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Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society.

Cnidarians are a disparate and ancient phylum, encompassing corals and jellyfish, and occupy both the pelagic and benthic realms. They have a rich fossil record from the Phanerozoic eon lending insight into the early history of the group but, although cnidarians diverged from other animals in the Precambrian period, their record from the Ediacaran period (635–542 million years ago) is controversial. Here, we describe a new fossil cnidarian—Auroralumina attenboroughii gen. et sp. nov.—from the Ediacaran of Charnwood Forest (557–562 million years ago) that shows two bifurcating polyps enclosed in a rigid, polyhedral, organic skeleton with evidence of simple, densely packed tentacles. Auroralumina displays a suite of characters allying it to early medusozoans but shows others more typical of Anthozoa. Phylogenetic analyses recover Auroralumina as a stem-group medusozoan and, therefore, the oldest crown-group cnidarian. Auroralumina demonstrates both the establishment of the crown group of an animal phylum and the fixation of its body plan tens of millions of years before the Cambrian diversification of animal life.

Adjuvant intravesical chemotherapy following tumour resection is recommended for intermediate-risk non-muscle-invasive bladder cancer (NMIBC).To assess the efficacy and safety of adjuvant intravesical chemohyperthermia (CHT) for intermediate-risk NMIBC.HIVEC-II is an open-label, phase 2 randomised controlled trial of CHT versus chemotherapy alone in patients with intermediate-risk NMIBC recruited at 15 centres between May 2014 and December 2017 (ISRCTN 23639415). Randomisation was stratified by treating hospital.Patients were randomly assigned (1:1) to adjuvant CHT with mitomycin C at 43°C or to room-temperature mitomycin C (control). Both treatment arms received six weekly instillations of 40 mg of mitomycin C lasting for 60 min.The primary endpoint was 24-mo disease-free survival as determined via cystoscopy and urinary cytology. Analysis was by intention to treat.A total of 259 patients (131 CHT vs 128 control) were randomised. At 24 mo, 42 patients (32%) in the CHT group and 49 (38%) in the control group had experienced recurrence. Disease-free survival at 24 mo was 61% (95% confidence interval [CI] 51-69%) in the CHT arm and 60% (95% CI 50-68%) in the control arm (hazard ratio [HR] 0.92, 95% CI 0.62-1.37; log-rank p = 0.8). Progression-free survival was higher in the control arm (HR 3.44, 95% CI 1.09-10.82; log-rank p = 0.02) on intention-to-treat analysis but was not significantly higher on per-protocol analysis (HR 2.87, 95% CI 0.83-9.98; log-rank p = 0.06). Overall survival was similar (HR 2.55, 95% CI 0.77-8.40; log-rank p = 0.09). Patients undergoing CHT were less likely to complete their treatment (n =75, 59% vs n = 111, 89%). Adverse events were reported by 164 patients (87 CHT vs 77 control). Major (grade III) adverse events were rare (13 CHT vs 7 control).CHT cannot be recommended over chemotherapy alone for intermediate-risk NMIBC. Adverse events following CHT were of low grade and short-lived, although patients were less likely to complete their treatment.The HIVEC-II trial investigated the role of heated chemotherapy instillations in the bladder for treatment of intermediate-risk non-muscle-invasive bladder cancer. We found no cancer control benefit from heated chemotherapy instillations over room-temperature chemotherapy. Adverse events following heated chemotherapy were low grade and short-lived, although these patients were less likely to complete their treatment.

Hybrid hydroclimatic forecasting systems employ data-driven (statistical or machine learning) methods to harness and integrate a broad variety ofpredictions from dynamical, physics-based models - such as numerical weather prediction, climate, land, hydrology, and Earth system models - into a final prediction product. They are recognized as a promising way of enhancing the prediction skill of meteorological and hydroclimatic variables and events, including rainfall, temperature, streamflow, floods, droughts, tropical cyclones, or atmospheric rivers. Hybrid forecasting methods are now receiving growing attention due to advances in weather and climate prediction systems at subseasonal to decadal scales, a better appreciation of the strengths of AI, and expanding access to computational resources and methods. Such systems are attractive because they may avoid the need to run a computationally expensive offline land model, can minimize the effect of biases that exist within dynamical outputs, benefit from the strengths of machine learning, and can learn from large datasets, while combining different sources of predictability with varying time horizons. Here we review recent developments in hybrid hydroclimatic forecasting and outline key challenges and opportunities for further research. These include obtaining physically explainable results, assimilating human influences from novel data sources, integrating new ensemble techniques to improve predictive skill, creating seamless prediction schemes that merge short to long lead times, incorporatinginitial land surface and ocean/ice conditions, acknowledging spatial variability in landscape and atmospheric forcing, and increasing the operational uptake of hybrid prediction schemes., Hydrology and Earth System Sciences, 27 (9), ISSN:1027-5606, ISSN:1607-7938

