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First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Characterization of nanobioparticles is a demanding task. This problem is particularly evident in the case of biomedical applications of nanoparticles where toxicological indices and ADME parameters are the result of complex interactions of the nanoparticle at the molecular, cellular and tissue levels. Furthermore, particles of this size frequently behave in ways that are intrinsically different than those at meso and sub-nano scale. The success of the biological application of nanoparticles depends, however, to a large extent, on our ability to characterize, and eventually predict and control, the properties and behavior of nanoscale particles in realistic biological environments. To help this process, the development of computer-aided nanoparticle characterization approaches is highly desirable. Nanobioparticles include a large array of dissimilar materials under a common name, making the definition of common microscopic criteria matching the modeled molecular properties with the macroscopically observed ones, a daunting task. In this presentation we will review our efforts at devising strategies that, from in-silico simulations of nanoparticles, will help us infer their behavior in complex environments. The approaches presented rely on the application of sensitivity analysis techniques that probe the intrinsic stability of the particle. Particles will be suitable candidates for biological use only if they show low sensitivity to those challenges. The nature of the parameters explored and the possible generalization of this approach will be discussed by presenting our results using metal-loaded fullerenes, gold particles and dendrimers. This work has been funded in part with funds from the NCI-NIH (Contract No. NO1-CO-12400). The contents of this publication do not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
To investigate whether adherence to the adapted Mediterranean Diet Score for Adolescents (MDS_A) and the adapted Mediterranean Diet Quality Index for Adolescents (KIDMED_A) is associated with better food/nutrient intakes and nutritional biomarkers.
The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study is a cross-sectional study aiming to obtain comparable data on a variety of nutritional and health-related parameters in European adolescents aged 12·5–17·5 years.
Nine European countries.
European adolescents (n 2330) recruited to the HELENA study. Dietary intake was obtained with 24 h dietary recalls, an FFQ and a Food Choices and Preferences questionnaire. MDS_A was calculated as a categorical variable using cut-offs (MDS_A), as a continuous variable (zMDS_A) and with energy adjustments (zEnMDS_A). The KIDMED_A score was also calculated.
Multilevel linear regression analysis showed positive associations for zMDS_A and KIDMED_A with serum levels of vitamin D, vitamin C, plasma folate, holo-transcobalamin, β-carotene and n-3 fatty acids, while negative associations were observed with trans-fatty acid serum levels. For categorical indices, blood biomarkers showed few significant results. zMDS_A and KIDMED_A showed positive associations with vegetables and fruits intake, and negative associations with energy-dense and low-nutritious foods. zMDS_A and KIDMED_A were positively associated with all macronutrients, vitamins and minerals (all P < 0·0001), except with monosaccharides and PUFA for KIDMED_A and cholesterol for both indices (P < 0·05).
zMDS_A and KIDMED_A have shown the strongest associations with the dietary indicators and biomarkers that have been associated with the Mediterranean diet before, and are therefore considered the most appropriate and valid Mediterranean diet scores for European adolescents.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
We examined maternal depression and maternal sensitivity as mediators of the association between maternal childhood adversity and her child's temperament in 239 mother–child dyads from a longitudinal, birth cohort study. We used an integrated measure of maternal childhood adversity that included the Childhood Trauma Questionnaire and the Parental Bonding Index. Maternal depression was assessed with the Edinburgh Postnatal Depression Scale at 6 months postpartum. Maternal sensitivity was assessed with the Ainsworth maternal sensitivity scales at 6 months. A measure of “negative emotionality/behavioral dysregulation” was derived from the Early Childhood Behaviour Questionnaire administered at 36 months. Bootstrapping-based mediation analyses revealed that maternal depression mediated the effect of maternal childhood adversity on offspring negative emotionality/behavioral dysregulation (95% confidence interval [0.026, 0.144]). We also found a serial, indirect effect of maternal childhood adversity on child negative emotionality/behavioral mediated first by maternal depression and then by maternal sensitivity (95% confidence interval [0.031, 0.156]). Results suggest the intergenerational transmission of the effects of maternal childhood adversity to the offspring occurs through a two-step, serial pathway, involving maternal depression and maternal sensitivity.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
The disease caused by the influenza virus is a global public health problem due to its high rates of morbidity and mortality. Thus, analysis of the information generated by epidemiological surveillance systems has vital importance for health decision making. A retrospective analysis was performed using data generated by the four molecular diagnostic laboratories of the Mexican Social Security Institute between 2010 and 2016. Demographics, influenza positivity, seasonality, treatment choices and vaccination status analyses were performed for the vaccine according to its composition for each season. In all cases, both the different influenza subtypes and different age groups were considered separately. The circulation of A/H1N1pdm09 (48.7%), influenza A/H3N2 (21.1%), influenza B (12.6%), influenza A not subtyped (11%) and influenza A/H1N1 (6.6%) exhibited well-defined annual seasonality between November and March, and there were significant increases in the number of cases every 2 years. An inadequate use of oseltamivir was determined in 38% of cases, and the vaccination status in general varied between 12.1 and 18.5% depending on the season. Our results provide current information about influenza in Mexico and demonstrate the need to update both operational case definitions and medical practice guidelines to reduce the inappropriate use of antibiotics and antivirals.
