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Abstract Patient involvement is crucial in healthcare, a factor increasingly recognised by life sciences companies and research institutes. This article presents a case study on Servier, a life sciences company that founded a patient expert board, ahead of launching a new research and development (R&D) institute. The aim was to foster a patient-centric culture within the company. The case study explores key developments in patient and public involvement, emphasising a shift from paternalistic to patient-centred approaches, noting few available case studies on patient board collaborations in life sciences. It outlines the evolution of the board, its impact, and practical lessons learned, with related recommendations. The patient board resulted from a three-way collaboration between the company, Patvocates (a patient consultancy), and patient experts recruited. The patient consultancy played a crucial role in project management, governance, and facilitating relationships. The case study provides the context, timeframe, foundations laid, engagement of patient experts, and foundational values, including: co-creation, fair market value remuneration, voluntary participation, and patient-centric meeting protocol. Eighteen patient experts, representing ten disease areas and ten European countries, joined the board and helped prioritise and co-create projects. Ideas for activities were sourced from brainstorming sessions and an in-company challenge. The collaboration yielded five core ideas, each forming a working group. The study describes the groups and their outputs: a patient advisory council, an interactive gallery of patient experience in R&D, patient engagement and entrepreneurship in life sciences, creating patient-focused decentralised trials (DCTs), and staff training on patient engagement. The article emphasises how the organic evolution of the collaboration led to significant insights. Hurdles faced by the company included: upstream planning, cross-company buy-in, compliance, and internal resource allocation. Recommendations for the wider community included: identifying and contracting patient partners; clarifying roles; managing expectations; building trust; logistics; and sustainability. This case study presents a practical, positive example of patient engagement within a life sciences company, offering insights into the establishing, running, and the impact of collaborating with a patient expert board. Lessons learned and recommendations may serve as a model for other companies seeking to engage with patients and evolve towards a more patient-centric approach in their strategies.

Abstract De novo mutations (DNMs) are drivers of genetic disorders. However, the study of DNMs is hampered by technological limitations preventing accurate quantification of ultra-rare mutations. Duplex Sequencing (DS) theoretically has T. Blood MF and substitution spectrum were similar to those reported in blood cells with an orthogonal method. The sperm MF was in the same order of magnitude and had a strikingly similar spectrum to DNMs from publicly available whole genome sequencing data from human pedigrees (1.2 × 10− 8 per bp). DS revealed much larger numbers of insertions and deletions in sperm over blood, driven by an abundance of putative extra-chromosomal circular DNAs. The study indicates the strong potential of DS to characterize human DNMs to inform factors that contribute to disease susceptibility and heritable genetic risks.

Abstract Plant-based diets have gained attention for their potential benefits on both human health and environmental sustainability. The objective of this study was to investigate the association of plant-based dietary patterns with the endogenous metabolites of healthy individuals and identify metabolites that may act as mediators of the associations between dietary intake and modifiable disease risk factors. Adherence to plant-based dietary patterns was assessed for 170 healthy adults using plant-based diet indexes (PDI). Individuals with higher healthful PDI had lower BMI and fasting glucose and higher HDL-C, while those with higher unhealthful PDI had higher BMI, triacylglycerol and fasting glucose and lower HDL-C. Unhealthful PDI was associated with higher levels of several amino acids and biogenic amines previously associated with cardiometabolic diseases and an opposite pattern was observed for healthful PDI. Furthermore, healthful PDI was associated with higher levels of glycerophosphocholines containing very long-chain fatty acids. Glutamate, isoleucine, proline, tyrosine, α-aminoadipate and kynurenine had a statistically significant mediation effect on the associations between PDI scores and LDL-C, HDL-C and fasting glucose. These findings contribute to the growing evidence supporting the role of plant-based diets in promoting metabolic health and shed light on the potential mechanisms explaining their beneficial health effects.

