCI) could be help in discharge planning. The aim of this study was to define the items and format of a PCI-Ward Discharge (PCI-WD) and undertake a small pilot. Items appropriate for the PCI-WD were formulated through discussion with patients, carers, ward staff, Head and Neck Clinical Nurse Specialists, and clinicians. The pilot took place over three months from December 2019 through to February 2020. Audit approval was given by the hospital Audit Department. The PCI-WD comprises 43 items. Items from existing PCIs for use at diagnosis and follow-up consultations were reduced in number and 38 new or modified items added; six treatment related, five social care and social well-being, four psychological, emotional, and spiritual well-being, seven physical and functional well-being, and 16 discharge related. The pilot involved 14 free-tissue transfer patients, seven male, seven female, with an age range of 57 to 87 and a mean age of 72. Eight PCI-WD were returned. PCI-WD items identified most frequently were 'surgery site other than head/neck', 'when do I come back to hospital', 'dental check-up/oral health care' and 'diet/eating'. Early findings suggest that PCI-WD could be a useful tool in aiding the discharge process. Further evaluation is required.

Idiopathic systemic capillary leak syndrome (Clarkson's disease) presenting with recurrent hypovolemic shock.

A 49-year old male with a past medical history of myocardial infarction and compartment syndromes requiring fasciotomies presented on five occasions with hypovolemic shock. We describe his admissions and presumptive diagnoses which required large volumes of intravenous fluids, admission to intensive care for vasopressors and renal replacement therapy. The presentations were always precipitated by a prodrome of fatigue and pre-syncopal episodes. On his last admission, a diagnosis of Idiopathic systemic capillary leak syndrome (ISCLS), also known as Clarkson's Disease, was reached. He is currently receiving high dose intravenous immunoglobulins on a monthly basis.

Using a Sweating Residuum/socket Interface Simulator for the Evaluation of Sweat Management Liners in Lower Limb Prosthetics.

BACKGROUND: Lab-based simulators can help to reduce variability in prosthetics research. However, they have not yet been used to investigate the effects of sweating at the residuum-liner interface. This work sought to create and validate a simulator to replicate the mechanics of residual limb perspiration. The developed apparatus was used to assess the effects of perspiration and different liner designs. METHODOLOGY: By scanning a cast, an artificial residuum was manufactured using a 3D-printed, transtibial bone model encased in silicone, moulded with pores. The pores allowed water to emit from the residuum surface, simulating sweating. Dry and sweating cyclic tests were performed by applying compressive and tensile loading, while measuring the displacement of the residuum relative to the socket. Tests were conducted using standard and perforated liners. FINDINGS: Although maximum displacement varied between test setups, its variance was low (coefficient of variation <1%) and consistent between dry tests. For unperforated liners, sweating increased the standard deviation of maximum displacement approximately threefold (0.04mm v 0.12mm, p<0.001). However, with the perforated liner, sweating had little effect on standard deviation compared to dry tests (0.04mm v 0.04mm, p=0.497). CONCLUSIONS: The test apparatus was effective at simulating the effect of perspiration at the residual limb. Moisture at the skin-liner interface can lead to inconsistent mechanics. Perforated liners help to remove sweat from the skin-liner interface, thereby mitigating these effects.

Detection of SARS-CoV-2 within the healthcare environment: a multi-centre study conducted during the first wave of the COVID-19 outbreak in England.

BACKGROUND: Understanding how severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is spread within the hospital setting is essential in order to protect staff, implement effective infection control measures, and prevent nosocomial transmission. METHODS: The presence of SARS-CoV-2 in the air and on environmental surfaces around hospitalized patients, with and without respiratory symptoms, was investigated. Environmental sampling was undertaken within eight hospitals in England during the first wave of the coronavirus disease 2019 outbreak. Samples were analysed using reverse transcription polymerase chain reaction (PCR) and virus isolation assays. FINDINGS: SARS-CoV-2 RNA was detected on 30 (8.9%) of 336 environmental surfaces. Cycle threshold values ranged from 28.8 to 39.1, equating to 2.2 x 105 to 59 genomic copies/swab. Concomitant bacterial counts were low, suggesting that the cleaning performed by nursing and domestic staff across all eight hospitals was effective. SARS-CoV-2 RNA was detected in four of 55 air samples taken <1 m from four different patients. In all cases, the concentration of viral RNA was low and ranged from <10 to 460 genomic copies/m3 air. Infectious virus was not recovered from any of the PCR-positive samples analysed. CONCLUSIONS: Effective cleaning can reduce the risk of fomite (contact) transmission, but some surface types may facilitate the survival, persistence and/or dispersal of SARS-CoV-2. The presence of low or undetectable concentrations of viral RNA in the air supports current guidance on the use of specific personal protective equipment for aerosol-generating and non-aerosol-generating procedures.