330 research outputs found

    Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

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    Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

    Radon--Nikodym representations of Cuntz--Krieger algebras and Lyapunov spectra for KMS states

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    We study relations between (H,β)(H,\beta)--KMS states on Cuntz--Krieger algebras and the dual of the Perron--Frobenius operator L−βH∗\mathcal{L}_{-\beta H}^{*}. Generalising the well--studied purely hyperbolic situation, we obtain under mild conditions that for an expansive dynamical system there is a one--one correspondence between (H,β)(H,\beta)--KMS states and eigenmeasures of L−βH∗\mathcal{L}_{-\beta H}^{*} for the eigenvalue 1. We then consider representations of Cuntz--Krieger algebras which are induced by Markov fibred systems, and show that if the associated incidence matrix is irreducible then these are ∗\ast--isomorphic to the given Cuntz--Krieger algebra. Finally, we apply these general results to study multifractal decompositions of limit sets of essentially free Kleinian groups GG which may have parabolic elements. We show that for the Cuntz--Krieger algebra arising from GG there exists an analytic family of KMS states induced by the Lyapunov spectrum of the analogue of the Bowen--Series map associated with GG. Furthermore, we obtain a formula for the Hausdorff dimensions of the restrictions of these KMS states to the set of continuous functions on the limit set of GG. If GG has no parabolic elements, then this formula can be interpreted as the singularity spectrum of the measure of maximal entropy associated with GG.Comment: 30 pages, minor changes in the proofs of Theorem 3.9 and Fact

    Monkey anti-placental serum as an abortifacient,

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    Pregnant Rhesus monkeys can be aborted by injection of heterologous (autologous) placental globulin without any notable harm to the mother. Presumably, anti-placental globulin reacts with trophoblastic tissue in the presence of complement, which then destroys tissues, and abortion follows. Within this experimental model, neither MPL nor MCG appear as responsible antigenic elements; but rather, a placental specific antigen(s) as yet unidentified.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34204/1/0000493.pd

    Intelligence and neuroticism in relation to depression and psychological distress: Evidence from two large population cohorts

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    BACKGROUND: Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-relationships of neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined. METHODS: Associations and interactions between neuroticism and general intelligence (g) on MDD, self-reported depression, and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, n=19,200) and UK Biobank (n=90,529). The Eysenck Personality Scale Short Form-Revised measured neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS. RESULTS: Neuroticism was strongly associated with increased risk for depression and higher psychological distress in both samples. Although intelligence conferred no consistent independent effects on depression, it did increase the risk for depression across samples once neuroticism was adjusted for. Results suggest that higher intelligence may ameliorate the association between neuroticism and self-reported depression although no significant interaction was found for clinical MDD. Intelligence was inversely associated with psychological distress across cohorts. A small interaction was found across samples such that lower psychological distress associates with higher intelligence and lower neuroticism, although effect sizes were small. CONCLUSIONS: From two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of neuroticism on psychological distress. Intelligence does not confer protection against diagnosis of depression in those high in neuroticism

    Influence of Concussion Education Exposure on Concussion-Related Educational Targets and Self-Reported Concussion Disclosure among First-Year Service Academy Cadets

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    Concussion disclosure is often essential for military personnel to receive appropriate care following concussive injury. Concussion-related education and training may play a role in improving disclosure and recognition among peers, allowing for more timely concussion identification and treatment. The objectives of this study were to: (1) describe concussion education exposure among first-year service academy cadets and (2) examine the association between exposure to concussion education sources (multiple vs. only one) and concussion-related knowledge, attitudes, perceived social norms, intention to disclose symptoms, and disclosure behaviors. Materials and Methods: First-year service academy cadets completed a cross-sectional survey to assess perceptions of concussion disclosure during preseason concussion baseline testing sessions. Associations between key cadet characteristics and exposure to multiple concussion education sources were examined using odds ratios and 95% confidence intervals. Linear regression was used to model the continuous measures of concussion-related knowledge, attitudes, and perceived social norms. Log-binomial regression was used to model the categorical outcomes of high perceived control over concussion disclosure (higher vs. lower), intention to disclose (higher vs. lower), and disclosure of all possible concussive events at the time of injury (yes vs. no). The primary predictor for all models was exposure to multiple sources of concussion education (video, coach, medical professional, or other) vs. exposure to only one educational source. All models were adjusted for gender, high school contact sport participation, and previous concussion history. Results: Of the 972 first-year cadets (85% response; age = 18.4 ± 0.9 years; 21.7% female, 29.0% NCAA student-athlete), 695 (71.5%) reported receiving some type of previous concussion education and 229 (23.6%) reported a previous concussion history (206/229 reported the actual number they experienced). Of those reporting previous concussion-related education (n = 695), 542 (78.0%) watched a video, 514 (74.0%) talked with a coach about concussion, 433 (62.3%) talked with a medical professional, and 61 (8.8%) reported other sources of education ranging from anatomy teachers to brochures. Overall, 527 (75.8%) reported receiving more than one source of concussion education. Having played a contact sport in high school and having a history of concussion were associated with having multiple concussion education exposures. Being female was associated with lower odds of multiple exposures. Exposure to multiple sources of concussion education was not associated with knowledge, attitudes, perceived norms, or higher intention to disclose concussion symptoms. However, among those with a concussion history, exposure to multiple sources of concussion education was associated with a nearly 40% higher prevalence of disclosing all concussions at the time of injury compared to only one source of educational exposure (67.1% vs. 48.3%; prevalence ratio = 1.4; 95% confidence interval: 0.9, 2.1). Thus, although multiple sources of education may not influence intermediate variables of knowledge, attitudes, perceived norms and intentions, exposure to multiple sources of concussion education may influence actual decision-making around concussion disclosure among first-year service academy cadets. Conclusion: These data suggest disparities in concussion education exposure that can be addressed in first-year cadets. Additionally, findings support the importance and use of multiple sources of concussion education in improving cadet's concussion-related decision-making

