Treatment of cystic fibrosis (CF) has been revolutionized by the use of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) ...triple therapy. Prior studies support a role for type 2 (T2) inflammation in many people with CF (PwCF) and CF-asthma overlap syndrome (CFAOS) is considered a separate clinical entity. It is unknown whether initiation of ETI therapy impacts T2 inflammation in PwCF. We hypothesized that ETI initiation decreases T2 inflammation in PwCF.
A single center retrospective chart review was conducted for adult PwCF. As markers of T2 inflammation, absolute eosinophil count (AEC) and total immunoglobulin E (IgE) data were collected longitudinally 12 months prior to ETI therapy initiation and 12 months following therapy initiation. Multivariable analyses adjusted for the age, gender, CFTR mutation, disease severity, inhaled steroid use, and microbiological colonization.
There was a statistically significant reduction (20.10%, p < 0.001) in 12-month mean total IgE following ETI initiation; this change remained statistically significant in the multivariate model. The longitudinal analysis demonstrated no change in AEC following therapy initiation.
This study demonstrates that there is a statistically significant percent reduction in mean total IgE but no change in AEC following ETI initiation. ETI may lead to decreased antigen and superantigen load in the airway as a result of improved mucociliary clearance and these changes may drive the decline in total IgE, without influencing the epigenetic drivers of eosinophilic inflammation. Further studies are warranted to determine the underlying mechanism of ETI impact on T2 inflammation and possible role for asthma immunomodulator therapy post ETI initiation in CFAOS.
We report the case of a 46-year-old male patient with a history of cystic fibrosis who received bilateral lung transplantation from a donor who died secondary to complications of heparin-induced ...thrombocytopenia. Postoperatively, he exhibited transient focal neurologic deficits and radiographic evidence of multiple cortical and subcortical infarctions. He was treated with a combination of fondaparinux and standard immunosuppressive therapy, made a full recovery, and experienced significantly improved lung function compared to pretransplantation capacity.
Background
Anxiety disorders in children and young people are common and bring significant personal and societal costs. Over the last two decades, there has been a substantial increase in research ...evaluating psychological and pharmacological treatments for anxiety disorders in children and young people and exciting and novel research has continued as the field strives to improve efficacy and effectiveness, and accessibility of interventions. This increase in research brings potential to draw together data across studies to compare treatment approaches and advance understanding of what works, how, and for whom. There are challenges to these efforts due largely to variation in studies’ outcome measures and variation in the way study characteristics are reported, making it difficult to compare and/or combine studies, and this is likely to lead to faulty conclusions. Studies particularly vary in their reliance on child, parent, and/or assessor‐based ratings across a range of outcomes, including remission of anxiety diagnosis, symptom reduction, and other domains of functioning (e.g., family relationships, peer relationships).
Methods
To address these challenges, we convened a series of international activities that brought together the views of key stakeholders (i.e., researchers, mental health professionals, young people, parents/caregivers) to develop recommendations for outcome measurement to be used in treatment trials for anxiety disorders in children and young people.
Results and Conclusions
This article reports the results of these activities and offers recommendations for selection and reporting of outcome measures to (a) guide future research and (b) improve communication of what has been measured and reported. We offer these recommendations to promote international consistency in trial reporting and to enable the field to take full advantage of the great opportunities that come from data sharing going forward.
Climate warming can reduce food resources for animal populations. In species exhibiting parental care, parental effort is a ‘barometer’ of changes in environmental conditions. A key issue is the ...extent to which variation in parental effort can buffer demographic rates against environmental change.
Seabirds breed in large, dense colonies and globally are major predators of small fish that are often sensitive to ocean warming. We explored the causes and consequences of annual variation in parental effort as indicated by standardised checks of the proportions of chicks attended by both, one or neither parent, in a population of common guillemots Uria aalge over four decades during which there was marked variation in marine climate and chick diet. We predicted that, for parental effort to be an effective buffer, there would be a link between environmental conditions and parental effort, but not between parental effort and demographic rates.
Environmental conditions influenced multiple aspects of the prey delivered by parents to their chicks with prey species, length and energy density all influenced by spring sea surface temperature (sSST) in the current and/or previous year. Overall, the mean annual daily energy intake of chicks declined significantly when sSST in the current year was higher.
In accordance with our first prediction, we found that parental effort increased with sSST in the current and previous year. However, the increase was insufficient to maintain chick daily energy intake. In contrast to our second prediction, we found that increased parental effort had major demographic consequences such that growth rate and fledging success of chicks, and body mass and overwinter survival of breeding adults all decreased significantly.
Common guillemot parents were unable to compensate effectively for temperature‐mediated variation in feeding conditions through behavioural flexibility, resulting in immediate consequences for breeding population size because of lower adult survival and potentially longer‐term impacts on recruitment because of lower productivity. These findings highlight that a critical issue for species' responses to future climate change will be the extent to which behavioural buffering can offer resilience to deteriorating environmental conditions.
Behavioural responses are rarely incorporated into studies investigating mechanisms linking prey availability and predator demography, limiting the current understanding of climatically‐mediated pathways needed to predict the effects of future climate change on predator populations. These results highlight that it is not appropriate to assume that behavioural buffering will be effective (The image was created by Sam Langlois Lopez).
Over four decades (1982–2019) there were pronounced within‐season changes in the proportion of a key prey species (Lesser Sandeel Ammodytes marinus) in Common Guillemot Uria aalge chick diet. As ...Sandeels became scarcer their occurrence was largely confined to the early part of the chick period. Consequently, the mean annual proportion of Sandeels was poorly estimated if sampling occurred within a short time window, particularly if this was early or late in the season. Within‐season variation is rarely considered in diet monitoring but our results highlight the need for further analyses across other species and sites to develop a deeper understanding of how best to optimize sampling protocols.
