Low thrust propulsion in a coplanar circular restricted four body problem

This paper formulates a circular restricted four body problem (CRFBP), where the three primaries are set in the stable Lagrangian equilateral triangle configuration and the fourth body is massless. The analysis of this autonomous coplanar CRFBP is undertaken, which identies eight natural equilibria; four of which are close to the smaller body, two stable and two unstable, when considering the primaries to be the Sun and two smaller bodies of the solar system. Following this, the model incorporates `near term' low-thrust propulsion capabilities to generate surfaces of articial equilibrium points close to the smaller primary, both in and out of the plane containing the celestial bodies. A stability analysis of these points is carried out and a stable subset of them is identied. Throughout the analysis the Sun-Jupiter-Asteroid-Spacecraft system is used, for conceivable masses of a hypothetical asteroid set at the libration point L4. It is shown that eight bounded orbits exist, which can be maintained with a constant thrust less than 1:5 10􀀀4N for a 1000kg spacecraft. This illustrates that, by exploiting low-thrust technologies, it would be possible to maintain an observation point more than 66% closer to the asteroid than that of a stable natural equilibrium point. The analysis then focusses on a major Jupiter Trojan: the 624-Hektor asteroid. The thrust required to enable close asteroid observation is determined in the simplied CRFBP model. Finally, a numerical simulation of the real Sun-Jupiter-624 Hektor-Spacecraft is undertaken, which tests the validity of the stability analysis of the simplied model

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Síndrome de burnout en la educación superior: revisión de la literatura

Introducción: El síndrome de burnout es una respuesta al estrés crónico diario e incluye: agotamiento emocional, despersonalización y baja realización personal. Los más afectados son aquellos profesionales que trabajan directamente con el público, tales como docentes. Este estudio tuvo como objetivo analizar los artículos sobre el síndrome de burnout en los profesores en la educación superior. Material y método: Fueron consultadas las bases de datos Scielo, Lilacs, PubMed y PsycINFO y seleccionados 15 artículos, que tuvieran como tema el síndrome de burnout en profesores de la educación superior, de lengua española, inglesa o portuguesa; publicados entre 2011 y 2015. Resultados: Se observó una variación en la prevalencia de 14,2% a 63,5%, similar en los países latinos, siendo que las mujeres tenían más probabilidades de desarrollar el síndrome. En relación el agotamiento emocional, los estudios han demostrado que existe una alta prevalencia en jóvenes profesores, los que trabajan a tiempo completo, en los profesores que enseñaban en los niveles más bajos de educación (infantil, primaria/básica y secundaria/media) y también en las mujeres. Hubo una tendencia de los estudios en el uso de la escala de Maslach Burnout Inventory (MBI) como una herramienta para la evaluación de este síndrome, siendo empleada de forma generalizada en el ámbito científico. El análisis de las condiciones físicas y psicológicas, los factores de riesgo relacionados con el desarrollo del síndrome fueron el estrés prolongado, la tendencia a la neurosis y la depresión. Los factores considerados protectores fueron la satisfacción con la vida, autoeficacia que genera una mayor satisfacción personal y un mayor nivel de participación en el trabajo. Conclusiones: Existe la necesidad de desarrollar estudios encaminados a reducir al mínimo las limitaciones encontradas y futuras investigaciones sobre los factores personales y ambientales asociados con el síndrome y cómo modificarlos para prevenirlo

Genetic variability and gene flow in geographical populations of Ceratitis capitata (Wied.) (medfly).

TwoAfrican populations of Ceratitis capitata (Kenya and Reunion IsL) and two Mediterranean ones (Sardinia and Procida IsI.) have been studied for genetic variability at 25 foci by electro- phoresis. Wright's F5 Slatkin's Nm gene flow estimator, Nei's distance (D) together with measures of variability such as 1-1, P, A have been used to compare the population from Kenya with the other three. Parameters using gene frequencies (F51, D, Nm) indicate the presence of substantial geographic heterogeneity, largely attributable to genetic drift and correlated with dispersion of the medfly from its source area (Subsaharan Africa) to the periphery. The Kenyan population has high genetic variability (assessed by H, P and A), as might be expected given its native status. Significant gene flow estimates between Kenya and the derived Mediterranean populations supports the hypothesis of recent colonization. Part of the geographic heterogeneity is related to the presence of fixed alleles in the more differentiated Reunion population although it maintains the genetic attributes of the ancestral population. Selection or other forces may have played an important role in the differentiation of this population