Most of the genetic covariation between major depressive and alcohol use disorders is explained by trait measures of negative emotionality and behavioral control

Background Mental health disorders commonly co-occur, even between conceptually distinct syndromes, such as internalizing and externalizing disorders. The current study investigated whether phenotypic, genetic, and environmental variance in negative emotionality and behavioral control account for the covariation between major depressive disorder (MDD) and alcohol use disorder (AUD). Method A total of 3623 members of a national twin registry were administered structured diagnostic telephone interviews that included assessments of lifetime histories of MDD and AUD, and were mailed self-report personality questionnaires that assessed stress reactivity (SR) and behavioral control (CON). A series of biometric models were fitted to partition the proportion of covariance between MDD and AUD into SR and CON. Results A statistically significant proportion of the correlation between MDD and AUD was due to variance specific to SR (men = 0.31, women = 0.27) and CON (men = 0.20, women = 0.19). Further, genetic factors explained a large proportion of this correlation (0.63), with unique environmental factors explaining the rest. SR explained a significant proportion of the genetic (0.33) and environmental (0.23) overlap between MDD and AUD. In contrast, variance specific to CON accounted for genetic overlap (0.32), but not environmental overlap (0.004). In total, SR and CON accounted for approximately 70% of the genetic and 20% of the environmental covariation between MDD and AUD. Conclusions This is the first study to demonstrate that negative emotionality and behavioral control confer risk for the co-occurrence of MDD and AUD via genetic factors. These findings are consistent with the aims of NIMH's RDoC proposal to elucidate how transdiagnostic risk factors drive psychopathology

Childhood risk factors for lifetime bulimic or compulsive eating by age 30 years in a British national birth cohort.

OBJECTIVE: To examine whether previously identified childhood risk factors for bulimia or compulsive eating (BCE) predict self-reported lifetime BCE by age 30 years in a prospective birth cohort. METHOD: Using data from the 1970 British Cohort Study at birth, 5, and 10 years, associations between 22 putative childhood risk factors and self-reported lifetime BCE at 30 years were examined, adjusting for sex and socioeconomic status. RESULTS: Only female sex (odds ratio (OR): 9.2; 95% confidence interval (CI): 1.9-43.7; p = 0.005), low self-esteem (OR:2.9; 95%CI: 1.1-7.5; p = 0.03) and high maternal education (OR:5.4; 95%CI: 2.0-14.8; p = 0.001) were significantly associated with higher risk of BCE, whereas high SES at 10 years was significantly protective (OR:0.2; 95%CI: 0.1-0.8; p = 0.022) of BCE in fully adjusted multivariable logistic regression analysis. DISCUSSION: Our findings do not support a strong role for childhood weight status and eating behaviours in the development of bulimia and compulsive eating pathology, rather suggesting a focus on self esteem may have greater relative importance. Findings in relation to maternal education and SES need further exploration

Cannabis and depression: A twin model approach to co-morbidity

Cannabis use disorder (CUD) co-occurs with major depressive disorder (MDD) more frequently than would be expected by chance. However, studies to date have not produced a clear understanding of the mechanisms underlying this co-morbidity. Genetically informative studies can add valuable insight to this problem, as they allow the evaluation of competing models of co-morbidity. This study uses data from the Australian Twin Registry to compare 13 co-morbidity twin models initially proposed by Neale and Kendler (Am J Hum Genet 57:935–953, 1995). The analysis sample comprised 2410 male and female monozygotic and dizygotic twins (average age 32) who were assessed on CUD and MDD using the SSAGA-OZ interview. Data were analyzed in OpenMx. Of the 13 different co-morbidity models, two fit equally well: CUD causes MDD and Random Multiformity of CUD. Both fit substantially better than the Correlated Liabilities model. Although the current study cannot differentiate between them statistically, these models, in combination, suggest that CUD risk factors may causally influence the risk to develop MDD, but only when risk for CUD is high

Time to endoscopic intervention in patients with upper gastrointestinal patients can be improved with pathway provision

