Proactive Management of Pneumonia Epizootics in Bighorn Sheep in Montana—Project Update

Pneumonia epizootics are a major challenge for effective management of bighorn sheep (Ovis canadensis). Approximately half of the herds in Montana have suffered die-offs since the 1980s, many of which were pneumonia events. A set of models that identify risk of pneumonia and the best management decisions given that risk would be of great value for proactive management of pneumonia epizootics. Our first objective is to design and test a risk model that will help predict a herd’s risk of pneumonia. We hypothesize that various factors increase risk through pathogen exposure, pathogen spread, and disease susceptibility. Analysis of these factors comparing herds with and without recent pneumonia histories using Bayesian logistic regression will allow us to design a risk model. Our second objective is to develop a proactive decision model that incorporates estimates of pneumonia risk to help evaluate costs and benefits of alternative proactive actions appropriate to those estimates. We will use a Structured Decision Making framework, which provides a deliberative, transparent, and defensible decision-making process that is particularly valuable in complex decision-making environments such as wildlife disease management. Together the resulting risk and decision models, to be completed this year, will help managers estimate pneumonia risk and identify the best management action based on both the severity of each herd’s predicted risk and costs and benefits of competing management alternatives. Ultimately, this project will demonstrate the development and application of risk and decision models for proactive wildlife health programs in Montana Fish, Wildlife and Parks

A Risk Model for Proactive Management of Pneumonia Epizootics in Bighorn Sheep

Pneumonia epizootics are a major challenge for management of bighorn sheep (Ovis canadensis). Risk factors associated with the disease are poorly understood, making pneumonia epizootics hard to predict; such epizootics are thus managed reactively rather than proactively. We developed a model that identifies risk factors and addresses biological questions about risk. Using Bayesian logistic regression with repeated measures, we found that private land, weed control using domestic sheep or goats, pneumonia history, and herd density were associated with risk of pneumonia in 43 herds in Montana that experienced 22 epizootics out of 637 herd years from 1979–2013. Within high-risk areas occupied by herds, risk increased with greater amounts of private land and use of domestic sheep or goats for weed control. Herds had >10 times greater odds of having a pneumonia epizootic if they or neighboring herds within high-risk areas had a history of pneumonia. Risk greatly increased when herds were at high density, with nearly 15 times greater odds of pneumonia compared to herds at low density. Number of federal sheep and goat allotments, proximity to nearest herds, ram:ewe ratios, normality of winter and spring precipitation, and herds with native versus mixed or reintroduced origin were not associated with increased risk. We conclude that factors associated with risk of pneumonia are complex and may not always be from the most obvious sources. The ability to identify high risk herds will help determine where to focus management efforts and what risk factors most affect each herd, facilitating more effective, proactive management

Modeling Proactive Decisions to Manage Pneumonia Epizootics in Bighorn Sheep

Pneumonia epizootics in bighorn sheep (Ovis canadensis) are a major challenge for wildlife agencies due to the complexity of the disease, long-term impacts, and lack of tools to manage risk. We developed a decision model to facilitate proactive management of pneumonia epizootics in bighorn sheep in Montana. Our decision model integrates a risk model to predict probability of pneumonia epizootics based on identified risk factors. It uses a structured decision making (SDM) approach to analyze potential decisions based on predictions from the risk model, herd-specific management objectives, and predicted consequences and trade-offs. We demonstrated our model’s use with an analysis of representative herds and analyzed the recommended decisions to understand them clearly. We learned that proactive management for each herd was expected to outperform in meeting multiple, competing management objectives compared to ongoing status quo management. Based on sensitivity analyses, we also learned that the recommended decisions were relatively robust with limited sensitivity to variations in model inputs and uncertainties; we expect this to be the case in future analyses as well. Our decision model addressed the challenges of uncertainty, risk tolerance, and the multi-objective nature of management of bighorn sheep while providing a consistent, transparent, and deliberative approach for making decisions for each herd. It is a unique tool for managing pneumonia epizootics using an accessible framework for biologists and managers. Our work also provides a case study for developing similar SDM-based decision models, particularly for other wildlife diseases, to address challenges of making complex decisions

Mathematical stories: Why do more boys than girls choose to study mathematics at AS-level in England?

