A hierarchical frailty model applied to two-generation melanoma data

We present a hierarchical frailty model based on distributions derived from non-negative Lévy processes. The model may be applied to data with several levels of dependence, such as family data or other general clusters, and is an alternative to additive frailty models. We present several parametric examples of the model, and properties such as expected values, variance and covariance. The model is applied to a case-cohort sample of age at onset for melanoma from the Swedish Multi-Generation Register, organized in nuclear families of parents and one or two children. We compare the genetic component of the total frailty variance to the common environmental term, and estimate the effect of birth cohort and gender. © 2010 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Leadership styles and safety performance in high-risk industries: a systematic review

The importance of leadership on safety has been well acknowledged and studied for many years in various high-risk industries. This paper aims at (1) synthesising the existing safety leadership research by performing a systematic literature review to gain an overview of the relationship between various leadership styles and safety performance in high-risk industries with a main focus on health and workplace safety and (2) analysing and comparing the major results from the reviewed studies. The results show that nine leadership styles – transformational leadership, transactional leadership, leader–member exchange, authentic leadership, empowering leadership, ethical leadership, paternalistic leadership, charismatic leadership and passive leadership – have been frequently used in the development and validation of safety leadership theories as well as in understanding the leadership influence towards safety climate, safety compliance and safety participation in various contexts. However, blurred boundaries among the constructs of leadership styles alongside inconsistency in the conceptualisation and measurement of safety performance hinder the advancement of understanding safety leadership’s influence on safety performance. It is therefore of importance that further research develops consistent measurement instruments and conceptualisation and that systems thinking is applied to the study of leadership styles’ influence on safety performance.publishedVersio

Biomarkers of cardiovascular risk across phenotypes of osteoarthritis

Abstract: Background: The objective of this study was to explore the associations between ultrasonographic and radiographic joint scores and levels of arterial CVD risk markers in patients with osteoarthritis (OA). Secondly, to compare the levels of arterial CVD risk markers between OA phenotypes and controls. Method: The “Musculoskeletal pain in Ullensaker” Study (MUST) invited residents of Ullensaker municipality with self-reported OA to a medical examination. OA was defined according to the American College of Rheumatology (ACR) criteria and phenotyped based on joint distribution. Joints of the hands, hips and knees were examined by ultrasonography and conventional radiography, and scored for osteosteophytes. Hands were also scored for inflammation by grey scale (GS) synovitis and power Doppler (PD) signal. Control populations were a cohort of inhabitants of Oslo (OCP), and for external validation, a UK community-based register (UKPC). Pulse pressure augmentation index (AIx) and pulse wave velocity (PWV) were measured using the Sphygmocor apparatus (Atcor®). Ankel-brachial index (ABI) was estimated in a subset of patients. In separate adjusted regression models we explored the associations between ultrasonography and radiograph joint scores and AIx, PWV and ABI. CVD risk markers were also compared between phenotypes of OA and controls in adjusted analyses. Results: Three hundred and sixty six persons with OA were included (mean age (range); 63.0 (42.0–75.0)), (females (%); 264 (72)). Of these, 155 (42.3%) had isolated hand OA, 111 (30.3%) had isolated lower limb OA and 100 (27.3%) had generalized OA. 108 persons were included in the OCP and 963 persons in the UKPC; (mean age (range); OCP: 57.2 (40.4–70.4), UKPC: 63.9 (40.0–75.0), females (%); OCP: 47 (43.5), UKPC: 543 (56.4%). Hand osteophytes were associated with AIx while GS and PD scores were not related to CVD risk markers. All OA phenotypes had higher levels of AIx compared to OCP in adjusted analyses. External validation against UKPC confirmed these findings. Conclusions: Hand osteophytes might be related to higher risk of CVD. People with OA had higher augmented central pressure compared to controls. Words 330

Fitness of Escherichia coli during Urinary Tract Infection Requires Gluconeogenesis and the TCA Cycle

Microbial pathogenesis studies traditionally encompass dissection of virulence properties such as the bacterium's ability to elaborate toxins, adhere to and invade host cells, cause tissue damage, or otherwise disrupt normal host immune and cellular functions. In contrast, bacterial metabolism during infection has only been recently appreciated to contribute to persistence as much as their virulence properties. In this study, we used comparative proteomics to investigate the expression of uropathogenic Escherichia coli (UPEC) cytoplasmic proteins during growth in the urinary tract environment and systematic disruption of central metabolic pathways to better understand bacterial metabolism during infection. Using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) and tandem mass spectrometry, it was found that UPEC differentially expresses 84 cytoplasmic proteins between growth in LB medium and growth in human urine (P<0.005). Proteins induced during growth in urine included those involved in the import of short peptides and enzymes required for the transport and catabolism of sialic acid, gluconate, and the pentose sugars xylose and arabinose. Proteins required for the biosynthesis of arginine and serine along with the enzyme agmatinase that is used to produce the polyamine putrescine were also up-regulated in urine. To complement these data, we constructed mutants in these genes and created mutants defective in each central metabolic pathway and tested the relative fitness of these UPEC mutants in vivo in an infection model. Import of peptides, gluconeogenesis, and the tricarboxylic acid cycle are required for E. coli fitness during urinary tract infection while glycolysis, both the non-oxidative and oxidative branches of the pentose phosphate pathway, and the Entner-Doudoroff pathway were dispensable in vivo. These findings suggest that peptides and amino acids are the primary carbon source for E. coli during infection of the urinary tract. Because anaplerosis, or using central pathways to replenish metabolic intermediates, is required for UPEC fitness in vivo, we propose that central metabolic pathways of bacteria could be considered critical components of virulence for pathogenic microbes

