Integrating physiological data with the conservation and management of fishes: A meta-analytical review using the threatened green sturgeon (Acipenser medirostris)

Reversing global declines in the abundance and diversity of fishes is dependent on science-based conservation solutions. A wealth of data exist on the ecophysiological constraints of many fishes, but much of this information is underutilized in recovery plans due to a lack of synthesis. Here, we used the imperiled green sturgeon (Acipenser medirostris) as an example of how a quantitative synthesis of physiological data can inform conservation plans, identify knowledge gaps and direct future research actions. We reviewed and extracted metadata from peer-reviewed papers on green sturgeon. A total of 105 publications were identified, spanning multiple disciplines, with the primary focus being conservation physiology (23.8%). A meta-analytical approach was chosen to summarize the mean effects of prominent stressors (elevated temperatures, salinity, low food availability and contaminants) on several physiological traits (growth, thermal tolerance, swimming performance and heat shock protein expression). All examined stressors significantly impaired green sturgeon growth, and additional stressor-specific costs were documented. These findings were then used to suggest several management actions, such as mitigating salt intrusion in nursery habitats and maintaining water temperatures within optimal ranges during peak spawning periods. Key data gaps were also identified; research efforts have been biased towards juvenile (38.1%) and adult (35.2%) life-history stages, and less data are available for early life-history stages (embryonic, 11.4%; yolk-sac larvae, 12.4%; and post yolk-sac larvae, 16.2%). Similarly, most data were collected from single-stressor studies (91.4%) and there is an urgent need to understand interactions among stressors as anthropogenic change is multi-variate and dynamic. Collectively, these findings provide an example of how meta-analytic reviews are a powerful tool to inform management actions, with the end goal of maximizing conservation gains from research efforts

Predictors of Medication Adherence in the Elderly: The Role of Mental Health

The aging population routinely has comorbid conditions requiring complicated medication regimens, yet nonadherence can preclude optimal outcomes. This study explored the association of adherence in the elderly with demographic, socioeconomic, and disease burden measures. Data were from the fifth visit (2011-2013) for 6,538 participants in the Atherosclerosis Risk in Communities Study, conducted in four communities. The Morisky–Green–Levine Scale measured self-reported adherence. Forty percent of respondents indicated some nonadherence, primarily due to poor memory. Logit regression showed, surprisingly, that persons with low reading ability were more likely to report being adherent. Better self-reported physical or mental health both predicted better adherence, but the magnitude of the association was greater for mental than for physical health. Compared with persons with normal or severely impaired cognition, mild cognitive impairment was associated with lower adherence. Attention to mental health measures in clinical settings could provide opportunities for improving medication adherence

Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy : diagnosis and long-term follow-up

Background Immune checkpoint inhibitors (ICIs) have produced significant survival benefit across many tumor types. However, immune-related adverse events are common including autoimmune responses against different endocrine organs. Here, a case of ICI-mediated hypoparathyroidism focusing on long-term follow-up and insights into its etiology is presented. Case and methods A 73-year-old man developed severe symptomatic hypocalcemia after the initiation of ipilimumab and nivolumab for the treatment of metastatic melanoma. Hypoparathyroidism was diagnosed with undetectable intact parathyroid hormone (PTH). Immunoprecipitation assays, ELISAs, and cell-based functional assays were used to test the patient for antibodies against the calcium-sensing receptor (CaSR). NACHT leucine-rich repeat protein 5 (NALP5) and cytokine antibodies were measured in radioligand binding assays and ELISAs, respectively. Results The patient’s symptoms improved with aggressive calcium and vitamin D supplementation. At 3 years and 3 months since the diagnosis of hypoparathyroidism, PTH was still inappropriately low at 7.6 pg/mL, and attempted discontinuation of calcium and calcitriol resulted in recurrent symptomatic hypocalcemia. Analysis for an autoimmune etiology of the patient’s hypoparathyroidism indicated that CaSR antibodies were negative before treatment and detected at multiple time points afterwards, and corresponded to the patient’s clinical course of hypoparathyroidism. CaSR antibodies purified from the patient’s serum activated the human CaSR. The patient was seronegative for NALP5 and cytokine antibodies, indicating that their hypoparathyroidism was not a manifestation of autoimmune polyendocrine syndrome type 1. Conclusion The etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid

Contribution of medications and risk factors to QTc interval lengthening in the atherosclerosis risk in communities (ARIC) study

