Relieving Mucus Flake Burden in Cystic Fibrosis

Dehydration of the mucus in the lung airway is a hallmark of cystic fibrosis (CF) airway disease. In CF, mucins—the key gel-forming polymeric component of mucus—are elevated in airway mucus. Roughly half of the mucins present in mucus are found in non-swelling gels termed “mucus flakes.” Elevated mucus flake density is an indicator of CF disease and airflow obstruction. However, little is known about the factors that instruct flake formation or whether flakes can be therapeutically dissolved. Progress in understanding flakes is limited by the complexities of collecting and analyzing samples from human subjects. We aim to identify the factors that promote mucus flake formation, allowing us to develop novel therapeutic approaches to dissolve them. A unique feature of our approach includes the de novo synthesis of mucus flakes from mucins isolated from human epithelial cells as a strategy to mimic flake structure and biochemical interactions. This strategy provides experimental tunability that will greatly enhance our understanding of flake formation and provide a platform to screen novel therapies to dissolve them. We tested the effects of various doses and combinations of a calcium chelator, reducing agent, surfactant, and known mucolytic as potential mucus flake dissolution agents. We found that the reducing agent, calcium chelator, surfactant, and cocktails of these reagents triggered significant flake swelling, resulting in increased water solubility, which may improve airway mucosal clearance. The calcium chelator and treatment cocktails also reduced flake number, which may reflect the dissolution of flakes, whereas the reducing agent and surfactant increased flake number and may demonstrate flake crumbling. This flake dissolution and crumbling may revert CF mucus to a healthy state. This novel approach allows us to screen potential early treatments to delay the onset of lung disease in CF patients and to establish treatment effectiveness.Bachelor of Scienc

A systematic review of economic evaluations of interventions targeting childhood overweight and obesity

This systematic review critically appraised and synthesized evidence from economic evaluations of interventions targeting childhood excess weight. We conducted systematic searches in 11 databases from inception to April 19, 2023. Studies were eligible if they evaluated interventions targeting children up to 18 years and the study intervention(s) targeted childhood excess weight or sought to improve diet or physical activity, regardless of the type of economic evaluation or the underpinning study design. We synthesized evidence using narrative synthesis methods. One-hundred fifty-one studies met the eligibility criteria and were classified into three groups based on the intervention approach: prevention-only (13 studies), prevention and treatment (100 studies), and treatment-only (38 studies). The predominant setting and study design differed considerably between the three groups of studies. However, compared with usual care, most interventions were deemed cost-effective. The study participants' ages, sex, and socioeconomic status were crucial to intervention cost-effectiveness. Interventions whose effects were projected beyond childhood, such as bariatric surgery, lower protein infant formula, and home-based general practitioner consultations, tended to be cost-effective. However, cost-effectiveness was sensitive to the assumptions underlying the persistence and intensity of such effects. Our findings can inform future recommendations on the conduct of economic evaluations of interventions targeting childhood overweight and obesity, as well as practice and policy recommendations

Addressing the Gender Gap in Distinguished Speakers at Professional Ecology Conferences

Keynote and plenary speakers at professional conferences serve as highly visible role models for early-career scientists and provide recognition of scientific excellence. This recognition may be particularly important for women, who are underrepresented in senior positions in the biological sciences. To evaluate whether conferences fulfill this potential, we examined distinguished speakers at North American ecology conferences between 2000 and 2015 and compared these data with the percentage of women ecologists at diverse career stages. We found that 15%–35% (x = 28%, n = 809) of the distinguished speakers were women, which is significantly lower than the percentage of female ecology graduate students (x = 55%, n = 26,802) but consistent with the percentage of women in assistant- and associate-faculty positions. We recommend that conference organizers institute policies to enhance speaker gender balance, to provide support for speakers with family responsibilities, and to actively monitor gender-related trends in their societies to achieve the equitable representation of women in distinguished speaking roles

Addressing the Gender Gap in Distinguished Speakers at Professional Ecology Conferences

Keynote and plenary speakers at professional conferences serve as highly visible role models for early-career scientists and provide recognition of scientific excellence. This recognition may be particularly important for women, who are underrepresented in senior positions in the biological sciences. To evaluate whether conferences fulfill this potential, we examined distinguished speakers at North American ecology conferences between 2000 and 2015 and compared these data with the percentage of women ecologists at diverse career stages. We found that 15%–35% (x = 28%, n = 809) of the distinguished speakers were women, which is significantly lower than the percentage of female ecology graduate students (x = 55%, n = 26,802) but consistent with the percentage of women in assistant- and associate-faculty positions. We recommend that conference organizers institute policies to enhance speaker gender balance, to provide support for speakers with family responsibilities, and to actively monitor gender-related trends in their societies to achieve the equitable representation of women in distinguished speaking roles

