Can exploring natural recovery from substance misuse in psychosis assist with treatment? A review of current research

Substance misuse in people with psychosis presents significant problems, but trials of treatments to address it show little sustained advantage over control conditions. An examination of mechanisms underpinning unassisted improvements may assist in the refinement of co-morbidity treatments. This study reviewed existing research on natural recovery from substance misuse in people with psychosis. To address this issue, a systematic search identified only 7 articles that fulfilled the criteria. Their results suggest that people with psychosis report similar reasons to change as do non-psychotic groups, although they did not clarify whether the relative frequencies or priority orders were the same. Differences involved issues relating to the disorder and the functional problems faced by this group: receipt of treatment for mental health difficulties, worsening of mental health difficulties, and homelessness. The current research on reasons for change in people with psychosis is sparse and has significant limitations, and as yet it offers little inspiration for new treatments. A more fertile source may prove to be a detailed investigation of successful substance control strategies that are used in self-management by this group.

A case of true hermaphroditism reveals an unusual mechanism of twinning

Traditionally twins are classified as dizygous or fraternal and monozygous or identical (Hall Twinning, 362, 2003 and 735-743). We report a rare case of 46,XX/46,XY twins: Twin A presented with ambiguous genitalia and Twin B was a phenotypically normal male. These twins demonstrate a third, previously unreported mechanism for twinning. The twins underwent initial investigation with 17-hydroxyprogesterone and testosterone levels, pelvic ultrasound and diagnostic laparoscopy. Cytogenetic analysis was performed on peripheral blood cells and skin fibroblasts. Histological examination and Fluorescence in situ hybridization studies on touch imprints were performed on gonadal biopsies. DNA analysis using more than 6,000 DNA markers was performed on skin fibroblast samples from the twins and on peripheral blood samples from both parents. Twin A was determined to be a true hermaphrodite and Twin B an apparently normal male. Both twins had a 46,XX/46,XY chromosome complement in peripheral lymphocytes, skin fibroblasts, and gonadal biopsies. The proportion of XX to XY cells varied between the twins and the tissues evaluated. Most significantly the twins shared 100% of maternal alleles and approximately 50% of paternal alleles in DNA analysis of skin fibroblasts. The twins are chimeric and share a single genetic contribution from their mother but have two genetic contributions from their father thus supporting the existence of a third, previously unreported type of twinning.

Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia

The discovery of genetic factors that contribute to schizophrenia susceptibility is a key challenge in understanding the etiology of this disease. Here, we report the identification of a novel schizophrenia candidate gene on chromosome 1q32, plexin A2 (PLXNA2), in a genome-wide association study using 320 patients with schizophrenia of European descent and 325 matched controls. Over 25,000 single-nucleotide polymorphisms (SNPs) located within approximately 14,000 genes were tested. Out of 62 markers found to be associated with disease status, the most consistent finding was observed for a candidate locus on chromosome 1q32. The marker SNP rs752016 showed suggestive association with schizophrenia (odds ratio (OR) = 1.49, P = 0.006). This result was confirmed in an independent case-control sample of European Americans (combined OR = 1.38, P = 0.035) and similar genetic effects were observed in smaller subsets of Latin Americans (OR = 1.26) and Asian Americans (OR = 1.37). Supporting evidence was also obtained from two family-based collections, one of which reached statistical significance (OR = 2.2, P = 0.02). High-density SNP mapping showed that the region of association spans approximately 60 kb of the PLXNA2 gene. Eight out of 14 SNPs genotyped showed statistically significant differences between cases and controls. These results are in accordance with previous genetic findings that identified chromosome 1q32 as a candidate region for schizophrenia. PLXNA2 is a member of the transmembrane semaphorin receptor family that is involved in axonal guidance during development and may modulate neuronal plasticity and regeneration. The PLXNA2 ligand semaphorin 3A has been shown to be upregulated in the cerebellum of individuals with schizophrenia. These observations, together with the genetic results, make PLXNA2 a likely candidate for the 1q32 schizophrenia susceptibility locus.

G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension

-Essential hypertensives display enhanced signal transduction through pertussis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein beta3 subunit gene (GNB3) induces formation of a splice variant (Gbeta3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with BseDI, which either cut (C allele) or did not cut (T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (chi2=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105+/-7, 109+/-16, and 128+/-28 mm Hg (mean+/-SD) for CC, CT, and TT, respectively (P=0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele (P=0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein beta3 subunit gene in the causation of essential hypertension.

