Adult onset lung disease following transient disruption of fetal stretch-induced differentiation

One of the mechanisms by which adult disease can arise from a fetal origin is by in utero disruption of organogenesis. These studies were designed to examine respiratory function changes in aging rats following transient disruption of lung growth at 16 days gestation. Fetuses were treated in utero with a replication deficient adenovirus containing the cystic fibrosis conductance transmembrane regulator (CFTR) gene fragment cloned in the anti-sense direction. The in utero-treated rats demonstrated abnormal lung function beginning as early as 30 days of age and the pathology progressed as the animals aged. The pulmonary function abnormalities included decreased static compliance as well as increased conducting airway resistance, tissue damping, and elastance. Pressure volume (PV) curves demonstrated a slower early rise to volume and air trapping at end-expiration. The alterations of pulmonary function correlated with lung structural changes determined by morphometric analysis. These studies demonstrate how transient disruption of lung organogensis by single gene interference can result in progressive change in lung function and structure. They illustrate how an adult onset disease can arise from subtle changes in gene expression during fetal development

Measuring vaccine confidence: introducing a global vaccine confidence index.

BACKGROUND: Public confidence in vaccination is vital to the success of immunisation programmes worldwide. Understanding the dynamics of vaccine confidence is therefore of great importance for global public health. Few published studies permit global comparisons of vaccination sentiments and behaviours against a common metric. This article presents the findings of a multi-country survey of confidence in vaccines and immunisation programmes in Georgia, India, Nigeria, Pakistan, and the United Kingdom (UK) - these being the first results of a larger project to map vaccine confidence globally. METHODS: Data were collected from a sample of the general population and from those with children under 5 years old against a core set of confidence questions. All surveys were conducted in the relevant local-language in Georgia, India, Nigeria, Pakistan, and the UK. We examine confidence in immunisation programmes as compared to confidence in other government health services, the relationships between confidence in the system and levels of vaccine hesitancy, reasons for vaccine hesitancy, ultimate vaccination decisions, and their variation based on country contexts and demographic factors. RESULTS: The numbers of respondents by country were: Georgia (n=1000); India (n=1259); Pakistan (n=2609); UK (n=2055); Nigerian households (n=12554); and Nigerian health providers (n=1272). The UK respondents with children under five years of age were more likely to hesitate to vaccinate, compared to other countries. Confidence in immunisation programmes was more closely associated with confidence in the broader health system in the UK (Spearman's ρ=0.5990), compared to Nigeria (ρ=0.5477), Pakistan (ρ=0.4491), and India (ρ=0.4240), all of which ranked confidence in immunisation programmes higher than confidence in the broader health system. Georgia had the highest rate of vaccine refusals (6 %) among those who reported initial hesitation. In all other countries surveyed most respondents who reported hesitating to vaccinate went on to receive the vaccine except in Kano state, Nigeria, where the percentage of those who ultimately refused vaccination after initially hesitating was as high as 76%) Reported reasons for hesitancy in all countries were classified under the domains of "confidence," "convenience," or "complacency," and confidence issues were found to be the primary driver of hesitancy in all countries surveyed

Barking up the right tree: Understanding local attitudes towards dogs in villages surrounding Ranomafana National Park, Madagascar can benefit applied conservation

Exotic carnivores, particularly feral and domestic dogs, represent a serious threat to Madagascar’s endemic fauna. We obtained information from the local community about dogs in villages in and around Ranomafana National Park (RNP), Madagascar. Surveys were conducted (N=359) to assess local opinions of dogs, reasons for owning dogs, and the willingness of dog owners to participate in spay/neuter/vaccine programs. Of surveyed individuals without dogs (N=211), 58.9% of respondents reported negative feelings towards free-roaming dogs, with only 1% of respondents identifying free-roaming dogs as a positive aspect of village life. Of individuals with dogs (N=148), 8.1% of respondents reported using their dog for hunting, and 41.2% reported that their dog had killed at least one wild animal, with 11.8% reporting that this occurred on a weekly basis. Villagers approve of spay/neuter/vaccine programs and 90.3% of respondents with dogs state they would use them if freely available. The interest in veterinary services combined with a generally negative attitude towards free-roaming dogs indicates that a spay/neuter/vaccine program would be an effective means of controlling dog populations.RÉSUMÉLes carnivores exotiques, particulièrement les chiens domestiques et ceux retournés à l’état sauvage, représentent une menace sérieuse pour la faune endémique de Madagascar. Nous avons récolté des informations auprès des communautés riveraines sur les chiens vivant dans les villages et autour du Parc National de Ranomafana (RNP) au sud-est de Madagascar. Nous avons mené des enquêtes (N=359) afin d’évaluer les avis de la communauté locale sur les chiens, les raisons pour lesquelles les gens possèdent ces animaux et la volonté des propriétaires pour s’engager dans un programme de stérilisation/vaccination canine. Les villageois qui ne possédaient pas de chiens (N=211) représentaient 58,9 % des personnes interrogées ; ils ont rapporté avoir des sentiments négatifs envers les chiens errants et seulement 1 % des personnes interrogées ont vu un aspect positif pour la vie du village dans les chiens errants. Parmi les propriétaires de chiens (N=148), 8,1 % des personnes interrogées ont rapporté utiliser leur chien pour la chasse et 41,2% des personnes interrogées indiquent que leur chien a déjà tué au moins un animal sauvage, dont 11,8 % rapportant que cela arrivait toutes les semaines. Les villageois approuvent le programme de stérilisation/ vaccination canine et 90,3 % des propriétaires de chiens y auraient volontiers recours si celui-ci était gratuit et librement disponible

