Evidence Against an Association Between Gamma-Ray Bursts and Type I Supernovae

We present a rigorous method, based on Bayesian inference, for calculating the odds favoring the hypothesis that any particular class of astronomical transients produce gamma-ray bursts over the hypothesis that they do not. We then apply this method to a sample of 83 Type Ia supernovae and a sample of 20 Type Ib-Ic supernovae. We find overwhelming odds against the hypothesis that all Type Ia supernovae produce gamma-ray bursts, whether at low redshift ($10^{9}:1$) or high-redshift ($10^{12}:1$), and very large odds ($6000:1$) against the hypothesis that all Type Ib, Ib/c, and Ic supernovae produce observable gamma-ray bursts. We find large odds ($34:1$) against the hypothesis that a fraction of Type Ia supernovae produce observable gamma-ray bursts, and moderate odds ($6:1$) against the hypothesis that a fraction of Type Ib-Ic supernovae produce observable bursts. We have also re-analyzed both a corrected version of the Wang & Wheeler sample of Type Ib-Ic SNe and our larger sample of 20 Type Ib-Ic SNe, using a generalization of their frequentist method. We find no significant evidence in either case of a correlation between Type Ib-Ic SNe and GRBs, consistent with the very strong evidence against such a correlation that we find from our Bayesian analysis.Comment: 45 pages, 2 PostScript figures. Uses AASTEX macros. Submitted to The Astrophysical Journa

Why worry about awareness in choice problems? Econometric analysis of screening for cervical cancer

Cervical cancer is one of the most preventable and curable forms of cancer. Since 1991 there has been a concerted effort in Australia to recommend and encourage women to have Pap smears every two years. Part of the success of this National Cervical Screening Program can be gauged by exploring the determinants of screening for cervical cancer among high-risk women and by addressing the specific question of whether screening is associated with socio-economic status. Accessibility to health services remains a core goal in health policy in Australia but evidence on whether the goal is being met is limited. Using unit record data from the 1995 National Health Survey, an econometric model is developed for whether women have ever screened or not. A proportion of women in the sample contend that they have never heard of a Pap test. The analysis characterizes this group of women and accounts for their presence in our modellingScreening choice; Awareness; Censored probit; Cervical cancer

Attractors of directed graph IFSs that are not standard IFS attractors and their Hausdorff measure

For directed graph iterated function systems (IFSs) defined on R, we prove that a class of 2-vertex directed graph IFSs have attractors that cannot be the attractors of standard (1-vertex directed graph) IFSs, with or without separation conditions. We also calculate their exact Hausdorff measure. Thus we are able to identify a new class of attractors for which the exact Hausdorff measure is known

Optimal management of urinary tract infections in older people

Urinary tract infections (UTI) occur frequently in older people. Unfortunately, UTI is commonly overdiagnosed and overtreated on the basis of nonspecific clinical signs and symptoms. The diagnosis of a UTI in the older patient requires the presence of new urinary symptoms, with or without systemic symptoms. Urinalysis is commonly used to diagnose infection in this population, however, the evidence for its use is limited. There is overwhelming evidence that asymptomatic bacteriuria should not be treated. Catheter associated urinary tract infection accounts for a significant amount of hospital-associated infection. Indwelling urinary catheters should be avoided where possible and alternatives sought. The use of narrow spectrum antimicrobial agents for urinary tract infection is advocated. Local guidelines are now widely used to reflect local resistance patterns and available agents. Guidelines need to be updated to reflect changes in antimicrobial prescribing and a move from broad to narrow spectrum antimicrobials

Cervical Cancer-Associated Human Papillomavirus 16 E7 Oncoprotein Inhibits Induction of Anti-Cancer Immunity by a CD4+ T Cell Dependent Mechanism

Attempts to develop therapeutic vaccines against cervical cancer have been proven difficult. One of the major causes of the failure is due to the use of the wrong mouse models based on transplantable tumours in testing the efficacy of vaccines. Now that a transgenic epithelial mouse model has been developed to closely mimic cervical cancer, the mechanisms needed to eliminate this type of cancer could be studied. The E7 oncoprotein of Human Papillomavirus (HPV) is the most expressed HPV protein in cervical cancers and its continuous production is essential to maintain the cancerous state and therefore the obvious target in the development of vaccines. Skin grafts expressing the HPV 16 E7 protein (E7 autografts) are not spontaneously rejected from an MHC matched immunocompetent host. Interestingly, simultaneous placement of an MHC mismatched skin (allograft) next to an E7 autograft results in the E7 autograft rejection. However when the allograft also expresses E7, the E7 autograft is rejected more slowly. Autograft rejection requires CD8+ T cells, and is accelerated by removal of CD4+ T cells after placement of the E7 expressing allograft, suggesting induction of an E7 specific CD4+ regulatory T cell population by the E7 expressing allograft. This observation may have implications in designing effective vaccines and immunotherapy against cervical cancers in women

