2,730 research outputs found

    Wills - Renunciation in Behalf of Incompetent Widow

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    Distribution and habitats of forked aster (Aster furcatus), a threatened Wisconsin plant

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    We describe the locations and habitat characteristics of 10 of the 14 known populations of Aster furcatus in Wisconsin. We were unable to identify any particularly unusual features of A. furcatus habitats which could be related to its rarity. The rarity of forked aster is probably not related to specialized habitats, but is most likely the result of requirements for moderate disturbance, inability to withstand competition, poor reproduction from seed, and low genetic variance

    Synthesis of 125 I‐labeled 14‐iodo‐9‐tetradecynoic acid

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    The synthesis and radioiodide exchange labelling of 14‐iodo‐9‐tetradecynoic acid (1), a potential suicide inhibitor of acyl‐CoA dehydrogenase or enoyl‐CoA isomerase, is presented. Tissue distribution data in dogs are reported.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90063/1/2580180911_ftp.pd

    Slowing of Motor Nerve Conduction Velocity in Streptozotocin-induced Diabetic Rats is Preceded by Impaired Vasodilation in Arterioles that Overlie the Sciatic Nerve

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    Diabetes mellitus produces marked abnormalities in motor nerve conduction, but the mechanism is not clear. In the present study we hypothesized that in the streptozotocin (STZ)-induced diabetic rat impaired vasodilator function in arterioles that provide circulation to the region of the sciatic nerve is associated with reduced endoneural blood flow (EBF) and that these defects precede slowing of motor nerve conduction velocity, and thereby may contribute to nerve dysfunction. As early as three days after the induction of diabetes endoneural blood flow was reduced in the STZ-induced diabetic rat. Furthermore, after 1 week of diabetes acetylcholine- induced vasodilation was found to be impaired. This was accompanied by an increase in the superoxide level in arterioles that provide circulation to the region of the sciatic nerve as well as changes in the level of other markers of oxidative stress including an increase in serum levels of thiobarbituric acid reactive substances and a decrease in lens glutathione level. In contrast to the vascular related changes that occur within 1 week of diabetes, motor nerve conduction velocity and sciatic nerve Na+/k+ ATPase activity were significantly reduced following 2 and 4 weeks of diabetes, respectively. These studies demonstrate that changes in vascular function in the STZ-induced diabetic rat precede the slowing of motor nerve conduction velocity (MNCV) and are accompanied by an increase in superoxide levels in arterioles that provide circulation to the region of the sciatic nerve

    Whose Side are Ethics Codes On? Power, Responsibility and the Social Good

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    The moral authority of ethics codes stems from an assumption that they serve a unified society, yet this ignores the political aspects of any shared resource. The sociologist Howard S. Becker challenged researchers to clarify their power and responsibility in the classic essay: Whose Side Are We On. Building on Becker's hierarchy of credibility, we report on a critical discourse analysis of data ethics codes and emerging conceptualizations of beneficence, or the "social good", of data technology. The analysis revealed that ethics codes from corporations and professional associations conflated consumers with society and were largely silent on agency. Interviews with community organizers about social change in the digital era supplement the analysis, surfacing the limits of technical solutions to concerns of marginalized communities. Given evidence that highlights the gulf between the documents and lived experiences, we argue that ethics codes that elevate consumers may simultaneously subordinate the needs of vulnerable populations. Understanding contested digital resources is central to the emerging field of public interest technology. We introduce the concept of digital differential vulnerability to explain disproportionate exposures to harm within data technology and suggest recommendations for future ethics codes.Comment: Conference on Fairness, Accountability, and Transparency (FAT* '20), January 27-30, 2020, Barcelona, Spain. Correcte

