136 research outputs found

    Natural Born in the U.S.A.: The Striking Unfairness and Dangerous Ambiguity of the Constitution’s Presidential Qualifications Clause and Why We Need to Fix It

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    This article explores the controversy surrounding the natural born citizenship proviso in order to demonstrate why a constitutional amendment is necessary to eliminate its inherent inequity and uncertain applicability, and to offer substantive recommendations for initiating such an amendment. Part I begins with a brief discussion of the historical and legal context of the natural born citizenship proviso. Part II explores the elusive nature of the term natural bom Citizen, and Part III focuses on the perils of passively awaiting judicial resolution of its meaning. The structural and policy reasons why limiting the Presidency to natural born citizens is inconsistent with the spirit of modern American democracy are discussed in Part IV, and Part V concludes with an examination of past efforts to modify the proviso and offers substantive recommendations for doing so today

    Natural Born in the U.S.A.: The Striking Unfairness and Dangerous Ambiguity of the Constitution’s Presidential Qualifications Clause and Why We Need to Fix It

    Get PDF
    This article explores the controversy surrounding the natural born citizenship proviso in order to demonstrate why a constitutional amendment is necessary to eliminate its inherent inequity and uncertain applicability, and to offer substantive recommendations for initiating such an amendment. Part I begins with a brief discussion of the historical and legal context of the natural born citizenship proviso. Part II explores the elusive nature of the term natural bom Citizen, and Part III focuses on the perils of passively awaiting judicial resolution of its meaning. The structural and policy reasons why limiting the Presidency to natural born citizens is inconsistent with the spirit of modern American democracy are discussed in Part IV, and Part V concludes with an examination of past efforts to modify the proviso and offers substantive recommendations for doing so today

    Reaching Out to Promote Campus Diversity in the 21st Century

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    National Outreach Scholarship Conference, Michigan State University, October 2 - 4, 2011https://deepblue.lib.umich.edu/bitstream/2027.42/149614/1/2011_Collins_ReachingOuttoPromoteCollegeDiversityinthe21stCentury.pd

    A prescribed walking regimen plus arginine supplementation improves function and quality of life for patients with pulmonary arterial hypertension: a pilot study

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    Current evidence suggests that exercise training is beneficial in pulmonary arterial hypertension (PAH). Unfortunately, the standard supervised, hospital-based programs limit patient accessibility to this important intervention. Our proof-of-concept study aimed to provide insight into the usefulness of a prescribed walking regimen along with arginine supplementation to improve outcomes for patients with PAH. Twelve PAH patients (all women) in New York Heart Association (NYHA) functional class (FC) II (n = 7) or III (n = 5) and in stable condition for ≥ 3 months were enrolled. Patients performed home- and fitness-center- based walking at 65–75% heart rate (HR) reserve for 45 min, six sessions/week for 12 weeks. Concomitant L-arginine supplementation (6000 mg/day) was provided to maximize beneficial endothelial training adaptations. Cardiopulmonary exercise testing, 6-min walk testing (6MWT), echocardiography, laboratory studies, and quality of life (QoL) survey (SF-36) were performed at baseline and 12 weeks. Eleven patients completed the study (72 session adherence rate = 96 ± 3%). Objective improvement was demonstrated by the 6MWT distance (increased by 40 ± 13 m, P = 0.01), VO2max (increased by 2 ± 0.7 mL/kg/min, P = 0.02), time-to-VO2max (increased by 2.5 ± 0.6 min, P = 0.001), VO2 at anaerobic threshold (increased by 1.3 ± 0.5 mL/kg/min, P = 0.04), HR recovery (reduced by 68 ± 23% in slope, P = 0.01), and SF-36 subscales of Physical Functioning and Energy/Fatigue (increased by 70 ± 34% and 74 ± 34%, respectively, P < 0.05). No adverse events occurred, and right ventricular function and brain natriuretic peptide levels remained stable, suggesting safety of the intervention. This proof-of-concept study indicates that a simple walking regimen with arginine supplementation is a safe and efficacious intervention for clinically stable PAH patients, with gains in objective function and QoL measures. Further investigation in a randomized controlled trial is warranted

    Marrow transplants from unrelated donors for patients with aplastic anemia: Minimum effective dose of total body irradiation

