Graph 'texture' features as novel metrics that can summarize complex biological graphs.

Objective.Image texture features, such as those derived by Haralicket al, are a powerful metric for image classification and are used across fields including cancer research. Our aim is to demonstrate how analogous texture features can be derived for graphs and networks. We also aim to illustrate how these new metrics summarize graphs, may aid comparative graph studies, may help classify biological graphs, and might assist in detecting dysregulation in cancer.Approach.We generate the first analogies of image texture for graphs and networks. Co-occurrence matrices for graphs are generated by summing over all pairs of neighboring nodes in the graph. We generate metrics for fitness landscapes, gene co-expression and regulatory networks, and protein interaction networks. To assess metric sensitivity we varied discretization parameters and noise. To examine these metrics in the cancer context we compare metrics for both simulated and publicly available experimental gene expression and build random forest classifiers for cancer cell lineage.Main results.Our novel graph 'texture' features are shown to be informative of graph structure and node label distributions. The metrics are sensitive to discretization parameters and noise in node labels. We demonstrate that graph texture features vary across different biological graph topologies and node labelings. We show how our texture metrics can be used to classify cell line expression by lineage, demonstrating classifiers with 82% and 89% accuracy.Significance.New metrics provide opportunities for better comparative analyzes and new models for classification. Our texture features are novel second-order graph features for networks or graphs with ordered node labels. In the complex cancer informatics setting, evolutionary analyses and drug response prediction are two examples where new network science approaches like this may prove fruitful.

Genomic Characterization of Mycoplasma arginini Isolated from a Housefly on a Dairy Farm and Comparison with Isolates from Bovine Milk and Lung Tissue.

Mycoplasma mastitis can be highly contagious, unresponsive to treatment, and cause severe economic problems in affected herds. Notable routes of Mycoplasma spp. transmissions are contaminated milking equipment and animal contact through respiratory secretions. Only a few studies report the environment as a possible source of infection. Our group studied the presence of pathogens in houseflies (Musca domestica) in a New York State dairy in the United States. Among others, a Mycoplasma spp. was found in the gut of a housefly captured in the sick pen and identified as M. arginini. Here, we characterized its genome and investigated its relatedness with eight isolates from milk, one isolate from lung tissue collected in the same dairy, and five other dairies in New York State. We applied whole-genome sequencing and phylogenetic analysis based on the sequences of the 16S rRNA gene and 76 conserved proteins. We also assessed an in silico virulence profile by considering a panel of 94 putative virulence genes. As a result of the genome analysis, the housefly M. arginini isolate was highly similar to the milk isolates; interestingly, the similarity was highest with M. arginini isolated from milk on the same dairy farm where the housefly was captured. The housefly and milk M. arginini isolates possessed 54 of the 94 pathogenicity genes considered. Our data support the hypothesis that houseflies are carriers of Mycoplasma spp. and can be considered within the possible roots of environmental transmission of infection in dairy cows. Nevertheless, M. arginini pathogenicity will need to be investigated with dedicated studies. IMPORTANCE It is critical to control the spread of bovine mastitis caused by Mycoplasma spp., as this disease can be highly contagious and have a severe economic impact on affected dairies. A better understanding of possible transmission routes is crucial for infection control and prevention. Based on our data, the composite milk isolates are genetically similar to the housefly isolate. This provides evidence that the same Mycoplasma species found in milk and associated with mastitis can also be isolated from houseflies captured in the dairy environment.

Pathogens associated with houseflies from different areas within a New York State dairy.

