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To biomechanically investigate a novel modified all-suture construct compared with commercially available suspensory button fixation for stabilization of the syndesmosis.Eight matched pairs of cadaver lower limbs were obtained. We used a material testing machine (MTS) and Optotrak optoelectronic 3D motion measurement system for testing. Syndesmotic injuries were simulated, and specimens were fixed with either a suspensory suture button or modified all suture construct. Repaired specimens were then cyclically loaded for 500 cycles. Spatial relationship of the tibia and fibula were continuously monitored for the intact, destabilized, and repaired states. Results were analyzed using independent samples t test.There was no significant difference in sagittal or coronal plane translation between intact and either repair. Compared to the intact state, both repair techniques demonstrated significantly more external rotation of the fibula relative to the tibia, and decreased construct stiffness. Cycling of the specimens did not significantly increase coronal or sagittal plane translation, however external rotation of the fibula relative to the tibia increased and stiffness decreased with cycling for both repair techniques.Our data suggests that sagittal and coronal plane translation is no different from the intact state for both fixation techniques. However, rotation of the fibula relative to the tibia was increased and construct stiffness was decreased compared to the intact state for both fixation techniques. These findings suggest that an all-suture construct could offer syndesmotic fixation comparable to proprietary suspensory button fixation in a cadaver model.

Machining silicon carbide (SiC) is challenging due to its brittle and maximum tensile nature. Lapping or laser beam are done with a high cost of manufacturing and low material removal rates. Water abrasive jet cutting is a promising candidate since the machining temperatures and processing force of ceramics are extremely low. Investigation into the abrasive water jet machining of silicon carbide is carried out in the present work.The variations in traverse speed while abrasive water jet cutting of silicon carbide and its effect on the surface roughness and kerf characteristics are studied. Silicon Carbide abrasive material is used as garnet consisting of 80 mesh. The surface roughness was calculated along with the depth of the cut made during the processing.The outcomes demonstrated that the traverse speed is more effective upon the surface roughness and is an important factor that damages the top kerf width and the kerf taper angle.Based on the hardness and thickness of the SiC plate, the taper angle is high, and for a feed rate of 10 mm/min, the surface roughness is low. Less thickness of the SiC plate could have a lower taper angle than with high thickness. The erosive force is provided by abrasive material along with the jet stream.Water abrasive fine jet could effectively machinate silicon carbide ceramic material with a better surface finish accurately. Suitable surface roughness with higher productivity can be attained with medium traverse speed.The effect of process parameters on kerf taper angle and top kerf width in the abrasive water jet machining of silicon carbide is explored, considering surface roughness as an important output parameter.

Malreduced syndesmotic injuries lead to poor outcomes. No consensus exists regarding preferred surgical treatment. This study aims to assess clinical and radiographic outcomes in patients undergoing distal tibiofibular arthrodesis or stabilization. Retrospective review identified patients undergoing distal tibiofibular arthrodesis or stabilization between 2003 and 2019. Surgical factors, revision surgeries, and American Orthopedic Foot and Ankle Score ankle-hindfoot scores were collected. Radiographs were independently evaluated by 4 surgeons. Seventy patients were included. Mean American Orthopedic Foot and Ankle Score scores (n = 33) improved from 48 ± 16 preoperatively to 85 ± 14 (p.001) at a median follow-up of 31.1 months. Mean Kellgren scores (n = 47) increased from 2.1 ± 1 to 2.5 ± 1 (p.001) and the mean medial clear space decreased from 3.2 mm ± 0.8 mm to 2.8 mm ± 0.8 mm (p.001) with no differences between the arthrodesis and stabilization groups. Zero patients progressed to arthroplasty or fusion. Patients demonstrated significant functional improvement after distal tibiofibular arthrodesis and stabilization. Progression of arthritis, while statistically significant, was not clinically significant.