Rationale, aims, and objectives: Prolongation of the corrected QT (QTc) interval is associated with increased morbidity and mortality. The association between QTc interval–prolonging medications (QTPMs) and risk factors with magnitude of QTc interval lengthening is unknown. We examined the contribution of risk factors alone and in combination with QTPMs to QTc interval lengthening. Method: The Atherosclerosis Risk in Communities study assessed 15 792 participants with a resting, standard 12-lead electrocardiogram and ≥1 measure of QTc interval over 4 examinations at 3-year intervals (1987-1998). From 54 638 person-visits, we excluded participants with QRS ≥ 120 milliseconds (n = 2333 person-visits). We corrected the QT interval using the Bazett and Framingham formulas. We examined QTc lengthening using linear regression for 36 602 person-visit observations for 14 160 cohort members controlling for age ≥ 65 years, female sex, left ventricular hypertrophy, QTc > 500 milliseconds at the prior visit, and CredibleMeds categorized QTPMs (Known, Possible, or Conditional risk). We corrected standard errors for repeat observations per person. Results: Eighty percent of person-visits had at least one risk factor for QTc lengthening. Use of QTPMs increased over the 4 visits from 8% to 17%. Among persons not using QTPMs, history of prolonged QTc interval and female sex were associated with the greatest QTc lengthening, 39 and 12 milliseconds, respectively. In the absence of risk factors, Known QTPMs and ≥2 QTPMs were associated with modest but greater QTc lengthening than Possible or Conditional QTPMs. In the presence of risk factors, ≥2 QTPM further increased QTc lengthening. In combination with risk factors, the association of all QTPM categories with QTc lengthening was greater than QTPMs alone. Conclusion: Risk factors, particularly female sex and history of prolonged QTc interval, have stronger associations with QTc interval lengthening than any QTPM category alone. All QTPM categories augmented QTc interval lengthening associated with risk factors

From Household Size to the Life Course

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66696/2/10.1177_000276427702100207.pd

COVID-19 in Multiple Sclerosis: Clinically reported outcomes from the UK Multiple Sclerosis Register

Background: In March 2020, the United Kingdom Multiple Sclerosis Register (UKMSR) established an electronic case return form, designed collaboratively by MS neurologists, to record data about COVID-19 infections in people with MS (pwMS). Objectives: Examine how hospital admission and mortality are affected by disability, age and disease modifying treatments (DMTs) in people with Multiple Sclerosis with COVID-19. Methods: Anonymised data were submitted by clinical teams. Regression models were tested for predictors of hospitalisation and mortality outcomes. Separate analyses compared the first and second ‘waves’ of the pandemic. Results: Univariable analysis found hospitalisation and mortality were associated with increasing age, male gender, comorbidities, severe disability, and progressive MS; severe disability showed the highest magnitude of association. Being on a DMT was associated with a small, lower risk. Multivariable analysis found only age and male gender were significant. Post hoc analysis demonstrated that factors were significant for hospitalisation but not mortality. In the second wave, hospitalisation and mortality were lower. Separate models of the first and second wave using age and gender found they had a more important role in the second wave. Conclusions: Features associated with poor outcome in COVID-19 are similar to other populations and being on a DMT was not found to be associated with adverse outcomes, consistent with smaller studies. Once in hospital, no factors were predictive of mortality. Reassuringly, mortality appears lower in the second wave

The Society for Environmental Geochemistry and Health (SEGH): building for the future of early career researchers

In a 2019 editorial entitled ‘The Society for Environmental Geochemistry and Health (SEGH): building for the future’ (Watts et al. 2019), SEGH President Dr Michael Watts and all current board members outlined their aspirations and initiatives for the Society’s expansion into the new decade and beyond. Central to these efforts was the establishment of a dedicated group of early career researchers (ECRs) within SEGH to foster interaction, collaboration, mentorship and ultimately the expansion of this demographic. SEGH defines ECRs as undergraduate or postgraduate (Masters/PhD) students or as scientists having received their highest degree (BSc, MSc or PhD) within the past 5 years. ECRs currently make up approximately 20% of SEGH memberships, and nurturing growth at grassroots level is a critical strategy in preserving the Society’s long-term future if it is to remain relevant in an ever more competitive research landscape. With this in mind, ECR representatives currently sitting on the board took the initiative to follow up the 2019 editorial from an ECR perspective, with contributions made exclusively by members of this group. Drawing from personal experiences, we focus on key aspects of SEGH as a society and a community, but more importantly as a wider discipline and career path. We highlight the unique selling points of SEGH membership to ECRs, while voicing our wishes for improvement with the overall aim of promoting the society, and the society’s core values. Our hope is that we can attract more ECRs to our diverse community and enhance the experience of our current members

The Physics of Star Cluster Formation and Evolution

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00689-4.Star clusters form in dense, hierarchically collapsing gas clouds. Bulk kinetic energy is transformed to turbulence with stars forming from cores fed by filaments. In the most compact regions, stellar feedback is least effective in removing the gas and stars may form very efficiently. These are also the regions where, in high-mass clusters, ejecta from some kind of high-mass stars are effectively captured during the formation phase of some of the low mass stars and effectively channeled into the latter to form multiple populations. Star formation epochs in star clusters are generally set by gas flows that determine the abundance of gas in the cluster. We argue that there is likely only one star formation epoch after which clusters remain essentially clear of gas by cluster winds. Collisional dynamics is important in this phase leading to core collapse, expansion and eventual dispersion of every cluster. We review recent developments in the field with a focus on theoretical work.Peer reviewe

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