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Evaluation of a strategy to enhance the efficacy and ease of application of porcine reproductive and respiratory syndrome virus vaccines
Get PDFControl of porcine reproductive and respiratory syndrome viruses (PRRSV) is sometimes hindered by the suboptimal immunogenicity and efficacy of existing vaccines. In addition, not following vaccine storage and administration conditions on-farm can negatively impact on the efficacy of current vaccines and present barriers to the development of more efficacious vaccination strategies. To address these challenges, we evaluated whether a 'prime and pull' immunisation strategy combining a prime with a ‘needle-free’ solid dose formulation of modified live PRRSV-1 vaccine (MLV), and a nasal boost with inactivated PRRSV-1 administered by an automated jet device can enhance protection against challenge infection. Forty-five, 4-week-old, PRRSV naïve, piglets were divided into 5 groups; including a benchmark group (10 pigs, vaccinated with a liquid MLV delivered by intramuscular injection), a prime only group (10 pigs vaccinated with the solid dose MLV), a prime/pull group (10 pigs vaccinated with the solid dose MLV and boosted 3 weeks later by nasal inoculation with inactivated MLV), an unvaccinated challenge control group (10 pigs) and a naïve group (5 pigs, without vaccination and PRRSV challenge). Pigs were challenged with a PRRSV-1 field strain 35 days post-vaccination and necropsied 10 days post-challenge. PRRSV viremia and nasal shedding were inferred by RT-qPCR, and antibody responses were assessed in serum and bronchoalveolar lavage by ELISA and virus neutralisation test. Whilst the nasal inactivated vaccine boost failed to augment efficacy, the solid dose vaccine provided neutralising antibody responses and protection (reduced viremia, virus shedding and gross lung lesions) comparable to the standard needle and syringe inoculation of PRRSV MLV suspension. These data support the further development of the solid dose formulation technology as a practical alternative to conventional delivery of PRRSV MLV and other vaccines to pigs
Three maxims for countering sex essentialism in scientific research
Get PDFTo explain observed disparities in health outcomes between men and women, sex essentialist approaches assign causal primacy to sex-related biology. In this essay, we present three case studies to illustrate how sex essentialism can distort human biomedical research and distill three maxims for countering this distortion: (1) engage in responsible citation practices; (2), generate and weigh alternative hypotheses for apparent observations of sex differences; (3) take care in constructing the appropriate denominator when making sex comparisons. We offer these maxims as broadly applicable standards of evidence to guide biomedical research that includes analysis of potential sex differences, as well as to support Institutional Review Boards (IRBs), funders, publishers, and peer reviewers in evaluating sex difference findings. If widely applied, these maxims would substantially improve the rigor, precision, and utility of the knowledge base of sex and gender science
Preserved circadian variation in cortisol and androgens during a ski traverse of Antarctica in summer
Get PDFAntarctic expeditions present extreme physiological challenges due to cold temperatures, high physical exertion, and 24-hour daylight. This observational study evaluated endocrine adaptation in nine participants (six men, three women) during a 47-day, 1,000 km unassisted ski traverse. Detailed salivary sampling was conducted before, during and after the expedition, corroborated by blood and hair sampling before and after the expedition. Cortisol, testosterone, and androstenedione were measured using mass spectrometry, and thyroid hormones via immunoassay. Diurnal cortisol, androstenedione and testosterone variation was preserved, while the morning cortisol increased during the expedition, suggesting that exercise demands overshadow the effects of continuous daylight in controlling hypothalamic-pituitary-adrenal and gonadal axis function. Morning testosterone decreased during the expedition, with a greater effect seen among men. No significant changes were seen in blood or hair steroid hormones. Gonadotropins in women indicated central suppression pre-expedition, normalizing post-expedition. Thyroid-stimulating hormone levels increased post-expedition without significant changes in free T3 or T4, consistent with mild polar T3 syndrome. These findings highlight the adaptability of hypothalamic-pituitary function to combined stressors of exercise, energy deficit, and cold. This is the first study to capture in situ endocrine responses during an Antarctic traverse, advancing our understanding of human adaptation in extreme environments.</p
Epicardial Adipose Tissue as an Independent Risk Factor for Mortality in Pulmonary Arterial Hypertension