Impulse control and/or gambling disorders can be triggered by dopamine agonist therapies used to treat Parkinson's disease, but the cognitive and neurobiological mechanisms underlying these adverse effects are unknown. Recent data show that adding win-paired sound and light cues to the rat gambling task (rGT) potentiates risky decision-making and impulsivity via the dopamine system, and that changing dopaminergic tone has a greater influence on behavior while subjects are learning task contingencies. Dopamine agonist therapy may therefore be potentiating risk-taking by amplifying the behavioral impact of gambling-related cues on novel behavior. Here, we show that ropinirole treatment in male rats transiently increased motor impulsivity but robustly and progressively increased choice of the high-risk/high-reward options when administered during acquisition of the cued but not uncued rGT. Early in training, ropinirole increased win-stay behavior after large unlikely wins on the cued rGT, indicative of enhanced model-free learning, which mediated the drug's effect on later risk preference.Ex vivocFos imaging showed that both chronic ropinirole and the addition of win-paired cues suppressed the activity of dopaminergic midbrain neurons. The ratio of midbrain:prefrontal cFos+neurons was lower in animals with suboptimal choice patterns and tended to predict risk preference across all rats. Network analyses further suggested that ropinirole induced decoupling of the dopaminergic cells of the VTA and nucleus accumbens but only when win-paired cues were present. Frontostriatal activity uninformed by the endogenous dopaminergic teaching signal therefore appeared to perpetuate risky choice, and ropinirole exaggerated this disconnect in synergy with reward-paired cues.SIGNIFICANCE STATEMENTD2/3receptor agonists, used to treat Parkinson's disease, can cause gambling disorder through an unknown mechanism. Ropinirole increased risky decision-making in rats, but only when wins were paired with casino-inspired sounds and lights. This was mediated by increased win-stay behavior after large unlikely wins early in learning, indicating enhanced model-free learning. cFos imaging showed that ropinirole suppressed activity of midbrain dopamine neurons, an effect that was mimicked by the addition of win-paired cues. The degree of risky choice rats exhibited was uniquely predicted by the ratio of midbrain dopamine:PFC activity. Depriving the PFC of the endogenous dopaminergic teaching signal may therefore drive risky decision-making on-task, and ropinirole acts synergistically with win-paired cues to amplify this.

Arguably the greatest responsibility of a coach is to help an athlete move better. From sports to strength and conditioning training, the athlete is constantly in motion and utilizing basic movement patterns to achieve an array of goals. With this in mind the ability of a coach to work with athletes of different autism profiles is necessary to provide a comprehensive curriculum. Of importance, the rise of autism diagnoses has dramatically increased with a 787% increase in diagnoses from 1998 to 2018. With this increase in autism diagnoses the need for coaching capacity to meet this influx is vital, with responsibility falling on coaching educators. Offering coaches continuing education to efficiently work with this population can help to promote inclusive sports and gym settings. Among these new curricula being developed, adaptive coaches have created a novel movement assessment that can be used with autistic athletes. The WES Scale movement assessment was originally created by autistic coach educator Julien Pineau. This curriculum serves to produce well-rounded coaches and gym environments where movement development can be shared with autistic athlete profiles through precise movement assessment.

Public Significance Statement This meta-analysis shows that the Structured Assessment of Protective Factors for violence risk (SAPROF), a risk assessment tool that focuses exclusively on protective factors, can significantly predict the absence of violent behavior in an institution and after discharge into the community. It highlights the importance of adding dynamic protective factors to structured risk assessment to lower the risk of future violence.Although the inclusion of protective factors in risk assessment is believed to improve prediction, most risk assessment tools emphasize risk factors. In response, the Structured Assessment of Protective Factors for violence risk (SAPROF) has been developed, which focuses exclusively on protective factors and is used in conjunction with a structured risk assessment tool. It has received increasing attention from both researchers and forensic mental health practitioners, and additional versions have been developed for use with adolescents (SAPROF-YV) and sex offenders (SAPROF-SO). To assess their psychometric performance, we conducted a meta-analysis of validation studies. Our final sample included 39 articles with 5,434 subjects from 16 countries. Overall, the SAPROF(-YV/-SO) showed good interrater reliability and moderate-to-good predictive performance for the absence of recidivism and institutional misconduct. All three instruments exhibited incremental validity when used in conjunction with a risk-focused assessment tool. Our meta-analysis additionally showed that changes on the SAPROF are associated with decreased violent and general recidivism after controlling for baseline risk. We also uncovered several shortcomings in current research with the SAPROF(-YV/-SO). Studies did not report calibration indices and most studies were retrospective and limited to male offenders. The present findings provide support for the relevance of protective factors in risk assessment, but future research should focus on their hypothesized role in treatment and risk management.

