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Rationale: The past 25 years have seen huge progress in understanding of the pathobiology of type-2 (T2) asthma, identification of measurable biomarkers, and the emergence of novel monoclonal antibody treatments. Although present in a minority of patients with severe asthma, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research. Objectives: The objective of this study was to explore the differences between study exacerbators and nonexacerbators, to describe physiological changes at exacerbation in those who are T2 HIGH and T2 LOW at the time of exacerbation, and to evaluate the stability of inflammatory phenotypes when stable and at exacerbation. Methods: Exacerbation assessment was a prespecified secondary analysis of data from a 48-week, multicenter, randomized controlled clinical study comparing the use of biomarkers and symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2 LOW (fractional exhaled nitric oxide < 20 ppb and blood eosinophil count < 150 cells/ml) or T2 HIGH (fractional exhaled nitric oxide. 20 or blood eosinophil count. 150) at study enrollment and at each exacerbation. Here, we report the findings of the exacerbation analyses, including comparison of exacerbators and nonexacerbators, the physiological changes at exacerbation in those who had evidence of T2 biology at exacerbation versus those that did not, and the stability of inflammatory phenotypes when stable and at exacerbation.Measurements and Main Results: Of the 301 participants, 60.8% (183) had one or more self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher body mass index, and have more exacerbations requiring oral corticosteroid and unscheduled primary care attendances for exacerbations. At enrollment, 23.6% (71) were T2 LOW and 76.4% (230) T2 HIGH. The T2 LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU (high dependency unit)/ICU and to be receiving maintenance oral corticosteroids. At exacerbation, the T2 LOW events were indistinguishable from T2 HIGH exacerbations in terms of lung function (mean fall in T2 LOW FEV 1, 200 [400] ml vs. T2 HIGH 200 [300] ml; P = 0.93) and symptom increase (ACQ5: T2 LOW, 1.4 [0.8] vs. T2 HIGH, 1.3 [0.8]; P = 0.72), with no increase in T2 biomarkers from stable to exacerbation state in the T2 LOW exacerbations. The inflammatory phenotype within individual patients was dynamic; inflammatory phenotype at study entry did not have a significant association with exacerbation phenotype. Conclusions: Asthma exacerbations demonstrating a T2 LOW phenotype were physiologically and symptomatically similar to T2 HIGH exacerbations. T2 LOW asthma was an unstable phenotype, suggesting that exacerbation phenotyping should occur at the time of exacerbation. The clinically significant exacerbations in participants without evidence of T2 biology at the time of exacerbation highlight the unmet and pressing need to further understand the mechanisms at play in non-T2 asthma.

Hypothesis: miR-433-3p is a potential therapeutic target to reduce the excess endothelial permeability seen in peripheral skeletal muscle of diabetes. Background: Peripheral arterial disease (PAD) is a complication of systemic atherosclerosis that results from occlusions in the large arteries of the leg(s). Though best known as a large vessel disease, patients with PAD also have microvascular disease including excess vascular permeability. Patients with diabetes have an increased risk to develop PAD and more severe symptoms compared to nondiabetic patients with PAD patients. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that modulate gene expression by targeting mRNA post-transcriptionally. Methods: Age-, sex-, and risk factor-controlled plasma samples were selected from a PAD biobank. Plasma samples from non-PAD controls, patients with intermittent claudication (IC), or with critical limb ischemia (CLI), with or without diabetes, were selected and miR-433-3p expression was assessed by RT-qPCR. MiR-433-3p expression was analyzed in human ECs after high glucose (HG) (25 mM) or osmolar control (25 mM Mannitol) treatment under normoxia or hypoxia-serum starvation. ECs were also treated with miR-433 inhibitor or negative control. Endothelial vascular permeability, angiogenesis, and cell viability/survival were tested. Vascular permeability by Evans Blue Dye (EBD) was measured in High Fat Diet (HFD) mice versus C57BL/6 mice treated with 100 μM hind-limb, intramuscular injections of miR-433-3p inhibitor, or scramble. Results: Plasma levels of miR-433-3p were elevated in CLI patients with diabetes. In human ECs, miR-433-3p expression was also elevated after high glucose treatment. Endothelial barrier function was impaired after HG, which was restored by miR-433 inhibition. Similarly, miR-433-3p inhibitor improved angiogenesis and cell survival after HG treatment in ECs. HFD mice demonstrated an increased vascular permeability compared to C57BL/6 mice which was attenuated by miR-433-3p inhibition. Conclusion: These data suggest miR-433-3p’s effect on vascular permeability which may contribute to the very poor clinical course seen in PAD and DM. Improved EC permeability with miR-433-3p inhibition may improve skeletal muscle perfusion and create a novel approach for patients with PAD, diabetes, or both. NIH 5R01HL150003-03 (BHA) and AHA CDA932159 (AK) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

