The intent of this work was to examine the intersection of COVID-19 fear with social vulnerabilities and mental health consequences among adults living in the United States. Data are from a ...nationally representative sample (n = 10,368) of U.S. adults surveyed online during demographic subgroups (gender, age, income, race and ethnicity, geography). The sample week of March 23, 2020. The sample was poststratification weighted to ensure a balanced representation across social and demographic subgroups (gender, age, income, race or ethnicity, geography). The sample comprised 51% female; 23% non-White; 18% Hispanic; 25% of households with children under 18 years of age; 55% unmarried; and nearly 20% unemployed, laid off, or furloughed at the time of the interview. Respondents were fearful, averaging a score of nearly 7 on a scale of 10 when asked how fearful they were of COVID-19. Preliminary analysis suggests clear spatial diffusion of COVID-19 fear. Fear appears to be concentrated in regions with the highest reported COVID-19 cases. Significant differences across several U.S. census regions are noted (p < .01). Additionally, significant bivariate relationships were found between socially vulnerable respondents (female, Asians, Hispanic, foreign-born, families with children) and fear, as well as with mental health consequences (anxiety and depressive symptoms). Depressive symptoms, on average, were high (16+ on the Center for Epidemiologic Studies Depression scale), and more than 25% of the sample reported moderate to severe anxiety symptoms. More in-depth psychosocial research is needed using nationally representative samples that can help to inform potential mental health risks, as well as by targeting specific mental health interventions.
Hybridization, genetic mixture of distinct populations, gives rise to myriad recombinant genotypes. Characterizing the genomic composition of hybrids is critical for studies of hybrid zone dynamics, ...inheritance of traits, and consequences of hybridization for evolution and conservation. Hybrid genomes are often summarized either by an estimate of the proportion of alleles coming from each ancestral population or classification into discrete categories like F1, F2, backcross, or merely "hybrid" vs. "pure". In most cases, it is not realistic to classify individuals into the restricted set of classes produced in the first two generations of admixture. However, the continuous ancestry index misses an important dimension of the genotype. Joint consideration of ancestry together with interclass heterozygosity (proportion of loci with alleles from both ancestral populations) captures all of the information in the discrete classification without the unrealistic assumption that only two generations of admixture have transpired.
I describe a maximum likelihood method for joint estimation of ancestry and interclass heterozygosity. I present two worked examples illustrating the value of the approach for describing variation among hybrid populations and evaluating the validity of the assumption underlying discrete classification.
Naively classifying natural hybrids into the standard six line cross categories can be misleading, and false classification can be a serious problem for datasets with few molecular markers. My analysis underscores previous work showing that many (50 or more) ancestry informative markers are needed to avoid erroneous classification.
Although classification of hybrids might often be misleading, valuable inferences can be obtained by focusing directly on distributions of ancestry and heterozygosity. Estimating and visualizing the joint distribution of ancestry and interclass heterozygosity is an effective way to compare the genetic structure of hybrid populations and these estimates can be used in classic quantitative genetic methods for assessing additive, dominant, and epistatic genetic effects on hybrid phenotypes and fitness. The methods are implemented in a freely available package "HIest" for the R statistical software ( http://cran.r-project.org/web/packages/HIest/index.html).
Abstract Context In the past few years, there has been a rapid increase in the number of therapies available to treat metastatic castration-resistant prostate cancer (mCRPC). Currently, approved ...treatments consist of the taxane class of cytotoxic drugs and androgen-targeted therapies. The challenge for clinicians is to decide the best sequence in which to give these therapies to provide the greatest benefit to their patients. Objective To review recent research into the mechanism of action of taxanes in prostate cancer (PCa) cells and the clinical evidence for an interaction between taxanes and androgen-targeted therapies. The implications of these findings for clinical practice are discussed. Evidence acquisition A nonsystematic review of the relevant medical literature between 2004 and the present, in combination with clinical trial data reported at oncology meetings during 2012, was undertaken. Our perspective, focussing on the potential implications for sequencing of therapies for mCRPC, is provided. Evidence synthesis Taxanes are shown to interact with androgen signalling in PCa cells at both the cytoplasmic level (via microtubules) and the nuclear level, affecting transcriptional regulators of androgen-responsive gene expression. Data from clinical trials suggest that androgen deprivation can potentially decrease the efficacy of taxanes in treating PCa. Conclusions These findings have important implications for clinical practice, and there is an urgent need for strong clinical data to support a recommendation for an optimal sequence of therapies.
