Does 5-HTTLPR moderate the effect of the quality of environmental context on maternal sensitivity? Testing the differential susceptibility hypothesis

Evidence documenting associations between 5-HTTLPR and parenting behavior led to testing the hypothesis that this polymorphism moderates the effect of the quality of environmental context on maternal sensitivity. Participants were 210 Portuguese mothers and their preschool children, recruited from the community. An index reflecting the quality of the environmental context was derived based on nine markers (e.g. single parenthood; parental education, economic difficulties, family conflict, maternal psychopathology). Maternal sensitivity was measured observationally. Maternal saliva was collected with OraGene kits for genetic analysis. Results revealed a gene-X-environment interaction, such that short-allele homozygotes proved more sensitive to the family context than long-allele carriers (i.e. sL/LL), displaying the highest and lowest levels of maternal sensitivity, depending on, respectively, low and high quality levels of the environmental context. Because even mothers carrying the long allele evinced similar responsiveness to the environmental context, but to a lesser extent, findings proved consistent with the weak differential susceptibility model of person-X-context interaction. Results are discussed in light of prior and related gene-X-environment findings.This work was supported by the Fundacao para a Ciencia e a Tecnologia FCT (Portuguese Foundation for Science and Technology) (grant numbers SFRH/BD/96001/2013, PTDC/PSI-PCL/116897/2010 and IF/00750/2015). The funder was not involved in conducting the research or preparation/submission of the manuscript

Child's oxytocin response to mother-child interaction: The contribution of child genetics and maternal behavior

The oxytocinergic system is a primary biological system involved in regulating a child's needs for bonding and for protection from threats. It is responsive to social experiences in close relationships, though evidence across studies is not entirely consistent. Guided by previous literature, we investigated individual and environmental factors predicting and presumably affecting children's oxytocin (OT) response during mother-child interaction. by focusing on children's OXTR genotype, and maternal behavior, respectively. This was achieved by assessing salivary OT levels of 88 Portuguese preschoolers prior to and following a mother-child interaction task, and by genotyping children's OXTR SNP rs53576. Maternal interactive behavior was assessed using Ainsworth scales.Results indicated that child genotype and mother's sensitive responsiveness interacted in predicting change in child OT concentrations from before to after the interaction. Specifically, Genotypic differences emerged under conditions of low maternal sensitive responsiveness: OT levels increased over time for children with the GG genotype when maternal sensitive responsiveness was low, but no such genotypic differences were evident when mothers were highly sensitive responsive.Findings provide preliminary support for the notion that increased understanding of children's OT and close relationships requires consideration of both individual and environmental factors.This work was supported by the Fundacao para a Ciencia e a Tecnologia FCT (Portuguese Foundation for Science and Technology) [grant numbers SFRH/BD/96001/2013, PTDC/PSI-PCL/116897/2010 and IF/00750/2015]

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research

Analysis of ELM stability with extended MHD models in JET, JT-60U and future JT-60SA tokamak plasmas

The stability with respect to a peelingballooning mode (PBM) was investigated numerically with extended MHD simulation codes in JET, JT-60U and future JT-60SA plasmas. The MINERVA-DI code was used to analyze the linear stability, including the effects of rotation and ion diamagnetic drift (w∗i), in JET-ILW and JT-60SA plasmas, and the JOREK code was used to simulate nonlinear dynamics with rotation, viscosity and resistivity in JT-60U plasmas. It was validated quantitatively that the ELM trigger condition in JET-ILW plasmas can be reasonably explained by taking into account both the rotation and w∗i effects in the numerical analysis. When deuterium poloidal rotation is evaluated based on neoclassical theory, an increase in the effective charge of plasma destabilizes the PBM because of an acceleration of rotation and a decrease in w∗i. The difference in the amount of ELM energy loss in JT-60U plasmas rotating in opposite directions was reproduced qualitatively with JOREK. By comparing the ELM affected areas with linear eigenfunctions, it was confirmed that the difference in the linear stability property, due not to the rotation direction but to the plasma density profile, is thought to be responsible for changing the ELM energy loss just after the ELM crash. A predictive study to determine the pedestal profiles in JT-60SA was performed by updating the EPED1 model to include the rotation and w∗i effects in the PBM stability analysis. It was shown that the plasma rotation predicted with the neoclassical toroidal viscosity degrades the pedestal performance by about 10% by destabilizing the PBM, but the pressure pedestal height will be high enough to achieve the target parameters required for the ITER-like shape inductive scenario in JT-60SA