A conceptual framework to assess the effectiveness of HIV prevention

Aim: The relative effectiveness of different methods of prevention of HIV transmission is a subject of debate that is renewed with the integration of each new method. The relative weight of values and evidence in decision-making is not always clearly defined. Debate is often confused, as the proponents of different approaches address the issue at different levels of implementation. This paper defines and delineates the successive levels of analysis of effectiveness, and proposes a conceptual framework to clarify debate. Method / Issue: Initially inspired from work on contraceptive effectiveness, a first version of the conceptual framework was published in 1993 with definition of the Condom Effectiveness Matrix (Spencer, 1993). The framework has since integrated and further developed thinking around distinctions made between efficacy and effectiveness and has been applied to HIV prevention in general. Three levels are defined: theoretical effectiveness (ThE), use-effectiveness (UseE) and population use-effectiveness (PopUseE). For example, abstinence and faithfulness, as proposed in the ABC strategy, have relatively high theoretical effectiveness but relatively low effectiveness at subsequent levels of implementation. The reverse is true of circumcision. Each level is associated with specific forms of scientific enquiry and associated research questions: basic and clinical sciences with ThE; clinical and social sciences with UseE; epidemiology and social, economic and political sciences with PopUseE. Similarly, the focus of investigation moves from biological organisms, to the individual at the physiological and then psychological, social and ecological level, and finally takes as perspective populations and societies as a whole. The framework may be applied to analyse issues on any approach. Hence, regarding consideration of HIV treatment as a means of prevention, examples of issues at each level would be: ThE: achieving adequate viral suppression and non-transmission to partners; UseE: facility and degree of adherence to treatment and medical follow-up; PopUseE: perceived validity of strategy, feasibility of achieving adequate population coverage. Discussion: Use of the framework clarifies the questions that need to be addressed at all levels in order to improve effectiveness. Furthermore, the interconnectedness and complementary nature of research from the different scientific disciplines and the relative contribution of each become apparent. The proposed framework could bring greater rationality to the prevention effectiveness debate and facilitate communication between stakeholders.

Forensic intelligence framework. Part II: study of the main generic building blocks and challenges through the examples of illicit drugs and false identity documents monitoring

The development of forensic intelligence relies on the expression of suitable models that better represent the contribution of forensic intelligence in relation to the criminal justice system, policing and security. Such models assist in comparing and evaluating methods and new technologies, provide transparency and foster the development of new applications. Interestingly, strong similarities between two separate projects focusing on specific forensic science areas were recently observed. These observations have led to the induction of a general model (Part I) that could guide the use of any forensic science case data in an intelligence perspective. The present article builds upon this general approach by focusing on decisional and organisational issues. The article investigates the comparison process and evaluation system that lay at the heart of the forensic intelligence framework, advocating scientific decision criteria and a structured but flexible and dynamic architecture. These building blocks are crucial and clearly lay within the expertise of forensic scientists. However, it is only part of the problem. Forensic intelligence includes other blocks with their respective interactions, decision points and tensions (e.g. regarding how to guide detection and how to integrate forensic information with other information). Formalising these blocks identifies many questions and potential answers. Addressing these questions is essential for the progress of the discipline. Such a process requires clarifying the role and place of the forensic scientist within the whole process and their relationship to other stakeholders.

Multi-scale integration and predictability in resting state brain activity.

The human brain displays heterogeneous organization in both structure and function. Here we develop a method to characterize brain regions and networks in terms of information-theoretic measures. We look at how these measures scale when larger spatial regions as well as larger connectome sub-networks are considered. This framework is applied to human brain fMRI recordings of resting-state activity and DSI-inferred structural connectivity. We find that strong functional coupling across large spatial distances distinguishes functional hubs from unimodal low-level areas, and that this long-range functional coupling correlates with structural long-range efficiency on the connectome. We also find a set of connectome regions that are both internally integrated and coupled to the rest of the brain, and which resemble previously reported resting-state networks. Finally, we argue that information-theoretic measures are useful for characterizing the functional organization of the brain at multiple scales.

