Integration of pre-aligned liquid metal electrodes for neural stimulation within a user-friendly microfluidic platform

Electrical stimulation of nervous tissue is used clinically for the treatment of multiple neurological disorders and experimentally for basic research. With the increase of optical probes to record neuronal activity, simple and user-friendly methods are desired to stimulate neurons and their subcellular compartments for biological experimentation. Here we describe the novel integration of liquid metal electrodes with microfluidic culture platforms to accomplish this goal. We integrated electrode and cell channels into a single poly(dimethylsiloxane) (PDMS) chip, eliminating entirely the need to align electrodes with microchannels. We designed the electrode channels such that the metal can be injected by hand and when the device is non-covalently bound to glass. We demonstrated the biocompatibility of the electrodes for long-term cultures (12 days) using hippocampal neurons. We demonstrated the use of these electrodes to depolarize neurons and recorded neuronal activity using the calcium indicator dye, Fluo-4. We established optimal stimulation parameters that induce neuronal spiking without inducing damage. We showed that the liquid metal electrode evoked larger calcium responses in somata than bath electrodes using the same stimulus parameters. Lastly we demonstrated the use of these liquid metal electrodes to target and depolarize axons. In summary, the integration of liquid metal electrodes with neuronal culture platforms provides a user-friendly and targeted method to stimulate neurons and their subcellular compartments, thus providing a novel tool for future biological investigations

Multi-compartment 3D-cultured organ-on-a-chip: Towards a biomimetic lymph node for drug development

The interaction of immune cells with drugs and/or with other cell types should be mechanistically investigated in order to reduce attrition of new drug development. However, they are currently only limited technologies that address this need. In our work, we developed initial but significant building blocks that enable such immune-drug studies. We developed a novel microfluidic platform replicating the Lymph Node (LN) microenvironment called LN-on-a-chip, starting from design all the way to microfabrication, characterization and validation in terms of architectural features, fluidics, cytocompatibility, and usability. To prove the biomimetics of this microenvironment, we inserted different immune cell types in a microfluidic device, which showed an in-vivo-like spatial distribution. We demonstrated that the developed LN-on-a-chip incorporates key features of the native human LN, namely, (i) similarity in extracellular matrix composition, morphology, porosity, stiffness, and permeability, (ii) compartmentalization of immune cells within distinct structural domains, (iii) replication of the lymphatic fluid flow pattern, (iv) viability of encapsulated cells in collagen over the typical timeframe of immunotoxicity experiments, and (v) interaction among different cell types across chamber boundaries. Further studies with this platform may assess the immune cell function as a step forward to disclose the effects of pharmaceutics to downstream immunology in more physiologically relevant microenvironments

Evaluation of Herpes Simplex Virus Type 2 Serological Tests for Use With Dried Blood Spots in Kenya

We evaluated two assays to detect antibodies to HSV- 2 in dried blood spots (DBS) prepared from blood specimens submitted to a reference laboratory in Kenya. DBS did not perform well with the Kalon HSV-2 assay. Focus HerpeSelect 2 was 98.8% sensitive and 98.9% specific with dried blood spots

Keeping Adolescent Orphans in School to Prevent Human Immunodeficiency Virus Infection: Evidence From a Randomized Controlled Trial in Kenya

We report findings from a pilot study in western Kenya, using an experimental design to test whether comprehensive support to keep adolescent orphans in school can reduce HIV risk factors

