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ObjectiveTo evaluate the relative strengths of 3 frailty assessment instruments for predicting mortality and prolonged hospitalization in acute coronary syndrome patients.DesignProspective cohort study.SettingAcute cardiac care units in New Zealand.Participants1174 patients >70 years of age hospitalized with an acute coronary syndrome.InterventionsThe Clinical Frailty Scale (CFS), Edmonton Frail Scale (EFS) and Fried Criteria (Fried), were completed during hospital admission following an acute coronary syndrome when the patient was clinically stable.Primary and secondary outcome measuresAll-cause mortality over the next ~5 years and hospitalization for >10 days in the next year determined from national administrative data.ResultsDuring median follow-up of 5.1 years there were 353 deaths. Harrell's C-statistic for mortality for EFS was 0.663, Fried 0.648 and CFS 0.640 (p10 days (n = 267, 22%) were EFS 0.649, Fried 0.628, and CFS 0.584 (pConclusionIn older patients assessed following an acute coronary syndrome the EFS discriminated the risk of all cause mortality and prolonged hospitalization better than the CFS and Fried tests, and improved risk discrimination when added to clinical risk scores.

Abstract Previous research suggests that sharing emotionally intense experiences with others, for example by undergoing dysphoric collective rituals together, can lead to “identity fusion,” a visceral feeling of oneness that predicts group cohesion and self-sacrifice for the group. In this pre-registered research, we provide the first quantitative investigation of identity fusion following participation in a national funeral, surveying 1632 members of the British public. As predicted, individuals reporting intense sadness during Queen Elizabeth II’s funeral exhibited higher levels of identity fusion and pro-group commitment, as evidenced by generosity pledges to a British Monarchist charity. Also consistent with our hypotheses, feelings of unity in grief and emotional sharedness during the event mediated the relationship between sadness intensity and pro-group commitment. These findings shed light on importance of collective rituals in fostering group cohesion, cooperation, and the dynamics of shared emotional experiences within communities.

Objectives: This review aimed to 1) identify existing rural strengths in the literature that proposed a relationship to mental health, 2) classify strengths into a socioecological framework, and 3) identify which strengths make a conceptual link to improved mental health. Methods: Literature was systematically reviewed using online databases (PubMed, PsycInfo, CINAHL, and Scopus). Applicable original research studies that met the inclusion criteria, published (1990–2022) from Australia, Canada, and the United States were thematically analysed. Results: Sixty-one articles from Australia (n=28, 46%), Canada (n=8, 13%), and the United States (n=25, 41%) identified mental health-strengths relationships (e.g. social networks, nature). Twenty-seven studies proposed conceptual links to improved mental health and identified potential 'mechanisms' to harness strengths (e.g. identification, referral). Conclusions: Despite an entrenched rural deficit discourse, many strengths of rural communities were identified in the literature that, using an adapted socioecological framework to categorise, may be harnessed to improve the mental health of communities across the socioecological continuum. Implications for public health: Understanding existing strengths that are embedded in rural communities can inform future mental health policy and commissioning models in a way that is relevant and sustainable for communities, while recognising rural agency.

Objective: The objective of this study was to determine regional variation in need for mental health care for Aboriginal and Torres Strait Islander adults (18+ years). Methods: Three Australian Indigenous health surveys were analysed, and prevalence rates of high/very high psychological distress (as per the Kessler-5 tool) by the Index of Relative Socio-economic Disadvantage were computed and combined via meta-analysis. These estimates were applied to census population data to estimate regional needs and summed to geographic planning regions. Final estimates were assessed for face validity by comparing with other existing estimates of mental health need. Results: The Index of Relative Socioeconomic Disadvantage had a dose–response relationship with high/very high psychological distress, whereby the more disadvantaged an area, the greater the levels of reported distress. This methodology resulted in varying levels of need within South East Queensland. Conclusions: The approach was found to have good face validity and provides a data-driven method to determine relative levels of need. Implications for Public Health: To ensure equity of mental health service provision, planners should account for variation in levels of need within a catchment. This method may be used throughout Australia to determine regional variation in need for care where other data are lacking to ensure evidence-based investment planning decisions at the local level.

This paper presents a comprehensive exploration of data quality terminology, revealing a significant lack of standardisation in the field. The goal of this work was to conduct a comparative analysis of data quality terminology across different domains and structure it into a hierarchical data model. We propose a novel approach for aggregating disparate data quality terms used to describe the multiple facets of data quality under common umbrella terms with a focus on the ISO 25012 standard. We introduce four additional data quality dimensions: governance, usefulness, quantity, and semantics. These dimensions enhance specificity, complementing the framework established by the ISO 25012 standard, as well as contribute to a broad understanding of data quality aspects. The ISO 25012 standard, a general standard for managing the data quality in information systems, offers a foundation for the development of our proposed Data Quality Data Model. This is due to the prevalent nature of digital systems across a multitude of domains. In contrast, frameworks such as ALCOA+, which were originally developed for specific regulated industries, can be applied more broadly but may not always be generalisable. Ultimately, the model we propose aggregates and classifies data quality terminology, facilitating seamless communication of the data quality between different domains when collaboration is required to tackle cross-domain projects or challenges. By establishing this hierarchical model, we aim to improve understanding and implementation of data quality practices, thereby addressing critical issues in various domains.

Some of the most pressing challenges facing our planet—such as climate change, biodiversity loss, warfare and extreme poverty—require social cohesion and prosocial action on a global scale. How can this be achieved? Previous research suggests that identity fusion—a strong form of group cohesion motivating prosocial action—results from perceptions of shared personally transformative experiences or of common biological essence. Here, we present results from two studies with United States samples exploring each pathway to identity fusion on a global scale. Study 1 focused on globally shared motherhood experiences and found that US mothers were more fused with women around the world if they shared motherhood experiences with them, which was also reflected in money allocation behaviour. Study 2 showed that exposure to a talk about globally shared biology increased fusion with humanity at large, Americans and the extended family suggesting that fusion with humanity does not need to weaken fusion with nation or extended family. We discuss implications of our results for future research on bonding with humanity at large and for addressing collective action problems on a global scale.

Abstract Background The aim of this study was to demonstrate the application of a needs-based mental health service planning model in Tasmania, Australia to identify indicative directions for future service development that ensure the equitable provision of mental health services across the State. Methods The activity and capacity of Tasmania’s 2018–19 mental health services were compared to estimates of required care by: (1) generating estimates of required care using the National Mental Health Service Planning Framework (NMHSPF); (2) collating administrative mental health services data; (3) aligning administrative data to the NMHSPF; and (4) comparing aligned administrative data and NMHSPF estimates to identify priority areas for service development. Findings were contextualised using information about service location, population demographics, and upcoming service development. Results Bed-based services capacity reached 85% of the NMHSPF estimate. However, access to certain bed types was inequitable across regional areas. Access to jurisdictional clinical ambulatory team-based services was lowest in the South, while overall full-time equivalent staff capacity reached 58% of the NMHSPF estimate. Access to Primary Health Tasmania (PHT) primary care services was highest in the North West; access to Medicare services was highest in the South. Collectively, activity across primary care (PHT, headspace and Medicare) reached 43% of the NMHSPF estimate. Over half of Community Managed Mental Health Support Services were state-wide services. Conclusions This study demonstrates the application of a needs-based planning model for mental health services. Findings revealed service priority areas across Tasmania and highlight considerations for needs-based planning.