B2B Integration in Global Supply Chains: An Identification of Technical Integration Scenarios

The competitiveness of businesses is increasingly dependent on their electronic networks with customers, suppliers, and partners. While the strategic and operational impact of external integration and IOS adoption has been extensively studied, much less attention has been paid to the organizational and technical design of electronic relationships. The objective of our longitudinal research project is the development of a framework for understanding and explaining B2B integration. Drawing on existing literature and empirical cases we present a reference model (a classification scheme for B2B Integration). The reference model comprises technical, organizational, and institutional levels to reflect the multiple facets of B2B integration. In this paper we onvestigate the current state of electronic collaboration in global supply chains focussing on the technical view. Using an indepth case analysis we identify five integration scenarios. In the subsequent confirmatory phase of the research we analyse 112 real-world company cases to validate these five integration scenarios. Our research advances and deepens existing studies by developing a B2B reference model, which reflects the current state of practice and is independent of specific implementation technologies. In the next stage of the research the emerging reference model will be extended to create an assessment model for analysing the maturity level of a given company in a specific supply chain.

The connectome viewer toolkit: an open source framework to manage, analyze, and visualize connectomes.

Advanced neuroinformatics tools are required for methods of connectome mapping, analysis, and visualization. The inherent multi-modality of connectome datasets poses new challenges for data organization, integration, and sharing. We have designed and implemented the Connectome Viewer Toolkit - a set of free and extensible open source neuroimaging tools written in Python. The key components of the toolkit are as follows: (1) The Connectome File Format is an XML-based container format to standardize multi-modal data integration and structured metadata annotation. (2) The Connectome File Format Library enables management and sharing of connectome files. (3) The Connectome Viewer is an integrated research and development environment for visualization and analysis of multi-modal connectome data. The Connectome Viewer's plugin architecture supports extensions with network analysis packages and an interactive scripting shell, to enable easy development and community contributions. Integration with tools from the scientific Python community allows the leveraging of numerous existing libraries for powerful connectome data mining, exploration, and comparison. We demonstrate the applicability of the Connectome Viewer Toolkit using Diffusion MRI datasets processed by the Connectome Mapper. The Connectome Viewer Toolkit is available from http://www.cmtk.org/

MR connectomics: a conceptual framework for studying the developing brain.

THE COMBINATION OF ADVANCED NEUROIMAGING TECHNIQUES AND MAJOR DEVELOPMENTS IN COMPLEX NETWORK SCIENCE, HAVE GIVEN BIRTH TO A NEW FRAMEWORK FOR STUDYING THE BRAIN: "connectomics." This framework provides the ability to describe and study the brain as a dynamic network and to explore how the coordination and integration of information processing may occur. In recent years this framework has been used to investigate the developing brain and has shed light on many dynamic changes occurring from infancy through adulthood. The aim of this article is to review this work and to discuss what we have learned from it. We will also use this body of work to highlight key technical aspects that are necessary in general for successful connectome analysis using today's advanced neuroimaging techniques. We look to identify current limitations of such approaches, what can be improved, and how these points generalize to other topics in connectome research.

A New Look at Emotional Intelligence: A Dual-Process Framework

In this article, the author provides a framework to guide¦research in emotional intelligence. Studies conducted up¦to the present bear on a conception of emotional intelligence¦as pertaining to the domain of consciousness and¦investigate the construct with a correlational approach.¦As an alternative, the author explores processes underlying¦emotional intelligence, introducing the distinction¦between conscious and automatic processing as a potential¦source of variability in emotionally intelligent¦behavior. Empirical literature is reviewed to support the¦central hypothesis that individual differences in emotional¦intelligence may be best understood by considering¦the way individuals automatically process emotional¦stimuli. Providing directions for research, the author¦encourages the integration of experimental investigation¦of processes underlying emotional intelligence with¦correlational analysis of individual differences and¦fosters the exploration of the automaticity component¦of emotional intelligence.