HLA-G expression has been detected in early preimplantation embryos and it has been postulated that a relationship between embryonic expression of this factor and successful pregnancy may exist. Forty-six patients were prospectively selected from our centre ‘Unidad de Reproducción Humana, Hospital Universitario de Canarias’ for conducting this study. In all cases, metaphase II (MII) oocytes were fertilized using intracytoplasmic sperm injection 2–4 h after retrieval. Embryos were cultured individually in 20 µl droplets of G-1 medium (VitroLife) under oil at 37°C and a 6% CO2 environment. Fertilization was assessed at 18 h postinsemination and all oocytes fertilized were passed into a new culture plaque individually in 300 µl culture medium until day 3 of culture. The culture medium was examined for the expression and secretion of sHLA-G with a sandwich enzyme-linked immunosorbent assay kit (BioVendor, Heidelberg, Germany) according to the manufacturer’s instructions. We found statistical significance between higher levels of sHLA-G secretion and pregnancy rate. When both groups were compared there was no difference in embryo quality of transferred embryos, but a significant difference in the number of oocytes and the embryo quality of the cohort existed that was greater in the pregnant group. A standardized sHLA-G assay with a specifically defined range and standard units provides a non-invasive method to identify the most competent embryos for transfer.
Filamentary structures can form within the beam of protons accelerated during the interaction of an intense laser pulse with an ultrathin foil target. Such behaviour is shown to be dependent upon the formation time of quasi-static magnetic field structures throughout the target volume and the extent of the rear surface proton expansion over the same period. This is observed via both numerical and experimental investigations. By controlling the intensity profile of the laser drive, via the use of two temporally separated pulses, both the initial rear surface proton expansion and magnetic field formation time can be varied, resulting in modification to the degree of filamentary structure present within the laser-driven proton beam.
The climate of north-western Spain, with high temperatures and relative humidity during the grapevine vegetative cycle, can especially favour the development of fungal diseases in vineyards. One of the most important diseases is downy mildew, caused by the fungus Plasmopara viticola. The aim of the current study is to propose a system containing phenological data, biological sensors of pathogen indicator and the agrometeorological Goidanich Index in order to optimize the application of downy mildew fungicide treatments. The study was conducted in a vineyard of the ‘Ribeiro’ Designation of Origin region from 2005 to 2016 during the Vitis vegetative period. Aerobiological sampling was performed using a LANZONI VPPS-2000 volumetric trap. The highest number of infection cycles was recorded during the 2009 harvest, with a total of 16 cycles. Years with fewer infection cycles were 2008, 2011 and 2012 (13 cycles). Primary infections were produced during the third fortnight of April and a high amount of secondary infection cycles were detected by the Goidanich algorithm during the fruit development and berry ripening stages. The best estimators of the P. viticola spore concentrations were the fungus spore levels during the previous day, the average temperature 5 days before and rainfall 2 days before. The regression equation obtained accounted for the 95.9% of the spore concentration variation. The combination of the Goidanich index and biological sensors provides a valuable tool to establish an accurate, modern, integrated downy mildew pest-management strategy.