Can screening and brief intervention lead to population-level reductions in alcohol-related harm?

A distinction is made between the clinical and public health justifications for screening and brief intervention (SBI) against hazardous and harmful alcohol consumption. Early claims for a public health benefit of SBI derived from research on general medical practitioners' (GPs') advice on smoking cessation, but these claims have not been realized, mainly because GPs have not incorporated SBI into their routine practice. A recent modeling exercise estimated that, if all GPs in England screened every patient at their next consultation, 96% of the general population would be screened over 10 years, with 70-79% of excessive drinkers receiving brief interventions (BI); assuming a 10% success rate, this would probably amount to a population-level effect of SBI. Thus, a public health benefit for SBI presupposes widespread screening; but recent government policy in England favors targeted versus universal screening, and in Scotland screening is based on new registrations and clinical presentation. A recent proposal for a national screening program was rejected by the UK National Health Service's National Screening Committee because 1) there was no good evidence that SBI led to reductions in mortality or morbidity, and 2) a safe, simple, precise, and validated screening test was not available. Even in countries like Sweden and Finland, where expensive national programs to disseminate SBI have been implemented, only a minority of the population has been asked about drinking during health-care visits, and a minority of excessive drinkers has been advised to cut down. Although there has been research on the relationship between treatment for alcohol problems and population-level effects, there has been no such research for SBI, nor have there been experimental investigations of its relationship with population-level measures of alcohol-related harm. These are strongly recommended. In this article, conditions that would allow a population-level effect of SBI to occur are reviewed, including their political acceptability. It is tentatively concluded that widespread dissemination of SBI, without the implementation of alcohol control measures, might have indirect influences on levels of consumption and harm but would be unlikely on its own to result in public health benefits. However, if and when alcohol control measures were introduced, SBI would still have an important role in the battle against alcohol-related harm

Predicting reliability through structured expert elicitation with the repliCATS (Collaborative Assessments for Trustworthy Science) process

As replications of individual studies are resource intensive, techniques for predicting the replicability are required. We introduce the repliCATS (Collaborative Assessments for Trustworthy Science) process, a new method for eliciting expert predictions about the replicability of research. This process is a structured expert elicitation approach based on a modified Delphi technique applied to the evaluation of research claims in social and behavioural sciences. The utility of processes to predict replicability is their capacity to test scientific claims without the costs of full replication. Experimental data supports the validity of this process, with a validation study producing a classification accuracy of 84% and an Area Under the Curve of 0.94, meeting or exceeding the accuracy of other techniques used to predict replicability. The repliCATS process provides other benefits. It is highly scalable, able to be deployed for both rapid assessment of small numbers of claims, and assessment of high volumes of claims over an extended period through an online elicitation platform, having been used to assess 3000 research claims over an 18 month period. It is available to be implemented in a range of ways and we describe one such implementation. An important advantage of the repliCATS process is that it collects qualitative data that has the potential to provide insight in understanding the limits of generalizability of scientific claims. The primary limitation of the repliCATS process is its reliance on human-derived predictions with consequent costs in terms of participant fatigue although careful design can minimise these costs. The repliCATS process has potential applications in alternative peer review and in the allocation of effort for replication studies

The caribbean coastal marine productivity program (CARICOMP)

CARICOMP is a regional scientific program to study land-sea interaction processes in the Caribbean coastal zone. It has been collecting data since 1992, when a Data Management Centre was established at the University of the West Indies in Jamaica. Initially it focuses on documenting the structure and productivity of major coastal communities (mangrove forests, seagrass meadows and coral reefs) at relatively undisturbed sites in diverse physical settings. Second, by regular recording of physical and biological parameters, it monitors for change, seeking to distinguish natural from anthropogenic disturbance. Third, it constitutes a regional network of observers, able to collaborate on studies of region-wide events. Examples are presented of the diverse data sets collected by the Program.Fil: Alcolado, Pedro M.. Instituto de Oceanología; CubaFil: Alleng, Gerard. No especifíca;Fil: Bonair, Kurt. No especifíca;Fil: Bone, David. Universidad Simón Bolívar; VenezuelaFil: Buchan, Kenneth. No especifíca;Fil: Bush, Phillippe G.. Protection and Conservation Unit; Islas CaimánFil: De Meyer, Kalli. No especifíca;Fil: Garcia, Jorge R.. Universidad de Puerto Rico; Puerto RicoFil: Garzón Ferreira, Jaime. Instituto de Investigaciones Marinas y Costeras; ColombiaFil: Gayle, Peter M. H.. Discovery Bay Marine Laboratory; JamaicaFil: Gerace, Donald T.. Bahamian Field Station; BahamasFil: Geraldes, Francisco X.. Universidad Autonoma de Santo Domingo.; República DominicanaFil: Dahlgren, Eric Jordán. Universidad Nacional Autónoma de México; MéxicoFil: Kjferve, Björn. University of South Carolina; Estados UnidosFil: Klein, Eduardo. Universidad Simón Bolívar; VenezuelaFil: Koltes, Karen. Smithsonian Institution; Estados UnidosFil: Laydoo, Richard S.. No especifíca;Fil: Linton, Dulcie M.. University of the West Indies ; JamaicaFil: Ogden, John C.. Florida Institute of Oceanography; Estados UnidosFil: Oxenford, Hazel A.. McGill University; BarbadosFil: Parker, Christoph. McGill University; BarbadosFil: Penchaszadeh, Pablo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Pors, Leon P. P. J.. Universidad Simón Bolívar; VenezuelaFil: Ramírez Ramírez, Javier. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados. Departamento de Física; MéxicoFil: Ruiz Rentería, Francisco. Universidad Nacional Autónoma de México; MéxicoFil: Ryan, Joseph D.. Centro de Investigación y Documentación de la Costa Atlántica; NicaraguaFil: Smith, Struan R.. Bermuda Biological Station for Research; BermudasFil: Tschirky, John. Latin American and Caribbean Division; Estados UnidosFil: Varela, Ramon. Estación de Investigaciones Marinas de Margarita; VenezuelaFil: Walker, Susan. No especifíca;Fil: Weil, Ernesto. Universidad de Puerto Rico; Puerto RicoFil: Wiebe, William J.. University of Georgia; Estados UnidosFil: Woodley, Jeremy D.. University of the West Indies; JamaicaFil: Zieman, Joseph C.. University of Virginia; Estados Unido