A Christ-Like Attitude

This convocation address was given at the BYU Law School on April 24, 1981

Characterisation of community-derived Hymenolepis infections in Australia

Hymenolepis nana is a ubiquitous parasite, found throughout many developing and developed countries. Globally, the prevalence of H. nana is alarmingly high, with estimates of up to 75 million people infected. In Australia, the rates of infection have increased substantially in the last decade, from less than 20% in the early 1990's to 55 - 60% in these same communities today. Our knowledge of the epidemiology of infection of H. nana is hampered by the confusion surrounding the host specificity and taxonomy of this parasite. The suggestion of the existence of two separate species, Hymenolepis nana von Siebold 1852 and Hymenolepis fraterna Stiles 1906, was first proposed at the beginning of the 20th century. Despite ongoing discussions in the subsequent years it remained unclear, some 90 years later, whether there were two distinct species, that are highly host specific, or whether they were simply the same species present in both rodent and human hosts. The ongoing controversy surrounding the taxonomy of H. nana has not yet been resolved and remains a point of difference between the taxonomic and medical literature. The epidemiology of infection with H. nana in Australian communities is not well understood as the species present in these communities has never been identified with certainty. It is not clear which form of transmission commonly occurs in Australia, whether the H. nana 'strain/species' present in the north-west of Western Australia is present in human and rodent hosts, or whether humans harbour their own 'strain/sub-species' of Hymenolepis. Furthermore, it is not known whether mice are a potential zoonotic source for transmission of Hymenolepis to human hosts. In this study, 51 human isolates of H. nana were inoculated into highly susceptible laboratory rodent species. However, these failed to develop into adult worms in all instances, including when rodent species were chemically and genetically immunosuppressed. In addition, 24 of these human isolates were also cross-tested in the flour beetle intermediate host, Tribolium confusum. Of these, only one isolate developed to the cysticercoid stage in beetles, yet when inoculated into laboratory rodents, the cysticercoids also failed to develop into adult stage. Since isolates of H. nana infecting humans and rodents are morphologically indistinguishable, the only way they can be reliably identified is by comparing the parasite in each host using molecular criteria. In the current study, three regions of ribosomal DNA, the small subunit (18S), the first internal transcribed spacer (ITS1) and the intergenic spacer (IGS) were chosen for genetic characterisation of Hymenolepis spp. from rodent and human hosts from a broad geographic range. In addition, a mitochondrial gene, the cytochrome c oxidase subunit 1 (C01) gene and a non-ribosomal nuclear gene, paramyosin, were characterised in a number of Hymenolepis isolates from different hosts. A small PCR fragment of 369 bp, plus a larger fragment of 1223 bp, were sequenced from the 18S gene of reference isolates of H. nana and the rat tapeworm H. diminuta. Minimal sequence variation was found in the two regions of the 18S between these two morphologically distinct, phylogenetically recognised species, H. nana and H. diminuta, and this indicated that the 18S gene was too conserved for further genetic characterisation of isolates of H. nana from different hosts. A large number of human isolates of H. nana (104) were characterised at the ITS1 using PCRrestriction length fragment polymorphism (PCR-RFLP). The profiles obtained were highly variable and often exceeded the original size of the uncut fragment. This was highly suggestive of the existence of ribosomal spacers that, whilst identical in length, were highly variable in sequence. To overcome the problems of the variable PCR-RFLP profiles, further characterisation of the ITS1, by cloning and sequencing 23 isolates of H. nana, was conducted and this confirmed the existence of spacers which, although similar in length (approximately 646 bp), differed in their primary sequences. The sequence differences led to the separation of the isolates into two clusters when analysed phylogenetically. This sequence variation was not, however, related to the host of origin of the isolate, thus was not a marker of genetic distinction between H. nana from rodents and humans. Indeed, the levels of variability were often higher within an individual isolate than between isolates, regardless of whether they were collected from human or mice hosts, which was problematic for phylogenetic analysis. In addition, mixed parasite infections of H. nana and the rodent tapeworm H. microstoma were identified in four humans in this study, which was unexpected and surprising, as there have been no previous reports in the literature documenting humans as definitive hosts for this parasite. Further studies are required, however, to determine if the detection of H. microstoma in humans reflects a genuine, patent infection or an atypical, accidental occurrence. Sequencing of the mitochondrial cytochrome c oxidase 1 gene (C01) in a number of isolates of Hymenolepis nana from rodents and humans identified a phylogenetically supported genetic divergence of approximately 5% between some mouse isolates compared to isolates of H. nana from humans. This provided evidence that the mitochondrial C01 gene was useful for identifying genetic divergences in H. nana that were not resolvable using nuclear loci. Despite a morphological identity between isolates of H. nana from rodent and human hosts, the genetic divergence observed between isolates at the mitochondrial locus was highly suggestive that H. nana is a species complex, or 'cryptic' species (= morphologically identical yet genetically distinct). In addition, whilst not supported by high bootstrap values, a clustering of the Australian human isolates into one uniform genetic group that was phylogenetically separated from all the mouse isolates was well supported by biological data obtained in this study. To confirm the phylogeny of the C01 tree a small segment of the nuclear gene, paramyosin, was sequenced in a number of isolates from humans and rodents. However, this gene did not provide the level of heterogeneity required to distinguish between isolates from rodent and human hosts. The high sequence conservation of the paramyosin gene characterised in this study did not refute the finding that H. nana may be a cryptic species that is becoming host adapted. It simply did not provide additional data to that already obtained. A DNA fingerprinting tool, PCR-RFLP, of the ribosomal intergenic spacer (IGS), was developed in this study in order to evaluate its usefulness in tracing particular genotypes within a community, thus determining transmission patterns of H. nana between rodent and human hosts. Analysis of the IGS of numerous H. nana isolates by PCR-RFLP identified the presence of copies of the IGS that, whilst similar in length, differed in their sequence. Similar to that observed in the ITS1, the existence of different IGS copies was found in both rodent and human isolates of H. nana, thus the variability was not evidence of the existence of a rodent- or humanspecific genotype. Evaluation of the intergenic spacer (IGS) as a fingerprinting tool suggests that this region of DNA is too variable within individuals and thus, cannot be effectively used for the study of transmission patterns of the tapeworm H. nana between different hosts. In summary, it appears that the life cycle of H. nana that exists in remote communities in the north-west of Western Australia is likely to involve mainly 'human to human' transmission. This is supported by both the biological and genetic data obtained for the mitochondrial locus in this study. The role of the intermediate hosts, such as Tribolium spp., in the Hymenolepis life cycle is still unclear, however it would appear that it may be greatly reduced in the transmission of this parasite in remote Australian communities. In the future, it is recommended that further genetic characterisation of faster evolving mitochondrial genes, and/or suitable nuclear genes be characterised in a larger number of isolates of H. nana. The use of techniques which can combine the characterisation of genotype and phenotype, such as proteomics, may also be highly valuable for studies on H. nana from different hosts

