35 research outputs found

    Making Lemon-Aid From the Supreme Court\u27s Lemon: Why Current Establishment Clause Jurisprudence Should be Replaced by a Modified Coercion Test

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    In order to eliminate inconsistent results and promote predictability in litigation, a more uniform test should be developed and applied in Establishment Clause cases. Part I of this Comment will delineate the inherent problems with the two main tests currently utilized by the Supreme Court in Establishment Clause cases: the Lemon test and the endorsement test. Part II will further highlight the flaws of the Lemon and endorsement tests by examining their application to holiday display cases and the recent Ten Commandments cases. Part III will argue that applying a modified coercion test is the best means for achieving the most consistent results, even though it too has its limitation. Part IV will compare the practical application of the modified coercion test to the holiday display cases, the recent Ten Commandments cases, and the Pledge of Allegiance case. Part V will conclude that keeping Church and State separate does not require the complete bifurcation of all things religious from the rest of society, and that the modified coercion test is best suited for achieving the goal of appreciation of and tolerance for divergent points of view in the United States

    Operationalizing the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations: A Standardized Scoring System

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    Background: Following the publication of the 2018 World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) Third Expert Report, a collaborative group was formed to develop a standardized scoring system and provide guidance for research applications. Methods: The 2018 WCRF/AICR Cancer Prevention Recommendations, goals, and statements of advice were examined to define components of the new Score. Cut-points for scoring were based on quantitative guidance in the 2018 Recommendations and other guidelines, past research that operationalized 2007 WCRF/AICR Recommendations, and advice from the Continuous Update Project Expert Panel. Results: Eight of the ten 2018 WCRF/AICR Recommendations concerning weight, physical activity, diet, and breastfeeding (optional), were selected for inclusion. Each component is worth one point: 1, 0.5, and 0 points for fully, partially, and not meeting each recommendation, respectively (Score: 0 to 7–8 points). Two recommendations on dietary supplement use and for cancer survivors are not included due to operational redundancy. Additional guidance stresses the importance of accounting for other risk factors (e.g., smoking) in relevant models. Conclusions: The proposed 2018 WCRF/AICR Score is a practical tool for researchers to examine how adherence to the 2018 WCRF/AICR Recommendations relates to cancer risk and mortality in various adult populations.

    The Provision of Assistance Does Not Substantially Impact the Accuracy of 24-Hour Dietary Recalls Completed Using the Automated Self-Administered 24-H Dietary Assessment Tool Among Women With Low Incomes

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    Background: Evidence is lacking informing the use of the Automated Self-Administered 24-h Dietary Assessment Tool (ASA24) with populations characterized by low income. Objective: This study was conducted among women with low incomes to evaluate the accuracy of ASA24 recalls completed independently and with assistance. Methods: Three hundred and two women, aged ≥18 y and with incomes below the Supplemental Nutrition Assistance Program thresholds, served themselves from a buffet; amounts taken as well as plate waste were unobtrusively weighed to enable calculation of true intake for 3 meals. The following day, women completed ASA24-2016 independently (n = 148) or with assistance from a trained paraprofessional in a small group (n = 154). Regression modeling examined differences by condition in agreement between true and reported foods; energy, nutrient, and food group intakes; and portion sizes. Results: Participants who completed ASA24 independently and those who received assistance reported matches for 71.9% and 73.5% (P = 0.56) of items truly consumed, respectively. Exclusions (consumed but not reported) were highest for lunch (at which participants consumed approximately 2 times the number of distinct foods and beverages compared with breakfast and dinner). Commonly excluded foods were additions to main dishes (e.g., tomatoes in salad). On average, excluded foods contributed 43.6 g (46.2 kcal) and 40.1 g (43.2 kcal) among those in the independent and assisted conditions, respectively. Gaps between true and reported intake were different between conditions for folate and iron. Within conditions, significant gaps were observed for protein, vitamin D, and meat (both conditions); vitamin A, iron, and magnesium (independent); and folate, calcium, and vegetables (assisted). For foods and beverages for which matches were reported, no difference in the gap between true and reported portion sizes was observed by condition (P = 0.22). Conclusions: ASA24 performed relatively well among women with low incomes; however, accuracy was somewhat lower than previously observed among adults with a range of incomes. The provision of assistance did not significantly impact accuracy

    Microglial inclusions and neurofilament light chain release follow neuronal α-synuclein lesions in long-term brain slice cultures.

