22 research outputs found

    Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

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    <p>Abstract</p> <p>Background</p> <p>Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems.</p> <p>Methods</p> <p>Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations). Cows were examined and blood sampled every three weeks from four weeks ante partum (ap) to nine weeks postpartum (pp). Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA), insulin, ÎČ-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol.</p> <p>Results</p> <p>All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed.</p> <p>Conclusion</p> <p>NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds.</p

    Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

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    Purpose We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis

    Methods for Evaluating the Combined Effects of Chemical and Nonchemical Exposures for Cumulative Environmental Health Risk Assessment

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    Cumulative risk assessment (CRA) has been proposed as a means of evaluating possible additive and synergistic effects of multiple chemical, physical and social stressors on human health, with the goal of informing policy and decision-making, and protecting public health. Routine application of CRA to environmental regulatory and policy decision making, however, has been limited due to a perceived lack of appropriate quantitative approaches for assessing combined effects of chemical and nonchemical exposures. Seven research projects, which represented a variety of disciplines, including population health science, laboratory science, social sciences, geography, statistics and mathematics, were funded by the US Environmental Protection Agency (EPA) to help address this knowledge gap. We synthesize key insights from these unique studies to determine the implications for CRA practice and priorities for further research. Our analyses of these seven projects demonstrate that the necessary analytical methods to support CRA are available but are ultimately context-dependent. These projects collectively provided advancements for CRA in the areas of community engagement, characterization of exposures to nonchemical stressors, and assessment of health effects associated with joint exposures to chemical and psychosocial stressors

    Biliary Stenting in Patients with Pancreatic Cancer : Results from a Population-Based Cohort Study

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    Objective We aimed to describe management of biliary obstruction (BO) in the context of pancreatic cancer within a population-based cohort. Methods We examined management of BO in 1863 patients diagnosed as having pancreatic cancer in 2010/2011. We used descriptive statistics and logistic regression to describe patterns of biliary stent usage, complications and duration of patency, associations between preoperative stenting and surgical outcomes, and between patient factors and management of jaundice. Results Almost half of the people in the cohort (n = 909) were jaundiced within 12 months of diagnosis. Two-thirds of these had at least 1 stent inserted. Preoperative stenting, mostly with plastic stents, occurred for 72% of patients who experienced jaundice prior to an attempted resection but was not associated with surgical outcomes. Seventy percent of the jaundiced patients who did not have an attempted resection were stented. Metal stents were less frequently replaced within 30 days than plastic (9% vs 42%). Living in a rural area was associated with reduced likelihood of having jaundice managed. Conclusions Plastic stents were still used frequently, despite guidelines recommending metal in most contexts. Patients living in rural areas were less likely to have BO managed. This work highlights the need to monitor current practice.</p

    Chemotherapy in patients with unresected pancreatic cancer in Australia: A population-based study of uptake and survival

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    Palliative chemotherapy improves symptom control and prolongs survival in patients with unresectable pancreatic cancer, but there is a paucity of data describing its use and effectiveness in everyday practice. We explored patterns of chemotherapy use in patients with unresected pancreatic cancer in Australia and the impact of use on survival.We reviewed the medical records of residents of New South Wales or Queensland, Australia, diagnosed with unresectable pancreatic adenocarcinoma between July 2009 and June 2011. Associations between receipt of chemotherapy and sociodemographic, clinical and health service factors were evaluated using logistic regression. We used Cox proportional hazards models to analyze associations between chemotherapy use and survival.Data were collected for 1173 eligible patients. Chemotherapy was received by 44% (n\ua0=\ua0184/414) of patients with localized pancreatic cancer and 53% (n\ua0=\ua0406/759) of patients with metastases. Chemotherapy receipt depended on clinical factors, such as performance status and comorbidity burden, and nonclinical factors, such as age, place of residence, multidisciplinary team review and the type of specialist first encountered. Consultation with an oncologist mitigated most of the sociodemographic and service-related disparities in chemotherapy use. The receipt of chemotherapy was associated with prolonged survival in patients with inoperable pancreatic cancer, including after adjusting for common prognostic factors.These findings highlight the need to establish referral pathways to ensure that all patients have the opportunity to discuss treatment options with a medical oncologist. This is particularly relevant for health care systems covering areas with a geographically dispersed population

    Describing patterns of care in pancreatic cancer a population-based study

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    Objectives: Despite pancreatic cancer being the fifth highest cause of cancer death in developed regions, there is a paucity of populationbased management details for patients with pancreatic cancer. The objective of this study was to reflect on current practice and outcomes to facilitate future improvement. Methods: A comprehensive population-based patterns-of-care study in 2 Australian states was conducted. Patients diagnosed with pancreatic adenocarcinoma between July 2009 and June 2011 were identified by cancer registries, and detailed clinical data were collected from medical records. Results: Data were collected for 1863 patients, 96% of those eligible. The majority resided in major cities; their median age was 72 years, and 54% were men. Over half of the cases (58%) had metastatic disease at diagnosis. Resection was attempted for 20% of patients but only completed in 15%. The uptake of adjuvant chemotherapy (76%) and the proportion alive at 1-year (22%) were higher than reported in previous population-based reports. Of those with no complete surgical resection, 43% received palliative chemotherapy. Conclusions: This population-based overview of the management of patients with pancreatic cancer suggests that, despite evidence that the proportion surviving and the use of adjuvant chemotherapy has increased, there may still be underutilization of cancer-directed therapies
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