User producer interaction in context

User producer interaction (UPI) increases chances for successful innovations. It is not always clear, however, what type of interaction is necessary in a particular context. This article identifies seven different types of UPI: constructing linkages, broadening, characterizing users, upstream involvement, first user enrollment, feedback, and downstream innovation. Specific contextual dimensions from which these UPI types derive relevance are discussed. The technological dimension of this context is conceptualized based on a distinction between types of technologies that differ in the degree to which they are customizable to user demands. Four case studies show that technological characteristics indeed matter for UPI, as do the heterogeneity of users and the phase of technology development

Exploring the feasibility of introducing triple artemisinin-based combination therapy in the malaria treatment policy in Vietnam

BACKGROUND: This study investigates the processes regarding changing malaria treatment policies in Vietnam. Moreover, it explores the feasibility of introducing triple artemisinin-based combination therapy (TACT) in Vietnam to support the national malaria control and elimination plan. METHODS: Data were collected via 12 in-depth interviews with key stakeholders, combined with a review of policy documents. RESULTS: TACT is considered as a useful backup strategy in case future treatment failures with current artemisinin-based combination therapy (ACT) would occur. Moreover, TACT is also considered as a promising strategy to prevent the re-establishment of malaria. However, regulatory procedures and implementation timelines for TACT were expected to be lengthy. Therefore, strategies to engage national decision-makers, regulators, and suppliers should be initiated soon, stipulating the benefits of TACT deployment. In Vietnam, a procedure to apply for an import permit without registration that has previously been applied to the introduction of artesunate-pyronaridine was proposed to accelerate the introduction of TACT. Global-level support through the World Health Organization recommendations and prequalification were considered critical for supporting the introduction of TACT in Vietnam. CONCLUSIONS: Appropriate approach strategies and early stakeholder engagement will be needed to accelerate the introduction of TACT in Vietnam

Mental models of the protein shift: Exploring consumers' perceptions of the transition

The protein transition is one of today's major societal challenges to mitigate climate change. To support lasting consumer engagement, it has been suggested to look into consumers' understanding of the protein transition to identify barriers that go beyond the practical issues of changing one's diet. The current study explored consumers' mental models of how the transition unfolds to examine which factors consumers perceive as important drivers of the transition. With a fixed set of factors and actors identified with a questionnaire, Dutch consumers (N = 214) mapped their mental models. The content and structure of the mental models were analyzed with a focus on how consumers perceive their own role. Animal well-being and environmental concerns were most often included as important drivers. The findings showed a lack of consensus about which actor(s) drive the transition (i.e., none of the actors were included by a majority of the participants). This diffusion of responsibility may be a barrier for consumers to act. Moreover, the relative simplicity of the observed mental models suggests that consumers do not yet employ systems thinking. A systems thinking mindset may help consumers understand how the system behind the transition works and how their individual contributions matter. Two avenues to encourage consumer engagement were identified: 1) emphasizing the responsibility of different actors and what consumers can contribute, and 2) encouraging a systems thinking mindset

Translatability of preclinical to early clinical tolerable and pharmacologically active dose ranges for central nervous system active drugs

The primary purpose of this study was to assess the translatability of preclinical to early clinical tolerable and pharmacologically active dose ranges for central nervous system (CNS) active drugs. As a part of this, IBs were reviewed on reporting quality. Investigator's Brochures (IBs) of studies performed at the Centre for Human Drug Research (CHDR) reporting statistically significant results of CNS activity related to the drug's mechanism of action were included. The quality of IBs was assessed based on the presence of a rationale for the chosen animal model, completeness of pharmacokinetic (PK) results in reporting and internal validity information of the preclinical evidence. The IB-derisk tool was used to generate preclinical and early clinical data overviews data. For each compound, the overlap between pharmacologically active dose ranges and well-tolerated levels was calculated for three pharmacokinetic (PK) parameters: human equivalent dose (HED), maximum plasma concentration (C max) and area under the curve (AUC). Twenty-five IBs were included. In general, the quality of reporting in IBs was assessed as poor. About a third of studies did not explore the entire concentration-effect curve (pre)clinically. Single dose tolerability ranges were most accurately predicted by C max. Human equivalent dose and AUC were the best predictors of pharmacologically active ranges. Tolerable and pharmacologically active dose ranges in healthy volunteers can be reasonably well predicted from preclinical data with the IB-derisk tool. The translatability of preclinical studies can be improved by applying a higher reporting standard in IBs including comparable PK measurements across all preclinical and clinical studies

Strategies for deploying triple artemisinin-based combination therapy in the Greater Mekong Subregion

