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A soundscape approach was used for a co-housing development in Newcastle upon Tyne, UK. The outcomes are compared and contrasted with a conventional noise impact assessment. In-situ soundwalks were conducted with the co-housing group during daytime and night-time periods, covering locations with varied sounds and future uses. A virtual soundwalk, including external and internal scenes (with windows open and closed), was created using binaural recordings from the in-situ soundwalk. A separate virtual soundwalk event was organised for the public to investigate the ecological validity of the auralisations. Data collection and analysis methods followed ISO 12913. The questionnaire responses revealed quite different assessments of the acoustic environment compared with the measured decibel values of LAeq,T. These differences could be explained by the perception of the acoustic environment. The process helped the co-housing group to identify their expectations and preferences of the sound environment of their future homes. Ideas to encourage and highlight positive (natural) sounds were identified, as were different uses for external areas. The study illustrates the potential and challenges of using a soundscape approach for residential developments, highlighting the aspects of co-creation and inclusivity.

BackgroundDespite the availability of vaccines and therapies, patients are being hospitalised with coronavirus disease 2019 (COVID-19). Interferon (IFN)-β is a naturally occurring protein that stimulates host immune responses against most viruses, including severe acute respiratory syndrome coronavirus 2. SNG001 is a recombinant IFN-β1a formulation delivered to the lungsvianebuliser. SPRINTER assessed the efficacy and safety of SNG001 in adults hospitalised due to COVID-19 who required oxygenvianasal prongs or mask.MethodsPatients were randomised double-blind to SNG001 (n=309) or placebo (n=314) once daily for 14 days plus standard of care (SoC). The primary objective was to evaluate recovery after administration of SNG001versusplacebo, in terms of times to hospital discharge and recovery to no limitation of activity. Key secondary end-points were progression to severe disease or death, progression to intubation or death and death.ResultsMedian time to hospital discharge was 7.0 and 8.0 days with SNG001 and placebo, respectively (hazard ratio (HR) 1.06 (95% CI 0.89–1.27); p=0.51); time to recovery was 25.0 days in both groups (HR 1.02 (95% CI 0.81–1.28); p=0.89). There were no significant SNG001–placebo differences for the key secondary end-points, with a 25.7% relative risk reduction in progression to severe disease or death (10.7% and 14.4%, respectively; OR 0.71 (95% CI 0.44–1.15); p=0.161). Serious adverse events were reported by 12.6% and 18.2% patients with SNG001 and placebo, respectively.ConclusionsAlthough the primary objective of the study was not met, SNG001 had a favourable safety profile, and the key secondary end-points analysis suggested that SNG001 may have prevented progression to severe disease.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a class of anti-hyperglycaemic agents widely used in the treatment of type 2 diabetes mellitus (T2DM). They function by reducing renal glucose reabsorption and thereby promote urinary glucose excretion, resulting in improvement in glycaemic control. In large-scale clinical trials, SGLT2i have been shown to reduce cardiovascular mortality, non-fatal myocardial infarction and stroke significantly. In addition, clinical evidence suggests that they are renal protective as their use reduces the relative risk of end-stage renal disease and death from renal causes. These positive results have led to a rapid uptake of SGLT2i in clinical practice. Recently, clinical studies and case reports have suggested a link between SGLT2i therapy and erythrocytosis. The authors discuss possible mechanisms at cellular level that may cause erythrocytosis and explore its clinical relevance in people living with T2DM who are taking SGLT2i therapy.

