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Daniel R Reed,1 Ramey Z Elsarrag,2 Amy L Morris,3 Michael K Keng11Division of Hematology/Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA; 2Department of Medicine, University of Virginia, Charlottesville, VA, USA; 3Department of Pharmacy Services, University of Virginia, Charlottesville, VA, USACorrespondence: Michael K KengDepartment of Medicine, Division of Hematology/Oncology, University of Virginia, 1300 Jefferson Park Avenue, West Complex, Room 6009, Charlottesville, VA 22908, USATel +1 434 924 4257Fax +1 434 244 7534Email MK2PV@virginia.eduAbstract: Recently there has been a significant progression in the understanding of molecular mutations driving biochemical and cellular signaling changes leading to survival and proliferation of leukemia cells in patients with acute myeloid leukemia (AML). Preclinical studies have demonstrated a mutated enzyme in the citric acid cycle, isocitrate dehydrogenase (IDH), leads to the production of an oncogenic metabolite R-2-hydroxy-glutarate (R-2-HG). This causes the arrest in the differentiation of hematopoietic stem cells leading to the promotion of leukemia. Inhibitors of the IDH enzyme have been shown in preclinical studies to reduce the production of R-2-HG, resulting in terminal differentiation of leukemia blast cells. In recent phase I and II trials, the IDH2 inhibitor enasidenib has shown clinical activity in patients with relapsed and refractory (R/R) AML. This review will describe the preclinical and clinical developments of enasidenib and its Food and Drug Administration approval in R/R AML, treatment recommendations and management will be outlined.Keywords: isocitrate dehydrogenase, IDH 2, relapsed/refractory, R/R acute myeloid leukemia AML, enasidenib, IDH, AML

One of the early key empirical findings of the happiness literature is that at higher levels of per capita real income there appears to be diminishing returns to income at least with regards to marginal changes in ‘happiness’ measured by various survey instruments. Although these results have been recently challenged, these earlier findings and the results of many contemporary studies suggest that an inelastic relationship exists between real per capita income and happiness after a relatively low threshold of per capita income is reached. Appling some of the results of prospect theory I argue that even if it were true that the marginal effect of income on happiness is zero, a reduction in income would probably reduce the level of happiness, yielding a kink in the ‘happiness curve’. Also, applying a target income approach to the happiness literature, one can argue that pursuing higher target income, in itself, is a means of increasing life satisfaction. These two theoretical instruments yield results consistent with some of the most recent empirical finding based on Gallup Poll Survey data. In addition, applying insights from the capabilities approach, I argue, that increasing income is a means of purchasing the capabilities to increase individual levels of happiness through the production of public goods, such as health care and education. A given marginal increase in income need not generate any increase in happiness if this income increase is highly unequally distributed in a population or is not used to purchase goods and services that contribute to increases in the level of happiness.

Gaps in financial literacy are arguably responsible for significant errors in decision-making by consumers and investors alike. Unlike the conventional neoclassical economic wisdom, behavioral economics opens the analytical door to the significance of financial literacy for decision-making. This paper presents evidence on the importance of financial literacy as well presenting the different analytical approaches to financial literacy that flow from neoclassical economics and from the different methodological approaches to behavioral economics. Of particular importance is the errors and biases approach, which attributes much of financial illiteracy to the cognitive shortcomings of the human brain. Whereas the bounded rationality approach focuses on informational gaps (complex and asymmetric information), framing effects, institutional design problems, and human capital deficits (inclusive of experiential learning), as key to understanding documented gaps in financial literacy. The behavioral approaches have significant implications for analyses and public policy.