BACKGROUND:Patients with upper gastrointestinal malignancy often require admission to hospital with dysphagia or jaundice requiring therapeutic endoscopy. Endoscopic intervention is often effective permitting rapid discharge. An efficient service would permit rapid discharge for patients who are often at the end of life. We noted that a majority of patients in hospital under the gastroenterological oncology were admitted with symptoms requiring therapeutic endoscopy. METHODS: We conducted an audit cycle of the inpatient days before and after pathway implementation. A wait of 1 day was set as acceptable for patients with bleeding as defined by NICE guidance and we set an arbitrary standard of 2 days for patients without bleeding but requiring therapeutic endoscopy. Between the audit cycles, a pathway was built to accommodate these patients. RESULTS: Inpatient waits improved from a median of 3 days to 1 day. There was no difference in outcome between those presenting with bleeding and other symptoms or any difference in patients requiring different procedures. CONCLUSIONS: Waiting times for endoscopy can be improved with the introduction of a targeted pathway of cancer patients. Further issues including cost, quality of life and nutrition require further intervention

Reliability and validity of pressure and temporal parameters recorded using a pressure-sensitive insole during running.

Running biomechanics has received increasing interest in recent literature on running-related injuries, calling for new, portable methods for large-scale measurements. Our aims were to define running strike pattern based on output of a new pressure-sensitive measurement device, the Runalyser, and to test its validity regarding temporal parameters describing running gait. Furthermore, reliability of the Runalyser measurements was evaluated, as well as its ability to discriminate different running styles. Thirty-one healthy participants (30.3±7.4 years, 1.78±0.10m and 74.1±12.1kg) were involved in the different study parts. Eleven participants were instructed to use a rearfoot (RFS), midfoot (MFS) and forefoot (FFS) strike pattern while running on a treadmill. Strike pattern was subsequently defined using a linear regression (R2=0.89) between foot strike angle, as determined by motion analysis (1000Hz), and strike index (SI, point of contact on the foot sole, as a percentage of foot sole length), as measured by the Runalyser. MFS was defined by the 95% confidence interval of the intercept (SI=43.9-49.1%). High agreement (overall mean difference 1.2%) was found between stance time, flight time, stride time and duty factor as determined by the Runalyser and a force-measuring treadmill (n=16 participants). Measurements of the two devices were highly correlated (R≥0.80) and not significantly different. Test-retest intra-class correlation coefficients for all parameters were ≥0.94 (n=14 participants). Significant differences (p<0.05) between FFS, RFS and habitual running were detected regarding SI, stance time and stride time (n=24 participants). The Runalyser is suitable for, and easily applicable in large-scale studies on running biomechanics. © 2013 Elsevier B.V

Sellar Remodeling after Surgery for Nonfunctioning Pituitary Adenoma: Intercarotid Distance as a Predictor of Recurrence

Introduction  As they grow, pituitary adenoma can remodel the sella turcica and alter anatomical relationships with adjacent structures. The intercarotid distance (ICD) at the level of the sella is a measure of sella width. The purpose of this study was to (1) assess how ICD changes after transsphenoidal surgery and (2) explore whether the extent of ICD change is associated with tumor recurrence. Methods  A retrospective analysis of preoperative and postoperative coronal magnetic resonance imaging (MRI) scans was carried out by two independent assessors on patients who underwent transsphenoidal surgery for nonfunctioning pituitary macroadenomas. Preoperative tumor volume and any change in ICD following surgery were recorded and compared between groups. Logistic regression models of recurrence were generated. Results  In 36 of 42 patients, ICD fell after surgery (mean = 1.8 mm) and six cases were static. At time of follow-up (mean = 77 months), 25 had not required further intervention and 17 had undergone second surgery or radiosurgery. In patients in whom no further intervention has yet been necessary, the postoperative reduction in ICD was significantly smaller than in those who required repeat intervention (1.1 vs. 2.7 mm respectively, p  < 0.01). ICD decrease was weakly correlated with tumor volume ( r  = 0.35). ICD decrease was a significant predictor of recurrence (odds ratio [OR] = 3.15; 95% confidence interval [CI]: 1.44–6.87), largely independent of tumor volume. Conclusion  For most patients, ICD falls following surgical excision of a nonfunctioning pituitary macroadenoma. A greater reduction in ICD postsurgery appears to predict recurrence. Change in ICD shows promise as a radiographic tool for prognosticating clinical course after surgery