BackgroundApproximately 5% to 10% of patients with asthma have severe disease, with a consistent preponderance in females. Current asthma guidelines recommend stepwise treatment to achieve symptom control with no differential treatment considerations for either sex.ObjectiveTo examine whether patient sex affects outcomes when using a composite T2-biomarker score to adjust corticosteroid (CS) treatment in patients with severe asthma compared with standard care.MethodsThis is a post hoc analysis, stratifying patient outcomes by sex, of a 48-week, multicenter, randomized controlled clinical trial comparing a biomarker-defined treatment algorithm with standard care. The primary outcome was the proportion of patients with a reduction in CS treatment (inhaled and oral corticosteroids). Secondary outcomes included exacerbation rates, hospital admissions, and lung function.ResultsOf the 301 patients randomized, 194 (64.5%) were females and 107 (35.5%) were males. The biomarker algorithm led to a greater proportion of females being on a lower CS dose versus standard care, which was not seen in males (effect estimate: females, 3.57; 95% CI, 1.14-11.18 vs males, 0.54; 95% CI, 0.16-1.80). In T2-biomarker–low females, reducing CS dose was not associated with increased exacerbations. Females scored higher in all domains of the 7-item Asthma Control Questionnaire, apart from FEV1, but with no difference when adjusted for body mass index/anxiety and/or depression. Dissociation between symptoms and T2 biomarkers were noted in both sexes, with a higher proportion of females being symptom high/T2-biomarker low (22.8% vs 15.6%; P = .0002), whereas males were symptom low/T2-biomarker high (22.3% vs 11.4%; P < .0001).ConclusionsThis exploratory post hoc analysis identified that females achieved a greater benefit from biomarker-directed CS optimization versus symptom-directed treatment.

Purpose The paper aims to consider whether social enterprise, who are growing in number and seemingly a politically popular alternative to mainstream employment are a potential conduit for social change. Discussions relating to the value of (stable) employment in reducing and preventing (re)offending are not new. For many ex-offenders, a multitude of barriers stand between them and access to the labour market. As a potential conduit for social change, social enterprises are a growing and seemingly politically popular alternative to mainstream employment. Design/methodology/approach Focusing on the qualitative lived experiences of young people (aged between 16 and 18) with criminal convictions enrolled in one such enterprise, this paper examines the extent to which work-integrated social enterprise can assist in overcoming existing barriers to the labour market. Findings The paper highlights the value of social enterprise(s) in addressing the complex needs and precarities of criminalised youths, promoting social inclusion and assisting with progression into future employment. The paper also discusses the limitations of social enterprise(s) in overcoming external structural barriers to meaningful employment for those with an offending history and the implications for young people who aspire to more than precariat work. Originality/value Justice-orientated social enterprises are allowing young people with criminal records the opportunity to build social capita and access precarious work, previously unattainable for many. By focusing on the concept of “precarity”, this paper builds upon existing research on the collateral consequences of criminal convictions offering insights into the various challenges facing criminalised youths attempting to build a positive pro-social work identity within contemporary labour markets

RATIONALE: Shared symptoms and genetic architecture between COVID-19 and lung fibrosis suggests SARS-CoV-2 infection may lead to progressive lung damage.OBJECTIVES: The UKILD Post-COVID study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 based on risk strata.METHODS: The Post-HOSPitalisation COVID Study (PHOSP-COVID) was used for capture of routine and research follow-up within 240 days from discharge. Thoracic CTs linked by PHOSP-COVID identifiers were scored for percentage of residual lung abnormalities (ground glass opacities and reticulations). Risk factors in linked CT were estimated with Bayesian binomial regression and risk strata were generated. Numbers within strata were used to estimate post-hospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol driven research follow-up.MEASUREMENTS AND MAIN RESULTS: The interim cohort comprised 3700 people. Of 209 subjects with linked CTs (median 119 days, interquartile range 83-155), 166 people (79.4%) had >10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (RR 1·21 95%CrI 1·05; 1·40), percent predicted DLcoCONCLUSIONS: Residual lung abnormalities were estimated in up to 11% of people discharged following COVID-19 related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Ali CMB Polarization Telescope (AliCPT) is the first Cosmic Microwave Background (CMB) polarimeter with a large focal plane camera to be deployed in the Northern Hemisphere, in the Tibetan Plateau. Here we present the design of a dichroic (90/150 GHz) focal plane camera capable of hosting up to 32,376 Transition-Edge Sensor (TES) bolometers operating from a base temperature of 280 mK. Detectors are fabricated as monolithic arrays of 1,704 feedhorn-coupled and polarization-sensitive TES bolometers that are packaged in independent modules and read out with a microwave multiplexing architecture. A custom RFSoC-based system manages the multiplexing readout. Prototype AliCPT pixels have been fabricated and characterized, demonstrating passband performance within 2.5% of design and cross-polarization systematic sensitivity $\leq$ 2%.

