Biological variability dominates and influences analytical variance in HPLC-ECD studies of the human plasma metabolome

<p>Abstract</p> <p>Background</p> <p>Biomarker-based assessments of biological samples are widespread in clinical, pre-clinical, and epidemiological investigations. We previously developed serum metabolomic profiles assessed by HPLC-separations coupled with coulometric array detection that can accurately identify <it>ad libitum </it>fed and caloric-restricted rats. These profiles are being adapted for human epidemiology studies, given the importance of energy balance in human disease.</p> <p>Methods</p> <p>Human plasma samples were biochemically analyzed using HPLC separations coupled with coulometric electrode array detection.</p> <p>Results</p> <p>We identified these markers/metabolites in human plasma, and then used them to determine which human samples represent blinded duplicates with 100% accuracy (N = 30 of 30). At least 47 of 61 metabolites tested were sufficiently stable for use even after 48 hours of exposure to shipping conditions. Stability of some metabolites differed between individuals (N = 10 at 0, 24, and 48 hours), suggesting the influence of some biological factors on parameters normally considered as analytical.</p> <p>Conclusion</p> <p>Overall analytical precision (mean median CV, ~9%) and total between-person variation (median CV, ~50–70%) appear well suited to enable use of metabolomics markers in human clinical trials and epidemiological studies, including studies of the effect of caloric intake and balance on long-term cancer risk.</p

Medical students' and facilitators' experiences of an Early Professional Contact course: Active and motivated students, strained facilitators

Background: Today, medical students are introduced to patient contact, communication skills, and clinical examination in the preclinical years of the curriculum with the purpose of gaining clinical experience. These courses are often evaluated from the student perspective. Reports with an additional emphasis on the facilitator perspective are scarce. According to constructive alignment, an influential concept from research in higher education, the learning climate between students and teachers is also of great importance. In this paper, we approach the learning climate by studying both students' and facilitators' course experiences.\ud \ud In 2001, a new "Early Professional Contact" longitudinal strand through term 1–4, was introduced at the Sahlgrenska Academy, University of Gothenburg, Sweden. General practitioners and hospital specialists were facilitators.\ud \ud The aim of this study was to assess and analyse students' and clinical facilitators' experiences of the Early Professional Contact course and to illuminate facilitators' working conditions.\ud \ud Methods: Inspired by a Swedish adaptation of the Course Experience Questionnaire, an Early Professional Contact Questionnaire was constructed. In 2003, on the completion of the first longitudinal strand, a student and facilitator version was distributed to 86 students and 21 facilitators. In the analysis, both Chi-square and the Mann-Whitney tests were used.\ud \ud Results: Sixty students (70%) and 15 facilitators (71%) completed the questionnaire. Both students and facilitators were satisfied with the course. Students reported gaining [inspiration] for their future work as doctors along with increased confidence in meeting patients. They also reported increased motivation for biomedical studies. Differences in attitudes between facilitators and students were found. Facilitators experienced a greater workload, less reasonable demands and less support, than students.\ud \ud Conclusion: In this project, a new Early Professional Contact course was analysed from both student and facilitator perspectives. The students experienced the course as providing them with a valuable introduction to the physician's professional role in clinical practice. In contrast, course facilitators often experienced a heavy workload and lack of support, despite thorough preparatory education. A possible conflict between the clinical facilitator's task as educator and member of the workplace is suggested. More research is needed on how doctors combine their professional tasks with work as facilitators

The Prevalence and Psychopathological Correlates of Sibling Bullying in Children with and without Autism Spectrum Disorder

Using data from a prospective population based study, the prevalence and psychopathological correlates of sibling bullying in children with and without autism spectrum disorder (ASD) were estimated. There were 475 children with ASD and 13,702 children without ASD aged 11 years. Children with ASD were more likely to be bullied by their siblings compared to those without ASD. They were also more likely than those without ASD to both bully and be bullied by their siblings, which was associated with lower prosocial skills as well as more internalizing and externalizing problems compared to those not involved in any sibling bullying. Interventions to improve social and emotional outcomes in children with ASD should focus on both the affected and the unaffected sibling

Translocations as Experiments in the Ecological Resilience of an Asocial Mega-Herbivore

Species translocations are remarkable experiments in evolutionary ecology, and increasingly critical to biodiversity conservation. Elaborate socio-ecological hypotheses for translocation success, based on theoretical fitness relationships, are untested and lead to complex uncertainty rather than parsimonious solutions. We used an extraordinary 89 reintroduction and 102 restocking events releasing 682 black rhinoceros (Diceros bicornis) to 81 reserves in southern Africa (1981–2005) to test the influence of interacting socio-ecological and individual characters on post-release survival. We predicted that the socio-ecological context should feature more prominently after restocking than reintroduction because released rhinoceros interact with resident conspecifics. Instead, an interaction between release cohort size and habitat quality explained reintroduction success but only individuals' ages explained restocking outcomes. Achieving translocation success for many species may not be as complicated as theory suggests. Black rhino, and similarly asocial generalist herbivores without substantial predators, are likely to be resilient to ecological challenges and robust candidates for crisis management in a changing world

Using indirect methods to constrain symbiotic nitrogen fixation rates : a case study from an Amazonian rain forest