Evaluation of visual stress symptoms in Age-matched Dyslexic, Meares–Irlen syndrome (MIS) and normal adults

AIM To examine the prevalence of dyslexia and Meares–Irlen syndrome (MIS) among female students and determine their level of visual stress in comparison with normal subjects. METHODS A random sample of 450 female medical students of King Saud University Riyadh (age range, 18 - 30 years) responded to a wide range of questions designed to accomplish the aims of this study. The detailed questionnaire consisted of 54 questions with twelve questions enquiring on ocular history and demography of participants while 42 questions were on visual symptoms. Items were categorized into; critical and non-critical questions (CQ and NCQ) and were rated on four point Likert scale. Based on the responses obtained, the subjects were grouped into normal (control), dyslexic with or without MIS (Group 1) and subjects with MIS only (Group 2). Responses were analysed as averages and mean scores were calculated and compared between-groups using one way analysis of variance to evaluate total (TVSS = NCQ + CQ), critical and non-critical visual stress scores. The relationship between categorical variables such as age, handedness and condition were assessed with Chi- Square test. RESULTS The completion rate was 96.8% and majority of the respondents (92%) were normal readers, 2% dyslexic and 6% had MIS. They were age-matched. More than half of the participants had visited an eye care practitioner in the last 2yrs. About 13% were recommended eye exercises and one participant experienced pattern glare. Hand preference was not associated with any condition but Group 1 subjects (3/9, 33%) were significantly more likely to be diagnosed of lazy eye than Group 2 (2/27, 7%) and control (27/414, 5%) subjects. The mean ± SD of TVSS responses were 63 ± 14 but it was 44 ± 9 for CQ and 19 ± 5 for NCQ. Responses from all three variables were normally distributed but the CQ responses were on the average more positive (82%) in Group 2 and less positive (46%) in Group 1 than control. With NCQ, the responses were equally less positive in Group 1 and 2 than control. Group 2 subjects showed significantly higher TVSS (P = 0.002), NCQ (P = 0.006) and CQ (P = 0.008) visual stress scores than control but no difference between Group 1 and control subjects, was observed for all scores (P > 0.05, for all comparisons). CONCLUSION The prevalence of dyslexia and MIS among Saudi female students was 2 and 6%, respectively. Critical questions performed best for assessing visual stress symptoms in dyslexic and MIS subjects. Generally, students with MIS were more sensitive to visual stress than normal students but dyslexics were more likely to present with a lazy eye than MIS and normal readers.

Age and leadership: The moderating role of legacy beliefs

Age and age-related motivations have been neglected in leadership research. This study examined the moderating influence of legacy beliefs on the relationships between age and transformational, transactional, and passive-avoidant leadership behaviors. Legacy beliefs involve individuals' convictions about whether they and their actions will be remembered, have an enduring influence, and leave something behind after death. It was expected that at higher ages, low legacy beliefs impede transformational and transactional leadership behaviors and boost passive-avoidant leadership behaviors. One hundred and six university professors, between 30 and 70 years old, provided ratings of their legacy beliefs; each professor's leadership behaviors were evaluated by one of his or her employees. Results confirmed the assumptions for overall transformational leadership and its charisma subdimension as well as for overall transactional leadership and its active management-by-exception subdimension but not for passive-avoidant leadership.

Comparing China's city transportation and economic networks

The city system has been a prevailing research issue in the fields of urban geography and regional economics. Not only do the relationships between cities in the city system exist in the form of rankings, but also in a more general network form. Previous work has examined the spatial structure of the city system in terms of its separate industrial networks, such as in transportation and economic activity, but little has been done to compare different networks. To rectify this situation, this study analyzes and reveals the spatial structural features of China’s city system by comparing its transportation and economic urban networks, thus providing new avenues for research on China’s city network. The results indicate that these two networks relate with each other by sharing structural equivalence with a basic diamond structure and a layered intercity structure decreasing outwards from the national centers. A decoupling effect also exists between them as the transportation network contributes to a balanced regional development, while the economic network promotes agglomeration economies. The law of economic development and the government both play important roles in the articulation between these two networks, and the gap between them can be shortened by related policy reforms and the improvement of the transportation network.

Career adaptability and career entrenchment

Career adaptability constitutes a resource that can help employees to effectively manage career changes and challenges. The goal of this study was to investigate the relationship between the two higher-order constructs of career adaptability and career entrenchment (i.e., the perceived inability and/or unwillingness to pursue new career opportunities), as well as relationships among the dimensions of career adaptability and career entrenchment. We hypothesized a negative relationship between overall career adaptability and career entrenchment, and more differentiated associations among their dimensions. Data for this study came from 404 employees in Brazil. Results of structural equation modeling showed that overall career adaptability weakly negatively predicted overall career entrenchment (standardized effect = − .13), after controlling for age, gender, education, and job tenure. More differentiated findings emerged at the dimension level. Future research should examine the mechanisms and boundary conditions of the relationship between career adaptability and career entrenchment.

