Total syntheses of 11-acetoxy-4-deoxyasbestinin D, 4-deoxyasbestinin C, asbestinin-10, -20, -21 and -23

Six members of the asbestinin family of marine diterpene natural products have been synthesized in an efficient and stereoselective manner from a single oxa‐bridged intermediate. Five of these natural products have not been synthesized previously and the structures of four of them have been confirmed as those proposed originally or following revisions to the original structures. The fifth natural product—asbestinin‐21—has been shown to be a diastereomer of the compound that had been proposed previously

Synthesis of 2-BMIDA 6,5-bicyclic heterocycles by Cu(I)/Pd(0)/Cu(II) cascade catalysis of 2-iodoaniline/phenols

A one-pot cascade reaction for the synthesis of 2-BMIDA 6,5-bicyclic heterocycles has been developed using Cu(I)/Pd(0)/Cu(II) catalysis. 2-Iodoanilines and phenols undergo a Cu(I)/Pd(0)-catalyzed Sonogashira reaction with ethynyl BMIDA followed by in situ Cu(II)-catalyzed 5-endo-dig cyclization to generate heterocyclic scaffolds with a BMIDA functional group in the 2-position. The method provides efficient access to borylated indoles, benzofurans, and aza-derivatives, which can be difficult to access through alternative methods

Is referral of postsurgical colorectal cancer survivors to cardiac rehabilitation feasible and acceptable? A pragmatic pilot randomised controlled trial with embedded qualitative study

Objectives: (1) Assess whether cardiac rehabilitation (CR) is a feasible and acceptable model of rehabilitation for postsurgical colorectal cancer (CRC) survivors, (2) evaluate trial procedures. This article reports the results of the first objective. Design and setting: A pragmatic pilot randomised controlled trial with embedded qualitative study was conducted in 3 UK hospitals with CR facilities. Descriptive statistics were used to summarise trial parameters indicative of intervention feasibility and acceptability. Interviews and focus groups were conducted and data analysed thematically. Participants: People with CRC were considered for inclusion in the trial if they were ≥18 years old, diagnosed with primary CRC and in the recovery period postsurgery (they could still be receiving adjuvant therapy). 31% (n=41) of all eligible CRC survivors consented to participate in the trial. 22 of these CRC survivors, and 8 people with cardiovascular disease (CVD), 5 CRC nurses and 6 CR clinicians participated in the qualitative study. Intervention: Referral of postsurgical CRC survivors to weekly CR exercise classes and information sessions. Classes included CRC survivors and people with CVD. CR nurses and physiotherapists were given training about cancer and exercise. Results: Barriers to CR were protracted recoveries from surgery, ongoing treatments and poor mobility. No adverse events were reported during the trial, suggesting that CR is safe. 62% of participants completed the intervention as per protocol and had high levels of attendance. 20 health professionals attended the cancer and exercise training course, rating it as excellent. Participants perceived that CR increased CRC survivors' confidence and motivation to exercise, and offered peer support. CR professionals were concerned about CR capacity to accommodate cancer survivors and their ability to provide psychosocial support to this group of patients. Conclusions: CR is feasible and acceptable for postsurgical CRC survivors. A large-scale effectiveness trial of the intervention should be conducted. </p

ScotCap - A large observational cohort study

ACKNOWLEDGEMENTS We would like to thank all patients and sites that participated in the ScotCap evaluation. Funding Information: This study was funded by the Scottish Government which had no role in the study design, data collection, analysis or interpretation of results, or writing of this report. We would like to thank all patients and sites that participated in the ScotCap evaluation. Publisher Copyright: © 2021 Association of Coloproctology of Great Britain and Ireland.Peer reviewedPublisher PD

Testing the impact of local alcohol licencing policies on reported crime rates in England.

BACKGROUND: Excessive alcohol use contributes to public nuisance, antisocial behaviour, and domestic, interpersonal and sexual violence. We test whether licencing policies aimed at restricting its spatial and/or temporal availability, including cumulative impact zones, are associated with reductions in alcohol-related crime. METHODS: Reported crimes at English lower tier local authority (LTLA) level were used to calculate the rates of reported crimes including alcohol-attributable rates of sexual offences and violence against a person, and public order offences. Financial fraud was included as a control crime not directly associated with alcohol abuse. Each area was classified as to its cumulative licensing policy intensity for 2009-2015 and categorised as 'passive', low, medium or high. Crime rates adjusted for area deprivation, outlet density, alcohol-related hospital admissions and population size at baseline were analysed using hierarchical (log-rate) growth modelling. RESULTS: 284 of 326 LTLAs could be linked and had complete data. From 2009 to 2013 alcohol-related violent and sexual crimes and public order offences rates declined faster in areas with more 'intense' policies (about 1.2, 0.10 and 1.7 per 1000 people compared with 0.6, 0.01 and 1.0 per 1000 people in 'passive' areas, respectively). Post-2013, the recorded rates increased again. No trends were observed for financial fraud. CONCLUSIONS: Local areas in England with more intense alcohol licensing policies had a stronger decline in rates of violent crimes, sexual crimes and public order offences in the period up to 2013 of the order of 4-6% greater compared with areas where these policies were not in place, but not thereafter