Planar bismuth compounds exhibit tunable Lewis acidity and high catalytic activity for lactone polymerization.

Friction drilling is a unique way of creating holes in steel. In a solitary advance, a rotating conical tool is utilized to enter by penetrating as an opening on the surface of the sheet and making a bushing without making a chip. During this process, the heat produced by the frictional power linking the device and the sheet metal workpiece is used to pierce and make a bushing out of work. The goal of this novel hole-making process is to improve the bushing length in the thin-walled sheet metals by forming a bush and then combining thin sheet metals. The inconceivable utilizations of warm grating penetrating in a few modern areas will introduce another period of interfacing processes for different work materials in automobiles.Researchers have undergone numerous experiments based on the machining parameters, including spindle speed, feed rates, Friction Contact Ratio (FACR), tool angle, tool diameter, sheet thickness, and the output of the friction drilling, includes the bushing length, surface roughness, tool wear, hardness, thrust force, torque and microstructural evaluation.The crucial concerns that should be addressed and researched by researchers in the near future, such as determining the optimal machining parameters of such process and analysing, bushing length, microstructural impacts on the many aspects and their performance, are highlighted.This research paper tends to examine the advancements in research on the friction drilling method and its applications, taking into account the benefits and limits of friction drilling.The present paper identifies the machining parameters and their contribution towards the output level of various materials like Stainless steel, Brass, aluminium, titanium, tempered steel and nickel-based compounds of different thickness.The machining parameters like spindle speeds, feed rate, tool angles, thrust force, Torque, surface roundness, bushing height, frictional heat and tool diameter are optimized in the friction drilling. The incorrect bushing is formed due to the high thrust force, and Low temperatures cause ductility and softening issues.

Following annealing at sufficiently high temperatures, well-controlled thin-film bilayers exhibit thermal changes in phase-composition, phase-volume and interfacial roughness that are reversible, irrespective of the starting layer compositions.

Fifteen percent of individuals who sustain a concussion develop persistent concussion symptoms (PCS). Recent literature has demonstrated atrophy of the frontal, parietal, and cerebellar regions following acute concussive injury. The frontoparietal-cerebellar network is essential for the performance of visuomotor transformation tasks requiring cognitive-motor integration (CMI), important for daily function.We investigated cortical and subcortical structural differences and how these differences are associated with CMI performance in those with PCS versus healthy controls.Twenty-six age-matched female participants (13 PCS, 13 healthy) completed four visuomotor tasks. Additionally, MR-images were analyzed for cortical thickness and volume, and cerebellar lobule volume.No statistically significant group differences were found in CMI performance. However, those with PCS demonstrated a significantly thicker and larger precuneus, and significantly smaller cerebellar lobules (VIIIa, VIIIb, X) compared to controls. When groups were combined, volumes of both the cerebellar lobules and cortical regions were associated with CMI task performance.The lack of behavioral differences combined with the structural differences may reflect a compensatory mechanism for those with PCS. In addition, this study highlights the effectiveness of CMI tasks in estimating the structural integrity of the frontoparietal-cerebellar network and is among the first to demonstrate structural correlates of PCS.