Premature birth is an independent predictor of long-term cardiovascular risk. Individuals affected are reported to have a lower rate of oxygen consumption at peak exercise intensity and at ventilatory anaerobic threshold, but little is known about their response to exercise training.To explore if peak exercise oxygen consumption and ventilatory anaerobic threshold responses to exercise training differ between preterm-born and term-born individuals.Fifty-two preterm-born and 151 term-born participants were randomly assigned (1:1) to 16-weeks of aerobic exercise training (n=102) or a control group (n=101). Cardiopulmonary exercise tests were conducted before and after the intervention to measure oxygen consumption at peak exercise intensity and the ventilatory anaerobic threshold. A prespecified subgroup analysis was conducted by fitting an interaction term for preterm and term birth history and exercise group allocation.Within term-born participants, peak exercise oxygen consumption increased by 3.1 (95% confidence interval: 1.7 to 4.4)ml/kg/min and ventilatory anaerobic threshold increased by 2.3 (95% confidence interval: 0.7 to 3.8)ml/kg/min in the intervention group versus controls. Within preterm-born participants, peak exercise oxygen consumption increased by 1.8 (95% confidence interval: -0.4 to 3.9)ml/kg/min and ventilatory anaerobic threshold increased by 4.6 (95% confidence interval: 2.1 to 7.0)ml/kg/min in the intervention group versus controls. No significant interaction was observed for peak exercise oxygen consumption (p=0.32) or ventilatory anaerobic threshold (p=0.12).The training intervention led to significant improvements in peak exercise oxygen consumption and ventilatory anaerobic threshold, with no evidence of a statistically different response based on birth history. Clinical trial registration available at www.gov, ID: NCT02723552. 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/).

Dispersal is a key influence on species’ persistence, particularly in the context of habitat fragmentation and environmental change. Previously, residual population synchrony has been demonstrated to be an effective proxy for dispersal in mobile butterflies (Powney et al. 2012). Here, we highlight the utility and limitations of population synchrony as an indicator of functional connectivity and persistence, at a range of spatial scales, in a specialist, sedentary butterfly. While at the local scale, population synchrony is likely indicative of dispersal in the pearl-bordered fritillary, Boloria euphrosyne, over larger scales, habitat is likely to influence population dynamics. Although declines in local-scale synchrony conformed to typical movement in this species, synchrony showed no significant trend with distance when studied at larger (between-site) scales. By focusing on specific site comparisons, we draw the conclusion that heterogeneity in habitat successional stage drives asynchrony between sites at larger distances and is, therefore, likely to be a more important driver of population dynamics over large distances than dispersal. Within-site assessments of synchrony highlight differences in dispersal based on habitat type, with movement shown to be most inhibited between transect sections with contrasting habitat permeability. While synchrony has implications for metapopulation stability and extinction risk, no significant difference was found in average site synchrony between sites that had gone extinct during the study period and those remaining occupied. We demonstrate that population synchrony may be used to assess local-scale movement between sedentary populations, as well as to understand barriers to dispersal and guide conservation management.

Background: Pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention is highly effective. Pharmacists can increase PrEP accessibility through pharmacist prescribing. This study aimed to determine pharmacists’ acceptance of a pharmacist PrEP prescribing service in Nova Scotia. Methods: A triangulation mixed methods study consisting of an online survey and qualitative interviews was conducted with Nova Scotia community pharmacists. The survey questionnaire and qualitative interview guide were underpinned by the 7 constructs of the Theoretical Framework of Acceptability (affective attitude, burden, ethicality, opportunity costs, intervention coherence, perceived effectiveness and self-efficacy). Survey data were analyzed descriptively and with ordinal logistic regression to determine associations between variables. Interview transcripts were deductively coded according to the same constructs and then inductively coded to identify themes within each construct. Results: A total of 214 community pharmacists completed the survey, and 19 completed the interview. Pharmacists were positive about PrEP prescribing in the constructs of affective attitude (improved access), ethicality (benefits communities), intervention coherence (practice alignment) and self-efficacy (role). Pharmacists expressed concerns about burden (increased workload), opportunity costs (time to provide the service) and perceived effectiveness (education/training, public awareness, laboratory test ordering and reimbursement). Conclusion: A PrEP prescribing service has mixed acceptability to Nova Scotia pharmacists yet represents a model of service delivery to increase PrEP access to underserved populations. Future service development must consider pharmacists’ workload, education and training as well as factors relating to laboratory test ordering and reimbursement.

Background: This study sought to identify the differences between training models for pharmacist prescribing across three countries according to the funding, model of prescribing the pharmacist will practice after training, training course framework, method of delivery, assessment, continuing professional development, and barriers and facilitators to enrolment. Methods: An online quantitative/qualitative snapshot survey was sent to academics of pharmacist prescribing courses and Deans of different pharmacy schools in the UK (n=49), Australia (n=12), and Canada (n=10). A narrative analysis was undertaken. Results: Seventeen pharmacy schools responded (24% response rate). The UK provides postgraduate training courses funded by the government. Canada incorporates prescribing competencies into entry-t- practice courses. Australia does not provide courses yet. Conclusion: Pharmacist prescribing is still under-utilised in many countries. Standardisation would reduce variation and improve uptake in countries implementing pharmacist prescribing roles. However, there is currently no international unified system or curriculum for pharmacists' prescribing courses.

Facies variability of mudstones is likely greater than generally perceived, with important implications for their behaviour in major civil engineering, energy and waste disposal applications. Here, we explore this variability for the UK Oxford Clay, a widely studied Middle/Upper Jurassic mudstone. Evidence from wire-line logs, geochemistry, sequence stratigraphy and biofacies analyses are combined to reveal heterogeneity within the Peterborough Member (Lower Oxford Clay) and to explore the extent to which it blanketed basin features or responded dynamically to them. Thickness modelling suggests that the Mid North Sea High, formed by Mid Jurassic thermal doming, likely influenced sediment pathways, favouring thick sediment accumulation in the Wessex Basin, thinner successions across the East Midlands Shelf, and sediment starvation in the Weald Basin. Biofacies patterns, determined using a novel combination of detrended correspondence and cluster analysis, vary significantly and suggest a complex patchwork of environments related to local basin setting. The Type Section of the Peterborough Member seems to represent only a narrow range of conditions that influenced its deposition, and cautions against developing basin-scale models based on a few well exposed and heavily researched outcrop successions.

