Iron metabolism and biomarkers in idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disease characterised by increased vascular resistance and remodelling of the pulmonary vasculature. This causes strain on the right ventricle, leading eventually to failure and death. Iron status is thought to influence pulmonary vascular tone, particularly in hypoxia, and may be important in IPAH. Proteomic studies of lung tissues from IPAH patients versus control lobectomy samples revealed downregulated levels of the haemoglobin- and haem-scavenging proteins haptoglobin (Hp) and haemopexin. Plasma levels of Hp were also reduced in IPAH and related to the Hp genotype. Consistently low Hp levels were associated with dysregulated iron homeostasis in IPAH patients. Iron deficiency, as defined by raised plasma soluble transferrin receptor (sTfR) levels, was prevalent in IPAH patients and related to increased levels of the master iron regulator hepcidin. Iron deficiency was also associated with poor exercise capacity, disease progression and mortality. Circulating sTfR levels were compared against other iron-related and established prognostic biomarkers in IPAH, including N-terminal brain natriuretic peptide (NT-proBNP), red cell distribution width (RDW), growth differentiation factor-15 and interleukin-6. All predicted survival and related to disease severity in IPAH, but RDW and NT-proBNP provided the most information when clinical and haemodynamic indices were considered. Dysfunctional bone morphogenetic protein (BMP) receptor type II (BMPR2) signalling contributes to idiopathic as well as heritable PAH. Downregulation of BMPR2, but not the other type II BMP receptors ActRIIA and ActRIIB, led to increased hepcidin expression and secretion in response to BMP-6 stimulation in hepatocellular carcinoma HepG2 cells. Hepcidin expression was also enhanced in rat lung tissue following 1 or 2 weeks exposure to hypoxia. In conclusion, dysregulation of iron homeostasis is common in IPAH and appears to be important clinically. Increased hepcidin levels may contribute to this phenomenon and reflect the dysfunctional BMPR2 signalling associated with the disease

Evangelical violence: Western Christianity and the use of force against the Third World

Accepted manuscrip

A comparison of traffic, parking, and pedestrian control strategies for universities on football gamedays

In recent years, fan support and interest in division I-A college football has increased. Increased attendance, financial support from donors and alumni, and the commercialization of college football programs have transcended to the building of larger stadiums or additions to existing structures. This increase in stadium capacity in turn relates to an increase in traffic congestion on campus, a greater demand for nearby parking, and escalation in pedestrian movement adjacent to the stadium. Due to these aforementioned items university officials, police departments, and traffic engineers have implemented different plans to manage vehicular and pedestrian traffic along with parking demands for numerous football facilities throughout the nation. This study focused on identifying and analyzing what procedures are effective to manage traffic, pedestrians, and parking on a selected number of college campuses as well as strategies that have proven to be inadequate. In a national survey, 110 university police chiefs and university parking administrators were asked to assess their gameday traffic, pedestrian, and parking plan for their respective campus. From these surveys, an extensive list of tools and strategies for gameday traffic management was developed. Data were also compiled to illustrate which strategies have proven to be effective and ineffective for varying university types (public or private), stadium location, and whether the stadium is an on- or off-campus facility

Can Ecological Interactions be Inferred from Spatial Data?

The characterisation and quantication of ecological interactions, and the construction of species distributions and their associated ecological niches, is of fundamental theoretical and practical importance. In this paper we give an overview of a Bayesian inference framework, developed over the last 10 years, which, using spatial data, offers a general formalism within which ecological interactions may be characterised and quantied. Interactions are identied through deviations of the spatial distribution of co-occurrences of spatial variables relative to a benchmark for the non-interacting system, and based on a statistical ensemble of spatial cells. The formalism allows for the integration of both biotic and abiotic factors of arbitrary resolution. We concentrate on the conceptual and mathematical underpinnings of the formalism, showing how, using the Naive Bayes approximation, it can be used to not only compare and contrast the relative contribution from each variable, but also to construct species distributions and niches based on arbitrary variable type. We show how the formalism can be used to quantify confounding and therefore help disentangle the complex causal chains that are present in ecosystems. We also show species distributions and their associated niches can be used to infer standard "micro" ecological interactions, such as predation and parasitism. We present several representative use cases that validate our framework, both in terms of being consistent with present knowledge of a set of known interactions, as well as making and validating predictions about new, previously unknown interactions in the case of zoonoses

