Confirmation practice in pharmacogenetic testing; how good is good enough?

Personalised Therapeutic

Double effort: parental behavior of wild Azara's owl monkeys in the face of twins

In species of mammals that habitually bear single offspring, like most anthropoid primates, the occurrence of twins is expected to impose considerable energetic costs on the caretakers. The question then arises of how caregivers cope with the potentially increased costs of raising twins. These increased costs should lead to differing developmental rates in twins when compared to singletons, and/or to changes in the caregivers' behavior. Likewise, time budgets of parents of singletons are expected to differ from those of adults without offspring. Additionally, if twinning was an adaptive response to favorable ecological conditions, it should be more likely in years with high food abundance. Following the birth in 2011 of two sets of twins in a wild population of pair-living Azara's owl monkeys (Aotus azarae) in Northern Argentina, we used long-term demographic, behavioral, and phenological data to compare a) the proportion of time that singleton and twin infants were carried by either parent, b) adult time-budgets and ranging behavior in groups with zero, one, or two infants, and c) the availability of food in 2011 with food availability in other years. Twins, like singletons, were carried nearly exclusively by the male, and they were carried slightly more than singletons, suggesting a relatively inflexible pattern of infant care in the species. Time budgets showed that twin parents foraged more and moved less than singleton parents or groups without infants, despite the fact that phenological data indicate that fruit availability in 2011 was not substantially higher than in some of the other years. Overall, twinning thus presumably increased costs to breeders, especially males, but its effect on animals’ long-term reproductive success remains unclear.National Science Foundation (BCS-1219368); National Geographic Society (9053-11); German Science Foundation (HU1746-2 & 3); het Vreedefonds; Stichting Fundatie van de Vrijvrouwe van Renswoude te‘s-Gravenhage; Stichting Jo Kolk Studiefonds; de Stichting dr.Hendrik Muller's VaderlandschFonds; Wenner-Gren Foundation; L.S.B. Leakey Foundation; National Science Foundation (BCS- 0621020); the University of Pennsylvania Research Foundation; Zoological Society of San Dieg

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines

Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual's starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score, DPYD genotyping is considered "essential", therefore directing DPYD testing prior to initiating fluoropyrimidines

Representing decision-makers using styles of behavior: an approach designed for group decision support systems

Supporting decision-making processes when the elements of a group are geographically dispersed and on a tight schedule is a complex task. Aiming to support decision-makers anytime and anywhere, Web-based group decision support systems have been studied. However, the limitations in the decision-makers’ interactions associated to this scenario bring new challenges. In this work, we propose a set of behavioral styles from which decision-makers’ intentions can be modelled into agents. The goal is that, besides having agents represent typical preferences of the decision-makers (towards alternatives and criteria), they can also represent their intentions. To do so, we conducted a survey with 64 participants in order to find homogeneous operating values so as to numerically define the proposed behavioral styles in four dimensions. In addition, we also propose a communication model that simulates the dialogues made by decision-makers in face-to-face meetings. We developed a prototype to simulate decision scenarios and found that agents are capable of acting according to the decision-makers’ intentions and fundamentally benefit from different possible behavioral styles, just as a face-to-face meeting benefits from the heterogeneity of its participants.This work was supported by COMPETE Programme (operational programme for competitiveness) within Project POCI-01-0145-FEDER-007043, by National Funds through the FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within the Projects UID/CEC/00319/2013, UID/EEA/00760/2013, and the Ph.D. grants SFRH/BD/89697/2012 and SFRH/BD/89465/2012 attributed to João Carneiro and Pedro Saraiva, respectively.info:eu-repo/semantics/publishedVersio

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction of DPYD and fluoropyrimidines

Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual’s starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therap