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By A. Abe. Cedarville University.

If applied appropriately and linked to efective assessment order 120 mg cardizem visa, this approach allows each school or country to have a distinct profle and to focus on particular areas of strength (e generic cardizem 60 mg on line. Such concerns led to the Bologna Declaration (European Ministers of Education buy cardizem 60mg line, 1999) and the ongoing ‘Bologna Process’ which seeks to create a system of easily readable and comparable degrees and the establishment of a European Higher Education Area buy cheap cardizem 60mg on-line. A three-cycle system of higher education degrees - Bachelors, Masters and Doctorate - normally equating to two or three years of study each. The “Dublin Descriptors” are generic outlines of the level of academic achievement for each cycle (Joint Quality Initiative informal group, 004). A qualifcations framework describing the typical learning outcomes/ competences for each cycle and discipline. The Tuning Project Making vocational degree qualifcations comparable and easily readable is at the heart of the Bologna Process. Methods of achieving this based purely on duration of study are fallible and give little information as to how graduates will perform in the workplace. A more robust outcome-based approach was developed by the Tuning Project (http://tuning. Initiated in 000, the Tuning Project is led by Julia González (University of Deusto) and Robert Wagenaar (University of Groningen). Several disciplines, including nursing, developed learning outcomes during the initial phases of the Tuning Project (Tuning Educational Structures in Europe. They describe particular items of learning related to a component of a degree programme, such as a lecture, tutorial, module or attachment. Learning outcomes are also set and described by teaching staf, but refer to the whole degree programme and relate to the point of graduation. They are usually specifed with a hierarchy of levels, with a top level consisting of large domains of learning. Competences are acquired by, and belong to, students or graduates, rather than teachers. For a graduate who has successfully completed the degree programme, their competences should be at least equivalent to the prescribed learning outcomes (although they are very likely to have developed further in particular areas of learning). In that sense, when referring to the point of graduation, specifed learning outcomes can be viewed as equivalent to core graduate competences, and the same descriptors can be used. The Tuning Project (Medicine) is led by the University of Edinburgh, with a local steering group and a European Task Force (Appendix C). Previous work A great deal of work has already been done to defne curriculum-level outcomes/ competences for medical education. Many other national and institutional outcomes frameworks have been developed in Europe and elsewhere. Process and methods The Tuning Project (Medicine) was funded by the European Commission on the basis that the methodology would be similar and results comparable with the “parent” Tuning Project (Tuning Educational Structures in Europe. Existing learning outcomes/competency frameworks were reviewed by the Project steering group. A preliminary draft learning outcomes framework for Tuning (Medicine) was generated by the Project steering group. In a series of European workshops, members of the Tuning (Medicine) Taskforce sequentially reviewed and refned the draft document in the light of expert opinion and the Internet opinion survey (see below). Workshops were held in Budapest (April 005), Amsterdam (September 005), Edinburgh (February 006), Prague (May 006), Genoa (September 006), Oslo (May 007) and Antalya (September 007). In addition, presentations of the draft framework were made and feedback obtained at numerous other meetings in Europe and elsewhere. Tuning methodology specifes an opinion survey, to include academics, graduates and employers, who are asked to rate learning outcomes in terms of their importance for graduates. These rankings inform the formulation of the fnal outcomes framework by the Task Force. For Tuning (Medicine), a detailed questionnaire was created using an online survey instrument (www.

