Urinary diversion: evidence-based outcomes assessment and integration into patient decision-making

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72842/1/j.1464-410X.2008.07978.x.pd

Bacterial cooperation through horizontal gene transfer

Cooperation exists across all scales of biological organization, from genetic elements to complex human societies. Bacteria cooperate by secreting molecules that benefit all individuals in the population (i.e., public goods). Genes associated with cooperation can spread among strains through horizontal gene transfer (HGT). We discuss recent findings on how HGT mediated by mobile genetic elements promotes bacterial cooperation, how cooperation in turn can facilitate more frequent HGT, and how the act of HGT itself may be considered as a form of cooperation. We propose that HGT is an important enforcement mechanism in bacterial populations, thus creating a positive feedback loop that further maintains cooperation. To enforce cooperation, HGT serves as a homogenizing force by transferring the cooperative trait, effectively eliminating cheaters

Measuring health-related quality of life outcomes in bladder cancer patients using the Bladder Cancer Index (BCI)

BACKGROUND. Health-related quality of life (HRQOL) has not been adequately measured in bladder cancer. A recently developed reliable and disease-specific quality of life instrument (Bladder Cancer Index, BCI) was used to measure urinary, sexual, and bowel function and bother domains in patients with bladder cancer managed with several different interventions, including cystectomy and endoscopic-based procedures. METHODS. Patients with bladder cancer were identified from a prospective bladder cancer outcomes database and contacted as part of an Institutional Review Board-approved study to assess treatment impact on HRQOL. HRQOL was measured using the BCI across stratified treatment groups. Bivariate and multivariable analyses adjusted for age, gender, income, education, relationship status, and follow-up time were performed to compare urinary, bowel, and sexual domains between treatment groups. RESULTS. In all, 315 bladder cancer patients treated at the University of Michigan completed the BCI in 2004. Significant differences were seen in mean BCI function and bother scores between cystectomy and native bladder treatment groups. In addition, urinary function scores were significantly lower among cystectomy patients treated with continent neobladder compared with those treated with ileal conduit (all pairwise P < .05). CONCLUSIONS. The BCI is responsive to functional and bother differences in patients with bladder cancer treated with different surgical approaches. Significant differences between therapy groups in each of the urinary, bowel, and sexual domains exist. Among patients treated with orthotopic continent urinary diversion, functional impairments related to urinary incontinence and lack of urinary control account for the low observed urinary function scores. Cancer 2007. © 2007 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55989/1/22556_ftp.pd

Infrared multiphoton dissociation of two perfluorobutenes

Photofragment translational spectroscopy was used to examine the infrared multiphotondissociation of octafluoro-1-butene and octafluoro-2-butene. The predominant unimolecular reaction in octafluoro-1-butene at moderate laser fluences is cleavage of a carbon–carbon single bond to give the products CF3 and C3F5. The two other reactions that take place are CF2 elimination and the formation of equal weight fragments with the chemical compositionC2F4; both reactions take place via a diradical intermediate. Dissociation of octafluoro-1-butene to the resonance stabilized perfluoroallyl radical is suggested to account for the favoring of simple bond rupture. These three reaction pathways were also observed in octafluoro-2-butene dissociation, however, the branching fraction is different than from octafluoro-1-butene. In octafluoro-2-butene all three channels occur with roughly equal probability. The reactions involving CF2 loss and C2F4 formation in octafluoro-2-butene are thought to proceed through the same diradical intermediate as in octafluoro-1-butene, necessitating a 1,2-fluorine migration

Delays in diagnosis and bladder cancer mortality

BACKGROUND: Mortality from invasive bladder cancer is common, even with high-quality care. Thus, the best opportunities to improve outcomes may precede the diagnosis. Although screening currently is not recommended, better medical care of patients who are at risk (ie, those with hematuria) has the potential to improve outcomes. METHODS: The authors used the Surveillance, Epidemiology, and End Results-Medicare linked database for the years 1992 through 2002 to identify 29,740 patients who had hematuria in the year before a bladder cancer diagnosis and grouped them according to the interval between their first claim for hematuria and their bladder cancer diagnosis. Cox proportional hazards models were fitted to assess relations between these intervals and bladder cancer mortality, adjusting first for patient demographics and then for disease severity. Adjusted logistic models were used to estimate the patient's probability of receiving a major intervention. RESULTS: Patients (n = 2084) who had a delay of 9 months were more likely to die from bladder cancer compared with patients who were diagnosed within 3 months (adjusted hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.20-1.50). This risk was not markedly attenuated after adjusting for disease stage and tumor grade (adjusted HR, 1.29; 95% CI, 1.14-1.45). In fact, the effect was strongest among patients who had low-grade tumors (adjusted HR, 2.11; 95% CI, 1.69-2.64) and low-stage disease (ie, a tumor [T] classification of Ta or tumor in situ; adjusted HR, 2.02; 95% CI, 1.54-2.64). CONCLUSIONS: A delay in the diagnosis of bladder cancer increased the risk of death from disease independent of tumor grade and or disease stage. Understanding the mechanisms that underlie these delays may improve outcomes among patients with bladder cancer. Cancer 2010. © 2010 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78303/1/25310_ftp.pd

Implementation and assessment of a novel non-clinical skills curriculum for urology residents

BackgroundUrology is an increasingly competitive specialty that procures a highly selected and clinically excellent cohort of residents. However, other training needs such as leadership and professional development go underrecognized despite an identified need for formal training in these areas. The aim of this study was to implement, evaluate, and pilot a non-clinical skills curriculum, a novel individualized professional development workshop series, at a single institution.MethodsEighteen urology residents (15/year, 3 graduates/year) participated in this study over the course of two academic years. A pre-curriculum needs assessment was completed by 15 residents in Year 1 for purposes of curriculum design. The curriculum itself was a series of 1-hour monthly workshops given by an expert speaker on topics relevant to healthcare delivery, leadership and career promotion across various contexts. Survey-based assessments tracked gains in subject knowledge and satisfaction via a pre-post test design.ResultsThe pre-curriculum needs assessment indicated that trainees desired additional instruction in non-clinical skills (ps&gt;0.1) and endorsed formal teaching to ensure success in their future careers (p&lt;0.001). Trainees reported pre- to post-curriculum gains across each individual learning topic (Mean=20%, p&lt;0.001) with an aggregate increase in subject knowledge of 17% for senior residents and 21% for junior residents (p&lt;0.001).ConclusionA non-clinical skills curriculum implemented as a pilot ‘Hidden Curriculum’ for urology trainees was feasible and resulted in significant gains in non-clinical subject knowledge. Workshops were highly rated and trainees reported high satisfaction with the curriculum

Therapeutic targeting of integrin αvβ6 in breast cancer

BACKGROUND: Integrin ?v?6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of ?v?6 has yet to be elucidated in breast cancer.METHODS: Protein expression of integrin subunit beta6 (?6) was measured in breast cancers by immunohistochemistry (n &gt; 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of ?6 in breast cell lines, the role of ?v?6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ? 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.RESULTS: High expression of either the mRNA or protein for the integrin subunit ?6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of ?6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P &lt; .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.CONCLUSIONS: Targeting ?v?6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.<br/