Evil-scepticism comes in two varieties: one variety is descriptive, where it is claimed that the concept of evil does not successfully denote anything in the world; the other variety is normative, where it is claimed that the concept of evil is not a helpful or useful concept to be employing in either our social or interpersonal lives. This paper argues that evil-scepticism can be responded to by understanding the concept of evil as a thin moral concept. Understood in this thin way, the descriptive challenge fades, because the concept of evil does not even purport to denote anything in the world (it is purely evaluative), and so does the normative argument, since the thinness of the concept means that, first, it is ineliminable anyway, and, second, its malleability allows for it to be used for progressive and constructive means.

INTRODUCTION: High grade, non-muscle invasive bladder cancer (NMIBC) is usually treated with intravesical Bacillus Calmette–Guérin. Chemohyperthermia therapy (CHT) may be a novel alternative therapy for the treatment of NMIBC. OBJECTIVE: To evaluate the recurrence-free survival (RFS) of patients treated with CHT using the Combat bladder recirculation system (BRS) for NMIBC. METHODS: This was a prospective multi-institutional study of 1,028 consecutive patients with NMIBC undergoing CHT between 2012 and 2020. A total of 835 patients were treated with CHT with Mitomycin C (MMC). Disease was confirmed on transurethral resection of bladder tumor (TURBT) prior to starting CHT. Follow-up included cystoscopy and subsequent TURBT if recurrence/progression was suspected. The primary endpoint was RFS. Secondary endpoints were progression-free survival (PFS) and adverse events from CHT. RESULTS AND LIMITATIONS: Median follow up was 22.4 months (Interquartile range (IQR): 12.8 –35.8). Median age was 70.4 years (IQR: 62.1 –78.6). A total of 557 (66.7%), 172 (20.6) and 74 (8.9%) of patients were classified to BCG naïve, BCG unresponsive and BCG failure, respectively. The RFS at 12 months and 24 months for BCG naïve was 87.6% (95% CI 85.0% - 90.4%) and 75.0% (95% CI 71.3% - 78.8%), respectively. The RFS at 12 months and 24 months for BCG unresponsive cohort was 78.1% (95% CI 72.0% - 84.7%) and 57.4% (95% CI 49.7% - 66.3%), respectively. The RFS at 24 months for the BCG unresponsive cohort for CIS with/without papillary disease and papillary only disease were 43.6% (95% CI 31.4% –60.4%) and 64.5% (95% CI 55.4% - 75.1%), respectively. Minor adverse events occurred in 216 (25.6%) patients and severe events occurred in 17 (2.0%) patients. CONCLUSIONS: CHT with MMC using the Combat BRS is effective in the medium term and has a favorable adverse event profile.

Relating drought indicators and real-world impacts is fundamental for understanding and addressing drought vulnerability. We link drought indices and impacts from newspapers compiled in the Irish Drought Impacts Database (IDID) for the period 1900–2016. For three catchment clusters across the island of Ireland we link the Standardized Precipitation Index (SPI) with land-based impacts and the Standardized Streamflow Index (SSI) with water-based impacts by matching total reported articles per month with concurrent drought indices. Using logistic regression we find SPI-3 links best with land-based impact reports, whereas SSI-2 links best with water-based impact reports. Catchments in the east/southeast display the highest sensitivity to land- and water-based impacts; however, in summer months at low deficits northwestern catchments show a higher likelihood of impact reports. In winter months the likelihood of water-based impacts is considerably greater than the land-based equivalent, particularly in east/southeastern catchments. Moreover, the likelihood of news-worthy drought impacts has changed over the 117 year period. More severe deficits are required to induce a high likelihood (0.6) of land- and water-based impacts in east/southeastern and southwestern catchments during 1961–2016 compared with 1900–1960. Largest changes emerge in the southwest with SPI-3 values of −2.51 (

Aim: The aim of this narrative literature review was to describe the existing evidence for a post-graduate experiential learning program, such as a foundational pharmacy residency, to support the competency development for early-career pharmacists in conducting education, leadership and supporting innovation. Methods: We identified publications that addressed research in skills development within foundational pharmacy residency programs. Articles were identified using the databases Scopus and Embase. Results: It was found that foundational residency programs have supported competency development in delivering education, leadership and management, and support of innovation and quality improvement. Residency programs have fostered these skills development through the use of courses, assessments and activities, but to varying degrees. Many of these skills are attained as a benefit of inclusion and mentorship in non-clinical tasks. Conclusion: Residency programs can serve as a strong platform for the development of non-clinical skills in education, leadership and innovation. A mix of activities and course-specific skills building courses have demonstrated levels of success in developing skills in education, leadership and innovation when implemented Refereed/Peer-reviewed

Objectives To explore micro-credentialing for postgraduate study in pharmacy practice. Methods An online survey of practicing or intern pharmacists in New Zealand was designed to identify learner preferences for education, determine interest and demand for microcredentials and elicit preferred ‘willingness-to-pay’ thresholds. Key findings A total of 430 responses were obtained. A stacked microcredential programme was preferred by 88% over traditional courses. Interest, skill development and career development were the top-ranked aspects. Participants favoured the lowest cost option ($300 NZD per microcredential). Conclusions Pharmacists in New Zealand are supportive of microcredentials for postgraduate study as an alternative to traditional programmes.