Behavioral neuroscience requires precise and unbiased methods for animal behavior assessment to elucidate complex brain–behavior interactions. Traditional manual scoring methods are often labor-intensive and can be prone to error, necessitating advances in automated techniques. Recent innovations in computer vision have led to both marker- and markerless-based tracking systems. In this protocol, we outline the procedures required for utilizing Augmented Reality University of Cordoba (ArUco) markers, a marker-based tracking approach, to automate the assessment and scoring of rodent engagement during an established intracortical microstimulation-based nose-poking go/no-go task. In short, this protocol involves detailed instructions for building a suitable behavioral chamber, installing and configuring all required software packages, constructing and attaching an ArUco marker pattern to a rat, running the behavioral software to track marker positions, and analyzing the engagement data for determining optimal task durations. These methods provide a robust framework for real-time behavioral analysis without the need for extensive training data or high-end computational resources. The main advantages of this protocol include its computational efficiency, ease of implementation, and adaptability to various experimental setups, making it an accessible tool for laboratories with diverse resources. Overall, this approach streamlines the process of behavioral scoring, enhancing both the scalability and reproducibility of behavioral neuroscience research. All resources, including software, 3D models, and example data, are freely available at https://github.com/tomcatsmith19/ArucoDetection.

Abstract NOAA Daily Optimum Interpolation Sea Surface Temperature (DOISST) and other similar sea surface temperature (SST) products indicate that the globally averaged SST set a new daily record in March 2023. The record‐high SST in March was immediately broken in April, and new daily records were set again in July and August 2023. The SST anomaly (SSTA) persisted at a record high from mid‐March to the remainder of 2023. Our analysis indicates that the record‐high SSTs, and associated marine heatwaves (MHWs) and even super‐MHWs, are attributed to three factors: (a) a long‐term warming trend, (b) a shift to the warm phase of the multi‐decadal Pacific‐Atlantic‐Arctic (PAA) mode, and (c) the transition from the triple‐dip succession of La Niña events to the 2023–24 El Niño event.

Objective To determine and identify distance patterns in the movements of medical students and junior doctors between their training locations.Design A retrospective cohort study of UK medical students from 2002 to 2015 (UKMED data).Setting All UK medical schools, foundations and specialty training organisation.Participants All UK medical students from 2002 to 2015, for a total of 97 932 participants.Outcome measures Individual movements and number of movements by county of students from family home to medical school training, from medical school to foundation training and from foundation to specialty training.Methods Leslie matrix, principal components analysis, Gini coefficient, χ2 test, generalised linear models and variable selection methods were employed to explore the different facets of students’ and junior doctors’ movements from the family home to medical school and for the full pathway (from family home to specialty training).Results The majority of the movements between the different stages of the full pathway were restricted to a distance of up to 50 km; although the proportion of movements changed from year-to-year, with longer movements during 2007–2008. At the individual level, ethnicity, socioeconomic class of the parent(s) and the deprivation score of the family home region were found to be the most important factors associated with the length of the movements from the family home to medical school. Similar results were found when movements were aggregated at the county level, with the addition of factors such as gender and qualification at entry (to medical school) being statistically associated with the number of new entrant students moving between counties.Conclusion Our findings show that while future doctors do not move far from their family home or training location, this pattern is not homogeneous over time. Distances are influenced by demographics, socioeconomic status and deprivation. These results may contribute in designing interventions aimed at solving the chronic problems of maldistribution and underdoctoring in the UK.