Houseflies (Musca domestica) are nonbiting muscoids of importance because they can be mechanical vectors of many kinds of pathogens such as bacteria, protozoa, viruses, and helminth eggs. This study aimed to evaluate the bacterial communities associated with houseflies captured in 3 different areas on a dairy farm located in New York State. Variations in the bacterial community were also evaluated based on the flies' sex and external or internal location where the bacteria were isolated. A total of 101 flies were collected: 27 flies from the sick pen, 42 from calf hutches, and 32 from the milking parlor. A total of 485 organisms were isolated, 233 (48.0%) from 53 female flies and 252 (52.0%) from 48 male flies. Most (74%) bacteria were found in the internal parts of the flies, with only 26% isolated from the external surfaces. The number of isolates detected per fly ranged between 1 and 11. A total of 392 bacteria were identified at the species level. We isolated 26 species reported to be bovine contagious or environmental mastitis pathogens. Within the group of organisms considered contagious, we isolated Staphylococcus aureus and Mycoplasma arginini. This was the first time that a Mycoplasma species was isolated from houseflies. We identified 5 organisms considered foodborne pathogens that affect human health: Salmonella spp., Escherichia coli, Staph. aureus, Bacillus cereus, and Bacillus subtilis. Four of the organisms isolated in this study were also linked with milk spoilage, including Pseudomonas aeruginosa, Bacillus cereus, Bacillus licheniformis, and Paenibacillus lactis. This study confirmed that houseflies carry a high bacterial diversity, including organisms associated with animal infections, organisms that could be a concern for public health, or organisms that could negatively affect milk quality.

Investigating the role of hallucinatory experiences in the transition from suicidal thoughts to attempts.

OBJECTIVE: Psychotic experiences, including auditory hallucinatory experiences (HEs), are strongly associated with both suicidal thoughts and behaviour. This study examined their role in the ideation-to-attempt transition in adolescents, including their direct and indirect effect via potential mediators. METHOD: Participants were from an Australian prospective longitudinal cohort of 1669 adolescents (12-17 years); of which a subsample endorsing baseline suicidal ideation (n = 216) was the focus of most analyses. Suicidal thoughts and behaviours were measured using the Self-Harm Behaviour Questionnaire. The Diagnostic Interview Schedule for Children was used to assess auditory HEs. Potential mediators of interest were psychological distress and Interpersonal Theory of Suicide (IPTS) constructs. RESULTS: Among adolescents reporting suicidal ideation at baseline (n = 216), 6.5% had attempted suicide during follow-up. The size of auditory HEs' univariate effect suggests a possible strong relationship with increased risk of incident suicide attempts (OR = 2.40; 95%CI = 0.76-7.56); however, there was inadequate statistical power to produce a precise estimate. When HEs were accompanied by distress there was a nine-fold increased risk of acting on suicidal thoughts. Distress was independently associated with risk of attempt transition (OR = 4.09), whereas IPTS constructs were poor explanatory variables in most models. CONCLUSION: Adolescents with psychological distress and auditory HEs are at high risk of incident suicide attempts. Further investigations on the role of negative/distressing content of hallucinations in the ideation-to-attempt transition are warranted.

Smokin' hot: adolescent smoking and the risk of psychosis.

OBJECTIVE: Daily smoking has been associated with a greater risk of psychosis. However, we are still lacking studies to adjust for baseline psychotic experiences and other substance use. We examined associations between daily smoking and psychosis risk in a 15-year follow-up while accounting for these covariates in a prospective sample (N = 6081) from the Northern Finland Birth Cohort 1986. METHODS: Self-report questionnaires on psychotic experiences (PROD-screen), tobacco smoking and other substance use were completed when the cohort members were 15-16 years old. Tobacco smoking was categorized into three groups (non-smokers, 1-9 cigarettes and ≥10 cigarettes/day). Psychosis diagnoses were obtained from national registers until the age of 30 years. RESULTS: Subjects in heaviest smoking category were at increased risk of subsequent psychosis (unadjusted HR = 3.15; 95% CI 1.94-5.13). When adjusted for baseline psychotic experiences the association persisted (HR = 2.87; 1.76-4.68) and remained significant even after adjustments for multiple known risk factors such as cannabis use, frequent alcohol use, other illicit substance use, parental substance abuse, and psychosis. Furthermore, number of smoked cigarettes increased psychosis risk in a dose-response manner (adjusted OR = 1.05; 1.01-1.08). CONCLUSION: Heavy tobacco smoking in adolescence was associated with a greater risk for psychosis even after adjustment for confounders.

Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience.

