Novel technologies and emerging biomarkers for personalized cancer immunotherapy

The culmination of over a century's work to understand the role of the immune system in tumor control has led to the recent advances in cancer immunotherapies that have resulted in durable clinical responses in patients with a variety of malignancies. Cancer immunotherapies are rapidly changing traditional treatment paradigms and expanding the therapeutic landscape for cancer patients. However, despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Thus, there is a growing need to identify predictive and prognostic biomarkers that enhance our understanding of the mechanisms underlying the complex interactions between the immune system and cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) reconvened an Immune Biomarkers Task Force to review state of the art technologies, identify current hurdlers, and make recommendations for the field. As a product of this task force, Working Group 2 (WG2), consisting of international experts from academia and industry, assembled to identify and discuss promising technologies for biomarker discovery and validation. Thus, this WG2 consensus paper will focus on the current status of emerging biomarkers for immune checkpoint blockade therapy and discuss novel technologies as well as high dimensional data analysis platforms that will be pivotal for future biomarker research. In addition, this paper will include a brief overview of the current challenges with recommendations for future biomarker discovery

Asthma hospitalisation trends from 2010 to 2015: variation among rural and metropolitan Australians

Abstract Background Asthma remains a leading cause of illness, where primary care can assist to reduce hospitalisations through prevention, controlling acute episodes, and overall management of asthma. In Victoria, Asthma hospitalisations were as high as 3.1 hospitalisations per 1000 population in 1993–94. The primary aims of this study are to: determine if changes in asthma hospitalisations have occurred between 2010 and 2015; determine the key factors that impact asthma hospitalisation over time; and verify whether rural and urban asthma hospitalisations are disparate. A secondary aim of the study is to compare 2010–2015 results with asthma data prior to 2010. Methods Hospital separation data from 1 July 2010 to 30 June 2015 were obtained through the Victorian Admitted Episodes Dataset and other agencies. Data included sex, age, Local Government Area, private or public patient, length of stay, and type of discharge. Asthma and predictor variables were analysed according to hospital separation rates after adjusting for smoking and sex. Hierarchical multiple regression examined the association between asthma and predictor variables. Results During the study period, 49,529 asthma hospital separations occurred, of which 77.5% were in metropolitan hospitals, 55.4% hospital separations were aged 0–14 years, and 21.7% were privately funded. State-wide hospital separations were 1.85 per 1000 population and were consistently higher in metropolitan compared to rural areas (1.93 vs 1.64 per 1000 population). When data among metropolitan adults aged 15 and over were analysed, an increase in the proportion of smokers in the population was reflected by an increase in the number of hospital separations (Adj OR 1.035). Further, among rural and metropolitan children aged 0–14 the only predictor of asthma hospital separations was sex, where metropolitan male children had higher odds of separation than metropolitan females of the same age (Adj OR 4.297). There was no statistically meaningful difference for separation rates between males and females in rural areas. Conclusions We demonstrated a higher overall hospital separation rate in metropolitan Victoria. For children in metropolitan areas, males were hospitalised at higher rates than females, while the inverse was demonstrated for children residing in rural areas. Therefore, optimising asthma management requires consideration of the patient’s age, gender and residential context. Primary health care may play a leading role in increasing health literacy for patients in order to improve self-management and health-seeking behaviour

The impact of ADHD and conduct disorder in childhood on adult delinquency: A 30 years follow-up study using official crime records

<p>Abstract</p> <p>Background</p> <p>Few longitudinal studies have explored lifetime criminality in adults with a childhood history of severe mental disorders. In the present study, we wanted to explore the association between adult delinquency and several different childhood diagnoses in an in-patient population. Of special interest was the impact of disturbance of activity and attention (ADHD) and mixed disorder of conduct and emotions on later delinquency, as these disorders have been variously associated with delinquent development.</p> <p>Methods</p> <p>Former Norwegian child psychiatric in-patients (n = 541) were followed up 19-41 years after hospitalization by record linkage to the National Register of Criminality. On the basis of the hospital records, the patients were re-diagnosed according to ICD-10. The association between diagnoses and other baseline factors and later delinquency were investigated using univariate and multivariate Cox regression analyses.</p> <p>Results</p> <p>At follow-up, 24% of the participants had been convicted of criminal activity.</p> <p>In the multivariate Cox regression analysis, conduct disorder (RR = 2.0, 95%CI = 1.2-3.4) and hyperkinetic conduct disorder (RR = 2.7, 95% CI = 1.6-4.4) significantly increased the risk of future criminal behaviour. Pervasive developmental disorder (RR = 0.4, 95%CI = 0.2-0.9) and mental retardation (RR = 0.4, 95%CI = 0.3-0.8) reduced the risk for a criminal act. Male gender (RR = 3.6, 95%CI = 2.1-6.1) and chronic family difficulties (RR = 1.3, 95% CI = 1.1-1.5) both predicted future criminality.</p> <p>Conclusions</p> <p>Conduct disorder in childhood was highly associated with later delinquency both alone or in combination with hyperactivity, but less associated when combined with an emotional disorder. ADHD in childhood was no more associated with later delinquency than the rest of the disorders in the study population. Our finding strengthens the assumption that there is no direct association between ADHD and criminality.</p