The Simons Observatory is a ground-based cosmic microwave background survey experiment that consists of three 0.5 m small-aperture telescopes and one 6 m large-aperture telescope, sited at an elevation of 5200 m in the Atacama Desert in Chile. SO will deploy 60,000 transition-edge sensor (TES) bolometers in 49 separate focal-plane modules across a suite of four telescopes covering 30/40 GHz low frequency (LF), 90/150 GHz mid frequency (MF), and 220/280 GHz ultra-high frequency (UHF). Each MF and UHF focal-plane module packages 1720 optical detectors spreading across 12 detector bias lines that provide voltage biasing to the detectors. During observation, detectors are subject to varying atmospheric emission and hence need to be re-biased accordingly. The re-biasing process includes measuring the detector properties such as the TES resistance and responsivity in a fast manner. Based on the result, detectors within one bias line then are biased with suitable voltage. Here we describe a technique for re-biasing detectors in the modules using the result from bias-step measurement.

Background: Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide [FENO], blood eosinophils, and serum periostin) with a standardised symptom–risk-based algorithm (control). Methods: We did a single-blind, parallel group, randomised controlled trial in adults (18–80 years of age) with severe asthma (at treatment steps 4 and 5 of the Global Initiative for Asthma) and FENO of less than 45 parts per billion at12 specialist severe asthma centres across England, Scotland, and Northern Ireland. Patients were randomly assigned (4:1) to either the biomarker strategy group or the control group by an online electronic case-report form, in blocks of ten, stratified by asthma control and use of rescue systemic steroids in the previous year. Patients were masked to study group allocation throughout the entirety of the study. Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment-group-specific algorithms: those in the biomarker strategy group received a default advisory to maintain treatment and those in the control group had their treatment adjusted according to the steps indicated by the trial algorithm. The primary outcome was the proportion of patients with corticosteroid dose reduction at week 48, in the intention-to-treat (ITT) population. Secondary outcomes were inhaled corticosteroid (ICS) dose at the end of the study; cumulative dose of ICS during the study; proportion of patients on maintenance oral corticosteroids (OCS) at study end; rate of protocol-defined severe exacerbations per patient year; time to first severe exacerbation; number of hospital admissions for asthma; changes in lung function, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score, and T2 biomarkers from baseline to week 48; and whether patients declined to progress to OCS. A secondary aim of our study was to establish the proportion of patients with severe asthma in whom T2 biomarkers remained low when corticosteroid therapy was decreased to a minimum ICS dose. This study is registered with ClinicalTrials.gov, NCT02717689 and has been completed. Findings: Patients were recruited from Jan 8, 2016, to July 12, 2018. Of 549 patients assessed, 301 patients were included in the ITT population and were randomly assigned to the biomarker strategy group (n=240) or to the control group(n=61). 28·4% of patients in the biomarker strategy group were on a lower corticosteroid dose at week 48 compared with 18·5% of patients in the control group (adjusted odds ratio [aOR] 1·71 [95% CI 0·80–3·63]; p=0·17). In the per-protocol (PP) population (n=121), a significantly greater proportion of patients were on a lower corticosteroid dose at week 48 in the biomarker strategy group (30·7% of patients) compared with the control group (5·0% of patients; aOR 11·48 [95% CI 1·35–97·83]; p=0·026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study groups and no loss of asthma control among patients in the biomarker strategy group who reduced their corticosteroid dose. Interpretation: Biomarker-based corticosteroid adjustment did not result in a greater proportion of patients reducing corticosteroid dose versus control. Understanding the reasons for patients not following treatment advice in both treatment strategies is an important area for future research. The prevalence of T2 biomarker-low severe asthma was low.

Noncovalent interactions between alkali metals and amino acids are critical for many biological processes, especially for proper function of protein ion channels; however, many precise binding affinities between alkali metals and amino acids still need to be measured. This study addresses this need by using threshold collision-induced dissociation with a guided ion beam tandem mass spectrometer to measure binding affinities between potassium cations and the aliphatic amino acids: Gly, Ala, hAla, Val, Leu, and Ile. These measurements are supplemented by theoretical calculations and include commentary on effects of enthalpy, entropy, and structural preference. Notably, all levels of theory indicate that the lowest-lying isomers at 298 K have K

