Practical pursuit in stem cell biology: Innovation, translation, and incomplete theorization.

This paper aims to contribute to the study of practical pursuit-worthiness in science by engaging with a case in therapeutic stem cell biology. Induced pluripotent stem cell (iPSC) research emerged from research in developmental biology and the molecular biology of cell fate conversion. It took on practical significance when proposed as an alternative to therapeutic stem cell research that used human embryonic stem cells. The supposed ability of iPSC research to tackle ethical and regulatory constraints on research at the beginning of the twentieth century was a central part of the heuristic assessment of iPSC. However, the development and transfer of knowledge from experimental and theoretical biology to preclinical pursuit conflicted with the framing of biomedical innovation in public policy. The framing of innovation operated as part of the heuristic assessment of the pursuit-worthiness of iPSCs in the United States and was characterized by attempts to underdetermine conflicting ethical and socio-economic values - to seek innovations that are "incompletely theorized" in the sense that they purportedly allow stakeholders to refrain from engagement with the divisive values that created impediments to research in stem cell biology. When conflict arose with the epistemic standards in preclinical pursuit required to ensure the safety and efficacy of biomedical innovations, it resulted in the critical appraisal of the values used to rationalize policies for the distribution of federal resources for biomedical research. The case demonstrates how non-epistemic values impinge on standards of assessment in translational science, how background assumptions about innovation can drive practical pursuit, and how conflicting values and goals in research creates an important context for the appraisal of emerging science, technology and policy.

Evaluation of a specialty hepatitis C virus telephone pharmacy service.

PURPOSE: Direct-acting antivirals (DAAs) used to treat hepatitis C virus (HCV) infection are associated with significant drug-drug interactions (DDIs). Pharmacists are well positioned to identify and mitigate these DDIs. Data to guide assessment of the impact of HCV specialty pharmacy services on identifying and addressing DDIs with DAAs are lacking. The overall purpose of the study described here was to determine the incidence and severity of DDIs identified by specialty pharmacists among patients treated with DAAs prior to and 1 month into therapy. METHODS: An observational, retrospective study was conducted to evaluate the impact of specialty pharmacy services in mitigating DDIs associated with use of DAAs. Adult patients with HCV infection (n = 200) who received DAAs and were enrolled with a specialty pharmacy service over a 1-year period were included. Endpoints included number, severity, and type of DDIs and DDIs per patient at baseline and 1 month into therapy, pharmacists' interventions, and safety and clinical outcomes. RESULTS: Fifty-nine percent of patients had at least 1 DDI. A total of 170 DDIs were identified (137 at baseline and 33 at 1-month follow-up), and the mean number of DDIs per patient significantly decreased from baseline to 1-month follow-up (from 1.38 to 0.16, P < 0.0001). The rate of "potentially clinically significant" or "critical" interactions was significantly lower at 1-month follow-up vs baseline assessment (69.6% vs 81.7%, P < 0.0001). The most commonly identified DDIs involved acid suppressive medications (49.6% and 66.6% of DDIs at baseline and follow-up assessment, respectively) and cardiovascular medications (26.2% and 21.2%, respectively). Total number of DDI interventions was 131, with an acceptance rate of 85%. Most common intervention was patient education and monitoring. CONCLUSION: Approximately 60% of patients had DDIs with DAAs. Implementing HCV specialty pharmacy services significantly decreased DDIs while maintaining SVR12.

Evaluation of recruitment and selection for specialty training in public health: interim results of a prospective cohort study to measure the predictive validity of the selection process.

BACKGROUND: The recruitment process for public health specialty training includes an assessment centre (AC) with three components, Rust Advanced Numerical Reasoning Appraisal (RANRA), Watson-Glaser Critical Thinking Appraisal (WGCT) and a Situation Judgement Test (SJT), which determines invitation to a selection centre (SC). The scores are combined into a total recruitment (TR) score that determines the offers of appointment. METHODS: A prospective cohort study using anonymous record linkage to investigate the association between applicant's scores in the recruitment process and registrar's progress through training measured by results of Membership Faculty Public Health (MFPH) examinations and outcomes of the Annual Review of Competence Progression (ARCP). RESULTS: Higher scores in RANRA, WGCT, AC, SC and TR were all significantly associated with higher adjusted odds of passing Part A MFPH exam at the first attempt. Higher scores in AC, SC and TR were significantly associated with passing Part B exam at the first attempt. Higher scores in SJT, AC and SC were significantly associated with satisfactory ARCP outcomes. CONCLUSIONS: The current UK national recruitment and selection process for public health specialty training has good predictive validity. The individual components of the process are testing different skills and abilities and together they are providing additive value.

Early and late outcomes after cardiac retransplantation.

BACKGROUND: Cardiac retransplantation remains the most viable option for patients with allograft heart failure; however, careful patient selection is paramount considering limited allograft resources. We analyzed clinical outcomes following retransplantation in an academic, tertiary care institution. METHODS: Between 1981 and 2011, 593 heart transplantations, including 22 retransplantations were performed at our institution. We analyzed the preoperative demographic characteristics, cause of allograft loss, short- and long-term surgical outcomes and cause of death among patients who had cardiac retransplantations. RESULTS: Twenty-two patients underwent retransplantation: 10 for graft vascular disease, 7 for acute rejection and 5 for primary graft failure. Mean age at retransplantation was 43 (standard deviation [SD] 15) years; 6 patients were women. Thirteen patients were critically ill preoperatively, requiring inotropes and/or mechanical support. The median interval between primary and retransplantation was 2.2 (range 0-16) years. Thirty-day mortality was 31.8%, and conditional (> 30 d) 1-, 5- and 10-year survival after retransplantation were 93%, 79% and 59%, respectively. A diagnosis of allograft vasculopathy (p = 0.008) and an interval between primary and retransplantation greater than 1 year (p = 0.016) had a significantly favourable impact on 30-day mortality. The median and mean survival after retransplantation were 3.3 and 5 (SD 6, range 0-18) years, respectively; graft vascular disease and multiorgan failure were the most common causes of death. CONCLUSION: Long-term outcomes for primary and retransplantation are similar if patients survive the 30-day postoperative period. Retransplantation within 1 year of the primary transplantation resulted in a high perioperative mortality and thus may be a contraindication to retransplantation.

Explaining explanation in chemistry.

The notion that explanations are arguments, central to the covering law account, persists in developments of accounts of explanation in general philosophy of science. I argue that these developments fail to capture chemical explanation-motivating the explanatory autonomy of chemistry requires the investigation of alternative accounts. Ubiquitous use of models in chemistry is indicative of their importance to explanation. I argue that contemporary accounts of models that emphasize their partial autonomy from fundamental physical laws provide a basis for investigating explanation in chemistry. Furthermore, I sketch the importance of the semantic view of theories in articulating model autonomy, and thus why the semantic view might fulfill a significant role in explicating the explanatory autonomy of chemistry.