Parent-infant psychotherapy for improving parental and infant mental health

Background: Parent-infant psychotherapy (PIP) is a dyadic intervention that works with parent and infant together, with the aim of improving the parent-infant relationship and promoting infant attachment and optimal infant development. PIP aims to achieve this by targeting the mother’s view of her infant, which may be affected by her own experiences, and linking them to her current relationship to her child, in order to improve the parent-infant relationship directly. / Objectives: 1. To assess the effectiveness of PIP in improving parental and infant mental health and the parent-infant relationship. / 2. To identify the programme components that appear to be associated with more effective outcomes and factors that modify intervention effectiveness (e.g. programme duration, programme focus). / Search methods: We searched the following electronic databases on 13 January 2014: Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 1), Ovid MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS Citation Index, Science Citation Index, ERIC, and Sociological Abstracts. We also searched the metaRegister of Controlled Trials, checked reference lists, and contacted study authors and other experts. / Selection criteria: Two review authors assessed study eligibility independently. We included randomised controlled trials (RCT) and quasi-randomised controlled trials (quasi-RCT) that compared a PIP programme directed at parents with infants aged 24 months or less at study entry, with a control condition (i.e. waiting-list, no treatment or treatment-as-usual), and used at least one standardised measure of parental or infant functioning. We also included studies that only used a second treatment group. / Data collection and analysis: We adhered to the standard methodological procedures of The Cochrane Collaboration. We standardised the treatment effect for each outcome in each study by dividing the mean difference (MD) in post-intervention scores between the intervention and control groups by the pooled standard deviation. We presented standardised mean differences (SMDs) and 95% confidence intervals (CI) for continuous data, and risk ratios (RR) for dichotomous data. We undertook meta-analysis using a random-effects model. / Main results: We included eight studies comprising 846 randomised participants, of which four studies involved comparisons of PIP with control groups only. Four studies involved comparisons with another treatment group (i.e. another PIP, video-interaction guidance, psychoeducation, counselling or cognitive behavioural therapy (CBT)), two of these studies included a control group in addition to an alternative treatment group. Samples included women with postpartum depression, anxious or insecure attachment, maltreated, and prison populations. We assessed potential bias (random sequence generation, allocation concealment, incomplete outcome data, selective reporting, blinding of participants and personnel, blinding of outcome assessment, and other bias). Four studies were at low risk of bias in four or more domains. Four studies were at high risk of bias for allocation concealment, and no study blinded participants or personnel to the intervention. Five studies did not provide adequate information for assessment of risk of bias in at least one domain (rated as unclear). / Six studies contributed data to the PIP versus control comparisons producing 19 meta-analyses of outcomes measured at post-intervention or follow-up, or both, for the primary outcomes of parental depression (both dichotomous and continuous data); measures of parent-child interaction (i.e. maternal sensitivity, child involvement and parent engagement; infant attachment category (secure, avoidant, disorganised, resistant); attachment change (insecure to secure, stable secure, secure to insecure, stable insecure); infant behaviour and secondary outcomes (e.g. infant cognitive development). The results favoured neither PIP nor control for incidence of parental depression (RR 0.74, 95% CI 0.52 to 1.04, 3 studies, 278 participants, low quality evidence) or parent-reported levels of depression (SMD -0.22, 95% CI -0.46 to 0.02, 4 studies, 356 participants, low quality evidence). There were improvements favouring PIP in the proportion of infants securely attached at post-intervention (RR 8.93, 95% CI 1.25 to 63.70, 2 studies, 168 participants, very low quality evidence); a reduction in the number of infants with an avoidant attachment style at post-intervention (RR 0.48, 95% CI 0.24 to 0.95, 2 studies, 168 participants, low quality evidence); fewer infants with disorganised attachment at post-intervention (RR 0.32, 95% CI 0.17 to 0.58, 2 studies, 168 participants, low quality evidence); and an increase in the proportion of infants moving from insecure to secure attachment at post-intervention (RR 11.45, 95% CI 3.11 to 42.08, 2 studies, 168 participants, low quality evidence). There were no differences between PIP and control in any of the meta-analyses for the remaining primary outcomes (i.e. adverse effects), or secondary outcomes. / Four studies contributed data at post-intervention or follow-up to the PIP versus alternative treatment analyses producing 15 meta-analyses measuring parent mental health (depression); parent-infant interaction (maternal sensitivity); infant attachment category (secure, avoidant, resistant, disorganised) and attachment change (insecure to secure, stable secure, secure to insecure, stable insecure); infant behaviour and infant cognitive development. None of the remaining meta-analyses of PIP versus alternative treatment for primary outcomes (i.e. adverse effects), or secondary outcomes showed differences in outcome or any adverse changes. / We used the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) approach to rate the overall quality of the evidence. For all comparisons, we rated the evidence as low or very low quality for parental depression and secure or disorganised infant attachment. Where we downgraded the evidence, it was because there was risk of bias in the study design or execution of the trial. The included studies also involved relatively few participants and wide CI values (imprecision), and, in some cases, we detected clinical and statistical heterogeneity (inconsistency). Lower quality evidence resulted in lower confidence in the estimate of effect for those outcomes. / Authors' conclusions: Although the findings of the current review suggest that PIP is a promising model in terms of improving infant attachment security in high-risk families, there were no significant differences compared with no treatment or treatment-as-usual for other parent-based or relationship-based outcomes, and no evidence that PIP is more effective than other methods of working with parents and infants. Further rigorous research is needed to establish the impact of PIP on potentially important mediating factors such as parental mental health, reflective functioning, and parent-infant interaction