ABSTRACT IntroductionThis study aimed to assess the prevalence of risk behaviors and the impact of electronic risk behavior screening with personalized feedback among adolescents seeking care in the emergency department (ED). MethodsRandomized control trial of tablet-based screening and feedback among adolescents presenting to the ED. Intervention youth received screening with individualized feedback. Control youth completed risk behavior screening only. All participants received 3-month online follow up surveys re-assessing health behaviors. Results296 subjects were enrolled and randomized. Approximately half were female (52.4%) and half white (54.4%) with a mean age of 15.4 years. The response rate at 3-month follow-up was 70.6%.  The most frequently reported risk behaviors were those negatively impacting long-term health: sleeping less than 8 hours per night (142/296=48%), drinking more than 2 sugary drinks per day (99/296=33.4%) and getting less than 3 days of physical activity per week (96/296=32.4%). The prevalence of high-risk behaviors with more immediate health consequences were depression (92/296 =31.1%); high alcohol (47/296=15.9%) or marijuana use (55/296=18.6%); texting when driving (41/296=13.8%) and inconsistent birth control or condom use (42/296=14.2%). There was no significant difference between groups in risk behavior changes from baseline to 3 months. ConclusionsWhile risk behavior prevalence was high in this population, electronic personalized feedback alone was insufficient to induce change in behaviors. More research is warranted to understand the best strategies for reducing risk among youth presenting to the ED.

The highly automated macromolecular crystallography beamline AMX/17-ID-1 is an undulator-based high-intensity (>5 × 1012 photons s−1), micro-focus (7 µm × 5 µm), low-divergence (1 mrad × 0.35 mrad) energy-tunable (5–18 keV) beamline at the NSLS-II, Brookhaven National Laboratory, Upton, NY, USA. It is one of the three life science beamlines constructed by the NIH under the ABBIX project and it shares sector 17-ID with the FMX beamline, the frontier micro-focus macromolecular crystallography beamline. AMX saw first light in March 2016 and started general user operation in February 2017. At AMX, emphasis has been placed on high throughput, high capacity, and automation to enable data collection from the most challenging projects using an intense micro-focus beam. Here, the current state and capabilities of the beamline are reported, and the different macromolecular crystallography experiments that are routinely performed at AMX/17-ID-1 as well as some plans for the near future are presented.

Abstract Background Efforts to improve the impact of long-lasting insecticidal nets (LLINs) should be informed by understanding of the causes of decay in effect. Holes in LLINs have been estimated to account for 7–11% of loss in effect on vectorial capacity for Plasmodium falciparum malaria in an analysis of repeated cross-sectional surveys of LLINs in Kenya. This does not account for the effect of holes as a cause of net attrition or non-use, which cannot be measured using only cross-sectional data. There is a need for estimates of how much these indirect effects of physical damage on use and attrition contribute to decay in effectiveness of LLINs. Methods Use, physical integrity, and survival were assessed in a cohort of 4514 LLINs followed for up to 4 years in Kenya. Flow diagrams were used to illustrate how the status of nets, in terms of categories of use, physical integrity, and attrition, changed between surveys carried out at 6-month intervals. A compartment model defined in terms of ordinary differential equations (ODEs) was used to estimate the transition rates between the categories. Effects of physical damage to LLINs on use and attrition were quantified by simulating counterfactuals in which there was no damage. Results Allowing for the direct effect of holes, the effect on use, and the effect on attrition, 18% of the impact on vectorial capacity was estimated to be lost because of damage. The estimated median lifetime of the LLINs was 2.9 years, but this was extended to 5.7 years in the counterfactual without physical damage. Nets that were in use were more likely to be in a damaged state than unused nets but use made little direct difference to LLIN lifetimes. Damage was reported as the reason for attrition for almost half of attrited nets, but the model estimated that almost all attrited nets had suffered some damage before attrition. Conclusions Full quantification of the effects of damage will require measurement of the supply of new nets and of household stocks of unused nets, and also of their impacts on both net use and retention. The timing of mass distribution campaigns is less important than ensuring sufficient supply. In the Kenyan setting, nets acquired damage rapidly once use began and the damage led to rapid attrition. Increasing the robustness of nets could substantially increase their lifetime and impact but the impact of LLIN programmes on malaria transmission is ultimately limited by levels of use. Longitudinal analyses of net integrity data from different settings are needed to determine the importance of physical damage to nets as a driver of attrition and non-use, and the importance of frequent use as a cause of physical damage in different contexts.

