The HY5-PIF regulatory module coordinates light and temperature control of photosynthetic gene transcription

The ability to interpret daily and seasonal alterations in light and temperature signals is essential for plant survival. This is particularly important during seedling establishment when the phytochrome photoreceptors activate photosynthetic pigment production for photoautotrophic growth. Phytochromes accomplish this partly through the suppression of phytochrome interacting factors (PIFs), negative regulators of chlorophyll and carotenoid biosynthesis. While the bZIP transcription factor long hypocotyl 5 (HY5), a potent PIF antagonist, promotes photosynthetic pigment accumulation in response to light. Here we demonstrate that by directly targeting a common promoter cis-element (G-box), HY5 and PIFs form a dynamic activation-suppression transcriptional module responsive to light and temperature cues. This antagonistic regulatory module provides a simple, direct mechanism through which environmental change can redirect transcriptional control of genes required for photosynthesis and photoprotection. In the regulation of photopigment biosynthesis genes, HY5 and PIFs do not operate alone, but with the circadian clock. However, sudden changes in light or temperature conditions can trigger changes in HY5 and PIFs abundance that adjust the expression of common target genes to optimise photosynthetic performance and growth

Economic-demographic interactions in long-run growth

Cliometrics confirms that Malthus’ model of the pre-industrial economy, in which increases in productivity raise population but higher population drives down wages, is a good description for much of demographic/economic history. A contributor to the Malthusian equilibrium was the Western European Marriage Pattern, the late age of female first marriage, which promised to retard the fall of living standards by restricting fertility. The demographic transition and the transition from Malthusian economies to modern economic growth attracted many Cliometric models surveyed here. A popular model component is that lower levels of mortality over many centuries increased the returns to, or preference for, human capital investment so that technical progress eventually accelerated. This initially boosted birth rates and population growth accelerated. Fertility decline was earliest and most striking in late eighteenth century France. By the 1830s the fall in French marital fertility is consistent with a response to the rising opportunity cost of children. The rest of Europe did not begin to follow until end of the nineteenth century. Interactions between the economy and migration have been modelled with Cliometric structures closely related to those of natural increase and the economy. Wages were driven up by emigration from Europe and reduced in the economies receiving immigrants

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation

Use of the CONSIDER statement by eye health researchers when conducting and reporting research involving Indigenous peoples: an online survey

Background: Indigenous peoples experience worse eye health compared to non-Indigenous peoples. Service providers and researchers must avoid perpetuating this inequity. To help achieve this, researchers can use the CONSolIDated critERia for strengthening the reporting of health research involving Indigenous peoples (CONSIDER) statement. This study aimed to identify the degree to which the CONSIDER statement has been used by eye health researchers when conducting and reporting research with an Indigenous component, and how they perceive its relevance in their future research. Methods: We used purposive sampling to recruit eye health researchers from any country who have undertaken research with an Indigenous component. The online survey collected quantitative and qualitative data and was analysed using descriptive statistics and reflexive thematic analysis. Responses were gathered on a four-point Likert scale (1 to 4), with four being the most positive statement. Results: Thirty-nine eye health researchers from nine countries completed the survey (Aotearoa New Zealand, Argentina, Australia, Brazil, Canada, Colombia, Guatemala, Panama, Peru); almost two-thirds (n = 24) undertake epidemiological research. On average, participants disclosed only ‘sometimes’ previously reporting CONSIDER items (2.26 ± 1.14), but they thought the items were relevant to eye health research and were motivated to use these guidelines in their future research. Some participants requested clarity about how CONSIDER aligned with existing guidelines, and when and how to apply the statement. Others shared rich experiences of the benefits to their research of Indigenous leadership and collaboration. Conclusions: The CONSIDER statement is perceived as a valuable tool by these eye health researchers, and there are opportunities to maximise uptake and use, including increasing awareness of the statement, clarity about when it applies, and availability of institutional-level support

Burnout among chiropractic practitioners: real or imagined an exploratory study protocol

Burnout is a psychological syndrome of emotional exhaustion, depersonalization and reduced personal accomplishment that has been found to exist in a significant number of healthcare and helping professionals. It imposes a significant societal burden by shortened practitioner lifespan, decreased efficiency, negative health outcomes and poorer levels of patient care. Theoretical models suggest that it appears to be the result of a complex interaction between job resources and job demands. It may be reasonable to conclude that Chiropractic professionals experience similar vocational demands and thus experience significant levels of occupational stress and subsequent burnout. However the data on burnout within the chiropractic profession is limited. It is possible that this results in significant negative outcomes on chiropractors and their patients. Therefore, the objective of this paper is to demonstrate the need to explore burnout in chiropractic practice and offer a research protocol for a potential study