Ethnicity, voter alignment and political party affiliation - an African case: Zambia

Conventional wisdom holds that ethnicity provides the social cleavage for voting behav-iour and party affiliation in Africa. Because this is usually inferred from aggregate data of national election results, it might prove to be an ecological fallacy. The evidence based on individual data from an opinion survey in Zambia suggests that ethnicity matters for voter alignment and even more so for party affiliation, but it is certainly not the only factor. The analysis also points to a number of qualifications which are partly methodology-related. One is that the degree of ethnic voting can differ from one ethno-political group to the other depending on various degrees of ethnic mobilisation. Another is that if smaller eth-nic groups or subgroups do not identify with one particular party, it is difficult to find a significant statistical correlation between party affiliation and ethnicity - but that does not prove that they do not affiliate along ethnic lines.Wahlverhalten und Mitgliedschaft in politischen Parteien Afrikas ist nur wenig untersucht worden. Gewöhnlich wird argumentiert, dass Ethnizität als soziale Konfliktlinie das Wahlverhalten und die Parteienmitgliedschaft strukturiert. Da dieses Argument auf hoch aggregierten Wahldaten beruht, kann hier ein ökologischer Fehlschuss vorliegen. Die vorliegende Analyse beruht deshalb auf individuellen Umfragedaten aus Sambia. Das Ergebnis ist, dass Ethnizität tatsächlich eine Rolle für das Wahlverhalten und die Parteienmitgliedschaft spielt, aber keineswegs den einzigen Erklärungsfaktor darstellt. Die Analyse offenbart zudem eine Reihe von Einschränkungen und Qualifizierungen, die teilweise methodischer Natur sind. Eine ist, dass ethnisches Wahlverhalten und Parteienmitgliedschaft von einer ethnischen Gruppe zur anderen unterschiedlich ist, dass, wenn sich kleinere ethnische Gruppen oder Untergruppen mit keiner Partei identifizieren, es schwierig wird, statistisch signifikante Korrelationen zu finden - was indessen noch nicht beweist, dass Ethnizität keine Rolle spielt

Is referral of postsurgical colorectal cancer survivors to cardiac rehabilitation feasible and acceptable? A pragmatic pilot randomised controlled trial with embedded qualitative study

Objectives (1) Assess whether cardiac rehabilitation (CR) is a feasible and acceptable model of rehabilitation for postsurgical colorectal cancer (CRC) survivors, (2) evaluate trial procedures. This article reports the results of the first objective. Design and setting A pragmatic pilot randomised controlled trial with embedded qualitative study was conducted in 3 UK hospitals with CR facilities. Descriptive statistics were used to summarise trial parameters indicative of intervention feasibility and acceptability. Interviews and focus groups were conducted and data analysed thematically. Participants People with CRC were considered for inclusion in the trial if they were ≥18 years old, diagnosed with primary CRC and in the recovery period postsurgery (they could still be receiving adjuvant therapy). 31% (n=41) of all eligible CRC survivors consented to participate in the trial. 22 of these CRC survivors, and 8 people with cardiovascular disease (CVD), 5 CRC nurses and 6 CR clinicians participated in the qualitative study. Intervention Referral of postsurgical CRC survivors to weekly CR exercise classes and information sessions. Classes included CRC survivors and people with CVD. CR nurses and physiotherapists were given training about cancer and exercise. Results Barriers to CR were protracted recoveries from surgery, ongoing treatments and poor mobility. No adverse events were reported during the trial, suggesting that CR is safe. 62% of participants completed the intervention as per protocol and had high levels of attendance. 20 health professionals attended the cancer and exercise training course, rating it as excellent. Participants perceived that CR increased CRC survivors’ confidence and motivation to exercise, and offered peer support. CR professionals were concerned about CR capacity to accommodate cancer survivors and their ability to provide psychosocial support to this group of patients. Conclusions CR is feasible and acceptable for postsurgical CRC survivors. A large-scale effectiveness trial of the intervention should be conducted

The Distribution of Fitness Effects of Beneficial Mutations in Pseudomonas aeruginosa

Understanding how beneficial mutations affect fitness is crucial to our understanding of adaptation by natural selection. Here, using adaptation to the antibiotic rifampicin in the opportunistic pathogen Pseudomonas aeruginosa as a model system, we investigate the underlying distribution of fitness effects of beneficial mutations on which natural selection acts. Consistent with theory, the effects of beneficial mutations are exponentially distributed where the fitness of the wild type is moderate to high. However, when the fitness of the wild type is low, the data no longer follow an exponential distribution, because many beneficial mutations have large effects on fitness. There is no existing population genetic theory to explain this bias towards mutations of large effects, but it can be readily explained by the underlying biochemistry of rifampicin–RNA polymerase interactions. These results demonstrate the limitations of current population genetic theory for predicting adaptation to severe sources of stress, such as antibiotics, and they highlight the utility of integrating statistical and biophysical approaches to adaptation