Search

A common risk to personnel is from Whole Body Vibration (WBV) and shock when transiting at speed in heavy seas, and much research has been done by maritime organisations to reduce this risk and the associated health impacts. It is well known that coxswain 'driving style' can radically affect exposure levels for a given sea state and sustained transit speed. A data-driven approach to define what makes a good coxswain from a WBV perspective is currently being developed by the Naval Design Partnering team (NDP). In phase 1, a systematic coxswain behaviour tracking methodology has been developed and demonstrated using a motion platform-based fast craft simulator at MARIN. The performance of several experienced volunteer coxswains from MOD, RNLI and KNRM has been evaluated based on a set pattern of tests. The advantages of using the simulator, over a sea trial, have been demonstrated: it is more repeatable, more controllable, accurate and more accessible. The potential disadvantages of the approach are also discussed with reference to feedback gathered from coxswains. Analysis has shown effective throttle control is much more important than steering to reduce WBV. Several interesting trends in WBV reduction potential have been shown which it is thought, with further validation, could aid mission planning, mission execution and provide data for training autonomous feedback/control algorithms. Further work is required before the findings of this study can be fully exploited. These subsequent phases, which include sea trials, aim to provide validation and further evidence to support the initial findings. [ABSTRACT FROM AUTHOR]

Highlights: [•] We demonstrate the application of systematic model reduction to a complex crop model. [•] The model was manipulated under software control replacing variables with constants. [•] Redundancy in representation of nitrogen physiology and temperature was found. [•] The level of detail in Sirius is defensible if detailed prediction is required. [•] The approach increases the efficiency and rigour of model evaluation. [Copyright &y& Elsevier]

Abstract: Injuries to the superficial digital flexor tendon (SDFT) are an important cause of morbidity and mortality in equine athletes, but the healing response is poorly understood. One important drive for the healing of connective tissues is the inflammatory cascade, but the role of inflammation in tendinopathy has been contentious in the literature. This article reviews the processes involved in the healing of tendon injuries in natural disease and experimental models. The importance of inflammatory processes known to be active in tendon disease is discussed with particular focus on recent findings related specifically to the horse. Whilst inflammation is necessary for debridement after injury, persistent inflammation is thought to drive fibrosis, a perceived adverse consequence of tendon healing. Therefore the ability to resolve inflammation by the resident cell populations in tendons at an appropriate time would be crucial for successful outcome. This review summarises new evidence for the importance of resolution of inflammation after tendon injury. Given that many anti-inflammatory drugs suppress both inflammatory and resolving components of the inflammatory response, prolonged use of these drugs may be contraindicated as a therapeutic approach. We propose that these findings have profound implications not only for current treatment strategies but also for the possibility of developing novel therapeutic approaches involving modulation of the inflammatory process. [Copyright &y& Elsevier]

Abstract: Background: Control of periodontal tissue inflammation during orthodontic treatment is very important in achieving a favourable therapeutic goal. We previously demonstrated that orally applied bovine lactoferrin (bLF) inhibited LPS-induced bone resorption but not orthodontic force-induced tooth movement in vivo. This study is designed to examine the underlying mechanism of it. Methods: We examined the inhibitory effects of bLF on the expression of RANKL, OPG, TNF-α and COX-2 in osteoblasts loaded with compressive stress (CS) in comparison with LPS stimulated osteoblasts. Formation of osteoclasts was evaluated by co-culture system. Results: Both CS- and LPS-applications upregulated COX-2 and RANKL but downregulated OPG. TNF-α was upregulated in LPS-stimulated osteoblasts but downregulated in CS-loaded osteoblasts. NS398 (a specific inhibitor of COX-2) significantly inhibited CS-induced RANKL-upregulation but not LPS-induced RANKL upregulation, indicating a critical role of COX-2/PGE2 pathway in CS-induced osteoclastogenesis. bLF significantly downregulated LPS-induced upregulation of RANKL and eliminated OPG suppression but not affected in CS-induced changes. Moreover, bLF significantly decreased LPS-induced osteoclast formation, whereas bLF had no effect on PGE2-induced osteoclast formation. Conclusions: bLF can effectively suppress harmful bone destruction associated with periodontitis without inhibiting bone remodelling by CS-loading. Therefore, oral administration of bLF may be highly beneficial for control of periodontitis in orthodontic patients. [Copyright &y& Elsevier]