Abstract Background In cluster randomized trials (CRTs) or stepped wedge cluster randomized trials (SWCRTs) of malaria interventions, mosquito movement leads to contamination between trial arms unless buffer zones separate the clusters. Contamination can be accounted for in the analysis, yielding an estimate of the contamination range, the distance over which contamination measurably biases the effectiveness. Methods A previously described analysis for CRTs is extended to SWCRTs and estimates of effectiveness are provided as a function of intervention coverage. The methods are applied to two SWCRTs of malaria interventions, the SolarMal trial on the impact of mass trapping of mosquitoes with odor-baited traps and the AvecNet trial on the effect of adding pyriproxyfen to long-lasting insecticidal nets. Results For the SolarMal trial, the contamination range was estimated to be 146 m ( $$95\%$$ 95 % credible interval $$[0.052,\,0.923]$$ [ 0.052 , 0.923 ] km), together with a $$31.9\%$$ 31.9 % ( $$95\%$$ 95 % credible interval $$[15.3,\,45.8]\%$$ [ 15.3 , 45.8 ] % ) reduction of Plasmodium infection, compared to the $$30.0\%$$ 30.0 % reduction estimated without accounting for contamination. The estimated effectiveness had an approximately linear relationship with coverage. For the AvecNet trial, estimated contamination effects were minimal, with insufficient data from the cluster boundary regions to estimate the effectiveness as a function of coverage. Conclusions The contamination range in these trials of malaria interventions is much less than the distances Anopheles mosquitoes can fly. An appropriate analysis makes buffer zones unnecessary, enabling the design of more cost-efficient trials. Estimation of the contamination range requires information from the cluster boundary regions and trials should be designed to collect this.

Abstract Background In cluster randomized trials (CRTs) of interventions against malaria, mosquito movement between households ultimately leads to contamination between intervention and control arms, unless they are separated by wide buffer zones. Methods This paper proposes a method for adjusting estimates of intervention effectiveness for contamination and for estimating a contamination range between intervention arms, the distance over which contamination measurably biases the estimate of effectiveness. A sigmoid function is fitted to malaria prevalence or incidence data as a function of the distance of households to the intervention boundary, stratified by intervention status and including a random effect for the clustering. The method is evaluated in a simulation study, corresponding to a range of rural settings with varying intervention effectiveness and contamination range, and applied to a CRT of insecticide treated nets in Ghana. Results The simulations indicate that the method leads to approximately unbiased estimates of effectiveness. Precision decreases with increasing mosquito movement, but the contamination range is much smaller than the maximum distance traveled by mosquitoes. For the method to provide precise and approximately unbiased estimates, at least 50% of the households should be at distances greater than the estimated contamination range from the discordant intervention arm. Conclusions A sigmoid approach provides an appropriate analysis for a CRT in the presence of contamination. Outcome data from boundary zones should not be discarded but used to provide estimates of the contamination range. This gives an alternative to “fried egg” designs, which use large clusters (increasing costs) and exclude buffer zones to avoid bias.

Introduction: In this study we aimed to assess the impact of an electronic health assessment with individualized feedback for risk behaviors in adolescents seeking care in a pediatric emergency department (ED). Methods: We conducted a randomized control trial using a tablet-based screening program with a study population of adolescents in a busy pediatric ED. The intervention group received the screening program with individualized feedback. The control group received the screening program without feedback. All participants received one-day and three-month follow-up surveys to assess behaviors and attitudes toward health behaviors. Results: A total of 296 subjects were enrolled and randomized. There was no difference in changes in risky behaviors between the control and experimental groups. A higher proportion of participants in the intervention groups reported that the screener changed the way they thought about their health at one-day follow-up (27.0%, 36/133) compared to the control group (15.5%, 20/129, P = .02). Conclusion: This study successfully tested a multivariable electronic health screener in a real-world setting of a busy pediatric ED. The tool did not significantly change risky health behaviors in the adolescent population screened. However, our finding that the intervention changed adolescents’ perceptions of their health opens a door to the continued development of electronic interventions to screen for and target risk behaviors in adolescents in the ED setting.