Macroinvertebrates can be highly sensitive to elevated salinity in freshwater environments, and are known to respond to saline discharges. Magnesium (Mg) is a mine-related contaminant and is a potential environmental risk to a seasonally-flowing, receiving water stream in Kakadu National Park, located in the wet-dry tropics of Australia. The macroinvertebrate assemblage in the stream in the was characterised at four hydrographic phases, from early wet season flow to early dry season pools at flow cessation. On each of the four occasions representing the respective phases, individuals from the most abundant macroinvertebrate species present were collected and acutely exposed to a range (up to 19) of Mg concentrations under laboratory conditions. Sensitivity of taxa to Mg ranged between 39 mg/L Mg (Caenidae: Tasmanocoenis spp.) and 4400 mg/L Mg (Dytiscidae: Clypeodytes feryi), based on the 50% Lethal Concentration (LC50). Characterisation of the macroinvertebrate assemblage at each hydrographic phase indicated the seasons when Mg-sensitive species were present. Whilst no statistical differences in measures of seasonal sensitivity were found, the macroinvertebrate assemblages present during the early flow period had higher Mg-sensitivity than the assemblages present during other hydrographic phases. This could be attributed to the greater relative proportions of Mg-sensitive taxa (e.g. Ephemeroptera) present at early flow compared to greater relative proportions of more Mg-tolerant taxa (C. feryi and Hydacarina spp.) present during later hydrograph phases, especially periods of lower, or no, flow.

Geometrically complex masonry structures built with traditional techniques typically require either temporary scaffolding or skilled masons. This paper presents a novel fabrication process for the assembly of full-scale masonry vaults without the use of falsework. The fabrication method is based on a cooperative assembly approach in which two robots alternate between placement and support to first build a stable central arch. Subsequently, the construction is continued individually by the robots - building out from the central arch based on an interlocking diagonal brick sequence. This proposed method is validated through its successful implementation in a full-scale vault structure consisting of 256 glass and concrete standardized bricks. The paper includes strategies for developing the design, sequencing, and robotic assembly methods used to build the vault.

The ‘culturalisation of violence’ – a process through which culture is credited as being the sole or principal cause of violence – has resulted in ‘honour’-based violence/abuse being commonly (mis)understood and (mis)interpreted as being an imported cultural practice unique to particular black, Asian and minority ethnic communities living in the West. Addressing a vital gap in the literature, this article considers the conceptual shortcomings of these culturalised narratives on honour and ‘honour’-based violence/abuse, as well as the impact that they have upon service provision in rural areas of England and Wales – areas often conceptualised as ‘white spaces’ lacking in ethnic diversity. This article draws upon semi-structured interviews with both victims/survivors and rural front-line service providers. It is argued that under culturalised narratives, not only does ethnicity remain a key indicator for ‘honour’-based violence/abuse cases, but, as such, and given their perceived lack of ethnic diversity, rural regions are also increasingly identified as ‘safe spaces’ to relocate black, Asian and minority ethnic victims/survivors away from the reach of their ‘problematic’ culture. Ultimately, the core contention of this article is that by founding policy, legislative and support responses on culturalised understandings of violence, service providers are destined to fail to meet the intersectional needs of black, Asian and minority ethnic victims/survivors.

LiteBIRD is a cosmic microwave background polarization experiment with the goal of measuring the tensor-to-scalar ratio with a total uncertainty of $$\delta r

SummaryObjectivesTo investigate the experience of people who continue to be unwell after acute COVID-19, often referred to as ‘long COVID’, both in terms of their symptoms and their interactions with healthcare.DesignWe conducted a mixed-methods analysis (quantitative and qualitative) of responses to a survey accessed through a UK online post-COVID support and information hub between April 2020 and December 2020 about people’s experiences after having acute COVID-19.ParticipantsOf 3290 respondents, 78% were female, median age range 45-54 years, 92.1% reported white ethnicity; 12.7% had been hospitalised. 494 respondents (16.5%) completed the survey between 4 and 8 weeks of the onset of their symptoms, 641 (21.4%) between 8 and 12 weeks and 1865 (62.1%) more than 12 weeks after.ResultsThe ongoing symptoms most frequently reported were; breathing problems (92.1%), fatigue (83.3%), muscle weakness or joint stiffness (50.6%), sleep disturbances (46.2%), problems with mental abilities (45.9%) changes in mood, including anxiety and depression (43.1%) and cough (42.3%). Symptoms did not appear to be related to the severity of the acute illness or to the presence of pre-existing medical conditions. Analysis of free text responses revealed three main themes (1) Experience of living with COVID-19 – physical and psychological symptoms that fluctuate unpredictably; (2) Interactions with healthcare; (3) Implications for the future – their own condition, society and the healthcare system and the need for researchConclusionPeople living with persistent problems after the acute phase of COVID-19 report multiple and varying symptoms that are not necessarily associated with initial disease severity or the presence of pre-existing health conditions. Many have substantial unmet needs and experience barriers to accessing healthcare. Consideration of patient perspective and experiences will assist in the planning of services to address this.Ethical approvalEthical approval was granted by Imperial College Research and Integrity Team (IREC; 20IC6625).What we already know on this subjectMany people who develop COVID-19 will go on to endure persistent symptoms past the acute phase of the disease, commonly termed long-COVID.Knowledge gaps exist regarding the lived experience and symptom frequency, in people with long-COVID, particularly in those who were not admitted to hospital during the acute phase of their illness.What this study addsThe findings from this large population, many of whom were not hospitalised during the acute phase of their illness, demonstrate the varying patterns and persistence of symptoms of long-COVID, which do not appear to be associated with severity of the acute phase of the disease or pre-existing medical conditions.Qualitative findings revealing the patient experience of long-COVID symptoms, healthcare, and suggestions for future research and service adaptation.

