Booster vaccination of toddlers with reduced antigen content diphtheria-tetanus-acellular pertussis vaccine

Immunogenicity and reactogenicity of DTPa and reduced antigen dTpa booster vaccines were compared to a hepatitis A control vaccine in DTPa-primed toddlers aged 18-20 months. Post-booster, all DTPa and dTpa recipients were seroprotected against diphtheria and tetanus, and >= 93.3% had a booster response to pertussis. There were similar reactogenicity rates in the DTPa and dTpa vaccine recipients. Few Grade 3 symptoms were reported. Just over one in four children in the control group had diphtheria antibody at or potentially below the correlate of protection benchmark (0.016 IU/ml). Larger studies should evaluate potential benefits of reduced antigen vaccines and seroprotection in children who do not receive a booster dose of DTPa at this age, including protection against diphtheria until subsequent booster doses are given. (C) 2009 Elsevier Ltd. All rights reserved.

InterLACE : a new international collaboration for a Life course approach to women's reproductive health and chronic disease events.

Evidence from population-based studies of women increasingly points to the inter-related nature of reproductive health, lifestyle, and chronic disease risk. This paper describes the recently established International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease. InterLACE aims to advance the evidence base for women's health policy beyond associations from disparate studies by means of systematic and culturally sensitive synthesis of longitudinal data. Currently InterLACE draws on individual level data for reproductive health and chronic disease among 200,000 women from over thirteen studies of women's health in seven countries. The rationale for this multi-study research programme is set out in terms of a life course perspective to reproductive health. The research programme will build a comprehensive picture of reproductive health through life in relation to chronic disease risk. Although combining multiple international studies poses methodological challenges, InterLACE represents an invaluable opportunity to strength evidence to guide the development of timely and tailored preventive health strategies.

Exchanging data between Digital Human Modelling systems : a review of data formats

Digital human modeling (DHM) systems underwent significant development within the last years. They achieved constantly growing importance in the field of ergonomic workplace design, product development, product usability, ergonomic research, ergonomic education, audiovisual marketing and the entertainment industry. They help to design ergonomic products as well as healthy and safe socio-technical work systems. In the domain of scientific DHM systems, no industry specific standard interfaces are defined which could facilitate the exchange of 3D solid body data, anthropometric data or motion data. The focus of this article is to provide an overview of requirements for a reliable data exchange between different DHM systems in order to identify suitable file formats. Examples from the literature are discussed in detail. Methods: As a first step a literature review is conducted on existing studies and file formats for exchanging data between different DHM systems. The found file formats can be structured into different categories: static 3D solid body data exchange, anthropometric data exchange, motion data exchange and comprehensive data exchange. Each file format is discussed and advantages as well as disadvantages for the DHM context are pointed out. Case studies are furthermore presented, which show first approaches to exchange data between DHM systems. Lessons learnt are shortly summarized. Results: A selection of suitable file formats for data exchange between DHM systems is determined from the literature review.

Bayesian networks in environmental and resource management

This overview article for the special series “Bayesian Networks in Environmental and Resource Management” reviews 7 case study articles with the aim to compare Bayesian network (BN) applications to different environmental and resource management problems from around the world. The article discusses advances in the last decade in the use of BNs as applied to environmental and resource management. We highlight progress in computational methods, best-practices for model design and model communication. We review several research challenges to the use of BNs in environmental and resource management that we think may find a solution in the near future with further research attention.

Business process mining success

Process mining has developed into a popular research discipline and nowadays its associated techniques are widely applied in practice. What is currently ill-understood is how the success of a process mining project can be measured and what the antecedent factors of process mining success are. We consider an improved, grounded understanding of these aspects of value to better manage the effectiveness and efficiency of process mining projects in practice. As such, we advance a model, tailored to the characteristics of process mining projects, which identifies and relates success factors and measures. We draw inspiration from the literature from related fields for the construction of a theoretical, a priori model. That model has been validated and re-specified on the basis of a multiple case study, which involved four industrial process mining projects. The unique contribution of this paper is that it presents the first set of success factors and measures on the basis of an analysis of real process mining projects. The presented model can also serve as a basis for further extension and refinement using insights from additional analyses.

A flexible optimisation model for the railway crew scheduling problem

Addressing the Crew Scheduling Problem (CSP) in transportation systems can be too complex to capture all details. The designed models usually ignore or simplify features which are difficult to formulate. This paper proposes an alternative formulation using a Mixed Integer Programming (MIP) approach to the problem. The optimisation model integrates the two phases of pairing generation and pairing optimisation by simultaneously sequencing trips into feasible duties and minimising total elapsed time of any duty. Crew scheduling constraints in which the crew have to return to their home depot at the end of the shift are included in the model. The flexibility of this model comes in the inclusion of the time interval of relief opportunities, allowing the crew to be relieved during a finite time interval. This will enhance the robustness of the schedule and provide a better representation of real-world conditions.