Trees Wanted—Dead or Alive! Host Selection and Population Dynamics in Tree-Killing Bark Beetles

Bark beetles (Coleoptera: Curculionidae, Scolytinae) feed and breed in dead or severely weakened host trees. When their population densities are high, some species aggregate on healthy host trees so that their defences may be exhausted and the inner bark successfully colonized, killing the tree in the process. Here we investigate under what conditions participating with unrelated conspecifics in risky mass attacks on living trees is an adaptive strategy, and what this can tell us about bark beetle outbreak dynamics. We find that the outcome of individual host selection may deviate from the ideal free distribution in a way that facilitates the emergence of tree-killing (aggressive) behavior, and that any heritability on traits governing aggressiveness seems likely to exist in a state of flux or cycles consistent with variability observed in natural populations. This may have implications for how economically and ecologically important species respond to environmental changes in climate and landscape (forest) structure. The population dynamics emerging from individual behavior are complex, capable of switching between “endemic” and “epidemic” regimes spontaneously or following changes in host availability or resistance. Model predictions are compared to empirical observations, and we identify some factors determining the occurrence and self-limitation of epidemics

Use of Zebrafish to Probe the Divergent Virulence Potentials and Toxin Requirements of Extraintestinal Pathogenic Escherichia coli

Extraintestinal pathogenic E. coli (ExPEC) cause an array of diseases, including sepsis, neonatal meningitis, and urinary tract infections. Many putative virulence factors that might modulate ExPEC pathogenesis have been identified through sequencing efforts, epidemiology, and gene expression profiling, but few of these genes have been assigned clearly defined functional roles during infection. Using zebrafish embryos as surrogate hosts, we have developed a model system with the ability to resolve diverse virulence phenotypes and niche-specific restrictions among closely related ExPEC isolates during either localized or systemic infections. In side-by-side comparisons of prototypic ExPEC isolates, we observed an unexpectedly high degree of phenotypic diversity that is not readily apparent using more traditional animal hosts. In particular, the capacity of different ExPEC isolates to persist and multiply within the zebrafish host and cause disease was shown to be variably dependent upon two secreted toxins, α-hemolysin and cytotoxic necrotizing factor. Both of these toxins appear to function primarily in the neutralization of phagocytes, which are recruited in high numbers to sites of infection where they act as an essential host defense against ExPEC as well as less virulent E. coli strains. These results establish zebrafish as a valuable tool for the elucidation and functional analysis of both ExPEC virulence factors and host defense mechanisms

Complex chloroplast RNA metabolism: just debugging the genetic programme?

<p>Abstract</p> <p>Background</p> <p>The gene expression system of chloroplasts is far more complex than that of their cyanobacterial progenitor. This gain in complexity affects in particular RNA metabolism, specifically the transcription and maturation of RNA. Mature chloroplast RNA is generated by a plethora of nuclear-encoded proteins acquired or recruited during plant evolution, comprising additional RNA polymerases and sigma factors, and sequence-specific RNA maturation factors promoting RNA splicing, editing, end formation and translatability. Despite years of intensive research, we still lack a comprehensive explanation for this complexity.</p> <p>Results</p> <p>We inspected the available literature and genome databases for information on components of RNA metabolism in land plant chloroplasts. In particular, new inventions of chloroplast-specific mechanisms and the expansion of some gene/protein families detected in land plants lead us to suggest that the primary function of the additional nuclear-encoded components found in chloroplasts is the transgenomic suppression of point mutations, fixation of which occurred due to an enhanced genetic drift exhibited by chloroplast genomes. We further speculate that a fast evolution of transgenomic suppressors occurred after the water-to-land transition of plants.</p> <p>Conclusion</p> <p>Our inspections indicate that several chloroplast-specific mechanisms evolved in land plants to remedy point mutations that occurred after the water-to-land transition. Thus, the complexity of chloroplast gene expression evolved to guarantee the functionality of chloroplast genetic information and may not, with some exceptions, be involved in regulatory functions.</p