Radical Reactions with Chiral Acylammonium Salts: Synthesis of Functionalized δ-Lactams through Giese-Initiated Organocascades.

Enantioselective Giese reactions employing chiral α,ß-unsaturated acylammonium salts and subsequent diastereoselective trapping followed by lactamization deliver optically active δ-lactams. Alkyl iodides bearing tosylamides undergo radical initiation using triethylborane at low temperatures to provide carbon-centered radicals to initiate the described organocascade. Subsequent diastereoselective inter- or intramolecular trapping of the incipient α-radical leads to highly functionalized, enantioenriched mono- and bicyclic δ-lactams (up to 99:1 er, > 19:1 dr) bearing up to three stereogenic centers. Interestingly, benzotetramisole imparts diastereoselectivity that contradicts steric considerations alone. Results from DFT calculations rationalized the observed enantio- and diastereoselectivities, revealed an electrostatic interaction between the sulfone oxygens and the ammonium cation in the initial α-radical intermediate, and aided in application of this methodology to bicyclic δ-lactams through intramolecular trapping of the α-radical intermediate.

The power of weak, transient interactions across biology: A paradigm of emergent behavior.

A growing list of diverse biological systems and their equally diverse functionalities provides realizations of a paradigm of emergent behavior. In each of these biological systems, pervasive ensembles of weak, short-lived, spatially local interactions act autonomously to convey functionalities at larger spatial and temporal scales. In this article, a range of diverse systems and functionalities are presented in a cursory manner with literature citations for further details. Then two systems and their properties are discussed in more detail: yeast chromosome biology and human respiratory mucus.

Effect of an antimicrobial stewardship intervention on the prescribing behaviours of companion animal veterinarians: A pre-post study.

BACKGROUND: Antimicrobial stewardship is a cornerstone of efforts to combat antimicrobial resistance. We evaluated the impact of a formal discussion of antimicrobial stewardship for dogs and cats on systemic antimicrobial prescribing behaviours among companion animal veterinarians. METHODS: Electronic health records including information about the prescription of antimicrobials were collected from a multisite UK veterinary practice between 2017 and 2020. We undertook interrupted time series analysis using a quasi-Poisson model to compare the pre- and postintervention change in level and slope for multiple outcomes. RESULTS: After the intervention, there were sustained reductions in the prescription rate of cefovecin to cats and metronidazole to dogs and increases in amoxicillin-clavulanic acid prescribing. There was no evidence for an immediate change in overall prescribing rates in either species, although rates increased over the 12 months after the intervention. There was a transient increase in the proportion of dogs who had their weight recorded at the time of prescription. Results suggest decreases in the prescription of off-licence antimicrobials in both species and the likelihood of underdosing in dogs. CONCLUSIONS: Discussion of antimicrobial stewardship is more likely to influence the antimicrobial choice than whether to prescribe or not. Interventions may benefit by focusing on appropriate antimicrobial selection rather than overall prescription frequency.

Interventions for treating recurrent stress urinary incontinence after failed minimally invasive synthetic midurethral tape surgery in women.

