Synthesis of Diarylheptanoid Scaffolds Inspired by Calyxins I and J

γ,δ-Unsaturated alcohols are prepared efficiently in two steps from <i>o</i>-hydroxycinnamaldehyde. The TMSOTf-mediated reaction of the γ,δ-unsaturated alcohols with aldehydes creates two oxygen heterocycles and three new stereocenters in a single pot. The approach is versatile, and by varying the boronic acid, Grignard reagent, and aldehyde, different substituents may be introduced, while use of a chiral base in the conjugate addition gives enantioenriched products

Targeting Exclusion, Disaffection and Truancy in Secondary Schools: An Evaluation of An Alternative Curriculum for Older Pupils

This article begins with a cursory discussion on rates and causes of school exclusion as well as curriculum initiatives intended to minimise exclusion risks and improve school attendance. Focus is then placed upon an evaluation of an innovative programme designed to provide support to those at risk of exclusion from secondary schools. Consideration is given to recent government thinking and initiatives intended to help schools to reduce rates of disaffection, truancy and exclusion. The implications of these initiatives for those who have – and others at risk of developing – an identified special educational need are also considered

Contribution of chromosomal polymorphisms to the G-matrix of Mimulus guttatus

This is the peer reviewed version of the following article: Scoville, A., Lee, Y. W., Willis, J. H., & Kelly, J. K. (2009). Contribution of chromosomal polymorphisms to the G-matrix of Mimulus guttatus. The New Phytologist, 183(3), 803–815. http://doi.org/10.1111/j.1469-8137.2009.02947.x, which has been published in final form at http://doi.org/10.1111/j.1469-8137.2009.02947.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Evolution of genetic (co)variances (the G-matrix) fundamentally influences multitrait divergence. Here, we isolated the contribution of two chromosomal quantitative trait loci (QTLs), a meiotic drive locus and a polymorphic inversion, to the overall G-matrix for a suite of floral, phenological and male fitness traits in a population of Mimulus guttatus. This allowed us to predict the evolution of trait means and genetic (co)variances as a function of allele frequencies, and to evaluate theories about the maintenance of genetic variation in fitness. Individuals generated using a replicated F2 breeding design were grown under common conditions, genotyped and measured for trait values. Significant additive genetic variance existed for all traits, and most genetic covariances were significantly nonzero. Both QTLs contribute to the additive genetic (co)variances of multiple traits. Pleiotropy was not generally consistent, either between QTLs or with the genetic background. Shifts in allele frequencies at either QTL are predicted to result in substantial changes in the G-matrix. Both QTLs contribute substantially to the genetic variation in pollen viability. The Drive QTL, and perhaps also the inversion, demonstrates the contribution of balancing selection to the maintenance of genetic variation in fitness

(Re)theorising laddish masculinities in higher education

In the context of renewed debates and interest in this area, this paper reframes the theoretical agenda around laddish masculinities in UK higher education, and similar masculinities overseas. These can be contextualised within consumerist neoliberal rationalities, the neoconservative backlash against feminism and other social justice movements, and the postfeminist belief that women are winning the ‘battle of the sexes’. Contemporary discussions of ‘lad culture’ have rightly centred sexism and men¹s violence against women: however, we need a more intersectional analysis. In the UK a key intersecting category is social class, and there is evidence that while working class articulations of laddism proceed from being dominated within alienating education systems, middle class and elite versions are a reaction to feeling dominated due to a loss of gender, class and race privilege. These are important differences, and we need to know more about the conditions which shape and produce particular performances of laddism, in interaction with masculinities articulated by other social groups. It is perhaps unhelpful, therefore, to collapse these social positions and identities under the banner of ‘lad culture’, as has been done in the past

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

MASTREE+: Time-series of plant reproductive effort from six continents.

Significant gaps remain in understanding the response of plant reproduction to environmental change. This is partly because measuring reproduction in long-lived plants requires direct observation over many years and such datasets have rarely been made publicly available. Here we introduce MASTREE+, a data set that collates reproductive time-series data from across the globe and makes these data freely available to the community. MASTREE+ includes 73,828 georeferenced observations of annual reproduction (e.g. seed and fruit counts) in perennial plant populations worldwide. These observations consist of 5971 population-level time-series from 974 species in 66 countries. The mean and median time-series length is 12.4 and 10 years respectively, and the data set includes 1122 series that extend over at least two decades (≥20 years of observations). For a subset of well-studied species, MASTREE+ includes extensive replication of time-series across geographical and climatic gradients. Here we describe the open-access data set, available as a.csv file, and we introduce an associated web-based app for data exploration. MASTREE+ will provide the basis for improved understanding of the response of long-lived plant reproduction to environmental change. Additionally, MASTREE+ will enable investigation of the ecology and evolution of reproductive strategies in perennial plants, and the role of plant reproduction as a driver of ecosystem dynamics

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council