Genome-wide association studies have successfully identified associations between common diseases and a large number of single nucleotide polymorphisms (SNPs) across the genome. We investigate the effectiveness of several statistics, including p-values, likelihoods, genetic map distance and linkage disequilibrium between SNPs, in filtering SNPs in several disease-associated regions. We use simulated data to compare the efficacy of filters with different sample sizes and for causal SNPs with different minor allele frequencies (MAFs) and effect sizes, focusing on the small effect sizes and MAFs likely to represent the majority of unidentified causal SNPs. In our analyses, of all the methods investigated, filtering on the ranked likelihoods consistently retains the true causal SNP with the highest probability for a given false positive rate. This was the case for all the local linkage disequilibrium patterns investigated. Our results indicate that when using this method to retain only the top 5% of SNPs, even a causal SNP with an odds ratio of 1.1 and MAF of 0.08 can be retained with a probability exceeding 0.9 using an overall sample size of 50,000. [ABSTRACT FROM AUTHOR]

Abstract: Our article presents a robust and flexible statistical model of the age–length relationship of cardinalfish (Epigonus crassicaudus). Specifically, we consider a non-linear regression model in which the error distribution allows for heteroskedasticity and belongs to the skew-normal (SMSN) distributions family of scale mixtures, thus eliminating the need to transform the dependent variable using techniques such as the Box–Cox transformation. The SMSN is a tractable and flexible class of asymmetric, heavy-tailed distributions that is useful for robust inference when the normality assumption for the error distribution is questionable. Two well-known important members of this class are the proper skew-normal and skew-t distributions. In this work, the skew-t model is emphasised. However, the proposed methodology can be adapted for each of the SMSN models with some basic changes. The present work is motivated by a previous analysis of cardinalfish where the oldest specimen was 15 years of age. In this study, we use the proposed methodology on a data set based on an otolith sample where the determined longevity is higher than 54 years. [Copyright &y& Elsevier]

Abstract: Background: Chronic Stenotrophomonas maltophilia infection is an independent risk factor for severe pulmonary exacerbations in cystic fibrosis (CF) patients. The goal of this study was to determine the effect of chronic S. maltophilia infection on mortality and the need for lung transplantation in a longitudinal study of children and adults with CF. Methods: This was a cohort study of CF patients from the Hospital for Sick Children and St Michael's Hospital (Toronto, Canada) from 1997 to 2008. A Cox Regression model was used to estimate the hazard ratio (HR) to time of death or lung transplantation adjusting for age, gender, genotype, pancreatic status, CF related diabetes (CFRD), forced expiratory volume in 1s (FEV1), body mass index, number of pulmonary exacerbations, Pseudomonas aeruginosa, Burkholderia cepacia complex, Aspergillus and chronic S. maltophilia infection. Results: A total of 687 patients were followed over the 12year study period; 95 patients underwent a lung transplantation (of which 26 died) and an additional 49 patients died (total 144 events). In a Cox Regression model adjusting for baseline FEV1, baseline infection with B. cepacia complex (HR 1.72, 95% CI 1.09–2.71) and baseline chronic S. maltophilia infection (HR 2.80, 95% CI 1.65–4.76) were significantly associated with death or lung transplant. However, in a time-varying model, infection with B. cepacia complex and chronic S. maltophilia infection were no longer significant. Conclusions: Baseline chronic S. maltophilia infection is associated with an almost three-fold increased risk of death or lung transplant in CF patients. It is still unclear, however, whether chronic S. maltophilia infection is simply a marker of severity of disease and ultimate mortality or whether it is causally related to disease progression. [Copyright &y& Elsevier]

Background: In statistical modeling, finding the most favorable coding for an exploratory quantitative variable involves many tests. This process involves multiple testing problems and requires the correction of the significance level. Methods: For each coding, a test on the nullity of the coefficient associated with the new coded variable is computed. The selected coding corresponds to that associated with the largest statistical test (or equivalently the smallest pvalue). In the context of the Generalized Linear Model, Liquet and Commenges (Stat Probability Lett,71:33-38,2005) proposed an asymptotic correction of the significance level. This procedure, based on the score test, has been developed for dichotomous and Box-Cox transformations. In this paper, we suggest the use of resampling methods to estimate the significance level for categorical transformations with more than two levels and, by definition those that involve more than one parameter in the model. The categorical transformation is a more flexible way to explore the unknown shape of the effect between an explanatory and a dependent variable. Results: The simulations we ran in this study showed good performances of the proposed methods. These methods were illustrated using the data from a study of the relationship between cholesterol and dementia. Conclusion: The algorithms were implemented using R, and the associated CPMCGLM R package is available on the CRAN. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE2) production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE2 promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE2-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2) expression and decreased nitric oxide (NO) production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens. [ABSTRACT FROM AUTHOR]