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    AbstractPatients with aplastic anemia who do not have suitably HLA-matched, related donors generally receive immunosuppressive treatment as first-line therapy and are considered for transplantation from an unrelated donor only if they fail to respond to immunosuppressive treatment. In this setting, rates of transplantation-related morbidity and mortality have been high. We conducted a prospective study to determine the minimal dose of total body irradiation (TBI) sufficient to achieve sustained engraftment when it is used in combination with 3 cycles of 30 mg/kg of antithymocyte globulin (ATG) and 4 cycles of 50 mg/kg of cyclophosphamide (CY). We also wanted to determine the tolerability and toxicity of the regimen. The starting dosage of TBI was 3 x 200 cGy given over 2 days following CY/ATG. The TBI dose was to be escalated in increments of 200 cGy if graft failure occurred in the absence of prohibitive toxicity, and de-escalated for toxicity in the absence of graft failure. Twenty-one female and 29 male patients aged 1.3 to 46.5 years (median age, 14.4 years) underwent transplantation at 14 medical centers. The time interval from diagnosis to transplantation was 2.8 to 264 months (median, 14.5 months). All patients had been transfused multiple times and all had received 1 to 11 courses (median, 4 courses) of immunosuppressive treatment and other modalities of treatment. In 38 cases, the donors were HLA-A, -B and -DR phenotypically matched with the patients, and, in 12 cases, the donor phenotype differed from that of the recipient by 1 HLA antigen. Recipients of mismatched transplants were considered separately for TBI dose modification, and this study is still ongoing. Seven patients did not tolerate ATG and were prepared with 6 x 200 cGy of TBI plus 120 mg/kg of CY. Of the HLA-matched recipients prepared with CY/ATG/TBI, all 20 who received 3 x 200 or 2 x 200 cGy of TBI achieved engraftment, and 10 are alive. Of the 13 patients who received 1 x 200 cGy of TBI, 1 failed to engraft, and 8 are alive. Each of 10 patients who received an HLA-nonidentical transplant achieved engraftment, and 3 of 6 who were given 3 x 200 cGy of TBI, and 4 of 4 who were given 2 x 200 cGy are alive. Pulmonary toxicity occurred in 8 of 30 patients who were given 3 x 200 or 2 x 200 cGy of TBI concurrently with ATG and CY at 200 mg/kg, and in 2 of 13 patients who received 1 x 200 cGy of TBI, a pattern that suggests a decrease in toxicity with TBI dose de-escalation. Overall, the highest probability of survival (73%) was observed among patients who underwent transplantation within 1 year of diagnosis, compared with patients who underwent transplantation after a longer period of disease. In addition, younger patients (aged < or = 20 years) were more likely to survive than older patients (aged > 20 years). Thus, for patients with an HLA-matched, unrelated donor, a TBI dose of 200 cGy (in combination with CY/ATG) was sufficient to allow for engraftment without inducing prohibitive toxicity. As in previous studies, patient age and pretransplantation disease duration remain important prognostic factors.Biol Blood Marrow Transplant 2001;7(4):208-15

    Treatment of autosomal dominant hypocalcemia Type 1 with the calcilytic NPSP795 (SHP635)

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    Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain‐of‐function mutations of the calcium‐sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1. Five adults with ADH1 due to 4 distinct CAR mutations received escalating doses of the calcilytic compound NPSP795 (SHP635) on 3 consecutive days. Pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed. Parallel in vitro testing with subject CaR mutations assessed the effects of NPSP795 on cytoplasmic calcium concentrations (Ca2+i), and ERK and p38MAPK phosphorylation. These effects were correlated with clinical responses to administration of NPSP795. NPSP795 increased plasma PTH levels in a concentration‐dependent manner up to 129% above baseline (p=0.013) at the highest exposure levels. Fractional excretion of calcium (FECa) trended down but not significantly so. Blood ionized calcium levels remained stable during NPSP795 infusion despite fasting, no calcitriol and little calcium supplementation. NPSP795 was generally safe and well‐tolerated. There was significant variability in response clinically across genotypes. In vitro, all mutant CaRs were half‐maximally activated (EC50) at lower concentrations of extracellular calcium (Ca2+o) compared to wild type (WT) CaR; NPSP795 exposure increased the EC50 for all CaR activity readouts. However, the in vitro responses to NPSP795 did not correlate with any clinical parameters. NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose‐dependent manner, and thus, serves as proof‐of‐concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype, or the response to calcilytics, suggesting that other parameters impact the response to the drug