The medication expertise of pharmacists is widely acknowledged and there is ongoing interest in their potential role to reduce medication-related harm amongst residents living in residential aged care facilities (RACFs). An increased understanding of how these interventions are evaluated could support adoption of these interventions in the real world.To systematically explore the application of evaluation approaches, evaluation tools and aspects of implementation (implementation factors i.e. barriers and facilitators, and assessing implementation fidelity) used in pharmacist intervention in RACF peer-reviewed literature.A search strategy was applied to MEDLINE, CINAHL, Cochrane Library and Web of Science databases for publications between 1 January 2000 and 27 August 2020 based on defined inclusion and exclusion criteria. Articles that reported on evaluated pharmacist interventions impacting residents in RACFs or which outlined study participant perspectives in relation to these interventions were included.2003 published articles were identified, out of which 56 articles met the inclusion criteria. Fifty-three articles reported on outcome evaluations. Four articles used evaluation guidance with 1 article explicitly guided by an evaluation framework. Relationships, trust and respect between pharmacists and RACF health care team members were one of the most reported factors influencing intervention success. None of the 56 articles used a theory or model, assessed implementation fidelity or employed a logic model.To date there appears to be sparse utilisation of available evaluation approaches, evaluation tools and implementation aspects in pharmacist intervention in RACF peer-reviewed literature. By embracing these evaluation approaches, evaluation tools and aspects of implementation, pharmacy practice researchers have an opportunity to contribute to evaluation research in RACFs and beyond.

In the marine ecosystem, mesozooplankton, especially large copepods, have an important role both in the mediation of primary production to higher trophic levels and in the transportation of organic materials from the surface to the deep ocean, termed the biological pump. Continuous Plankton Recorder (CPR) surveys have been used as a long-term monitoring method for mesozooplankton over wide geographical areas, including the North Pacific, where a CPR survey began in 2000. In this study, we used CPR samples collected in the western subarctic Pacific during 2001-2015 to investigate the abundance and population structure of five large, dominant copepods (Neocalanus cristatus, N. flemingeri, N. plumchrus, Eucalanus bungii and Metridia pacifica) and evaluate the differences in season, region, and diel scales between species. Significant seasonal changes in abundance and population structure were detected, and these changes were considered to reflect the life history of each species. Regional differences were detected for the three Necalanus species and were considered to be related to sea surface temperature and food availability. Diel changes in abundance were observed for N. cristatus and M. pacifica, with both species more abundant near the surface at night suggesting diel vertical migration.

Re-examination of the Turoe stone, Co. Galway, Ireland, a small granite pillar decorated with Celtic art, has revealed a possible, previously un-noticed, stylised boar’s head.

If researchers are to understand the impacts of lockdown on children and young people, then the experiences of lockdown need to be explored from the perspective of the child. Young people participate in leisure for a multitude of reasons, yet, within the UK, children were largely unable to access their regular leisure activities for a six-month period during the first national lockdown. Within the context of this paper, leisure includes outdoor sports and physical activities within blue spaces. Following interviews with parents and young people (aged 11–16) focused on experiences of leisure during the Covid-19 pandemic, this qualitative study identified that children felt an intense sense of missing out on opportunities and found day-to-day life without leisure monotonous. However, there were some positive impacts of reduced leisure, such as a greater appreciation for what was once a regular activity. This research empowered the voice of children, so their distinct experiences were made visible to those who aim to support their wellbeing. Findings suggest that the promotion of leisure activities in the current climate could mitigate poor wellbeing among children associated with the Covid-19 pandemic.

Background Subanesthetic ketamine infusions can elicit rapid and sustained antidepressant effects, yet the potential cognitive impact of ketamine has not been thoroughly examined. This study measured changes in objective and subjective cognitive function following repeated ketamine treatment. Methods Thirty-eight patients with treatment-resistant depression were administered cognitive assessments before and after undergoing 7 i.v. ketamine infusions (0.5 mg/kg over 40 minutes) within a clinical trial examining the efficacy of single and repeated administrations. Depression severity and perceived concentration were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms Self-Report. Results Twenty-three participants (60.5%) responded after repeated infusions (≥50% decrease in MADRS total scores). We measured significant improvements in several cognitive domains, including attention, working memory, verbal, and visuospatial memory (effect sizes ranging from Cohen d = 0.37–0.79). Cognitive changes were attributed to reduction in depressive symptoms except for improvement in verbal memory, which remained significant after adjustment for change in MADRS total score (P = .029, η p2 = 0.13). Only responders reported improvement in subjective cognitive function with repeated ketamine administration (MADRS item 6, P Conclusion A short course of repeated ketamine infusions did not impair neurocognitive function in patients with treatment-resistant depression. Further research is required to understand the potential mediating role of response and remission on improved cognitive function accompanying ketamine treatment as well as to examine longer-term safety outcomes. ClinicalTrials.gov identifier NCT01945047