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children

Sleep is crucial for maintaining the recovery and restoration of the body and brain. Less sleep is associated with poor mental and physical performance. Seasonal changes in sleep patterns can be observed. This paper examines seasonal effects on sleep timing, duration, and problems in two Cree First Nation communities in Saskatchewan, Canada. Data were available from a community survey of 588 adults aged 18 years and older (range: 18–78 years) with 44.2% males and 55.8% females. Results are presented using descriptive statistics and a binary logistic-regression model to identify the association between seasonal changes in sleep patterns, and demographic, social, and environmental factors. The participants reported sleeping the least during the spring and summer months and sleeping the most during the fall and winter months. This was further confirmed by sleep hours and the lower proportion of recommended hours of sleep during the spring and summer, and a higher proportion of longer sleep duration during the fall and winter months. There was no significant variation in sleeping onset and wake-up times by season. Overall, there were no significant differences in the prevalence of sleep deprivation, insomnia, and excessive daytime sleepiness by season. When stratified by age group and sex, some differences existed in the prevalence of sleep problems by season. More than two-thirds (68.6%) of the participants reported that there was a change in sleep patterns across seasons, and about 26.0% reported a very or extremely marked change in sleep patterns across seasons. Changes in sleep patterns by season were related to money left at the end of the month and damage caused by dampness in the house.

Training recommendations for novice to intermediate lifters include loads that correspond to a 10RM, yet there has not been normative data established for college aged females. Therefore, the purpose of this study was to provide 10RM normative reference values for various strength exercises for 18 to 25-year-old females. The exercises for this study included were the Lat Pulldown, Bench Press, Seated Front Press, Preacher Curl, and the Leg Press. Every testing and training occurred using the same equipment and in the same facility. Testing occurred prior to the structured training program began and then again upon completion of 12 weeks of training. A total of 371 subjects (age = 19.86 +1.43years; height = 64.51 +2.90 inches; pre-test bodyweight = 151.19 +36.05 pounds; pre-test body fat percentage = 29.20 +8.89 percent body fat; post-test bodyweight = 153.66 +36.80 pounds; post-test body fat percentage = 30.76 +8.44 percent body fat; years of strength training experience = 2.28 +2.38 years), participated in the study. Bodyweight categories were derived based upon two established classification systems used in competitive lifting sports. Percentiles and performance rankings for each weight category were reported, where the weighted average method was used to determine the percentile break points. These norms provide a range of possible 10RM loads as well as a reference to the strength levels, which could be useful to more effectively assess and design resistance training programs.

Space-time adaptive processing (STAP) is a well-known and effective method to detect targets, obscured by interference, from airborne radars that works by coherently combining signals from a phased antenna array (spatial domain) with multiple radar pulses (temporal domain). As widely demonstrated, optimum STAP, in the sense of maximizing the output signal to interference plus noise ratio (SINR), is a coherent, linear, transversal filter (i.e., tapped delay line), that can be synthesized by a complex-valued weight vector. This paper extends previous work that focused on adaptive spatial-only nulling; it derives the optimum phase-only STAP, namely, the optimal weight vector that maximizes the SINR subject to the constraint it belongs to the $N$ -torus of phase-only complex vectors, where $N$ is the number of spatio-temporal degrees of freedom. Because this problem does not admit a closed-form solution, it is solved numerically using the phase-only conjugate gradient method (CGM). The effectiveness of phase-only STAP is demonstrated using both SINR values and receiving beampattern shape, comparing it with the optimum fully-adapted STAP and the nonadapted beam former responses as well as other possible counterparts. Additionally, several analyses of practical utility also demonstrate the benefits provided by phase-only STAP.