The stagnation in drug development for schizophrenia highlights the need for better translation between basic and clinical research. Understanding the neurobiology of schizophrenia presents substantial challenges but a key feature continues to be the involvement of subcortical dopaminergic dysfunction in those with psychotic symptoms. Our contemporary knowledge regarding dopamine dysfunction has clarified where and when dopaminergic alterations may present in schizophrenia. For example, clinical studies have shown patients with schizophrenia show increased presynaptic dopamine function in the associative striatum, rather than the limbic striatum as previously presumed. Furthermore, subjects deemed at high risk of developing schizophrenia show similar presynaptic dopamine abnormalities in the associative striatum. Thus, our view of subcortical dopamine function in schizophrenia continues to evolve as we accommodate this newly acquired information. However, basic research in animal models has been slow to incorporate these clinical findings. For example, psychostimulant-induced locomotion, the commonly utilised phenotype for positive symptoms in rodents, is heavily associated with dopaminergic activation in the limbic striatum. This anatomical misalignment has brought into question how we assess positive symptoms in animal models and represents an opportunity for improved translation between basic and clinical research. The current review focuses on the role of subcortical dopamine dysfunction in psychosis and schizophrenia. We present and discuss alternative phenotypes that may provide a more translational approach to assess the neurobiology of positive symptoms in schizophrenia. Incorporation of recent clinical findings is essential if we are to develop meaningful translational animal models.

Why are psychotic experiences associated with self-injurious thoughts and behaviours? A systematic review and critical appraisal of potential confounding and mediating factors.

Psychotic experiences (PEs), including hallucination- and delusion-like experiences, are robustly associated with self-injurious thoughts and behaviours (SITB) in the general population. However, it remains unclear as to why there is an association. The purpose of this systematic review was to elucidate the role of other factors that influence the association between PEs and SITB and, in doing so, highlight potential mechanisms underlying the relationship. A search of electronic international databases was undertaken, including PubMed, PsycINFO and EMBASE, and eligible studies were grouped according to seven confounder categories: sociodemographics, mental disorders, alcohol and substance use, environmental, psychological, intervention and family history/genetic factors. The systematic search strategy identified 41 publications reporting on 1 39 427 participants from 16 different countries. In the majority of studies, where adjustment for other variables occurred, the association between PEs and SITB persisted, suggesting PEs have an independent role. Common mental disorders, psychological distress and negative environmental exposures explained a substantial amount of the variance and therefore need to be considered as potential underlying mechanisms. There was high variability in the variables adjusted for in these studies, and so the question still remains as to whether the association between PEs and self-harm/suicidality can be attributed (fully or in part) to confounding and mediating factors or directly causal mechanisms. Regardless of causality, the now extensive literature reporting an association between these two clinical phenomena supports the broad usefulness of PEs as an indicator of risk for SITB.

The association between adolescent psychopathology and subsequent physical activity in young adulthood: a 21-year birth cohort study.

BACKGROUND: The beneficial effects of physical activity (PA) for both physical and mental wellbeing are well established. Given that adolescence presents a critical developmental period during which life-long patterns of PA become established, the exploration of the longitudinal impact of adolescent psychopathology on adult PA status is of interest. METHODS: We analysed prospective data from 3663 young adults who participated in the Mater-University of Queensland Study of Pregnancy. Psychopathology was measured using the Youth Self-Report (YSR) at age 14. Participants' engagement in three types of PA (vigorous exercise, moderate exercise and walking) at age 21 were dichotomised into either 'none' or 'any'. For our main analysis, we examined the association between the YSR score and subsequent PA engagement using logistic regression. We also conducted sensitivity analyses of longitudinal associations between the YSR internalising and externalising symptoms score at age 14 and PA engagement at age 21. RESULTS: We found no longitudinal association between the total YSR score at age 14 and PA engagement at age 21. In addition, there was no longitudinal association between the YSR internalising or externalising symptoms and PA engagement. CONCLUSION: Our findings suggest that there is no longitudinal association between adolescent psychopathology and PA in young adulthood.

American Brachytherapy Society consensus statement for soft tissue sarcoma brachytherapy.