Effects of supplemental methionine on antiserum-induced dysmorphology in rat embryos cultured in vitro buy cardizem 120mg. Correlations between brain tryptophan and plasma neutral amino acid levels following food consumption in rats cheap 60 mg cardizem overnight delivery. Short-term neuroendocrine effects of a large oral dose of monosodium glutamate in fasting male subjects discount cardizem 120mg. Rat embryo development on human sera is related to numbers of previous spontaneous abortions and nutritional factors cardizem 180 mg sale. Correlation of aspartate dose, plasma dicarboxylic amino acid concentration, and neuronal necrosis in infant mice. Aspartate-induced neuronal necrosis in infant mice: Protective effect of carbohydrate and insulin. The 24-h whole body leucine and urea kinetics at normal and high protein intakes with exercise in healthy adults. Resting metabolic rate and body composi- tion of healthy Swedish women during pregnancy. Effect of chronic dietary treatment with L-tryptophan on spontaneous salt appetite of rats. Role of insulin and branched-chain amino acids in regulating protein metabolism during fast- ing. Impact of supplemental lysine or tryptophan on pregnancy course and outcome in rats. Adaptation of protein metabolism in relation to limits to high dietary protein intake. Human protein requirements: The effect of variations in energy intake within the maintenance range. Mutagenic activity of glycine upon nitrosation in the presence of chloride and human gastric juice: A possible role in gastric carcinogenesis. Protein-energy requirements of prepubertal school-age boys determined by using the nitrogen-balance response to a mixed-protein diet. Protein-energy requirements of boys 12-14 y old determined by using the nitrogen-balance response to a mixed-protein diet. Gaudichon C, Mahe S, Benamouzig R, Luengo C, Fouillet H, Dare S, Van Oycke M, Ferriere F, Rautureau J, Tome D. Net postprandial utilization of [15N]-labeled milk protein nitrogen is influenced by diet composition in humans. Multicenter, double blind, placebo-controlled, multiple-challenge evaluation of reported reactions to monosodium glutamate. Oral L-histidine fails to reduce taste and smell acuity but induces anorexia and urinary zinc excretion. Effect of oral alanine on blood beta-hydroxybutyrate and plasma glucose, insulin, free fatty acids, and growth hormone in normal and diabetic subjects. Human protein requirements: Assessment of the adequacy of the current Recommended Dietary Allowance for dietary protein in elderly men and women. Mutagenicity spectra in Salmonella typhimurium strains of glutathione, L-cysteine and active oxygen species. Effects of central administration of alanine on body temperature of the rabbit: Comparisons with the effects of serine, glycine and taurine. Substituting ornithine for arginine in total parenteral nutrition eliminates enhanced tumor growth. Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. Influence of leucine on arterial concen- trations and regional exchange of amino acids in healthy subjects. Serum amino acid patterns and toxicity symptoms following the absorption of irrigant containing glycine in transurethral prostatic surgery. Hara S, Shibuya T, Nakakawaji K, Kyu M, Nakamura Y, Hoshikawa H, Takeuchi T, Iwao T, Ino H. Observations of pharmacological actions and toxicity of sodium glutamate, with comparisons between natural and synthetic products.

A number of short- and long-term intervention studies have been con- ducted on normal-weight or moderately obese individuals to ascertain the effects of altering the fat and energy density content of the diet on body weight (Table 11-1) cardizem 180 mg. The only study that provided isocaloric diets showed no dif- ferences in weight gain or loss discount cardizem 60 mg without a prescription, despite a wide range in the percent of energy from fat (Leibel et al discount cardizem 60 mg free shipping. Four meta-analyses of long-term intervention studies associating a low fat diet with body weight concluded that lower fat diets lead to modest weight loss or prevention of weight gain (Astrup et al cardizem 60 mg sale. These studies thus suggest that low fat diets (low percentage of fat) tend to be slightly hypocaloric compared to higher fat diets when com- pared in outpatient intervention trials. The finding that higher fat diets are moderately hypercaloric when compared with reduced fat intakes under ad libitum conditions provides a rationale for setting an upper boundary for percentage of fat intake in a population that already has a high prevalence of overweight and obesity. However, a second issue must also be addressed: whether the distribution of fat and carbohydrate modifies the metabolic consequences of over- weight and obesity. In populations where people are routinely physically active and lean, the atherogenic lipoprotein phenotype is mini- mally expressed. In sedentary populations that tend to be overweight or obese, very low fat, high carbohydrate diets clearly promote the develop- ment of this phenotype. Risk of Hyperinsulinemia, Glucose Intolerance, and Type 2 Diabetes Other potential abnormalities accompanying changes in distribution of fat and carbohydrate intakes include increased postprandial responses in plasma glucose and insulin concentrations. These abnormalities are more likely to occur with low fat, high carbohydrate diets. In particular, repeated daily elevations in postprandial glucose and insulin concentrations could “exhaust” pancreatic β-cells of insulin supply, which could hasten the onset of type 2 diabetes. Some investigators have further suggested these repeated elevations could worsen baseline insulin sensitivity, which could cause susceptible persons to be at increased risk for type 2 diabetes. This form of diabetes, defined by an elevation of fasting serum glucose concentration, is characterized by two defects in glucose metabolism: insulin resistance, a defect in insulin-mediated uptake of glucose by cells, particularly skeletal muscle cells, and a decline in insulin secretory capacity by pancreatic β-cells (Turner and Clapham, 1998). Insulin resistance typi- cally precedes the development of type 2 diabetes by many years. It is known to be the result of obesity, physical inactivity, and genetic factors (Turner and Clapham, 1998). Before the onset of diabetic hyperglycemia, the pancreatic β-cells are able to respond to insulin resistance with an increased insulin secretion, enough to maintain normoglycemia. However, in some persons who are insulin resistant, insulin secretory capacity declines and hyperglycemia ensues (Reaven, 1988, 1995). The mechanisms for the decline in insulin secretion are not well understood, but one theory is that continuous overstimulation of insulin secretion by the presence of insulin resistance leads to “insulin exhaustion” and hence to decreased insulin secretory capacity (Turner and Clapham, 1998). Whether insulin exhaustion is secondary to a metabolic dysfunction of cellular production of insulin or to a loss of β-cells is uncertain. The accumulation of pancreatic islet-cell amyloidosis may be one mechanism for loss of insulin-secretory capacity (Höppener et al. High carbohydrate diets frequently causes greater insulin and plasma glucose responses than do low carbohydrate diets (Chen et al. These excessive responses theoretically could pre- dispose individuals to the development of type 2 diabetes because of pro- longed overstimulation of insulin secretion (Grill and Björklund, 2001). None- theless, in the mind of some investigators, it deserves serious consideration. Other consequences of hyperglycemic responses to high carbohydrate diets might be considered. For example, higher postprandial glucose responses might lead to other changes such as “desensitization” of β-cells for insulin secretion and production of glycated products or advanced glycation end-products, which could either promote atherogenesis or the “aging” process (Lopes-Virella and Virella, 1996). A number of noninterventional, epidemio- logical studies have shown no relationship between carbohydrate intake and risk of diabetes (Colditz et al. Interventional studies in healthy individuals on the influence of high carbohydrate diets on biomarker precursors for type 2 diabetes are lacking and the available data are mixed (Table 11-4) (Beck- Nielsen et al. Factors such as carbo- hydrate quality, body weight, exercise, and genetics make the interpretation of such findings difficult. For usual diets that are low in total fat, the intake of essential fatty acids, such as n-6 polyunsaturated fatty acids, will be low (Appendix K).