Background: Empirical studies on the association between self-rated health (SRH) and subsequent mortality are generally lacking in low- and middle-income countries. The evidence on whether socio-economic status and education modify this association is inconsistent. This study aims to fill these gaps using longitudinal data from a Health and Demographic Surveillance System (HDSS) site in Indonesia. Methods: In 2010, we assessed the mortality status of 11,753 men and women aged 50+ who lived in Purworejo HDSS and participated in the INDEPTH WHO SAGE baseline in 2007. Information on self-rated health, socio-demographic indicators, disability and chronic disease were collected through face-to-face interview at baseline. We used Cox-proportional hazards regression for mortality and included all variables measured at baseline, including interaction terms between SRH and both education and socio-economic status (SES). Results: During an average of 36 months follow-up, 11% of men and 9.5% of women died, resulting in death rates of 3.1 and 2.6 per 1,000 person-months, respectively. The age-adjusted Hazard Ratio (HR) for mortality was 17% higher in men than women (HR = 1.17; 95% CI = 1.04-1.31). After adjustment for covariates, the hazard ratios for mortality in men and women reporting bad health were 3.0 (95% CI = 2.0-4.4) and 4.9 (95% CI = 3.2-7.4), respectively. Education and SES did not modify this association for either sex. Conclusions: This study supports the predictive power of bad self-rated health for subsequent mortality in rural Indonesian men and women 50 years old and over. In these analyses, education and household socio-economic status do not modify the relationship between SRH and mortality. This means that older people who rate their own health poorly should be an important target group for health service interventions. [ABSTRACT FROM AUTHOR]

Understanding the extent to which immigration is a predominantly permanent or transitory phenomenon is essential for host countries insofar as it affects the strategic design of their admission, reception, and integration policies. Beyond the determination of the volume of returns, it is crucial to also determine which covariates connect better with a greater or lesser propensity of return. An adequate approach to the dynamics of the return requires considering this decision conditioned by the time elapsed since the arrival of the immigrant. From this perspective, the variable of interest would not be the intention of return, but the elapsed time between the arrival of the immigrant and the moment that return is considered as an option, as well as what are the factors affecting a greater or lesser duration of the stay. In this context, the article explores the relative importance of various personal and migration characteristics in the intention of return of immigrants conditional at the time of residence through the application of a Cox model of duration. [ABSTRACT FROM AUTHOR]

The majority of metabolic principles are evolutionarily conserved from nematodes to humans. Caenorhabditis elegans has widely accelerated the discovery of new genes important to maintain organismic metabolic homeostasis. Various methods exist to assess the metabolic state in worms, yet they often require large animal numbers and tend to be performed as bulk analyses of whole worm homogenates, thereby largely precluding a detailed studies of metabolic changes in specific worm tissues. Here, we have adapted well-established histochemical methods for the use on C. elegans fresh frozen sections and demonstrate their validity for analyses of morphological and metabolic changes on tissue level in wild type and various mutant strains. We show how the worm presents on hematoxylin and eosin (H&E) stained sections and demonstrate their usefulness in monitoring and the identification of morphological abnormalities. In addition, we demonstrate how Oil-Red-O staining on frozen worm cross-sections permits quantification of lipid storage, avoiding the artifact-prone fixation and permeabilization procedures of traditional whole-mount protocols. We also adjusted standard enzymatic stains for respiratory chain subunits (NADH, SDH, and COX) to monitor metabolic states of various C. elegans tissues. In summary, the protocols presented here provide technical guidance to obtain robust, reproducible and quantifiable tissue-specific data on worm morphology as well as carbohydrate, lipid and mitochondrial energy metabolism that cannot be obtained through traditional biochemical bulk analyses of worm homogenates. Furthermore, analysis of worm cross-sections overcomes the common problem with quantification in three-dimensional whole-mount specimens. [ABSTRACT FROM AUTHOR]

Objectives: We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). Methods: Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997-2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (<30 days after AIDS event) or deferred (30-270 days after AIDS event) cART. Results: The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/μL and 5.2 (4.5, 5.7) log10 copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p = 0.20). Conclusions: Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting. [ABSTRACT FROM AUTHOR]