Floral field margins are known to benefit invertebrate species diversity and abundance within agricultural landscapes, but variation in success limits widespread uptake. Understanding how variation within floral field margins can affect certain entomological groupings is lacking but would allow for a more individualised design of margins to enhance biological control. This meta-analysis aims to answer the question; do floral field margins benefit biological pest control over grassy field margins? We found that floral margins significantly benefit the natural enemy community and biological control services, relative to non-floral grass margins. We confirm that field mar-gin type is linked to higher abundance and diversity of natural enemies, lower numbers of herbivorous invertebrate pests, and reduced crop damage. We consider whether specific characterisations of natural enemies and pest communities vary between these margin types, finding key differences in the abundances of aerial and epigeal enemies, the diversity of parasitoid and predatory enemies and pest abundances found in naturally regenerating and sown floral field margins. The finding here cements the implementation of floral field margins as a legitimate control method for crop pests in the face of losses due to pesticides and high-lights design and management considerations for the success of floral margins.

Global efforts to upgrade water, drainage, and sanitation services are hampered by hydrometeorological data-scarcity plus uncertainty about climate change. Intensity–duration–frequency (IDF) tables are used routinely to design water infrastructure so offer an entry point for adapting engineering standards. This paper begins with a novel procedure for guiding downscaling predictor variable selection for heavy rainfall simulation using media reports of pluvial flooding. We then present a three-step workflow to: (1) spatially downscale daily rainfall from grid-to-point resolutions; (2) temporally scale from daily series to sub-daily extreme rainfalls and; (3) test methods of temporal scaling of extreme rainfalls within Regional Climate Model (RCM) simulations under changed climate conditions. Critically, we compare the methods of moments and of parameters for temporal scaling annual maximum series of daily rainfall into sub-daily extreme rainfalls, whilst accounting for rainfall intermittency. The methods are applied to Kampala, Uganda and Kisumu, Kenya using the Statistical Downscaling Model (SDSM), two RCM simulations covering East Africa (CP4 and P25), and in hybrid form (RCM-SDSM). We demonstrate that Gumbel parameters (and IDF tables) can be reliably scaled to durations of 3 h within observations and RCMs. Our hybrid RCM-SDSM scaling reduces errors in IDF estimates for the present climate when compared with direct RCM output. Credible parameter scaling relationships are also found within RCM simulations under changed climate conditions. We then discuss the practical aspects of applying such workflows to other city-regions.

Spinal surgeries to treat chronic low back pain (CLBP) have variable success rates, and despite the significant personal and socioeconomic implications, we lack consensus for prognostic factors. This systematic review and meta-analysis evaluated the evidence for preoperative predictors of return to work (RTW) after spinal surgery for CLBP. We searched electronic databases and references (January 1984 to March 2021), screened 2,622 unique citations, and included 8 reports (5 low and 3 high risk-of-bias) which involved adults with ≥3 months duration of CLBP with/without leg pain undergoing first elective lumbar surgery with RTW assessed ≥3 months later. Narrative synthesis and meta-analysis where possible found that individuals less likely to RTW were older (odds ratio [OR] = .58; 95% confidence interval [CI]: 0.46-0.72), not working before surgery, had longer sick leave (OR = .95; 95% CI: 0.93-0.97), higher physical workload, legal representation (OR = .61; 95% CI: 0.53-0.71), psychiatric comorbidities and depression (moderate quality-of-evidence, QoE), and longer CLBP duration and opioid use (low QoE), independent of potential confounders. Low quality and small number of studies limit our confidence in other associations. In conclusion, RTW after spinal surgery for CLBP likely depends on sociodemographic and affective psychological factors, and potentially also on symptom duration and opioid use. PERSPECTIVE: This systematic review and meta-analysis synthesizes and evaluates existing evidence for preoperative predictors of return to work after spinal surgery for chronic low back pain. Demonstrated associations between return to work and sociodemographic, health-related, and psychological factors can inform clinical decision-making and guide further research.

ObjectivesSuccess rates of spinal surgeries to treat chronic back pain are highly variable and useable prognostic indicators are lacking. We aimed to identify and evaluate preoperative predictors of pain and disability after spinal surgery for chronic low back/leg pain.MethodsElectronic database (01/1984-03/2021) and reference searches identified 2622 unique citations. Eligible studies included adults with chronic low back/leg pain lasting ≥3 months undergoing first elective lumbar spine surgery, and outcomes defined as change in pain (primary)/disability (secondary) after ≥3 months. We included 21 reports (6899 participants), 7 were judged to have low and 14 high risks of bias. We performed narrative synthesis and determined the quality of evidence (QoE).ResultsBetter pain outcomes were associated with younger age, higher education, and no spinal stenosis (low QoE); lower preoperative pain, fewer comorbidities, lower pain catastrophizing, anxiety and depression (very low QoE); but not with symptom duration (moderate QoE), other sociodemographic factors (low QoE), disability, or sensory testing (very low QoE). More favorable disability outcomes were associated with preoperative sensory loss (moderate QoE); lower job-related resignation and neuroticism (very low QoE); but not with socioeconomic factors, comorbidities (low QoE), demographics, pain, or pain-related psychological factors (very low QoE).DiscussionIn conclusion, absence of spinal stenosis potentially predicts greater pain relief and preoperative sensory loss likely predicts reduction in disability. Overall, QoE for most identified associations was low/very low.

Critical reflection is a mainstay in the training of health professionals, yet assessment of reflection is commonly described as difficult, taxing, and resulting in inconsistent scoring across assessors. At the same time, there is evidence from experiential and simulation settings that assessors' mental effort may explain assessor variability, which could be a target for simplifications in assessment design. Assessors' mental effort for assessment of reflection is currently unknown. This study aimed to determine reliability of rubric scoring of critical reflection, variation in pass-fail rates, and the relationship between reflection scores and assessors' perceived mental effort.Eleven assessors were recruited to assess six reflection assignments using a published rubric. Mental effort was measured using the Paas scale for each assignment assessed and was correlated with rubric scores for each assignment.Findings showed inconsistency in scoring between assessors, resulting in varying pass rates for each assignment (55-100%). All assignments demonstrated negative correlations between rubric scores and perceived mental effort (r = -0.115 to -0.649).Findings support the notion that more work should be done to optimize assessment of critical reflection. Future studies should focus on disentangling the influence on mental effort of scoring tools, assignment structures, and writing quality.