The aim of this study is to determine if donor gamete use is associated with patients' decisions regarding disposition of supernumerary embryos.Patients who intended to undergo an IVF cycle at a single academic center signed an embryo disposition consent form to indicate their disposition preferences for any supernumerary embryos. A retrospective chart review was performed to obtain the embryo disposition declarations and demographic information. The primary outcome was the distribution of embryo disposition choices between patients who used donor gametes compared to patients who did not use donor gametes. Fisher's exact test was used to compare groups. Logistic regression models were created to determine the association between donor gamete use and disposition decision after adjusting for patient age, body mass index, and nulliparity.Five hundred six patients were included. Ninety-one (18.0%) patients used donor gametes [46 (9.0%) donor oocytes, 52 (10.3%) donor sperm]. Patients using donor gametes differed from those not using donor gametes when making decisions concerning death of the patient (P 0.01), simultaneous death (P = 0.04), separation (P 0.01), discontinuation of ART (P = 0.01), and time-limited storage (P 0.01). Most patients, regardless of donor or autologous gamete use, awarded embryos to themselves or their partner if given the option. For patients who did not choose this option, excess embryos were generally awarded to research or discarded rather than donating to another couple. Patients using donor gametes were more likely to award embryos to research over discarding.Patients using donor gametes made different choices regarding supernumerary embryo disposition compared to patients not using donor gametes.

BackgroundThe COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear.ObjectiveTo evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial).DesignACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]).Setting94 hospitals in 10 countries (86% U.S. participants).ParticipantsAdults hospitalized with COVID-19.InterventionSOC.Measurements28-day mortality and recovery.ResultsAlthough outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages.LimitationUnmeasured confounding.ConclusionChanges in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas.Primary funding sourceNational Institute of Allergy and Infectious Diseases.

The effectiveness of a third mRNA COVID-19 vaccine dose (booster dose) against the Omicron (B.1.1.529) variant is uncertain, especially in older, high-risk populations.To determine mRNA booster vaccine effectiveness (VE) against SARS-CoV-2 infection, hospitalization, and death in the Omicron era by booster type, primary vaccine type, time since primary vaccination, age, and comorbidity burden.Retrospective matched cohort study designed to emulate a target trial of booster vaccination versus no booster, conducted from 1 December 2021 to 31 March 2022.U.S. Department of Veterans Affairs health care system.Persons who had received 2 mRNA COVID-19 vaccine doses at least 5 months earlier.Booster monovalent mRNA vaccination (Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273) versus no booster.Booster VE.Each group included 490 838 well-matched persons, who were predominantly male (88%), had a mean age of 63.0 years (SD, 14.0), and were followed for up to 121 days (mean, 79.8 days). Booster VE more than 10 days after a booster dose was 42.3% (95% CI, 40.6% to 43.9%) against SARS-CoV-2 infection, 53.3% (CI, 48.1% to 58.0%) against SARS-CoV-2-related hospitalization, and 79.1% (CI, 71.2% to 84.9%) against SARS-CoV-2-related death. Booster VE was similar for different booster types (BNT162b2 or mRNA-1273), age groups, and primary vaccination regimens but was significantly higher with longer time since primary vaccination and higher comorbidity burden.Predominantly male population.Booster mRNA vaccination was highly effective in preventing death and moderately effective in preventing infection and hospitalization for up to 4 months after administration in the Omicron era. Increased uptake of booster vaccination, which is currently suboptimal, should be pursued to limit the morbidity and mortality of SARS-CoV-2 infection, especially in persons with high comorbidity burden.U.S. Department of Veterans Affairs.

