Investigating the genetic and environmental aetiologies of non-suicidal and suicidal self-harm: a twin study

BACKGROUND: Self-harm is a major health concern, not only as a signal of distress but also as a strong predictor of later suicide. Self-harm can be further refined into suicidal self-harm (SSH, i.e. suicide attempt) and non-suicidal self-harm (NSSH). Understanding the aetiologies of NSSH and SSH can help inform suicide prevention strategies. Using a twin design, we investigated the phenotypic and aetiological relationships between NSSH and SSH, and their aetiological overlap with mental health problems. METHODS: We analysed data from the Twins Early Development Study using structural equation modelling. At age 21 years, 9063 twins (62.4% female) answered questions related to self-harm. At age 16 years, 19 self- or parent-reported mental health measures were administered, including measures of internalising and externalising problems, psychotic-like experiences and substance abuse. RESULTS: Prevalences for NSSH and SSH were 21.9% and 10.5%, respectively. Additive genetic factors explained half of the variance in NSSH (55%) and SSH (50%), with the rest explained by non-shared environmental factors. Phenotypically, NSSH and SSH were strongly correlated (r = 0.87) with their correlation explained by genetic (57%) and non-shared environmental (43%) factors. We found no evidence that NSSH and SSH differed in their phenotypic and aetiological relationships with mental health measures. CONCLUSION: Our findings suggest no aetiological difference between NSSH and SSH. NSSH and SSH should be regarded as two different ends of a continuum, rather than as two distinct categories

Shrinking and Splitting of drainage basins in orogenic landscapes from the migration of the main drainage divide

International audienceClimate, and in particular **the spatial pattern of precipitation, is thought to affect* *the topographic and tectonic evolution of mountain belts through erosion. Numerical model simulations of landscape erosion controlled **by horizontal tectonic motion or orographic precipitation result in the asymmetric topography that characterizes most natural mountain belts, and in a continuous migration of the main drainage divide. The effects of such a migration have, however, been challenging to observe in natural settings. Here I document the effects of a lateral precipitation gradient on a landscape undergoing constant uplift in a laboratory modelling experiment. In the experiment, the drainage divide migrates towards the drier, leeward side of the mountain range, causing the drainage basins on the leeward side to shrink and split into* *smaller basins. This mechanism results in a progressively increasing number of drainage basins on the leeward side of the mountain range as the divide migrates, such that the expected relationship between the spacing of drainage basins and the location of the main drainage divide is maintained. I propose that this mechanism could clarify the drainage divide migration and topographic asymmetry found in active orogenic mountain ranges, as exemplified by the Aconquija Range of Argentin

Identifying Potential Causal Risk Factors for Self-Harm: A Polygenic Risk Scoring and Mendelian Randomisation Approach

BACKGROUND: Multiple individual vulnerabilities and traits are phenotypically associated with suicidal and non-suicidal self-harm. However, associations between these risk factors and self-harm are subject to confounding. We implemented genetically informed methods to better identify individual risk factors for self-harm. METHODS: sing genotype data and online Mental Health Questionnaire responses in the UK Biobank sample (N = 125,925), polygenic risk scores (PRS) were generated to index 24 plausible individual risk factors for self-harm in the following domains: mental health vulnerabilities, substance use phenotypes, cognitive traits, personality traits and physical traits. PRS were entered as predictors in binomial regression models to predict self-harm. Multinomial regressions were used to model suicidal and non-suicidal self-harm. To further probe the causal nature of these relationships, two-sample Mendelian Randomisation (MR) analyses were conducted for significant risk factors identified in PRS analyses. OUTCOMES: Self-harm was predicted by PRS indexing six individual risk factors, which are major depressive disorder (MDD), attention deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, alcohol dependence disorder (ALC) and lifetime cannabis use. Effect sizes ranged from β = 0.044 (95% CI: 0.016 to 0.152) for PRS for lifetime cannabis use, to β = 0.179 (95% CI: 0.152 to 0.207) for PRS for MDD. No systematic distinctions emerged between suicidal and non-suicidal self-harm. In follow-up MR analyses, MDD, ADHD and schizophrenia emerged as plausible causal risk factors for self-harm. INTERPRETATION: Among a range of potential risk factors leading to self-harm, core predictors were found among psychiatric disorders. In addition to MDD, liabilities for schizophrenia and ADHD increased the risk for self-harm. Detection and treatment of core symptoms of these conditions, such as psychotic or impulsivity symptoms, may benefit self-harming patients. FUNDING: Lim is funded by King’s International Postgraduate Research Scholarship. Dr Pingault is funded by grant MQ16IP16 from MQ: Transforming Mental Health. Dr Coleman is supported by the UK National Institute of Health Research Maudsley Biomedical Research Centre. MRC grant MR/N015746/1 to CML and PFO’R. Dr Hagenaars is funded by the Medical Research Council (MR/S0151132). Kylie P. Glanville is funded by the UK Medical Research Council (PhD studentship; grant MR/N015746/1). This paper represents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care