Appraisal of health care: from patient value to societal benefit

Aim: This paper summarizes the deficiencies and weaknesses of the most frequently used methods for the allocation of health-care resources. New, more transparent and practical methods for optimizing the allocation of these resources are proposed. Method: The examples of quality-adjusted life years (QALYs) and efficiency frontier (EF) are analyzed to describe weaknesses and problems in decisions regulating health-care provision. After conducting a literature search and discussions with an international group of professionals, three groups of professionals were formed to discuss the assessment and appraisal of health-care services and allocation of available resources. Results: At least seven essential variables were identified that should be heeded when applying the concept of QALYs for decisions concerning health-care provision. The efficiency frontier (EF) concept can be used to set a ceiling price and perform a cost-benefit analysis of provision, but different stakeholders—a biostatistician (efficacy), an economist (costs), a clinician (effectiveness), and the patient (value)—could provide a fairer appraisal of health-care services. Efficacy and costs are often based on falsifiable data. Effectiveness and value depend on the success with which a particular clinical problem has been solved. These data cannot be falsified. The societal perspective is generated by an informal cost-benefit analysis including appraisals by the above-mentioned stakeholders and carried out by an authorized institution. Conclusion: Our analysis suggests that study results expressed in QALYs or as EF cannot be compared unless the variables included in the calculation are specified. It would be far more objective and comprehensive if an authorized institution made an informal decision based on formal assessments of the effectiveness of health-care services evaluated by health-care providers, of the value assessed by consumers, of efficacy described by biostatisticians, and of costs calculated by economists

Diffusion of School-Based Prevention Programs in Two Urban Districts: Adaptations, Rationales, and Suggestions for Change

The diffusion of school-based preventive interventions involves the balancing of high-fidelity implementation of empirically-supported programs with flexibility to permit local stakeholders to target the specific needs of their youth. There has been little systematic research that directly seeks to integrate research- and community-driven approaches to diffusion. The present study provides a primarily qualitative investigation of the initial roll-out of two empirically-supported substance and violence prevention programs in two urban school districts that serve a high proportion of low-income, ethnic minority youth. The predominant ethnic group in most of our study schools was Asian American, followed by smaller numbers of Latinos, African Americans, and European Americans. We examined the adaptations made by experienced health teachers as they implemented the programs, the elicitation of suggested adaptations to the curricula from student and teacher stakeholders, and the evaluation of the consistency of these suggested adaptations with the core components of the programs. Data sources include extensive classroom observations of curricula delivery and interviews with students, teachers, and program developers. All health teachers made adaptations, primarily with respect to instructional format, integration of real-life experiences into the curriculum, and supplementation with additional resources; pedagogical and class management issues were cited as the rationale for these changes. Students and teachers were equally likely to propose adaptations that met with the program developers’ approval with respect to program theory and implementation logistics. Tensions between teaching practice and prevention science—as well as implications for future research and practice in school-based prevention—are considered

Implementing the LifeSkills Training drug prevention program: factors related to implementation fidelity

<p>Abstract</p> <p>Background</p> <p>Widespread replication of effective prevention programs is unlikely to affect the incidence of adolescent delinquency, violent crime, and substance use until the quality of implementation of these programs by community-based organizations can be assured.</p> <p>Methods</p> <p>This paper presents the results of a process evaluation employing qualitative and quantitative methods to assess the extent to which 432 schools in 105 sites implemented the LifeSkills Training (LST) drug prevention program with fidelity. Regression analysis was used to examine factors influencing four dimensions of fidelity: adherence, dosage, quality of delivery, and student responsiveness.</p> <p>Results</p> <p>Although most sites faced common barriers, such as finding room in the school schedule for the program, gaining full support from key participants (i.e., site coordinators, principals, and LST teachers), ensuring teacher participation in training workshops, and classroom management difficulties, most schools involved in the project implemented LST with very high levels of fidelity. Across sites, 86% of program objectives and activities required in the three-year curriculum were delivered to students. Moreover, teachers were observed using all four recommended teaching practices, and 71% of instructors taught all the required LST lessons. Multivariate analyses found that highly rated LST program characteristics and better student behavior were significantly related to a greater proportion of material taught by teachers (adherence). Instructors who rated the LST program characteristics as ideal were more likely to teach all lessons (dosage). Student behavior and use of interactive teaching techniques (quality of delivery) were positively related. No variables were related to student participation (student responsiveness).</p> <p>Conclusion</p> <p>Although difficult, high implementation fidelity by community-based organizations can be achieved. This study suggests some important factors that organizations should consider to ensure fidelity, such as selecting programs with features that minimize complexity while maximizing flexibility. Time constraints in the classroom should be considered when choosing a program. Student behavior also influences program delivery, so schools should train teachers in the use of classroom management skills. This project involved comprehensive program monitoring and technical assistance that likely facilitated the identification and resolution of problems and contributed to the overall high quality of implementation. Schools should recognize the importance of training and technical assistance to ensure quality program delivery.</p