Background: To fulfil the desire for evidence-based practice, there is impetus for occupational therapy (OT) to make research a priority and to encourage research engagement. Purpose: This study’s aim was to explore occupational therapists’ reasons for and for not getting involved in research and to determine potential barriers and enablers to engaging in research. Methods: Three focus groups were conducted with five participants each. Data were thematically analysed. Findings: Occupational therapists’ reasons for expressing interest in getting involved in research were having an interest in the condition and/or the symptoms being studied; promoting client support and service development; and ‘upskilling’. Three themes emerged from the thematic analysis: (1) motivation to get involved in research can be influenced; (2) ‘firefighting’: barriers and organisational culture; and (3) The nature of research needs consideration from an occupational therapist perspective. Implications: Findings suggest that though occupational therapists are able to get involved in research, it remains that there are difficulties in doing so (e.g., organisational culture); and such difficulties may outweigh both reasons and enablers to such involvement. Reasons for expressing interest, enablers, barriers and the relationships among them warrant further investigation and consideration with respect to involving occupational therapists in research.

Cyanobacterial N

Most bee species are ground-nesters, yet knowledge on the nesting behaviour of this diverse group remains sparse. Evidence on the effectiveness of ground-nesting bee species as crop pollinators is growing, but there is limited information on their nesting habits and preferences and how to manage habitats to enhance populations on farms. In this study, artificially prepared plots of bare soil were constructed with the aim to attract ground-nesting bees to nest in a commercial orchard in Kent, UK. Nine soil parameters were measured to determine their preferred soil properties: hydraulic conductivity, soil compaction, soil moisture, soil temperature, soil stoniness, soil organic matter, soil root biomass, soil texture and vegetation cover. Eighteen non-parasitic ground-nesting bee species (7 Andrena, 9 Lasioglossum, 1 Halictus and 1 Colletes spp.) were recorded in the study plots. Soil stoniness and soil temperature at 10cm depth were positively correlated, and vegetation cover and hydraulic conductivity were negatively correlated with the number of ground-nesting bees on the plots. We show that artificially created habitats can be exploited for nesting by several ground-nesting bee species. This study’s findings can inform management practices to enhance ground-nesting bee populations in agricultural and urban areas.

The current review theorizes that self-regulatory principles can be applied to the commute experience to better understand how spatial navigation and role transition processes interface with each other. Using a multiple goal framework, spatial navigation and role transitions are conceptualized as simultaneous goals, each with their own set of effort allocation processes. Furthermore, the review describes how dynamic and stable features of the commute and of the different roles individuals enact come together to impact spatial navigation and role transition effectiveness, along with well-being and effectiveness in individuals’ “home” and “workplace” roles. The proposed framework offers novel predictions about how and why these two activities impact each other in different ways, providing testable propositions that will help researchers begin to better understand the commute as a time for multiple goal regulation. The review concludes with suggestions for future research aimed at investigating these processes.

The use of the robot in general surgery has exploded in the last decade. The Veterans Health Administration presents a unique opportunity to study differences between surgical approaches due to the ability to control for health system and insurance variability. This study compares clinical outcomes between robot-assisted and laparoscopic or open techniques for three general surgery procedures.A retrospective observational study using the Veterans Affair Surgical Quality Improvement Program database. Operative time, length of stay, and complications were compared for cholecystectomy (robot-assisted versus laparoscopic), ventral, and inguinal hernia repair (robot-assisted versus laparoscopic or open) from 2015 to 2019.More than 80,000 cases were analyzed (21,652 cholecystectomy, 9214 ventral hernia repairs, and 51,324 inguinal hernia repairs). Median operative time was longer for all robot-assisted approaches as compared to laparoscopic or open techniques with the largest difference seen between open and robot-assisted primary ventral hernia repair (unadjusted difference of 93 min, P 0.001). Median length of stay was between 1 and 4 d and significantly for robot-assisted ventral hernia repairs (versus open, P 0.01; versus lap for recurrent hernia, P 0.05). Specific postoperative outcomes of interest were overall low with few differences between techniques.While the robotic platform was associated with longer operative time, these findings must be interpreted in the context of a learning curve and indications for use (i.e., use of the robot for technically challenging cases). Our findings suggest that at the Veterans Health Administration, the robot is as safe a platform for common general surgery procedures as traditional approaches. Future studies should focus on patient-centered outcomes including pain and cosmesis.