Assessment of conjunctival goblet cell density using laser scanning confocal microscopy versus impression cytology

Purpose To determine the association between conjunctival goblet cell density (GCD) assessed using in vivo laser scanning confocal microscopy and conjunctival impression cytology in a healthy population. Methods Ninety (90) healthy participants undertook a validated 5-item dry eye questionnaire, non-invasive tear film break-up time measurement, ocular surface fluorescein staining and phenol red thread test. These tests where undertaken to diagnose and exclude participants with dry eye. The nasal bulbar conjunctiva was imaged using laser scanning confocal microscopy (LSCM). Conjunctival impression cytology (CIC) was performed in the same region a few minutes later. Conjunctival goblet cell density was calculated as cells/mm2. Results There was a strong positive correlation of conjunctival GCD between LSCM and CIC (ρ = 0.66). Conjunctival goblet cell density was 475 ± 41 cells/mm2 and 466 ± 51 cells/mm2 measured by LSCM and CIC, respectively. Conclusions The strong association between in vivo and in vitro cellular analysis for measuring conjunctival GCD suggests that the more invasive CIC can be replaced by the less invasive LSCM in research and clinical practice.

Cointegration and causal relationships between energy consumption and output: Assessing the evidence from Australia

In this paper, we describe our investigation of the cointegration and causal relationships between energy consumption and economic output in Australia over a period of five decades. The framework used in this paper is the single-sector aggregate production function, which is the first comprehensive approach used in an Australian study of this type to include energy, capital and labour as separate inputs of production. The empirical evidence points to a cointegration relationship between energy and output and implies that energy is an important variable in the cointegration space, as are conventional inputs capital and labour. We also find some evidence of bidirectional causality between GDP and energy use. Although the evidence of causality from energy use to GDP was relatively weak when using the thermal aggregate of energy use, once energy consumption was adjusted for energy quality, we found strong evidence of Granger causality from energy use to GDP in Australia over the investigated period. The results are robust, irrespective of the assumptions of linear trends in the cointegration models, and are applicable for different econometric approaches.

8-13 Hz fluctuations in rectal pressure are an objective marker of clitorally-induced orgasm in women

Orgasm is a subjective experience accompanied by involuntary muscle contractions. We hypothesized that orgasm in women would be distinguishable by frequency analysis of a perineal muscle-derived signal. Rectal pressure, an index of perineal muscle activity, was measured continuously in 23 healthy women during different sexual tasks: receiving clitoral stimulation, imitation of orgasm, and attempt to reach orgasm, in which case the women were asked to report whether orgasm had been reached ("orgasm") or not ("failed orgasm attempt"). We performed spectral analysis on the rectal pressure data and calculated the spectral power in the frequency bands delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-25 Hz). The most significant and most important difference in spectral power between orgasm and both control motor tasks (imitation of orgasm and failed orgasm attempt) was found in the alpha band. An objective rule based on spectral power in the alpha band recognized 94% (29/31) of orgasms and correctly labeled 69% (44/64) of all orgasm attempts as either successful or failed. Because outbursts of alpha fluctuations in rectal pressure only occurred during orgasm and not during voluntary imitation of orgasm or failed attempts, we propose that they represent involuntary contractions of muscles in the rectal vicinity. This is the first objective and quantitative measure that has a strong correspondence with the subjective experience of orgasm.

Family-based interventions in preventing children and adolescents from using tobacco: A systematic review and meta-analysis

- Background Tobacco is the main preventable cause of death and disease worldwide. Adolescent smoking is increasing in many countries with poorer countries following the earlier experiences of affluent countries. Preventing adolescents starting smoking is crucial to decreasing tobacco-related illness. - Objective To assess effectiveness of family-based interventions alone and combined with school-based interventions to prevent children and adolescents from initiating tobacco use. - Data Sources 14 bibliographic databases and the Internet, journals hand-searched, experts consulted. - Study Eligibility Criteria, Participants, and Interventions Randomised controlled trials (RCTs) with children or adolescents and families, interventions to prevent starting tobacco use, follow-up ≥ 6 months. - Study Appraisal/Synthesis methods Abstracts/titles independently assessed and data independently entered by two authors. Risk-of-bias assessed with the Cochrane Risk-of-Bias tool. - Results Twenty-seven RCTs were included. Nine trials of never-smokers compared to a control provided data for meta-analysis. Family intervention trials had significantly fewer students who started smoking. Meta-analysis of twoRCTs of combined family and school interventions compared to school only, showed additional significant benefit. The common feature of effective high intensity interventions was encouraging authoritative parenting. - Limitations Only 14 RCTs provided data for meta-analysis (about 1/3 of participants). Of the 13 RCTs which did not provide data for meta-analysis eight compared a family intervention to no intervention and one found significant effects, and five compared a family + school intervention to a school intervention and none found additional significant effects. - Conclusions and Implications of Key Findings There is moderate quality evidence that family-based interventions prevent children and adolescents starting to smoke.

