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

Genetic differentiation and geographical Relationship of Asian barley landraces using SSRs

Genetic diversity in 403 morphologically distinct landraces of barley (Hordeum vulgare L. subsp. vulgare) originating from seven geographical zones of Asia was studied using simple sequence repeat (SSR) markers from regions of medium to high recombination in the barley genome. The seven polymorphic SSR markers representing each of the chromosomes chosen for the study revealed a high level of allelic diversity among the landraces. Genetic richness was highest in those from India, followed by Pakistan while it was lowest for Uzbekistan and Turkmenistan. Out of the 50 alleles detected, 15 were unique to a geographic region. Genetic diversity was highest for landraces from Pakistan (0.70 ± 0.06) and lowest for those from Uzbekistan (0.18 ± 0.17). Likewise, polymorphic information content (PIC) was highest for Pakistan (0.67 ± 0.06) and lowest for Uzbekistan (0.15 ± 0.17). Diversity among groups was 40% compared to 60% within groups. Principal component analysis clustered the barley landraces into three groups to predict their domestication patterns. In total 51.58% of the variation was explained by the first two principal components of the barley germplasm. Pakistan landraces were clustered separately from those of India, Iran, Nepal and Iraq, whereas those from Turkmenistan and Uzbekistan were clustered together into a separate group

Rab-GTPase binding effector protein 2 (RABEP2) is a primed substrate for Glycogen Synthase kinase-3 (GSK3)

Glycogen synthase kinase-3 (GSK3) regulates many physiological processes through phosphorylation of a diverse array of substrates. Inhibitors of GSK3 have been generated as potential therapies in several diseases, however the vital role GSK3 plays in cell biology makes the clinical use of GSK3 inhibitors potentially problematic. A clearer understanding of true physiological and pathophysiological substrates of GSK3 should provide opportunities for more selective, disease specific, manipulation of GSK3. To identify kinetically favourable substrates we performed a GSK3 substrate screen in heart tissue. Rab-GTPase binding effector protein 2 (RABEP2) was identified as a novel GSK3 substrate and GSK3 phosphorylation of RABEP2 at Ser200 was enhanced by prior phosphorylation at Ser204, fitting the known consensus sequence for GSK3 substrates. Both residues are phosphorylated in cells while only Ser200 phosphorylation is reduced following inhibition of GSK3. RABEP2 function was originally identified as a Rab5 binding protein. We did not observe co-localisation of RABEP2 and Rab5 in cells, while ectopic expression of RABEP2 had no effect on endosomal recycling. The work presented identifies RABEP2 as a novel primed substrate of GSK3, and thus a potential biomarker for GSK3 activity, but understanding how phosphorylation regulates RABEP2 function requires more information on physiological roles of RABEP2

Surgical preferences of patients at risk of hip fractures: hemiarthroplasty versus total hip arthroplasty

BACKGROUND: The optimal treatment of displaced femoral neck fractures in patients over 60 years is controversial. While much research has focused on the impact of total hip arthroplasty (THA) and hemiarthroplasty (HA) on surgical outcomes, little is known about patient preferences for either alternative. The purpose of this study was to elicit surgical preferences of patients at risk of sustaining hip fracture using a novel decision board. METHODS: We developed a decision board for the surgical management of displaced femoral neck fractures presenting risks and outcomes of HA and THA. The decision board was presented to 81 elderly patients at risk for developing femoral neck fractures identified from an osteoporosis clinic. The participants were faced with the scenario of sustaining a displaced femoral neck fracture and were asked to state their treatment option preference and rationale for operative procedure. RESULTS: Eighty-five percent (85%) of participants were between the age of 60 and 80 years; 89% were female; 88% were Caucasian; and 49% had some post-secondary education. Ninety-three percent (93%; 95% confidence interval [CI], 87-99%) of participants chose THA as their preferred operative choice. Participants identified several factors important to their decision, including the perception of greater walking distance (63%), less residual pain (29%), less reoperative risk (28%) and lower mortality risk (20%) with THA. Participants who preferred HA (7%; 95% CI, 1-13%) did so for perceived less invasiveness (50%), lower dislocation risk (33%), lower infection risk (33%), and shorter operative time (17%). CONCLUSION: The overwhelming majority of patients preferred THA to HA for the treatment of a displaced femoral neck fracture when confronted with risks and outcomes of both procedures on a decision board