Abstract Objective To investigate the associations between low education and risk of mental disorders, substance use disorders and self‐harm in different age‐groups. Methods All subjects in Stockholm born between 1931 and 1990 were linked to their own or their parent's highest education in 2000 and followed‐up for these disorders in health care registers 2001–2016. Subjects were stratified into four age‐groups: 10–18, 19–27, 28–50, and 51–70 years. Hazard Ratios with 95% Confidence Intervals (CIs) were estimated with Cox proportional hazard models. Results Low education increased the risk of substance use disorders and self‐harm in all age‐groups. Males aged 10–18 with low education had increased risks of ADHD and conduct disorders, and females a decreased risk of anorexia, bulimia and autism. Those aged 19–27 years had increased risks of anxiety and depression, and those aged 28–50 had increased risks of all mental disorders except anorexia and bulimia in males with Hazard Ratios ranging from 1.2 (95% CIs 1.0–1.3) for bipolar disorder to 5.4 (95% CIs 5.1–5.7) for drug use disorder. Females aged 51–70 years had increased risks of schizophrenia and autism. Conclusion Low education is associated with risk of most mental disorders, substance use disorders and self‐harm in all age‐groups, but especially among those aged 28–50 years.

Abstract Claims to supernatural power have been used as a basis for authority in a wide range of societies, but little is known about developmental origins of the link between supernatural power and worldly authority. Here, we show that 12- to 16-month-old infants expect agents exhibiting counterintuitive capacities to win out in a two-way standoff over a contested resource. Infants watched two agents gain a reward using either physically intuitive or physically counterintuitive methods, the latter involving simple forms of levitation or teleportation. Infants looked longer, indicating surprise, when the physically intuitive agent subsequently outcompeted a physically counterintuitive agent in securing a reward. Control experiments indicated that infants’ expectations were not simply motived by the efficiency of agents in pursuing their goals, but specifically the deployment of counterintuitive capacities. This suggests that the link between supernatural power and worldly authority has early origins in development.

This report describes the current canonical time-series dataset named “Equinox2020,” a subset of Seshat: Global History Databank data for a well-curated list of polities and variables available on the Seshat Data Browser. The report provides an introduction to the methods and procedures of the Seshat project relating to the curation and release of the Equinox2020 dataset.

Background The treatment coverage for major depressive disorder (MDD) is low in many parts of the world despite MDD being a major contributor to disability globally. Most existing reviews of MDD treatment coverage do not account for potential sources of study-level heterogeneity that contribute to variation in reported treatment rates. This study aims to provide a comprehensive review of the evidence and analytically quantify sources of heterogeneity to report updated estimates of MDD treatment coverage and gaps by location and treatment type between 2000 and 2019. Methods and findings A systematic review of the literature was conducted to identify relevant studies that provided data on treatment rates for MDD between January 1, 2000, and November 26, 2021, from 2 online scholarly databases PubMed and Embase. Cohort and cross-sectional studies were included if treatment rates pertaining to the last 12 months or less were reported directly or if sufficient information was available to calculate this along with 95% uncertainty intervals (UIs). Studies were included if they made use of population-based surveys that were representative of communities, countries, or regions under study. Studies were included if they used established diagnostic criteria to diagnose cases of MDD. Sample and methodological characteristics were extracted from selected studies. Treatment rates were modeled using a Bayesian meta-regression approach and adjusted for select covariates that quantified heterogeneity in the data. These covariates included age, sex, treatment type, location, and choice of MDD assessment tool. A total of 149 studies were included for quantitative analysis. Treatment coverage for health service use ranged from 51% [95% UI 20%, 82%] in high-income locations to 20% [95% UI 1%, 53%] in low- and lower middle-income locations. Treatment coverage for mental health service use ranged from 33% [95% UI 8%, 66%] in high-income locations to 8% [95% UI Conclusions In this study, we observed that the treatment coverage for MDD continues to be low in many parts of the world and in particular in low- and lower middle-income countries. There is a continued need for routine data collection that will help obtain more accurate estimates of treatment coverage globally. In a systematic review and Bayesian meta-regression analysis, Modhurima Moitra and colleagues estimate major depressive disorder treatment coverage in 84 countries. Author summary Why was this study done? ➢ Major depressive disorder (MDD) is one of the major contributors to disability worldwide, but treatment rates for this condition are remarkably low. ➢ To the best of our knowledge, previous systematic reviews on this topic provide more descriptive summaries of treatment rates without accounting for differences in study attributes that may contribute to variation in reported treatment rates. ➢ An updated systematic review that is more reflective of the recent literature on treatment rates as well as an improved analytical approach may provide more accurate estimates of treatment rates by resource setting and geography. What did the researchers do and find? ➢ We conducted a systematic review and meta-regression analysis using data on treatment rates for MDD from 149 studies and 84 countries between 2000 and 2021. ➢ We estimated pooled treatment rates adjusted for parameters of interest including age, sex, treatment type, study methods, and location. ➢ Mental health service use ranged from 33% (95% uncertainty interval (UI) 8, 66) in high-income countries to 8% (95% UI What do these findings mean? ➢ This systematic review provides updated evidence on treatment rates for MDD, and results suggest that there are wide disparities in treatment rates by resource setting. ➢ More high-quality data on depression treatment coverage and adequacy are needed from low- and lower middle-income countries. ➢ These findings may help prioritize efforts to scale up depression treatment in locations with clearly identified treatment gaps.

Background: The treated prevalence of psychotic disorders in remote communities of Cape York and the Torres Strait, Australia, has been shown to be elevated compared with the Australian population. Our study used a unique dataset to assess treated incidence and prevalence of psychotic disorders and mortality over a 23-year period in the adult Indigenous population of this region. Methods: Data was collated from a clinical database that contains complete psychiatric records from 1992 to 2015, extracted for all Indigenous patients who received treatment for a psychotic disorder from the Remote Area Mental Health Service, and linked to the Queensland Deaths Registry. We calculated 12-month treated prevalence and incidence for each calendar year. Mortality rates were compared to the overall and Indigenous population death rates in Queensland. Findings: Between 1992 and 2015, 424 patients were treated for psychosis – an age-standardised 12-month prevalence of 1·7% in 2015, approximately two times higher in men than women, and three times higher in Aboriginal versus Torres Strait Islander populations. The highest treated prevalence was observed in 2015 in Aboriginal men (4.0%). A range of psychotic disorders were detected, including many substance-induced cases (n = 93) and schizophrenia (n = 252). The age-standardised 12-month incidence rate over the study period was 3.61 per 1000 person-years for women and 4.23 per 1000 person-years for men. Treated prevalence increased throughout the study period, largely attributable to increases in incidence of schizophrenia and schizoaffective disorder – in contrast, the incidence and prevalence of bipolar and mood disorders remained low and stable. Increased mortality risk compared to the Queensland Indigenous population (SMR = 1.9; 95% CI 1.4–2.6) was attributable to the elevated risk shown in the Aboriginal population in our study (SMR = 2.6; 95% CI 1.8–3.7). Interpretation: Our results show extremely high prevalence rates of psychosis; increasing prevalence over time; differences in the distribution of psychosis between Aboriginal and Torres Strait Islander populations; and increased mortality risk for Aboriginal people living with psychosis in this region. These observations strongly suggest an aetiological role of environmental and neurodevelopmental factors, and the contribution of social factors to vulnerability and premature mortality. Role of the funding source: This study was funded by Queensland Health who are the custodians of this database. The funder had no role in study design, data analysis, data interpretation, writing of the report, or submission for publication. All authors had full access to all the study data. The corresponding author had final responsibility for the decision to submit for publication. FJC is supported by an Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1138488). Keywords: Mental health, Indigenous populations, Psychosis

