Targeted Metabolomics for Clinical Biomarker Discovery in Multifactorial Diseases

Diseases & disorder

"I'd been like freaking out the whole night": exploring emotion regulation based on junior doctors' narratives

The importance of emotions within medical practice is well documented. Research suggests that how clinicians deal with negative emotions can affect clinical decision-making, health service delivery, clinician well-being, attentiveness to patient care and patient satisfaction. Previous research has identified the transition from student to junior doctor (intern) as a particularly challenging time. While many studies have highlighted the presence of emotions during this transition, how junior doctors manage emotions has rarely been considered. We conducted a secondary analysis of narrative data in which 34 junior doctors, within a few months of transitioning into practice, talked about situations for which they felt prepared or unprepared for practice (preparedness narratives) through audio diaries and interviews. We examined these data deductively (using Gross’ theory of emotion regulation: ER) and inductively to answer the following research questions: (RQ1) what ER strategies do junior doctors describe in their preparedness narratives? and (RQ2) at what point in the clinical situation are these strategies narrated? We identified 406 personal incident narratives: 243 (60%) contained negative emotion, with 86 (21%) also containing ER. Overall, we identified 137 ER strategies, occurring prior to (n = 29, 21%), during (n = 74, 54%) and after (n = 34, 25%) the situation. Although Gross’ theory captured many of the ER strategies used by junior doctors, we identify further ways in which this model can be adapted to fully capture the range of ER strategies participants employed. Further, from our analysis, we believe that raising medical students

Personalized ovarian stimulation for assisted reproductive technology : study design considerations to move from hype to added value for patients

Peer reviewedPublisher PD

8th Biennial Midwest/Midsouth Bankruptcy Institute

Materials from the 8th Biennial Midwest/Midsouth Bankruptcy Institute held December 1997

Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules

Celiac disease is caused by an abnormal intestinal T-cell response to gluten proteins of wheat, barley and rye. Over the last few years, a number of gluten T-cell epitopes restricted by celiac disease associated HLA-DQ molecules have been characterized. In this work, we give an overview of these epitopes and suggest a comprehensive, new nomenclature

Sudden cardiac death due to deficiency of the mitochondrial inorganic pyrophosphatase PPA2

We have used whole exome sequencing to identify biallelic missense mutations in the nuclearencoded mitochondrial inorganic pyrophosphatase (PPA2) in ten individuals from four unrelated pedigrees that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis and cardiac arrhythmia and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutated PPA2 containing mitochondria from fibroblasts showed the activity of inorganic pyrophosphatase significantly reduced in affected individuals. Recombinant PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated with disease severity. These findings confirm the pathogenicity of PPA2 mutations, and suggest that PPA2 is a new cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Impacts of Warming and Acidification on Coral Calcification Linked to Photosymbiont Loss and Deregulation of Calcifying Fluid pH

Corals are globally important calcifiers that exhibit complex responses to anthropogenic warming and acidification. Although coral calcification is supported by high seawater pH, photosynthesis by the algal symbionts of zooxanthellate corals can be promoted by elevated pCO2. To investigate the mechanisms underlying corals’ complex responses to global change, three species of tropical zooxanthellate corals (Stylophora pistillata, Pocillopora damicornis, and Seriatopora hystrix) and one species of asymbiotic cold-water coral (Desmophyllum pertusum, syn. Lophelia pertusa) were cultured under a range of ocean acidification and warming scenarios. Under control temperatures, all tropical species exhibited increased calcification rates in response to increasing pCO2. However, the tropical species’ response to increasing pCO2 flattened when they lost symbionts (i.e., bleached) under the high-temperature treatments—suggesting that the loss of symbionts neutralized the benefit of increased pCO2 on calcification rate. Notably, the cold-water species that lacks symbionts exhibited a negative calcification response to increasing pCO2, although this negative response was partially ameliorated under elevated temperature. All four species elevated their calcifying fluid pH relative to seawater pH under all pCO2 treatments, and the magnitude of this offset (Δ[H+]) increased with increasing pCO2. Furthermore, calcifying fluid pH decreased along with symbiont abundance under thermal stress for the one species in which calcifying fluid pH was measured under both temperature treatments. This observation suggests a mechanistic link between photosymbiont loss (‘bleaching’) and impairment of zooxanthellate corals’ ability to elevate calcifying fluid pH in support of calcification under heat stress. This study supports the assertion that thermally induced loss of photosymbionts impairs tropical zooxanthellate corals’ ability to cope with CO2-induced ocean acidification

Identification of the CRE-1 Cellulolytic Regulon in Neurospora crassa

Background: In filamentous ascomycete fungi, the utilization of alternate carbon sources is influenced by the zinc finger transcription factor CreA/CRE-1, which encodes a carbon catabolite repressor protein homologous to Mig1 from Saccharomyces cerevisiae. In Neurospora crassa, deletion of cre-1 results in increased secretion of amylase and b-galactosidase. Methodology/Principal Findings: Here we show that a strain carrying a deletion of cre-1 has increased cellulolytic activity and increased expression of cellulolytic genes during growth on crystalline cellulose (Avicel). Constitutive expression of cre-1 complements the phenotype of a N. crassa Dcre-1 strain grown on Avicel, and also results in stronger repression of cellulolytic protein secretion and enzyme activity. We determined the CRE-1 regulon by investigating the secretome and transcriptome of a Dcre-1 strain as compared to wild type when grown on Avicel versus minimal medium. Chromatin immunoprecipitation-PCR of putative target genes showed that CRE-1 binds to only some adjacent 59-SYGGRG-39 motifs, consistent with previous findings in other fungi, and suggests that unidentified additional regulatory factors affect CRE-1 binding to promoter regions. Characterization of 30 mutants containing deletions in genes whose expression level increased in a Dcre-1 strain under cellulolytic conditions identified novel genes that affect cellulase activity and protein secretion