969 research outputs found

    A Free Trade Agreement between the United States and Mexico: The Right Choice

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    In this Article, Messrs. Silva and Dunn demonstrate that the intended Free Trade Agreement (FTA) between the United States and Mexico is a natural and necessary step in the two countries\u27 economic relations. Their approach is to trace the steps which have led to the FTA and to analyze the evolution and progression of Mexican economic, legal, and political polices which have reached a point permitting and necessitating a trade pact. An agreement between the two countries is both logical and compelled though it will have permanent consequences and potential obstacles. Nevertheless, the agreement must be implemented and with an ample degree of haste

    A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo

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    The pancreatic islet is a complex micro-organ containing numerous cell types, including endocrine, immune, and endothelial cells. The communication of these systems is lost upon isolation of the islets, and therefore the pathogenesis of diabetes can only be fully understood by studying this organized, multicellular environment in vivo. We have developed several adaptable tools to create a versatile platform to interrogate β-cell function in vivo. Specifically, we developed β-cell-selective virally-encoded fluorescent protein biosensors that can be rapidly and easily introduced into any mouse. We then coupled the use of these biosensors with intravital microscopy, a powerful tool that can be used to collect cellular and subcellular data from living tissues. Together, these approaches allowed the observation of in vivo β-cell-specific ROS dynamics using the Grx1-roGFP2 biosensor and calcium signaling using the GcAMP6s biosensor. Next, we utilized abdominal imaging windows (AIW) to extend our in vivo observations beyond single-point terminal measurements to collect longitudinal physiological and biosensor data through repeated imaging of the same mice over time. This platform represents a significant advancement in our ability to study β-cell structure and signaling in vivo, and its portability for use in virtually any mouse model will enable meaningful studies of β-cell physiology in the endogenous islet niche

    Classical BI: Its Semantics and Proof Theory

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    We present Classical BI (CBI), a new addition to the family of bunched logics which originates in O'Hearn and Pym's logic of bunched implications BI. CBI differs from existing bunched logics in that its multiplicative connectives behave classically rather than intuitionistically (including in particular a multiplicative version of classical negation). At the semantic level, CBI-formulas have the normal bunched logic reading as declarative statements about resources, but its resource models necessarily feature more structure than those for other bunched logics; principally, they satisfy the requirement that every resource has a unique dual. At the proof-theoretic level, a very natural formalism for CBI is provided by a display calculus \`a la Belnap, which can be seen as a generalisation of the bunched sequent calculus for BI. In this paper we formulate the aforementioned model theory and proof theory for CBI, and prove some fundamental results about the logic, most notably completeness of the proof theory with respect to the semantics.Comment: 42 pages, 8 figure

    A prospective study to assess the value of MMP-9 in improving the appropriateness of urgent referrals for colorectal cancer

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    Background Bowel cancer is common and is a major cause of death. Most people with bowel symptoms who meet the criteria for urgent referral to secondary care will not be found to have bowel cancer, and some people who are found to have cancer will have been referred routinely rather than urgently. If general practitioners could better identify people who were likely to have bowel cancer or conditions that may lead to bowel cancer, the pressure on hospital clinics may be reduced, enabling these patients to be seen more quickly. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with such conditions, and this can be measured from a blood sample. This study aims to find out whether measuring MMP-9 levels could improve the appropriateness of urgent referrals for patients with bowel symptoms. Methods People aged 18 years or older referred to a colorectal clinic will be asked to complete a questionnaire about symptoms, recent injuries or chronic illnesses (these can increase the level of matrix metalloproteinases) and family history of bowel cancer. A blood sample will be taken from people who consent to take part to assess MMP-9 levels, and the results of examination at the clinic and/or investigations arising from the clinic visit will be collected from hospital records. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the resulting diagnosis. The combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined. Discussion Although guidelines are in place to facilitate referrals to colorectal clinics, symptoms alone do not adequately distinguish people with malignancy from people with benign conditions. This study will establish whether MMP-9 could assist this process. If this were the case, measurement of MMP-9 levels could be used by general practitioners to assist in the identification of people who were most likely to have bowel cancer or conditions that may lead to bowel cancer, and who should, therefore, be referred most urgently to secondary car

    Health literacy and the health status of men with prostate cancer

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    OBJECTIVE: To test the Health Literacy Questionnaire (HLQ) in a sample of men with prostate cancer and examine the components of health literacy that are most strongly associated with mental and physical health‐related quality of life in men with prostate cancer. METHOD: Members (N = 565) of a state‐wide prostate cancer support network in Queensland, Australia (Mage = 71.14, SD = 8.68) completed the HLQ along with the Medical Outcomes Study, 36‐item short‐form health survey (SF‐36). Confirmatory factor analysis was employed to assess the internal structure of the HLQ. The effects (bs) of each of the nine health literacy factors on mental and physical health status were graphed and compared using Fishers exact test for comparing parameter estimates. RESULTS: Fit indices including RMSEA (0.069, CI = 0.066‐0.072), CFI (.853), and TLI (.839), alongside item loadings and internal consistency (Cronbach alphas >0.80) for the nine‐factor model, supported the robustness of the HLQ for use in this prostate cancer sample. Health literacy factors reflecting social and health provider support, navigating health systems, finding and understanding health information, and active engagement with providers shared small to moderate associations with mental health status and little to no association with physical health status. CONCLUSION: Findings provide support for the use of the HLQ as a valid and reliable measure of health literacy in men with prostate cancer. Although further research is required to establish causality, interventions that aim to improve skills in connecting and effectively communicating with health care services and providers might lead to better mental health related quality of life for men with prostate cancer

    Psychopathology and affect dysregulation across the continuum of psychosis: A multiple comparison group study

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    This is the peer reviewed version of the following article: Taylor, H. E., Stewart, S. L. K., Dunn, G., Parker, S., Bentall, R. P., Birchwood, M., & Morrison, A. P. (2014). Psychopathology and affect dysregulation across the continuum of psychosis: A multiple group comparison study. Early Intervention in Psychiatry, 8(3), 221-228. DOI: 10.1111/eip.12064, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/eip.12064/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingAim: There is evidence that psychotic-like phenomena can be detected within the general population and that psychotic experiences lie on a continuum which also spans affective states. We aimed to investigate comparisons of a first episode psychosis group, an ‘at-risk mental state group’ and a help-seeking control group with non-patients to explore whether affective states lie on a continuum of psychosis. Method: Measures of psychotic-like experiences, social anxiety and depression were administered to 20 patients experiencing first episode psychosis (FEP), 113 patients experiencing an ‘at-risk’ mental state (ARMS), 28 patients who were help-seeking but not experiencing a FEP or ARMS (HSC) and 30 non-clinical participants (NC). Results: For distress in relation to psychotic-like experiences, the FEP, ARMS and HSC groups scored significantly higher than the NC group for the perceptual abnormalities and non-bizarre ideas. In terms of severity of psychotic experiences, the FEP scored the highest, followed by the ARMS group, followed by the HSC and NC group. The clinical groups scored significantly higher for depression than the non-clinical group. Interestingly, only the FEP and the ARMS group scored significantly higher than non-patients for social anxiety. Conclusions: These findings suggest that a psychosis continuum exists, however this does not suggest that both psychosis and affective symptoms lie on the same continuum, rather it would appear that the presence of such affective states that may affect help-seeking behavior and clinical status. The implications of these findings for clinical practice are discussed

    Metabolomics to unveil and understand phenotypic diversity between pathogen populations

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    Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance
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