BACKGROUND: Surgery is a common treatment modality for stress urinary incontinence (SUI), usually offered to women for whom conservative treatments have failed. Midurethral tapes have superseded colposuspension because cure rates are comparable and recovery time is reduced. However, some women will not be cured after midurethral tape surgery. Currently, there is no consensus on how to manage the condition in these women.This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To assess the effects of interventions for treating recurrent stress urinary incontinence after failed minimally invasive synthetic midurethral tape surgery in women; and to summarise the principal findings of economic evaluations of these interventions. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 9 November 2018). We also searched the reference lists of relevant articles. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials in women who had recurrent stress urinary incontinence after previous minimally invasive midurethral tape surgery. We included conservative, pharmacological and surgical treatments. DATA COLLECTION AND ANALYSIS: Two review authors checked the abstracts of identified studies to confirm their eligibility. We obtained full-text reports of relevant studies and contacted study authors directly for additional information where necessary. We extracted outcome data onto a standard proforma and processed them according to the guidance in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We included one study in this review. This study was later reported in an originally unplanned secondary analysis of 46 women who underwent transobturator tape for recurrent SUI after one or more previous failed operations. We were unable to use the data, as they were not presented according to the nature of the first operation.We excluded 12 studies, five because they were not randomised controlled trials (RCTs) and four because previous incontinence surgery was not performed using midurethral tape. We considered a further three to be ineligible because neither the trial report nor personal communication with the trialists could confirm whether any of the participants had previously undergone surgery with tape.We had also planned to develop a brief economic commentary summarising the principal findings of relevant economic evaluations but supplementary systematic searches did not identify any such studies. AUTHORS' CONCLUSIONS: There were insufficient data to assess the effects of any of the different management strategies for recurrent or persistent stress incontinence after failed midurethral tape surgery. No published papers have reported exclusively on women whose first operation was a midurethral tape. Evidence from further RCTs and economic evaluations is required to address uncertainties about the effects and costs of these treatments.

Changing medical student attitudes to patient safety: a multicentre study.

BACKGROUND: Although patient safety is becoming widely taught in medical schools, its effect has been less rigorously evaluated. We describe a multicentre study to evaluate student changes in patient safety attitudes using a standardised instrument, the Attitudes to Patient Safety Questionnaire3 (APSQ3). METHODS: A patient safety training package designed for medical students was delivered in the first year and second year in four Australian medical schools. It comprises eight face-to-face modules, each of two hours. Seminars start with an interactive introduction using questions, video and role play, followed by small group break-outs to discuss a relevant case study. Groups are led by medical school tutors with no prior training in patient safety. Students and tutors then reassemble to give feedback and reinforce key concepts. Knowledge and attitudes to patient safety were measured using the APSQ3, delivered prior to safety teaching, at the end of the first and second years and 12 months after teaching ceased. RESULTS: A significant improvement in attitude over time was demonstrated for four of nine key items measured by the APSQ3: value of patient safety teaching; danger of long working hours, value of team work and the contribution patients can make in reducing error. Informal feedback from students was very positive. CONCLUSION: We showed persistent, positive learning from a patient safety education intervention 12 months after teaching finished. Building on the introduction of patient safety teaching into medical schools, pathways for motivated students such as appropriate electives, option terms and team-based research projects would be of value.

Observational Study of Neural Respiratory Drive During Sleep at High Altitude.

Steier, Joerg, Nic Cade, Ben Walker, John Moxham, and Caroline Jolley. Observational study of neural respiratory drive during sleep at high altitude. High Alt Med Biol. 18:242-248, 2017. AIMS: Ventilation at altitude changes due to altered levels of pO2, pCO2 and the effect on blood pH. Nocturnal ventilation is particularly exposed to these changes. We hypothesized that an increasing neural respiratory drive (NRD) is associated with the severity of sleep-disordered breathing at altitude. METHODS: Mountaineers were studied at sea level (London, United Kingdom), and at altitude at the Aconcagua (Andes, Argentina). NRD was measured as electromyogram of the diaphragm (EMGdi) overnight by a transesophageal multi-electrode catheter; results were reported for sea level, 3,380 m, 4,370 m, and 5,570 m. RESULTS: Four healthy subjects (3 men, age 31(3)years, body mass index 23.6(0.9)kg/m2, neck circumference 37.0(2.7)cm, forced expiratory volume in 1 second 111.8(5.1)%predicted, and forced vital capacity 115.5(6.3)%predicted) were studied. No subject had significant sleep abnormalities at sea level. Time to ascent to 3,380 m was 1 day, to 4,370 m was 5 days, and the total nights at altitude were 21 days. The oxygen desaturation index (4% oxygen desaturation index [ODI] 0.8(0.4), 22.0 (7.2), 61.4 (26.9), 144.9/hour, respectively) and the EMGdi (5.2 (1.9), 12.8 (5.1), 14.1 (3.4), 18.5%, respectively) increased with the development of periodic breathing at altitude, whereas the average SpO2 declined (97.5 (1.3), 84.8 (0.5), 81.0 (4.1), 68.5%, respectively). The average EMGdi correlated well with the 4%ODI (r = 0.968, p = 0.032). CONCLUSION: NRD sleep increases at altitude in relation to the severity of periodic breathing.