What have been the causes and consequences of technological evolution in world history? In particular, what propels innovation and diffusion of military technologies, details of which are comparatively well preserved and which are often seen as drivers of broad socio-cultural processes? Here we analyze the evolution of key military technologies in a sample of pre-industrial societies world-wide covering almost 10,000 years of history using Seshat: Global History Databank. We empirically test previously speculative theories that proposed world population size, connectivity between geographical areas of innovation and adoption, and critical enabling technological advances, such as iron metallurgy and horse riding, as central drivers of military technological evolution. We find that all of these factors are strong predictors of change in military technology, whereas state-level factors such as polity population, territorial size, or governance sophistication play no major role. We discuss how our approach can be extended to explore technological change more generally, and how our results carry important ramifications for understanding major drivers of evolution of social complexity.

A growing body of evidence suggests that two distinct forms of group alignment are possible: identification and fusion (the former asserts that group and personal identity are distinct, while the latter asserts group and personal identities are functionally equivalent and mutually reinforcing). Among highly fused individuals, group identity taps directly into personal agency and so any attack on the group is perceived as a personal attack and motivates a willingness to fight and possibly even die as a defensive response. As such, identity fusion is relevant in explaining violent extremism, including suicidal terrorist attacks. Identity fusion is theorized to arise as a result from experiences which are (1) perceived as shared and (2) transformative, however evidence for this relationship remains limited. Here, we present a pre-registered study in which we examine the role of transformativeness and perceived sharedness of group-defining events in generating identity fusion. We find that both of these factors are predictive of identity fusion but that the relationship with transformativeness was more consistent than perceived sharedness across analyses in a sample of Indonesian Muslims.

Abstract Background Clinically operated community-based residential rehabilitation units (Community Rehabilitation Units) are resource intensive services supporting a small proportion of the people with severe and persisting mental illness who experience difficulties living in the community. Most consumers who engage with these services will be diagnosed with schizophrenia or a related disorder. This review seeks to: generate a typology of service models, describe the characteristics of the consumers accessing these services, and synthesise available evidence about consumers’ service experiences and outcomes. Method A systematic review was undertaken to identify studies describing Community Rehabilitation Units in Australia, consumer characteristics, and evidence about consumer experiences and outcomes. Search strings were applied to multiple databases; additional records were identified through snowballing. Records presenting unique empirical research were subject to quality appraisal. Results The typology defined two service types, Community-Based Residential Care (C-BRC), which emerged in the context of de-institutionalisation, and the more recent Transitional Residential Rehabilitation (TRR) approach. Key differentiating features were the focus on transitional care and ‘recovery’ under TRR. Schizophrenia spectrum disorders were the most common primary diagnosis under both service types. TRR consumers were more likely to be male, referred from community settings, and less likely to be subject to involuntary treatment. Regarding outcomes, the limited quantitative evidence (4 records, 2 poor quality) indicated C-BRC was successful in supporting the majority of consumers transferred from long-term inpatient care to remain out of hospital. All qualitative research conducted in C-BRC settings was assessed to be of poor quality (3 records). No methodologically sound quantitative evidence on the outcomes of TRR was identified. Qualitative research undertaken in these settings was of mixed quality (9 records), and the four records exploring consumer perspectives identified them as valuing the service provided. Conclusions While there is qualitative evidence to suggest consumers value the support provided by Community Rehabilitation Units, there is an absence of methodologically sound quantitative research about the consumer outcomes achieved by these services. Given the ongoing and increasing investment in these facilities within the Australian context, there is an urgent need for high-quality research examining their efficiency and effectiveness. Trial registration PROSPERO (CRD42018097326).

Background Identification of patients with stable coronary heart disease who are at significant residual risk could be helpful for targeted prevention. Our aim was to determine the prognostic value of the recently introduced ceramide‐ and phospholipid‐based risk score, the Cardiovascular Event Risk Test (CERT2), in patients with stable coronary heart disease on optimal medical therapy and to identify biological processes that contribute to the CERT2 score. Methods and Results Plasma samples (n=11 222) obtained from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were analyzed using a tandem liquid chromatography‐mass spectrometry method. STABILITY was a trial in patients with stable coronary heart disease randomized to the lipoprotein‐associated phospholipase A2 inhibitor darapladib or placebo on optimized medical therapy at baseline, with a median follow‐up of 3.7 years. Hazard ratios per SD for the CERT2 risk score were 1.32 (95% CI, 1.25–1.39) for major adverse cardiovascular event, 1.47 (95% CI, 1.35–1.59) for cardiovascular death, 1.32 (95% CI, 1.16–1.49) for stroke, 1.23 (95% CI, 1.14–1.33) for myocardial infarction, and 1.56 (95% CI, 1.39–1.76) for hospitalization due to heart failure, when adjusted for traditional cardiovascular risk factors. CERT2 showed correlation (P0.2) with inflammatory markers high‐sensitivity C‐reactive protein, interleukin 6, the heart failure marker N‐terminal pro‐B‐type natriuretic peptide, and low‐density lipoprotein cholesterol. After also adjusting for levels of other prognostic biomarkers, the CERT2 score was still independently related to the risk of cardiovascular death but not to nonfatal events. Conclusions The CERT2 risk score can detect residual risk in patients with stable coronary heart disease and is associated with biomarkers indicating inflammation, myocardial necrosis, myocardial dysfunction, renal dysfunction, and dyslipidemia. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT00799903.

Abstract Background To evaluate the planned implementation of group based Cognitive Remediation therapy (CR) and Social Cognitive Interaction Training (SCIT) into routine psychosis care in a mental health service in Australia. Method The study was conducted over 3 years in a mental health service in a metropolitan city in Australia. Participants were 22 program facilitators and 128 patients attending the programs. Implementation outcomes were assessed using administrative data, staff surveys and program audits. Results There was fidelity to the particular therapies at a program level. Programs were assessed as being feasible within the study setting with each hospital district developing a capacity to run CR and SCIT. The establishment of new programs improved the reach, but waiting lists indicate a need to expand capacity. There was a relatively high dropout and several factors impacted on completion of the programs - notably, acute exacerbation of psychosis. Once initiated the therapies were acceptable with no-one ceasing SCIT due to loss of interest and only 10% of participants ceasing CR due to loss of interest. Annual audits of programs found programs established were maintained and facilitators were retained. Conclusion SCIT and CR programs were successfully implemented in three hospital districts. Several factors impeded participants receiving the recommended “dose” of the programs. The maintenance of the programs in the short term is encouraging in regards to organisational fit. Dissemination of cognitive rehabilitation programs to a service population takes planning. An implementation plan is essential for guiding development and maintenance of programs. These therapies are best suited to people in a stable phase of illness. Service user co-production is recommended to improve recruitment in future studies.