Implementation of robot-assisted procedures is growing. Utilization within the country's largest healthcare network, the Veterans Health Administration, is unclear.A retrospective cohort study using data from the Department of Veterans Affairs Corporate Data Warehouse from January 2015 through December 2019. Trends in robot utilization for cholecystectomy, ventral hernia repair, and inguinal hernia repair were characterized nationally and regionally by Veterans Integrated Services Network. Patients, who underwent laparoscopic repairs for these procedures and open hernia repairs, were included to determine proportion performed robotically.We identified 119,191 patients, of which 5689 (4.77%) received a robotic operation. The proportion of operations performed robotically increased from 1.49% to 10.55% (7.08-fold change; slope, 2.14% per year; 95% confidence interval [0.79%, 3.49%]). Ventral hernia repair had the largest growth in robotic procedures (1.51% to 13.94%; 9.23-fold change; slope, 2.86% per year; 95% confidence interval [1.04%, 4.68%]). Regions with the largest increase in robotic utilization were primarily along the Northeast, Midwest, and West Coast.Robot utilization in general surgery is increasing at different rates across the United States in the Veterans Health Administration. Future studies should investigate the regional disparities and drivers of this approach.

We present a 54-year-old Caucasian woman, who presented with acute symptomatic type B aortic dissection with deteriorating renal function. She was a known smoker with a 2-year history of dysphagia. CT angiography documented the artery of lusoria arising from the mid-thoracic aorta, aneurysmal dilation of her descending aorta, and kinetic and static flaps around her visceral ostia. The patient was managed by staged hybrid single lumen reconstruction and bilateral subclavian to carotid transpositions. During follow-up, there was no aortic rupture or retrograde type A dissection. There were no renal, visceral, cardiac, pulmonary or spinal complications. The patient went off her antihypertensive medication with a normal estimated glomerular filtration rate and accelerated aortic modulation.

Introduced non-native species can threaten native species through interspecific hybridisation and genetic introgression. We assessed the prevalence of hybridisation and introgression between introduced European brown hare, Lepus europaeus, and the endemic Irish hare, L. timidus hibernicus. Roadkill hares (n = 56) were sequenced for a 379bp section of the mitochondrial DNA D-loop and a 474bp segment of the nuclear transferrin (Tf) gene. A species-specific indel in the transferrin gene was present in L.t. hibernicus and absent in L. europaeus. Excluding three hares from which molecular data could not be recovered, 28 hares (53%) were native L.t. hibernicus, 7 (13%) were non-native L. europaeus and 18 (34%) were hybrids; of which 5 (28%) were first generation (F1) involving bidirectional crosses with mismatched nuclear and mtDNA (3 ♂ europaeus x ♀ hibernicus and 2 ♂ hibernicus x ♀ europaeus). Mixed nuclear transferrin sequences suggested 13 (72%) of hybrids were at least 2nd generation (F2) with 9 (69%) possessing L.t. hibernicus and 4 (31%) L. europaeus mtDNA (the latter indicative of hybrid backcrossing with the non-native). The prevalence of hybridisation at similar mountain-brown hare contact zones throughout Europe is notably lower (4–16%) and typically unidirectional (♂ europaeus x ♀ timidus). A high prevalence of bidirectional hybridisation and introgression (in association with projected climate change) may favour the introduced species over the native. Genetic surveillance and population monitoring are needed to further explore the potential conservation implications of European brown hare in Ireland.