Insomnia is a common problem in Canada and has been associated with increased use of health care services and economic burden. This paper examines the prevalence and risk factors for insomnia in two Cree First Nation communities in Saskatchewan, Canada. Five hundred and eighty-eight adults participated in a baseline survey conducted as part of the First Nations Sleep Health Collaborative Project. The prevalence of insomnia was 19.2% among participants with an Insomnia Severity Index score of ≥15. Following the definition of nighttime insomnia symptoms, however, the prevalence of insomnia was much higher, at 32.6%. Multivariate logistic regression modeling revealed that age, physical health, depression diagnosis, chronic pain, prescription medication use for any health condition, and waking up during the night due to terrifying dreams, nightmares, or flashbacks related to traumatic events were risk factors for insomnia among participants from two Saskatchewan Cree First Nation communities.

Turbulent fluxes make a substantial and growing contribution to the energy balance of ice surfaces globally, but are poorly constrained owing to challenges in estimating the aerodynamic roughness length (z0). Here, we used structure from motion (SfM) photogrammetry and terrestrial laser scanning (TLS) surveys to make plot-scale 2-D and 3-D microtopographic estimations of z0 and upscale these to map z0 across an ablating mountain glacier. At plot scales, we found spatial variability in z0 estimates of over two orders of magnitude with unpredictable z0 trajectories, even when classified into ice surface types. TLS-derived surface roughness exhibited strong relationships with plot-scale SfM z0 estimates. At the glacier scale, a consistent increase in z0 of ~0.1 mm d−1 was observed. Space-for-time substitution based on time since surface ice was exposed by snow melt confirmed this gradual increase in z0 over 60 d. These measurements permit us to propose a scale-dependent temporal z0 evolution model where unpredictable variability at the plot scale gives way to more predictable changes of z0 at the glacier scale. This model provides a critical step towards deriving spatially and temporally distributed representations of z0 that are currently lacking in the parameterisation of distributed glacier surface energy balance models.

Objectives Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.Design A multicentre, international, collaborative cohort study.Setting 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Participants Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measure All-cause mortality at 30 days and 90 days.Results 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p

Abstract Background Patients with multiple sclerosis (MS) have a higher incidence of uveitis compared with the general population. Fingolimod, a first line disease modifying drug used in multiple sclerosis, may cause macular edema and thus requires ophthalmic examination. However, murine models and anecdotal reports suggest fingolimod may reduce the incidence of uveitis. Purpose To report the incidence of uveitis and macular edema among those on fingolimod 0.5 mg (Gilenya®) therapy for multiple sclerosis (MS). Methods Retrospective review of patients on fingolimod who developed uveitis and/or macular edema. Results No patients had an occurrence or history of uveitis. Four of the 188 (2.13%) patients developed macular edema without ocular inflammation. One of the 188 (0.53%) patients developed Acute Macular Neuroretinopathy. Conclusion Patients taking fingolimod have a lower incidence of uveitis than expected in a population of MS patients.

Worldwide, early intervention services for young people with recent-onset psychosis have been associated with improvements in outcomes, including reductions in hospitalization, symptoms, and improvements in treatment engagement and work/school participation. States have received federal mental health block grant funding to implement team-based, multi-element, evidence-based early intervention services, now called coordinated specialty care (CSC) in the USA. New York State’s CSC program, OnTrackNY, has grown into a 23-site, statewide network, serving over 1800 individuals since its 2013 inception. A state-supported intermediary organization, OnTrackCentral, has overseen the growth of OnTrackNY. OnTrackNY has been committed to quality improvement since its inception. In 2019, OnTrackNY was awarded a regional hub within the National Institute of Mental Health-sponsored Early Psychosis Intervention Network (EPINET). The participation in the national EPINET initiative reframes and expands OnTrackNY’s quality improvement activities. The national EPINET initiative aims to develop a learning healthcare system (LHS); OnTrackNY’s participation will facilitate the development of infrastructure, including a systematic approach to facilitating stakeholder input and enhancing the data and informatics infrastructure to promote quality improvement. Additionally, this infrastructure will support practice-based research to improve care. The investment of the EPINET network to build regional and national LHSs will accelerate innovations to improve quality of care.