There is a growing interest in single-class modelling and out-of-distribution detection as fully supervised machine learning models cannot reliably identify classes not included in their training. The long tail of infinitely many out-of-distribution classes in real-world scenarios, e.g., for screening, triage, and quality control, means that it is often necessary to train single-class models that represent an expected feature distribution, e.g., from only strictly healthy volunteer data. Conventional supervised machine learning would require the collection of datasets that contain enough samples of all possible diseases in every imaging modality, which is not realistic. Self-supervised learning methods with synthetic anomalies are currently amongst the most promising approaches, alongside generative auto-encoders that analyse the residual reconstruction error. However, all methods suffer from a lack of structured validation, which makes calibration for deployment difficult and dataset-dependant. Our method alleviates this by making use of multiple visually-distinct synthetic anomaly learning tasks for both training and validation. This enables more robust training and generalisation. With our approach we can readily outperform state-of-the-art methods, which we demonstrate on exemplars in brain MRI and chest X-rays. Code is available at https://github.com/matt-baugh/many-tasks-make-light-work ., Early accepted to MICCAI 2023

This technical report outlines our submission to the zero-shot track of the Visual Anomaly and Novelty Detection (VAND) 2023 Challenge. Building on the performance of the WINCLIP framework, we aim to enhance the system's localization capabilities by integrating zero-shot segmentation models. In addition, we perform foreground instance segmentation which enables the model to focus on the relevant parts of the image, thus allowing the models to better identify small or subtle deviations. Our pipeline requires no external data or information, allowing for it to be directly applied to new datasets. Our team (Variance Vigilance Vanguard) ranked third in the zero-shot track of the VAND challenge, and achieve an average F1-max score of 81.5/24.2 at a sample/pixel level on the VisA dataset., Ranked 3rd in zero-shot track of the Visual Anomaly and Novelty Detection (VAND) 2023 Challenge

This qualitative study uses interview data to explore clinician perspectives on the function of multidisciplinary tumor boards beyond clinical decision-making.

Aerosol-cloud interaction contributes to one of the highest uncertainties in radiative forcing estimations. Aerosols from ship emissions alter the cloud properties and have become an important source of anthropogenic air pollution in recent decades. We have measured the size distributions and number concentrations of aerosols in the cloud and outside clouds using various onboard instruments such as cloud droplet probe (CDP; DMT), passive cavity aerosol spectrometer (PCASP, DMT), Scanning Mobility Particle Sizer (SMPS) and Single Particle Soot Photometer (SP2; DMT). The measurements were performed in the ship emission-dominated environments and relatively cleaner regions of the Celtic Sea. We discuss the difference in the characteristics of in-cloud and out-cloud measurements in these relatively contrasting environments. The measurements were made between 29th September and 12th October 2021 using the Facility for Airborne Atmospheric Measurements (FAAM) research aircraft as a part of the Atmospheric Composition and Radiative forcing changes due to UN International Ship Emissions regulations (ACRUISE) Project.

