Effect of secular trends on age-related trajectories of cardiovascular risk factors: the Whitehall II longitudinal study 1985-2009

Secular trends in cardiovascular risk factors have been described, but few studies have examined simultaneously the effects of both ageing and secular trends within the same cohort

Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.

Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio

Primary resection versus neoadjuvant chemoradiation followed by resection for locally resectable or potentially resectable pancreatic carcinoma without distant metastasis. A multi-centre prospectively randomised phase II-study of the Interdisciplinary Working Group Gastrointestinal Tumours (AIO, ARO, and CAO)

BACKGROUND: The disappointing results of surgical therapy alone of ductal pancreatic cancer can only be improved using multimodal approaches. In contrast to adjuvant therapy, neoadjuvant chemoradiation is able to facilitate resectability with free margins and to lower lymphatic spread. Another advantage is better tolerability which consecutively allows applying multimodal treatment in a higher number of patients. Furthermore, the synopsis of the overall survival results of neoadjuvant trials suggests a higher rate compared to adjuvant trials. METHODS/DESIGN: As there are no prospectively randomised studies for neoadjuvant therapy, the Interdisciplinary Study Group of Gastrointestinal Tumours of the German Cancer Aid has started such a trial. The study investigates the effect of neoadjuvant chemoradiation in locally resectable or probably resectable cancer of the pancreatic head without distant metastasis on median overall survival time compared to primary surgery. Adjuvant chemotherapy is integrated into both arms. DISCUSSION: The protocol of the study is presented in condensed form after an introducing survey on adjuvant and neoadjuvant therapy in pancreatic cancer

Analyzing models of work addiction: single factor and bi-factor models of the Bergen Work Addiction Scale

Work addiction ('workaholism') has become an increasingly studied topic in the behavioral addictions literature and had led to the development of a number of instruments to assess it. One such instrument is the Bergen Work Addiction Scale (BWAS - Andreassen et al. 2012 Scandinavian Journal of Psychology, 53, 265-272). However, the BWAS has never been investigated in Eastern-European countries. The goal of the present study was to examine the factor structure, the reliability and cut-off scores of the BWAS in a comprehensive Hungarian sample. This study is a direct extension of the original validation of BWAS by providing results on the basis of representative data and the development of appropriate cut-off scores The study utilized an online questionnaire with a Hungarian representative sample including 500 respondents (F = 251; M age = 35.05 years) who completed the BWAS. A series of confirmatory factor analyses were carried out leading to a short, 7-item first-order factor structure and a longer 14-item seven-factor nested structure. Despite the good validity of the longer version, its reliability was not as high as it could have been. One-fifth (20.6 %) of the Hungarians who used the internet at least weekly were categorized as work addicts using the BWAS. It is recommended that researchers use the original seven items from the Norwegian scale in order to facilitate and stimulate cross-national research on addiction to work

Down selecting adjuvanted vaccine formulations: a comparative method for harmonized evaluation.

The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. Here we describe a method which may enable vaccine and adjuvant developers to compare antigen/adjuvant combinations in a harmonized fashion. Three reference antigens: Plasmodium falciparum apical membrane antigen 1 (AMA1), hepatitis B virus surface antigen (HBsAg), and Mycobacterium tuberculosis antigen 85A (Ag85A), were selected as model antigens and were each formulated with three adjuvants: aluminium oxyhydroxide, squalene-in-water emulsion, and a liposome formulation mixed with the purified saponin fraction QS21. The nine antigen/adjuvant formulations were assessed for stability and immunogenicity in mice in order to provide benchmarks against which other formulations could be compared, in order to assist subsequent down selection of adjuvanted vaccines. Furthermore, mouse cellular immune responses were analyzed by measuring IFN-γ and IL-5 production in splenocytes by ELISPOT, and humoral responses were determined by antigen-specific ELISA, where levels of total IgG, IgG1, IgG2b and IgG2c in serum samples were determined. The reference antigens and adjuvants described in this study, which span a spectrum of immune responses, are of potential use as tools to act as points of reference in vaccine development studies. The harmonized methodology described herein may be used as a tool for adjuvant/antigen comparison studies

Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution

August 1, 2010Bisulfite sequencing measures absolute levels of DNA methylation at single-nucleotide resolution, providing a robust platform for molecular diagnostics. Here, we optimize bisulfite sequencing for genome-scale analysis of clinical samples. Specifically, we outline how restriction digestion targets bisulfite sequencing to hotspots of epigenetic regulation; we show that 30ng of DNA are sufficient for genome-scale analysis; we demonstrate that our protocol works well on formalinfixed, paraffin-embedded (FFPE) samples; and we describe a statistical method for assessing significance of altered DNA methylation patterns.National Institutes of Health (U.S.) (Grant R01HG004401)National Institutes of Health (U.S.) (Grant U54HG03067)National Institutes of Health (U.S.) (Grant U01ES017155

Barx1-Mediated Inhibition of Wnt Signaling in the Mouse Thoracic Foregut Controls Tracheo-Esophageal Septation and Epithelial Differentiation