Environmental conditions experienced during early growth and development markedly shape phenotypic traits. Consequently, individuals of the same cohort may show similar life-history tactics ...throughout life. Conditions experienced later in life, however, could fine-tune these initial differences, either increasing (cumulative effect) or decreasing (compensatory effect) the magnitude of cohort variation with increasing age. Our novel comparative analysis that quantifies cohort variation in individual body size trajectories shows that initial cohort variation dissipates throughout life, and that lifetime patterns change both across species with different paces of life and between sexes. We used longitudinal data on body size (mostly assessed using mass) from 11 populations of large herbivores spread along the "slow-fast" continuum of life histories. We first quantified cohort variation using mixture models to identify clusters of cohorts with similar initial size. We identified clear cohort clusters in all species except the one with the slowest pace of life, revealing that variation in early size is structured among cohorts and highlighting typological differences among cohorts. Growth trajectories differed among cohort clusters, highlighting how early size is a fundamental determinant of lifetime growth patterns. In all species, among-cohort variation in size peaked at the start of life, then quickly decreased with age and stabilized around mid-life. Cohort variation was lower in species with a slower than a faster pace of life, and vanished at prime age in species with the slowest pace of life. After accounting for viability selection, compensatory/catch-up growth in early life explained much of the decrease in cohort variation. Females showed less phenotypic variability and stronger compensatory/catch-up growth than males early in life, whereas males showed more progressive changes throughout life. These results confirm that stronger selective pressures for rapid growth make males more vulnerable to poor environmental conditions early in life and less able to recover after a poor start. Our comparative analysis illustrates how variability in growth changes over time in closely related species that span a wide range on the slow-fast continuum, the main axis of variation in life-history strategies of vertebrates.
•The COVID-19 pandemic resulted in the use of telehealth to deliver the cystic fibrosis (CF) care model.•Fewer individuals with CF met recommendations for care in 2020 despite widespread use of ...telehealth.•Use of telehealth did not equate to adherence to all aspects of CF care.•Certain demographic, socioeconomic and CF-related disease factors are associated with telehealth use.
The COVID-19 pandemic resulted in the use of telehealth to deliver the cystic fibrosis (CF) care model, which recommends routine follow-up for monitoring of nutritional status, bacterial culture surveillance, pulmonary function testing, and screening for CF-related complications such as diabetes or osteoporosis.
The objective of this study was to use Cystic Fibrosis Foundation Patient Registry (CFFPR) data to quantify the extent to which persons with CF received the recommended components of the care model in 2019 versus 2020. A risk factor analysis was implemented to identify patient characteristics associated with attaining the recommended CF care and use of any telehealth using multivariable logistic regression.
A total of 28,132 CFFPR participants were included in the study. The proportion of individuals meeting the recommendations for CF care was lower in 2020 for every indicator, and lower in adults compared to children. In adults, demographic, socioeconomic and CF-related disease covariates were significantly associated with both achieving an aggregate level of care and use of telehealth. In the pediatric population, minority race/ethnicity and markers of lower socioeconomic status were associated with a lower odds of telehealth use. In all analyses, having received the recommended level of care in 2019 was associated with a higher odds of both reported telehealth use and achieving the recommended elements of the CF care model in 2020.
Fewer participants met recommendations for care in 2020 despite widespread use of telehealth, and use of telehealth did not equate to adherence to all aspects of CF care.
AIMS To investigate changes in the mechanical compliance of ex vivo human lamina cribrosa with age. METHODS A laser scanning confocal microscope was used to image the surface of the fluorescently ...labelled lamina cribrosa in cadaver eyes. A method was developed to determine changes in the volume and strain of the lamina cribrosa created by increases in pressure. The ability of the lamina cribrosa to reverse its deformation on removal of pressure was also measured. RESULTS Volume and strain measurements both demonstrated that the lamina cribrosa increased in stiffness with age and the level of pressure applied. The ability of the lamina cribrosa to regain its original shape and size on removal of pressure appeared to decrease with age, demonstrating an age related decrease in resilience of the lamina cribrosa. CONCLUSIONS The mechanical compliance of the human lamina cribrosa decreased with age. Misalignment of compliant cribriform plates in a young eye may exert a lesser stress on nerve axons, than that exerted by the rigid plates of an elderly lamina cribrosa. The resilience of the lamina cribrosa also decreased with age, suggesting an increased susceptibility to plastic flow and permanent deformation. Such changes may be of importance in the explanation of age related optic neuropathy in primary open angle glaucoma.
Capsule: Common Guillemots Uria aalge show delayed breeding and marked age-related changes in reproductive success consistent with improved performance with experience.
Aims: To determine age of ...first breeding and age-related effects on breeding phenology and success of Common Guillemots.
Methods: Resighting data from a long-term colour-ringing study of Common Guillemot chicks were combined with observations of breeding phenology and success to follow the recruitment process, breeding phenology and success of 62 birds at a major North Sea colony over a 30-year period.
Results: The median age of first breeding of Common Guillemots was 6.6 years. There were no detectable costs of first breeding on return rates or the likelihood of breeding the next season but first time breeders bred later and less successfully. Age of first breeding and lifetime breeding success both varied among individuals but there was no clear optimal age of first breeding and early first breeding was not associated with higher lifetime breeding success.
Conclusions: Common Guillemots in the Isle of May population delayed breeding for 3-4 years beyond physiological maturity. The marked increase in breeding success with age was consistent with improved performance with experience rather than selection for higher quality individuals. Findings from this study will inform population models by providing improved estimates of age of first breeding and age-related changes in reproductive performance.
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