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

Item response modeling of DSM-IV mania symptoms in two representative US epidemiological samples

BACKGROUND: There is considerable debate surrounding the effective measurement of DSM-IV symptoms used to assess manic disorders in epidemiological samples. METHODS: Using two nationally representative datasets, the National Epidemiological Survey of Alcohol and Related Conditions (NESARC, N=43,093 at Wave 1, N=34,653 at 3-year follow-up) and the National Comorbidity Survey-Replication (NCS-R, N=9,282), we examined the psychometric properties of symptoms used to assess DSM-IV mania. The predictive utility of the mania factor score was tested using the 3-year follow-up data in NESARC. RESULTS: Criterion B symptoms were unidimensional (single factor) in both samples. The symptoms assessing flight of ideas, distractibility and increased goal-directed activities had high factor loadings (0.70–0.93) with moderate rates of endorsement thus providing good discrimination between individuals with and without mania. The symptom assessing grandiosity performed less well in both samples. The quantitative mania factor score was a good predictor of more severe disorders at 3-year follow-up in the NESARC sample, even after controlling for a past history of DSM-IV diagnosis of manic disorder. CONCLUSION: These analyses suggest that questions based on some DSM symptoms effectively discriminate between individuals at high and low liability to mania, while others do not. A quantitative mania factor score may aid in predicting recurrence for patients with a history of mania. Methods for assessing mania using structured interviews in the absence of clinical assessment require further refinement

Patients' beliefs towards contingency management: target behaviours, incentives and the remote application of these interventions

Abstract: Introduction: Contingency management interventions are among the most efficacious psychosocial interventions in promoting abstinence from smoking, alcohol and substance use. The aim of this study was to assess the beliefs and objections towards contingency management among patients in UK‐based drug and alcohol services to help understand barriers to uptake and support the development and implementation of these interventions. Methods: The Service User Survey of Incentives was developed and implemented among patients (N = 181) at three UK‐based drug and alcohol treatment services. Descriptive analyses were conducted to ascertain positive and negative beliefs about contingency management, acceptability of different target behaviours, incentives and delivery mechanisms including delivering incentives remotely using technology devices such as mobile telephones. Results: Overall, 81% of participants were in favour of incentive programs, with more than 70% of respondents agreeing with the majority of positive belief statements. With the exception of two survey items, less than a third of participants agreed with negative belief statements. The proportion of participants indicating a neutral response was higher for negative statements (27%) indicating greater levels of ambiguity towards objections and concerns regarding contingency management. Discussion and Conclusions: Positive beliefs towards contingency management interventions were found, including high levels of acceptability towards a range of target behaviours, incentives and the use of technology devices to remotely monitor behaviour and deliver incentives. These findings have implications for the development and implementation of remote contingency management interventions within the UK drug treatment services

RocA truncation underpins hyper-encapsulation, carriage longevity and transmissibility of serotype M18 group A streptococci

Group A streptococcal isolates of serotype M18 are historically associated with epidemic waves of pharyngitis and the non-suppurative immune sequela rheumatic fever. The serotype is defined by a unique, highly encapsulated phenotype, yet the molecular basis for this unusual colony morphology is unknown. Here we identify a truncation in the regulatory protein RocA, unique to and conserved within our serotype M18 GAS collection, and demonstrate that it underlies the characteristic M18 capsule phenotype. Reciprocal allelic exchange mutagenesis of rocA between M18 GAS and M89 GAS demonstrated that truncation of RocA was both necessary and sufficient for hyper-encapsulation via up-regulation of both precursors required for hyaluronic acid synthesis. Although RocA was shown to positively enhance covR transcription, quantitative proteomics revealed RocA to be a metabolic regulator with activity beyond the CovR/S regulon. M18 GAS demonstrated a uniquely protuberant chain formation following culture on agar that was dependent on excess capsule and the RocA mutation. Correction of the M18 rocA mutation reduced GAS survival in human blood, and in vivo naso-pharyngeal carriage longevity in a murine model, with an associated drop in bacterial airborne transmission during infection. In summary, a naturally occurring truncation in a regulator explains the encapsulation phenotype, carriage longevity and transmissibility of M18 GAS, highlighting the close interrelation of metabolism, capsule and virulence

Основні етапи та особливості правового регулювання фінансування будівництва залізниць на території України в другій половині ХІХ – на початку ХХ ст.

