MARKET SEGMENTATION WITHIN CONTINGENT VALUATION

A finite probability mixture model is combined with a contingent valuation model to analyze the existence of differential market segments in a hypothetical market. The approach has at least two principle benefits. First, the model is capable of identifying market segments within the hypothetical market. Second, the model can be used to estimate WTP/WTA within each segment. The model is illustrated using a data set collected on consumer response to genetically modified foods in Norway.Agribusiness,

A Mixture Model of Consumers' Intended Purchase Decisions for Genetically Modified Foods

A finite probability mixture model is used to analyze the existence of multiple market segments for a pre-market good. The approach has at least two principal benefits. First, the model is capable of identifying likely market segments and their differentiating characteristics. Second, the model can be used to estimate the discount different consumer groups require to purchase the good. The model is illustrated using stated preference survey data collected on consumer responses to the potential introduction in Norway of bread made with genetically modified wheat.

Development of outbred CD1 mouse colonies with distinct standardized gut microbiota profiles for use in complex microbiota targeted studies.

Studies indicate that the gut microbiota (GM) can significantly influence both local and systemic host physiologic processes. With rising concern for optimization of experimental reproducibility and translatability, it is essential to consider the GM in study design. However, GM profiles can vary between rodent producers making consistency between models challenging. To circumvent this, we developed outbred CD1 mouse colonies with stable, complex GM profiles that can be used as donors for a variety of GM transfer techniques including rederivation, co-housing, cross-foster, and fecal microbiota transfer (FMT). CD1 embryos were surgically transferred into CD1 or C57BL/6 surrogate dams that varied by GM composition and complexity to establish four separate mouse colonies harboring GM profiles representative of contemporary mouse producers. Using targeted 16S rRNA amplicon sequencing, subsequent female offspring were found to have similar GM profiles to surrogate dams. Furthermore, breeding colonies of CD1 mice with distinct GM profiles were maintained for nine generations, demonstrating GM stability within these colonies. To confirm GM stability, we shipped cohorts of these four colonies to collaborating institutions and found no significant variation in GM composition. These mice are an invaluable experimental resource that can be used to investigate GM effects on mouse model phenotype

Qualitative evaluation of a physical activity-based chronic disease prevention program in a low-income, rural South African setting

Introduction: Chronic diseases, an increasing global concern, are prevalent in the low-income communities of South Africa, where rural health systems bear the double burden of infectious and chronic diseases. The Discovery Healthy Lifestyle Programme (DHLP) is a physical activity-based chronic disease prevention program that has been implemented in a low-income, rural setting in South Africa. The DHLP consists of both school- and primary healthcare clinic-based interventions for learners (Healthnutz) and adults (Live it Up), facilitated by teachers, nurses and community volunteers. The aim of this evaluation was to qualitatively assess the process by which the DHLP was implemented, identifying enabling factors and barriers. Methods: Data were collected in target communities at schools and clinics from semi-structured focus groups of program leaders and members, teachers and community members (n=45), situational analyses of the school physical activity environment, informal community observations and informal interviews with program coordinators. Results: The target communities faced socioeconomic and health inequalities and remained under-resourced and under-served. In spite of these and other challenges, the DHLP was well received by community members and stakeholders. It was valued by respondents for its health and psychosocial outcomes, evidenced by increased knowledge and awareness of the importance of physical activity and healthy lifestyles, and positively altered perceptions of physical activity. Program implementers believed the Live it Up component was growing, and this suggested the sustainability of the program. There were, however, some concerns about the fidelity of the Healthnutz intervention, due to timetabling difficulties. Despite this, teachers were positive about the program and its value for their learners, staff and school. The community characteristics of being under-resourced and underserved appeared to positively influence DHLP implementation. Local government involvement in the DHLP resulted in greater ownership of the program, which enabled successful implementation. Conclusions: This study presents a unique opportunity to assess the implementation and sustainability requirements of programs in environments of limited resources, considerable burden of infectious and chronic diseases and extensive socioeconomic challenges. The findings suggest that through enhancement of knowledge, transfer of appropriate skills and the provision of an enabling environment, participation in physical activity can be effectively promoted in a low-income, rural setting. Physical activity interventions that promote the participation and empowerment of rural communities can be feasible and accessible, thereby assisting in addressing the growing burden of chronic diseases in low-income

The Mutant Mouse Resource and Research Center (MMRRC): the NIH-supported National Public Repository and Distribution Archive of Mutant Mouse Models in the USA.