Abstract Background Indigenous people in Australia, Canada, New Zealand and the United States of America experience disproportionately poor mental health compared to their non-Indigenous counterparts. To optimally allocate resources, health planners require information about the services Indigenous people use for mental health, their unmet treatment needs and the barriers to care. We reviewed population surveys of Indigenous people to determine whether the information needed to guide service development is being collected. Methods We sought national- or state-level epidemiological surveys of Indigenous populations conducted in each of the four selected countries since 1990 that asked about service use for mental health. Surveys were identified from literature reviews and web searches. We developed a framework for categorising the content of each survey. Using this framework, we compared the service use content of the surveys of Indigenous people to each other and to general population mental health surveys. We focused on identifying gaps in information coverage and topics that may require Indigenous-specific questions or response options. Results Nine surveys met our inclusion criteria. More than half of these included questions about health professionals consulted, barriers to care, perceived need for care, medications taken, number, duration, location and payment of health professional visits or use of support services or self-management. Less than half included questions about interventions received, hospital admissions or treatment dropout. Indigenous-specific content was most common in questions regarding use of support services or self-management, types of health professionals consulted, barriers to care and interventions received. Conclusions Epidemiological surveys measuring service use for mental health among Indigenous populations have been less comprehensive and less standardised than surveys of the general population, despite having assessed similar content. To better understand the gaps in mental health service systems for Indigenous people, systematically-collected subjective and objective indicators of the quality of care being delivered are needed.

Does the experience of childbirth create social bonds among first-time mothers? Previous research suggests that sharing emotionally intense or painful experiences with others leads to "identity fusion," a visceral feeling of oneness with a group that predicts strong forms of prosocial action and self-sacrifice for other group members. This study compared identity fusion with other mothers during pregnancy versus after childbirth in a sample of 164 U.S. women. Eighty-nine mothers in our sample were pregnant with their firstborn, and 75 mothers had given birth to their firstborn up to 6 months prior to the time of data collection. Results demonstrated that identity fusion with other mothers was higher for postpartum mothers than for antenatal mothers. As predicted, among postpartum mothers, those who thought that their childbirth was more painful than a typical childbirth experience reported greater identity fusion with mothers who reported having had a very difficult birth. Postpartum mothers' ruminative thought about the birth mediated the association between level of dysphoria and identity fusion, and identity fusion moderated the association between postpartum mothers' ruminative and reflective thought about the birth and their posttraumatic growth in complex ways. These findings provide evidence that perceived sharedness of the childbirth experience and thoughts about the birth are important to the process of identity fusion with other mothers, and highlight the importance of post-event processing for psychological health.

Abstract The world faces serious environmental problems. To solve them we must work together. Fortunately, humans are a very cooperative species. We have faced a range of cooperative problems in the past, and have evolved and invented a range of cooperative solutions to them—kin altruism, mutualism, reciprocity, heroism, deference, fairness, and property rights. Here, we illustrate how each of these solutions can be pressed into the service of conservation goals. Unlocking this potential will require overcoming conservationists' current cycloptic focus on only one type of cooperative problem (the prisoner's dilemma) and one type of solution (reciprocity). Only then will policy makers be able draw on the full range of cooperative dispositions and design more systematic and effective environmental interventions.

Background: Community Care Units (CCUs) are a model of community-based residential rehabilitation support available in Australia that assists people affected by severe and persistent mental illness to enhance their independent living skills and community involvement. These services have been subject to limited evaluation, and available descriptions of consumer cohorts lack relevance to the understanding of their rehabilitation needs.Method: A clinical assessment battery covering a broad range of relevant domains was completed with consumers commencing at three CCUs in Queensland, Australia, between December 2014 and December 2017 (N = 145). The cohort was described based on demographic, diagnostic, treatment-related variables, and the assessment battery. The comparability of included sites was assessed. This contemporary cohort was also compared to the pooled cohort of Australian community-based residential rehabilitation services emerging from a previous systematic review. Additionally, cluster analysis (CA) was completed in two stages based on the clinician-rated assessments: hierarchical CA (Wards method) to identify the optimal number of clusters, followed by K-means clustering.Results: Dominant features of the cohort were male sex and the primary diagnoses of schizophrenia spectrum disorders. The average consumer age was 31.4 years. Most consumers were referred from the community, had been living with family, and were not subject to involuntary treatment orders. No site-based differences were observed on demographic, diagnostic and treatment-related variables. However, some site-based variation in levels of symptoms and functional impairment emerged. Overall, the cohort was comparable with the Transitional Residential Rehabilitation (TRR) cohort defined in a previous systematic review. Through CA, a three-cluster solution emerged: Cluster 1 (15%) was characterised by higher levels of substance use comorbidity; Cluster 2 (39%) was characterised by higher levels of disability and symptoms; and Cluster 3 (46%) was distinguished by lower levels of general psychiatric symptoms.Conclusions: The cohort was generally comparable to the TRR cohort. Site-based variability in the characteristics of admitted consumers was minimal. The CA solution suggested that three different sub-groups of consumers are admitted to CCUs, which have implications for adapting the approach to rehabilitation. Recommendations include ensuring early availability of interventions to address co-morbidities and pacing rehabilitation expectations to consumers stage of recovery.

Summary: Background: Although the burden of disease in sub-Saharan Africa continues to be dominated by infectious diseases, countries in this region are undergoing a demographic transition leading to increasing prevalence of non-communicable diseases (NCDs). To inform health system responses to these changing patterns of disease, we aimed to assess changes in the burden of NCDs in sub-Saharan Africa from 1990 to 2017. Methods: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to analyse the burden of NCDs in sub-Saharan Africa in terms of disability-adjusted life-years (DALYs)—with crude counts as well as all-age and age-standardised rates per 100 000 population—with 95% uncertainty intervals (UIs). We examined changes in burden between 1990 and 2017, and differences across age, sex, and regions. We also compared the observed NCD burden across countries with the expected values based on a country's Socio-demographic Index. Findings: All-age total DALYs due to NCDs increased by 67·0% between 1990 (90·6 million [95% UI 81·0–101·9]) and 2017 (151·3 million [133·4–171·8]), reflecting an increase in the proportion of total DALYs attributable to NCDs (from 18·6% [95% UI 17·1–20·4] to 29·8% [27·6–32·0] of the total burden). Although most of this increase can be explained by population growth and ageing, the age-standardised DALY rate (per 100 000 population) due to NCDs in 2017 (21 757·7 DALYs [95% UI 19 377·1–24 380·7]) was almost equivalent to that of communicable, maternal, neonatal, and nutritional diseases (26 491·6 DALYs [25 165·2–28 129·8]). Cardiovascular diseases were the second leading cause of NCD burden in 2017, resulting in 22·9 million (21·5–24·3) DALYs (15·1% of the total NCD burden), after the group of disorders categorised as other NCDs (28·8 million [25·1–33·0] DALYs, 19·1%). These categories were followed by neoplasms, mental disorders, and digestive diseases. Although crude DALY rates for all NCDs have decreased slightly across sub-Saharan Africa, age-standardised rates are on the rise in some countries (particularly those in southern sub-Saharan Africa) and for some NCDs (such as diabetes and some cancers, including breast and prostate cancer). Interpretation: NCDs in sub-Saharan Africa are posing an increasing challenge for health systems, which have to date largely focused on tackling infectious diseases and maternal, neonatal, and child deaths. To effectively address these changing needs, countries in sub-Saharan Africa require detailed epidemiological data on NCDs. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Centre (Australia).

