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In 1994, to guide patients and surgeons in making informed decisions about organ transplantation and reduce transplant-mediated infectious disease transmission, the Centers for Disease Control and Prevention announced the Public Health Service guidelines for increased risk donor (IRD) organs. This classification identifies donors associated with greater risk for contracting human immunodeficiency virus, hepatitis B virus, and hepatitis C virus as increased risk donors. These donor organs are discarded at higher rates than non-IRD organs, despite equivalent patient and graft survival rates following transplantation. Biases and stigmas, as well as misunderstandings about the term “increased risk,” may contribute to the discard of these high-quality organs. Novel communication strategies regarding the risk of disease transmission from IRD organs are needed to reduce misunderstandings between patients and providers and shift the conversation from probabilities and statistics to patient-centered values and expectations.Using a standardized tool such as Best Case/Worst Case to elicit patients’ preferences and share expected outcomes of accepting versus rejecting an IRD organ has the potential to improve IRD risk communication. The purpose of this article is to elucidate the underutilization of IRD organs, through the example of a potential kidney transplantation, to demystify this complex and high-stakes decision utilizing a novel communication strategy and to propose policy changes to IRD organ management that could result in hundreds of additional lives saved each year.

Urban resilience in Canada : research priorities and best practices for climate resilience in cities.

Prions consist of assemblies of aberrantly folded cellular prion protein (PrPC) upon template-assisted conversion and propagation of disease-associated PrP. To dissect the N-terminal residues critical for efficient prion propagation, we generated a library of point, double, or triple alanine replacements within residues 23-111 of PrP, stably expressed them in cells silenced for endogenous mouse PrPC and challenged the reconstituted cells with four mouse prion strains. Amino acids (aa) 105-111 of Charge Cluster 2 (CC2), which is disordered in PrPC, were required for propagation of all four prion strains; other residues had no effect or exhibited strain-specific effects. Replacements in CC2, including aa105-111, dominantly inhibited prion propagation in the presence of endogenous wild type PrPC whilst other changes were not inhibitory. Single alanine replacements within aa105-111 identified leucine 108 and valine 111 or the cluster of lysine 105, threonine 106 and asparagine 107 as critical for prion propagation. These residues mediate specific ordering of CC2 in the prion fibrils from Rocky Mountain Laboratory (RML) and ME7 mouse prion strains.

ObjectiveRugby union (‘rugby’) is popular globally, with most of its participants being amateur. Concern regarding sport-related concussion (SRC) sustained during rugby is increasing. SRC occurs most frequently in the tackle, yet few interventions have aimed to mitigate this risk factor. This study investigated the influence of a lowered legal tackle height on SRC incidence in amateur rugby.DesignCross-sectional analytical study: 2018 (control—standard tackle height) and 2019 (intervention—lowered legal tackle height) seasons.SettingSouth African collegiate student rugby competition.ParticipantsBetween 800 and 900 male amateur student players (age: 20±1.6 years) in each year.InterventionMaximum legal tackle height lowered from line of the shoulder on the ball carrier to the line of the armpit.Outcome measuresNumber of overall (medical attention) and time-loss (≥1 day lost) injuries, head injuries and SRCs in 2018 and 2019 (dependent variables); events associated with injury incidents (independent variables).ResultsThere was no statistically significant difference in incidences of time-loss injuries (IRR: 0.79; 95% CI: 0.6 to 1.1; p=0.13), head injuries (IRR: 0.83; 95% CI: 0.5 to 1.3; p=0.42) and SRC (IRR: 0.69; 95% CI: 0.4 to 1.2; p=0.20). In 2018 and 2019, most time-loss head injuries (57%, n=43) and SRCs (55%, n=26) occurred during the tackle.ConclusionsDespite a trend towards reducing injuries, head injuries and SRC, lowering maximum legal tackle height to armpit level did not change SRC incidence in this amateur male rugby cohort. Most time-loss head injuries and SRCs occurred during the tackle. Further tackle-related interventions to reduce SRC incidence require investigation.