PURPOSE: Radiation therapy represents an essential treatment option in the management of soft tissue sarcomas (STS). Brachytherapy represents an important subset of radiation therapy techniques used for STS, with evolving indications and applications. Therefore, the purpose of this guideline was to update clinicians regarding the data surrounding brachytherapy (BT) and provide recommendations for the utilization of BT in patients with STS. METHODS AND MATERIALS: Members of the American Brachytherapy Society with expertise in STS, and STS BT in particular, created an updated guideline for the use of BT in STS based on a literature review and clinical experience. RESULTS: Guidelines are presented with respect to dose and fractionation and technical features to improve outcomes and potentially reduce the risk of toxicity. Brachytherapy as monotherapy can be considered in low-risk cases or in situations where re-irradiation is being considered. Brachytherapy boost can be considered in cases at higher risk of recurrence or where BT alone cannot adequately cover the target volume. To limit wound complications, the start of BT delivery should be delayed until final wound closure, or if after immediate reconstruction, started after postoperative Day 5. CONCLUSIONS: The current guidelines have been created to provide clinicians with a review of the data supporting BT in the management of STS as well as providing indications and technique guidelines to ensure optimal patient selection and clinical outcomes.

The global coverage of prevalence data for mental disorders in children and adolescents.

AIMS: Children and adolescents make up almost a quarter of the world's population with 85% living in low- and middle-income countries (LMICs). Globally, mental (and substance use) disorders are the leading cause of disability in young people; however, the representativeness or 'coverage' of the prevalence data is unknown. Coverage refers to the proportion of the target population (ages 5-17 years) represented by the available data. METHODS: Prevalence data for conduct disorder (CD), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), eating disorders (EDs), depression, and anxiety disorders were sourced from systematic reviews conducted for the Global Burden of Disease Study 2010 (GBD 2010) and 2013 (GBD 2013). For each study, the location proportion was multiplied by the age proportion to give study coverage. Location proportion was calculated by dividing the total study location population by the total study location population. Age proportion was calculated by dividing the population of the country aged within the age range of the study sample by the population of the country aged within the age range of the study sample. If a study only sampled one sex, study coverage was halved. Coverage across studies was then summed for each country to give coverage by country. This method was repeated at the region and global level, and separately for GBD 2013 and GBD 2010. RESULTS: Mean global coverage of prevalence data for mental disorders in ages 5-17 years was 6.7% (CD: 5.0%, ADHD: 5.5%, ASDs: 16.1%, EDs: 4.4%, depression: 6.2%, anxiety: 3.2%). Of 187 countries, 124 had no data for any disorder. Many LMICs were poorly represented in the available prevalence data, for example, no region in sub-Saharan Africa had more than 2% coverage for any disorder. While coverage increased between GBD 2010 and GBD 2013, this differed greatly between disorders and few new countries provided data. CONCLUSIONS: The global coverage of prevalence data for mental disorders in children and adolescents is limited. Practical methodology must be developed and epidemiological surveys funded to provide representative prevalence estimates so as to inform appropriate resource allocation and support policies that address mental health needs of children and adolescents.

Diversity of knockdown resistance alleles in a single house fly population facilitates adaptation to pyrethroid insecticides.

Insecticide use exerts a tremendous selection force on house fly populations, but the frequencies of the initial resistance mutations may not reach high levels if they have a significant fitness cost in the absence of insecticides. However, with the continued use of the same (or similar) insecticides, it is expected that new mutations (conferring equal or greater resistance, but less of a fitness cost) will evolve. Pyrethroid insecticides target the insect voltage sensitive sodium channel (VSSC) and have been widely used for control of house flies at animal production facilities for more than three decades. There are three Vssc mutations known that cause resistance to pyrethroids in house flies: knockdown resistance (kdr, L1014F), kdr-his (L1014H) and super-kdr (M918T + L1014F). Whether or not there are any new mutations in house fly populations has not been examined for decades. We collected house flies from a dairy in Kansas (USA) and selected this population for three generations. We discovered multiple new Vssc alleles, including two that give very high levels of resistance to most pyrethroids. The importance of these findings to understanding the evolution of insecticide resistance, designing appropriate resistance monitoring and management schemes, and the future of pyrethroids for house fly control are discussed.

Correlates of physical activity in people living with psychotic illness.