K-Space at TRECVID 2008

In this paper we describe K-Space’s participation in TRECVid 2008 in the interactive search task. For 2008 the K-Space group performed one of the largest interactive video information retrieval experiments conducted in a laboratory setting. We had three institutions participating in a multi-site multi-system experiment. In total 36 users participated, 12 each from Dublin City University (DCU, Ireland), University of Glasgow (GU, Scotland) and Centrum Wiskunde and Informatica (CWI, the Netherlands). Three user interfaces were developed, two from DCU which were also used in 2007 as well as an interface from GU. All interfaces leveraged the same search service. Using a latin squares arrangement, each user conducted 12 topics, leading in total to 6 runs per site, 18 in total. We officially submitted for evaluation 3 of these runs to NIST with an additional expert run using a 4th system. Our submitted runs performed around the median. In this paper we will present an overview of the search system utilized, the experimental setup and a preliminary analysis of our results

Genetic and environmental determinants of diastolic heart function

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of the UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between genetically-determined ventricular stiffness and incident heart failure. Our results provide insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and potential tractable targets

Pleistocene environments, climate, and human activity in Britain during Marine Isotope Stage 7: insights from Oak Tree Fields, Cerney Wick, Gloucestershire

Investigations at Oak Tree Fields, Cerney Wick, Gloucestershire, in western England have revealed a sequence of fluvial deposits dating from Marine Oxygen Isotope Stage (MIS) 7 to 5. At the base of the sequence, a series of gravel and sand facies were deposited, initially as part of a meandering river. Reductions in flow energy of the latter and avulsion led to the development of short-lived channels and episodic backwater environments, the deposits of which are recorded as Facies Associations 1–3. Poorly sorted, probably colluvial deposits formed beyond the limit of the channel (Facies Association 4). Mollusca, Coleoptera, plant macrofossils, pollen and vertebrates recovered from the channel facies indicate broadly similar climatic conditions throughout accretion. Temperature ranges derived from mutual climatic range analysis of the Coleoptera almost completely overlap with those of Cerney Wick at the present day, albeit that winters may have been cooler when the channel was active. Further, the floral and faunal data suggest that the meandering river flowed through an open grassland environment, the latter heavily grazed by large vertebrates, most notably mammoth. Most of the botanical and faunal remains, together with four optically stimulated luminescence (OSL) age estimates ranging from 225 ± 23 to 187 ± 19 ka, suggest correlation of the channel deposits with MIS 7. The basal deposits (Facies Association 1) yielded the majority of vertebrate remains and all the lithic artefacts, most of which seem likely to have travelled only a short distance. Although only a few artefacts were recovered, they add to the relatively limited evidence of human activity from the upper Thames. The channel deposits are overlain by sheet gravels (Facies Association 5) which are attributed to the Northmoor Member of the Upper Thames Formation. These were likely to have been deposited as bedload in a braided stream environment, while two OSL age estimates of 129 ± 14 and 112 ± 11 ka suggest accumulation during MIS 5

Prevalence and diversity of type VI secretion systems in a model beneficial symbiosis

The type VI secretion system (T6SS) is widely distributed in diverse bacterial species and habitats where it is required for interbacterial competition and interactions with eukaryotic cells. Previous work described the role of a T6SS in the beneficial symbiont, Vibrio fischeri, during colonization of the light organ of Euprymna scolopes squid. However, the prevalence and diversity of T6SSs found within the distinct symbiotic structures of this model host have not yet been determined. Here, we analyzed 73 genomes of isolates from squid light organs and accessory nidamental glands (ANGs) and 178 reference genomes. We found that the majority of these bacterial symbionts encode diverse T6SSs from four distinct classes, and most share homology with T6SSs from more distantly related species, including pathogens of animals and humans. These findings indicate that T6SSs with shared evolutionary histories can be integrated into the cellular systems of host-associated bacteria with different effects on host health. Furthermore, we found that one T6SS in V. fischeri is located within a genomic island with high genomic plasticity. Five distinct genomic island genotypes were identified, suggesting this region encodes diverse functional potential that natural selection can act on. Finally, analysis of newly described T6SSs in roseobacter clade ANG isolates revealed a novel predicted protein that appears to be a fusion of the TssB-TssC sheath components. This work underscores the importance of studying T6SSs in diverse organisms and natural habitats to better understand how T6SSs promote the propagation of bacterial populations and impact host health