168 research outputs found

    Optimism in Independence: The European Central Bank after the 2008 Global Financial Crisis

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    The effects of the 2008 Global Financial Crisis (GFC) on finance and monetary policy continue to be widespread. Now, policymakers are seeking to determine the best approach for managing and resolving the crisis; one such strategy has been to delegate more legitimacy to independent central banks. When will a political leader support or undermine the legitimacy of an independent central bank in the aftermath of an economic crisis? We argue that the central mechanism for determining a change in views of central bank legitimacy is the optimism of the political elites. Therefore, if a government is optimistic about its chances of retaining power and securing economic recovery, it will be more likely to issue positive, legitimizing statements toward its independent central bank. We test this argument using the compelling and critically important case of the European Central Bank following the 2008 Global Financial Crisis, and we determine that the level of political optimism has a strong impact on the continued legitimacy of independent central banks. In so doing, our study highlights the complicated strategic political choice of using central banks to respond to financial crises

    Interventional Radiology Readiness Assessment Tool for Global Health

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    The Interventional Radiology Readiness Assessment Tool for Global Health is a new tool to methodically evaluate the environment of a medical institution for interventional radiology services given the existing infrastructure. Global health provides an exciting opportunity for interventional radiology to impact health outcomes in developing countries. A systematic and thoughtful approach to integrating interventional radiology services in the health care institutions of resource poor countries is needed in order to maximize global health efforts and outcomes. The IR Readiness Assessment Tool is available as on online form and in PDF format under Additional Files below

    Identification of a novel loss-of-function PHEX mutation, Ala720Ser, in a sporadic case of adult-onset hypophosphatemic osteomalacia

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    Adults presenting with sporadic hypophosphatemia and elevations in circulating fibroblast growth factor-23 (FGF23) concentrations are usually investigated for an acquired disorder of FGF23 excess such as tumor induced osteomalacia (TIO). However, in some cases the underlying tumor is not detected, and such patients may harbor other causes of FGF23 excess. Indeed, coding-region and 3’UTR mutations of phosphate-regulating neutral endopeptidase (PHEX), which encodes a cell-surface protein that regulates circulating FGF23 concentrations, can lead to alterations in phosphate homeostasis, which are not detected until adulthood. Here, we report an adult female who presented with hypophosphatemic osteomalacia and raised serum FGF23 concentrations. The patient and her parents, who were her only first-degree relatives, had no history of rickets. The patient was thus suspected of having TIO. However, no tumor had been identified following extensive localization studies. Mutational analysis of the PHEX coding-region and 3’UTR was undertaken, and this revealed the patient to be heterozygous for a novel germline PHEX mutation (c.2158G>T; p.Ala720Ser). In vitro studies involving the expression of WT and mutant PHEX proteins in HEK293 cells demonstrated the Ala720Ser mutation to impair trafficking of PHEX, with 80% cell surface expression for WT PHEX (p<0.05). Thus, our studies have identified a pathogenic PHEX mutation in a sporadic case of adult-onset hypophosphatemic osteomalacia, and these findings highlight a role for PHEX gene analysis in some cases of suspected TIO, particularly when no tumor has been identified

    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

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    Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

    The design of a community lifestyle programme to improve the physical and psychological well-being of pregnant women with a BMI of 30 kg/m2 or more

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    <p>Abstract</p> <p>Background</p> <p>Obesity is a global public health issue. Having a BMI of 30 kg/m<sup>2 </sup>or more (classifying a person as obese) at the start of pregnancy is a significant risk factor for maternal and fetal morbidity. There is a dearth of evidence to inform suitable inteventions to support pregnant women with a BMI of 30 kg/m<sup>2 </sup>or more. Here we describe a study protocol to test the feasibility of a variety of potential healthy lifestyle interventions for pregnant women with a BMI of 30 kg/m<sup>2 </sup>or more in a community based programme.</p> <p>Methods/Design</p> <p>Four hundred women will be approached to attend a 10-week community lifestyle programme. The programme will be provided as a supplement to standard antenatal care. The programme is multi-faceted, aimed at equipping participants with the skills and knowledge needed to adopt healthy behaviours. The social (cognitive) learning theory will be used as a tool to encourage behaviour change, the behaviour change techniques are underpinned by five theoretical components; self-efficacy, outcome expectancies, goal setting, feedback and positive reinforcement.</p> <p>The main outcomes are pregnancy weight gain and caesarean section rate. Other important outcomes include clinical outcomes (e.g., birth weight) and psychological outcomes (e.g., well-being). Secondary outcomes include women's experience of pregnancy and health care services, amount of physical activity, food intake and the suitability of the intervention components.</p> <p>A prospective study using quantitative and qualitative methods will inform the feasibility of implementing the community lifestyle programme with pregnant women with a BMI of 30 kg/m<sup>2 </sup>or more. Mixed methods of data collection will be used, including diaries, focus groups/interviews, pedometers, validated and specifically designed questionnaires, a programme register, weight gain during pregnancy and perinatal outcome data.</p> <p>Discussion</p> <p>Findings from this current feasibility study will inform future interventions and NHS services and add to the evidence-base by providing information about the experiences of pregnant women with a BMI of 30 kg/m<sup>2 </sup>or more undertaking a community lifestyle programme. The study will lead on to a randomised control trial of a suitable intervention to improve the pregnancy outcomes of this target group.</p> <p>Trail Registration</p> <p>ISRCTN29860479.</p