Copyright @ 2005 Taylor & FrancisIn this paper I address the question: How is it that people come to choose mathematics and in what ways is this process gendered? I draw on the findings of a qualitative research study involving interviews with 43 young people all studying mathematics in post-compulsory education in England. Working within a post-structuralist framework, I argue that gender is a project and one that is achieved in interaction with others. Through a detailed reading of Toni and Claudia’s stories I explore the tensions for young women who are engaging in mathematics, something that is discursively inscribed as masculine, while (understandably) being invested in producing themselves as female. I conclude by arguing that seeing ‘doing mathematics’ as ‘doing masculinity’ is a productive way of understanding why mathematics is so male dominated and by looking at the implications of this understanding for gender and mathematics reform work.This work is funded by the ESR

Molecular characterization of adipose tissue in the African elephant (Loxodonta africana)

Adipose tissue (AT) is a dynamic and flexible organ with regulatory roles in physiological functions including metabolism, reproduction and inflammation; secreted adipokines, including leptin, and fatty acids facilitate many of these roles. The African elephant (Loxodonta africana) is experiencing serious challenges to optimal reproduction in captivity. The physiological and molecular basis of this impaired fertility remains unknown. AT production of leptin is a crucial molecular link between nutritional status, adiposity and fertility in many species. We propose that leptin has a similar function in the African elephant. African elephant visceral and subcutaneous adipose tissue (AT) was obtained from both sexes and a range of ages including females with known pregnancy status. RNA was extracted and histological sections created and analyzed by microarray, PCR and immunohistochemistry respectively. Gas-chromatography was used to determine the fatty acid composition of AT. Microarray expression profiling was used to compare gene expression profiles of AT from pre-pubertal versus reproductively competent adult African elephants. This study demonstrates, for the first time, leptin mRNA and protein expression in African elephant AT. The derived protein sequence of the elephant leptin protein was exploited to determine its relationship within the class I helical cytokine superfamily, which indicates that elephant leptin is most closely related to the leptin orthologs of Oryctolagus cuniculus (European rabbit), Lepus oiostolus (woolly hare), and members of the Ochotonidae (Pika). Immunohistological analysis identified considerable leptin staining within the cytoplasm of adipocytes. Significant differences in fatty acid profiles between pregnant and non-pregnant animals were revealed, most notably a reduction in both linoleic and α linoleic acid in pregnant animals. This report forms the basis for future studies to address the effect of nutrient composition and body condition on reproduction in captive and wild elephants

Justice Beyond Borders? Australia and the International Criminal Court

The International Criminal Court (ICC) came into being on 1 July 2002. A four-person team opened an office in The Hague and will collect reports and allegations of genocide, war crimes and crimes against humanity until judges and a prosecutor are appointed towards the end of 2003. Although the court was heralded by many states and international lawyers as the most important positive development in international law since the formation of the United Nations, it did not get off to an auspicious start. The Bush administration was concerned that US military forces operating overseas would be particularly vulnerable to what it described as 'politicised' prosecutions. It therefore insisted that not only would it not be a part of the ICC, but also that it would not sanction the continuation of UN peacekeeping operations. Closer to home, the Australian Senate only ratified the ICC's founding treaty, the Rome Statute, after a bitter debate that split both the Liberal and National parties. This was the case even though the Howard government-and Foreign Minister Alexander Downer in particular-had been a leading advocate of the court and ratification of the Rome Statute had been a Liberal Party election promise in 2001. The cost that Downer, and pro-ICC Attorney-General Daryl Williams had to pay in order to appease restive conservative backbenchers, the National Party, and an increasingly reluctant (and pro-US) Prime Minister and secure the ratification was a declaration that reaffirmed the primacy of the Australian judicial system over the ICC. The declaration insisted that no Australian would be prosecuted by the court without the consent of the Attomey-General, and asserted Australia's right to define what is meant by the crimes of genocide, war crimes, and crimes against humanity. We argue that although Downer and Williams should be commended for their commitment to international justice, the declaration attached to Australia's ratification was unnecessary and unhelpful. The first and third aspects of the declaration were unnecessary: the principle of complementarity enshrined in the Rome Statute means that the ICC already recognises the primacy of domestic jurisdiction, and the crimes covered are already considered to fall under universal jurisdiction, as the Nuremberg, Tokyo and more recent Pinochet trials showed (see Weller 1999). The second is unhelpful because it contravenes both the letter and the spirit of the Rome Statute. We will begin, then, by tracing the development of the ICC debate in Australian politics. In 1998, the government was an enthusiastic advocate of the court but by 2002 an alliance of an ardently pro-US Prime Minister, vocal right-wing parliamentarians and their supporters, and The Australian (and its foreign affairs editor Greg Sheridan in particular) combined to put ratification in doubt. Contrary to Prime Minister John Howard's claims, this debate was not well informed. Instead, it was characterised by hearsay, inaccuracy and scare-mongering. The subsequent section of the article demonstrates this by focusing on the background to, and creation of, the Rome Statute