Cluster analysis in severe emphysema subjects using phenotype and genotype data: an exploratory investigation

Background: Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity. Methods: We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster. Results: We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1) post-bronchodilator FEV1 percent predicted, 2) percent bronchodilator responsiveness, and quantitative CT measurements of 3) apical emphysema and 4) airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1) emphysema predominant, 2) bronchodilator responsive, with higher FEV1; 3) discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4) airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant) was associated with TGFB1 SNP rs1800470. Conclusions: Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies

Capsaicin- resistant arterial baroreceptors

BACKGROUND: Aortic baroreceptors (BRs) comprise a class of cranial afferents arising from major arteries closest to the heart whose axons form the aortic depressor nerve. BRs are mechanoreceptors that are largely devoted to cardiovascular autonomic reflexes. Such cranial afferents have either lightly myelinated (A-type) or non-myelinated (C-type) axons and share remarkable cellular similarities to spinal primary afferent neurons. Our goal was to test whether vanilloid receptor (TRPV1) agonists, capsaicin (CAP) and resiniferatoxin (RTX), altered the pressure-discharge properties of peripheral aortic BRs. RESULTS: Periaxonal application of 1 μM CAP decreased the amplitude of the C-wave in the compound action potential conducting at <1 m/sec along the aortic depressor nerve. 10 μM CAP eliminated the C-wave while leaving intact the A-wave conducting in the A-δ range (<12 m/sec). These whole nerve results suggest that TRPV1 receptors are expressed along the axons of C- but not A-conducting BR axons. In an aortic arch – aortic nerve preparation, intralumenal perfusion with 1 μM CAP had no effect on the pressure-discharge relations of regularly discharging, single fiber BRs (A-type) – including the pressure threshold, sensitivity, frequency at threshold, or maximum discharge frequency (n = 8, p > 0.50) but completely inhibited discharge of an irregularly discharging BR (C-type). CAP at high concentrations (10–100 μM) depressed BR sensitivity in regularly discharging BRs, an effect attributed to non-specific actions. RTX (≤ 10 μM) did not affect the discharge properties of regularly discharging BRs (n = 7, p > 0.18). A CAP-sensitive BR had significantly lower discharge regularity expressed as the coefficient of variation than the CAP-resistant fibers (p < 0.002). CONCLUSION: We conclude that functional TRPV1 channels are present in C-type but not A-type (A-δ) myelinated aortic arch BRs. CAP has nonspecific inhibitory actions that are unlikely to be related to TRV1 binding since such effects were absent with the highly specific TRPV1 agonist RTX. Thus, CAP must be used with caution at very high concentrations

How can chiropractic become a respected mainstream profession? The example of podiatry

<p>Abstract</p> <p>Background</p> <p>The chiropractic profession has succeeded to remain in existence for over 110 years despite the fact that many other professions which had their start at around the same time as chiropractic have disappeared. Despite chiropractic's longevity, the profession has not succeeded in establishing cultural authority and respect within mainstream society, and its market share is dwindling. In the meantime, the podiatric medical profession, during approximately the same time period, has been far more successful in developing itself into a respected profession that is well integrated into mainstream health care and society.</p> <p>Objective</p> <p>To present a perspective on the current state of the chiropractic profession and to make recommendations as to how the profession can look to the podiatric medical profession as a model for how a non-allopathic healthcare profession can establish mainstream integration and cultural authority.</p> <p>Discussion</p> <p>There are several key areas in which the podiatric medical profession has succeeded and in which the chiropractic profession has not. The authors contend that it is in these key areas that changes must be made in order for our profession to overcome its shrinking market share and its present low status amongst healthcare professions. These areas include public health, education, identity and professionalism.</p> <p>Conclusion</p> <p>The chiropractic profession has great promise in terms of its potential contribution to society and the potential for its members to realize the benefits that come from being involved in a mainstream, respected and highly utilized professional group. However, there are several changes that must be made within the profession if it is going to fulfill this promise. Several lessons can be learned from the podiatric medical profession in this effort.</p