Abstract Background To determine if the number of endoscopic treatments of urethral stricture disease (USD) prior to urethroplasty has changed in the context of new AUA guidelines on management of USD. In addition to an increase in practicing reconstructive urologists and published reconstructive literature, the AUA guidelines regarding the management of male USD were presented in May 2016, advocating consideration of urethroplasty in patients with 1 prior failed endoscopic treatment. Methods A retrospective review of a prospectively maintained, multi-institutional urethral stricture database of high volume, geographically diverse institutions was performed from 2006 to 2017. We performed a review of relevant literature and evaluated pre-urethroplasty endoscopic treatment patterns prior to and after the AUA male stricture guideline. Results 2964 urethroplasties were reviewed in 10 institutions. There was both a decrease in the number of endoscopic treatments prior to urethroplasty in the pre-May 2016 compared to post-May 2016 cohorts both for overall urethroplasties (2.3 vs 1.6, P = 0.0012) and a gradual decrease in the number of pre-urethroplasty endoscopic treatments over the entire study period. Conclusion There was a decrease in the number of endoscopic treatments of USD prior to urethroplasty in the observed period of interest. Declining endoscopic USD management is not likely to be a reflection of a solely unique influence of the guidelines as endoscopic treatment decreased over the entire study period. Further research is needed to determine if there will be a continued trend in the declining use of endoscopic treatment and elucidate the barriers to earlier urethroplasty in patients with USD.

PICO question In cats with feline interstitial cystitis, which therapy brings a faster resolution of clinical signs: meloxicam or prednisolone? Clinical bottom line Category of research question Treatment The number and type of study designs reviewed Two papers evaluated as relevant to the PICO question were critically reviewed. Both were double-blinded randomised controlled trials. One paper not related to the PICO question, a single-blinded randomised controlled trial, was also reviewed as it is touched upon in the discussion section Strength of evidence Appraisal of the literature reveals weak evidence that meloxicam and prednisolone are of equivalent effectiveness when treating feline interstitial cystitis, also known as feline idiopathic cystitis (FIC) Outcomes reported There is no statistically significant difference in the reduction of clinical signs when meloxicam is compared with a placebo for the treatment of FIC. There is no statistically significant difference in reduction of clinical signs when prednisolone is compared with a placebo for the treatment of FIC. No studies were available for review which directly compared meloxicam against prednisolone as treatment options for FIC Conclusion In cats with FIC, insufficient evidence exists to truly conclude whether meloxicam or prednisolone is the most efficacious therapy for the reduction of clinical signs. Two double-blinded randomised controlled trials were evaluated – one compared the efficacy of meloxicam against a placebo; the other compared the efficacy of prednisolone against a placebo. Neither study found a statistically significant difference between the assessed treatment modality and the placebo used in reducing the clinical signs of FIC. As such, weak evidence exists that there is no significant difference between the use of meloxicam and a placebo, and prednisolone and a placebo in the reduction of clinical signs of FIC. Additionally, it could therefore be hypothesised that no significant difference exists in the reduction of clinical signs when comparing meloxicam against prednisolone as treatments for FIC however, no study was discoverable which was able to substantiate this claim How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Cerium dioxide CeO _2 (ceria) is an important material in catalysis and energy applications. The intrinsic Frenkel and Schottky defects can impact a wide range of material properties including the oxygen storage capacity, the redox cycle, and the ionic and thermal transport. Here, we study the impact of Frenkel and Schottky defects on the structural dynamics and thermal properties of ceria using density functional theory. The phonon contributions to the free energy are found to reduce the defect formation free energies at elevated temperature. The phonon dispersions of defective CeO _2 show significant broadening of the main branches compared to stoichiometric ceria. Phonon modes associated with the defects are identifiable in the infrared spectra through characteristic shoulders on the main features of the stoichiometric fluorite structure. Finally, the presence of Frenkel and Schottky defects are also found to reduce the thermal conductivity by up to 88% compared to stoichiometric CeO _2 .

Objectives: Sleep deprivation is a common problem in Canada and is associated with many health problems. More than a quarter of Canadians get fewer than the recommended sleep hours (