Effective on-street parking is key to reduce urban traffic and pollution in densely populated cities. Thus, researchers have focused on forecasting future occupancy values depending on factors like time, space, or weather. This approach shows high average performances, but fails in predicting congested scenarios, actually the most critical. This work proposes a data-driven parking level of service (LOS) predictor that outperforms traditional methods, solving its inherent class imbalance issue by means of Random Undersampling Boost classifiers. We trained and validated the LOS classifiers using 13 months of data collected from the smart parking system in the city of Madrid, Spain. Results display average recall values above 0.94 and 0.87 at prediction horizons up to 10 and 60 minutes respectively. We compare these results with traditional regression-based occupancy predictors showing that our classifier clearly outperforms the formers predicting the minority classes, which carry the most significant information for drivers and parking managers. We further analyze the impact on performance of temporal and spatial features, revealing mid-term temporal data as the most relevant forecasting information, and low correlations between parking behaviors in bordering neighborhoods. In the light of these results, we believe that the proposed data-driven parking LOS classification has the potential to open a novel perspective on the parking occupancy forecasting field.

International audience; In this paper, a novel concept for a phantom of the prostate is introduced. To study and improve automated, robotized medical interventions, reliable phantoms are essential. During brachytherapy and biopsy, the prostate will undergo displacements and changes in orientation due to the needle insertion. Therefore, there is a shift in the target regions for radioactive seed deposition or biopsy acquisition. These shifts need to be taken into account for precise dosimetry. Furthermore, the organ can undergo deformations due to edemas with the same shifting result. Therefore, in this paper we propose a bioinspired phantom (BIP) for the prostate that is equipped with sensors and coupled with a numerical simulation for estimating deformations due to external forces. We have also put in place a cavity inside the phantom where pressure can be applied to enable the emulation of prostate growth due to inflammation. The phantom is conceived in such a way that it will be MRIsafe. It can thus be deployed for the in-bore study of automated brachytherapy and biopsy. In our evaluation, we verify that the changes in pose of the phantom can be correctly estimated and that these motions are plausible from a clinical point of view.

Statistical and dynamical downscaling techniques are widely applied in the development of local climate change scenarios. This talk traces the conceptual development of downscaling as a decision-support tool for climate risk assessment, resilience and adaptation planning. Four epochs are identified: (1) early exploration of local changes in key climate variables, such as temperature and precipitation extremes; (2) application of downscaled scenarios to climate impacts modelling (such as for agriculture yield or water resource assessments); (3) advent of ensemble-based methods and more sophisticated handling of uncertainty in the downscaling-impacts workflow; and (4) use of downscaled scenarios to stress-test adaptation options under plausible ranges of climate and non-climatic conditions. Each phase is illustrated by and reflected in the development of the Statistical DownScaling Model – Decision Centric (SDSM-DC) over more than two decades. Questions around fitness for purpose and appropriate uses of the tool are explored. The talk concludes by considering: where next for downscaling?

Large ensemble simulations may be exploited to appreciate plausible extreme climate impacts that we may not yet have seen. Such information can be vital for decision makers to anticipate otherwise unforeseen impacts. Large ensemble simulations can generate larger data samples than the observed record but biases are likely to exist, which may occasionally produce unrealistic extreme events. Interpreting simulated 'unseen' events that are more extreme than those seen in historical records is therefore crucial, but adequate evaluation is complicated by observational uncertainties and natural variability. In this talk, we introduce a three-step procedure to assess the realism of simulated extreme events based on the model properties (step 1), statistical features (step 2), and physical credibility of the extreme events (step 3). We use the global climate model EC-Earth and global hydrological model PCR-GLOBWB to demonstrate these steps for a 2000 year Amazon monthly flood ensemble. The spatial model resolution of 1x1° and daily temporal resolution is coarse, but no reason to dismiss monthly flood simulations over the Amazon a priori. We find that the simulations are statistically inconsistent with the observations, but we cannot determine whether simulations outside observed variability are inconsistent for the right physical reasons. For example, there could be legitimate discrepancies between simulations and observations resulting from infrequent temporal compounding of multiple flood peaks, rarely seen in observations. Physical credibility checks are crucial to assessing their realism and show that the unseen Amazon monthly floods were generated by an unrealistic bias correction of precipitation. Based on this case study, we discuss the takeaway challenges when evaluating extreme climate impacts from large ensemble simulations. Understanding the drivers of simulations outside observed variability helps to gain trust in unseen simulations. Uncovering the characteristics of events in the models may reveal the most important model deficiencies or improve our scientific understanding of unseen events.

Rainfall estimation in ungauged areas is becoming one of the research hotspots recently. From a case study in the UK, this study builds a sub-daily rainfall estimation model based on more widely available daily series data from 151 gauges. In this study, we stratify the scaling properties of UK rainfall into homogenous rainfall zones, geophysical factors, seasons, and air masses to investigate how these scaling properties change temporally and spatially. We use temporal scaling techniques to extract the scaling relationship between sub-daily rainfall intensity and annual maximum series along with all possible factors introduced above. The estimated rainfall is validated with observed rainfall data and shows a higher degree of agreement. Finally, we compare the IDF (Intensity-Duration-Frequency) curves for both estimated and observed data. Such scaling relationships can support scientists and governments to estimate extreme rainfall at a specific duration and return period in ungauged regions. This method can also generate design rainfall time series for flood simulation models to evaluate present and future pluvial flood risks in urban areas.