We regard smaller projects on the recommended path as preferable to larger purchase cardizem 60 mg on-line, narrower initiatives that would distract attention and resources from these reforms buy 180mg cardizem with visa. We think the impediments can best be overcome and the optimum design of the Information Commons discount cardizem 180mg, Knowledge Network generic 120 mg cardizem visa, and the New Taxonomy best emerge in the context of pilot projects of increasing scope and scale. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 66 Even some stakeholders in the health-care system who find the Committee’s basic vision compelling may ask whether or not a special, organized effort is required to achieve the Committee’s goals. In particular, some might argue that there are already enough examples— many have been cited in this report—in which data-intensive laboratory tests have such clear benefits for patients that the traditional system of test development and insurance reimbursement will allow a smooth transition to a new era of molecular medicine. Indeed, there is real risk of a backlash against premature claims of the efficacy of genomic medicine (Kolata 2011). The key to avoiding such a backlash is development of a robust system for discovering applications that have real clinical benefits and validating those claims through open processes. The Committee believes that expecting or pressuring payers in the health-care system to bear the costs of integrating data-intensive biology and medicine without clear evidence of the safety, efficacy, and economic feasibility of particular applications would fail—indeed, such an effort could easily be counter-productive. On the other hand, as some of the scenarios sketched above indicate, the Committee believes that a well planned public investment in creating the system the Committee envisions would lead relatively quickly to robust public-private partnerships that would allow all stakeholders to build on early successes. Perhaps even more importantly, the Committee believes that its approach offers the most realistic available path to ultimate sustainability of precision medicine. Public investment in research can play an essential role in building a solid foundation for precision medicine, but it cannot sustain its dissemination: precision medicine will only become a routine aspect of health care when it pays its own way. To bring the discussion back to the Committee’s core mission, we close by re- emphasizing our view toward disease taxonomy. Accurately and precisely defining a patient’s condition does not assure effective treatment, but it is unequivocally the place to start. Hence, in exploiting the convergent forces acting throughout the health-care system, a long-term focus on developing the new informational resources proposed in this report would be a powerful unifying principle for biomedical researchers, physicians, patients, and all stakeholders in this vast enterprise. However, the Committee believes that implementation of its core recommendations would bring many new allies to the cause of improving this patient’s health prospects and would equip these diverse players with powerful new tools and resources that are unlikely to emerge without an organized effort to create them. Medium-term exposure to traffic-related air pollution and markers of inflammation and endothelial function. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Physical activity and endometrial cancer in a population-based case-control study. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 68 Biesecker, L. The ClinSeq project: Piloting large- scale genome sequencing for research in genomic medicine. The effect of altitude change on anemia treatment response in hemodialysis patients. Surveillance Sans Frontières: Internet-based emerging infectious disease intelligence and the HealthMap project. Rapid identification of myocardial infarction risk associated with diabetes medications using electronic medical records. Interactions between genetic variants and breast cancer risk factors in the breast and prostate cancer cohort consortium. Self-reported racial discrimination, response to unfair treatment, and coronary calcification in asymptomatic adults: The North Texas Healthy Heart study. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease ͸ͻ Caspi, A. Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. Genome-wide methylation profile of nasal polyps: Relation to aspirin hypersensitivity in asthmatics. Time to move from presumptive malaria treatment to laboratory-confirmed diagnosis and treatment in African children with fever. Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 70 http://www.

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