Sex bias in autoimmune disease (AID) prevalence is known, but the role of estrogen in disease progression is more complex. Estrogen can even be protective in some AIDs; but in systemic lupus ...erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc), estrogen, its metabolites, and its receptors have been demonstrated to play critical, localized inflammatory roles. Estrogen is instrumental to the fibrosis seen in RA, SLE, SSc and other disease states, including breast cancer and uterine leiomyomas. Fibrotic diseases tend to share a common pattern in which lymphocyte–monocyte interactions generate cytokines which stimulate the deposition of fibrogenic connective tissue. RA, SLE, SSc and thyroid eye disease (TED) have very similar inflammatory and fibrotic patterns—from pathways to tissue type. The thorough investigations that demonstrated estrogen’s role in the pathology of RA, SLE, and SSc could, and possibly should, be carried out in TED. One might even expect to find an even greater role for estrogen, and sex steroid homeostasis in TED, given that TED is typically sequalae to Graves’ disease (GD), or Hashimoto’s disease (HD), and these are endocrine disorders that can create considerable sex steroid hormone dysregulation. This paper highlights the pathophysiology similarities in 4 AIDs, examines the evidence of sex steroid mediated pathology across 3 AIDs and offers a case study and speculation on how this may be germane to TED.
Previous studies find preventative behaviors designed to reduce the number of infections during emerging disease outbreaks are associated with perceived risk of disease susceptibility. Few studies ...have attempted to identify underlying factors that explain differences in perceptions of risk during an infectious disease outbreak. Drawing from two early waves of American Trends Panel (n=7,441), as well as a National Science Foundation funded, Qualtrics national panel survey from the early stages of the pandemic (n=10,368), we test whether race and ethnicity, gender, and age were associated with six perceived threat and fear outcomes related to COVID-19. Results demonstrate race and ethnicity, gender, and age play a significant role in shaping threat and fear perceptions of COVID-19, but depending on the outcome, relationships vary in direction and magnitude. In some cases, historically marginalized racial and ethnic groups were more likely to report high fear and perceive coronavirus as a major threat to population and individual health, whereas, in others cases, the same marginalized racial and ethnic groups were less likely to perceive coronavirus to be a serious threat to the immune-comprised and the elderly population. We also find women were generally more likely to report high levels of threat and fear of COVID-19. Finally, we observe a clear age difference, whereby adults in older age groups report high-risk perceptions of COVID-19. Findings can inform public health programs designed to educate communities on the benefits of engaging in effective preventative practices during emerging infectious disease outbreaks.
•Racial and ethnic minorities are more likely to report high fear of coronavirus.•Racial and ethnic minorities are more likely to perceive coronavirus as a major threat to population.•Racial and ethnic minorities are more likely to perceive coronavirus as a major threat to individual health.•Women are generally more likely to report high levels of threat and fear of COVID-19.•In general, older age groups report high-risk perceptions of COVID-19.
Background Asthma in children is a heterogeneous disorder with many phenotypes. Although unsupervised cluster analysis is a useful tool for identifying phenotypes, it has not been applied to ...school-age children with persistent asthma across a wide range of severities. Objectives This study determined how children with severe asthma are distributed across a cluster analysis and how well these clusters conform to current definitions of asthma severity. Methods Cluster analysis was applied to 12 continuous and composite variables from 161 children at 5 centers enrolled in the Severe Asthma Research Program. Results Four clusters of asthma were identified. Children in cluster 1 (n = 48) had relatively normal lung function and less atopy. Children in cluster 2 (n = 52) had slightly lower lung function, more atopy, and increased symptoms and medication use. Cluster 3 (n = 32) had greater comorbidity, increased bronchial responsiveness, and lower lung function. Cluster 4 (n = 29) had the lowest lung function and the greatest symptoms and medication use. Predictors of cluster assignment were asthma duration, the number of asthma controller medications, and baseline lung function. Children with severe asthma were present in all clusters, and no cluster corresponded to definitions of asthma severity provided in asthma treatment guidelines. Conclusion Severe asthma in children is highly heterogeneous. Unique phenotypic clusters previously identified in adults can also be identified in children, but with important differences. Larger validation and longitudinal studies are needed to determine the baseline and predictive validity of these phenotypic clusters in the larger clinical setting.