Improvements and Applications of AMS Radiocarbon Measurement at Peking University

AMS radiocarbon measurements were started at Peking University in 1992 with a modified HICONEX 834 ion source. Some archaeological samples were measured at a sensitivity of 10(-14) with ca. 1.7% precision for modern samples. We have made many improvements in our first two years of operation: a high-intensity Cs sputtering ion source was installed; the graphite sample preparation technique was investigated; and the system stability has been improved. The blank sample background is currently ca. 0.006 MC and a precision within 1% can be reached for modern samples. Geological, archaeological, environmental and biomedical samples can be measured routinely. We present some typical applications.Geochemistry & GeophysicsSCI(E)

Contractile and structural properties of detrusor from children with neurogenic lower urinary tract dysfunction

Neurogenic lower urinary tract (NLUT) dysfunction in paediatric patients can arise after congenital or acquired conditions that affect bladder innervation. With some patients, urinary tract dysfunction remains and is more difficult to treat without understanding the pathophysiology. We measured in vitro detrusor smooth muscle function of samples from such bladders and any association with altered Wnt-signalling pathways that contribute to both foetal development and connective tissue deposition. A comparator group was tissue from children with normally functioning bladders. Nerve-mediated and agonist-induced contractile responses and passive stiffness were measured. Histology measured smooth muscle and connective tissue proportions, and multiplex immunohistochemistry recorded expression of protein targets associated with Wnt-signalling pathways. Detrusor from the NLUT group had reduced contractility and greater stiffness, associated with increased connective tissue content. Immunohistochemistry showed no major changes to Wnt-signalling components except down-regulation of c-Myc, a multifunctional regulator of gene transcription. NLUT is a diverse term for several diagnoses that disrupt bladder innervation. While we cannot speculate about the reasons for these pathophysiological changes, their recognition should guide research to understand their ultimate causes and develop strategies to attenuate and even reverse them. The role of changes to the Wnt-signalling pathways was minor. View Full-Tex

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Efficient Organic Photovoltaics Utilizing Nanoscale Heterojunctions in Sequentially Deposited Polymer/fullerene Bilayer

A highly efficient sequentially deposited bilayer (SD-bilayer) of polymer/fullerene organic photovoltaic (OPV) device is developed via the solution process. Herein, we resolve two essential problems regarding the construction of an efficient SD-bilayer OPV. First, the solution process fabrication of the SD-bilayer is resolved by incorporating an ordering agent (OA) to the polymer solution, which improves the ordering of the polymer chain and prevents the bottom-layer from dissolving into the top-layer solution. Second, a non-planar heterojunction with a large surface area is formed by the incorporation of a heterojunction agent (HA) to the top-layer solution. Poly[[9-(1-octylnonyl)-9H-carbazole-2,7-diyl]-2,5-thiophenediyl-2,1,3-benzothiadiazole- 4,7-diyl-2,5-thiophenediyl] (PCDTBT) is used for the bottom-layer and phenyl-C71-butyric-acid-methyl ester (PC70BM) is used for the top-layer. The SD-bilayer OPV produced utilizing both an OA and HA exhibits a power conversion efficiency (PCE) of 7.12% with a high internal quantum efficiency (IQE). We believe our bilayer system affords a new way of forming OPVs distinct from bulk heterojunction (BHJ) systems and offers a chance to reconsider the polymers that have thus far shown unsatisfactory performance in BHJ systemsope