Background: understanding why patients with severe asthma do not follow healthcare provider (HCP) advice to adjust treatment is critical to achieving personalised disease management.Methods: we reviewed patient choice to follow HCP advice to adjust asthma treatment in a randomised, controlled, single-blind (study participant), multi-centre, parallel group 48-week clinical study comparing biomarker directed treatment adjustment to standard care in severe asthma.Results: of 1572 treatment advisories (301 participants), instructions were followed in 1377 cases (87.6%). Patients were more likely to follow advice to remain on treatment (96.7%) than to either reduce (70.3%) or increase (67.1%) their treatment, with 64% of patients following all treatment advice. Multivariate analysis associated belonging to an ethnic minority group (OR: 3.10; 95% CI: 1.68, 5.73) and prior study medication changes (≥2 OR: 2.77, 95% CI: 1.51, 5.10) with failure to follow treatment advice. In contrast, emergency room attendance in the prior year (OR: 0.54, 95% CI: 0.32, 0.92) was associated with following treatment advice. The largest effect was seen with transition onto or off oral corticosteroids (OR: 29.28; 95% CI: 16.07, 53.36) when compared to those requested to maintain treatment. Centre was also an important determinant regarding the likelihood of patients to follow treatment advice.Conclusions: belonging to an ethnic minority group and multiple prior treatment adjustments were associated with not following HCP treatment advice. Patients also responded differently to HCP advice across UK specialist centres. These findings have implications for generalisability for models of care in severe asthma and require further focussed studies.

Rupert Jones,1– 3 Andrew Davis,1,2 Brooklyn Stanley,1,2 Steven Julious,4 Dermot Ryan,5 David J Jackson,6 David MG Halpin,7 Katherine Hickman,8 Hilary Pinnock,9 Jennifer K Quint,10 Kamlesh Khunti,11 Liam G Heaney,12 Phillip Oliver,4 Salman Siddiqui,13 Ian Pavord,14 David HM Jones,15 Michael Hyland,3,16 Lewis Ritchie,17 Pam Young,18 Tony Megaw,18 Steve Davis,19 Samantha Walker,20 Stephen Holgate,21 Sue Beecroft,22 Anu Kemppinen,1,2 Francis Appiagyei,1,2 Emma-Jane Roberts,1,2 Megan Preston,1,2 Antony Hardjojo,1,2 Victoria Carter,1,2 Marije van Melle,1,2 David Price1,2,17 1Optimum Patient Care, Cambridge, UK; 2Observational and Pragmatic Research Institute, Singapore, Singapore; 3Faculty of Health, University of Plymouth, Plymouth, UK; 4University of Sheffield, South Yorkshire, UK; 5Usher Institute, University of Edinburgh, Edinburgh, UK; 6Guy’s & St Thomas’ NHS Trust, School of Immunology & Microbial Sciences, King’s College London, London, UK; 7University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 8Bradford and Leeds Clinical Commissioning Group, Leeds, UK; 9Asthma UK Centre for Applied Research, Usher Institute, The University of Edinburgh, Edinburgh, UK; 10National Heart & Lung Institute, Imperial College London, London, UK; 11Diabetes Research Centre, University of Leicester, Leicester, UK; 12Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern Ireland; 13Institute for Lung Health, Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester, UK; 14Respiratory Medicine Unit and Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 15Box Surgery, Wiltshire, UK; 16Plymouth Marjon University, Plymouth, UK; 17Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 18Wellbeing Software, Mansfield, UK; 19Interface Clinical Services, Leeds, UK; 20Asthma UK & British Lung Foundation, London, UK; 21Clinical and Experimental Sciences, University of Southampton, Southampton, UK; 22OPEN Health, Buckinghamshire, UKCorrespondence: David PriceAcademic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UKTel +65 3105 1489Email dprice@opri.sgIntroduction: Symptoms may persist after the initial phases of COVID-19 infection, a phenomenon termed long COVID. Current knowledge on long COVID has been mostly derived from test-confirmed and hospitalized COVID-19 patients. Data are required on the burden and predictors of long COVID in a broader patient group, which includes both tested and untested COVID-19 patients in primary care.Methods: This is an observational study using data from Platform C19, a quality improvement program-derived research database linking primary care electronic health record data (EHR) with patient-reported questionnaire information. Participating general practices invited consenting patients aged 18– 85 to complete an online questionnaire since 7th August 2020. COVID-19 self-diagnosis, clinician-diagnosis, testing, and the presence and duration of symptoms were assessed via the questionnaire. Patients were considered present with long COVID if they reported symptoms lasting ≥ 4 weeks. EHR and questionnaire data up till 22nd January 2021 were extracted for analysis. Multivariable regression analyses were conducted comparing demographics, clinical characteristics, and presence of symptoms between patients with long COVID and patients with shorter symptom duration.Results: Long COVID was present in 310/3151 (9.8%) patients with self-diagnosed, clinician-diagnosed, or test-confirmed COVID-19. Only 106/310 (34.2%) long COVID patients had test-confirmed COVID-19. Risk predictors of long COVID were age ≥ 40 years (adjusted Odds Ratio [AdjOR]=1.49 [1.05– 2.17]), female sex (adjOR=1.37 [1.02– 1.85]), frailty (adjOR=2.39 [1.29– 4.27]), visit to A&E (adjOR=4.28 [2.31– 7.78]), and hospital admission for COVID-19 symptoms (adjOR=3.22 [1.77– 5.79]). Aches and pain (adjOR=1.70 [1.21– 2.39]), appetite loss (adjOR=3.15 [1.78– 5.92]), confusion and disorientation (adjOR=2.17 [1.57– 2.99]), diarrhea (adjOR=1.4 [1.03– 1.89]), and persistent dry cough (adjOR=2.77 [1.94– 3.98]) were symptom features statistically more common in long COVID.Conclusion: This study reports the factors and symptom features predicting long COVID in a broad primary care population, including both test-confirmed and the previously missed group of COVID-19 patients.Keywords: SARS-CoV-2, questionnaire, observational study, frailty, chronic diseases

