Multiobjective genetic programming can improve the explanatory capabilities of mechanism-based models of social systems

The generative approach to social science, in which agent-based simulations (or other complex systems models) are executed to reproduce a known social phenomenon, is an important tool for realist explanation. However, a generative model, when suitably calibrated and validated using empirical data, represents just one viable candidate set of entities and mechanisms. The model only partially addresses the needs of an abductive reasoning process - specifically it does not provide insight into other viable sets of entities or mechanisms, nor suggest which of these are fundamentally constitutive for the phenomenon to exist. In this paper, we propose a new model discovery framework that more fully captures the needs of realist explanation. The framework exploits the implicit ontology of an existing human-built generative model to propose and test a plurality of new candidate model structures. Genetic programming is used to automate this search process. A multi-objective approach is used, which enables multiple perspectives on the value of any particular generative model - such as goodness-of-fit, parsimony, and interpretability - to be represented simultaneously. We demonstrate this new framework using a complex systems modeling case study of change and stasis in societal alcohol use patterns in the US over the period 1980-2010. The framework is successful in identifying three competing explanations of these alcohol use patterns, using novel integrations of social role theory not previously considered by the human modeler. Practitioners in complex systems modeling should use model discovery to improve the explanatory utility of the generative approach to realist social science

Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness.

In the fourth article of a five-part series providing a global perspective on integrating mental health, Sylvia Kaaya and colleagues discuss the importance of integrating mental health interventions into HIV prevention and treatment platforms. Please see later in the article for the Editors' Summary

Characteristics and drinking behaviour of patients on antiretroviral therapy who drink and attend HIV clinics in Tshwane, South Africa: Implications for intervention

Background. Patients on antiretroviral therapy (ART) who drink alcohol are at risk of poor medication adherence and negative health outcomes.Objectives. To explore the drinking behaviour of patients on ART and assess the associations between drinking, adherence to ART and viral load, and in particular factors associated with binge drinking (≥6 drinks per occasion) at least monthly.Methods. We recruited 623 HIV patients from six hospitals in the Tshwane metropole who scored positive on the Alcohol Use Disorders Identification Test (AUDIT-C) but were ‘non-dependent’ drinkers into a randomised controlled trial. This article reports on baseline data.Results. Of the patients, 51% reported drinking in the past week, 60% of men and 33% of women consumed ≥6 standard drinks on a typical drinking day, and 19% of men and 5% of women were identified as drinking at harmful levels. Over a quarter reported having a friend or relative, or a doctor or other healthcare worker, express concern about their drinking or suggest that they cut down. AUDIT total scores were significantly negatively correlated with self-reported adherence to ART and positively correlated with viral load. Number of years on ART was not significantly associated with binge drinking. Persons who were employed part time (odds ratio (OR) 1.474) or were self-employed (OR 2.135) were more likely to binge-drink than unemployed persons. Beer drinkers (OR 1.716) were more at risk for binge drinking than non-beer drinkers, and persons who drank monthly or less (OR 0.053) or 2 - 4 times a month (OR 0.168) were less at risk for bingeing than those who drank ≥4 times per week.Conclusions. The high volume of alcohol consumed per occasion by patients on ART, especially beer and spirits drinkers, is a concern. Interventions that address structural drivers of heavy drinking and target HIV patients at risk of heavy drinking are needed.

HIV Prevention in Care and Treatment Settings: Baseline Risk Behaviors among HIV Patients in Kenya, Namibia, and Tanzania.

HIV care and treatment settings provide an opportunity to reach people living with HIV/AIDS (PLHIV) with prevention messages and services. Population-based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV, yet data are limited regarding HIV risk behaviors of PLHIV in clinical care. This paper describes the baseline sociodemographic, HIV transmission risk behaviors, and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa. The study was a longitudinal group-randomized trial in 9 intervention clinics and 9 comparison clinics in Kenya, Namibia, and Tanzania (N = 3538). Baseline participants were mostly female, married, had less than a primary education, and were relatively recently diagnosed with HIV. Fifty-two percent of participants had a partner of negative or unknown status, 24% were not using condoms consistently, and 11% reported STI symptoms in the last 6 months. There were differences in demographic and HIV transmission risk variables by country, indicating the need to consider local context in designing studies and using caution when generalizing findings across African countries. Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors, which supports the need for prevention with PLHIV (PwP). TRIAL REGISTRATION: ClinicalTrials.gov NCT01256463

Implementing Evidence-Based Alcohol Interventions in a Resource-Limited Setting: Novel Delivery Strategies in Tomsk, Russia

Effective implementation of evidence-based interventions in “real-world” settings can be challenging. Interventions based on externally valid trial findings can be even more difficult to apply in resource-limited settings, given marked differences—in provider experience, patient population, and health systems—between those settings and the typical clinical trial environment. Under the auspices of the Integrated Management of Physician-Delivered Alcohol Care for Tuberculosis Patients (IMPACT) study, a randomized, controlled effectiveness trial, and as an integrated component of tuberculosis treatment in Tomsk, Russia, we adapted two proven alcohol interventions to the delivery of care to 200 patients with alcohol use disorders. Tuberculosis providers performed screening for alcohol use disorders and also delivered naltrexone (with medical management) or a brief counseling intervention either independently or in combination as a seamless part of routine care. We report the innovations and challenges to intervention design, training, and delivery of both pharmacologic and behavioral alcohol interventions within programmatic tuberculosis treatment services. We also discuss the implications of these lessons learned within the context of meeting the challenge of providing evidence-based care in resource-limited settings. (Harv Rev Psychiatry 2012;20:58–67.