Trees Wanted—Dead or Alive! Host Selection and Population Dynamics in Tree-Killing Bark Beetles

Bark beetles (Coleoptera: Curculionidae, Scolytinae) feed and breed in dead or severely weakened host trees. When their population densities are high, some species aggregate on healthy host trees so that their defences may be exhausted and the inner bark successfully colonized, killing the tree in the process. Here we investigate under what conditions participating with unrelated conspecifics in risky mass attacks on living trees is an adaptive strategy, and what this can tell us about bark beetle outbreak dynamics. We find that the outcome of individual host selection may deviate from the ideal free distribution in a way that facilitates the emergence of tree-killing (aggressive) behavior, and that any heritability on traits governing aggressiveness seems likely to exist in a state of flux or cycles consistent with variability observed in natural populations. This may have implications for how economically and ecologically important species respond to environmental changes in climate and landscape (forest) structure. The population dynamics emerging from individual behavior are complex, capable of switching between “endemic” and “epidemic” regimes spontaneously or following changes in host availability or resistance. Model predictions are compared to empirical observations, and we identify some factors determining the occurrence and self-limitation of epidemics

Preventing Violence in Seven Countries: Global Convergence in Policies

Do governments take the measures that are supported by the best scientific evidence available? We present a brief review of the situation in: Australia, Canada, Germany, the Netherlands, Spain, the United Kingdom, and the United States. Our findings show surprisingly similar developments across countries. While all seven countries are moving towards evidence-based decision making regarding policies and programs to prevent violence, there remain a number of difficulties before this end can be achieved. For example, there continue to be few randomized controlled trials or rigorous quasi-experimental studies on aggression and violence. Results from experimental research are essential to both policy makers and researchers to determine the effectiveness of programs as well as increase our knowledge of the problem. Additionally, all noted that media attention for violence is high in their country, often leading to management by crisis with the result that policies are not based on evidence, but instead seek to appease public outrage. And perhaps because of attendant organizational problems (i.e., in many countries violence prevention was not under the guise of one particular agency or ministry), most have not developed a coordinated policy focusing on the prevention of violence and physical aggression. It is hypothesized that leaders in democratic countries, who must run for election every 4 to 6 years, may feel a need to focus on short-term planning rather than long-term preventive policies since the costs, but not the benefits for the latter would be incurred while they still served in office. We also noted a general absence of expertise beyond those within scientific circles. The need for these ideas to be more widely accepted will be an essential ingredient to real and sustaining change. This means that there must be better communication and increased understanding between researchers and policy makers. Toward those ends, the recent establishment of the Campbell Collaboration, formed to provide international systematic reviews of program effectiveness, will make these results more available and accessible to politicians, administrators and those charged with making key policy decision