Sympatric speciation, the evolution of reproductive isolation without geographic barriers, remains highly contentious. As a result of new empirical examples and theory, it is now generally accepted ...that sympatric speciation has occurred in at least a few instances, and is theoretically plausible. Instead, debate has shifted to whether sympatric speciation is common, and whether models' assumptions are generally met in nature. The relative frequency of sympatric speciation will be difficult to resolve, because biogeographic changes have obscured geographical patterns underlying many past speciation events. In contrast, progress is being made on evaluating the empirical validity of key theoretical conditions for sympatric speciation. Disruptive selection and direct selection on mating traits, which should facilitate sympatric speciation, are biologically well supported. Conversely, costs to assortative mating are also widely documented, but inhibit speciation. Evaluating the joint incidence of these key factors may illuminate why sympatric speciation appears to be relatively uncommon.
Summary In 2010, the International Society of Geriatric Oncology (SIOG) developed treatment guidelines for men with prostate cancer who are older than 70 years old. In 2013, a new multidisciplinary ...SIOG working group was formed to update these recommendations. The consensus of the task force is that older men with prostate cancer should be managed according to their individual health status, not according to age. On the basis of a validated rapid health status screening instrument and simple assessment, the task force recommends that patients are classed into three groups for treatment: healthy or fit patients who should have the same treatment options as younger patients; vulnerable patients with reversible impairment who should receive standard treatment after medical intervention; and frail patients with non-reversible impairment who should receive adapted treatment.
Background Studies of asthma phenotypes have identified obesity as a component of a group characterized by a high proportion of subjects with adult-onset asthma. However, whether age of asthma onset ...modifies the association between obesity and asthma is unknown. Objectives We sought to compare the associations between body mass index (BMI) categories with physiological, inflammatory, and clinical parameters across age of asthma onset phenotypes; and to compare the rate of BMI change in relation to asthma duration, by age of onset asthma phenotypes. Methods From the Severe Asthma Research Program, we defined age of asthma onset as early (<12 years of age) and late (≥12 years of age). Comparisons of BMI categories were done within age-of-onset groups, and obesity was also compared across these groups. Multivariable logistic regression analysis was done to evaluate the association between BMI categories with health care use and respiratory symptoms and multivariable linear regression for the association between duration of asthma and weight gain (BMI change per year). An interaction between obesity and age of asthma onset was included in the multivariable analyses. Results The study population consisted of 1049 subjects, and the median age for asthma onset was 10 years (interquartile range, 4-25 years); 48% had late-onset asthma (≥12 years of age), and 52% had early-onset asthma (<12 years of age). Compared with obese subjects with late-onset asthma, obese subjects with early-onset asthma had more airway obstruction, bronchial hyperresponsiveness, and higher odds ratios of ever having 3 or more previous oral steroid tapers per year or intensive care unit admissions for asthma per preceding year (interactions between obesity and age of asthma onset were P = .055 and P = .02, respectively). In subjects with early-onset asthma but not in subjects with late-onset asthma, there was a significant association between increasing BMI and duration of asthma after adjusting for confounders. The interaction between asthma duration and age of asthma onset was a P value of less than .01. Conclusion Asthmatic subjects are differentially affected by obesity based on whether they had asthma early (<12 years of age) or later in life. These results highlight the need to understand obesity as a comorbidity that affects specific clinical phenotypes and not all asthma subjects alike.
Prehistoric colonization of East Polynesia represents the last and most extensive of human migrations into regions previously uninhabited. Although much of East Polynesia is tropical, the southern ...third, dominated by New Zealand-by far the largest Polynesian landmass-ranges from a warm- to cool-temperate climate with some islands extending into the Subantarctic. The substantial latitudinal variation implies questions about biocultural adaptations of tropical people to conditions in which most of their familiar resources were absent and their agriculture marginal. Perhaps the most basic question, but one which has never been explored, is the extent to which sailing out of the tropics on long-distance colonizing voyages imposed physiological stress on canoe crews and passengers. In this paper we use trajectories of simulated voyages from Tahiti to New Zealand and Tahiti to Hawaii to obtain along-trip environmental parameters which are then used to model the energy expenditure of these long overseas journeys. Results show that travelers to New Zealand are exposed to much harsher environmental conditions, leading to significantly greater in-trip thermoregulatory demands. For both destinations, travelers with larger body sizes exhibit lower modeled heat loss and hence obtain an energetic advantage, with greater gains for females. Such physiological features, notably of Samoans who probably formed the founding population in East Polynesia, may help explain successful voyaging to temperate latitudes.
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