Symptoms associated with victimization in patients with schizophrenia and related disorders

Background: Patients with psychoses have an increased risk of becoming victims of violence. Previous studies have suggested that higher symptom levels are associated with a raised risk of becoming a victim of physical violence. There has been, however, no evidence on the type of symptoms that are linked with an increased risk of recent victimization. Methods: Data was taken from two studies on involuntarily admitted patients, one national study in England and an international one in six other European countries. In the week following admission, trained interviewers asked patients whether they had been victims of physical violence in the year prior to admission, and assessed symptoms on the Brief Psychiatric Rating Scale (BPRS). Only patients with a diagnosis of schizophrenia or related disorders (ICD-10 F20–29) were included in the analysis which was conducted separately for the two samples. Symptom levels assessed on the BPRS subscales were tested as predictors of victimization. Univariable and multivariable logistic regression models were fitted to estimate adjusted odds ratios. Results: Data from 383 patients in the English sample and 543 patients in the European sample was analysed. Rates of victimization were 37.8% and 28.0% respectively. In multivariable models, the BPRS manic subscale was significantly associated with victimization in both samples. Conclusions: Higher levels of manic symptoms indicate a raised risk of being a victim of violence in involuntary patients with schizophrenia and related disorders. This might be explained by higher activity levels, impaired judgement or poorer self-control in patients with manic symptoms. Such symptoms should be specifically considered in risk assessments

Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”

Use of the dioxin toxic equivalency factor (TEF) approach in human risk assessments assumes that the combined effects of dioxin-like compounds in a mixture can be predicted based on a potency-adjusted dose-additive combination of constituents of the mixture. In this study, we evaluated the TEF approach in experimental 2-year rodent cancer bioassays with female Harlan Sprague-Dawley rats receiving 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of the three compounds. Statistically based dose–response modeling indicated that the shape of the dose–response curves for hepatic, lung, and oral mucosal neoplasms was the same in studies of the three individual chemicals and the mixture. In addition, the dose response for the mixture could be predicted from a combination of the potency-adjusted doses of the individual compounds. Finally, we showed that use of the current World Health Organization dioxin TEF values adequately predicted the increased incidence of liver tumors (hepatocellular adenoma and cholangiocarcinoma) induced by exposure to the mixture. These data support the use of the TEF approach for dioxin cancer risk assessments

The Potential of MLN3651 in Combination with Selumetinib as a Treatment for Merlin-Deficient Meningioma

Meningioma is the most common primary intracranial tumour, and surgical resection is the main therapeutic option. Merlin is a tumour suppressor protein that is frequently mutated in meningioma. The activity of the E3 ubiquitin ligase complex, CRL4-DCAF1, and the Raf/MEK/ERK scaffold protein Kinase suppressor of Ras 1 (KSR1) are upregulated in Merlin-deficient tumours, which drives tumour growth. Identifying small molecules that inhibit these key pathways may provide an effective treatment option for patients with meningioma. We used meningioma tissue and primary cells derived from meningioma tumours to investigate the expression of DDB1 and Cullin 4-associated factor 1 (DCAF1) and KSR1, and confirmed these proteins were overexpressed. We then used primary cells to assess the therapeutic potential of MLN3651, a neddylation inhibitor which impacts the activity of the CRL family of E3 ubiquitin ligases and the MAPK/ERK kinase (MEK1/2) inhibitor selumetinib. MLN3651 treatment reduced proliferation and activated apoptosis, whilst increasing Raf/MEK/ERK pathway activation. The combination of MLN3651 and the MEK1/2 inhibitor selumetinib prevented the increase in Raf/MEK/ERK activity, and had an additive effect compared with either treatment alone. Therefore, the combined targeting of CRL4-DCAF1 and Raf/MEK/ERK activity represents an attractive novel strategy in the treatment of Merlin-deficient meningioma.</jats:p