    L-VRAP-a lunar volatile resources analysis package for lunar exploration

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    The Lunar Volatile Resources Analysis Package (L-VRAP) has been conceived to deliver some of the objectives of the proposed Lunar Lander mission currently being studied by the European Space Agency. The purpose of the mission is to demonstrate and develop capability; the impetus is very much driven by a desire to lay the foundations for future human exploration of the Moon. Thus, LVRAP has design goals that consider lunar volatiles from the perspective of both their innate scientific interest and also their potential for in situ utilisation as a resource. The device is a dual mass spectrometer system and is capable of meeting the requirements of the mission with respect to detection, quantification and characterisation of volatiles. Through the use of appropriate sampling techniques, volatiles from either the regolith or atmosphere (exosphere) can be analysed. Furthermore, since L-VRAP has the capacity to determine isotopic compositions, it should be possible for the instrument to determine the sources of the volatiles that are found on the Moon (be they lunar per se, extra-lunar, or contaminants imparted by the mission itself

    Beware Biofilm! Dry biofilms containing bacterial pathogens on multiple healthcare surfaces; a multicentre study

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    BackgroundWet biofilms associated with medical devices have been widely studied and their link with healthcare-associated infections (HCAIs) is well recognized. Little attention has been paid to the presence of dry biofilms on environmental surfaces in healthcare settings.AimTo investigate the occurrence, prevalence, and diversity of dry biofilms on hospital surfaces.MethodsSixty-one terminally cleaned items were received from three different UK hospitals. The presence of dry biofilm was investigated using culture-based methods and scanning electron microscopy (SEM). Bacterial diversity within biofilms was investigated using ribosomal RNA intergenic spacer analysis (RISA)–polymerase chain reaction and next-generation sequencing.FindingsMulti-species dry biofilms were recovered from 95% of 61 samples. Abundance and complexity of dry biofilms were confirmed by SEM. All biofilms harboured Gram-positive bacteria including pathogens associated with HCAI; 58% of samples grew meticillin-resistant Staphylococcus aureus. Dry biofilms had similar physical composition regardless of the type of items sampled or the ward from which the samples originated. There were differences observed in the dominance of particular species: dry biofilms from two hospitals contained mostly staphylococcal DNA, whereas more Bacillus spp. DNA was found on surfaces from the third hospital.ConclusionThe presence of dry biofilms harbouring bacterial pathogens is virtually universal on commonly used items in healthcare settings. The role of dry biofilms in spreading HCAIs may be underestimated. The risk may be further exacerbated by inefficient cleaning and disinfection practices for hospital surface

    A conceptual framework for the emerging discipline of conservation physiology

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    Current rates of biodiversity decline are unprecedented and largely attributed to anthropogenic influences. Given the scope and magnitude of conservation issues, policy and management interventions must maximize efficiency and efficacy. The relatively new field of conservation physiology reveals the physiological mechanisms associated with population declines, animal- environment relationships and population or species tolerance thresholds, particularly where these relate to anthropogenic factors that necessitate conservation action. We propose a framework that demonstrates an integrative approach between physiology, conservation and policy, where each can inform the design, conduct and implementation of the other. Each junction of the conservation physiology process has the capacity to foster dialogue that contributes to effective implementation, monitoring, assessment and evaluation. This approach enables effective evaluation and implementation of evidence-based conservation policy and management decisions through a process of ongoing refinement, but may require that scientists (from the disciplines of both physiology and conservation) and policy-makers bridge interdisciplinary knowledge gaps. Here, we outline a conceptual framework that can guide and lead developments in conservation physiology, as well as promote innovative research that fosters conservation-motivated policy
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