Description: Various structure–function relationships regarding drought-induced cavitation resistance of secondary xylem have been postulated. These hypotheses were tested on wood of 10 Prunus species showing a range in P 50 (i.e., the pressure corresponding to 50% loss of hydraulic conductivity) from –3.54 to –6.27 MPa. Hydraulically relevant wood characters were quantified using light and electron microscopy. A phylogenetic tree was constructed to investigate evolutionary correlations using a phylogenetically independent contrast (PIC) analysis. Vessel-grouping characters were found to be most informative in explaining interspecific variation in P 50 , with cavitation-resistant species showing more solitary vessels than less resistant species. Co-evolution between vessel-grouping indices and P 50 was reported. P 50 was weakly correlated with the shape of the intervessel pit aperture, but not with the total intervessel pit membrane area per vessel . A negative correlation was found between P 50 and intervessel pit membrane thickness, but this relationship was not supported by the PIC analysis. Cavitation resistance has co-evolved with vessel grouping within Prunus and was mainly influenced by the spatial distribution of the vessel network.

Description: Nutritional conditions in early life may affect adult health, but prior studies of mortality have been limited to small samples. We evaluated the relationship between pre-/perinatal famine exposure during the Dutch Hunger Winter of 1944–1945 and mortality through age 63 years among 41,096 men born in 1944–1947 and examined at age 18 years for universal military service in the Netherlands. Of these men, 22,952 had been born around the time of the Dutch famine in 6 affected cities; the remainder served as unexposed controls. Cox proportional hazards models were used to estimate hazard ratios for death from cancer, heart disease, other natural causes, and external causes. After 1,853,023 person-years of follow-up, we recorded 1,938 deaths from cancer, 1,040 from heart disease, 1,418 from other natural causes, and 523 from external causes. We found no increase in mortality from cancer or cardiovascular disease after prenatal famine exposure. However, there were increases in mortality from other natural causes (hazard ratio = 1.24, 95% confidence interval: 1.03, 1.49) and external causes (hazard ratio = 1.46, 95% confidence interval: 1.09, 1.97) after famine exposure in the first trimester of gestation. Further follow-up of the cohort is needed to provide more accurate risk estimates of mortality from specific causes of death after nutritional disturbances during gestation and very early life.

Description: Background: The manipulation of pregnancy diets in animals can lead to changes in DNA methylation with phenotypic consequences in the offspring. Human studies have concentrated on the effects of nutrition during early gestation. Lacking in humans is an epigenome-wide association study of DNA methylation in relation to perturbations in nutrition across all gestation periods. Methods: We used the quasi-experimental setting of the Dutch famine of 1944–45 to evaluate the impact of famine exposure during specific 10-week gestation periods, or during any time in gestation, on genome-wide DNA methylation levels at age ~ 59 years. In addition, we evaluated the impact of exposure during a shorter pre- and post-conception period. DNA methylation was assessed using the Illumina 450k array in whole blood among 422 individuals with prenatal famine exposure and 463 time- or sibling-controls without prenatal famine exposure. Results: Famine exposure during gestation weeks 1–10, but not weeks 11–20, 21–30 or 31-delivery, was associated with an increase in DNA methylation of CpG dinucleotides cg20823026 ( FAM150B ), cg10354880 ( SLC38A2 ) and cg27370573 ( PPAP2C ) and a decrease of cg11496778 ( OSBPL5 / MRGPRG) ( P 〈 5.9 x 10 –7 , P FDR 〈 0.031). There was an increase in methylation of TACC1 and ZNF385A after exposure during any time in gestation ( P 〈 2.0 x 10 –7 , P FDR = 0.034) and a decrease of cg23989336 ( TMEM105 ) after exposure around conception. These changes represent a shift of 0.3–0.6 standard deviations and are linked to genes involved in growth, development and metabolism. Conclusion: Early gestation, and not mid or late gestation, is identified as a critical time-period for adult DNA methylation changes in whole blood after prenatal exposure to famine.

Description: Background Household characteristics are important influences on the risk of child death. However, little is known about this influence in HIV-endemic areas. We describe the effects of household characteristics on children’s risk of dying in rural South Africa. Methods We use data describing the mortality of children younger than 5 years living in the Agincourt health and socio-demographic surveillance system study population in rural northeast South Africa during the period 1994–2008. Using discrete time event history analysis we estimate children’s probability of dying by child characteristics and household composition (other children and adults other than parents) ( N = 924 818 child-months), and household socio-economic status ( N = 501 732 child-months). Results Children under 24 months of age whose subsequent sibling was born within 11 months experience increased odds of dying (OR 2.5; 95% CI 1.1–5.7). Children also experience increased odds of dying in the period 6 months (OR 2.1; 95% CI 1.2–3.6), 3–5 months (OR 3.0; 95% CI 1.5–5.9), and 2 months (OR 11.8; 95% CI 7.6–18.3) before another household child dies. The odds of dying remain high at the time of another child’s death (OR 11.7; 95% CI 6.3–21.7) and for the 2 months following (OR 4.0; 95% CI 1.9–8.6). Having a related but non-parent adult aged 20–59 years in the household reduces the odds (OR 0.6; 95% CI 0.5–0.8). There is an inverse relationship between a child’s odds of dying and household socio-economic status. Conclusions This detailed household profile from a poor rural setting where HIV infection is endemic indicates that children are at high risk of dying when another child is very ill or has recently died. Short birth intervals and additional children in the household are further risk factors. Presence of a related adult is protective, as is higher socio-economic status. Such evidence can inform primary health care practice and facilitate targeting of community health worker efforts, especially when covering defined catchment areas.

Description: Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.

Description: The database of 3D interacting domains (3did, available online for browsing and bulk download at http://3did.irbbarcelona.org ) is a catalog of protein–protein interactions for which a high-resolution 3D structure is known. 3did collects and classifies all structural templates of domain–domain interactions in the Protein Data Bank, providing molecular details for such interactions. The current version also includes a pipeline for the discovery and annotation of novel domain–motif interactions. For every interaction, 3did identifies and groups different binding modes by clustering similar interfaces into ‘interaction topologies’. By maintaining a constantly updated collection of domain-based structural interaction templates, 3did is a reference source of information for the structural characterization of protein interaction networks. 3did is updated every 6 months.

Description: This document defines and prioritises the key objectives of dissemination of REFLECT and details the steps to be taken during the project’s lifetime in order to achieve maximum impact and reach relevant audiences. It also sets the framework to facilitate communication among Consortium members, and between the Consortium and stakeholders or the general public.

Description: This document corresponds to Deliverable D6.2 of the ongoing Horizon 2020 project REFLECT and is part of the Work Package 6. The deliverable “Stakeholder matrix” aims to define the approach for engaging stakeholders and involving them into the project in the most efficient way in order to achieve quality final results and successful implementation of the project final product. The document defines the main groups of the potential stakeholders and provides general guidelines on how to categorise them, how to establish the first contact and how to engage them.

Description: This deliverable presents the logo and the style guide of the REFLECT project. It defines the visual identity of the project and establishes a standard visual style to ensure consistency and maximise outreach.