© The Authors 2009. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Biogeochemistry 99 (2010): 1-13, doi:10.1007/s10533-009-9392-y.Human activities have profoundly altered the global nitrogen (N) cycle. Increases in anthropogenic N have had multiple effects on the atmosphere, on terrestrial, freshwater and marine ecosystems, and even on human health. Unfortunately, methodological limitations challenge our ability to directly measure natural N inputs via biological N fixation (BNF)—the largest natural source of new N to ecosystems. This confounds efforts to quantify the extent of anthropogenic perturbation to the N cycle. To address this gap, we used a pair of indirect methods—analytical modeling and N balance—to generate independent estimates of BNF in a presumed hotspot of N fixation, a tropical rain forest site in central Rondônia in the Brazilian Amazon Basin. Our objectives were to attempt to constrain symbiotic N fixation rates in this site using indirect methods, and to assess strengths and weaknesses of this approach by looking for areas of convergence and disagreement between the estimates. This approach yielded two remarkably similar estimates of N fixation. However, when compared to a previously published bottom-up estimate, our analysis indicated much lower N inputs via symbiotic BNF in the Rondônia site than has been suggested for the tropics as a whole. This discrepancy may reflect errors associated with extrapolating bottom-up fluxes from plot-scale measures, those resulting from the indirect analyses, and/or the relatively low abundance of legumes at the Rondônia site. While indirect methods have some limitations, we suggest that until the technological challenges of directly measuring N fixation are overcome, integrated approaches that employ a combination of model-generated and empirically-derived data offer a promising way of constraining N inputs via BNF in natural ecosystems.We acknowledge and are grateful for financial support from the Andrew W. Mellon Foundation (C.C. and B.H.), the National Science Foundation (NSF DEB-0515744 to C.C. and A.T. and DEB-0315656 to C.N.), and the NASA LBA Program (NCC5-285 to C.N.)

Catalytic living ring-opening metathesis polymerization

In living ring-opening metathesis polymerization (ROMP), a transition-metal–carbene complex polymerizes ring-strained olefins with very good control of the molecular weight of the resulting polymers. Because one molecule of the initiator is required for each polymer chain, however, this type of polymerization is expensive for widespread use. We have now designed a chain-transfer agent (CTA) capable of reducing the required amount of metal complex while still maintaining full control over the living polymerization process. This new method introduces a degenerative transfer process to ROMP. We demonstrate that substituted cyclohexene rings are good CTAs, and thereby preserve the ‘living’ character of the polymerization using catalytic quantities of the metal complex. The resulting polymers show characteristics of a living polymerization, namely narrow molecular-weight distribution, controlled molecular weights and block copolymer formation. This new technique provides access to well- defined polymers for industrial, biomedical and academic use at a fraction of the current costs and significantly reduced levels of residual ruthenium catalyst

High major histocompatibility complex class I polymorphism despite bottlenecks in wild and domesticated populations of the zebra finch ()

Background Two subspecies of zebra finch, Taeniopygia guttata castanotis and T. g. guttata are native to Australia and the Lesser Sunda Islands, respectively. The Australian subspecies has been domesticated and is now an important model system for research. Both the Lesser Sundan subspecies and domesticated Australian zebra finches have undergone population bottlenecks in their history, and previous analyses using neutral markers have reported reduced neutral genetic diversity in these populations. Here we characterize patterns of variation in the third exon of the highly variable major histocompatibility complex (MHC) class I α chain. As a benchmark for neutral divergence, we also report the first mitochondrial NADH dehydrogenase 2 (ND2) sequences in this important model system. Results Despite natural and human-mediated population bottlenecks, we find that high MHC class I polymorphism persists across all populations. As expected, we find higher levels of nucleotide diversity in the MHC locus relative to neutral loci, and strong evidence of positive selection acting on important residues forming the peptide-binding region (PBR). Clear population differentiation of MHC allele frequencies is also evident, and this may be due to adaptation to new habitats and associated pathogens and/or genetic drift. Whereas the MHC Class I locus shows broad haplotype sharing across populations, ND2 is the first locus surveyed to date to show reciprocal monophyly of the two subspecies. Conclusions Despite genetic bottlenecks and genetic drift, all surveyed zebra finch populations have maintained high MHC Class I diversity. The diversity at the MHC Class I locus in the Lesser Sundan subspecies contrasts sharply with the lack of diversity in previously examined neutral loci, and may thus be a result of selection acting to maintain polymorphism. Given uncertainty in historical population demography, however, it is difficult to rule out neutral processes in maintaining the observed diversity. The surveyed populations also differ in MHC Class I allele frequencies, and future studies are needed to assess whether these changes result in functional immune differences

Genomics in neurodevelopmental disorders: an avenue to personalized medicine

Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in genomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered, the etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype- based diagnosis of individual patients has become a requisite. In this review we look at recent advancements in genomic analysis and their translation into clinical practice

Risk of chronic kidney disease after cancer nephrectomy.

The incidence of early stage renal cell carcinoma (RCC) is increasing and observational studies have shown equivalent oncological outcomes of partial versus radical nephrectomy for stage I tumours. Population studies suggest that compared with radical nephrectomy, partial nephrectomy is associated with decreased mortality and a lower rate of postoperative decline in kidney function. However, rates of chronic kidney disease (CKD) in patients who have undergone nephrectomy might be higher than in the general population. The risks of new-onset or accelerated CKD and worsened survival after nephrectomy might be linked, as kidney insufficiency is a risk factor for cardiovascular disease and mortality. Nephron-sparing approaches have, therefore, been proposed as the standard of care for patients with type 1a tumours and as a viable option for those with type 1b tumours. However, prospective data on the incidence of de novo and accelerated CKD after cancer nephrectomy is lacking, and the only randomized trial to date was closed prematurely. Intrinsic abnormalities in non-neoplastic kidney parenchyma and comorbid conditions (including diabetes mellitus and hypertension) might increase the risks of CKD and RCC. More research is needed to better understand the risk of CKD post-nephrectomy, to develop and validate predictive scores for risk-stratification, and to optimize patient management