Hypothesis testing near singularities and boundaries

The likelihood ratio statistic, with its asymptotic $\chi^2$ distribution at regular model points, is often used for hypothesis testing. At model singularities and boundaries, however, the asymptotic distribution may not be $\chi^2$, as highlighted by recent work of Drton. Indeed, poor behavior of a $\chi^2$ for testing near singularities and boundaries is apparent in simulations, and can lead to conservative or anti-conservative tests. Here we develop a new distribution designed for use in hypothesis testing near singularities and boundaries, which asymptotically agrees with that of the likelihood ratio statistic. For two example trinomial models, arising in the context of inference of evolutionary trees, we show the new distributions outperform a $\chi^2$.Comment: 32 pages, 12 figure

Attitudes of Healthcare Workers towards Older People in a Rural Population: A Survey Using the Kogan Scale

With the global trend towards an increasingly ageing population, it is clear that nurses need to be equipped with the knowledge and skills to fulfil significant roles in responding to future health and support needs. This paper reports the results of a survey that aimed to identify and evaluate the attitudes of nurses, healthcare assistants, and nursing students towards older people. The survey was undertaken in a rural county in the Republic of Ireland. It is reassuring that in our study, we found that these healthcare workers hold positive attitudes towards older people. In addition, we found that study to a higher level at university appears to mitigate towards holding more positive attitudes, and this is an important finding in light of the shift towards nursing as an all-graduate profession

Cardiorespiratory Fitness Is Inversely Associated With Clustering of Metabolic Syndrome Risk Factors: The Ball State Adult Fitness Program Longitudinal Lifestyle Study

Objective: The focus of this study was the association between the metabolic syndrome (MetSyn) and cardiorespiratory fitness (CRF) defined as maximal oxygen uptake (VO2max). Although previous research has shown a relationship between MetSyn and CRF, most studies are based on less objective measures of CRF and different cardiometabolic risk factor thresholds from earlier guidelines

A generalized AIC for models with singularities and boundaries

The Akaike information criterion (AIC) is a common tool for model selection. It is frequently used in violation of regularity conditions at parameter space singularities and boundaries. The expected AIC is generally not asymptotically equivalent to its target at singularities and boundaries, and convergence to the target at nearby parameter points may be slow. We develop a generalized AIC for candidate models with or without singularities and boundaries. We show that the expectation of this generalized form converges everywhere in the parameter space, and its convergence can be faster than that of the AIC. We illustrate the generalized AIC on example models from phylogenomics, showing that it can outperform the AIC and gives rise to an interpolated effective number of model parameters, which can differ substantially from the number of parameters near singularities and boundaries. We outline methods for estimating the often unknown generating parameter and bias correction term of the generalized AIC.Comment: 21 pages, 5 figure

Guanylate cyclase C limits systemic dissemination of a murine enteric pathogen

BACKGROUND: Guanylate Cyclase C (GC-C) is an apically-oriented transmembrane receptor that is expressed on epithelial cells of the intestine. Activation of GC-C by the endogenous ligands guanylin or uroguanylin elevates intracellular cGMP and is implicated in intestinal ion secretion, cell proliferation, apoptosis, intestinal barrier function, as well as the susceptibility of the intestine to inflammation. Our aim was to determine if GC-C is required for host defense during infection by the murine enteric pathogen Citrobacter rodentium of the family Enterobacteriacea. METHODS: GC-C(+/+) control mice or those having GC-C genetically ablated (GC-C(−/−)) were administered C. rodentium by orogastric gavage and analyzed at multiple time points up to post-infection day 20. Commensal bacteria were characterized in uninfected GC-C(+/+) and GC-C(−/−) mice using 16S rRNA PCR analysis. RESULTS: GC-C(−/−) mice had an increase in C. rodentium bacterial load in stool relative to GC-C(+/+). C. rodentium infection strongly decreased guanylin expression in GC-C(+/+) mice and, to an even greater degree, in GC-C(−/−) animals. Fluorescent tracer studies indicated that mice lacking GC-C, unlike GC-C(+/+) animals, had a substantial loss of intestinal barrier function early in the course of infection. Epithelial cell apoptosis was significantly increased in GC-C(−/−) mice following 10 days of infection and this was associated with increased frequency and numbers of C. rodentium translocation out of the intestine. Infection led to significant liver histopathology in GC-C(−/−) mice as well as lymphocyte infiltration and elevated cytokine and chemokine expression. Relative to naïve GC-C(+/+) mice, the commensal microflora load in uninfected GC-C(−/−) mice was decreased and bacterial composition was imbalanced and included outgrowth of the Enterobacteriacea family. CONCLUSIONS: This work demonstrates the novel finding that GC-C signaling is an essential component of host defense during murine enteric infection by reducing bacterial load and preventing systemic dissemination of attaching/effacing-lesion forming bacterial pathogens such as C. rodentium

The Necessity of Observer Programs in the World’s Fisheries

The marine environment is experiencing increased human-induced stress, compounded by natural and human-induced (global warming) climatic changes. “Freedom of the sea” is no longer a viable option as marine resources become increasingly scarce. Both fishermen and managers must work cooperatively and diligently to monitor the existing limited resources. In order to effectively monitor a fishery, managers need to quantify how much is removed from the sea. Observer programs are the best way to achieve this objective and without them, managers are operating on guesswork. Observer data is used throughout the globe by conservation groups, international agencies, economists, and a wide array of scientists. Almost all of the catch values from commercial fishing vessels cited in publications by these institutions originate from observer program data. Self-reporting of catch data has proven to be inaccurate and ineffective in monitoring stocks. This is because most fishermen are concentrating on commercially valuable species, boat maintenance and compliance to those regulations that are easily and most often checked by enforcement officials. There is a prevailing naivety throughout societies regarding the true cost of eating fish. This must be addressed by fisheries economists so that vital monitoring systems don't fall by the wayside.Keywords: fisheries observer, monitoring resources, fisheries management, fisheries data, funding observer program

A generic expression system to produce proteins that co-assemble with alkane thiol SAM

Surface biology aims to observe and control biological processes by combining bio-, surface, and physical chemistry. Self-assembled monolayers (SAM) on gold surfaces have provided excellent methods for nanoscale surface preparation for such studies. However, extension of this work requires the specific immobilization of whole protein domains and the direct incorporation of recombinant proteins into SAM is still problematic. In this study a short random coil peptide has been designed to insert into thioalkane layers by formation of a hydrophobic helix. Surface plasmon resonance (SPR) studies show that specific immobilization via the internal cysteine is achieved. Addition of the peptide sequence to the terminus of a protein at the genetic level enables the production of a range of recombinant fusion-proteins with good yield. SPR shows that the proteins display the same gold-binding behavior as the peptide. It is shown that cell growth control can be achieved by printing the proteins using soft lithography with subsequent infilling with thioalkanes The expression plasmid is constructed so that any stable protein domain can be easily cloned, expressed, purified and immobilized