247 research outputs found
Diversification of U.S. medical schools via affirmative action implementation
BACKGROUND: The diversification of medical school student and faculty bodies via race-conscious affirmative action policy is a societal and legal option for the U.S. Supreme Court has recently ruled its use constitutional. This paper investigates the implications of affirmative action, particularly race-conscious compared to race-blind admissions policy; explains how alternative programs are generally impractical; and provides a brief review of the history and legality of affirmative action in the United States. DISCUSSION: Selection based solely on academic qualifications such as GPA and MCAT scores does not achieve racial and ethnic diversity in medical school, nor does it adequately predict success as practicing physicians. However, race-conscious preference yields greater practice in underserved and often minority populations, furthers our biomedical research progression, augments health care for minority patients, and fosters an exceptional medical school environment where students are better able to serve an increasingly multicultural society. SUMMARY: The implementation of race-conscious affirmative action results in diversity in medicine. Such diversity has shown increased medical practice in underserved areas, thereby providing better health care for the American people
GPIIb/IIIa Receptor Antagonism Using Small Molecules Provides no Additive Long-Term Protection after Percutaneous Coronary Intervention as Compared to Clopidogrel Plus Aspirin
Background: There is some controversy as to whether tirofiban or eptifibatide, two small anti-aggregating drugs (AAD), may reduce the incidence of composite ischemic events within one year in patients undergoing percutaneous coronary intervention (PCI) in the real clinical world. Methods: We compared consecutive patients on oral double AAD (with clopidogrel and aspirin) who underwent PCI (n=207) and patients who were on single AAD and received a second AAD, just prior to PCI, and either high-dose tirofiban or double-bolus eptifibatide (double AAD plus small molecules group, n=666). The primary end point (incidence of composite ischemic events within one year) included death, acute myocardial infarction, unstable angina, stent thrombosis or repeat PCI or coronary bypass surgery (related to the target vessel PCI failure) and was modelled by Cox's regression. Results: There were 89 composite ischemic events: 24 (11.6%) in double AAD alone and 65 (9.8%) in double AAD plus small molecules groups (log-rank test: p=0.36). Incidences by type of ischemic events were similar between the 2 groups. Based on 21 potential covariates fitted simultaneously, adjusted hazard ratios (HR and 95% confidence intervals) showed that age (HR 1.03, 1.01-1.06, p=0.01), diabetes (HR 1.68, 1.01-2.79, p=0.05) and intra aortic balloon pump (HR 5.12, 2.36-11.10, p=0.0001) were significant risk factors whereas thrombolysis by tenecteplase (HR 0.35, 0.13-0.98, p=0.05) and having had hypertension or anti-hypertensive treatment (HR 0.58, 0.36-0.93, p=0.03) were significant protectors for events. Whether small molecules were present provided a non significant additional benefit as compared to double AAD alone (HR 0.83, 0.51-1.36, p=0.46). Pre-PCI CK-MB were not useful to predict events (HR 1.01, 0.99-1.01, p=0.17). Conclusions: In clinical world patients undergoing PCI (rescue plus primary <13%) while on double AAD, based on clopidogrel plus aspirin, small molecules (tirofiban or eptifibatide) provided no additive long-term protection against the occurrence of composite ischemic events whereas thrombolysis by tenecteplase did. © Schiariti et al
Risk of urinary bladder cancer: a case-control analysis of industry and occupation
<p>Abstract</p> <p>Background</p> <p>Uncertainty remains about urinary bladder cancer (UBC) risk for many occupations. Here, we investigate the association between occupation, industry and UBC.</p> <p>Methods</p> <p>Lifetime occupational history was collected by in-person interview for 604 newly diagnosed UBC patients and 604 cancer-free controls. Each job title was assigned a two-digit industry code and a three-digit occupation code. Odds ratios (ORs) for UBC associated with ever being employed in an industry or occupation were calculated by unconditional logistic regression adjusting for age, gender and smoking status. We also examined UBC risk by duration of employment (>0 to <10, ≥10 years) in industry or occupation.