Sulfur dioxide (SO2) plays a pivotal role in the chemistry of the troposphere, ultimately affecting the Earth’s radiation balance and climate. Within the atmosphere, SO2 is oxidised by gas- and aqueous-phase chemistry to sulfate and is therefore a major precursor to atmospheric aerosols, particularly in the remote marine atmosphere. Both the direct radiative forcing from aerosols and the indirect forcing from aerosol-cloud interactions are poorly understood and produce large uncertainties in climate models. Therefore, it is of interest to precisely quantify the concentration of atmospheric SO2 if we are to predict the effects of changing emission rates on both climate and air quality.Anthropogenic SO2 emissions have fallen dramatically in recent decades, resulting in significant reductions in atmospheric concentrations. Current commercial SO2 detection techniques, for example pulsed fluorescence, are no longer sensitive enough to detect trace levels of SO2 such as those found in remote marine environments. We report the development of a laser-induced fluorescence instrument for in situ SO2 measurements using a custom-built, tunable fiber-amplified laser system. Based on the system initially developed by Rollins et al. (2016), the University of York LIF-SO2 system has a detection limit of 50 ppt for 30 seconds and its relatively small size, weight and power requirements makes this instrument suitable for a variety of field campaigns.Here we present aircraft measurements of SO2 made by the York LIF-SO2 instrument on board the UK FAAM research aircraft in both the remote and polluted marine boundary layer. These are then compared to simultaneous SO2 measurements made by the University of Manchester I- chemical ionisation mass spectrometer (I- CIMS) instrument and the FAAM pulsed fluorescence commercial SO2 detector.

Since 1st January 2020 the legal sulphur content of shipping fuel was decreased – from 3.5% to 0.5% by mass outside of the Sulphur Emission Control Areas (SECAs) to improve coastal air quality. A possible downside of this change was acceleration of climate change since sulphur is believed to be a negative climate forcer and sipping is one of its main sources. Further question was the level of compliance to the new rules, especially in the open waters. Another climate related aspect of shipping is recent growth in the liquified natural gas (LNG) tanker fleets. LNG is considered the greenest of the fossil fuels, however there are few empirical studies of methane emissions from marine LNG transport.The Atmospheric Composition and Radiative forcing changes due to UN International Ship Emissions regulations (ACRUISE) project aims to address the above considerations. During three field campaigns the FAAM Airborne Laboratories’ large research aircraft was deployed to target ships in coastal shipping lanes and open waters. First measurements were performed in July 2019 (before regulation change) in shipping lanes along the Portuguese coast, the English Channel SECA and the Celtic Sea. Further two campaigns were delayed by the COVID-19 pandemic until September 2021 and April 2022, targeting ships in the Bay of Biscay, the English Channel SECA and the Celtic Sea. Throughout the project, nearly 300 ships were measured during 30 research flights, varying from plume aging and cloud interaction studies, through collecting bulk statistics in busy shipping lanes to comparing emissions in and out of SECA. This work focuses on the gaseous species measurements (SO2, CO2, CH4 and VOCs from whole air samples). They are used to study changes in apparent sulphur fuel content of the ships observed throughout ACRUISE, plume composition and methane emissions from LNG tankers.

Liposomal daunorubicin and cytarabine (CPX-351) improves overall survival (OS) compared to 7+3 chemotherapy in older patients with secondary acute myeloid leukaemia (AML); to date there have been no randomized studies in younger patients. The high-risk cohort of the UK NCRI AML19 trial (ISRCTN78449203) compared CPX-351 with FLAG-Ida in younger adults with newly-diagnosed adverse cytogenetic AML or high-risk myelodysplastic syndromes (MDS). 189 patients were randomized (median age 56y). By clinical criteria 49% had de novo AML, 20% secondary AML and 30% high risk MDS. MDS-related cytogenetics were present in 73% of patients, with complex karyotype in 49%. TP53 was the most commonly mutated gene, in 43%. Myelodysplasia-related gene mutations were present in 75 patients (44%). The overall response rate (CR + CRi) after course two was 64% and 76% for CPX-351 and FLAG-Ida (OR:0.54, 95%CI 0.28-1.04, p=0.06). There was no difference in OS (13.3 months vs 11.4 months, HR:0.78, 95%CI 0.55-1.12, p=0.17) or event-free survival (HR:0.90, 95%CI 0.64-1.27, p=0.55) in multivariable analyses. However, relapse-free survival was significantly longer with CPX-351 (median 22.1 vs 8.35 months, HR:0.58, 95% CI 0.36-0.95, p=0.03). There was no difference between the treatment arms in patients with clinically defined secondary AML (HR:1.1, 95%CI 0.52-2.30) or those with MDS-related cytogenetic abnormalities (HR:0.94, 95%CI 0.63-1.40), however an exploratory sub-group of patients with MDS-related gene mutations had significantly longer OS with CPX-351 (median 38.4 vs 16.3 months, HR:0.42, 95%CI 0.21-0.84, heterogeneity p=0.05). In conclusion, OS in younger patients with adverse risk AML/MDS was not significantly different between CPX-351 and FLAG-Ida.