The swordfish (Xiphias gladius) is an epi- and mesopelagic oceanic species with a wide geographical range within the tropical and temperate waters of all oceans, and is one of the most important target species in surface-longline fisheries. In order to study the vertical habitat-use and migration patterns of swordfish, and to help delimit the stock boundaries and mixing rate of swordfish between the Mediterranean Sea and the North and South Atlantic, satellite telemetry tagging is used. A total of 26 miniPAT tags have been deployed so far in the North (n = 13) and South Atlantic Oceans (n = 9) and the Mediterranean Sea (n = 4). Of the deployed tags, eight individuals suffered post-release mortality; one was fished after one day; three did not transmit; three tags had premature releases with less than 30 days; four had premature releases with more than 30 days; six tags reached full term; and one individuals’ tag is still at large. The data from ten tags were analyzed for horizontal and vertical habitat use. The results presented herein are preliminary, as more tag deployments are planned. The results show that swordfish moved in several directions, travelling considerable distances in both the North and South Atlantic Ocean, while having shorter displacements in the Mediterranean Sea. Regarding vertical habitat use, swordfish spent most of the day-time in deeper waters, and were closer to the surface during the night-time. The deepest dive recorded was 1480 m. Regarding temperature, swordfish inhabited waters with temperatures ranging from 3.9 ◦C to 30.5 ◦C, mostly residing in waters between 10–12 ◦C during the day-time and in waters >20 ◦C during the night-time. The migration of swordfish in this study agrees with the current stock boundaries defined for this species in the Atlantic Ocean, and shows a high vertical overlap with pelagic longline fisheries that are set during the night-time, SI

Background Many Intensive Care Unit (ICU) survivors suffer from a multi- system disability, termed the post-intensive care syndrome. There is no current national coordination of either rehabilitation pathways or related data collection for them. In the last year, the need for tools to systematically identify the multidisciplinary rehabilitation needs of severely affected COVID-19 survivors has become clear. Such tools offer the opportunity to improve rehabilitation for all critical illness survivors through provision of a personalised Rehabilitation Prescription (RP). The initial development and secondary refinement of such an assessment and data tools is described in the linked paper. We report here the clinical and workforce data that was generated as a result. Methods Prospective service evaluation of 26 acute hospitals in England using the Post-ICU Presentation Screen (PICUPS) tool and the RP. The PICUPS tool comprised items in domains of a) Medical and essential care, b) Breathing and nutrition; c) Physical movement and d) Communication, cognition and behaviour. Results No difference was seen in total PICUPS scores between patients with or without COVID-19 (77 (IQR 60-92) vs. 84 (IQR 68-97); Mann-Whitney z = −1.46, p = 0.144. A network analysis demonstrated that requirements for physiotherapy, occupational therapy, speech and language therapy, dietetics and clinical psychology were closely related and unaffected by COVID-19 infection status. A greater proportion of COVID-19 patients were referred for inpatient rehabilitation (13% vs. 7%) and community-based rehabilitation (36% vs.15%). The RP informed by the PICUPS tool generally specified a greater need for multi-professional input when compared to rehabilitation plans instituted. Conclusions The PICUPS tool is feasible to implement as a screening mechanism for post-intensive care syndrome. No differences are seen in the rehabilitation needs of patients with and without COVID-19 infection. The RP could be the vehicle that drives the professional interventions across the transitions from acute to community care. No single discipline dominates the rehabilitation requirements of these patients, reinforcing the need for a personalised RP for critical illness survivors.

