`c' is the speed of light, isn't it?

Theories proposing a varying speed of light have recently been widely promoted under the claim that they offer an alternative way of solving the standard cosmological problems. Recent observational hints that the fine structure constant may have varied during over cosmological scales also has given impetus to these models. In theoretical physics the speed of light, $c$, is hidden in almost all equations but with different facets that we try to distinguish. Together with a reminder on scalar-tensor theories of gravity, this sheds some light on these proposed varying speed of light theories.Comment: 14 pages, Late

HPV Vaccination in the Virginia Context: Demographic Disparities, Patient-Provider Gender Concordance and the Impact of Changing Recommendations

Objective: Despite its effectiveness in preventing several cancers, there are marked disparities in HPV vaccination initiation and series completion. The present study sought to understand disparities in HPV vaccinations among patients in northern Virginia (ages 9-26) and the impact of patient and provider gender concordance, in lieu of CDC’s vaccine recommendation changes in 2016, which reduced the recommended doses from three to two, in this population. Design: Analyses of electronic medical records collected from 2012 to 2017. Setting: A large health care system in Northern Virginia. Participants: A total of 37,427 patients, ages 9 to 26, were included in analyses. Main outcome measures: We examined odds of initiating vaccination, completing vaccination at 6 months, completing vaccination at 12 months and clinical completion. We examined if patient and provider characteristics were associated with initiating vaccination and vaccination completion at different durations. Results: Racial minorities had higher odds of getting vaccinated, relative to non-Latino whites. Each additional year between the patient’s first and last visit was associated with higher odds of initiating vaccination, completing vaccination at both 6 and 12 months, and clinical completion. Compared to female patients who were 19 years and older, female patients aged 9-18 years had higher odds of initiating vaccination and clinical completion. Compared to male patients who were 19 years and older, female patients aged 9-18 years had higher odds of clinical completion Female and male patients had better outcomes when seen by female primary care providers than male primary care providers. Conclusions and Relevance: Further research should investigate the observed benefit of female providers and to understand the long-term impact of changes in CDC recommendations

Cardiopulmonary phenotype associated with human PHD2 mutation.

Oxygen-dependent regulation of the erythropoietin gene is mediated by the hypoxia-inducible factor (HIF) family of transcription factors. When oxygen is plentiful, HIF undergoes hydroxylation by a family of oxygen-dependent prolyl hydroxylase domain (PHD) proteins, promoting its association with the von Hippel-Lindau (VHL) ubiquitin E3 ligase and subsequent proteosomal degradation. When oxygen is scarce, the PHD enzymes are inactivated, leading to HIF accumulation and upregulation not only of erythropoietin expression, but also the expression of hundreds of other genes, including those coordinating cardiovascular and ventilatory adaptation to hypoxia. Nevertheless, despite the identification of over 50 mutations in the PHD-HIF-VHL pathway in patients with previously unexplained congenital erythrocytosis, there are very few reports of associated cardiopulmonary abnormalities. We now report exaggerated pulmonary vascular and ventilatory responses to acute hypoxia in a 35-year-old man with erythrocytosis secondary to heterozygous mutation in PHD2, the most abundant of the PHD isoforms. We compare this phenotype with that reported in patients with the archetypal disorder of cellular oxygen sensing, Chuvash polycythemia, and discuss the possible clinical implications of our findings, particularly in the light of the emerging role for small molecule PHD inhibitors in clinical practice

Manacled to Identity: Cosmopolitanism, Class, and ‘The Culture Concept’ in Stephen Crane

This article begins with a close reading of Stephen Crane’s short story ‘Manacled’ from 1900, which situates this rarely considered short work within the context of contemporary debates about realism. I then proceed to argue that many of the debates raised by the tale have an afterlife in our own era of American literary studies, which has frequently focused on questions of ‘identity’ and ‘culture’ in its reading of realism and naturalism to the exclusion of the importance of cosmopolitan discourses of diffusion and exchange across national borders. I then offer a brief reading of Crane’s novel George’s Mother, which follows Walter Benn Michaels in suggesting that the recent critical attention paid to particularities of cultural difference in American studies have come to conflate ideas of class and social position with ideas of culture in ways that have ultimately obscured the presence of genuine historical inequalities in US society. In order to challenge this critical commonplace, I situate Crane’s work within a history of transatlantic cosmopolitanism associated with the ideas of Franz Boas and Matthew Arnold to demonstrate the ways in which Crane’s narratives sought out an experience of the universal within their treatments of the particular