The Mutant Mouse Resource and Research Center (MMRRC) Program is the pre-eminent public national mutant mouse repository and distribution archive in the USA, serving as a national resource of mutant mice available to the global scientific community for biomedical research. Established more than two decades ago with grants from the National Institutes of Health (NIH), the MMRRC Program supports a Consortium of regionally distributed and dedicated vivaria, laboratories, and offices (Centers) and an Informatics Coordination and Service Center (ICSC) at three academic teaching and research universities and one non-profit genetic research institution. The MMRRC Program accepts the submission of unique, scientifically rigorous, and experimentally valuable genetically altered and other mouse models donated by academic and commercial scientists and organizations for deposition, maintenance, preservation, and dissemination to scientists upon request. The four Centers maintain an archive of nearly 60,000 mutant alleles as live mice, frozen germplasm, and/or embryonic stem (ES) cells. Since its inception, the Centers have fulfilled 13,184 orders for mutant mouse models from 9591 scientists at 6626 institutions around the globe. Centers also provide numerous services that facilitate using mutant mouse models obtained from the MMRRC, including genetic assays, microbiome analysis, analytical phenotyping and pathology, cryorecovery, mouse husbandry, infectious disease surveillance and diagnosis, and disease modeling. The ICSC coordinates activities between the Centers, manages the website (mmrrc.org) and online catalog, and conducts communication, outreach, and education to the research community. Centers preserve, secure, and protect mutant mouse lines in perpetuity, promote rigor and reproducibility in scientific experiments using mice, provide experiential training and consultation in the responsible use of mice in research, and pursue cutting edge technologies to advance biomedical studies using mice to improve human health. Researchers benefit from an expansive list of well-defined mouse models of disease that meet the highest standards of rigor and reproducibility, while donating investigators benefit by having their mouse lines preserved, protected, and distributed in compliance with NIH policies

‘Only twice a year’: a qualitative exploration of 6-month antiretroviral treatment refills in adherence clubs for people living with HIV in Khayelitsha, South Africa

Objective Longer intervals between routine clinic visits and medication refills are part of patient-centred, differentiated service delivery (DSD). They have been shown to improve patient outcomes as well as optimise health services—vital as ‘universal test-and-treat’ targets increase numbers of HIV patients on antiretroviral treatment (ART). This qualitative study explored patient, healthcare worker and key informant experiences and perceptions of extending ART refills to 6 months in adherence clubs in Khayelitsha, South Africa. Design and setting In-depth interviews were conducted in isiXhosa with purposively selected patients and in English with healthcare workers and key informants. All transcripts were audio-recorded, transcribed and translated to English, manually coded and thematically analysed. The participants had been involved in a randomised controlled trial evaluating multi-month ART dispensing in adherence clubs, comparing 6-month and 2-month refills. Participants Twenty-three patients, seven healthcare workers and six key informants. Results Patients found that 6-month refills increased convenience and reduced unintended disclosure. Contrary to key informant concerns about patients’ responsibility to manage larger quantities of ART, patients receiving 6-month refills were highly motivated and did not face challenges transporting, storing or adhering to treatment. All participant groups suggested that strict eligibility criteria were necessary for patients to realise the benefits of extended dispensing intervals. Six-month refills were felt to increase health system efficiency, but there were concerns about whether the existing drug supply system could adapt to 6-month refills on a larger scale. Conclusions Patients, healthcare workers and key informants found 6-month refills within adherence clubs acceptable and beneficial, but concerns were raised about the reliability of the supply chain to manage extended multi-month dispensing. Stepwise, slow expansion could avoid overstressing supply and allow time for the health system to adapt, permitting 6-month ART refills to enhance current DSD options to be more efficient and patient-centred within current health system constraints

Deglutarylation of glutaryl-CoA dehydrogenase by deacylating enzyme SIRT5 promotes lysine oxidation in mice

A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal that glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We also demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a feedback loop model within the lysine/tryptophan oxidation pathway in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues and can be relieved by SIRT5 deacylation activity

Proteomics approaches to fibrotic disorders

This review provides an introduction to mass spectrometry based proteomics and discusses several proteomics approaches that are relevant in understanding the pathophysiology of fibrotic disorders and the approaches that are frequently used in biomarker discovery

Unearthing how, why, for whom and under what health system conditions the antiretroviral treatment adherence club intervention in South Africa works: A realist theory refining approach

BACKGROUND: Poor retention in care and suboptimal adherence to antiretroviral treatment (ART) undermine its successful rollout in South Africa. The adherence club intervention was designed as an adherence-enhancing intervention to enhance the retention in care of patients on ART and their adherence to medication. Although empirical evidence suggests the effective superiority of the adherence club intervention to standard clinic ART care schemes, it is poorly understood exactly how and why it works, and under what health system contexts. To this end, we aimed to develop a refined programme theory explicating how, why, for whom and under what health system contexts the adherence club intervention works (or not). METHODS: We undertook a realist evaluation study to uncover the programme theory of the adherence club intervention. We elicited an initial programme theory of the adherence club intervention and tested the initial programme theory in three contrastive sites. Using a cross-case analysis approach, we delineated the conceptualisation of the intervention, context, actor and mechanism components of the three contrastive cases to explain the outcomes of the adherence club intervention, guided by retroductive inferencing. RESULTS: We found that an intervention that groups clinically stable patients on ART in a convenient space to receive a quick and uninterrupted supply of medication, health talks, counselling, and immediate access to a clinician when required works because patients’ self-efficacy improves and they become motivated and nudged to remain in care and adhere to medication. The successful implementation and rollout of the adherence club intervention are contingent on the separation of the adherence club programme from other patients who are HIV-negative. In addition, there should be available convenient space for the adherence club meetings, continuous support of the adherence club facilitators by clinicians and buy-in from the health workers at the health-care facility and the community. CONCLUSION: Understanding what aspects of antiretroviral club intervention works, for what sections of the patient population, and under which community and health systems contexts, could inform guidelines for effective implementation in different contexts and scaling up of the intervention to improve population-level ART adherence