The realization of spin liquid states born from the near-critical regime of the triangular lattice Hubbard model in inorganic materials remains a long-standing challenge, where weak spin-orbit coupling and other small perturbations often induce conventional spin freezing or order. Strong enough spin-orbit coupling, however, can renormalize the electronic wave function and induced anisotropic exchange interactions that promote magnetic frustration. Through the cooperative interplay of spin-orbit coupling and correlation effects, here we show that the triangular lattice magnet NaRuO2 hosts an inherently fluctuating magnetic ground state with thermodynamic properties suggestive of a crossover between dynamic ground states. Despite the presence of a charge gap, we find that low-temperature spin excitations generate a metal-like term in the specific heat and continuum excitations in neutron scattering, reminiscent of spin liquid states found in triangular lattice organic magnets. Further cooling reveals that these fluctuations crossover into a state whose dynamic spin autocorrelation function reflects persistent fluctuations within a highly disordered spin state. These findings instantiate NaRuO2 as a unique, Heisenberg-Kitaev cousin to organic, Heisenberg spin liquid compounds with a low-temperature crossover in quantum disorder driven via the interplay between geometric frustration, extended hopping, and relativistic spin-orbit coupling.

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.FUNDING: US National Institutes of Health and Operation Warp Speed.

Nanoporous materials have attracted great attention for gas storage, however, high volumetric storage capacity remains still a challenge. Here we investigate a magnesium borohydride framework with small pores and a unique partially negatively-charged non-flat interior for hydrogen and nitrogen uptake using neutron powder diffraction, volumetric gas adsorption, and inelastic neutron scattering. Hydrogen and nitrogen occupy distinctly different adsorption sites in the pores with very different limiting capacities: 2.33 H2 and 0.66 N2 per Mg(BH4)2. Molecular hydrogen is packed extremely dense with about twice the density of liquid hydrogen (144 - 132 g H2/L of pore volume), independently measured by three experimental methods. This study reveals that densely packed hydrogen can be stabilized in small-pore materials at ambient pressures.

By using risk-adjusted price signals to transfer responsibility for property-level flood protection and recovery from governments to property owners, flood insurance represents a key tenet of the flood risk management (FRM) paradigm. The Government of Canada has worked with insurers to introduce flood insurance for the first time as a part of a broader shift towards FRM to limit the growing costs of flooding. The viability of flood insurance in Canada, however, has been questioned by research that disputes the utility of purchasing coverage by property owners. This study tested this assumption by drawing on public opinion survey data to assess factors that influence decisions about the utility of insurance. The findings reveal that Canadians have limited knowledge of flood insurance coverage, exhibit a low willingness-to-pay for both insurance and property-level flood protection measures, and expect governments to shoulder much of the financial burden of flood recovery through disaster assistance.

Objectives The PROSE trial purpose is to investigate whether the incidence of thromboembolic—related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.—On-X) compared with a previous generation mechanical prosthesis (St Jude Medical—SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. Methods The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. Results The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. Conclusions The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

The Opioid Prescribing Engagement Network (OPEN) at the University of Michigan was established in 2016 with the goal of reducing excessive opioid prescribing after surgery using evidence-based prescribing guidelines. Beginning in July 2016, OPEN began a statewide quality improvement campaign to educate providers and share prescribing best practices. In October 2017, the first prescribing guidelines were released. Although these efforts have been associated with significant decreases in postoperative opioid prescribing, it is unknown whether the incidence of new persistent opioid use after surgery has changed as well. This retrospective study examines the effect of these efforts on new persistent opioid use after surgery compared to the rest of the United States - including other states where no such program existed - using a difference-in-differences approach.