Background Vascular risk factors have been associated with differences in cognitive performance in epidemiological studies, but evidence in patients with coronary heart disease is more limited. Methods and Results The Montreal Cognitive Assessment score obtained 3.2±0.37 years after randomization to darapladib, a reversible inhibitor of lipoprotein phospholipase A2 or placebo was evaluated for 10 634 patients with coronary heart disease from 38 countries in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. The Montreal Cognitive Assessment scores for darapladib and placebo groups were similar (mean±SD, 25.3±3.84 versus 25.4±3.73, respectively; P=0.27) and the adjusted odds ratio (OR) for mild cognitive impairment (Montreal Cognitive Assessment score 8 years/trade school versus college/university, OR, 1.38 [1.25–1.52] and geographic grouping). Cardiovascular risk factors independently associated with cognitive impairment were history of stroke (OR, 1.43 [1.20–1.71]);

Social Evolution Forum.

We present the first neurophysiological signatures showing distinctive effects of group social context and emotional arousal on cultural perceptions, such as the efficacy of religious rituals. Using a novel protocol, EEG data were simultaneously recorded from ethnic Chinese religious believers in group and individual settings as they rated the perceived efficacy of low, medium, and high arousal spirit-medium rituals presented as video clips. Neural oscillatory patterns were then analyzed for these perceptual judgements, categorized as low, medium, and high efficacy. The results revealed distinct neural signatures and behavioral patterns between the experimental conditions. Arousal levels predicted ratings of ritual efficacy. Increased efficacy was marked by suppressed alpha and beta power, regardless of group or individual setting. In groups, efficacy ratings converged. Individual setting showed increased within-participant phase synchronization in alpha and beta bands, while group setting enhanced between-participant theta phase synchronization. This reflected group participants' orientation toward a common perspective and social coordination. These findings suggest that co-presence in groups leads to a social-tuning effect supported by between-participant theta phase synchrony. Together these neural synchrony patterns reveal how collective rituals have both individual and communal dimensions. The emotionality of spirit-medium rituals drives individual perceptions of efficacy, while co-presence in groups signals the significance of an event and socially tunes enhanced agreement in perceptual ratings. In other words, mass gatherings may foster social cohesion without necessarily requiring group-size scaling limitations of direct face-to-face interaction. This could have implications for the scaling computability of synchrony in large groups as well as for humanistic studies in areas such as symbolic interactionism.

Can moments of viral media activity transform into enduring activist movements? The killing of Cecil the lion by a trophy hunter in Zimbabwe in 2015 attracted global attention and generated enduring conservation activism in the form of monetary donations to the research unit that was studying him (WildCRU). Utilizing a longitudinal survey design, we found that intensely dysphoric reactions to Cecil's death triggered especially strong social cohesion (i.e., “identity fusion”) amongst donors. Over a 6-month period, identity fusion to WildCRU increased amongst donors. In addition, in line with an emerging psychological model of the experiential antecedents of identity fusion, cohesion amongst donors increased most for those who continued to reflect deeply on Cecil's death and felt his death to be a central event in their own lives. Our results highlight the profound capabilities of humans to commit resources to supporting others who are distant in space and time, unrelated culturally or biologically, and even (as in this case) belonging to another species altogether. In addition, our findings add to recent interdisciplinary work uncovering the precise social mechanisms by which intense group cohesion develops.

This paper presents contemporary cognitive approaches to the evolution of religious beliefs. Arguments are put forward that different types of beliefs, or ‘modes of religiosity’, occur as a result of a number of evolutionary factors (biological, cultural, socio-political etc). At the same time, religions across the world retain a significant level of common and shared elements, also explained in evolutionary terms.

The burden of mental, neurological, and substance use (MNS) disorders increased by 41% between 1990 and 2010 and now accounts for one in every 10 lost years of health globally. This sobering statistic does not take into account the substantial excess mortality associated with these disorders or the social and economic consequences of MNS disorders on affected persons, their caregivers, and society. A wide variety of effective interventions, including drugs, psychological treatments, and social interventions, can prevent and treat MNS disorders. At the population-level platform of service delivery, best practices include legislative measures to restrict access to means of self-harm or suicide and to reduce the availability of and demand for alcohol. At the community-level platform, best practices include life-skills training in schools to build social and emotional competencies. At the health-care-level platform, we identify three delivery channels. Two of these delivery channels are especially relevant from a public health perspective: self-management (eg, web-based psychological therapy for depression and anxiety disorders) and primary care and community outreach (eg, non-specialist health worker delivering psychological and pharmacological management of selected disorders). The third delivery channel, hospital care, which includes specialist services for MNS disorders and first-level hospitals providing other types of services (such as general medicine, HIV, or paediatric care), play an important part for a smaller proportion of cases with severe, refractory, or emergency presentations and for the integration of mental health care in other health-care channels, respectively. The costs of providing a significantly scaled up package of specified cost-effective interventions for prioritised MNS disorders in low-income and lower-middle-income countries is estimated at US$3-4 per head of population per year. Since a substantial proportion of MNS disorders run a chronic and disabling course and adversely affect household welfare, intervention costs should largely be met by government through increased resource allocation and financial protection measures (rather than leaving households to pay out-of-pocket). Moreover, a policy of moving towards universal public finance can also be expected to lead to a far more equitable allocation of public health resources across income groups. Despite this evidence, less than 1% of development assistance for health and government spending on health in low-income and middle-income countries is allocated to the care of people with these disorders. Achieving the health gains associated with prioritised interventions will require not just financial resources, but committed and sustained efforts to address a range of other barriers (such as paucity of human resources, weak governance, and stigma). Ultimately, the goal is to massively increase opportunities for people with MNS disorders to access services without the prospect of discrimination or impoverishment and with the hope of attaining optimal health and social outcomes.