The current study explored how young females who compete in aesthetic sports adopt self-presentation strategies on social media. Data from semi-structured interviews with 10 collegiate female trampolinists (aged 19–24 years) were analyzed through reflective thematic analysis, and six themes were generated; self-analysis, the best you, emotional consequences, judgment, social media perceptions, and acceptance. Framed around these themes, creative nonfiction techniques were employed to present the results as an ethnodrama. Findings illustrated how participants demonstrated a high need to present their “best self”, as failure to do so results in fear of judgment, extreme self-criticism, and, subsequently, post-prevention. Moreover, participants used upward social comparisons, and when they felt they did not match the ‘thin ideal’, often made negative associations between weight gain and attractiveness. This study contributes to body image literature by demonstrating a more detailed understanding of how social media influences one’s need to alter their self-presentation to fit in with highly pressured societal ideals. In addition, the ethnodrama provides an educational tool to stimulate reflection about the extremity of this issue in today’s modern world.

Future CPU-manycore heterogeneous systems can provide high peak throughput by integrating thousands of simple, independent, energy-efficient cores in a single die. However, there are two key challenges to translating this high peak throughput into improved end-to-end workload performance: (1) manycore co-processors rely on simple hardware putting significant demands on the software programmer; and (2) manycore co-processors use in-order cores that struggle to tolerate long memory latencies. To address the manycore programmability challenge, this paper presents a dense and sparse tensor processing framework based on PyTorch that enables domain experts to easily accelerate off-the-shelf workloads on CPUmanycore heterogeneous systems. To address the manycore memory latency challenge, we use our extended PyTorch framework to explore the potential for decoupled access/execute (DAE) software and hardware mechanisms. More specifically, we propose two software-only techniques, naive-software DAE and systolic-software DAE, along with a lightweight hardware access accelerator to further improve area-normalized throughput. We evaluate our techniques using a combination of PyTorch operator microbenchmarking and real-world PyTorch workloads running on a detailed register-transfer-level model of a 128-core manycore architecture. Our evaluation on three real-world dense and sparse tensor workloads suggest these workloads can achieve approximately 2-6× performance improvement when scaled to a future 2,000-core CPU-manycore heterogeneous system compared to an 18-core out-of-order CPU baseline, while potentially achieving higher area-normalized throughput and improved energyefficiency compared to general-purpose graphics processing units.

Methodological transparency and reproducibility are essential for systematic reviews. Peer review of systematic review manuscripts ensures researchers achieve transparency and reproducibility. Using critical appraisal and quality assessment tools is a methodological way for peer reviewers to conduct a thorough critique to assess the rigor and transparency of the systematic review.

This article describes the methods, successes and challenges of engaging parents while studying the impacts of COVID-19 on healthy children and families. Parent partners in a Parent and Clinician Team (PACT) informed study aims, supported feasibility and recommended changes to enhance participation. PACT members stated that they felt a sense of connectedness and purpose by contributing to COVID-19 research. Engagement increased by parents acquiring new roles, attending more frequent meetings and co-creating alternative methods of engagement. Recruiting new PACT members was challenging, likely due to limited time and resources available to parents of young children during a pandemic.

The transition metal-promoted in situ nucleophilic addition of triethanolamine (teaH3) and N-methyldiethanolamine (mdeaH2) to the dicyanonitrosomethanide (dcnm) anion results in the formation of [Cu(hbnm)]·MeOH (1) and [Cu(mbnm)]·2MeCN (2), (hbnm = hydroxyethylaminobis(ethoxy(imino)methyl(cyano)nitrosomethanide) and mbnm = methylaminobis(ethoxy(imino)methyl(cyano)nitrosomethanide). Complexes 1 and 2 are coordination polymers, each containing the addition products of two alcohol arms of teaH3 and mdeaH2 to dcnm anions.