An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion syndrome (22q11DS) is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes), we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure) as the affected core (A-core) of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs - chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, "de-centralizing" the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30-40% of 22q11DS patients develop.

Validity, reliability and responsiveness of the French language translation of the Western Ontario Shoulder Instability Index (WOSI).

BACKGROUND: The WOSI (Western Ontario Shoulder Instability Index) is a self-administered quality of life questionnaire designed to be used as a primary outcome measure in clinical trials on shoulder instability, as well as to measure the effect of an intervention on any particular patient. It is validated and is reliable and sensitive. As it is designed to measure subjective outcome, it is important that translation should be methodologically rigorous, as it is subject to both linguistic and cultural interpretation. OBJECTIVE: To produce a French language version of the WOSI that is culturally adapted to both European and North American French-speaking populations. MATERIALS AND METHODS: A validated protocol was used to create a French language WOSI questionnaire (WOSI-Fr) that would be culturally acceptable for both European and North American French-speaking populations. Reliability and responsiveness analyses were carried out, and the WOSI-Fr was compared to the F-QuickDASH-D/S (Disability of the Arm, Shoulder and Hand-French translation), and Walch-Duplay scores. RESULTS: A French language version of the WOSI (WOSI-Fr) was accepted by a multinational committee. The WOSI-Fr was then validated using a total of 144 native French-speaking subjects from Canada and Switzerland. Comparison of results on two WOSI-Fr questionnaires completed at a mean interval of 16 days showed that the WOSI-Fr had strong reliability, with a Pearson and interclass correlation of r=0.85 (P=0.01) and ICC=0.84 [95% CI=0.78-0.88]. Responsiveness, at a mean 378.9 days after surgical intervention, showed strong correlation with that of the F-QuickDASH-D/S, with r=0.67 (P<0.01). Moreover, a standardized response means analysis to calculate effect size for both the WOSI-Fr and the F-QuickDASH-D/S showed that the WOSI-Fr had a significantly greater ability to detect change (SRM 1.55 versus 0.87 for the WOSI-Fr and F-QuickDASH-D/S respectively, P<0.01). The WOSI-Fr showed fair correlation with the Walch-Duplay. DISCUSSION: A French-language translation of the WOSI questionnaire was created and validated for use in both Canadian and Swiss French-speaking populations. This questionnaire will facilitate outcome assessment in French-speaking settings, collaboration in multinational studies and comparison between studies performed in different countries. TYPE OF STUDY: Multicenter cohort study. LEVEL OF EVIDENCE: II.

Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.

Linking Global Youth Tobacco Survey (GYTS) data to the WHO Framework Convention on Tobacco Control (FCTC): the case for the Seychelles

Tobacco control has been recognized as a main public health concern in Seychelles for the past two decades. Tobacco advertising, sponsoring and promotion has been banned for years, tobacco products are submitted to high taxes, high-profile awareness programs are organized regularly, and several other control measures have been implemented. The Republic of Seychelles was the first country to ratify the WHO Framework Convention on Tobacco Control (FCTC) in the African region. Three population-based surveys have been conducted in adults in Seychelles and results showed a substantial decrease in the prevalence of smoking among adults between 1989 and 2004. A first survey in adolescents was conducted in Seychelles in 2002 (the Global Youth Tobacco Survey, GYTS) in a representative sample of 1321 girls and boys aged 13-15 years. The results show that approximately half of students had tried smoking and a quarter of both boys and girls had smoked at least one cigarette during the past 30 days. Although "current smoking" is defined differently in adolescents (>or=1 cigarette during the past 30 days) and in adults (>or=1 cigarette per day), which precludes direct comparison, the high smoking prevalence in youth in Seychelles likely predicts an increasing prevalence of tobacco use in the next adult generation, particularly in women. GYTS 2002 also provides important data on a wide range of specific individual and societal factors influencing tobacco use. Hence, GYTS can be a powerful tool for monitoring the situation of tobacco use in adolescents, for highlighting the need for new policy and programs, and for evaluating the impact of current and future programs.

