Prospectus, April 20, 1994

https://spark.parkland.edu/prospectus_1994/1006/thumbnail.jp

Prospectus, March 23, 1994

https://spark.parkland.edu/prospectus_1994/1004/thumbnail.jp

Breast-Cancer-Specific Mortality in Patients Treated Based on the 21-Gene Assay: A SEER Population-Based Study

The 21-gene Recurrence Score assay is validated to predict recurrence risk and chemotherapy benefit in hormone-receptor-positive (HR+) invasive breast cancer. To determine prospective breast-cancer-specific mortality (BCSM) outcomes by baseline Recurrence Score results and clinical covariates, the National Cancer Institute collaborated with Genomic Health and 14 population-based registries in the the Surveillance, Epidemiology, and End Results (SEER) Program to electronically supplement cancer surveillance data with Recurrence Score results. The prespecified primary analysis cohort was 40–84 years of age, and had node-negative, HR+, HER2-negative, nonmetastatic disease diagnosed between January 2004 and December 2011 in the entire SEER population, and Recurrence Score results (N = 38,568). Unadjusted 5-year BCSM were 0.4% (n = 21,023; 95% confidence interval (CI), 0.3–0.6%), 1.4% (n = 14,494; 95% CI, 1.1–1.7%), and 4.4% (n = 3,051; 95% CI, 3.4–5.6%) for Recurrence Score \u3c 18, 18–30, and ≥ 31 groups, respectively (P \u3c 0.001). In multivariable analysis adjusted for age, tumor size, grade, and race, the Recurrence Score result predicted BCSM (P \u3c 0.001). Among patients with node-positive disease (micrometastases and up to three positive nodes; N = 4,691), 5-year BCSM (unadjusted) was 1.0% (n = 2,694; 95% CI, 0.5–2.0%), 2.3% (n = 1,669; 95% CI, 1.3–4.1%), and 14.3% (n = 328; 95% CI, 8.4–23.8%) for Recurrence Score \u3c 18, 18–30, ≥ 31 groups, respectively (P \u3c 0.001). Five-year BCSM by Recurrence Score group are reported for important patient subgroups, including age, race, tumor size, grade, and socioeconomic status. This SEER study represents the largest report of prospective BCSM outcomes based on Recurrence Score results for patients with HR+, HER2-negative, node-negative, or node-positive breast cancer, including subgroups often under-represented in clinical trials

Unexpected Noncovalent Off-Target Activity of Clinical BTK Inhibitors Leads to Discovery of a Dual NUDT5/14 Antagonist

Cofactor mimicry represents an attractive strategy for the development of enzyme inhibitors but can lead to off-target effects due to the evolutionary conservation of binding sites across the proteome. Here, we uncover the ADP-ribose (ADPr) hydrolase NUDT5 as an unexpected, noncovalent, off-target of clinical BTK inhibitors. Using a combination of biochemical, biophysical, and intact cell NanoBRET assays as well as X-ray crystallography, we confirm catalytic inhibition and cellular target engagement of NUDT5 and reveal an unusual binding mode that is independent of the reactive acrylamide warhead. Further investigation of the prototypical BTK inhibitor ibrutinib also revealed potent inhibition of the largely unstudied NUDIX hydrolase family member NUDT14. By exploring structure–activity relationships (SARs) around the core scaffold, we identify a potent, noncovalent, and cell-active dual NUDT5/14 inhibitor. Cocrystallization experiments yielded new insights into the NUDT14 hydrolase active site architecture and inhibitor binding, thus providing a basis for future chemical probe design

Longitudinal strain is an independent predictor of survival and response to therapy in patients with systemic AL amyloidosis

