Risk factors for race-day fatality in flat racing Thoroughbreds in Great Britain (2000 to 2013)

A key focus of the racing industry is to reduce the number of race-day events where horses die suddenly or are euthanased due to catastrophic injury. The objective of this study was therefore to determine risk factors for race-day fatalities in Thoroughbred racehorses, using a cohort of all horses participating in flat racing in Great Britain between 2000 and 2013. Horse-, race- and course-level data were collected and combined with all race-day fatalities, recorded by racecourse veterinarians in a central database. Associations between exposure variables and fatality were assessed using logistic regression analyses for (1) all starts in the dataset and (2) starts made on turf surfaces only. There were 806,764 starts in total, of which 548,571 were on turf surfaces. A total of 610 fatalities were recorded; 377 (61.8%) on turf. In both regression models, increased firmness of the going, increasing racing distance, increasing average horse performance, first year of racing and wearing eye cover for the first time all increased the odds of fatality. Generally, the odds of fatality also increased with increasing horse age whereas increasing number of previous starts reduced fatality odds. In the ‘all starts’ model, horses racing in an auction race were at 1.46 (95% confidence interval (CI) 1.06–2.01) times the odds of fatality compared with horses not racing in this race type. In the turf starts model, horses racing in Group 1 races were at 3.19 (95% CI 1.71–5.93) times the odds of fatality compared with horses not racing in this race type. Identification of novel risk factors including wearing eye cover and race type will help to inform strategies to further reduce the rate of fatality in flat racing horses, enhancing horse and jockey welfare and safety

Cabozantinib in progressive medullary thyroid cancer

Purpose Cabozantinib, a tyrosine kinase inhibitor (TKI) of hepatocyte growth factor receptor (MET), vascular endothelial growth factor receptor 2, and rearranged during transfection (RET), demonstrated clinical activity in patients with medullary thyroid cancer (MTC) in phase I. Patients and Methods We conducted a double-blind, phase III trial comparing cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomly assigned (2:1) to cabozantinib (140 mg per day) or placebo. The primary end point was progression-free survival (PFS). Additional outcome measures included tumor response rate, overall survival, and safety. Results The estimated median PFS was 11.2 months for cabozantinib versus 4.0 months for placebo (hazard ratio, 0.28; 95% CI, 0.19 to 0.40; P < .001). Prolonged PFS with cabozantinib was observed across all subgroups including by age, prior TKI treatment, and RET mutation status (hereditary or sporadic). Response rate was 28% for cabozantinib and 0% for placebo; responses were seen regardless of RET mutation status. Kaplan-Meier estimates of patients alive and progression-free at 1 year are 47.3% for cabozantinib and 7.2% for placebo. Common cabozantinib-associated adverse events included diarrhea, palmar-plantar erythrodysesthesia, decreased weight and appetite, nausea, and fatigue and resulted in dose reductions in 79% and holds in 65% of patients. Adverse events led to treatment discontinuation in 16% of cabozantinib-treated patients and in 8% of placebo-treated patients. Conclusion Cabozantinib (140 mg per day) achieved a statistically significant improvement of PFS in patients with progressive metastatic MTC and represents an important new treatment option for patients with this rare disease. This dose of cabozantinib was associated with significant but manageable toxicity

Pichinde virus induces microvascular endothelial cell permeability through the production of nitric oxide

This report is the first to demonstrate infection of human endothelial cells by Pichinde virus (PIC). PIC infection induces an upregulation of the inducible nitric oxide synthase gene; as well as an increase in detectable nitric oxide (NO). PIC induces an increase in permeability in endothelial cell monolayers which can be abrogated at all measured timepoints with the addition of a nitric oxide synthase inhibitor, indicating a role for NO in the alteration of endothelial barrier function. Because NO has shown antiviral activity against some viruses, viral titer was measured after addition of the NO synthase inhibitor and found to have no effect in altering virus load in infected EC. The NO synthase inhibition also has no effect on levels of activated caspases induced by PIC infection. Taken together, these data indicate NO production induced by Pichinde virus infection has a pathogenic effect on endothelial cell monolayer permeability

Cecal obstruction due to primary intestinal tuberculosis: a case series

<p>Abstract</p> <p>Introduction</p> <p>Primary intestinal tuberculosis is a rare variant of tuberculosis. The preferred treatment is usually pharmaceutical, but surgery may be required for complicated cases.</p> <p>Case presentation</p> <p>We report two cases of primary intestinal tuberculosis where the initial diagnosis was wrong, with colonic cancer suggested in the first case and a Crohn's disease complication in the second. Both of our patients were Caucasians of Greek nationality. In the first case (a 60-year-old man), a right hemicolectomy was performed. In the second case (a 26-year-old man), excision was impossible due to the local conditions and peritoneal implantations. Histopathology revealed an inflammatory mass of tuberculous origin in the first case. In the second, cell culture and polymerase chain reaction tests revealed <it>Mycobacterium tuberculosis</it>. Both patients were given anti-tuberculosis therapy and their post-operative follow-up was uneventful.</p> <p>Conclusions</p> <p>Gastrointestinal tuberculosis still appears sporadically and should be considered in the differential diagnosis along with other conditions of the bowel. The use of immunosuppressants and new pharmaceutical agents can change the prevalence of tuberculosis.</p