Get PDFBackgroundIncreased epicardial adipose tissue (EAT) has adverse effects in cardiovascular diseases, independent of BMI. Estrogen levels may affect EAT accumulation. Little is known about the predictors and potential impact of EAT in pulmonary arterial hypertension (PAH).Research QuestionIs EAT associated with estrogen levels, disease severity, and mortality in PAH?Study Design and MethodsWe conducted a retrospective cohort study of patients with PAH enrolled in the Penn Pulmonary Hypertension registry and used chest CT scans to quantify EAT. Serum estrone and estradiol levels were also measured.ResultsA total of 221 patients were included in the analysis, with median follow-up of 88 months. Mean age was 55.1 years, 74.7% were female, mean BMI was 27.20 kg/m2, and the most common PAH etiology was connective tissue disease-associated PAH (43.0%) followed by idiopathic or heritable PAH (35.3%). Median EAT volume was 52.1 mL/m2. Of the 102 patients with a follow-up chest CT scan, EAT increased over time in 74 (71.8%). High EAT volume (hazard ratio, 2.62; 95% CI, 1.62-4.24; P < .001) and greater accumulation of EAT over time (hazard ratio, 1.09; 95% CI, 1.01-1.17; P = .03) were both independently associated with worse survival. Patients with high EAT volume had lower serum estrone (13.70 vs 30.60 pg/mL; P = .009) and estradiol (6.05 vs 19.40 pg/mL; P = .002) levels compared with those with low EAT volume.InterpretationIn patients with PAH, high EAT and a greater rate of accumulation of EAT volume were independently associated with worse survival. Higher EAT volume was also associated with lower estrogen levels. The association of EAT volume with survival was independent of BMI and disease severity, suggesting that EAT may be a marker for a unique PAH phenotype. Future research should investigate the role of EAT-modifying therapies in PAH and consider incorporating EAT into PAH risk models
Negative sensitivity of Southern Ocean circumpolar transport to increased wind stress controlled by residual overturning
Get PDFThe transport of the Southern Ocean’s Antarctic Circumpolar Current, closely linked to the global stratification to the north and in turn the inter-hemispheric overturning circulation, is a key metric for quantifying ocean circulation. Understanding the sensitivity of transport to changes in forcing is important in understanding the role of the Southern Ocean in past, present and future climates. Here, we report on an investigation of a negative sensitivity regime, whereby the circumpolar transport decreases with increasing wind forcing, a phenomenon previously reported in ocean modelling investigations where the residual overturning circulation is oriented opposite to the present-day configuration. The present study finds that this negative sensitivity is a subtle effect resulting from both eddy saturation and a negative residual overturning circulation, the latter referring to a poleward mass flux in the warm surface layers. The work provides an examination and rationalisation of the sensitivities relating to the Southern Ocean circumpolar transport, and additionally touches on a numerical methodology that is particularly adept for the study of equilibrium sensitivities, with implications for analogous explorations in the paleoclimate context
Children, disasters, and place attachment:A contemporary framework for understanding crisis in context
Get PDFPurpose of Review: This article critically examines the disaster literature from the past three years (2022–2025) to evaluate the relationship between place attachment and children’s experience of disaster response and recovery. Recent Findings: Place attachment offers a systematic lens through which we comprehensively map our understanding of the factors that shape, and are shaped by, lived experience of disaster amongst children. We outline why specific consideration of children’s health and wellbeing is significant through this lens, and further consider place attachment in relation to factors identified across relevant bodies of literature. Findings are synthesized across three interdependent, cyclical dimensions: (1) disaster context, including type, location, infrastructure, and planning, (2) children’s holistic experiences of place attachment, including emotional, physical, cultural, and identity-based connections; and (3) disaster outcomes such as displacement, recovery, and rebuilding. Summary: We propose suggestions for future research, particularly emphasizing the need for an expanded evidence-based, conceptual framework that builds on the model presented in this paper. Clinical trial number: Not applicable.</p
Autism ableism seen through research abstract contents:A mixed-methods analysis of language in NIH-funded genetic and genomic autism research