Explaining gender differences in non-fatal suicidal behaviour among adolescents: a population-based study

<p>Abstract</p> <p>Background</p> <p>While suicide is the second leading cause of death among young people in most industrial countries, non-fatal suicidal behaviour is also a very important public health concern among adolescents. The aim of this study was to investigate gender differences in prevalence and emotional and behavioural correlates of suicidal behaviour in a representative school-based sample of adolescents.</p> <p>Methods</p> <p>A cross-sectional design was used to assess suicidal behaviour and various areas of emotional and behavioural problems by using a self-report booklet including the Youth Self-Report. One hundred sixteen schools in a region of Southern Germany agreed to participate. A representative sample of 5,512 ninth-grade students was studied. Mean age was 14.8 years (SD 0.73); 49.8% were female.</p> <p>Results</p> <p>Serious suicidal thoughts were reported by 19.8% of the female students and 10.8% of the females had ever attempted suicide. In the male group, 9.3% had a history of suicidal thoughts and 4.9% had previously attempted suicide. Internalizing emotional and behavioural problems were shown to be higher in the female group (difference of the group means 4.41) while externalizing emotional and behavioural problems slightly predominated in male students (difference of the group means -0.65). However, the total rate of emotional and behavioural problems was significantly higher in the adolescent female group (difference of the group means 4.98). Using logistic regression models with suicidal thoughts or attempted suicide as dependent variables, the pseudo-R² of gender alone was only 2.7% or 2.3%, while it was 30% or 23.2% for emotional and behavioural problems measured by the YSR syndrome scales. By adding gender to the emotional and behavioural problems only an additional 0.3% of information could be explained.</p> <p>Conclusions</p> <p>The findings suggest that gender differences in non-fatal suicidal behaviour among adolescents can to a large extent be explained by the gender differences in emotional and behavioural problems during this age.</p

Research into the efficacy and cost-effectiveness of brief, free of charge and anonymous sex counselling to improve (mental) health in youth: Design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The capacity to form romantic relationships and sexual health of adolescents in the Netherlands are compromised by several factors, including young age of first intercourse and adolescent depression. Several thresholds like own expenses, trust and embarrassment prevent adolescents to seek help for their sexual problems. To overcome these thresholds, brief sex counselling has been developed. It has been used since 2006 within the Rotterdam-Rijnmond Public Health Service, but there is lack of information about the (cost-) effectiveness. In the current study we will evaluate the (cost-) effectiveness of brief sex counselling for sexual problems in adolescents and young adults between 18 and 25 years of age.</p> <p>Methods</p> <p>In a randomised controlled trial we will compare (1) brief sex counselling with (2) intensive sexological treatment, and (3) delayed treatment (waiting list). Embedded in this RCT will be a trial-based economic evaluation, looking at the cost-effectiveness and cost-utility of brief sex counselling versus the two other interventions. Four hundred fifty adolescents (aged 18-25) with sexual problems will be recruited among the persons who visit the Public Health Service (PHS) and through various websites. After a screening procedure, eligible participants will be randomly allocated to one of the three intervention groups. Primary outcome measure of the clinical evaluation is the severity of sexual problems. Other outcomes include psychological distress, especially depression. The economic evaluation will be performed from a societal perspective. Costs will be assessed continuously by a retrospective questionnaire covering the last 3 month. All outcome assessments (including those for the economic evaluation) will take place via the internet at baseline, and at 3, 6, 9, and 12 months after baseline.</p> <p>Discussion</p> <p>The proposed research project will be the first study to provide preliminary data about the effect and cost-effectiveness of brief sex counselling in youth in comparison with intensive sexological treatment and delayed treatment. It is anticipated that positive results in (cost-) effectiveness of the proposed intervention will contribute to the improvement of sexual health care for adolescents and young adults.</p> <p>Trial registration</p> <p>The study has been registered at the Netherlands Trial Register, part of the Dutch Cochrane Centre (NTR1952)</p