Medication errors in residential aged care facilities: A distributed cognition analysis of the information exchange process

Background Medication safety is a pressing concern for residential aged care facilities (RACFs). Retrospective studies in RACF settings identify inadequate communication between RACFs, doctors, hospitals and community pharmacies as the major cause of medication errors. Existing literature offers limited insight about the gaps in the existing information exchange process that may lead to medication errors. The aim of this research was to explicate the cognitive distribution that underlies RACF medication ordering and delivery to identify gaps in medication-related information exchange which lead to medication errors in RACFs. Methods The study was undertaken in three RACFs in Sydney, Australia. Data were generated through ethnographic field work over a period of five months (May–September 2011). Triangulated analysis of data primarily focused on examining the transformation and exchange of information between different media across the process. Results The findings of this study highlight the extensive scope and intense nature of information exchange in RACF medication ordering and delivery. Rather than attributing error to individual care providers, the explication of distributed cognition processes enabled the identification of gaps in three information exchange dimensions which potentially contribute to the occurrence of medication errors namely: (1) design of medication charts which complicates order processing and record keeping (2) lack of coordination mechanisms between participants which results in misalignment of local practices (3) reliance on restricted communication bandwidth channels mainly telephone and fax which complicates the information processing requirements. The study demonstrates how the identification of these gaps enhances understanding of medication errors in RACFs. Conclusions Application of the theoretical lens of distributed cognition can assist in enhancing our understanding of medication errors in RACFs through identification of gaps in information exchange. Understanding the dynamics of the cognitive process can inform the design of interventions to manage errors and improve residents’ safety.

CD1 expression and CD1-restricted T cell activity in normal and tumour-bearing human liver

CD1d-restricted natural killer T (NKT) cells expressing invariant Valpha14Jalpha18 T cell receptor alpha-chains are abundant in murine liver and are implicated in the control of malignancy, infection and autoimmunity. Invariant NKT cells have potent anti-metastatic effects in mice and phase I clinical trials involving their homologues in humans are ongoing. However, invariant NKT cells are less abundant in human liver ( approximately 0.5% of hepatic T cells) than in murine liver (up to 50%) and it is not known if other hepatic T cells are CD1-restricted. We have examined expression of CD1a, CD1b, CD1c and CD1d mRNA and protein in human liver and evaluated the reactivity of mononuclear cells (MNC) from histologically normal and tumour-bearing human liver specimens against these CD1 isoforms. Messenger RNA for all CD1 isotypes was detectable in all liver samples. CD1c and CD1d were expressed at the protein level by hepatic MNC. CD1d, only, was detectable at the cell surface, but CD1c and CD1d were found at an intracellular location in significant numbers of liver MNC. CD1b was not expressed by MNC from healthy livers but was detectable within MNC in all tumour samples tested. Hepatic T cells exhibited reactivity against C1R cells expressing transfected CD1c and CD1d, but neither CD1a nor CD1b. These cells secreted interferon-gamma (IFN-gamma) but not interleukin-4 (IL-4) upon stimulation. In contrast, similar numbers of peripheral T cells released 13- and 16-fold less IFN-gamma in response to CD1c and CD1d, respectively. CD1c and CD1d expression and T cell reactivity were not altered in tumour-bearing liver specimens compared to histologically normal livers. These data suggest that, in addition to invariant CD1d-restricted NKT cells, autoreactive T cells that recognise CD1c and CD1d and release inflammatory cytokines are abundant in human liver.

Automated feature engineering for HTTP tunnel detection

Generating discriminative input features is a key requirement for achieving highly accurate classifiers. The process of generating features from raw data is known as feature engineering and it can take significant manual effort. In this paper we propose automated feature engineering to derive a suite of additional features from a given set of basic features with the aim of both improving classifier accuracy through discriminative features, and to assist data scientists through automation. Our implementation is specific to HTTP computer network traffic. To measure the effectiveness of our proposal, we compare the performance of a supervised machine learning classifier built with automated feature engineering versus one using human-guided features. The classifier addresses a problem in computer network security, namely the detection of HTTP tunnels. We use Bro to process network traffic into base features and then apply automated feature engineering to calculate a larger set of derived features. The derived features are calculated without favour to any base feature and include entropy, length and N-grams for all string features, and counts and averages over time for all numeric features. Feature selection is then used to find the most relevant subset of these features. Testing showed that both classifiers achieved a detection rate above 99.93% at a false positive rate below 0.01%. For our datasets, we conclude that automated feature engineering can provide the advantages of increasing classifier development speed and reducing development technical difficulties through the removal of manual feature engineering. These are achieved while also maintaining classification accuracy.