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Background: Endoxifen is the most important active metabolite of tamoxifen. Several retrospective studies have suggested a minimal or threshold endoxifen systemic concentration of 14-16 nM is required for a lower recurrence rate. The aim of this study was to investigate the feasibility of reaching a predefined endoxifen level of ≥ 16 nM (5.97 ng/mL) over time using therapeutic drug monitoring (TDM).Methods: This prospective open-label intervention study enrolled patients who started treatment with a standard dose of tamoxifen 20 mg once daily for early breast cancer. An outpatient visit was combined with a TDM sample at 3, 4.5, and 6 months after initiation of the tamoxifen treatment. The tamoxifen dose was escalated to a maximum of 40 mg if patients had an endoxifen concentration < 16 nM. The primary endpoint of the study was the percentage of patients with an endoxifen level ≥ 16 nM at 6 months after the start of therapy compared with historical data, in other words, 80% of patients with endoxifen levels ≥ 16 nM with standard therapy.Results: In total, 145 patients were included. After 6 months, 89% of the patients had endoxifen levels ≥ 16 nM, compared with a literature-based 80% of patients with endoxifen levels ≥ 16 nM at baseline (95% confidence interval 82-94; P = 0.007). In patients with an affected CYP2D6 allele, it was not always feasible to reach the predefined endoxifen level of ≥ 16 nM. No increase in tamoxifen-related adverse events was reported after dose escalation.Conclusion: This study demonstrated that it is feasible to increase the percentage of patients with endoxifen levels ≥ 16 nM using TDM. TDM is a safe strategy that offers the possibility of nearly halving the number of patients with endoxifen levels < 16 nM. [ABSTRACT FROM AUTHOR]

Can behavioural interventions achieve energy savings in non-residential settings where users do not face the financial consequences of their behaviour? Our paper addresses this question by using high-frequency data, leveraging social comparison and responsibility assignment in a large provincial government office building with 24 floors, a total of 1008 occupants. Floors were divided into two treatments arms and a control group. Both treatment groups received regular emails encouraging recipients to turn off appliances and lights before leaving the office and weekly ranked energy consumption results by floors. Additionally, weekly "energy advocates" were assigned to each floor in treatment group two. Floors assigned to the control group received no intervention. Findings show that floors that participated only in the inter-floor competitions reduced energy consumption by 8%, 95% CI [− 0.41, − 0.02] while those additionally assigned floor-wise "energy advocates" reduced energy consumption by 13%, 95% CI [− 0.62, − 0.05] with a substantial reduction in energy use occurring after working hours. Results, however, show no statistical difference in energy consumption between treatment groups one and two. We further investigate the intervention effect for the monthly cumulative post-intervention period. Additional qualitative interviews were conducted to enable a better understanding of our results. [ABSTRACT FROM AUTHOR]

Background: Many cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea—active ingredient epigallocatechin-3-gallate (EGCG)—is one of the most commonly used dietary supplements among breast cancer patients. EGCG may alter the metabolism of tamoxifen. Therefore, the aim of this study was to investigate the influence of green tea supplements on the pharmacokinetics of endoxifen; the most relevant active metabolite of tamoxifen. Methods: In this single-center, randomized cross-over trial, effects of green tea capsules on endoxifen levels were evaluated. Patients treated with tamoxifen for at least 3 months were eligible for this study. After inclusion, patients were consecutively treated with tamoxifen monotherapy for 28 days and in combination with green tea supplements (1 g twice daily; containing 300 mg EGCG) for 14 days (or vice versa). Blood samples were collected on the last day of monotherapy or combination therapy. Area under the curve (AUC0–24h), maximum concentration (Cmax) and minimum concentration (Ctrough) were obtained from individual plasma concentration–time curves. Results: No difference was found in geometric mean endoxifen AUC0–24h in the period with green tea versus tamoxifen monotherapy (− 0.4%; 95% CI − 8.6 to 8.5%; p = 0.92). Furthermore, no differences in Cmax (− 2.8%; − 10.6 to 5.6%; p = 0.47) nor Ctrough (1.2%; − 7.3 to 10.5%; p = 0.77) were found. Moreover, no severe toxicity was reported during the whole study period. Conclusions: This study demonstrated the absence of a pharmacokinetic interaction between green tea supplements and tamoxifen. Therefore, the use of green tea by patients with tamoxifen does not have to be discouraged. [ABSTRACT FROM AUTHOR]