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    BACKGROUND: Proteopathic brain lesions are a hallmark of many age-related neurodegenerative diseases including synucleinopathies and develop at least a decade before the onset of clinical symptoms. Thus, understanding of the initiation and propagation of such lesions is key for developing therapeutics to delay or halt disease progression. METHODS: Alpha-synuclein (αS) inclusions were induced in long-term murine and human slice cultures by seeded aggregation. An αS seed-recognizing human antibody was tested for blocking seeding and/or spreading of the αS lesions. Release of neurofilament light chain (NfL) into the culture medium was assessed. RESULTS: To study initial stages of α-synucleinopathies, we induced αS inclusions in murine hippocampal slice cultures by seeded aggregation. Induction of αS inclusions in neurons was apparent as early as 1week post-seeding, followed by the occurrence of microglial inclusions in vicinity of the neuronal lesions at 2-3 weeks. The amount of αS inclusions was dependent on the type of αS seed and on the culture's genetic background (wildtype vs A53T-αS genotype). Formation of αS inclusions could be monitored by neurofilament light chain protein release into the culture medium, a fluid biomarker of neurodegeneration commonly used in clinical settings. Local microinjection of αS seeds resulted in spreading of αS inclusions to neuronally connected hippocampal subregions, and seeding and spreading could be inhibited by an αS seed-recognizing human antibody. We then applied parameters of the murine cultures to surgical resection-derived adult human long-term neocortical slice cultures from 22 to 61-year-old donors. Similarly, in these human slice cultures, proof-of-principle induction of αS lesions was achieved at 1week post-seeding in combination with viral A53T-αS expressions. CONCLUSION: The successful translation of these brain cultures from mouse to human with the first reported induction of human αS lesions in a true adult human brain environment underlines the potential of this model to study proteopathic lesions in intact mouse and now even aged human brain environments

    LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.

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    While the initial pathology of Parkinson's disease and other α-synucleinopathies is often confined to circumscribed brain regions, it can spread and progressively affect adjacent and distant brain locales. This process may be controlled by cellular receptors of α-synuclein fibrils, one of which was proposed to be the LAG3 immune checkpoint molecule. Here, we analysed the expression pattern of LAG3 in human and mouse brains. Using a variety of methods and model systems, we found no evidence for LAG3 expression by neurons. While we confirmed that LAG3 interacts with α-synuclein fibrils, the specificity of this interaction appears limited. Moreover, overexpression of LAG3 in cultured human neural cells did not cause any worsening of α-synuclein pathology ex vivo. The overall survival of A53T α-synuclein transgenic mice was unaffected by LAG3 depletion, and the seeded induction of α-synuclein lesions in hippocampal slice cultures was unaffected by LAG3 knockout. These data suggest that the proposed role of LAG3 in the spreading of α-synucleinopathies is not universally valid

    Operationalizing the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations: A Standardized Scoring System

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    Background: Following the publication of the 2018 World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) Third Expert Report, a collaborative group was formed to develop a standardized scoring system and provide guidance for research applications. Methods: The 2018 WCRF/AICR Cancer Prevention Recommendations, goals, and statements of advice were examined to define components of the new Score. Cut-points for scoring were based on quantitative guidance in the 2018 Recommendations and other guidelines, past research that operationalized 2007 WCRF/AICR Recommendations, and advice from the Continuous Update Project Expert Panel. Results: Eight of the ten 2018 WCRF/AICR Recommendations concerning weight, physical activity, diet, and breastfeeding (optional), were selected for inclusion. Each component is worth one point: 1, 0.5, and 0 points for fully, partially, and not meeting each recommendation, respectively (Score: 0 to 7–8 points). Two recommendations on dietary supplement use and for cancer survivors are not included due to operational redundancy. Additional guidance stresses the importance of accounting for other risk factors (e.g., smoking) in relevant models. Conclusions: The proposed 2018 WCRF/AICR Score is a practical tool for researchers to examine how adherence to the 2018 WCRF/AICR Recommendations relates to cancer risk and mortality in various adult populations.
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