Assessment of quality of obstetric care in Zimbabwe using the standard primipara

Background To improve maternity services in any country, there is need to monitor the quality of obstetric care. There is usually disparity of obstetric care and outcomes in most countries among women giving birth in different obstetric units. However, comparing the quality of obstetric care is difficult because of heterogeneous population characteristics and the difference in prevalence of complications. The concept of the standard primipara was introduced as a tool to control for these various confounding factors. This concept was used to compare the quality of obstetric care among districts in different geographical locations in Zimbabwe. Methods This was a substudy of the Zimbabwe Maternal and Perinatal Mortality Study. In the main study, cluster sampling was done with the provinces as clusters and 11 districts were randomly selected with one from each of the nine provinces and two from the largest province. This database was used to identify the standard primipara defined as; a woman in her first pregnancy without any known complications who has spontaneous onset of labour at term. Obstetric process and outcome indicators of the standard primipara were then used to compare the quality of care between rural and urban, across rural and across urban districts of Zimbabwe. Results A total of 45,240 births were recruited in the main study and 10,947 women met the definition of standard primipara. The maternal mortality ratio (MMR) and the perinatal mortality rate (PNMR) for the standard primiparae were 92/100000 live births and 15.4/1000 total births respectively. Compared to urban districts, the PNMR was higher in the rural districts (11/1000 total births vs 19/ 1000 total births, p < 0.001). In the urban to urban and rural to rural districts comparison, there were significant differences in most of the process indicators, but not in the PNMR. Conclusions The study has shown that the standard primipara can be used as a tool to measure and compare the quality of obstetric care in districts in different geographical areas. There is need to explore further how the quality of obstetric care can be improved in rural districts of Zimbabwe

The Qualitative Method of Impact Analysis

Consider the qualitative approach to evaluation design (as opposed to measurement) to be typified by a case study with a sample of just one. Although there have certainly been elaborate and emphatic defenses of the qualitative approach to program evaluation, such defenses rarely attempt to qualify the approach explicitly and rigorously as a method of impact analysis. The present paper makes that attempt. The problem with seeking to advance a qualitative method of impact analysis is that impact is a matter of causation and a non-quantitative approach to design is apparently not well suited to the task of establishing causal relations. The root of the difficulty is located in the counterfactual definition of causality, which is our only broadly accepted formal definition of causality for social science. It is not, however, the only definition we use informally. Another definition, labeled “physical causality,” is widely used in practice and has recently been formalized. Physical causality can be applied to the present problem. For example, it explains the persuasiveness of Striven’s “Modus Operandi” approach tailored case study design with a sample size of one in principle as strong a basis for making inferences program impact as a randomized experiment. Crucial program evaluation finding that people’s “operative reasons” for doing what they do are the physical actions. it is shown that external validity using this qualitative approach would have exceptional strengths.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67113/2/10.1177_109821409902000106.pd

The Mechanism of Flecainide Action in CPVT Does Not Involve a Direct Effect on RyR2

Rationale: Flecainide, a class 1c antiarrhythmic, has emerged as an effective therapy in preventing arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) refractory to β-adrenergic receptor blockade. It has been proposed that the clinical efficacy of flecainide in CPVT is because of the combined actions of direct blockade of ryanodine receptors (RyR2) and Na+ channel inhibition. However, there is presently no direct evidence to support the notion that flecainide blocks RyR2 Ca2+ flux in the physiologically relevant (luminal-to-cytoplasmic) direction. The mechanism of flecainide action remains controversial. Objective: To examine, in detail, the effect of flecainide on the human RyR2 channel and to establish whether the direct blockade of physiologically relevant RyR2 ion flow by the drug contributes to its therapeutic efficacy in the clinical management of CPVT. Methods and Results: Using single-channel analysis, we show that, even at supraphysiological concentrations, flecainide did not inhibit the physiologically relevant, luminal-to-cytosolic flux of cations through the channel. Moreover, flecainide did not alter RyR2 channel gating and had negligible effect on the mechanisms responsible for the sarcoplasmic reticulum charge-compensating counter current. Using permeabilized cardiac myocytes to eliminate any contribution of plasmalemmal Na+ channels to the observed actions of the drug at the cellular level, flecainide did not inhibit RyR2-dependent sarcoplasmic reticulum Ca2+ release. Conclusions: The principal action of flecainide in CPVT is not via a direct interaction with RyR2. Our data support a model of flecainide action in which Na+-dependent modulation of intracellular Ca2+ handling attenuates RyR2 dysfunction in CPVT

Genomic and molecular characterization of preterm birth.

Preterm birth (PTB) complications are the leading cause of long-term morbidity and mortality in children. By using whole blood samples, we integrated whole-genome sequencing (WGS), RNA sequencing (RNA-seq), and DNA methylation data for 270 PTB and 521 control families. We analyzed this combined dataset to identify genomic variants associated with PTB and secondary analyses to identify variants associated with very early PTB (VEPTB) as well as other subcategories of disease that may contribute to PTB. We identified differentially expressed genes (DEGs) and methylated genomic loci and performed expression and methylation quantitative trait loci analyses to link genomic variants to these expression and methylation changes. We performed enrichment tests to identify overlaps between new and known PTB candidate gene systems. We identified 160 significant genomic variants associated with PTB-related phenotypes. The most significant variants, DEGs, and differentially methylated loci were associated with VEPTB. Integration of all data types identified a set of 72 candidate biomarker genes for VEPTB, encompassing genes and those previously associated with PTB. Notably, PTB-associated genes RAB31 and RBPJ were identified by all three data types (WGS, RNA-seq, and methylation). Pathways associated with VEPTB include EGFR and prolactin signaling pathways, inflammation- and immunity-related pathways, chemokine signaling, IFN-γ signaling, and Notch1 signaling. Progress in identifying molecular components of a complex disease is aided by integrated analyses of multiple molecular data types and clinical data. With these data, and by stratifying PTB by subphenotype, we have identified associations between VEPTB and the underlying biology

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179