Background Homocysteine and vitamin D may play a role in the development of diabetic and hypertensive retinopathy in patients with diabetes mellitus (DM) and hypertension. Supplementing food with L-methylfolate and vitamin D theoretically may improve diabetic and hypertensive retinopathy, however, the outcome of these nutritional approaches has not been fully examined. A retrospective case review was done of cases of retinopathy reversal in patients on Ocufolin™ and a similar nonprescription multivitamin, Eyefolate™. In this study, they were administered L-methylfolate (2.7 mg and 3.0 mg, respectively) and vitamin D3 (4500 IU each). These dosages are significantly above the RDA but well below levels associated with toxicity. Case presentation Seven patients had nonproliferative diabetic retinopathy (NPDR) and some of them had hypertension. One patient had only hypertensive retinopathy. All patients were instructed to take Ocufolin™ medical food as a food supplement. Baseline genetic testing for MTHFR polymorphisms was conducted. Fundus photography was used to document the fundus condition of the enrolled eyes in 8 NPDR patients at the initial and follow-up visits. Microaneurysms (MA) and exudates were observed to be improved in some trial patients. All subjects had one or more MTHFR polymorphisms. All had diabetic retinopathy, hypertensive retinopathy, or both. MAs were resolved, and exudates were decreased in 8/8 cases after taking the medical food. Retinal edema was found in 2/8 cases and improved or resolved in both cases after taking the medical food or the supplement. The best corrected visual activity was stable or improved in 8/8 cases. Conclusion We report a series of diabetic and hypertensive retinopathy cases with MTHFR polymorphisms and the improvement of retinal microvasculature (mainly MAs) in serial fundus photography after taking a medical food or supplement containing L-methylfolate and vitamin D. It appears that the use of nutritional supplements and medical foods containing L-methylfolate and vitamin D may be effective in facilitating the improvement of diabetic and hypertensive retinopathy.

The quest to ‘green’ the built environment has been ongoing since the early 1970s and has intensified as the threat of exceeding 450 ppm of atmospheric carbon dioxide has become more real. As a result of this, many contemporary residential high-rise buildings are designed with hopes of achieving carbon emission reductions, while not sacrificing occupant satisfaction, or property value. Little is known about how the occupants of these buildings contribute to the energy and water consumed therein, nor the effects that these design aspirations have on occupant satisfaction. The present study relies on data collected in four recently built, Leadership in Energy and Environmental Design [LEED] certified, high-rise, residential buildings in Ontario, Canada. Using various sources of data (i.e., from energy and water submeters, questionnaire responses, interviews, and physical data relating to each suite) the extent to which physical, behavioural, and demographic variables explain suite-level energy and water consumption was explored. Energy use intensity differed by a factor of 7 between similar suites, electricity by a factor of 5, hot water by a factor of 13, cooling by a factor of 47, and heating by a factor of 67. Results show that physical building characteristics explain 43% of the heating variability, 16% of the cooling variability, and 40% of electricity variability, suggesting that the remainders could be a result of occupant behaviour and demographics. It was also discovered that 52% of respondents were not using their energy recovery ventilators [ERV] for the following reasons: acoustic dissatisfaction, difficulty with accessibility of filters, occupant knowledge and preferences, and a lack of engagement with training materials. Results suggest that abandoning mechanical ventilation in favour of passive ventilation could actually lead to greater satisfaction with indoor air quality and to decreased energy consumption. Using content analysis of questionnaire comments, the utility of contextual factors in understanding energy use and satisfaction in the study buildings, as well as their value in producing feedback for designers and managers, was explored. Combining quantitative and qualitative datasets was an effective approach to understanding energy use in this understudied building type.

ObjectivesThe PROSE trial purpose is to investigate whether the incidence of thromboembolic – related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc. – On-X) compared with a previous generation mechanical prosthesis (St Jude Medical – SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. MethodsThe PROSE study was conducted in 29 worldwide centres and incorporated 854 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors.ResultsThe total patient population (854) incorporated On-X population (461) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic & mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. ConclusionsThe preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