Abstract Background Increasing affordability of artemisinin combination therapy (ACT) in the African retail sector could be critical to expanding access to effective malaria treatment, but must be balanced by efforts to protect the efficacy of these drugs. Previous research estimates ACT adherence rates among public sector patients, but adherence among retail sector purchasers could differ substantially. This study aimed to estimate adherence rates to subsidized, over-the-counter ACT in rural Uganda. Methods An intervention study was conducted with four licensed drug shops in Eastern Uganda in December 2009. Artemether-lumefantrine (AL) was made available for sale at a 95% subsidy over-the counter. Customers completed a brief survey at the time of purchase and then were randomly assigned to one of three study arms: no follow-up, follow-up after two days or follow-up after three days. Surveyors recorded the number of pills remaining through blister pack observation or through self-report if the pack was unavailable. The purpose of the three-day follow-up arm was to capture non-adherence in the sense of an incomplete treatment course ("under-dosing"). The purpose of the two-day follow-up arm was to capture whether participants completed the full course too soon ("over-dosing"). Results Of the 106 patients in the two-day follow-up sample, 14 (13.2%) had finished the entire treatment course by the second day. Of the 152 patients in the three-day follow-up sample, 49 (32.2%) were definitely non-adherent, three (2%) were probably non-adherent and 100 (65.8%) were probably adherent. Among the 52 who were non-adherent, 31 (59.6%) had more than a full day of treatment remaining. Conclusions Overall, adherence to subsidized ACT purchased over-the-counter was found to be moderate. Further, a non-trivial fraction of those who complete treatment are taking the full course too quickly. Strategies to increase adherence in the retail sector are needed in the context of increasing availability and affordability of ACT in this sector.

Abstract Background Understanding the fitness consequences of inbreeding is of major importance for evolutionary and conservation biology. However, there are few studies using pedigree-based estimates of inbreeding or investigating the influence of environment and age variation on inbreeding depression in natural populations. Here we investigated the consequences of variation in inbreeding coefficient for three juvenile traits, birth date, birth weight and first year survival, in a wild population of red deer, considering both calf and mother's inbreeding coefficient. We also tested whether inbreeding depression varied with environmental conditions and maternal age. Results We detected non-zero inbreeding coefficients for 22% of individuals with both parents and at least one grandparent known (increasing to 42% if the dataset was restricted to those with four known grandparents). Inbreeding depression was evident for birth weight and first year survival but not for birth date: the first year survival of offspring with an inbreeding coefficient of 0.25 was reduced by 77% compared to offspring with an inbreeding coefficient of zero. However, it was independent of measures of environmental variation and maternal age. The effect of inbreeding on birth weight appeared to be driven by highly inbred individuals (F = 0.25). On the other hand first year survival showed strong inbreeding depression that was not solely driven by individuals with the highest inbreeding coefficients, corresponding to an estimate of 4.35 lethal equivalents. Conclusions These results represent a rare demonstration of inbreeding depression using pedigree-based estimates in a wild mammal population and highlight the potential strength of effects on key components of fitness.

Abstract Introduction Vernix Caseosa peritonitis is a rare post caesarean section complication with only 19 case reports in the literature to date. Vernix caseosa spilt at the time of caesarean section is thought to incite an inflammatory reaction, causing symptoms resembling an acute abdomen. Case Presentation We discuss three Caucasian patients (aged 32 to 43 years) who presented in our health sector in Sydney with vernix caseosa peritonitis. Each had a protracted course with significant comorbidities requiring surgical and medical intervention. This contrasts with other reports suggesting that a rapid resolution can be expected. This cluster may be a consequence of the rising caesarean section rate, a heightened local awareness of the condition and possibly a result of leaving material in the paracolic gutters intraoperatively. Conclusion Our aim is to increase awareness among our obstetric and surgical colleagues of the characteristic clinical presentation and intra-operative findings of vernix caseosa peritonitis. We also point out that, in contrast to those presented here, not all patients require laparotomy.

Abstract Background Pneumocystis pneumonia (PCP) remains a leading cause of morbidity and mortality in HIV-infected persons. Epidemiology of PCP in the recent era of highly active antiretroviral therapy (HAART) is not well known and the impact of HAART on outcome of PCP has been debated. Aim To determine the epidemiology of PCP in HIV-infected patients and examine the impact of HAART on PCP outcome. Methods We performed a retrospective cohort study of 262 patients diagnosed with PCP between January 2000 and December 2003 at a county hospital at an academic medical center. Death while in the hospital was the main outcome measure. Multivariate modeling was performed to determine predictors of mortality. Results Overall hospital mortality was 11.6%. Mortality in patients requiring intensive care was 29.0%. The need for mechanical ventilation, development of a pneumothorax, and low serum albumin were independent predictors of increased mortality. One hundred and seven patients received HAART before hospitalization and 16 patients were started on HAART while in the hospital. HAART use either before or during hospitalization was not associated with mortality. Conclusion Overall hospital mortality and mortality predictors are similar to those reported earlier in the HAART era. PCP diagnoses in HAART users likely represented failing HAART regimens or non-compliance with HAART.