Framework, principles and recommendations for utilising participatory methodologies in the co-creation and evaluation of public health interventions

Background: Due to the chronic disease burden on society, there is a need for preventive public health interventions to stimulate society towards a healthier lifestyle. To deal with the complex variability between individual lifestyles and settings, collaborating with end-users to develop interventions tailored to their unique circumstances has been suggested as a potential way to improve effectiveness and adherence. Co-creation of public health interventions using participatory methodologies has shown promise but lacks a framework to make this process systematic. The aim of this paper was to identify and set key principles and recommendations for systematically applying participatory methodologies to co-create and evaluate public health interventions. Methods: These principles and recommendations were derived using an iterative reflection process, combining key learning from published literature in addition to critical reflection on three case studies conducted by research groups in three European institutions, all of whom have expertise in co-creating public health interventions using different participatory methodologies. Results: Key principles and recommendations for using participatory methodologies in public health intervention co-creation are presented for the stages of: Planning (framing the aim of the study and identifying the appropriate sampling strategy); Conducting (defining the procedure, in addition to manifesting ownership); Evaluating (the process and the effectiveness) and Reporting (providing guidelines to report the findings). Three scaling models are proposed to demonstrate how to scale locally developed interventions to a population level. Conclusions: These recommendations aim to facilitate public health intervention co-creation and evaluation utilising participatory methodologies by ensuring the process is systematic and reproducible

OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes

Mutations in OPA1, a dynamin-related GTPase involved in mitochondrial fusion, cristae organization and control of apoptosis, have been linked to non-syndromic optic neuropathy transmitted as an autosomal-dominant trait (DOA). We here report on eight patients from six independent families showing that mutations in the OPA1 gene can also be responsible for a syndromic form of DOA associated with sensorineural deafness, ataxia, axonal sensory-motor polyneuropathy, chronic progressive external ophthalmoplegia and mitochondrial myopathy with cytochrome c oxidase negative and Ragged Red Fibres. Most remarkably, we demonstrate that these patients all harboured multiple deletions of mitochondrial DNA (mtDNA) in their skeletal muscle, thus revealing an unrecognized role of the OPA1 protein in mtDNA stability. The five OPA1 mutations associated with these DOA ‘plus’ phenotypes were all mis-sense point mutations affecting highly conserved amino acid positions and the nuclear genes previously known to induce mtDNA multiple deletions such as POLG1, PEO1 (Twinkle) and SLC25A4 (ANT1) were ruled out. Our results show that certain OPA1 mutations exert a dominant negative effect responsible for multi-systemic disease, closely related to classical mitochondrial cytopathies, by a mechanism involving mtDNA instability

Alterations in the metabolic and cardiorespiratory response to exercise in Huntington's Disease

Background: Limited data suggests that an altered metabolic and cardiorespiratory exercise response may affect exercise performance in individuals with Huntington's disease (HD). There is no clear exploration of the response in individuals at different stages of the disease or in relation to genetic markers. This study aimed to examine the exercise response and recovery of HD participants, and the relationship to genetic and clinical markers. Method: HD gene-positive participants (n = 31; 9 pre-manifest; 22 manifest HD) and a healthy control group (n = 29) performed an incremental exercise test until exhaustion. Performance, cardiorespiratory, metabolic and perceptual responses to exercise were determined from a maximal cycle ergometer test throughout the exercise test and during a recovery period. Results: During sub-maximal exercise, metabolic (lactate levels, oxygen uptake) and cardiorespiratory markers (heart rate) were elevated in HD participants compared to controls. Lactate elevation was specific to pre-manifest HD participants. Work capacity was reduced in both pre-manifest and manifest HD participants with tests terminated with no difference in metabolic, perceptual or cardiorespiratory markers. Submaximal oxygen uptake was correlated with motor score, whilst peak measures were unrelated to genetic or clinical markers. Heart rate recovery was attenuated in pre-manifest and manifest HD participants. Conclusions: Our findings confirm metabolic and cardiorespiratory deficits reduce exercise performance and affect recovery from an early stage in HD, with submaximal deficits related to phenotypic expression. Exercise capacity appears to be limited by an altered movement economy, thus clinicians should consider an altered exercise response and recovery may affect prescription in HD

Simultaneous genetic analysis of means and covariance structure: Pearson-Lawley selection rules