Adiposity, Cardiometabolic Risk, and Vitamin D Status: The Framingham Heart Study

OBJECTIVE: Because vitamin D deficiency is associated with a variety of chronic diseases, understanding the characteristics that promote vitamin D deficiency in otherwise healthy adults could have important clinical implications. Few studies relating vitamin D deficiency to obesity have included direct measures of adiposity. Furthermore, the degree to which vitamin D is associated with metabolic traits after adjusting for adiposity measures is unclear. RESEARCH DESIGN AND METHODS: We investigated the relations of serum 25-hydroxyvitamin D (25[OH]D) concentrations with indexes of cardiometabolic risk in 3,890 nondiabetic individuals; 1,882 had subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes measured by multidetector computed tomography (CT). RESULTS: In multivariable-adjusted regression models, 25(OH)D was inversely associated with winter season, waist circumference, and serum insulin (P < 0.005 for all). In models further adjusted for CT measures, 25(OH)D was inversely related to SAT (−1.1 ng/ml per SD increment in SAT, P = 0.016) and VAT (−2.3 ng/ml per SD, P < 0.0001). The association of 25(OH)D with insulin resistance measures became nonsignificant after adjustment for VAT. Higher adiposity volumes were correlated with lower 25(OH)D across different categories of BMI, including in lean individuals (BMI <25 kg/m2). The prevalence of vitamin D deficiency (25[OH]D <20 ng/ml) was threefold higher in those with high SAT and high VAT than in those with low SAT and low VAT (P < 0.0001). CONCLUSIONS: Vitamin D status is strongly associated with variation in subcutaneous and especially visceral adiposity. The mechanisms by which adiposity promotes vitamin D deficiency warrant further study.National Institutes of Health's National Heart, Lung, and Blood Institute (N01-HC-25195, R01-DK-80739): American Heart Associatio

A Single Visualization Technique for Displaying Multiple Metabolite-Phenotype Associations.

To assist with management and interpretation of human metabolomics data, which are rapidly increasing in quantity and complexity, we need better visualization tools. Using a dataset of several hundred metabolite measures profiled in a cohort of ~1500 individuals sampled from a population-based community study, we performed association analyses with eight demographic and clinical traits and outcomes. We compared frequently used existing graphical approaches with a novel 'rain plot' approach to display the results of these analyses. The 'rain plot' combines features of a raindrop plot and a conventional heatmap to convey results of multiple association analyses. A rain plot can simultaneously indicate effect size, directionality, and statistical significance of associations between metabolites and several traits. This approach enables visual comparison features of all metabolites examined with a given trait. The rain plot extends prior approaches and offers complementary information for data interpretation. Additional work is needed in data visualizations for metabolomics to assist investigators in the process of understanding and convey large-scale analysis results effectively, feasibly, and practically

A backwards approach to the formation of disk galaxies I. Stellar and gas content

A simple chemical enrichment code is described where the two basic mechanisms driving the evolution of the ages and metallicities of the stellar populations are the star formation efficiency and the fraction of gas ejected from the galaxy. Using the observed Tully-Fisher relation in different passbands as a constraint, it is found that a steep correlation between the maximum disk rotational velocity and star formation efficiency must exist either for a linear or a quadratic Schmidt law. Outflows do not play a major role. The redshift evolution of disk galaxies is explored, showing that a significant change in the slope of the Tully-Fisher relation is expected because of the different age distributions of the stellar components in high and low-mass disk galaxies. The slope measured in the rest frame B,K bands is found to change from 3(B); 4(K) at z=0 up to 4.5(B); 5(K) at z~1, with a slight dependence on formation redshift.Comment: Accepted for publication in ApJ. Uses emulateapj.sty. 12 pages with 10 embedded EPS figure

Spatial epidemiological patterns suggest mechanisms of land-sea transmission for Sarcocystis neurona in a coastal marine mammal.

Sarcocystis neurona was recognised as an important cause of mortality in southern sea otters (Enhydra lutris nereis) after an outbreak in April 2004 and has since been detected in many marine mammal species in the Northeast Pacific Ocean. Risk of S. neurona exposure in sea otters is associated with consumption of clams and soft-sediment prey and is temporally associated with runoff events. We examined the spatial distribution of S. neurona exposure risk based on serum antibody testing and assessed risk factors for exposure in animals from California, Washington, British Columbia and Alaska. Significant spatial clustering of seropositive animals was observed in California and Washington, compared with British Columbia and Alaska. Adult males were at greatest risk for exposure to S. neurona, and there were strong associations with terrestrial features (wetlands, cropland, high human housing-unit density). In California, habitats containing soft sediment exhibited greater risk than hard substrate or kelp beds. Consuming a diet rich in clams was also associated with increased exposure risk. These findings suggest a transmission pathway analogous to that described for Toxoplasma gondii, with infectious stages traveling in freshwater runoff and being concentrated in particular locations by marine habitat features, ocean physical processes, and invertebrate bioconcentration

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature

Concert recording 2021-11-15

[Track 1] Growth / Cole Powledge -- [Track 2] Day tripper ; Lady Madonna / Lennon/McCartney ; arranged by Tommy Emmanuel -- [Track 3] Disappear / Joshua Larson -- [Track 4] Sirabhorn / Pat Metheny -- [Track 5] Parisienne walkways / Gary Moore -- [Track 6] Songbird / Kenny G -- [Track 7] Drifting / Cody Lucas -- [Track 8] Slow dancing in a burning room / John Mayer -- [Track 9] Suites of morning