</p> <p>Results</p> <p>Significantly increased risk of UBC was observed among waiters and bartenders (OR 2.87; 95% CI 1.05 to 7.72) and occupations related to medicine and health (OR 2.17; 95% CI 1.21 to 3.92), agricultural production, livestock and animal specialties (OR 1.90; 95% CI 1.03 to 3.49), electrical assembly, installation and repair (OR 1.69; 95% CI 1.07 to 2.65), communications (OR 1.74; 95% CI 1.00 to 3.01), and health services (OR 1.58; 95% CI 1.02 to 2.44). For these occupations we also observed a significant excess risk of UBC for long-term work (i.e. ≥10 years), with the exception of waiters and bartenders. Employment for 10 years or more was associated with increased risk of UBC in general farmers (OR 9.58; 95% CI 2.18 to 42.05), agricultural production of crops (OR 3.36; 95% CI 1.10 to 10.27), occupations related to bench working (OR 4.76; 95% CI 1.74 to 13.01), agricultural, fishery, forestry & related (OR 4.58; 95% CI 1.97 to 10.65), transportation equipment (OR 2.68; 95% CI 1.03 to 6.97), and structural work (OR 1.85; 95% CI 1.16 to 2.95).</p> <p>Conclusions</p> <p>This study provides evidence of increased risk of UBC for occupations that were previously reported as at-risk. Workers in several occupation and industry groups have a significantly higher risk of UBC, particularly when duration of employment is 10 years or more.</p
A multi-region assessment of population rates of cardiac catheterization and yield of high-risk coronary artery disease
<p>Abstract</p> <p>Background</p> <p>There is variation in cardiac catheterization utilization across jurisdictions. Previous work from Alberta, Canada, showed no evidence of a plateau in the yield of high-risk disease at cardiac catheterization rates as high as 600 per 100,000 population suggesting that the optimal rate is higher. This work aims 1) To determine if a previously demonstrated linear relationship between the yield of high-risk coronary disease and cardiac catheterization rates persists with contemporary data and 2) to explore whether the linear relationship exists in other jurisdictions.</p> <p>Methods</p> <p>Detailed clinical information on all patients undergoing cardiac catheterization in 3 Canadian provinces was available through the Alberta Provincial Project for Outcomes Assessment in Coronary Heart (APPROACH) disease and partner initiatives in British Columbia and Nova Scotia. Population rates of catheterization and high-risk coronary disease detection for each health region in these three provinces, and age-adjusted rates produced using direct standardization. A mixed effects regression analysis was performed to assess the relationship between catheterization rate and high-risk coronary disease detection.</p> <p>Results</p> <p>In the contemporary Alberta data, we found a linear relationship between the population catheterization rate and the high-risk yield. Although the yield was slightly less in time period 2 (2002-2006) than in time period 1(1995-2001), there was no statistical evidence of a plateau. The linear relationship between catheterization rate and high-risk yield was similarly demonstrated in British Columbia and Nova Scotia and appears to extend, without a plateau in yield, to rates over 800 procedures per 100,000 population.</p> <p>Conclusions</p> <p>Our study demonstrates a consistent finding, over time and across jurisdictions, of linearly increasing detection of high-risk CAD as population rates of cardiac catheterization increase. This internationally-relevant finding can inform country-level planning of invasive cardiac care services.</p
Developmental and Lactational Exposure to Dieldrin Alters Mammary Tumorigenesis in Her2/neu Transgenic Mice
Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil), or dieldrin (0.45, 2.25, and 4.5 µg/g body weight) daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis
Formalization of the classification pattern: Survey of classification modeling in information systems engineering
Formalization is becoming more common in all stages of the development of information systems, as a better understanding of its benefits emerges. Classification systems are ubiquitous, no more so than in domain modeling. The classification pattern that underlies these systems provides a good case study of the move towards formalization in part because it illustrates some of the barriers to formalization; including the formal complexity of the pattern and the ontological issues surrounding the ‘one and the many’. Powersets are a way of characterizing the (complex) formal structure of the classification pattern and their formalization has been extensively studied in mathematics since Cantor’s work in the late 19th century. One can use this formalization to develop a useful benchmark. There are various communities within Information Systems Engineering (ISE) that are gradually working towards a formalization of the classification pattern. However, for most of these communities this work is incomplete, in that they have not yet arrived at a solution with the expressiveness of the powerset benchmark. This contrasts with the early smooth adoption of powerset by other Information Systems communities to, for example, formalize