Background Patients who have had prolonged stays in intensive care have ongoing rehabilitation needs. This is especially true of COVID-19 ICU patients, who can suffer diverse long-term ill effects. Currently there is no systematic data collection to guide the needs for therapy input for either of these groups nor to inform planning and development of rehabilitation services. These issues could be resolved in part by the systematic use of a clinical tool to support decision-making as patients progress from the Intensive Care Unit (ICU), through acute hospital care and onwards into rehabilitation. We describe (i) the development of such a tool (the Post-ICU Presentation Screen (PICUPS)) and (ii) the subsequent preparation of a person-centred Rehabilitation Prescription (RP) to travel with the patient as they continue down the care pathway. Methods PICUPS development was led by a core group of experienced clinicians representing the various disciplines involved in post-ICU rehabilitation. Key constructs and item-level descriptors were identified by group consensus. Piloting was performed as part of wider clinical engagement in 26 acute hospitals across England. Development and validation of such a tool requires clinimetric analysis, and this was based on classical test theory. Teams also provided feedback about the feasibility and utility of the tool. Results Initial PICUPS design yielded a 24-item tool. In piloting, a total of 552 records were collated from 314 patients, of which 121 (38.5%) had COVID-19. No obvious floor or ceiling effects were apparent. Exploratory factor analysis provided evidence of uni-dimensionality with strong loading on the first principal component accounting for 51% of the variance and Cronbach’s alpha for the full-scale score 0.95 – although a 3-factor solution accounted for a further 21%. The PICUPS was responsive to change both at full scale- and item-level. In general, positive responses were seen regarding the tool’s ability to describe the patients during their clinical course, engage and flag the relevant professionals needed, and to inform what should be included in an RP. Conclusions The PICUPS tool has robust scaling properties as a clinical measure and is potentially useful as a tool for identifying rehabilitation needs as patients step down from ICU and acute hospital care.

This study investigated stress experienced by NHS executives and their coping strategies following the development of sustainability and transformation partnerships (STPs). Lazarus and Folkman's (1984) transactional model of stress and coping was used to identify a range of stressors and coping strategies deployed by NHS executives to mitigate stress. An inductive qualitative approach was adopted using interview data, aiming to distinguish potentially harmful stressors from benign stressors and to discuss emotion-based and problem-based coping strategies. Finally, the authors strived to make clear recommendations for NHS England to develop leadership capability regarding inter-role conflict and the development of a regional culture of resilience among system-level executives.

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

Canada is a country in the midst of a flood management policy transition that is shifting part of the flood damage burden from the state to homeowners. This transition-as well as the large financial losses resulting from flooding-have created a window of opportunity for Canada to implement strategies that increase property owners' capacity to avoid and absorb the financial and physical risks associated with flooding. This work presents foundational research into the extent to which Canadians' flood experience, perceptions of flood risks and socio-demographics shape their intentions and adoption of property level flood protection (PLFP). A bilingual, national survey was deployed in Spring 2016 and was completed by 2300 respondents across all 10 Canadian provinces. The survey was developed using assumptions in existing literature on flood risk behaviours and the determinants of flood risk management in similar jurisdictions. The paper argues that property owners are not willing to accept greater responsibility for flood risk as envisioned by recent policy changes. This finding is consistent with other OECD jurisdictions, where flood risk engagement strategies have been developed that could be replicated in Canada to encourage risk-sharing behaviour.

AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%–79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%–20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients.

This is a post-peer-review, pre-copyedit version of an article published in Energy Efficiency. The final authenticated version is available online at http://dx.doi.org/10.1007/s12053-017-9578-4., In addition to a growing and aging population, Canada has experienced large shifts in its residential sector. There are more households, homes are larger with less people in them, and there are more appliances per household, all of which contribute to increased energy consumption. The present work explores the demographic determinants of residential energy efficiency adoption using the 2013 Households and Environment Survey. With binary logistic regressions, we predicted the odds of households adopting three energy-efficient actions: energy-saving lights, programmable thermostats, and changes to a dwelling following an energy audit. Although it was found that Canadian households are participating in energy efficiency, not all groups are participating equally. Similar to previous research, seniors appear to be more inclined to adopt less challenging measures such as energy-saving lights, as opposed to more intensive dwelling upgrades. Additionally, levels of education and income were positively related to the adoption of energy efficiency measures. However, the results showed household income to be less of a contributing factor for decisions regarding dwelling changes compared to the financial incentives offered via government grants. The results suggest a need to increase energy efficiency education and to continue offering financial incentives as the country increases its residential energy efficiency.