Hunter-gatherer mortuary practices identified in the Trent Valley region, ON are highly patterned for the Middle Woodland period (400 BCE-700 CE), but the importance of many of these mortuary sites can be recognized as far back as the Late Archaic period (2500–1000 BCE). A geospatial modelling approach is used to predict the distribution of mortuary sites based on ecological factors that may have influenced land use strategies. The assessment reveals that Late Archaic and Middle Woodland mortuary sites were primarily located near aerobic wetlands that were likely rich in emergent plant life. The predicted suitably of mineral soil horizons, when compared with Trent Valley floodplain behaviour, suggests that wild rice may have been a particularly abundant resource near mortuary sites. The position of wild rice in Anishinaabe traditional stories is discussed to contextualize its potential early food value to Indigenous occupants of the Trent Valley, prior to the resource’s documented historic importance. The highly selective positioning of mortuary sites and their continuity within the Trent Valley region shed light on how ancestral ties to key places were established and maintained in precolonial hunter-gatherer societies.

Although once considered a single disease entity, asthma is now known to be a complex inflammatory disease engaging a range of causal pathways. The most frequent forms of asthma are identified by sputum/blood eosinophilia and activation of type 2 inflammatory pathways involving interleukins-3, -4, -5, and granulocyte-macrophage colony-stimulating factor. The use of diagnostics that identify T2 engagement linked to the selective use of highly targeted biologics has opened up a new way of managing severe disease. Novel technologies, such as wearables and intelligent inhalers, enable real-time remote monitoring of asthma, creating a unique opportunity for personalized health care.

Viewed as a culmination of broader neoliberal governance within the UK, this paper examines the impact of the government’s Transforming Rehabilitation (TR) agenda on day-to-day working cultures at the frontline of probation work. TR has brought with it extensive structural and cultural changes to probation work in England and Wales. Once a single public-sector service with a social welfare ethos of ‘advise, assist and befriend’, probation has been dismantled, partially privatised and culturally transformed into a collection of fragmented, target-driven organisations, divided according to risk and with an official rhetoric emphasising public protection. The implications of TR are now starting to surface. While much of this attention has focused on the impact of TR on both the supervision of offenders and in terms of public protection, less research has been conducted on how these organisational changes have impacted upon staff. Drawing upon findings from qualitative research, this article suggests that deepening cuts, precarious working environments, and increasingly unmanageable caseloads inflict upon staff what we consider to be a pervasive form of systemic workplace harm, resulting in mental health issues, stress, and professional dissatisfaction.