The use of sodium-glucose co-transporter 2 (SGLT2) inhibitors has evolved over the past decade, from their initial indication as an adjunctive oral medication to treat hyperglycaemia in diabetics, to becoming part of guideline-directed therapy for the treatment of chronic kidney disease, heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. This transition was driven by data from large cardiovascular and renal outcome trials, which repeatedly demonstrated that SGLT2 inhibitors improve important endpoints in chronic kidney disease and heart failure. In chronic kidney disease, SGLT2 inhibition reduces decline in glomerular filtration rate, risk of progression to end-stage renal disease and death from renal causes. With respect to their use in heart failure, SGLT2 inhibitors decrease risk of major adverse cardiac events, hospitalisation for heart failure and death from cardiovascular causes. While the benefits of these medications have been demonstrated, the mechanisms by which they are conferred are less clear. Extensive investigation into potential mechanisms of benefits has been pursued internationally and current hypotheses include increased natriuresis and osmotic diuresis, improved glomerular haemodynamic, reduced body mass and reduced adipose tissue mediated inflammation, in addition to others. This review discusses the physiology underlying the therapeutic benefit of SGLT2 inhibition in chronic kidney disease and heart failure.

Constitutional transformation is one of the biggest political ideas Aotearoa must grapple with. Featuring educators and members of Matike Mai Aoteaora, the Independent Working Group on Constitutional Transformation, Professor Margaret Mutu and Dr Veronica Tawhai engaged with questions of collective action and change in the opening keynote panel of the conference. In a discussion facililtated by Tayla Cook and Safari Hynes, Whaea Margaret and Veronica not only talk about the importance of conscientisation and deep learning, but offer opportunities for it as well. The intergenerational kōrero between panelists provides critical insights into founding documents like He Whakaputanga o te Rangatiratanga o Nu Tireni and Te Tiriti o Waitangi, while also asking what it means to honour them. In doing so, they provide space for dreaming, imagining, and inspiring change. The following transcription both captures the critical conversations had and encourages ongoing collective action. As Veronica reminds us, ‘it is not just about raising self-awareness through education, it is also the action that accompanies or follows from this’.

With the ever-growing demand for conventional fuels, the improvement in the efficiency of the photovoltaic system is the need of the hour. Antireflection coatings enhance the availability of solar power by reducing the percentage of light reflected. A new coating has been developed to improve the solar cell's overall efficiency. This study focuses on enhancing the efficiency of the monocrystalline solar cell when a coating of ZnO-MoO3 is applied at a certain thickness. A layer of ZnO followed by MoO3 is deposited on a Silicon solar cell substrate using a Pulsed Laser Deposition process. Due to the transmissivity d between the two materials, they act as excellent antireflection coating. The layer thickness has been engineered to lie in the maximum absorption spectrum of monocrystalline silicon solar cells, which is between 400 and 800 nanometers. Based on the calculation of transmissivities for a given layer thickness of coating material, the coating has been done, and the efficiencies of the coated specimen were compared with the uncoated solar cell. The percentage improvement in the electrical efficiency of a single crystalline silicon solar cell with an anti-reflection coating at 1059 W/m2 is about 35.7%. Among the available antireflection coating materials, the combination that provides better efficiency when coated on top of a solar cell is hard to find. This anti-reflection coating could be a better solution to enhance the overall efficiency of the single crystalline silicon solar cell. Although ZnO and MoO3 coatings have been investigated separately for improvement in solar cell efficiency with varying levels of success, the hybrid coating of ZnO/MoO3 with a performance enhancement of 35.7% is a great leap.

Background: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. Methods: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. Findings: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. Interpretation: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. Funding: The UK National Institute for Health Research Health Technology Assessment Programme.