When the subjects in a study possess different demographic and disease characteristics and are exposed to more than one types of failure, a practical problem is to assess the covariate effects on each type of failure as well as on all-cause failure. The most widely used method is to employ the Cox models on each cause-specific hazard and the all-cause hazard. It has been pointed out that this method causes the problem of internal inconsistency. To solve such a problem, the additive hazard models have been advocated. In this paper, we model each cause-specific hazard with the additive hazard model that includes both constant and time-varying covariate effects. We illustrate that the covariate effect on all-cause failure can be estimated by the sum of the effects on all competing risks. Using data from a longitudinal study on breast cancer patients, we show that the proposed method gives simple interpretation of the final results, when the primary covariate effect is constant in the additive manner on each cause-specific hazard. Based on the given additive models on the cause-specific hazards, we derive the inferences for the adjusted survival and cumulative incidence functions. [ABSTRACT FROM AUTHOR]

Introduction: B cells may play an important role in promoting immune activation in the rheumatoid synovium and can produce prostaglandin E2 (PGE2) when activated. In its turn, PGE2 formed by cyclooxygenase (COX) and microsomal prostaglandin E2 synthase 1 (MPGES1) contributes to the rheumatoid arthritis (RA) pathological process. Therapeutic depletion of B cells results in important improvement in controlling disease activity in rheumatoid patients. Therefore we investigated the expression of PGE2 pathway enzymes in RA B cells and evaluated the effects of B cell depleting therapy on their expression in RA tissue. Methods: B cells expressing MPGES1 and COX-2 were identified by flow cytometry in in vitro stimulated and control mononuclear cells isolated from synovial fluid and peripheral blood of RA patients. Synovial biopsies were obtained from 24 RA patients before and at two consecutive time points after rituximab therapy. Expression of MPGES1, COX-1 and COX-2, as well as interleukin (IL)-1β and IL-6, known inducers of MPGES1, was quantified in immunostained biopsy sections using computerized image analysis. Results: Expression of MPGES1 or COX-2 was significantly upregulated upon stimulation of B cells from blood and synovial fluid while control cells displayed no detectable enzymes. In synovial biopsy sections, the expression of MPGES1, COX-1 or COX-2 was resistant to rituximab therapy at 8 or 16 weeks after start of treatment. Furthermore expression of IL-1β in the synovial tissue remained unchanged, while IL-6 tended to decrease after therapy. Conclusions: Therapy with B cell depleting agents, although efficient in achieving good clinical and radiographic response in RA patients, leaves important inflammatory pathways in the rheumatoid synovium essentially unaffected. [ABSTRACT FROM AUTHOR]

Background: The bioenergetic status of non-small cell lung cancer correlates with tumour aggressiveness. The voltage dependent anion channel type 1 (VDAC1) is a component of the mitochondrial permeability transition pore, regulates mitochondrial ATP/ADP exchange suggesting that its over-expression could be associated with energy dependent processes including increased proliferation and invasiveness. To test this hypothesis, we conducted an in vivo gene-expression meta-analysis of surgically resected non-small cell lung cancer (NSCLC) using 602 individual expression profiles, to examine the impact of VDAC1 on survival. Methodology/Principal Findings: High VDAC1 expression was associated with shorter overall survival with hazard ratio (HR) = 0.6639 (95% confidence interval (CI) 0.4528 to 0.9721), p = 0.035352 corresponding to 52 versus 101 months. VDAC1 predicted shorter time to recurrence and was shown to be an independent prognostic factor compared with histology, gender, age, nodal stage and tumour stage in a Cox multivariate analysis. Supervised analysis of all the datasets identified a 6-gene signature comprising HNRNPC, HSPA4, HSPA9, UBE2D2, CSNK1A1 and G3BP1 with overlapping functions involving regulation of protein turnover, RAS-RAF-MEK pathway and transcription. VDAC1 predicted survival in breast cancer and myeloma and an unsupervised analysis revealed enrichment of the VDAC1 signature in specific subsets. Conclusions: In summary, gene expression analysis identifies VDAC1 gene expression as a predictor of poor outcome in NSCLC and other cancers and is associated with dysregulation of a conserved set of biological pathways, which may be causally associated with aggressive tumour behaviour. [ABSTRACT FROM AUTHOR]