The SCRAMSPACE I scramjet flight design and construction

The design activities of the development of the SCRAMSPACE I scramjet-powered free-flight experiment are described in this paper. The objectives of this flight are first described together with the definition of the primary, secondary and tertiary experiments. The Scramjet configuration studied is first discussed together with the rocket motor system selected for this flight. The different flight sequences are then explained, highlighting the SCRAMSPACE I free-flyer separation and re-orientation procedures. A design trade-off study is then described considering vehicle stability, packaging, thermo-structural analysis and trajectory, discussing the alignment of the predicted performance with the mission scientific requirements. The global system architecture and instrumentation of the vehicle are then explained. The conclusions of this design phase are that a vehicle design has been produced which is able to meet the mission scientific goals and the procurement & construction of the vehicle are ongoing.

Why we should not cut P.E.

Thinking of cutting physical education? Think again. Even as we bemoan children's sedentary lifestyles, we often sacrifice school-based physical education in the name of providing more time for academics. In 2006, only 3.8 percent of elementary schools, 7.9 percent of middle schools, and 2.1 percent of high schools offered students daily physical education or its equivalent for the entire school year (Lee, Burgeson, Fulton, & Spain, 2007). We believe this marked reduction in school-based physical activity risks students' health and can't be justified on educational or ethical grounds. We'll get to the educational grounds in a moment. As to ethical reasons for keeping physical activity part of our young people's school days, consider the fact that childhood obesity is now one of the most serious health issues facing U.S. children (Ogden et al., 2006). School-based physical education programs engage students in regular physical activity and help them acquire skills and habits necessary to pursue an active lifestyle. Such programs are directly relevant to preventing obesity. Yet they are increasingly on the chopping block.

Head and neck squamous-cell cancer and its association with polymorphic enzymes of xenobiotic metabolism and repair

Tobacco smoking, alcohol drinking, and occupational exposures to polycyclic aromatic hydrocarbons are the major proven risk factors for human head and neck squamous-cell cancer (HNSCC). Major research focus on gene-environment interactions concerning HNSCC has been on genes encoding enzymes of metabolism for tobacco smoke constituents and repair enzymes. To investigate the role of genetically determined individual predispositions in enzymes of xenobiotic metabolism and in repair enzymes under the exogenous risk factor tobacco smoke in the carcinogenesis of HNSCC, we conducted a case-control study on 312 cases and 300 noncancer controls. We focused on the impact of 22 sequence variations in CYP1A1, CYP1B1, CYP2E1, ERCC2/XPD, GSTM1, GSTP1, GSTT1, NAT2, NQO1, and XRCC1. To assess relevant main and interactive effects of polymorphic genes on the susceptibility to HNSCC we used statistical models such as logic regression and a Bayesian version of logic regression. In subgroup analysis of nonsmokers, main effects in ERCC2 (Lys751Gln) C/C genotype and combined ERCC2 (Arg156Arg) C/A and A/A genotypes were predominant. When stratifying for smokers, the data revealed main effects on combined CYP1B1 (Leu432Val) C/G and G/G genotypes, followed by CYP1B1 (Leu432Val) G/G genotype and CYP2E1 (-70G>T) G/T genotype. When fitting logistic regression models including relevant main effects and interactions in smokers, we found relevant associations of CYP1B1 (Leu432Val) C/G genotype and CYP2E1 (-70G>T) G/T genotype (OR, 10.84; 95% CI, 1.64-71.53) as well as CYP1B1 (Leu432Val) G/G genotype and GSTM1 null/null genotype (OR, 11.79; 95% CI, 2.18-63.77) with HNSCC. The findings underline the relevance of genotypes of polymorphic CYP1B1 combined with exposures to tobacco smoke.

Structure and assembly of immature HIV

The major structural components of HIV are synthesized as a 55-kDa polyprotein, Gag. Particle formation is driven by the self-assembly of Gag into a curved hexameric lattice, the structure of which is poorly understood. We used cryoelectron tomography and contrast-transfer-function corrected subtomogram averaging to study the structure of the assembled immature Gag lattice to approximate to 17-angstrom resolution. Gag is arranged in the immature virus as a single, continuous, but incomplete hexameric lattice whose curvature is mediated without a requirement for pentameric defects. The resolution of the structure allows positioning of individual protein domains. High-resolution crystal structures were fitted into the reconstruction to locate protein-protein interfaces involved in Gag assembly, and to identify the structural transformations associated with virus maturation. The results of this study suggest a concept for the formation of nonsymmetrical enveloped viruses of variable sizes.

Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis

Current models of HIV-1 morphogenesis hold that newly synthesized viral Gag polyproteins traffic to and assemble at the cell membrane into spherical protein shells. The resulting late-budding structure is thought to be released by the cellular ESCRT machinery severing the membrane tether connecting it to the producer cell. Using electron tomography and scanning transmission electron microscopy, we find that virions have a morphology and composition distinct from late-budding sites. Gag is arranged as a continuous but incomplete sphere in the released virion. In contrast, late-budding sites lacking functional ESCRT exhibited a nearly closed Gag sphere. The results lead us to propose that budding is initiated by Gag assembly, but is completed in an ESCRT-dependent manner before the Gag sphere is complete. This suggests that ESCRT functions early in HIV-1 release-akin to its role in vesicle formation-and is not restricted to severing the thin membrane tether.