Досліджуються питання розвитку та вдосконалення залізничного транспорту України, який постає у державі як одна з ланок поліпшення соціально-економічного життя суспільства. Розкриваються проблеми нормативно-правового регулювання виникнення залізничного транспорту в Україні.Рассматриваются вопросы развития и усовершенствования железнодорожного транспорта Украины, который является для государства звеном улучшения социально-экономической жизни общества. Раскрываются проблемы нормативно-правового регулирования возникновения железнодорожного транспорта в Украине.The guestions of development and improvement of the Ukrainian railvay transport which is consideret to be as one of the directions of making better social-economic life of society are investigated. The problems of normative\loyal regulating of the appearing of railwaj transport in Ukraine (the second half of the nineteenth century)

Identification of commonly expressed exoproteins and proteolytic cleavage events by proteomic mining of clinically relevant UK isolates of Staphylococcus aureus

The range of exoproteins and core exoproteome of 14 Staphylococcus aureus isolates representing major lineages associated with asymptomatic carriage and clinical disease in the UK was identified by MS proteomics using a combined database incorporating sequences derived from 39 S. aureus genomes. In all, 632 different proteins were identified and, of these, only 52 (8 %) were found in all 14 isolates whereas 144 (23 %) were found in just a single isolate. Comparison of the observed mass of each protein (based on migration by SDS-PAGE) with its predicted mass (based on amino acid sequence) suggested that 95 % of the proteins identified were not subject to any major post-translational modification. Migration of 5 % of the proteins was not as expected: 1 % of the proteins migrated at a mass greater than predicted, while 4 % appeared to have undergone proteolytic cleavage; these included SsaA2, Aur, SspP, Ebh as well as BlaR1, MecR1, FsH, OatA and LtaS. Intriguingly, a truncated SasG was produced by a single CC8 USA300-like strain. The analysis provided evidence of the marked heterogeneity in protein expression by S. aureus in broth, while yielding a core but narrow common exoproteome

A behavioral genetic study of humor styles in an Australian sample

The present study investigated the extent to which individual differences in humor styles are attributable to genetic and/or environmental factors in an Australian sample. Participants were 934 same-sex pairs of adult twins from the Australian Twin Registry (546 monozygotic pairs, 388 dizygotic pairs) who completed the Humor Styles Questionnaire (HSQ). The HSQ measures four distinct styles of humor - affiliative, self-enhancing, aggressive, and self-defeating. Results revealed that additive genetic and non-shared environmental factors accounted for the variance in all four humor styles, thus replicating results previously obtained in a sample of twins from the United Kingdom. However, a study conducted with a U.S. sample produced different results and we interpret these findings in terms of cross-cultural differences in humor

The short-term consequences of early onset cannabis use

The associations between early onset (prior to 15 years of age) cannabis use and rates of mental health or adjustment problems during the period from 15 to 16 years of age were studied in a New Zealand birth cohort. Early onset cannabis users were at increased risks of later substance use behaviors, conduct/oppositional disorders, juvenile offending, severe truancy, school dropout, anxiety, depression, and suicidal ideation. Early cannabis users had odds of these outcomes ranging from 2.7 to 30.8 times higher than the odds for those who did not use cannabis prior to age 15. Most of the elevated risks of early onset users were explained by the fact that they were a high- risk group of adolescents characterized by family disadvantages, early adjustment problems, and high affiliations with substance-using or delinquent peers. Nonetheless, even after adjustment for a wide range of confounding factors, early onset users had increased risks of later cannabis use. It is concluded that while most of the elevated risks of early onset users were explained by social, family, and individual characteristics of this group, early onset users were at increased risks of later cannabis use