Causes and consequences of spatial variation in sex ratios in a declining bird species

1. Male-biased sex ratios occur in many bird species, particularly in those with small or declining populations, but the causes of these skews and their consequences for local population demography are rarely known. Within-species variation in sex ratios can help to identify the demographic and behavioural processes associated with such biases. 2. Small populations may be more likely to have skewed sex ratios if sex differences in survival, recruitment or dispersal vary with local abundance. Analyses of species with highly variable local abundances can help to identify these mechanisms and the implications for spatial variation in demography. Many migratory bird species are currently undergoing rapid and severe declines in abundance in parts of their breeding ranges, and thus have sufficient spatial variation in abundance to explore the extent of sex ratio biases, their causes and implications. 3. Using national-scale bird ringing data for one such species (willow warbler, Phylloscopus trochilus), we show that sex ratios vary greatly across Britain, and that male-biased sites are more frequent in areas of low abundance, which are now widespread across much of south and east England. These sex ratio biases are sufficient to impact local productivity, as the relative number of juveniles caught at survey sites declines significantly with increasing sex ratio skew. 4. Sex differences in survival could influence this sex ratio variation, but we find little evidence for sex differences in survival increasing with sex ratio skew. In addition, sex ratios have become male-biased over the last two decades but there are no such trends in adult survival rates for males or females. This suggests that lower female recruitment into low abundance sites is contributing to these skews. 5. These findings suggest that male-biased sex ratios in small and declining populations can arise through local-scale sex-differences in survival and dispersal, with females recruiting disproportionately into larger populations. Given the high level of spatial variation in population declines and abundance of many migratory bird species across Europe at present, male-biased small populations may be increasingly common. As singing males are the primary records used in surveys of these species, and as unpaired males often sing throughout the breeding season, local sex ratio biases could also be masking the true extent of these population declines

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research

Common but poorly known: information derived from 32 years of Coot (Fulica atra) ringing in the Camargue, Southern France

This is the postprint version of the article.Rallidae are common and widespread, yet relatively poorly studied. We analysed the ringing data from more than 8,000 Common Coot Fulica atra accumulated between 1950 and 1982 in Camargue, Southern France, in terms of dynamics of their biometrics throughout the year, migratory pathways and annual survival rate. Mean monthly body mass and wing length indicate monthly differences, with birds captured in autumn and winter being heavier and larger than those captured in spring and summer. More than 950 ring recoveries were obtained, whose distribution across Europe and through time indicates a mixing of sedentary and migratory birds. The capture-recapture analysis indicated lower annual survival rate during the year following ringing, and greater survival in adults and in males. Mean survival rate over sex and age classes more than one year after ringing was 55%. This is somewhat lower than in other studies, and may be related to the importance of Coot hunting in Camargue, especially during the years of this study