RNA Silencing of Mcl-1 Enhances ABT-737-Mediated Apoptosis in Melanoma: Role for a Caspase-8-Dependent Pathway

BACKGROUND: Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10) activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity

Copper binding to the Alzheimer’s disease amyloid precursor protein

Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). Copper binding to this domain has been shown to reduce Aβ levels and hence a molecular understanding of the interaction between metal and protein could lead to the development of novel therapeutics to treat the disease. We have recently determined the three-dimensional structures of apo and copper bound forms of CuBD. The structures provide a mechanism by which CuBD could readily transfer copper ions to other proteins. Importantly, the lack of significant conformational changes to CuBD on copper binding suggests a model in which copper binding affects the dimerisation state of APP leading to reduction in Aβ production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer’s disease

Plasma and Erythrocyte Fatty Acid Patterns in Patients with Recurrent Depression: A Matched Case-Control Study

The polyunsaturated fatty acid (PUFA) composition of (nerve) cell membranes may be involved in the pathophysiology of depression. Studies so far, focussed mainly on omega-3 and omega-6 PUFAs. In the present study, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and PUFAs of the omega-3, -6 and -9 series in plasma and erythrocytes of patients with recurrent major depressive disorder (MDD-R) were compared with controls.We carried out a case-control study. The sample consisted of 137 patients with MDD-R and 65 matched non-depressed controls. In plasma and erythrocytes of patients with MDD-R the concentrations of most of the SFAs and MUFAs, and additionally erythrocyte PUFAs, all with a chain length > 20 carbon (C) atoms, were significantly lower than in the controls. In contrast, the concentrations of most of the shorter chain members (< or = 18C) of the SFAs and MUFAs were significantly higher in the patients. Estimated activities of several elongases in plasma of patients were significantly altered, whereas delta-9 desaturase activity for C14:0 and C18:0 was significantly higher.The fatty acid status of patients with MDD-R not only differs with regard to omega-3 and omega-6 PUFAs, but also concerns other fatty acids. These alterations may be due to: differences in diet, changes in synthesizing enzyme activities, higher levels of chronic (oxidative) stress but may also result from adaptive strategies by providing protection against enhanced oxidative stress and production of free radicals

Molecular psychiatry of zebrafish

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research

Reproductive health and lifestyle factors associated with health-related quality of life among perinatally HIV-infected adolescents in Uganda

Background With increased survival of perinatally HIV - infected adolescents due to antiretroviral therapy (ART), the focus of HIV care has shifted to health-related quality of life (HRQoL) as a measure of disease progression, effects of ART co-morbidity and prognosis. We assessed factors associated with better HRQoL in perinatally HIV -infected adolescents in Uganda by determining the associations between sexual and reproductive health (SRH) or lifestyle experiences on HRQoL. Methods In a cross-sectional study, data on SRH, lifestyle experiences, socio demographic factors, communication with parents on sexuality and satisfaction of SRH services in ART clinics were collected from 614 HIV perinatally infected adolescents aged 10–19 using an interviewer-administered survey questionnaire. HRQoL data were collected using the Medical Outcomes Study HIV Health Survey instrument (MOS-HIV). Factors associated with better HRQoL were analysed using multiple logistic regression. Results The mean age was 16.2 ± 2.1 years, 362 (58.8 %) were females and 210 (34.2 %) were sexually active. Adolescents on ART were twice likely to present with better physical health (AOR = 2.07, 95 % CI: 1.24–3.46) and four times more likely to present with better mental health (AOR = 3.9, 95 % CI: 2.22–6.92) than those who were not on ART. There were no statistically significant associations between SRH (ever had sex, ever been pregnant, condom use, contraceptive use) or life style factors and physical health or mental health. Those with secondary or tertiary education were more likely to present with a better mental health (AOR = 5.3, 95 % CI: 1.86–15.41) compared those who had attained primary or no education. Participants who desired to have a child in future more likely (AOR 1.7, 95 % CI: 1.05–3.00) to present with a better mental health. Lack of communication with guardians on sexuality (AOR = 0.6, 95 % CI: 0.40–0.89), or dissatisfaction with SRH services (AOR 0.34, 95 % CI: 0.18–0.62) were associated with poorer mental health. Conclusion Among perinatally HIV-infected adolescents in Uganda, being on ART was associated with better physical and mental health while lack of communication with guardians on sexuality or dissatisfaction with SRH services was associated with poor mental health. Adolescents with pregnancy intentions were more likely to have a better mental health