Patient information leaflets (PILs) for UK randomised controlled trials : a feasibility study exploring whether they contain information to support decision making about trial participation

Peer reviewedPublisher PD

Is Violent Radicalisation Associated with Poverty, Migration, Poor Self-Reported Health and Common Mental Disorders?

BACKGROUND: Doctors, lawyers and criminal justice agencies need methods to assess vulnerability to violent radicalization. In synergy, public health interventions aim to prevent the emergence of risk behaviours as well as prevent and treat new illness events. This paper describes a new method of assessing vulnerability to violent radicalization, and then investigates the role of previously reported causes, including poor self-reported health, anxiety and depression, adverse life events, poverty, and migration and socio-political factors. The aim is to identify foci for preventive intervention. METHODS: A cross-sectional survey of a representative population sample of men and women aged 18-45, of Muslim heritage and recruited by quota sampling by age, gender, working status, in two English cities. The main outcomes include self-reported health, symptoms of anxiety and depression (common mental disorders), and vulnerability to violent radicalization assessed by sympathies for violent protest and terrorist acts. RESULTS: 2.4% of people showed some sympathy for violent protest and terrorist acts. Sympathy was more likely to be articulated by the under 20s, those in full time education rather than employment, those born in the UK, those speaking English at home, and high earners (>£75,000 a year). People with poor self-reported health were less likely to show sympathies for violent protest and terrorism. Anxiety and depressive symptoms, adverse life events and socio-political attitudes showed no associations. CONCLUSIONS: Sympathies for violent protest and terrorism were uncommon among men and women, aged 18-45, of Muslim heritage living in two English cities. Youth, wealth, and being in education rather than employment were risk factors

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Might Depression, Psychosocial Adversity, and Limited Social Assets Explain Vulnerability to and Resistance against Violent Radicalisation?

BACKGROUND: This study tests whether depression, psychosocial adversity, and limited social assets offer protection or suggest vulnerability to the process of radicalisation. METHODS: A population sample of 608 men and women of Pakistani or Bangladeshi origin, of Muslim heritage, and aged 18-45 were recruited by quota sampling. Radicalisation was measured by 16 questions asking about sympathies for violent protest and terrorism. Cluster analysis of the 16 items generated three groups: most sympathetic (or most vulnerable), most condemning (most resistant), and a large intermediary group that acted as a reference group. Associations were calculated with depression (PHQ9), anxiety (GAD7), poor health, and psychosocial adversity (adverse life events, perceived discrimination, unemployment). We also investigated protective factors such as the number social contacts, social capital (trust, satisfaction, feeling safe), political engagement and religiosity. RESULTS: Those showing the most sympathy for violent protest and terrorism were more likely to report depression (PHQ9 score of 5 or more; RR = 5.43, 1.35 to 21.84) and to report religion to be important (less often said religion was fairly rather than very important; RR = 0.08, 0.01 to 0.48). Resistance to radicalisation measured by condemnation of violent protest and terrorism was associated with larger number of social contacts (per contact: RR = 1.52, 1.26 to 1.83), less social capital (RR = 0.63, 0.50 to 0.80), unavailability for work due to housekeeping or disability (RR = 8.81, 1.06 to 37.46), and not being born in the UK (RR = 0.22, 0.08 to 0.65). CONCLUSIONS: Vulnerability to radicalisation is characterised by depression but resistance to radicalisation shows a different profile of health and psychosocial variables. The paradoxical role of social capital warrants further investigation

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Enrichment of Omnivorous Cercozoan Nanoflagellates from Coastal Baltic Sea Waters

Free-living nano-sized flagellates are important bacterivores in aquatic habitats. However, some slightly larger forms can also be omnivorous, i.e., forage upon both bacterial and eukaryotic resources. This hitherto largely ignored feeding mode may have pronounced implications for the interpretation of experiments about protistan bacterivory. We followed the response of an uncultured group of omnivorous cercozoan nanoflagellates from the Novel Clade 2 (Cerc_BAL02) to experimental food web manipulation in samples from the Gulf of Gdańsk (Southern Baltic Sea). Seawater was either prefiltered through 5 µm filters to exclude larger predators of nanoflagellates (F-treatment), or prefiltered and subsequently 1∶10 diluted with sterile seawater (F+D-treatment) to stimulate the growth of both, flagellates and bacteria. Initially, Cerc_BAL02 were rapidly enriched under both conditions. They foraged on both, eukaryotic prey and bacteria, and were highly competitive at low concentrations of food. However, these omnivores were later only successful in the F+D treatment, where they eventually represented almost one fifth of all aplastidic nanoflagellates. By contrast, their numbers stagnated in the F-treatment, possibly due to top-down control by a concomitant bloom of other, unidentified flagellates. In analogy with observations about the enrichment of opportunistically growing bacteria in comparable experimental setups we suggest that the low numbers of omnivorous Cerc_Bal02 flagellates in waters of the Gulf of Gdańsk might also be related to their vulnerability to grazing pressure

Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish

A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway

Repeated Assessments of Informed Consent Comprehension among HIV-Infected Participants of a Three-Year Clinical Trial in Botswana

Informed consent (IC) has been an international standard for decades for the ethical conduct of clinical trials. Yet frequently study participants have incomplete understanding of key issues, a problem exacerbated by language barriers or lack of familiarity with research concepts. Few investigators measure participant comprehension of IC, while even fewer conduct interim assessments once a trial is underway.We assessed comprehension of IC using a 20-question true/false quiz administered in 6-month intervals in the context of a placebo-controlled, randomized trial for the prevention of tuberculosis among HIV-infected adults in Botswana (2004-2009). Quizzes were offered in both Setswana and English. To enroll in the TB trial, participants were required to have ≥ 16/20 correct responses. We examined concepts understood and the degree to which understanding changed over three-years. We analyzed 5,555 quizzes from 1,835 participants. The participants' highest education levels were: 28% primary, 59% secondary, 9% tertiary and 7% no formal education. Eighty percent of participants passed the enrollment quiz (Quiz1) on their first attempt and the remainder passed on their second attempt. Those having higher than primary education and those who took the quiz in English were more likely to receive a passing score on their first attempt (adjusted odds ratios and 95% confidence intervals, 3.1 (2.4-4.0) and 1.5 (1.2, 1.9), respectively). The trial's purpose or procedures were understood by 90-100% of participants, while 44-77% understood randomization, placebos, or risks. Participants who failed Quiz1 on their initial attempt were more likely to fail quizzes later in the trial. Pass rates improved with quiz re-administration in subsequent years.Administration of a comprehension quiz at enrollment and during follow-up was feasible in a large, international collaboration and efficiently determined IC comprehension by trial participants. Strategies to improve understanding of concepts like placebos and randomization are needed. Comprehension assessments throughout a study may reinforce key concepts

Imaging and Modeling Data from the Hydrogen Epoch of Reionization Array

We analyze data from the Hydrogen Epoch of Reionization Array. This is the third in a series of papers on the closure phase delay-spectrum technique designed to detect the HI 21cm emission from cosmic reionization. We present the details of the data and models employed in the power spectral analysis, and discuss limitations to the process. We compare images and visibility spectra made with HERA data, to parallel quantities generated from sky models based on the GLEAM survey, incorporating the HERA telescope model. We find reasonable agreement between images made from HERA data, with those generated from the models, down to the confusion level. For the visibility spectra, there is broad agreement between model and data across the full band of $\sim 80$MHz. However, models with only GLEAM sources do not reproduce a roughly sinusoidal spectral structure at the tens of percent level seen in the observed visibility spectra on scales $\sim 10$ MHz on 29 m baselines. We find that this structure is likely due to diffuse Galactic emission, predominantly the Galactic plane, filling the far sidelobes of the antenna primary beam. We show that our current knowledge of the frequency dependence of the diffuse sky radio emission, and the primary beam at large zenith angles, is inadequate to provide an accurate reproduction of the diffuse structure in the models. We discuss implications due to this missing structure in the models, including calibration, and in the search for the HI 21cm signal, as well as possible mitigation techniques

Direct and indirect interactions between ants ( Pheidole megacephala ), scales ( Coccus viridis ) and plants ( Pluchea indica )

This study investigated direct and indirect interactions between the ant, Pheidole megacephala (Fabr.), the green scale, Coccus viridis (Green), and the scale's host plant, Pluchea indica (L.). To examine the influence of ants on scales and host plants, scale population densities, scale mortality rates, and plant performance were studied on control host plants with ants and host plants from which ants had been removed. Plants with ants present had significantly greater scale population densities and scale reproductive rates than did plants without ants. Scale mortality from both parasitism and other causes was increased on plants without ants relative to plants with ants. Predator introduction experiments showed that P. megacephala removes predatory coccinellid larvae, even when they are covered with a protective coating. Host plants from which ants had been removed had significantly higher degrees of honeydew accumulation, which resulted in greater colonization by sooty mold and greater rates of leaf death and abscission. Ants also removed herbivorous lepidopteran larvae from plants. Results are discussed in terms of the potential of P. megacephala to exert direct and indirect positive effects on scale populations and an indirect positive effect on Pluchea indica .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47790/1/442_2004_Article_BF00325261.pd