Advanced maternal age causes adverse programming of mouse blastocysts leading to altered growth and impaired cardiometabolic health in post-natal life

Study question: does advanced maternal age (AMA) in mice affect cardiometabolic health during post-natal life in offspring derived from an assisted reproduction technology (ART) procedure?Summary answer: offspring derived from blastocysts collected from aged female mice displayed impaired body weight gain, blood pressure, glucose metabolism and organ allometry during post-natal life compared with offspring derived from blastocysts from young females; since all blastocysts were transferred to normalized young mothers, this effect is independent of maternal pregnancy conditions.What is known already: although studies in mice have shown that AMA can affect body weight and behaviour of offspring derived from natural reproduction, data on the effects of AMA on offspring cardiometabolic health during post-natal development are not available. Given the increasing use of ART to alleviate infertility in women of AMA, it is pivotal to develop ART–AMA models addressing the effects of maternal aging on offspring health.Study design, size, duration: blastocysts from old (34–39 weeks) or young (8–9 weeks) C57BL/6 females mated with young CBA males (13–15 weeks) were either subjected to differential cell staining (inner cell mass and trophectoderm) or underwent embryo transfer (ET) into young MF1 surrogates (8–9 weeks) to produce young (Young-ET, 9 litters) and old (Old-ET, 10 litters) embryo-derived offspring. Offspring health monitoring was carried out for 30 weeks.Participants/materials, setting, methods: all animals were fed with standard chow. Blood pressure was measured at post-natal Weeks 9, 15 and 21, and at post-natal Week 30 a glucose tolerance test (GTT) was performed. Two days after the GTT mice were killed for organ allometry. Blastocyst cell allocation variables were evaluated by T-test and developmental data were analysed with a multilevel random effects regression model.Main results and the role of chance: the total number of cells in blastocysts from aged mice was decreased (P < 0.05) relative to young mice due to a lower number of cells in the trophectoderm (mean ± SEM: 34.5 ± 2.1 versus 29.6 ± 1.0). Weekly body weight did not differ in male offspring, but an increase in body weight from Week 13 onwards was observed in Old-ET females (final body weight at post-natal Week 30: 38.5 ± 0.8 versus 33.4 ± 0.8 g, P < 0.05). Blood pressure was increased in Old-ET offspring at Weeks 9–15 in males (Week 9: 108.5 ± 3.13 versus 100.8 ± 1.5 mmHg, Week 15: 112.9 ± 3.2 versus 103.4 ± 2.1 mmHg) and Week 15 in females (115.9 ± 3.7 versus 102.8 ± 0.7 mmHg; all P < 0.05 versus Young-ET). The GTT results and organ allometry were not affected in male offspring. In contrast, Old-ET females displayed a greater (P < 0.05) peak glucose concentration at 30 min during the GTT (21.1 ± 0.4 versus 17.8 ± 1.16 mmol/l) and their spleen weight (88.2 ± 2.6 ± 105.1 ± 4.6 mg) and several organ:body weight ratios (g/g × 103) were decreased (P < 0.05 versus Young-ET), including the heart (3.7 ± 0.06 versus 4.4 ± 0.08), lungs (4.4 ± 0.1 versus 5.0 ± 0.1), spleen (2.4 ± 0.06 versus 3.2 ± 0.1) and liver (36.4 ± 0.6 versus 39.1 ± 0.9).Limitations, reasons for caution: results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models that can produce hypotheses for eventual testing in the target species (i.e. humans).Wider implications of the findings: our data show that offspring from mouse embryos from aged mothers can develop altered phenotypes during post-natal development compared with embryos from young mothers. Because all embryos were transferred into young mothers for the duration of pregnancy to normalize the maternal in vivo environment, our findings indicate that adverse programming via AMA is already established at the blastocyst stage. Whilst human embryos display increased aneuploidy compared with mouse, we believe our data have implications for women of AMA undergoing assisted reproduction, including surrogacy programmes.Study funding/competeing interest(s): this work was supported through the European Union FP7-CP-FP Epihealth programme (278418) to T.P.F. and the BBSRC (BB/F007450/1) to T.P.F. The authors have no conflicts of interest to declar

Scheduling Jobs in Flowshops with the Introduction of Additional Machines in the Future

