The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Early entry in the NBA Draft: The influence of unraveling, human capital, and option value

ABSTRACT In an influential article, "Unraveling in Matching Markets," Li and Rosen (1998) note the first seven picks, and 17 among 29 first round selections of the 1997 NBA draft, were not college seniors. In 2004, the first pick in the NBA draft was a high school senior, and 25 of the first 29 picks were not college seniors. Li and Rosen (1998) suggest early entry is a form of unraveling in a labor market as firms attempt to secure the most promising player. We suggest recent NBA contract provisions implemented to slow the early entry of talented players have instead provided additional incentives to both players and firms for early entry into the NBA. In particular, the lowering of the fixed wage contract and lengthening of rookie contracts have given firms limited monopsonistic power and the ability to capture economic rents. We explore two competing models that predict why teams choose a talented player sooner under the new rookie contract system. The first model is the traditional human capital model, and the second is the Lazear (1995) option value model. To test why unraveling occurs, we use a panel study of all NBA players for 12 years from 1989 through 2002. The data include individual player performance statistics on a season-to-season basis, salary, and draft number.

Health inequities in unscheduled healthcare for children with intellectual disabilities in Ireland: a study protocol

Health inequities for children with intellectual disabilities are prevalent within different health systems, and children with intellectual disabilites have shorter life expectancies than the general population, higher mortality rates before the age of 17 and have a greater risk of potentially preventable hospitalisations. A health systems approach to research in this area provides a useful means through which research can inform policy and practice to ensure people with intellectual disabilities receive equitable healthcare; however, there is a paucity of evidence regarding how to address differences that have been described in the literature to date. The overall aim of this research is to establish the extent of health inequities for children with intellectual disabilities in Ireland compared to children without intellectual disabilities with respect to their utilisation of primary care and rates of hospitalisation, and to gain a better understanding of what influences utilisation of primary care and emergency department services in this population. The design of this research adopts a multi-methods approach: statistical analysis of health data to determine the extent of health inequities in relation to healthcare utilisation; discrete choice experiments to explore General Practitioners\u27 decision making and parental preferences for optimal care; and concept mapping to develop consensus between stakeholders on how to address current healthcare inequities. By applying a systems lens to the issue of health inequities for children with intellectual disabilities, the research hopes to gain a thorough understanding of the varying components that can contribute to the maintenance of such healthcare inequities. A key output from the research will be a set of feasible solutions and interventions that can address health inequities for this population

A Model for Osteonecrosis of the Jaw with Zoledronate Treatment following Repeated Major Trauma

<div><p>This study aims to develop a reproducible rat model for post-traumatic bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our previous studies using dental extraction as an inducing factor, only 30% - 60% of zoledronate-treated animals fulfilled the definition of clinical BRONJ. We modified the zoledronate regimen and introduced repeated surgical extraction to illicit quantifiable BRONJ in all animals. Eighty retired-breeder female Sprague-Dawley rats were divided between the treatment (IV zoledronate; 80 μg/kg/week for 13 weeks) and control (saline) groups. On week 13, the left mandibular first molar was surgically extracted, followed by the second molar a week later. Animals were euthanized at 1-week, 2-weeks, and 8-weeks following extraction. The occurrence and severity of BRONJ were scored in each animal based on gross and MicroCT analysis. Parameters of bone formation and osteoclast functions at the extraction site were compared between groups. All zoledronate-treated animals developed a severe case of BRONJ that fulfilled the clinical definition of the condition in humans. Osteoclast attachment continued to be defective eight weeks after stopping the treatment. There were no signs of kidney or liver toxicity. Our data confirmed that repeated surgical extraction (major trauma) by itself consistently precipitated massive bone necrosis in ZA-treated animals, eliminating the need to induce pre-existing infection or comorbidity. These results will be the basis for further studies examining the <i>in-vivo</i> pathogenesis and prevention of BRONJ.</p></div

Systemic effects of ZA treatment.

<p>A: No significant difference in kidney histology or BUN serum level between control and ZA-treated animals. 9B: No significant difference in liver histology or ALT activity, used to evaluate liver function between the two groups. 9C: No significant difference in body weights between the two groups.</p