The object of this paper is to indicate that the Pearson-Lawley selection rules form a plausible general theory for the simultaneous genetic analysis of means and covariance structure. Models are presented based on phenotypic selection and latent selection. Previously presented quantitative genetic models to decompose means and covariance structure simultaneously are reconsidered as instances of latent selection. The selection rules are very useful in the context of behavior genetic modeling because they lead to testable models and a conceptual framework for explaining variation between and within groups by the same genetic and environmental factors. © 1994 Plenum Publishing Corporation

The complex X-ray spectrum of NGC 4507

XMM-Newton and Chandra/HETG spectra of the Compton-thin (NH 4x10^{23} cm^{-2}) Seyfert 2 galaxy, NGC 4507, are analyzed and discussed. The main results are: a) the soft X-ray emission is rich in emission lines; an (at least) two--zone photoionization region is required to explain the large range of ionization states. b) The 6.4 keV iron line is likely emitted from Compton-thick matter, implying the presence of two circumnuclear cold regions, one Compton-thick (the emitter), one Compton-thin (the cold absorber). c) Evidence of an Fe xxv absorption line is found in the Chandra/HETG spectrum. The column density of the ionized absorber is estimated to be a few x10^{22} cm^{-2}.Comment: accepted for publication in A&

Assessing Causality in the Relationship Between Adolescents’ Risky Sexual Online Behavior and Their Perceptions of this Behavior

The main aim of this study was to investigate the causal nature of the relationship between adolescents’ risky sexual behavior on the internet and their perceptions of this behavior. Engagement in the following online behaviors was assessed: searching online for someone to talk about sex, searching online for someone to have sex, sending intimate photos or videos to someone online, and sending one’s telephone number and address to someone exclusively known online. The relationship between these behaviors and adolescents’ perceptions of peer involvement, personal invulnerability, and risks and benefits was investigated. A two-wave longitudinal study among a representative sample of 1,445 Dutch adolescents aged 12–17 was conducted (49% females). Autoregressive cross-lagged structural equation models revealed that perceived peer involvement, perceived vulnerability, and perceived risks were all significant predictors of risky sexual online behavior 6 months later. No reverse causal paths were found. When the relationships between perceptions and risky sexual online behavior were modeled simultaneously, only perceived peer involvement was a determinant of risky sexual online behavior. Findings highlight the importance of addressing peer involvement in future interventions to reduce adolescents’ risky sexual online behavior

SerpinA3N is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice

Background: Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. To elucidate the possible mechanisms underlying these effects, a microarray-based transcriptomics approach was used to identify novel genes regulated by HFD and leptin in the mouse hypothalamus. Results: Mouse global array data identified serpinA3N as a novel gene highly upregulated by both a HFD and leptin challenge. In situ hybridisation showed serpinA3N expression upregulation by HFD and leptin in all major hypothalamic nuclei in agreement with transcriptomic gene expression data. Immunohistochemistry and studies in the hypothalamic clonal neuronal cell line, mHypoE-N42 (N42), confirmed that alpha 1-antichymotrypsin (α1AC), the protein encoded by serpinA3, is localised to neurons and revealed that it is secreted into the media. SerpinA3N expression in N42 neurons is upregulated by palmitic acid and by leptin, together with IL-6 and TNFα, and all three genes are downregulated by the anti-inflammatory monounsaturated fat, oleic acid. Additionally, palmitate upregulation of serpinA3 in N42 neurons is blocked by the NFκB inhibitor, BAY11, and the upregulation of serpinA3N expression in the hypothalamus by HFD is blunted in IL-1 receptor 1 knockout (IL-1R1−/−) mice. Conclusions: These data demonstrate that serpinA3 expression is implicated in nutritionally mediated hypothalamic inflammation

Self-prioritization and perceptual matching: The effects of temporal construal.

Recent research has revealed that self-referential processing enhances perceptual judgments - the so-called self-prioritization effect. The extent and origin of this effect remains unknown, however. Noting the multifaceted nature of the self, here we hypothesized that temporal influences on self-construal (i.e., past/future-self continuity) may serve as an important determinant of stimulus prioritization. Specifically, as representations of the self increase in abstraction as a function of temporal distance (i.e., distance from now), self-prioritization may only emerge when stimuli are associated with the current self. The results of three experiments supported this prediction. Self-relevance only enhanced performance in a standard perceptual-matching task when stimuli (i.e., geometric shapes) were connected with the current self; representations of the self in the future (Expts. 1 & 2) and past (Expt. 3) failed to facilitate decision making. To identify the processes underlying task performance, data were interrogated using a hierarchical drift diffusion model (HDDM) approach. Results of these analyses revealed that self-prioritization was underpinned by a stimulus bias (i.e., rate of information uptake). Collectively, these findings elucidate when and how self-relevance influences decisional processing