BACKGROUND: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. METHODS: We evaluated the utility of the Centers for Disease Control and Prevention’s COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. RESULTS: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. CONCLUSIONS: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

BackgroundInformation about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes in the setting of Omicron variant transmission and COVID-19 vaccination is limited.ObjectiveTo measure the effectiveness of nirmatrelvir-ritonavir and molnupiravir for outpatient treatment of COVID-19.DesignThree retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir.SettingVeterans Health Administration (VHA).ParticipantsNonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022.InterventionNirmatrelvir-ritonavir or molnupiravir pharmacotherapy.MeasurementsIncidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 days.ResultsEighty-seven percent of participants were male; the median age was 66 years, and 18% were unvaccinated. Compared with matched untreated control participants, those treated with nirmatrelvir-ritonavir (n = 9607) had lower 30-day risk for hospitalization (22.07 vs. 30.32 per 1000 participants; risk difference [RD], -8.25 [95% CI, -12.27 to -4.23] per 1000 participants) and death (1.25 vs. 5.47 per 1000 participants; RD, -4.22 [CI, -5.45 to -3.00] per 1000 participants). Among persons alive at day 31, reductions were seen in 31- to 180-day incidence of death (hazard ratio, 0.66 [CI, 0.49 to 0.89]) but not hospitalization (subhazard ratio, 0.90 [CI, 0.79 to 1.02]). Molnupiravir-treated participants (n = 3504) had lower 30-day and 31- to 180-day risks for death (3.14 vs. 13.56 per 1000 participants at 30 days; RD, -10.42 [CI, -13.49 to -7.35] per 1000 participants; hazard ratio at 31 to 180 days, 0.67 [CI, 0.48 to 0.95]) but not hospitalization. A difference in 30-day or 31- to 180-day risk for hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants.LimitationThe date of COVID-19 symptom onset for most veterans was unknown.ConclusionNirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death. Molnupiravir was associated with a benefit for 30-day mortality but not hospitalization. Further reductions in mortality from 31 to 180 days were observed with both antivirals.Primary funding sourceU.S. Department of Veterans Affairs.

There is an urgent need to develop new therapies for colorectal cancer that has metastasized to the liver and, more fundamentally, to develop improved preclinical platforms of colorectal cancer liver metastases (CRCLM) to screen therapies for efficacy. To this end, we developed a multi-well perfusable bioreactor capable of monitoring CRCLM patient-derived organoid response to a chemotherapeutic gradient. CRCLM patient-derived organoids were cultured in the multi-well bioreactor for 7 days and the subsequently established gradient in 5-fluorouracil (5-FU) concentration resulted in a lower IC50 in the region near the perfusion channel versus the region far from the channel. We compared behaviour of organoids in this platform to two commonly used PDO culture models: organoids in media and organoids in a static (no perfusion) hydrogel. The bioreactor IC50 values were significantly higher than IC50 values for organoids cultured in media whereas only the IC50 for organoids far from the channel were significantly different than organoids cultured in the static hydrogel condition. Using finite element simulations, we showed that the total dose delivered, calculated using area under the curve (AUC) was similar between platforms, however normalized viability was lower for the organoid in media condition than in the static gel and bioreactor. Our results highlight the utility of our multi-well bioreactor for studying organoid response to chemical gradients and demonstrate that comparing drug response across these different platforms is nontrivial.

Background Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population especially when the population affected is undefined. Methods We evaluated the utility of CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), COVID-19 Case Surveillance System (CCSS), and 2020 U.S. Census data to determine demographic representation in the four stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at U.S. ACTT sites, with the respective 95% confidence intervals, to the reference data in forest plots. Results U.S. ACTT sites enrolled 3,509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic or Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with U.S. Census and CCSS. The proportion of participants ages 65 years was either similar or lower than COVID-NET and higher than CCSS and U.S. Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions While surveillance data of hospitalized cases may not be available early in an outbreak, it is a better comparator than U.S. Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

People with severe mental illness (SMI) have a shorter life expectancy than the rest of the population. Multimorbidity and poorer physical health contribute to this health inequality. Cardiometabolic multimorbidity confers a significant mortality risk in this population. Multimorbidity is not restricted to older people and people with SMI present with multimorbidity earlier in life. Despite this, most screening, prevention and treatment strategies target older people. People under 40 years with SMI are underserved by current guidelines for cardiovascular risk assessment and reduction. Research is needed to develop and implement interventions to reduce cardiometabolic risk in this population.