BACKGROUND:We previously reported association of SCARB1 SNP rs10846744 with common carotid IMT (cIMT) and cardiovascular disease (CVD) events. Since rs10846744 has been reported in association with Lp-PLA2 mass and activity, we hypothesized that inflammatory pathways might mediate the association of rs10846744 with atherosclerosis. METHODS:We first examined association of rs10846744 in CVD in multiple large-scale consortium-based genome-wide association studies. We further examined 27 parameters of interest, including Lp-PLA2 mass and activity, inflammatory markers, and plasma phospholipid fatty acids, and fatty acid ratios in participants from the Multi-Ethnic Study of Atherosclerosis (MESA), as potential mediators in the pathway linking rs10846744 with cIMT and incident CVD. Finally, we examined the association of rs10846744 with Lp-PLA2 activity, cardiovascular outcomes, and interaction with the Lp-PLA2 inhibitor, darapladib, in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) and Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) studies. RESULTS:SCARB1 rs10846744 was associated with coronary artery disease events in CARDIoGRAMplusC4D (odds ratio 1.05; 95% CI [1.02, 1.07]; P = 1.4x10-4). In combined analysis across race/ethnic groups in MESA, rs10846744 was associated with Lp-PLA2 mass (P = 0.04) and activity (P = 0.001), homocysteine (P = 0.03), LDL particle number (P = 0.01), docosahexaenoic acid [DHA] (P = 0.01), docosapentaenoic acid [DPA] (P = 0.04), DPA/ eicosapentaenoic acid [EPA] ratio (P = 0.002), and DHA/EPA ratio (P = 0.008). Lp-PLA2 activity was identified as a mediator of rs10846744 with cIMT in a basic model (P = 8x10-5), but not after adjustment for CVD risk factors. There was no interaction or modifier effect of the Lp-PLA2 inhibitor darapladib assignment on the relationship between rs10846744 and major CVD events in either STABILITY or SOLID-TIMI 52. SUMMARY:SCARB1 rs10846744 is significantly associated with Lp-PLA2 activity, atherosclerosis, and CVD events, but Lp-PLA2 activity is not a mediator in the association of rs10846744 with cIMT in MESA.

Pledging lifelong loyalty to an ingroup can have far-reaching behavioural effects, ranging from ordinary acts of ingroup kindness to extraordinary acts of self-sacrifice. What motivates this important form of group commitment? Here, we propose one especially potent answer to this question-the experience of a visceral sense of oneness with a group (i.e., identity fusion). In a sample of British football fans, a population in which high levels of lifelong loyalty are thought to be common, we first examined the hypothesised relationship between fusion and perceptions of lifelong loyalty to one's club. We further explored the hypothesis that fusion and lifelong loyalty are not merely a reflection of past time investment in a group, but also reflect a deeper, memory-based process of feeling personally shaped by key group events, both euphoric and dysphoric. We found broad support for these hypotheses. Results suggest that feeling personally self-shaped by club events (e.g., crucial wins and losses), rather than time invested in the club, leads to greater identity fusion to one's club. In turn, fusion engenders a sense of lifelong club loyalty. We discuss our findings in relation to the growing literature on the experiential origins of intense social cohesion.

Social psychology is fundamentally the study of individuals in groups, yet there remain basic unanswered questions about group formation, structure, and change. We argue that the problem is methodological. Until recently, there was no way to track who was interacting with whom with anything approximating valid resolution and scale. In the current study we describe a new method that applies recent advances in image-based tracking to study incipient group formation and evolution with experimental precision and control. In this method, which we term "in vivo behavioral tracking," we track individuals' movements with a high definition video camera mounted atop a large field laboratory. We report results of an initial study that quantifies the composition, structure, and size of the incipient groups. We also apply in-vivo spatial tracking to study participants' tendency to cooperate as a function of their embeddedness in those crowds. We find that participants form groups of seven on average, are more likely to approach others of similar attractiveness and (to a lesser extent) gender, and that participants' gender and attractiveness are both associated with their proximity to the spatial center of groups (such that women and attractive individuals are more likely than men and unattractive individuals to end up in the center of their groups). Furthermore, participants' proximity to others early in the study predicted the effort they exerted in a subsequent cooperative task, suggesting that submergence in a crowd may predict social loafing. We conclude that in vivo behavioral tracking is a uniquely powerful new tool for answering longstanding, fundamental questions about group dynamics.

Naylin Bissessor1, Harvey White21Cardiology Research Fellow, 2Director of Coronary Care and Green Lane, Cardiovascular Research Unit, Green Lane Cardiovascular Research Unit, Auckland City Hospital, Auckland, New ZealandAbstract: The physiological role of the renin angiotensin aldosterone system (RAAS) is to maintain the integrity of the cardiovascular system. The effect of angiotensin II is mediated via the angiotensin type I receptor (AT1) resulting in vasoconstriction, sodium retention and myocyte growth changes. This causes myocardial remodeling which eventually leads to left ventricular hypertrophy, dilation and dysfunction. Inhibition of the RAAS with angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction has been shown to reduce cardiovascular morbidity and mortality. Angiotensin receptor blockers (ARBs) specifically inhibit the AT1 receptor. It has not been known until the performance of the VALIANT (valsartan in acute myocardial infarction trial) whether blockade of the angiotensin receptor with an ARB or combination of an ACE inhibitor and ARB leads to similar outcomes as an ACE inhibitor. The VALIANT trial demonstrated equal efficacy and non-inferiority of the ARB valsartan 160 mg bid compared with captopril 50 mg tds, when administered to high risk patients with left ventricular dysfunction or heart failure in the immediate post myocardial infarction period. The combination therapy showed no incremental benefit over ACE inhibition or an ARB alone and resulted in increased adverse effects. This review examines the role of valsartan in left ventricular dysfunction post myocardial infarction. We also discuss pharmacokinetics, dosing, side effects, and usage in the elderly.Keywords: valsartan, heart failure, left ventricular dysfunction, myocardial infarction

One of the central puzzles in the study of sociocultural evolution is how and why transitions from small-scale human groups to large-scale, hierarchically more complex ones occurred. Here we develop a spatially explicit agent-based model as a first step towards understanding the ecological dynamics of small and large-scale human groups. By analogy with the interactions between single-celled and multicellular organisms, we build a theory of group lifecycles as an emergent property of single cell demographic and expansion behaviours. We find that once the transition from small-scale to large-scale groups occurs, a few large-scale groups continue expanding while small-scale groups gradually become scarcer, and large-scale groups become larger in size and fewer in number over time. Demographic and expansion behaviours of groups are largely influenced by the distribution and availability of resources. Our results conform to a pattern of human political change in which religions and nation states come to be represented by a few large units and many smaller ones. Future enhancements of the model should include decision-making rules and probabilities of fragmentation for large-scale societies. We suggest that the synthesis of population ecology and social evolution will generate increasingly plausible models of human group dynamics.

Across three studies, we examined the role of shared negative experiences in the formation of strong social bonds--identity fusion--previously associated with individuals' willingness to self-sacrifice for the sake of their groups. Studies 1 and 2 were correlational studies conducted on two different populations. In Study 1, we found that the extent to which Northern Irish Republicans and Unionists experienced shared negative experiences was associated with levels of identity fusion, and that this relationship was mediated by their reflection on these experiences. In Study 2, we replicated this finding among Bostonians, looking at their experiences of the 2013 Boston Marathon Bombings. These correlational studies provide initial evidence for the plausibility of our causal model; however, an experiment was required for a more direct test. Thus, in Study 3, we experimentally manipulated the salience of the Boston Marathon Bombings, and found that this increased state levels of identity fusion among those who experienced it negatively. Taken together, these three studies provide evidence that shared negative experience leads to identity fusion, and that this process involves personal reflection.

This paper presents contemporary cognitive approaches to the evolution of religious beliefs. Arguments are put forward that different types of beliefs, or ‘modes of religiosity’, occur as a result of a number of evolutionary factors (biological, cultural, socio-po­litical etc). At the same time, religions across the world retain a sig­nificant level of common and shared elements, also explained in evolutionary terms.