    Indacaterol vs tiotropium in COPD patients classified as GOLD A and B

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    SummaryIntroductionAccording to current GOLD strategy, patients with COPD classified as groups A and B may be treated with inhaled bronchodilators, either long-acting β2-agonist (LABA) or long-acting muscarinic antagonist (LAMA). However, there is little guidance on which class of agent is preferred and a lack of prospective data to differentiate the two.MethodsIn this study, we performed post-hoc analyses of pooled data from two prospective, controlled clinical trials comparing the LABA indacaterol and LAMA tiotropium in 1422 patients with moderate airflow limitation and no history of exacerbations in the previous year. This population fits the definitions of GOLD A and B groups and could be further stratified by symptom severity using Baseline Dyspnea Index (i.e. modeling GOLD A or B) and inhaled corticosteroid (ICS) use at baseline. Outcomes measured after 12 weeks of treatment were lung function (forced expiratory volume in 1 s; FEV1), health status (St George's Respiratory Questionnaire; SGRQ), symptoms (Transition Dyspnea Index; TDI) and rescue medication use.ResultsIn ‘GOLD A’ patients not receiving ICS, differences favored indacaterol versus tiotropium (trough FEV1 0.05 L; rescue medication use −0.41 puffs/day; TDI total score 0.94 points; SGRQ total score −3.13 units, all p < 0.01). In ‘GOLD B, no ICS’ patients, compared with tiotropium, indacaterol treatment increased trough FEV1 (0.055 L, p < 0.05) and permitted a larger reduction in rescue medication use (−0.81 puffs/day, p = 0.004). In all patients, and in patients not using ICS, differences favored indacaterol for all variables.ConclusionsOur findings suggest that patients in GOLD groups A and B may experience greater benefits with indacaterol than with tiotropium

    Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration

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    Artesunate (AS) is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA). In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV), intramuscular (IM), oral or rectal routes. Intravenous AS is associated with high initial AS concentrations which subsequently decline rapidly, with typical AS half-life estimates of less than 15 minutes. AS clearance and volume estimates average 2 - 3 L/kg/hr and 0.1 - 0.3 L/kg, respectively. DHA concentrations peak within 25 minutes post-dose, and DHA is eliminated with a half-life of 30 - 60 minutes. DHA clearance and volume average between 0.5 - 1.5 L/kg/hr and 0.5 - 1.0 L/kg, respectively. Compared to IV administration, IM administration produces lower peaks, longer half-life values, and higher volumes of distribution for AS, as well as delayed peaks for DHA; other parameters are generally similar due to the high bioavailability, assessed by exposure to DHA, associated with IM AS administration (> 86%). Similarly high bioavailability of DHA (> 80%) is associated with oral administration. Following oral AS, peak AS concentrations (Cmax) are achieved within one hour, and AS is eliminated with a half-life of 20 - 45 minutes. DHA Cmax values are observed within two hours post-dose; DHA half-life values average 0.5 - 1.5 hours. AUC values reported for AS are often substantially lower than those reported for DHA following oral AS administration. Rectal AS administration yields pharmacokinetic results similar to those obtained from oral administration, with the exceptions of delayed AS Cmax and longer AS half-life. Drug interaction studies conducted with oral AS suggest that AS does not appreciably alter the pharmacokinetics of atovaquone/proguanil, chlorproguanil/dapsone, or sulphadoxine/pyrimethamine, and mefloquine and pyronaridine do not alter the pharmacokinetics of DHA. Finally, there is evidence suggesting that the pharmacokinetics of AS and/or DHA following AS administration may be altered by pregnancy and by acute malaria infection, but further investigation would be required to define those alterations precisely

    Antiadhesive Role of Apical Decay-accelerating Factor (CD55) in Human Neutrophil Transmigration across Mucosal Epithelia

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    Neutrophil migration across mucosal epithelium during inflammatory episodes involves the precise orchestration of a number a cell surface molecules and signaling pathways. After successful migration to the apical epithelial surface, apically localized epithelial proteins may serve to retain PMN at the lumenal surface. At present, identification of apical epithelial ligands and their PMN counter-receptors remain elusive. Therefore, to define the existence of apical epithelial cell surface proteins involved in PMN–epithelial interactions, we screened a panel of antibodies directed against epithelial plasma membranes. This strategy identified one antibody (OE-1) that both localized to the apical cell membrane and significantly inhibited PMN transmigration across epithelial monolayers. Microsequence analysis revealed that OE-1 recognized human decay-accelerating factor (DAF, CD55). DAF is a highly glycosylated, 70–80-kD, glycosyl-phosphatidyinositol–linked protein that functions predominantly as an inhibitor of autologous complement lysis. DAF suppression experiments using antisense oligonucleotides or RNA interference revealed that DAF may function as an antiadhesive molecule promoting the release of PMN from the lumenal surface after transmigration. Similarly, peptides corresponding to the antigen recognition domain of OE-1 resulted in accumulation of PMN on the apical epithelial surface. The elucidation of DAF as an apical epithelial ligand for PMN provides a target for novel anti-inflammatory therapies directed at quelling unwanted inflammatory episodes
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