Retaining leadership talent in schools

En este artículo nos centramos en la retención del talento de liderazgo como un componente de las soluciones locales para la sucesión del liderazgo y la gestión del talento en un contexto inglés y a partir de ahí, extraer conclusiones aplicables a diferentes contextos internacionales para aquellos que tratan de asegurar un suministro de líderes escolares de alta calidad. El artículo explora las percepciones de 70 directores, 191 líderes de nivel medio y 168 docentes provenientes de 70 escuelas primarias y secundarias en diferentes contextos en las Midlands y el noroeste de Inglaterra, mediante grupos focales y un cuestionario. Se pidió a los encuestados que informaran sobre los enfoques actuales de retención del talento de liderazgo en sus escuelas y la forma en que perciben si su administración local podría involucrarse más en la retención del talento de liderazgo. El artículo incluye también una entrevista en profundidad con un alto cargo responsable del desarrollo y retención del liderazgo de una gran administración ubicada en la región central de Inglaterra. Se sugiere que los propósitos nacionales y locales para aumentar las reservas de talento de liderazgo y retener a los líderes de alta calidad para el presente y para el futuro, deben tener en cuenta la inclusión y el flujo de individuos capaces de progresar a puestos clave de liderazgo que son difíciles de reemplazar, y que una estrategia enfocada a la creación de talento ligada a una visión del desarrollo, la mejora y el rendimiento de la escuela, puede representar una forma ideal de ir hacia adelanteIn this article we focus on leadership talent retention as a component of local solutions to leadership succession and talent management in an English context and then draw conclusions relevant to those seeking to ensure a supply of high-quality school leaders in a variety of international settings. Utilising focus groups and a questionnaire survey, the article explores the perceptions of 70 heads, 191 middle leaders and 168 classroom teachers drawn from 70 contextually different primary and secondary schools in the Midlands and north west of England. Respondents were asked to report on current approaches to retaining leadership talent in their schools and how they perceived that their local authority could become more helpfully involved in leadership talent retention. The article also includes an extended interview with a senior officer in charge of leadership development and retention from a large local authority located in the Midlands of England. It is suggested that national and local desires to grow leadership talent pools and retain high-quality leaders for now and for the future should take into account the inclusion and flow of individuals capable of progressing to key leadership positions that are difficult to replace and that a strategic approach to talent pool creation linked with a strategic view of the development, improvement and performance of the school could represent an ideal way forwar

Evolutionary Entropy Determines Invasion Success in Emergent Epidemics

Background: Standard epidemiological theory claims that in structured populations competition between multiple pathogen strains is a deterministic process which is mediated by the basic reproduction number (R0) of the individual strains. A new theory based on analysis, simulation and empirical study challenges this predictor of success. Principal Findings: We show that the quantity R0 is a valid predictor in structured populations only when size is infinite. In this article we show that when population size is finite the dynamics of infection by multi-strain pathogens is a stochastic process whose outcome can be predicted by evolutionary entropy, S, an information theoretic measure which describes the uncertainty in the infectious age of an infected parent of a randomly chosen new infective. Evolutionary entropy characterises the demographic stability or robustness of the population of infectives. This statistical parameter determines the duration of infection and thus provides a quantitative index of the pathogenicity of a strain. Standard epidemiological theory based on R0 as a measure of selective advantage is the limit as the population size tends to infinity of the entropic selection theory. The standard model is an approximation to the entropic selection theory whose validity increases with population size. Conclusion: An epidemiological analysis based on entropy is shown to explain empirical observations regarding the emergence of less pathogenic strains of human influenza during the antigenic drift phase. Furthermore, we exploit th

Regional differences in store-operated Ca2+ entry in the epithelium of the intact human lens

An elevated level of Ca2+ is an important factor in cataract, yet precisely how Ca2+ enters the lens is unknown. Lens epithelial cells contain a range of G-protein–coupled receptors and receptor tyrosine kinases that induce increases in intracellular Ca2+. Receptor-associated Ca2+ influx is, therefore, likely to be an important route for Ca2+ influx to the lens. The authors investigated stimulated and passive Ca2+ influx in in situ human lens epithelium. Ca2+ changes in equatorial (E) and central anterior (CA) epithelial cells were monitored with the use of a Ca2+ indicator (Fluo4) and confocal microscopy. Gene expression was monitored by RT-PCR and immunoblotting. Adenosine triphosphate (ATP) induced Ca2+ responses that were smaller in CA than E. Ca2+ store depletion, using ATP (100 µM) or thapsigargin (1 µM), revealed greater relative store capacity and Ca2+ influx in E. Ca2+ influx was blocked by La3+ (0.5 µM) in both regions. Unstimulated Ca2+ influx was greater in E than CA. Greater expression of Orai1 and STIM1 was detected in E than in CA. Greater Ca2+ store capacity and Ca2+ influx in E compared with CA reflects underlying differences in proliferation and differentiation between the regions. The relatively small resting Ca2+ influx in CA epithelium suggests that store-operated Ca2+ entry (SOCE) is the main route of Ca2+ influx in these cells. Greater resting influx and SOCE in E cells suggests that these are a major route for Ca2+ influx into the lens. Increased expression of Orai1 and STIM1 in E could account for the differences in Ca2+ entry. Receptor activation will modulate Ca2+ influx, and inappropriate activity may contribute to cortical cataract