International audience; In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system for integrated care with organizational health literacy. MASK (Mobile Airways Sentinel NetworK) (1), a new development of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health) (2), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life integrated care pathways (ICPs) (3)-centred around the patient with rhinitis and using mHealth monitoring of environmental exposure (4).An expert meeting took place at the Pasteur Institute in Paris, December 3, 2018. The aim was to discuss next-generation care pathways: (I) Patient participation, health literacy and self-care through technology-assisted “patient activation”; (II) Implementation of care pathways by pharmacists and (III) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) assessed by mobile technology.The EU (5) and global political agendas are of great importance in supporting health care transformation. MASK has been recognized by DG Santé as a Good Practice (6) in the field of digitally-enabled, integrated, person-centred care.The one-day meeting objectives were clear (Figure 1). The meeting was followed by a workshop. The present paper reports the background of the two-day meeting.

BackgroundAsthma exacerbations affect the quality of life of patients with asthma and have a major effect on the overall costs of asthma care. An asthma self-management plan that advises the temporary quadrupling of inhaled corticosteroid dose may prevent asthma exacerbations, but this needs to be confirmed before being adopted widely.ObjectivesTo compare the clinical effectiveness and cost-effectiveness of an asthma self-management plan that advises patients to temporarily quadruple the dose of inhaled corticosteroid when asthma control starts to deteriorate with a standard self-management plan.DesignA multicentre, parallel-group, pragmatic randomised trial, with follow-up for 12 months.SettingPrimary and secondary care across 207 sites in the UK.ParticipantsAsthma patients aged ≥ 16 years treated with an inhaled corticosteroid who had experienced at least one exacerbation in the previous 12 months.InterventionsParticipants were randomised (1 : 1) to a usual-care self-management plan or to a modified self-management plan that advised a temporary quadrupling of the inhaled corticosteroid at the point of asthma deterioration, both of which were actively implemented and supported by local research staff.Primary outcomeThe primary outcome of ‘time to first asthma exacerbation’ was defined as the need for systemic corticosteroids (for at least 3 consecutive days) and/or unscheduled health-care consultations for asthma (i.e. reaching zone 3 or 4 of the Asthma UK self-management plan).ResultsA total of 1922 participants were randomised: the primary analysis included 938 participants (97%) in the usual-care group and 933 participants (97%) in the modified self-management group. The number of participants having at least one exacerbation of asthma in the year after randomisation was 484 (51.6%) in the usual-care group and 420 (45.0%) in the modified self-management group [adjusted hazard ratio 0.81, 95% confidence interval (CI) 0.71 to 0.92;p = 0.002]. There were fewer serious adverse events reported in the modified self-management group than in the usual-care group (11 vs. 32, respectively). Eight and six events of pneumonia, lower respiratory tract infections or influenza were reported in the usual-care group and the modified self-management group, respectively. Health-care-related costs were lower in the modified self-management group. The modified self-management group was £24 (bootstrapped 95% CI –£122 to £71) less costly than usual care, with a greater quality-adjusted life-year gain of 0.02 (bootstrapped 95% CI –0.005 to 0.04). Therefore, the modified self-management group was ‘dominant’, with a 94–95% probability of being cost-effective at the £20,000–30,000 threshold.LimitationsAs the Fourfold Asthma STudy (FAST) was an open-label pragmatic trial, the possibility of treatment bias that may have affected the participants in the modified self-management group cannot be ruled out. Poorer than expected completion of participant diary cards, particularly within the usual-care self-management group, could have led to a null bias, underestimating the true effect of the intervention.ConclusionsAn asthma self-management plan that advises patients to temporarily quadruple their dose of inhaled corticosteroid at the point of asthma symptoms worsening does reduce clinically important asthma exacerbations. In addition, the plan is cost-effective compared with the usual-care self-management plan.Future workTo effectively implement asthma self-management plans that advise a temporary quadrupling of inhaled steroid at asthma deterioration into routine practice.Trial registrationCurrent Controlled Trials ISRCTN15441965.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 70. See the NIHR Journals Library website for further project information.

AIMS Venue capacity has been proposed as a factor associated with increased number of violent incidents on-premises, though no specific research has demonstrated this association, and instead has tended to focus on the relationship between crowding and aggression. The aim of current paper is to investigate the association between venue capacity and the number of violent incidents on-premises. METHODS Venue capacity data (the maximum capacity listed on the liquor license) were obtained for all venues in central Melbourne from 2010 until 2016. These data were then matched with police-recorded on-premises assaults that occurred within high-alcohol hours (Friday and Saturday 8 pm-6 am) inside the venue. RESULTS Analyses were conducted on 5729 venue-years (yearly assault counts per venue, per year) across central Melbourne. Compared with venues that have a maximum capacity of between 0 and 100 patrons, venues with higher capacities have increasingly more recorded assaults. Venues with maximum capacities between 501 and 1000 are 6.1 times more likely to have an assault recorded compared with venues with a maximum capacity between 0 and 100. Further, each additional high-alcohol hour that a venue can be open for is associated with a 72% increase in the number of recorded assaults. CONCLUSIONS Greater venue capacity was found to be strongly associated with an increased risk of violent incidents for any given venue. This was further exacerbated by late-night trading which substantially adds to the risk of assaults inside the venue.