This is a post-peer review, pre-copyedit version of an article published in Environment, Development and Sustainability. The final authenticated version is available online at https://doi.org/10.1007/s10668-016-9891-7 There are numerous challenges that evaluators face when determining the success of urban climate resilience initiatives (e.g., how to attribute impacts to initiatives). Fortunately, a growing body of literature --much of it dealing with climate change adaptation-- has emerged which can help address these challenges. This narrative review of academic and grey literature reviews various monitoring and evaluation methods that can assess the inputs, processes, outputs, outcomes, and impacts that result from climate resilience planning and action. Since there is no commonly accepted monitoring and evaluation approach, the literature stresses the importance of acknowledging the context in which resilience is being evaluated, in order to ensure that appropriate methods are chosen. This context includes the ways that the resilience framework and definition chosen for a project constrain and determine the monitoring and evaluation approaches which can be adopted. As a result of this, a blend of quantitative and qualitative approaches is often recommended, with sufficient evidence suggesting that qualitative approaches (e.g., outcome harvesting) are essential. Nuanced approaches to monitoring and evaluation give evaluators additional means of reporting progress, and of demonstrating success, which is especially important as cities begin to implement resilience initiatives in the coming years.

Diabetic retinopathy (DR) is a form of microangiopathy. Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina. New approaches are needed, which reduce the risk and improve the outcomes of DR while complementing current therapeutic approaches. Homocysteine (Hcy) elevation and oxidative stress are potential therapeutic targets in DR.Common genetic polymorphisms such as those of methylenetetrahydrofolate reductase (MTHFR), increase Hcy and DR risk and severity. Patients with DR have high incidences of deficiencies of crucial vitamins, minerals, and related compounds, which also lead to elevation of Hcy and oxidative stress. Addressing the effects of the MTHFR polymorphism and addressing comorbid deficiencies and insufficiencies reduce the impact and severity of the disease. This approach provides safe and simple strategies that support conventional care and improve outcomes.Suboptimal vitamin co-factor availability also impairs the release of neurotrophic and neuroprotective growth factors. Collectively, this accounts for variability in presentation and response of DR to conventional therapy. Fortunately, there are straightforward recommendations for addressing these issues and supporting traditional treatment plans.We have reviewed the literature for nutritional interventions that support conventional therapies to reduce disease risk and severity. Optimal combinations of vitamins B1, B2, B6, L-methylfolate, methylcobalamin (B12), C, D, natural vitamin E complex, lutein, zeaxanthin, alpha-lipoic acid, and n-acetylcysteine are identified for protecting the retina and choroid. Certain medical foods have been successfully used as therapy for retinopathy. Recommendations based on this review and our clinical experience are developed for clinicians to use to support conventional therapy for DR.DR from both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have similar retinal findings and responses to nutritional therapies.