Floods are natural phenomena, which can turn into disasters and cause widespread damage, health problems and deaths. This is particularly the case where rivers have been denied from their natural floodplains and are limited by embankments, and where housing and industrial buildings have been constructed in areas that are naturally liable to flooding. However, during the last few decades, flood observations from different parts of Europe do not show a clear increase in flood occurrence rate (Blöschl et al., 2019). In the present paper we present longer-term records of winter and summer floods in one of the largest river of Southeast Europe, the Sava River for the 1926-2021 period. We analysed three group of events that were based on three flood protection levels in Republic of Serbia defined for Sremska Mitrovica station. Regular protection level is set at 4120 m3/s and emergency flood defense level which is set at 5120 m3/s, that is, minor events are up to the regular protection level, strong events are up to the emergency level and extreme events are above emergency flood defense level. For the past 95 years, we find a decrease in both summer and winter flood occurrence rates. The reduction in winter flood occurrence can partly be attributed to reduced amount of precipitation during this period of the year. Further, on the basis of these data and methods, we find that for the Sava River can be stated the following: (1) downward but not significant trends in winter flood risk during the observed period, (2) Downward trends of summer floods was also observed, with only strong events being statistically significant. This decrease can be partially due to a projected decrease in cyclone frequency in the Mediterranean region. Presented results clearly demonstrate decreasing flood occurrence rate of the Sava River, as a consequence of decreasing precipitation and increasing evaporation (due to increasing temperature). ReferencesBlöschl, G., Hall, J., Parajka, J., Perdigão, A. P. R., Merz, B., Arheimer, B., Aronica, T. G., Bilibashi, A., Bonacci, O., Borga, M., Čanjevac, I., Castellarin, A., Chirico, B. G., Claps, P., Fiala, K., Frolova, N., Gorbachova, L., Gül, A., Hannaford, J., Harrigan, S., Kireeva, M., Kiss, A., Kjeldsen, R. T., Kohnová, S., Koskela, J. J., Ledvinka, O., Macdonald, N., Mavrova-Guirguinova, M., Mediero, L., Merz, R., Molnar, P., Montanari, A., Murphy, C., Osuch, M., Ovcharuk, V., Radevski, I., Rogger, M., Salinas, L. J., Sauquet, E., Šraj, M., Szolgay, J., Viglione, A., Volpi, E., Wilson, D., Zaimi, K. & Živković, N. (2019). Changing climate both increases and decreases European river floods. Nature 573 (7772), 108–111. https://doi.org/10.1038/s41586-019-1495-6.Acknowledgements This research was supported by ExtremeClimTwin project, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 952384.

Importance:Cerebrovascular changes are already evident in young adults with hypertension and exercise is recommended to reduce cardiovascular risk. To what extent exercise benefits the cerebrovasculature at an early stage of the disease remains unclear. Objective:To investigate whether structured aerobic exercise increases brain vessel lumen diameter or cerebral blood flow (CBF) and whether lumen diameter is associated with CBF. Design:Open, parallel, two-arm superiority randomized controlled (1:1) trial in the TEPHRA study on an intention-to-treat basis. The MRI sub-study was an optional part of the protocol. The outcome assessors remained blinded until the data lock. Setting:Single-centre trial in Oxford, UK. Participants:Participants were physically inactive (2and never been on prescribed hypertension medications. Out of 203 randomized participants, 135 participated in the MRI sub-study. Randomisation was stratified for sex, age (37weeks). Intervention:Study participants were randomised to a 16week aerobic exercise intervention targeting 3×60min sessions per week at 60 to 80% peak heart rate. Main outcomes and Measures:cerebral blood flow (CBF) maps from ASL MRI scans, internal carotid artery (ICA), middle cerebral artery (MCA) M1 and M2 segments, anterior cerebral artery (ACA), basilar artery (BA), and posterior cerebral artery (PCA) diameters extracted from TOF MRI scans. Results:Of the 135 randomized participants (median age 28years, 58% women) who had high quality baseline MRI data available, 93 participants also had high quality follow-up data available. The exercise group showed an increase in ICA (0.1cm, 95% CI 0.01 to 0.18, p=.03) and MCA M1 (0.05cm, 95% CI 0.01 to 0.10, p=.03) vessel diameter compared to the control group. Differences in the MCA M2 (0.03cm, 95% CI 0.0 to 0.06, p=.08), ACA (0.04cm, 95% CI 0.0 to 0.08, p=.06), BA (0.02cm, 95% CI −0.04 to 0.09, p=.48), and PCA (0.03cm, 95% CI −0.01 to 0.06, p=.17) diameters or CBF were not statistically significant. The increase in ICA vessel diameter in the exercise group was associated with local increases in CBF. Conclusions and Relevance:Aerobic exercise induces positive cerebrovascular remodelling in young people with early hypertension, independent of blood pressure. The long-term benefit of these changes requires further study. Trial Registration:Clinicaltrials.govNCT02723552, 30 March 2016