    Phenotypic and Genotypic Characterization and Treatment of a Cohort with Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome

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    Familial tumoral calcinosis (FTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is a rare disorder caused by mutations in the genes encoding fibroblast growth factor-23 (FGF23), N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO. The result is functional deficiency of, or resistance to, intact FGF23 (iFGF23), causing hyperphosphatemia, increased renal tubular reabsorption of phosphorus (TRP), elevated or inappropriately normal 1,25-dihydroxyvitamin D3 (1,25D), ectopic calcifications and/or diaphyseal hyperostosis. Eight subjects with FTC/HHS were studied and treated. Clinical manifestations varied, even within families, ranging from asymptomatic to large, disabling calcifications. All subjects had hyperphosphatemia, increased TRP, and elevated or inappropriately normal 1,25D. C-terminal FGF23 was markedly elevated while iFGF23 was comparatively low, consistent with increased FGF23 cleavage. Radiographs ranged from diaphyseal hyperostosis to massive calcification. Two subjects with severe calcifications also had overwhelming systemic inflammation and elevated C-reactive protein (CRP). GALNT3 mutations were identified in 7 subjects; no causative mutation was found in the eighth. Biopsies from 4 subjects showed ectopic calcification and chronic inflammation, with areas of heterotopic ossification observed in 1 subject. Treatment with low phosphate diet, phosphate binders, and phosphaturia-inducing therapies was prescribed with variable response. One subject experienced complete resolution of a calcific mass after 13 months of medical treatment. In the 2 subjects with systemic inflammation, interleukin-1 (IL-1) antagonists significantly decreased CRP levels with resolution of calcinosis cutis and peri-lesional inflammation in one subject and improvement of overall well-being in both subjects. This cohort expands the phenotype and genotype of FTC/HHS and demonstrates the range of clinical manifestations despite similar biochemical profiles and genetic mutations. Overwhelming systemic inflammation has not been described previously in FTC/HHS; the response to IL-1 antagonists suggests that anti-inflammatory drugs may be useful adjuvants. In addition, this is the first description of heterotopic ossification reported in FTC/HHS, possibly mediated by the adjacent inflammation

    2004 Wild Blueberry Project Progress Reports

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    The 2004 edition of the Wild Blueberry Project Progress Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Determination of Pesticide Residue Levels in Freshly Harvested and Processed Lowbush Blueberries 2. Effect of Wild Blueberry Products on Physical, Chemical, Microbiological and Sensory Quality of Soy-Based and Ground Beef Patties 3. Evaluation of Emerging Disinfection Technologies for Wild Blueberry Processing 4. Detection of Infested Blueberries using Near-Infrared Spectroscopy-Spectra Collection 5. Health Claims for Wild Blueberries 6. Wild blueberries and Arterial Functional Properties 7. Irrigation Water Use in Wild Blueberry Production 8. Insect Control Tactics for Blueberry Pest Insects & Program Base 9. Integrated Pest Management (IPM) Strategies 10. Biology and Ecology of Blueberry Insect Pests 11. Stem Blight/Dieback and Leaf Spot Diseases in Lowbush Blueberry Fields 12. . Evaluation of fungicide control of mummy berry blight in wild blueberries: a) ground application and b) aerial application 13. Effect of Foliar Copper Application on Growth and Yield of Wild Blueberries 14. Effect of Soil pH on Nutrient Uptake 15. Effect of Fertilizer Timing (prune year vs. crop year) on Wild Blueberry Growth and Productivity 16. Raising Foliar Nitrogen by Application of CoRoN 17. Effect of Manganese on Growth and Yield of Wild Blueberry 18. Assessment of Hexazinone Alternatives for Weed Control in Wild Blueberries and Field Cover Program Base 19. Evaluation of Fall Applications of Sulfonylurea Herbicides for Bunchberry Control in Wild Blueberries 20. Evaluation and Demonstration of Techniques for Filling in Bare Spots in Wild Blueberry Fields 21. Assessment of Evitol for Sedge Control in Wild Blueberries 22. Cultural Weed Management Using pH 23. 2004 Pesticide Groundwater Survey 24. Wild Blueberry Extension Education Program in 200