Class-D audio amplifiers are particularly efficient, and this efficiency has led to their ubiquity in a wide range of modern electronic appliances. Their output takes the form of a high-frequency square wave whose duty cycle (ratio of on-time to off-time) is modulated at low frequency according to the audio signal. A mathematical model is developed here for a second-order class-D amplifier design (i.e., containing one second-order integrator) with negative feedback. We derive exact expressions for the dominant distortion terms, corresponding to a general audio input signal, and confirm these predictions with simulations. We also show how the observed phenomenon of "pulse skipping" arises from an instability of the analytical solution upon which the distortion calculations are based, and we provide predictions of the circumstances under which pulse skipping will take place, based on a stability analysis. These predictions are confirmed by simulations. [ABSTRACT FROM AUTHOR]

Introduction and Aims. The Magistrates Early Referral Into Treatment (MERIT) program is a diversionary program for people with substance use (primarily illicit drug) problems, based in New South Wales, Australia. The aim of this study was to assess factors relevant to recidivism among MERIT participants. Design and Methods. A longitudinal study utilising administrative data was conducted. MERIT participants entering the program after 1 August 2004 and with a finalisation date of prior to 31 December 2005 were included in the study. Recidivism records for this cohort were obtained for the period 1 August 2004 and 31 December 2007 and linked to MERIT administrative data. Cox proportional hazards modelling was used to identify predictors of recidivism. Results. A total of 1160 MERIT participants were included in the analysis. Compared to non-completers, completion of the MERIT program was associated with a 30% reduction in risk of recidivism. Factors associated with increased risk of recidivism following MERIT included principal drug other than cannabis and higher number of prior convictions. Discussion and Conclusions. Although the design of this study does not permit causal conclusions, these results suggest the MERIT program may be associated with reduced criminal offending. The identification of factors associated with increased risk of recidivism may be helpful in identifying participants in need of higher intensity interventions.[Larney S, Martire KA. Factors affecting criminal recidivism among participants in the Magistrates Early Referral Into Treatment (MERIT) program in New South Wales, Australia. Drug Alcohol Rev 2010;29;684-688] [ABSTRACT FROM AUTHOR]

This study builds upon existing socio-cultural work into sports coaching by probing the meanings and varieties of the shared coach-athlete experience. Specifically, the paper utilises an autoethnographic approach in an attempt to chart the complex and dynamic relationship that existed between me, the principal author, as a rowing coxswain and my coach during the preparation for a national rowing championship. Data were drawn from a training diary, emails (both sent and received) and memories during the six months I spent with Coach. The data are presented through three separate yet inter-related stories. Here, the plot of the tale hinges on the tension between my personal perceptions of effective coaching and those employed by Coach. The findings are principally theorised through Nyberg's and Giddens' concepts of power and resistance, as a fruitful relationship between Coach and me (and the crew) soon turned into a dysfunctional one. The conclusion emphasises the importance of recognising the power-ridden nature of coaching and the value of the autoethnographic genre in exploring it. [ABSTRACT FROM AUTHOR]

Aquagenic syringeal acrokeratoderma is a newly described condition of the palms and soles characterized by hypopigmented papules and plaques, elicited after submersion in water. Symptoms include a burning pain and a tightening sensation in the palms, as well as hyperhidrosis. Initially thought to be rare, its frequent citation in the literature points to a more common entity. It is more often found in young women and has been linked to a number of medications and illnesses, including nonsteroidal anti-inflammatory drugs and cystic fibrosis. It is typically self-limiting, but certain medications such as topical aluminum chloride or salicylic acid ointment have been found to be an effective treatment option. This case details a collegiate-level coxswain who presented to the university athletic training room with a typical presentation of aquagenic syringeal acrokeratoderma. For an aquatic athlete, aquagenic syringeal acrokeratoderma can be a distressing condition that can limit training and athletic participation. As such, the sports medicine physician should be knowledgeable about aquagenic syringeal acrokeratoderma to provide effective counseling and treatment options for the athlete. [ABSTRACT FROM AUTHOR]

This article focuses on the possible analogical relevance of the ancient sport of sculling and dunking of the coxswain to the current technological and philosophical difficulties to make the social service system more responsive to the societal and individual needs. Like the rowers in the scull, service workers seem to face backward on the goal in order to have more leverage on their strokes and be more alert to the rhythmic chant of the coxswain. With administrators returned to membership in the human race it will be possible for service workers to get their attention when trying to engage them in a fuller exploration of traditional hierarchical lines, of authority. Once all of the people begin to see themselves as necessary parts of a viable system, they can cease efforts at upstaging each other for prominence on the stage of stature or importance. Then service providers will be ready to engage their full energies on the oars in their hands, even as others steer or the stroke pattern without deprecating the part any are playing to bring in the boat ahead of the rest.