Background This study aimed to develop and externally validate prediction models of spinal surgery outcomes based on a retrospective review of a prospective clinical database, uniquely comparing multivariate regression and random forest (machine learning) approaches, and identifying the most important predictors. Methods Outcomes were change in back and leg pain intensity and Core Outcome Measures Index (COMI) from baseline to the last available postoperative follow-up (3–24 months), defined as minimal clinically important change (MCID) and continuous change score. Eligible patients underwent lumbar spine surgery for degenerative pathology between 2011 and 2021. Data were split by surgery date into development (N = 2691) and validation (N = 1616) sets for temporal external validation. Multivariate logistic and linear regression, and random forest classification and regression models, were fit to the development data and validated on the external data. Results All models demonstrated good calibration in the validation data. Discrimination ability (area under the curve) for MCID ranged from 0.63 (COMI) to 0.72 (back pain) in regression, and from 0.62 (COMI) to 0.68 (back pain) in random forests. The explained variation in continuous change scores spanned 16%-28% in linear, and 15%-25% in random forests regression. The most important predictors included age, baseline scores on the respective outcome measures, type of degenerative pathology, previous spinal surgeries, smoking status, morbidity, and duration of hospital stay. Conclusions The developed models appear robust and generalisable across different outcomes and modelling approaches but produced only borderline acceptable discrimination ability, suggesting the need to assess further prognostic factors. External validation showed no advantage of the random forest approach.

Polarization vision is used by a wide range of animals for navigating, orienting, and detecting objects or areas of interest. Shallow marine and semi-terrestrial crustaceans are particularly well known for their abilities to detect predator-like or conspecific-like objects based on their polarization properties. On land, some terrestrial invertebrates use polarization vision for detecting suitable habitats, oviposition sites or conspecifics, but examples of threat detection in the polarization domain are less well known. To test whether this also applies to crustaceans that have evolved to occupy terrestrial habitats, we determined the sensitivity of two species of land and one species of marine hermit crab to predator-like visual stimuli varying in the degree of polarization. All three species showed an ability to detect these cues based on polarization contrasts alone. One terrestrial species, Coenobita rugosus, showed an increased sensitivity to objects with a higher degree of polarization than the background. This is the inverse of most animals studied to date, suggesting that the ecological drivers for polarization vision may be different in the terrestrial environment.

Peer reviewed: True, Acknowledgements: Research in the senior author’s laboratory is supported by the Cambridge NIHR Brain Injury MedTech Cooperative. MRNK is supported by a NIHR Clinician Scientist Award., INTRODUCTION: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. METHODS AND ANALYSIS: RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60-100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8-14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. STUDY DESIGN: Clinical trial protocol V.2.2 October 2020. ETHICS AND DISSEMINATION: Ethical approval has been obtained from HRA-Wales.The results will be presented at an international and national scientific conferences and in a peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN Number: ISRCTN16682024.

E-scooter services have multiplied worldwide as a form of urban transport. Their use has grown so quickly that policymakers and researchers still need to understand their interrelation with other transport modes. At present, e-scooter services are primarily seen as a first-and-last-mile solution for public transport. However, we demonstrate that $$50\,\%$$ 50 % of e-scooter trips are either substituting it or covering areas with little public transportation infrastructure. To this end, we have developed a novel data-driven methodology that autonomously classifies e-scooter trips according to their relation to public transit. Instead of predefined design criteria, the blind nature of our approach extracts the city’s intrinsic parameters from real data. We applied this methodology to Rome (Italy), and our findings reveal that e-scooters provide specific mobility solutions in areas with particular needs. Thus, we believe that the proposed methodology will contribute to the understanding of e-scooter services as part of shared urban mobility.

Despite the increasing emphasis on interprofessional education (IPE) in curricula and the potential benefits for student learning, there appears to be a lack of evidence directing authentic and accurate assessment of student-learning outcomes and translation of assessment data into scores and grades. Given the increasing importance of reflection and simulation in IPE, the purpose of this systematic review was to identify, appraise, and synthesize published literature using reflection and simulation as summative assessment tools to evaluate student outcomes following IPE activities. The Crowe Critical Appraisal Tool was used to appraise the included articles for quality. This systematic review yielded only five studies of marginal quality that could highlight the limited rigorous use of either reflection or simulation for summative assessment purposes. This review has identified a need for summative IPE assessment alongside formative assessments. Furthermore, training needs to be offered to both faculty assessors, to ensure they are competent and results are reproducible, and students, to equip them with the knowledge, critical thinking skills, and attitude for becoming reflective practitioners who are able to practice interprofessionally. The assessment of IPE remains a challenge, and there is a clear gap in the literature where research needs to grow.

BackgroundEvidence is limited regarding the cumulative effect of risk factors on cognitive decline and the added value of physical function for cognitive function trajectory stratification. We operationalize 13 modifiable dementia risk factors in a scoring system and investigate the relationship between this brain health score, combined with simple measures of physical function, and risk of cognitive decline.MethodsPopulation-based cohort study of persons aged 50 and older from the Irish Longitudinal Study on Ageing without a history of dementia at baseline who underwent repeated neuropsychological tests (8.08 ± 0.3-year follow-up) were included in the analyses. Exposures were the number of brain health metrics (defined by the Lancet Commission on Dementia Prevention, Intervention, and Care report) at recommended optimal levels. Physical function exposures included Timed Up and Go, dual-task walking speed, and grip strength. Each health metric and physical function measure at the recommended level was assigned a value of 1 and combined to generate brain health scores. Relationship with group-based trajectories of global cognitive function (multidomains composite score), estimated using K-means for longitudinal data, was assessed via ordinal logistic regressions.ResultsAmong 2 327 participants (mean age, 61 years; 54% women), each additional optimal metric on the brain health score (odds 0.67 [0.62, 0.73]) was associated with reduced odds of cognitive decline. Adding Timed Up and Go (odds 0.71 [0.59, 0.84]) and dual-task walking speed (odds 0.74 [0.63, 0.89]) further improved model fit (ΔAIC = 14.8).ConclusionThese findings support the promotion and maintenance of physical function in addition to brain health strategies to reduce the risk of cognitive decline.