Mesenchymal cells underlying the definitive endoderm in vertebrate animals play a vital role in digestive and respiratory organogenesis. Although several signaling pathways are implicated in foregut patterning and morphogenesis, and despite the clinical importance of congenital tracheal and esophageal malformations in humans, understanding of molecular mechanisms that allow a single tube to separate correctly into the trachea and esophagus is incomplete. The homoebox gene Barx1 is highly expressed in prospective stomach mesenchyme and required to specify this organ. We observed lower Barx1 expression extending contiguously from the proximal stomach domain, along the dorsal anterior foregut mesenchyme and in mesenchymal cells between the nascent esophagus and trachea. This expression pattern exactly mirrors the decline in Wnt signaling activity in late development of the adjacent dorsal foregut endoderm and medial mainstem bronchi. The hypopharynx in Barx1−/− mouse embryos is abnormally elongated and the point of esophago-tracheal separation shows marked caudal displacement, resulting in a common foregut tube that is similar to human congenital tracheo-esophageal fistula and explains neonatal lethality. Moreover, the Barx1−/− esophagus displays molecular and cytologic features of respiratory endoderm, phenocopying abnormalities observed in mouse embryos with activated ß-catenin. The zone of canonical Wnt signaling is abnormally prolonged and expanded in the proximal Barx1−/− foregut. Thus, as in the developing stomach, but distinct from the spleen, Barx1 control of thoracic foregut specification and tracheo-esophageal septation is tightly associated with down-regulation of adjacent Wnt pathway activity

Conceptualising population health: from mechanistic thinking to complexity science

The mechanistic interpretation of reality can be traced to the influential work by René Descartes and Sir Isaac Newton. Their theories were able to accurately predict most physical phenomena relating to motion, optics and gravity. This paradigm had at least three principles and approaches: reductionism, linearity and hierarchy. These ideas appear to have influenced social scientists and the discourse on population health. In contrast, Complexity Science takes a more holistic view of systems. It views natural systems as being 'open', with fuzzy borders, constantly adapting to cope with pressures from the environment. These are called Complex Adaptive Systems (CAS). The sub-systems within it lack stable hierarchies, and the roles of agency keep changing. The interactions with the environment and among sub-systems are non-linear interactions and lead to self-organisation and emergent properties. Theoretical frameworks such as epi+demos+cracy and the ecosocial approach to health have implicitly used some of these concepts of interacting dynamic sub-systems. Using Complexity Science we can view population health outcomes as an emergent property of CAS, which has numerous dynamic non-linear interactions among its interconnected sub-systems or agents. In order to appreciate these sub-systems and determinants, one should acquire a basic knowledge of diverse disciplines and interact with experts from different disciplines. Strategies to improve health should be multi-pronged, and take into account the diversity of actors, determinants and contexts. The dynamic nature of the system requires that the interventions are constantly monitored to provide early feedback to a flexible system that takes quick corrections

Genetic Mapping of Social Interaction Behavior in B6/MSM Consomic Mouse Strains

Genetic studies are indispensable for understanding the mechanisms by which individuals develop differences in social behavior. We report genetic mapping of social interaction behavior using inter-subspecific consomic strains established from MSM/Ms (MSM) and C57BL/6J (B6) mice. Two animals of the same strain and sex, aged 10 weeks, were introduced into a novel open-field for 10 min. Social contact was detected by an automated system when the distance between the centers of the two animals became less than ~12 cm. In addition, detailed behavioral observations were made of the males. The wild-derived mouse strain MSM showed significantly longer social contact as compared to B6. Analysis of the consomic panel identified two chromosomes (Chr 6 and Chr 17) with quantitative trait loci (QTL) responsible for lengthened social contact in MSM mice and two chromosomes (Chr 9 and Chr X) with QTL that inhibited social contact. Detailed behavioral analysis of males identified four additional chromosomes associated with social interaction behavior. B6 mice that contained Chr 13 from MSM showed more genital grooming and following than the parental B6 strain, whereas the presence of Chr 8 and Chr 12 from MSM resulted in a reduction of those behaviors. Longer social sniffing was observed in Chr 4 consomic strain than in B6 mice. Although the frequency was low, aggressive behavior was observed in a few pairs from consomic strains for Chrs 4, 13, 15 and 17, as well as from MSM. The social interaction test has been used as a model to measure anxiety, but genetic correlation analysis suggested that social interaction involves different aspects of anxiety than are measured by open-field test

Socio-economic inequalities in C-reactive protein and fibrinogen across the adult age span: Findings from Understanding Society

Systemic inflammation has been proposed as a physiological process linking socio-economic position (SEP) to health. We examined how SEP inequalities in inflammation -assessed using C-reactive protein (CRP) and fibrinogen- varied across the adult age span. Current (household income) and distal (education) markers of SEP were used. Data from 7,943 participants (aged 25+) of Understanding Society (wave 2, 1/2010-3/2012) were employed. We found that SEP inequalities in inflammation followed heterogeneous patterns by age, which differed by the inflammatory marker examined rather than by SEP measures. SEP inequalities in CRP emerged in 30s, increased up to mid-50s or early 60 s when they peaked and then decreased with age. SEP inequalities in fibrinogen decreased with age. Body mass index (BMI), smoking, physical activity and healthy diet explained part, but not all, of the SEP inequalities in inflammation; in general, BMI exerted the largest attenuation. Cumulative advantage theories and those considering age as a leveler for the accumulation of health and economic advantages across the life-span should be dynamically integrated to better understand the observed heterogeneity in SEP differences in health across the lifespan. The attenuating roles of health-related lifestyle indicators suggest that targeting health promotion policies may help reduce SEP inequalities in health