A Legal Lens: Brexit, Access, and Equity in the United Kingdom and the United States

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A phase 1b study evaluating the safety and preliminary efficacy of berzosertib in combination with gemcitabine in patients with advanced non-small cell lung cancer

OBJECTIVES: Berzosertib (formerly M6620, VX-970) is an intravenous, highly potent and selective, first-in-class ataxia telangiectasia and Rad3-related (ATR) protein kinase inhibitor. We assessed the safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of berzosertib plus gemcitabine in an expansion cohort of patients with advanced non-small cell lung cancer (NSCLC). The association of efficacy with TP53 status and other tumor markers was also explored. MATERIALS AND METHODS: Adult patients with advanced histologically confirmed NSCLC received berzosertib 210 mg/m2 (days 2 and 9) and gemcitabine 1000 mg/m2 (days 1 and 8) at the recommended phase 2 dose established in the dose escalation part of the study. RESULTS: Thirty-eight patients received at least one dose of study treatment. The most common treatment-emergent adverse events were fatigue (55.3%), anemia (52.6%), and nausea (39.5%). Gemcitabine had no apparent effect on the PK of berzosertib. The objective response rate (ORR) was 10.5% (4/38, 90% confidence interval [CI]: 3.7–22.5%). In the exploratory analysis, the ORR was 30.0% (3/10, 90% CI: 9.0–61.0%) in patients with high loss of heterozygosity (LOH) and 11.0% (1/9, 90% CI: 1.0–43.0%) in patients with low LOH. The ORR was 33.0% (2/6, 90% CI: 6.0–73.0%) in patients with high tumor mutational burden (TMB), 12.5% (2/16, 90% CI: 2.0–34.0%) in patients with intermediate TMB, and 0% (0/3, 90% CI: 0.0–53.6%) in patients with low TMB. CONCLUSIONS: Berzosertib plus gemcitabine was well tolerated in patients with advanced, pre-treated NSCLC. Based on the observed clinical efficacy, future clinical trials should involve genomically selected patients

Experiential learning and the acquisition of managerial tacit knowledge

Tacit knowledge is believed to be one factor that distinguishes successful managers from others. We sought to determine whether levels of accumulated managerial tacit knowledge (LAMTK) were associated with managers' dominant learning styles. Instruments used in the study, involving 356 Malaysian public sector employees, included Sternberg et al.'s (2000) Tacit Knowledge Inventory for Managers and a normative version of Kolb's (1999a) Learning Styles Inventory (LSI-Ill). Findings suggest that LAMTK is independent of the length of subjects' general work experience, but positively related to the amount of time spent working in a management context. Learning styles also had a significant relationship. Subjects who spent most of their time performing management functions and whose dominant learning styles were accommodating had significantly higher LAMTK than those with different learning styles. We also found support for the belief that learners with a strong preference for all four different abilities defined in Kolb's learning theory may be critical for effective experiential learning

Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)

Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months

Cognitive Processes in the Curry Learning Style Framework as Measured by the Learning Style Profile and the Myers-Briggs Type Indicator Among Non-Majors in College Biology

Curry\u27s (1983) model of learning style framework with Claxton & Murrell\u27s (1987) adaptations was used to study the profile of the non-major in a college biology course. The purpose of the study was to provide empirically derived data in both a qualitative and quantitative format of the non major (both successful and unsuccessful students) to improve the course. Over 600 students were administered the Learning Style Profile [(LSP) (National Association of Secondary School Principals) Indicator (MBTI) (NASSP) and the Myers-Briggs Type (Consulting Psychologists Press)] to determine the students\u27 learning styles as a predictor for Success in the course. The MBTI data were compared to published (McCaulley, 1977) profiles of other populations: biology majors, science majors and biologists. Using a logit model, Introversion (I) and spatial ability predict success with a probability of 0.67 (p\u3c.0005). The profile of the male non-major in biology which is most different from male science majors, by MBTI profile, is ESFP (Extroverted, Sensing, Feeling, and perceiving) (p\u3c.OOl). ESFPS and ENTPs occur more frequently among unsuccessful students (p\u3c.OOl). ISTJs (p\u3c.05) and ISFPs (p\u3c.Ol) occur more frequently among successful students. INTJs and INFPs are more numerous among both biology majors and biologists than among non-majors. Students who are most likely to score below 60% on the computer-managed testing system are E_P (Extroverted and Perceiving) (p\u3c.OOl). The only LSP subscale which showed a difference between students show were successful and those who were not was spatial ability (p\u3c. 01) . A three-factor interaction (p\u3c. 05) was observed when amount of analytic skill, question type (low, high, and image), and correct vs incorrect answers were submitted to an ANOVA on 96 students and six questions. Items which measure analytic ability were classified as spatial ability items. A 9 factor varimax rotation factor analysis for the LSP established the six item analytic scale. Canonical correlation shows that the LSP and the MBTI are related at a level of 0.5 for the first canonical variate, with verbal risk contributing most to the relationship between the LSP and the MBTI, with an explained variance of 24%. Recommendations for course improvement, following the McComb (1985) Instructional Systems Design (ISD) model include providing: opportunities for discussion, for hands-on experiences to concretize abstract concepts which may require spatial ability, less reliance on recall of memorized information, less than 92% of the course evaluation on the computer (multiple choice items). Other recommendations include providing remediation in some skills, such as analytic and spatial

Identification, Referral, and Evaluation Process Leading to the Initial Diagnosis of the Educable Mentally Handicapped

This study investigated referral and evaluation procedures in relation to the final diagnosis and placement of 176 children labeled mildly mentally retarded and described these children in terms of specific biographical and educational variables. Also, it examined reasons for referral of these children for evaluation, while surveying the prevalence of behavioral, emotional, social, linguistic, perceptual - motor, and other educational handicaps among them. In attending to the prevalence of certain characteristics and epidemiological trends associated with the mildly mentally handicapped population, descriptive statistics were used to report the results of this investigation in a meaningful form. Certain linguistic and socioeconomic differences were found to exist between Hispano and Anglo children prior to initial diagnosis and placement. While data indicated that the referral rationale differed among ethnic groups, it was found that different criteria for diagnosis based on psycho-educational evaluation was being used simultaneously by educational specialists