Which adverse events should be reported in an emergency department? A Delphi study.

OBJECTIVE: The aim of this study was to determine if emergency medicine specific triggers for completing an incident form could be agreed and if a common definition for contributory factors could be achieved. Such definitions could be used to improve safety within the emergency department (ED) and share learning across the specialty. PARTICIPANTS AND METHODS: One hundred and fifteen ED safety leads in the UK and Ireland were invited to participate in a Delphi study. This process took 1 year to complete. In the first round, participants listed 20 events that should be reported as an adverse event and 20 contributory factors that could contribute to risk or harm. An 80% concordance level was sought for both aspects. RESULTS: Eighty-four per cent of safety leads participated in the first round, although this decreased over subsequent rounds to 43%. Four hundred and eighty-five triggers were initially suggested; eventually, 27 triggers that should always or usually be reported achieved 80% concordance. Sixty-eight contributory factors were initially identified with eventual agreement being reached on 27 remediable contributory factors. CONCLUSION: The process demonstrated agreement amongst emergency physicians in the UK and Ireland on the type of events that should be formally reported. The lists emerging from this process should not be viewed as exhaustive; rather they should be used to encourage the reporting of incidents and designing safer systems and processes within the ED.

Have we got the selection process right? The validity of selection tools for predicting academic performance in the first year of undergraduate medicine.

This article was migrated. The article was marked as recommended. Content: There remains much debate over the 'best' method for selecting students in to medicine. This study aimed to assess the predictive validity of four different selection tools with academic performance outcomes in first-year undergraduate medical students. Methods: Regression analyses were conducted between admission scores on previous academic performance - the Australian Tertiary Admission Rank (ATAR), the Undergraduate Medicine and Health Sciences Admission Test (UMAT), Multiple-Mini Interview (MMI) and the Personal Qualities Assessment (PQA) with student performance in first-year assessments of Multiple Choice Questions, Short Answer Questions, Objective Structured Clinical Examinations (OSCE) and Problem-Based Learning (PBL) Tutor ratings in four cohorts of students (N = 604, 90%). Results: All four selection tools were found to have significant predictive associations with one or more measures of student performance in Year One of undergraduate medicine. UMAT, ATAR and MMI scores consistently predicted first year performance on a number of outcomes. ATAR was the only selection tool to predict the likelihood of making satisfactory progress overall. Conclusions: All four selection tools play a contributing role in predicting academic performance in first year medical students. Further research is required to assess the validity of selection tools in predicting performance in the later years of medicine.

The Role of Parental Misperception of Child's Body Weight in Childhood Obesity.

UNLABELLED: To investigate the accuracy of parental perceptions of their child's weight status and also the relationship between parental perceptions and the prevalence of childhood obesity in Mississippi. DESIGN AND METHODS: Data from multi-year surveys (2009-2012) with random samples of public school parents (N=14,808). Descriptive statistics and multiple logistic regression were conducted with quantitative data to examine the relationship between parental perception and childhood obesity. RESULTS: More than 2 out of 5 parents misperceived the weight status of their child (k-12). The greatest difference occurred with kindergartners, 83.9% of parents categorized them as "healthy", when only 28.3% actually were. Parents who misperceived their child's weight were almost 12 times more likely of having an obese child. CONCLUSIONS: Only half of the children in this study had a healthy weight (54.5%). Health care providers, nutritionists, social workers, teachers, and school health councils could play an important role in educating parents and children on how to recognize an unhealthy weight. PRACTICE IMPLICATIONS: The strongest predictor of childhood obesity was parental misperception of their child's weight status.

