The synthesis, structure–activity relationships (SAR) and biological evaluation of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was determined to be efficacious in a murine ...model for rheumatoid arthritis.
The synthesis, structure–activity relationships (SAR) and biological evaluation of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was determined to be orally efficacious in a murine model of rheumatoid arthritis.
A new series of tricyclic-based inhibitors of IKK have been derived from an earlier lead compound. The synthesis and structure–activity relationships (SAR) are described. Compound
4k inhibited TNF ...production in rats stimulated with LPS.
A new series of tricyclic-based inhibitors of IKK have been derived from an earlier lead compound. The synthesis and structure–activity relationships (SAR) are described. Compound
4k inhibited TNF production in rats stimulated with LPS.
Professor Harris' analysis of legal consequences effected through property rightly exposes how a theory of property can disempower and disembody the individual not afforded property rights. In these ...HIV experiments it is apparent that the non-recognition of property rights manifests itself as the conscious choice by the researchers to reject individual entitlements for the utilitarian goal of maximizing social welfare. Facilitating this choice is adherence to traditional notions of property rights, which Professor Peter Halewood has criticized for their reliance on the "conceptual structure of the radical dichotomy between subject and object." 73 Because the classical liberal conception of property rights is founded on formal equality, Halewood explains, analyzing the process wherein liberal legalism has severed the concept of "will" (subject) from the "body" (object) is vital to understanding how current legal theory and practice affects socially and culturally diverse individuals: "The legal subject's isolation from object relations means that subjects can have no particular defining material characteristics. Thus, to make the formal equality of persons possible, liberalism defines persons in their most bare form, stripped of all particularity so that each possesses a similar moral weight." 74 In other words, liberal legalism is structured upon an "essentialist premise" that universalizes the human "will" by removing it from cultural contexts and circumstances, such as gender, race, or class. 75 The problem, then, is that the body is "reduced to the status of `surplus' to human `essence,'" or will; the effect is to extinguish the body's significance and relevance to "personhood" (the "free will" and "essence" of an individual human being). 76 Challenging the allegations of unethical behavior, the CDC and other supporters of the tests argue that these critics are engaging in "ethical imperialism" by attempting to "export" the Westernized doctrine of informed consent to developing countries 44--which may have a communitarian outlook and lack the Western concept of an autonomous "self" or "personhood"--and by imposing American standards of care on nations which cannot afford them. 45 These justifications are espoused by leading doctors and bioethicists; for example, the esteemed AIDS researcher Dr. David D. Ho declares, "While the inclusion of this placebo group would not be acceptable in the United States, the sad truth is that giving nothing is the current standard of care in Africa." 46 Another doctor bluntly asserts, "the facts are different in different places." 47 Affirming this position, some doctors and researchers originating from the host countries have argued, "Americans should not impose their standards of care on developing countries," 48 and "local health experts, bioethicists and affected groups are best qualified to judge the risks and benefits of any medical research." 49 Thus, by focusing on the Western origins of the informed consent doctrine, the sponsors of these tests invoke a relativist argument that would preclude imposing burdensome American values and requirements on other nations.
Abstract only
Classically, the glycerol dehydration test (GDT) has been used to test for the presence of Ménière's disease and can cause acute alterations in vestibular reflexes in both normal and ...pathological states. The vestibulosympathetic reflex (VSR) elicits increases in muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction. We hypothesized that the GDT would attenuate the VSR through an acute fluid shift of the inner ear. Nine male subjects (27±1 years) performed head‐down rotation (HDR), which engages the VSR, before and after administration of either the GDT or saline. MSNA (microneurography), arterial blood pressure, and leg blood flow (venous occlusion plethysmography) were measured during HDR. Subjects performed 80‐degree head‐up tilt for up to 30 minutes after the post‐tests. Before drug administration, HDR significantly increased MSNA in burst frequency (Δ5±1 bursts/min, Δ8±1 bursts/min; p<0.01) and total activity (Δ44±13% Δ77±17%; p<0.01), and decreased calf vascular conductance (Δ15±6%, Δ20±3%; p<0.01), in both the saline and glycerol trials, respectively. Post‐saline injection, HDR still significantly increased MSNA (Δ6±2 bursts/min, Δ83±20% total activity; p<0.01) and decreased calf vascular conductance (Δ21±4%, p<0.01), which was not significantly different from pretesting. In contrast, post‐GDT resulted in an attenuation of MSNA (Δ3±1 bursts/min, Δ22±3% total activity) and reduction in calf vascular conductance (Δ7±4%) during HDR. These results suggest that a fluid shift of the inner ear via glycerol dehydration attenuates the VSR. These data provide support that dynamic fluid shifts can have a significant effect on the VSR.
Research supported by NIH DC006459, HL077670, & M01RR10732 and NSBRI CA00404
Section 3A1.1 of the Federal Sentencing Guidelines (Guidelines) establishes a sentencing enhancement for defendants who victimize unusually vulnerable persons. While the statute enumerates three ...explicit categories to consider when applying the provision--age, physical or mental condition--it also contains a catch-all phrase allowing judges to enhance the sentence if the victim was "otherwise particulary susceptible" to the criminal conduct. The seemingly limitless potential of this phrase has bred conflicting interpretations of the scope of Section 3A1.1. Consequently, the Guidelines' explicit goals of reducing sentencing disparity and promoting proportionality have been undermined. This Note examines the source of this conflict, the statutory language, and contends that those courts adopting a more restrictive method of applying the enhancement advance a principled approach that more effectively promotes the Guidelines' goals. While some courts base their analysis on a comparison of the victim to a more hypothetically robust victim, thereby greatly expanding the scope of the provision, other courts follow the examples illustrated in the Guidelines' commentary to restrict application to those defendants whose crimes truly evince greater depravity by preying on persons in need of greater societal protection. Thus, this Note analyzes cases decided under both approaches to demonstrate the need to restrict application of Section 3A1.1 to those defendants whose victims exhibit "unusual" or "unique" vulnerable traits equivalent to the type envisioned in the commentary.
For patients initially seen in the emergency department (ED) for panic attack, this study evaluated the effect of two brief psychological interventions in the ED on later utilization of emergency, ...psychiatric, and nonpsychiatric medical department services. Each of the two intervention groups received usual ED care, a brochure on panic disorder, and a referral to treatment at the psychiatry department; one of the two groups also received 20–30 minutes of contact with a representative from the psychiatry department. Both intervention groups were compared with a historical control group. The contact condition reduced ED use after the initial visit to the ED, although all three groups had more visits to the psychiatry department and to all nonpsychiatric departments. This decrease was statistically significant (P
=
0.0017) when compared with the brochure condition but not when compared with the historical control group (P
=
0.0672). The decrease seen in ED use is an important therapeutic and economic finding.
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