relations. One way of understanding the varying rates of adoption is recognizing that the different communities have different historical baggage. Many conceptual modeling communities emerged from work done on database design and this creates hurdles to the adoption of the high level of expressiveness of powersets. Another relevant factor is that these communities also often feel, particularly in the case of domain modeling, a responsibility to explain the semantics of whatever formal structures they adopt. This paper aims to make sense of the formalization of the classification pattern in ISE and surveys its history through the literature; starting from the relevant theoretical works of the mathematical literature and gradually shifting focus to the ISE literature. The literature survey follows the evolution of ISE’s understanding of how to formalize the classification pattern. The various proposals are assessed using the classical example of classification; the Linnaean taxonomy formalized using powersets as a benchmark for formal expressiveness. The broad conclusion of the survey is that (1) the ISE community is currently in the early stages of the process of understanding how to formalize the classification pattern, particularly in the requirements for expressiveness exemplified by powersets and (2) that there is an opportunity to intervene and speed up the process of adoption by clarifying this expressiveness. Given the central place that the classification pattern has in domain modeling, this intervention has the potential to lead to significant improvements.The UK Engineering and Physical Sciences Research Council (grant EP/K009923/1)
Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction
Congestive heart failure developing after acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Clinical trials of cell-based therapy after AMI evidenced only a moderate benefit. We could show previously that suspensions of apoptotic peripheral blood mononuclear cells (PBMC) are able to reduce myocardial damage in a rat model of AMI. Here we experimentally examined the biochemical mechanisms involved in preventing ventricular remodelling and preserving cardiac function after AMI. Cell suspensions of apoptotic cells were injected intravenously or intramyocardially after experimental AMI induced by coronary artery ligation in rats. Administration of cell culture medium or viable PBMC served as controls. Immunohistological analysis was performed to analyse the cellular infiltrate in the ischaemic myocardium. Cardiac function was quantified by echocardiography. Planimetry of the infarcted hearts showed a significant reduction of infarction size and an improvement of post AMI remodelling in rats treated with suspensions of apoptotic PBMC (injected either intravenously or intramoycardially). Moreover, these hearts evidenced enhanced homing of macrophages and cells staining positive for c-kit, FLK-1, IGF-I and FGF-2 as compared to controls. A major finding in this study further was that the ratio of elastic and collagenous fibres within the scar tissue was altered in a favourable fashion in rats injected with apoptotic cells. Intravenous or intramyocardial injection of apoptotic cell suspensions results in attenuation of myocardial remodelling after experimental AMI, preserves left ventricular function, increases homing of regenerative cells and alters the composition of cardiac scar tissue. The higher expression of elastic fibres provides passive energy to the cardiac scar tissue and results in prevention of ventricular remodelling
A Therapeutic Chemical Chaperone Inhibits Cholera Intoxication and Unfolding/Translocation of the Cholera Toxin A1 Subunit
Cholera toxin (CT) travels as an intact AB5 protein toxin from the cell surface to the endoplasmic reticulum (ER) of an intoxicated cell. In the ER, the catalytic A1 subunit dissociates from the rest of the toxin. Translocation of CTA1 from the ER to the cytosol is then facilitated by the quality control mechanism of ER-associated degradation (ERAD). Thermal instability in the isolated CTA1 subunit generates an unfolded toxin conformation that acts as the trigger for ERAD-mediated translocation to the cytosol. In this work, we show by circular dichroism and fluorescence spectroscopy that exposure to 4-phenylbutyric acid (PBA) inhibited the thermal unfolding of CTA1. This, in turn, blocked the ER-to-cytosol export of CTA1 and productive intoxication of either cultured cells or rat ileal loops. In cell culture studies PBA did not affect CT trafficking to the ER, CTA1 dissociation from the holotoxin, or functioning of the ERAD system. PBA is currently used as a therapeutic agent to treat urea cycle disorders. Our data suggest PBA could also be used in a new application to prevent or possibly treat cholera
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