Improving Quit Rates For Tobacco-Dependent Hospitalized Patients

Abstract Purpose: The purpose of this project was to evaluate outcomes of an existing inpatient tobacco cessation counseling program with 30-day follow-up among recently admitted tobacco-dependent patients who were tobacco-dependent. Background/Significance: Tobacco use is considered the number one most preventable cause of disease, disability, and death in the United States. Despite associated dangers, approximately 21% Americans currently smoke. This has led to increased hospital admissions and chronic disease management, costing the United States approximately $96 billion per year. Decades of research and evidence-based clinical practice guidelines substantiate that inpatient tobacco cessation counseling has the potential to improve quit rates post-hospital discharge. Method: This quality improvement project utilized existing hospital data containing demographic and medical information about patients and tobacco use behaviors. The goal was to answer the question: Does the provision of a tobacco cessation program initiated during hospitalization for persons who are tobacco-dependent (a) increase quit attempts or (b) reduce tobacco consumption? The electronic medical record was queried for data related to: demographics, insurance type, and diagnosis. Data related to smoking status and the intervention was extracted from a paper chart maintained by the certified tobacco treatment specialist. Results: Out of 176 tobacco-dependent patients admitted to the hospital, 100 (57%) indicated an intention to quit (at admission time) while only 40 (23%) reported having quit within 30 days post discharge (McNemar Test, p=0.000, n=176). The mean number of cigarettes smoked per day dropped from 19 cigarettes on admission to 13 cigarettes post discharge. [t (158)=6.7476, p=0.000]. Conclusions: This quality improvement project showed that although an inpatient smoking cessation program did not improve quit rates, it did significantly improve reduction in tobacco consumption