    How Influential Are Medical School Curriculum and Other Medical School Characteristics in Students’ Selecting Pathology as a Specialty?

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    There has been a significant decline in the number of United States allopathic medical students matching to pathology residency programs. Data acquired from the American Association of Medical Colleges (AAMC) show sustained variation in the medical school production of students who go on to pathology residency. When divided into groups based on the medical school\u27s historical volume of graduates entering pathology, the schools in groups labeled Group 1 and Group 2 produced significantly higher and lower proportions of pathology residents, respectively. This study aimed to identify what medical school curriculum elements and other medical school characteristics might explain the differences observed in the AAMC data. The Dean or another undergraduate medical education contact from the Group 1 and Group 2 schools was invited to participate in an interview. Pathology Program Directors and Pathology Department Chairs were also included in communications. Thirty interviews were completed with equal numbers from each group. Interview questions probed pathology experiences, existence, and structure of a pathology interest group, options for post-sophomore fellowships, recent curriculum changes, and the extent of mentoring programs. Surprisingly, the curriculum does not appear to be a predictor of a medical school\u27s production of students who enter pathology residency. A significantly greater percentage of Group 1 schools are public institutions compared to Group 2 schools. Other factors that may increase the number of students who go into pathology include mentoring, active learning versus observation, and post-sophomore fellowships or other opportunities to work in the capacity of a new pathology resident

    The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

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    Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients

    Geological interpretation of volcanism and segmentation of the Mariana back-arc spreading center between 12.7°N and 18.3°N

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    The relationships between tectonic processes, magmatism, and hydrothermal venting along ∼600 km of the slow-spreading Mariana back-arc between 12.7°N and 18.3°N reveal a number of similarities and differences compared to slow-spreading mid-ocean ridges. Analysis of the volcanic geomorphology and structure highlights the complexity of the back-arc spreading center. Here, ridge segmentation is controlled by large-scale basement structures that appear to predate back-arc rifting. These structures also control the orientation of the chains of cross-arc volcanoes that characterize this region. Segment-scale faulting is oriented perpendicular to the spreading direction, allowing precise spreading directions to be determined. Four morphologically distinct segment types are identified: dominantly magmatic segments (Type I); magmatic segments currently undergoing tectonic extension (Type II); dominantly tectonic segments (Type III); and tectonic segments currently undergoing magmatic extension (Type IV). Variations in axial morphology (including eruption styles, neovolcanic eruption volumes, and faulting) reflect magma supply, which is locally enhanced by cross-arc volcanism associated with N-S compression along the 16.5°N and 17.0°N segments. In contrast, cross-arc seismicity is associated with N-S extension and increased faulting along the 14.5°N segment, with structures that are interpreted to be oceanic core complexes—the first with high-resolution bathymetry described in an active back-arc basin. Hydrothermal venting associated with recent magmatism has been discovered along all segment types

    Perceptual and conceptual processing of visual objects across the adult lifespan

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    Abstract: Making sense of the external world is vital for multiple domains of cognition, and so it is crucial that object recognition is maintained across the lifespan. We investigated age differences in perceptual and conceptual processing of visual objects in a population-derived sample of 85 healthy adults (24–87 years old) by relating measures of object processing to cognition across the lifespan. Magnetoencephalography (MEG) was recorded during a picture naming task to provide a direct measure of neural activity, that is not confounded by age-related vascular changes. Multiple linear regression was used to estimate neural responsivity for each individual, namely the capacity to represent visual or semantic information relating to the pictures. We find that the capacity to represent semantic information is linked to higher naming accuracy, a measure of task-specific performance. In mature adults, the capacity to represent semantic information also correlated with higher levels of fluid intelligence, reflecting domain-general performance. In contrast, the latency of visual processing did not relate to measures of cognition. These results indicate that neural responsivity measures relate to naming accuracy and fluid intelligence. We propose that maintaining neural responsivity in older age confers benefits in task-related and domain-general cognitive processes, supporting the brain maintenance view of healthy cognitive ageing
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