We describe the design and measurement of feedhorn-coupled, transition-edge sensor (TES) polarimeters with two passbands centered at 220 GHz and 280 GHz, intended for observations of the cosmic microwave background. Each pixel couples polarized light in two linear polarizations by use of a planar orthomode transducer and senses power via four TES bolometers, one for each band in each linear polarization. Previous designs of this detector architecture incorporated passbands from 27 GHz to 220 GHz; we now demonstrate this technology at frequencies up to 315 GHz. Observational passbands are defined with an on-chip diplexer, and Fourier-transform-spectrometer measurements are in excellent agreement with simulations. We find coupling from feedhorn to TES bolometer using a cryogenic, temperature-controlled thermal source. We determine the optical efficiency of our device is $\eta$ = 77%$\pm$6% (75%$\pm$5%) for 220 (280) GHz, relative to the designed passband shapes. Lastly, we compare two power-termination schemes commonly used in wide-bandwidth millimeter-wave polarimeters and find equal performance in terms of optical efficiency and passband shape., Comment: Proceedings for the 18th International Workshop on Low Temperature Detectors (LTD18), submitted to the Journal of Low Temperature Physics

Cosmic microwave background (CMB) polarization experiments utilize arrays of low temperature detectors, such as superconducting transition-edge sensor (TES) bolometers. Voltage-biased TES bolometers must be embedded in a readout circuit that allows for stable operation. To ensure stability and to test our physical and electrothermal model of these devices, measurements aimed at characterizing the dynamics of the sensor over the range of detector bias and loading conditions relevant to our application are carried out for multiple bolometer designs. In this work, we present bolometer electrothermal properties derived from current-voltage curves, effective electrothermal time constant measurements, and complex impedance measurements of AlMn TES bolometers intended for the Ali CMB Polarization Telescope (AliCPT). All bolometers consist of 385nm thick 1400 ppma AlMn film with measured superconducting critical temperature Tc = 480 mK. The bolometers are well-described by a simple, one-pole electrothermal model with a natural time constant τ0 that we adjust by varying the leg geometry and the amount of PdAu thermal ballast on the bolometer island. From these measurements, we determine that the volumetric heat capacity of sputtered PdAu (atomic percentages 67.6%/32.4%) at 480mK is 0.22 fJ/(K·μm3). Finally, we present the TES parameters as a function of operational resistance and over a range of loading conditions.

Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airways diseases. Both are complex and heterogeneous. Traditionally, clinical guidelines have advocated a stepwise approach to pharmacotherapy of asthma and COPD, but there is increasing realization that both require a more personalized and precise management approach. To this end, a management strategy based on the so-called Treatable Traits has been proposed. Emerging evidence suggests that this model improves relevant outcomes in patients with chronic airway diseases but further research is needed to guide implementation. This review discusses the challenges, opportunities, and hurdles that its implementation will have to face.

The Simons Observatory (SO) is a cosmic microwave background (CMB) experiment from the Atacama Desert in Chile comprising three small-aperture telescopes (SATs) and one large-aperture telescope (LAT). In total, SO will field over 60,000 transition-edge sensor (TES) bolometers in six spectral bands centered between 27 and 280 GHz in order to achieve the sensitivity necessary to measure or constrain numerous cosmological quantities. In this work, we focus on the SATs which are optimized to search for primordial gravitational waves that are detected as parity-odd polarization patterns called a B-modes on degree scales in the CMB. Each SAT employs a single optics tube with TES arrays operating at 100 mK. The high throughput optics system has a 42 cm aperture and a 35-degree field of view coupled to a 36 cm diameter focal plane. The optics consist of three metamaterial anti-re ection coated silicon lenses. Cryogenic ring baffles with engineered blackbody absorbers are installed in the optics tube to minimize the stray light. The entire optics tube is cooled to 1 K. A cryogenic continuously rotating half-wave plate near the sky side of the aperture stop helps to minimize the effect of atmospheric uctuations. The telescope warm baffling consists of a forebaffle, an elevation stage mounted co-moving shield, and a fixed ground shield that together control the far side-lobes and mitigates ground-synchronous systematics. We present the status of the SAT development., Comment: 8 pages, 6 figures

Persistent ill health after acute COVID-19-referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition-has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression, and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.