Hydrogeophysical data integration at larger scales: Application of Bayesian sequential simulation for the characterization of heterogeneous alluvial aquifers

Knowledge of the spatial distribution of hydraulic conductivity (K) within an aquifer is critical for reliable predictions of solute transport and the development of effective groundwater management and/or remediation strategies. While core analyses and hydraulic logging can provide highly detailed information, such information is inherently localized around boreholes that tend to be sparsely distributed throughout the aquifer volume. Conversely, larger-scale hydraulic experiments like pumping and tracer tests provide relatively low-resolution estimates of K in the investigated subsurface region. As a result, traditional hydrogeological measurement techniques contain a gap in terms of spatial resolution and coverage, and they are often alone inadequate for characterizing heterogeneous aquifers. Geophysical methods have the potential to bridge this gap. The recent increased interest in the application of geophysical methods to hydrogeological problems is clearly evidenced by the formation and rapid growth of the domain of hydrogeophysics over the past decade (e.g., Rubin and Hubbard, 2005).

Quantitative and qualitative research on brief systemic therapies carried out within the framework of an ambulatory consultation for couples and families

Abstract: This article presents both a brief systemic intervention method (IBS) consisting in 6 sessions developed in an ambulatory service for couples and families, and two research projects done in collaboration with the Institute for Psychotherapy of the University of Lausanne. The first project is quantitative and it aims at evaluating the effectiveness of ISB. One of its main feature is that outcomes are assessed at different levels of individual and family functioning: 1) symptoms and individual functioning; 2) quality of marital relationship; 3) parental and co-parental relationships; 4) familial relationships. The second project is a qualitative case study about a marital therapy which identifies and analyses significant moments of the therapeutic process from the patients' perspective. Methodology was largely inspired by Daniel Stem's work about "moments of meeting" in psychotherapy. Results show that patients' theories about relationship and change are important elements that deepen our understanding of the change process in couple and family therapy. The interest of associating clinicians and researchers for the development and validation of a new clinical model is discussed.

Directed integration of new insulated lentiviral vectors to heterochromatin towards safer gene transfer to stem cells

The need for better gene transfer systems towards improved risk=benefit balance for patients remains a major challenge in the clinical translation of gene therapy (GT). We have investigated the improvement of integrating vectors safety in combining (i) new short synthetic genetic insulator elements (GIE) and (ii) directing genetic integration to heterochromatin. We have designed SIN-insulated retrovectors with two candidate GIEs and could identify a specific combination of insulator 2 repeats which translates into best functional activity, high titers and boundary effect in both gammaretro (p20) and lentivectors (DCaro4) (see Duros et al, abstract ibid). Since GIEs are believed to shield the transgenic cassette from inhibitory effects and silencing, DCaro4 has been further tested with chimeric HIV-1 derived integrases which comprise C-ter chromodomains targeting heterochromatin through either histone H3 (ML6chimera) or methylatedCpGislands (ML10). With DCaro4 only and both chimeras, a homogeneous expression is evidenced in over 20% of the cells which is sustained over time. With control lentivectors, less than 2% of cells express GFP as compared to background using a control double-mutant in both catalytic and ledgf binding-sites; in addition, a two-times increase of expression can be induced with histone deacetylase inhibitors. Our approach could significantly reduce integration into open chromatin sensitive sites in stem cells at the time of transduction, a feature which might significantly decrease subsequent genotoxicity, according to X-SCIDs patients data.Work performed with the support of EC-DG research within the FP6-Network of Excellence, CLINIGENE: LSHB-CT-2006-018933