Arsenic as an Endocrine Disruptor: Arsenic Disrupts Retinoic Acid Receptor–and Thyroid Hormone Receptor–Mediated Gene Regulation and Thyroid Hormone–Mediated Amphibian Tail Metamorphosis

Background: Chronic exposure to excess arsenic in drinking water has been strongly associated with increased risks of multiple cancers, diabetes, heart disease, and reproductive and developmental problems in humans. We previously demonstrated that As, a potent endocrine disruptor at low, environmentally relevant levels, alters steroid signaling at the level of receptor-mediated gene regulation for all five steroid receptors. Objectives: The goal of this study was to determine whether As can also disrupt gene regulation via the retinoic acid (RA) receptor (RAR) and/or the thyroid hormone (TH) receptor (TR) and whether these effects are similar to previously observed effects on steroid regulation. Methods and results: Human embryonic NT2 or rat pituitary GH3 cells were treated with 0.01–5 μM sodium arsenite for 24 hr, with or without RA or TH, respectively, to examine effects of As on receptor-mediated gene transcription. At low, noncytotoxic doses, As significantly altered RAR-dependent gene transcription of a transfected RAR response element–luciferase construct and the native RA-inducible cytochrome P450 CYP26A gene in NT2 cells. Likewise, low-dose As significantly altered expression of a transfected TR response element–luciferase construct and the endogenous TR-regulated type I deiodinase (DIO1) gene in a similar manner in GH3 cells. An amphibian ex vivo tail metamorphosis assay was used to examine whether endocrine disruption by low-dose As could have specific pathophysiologic consequences, because tail metamorphosis is tightly controlled by TH through TR. TH-dependent tail shrinkage was inhibited in a dose-dependent manner by 0.1– 4.0 μM As. Conclusions: As had similar effects on RAR- and TR-mediated gene regulation as those previously observed for the steroid receptors, suggesting a common mechanism or action. Arsenic also profoundly affected a TR-dependent developmental process in a model animal system at very low concentrations. Because RAR and TH are critical for both normal human development and adult function and their dysregulation is associated with many disease processes, disruption of these hormone receptor–dependent processes by As is also potentially relevant to human developmental problems and disease risk

Gastroesophageal reflux symptoms in infants in a rural population: longitudinal data over the first six months

<p>Abstract</p> <p>Background</p> <p>Increasing numbers of infants are receiving prescription medications for symptoms associated with gastroesophageal reflux. Our aim was to prospectively measure reported gastroesophageal reflux symptoms in healthy term infants for the first six months of life.</p> <p>Methods</p> <p>In a prospective cohort study in the rural Upper Peninsula of Michigan, 128 consecutive maternal-infant pairs were followed for six months and administered the Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R) at the one-month, two-month, four-month, and six-month well-child visits.</p> <p>Results</p> <p>The I-GERQ-R scores decreased with age. Average scores were 11.74 (SE = 5.97) at one-month, 9.97(4.92) at two-months, 8.44(4.39) at four-months, and 6.97(4.05) at six months. Symptoms associated with colic were greatest at one month of age.</p> <p>Conclusion</p> <p>Symptoms of gastroesophageal reflux as measured by the I-GERQ-R decrease with age in the first six months of life in otherwise healthy infants; however the I-GERQ-R may have difficulty differentiating gastroesophageal reflux disease from colic in those under 3 months of age.</p

The ecology of outdoor rape: The case of Stockholm, Sweden

The objective of this article is to report the results of an ecological study into the geography of rape in Stockholm, Sweden, using small area data. In order to test the importance of factors indicating opportunity, accessibility and anonymity to the understanding of the geography of rape, a two-stage modelling approach is implemented. First, the overall risk factors associated with the occurrence of rape are identified using a standard Poisson regression, then a local analysis using profile regression is performed. Findings from the whole-map analysis show that accessibility, opportunity and anonymity are all, to different degrees, important in explaining the overall geography of rape - examples of these risk factors are the presence of subway stations or whether a basområde is close to the city centre. The local analysis reveals two groupings of high risk of rape areas associated with a variety of risk factors: city centre areas with a concentration of alcohol outlets, high residential population turnover and high counts of robbery; and poor suburban areas with schools and large female residential populations where subway stations are located and where people express a high fear of crime. The article concludes by reflecting upon the importance of these results for future research as well as indicating the implications of these results for policy

The value of CCTV surveillance cameras as an investigative tool: an empirical analysis

There has been extensive research on the value of closed-circuit television (CCTV) for preventing crime, but little on its value as an investigative tool. This study sought to establish how often CCTV provides useful evidence and how this is affected by circumstances, analysing 251,195 crimes recorded by British Transport Police that occurred on the British railway network between 2011 and 2015. CCTV was available to investigators in 45% of cases and judged to be useful in 29% (65% of cases in which it was available). Useful CCTV was associated with significantly increased chances of crimes being solved for all crime types except drugs/weapons possession and fraud. Images were more likely to be available for more-serious crimes, and less likely to be available for cases occurring at unknown times or in certain types of locations. Although this research was limited to offences on railways, it appears that CCTV is a powerful investigative tool for many types of crime. The usefulness of CCTV is limited by several factors, most notably the number of public areas not covered. Several recommendations for increasing the usefulness of CCTV are discussed