In this article, the book review editor of Monumenta Nipponica, a Japanese studies journal based in Tokyo, describes the satisfactions and frustrations of the job and provides a nuts-and-bolts view of how he does it.

Musculoskeletal disorders are the most common cause of disability in the UK. They are associated with significant morbidity and polypharmacy, particularly in an ageing population with multiple co-morbidities. Two programmes of examination that have been developed include a screening assessment (Gait, Arms, Legs, Spine (GALS)) and a more in-depth Regional Examination of the Musculoskeletal System (REMS). These programmes provide a structured assessment, which enables competent and confident examination skills, ensuring an accurate diagnosis.

Nuclear export of influenza A virus (IAV) mRNAs occurs through the nuclear pore complex (NPC). Using the Auxin-Induced Degron (AID) system to rapidly degrade proteins, we show that among the nucleoporins localized at the nucleoplasmic side of the NPC, TPR is the key nucleoporin required for nuclear export of influenza virus mRNAs. TPR recruits the TRanscription and EXport complex (TREX)−2 to the NPC for exporting a subset of cellular mRNAs. By degrading components of the TREX-2 complex (GANP, Germinal-center Associated Nuclear Protein; PCID2, PCI domain containing 2), we show that influenza mRNAs require the TREX-2 complex for nuclear export and replication. Furthermore, we found that cellular mRNAs whose export is dependent on GANP have a small number of exons, a high mean exon length, long 3’ UTR, and low GC content. Some of these features are shared by influenza virus mRNAs. Additionally, we identified a 45 nucleotide RNA signal from influenza virus HA mRNA that is sufficient to mediate GANP-dependent mRNA export. Thus, we report a role for the TREX-2 complex in nuclear export of influenza mRNAs and identified RNA determinants associated with the TREX-2-dependent mRNA export.

Clinical characteristics of melanoma biopsies used in CYTOF

VISTA expression on immune cells in tumor dissociates by flow cytometry

Supplementary Data 6

Supplementary Table 1

PDF File - 35K, Annexin V staining by flow cytometry 24 hours after addition of 1nM docetaxel to MDA-MB-231 cells.

Purpose:Immunotherapies targeting costimulating and coinhibitory checkpoint receptors beyond PD-1 and CTLA-4 have entered clinical trials. Little is known about the relative abundance, coexpression, and immune cells enriched for each specific drug target, limiting understanding of the biological basis of potential treatment outcomes and development of predictive biomarkers for personalized immunotherapy. We sought to assess the abundance of checkpoint receptors during melanoma disease progression and identify immune cells enriched for them.Experimental Design: Multiplex immunofluorescence staining for immune checkpoint receptors (ICOS, GITR, OX40, PD-1, TIM-3, VISTA) was performed on 96 melanoma biopsies from 41 treatment-naïve patients, including patient-matched primary tumors, nodal metastases, and distant metastases. Mass cytometry was conducted on tumor dissociates from 18 treatment-naïve melanoma metastases to explore immune subsets enriched for checkpoint receptors.Results:A small subset of tumor-infiltrating leukocytes expressed checkpoint receptors at any stage of melanoma disease. GITR and OX40 were the least abundant checkpoint receptors, with +/CD103+/CD8+) were enriched for TIGIT (>70%) and other coinhibitory but not costimulatory receptors. The proportion of GITR+ T cells decreased from primary melanoma (>5%) to lymph node (P = 0.04) and distant metastases (P = 0.0005).Conclusions:This study provides the first comprehensive assessment of immune checkpoint receptor expression in any cancer and provides important data for rational selection of targets for trials and predictive biomarker development.

Antibodies used in CYTOF experiment

Schematic representation of trial design, patient recruitment, arm assignment, and assignment to endpoint investigations.