Wayne State University

About: Wayne State University is a education organization based out in Detroit, Michigan, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 42801 authors who have published 82738 publications receiving 3083713 citations. The organization is also known as: WSU & Wayne University.

Optimized Pre-Processing for Discrimination Prevention

Abstract: Non-discrimination is a recognized objective in algorithmic decision making. In this paper, we introduce a novel probabilistic formulation of data pre-processing for reducing discrimination. We propose a convex optimization for learning a data transformation with three goals: controlling discrimination, limiting distortion in individual data samples, and preserving utility. We characterize the impact of limited sample size in accomplishing this objective. Two instances of the proposed optimization are applied to datasets, including one on real-world criminal recidivism. Results show that discrimination can be greatly reduced at a small cost in classification accuracy.

Effects of tissue plasminogen activator for acute ischemic stroke at one year

Abstract: Background In 1995, the two-part National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator Stroke Study found that patients who were treated with tissue plasminogen activator (t-PA) within three hours after the onset of symptoms of acute ischemic stroke were at least 30 percent more likely than patients given placebo to have minimal or no disability three months after the stroke. It was unknown, however, whether the benefit would be sustained for longer periods. Methods In the NINDS trial, a total of 624 patients with stroke were randomly assigned to receive either t-PA or placebo. We collected outcome data over a period of 12 months after the occurrence of stroke. The primary outcome measure was a “favorable outcome,” defined as minimal or no disability as measured by the Barthel index, the modified Rankin Scale, and the Glasgow Outcome Scale. We assessed the treatment effect using a global statistic. Results Using an intention-to-treat analysis for the comb...

Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial

Abstract: Summary Background Patients with progressive disease after two or more HER2-directed regimens for recurrent or metastatic breast cancer have few effective therapeutic options. We aimed to compare trastuzumab emtansine, an antibody–drug conjugate comprising the cytotoxic agent DM1 linked to trastuzumab, with treatment of physician's choice in this population of patients. Methods This randomised, open-label, phase 3 trial took place in medical centres in 22 countries across Europe, North America, South America, and Asia-Pacific. Eligible patients (≥18 years, left ventricular ejection fraction ≥50%, Eastern Cooperative Oncology Group performance status 0–2) with progressive HER2-positive advanced breast cancer who had received two or more HER2-directed regimens in the advanced setting, including trastuzumab and lapatinib, and previous taxane therapy in any setting, were randomly assigned (in a 2:1 ratio) to trastuzumab emtansine (3·6 mg/kg intravenously every 21 days) or physician's choice using a permuted block randomisation scheme by an interactive voice and web response system. Patients were stratified according to world region (USA vs western Europe vs other), number of previous regimens (excluding single-agent hormonal therapy) for the treatment of advanced disease (two to three vs more than three), and presence of visceral disease (any vs none). Coprimary endpoints were investigator-assessed progression-free survival (PFS) and overall survival in the intention-to-treat population. We report the final PFS analysis and the first interim overall survival analysis. This study is registered with ClinicalTrials.gov, number NCT01419197. Findings From Sept 14, 2011, to Nov 19, 2012, 602 patients were randomly assigned (404 to trastuzumab emtansine and 198 to physician's choice). At data cutoff (Feb 11, 2013), 44 patients assigned to physician's choice had crossed over to trastuzumab emtansine. After a median follow-up of 7·2 months (IQR 5·0–10·1 months) in the trastuzumab emtansine group and 6·5 months (IQR 4·1–9·7) in the physician's choice group, 219 (54%) patients in the trastuzumab emtansine group and 129 (65%) of patients in the physician's choice group had PFS events. PFS was significantly improved with trastuzumab emtansine compared with physician's choice (median 6·2 months [95% CI 5·59–6·87] vs 3·3 months [2·89–4·14]; stratified hazard ratio [HR] 0·528 [0·422–0·661]; p vs 80 events [43%] in 184 patients). Neutropenia (ten [2%] vs 29 [16%]), diarrhoea (three [ vs eight [4%]), and febrile neutropenia (one [ vs seven [4%]) were grade 3 or worse adverse events that were more common in the physician's choice group than in the trastuzumab emtansine group. Thrombocytopenia (19 [5%] vs three [2%]) was the grade 3 or worse adverse event that was more common in the trastuzumab emtansine group. 74 (18%) patients in the trastuzumab emtansine group and 38 (21%) in the physician's choice group reported a serious adverse event. Interpretation Trastuzumab emtansine should be considered as a new standard for patients with HER2-positive advanced breast cancer who have previously received trastuzumab and lapatinib. Funding Genentech.

AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial

Abstract: Summary Background Gene transfer of glutamic acid decarboxylase ( GAD ) and other methods that modulate production of GABA in the subthalamic nucleus improve basal ganglia function in parkinsonism in animal models. We aimed to assess the effect of bilateral delivery of AAV2- GAD in the subthalamic nucleus compared with sham surgery in patients with advanced Parkinson's disease. Methods Patients aged 30–75 years who had progressive levodopa-responsive Parkinson's disease and an overnight off-medication unified Parkinson's disease rating scale (UPDRS) motor score of 25 or more were enrolled into this double-blind, phase 2, randomised controlled trial, which took place at seven centres in the USA between Nov 17, 2008, and May 11, 2010. Infusion failure or catheter tip location beyond a predefined target zone led to exclusion of patients before unmasking for the efficacy analysis. The primary outcome measure was the 6-month change from baseline in double-blind assessment of off-medication UPDRS motor scores. This trial is registered with ClinicalTrials.gov, NCT00643890. Findings Of 66 patients assessed for eligibility, 23 were randomly assigned to sham surgery and 22 to AAV2- GAD infusions; of those, 21 and 16, respectively, were analysed. At the 6-month endpoint, UPDRS score for the AAV2- GAD group decreased by 8·1 points (SD 1·7, 23·1%; p GAD group showed a significantly greater improvement from baseline in UPDRS scores compared with the sham group over the 6-month course of the study (RMANOVA, p=0·04). One serious adverse event occurred within 6 months of surgery; this case of bowel obstruction occurred in the AAV2- GAD group, was not attributed to treatment or the surgical procedure, and fully resolved. Other adverse events were mild or moderate, likely related to surgery and resolved; the most common were headache (seven patients in the AAV2- GAD group vs two in the sham group) and nausea (six vs two). Interpretation The efficacy and safety of bilateral infusion of AAV2- GAD in the subthalamic nucleus supports its further development for Parkinson's disease and shows the promise for gene therapy for neurological disorders. Funding Neurologix.