    2003 Wild Blueberry Project Reports

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    The 2003 edition of the Wild Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Factors Affecting the Microbial and Pesticide Residues Levels on Lowbush Blueberries 2. Effect of Blueberry Products on Oxidation in Ground Beef Patties 3. Infestation Detection using Near-Infrared Spectroscopy 4. Whole Wild Blueberries and Arterial Functional Properties 5. Irrigation Water use in Wild Blueberry Production 7. Control Tactics for Blueberry Pest Insects 8. IPM Strategies 9. Biology and Ecology of Blueberry Pest Insects, 2003 10. Wild Blueberry Pollination Research 11. Stem Blight/Dieback and Leaf Spot Diseases in Wild Blueberry Fields 12. Effect of Foliar N spray on Leaf N Concentration, Growth and Yield of Wild Blueberries 13. Effect of Foliar Spray (4-13-15) on Leaf Nutrient Concentration, Growth and Yield of Wild Blueberries 14. Effect of Foliar Copper Application on Growth and Yield of Wild Blueberries 15. Effect of Foliar Copper and/or Iron Application on Growth and Yield of Wild Blueberries 16. Effect of Soil pH on Nutrient Uptake. 17. Effect of Gibberellic Acid (GA3) and CPPU on Fruit Set and Yield of Wild Blueberry after low temperature flower stress 18. Effect of Fertilizer Timing (prune year vs. crop year) on Wild Blueberry Growth and Productivity. 19. Assessment of Hexazinone Alternatives for Weed Control in Wild Blueberries and Weed Control and Field Cover Program Base 20. Evaluation of Fall Applications of Sulfonylurea Herbicides for Bunchberry Control in Wild Blueberries 21. Assessment of clean-cut adapter on hand clippers for weed control in wild blueberries 22. Evaluation and Demonstration of Techniques for Filling in Bare Spots in Wild Blueberry Fields 23. Blueberry Extension Education Program in 2003 24. 2003 Pesticide Groundwater Survey 25. Cultural Weed Management using Sulfur to lower the p

    Accuracy of Risk Estimates from the iPrevent Breast Cancer Risk Assessment and Management Tool.

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    BACKGROUND: iPrevent is an online breast cancer (BC) risk management decision support tool. It uses an internal switching algorithm, based on a woman's risk factor data, to estimate her absolute BC risk using either the International Breast Cancer Intervention Study (IBIS) version 7.02, or Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm version 3 models, and then provides tailored risk management information. This study assessed the accuracy of the 10-year risk estimates using prospective data. METHODS: iPrevent-assigned 10-year invasive BC risk was calculated for 15 732 women aged 20-70 years and without BC at recruitment to the Prospective Family Study Cohort. Calibration, the ratio of the expected (E) number of BCs to the observed (O) number and discriminatory accuracy were assessed. RESULTS: During the 10 years of follow-up, 619 women (3.9%) developed BC compared with 702 expected (E/O = 1.13; 95% confidence interval [CI] =1.05 to 1.23). For women younger than 50 years, 50 years and older, and BRCA1/2-mutation carriers and noncarriers, E/O was 1.04 (95% CI = 0.93 to 1.16), 1.24 (95% CI = 1.11 to 1.39), 1.13 (95% CI = 0.96 to 1.34), and 1.13 (95% CI = 1.04 to 1.24), respectively. The C-statistic was 0.70 (95% CI = 0.68 to 0.73) overall and 0.74 (95% CI = 0.71 to 0.77), 0.63 (95% CI = 0.59 to 0.66), 0.59 (95% CI = 0.53 to 0.64), and 0.65 (95% CI = 0.63 to 0.68), respectively, for the subgroups above. Applying the newer IBIS version 8.0b in the iPrevent switching algorithm improved calibration overall (E/O = 1.06, 95% CI = 0.98 to 1.15) and in all subgroups, without changing discriminatory accuracy. CONCLUSIONS: For 10-year BC risk, iPrevent had good discriminatory accuracy overall and was well calibrated for women aged younger than 50 years. Calibration may be improved in the future by incorporating IBIS version 8.0b
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