293 research outputs found
Executive Privilege - With a Catch: How a Crime-Fraud Exception to Executive Privilege Would Facilitate Congressional Oversight of Executive Branch Malfeasance in Accordance with the Constitution\u27s Separation of Powers
A crime-fraud exception to assertions of executive privilege in response to congressional subpoenas would help level the playing field between the two branches in those moments when Congress is most needed to serve as a check and balance on the executive branch. A crime-fraud exception would signal to executive branch officials that executive privilege will not conceal their malfeasance; would counteract hyperpartisanship as a force that insulates executive branch officials from the consequences of their actions; and would rein in the expansive reach of protective assertions of executive privilege. For years, Congress has surrendered power to the executive branch. A crime-fraud exception to executive privilege would help it take some of that power back
Challenges and opportunities in abdominal aortic aneurysm research
AbstractAbdominal Aortic Aneurysms (AAAs) are associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Basic research studies have led to a better understanding of aneurysm disease over the past two decades. There has also been a growing appreciation that fundamental knowledge regarding the process of aneurysmal degeneration is still somewhat limted. Opportunities in research include: 1) the investigation of potential new mechanism-based pharmacologic interventions; 2) identify the genetic basis for an inherited predisposition; 3) develop and refine noninvasive approaches for the early detection; 4) examine potential novel surgical approaches and design new biomaterials; and 5) initiate and promote awareness programs for diagnosis and treatment of aortic aneurysms. The optimal approach to addressing these issues will require integrative, multidisciplinary research programs that involve basic scientists working in concert with vascular and cardiothoracic surgeons, as well as other clinical specialists with expertise in vascular disease
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Performance of Sequoyah Containment Anchorage System
Deformation of a steel containment anchorage system during a severe accident may result in a leakage path at the containment boundaries. Current design criteria are based on either ductile or brittle failure modes of headed bolts that do not account for factors such as cracking of the containment basemat or deformation of the anchor bolt that may affect the behavior of the containment anchorage system. The purpose of this study was to investigate the performance of a typical ice condenser containment`s anchorage system. This was accomplished by analyzing the Sequoyah Containment Anchorage System. Based on a strength of materials approach and assuming that the anchor bolts are resisting the uplift caused by the internal pressure, one can estimate that the failure of the anchor bolts would occur at a containment pressure of 79 psig. To verify these results and to calibrate the strength of materials equation, the Sequoyah containment anchorage system was analyzed with the ABAQUS program using a three-dimensional, finite-element model. The model included portions of the steel containment building, shield building, anchor bolt assembly, reinforced concrete mat and soil foundation material
Metabolomics to unveil and understand phenotypic diversity between pathogen populations
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
Recovery of ζ-chain expression and changes in spontaneous IL-10 production after PSA-based vaccines in patients with prostate cancer
Circulating T lymphocytes of patients with prostate cancer have been reported to have functional deficits, including low or absent ζ-chain expression. To determine whether these functional impairments could be reversed by prostate specific antigen-based vaccination therapy, 10 patients treated with recombinant human prostate specific antigen plus GM-CSF and eight others receiving prostate specific antigen plus oil emulsion in two pilot clinical trials were evaluated prior to and after vaccination for several immunologic end points, including ζ-chain expression and cytokine production by circulating T cells as well as the frequency of T cells able to respond to prostate specific antigen in ELISPOT assays. The flow cytometry assay for ζ-chain expression was standardized to allow for a reliable comparison of pre- vs post-vaccination samples. Prior to therapy, the patients were found to have significantly lower ζ-chain expression in circulating CD3+ cells and a higher percentage of ζ-chain negative CD3+ and CD4+ cells than normal donors. The patients' peripheral blood mononuclear cells spontaneously produced more IL-10 ex vivo than those of normal controls. After vaccination, recovery of ζ-chain expression was observed in 50% of patients in both clinical trials. Also, spontaneous IL-10 secretion by peripheral blood mononuclear cells decreased following immunotherapy in patients treated with prostate specific antigen and GM-CSF. The frequency of prostate specific antigen-reactive T cells was detectable in 7 out of 18 patients vs 4 out of 18 patients prior to vaccination. Only one of 18 patients was a clinical responder. The vaccine had stimulatory effects on the patients' immune system, but post-vaccine immune recovery could not be correlated to progression-free survival in this small cohort of patients with prostate cancer
Epigenetic management of major psychosis
Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychosis: (1) the role of epigenetic drugs in treating these disorders. At present, there are three categories of epigenetic drugs that are being actively investigated for their ability to treat psychosis: drugs inhibiting histone deacetylation; drugs decreasing DNA methylation; and drugs targeting microRNAs; and (2) the role of epigenetic mechanisms in electroconvulsive therapy in these disorders
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