Analysis of saccharification in Brachypodium distachyon stems under mild conditions of hydrolysis

Analysis of saccharification in Brachypodium distachyon stems unde

The association of genetic predisposition to depressive symptoms with non-suicidal and suicidal self-Injuries

Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of depressive symptoms with lifetime NSSI, suicidal ideation, and suicide attempts in a sample of 6237 Australian adult twins and their family members (3740 females, mean age\ua0=\ua042.4\ua0years). Polygenic risk scores for depressive symptoms significantly predicted suicidal ideation, and some predictive ability was found for suicide attempts; the polygenic risk scores explained a significant amount of variance in suicidal ideation (lowest p\ua0=\ua00.008, explained variance ranging from 0.10 to 0.16\ua0%) and, less consistently, in suicide attempts (lowest p\ua0=\ua00.04, explained variance ranging from 0.12 to 0.23\ua0%). Polygenic risk scores did not significantly predict NSSI. Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas we found no evidence that this is also the case for NSSI

Scan-Negative Cauda Equina Syndrome A Prospective Cohort Study

Objective: To describe clinical features relevant to diagnosis, mechanism, and etiology in patients with “scan-negative” cauda equina syndrome (CES). Methods: We carried out a prospective study of consecutive patients presenting with the clinical features of CES to a regional neurosurgery center comprising semi-structured interview and questionnaires investigating presenting symptoms, neurologic examination, psychiatric and functional disorder comorbidity, bladder/bowel/sexual function, distress, and disability. Results: A total of 198 patients presented consecutively over 28 months. A total of 47 were diagnosed with scan-positive CES (mean age 48 years, 43% female). A total of 76 mixed category patients had nerve root compression/displacement without CES compression (mean age 46 years, 71% female) and 61 patients had scan-negative CES (mean age 40 years, 77% female). An alternative neurologic cause of CES emerged in 14/198 patients during admission and 4/151 patients with mean duration 25 months follow-up. Patients with scan-negative CES had more positive clinical signs of a functional neurologic disorder (11% scan-positive CES vs 34% mixed and 68% scan-negative, p < 0.0001), were more likely to describe their current back pain as worst ever (41% vs 46% and 70%, p = 0.005), and were more likely to have symptoms of a panic attack at onset (37% vs 57% and 70%, p = 0.001). Patients with scan-positive CES were more likely to have reduced/absent bilateral ankle jerks (78% vs 30% and 12%, p < 0.0001). There was no significant difference between groups in the frequency of reduced anal tone and urinary retention. Conclusion: The first well-phenotyped, prospective study of scan-negative CES supports a model in which acute pain, medication, and mechanisms overlapping with functional neurologic disorders may be relevant

Assessing seal performance and parameter sensitivity with a full-shaft model

The Waste Isolation Pilot Plant (WIPP) is a planned geologic repository for permanent disposal of transuranic waste generated by US government defense programs. Located near Carlsbad in southeastern New Mexico, the facility`s disposal regions are mined from the bedded salt of the Salado Formation at a depth of approximately 652 m. Four shafts service the operational needs of the facility for air intake, exhaust, waste handling and salt handling. These shafts range in diameter from 3.5 to 6.1 m and extend from the ground surface to the repository. During repository closure, following an operational life of approximately 50 years, these shafts will be sealed in accordance with an acceptable design. Under contract to the US Department of Energy (DOE), the Repository Isolation Systems Department (RISD) of Sandia National Laboratories has developed a design for the WIPP shaft sealing system. This design has been reviewed by the US Environmental Protection Agency (EPA) as part of the 1996 WIPP Compliance Certification Application (CCA). An effective shaft sealing system for the WIPP will limit liquid and gas flows, and permanently prevent the migration of radiological or other hazardous constituents through the sealed shafts from repository to accessible environment. Because of these performance objectives, a significant effort has been directed toward evaluation of the seal design. Whereas RISD (1996) provides a comprehensive discussion, this paper focuses on only one aspect of the evaluation effort, namely a full shaft, fluid flow model