Get PDFIn recent years, genetic and genomic autism research has come under increasing scrutiny, moving to the center of debates about ableism, neurodiversity, autism acceptance, and the future of research and care. At the same time, both autism research and genetics and genomics research have, as fields, begun to reckon with the significance of the language researchers use in the course of their work and the harmful ideas that may thereby be reinforced. Although the language of research cannot be assumed to straightforwardly correspond to individual researchers’ beliefs, the presence of widespread ableist language may indicate structural and institutionalized ableism, including ableist assumptions at the foundations of research. We conducted a mixed-methods analysis of 166 genetic and genomic autism research projects funded by the US National Institutes of Health, in order to understand the prevalence of potentially ableist discourse, language, and stigmatizing language about autistic people. We found that such discourse and language was ubiquitous across our sample, including a discourse of prevention. This study lends empirical evidence to current debates about language in autism research. Evaluating language can prompt researchers and institutions to reflect on how they conceptualize, design, discuss, and pursue their work. Lay abstract: Genetic research about autism is controversial. Researchers are starting to think more carefully about the words they use to talk about autism and the way they do their research. Past research has found that researchers sometimes write about autism in ableist ways. This means that they write about autistic people as though they are less important than nonautistic people. We looked at the way genetics researchers have written about autism in the paperwork for their research. We found that they often write about autistic people in an ableist way. We think that researchers should think carefully about the way they write about autistic people, and how they plan and do their research.</p
Inequality trends in general health among young people across the 2001, 2011, and 2021 UK Censuses
Get PDFBackgroundEvidence on health inequalities among young people is patchy compared to that among adults and younger children. This study examined the association between self-rated general health and a family’s socioeconomic position among 10-24 year olds.MethodsWe utilised 2001, 2011 and 2021 census microdata from England and Wales, and 2001 and 2011 data from Scotland. Descriptive methods were used to determine differences in general health status by sociodemographic variables, and logistic regression analysis to calculate the odds of reporting poor health according to the National Statistics Socio-economic Classification (NS-SEC) of the household reference person (HRP). Logistic regression models controlled for the effects of age, gender, household-level deprivation of education and housing, and UK region.ResultsWe observed the same socioeconomic patterning of health over the period of twenty years. All occupational groups had higher rates of poor health compared to the least disadvantaged group of young people. Compared to young people from households where the HRP belonged to the managerial or professional NS-SEC group, all other groups, except those self-employed in 2001, had greater odds of reporting poor health. The odds were highest among young people from households where the HRP had never worked or was long-term unemployed: 2.7 times in 2001, 3.1 times in 2011 and 3.6 times in 2021 (p<0.001).ConclusionsWe observed a similar social gradient of self-reported poor health across the 2001, 2011 and 2021 census datasets; as disadvantage increased, the share of young people with fair or poor health increased
Once again on evolution equations with monotone operators in Hilbert spaces and applications
Get PDFExistence, uniqueness and stability of the solutions of linear stochastic evolution equations are investigated. The results obtained are used to prove theorems on solvability of linear second order stochastic partial differential equations in Lp-setting with singular lower-order coefficients.</p
Preserving Centromere Identity: Right Amounts of CENP-A at the Right Place and Time
Get PDFFour decades ago, the discovery of centromere protein-A (CENP-A) marked a pivotal breakthrough in chromosome biology, revealing the epigenetic foundation of centromere identity. CENP-A, a histone H3 variant, directs the formation of the microtubule-binding kinetochore complex, designating the chromosomal site for its assembly and underpins the accurate partitioning of genetic material during cell division. Errors in cell division can give rise to DNA instability and aneuploidy, implicated in human diseases such as cancer. Therefore, discovering the underlying pathways and mechanisms responsible for the formation, regulation and maintenance of the centromere is important to our understanding of genome stability, epigenetic inheritance, and in providing the knowledge to help generate possible treatments and therapeutics. Here, we review various molecular pathways and mechanisms implicated in maintaining centromere identity and highlight some of the key outstanding questions with a focus on the human centromere
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