South Africa, a main food exporter in SADC, is characterised by a dual agricultural economy consisting of a well-developed commercial sector and smallholder, often subsistence, farming. Using the Ricardian cross-sectional framework, we examine the impact of climate change on a nationwide sample of crop, horticulture, livestock and mixed commercial farming systems. We find that a simultaneous decrease in precipitation and an increase in temperature will reduce productivity; and that an increase in temperature alone negatively affects farm output more than a decrease in precipitation. One of the most robust findings is the difference in the extent to which different commercial production systems will be impacted. That is, the results indicate that the strongest impact will be amongst specialised commercial crop farming system. In contrast, mixed farming systems appear to be the least vulnerable. This finding is consistent with studies on small-holder farms in sub-Saharan Africa. Hence, it appears that despite the likely benefits derived from economies of scale, commercial farms are, somewhat, equally vulnerable to climate change. Further, a province-wise assessment revealed that areas that already face disadvantageous climatic conditions will become even less productive. Overall, the findings suggest that practicing mixed farming methods will strengthen the resilience of commercial farms to climate change and that access to extensions-insurance and irrigation-is likely to reduce the risks. [ABSTRACT FROM AUTHOR]

In this article we present results from the Cape Area Panel Study investigating how income comparisons affect the subjective well-being of young adults and parents. The article builds on previous research in this area by studying whether an individual's subjective well-being depends on the comparisons they make, not only to those around them, i.e., external comparisons, but to themselves across different time periods, i.e., internal comparisons. In the comparisons, we use both objective and subjective measures of relative income. Overall, we find strong evidence to suggest that income comparisons, both relative to neighbours and relative to oneself, affect subjective well-being. Another interesting observation is that, depending on the comparator, young adults and parents differ in their perceptions of their own well-being. Furthermore, and as expected, we found that objective, as well as subjective, measures of well-being influence well-being, but that this is more prevalent in external than internal comparisons. [ABSTRACT FROM AUTHOR]

International and domestic efforts to reduce greenhouse gas emissions require a coordinated effort from heterogeneous actors. In this context, using a public good game with a climate change framing, the experiment reported here examines whether groups of heterogeneous individuals can meet a collective emission-reduction target through individual contributions. In terms of the framing, participants differ in terms of their marginal costs of abatement. The experiment consists of two games: a counterfactual baseline scenario examining the scope for voluntary cooperation and a communication game examining the role of stakeholder participation in facilitating cooperation. During the communication game, subjects are able to communicate with one another in order to coordinate contribution strategies. The results suggest that relying on the voluntary cooperation of individuals will not be sufficient to meet the mitigation target. Furthermore, while communication plays a role in promoting cooperation, even when heterogeneity is present, the non-binding nature of communication results in significant levels of free-riding. In particular, with the introduction of communication, two dominant contribution norms of free-riding and perfect-cooperation emerge. This outcome emphasizes the importance of sanctioning opportunities in ensuring compliance with mitigation obligations. [ABSTRACT FROM AUTHOR]

This paper examines the impact of agriculture-related shocks on consumption patterns of rural farming households using 3 years of data from South Africa. We make two key observations. First, agriculture-related shocks reduce households' consumption. Second, natural resources and informal social capital somewhat counteract this reduction and sustain dietary requirements. In general, our findings suggest the promotion of informal social capital and natural resources as they are cheaper and more accessible coping strategies, in comparison to, for example, insurance, which remains unaffordable in most rural parts of sub-Saharan Africa. However, a lingering concern centres on the sustainability of these less conventional adaptation strategies. [ABSTRACT FROM AUTHOR]

Even though antiretroviral treatment is becoming more efficient and available, new HIV infections still occur, and this is particularly evident in the sub-Saharan Africa region. Heterosexual intercourse is still the main mode of HIV transmission in the region, and multiple and concurrent sex partners are arguably crucial for the spread of the epidemic. It is therefore problematic that sexual risk-taking, in terms of multiple and concurrent sex partners, persists in spite of HIV awareness and knowledge. This study examines the role of social norms on multiple and concurrent sex partnerships using longitudinal data of young adults residing in the metropolitan communities of Cape Town in South Africa. Overall, our results show that the social norms related to multiple and concurrent sex partners, in the community, have a positive and significant influence on young adults' choice of sex partners. This effect appears to be stronger amongst male young adults, than female young adults. [ABSTRACT FROM AUTHOR]

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Unfortunately, the original version of the article was published with incorrect copyright as "© Springer Science + Business Media, LLC, part of Springer Nature 2020". [ABSTRACT FROM AUTHOR]