Background This is a qualitative study to identify implementation challenges for deploying triple artemisinin-based combination therapy (TACT) in the Greater Mekong Subregion (GMS) of Southeast Asia and to explore strategies to overcome these challenges. Methods In-depth interviews were conducted in three countries that have repeatedly been confronted with ACT failures: Cambodia, Vietnam, and Lao PDR. Thirty-nine key stakeholders in the healthcare systems in these countries were interviewed. One participatory workshop was conducted in Cambodia, where scenarios for potential TACT deployment were discussed. Results The results section is organized around four strategic themes that emerged from the data: policy support, data and evidence, logistics and operation, and downstream engagement. The study revealed that countries in the GMS currently rely on ACT to eliminate Plasmodium falciparum malaria by 2025. TACT is, however, considered to be a useful backup strategy in case of future treatment failures and to prevent the re-establishment of malaria. The study showed that a major challenge ahead is to engage decision makers and healthcare providers into deploying TACT, given the low case incidence of falciparum malaria in the GMS. Interview respondents were also skeptical whether healthcare providers would be willing to engage in new therapies for a disease they hardly encounter anymore. Hence, elaborate information dissemination strategies were considered appropriate and these strategies should especially target village malaria workers. Respondents proposed several regulatory and programmatic strategies to anticipate the formation of TACT markets in the GMS. These strategies include early dossier submission to streamline regulatory procedures, early stakeholder engagement strategies to shorten implementation timelines, and inclusion of TACT as second-line therapy to accelerate their introduction in case they are urgently needed. Conclusions This paper presents a qualitative study to identify implementation challenges for deploying TACT in the GMS and to explore strategies to overcome these challenges. The findings could benefit researchers and decision makers in strategizing towards potential future deployment of TACT in the GMS to combat artemisinin and partner drug resistance

Automatic and Deliberate Affective Associations with Sexual Stimuli in Women with Superficial Dyspareunia

Current views suggest that in women with superficial dyspareunia the prospect of penile–vaginal intercourse automatically activates fear-related associations. The automatic activation of negative associations is assumed to interfere with the development of sexual arousal. In turn, this may further aggravate the dyspareunia-related complaints. To assess whether automatic negative associations are involved in this sexual pain disorder, women with superficial dyspareunia (n = 35) and a control group (n = 35) completed a modified pictorial Affective Simon Task (AST). Questioning the role of dysfunctional automatic associations in superficial dyspareunia, the AST indicated that symptomatic women displayed relatively positive rather than negative automatic associations with sexual stimuli. At the self-report level, however, affective associations with sex cues were significantly more negative for women with dyspareunia than for controls. This discrepancy between “reflective” and “reflexive” affective associations with sexual stimuli in women with dyspareunia points to the relevance of conscious appraisal and deliberate rather than automatic processes in the onset and maintenance of dyspareunia

Valsartan Improves Adipose Tissue Function in Humans with Impaired Glucose Metabolism: A Randomized Placebo-Controlled Double-Blind Trial

<div><h3>Background</h3><p>Blockade of the renin-angiotensin system (RAS) reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT) function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM).</p> <h3>Methodology/Principal Findings</h3><p>We performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d) or placebo (PLB) for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF) (¹³³Xe wash-out), systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). VAL treatment markedly reduced adipocyte size (<em>P</em><0.001), with a shift toward a higher proportion of small adipocytes. In addition, fasting (<em>P</em> = 0.043) and postprandial ATBF (<em>P</em> = 0.049) were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP)-1, TNF-α, adiponectin and leptin concentrations.</p> <h3>Conclusions/Significance</h3><p>26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL-induced decrease in adipocyte size was associated with reduced expression of macrophage infiltration markers in AT. Our findings suggest that interventions targeting the RAS may improve AT function, thereby contributing to a reduced risk of developing cardiovascular disease and type 2 diabetes.</p> <h3>Trial Registration</h3><p>Trialregister.nl NTR721 (ISRCTN Registry: ISRCTN<a href="http://www.controlled-trials.com/isrctn/pf/42786336">42786336</a>)</p> </div

From Mattering to Mattering More: ‘Goods’ and ‘Bads’ in Ageing and Innovation Policy Discourses

This paper provides an empirical ethics analysis of the goods and bads enacted in EU ageing and innovation policy discourses. It revolves around a case study of the persona Maria, developed as part of the EU’s Active and Healthy Ageing Policies. Drawing on Pols’ empirical ethics as a theoretical and methodological approach, we describe the variety of goods (practices/situations to be strived for) and bads (practices/situations to be avoided) that are articulated in Maria’s persona. We analyse how certain ideas about good and bad ageing—those associated with the use of sophisticated technologies—come to matter more in the solutions proposed for Maria and the framing of her unmet needs, while others which were initially seen as relevant and that describe her dreams, fears and interactions, are marginalised. The paper adds to existing studies of ageing and technology by analysing specific practices that render visible how the idea of technology and data sharing as evidently the right path towards futures of (good) ageing, comes to prevail