Investigating the chemical ecology of agricultural systems continues to be a salient part of integrated pest management programs. Apple maggot fly, a key pest of apple in eastern North America, is a visual specialist with attraction to host fruit-mimicking cues. These cues have been incorporated into red spherical traps used for both monitoring and behaviorally based management. Incorporating generalist or specialist olfactory cues can potentially increase the overall success of this management system. The primary aim of this study was to evaluate the attractiveness of a generalist olfactory cue, ammonium carbonate, and the specialist olfactory cue, a five-component apple volatile blend, when included as a component of a red attracticidal sphere system. Secondly, we assessed how critical it was to maintain minimal deviation from the optimal, full-round specialist visual stimulus provided by red spheres. Finally, attracticidal spheres were deployed with specialist olfactory cues in commercial apple orchards to evaluate their potential for effective management of apple maggot. Ammonium carbonate did not increase residency, feeding time, or mortality in the laboratory-based trials. Field deployment of specialist olfactory cues increased apple maggot captures on red spheres, while the generalist cue did not. Apple maggot tolerated some deviation from the optimal visual stimulus without reducing captures on red spheres. Attracticidal spheres hung in perimeter trees in orchards resulted in acceptable and statistically identical levels of control compared with standard insecticide programs used by growers. Overall, our study contributes valuable information for developing a reliable attract-and-kill system for apple maggot., (Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the United States.)

There have been only few events in the history of molecular biology that could be compared to the discovery of microRNAs and their role in cell physiology and pathology. MicroRNAs are small, single-stranded, noncoding RNAs composed of 19-25 nucleotides (∼22 nt), which have been proven to regulate gene expression at the posttranscriptional level. The regulatory function of microRNAs was demonstrated in normal and diseased conditions. In particular, it has been linked to cell cycle regulation, cell proliferation and differentiation, inflammatory response, and apoptosis. Altered expression profiles of microRNA have been observed in many pathologies, including diabetes, rheumatoid arthritis, and several cancers. To date, more than 700 human microRNAs have been identified and in silico-based analyses estimate at least 500 more to be identified. The purpose of this review is to present the current perspective on microRNAs structure and biogenesis as well as their contribution to the etiopathogenesis of gynecological tumors. We discuss results of the recent publications that indicate possibilities of microRNAs use as novel markers for tumors screening, early diagnosis, and treatment monitoring. The possible utilization of microRNAs as prognostic factors and specific therapy targets is also reviewed., (© 2010 Wiley Periodicals, Inc.)

Apple maggot, Rhagoletis pomonella (Walsh) (Diptera: Tephritidae), is a pest of major concern to apple, Malus x domestica (Borkh.) production in eastern North America. Host plant resistance to apple maggot among apple germplasm has been previously evaluated among a small number of exotic Malus accessions and domestic hybrid selections. However, a large number of exotic accessions housed in USDA collections have never been evaluated for their susceptibility to apple pests. Additionally, previous reports of resistance need to be confirmed under both field conditions and with more rigorous laboratory evaluations. Thus, studies were conducted to evaluate the susceptibility of a number of Malus accessions housed at the USDA Plant Genetic Resources Unit "core" collection. Contrary to earlier published reports, these results suggest that some selections previously described as "resistant" are in fact susceptible to both oviposition damage and larval feeding damage by apple maggot. One domestic, disease-resistant apple accession, 'E36-7' is resistant to survival of apple maggot larvae except when the fruit is nearly ripe in late fall. This is the first report of an apple cultivar that is confirmed to be resistant to larval feeding of apple maggot. Although adults can successfully oviposit on all accessions examined, larval survival was zero in a number of small-fruited crabapple accessions classified as resistant in previous studies and also in two accessions, Malus tschonoskii (Maxim) C. K. Schneid. and M. spectabilis (Aiton) Borkh., that have not been previously evaluated.

Laboratory bioassays and field tests were conducted to compare the effectiveness of the new insecticides, imidacloprid, indoxacarb, pyriproxyfen, spinosad, thiacloprid, and thiamethoxam, against apple maggot. The activity ranking of the compounds in reducing oviposition in laboratory bioassays was: imidacloprid, 95% reduction at 11 ppm > thiamethoxam, 91% and thiacloprid, 89% reduction at 100 ppm > spinosad, 98% reduction at 316 ppm > indoxacarb, 80% reduction at 1000 ppm > pyriproxyfen, 0% reduction at 38 ppm. In laboratory bioassays, the only insecticides that were toxic to flies at concentrations equal to or below the recommended field rates were imidacloprid, (50% of flies at 11 ppm), spinosad (90% of flies at rates > 10 ppm), and thiamethoxam (approximately 50% of flies at 32 ppm). In field trials, thiacloprid was the only material that consistently controlled apple maggot fruit infestation that was comparable to standard treatments of organophosphate insecticides. Spinosad applied at weekly intervals, and indoxacarb applied as biweekly sprays provided adequate control of apple maggot damage when infestation levels in the field were low, but were not effective in preventing damage in small plots when apple maggot pressure was high.

The efficacy and safety of ondansetron 8 mg BID compared with 8 mg TID for 3 days in the prevention of nausea and vomiting in 402 patients on cyclophosphamide (> or = 500 mg/m2)-based chemotherapy were evaluated in a multicenter, randomized, double-blind, stratified study. The percentage of patients with no emetic episodes over the 3-day study period was 61% in the ondansetron BID group compared with 58% in the ondansetron TID group. Among patients with at least one emetic episode, the mean time to emesis was 14 hr and 17 min in the ondansetron BID group compared with 12 hr and 48 min in the ondansetron TID group. Patients' daily appetite ratings and nausea scores were not significantly different between groups. Clinical laboratory and adverse event profiles were similar between groups. This study is the first large-scale, double-blind trial to demonstrate that ondansetron 8 mg BID for 3 days, a dosing regimen that may enhance patient convenience and compliance, is as effective as ondansetron 8 mg TID for 3 days in the prevention of nausea and vomiting associated with cyclophosphamide-based chemotherapy.

An important new approach to curative treatment of leukemia is vigorous treatment of autologous marrow to remove residual abnormal cells in vitro prior to reinfusion. This in vitro 'purging' must destroy the malignant cells while preserving sufficient normal precursors to allow re-establishment of normal in vivo function. We have confirmed that cortivazol (CVZ), a glucocorticoid with an unusual structure, can kill dexamethasone (DEX)-resistant leukemic cells and have examined its ability to purge DEX-sensitive (CEM-C7) and -resistant (ICR-27) human leukemic blasts artificially mixed with normal marrow mononuclear cells in vitro. By carefully defining time and dose, we established a 'therapeutic window' that allowed 'cure' of the artificial remission marrow. A sufficient number of viable normal myeloid precursor cells (CFU-GM) remained to suggest that normal marrow precursors adequate for successful marrow transplantation could survive such treatment. CVZ could be a useful drug for in vitro purging of bone marrow for autologous transplantation in patients with acute lymphoblastic leukemia or non-Hodgkin's lymphoma, sensitive or resistant to standard glucocorticoid.