Collision sports, such as Rugby Union (“Rugby”) have a particularly high risk of injury. Of all injuries common to collision sports, concussions have received the most attention due to the potentially negative cognitive effects in the short- and long-term. Despite non-professional Rugby players comprising the majority of the world’s playing population, there is relatively little research in this population. Stellenbosch Rugby Football Club (“Maties”), the official rugby club of Stellenbosch University, represents one of the world’s largest non-professional Rugby clubs, making this an ideal cohort for community-level injury surveillance. The aim of this study was to describe the incidence and events associated with concussion in this cohort. Baseline demographics were obtained on the 807 male student Rugby non-professional players who registered for the 10-week long 2018 season, which comprised 101 matches and 2,915 of exposure hours. All match-related injuries were captured by the medical staff of Stellenbosch Campus Health Service on an electronic form developed from the consensus statement for injury recording in Rugby. The mean age, height and weight of this cohort were 20 ± 2 years, 182 ± 7 cm and 88 ± 14 kg, respectively. Overall, there were 89 time-loss injuries, which equated to an injury rate of 30.6 per 1,000 match hours [95% confidence intervals (CIs): 24.2–36.9], or about one injury per match. The most common injury diagnosis was “concussion” (n = 27 out of 90 injuries, 30%), at a rate of 9.3 per 1,000 match hours (95% CIs: 5.8–12.8). The three most common mechanisms of concussion in the present study were performing a tackle (33%), accidental collision (30%) and being tackled (11%). Concussion was the most common injury in this population, at a rate that was six times higher than the most comparable study from the UK, which had far more exposure time over six seasons and wider range of player ability, from recreational to semi-professional. This might be explained by the training and vigilance of the club’s first aiders observing all matches for concussion. Future studies should try to explain this high rate and subsequently reduce these concussions. The addition of video surveillance data would assist in identifying the etiology of these concussions injuries in order to develop specific targeted interventions.

Although the importance of urban infrastructure resilience can be inferred, its terminology remains convoluted within the literature due to a lack of systematic review from a sustainable development planning perspective. This review paper was designed to elucidate connected research themes, scientific popularity, and conceptual boundaries of the term infrastructure resilience in an urban context. Three guiding research questions were asked: What does urban infrastructure resilience really mean? What are the most common research topics connected to urban infrastructure resilience? How can humanity further improve urban infrastructure resilience from a sustainable development planning perspective? To answer these research questions, a two-step literature analysis was adopted consisting of: (i) a scoping review to select relevant publications based on a specific search query; and (ii) a content analysis to reduce and synthesize the scoping review findings further based on the three most applicable publishing outlets. The scoping review reduced articles to 535, while content analysis further condensed it to 84 across three key journals. With North America and Europe leading, the findings corroborated that eight connected subject areas establish the conceptual boundaries of urban infrastructure resilience. The eight related research topics in decreasing abundance were: (1) climate change, (2) floods, (3) disasters, (4) environmental policy, (5) ecosystems, (6) risk assessment, (7) emergency preparedness, and (8) adaptation. In conclusion, these research topics should be pursued when creating urban infrastructure resilience strategies for moving towards sustainability.

Lung cancer is the leading cause of cancer related deaths. Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancers. Our understanding of driver mutations and genotype directed therapy has revolutionized the management of advanced NSCLC. Commonly described mutations include mutations in epidermal growth factor (EGFR) & BRAF and translocations in anaplastic lymphoma kinase (ALK) & rat osteosarcoma (ROS1). Drugs directed against these translocations have significantly improved progression free survival individually and have shown a survival benefit when studied in the Lung Cancer Mutation Consortium (median survival 3.5 vs. 2.4 years compared to standard therapy). In a related yet parallel universe, the number of bronchoscopic ablative modalities available for management of cancer related airway obstruction have increased exponentially over the past decade. A wealth of literature has given us a better understanding of the technical aspects, benefits and risks associated with these procedures. While they all show benefits in terms of relieving airway obstruction, symptom control, quality of life and lung function testing, their complication rates vary based on the modality. The overall complication rate was ~4% in the AQuIRE registry. Bronchoscopic therapeutic modalities include rigid bronchoscopy with mechanical debulking, laser, thermo-coagulation [electrocautery & argon plasma coagulation (APC)], cryotherapy, endobronchial brachytherapy (EBT), photodynamic therapy (PDT), intratumoral chemotherapy (ITC) and transbronchial needle injection (TBNI) of chemotherapy. Intuitively, one would assume that the science of driver mutations would crisscross with the science of bronchoscopic ablation as they overlap in the same patient population. Sadly, this is not the case and there is a paucity of literature looking at these fields together. This results in several unanswered questions about the interplay between these two therapies.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.