Update on Chemotherapy in the Treatment of Urothelial Carcinoma

Urothelial carcinoma is the fifth most common malignancy diagnosed each year in the United States. Neoadjuvant and adjuvant chemotherapy are given to decrease the risk of recurrent or metastatic disease with the more robust clinical data supporting the former. Bladder preservation utilizes a trimodality approach with maximal transurethral resection followed by concurrent chemotherapy and radiation and is appropriate for select patients. Gemcitabine and cisplatin is the current standard of care for first-line treatment in fit patients with metastatic disease. Optimal second-line therapy remains undefined, and targeted agents are under investigation. Clinical trial participation should be encouraged in patients with urothelial carcinoma of the bladder to help improve treatment regimens and outcomes. Synopsis. Chemotherapy is commonly used in the treatment of urothelial carcinoma of the bladder. This paper will review the role of chemotherapy in the neoadjuvant, adjuvant, bladder sparing, and metastatic settings

Automated synthesis of biodiversity knowledge requires better tools and standardised research output

As the impact of anthropogenic activity on the environment has grown, research into biodiversity change and associated threats has also accelerated. Synthesising this vast literature is important for understanding the drivers of biodiversity change and identifying those actions that will mitigate further ecological losses. However, keeping pace with an ever-increasing publication rate presents a substantial challenge to efficient syntheses, an issue which could be partly addressed by increasing levels of automation in the synthesis pipeline. Here, we evaluate the potential for automated tools to extract ecologically important information from the abstracts of articles compiled in the Living Planet Database. Specifically, we focused on extracting key information on taxonomy (studied species names), geographic location and estimated population trend, assessing the accuracy of automated versus manual information extraction, the potential for automated tools to introduce biases into syntheses, and evaluating if synthesising abstracts was enough to capture the key information from the full article. Taxonomic and geographic extraction tools performed reasonably well, although information on studied species was sometimes limited in the abstract (compared to the main text) preventing fast extraction. In contrast, extraction of trends was less successful, highlighting the challenges involved in automating information extraction from abstracts, such as deficiencies in the algorithms, linguistic complexity associated with ecological findings, and limited information when compared to the main text. In light of these results, we cautiously advocate for a wider use of automated taxonomic and geographic parsing tools for ecological synthesis. Additionally, to further the use of automated synthesis within ecology, we recommend a dual approach: development of improved computational tools to reduce biases; and enhanced protocols for abstracts (and associated metadata) to ensure key information is included in a format that facilitates machine-readability

The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate-resistant prostate cancer: results from a retrospective analysis of a randomized phase 3 clinical trial (CALGB 90401) (Alliance).

BACKGROUND: Preliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel. METHODS: In CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm. RESULTS: Baseline characteristics between patients who did (N=277) and did not (N=728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P=.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P=.342), the proportion achieving a decline ≥ 50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P=.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P=.366). CONCLUSIONS: As measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC

Undergraduate Research Participation in Electrical Engineering

During the 1990-2003 summers the Electrical Engineering Department at the University of Maine will offer ten undergraduate students the opportunity to actively participate in research. Students will receive financial awards plus a subsistence allowance. The available research projects include (1) Environmental Sensors; (2) Intelligent Systems for Automation; (3) Communications Devices and Applications; (4) Motion Control; (5) Microprocessor/Instrumentation Applications; (6) Growth and Characterization of Thin Film Materials; and (7) Power Systems Applications. At least five students will come from institutions where research opportunities are limited and at least four students will be women, minorities or students with disabilities. Students chosen for the program will have displayed a high degree of initiative and independence of thought in both laboratories and course work. Student research projects are chosen to match the student\u27s interest and educational level. In addition to extensive University facilities, students will also have access to facilities at various nearby industries such as Sensor Research and Development Corporation, BIODE Corporation, Bangor Hydro Electric and Central Maine Power Companies, James River, Champion, and Scott Paper Companies, Digital Equipment Corporation, Fairchild and National Semiconductor. At the program culmination a written report and an oral seminar are required from the student. Three academic credits are awarded to the student upon satisfactory completion of the program

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Automated synthesis of biodiversity knowledge requires better tools and standardised research output

As the impact of anthropogenic activity on the environment has grown, research into biodiversity change and associated threats has also accelerated. Synthesising this vast literature is important for understanding the drivers of biodiversity change and identifying those actions that will mitigate further ecological losses. However, keeping pace with an ever-increasing publication rate presents a substantial challenge to efficient syntheses, an issue which could be partly addressed by increasing levels of automation in the synthesis pipeline. Here, we evaluate the potential for automated tools to extract ecologically important information from the abstracts of articles compiled in the Living Planet Database. Specifically, we focused on extracting key information on taxonomy (studied species names), geographic location, and estimated population trend, assessing the accuracy of automated vs manual information extraction, the potential for automated tools to introduce biases into syntheses, and evaluating if synthesising abstracts was enough to capture the key information from the full article. Taxonomic and geographic extraction tools performed reasonably well, although information on studied species was sometimes limited in the abstract (compared to the main text) preventing fast extraction. In contrast, extraction of trends was less successful, highlighting the challenges involved in automating information extraction from abstracts, such as deficiencies in the algorithms, linguistic complexity associated with ecological findings, and limited information when compared to the main text. In light of these results, we cautiously advocate for a wider use of automated taxonomic and geographic parsing tools for ecological synthesis. Additionally, to further the use of automated synthesis within ecology, we recommend a dual approach: development of improved computational tools to reduce biases; and enhanced protocols for abstracts (and associated metadata) to ensure key information is included in a format that facilitates machine-readability