Abstract Rural landscapes in Europe have suffered considerable land-use change in the last 50 years, with agricultural intensification in western regions and land abandonment in eastern and southern regions. The negative impacts of agricultural intensification on butterflies and other insects in western Europe have been well studied. However, less is known about the impacts of abandonment on mountain and humid areas of eastern and southern Europe, where landscapes have remained more natural. We sampled butterfly communities in the Picos de Europa National Park (Spain), a region which is undergoing a process of rural abandonment. 19 hay meadows with different periods of abandonment were studied (long-term 18 years or mid-term abandoned, 3–7 years) and compared to meadows continuously managed in a traditional way. We examined how local meadow characteristics and landscape variables affected butterfly community response to abandonment. Butterfly communities were affected by abandonment, with an overall increase in the density of individuals in the long term. Community composition appears to undergo major change over time, with a species turnover of around 50% in the first few years of abandonment, rising to around 70% after 18 years of abandonment. There was a tendency for species with higher preference for closed habitats to increase their densities as time since abandonment proceeded. Landscape variables had a major impact on butterfly communities, stronger than the effect of meadow management. Community preference for closed habitats was associated with higher forest cover in the surroundings of the meadows, but heterogeneous landscapes (in their composition or configuration) mitigated this effect. Implications for insect conservation Our findings suggest that we should ensure that communities have time to react to the diverse stressors imposed by global change. Facilitating survival to all kinds of functional and taxonomic groups implies promoting landscape heterogeneity and connectivity.

Car-sharing systems have irrupted in our cities following the shared mobility paradigm. They have evolved the personal mobility market from product-based into service-oriented, which ultimately provides a positive impact on the city’s sustainability. Car sharing systems are a complex interactive service, whose dynamics can dramatically affect its operational viability. In order to better asses this viability, we must rely on data to produce novel metrics that characterize both the user behavior and the service performance. Up to date, research has focused on modeling the demand on the basis of the number of rentals that start within a specific time slot. However, this approach seems unable to provide a representative metric of the performance of a car-sharing system. In this paper, we propose a novel metric, the utilization rate of the fleet, which considers the precise number of vehicles within a fleet that are in service every minute of the day. From this basic metric, we derive a key performance indicator (KPI) to reflect the viability of any car-sharing system in economic and sustainability terms. We have applied this new metric and KPI to a dataset with 449 days of car2go data, collected in 10 European cities.

Introduction: Pharmacy students are facing academic and non-academic pressures that require emotional regulation. This study explored students’ possible self-management strategies when encountering situations known to deplete resilience. Methods: This was a qualitative think-aloud study designed to elicit final year pharmacy students’ reactions to situations known to deplete resilience and evoke emotional responses (racism, lack of trust, negative feedback, burnout, personal stress, sexual harassment). Thematic analysis was used to capture the strategies students used to self-manage their emotions. Results: Students made use of three types of processes to self-manage their emotions, which were used to construct three overarching strategies: the internalizer (avoidance, self-reflection), the seeker (asking for help or corroboration), and the confronter (approaching the situation and persons involved ‘head on’). Conclusion: Findings support the notion that students’ self-management is not a ‘one size fits all’ construct, and any approach to emotional skill development needs to recognize individualization within student responses.

The Asia-Pacific region is extremely vulnerable to climate variability and change. This reflects high exposure to hydroclimatic hazards such as tropical cyclones, floods, droughts, and heatwaves. Rapidly growing cities and low-lying coastal zones/estuaries also face threats from sea level rise and storm surges. However, climate model projections remain very uncertain about most of these risks, so water infrastructure and operations need to consider a range of plausible futures. Against this background, the Asian Development Bank (ADB) has been developing frameworks, tools, and capacities in climate risk and adaptation assessment and management. Project teams are often operating in data-scarce situations and under significant time constraints, so the emphasis has been on creating pragmatic guidance and training resources. This paper charts the transition of climate risk management (CRM) within the ADB from a predominantly scenario-led to decision-led approach to adaptation. Examples are given of light-touch procedures for screening climate risks, strengthening the transparency and rigour of scenario analysis, raising awareness of a broad range of adaptation options, streamlining identification of CRM options, and embedding allowances for climate change in detailed engineering designs. Such practical innovations would benefit communities of practice beyond the Asia-Pacific region. HIGHLIGHTS Water infrastructure and operating rules must be adapted such that they continue to deliver intended benefits despite climate change.; The Asian Development Bank has been developing frameworks, tools, and capacity for climate risk assessment and adaptation investments.; Pragmatic procedures for screening climate risk are particularly helpful in information- and resource-constrained situations.

Although even very advanced artificial systems do not meet the demanding conditions which are required for humans to be a proper participant in a social interaction, we argue that not all human-machine interactions (HMIs) can appropriately be reduced to mere tool-use. By criticizing the far too demanding conditions of standard construals of intentional agency we suggest a minimal approach that ascribes minimal agency to some artificial systems resulting in the proposal of taking minimal joint actions as a case of a social HMI. Analyzing such HMIs, we utilize Dennett’s stance epistemology, and argue that taking either an intentional stance or design stance can be misleading for several reasons, and instead propose to introduce a new stance that is able to capture social HMIs—the AI-stance.

Supplemental material, sj-pdf-1-cph-10.1177_17151635231152218 for Community pharmacists’ acceptance of prescribing for pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) by Connor Booker, Andrea L Murphy, Jennifer E. Isenor, Tasha D. Ramsey, Alesha J. Smith, Andrea Bishop, Deborah V. Kelly, Lisa Woodill, Greg Richard and Kyle John Wilby in Canadian Pharmacists Journal / Revue des Pharmaciens du Canada

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