Modelling Risk to US Military Populations from Stopping Blanket Mandatory Polio Vaccination

Objectives. Transmission of polio poses a threat to military forces when deploying to regions where such viruses are endemic. US-born soldiers generally enter service with immunity resulting from childhood immunization against polio; moreover, new recruits are routinely vaccinated with inactivated poliovirus vaccine (IPV), supplemented based upon deployment circumstances. Given residual protection from childhood vaccination, risk-based vaccination may sufficiently protect troops from polio transmission. Methods. This analysis employed a mathematical system for polio transmission within military populations interacting with locals in a polio-endemic region to evaluate changes in vaccination policy. Results. Removal of blanket immunization had no effect on simulated polio incidence among deployed military populations when risk-based immunization was employed; however, when these individuals reintegrated with their base populations, risk of transmission to nondeployed personnel increased by 19%. In the absence of both blanket- and risk-based immunization, transmission to nondeployed populations increased by 25%. The overall number of new infections among nondeployed populations was negligible for both scenarios due to high childhood immunization rates, partial protection against transmission conferred by IPV, and low global disease incidence levels. Conclusion. Risk-based immunization driven by deployment to polio-endemic regions is sufficient to prevent transmission among both deployed and nondeployed US military populations

Structural Investigations of Creatine Kinase

X-ray crystallographic and other structural studies have been carried out on creatine kinase isolated from rabbit skeletal muscle. As a consequence of the exploration of a wide range of crystallisation conditions, a previously unreported crystal form of creatine kinase has been characterised. This crystal form is monoclinic C2 with three subunits in the asymmetric unit and cell dimensions a = 248 A, b = 149 A, c = 52 A, beta = 9

Exact Wave Solutions to 6D Gauged Chiral Supergravity

We describe a broad class of time-dependent exact wave solutions to 6D gauged chiral supergravity with two compact dimensions. These 6D solutions are nontrivial warped generalizations of 4D pp-waves and Kundt class solutions and describe how a broad class of previously-static compactifications from 6D to 4D (sourced by two 3-branes) respond to waves moving along one of the uncompactified directions. Because our methods are generally applicable to any higher dimensional supergravity they are likely to be of use for finding the supergravity limit of time-dependent solutions in string theory. The 6D solutions are interesting in their own right, describing 6D shock waves induced by high energy particles on the branes, and as descriptions of the near-brane limit of the transient wavefront arising from a local bubble-nucleation event on one of the branes, such as might occur if a tension-changing phase transition were to occur.Comment: 22 pages, 1 figure. Minor clarifications added. Accepted in JHE

First record of an Odontaspidid shark in Ascension Island waters

The occurrence of the poorly understood shark species Odontapsis ferox is reported at an oceanic seamount in the central south Atlantic, within the Exclusive Economic Zone of Ascension Island. The presence of the species at this location is confirmed by the discovery of a tooth embedded in scientific equipment, and footage of at least one animal on autonomous underwater video. The new record of this shark species at this location demonstrates the knowledge gaps which still exist at many remote, oceanic structures and their candidacy for status as important conservation areas.info:eu-repo/semantics/publishedVersio

An efficient and robust approach to Mendelian randomization with measured pleiotropic effects in a high-dimensional setting.

Valid estimation of a causal effect using instrumental variables requires that all of the instruments are independent of the outcome conditional on the risk factor of interest and any confounders. In Mendelian randomization studies with large numbers of genetic variants used as instruments, it is unlikely that this condition will be met. Any given genetic variant could be associated with a large number of traits, all of which represent potential pathways to the outcome which bypass the risk factor of interest. Such pleiotropy can be accounted for using standard multivariable Mendelian randomization with all possible pleiotropic traits included as covariates. However, the estimator obtained in this way will be inefficient if some of the covariates do not truly sit on pleiotropic pathways to the outcome. We present a method that uses regularization to identify which out of a set of potential covariates need to be accounted for in a Mendelian randomization analysis in order to produce an efficient and robust estimator of a causal effect. The method can be used in the case where individual-level data are not available and the analysis must rely on summary-level data only. It can be used where there are any number of potential pleiotropic covariates up to the number of genetic variants less one. We show the results of simulation studies that demonstrate the performance of the proposed regularization method in realistic settings. We also illustrate the method in an applied example which looks at the causal effect of urate plasma concentration on coronary heart disease

Stressing Mitosis to Death

The final stage of cell division (mitosis), involves the compaction of the duplicated genome into chromatid pairs. Each pair is captured by microtubules emanating from opposite spindle poles, aligned at the metaphase plate, and then faithfully segregated to form two identical daughter cells. Chromatids that are not correctly attached to the spindle are detected by the constitutively active spindle assembly checkpoint (SAC). Any stress that prevents correct bipolar spindle attachment, blocks the satisfaction of the SAC, and induces a prolonged mitotic arrest, providing the cell time to obtain attachment and complete segregation correctly. Unfortunately, during mitosis repairing damage is not generally possible due to the compaction of DNA into chromosomes, and subsequent suppression of gene transcription and translation. Therefore, in the presence of significant damage cell death is instigated to ensure that genomic stability is maintained. While most stresses lead to an arrest in mitosis, some promote premature mitotic exit, allowing cells to bypass mitotic cell death. This mini-review will focus on the effects and outcomes that common stresses have on mitosis, and how this impacts on the efficacy of mitotic chemotherapies

The Oncogenic Functions of MASTL Kinase

MASTL kinase is a master regulator of mitosis, essential for ensuring that mitotic substrate phosphorylation is correctly maintained. It achieves this through the phosphorylation of alpha-endosulfine and subsequent inhibition of the tumor suppressor PP2A-B55 phosphatase. In recent years MASTL has also emerged as a novel oncogenic kinase that is upregulated in a number of cancer types, correlating with chromosome instability and poor patient survival. While the chromosome instability is likely directly linked to MASTL’s control of mitotic phosphorylation, several new studies indicated that MASTL has additional effects outside of mitosis and beyond regulation of PP2A-B55. These include control of normal DNA replication timing, and regulation of AKT/mTOR and Wnt/β-catenin oncogenic kinase signaling. In this review, we will examine the phenotypes and mechanisms for how MASTL, ENSA, and PP2A-B55 deregulation drives tumor progression and metastasis. Finally, we will explore the rationale for the future development of MASTL inhibitors as new cancer therapeutics

Organisational Skill Sets For the Information Professional

There has been a recent call for information professionals to possess work skills that span many disciplines. Skyme & Earl(1989) mapped out the characteristics of the business worker and saw technical, business, organisational and personal skills as being important. Organisations are devolving in span of operations and downsizing in personnel levels. Technology is under constant change and information professionals are being asked to cope with the need to develop differing skill sets. Against this scenario our survey mapped the organisational skill sets of the information systems, information services and managerial professional within a range of commercial and academic areas. The results of this survey showed that of the eleven organisational skill sets studied only one, being actively involved with information users, showed a significant difference (ANOVA) between the three groupings