This is the author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/expert-systems-with-applications/.The problem of scheduling jobs to minimize total weighted tardiness in flowshops,\ud with the possibility of evolving into hybrid flowshops in the future, is investigated in\ud this paper. As this research is guided by a real problem in industry, the flowshop\ud considered has considerable flexibility, which stimulated the development of an\ud innovative methodology for this research. Each stage of the flowshop currently has\ud one or several identical machines. However, the manufacturing company is planning\ud to introduce additional machines with different capabilities in different stages in the\ud near future. Thus, the algorithm proposed and developed for the problem is not only\ud capable of solving the current flow line configuration but also the potential new\ud configurations that may result in the future. A meta-heuristic search algorithm based\ud on Tabu search is developed to solve this NP-hard, industry-guided problem. Six\ud different initial solution finding mechanisms are proposed. A carefully planned\ud nested split-plot design is performed to test the significance of different factors and\ud their impact on the performance of the different algorithms. To the best of our\ud knowledge, this research is the first of its kind that attempts to solve an industry-guided\ud problem with the concern for future developments

Enhancing Communication about Paediatric Medicines: Lessons from a Qualitative Study of Parents' Experiences of Their Child's Suspected Adverse Drug Reaction

Background: There is little research on parents’ experiences of suspected adverse drug reactions in their children and hence little evidence to guide clinicians when communicating with families about problems associated with medicines. Objective: To identify any unmet information and communication needs described by parents whose child had a suspected adverse drug reaction. Methods: Semi-structured qualitative interviews with parents of 44 children who had a suspected adverse drug reaction identified on hospital admission, during in-patient treatment or reported by parents using the Yellow Card Scheme (the UK system for collecting spontaneous reports of adverse drug reactions). Interviews were conducted face-to-face or by telephone; most interviews were audiorecorded and transcribed. Analysis was informed by the principles of the constant comparative method. Results: Many parents described being dissatisfied with how clinicians communicated about adverse drug reactions and unclear about the implications for their child’s future use of medicines. A few parents felt that clinicians had abandoned their child and reported refusing the use of further medicines because they feared a repeated adverse drug reaction. The accounts of parents of children with cancer were different. They emphasised their confidence in clinicians’ management of adverse drug reactions and described how clinicians prospectively explained the risks associated with medicines. Parents linked symptoms to medicines in ways that resembled the established reasoning that clinicians use to evaluate the possibility that a medicine has caused an adverse drug reaction. Conclusion: Clinicians’ communication about adverse drug reactions was poor from the perspective of parents, indicating that improvements are needed. The accounts of parents of children with cancer indicate that prospective explanation about adverse drug reactions at the time of prescription can be effective. Convergence between parents and clinicians in their reasoning for linking children’s symptoms to medicines could be a starting point for improved communication

Intensive care utilisation and outcomes after high-risk surgery in Scotland: a population based cohort study.

Chief Scientist’s Office Scotland (grant no. CHZ/821/4)

Detecting change via competence model

In real world applications, interested concepts are more likely to change rather than remain stable, which is known as concept drift. This situation causes problems on predictions for many learning algorithms including case-base reasoning (CBR). When learning under concept drift, a critical issue is to identify and determine "when" and "how" the concept changes. In this paper, we developed a competence-based empirical distance between case chunks and then proposed a change detection method based on it. As a main contribution of our work, the change detection method provides an approach to measure the distribution change of cases of an infinite domain through finite samples and requires no prior knowledge about the case distribution, which makes it more practical in real world applications. Also, different from many other change detection methods, we not only detect the change of concepts but also quantify and describe this change. © 2010 Springer-Verlag

Assessment of the cortisol awakening response: expert consensus guidelines

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30–45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. The present report summarizes the results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research

Milk for a girl and bananas for a boy:recipes and reasons for sex-preference practices in a British Internet forum

Using postings from an internet forum, this paper explores the ways in which some women try to influence the sex of a future child. The extensive reproductive work involved give an indication of the women’s commitment to being able to choose a particular sex; in this case a preference for girls rather than boys. The findings revealed stereotypical views of masculinity and femininity at the heart of the preference. The presumption of fixed gendered identities helped to frame this desire as ‘natural,’ lessen the threat to maternal identities, and reinforce the logic of ‘choice,’ and support their reproductive work practices

Finite Hilbert stability of (bi)canonical curves

We prove that a generic canonically or bicanonically embedded smooth curve has semistable m-th Hilbert points for all m. We also prove that a generic bicanonically embedded smooth curve has stable m-th Hilbert points for all m \geq 3. In the canonical case, this is accomplished by proving finite Hilbert semistability of special singular curves with G_m-action, namely the canonically embedded balanced ribbon and the canonically embedded balanced double A_{2k+1}-curve. In the bicanonical case, we prove finite Hilbert stability of special hyperelliptic curves, namely Wiman curves. Finally, we give examples of canonically embedded smooth curves whose m-th Hilbert points are non-semistable for low values of m, but become semistable past a definite threshold. (This paper subsumes the previous submission and arXiv:1110.5960).Comment: To appear in Inventiones Mathematicae, 2012. The final publication is available at http://www.springerlink.co