Introducing CASCADEPOP: an open-source sociodemographic simulation platform for US health policy appraisal

Largescale individual-level and agent-based models are gaining importance in health policy appraisal and evaluation. Such models require the accurate depiction of the jurisdiction’s population over extended time periods to enable modeling of the development of non-communicable diseases under consideration of historical, sociodemographic developments. We developed CASCADEPOP to provide a readily available sociodemographic micro-synthesis and microsimulation platform for US populations. The micro-synthesis method used iterative proportional fitting to integrate data from the US Census, the American Community Survey, the Panel Study of Income Dynamics, Multiple Cause of Death Files, and several national surveys to produce a synthetic population aged 12 to 80 years on 01/01/1980 for five states (California, Minnesota, New York, Tennessee, and Texas) and the US. Characteristics include individuals’ age, sex, race/ethnicity, marital/employment/parental status, education, income and patterns of alcohol use as an exemplar health behavior. The microsimulation simulates individuals’ sociodemographic life trajectories over 35 years to 31/12/2015 accounting for population developments including births, deaths, and migration. Results comparing the 1980 micro-synthesis against observed data shows a successful depiction of state and US population characteristics and of drinking. Comparing the microsimulation over 30 years with Census data also showed the successful simulation of sociodemographic developments. The CASCADEPOP platform enables modelling of health behaviors across individuals’ life courses and at a population level. As it contains a large number of relevant sociodemographic characteristics it can be further developed by researchers to build US agent-based models and microsimulations to examine health behaviors, interventions, and policies

Separating chemotherapy-related developmental neurotoxicity from cytotoxicity in monolayer and neurosphere cultures of human fetal brain cells

Chemotherapy-induced neurotoxicity can reduce the quality of life of patients by affecting their intelligence, senses and mobility. Ten percent of safety-related late-stage clinical failures are due to neurological side effects. Animal models are poor in predicting human neurotoxicity due to interspecies differences and most in vitro assays cannot distinguish neurotoxicity from general cytotoxicity for chemotherapeutics. We developed in vitro assays capable of quantifying the paediatric neurotoxic potential for cytotoxic drugs. Mixed cultures of human fetal brain cells were differentiated in monolayers and as 3D-neurospheres in the presence of non-neurotoxic chemotherapeutics (etoposide, teniposide) or neurotoxicants (methylmercury). The cytotoxic potency towards dividing progenitors versus differentiated neurons and astrocytes was compared using: (1) immunohistochemistry staining and cell counts in monolayers; (2) through quantitative Western blots in neurospheres; and (3) neurosphere migration assays. Etoposide and teniposide, were 5–10 times less toxic to differentiated neurons compared to the mix of all cells in monolayer cultures. In contrast, the neurotoxicant methylmercury did not exhibit selectivity and killed all cells with the same potency. In 3D neurospheres, etoposide and teniposide were 24 to 10 times less active against neurons compared to all cells. These assays can be used prioritise drugs for local drug delivery to brain tumours

SMART syndrome: a late reversible complication after radiation therapy for brain tumours

With intensified treatment leading to longer survival, complications of therapy for brain tumours are more frequently observed. Regarding radiation therapy, progressive and irreversible white matter disease with cognitive decline is most feared. We report on four patients with reversible clinical and radiological features occurring years after radiation for brain tumours, suggestive for the so called SMART syndrome (stroke-like migraine attacks after radiation therapy). All four patients (males, age 36–60 years) had been treated with focal brain radiation for a primary brain tumour or with whole-brain radiation therapy for brain metastases. Ranging from 2 to 10 years following radiation therapy patients presented with headache and focal neurological deficits, suggestive for tumour recurrence. Two patients also presented with focal seizures. MRI demonstrated typical cortical swelling and contrast enhancement, primarily in the parieto-occipital region. On follow-up both clinical and MRI features improved spontaneously. Three patients eventually proved to have tumour recurrence. The clinical and radiological picture of these patients is compatible with the SMART syndrome, a rare complication of radiation therapy which is probably under recognized in brain tumour patients. The pathophysiology of the SMART syndrome is poorly understood but bears similarities with the posterior reversible encephalopathy syndrome (PRES). These four cases underline that the SMART syndrome should be considered in patients formerly treated with radiation therapy for brain tumours, who present with new neurologic deficits. Before the diagnosis of SMART syndrome can be established other causes, such as local tumour recurrence, leptomeningeal disease or ischemic disease should be ruled out

Developing a method to derive alcohol-attributable fractions for HIV/AIDS mortality based on alcohol's impact on adherence to antiretroviral medication

<p>Abstract</p> <p>Background</p> <p>Alcohol consumption is causally linked to nonadherence to antiretroviral treatment that in turn causes an increase in HIV/AIDS mortality. This article presents a method to calculate the percentage of HIV/AIDS deaths attributable to alcohol consumption and the associated uncertainty.</p> <p>Methods</p> <p>By combining information on risk relations from a number of published sources, we estimated alcohol-attributable fractions (AAFs) of HIV/AIDS in a stepwise procedure. First, we estimated the effect of alcohol consumption on adherence to antiretroviral treatment, and then we combined this estimate with the impact of nonadherence on death. The 95% uncertainty intervals were computed by estimating the variance of the AAFs using Taylor series expansions of one and multiple variables. AAFs were determined for each of the five Global Burden of Disease regions of Africa, based on country-specific treatment and alcohol consumption data from 2005.</p> <p>Results</p> <p>The effects of alcohol on HIV/AIDS in the African Global Burden of Disease regions range from 0.03% to 0.34% for men and from 0% to 0.17% for women, depending on region and age category. The detrimental effect of alcohol consumption was statistically significant in every region and age category except for the North Africa/Middle East region.</p> <p>Conclusions</p> <p>Although the method has its limitations, it was shown to be feasible and provided estimates of the impact of alcohol use on the mortality outcome of HIV/AIDS.</p