OBJECTIVE: In the light of the high prevalence of physical comorbidities in people with psychotic illness, there is a need to explore modifiable risk factors that may contribute to this disease burden. The benefits of physical activity to both physical and mental health have been well established. We aimed to examine the prevalence and correlates of physical activity in a national sample of adults living with psychotic illness. METHODS: Physical activity was assessed in 1801 people using the International Physical Activity Questionnaire. Participants were dichotomised into low and moderate-high physical activity groups and associations between physical activity and a range of sociodemographic, clinical and physical comorbidity variables were examined using logistic regression. RESULTS: More than half the participants were categorised in the moderate-high physical activity group with nearly half of the sample engaged in physical activity every day. There were significant associations between low physical activity and older age, unemployment, educational non-participation, antipsychotic medication use, social dysfunction, self-reported loneliness and obesity. However, there was no significant association between physical activity and sex, psychosis type, illness duration, physical comorbidity or negative symptoms. CONCLUSION: The findings from this study may inform future interventions designed to increase physical activity in people with psychotic illness.

Autoimmune encephalitis.

Over the past decade, the clinical spectrum of autoimmune encephalitis has expanded with the emergence of several new clinicopathological entities. In particular, autoimmune encephalitis has recently been described in association with antibodies to surface receptors and ion channels on neurological tissues. Greater clinician awareness has resulted in autoimmune encephalitis being increasingly recognised in patients with unexplained neurological and psychiatric symptoms and signs. The clinical spectrum of presentations, as well as our understanding of disease mechanisms and treatment regimens, is rapidly developing. An understanding of these conditions is important to all subspecialties of Internal Medicine, including neurology and clinical immunology, psychiatry, intensive care and rehabilitation medicine. This review provides a contemporary overview of the aetiology, investigations and treatment of the most recently described autoimmune encephalitides.

Bridging the gap: What have we done and what more can we do to reduce the burden of avoidable death in people with psychotic illness?

Despite overwhelming evidence demonstrating a persisting gap in life expectancy between those with psychotic illness and the general population, there has been no widespread implementation of interventions to improve the physical wellbeing of people with psychotic illness. This article explores opportunities to 'Bridge the Gap' in life expectancy. We describe an Australian evidence-based intervention that has substantially improved the physical health of young people recently commenced on antipsychotic medication. Further epidemiological research, accompanied by cultural change within mental health services, is an essential precursor to the implementation of effective and sustainable lifestyle interventions. There are other relatively neglected areas of physical wellbeing for people with psychotic illness, such as screening and diagnosis of malignancies, which need more research and clinical attention. While there has been progress with intervention development and evaluation, translation of evidence-based short-term intervention studies into feasible and sustainable system-wide changes within routine mental health service settings remains a challenge. Developing an implementation framework to support such change is an urgent priority so as to bridge the persisting premature mortality in people living with psychotic illness.

Overcoming super-knock down resistance (super-kdr) mediated resistance: multi-halogenated benzyl pyrethroids are more toxic to super-kdr than kdr house flies.

Target site insensitivity because of mutations in the voltage-sensitive sodium channel gene (Vssc) is a major mechanism of resistance to pyrethroid insecticides in the house fly, Musca domestica. There are three known Vssc alleles that confer resistance to pyrethroids in the house fly: knock down resistance (kdr; L1014F), super-kdr (M918T + L1014F) and kdr-his (L1014H), but there has been no side-by-side comparison of the resistance levels that they confer. We compared the levels of resistance conferred by the three Vssc alleles in congenic strains to 19 structurally diverse pyrethroids, and compared the full-length Vssc cDNA sequences from each strain. Generally, the levels of resistance conferred were kdr-his < kdr < super-kdr. However, there was significant variation in this pattern, especially for super-kdr, for which both high and low resistance ratios were observed for several pyrethroids. We also examined the levels of resistance in heterozygotes. Resistance in each of the hybrids was generally inherited as an incompletely recessive trait, except for the kdr-his/kdr hybrids, which showed incompletely to completely dominant resistance (ie had resistance levels comparable to kdr homozygotes). The importance of these results to understanding the frequencies of these resistance alleles in natural populations, the evolution of insecticide resistance and resistance management strategies are discussed.

Emotional and behavioral problems in adolescents and young adults with food allergy.