AIMS: Cardiac involvement, a major determinant of prognosis in AL (light-chain immunoglobulin) amyloidosis, is characterized by an impairment of longitudinal strain (LS%). We sought to evaluate the utility of LS% in a prospectively observed series of patients. METHODS AND RESULTS: A total of 915 serial newly diagnosed AL patients with comprehensive baseline assessments, inclusive of echocardiography, were included. A total of 628/915 (68.6%) patients had cardiac involvement. The LS% worsened with advancing cardiac stage with mean −21.1%, −17.1%, −12.9%, and −12.1% for stages I, II, IIIa, and IIIb, respectively (P < 0.0001). There was a highly significant worsening of overall survival (OS) with worsening LS% quartile: LS% ≤−16.2%: 80 months, −16.1% to −12.2%: 36 [95% confidence interval (CI) 20.9–51.1] months, −12.1% to −9.1%: 22 (95% CI 9.1–34.9) months, and ≥−9.0%: 5 (95% CI 3.2–6.8) months (P < 0.0001). Improvement in LS% was seen at 12 months in patients achieving a haematological complete response (CR) (median improvement from −13.8% to −14.9% in those with CR and difference between involved and uninvolved light chain <10 mg/L). Strain improvement was associated with improved OS (median not reached at 53 months vs. 72 months in patients without strain improvement, P = 0.007). Patients achieving an LS% improvement and a standard N-terminal pro-brain natriuretic peptide-based cardiac response survived longer than those achieving a biomarker-based cardiac response alone (P < 0.0001). CONCLUSION: Baseline LS% is a functional marker that correlates with worsening cardiac involvement and is predictive of survival. Baseline LS% and an absolute improvement in LS% are useful additional measures of prognosis and response to therapy in cardiac AL amyloidosis, respectively

What Will Happen If We Do Nothing To Control Trachoma: Health Expectancies for Blinding Trachoma in Southern Sudan

Summary measures of population health attempt to express disease burden in terms of a common “currency” and are useful in establishing public health priorities. Disability adjusted life years (DALYs), a health gap measure, have previously been used to estimate burden due to trachoma; however, their methods and results have limitations. This study demonstrates the application of the health expectancies to estimate burden due to trachoma. The study illustrates the future burden associated with doing nothing to control trachoma in Southern Sudan: a substantial proportion of remaining life expectancy spent with trichiasis and low vision or blindness for both men and women, with a disproportionate burden falling on women. The results presented are intuitively meaningful for policy makers and a non-technical audience and compare favourably with other indicators such as mortality and incidence rates or DALYs, which are not generally easily understood. Unless action is taken by further delivery of trachoma control interventions, then populations in Southern Sudan can expect to spend a substantial proportion of their life with low vision or blindness due to trachoma

Recommendations to facilitate the ideal fit note: are they achievable in practice?

Background: Although the UK fit note has been broadly welcomed as a tool to facilitate return to work, difficulties and uncertainties have resulted in wide variation in its use. Agreement on what constitutes the ‘ideal’ fit note from the perspective of all stakeholders is needed to inform best practice. A recent Delphi study conducted by the authors reached consensus on 67 recommendations for best practice in fit note use for employed patients. However, such recommendations are not necessarily followed in practice. The purpose of this study was therefore to investigate the perceived achievability of implementing these Delphi recommendations with a further reference panel of stakeholders. Methods: Potential participants were identified by the research team and study steering group. These included representatives of employers, government departments, trades unions, patient organisations, general and medical practitioners and occupational health organisations who were believed to have the knowledge and experience to comment on the recommendations. The consensus Delphi statements were presented to the participants on-line. Participants were invited to comment on whether the recommendations were achievable, and what might hinder or facilitate their use in practice. Free text comments were combined with comments made in the Delphi study that referred to issues of feasibility or practicality. These were synthesised and analysed thematically. Results: Twelve individuals representing a range of stakeholder groups participated. Many of the recommendations were considered achievable, such as improved format and use of the electronic fit note, completion of all fields, better application and revision of guidance and education in fit note use. However a number of obstacles to implementation were identified. These included: legislation governing the fit note and GP contracts; the costs and complexity of IT systems and software; the limitations of the GP consultation; unclear roles and responsibilities for the funding and delivery of education, guidance and training for all stakeholders, and the evaluation of practice. Conclusions: This study demonstrated that although many recommendations for the ideal fit note are considered achievable, there are considerable financial, legal, organisational and professional obstacles to be overcome in order for the recommendations to be implemented successfully

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC

2005- 2008 UNLV McNair Journal

Journal articles based on research conducted by undergraduate students in the McNair Scholars Program Table of Contents Biography of Dr. Ronald E. McNair Statements: Dr. Neal J. Smatresk, UNLV President Dr. Juanita P. Fain, Vice President of Student Affairs Dr. William W. Sullivan, Associate Vice President for Retention and Outreach Mr. Keith Rogers, Deputy Executive Director of the Center for Academic Enrichment and Outreach McNair Scholars Institute Staf