Are three contact efforts really reflective of a repeated high-intensity effort bout?

The use of 3 or more efforts (running and contact), separated by short recovery periods, is widely used to define a "repeated high-intensity effort" (RHIE) bout in rugby league. It has been suggested that due to fatigue, players become less effective after RHIE bouts; however, there is little evidence to support this. This study determined whether physical performance is reduced after performing 1, 2, or 3 efforts with minimal recovery. Twelve semiprofessional rugby league players (age: 24.5 ± 2.9 years) competed in 3 "off-side" small-sided games (2 × 10-minute halves) with a contact bout performed every 2 minutes. The rules of each game were identical except for the number of contact efforts performed in each bout. Players performed 1, 2, or 3 × 5-second wrestling bouts in the single-, double- and triple-contact game, respectively. Movement demands of each game were monitored using global positioning system units. From the first to the second half, there were trivial reductions in relative distance during the single-contact game (ES = -0.13 ± 0.12), small reductions during the double-contact game (ES = -0.47 ± 0.24), and moderate reductions during the triple-contact game (ES = -0.74 ± 0.27). These data show that running intensity is progressively reduced as the number of contact efforts per bout is increased. Targeting defensive players and forcing them to perform 2 or more consecutive contact efforts is likely to lead to greater reductions in running intensity. Conditioning performing multiple contact efforts while maintaining running intensity should therefore be incorporated into training for contact team sports.

Influence of prior knowledge of exercise duration on pacing strategies during game-based activities.

PURPOSE: To investigate the influence of prior knowledge of exercise duration on the pacing strategies employed during game-based activities. METHODS: Twelve semiprofessional team-sport athletes (mean ± SD age 22.8 ± 2.1 y) participated in this study. Players performed 3 small-sided games in random order. In one condition (Control), players were informed that they would play the small-sided game for 12 min and then completed the 12-min game. In a 2nd condition (Deception), players were told that they would play the small-sided game for 6 minutes, but after completing the 6-min game, they were asked to complete another 6 min. In a 3rd condition (Unknown), players were not told how long they would be required to play the small-sided game, but the activity was terminated after 12 min. Movement was recorded using a GPS unit sampling at 10 Hz. Post hoc inspection of video footage was undertaken to count the number of possessions and the number and quality of disposals. RESULTS: Higher initial intensities were observed in the Deception (130.6 ± 3.3 m/min) and Unknown (129.3 ± 2.4 m/min) conditions than the Control condition (123.3 ± 3.4 m/min). Greater amounts of high-speed running occurred during the initial phases of the Deception condition, and more low-speed activity occurred during the Unknown condition. A moderately greater number of total skill involvements occurred in the Unknown condition than the Control condition. CONCLUSIONS: These findings suggest that during game-based activities, players alter their pacing strategy based on the anticipated endpoint of the exercise bout.

The database for reaching experiments and models.

Reaching is one of the central experimental paradigms in the field of motor control, and many computational models of reaching have been published. While most of these models try to explain subject data (such as movement kinematics, reaching performance, forces, etc.) from only a single experiment, distinct experiments often share experimental conditions and record similar kinematics. This suggests that reaching models could be applied to (and falsified by) multiple experiments. However, using multiple datasets is difficult because experimental data formats vary widely. Standardizing data formats promises to enable scientists to test model predictions against many experiments and to compare experimental results across labs. Here we report on the development of a new resource available to scientists: a database of reaching called the Database for Reaching Experiments And Models (DREAM). DREAM collects both experimental datasets and models and facilitates their comparison by standardizing formats. The DREAM project promises to be useful for experimentalists who want to understand how their data relates to models, for modelers who want to test their theories, and for educators who want to help students better understand reaching experiments, models, and data analysis.