ESKOL, a B-lymphoblastoid cell line consisting of late differentiated cells, resembles hairy cell leukemia (HCL). It is pseudodiploid with a deleted 7q and an unbalanced translocation between chromosomes 4 and 6. It was screened by Northern hybridization for oncogenes, including H-ras, c-raf-2 (c-raf1p1), c-kit, c-myc, c-myb, c-fos, Fim-1, c-jun, ski, and c-mos, which are believed to contribute to B-cell differentiation and maturation. Interferon-alpha-2b (IFN) downregulates the expression of H-ras, c-raf-2, c-kit, c-myc, c-myb, c-fos, as determined by Northern hybridization of RNA isolated from cells harvested at time points during a 30 h time course. Downregulation of oncogenes H-ras, c-raf-2, c-kit, whose proteins are associated with cell surfaces or are cytosolar transducers, occurs before those oncogenes c-myc, c-myb, and c-fos, whose products are DNA binding proteins. This suggests a temporal perturbation of signal transduction by IFN. No change in oncogene expression occurred in non-treated cells nor were these oncogenes expressed in the non-transformed B-lymphoblast cell line, Wil-2, under the same treatment regimen. The basis for the IFN perturbation is not understood; yet the role of these oncogenes as signal transducers in differentiation and proliferation of human hematopoietic progenitors is unfolding, and ESKOL is an excellent system in which to study this phenomenon.

Didemnin B is a cyclic peptide isolated from the marine tunicate Trididemnin cyanophorum. It is a known potent inhibitor of RNA, DNA and protein synthesis, with activity against the murine B16 melanoma. Fourteen patients with disseminated malignant melanoma were evaluated in a Southwest Oncology Group phase II trial of didemnin B at 4.2 mg/m2 by 30 min i.v. infusion every 28 days (SWOG-8754). Only patients with no prior chemotherapy were eligible; prior radiation therapy, surgery and at most one prior biologic regimen were allowed. Patients with brain metastasis were eligible only if the disease in the brain had been treated and controlled. All patients had to have normal renal and hepatic function and adequate granulocyte and platelet counts, a performance status of 0-2, and bidimensionally measurable disease. Fourteen patients were entered on the study; five received one and nine received two courses of didemnin B. No responses were noted among the 11 patients evaluable for response. Five patients developed unusual but reversible hypersensitivity reactions during the second course of therapy. Other toxicity in this trial was nausea and vomiting and diarrhea, none of severity greater than grade 3. Given the lack of antitumor efficacy and the unusual toxicity, further evaluation of didemnin B in this dose and schedule in malignant melanoma is not warranted.

Purpose: This study compares the efficacy and safety of ondansetron alone with that of ondansetron plus dexamethasone in the prevention of emesis induced by high-dose cisplatin (> or = 100 mg/m2)., Patients and Methods: This multicenter study used a randomized, double-blind, parallel-group design. Chemotherapy-naive patients were randomized to receive intravenous (IV) ondansetron (Zofran, Cerenex Pharmaceuticals, Research Triangle Park, NC) 0.15 mg/kg for three doses every 4 hours beginning 30 minutes before cisplatin administration either alone or in combination with dexamethasone 20 mg administered 45 minutes before cisplatin. Cisplatin (> or = 100 mg/m2) was administered as a single infusion (< or = 3 hours). Patients were monitored for emetic episodes (EEs), adverse events, and laboratory safety parameters for 24 hours after cisplatin administration., Results: A total of 275 patients were enrolled. Of these, 245 were assessable for efficacy. Patients who received ondansetron plus dexamethasone had a higher complete antiemetic response rate (61% v 46%, P = .02) and less nausea (posttreatment visual analog scale mean 18.2 v 32.8, P < .001) than did those who received ondansetron alone. The time to the first EE was longer for patients in the group that received ondansetron plus dexamethasone (P = .005). Headache (12%), diarrhea (2%), and abdominal colic (1%) were the most common antiemetic-related adverse events reported. The incidence of adverse events was similar between the treatment groups., Conclusion: IV ondansetron in combination with dexamethasone is safe and more effective than ondansetron alone in the prevention of emesis induced by high-dose cisplatin.

Sixteen eligible patients with hepatocellular carcinoma, previously untreated, received merbarone 1000 mg/m2/d for five consecutive days every 21 days. No complete or partial response to treatment was obtained. Seven patients had grade 4 granulocytopenia. One patient died with renal failure. Merbarone in this dose and schedule was ineffective in the treatment of hepatocellular carcinoma.

Objective: To evaluate the efficacy and safety of oral ondansetron (Zofran) as an antiemetic in patients receiving cyclophosphamide-based chemotherapy., Design: A multicenter, randomized, double-blind, stratified, placebo-controlled trial conducted between March 1989 and January 1990., Setting: Twenty-seven oncology centers including university hospitals, community cancer centers, and private medical oncology practices., Patients: A total of 349 chemotherapy-naive patients having their first cycle of cyclophosphamide (> or = 450 mg/m2)-based chemotherapy. Patients also received methotrexate (> or = 30 mg/m2) or doxorubicin (> or = 35 mg/m2). All patients were evaluated for safety and 318 (91%) were evaluated for efficacy., Interventions: Patients were randomly assigned to one of four treatment groups: placebo, 1 mg, 4 mg, or 8 mg of ondansetron. Assigned study medication was taken three times per day for 3 consecutive days., Measurements: Time and number of emetic episodes as well as degree of nausea were recorded by patients for each of the 3 study days., Results: Compared with placebo, all three doses of ondansetron were superior (P < 0.001) in preventing vomiting and controlling nausea. A complete response (no emetic episodes) was observed in 19%, 57%, 65%, and 66% of patients in the placebo, 1-mg, 4-mg, and 8-mg ondansetron groups, respectively. For patients who received higher-dose cyclophosphamide and doxorubicin, a dose-related trend in antiemetic efficacy of ondansetron was observed. Mild headache and constipation were the most frequently reported adverse events. No extrapyramidal reactions were observed., Conclusion: Oral ondansetron is a safe and effective antiemetic that is more efficacious than placebo for patients receiving cyclophosphamide-based chemotherapy.

Despite recent advances in control of acute emesis, delayed nausea and vomiting following cisplatin-based chemotherapy remain a significant cause of treatment-related morbidity. Ondansetron, a selective 5HT3 receptor antagonist, is effective in preventing acute emesis in the initial 24-h period following high-dose cisplatin. The efficacy and safety of ondansetron in preventing the delayed emesis syndrome during days 2-5 after cisplatin (> or = 100 mg/m2) were evaluated in a double-blind, placebo-controlled multicentre trial. 50 patients having two or fewer emetic episodes during the first 24 h were randomised to receive ondansetron (16 mg) or placebo orally three times daily beginning 24 h after cisplatin. Rates of complete control of emesis were higher in ondansetron-treated patients during each study day, 59-78%, compared with 39-50% in placebo-treated patients, but the differences were statistically superior only on the third study day (P = 0.009). 40% of patients in the ondansetron treatment arm and 33% treated with placebo had complete control of emesis during the entire 4-day study period (P = 0.648). Withdrawal from study due to nausea and vomiting occurred in 13% of ondansetron-treated patients compared with 33% in the placebo arm (P = 0.102). Control of nausea was better with ondansetron, but differences were not statistically significant. Adverse effects of oral ondansetron given in this dose schedule were minimal. These data suggest that the delayed emesis syndrome may be partially mediated through the 5HT3 receptor, but that a serotonin antagonist alone provides inadequate control. Further investigation of ondansetron-based therapy in this clinical setting is warranted.