BACKGROUND: Adolescents with food allergy have poorer psychosocial outcomes compared with their nonallergic counterparts; however, few studies have prospectively examined the mental health of adolescents and young adults in this vulnerable population. Our objectives were to estimate the prevalence of emotional and behavioral problems in an epidemiological sample of adolescents and young adults with food allergy; determine whether food allergy is associated with adolescent and maternal reports of such problems; and examine the patterns of change in emotional and behavioral problems from adolescence to young adulthood among individuals with and without food allergy. METHODS: Data came from 1303 participants at 14 and 21 years of age in the Mater University Study of Pregnancy. Emotional and behavioral problems were measured using self- and maternal-reported symptoms of depression, anxiety, attention/deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder. RESULTS: Maternal, but not self-reports suggested that emotional and behavioral problems were higher among adolescents with food allergy. Food allergy was associated with increased odds of elevated levels of maternal-reported symptoms of depression [OR = 4.50 (1.83, 11.07)], anxiety [OR = 2.68 (1.12, 6.44)], and ADHD [OR = 3.14 (1.07, 9.19)] in adolescence. Food allergy was also associated with depressive symptoms that persisted from adolescence to young adulthood [OR = 2.05 (1.04, 4.03)]. CONCLUSIONS: Emotional and behavioral problems, particularly symptoms of depression, anxiety, and ADHD, are common among adolescents with food allergy in the general population and, in the case of elevated levels of depressive symptoms, persist into young adulthood. Healthcare professionals should seek adolescent and parental perspectives when assessing emotional and behavioral problems and monitor mental health during the transition to adulthood.

The epidemiology and global burden of autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASDs) are persistent disabling neurodevelopmental disorders clinically evident from early childhood. For the first time, the burden of ASDs has been estimated for the Global Burden of Disease Study 2010 (GBD 2010). The aims of this study were to develop global and regional prevalence models and estimate the global burden of disease of ASDs. METHOD: A systematic review was conducted for epidemiological data (prevalence, incidence, remission and mortality risk) of autistic disorder and other ASDs. Data were pooled using a Bayesian meta-regression approach while adjusting for between-study variance to derive prevalence models. Burden was calculated in terms of years lived with disability (YLDs) and disability-adjusted life-years (DALYs), which are reported here by world region for 1990 and 2010. RESULTS: In 2010 there were an estimated 52 million cases of ASDs, equating to a prevalence of 7.6 per 1000 or one in 132 persons. After accounting for methodological variations, there was no clear evidence of a change in prevalence for autistic disorder or other ASDs between 1990 and 2010. Worldwide, there was little regional variation in the prevalence of ASDs. Globally, autistic disorders accounted for more than 58 DALYs per 100 000 population and other ASDs accounted for 53 DALYs per 100 000. CONCLUSIONS: ASDs account for substantial health loss across the lifespan. Understanding the burden of ASDs is essential for effective policy making. An accurate epidemiological description of ASDs is needed to inform public health policy and to plan for education, housing and financial support services.

Psychotic experiences and psychological distress predict contemporaneous and future non-suicidal self-injury and suicide attempts in a sample of Australian school-based adolescents.

BACKGROUND: Recent cross-sectional studies have shown psychotic experiences (PEs) are associated with suicidal ideation and behaviours. We aimed to examine associations between psychotic experiences (including persistent PE), and contemporaneous and incident non-suicidal self-injury (NSSI) and suicide attempts. METHOD: Participants were from an Australian longitudinal cohort of 1896 adolescents (12-17 years). NSSI and suicide attempts were measured using the Self-Harm Behaviour Questionnaire. Items from the Diagnostic Interview Schedule for Children were used to assess psychotic experiences, and the General Health Questionnaire-12 measured psychological distress. RESULTS: Adolescents both psychologically distressed and endorsing psychotic experiences had increased odds of contemporaneous and incident NSSI and attempted suicide. Psychotic experiences alone did not predict future risk. Persistent psychotic experiences were associated with increased risk of NSSI and suicide attempts. CONCLUSIONS: Psychological distress with accompanying psychotic experiences and persistent psychotic experiences are important predictors of NSSI and suicide attempts. Screening these phenotypes in adolescents will assist in discerning those adolescents most at risk, providing opportunities for targeted suicide prevention strategies.