Counting the Founders: The Matrilineal Genetic Ancestry of the Jewish Diaspora

The history of the Jewish Diaspora dates back to the Assyrian and Babylonian conquests in the Levant, followed by complex demographic and migratory trajectories over the ensuing millennia which pose a serious challenge to unraveling population genetic patterns. Here we ask whether phylogenetic analysis, based on highly resolved mitochondrial DNA (mtDNA) phylogenies can discern among maternal ancestries of the Diaspora. Accordingly, 1,142 samples from 14 different non-Ashkenazi Jewish communities were analyzed. A list of complete mtDNA sequences was established for all variants present at high frequency in the communities studied, along with high-resolution genotyping of all samples. Unlike the previously reported pattern observed among Ashkenazi Jews, the numerically major portion of the non-Ashkenazi Jews, currently estimated at 5 million people and comprised of the Moroccan, Iraqi, Iranian and Iberian Exile Jewish communities showed no evidence for a narrow founder effect, which did however characterize the smaller and more remote Belmonte, Indian and the two Caucasus communities. The Indian and Ethiopian Jewish sample sets suggested local female introgression, while mtDNAs in all other communities studied belong to a well-characterized West Eurasian pool of maternal lineages. Absence of sub-Saharan African mtDNA lineages among the North African Jewish communities suggests negligible or low level of admixture with females of the host populations among whom the African haplogroup (Hg) L0-L3 sub-clades variants are common. In contrast, the North African and Iberian Exile Jewish communities show influence of putative Iberian admixture as documented by mtDNA Hg HV0 variants. These findings highlight striking differences in the demographic history of the widespread Jewish Diaspora

Evolutionary Analyses of Entire Genomes Do Not Support the Association of mtDNA Mutations with Ras/MAPK Pathway Syndromes

BACKGROUND: There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42). METHODS/PRINCIPAL FINDINGS: The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. CONCLUSIONS/SIGNIFICANCE: As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS

The establishment of the Standard Cosmological Model through observations

Over the last decades, observations with increasing quality have revolutionized our understanding of the general properties of the Universe. Questions posed for millenia by mankind about the origin, evolution and structure of the cosmos have found an answer. This has been possible mainly thanks to observations of the Cosmic Microwave Background, of the large-scale distribution of matter structure in the local Universe, and of type Ia supernovae that have revealed the accelerated expansion of the Universe. All these observations have successfully converged into the so-called "concordance model". In spite of all these observational successes, there are still some important open problems, the most obvious of which are what generated the initial matter inhomogeneities that led to the structure observable in today's Universe, and what is the nature of dark matter, and of the dark energy that drives the accelerated expansion. In this chapter I will expand on the previous aspects. I will present a general description of the Standard Cosmological Model of the Universe, with special emphasis on the most recent observations that have us allowed to consolidate this model. I will also discuss the shortfalls of this model, its most pressing open questions, and will briefly describe the observational programmes that are being planned to tackle these issues.Comment: Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

Mapping human dispersals into the Horn of Africa from Arabian Ice Age refugia using mitogenomes

Rare mitochondrial lineages with relict distributions can sometimes be disproportionately informative about deep events in human prehistory. We have studied one such lineage, haplogroup R0a, which uniquely is most frequent in Arabia and the Horn of Africa, but is distributed much more widely, from Europe to India. We conclude that: (1) the lineage ancestral to R0a is more ancient than previously thought, with a relict distribution across the Mediterranean/Southwest Asia; (2) R0a has a much deeper presence in Arabia than previously thought, highlighting the role of at least one Pleistocene glacial refugium, perhaps on the Red Sea plains; (3) the main episode of dispersal into Eastern Africa, at least concerning maternal lineages, was at the end of the Late Glacial, due to major expansions from one or more refugia in Arabia; (4) there was likely a minor Late Glacial/early postglacial dispersal from Arabia through the Levant and into Europe, possibly alongside other lineages from a Levantine refugium; and (5) the presence of R0a in Southwest Arabia in the Holocene at the nexus of a trading network that developed after ~3 ka between Africa and the Indian Ocean led to some gene flow even further afield, into Iran, Pakistan and India

High Brain Ammonia Tolerance and Down-Regulation of Na+:K+:2Cl- Cotransporter 1b mRNA and Protein Expression in the Brain of the Swamp Eel, Monopterus albus, Exposed to Environmental Ammonia or Terrestrial Conditions

10.1371/journal.pone.0069512PLoS ONE89-POLN

Association mapping of malting quality traits in UK spring and winter barley cultivar collections

Key Message: Historical malting quality data was collated from UK national and recommended list trial data and used in a GWAS. 25 QTL were identified, with the majority from spring barley cultivar sets. Abstract: In Europe, the most economically significant use of barley is the production of malt for use in the brewing and distilling industries. As such, selection for traits related to malting quality is of great commercial interest. In order to study the genetic basis of variation for malting quality traits in UK cultivars, a historical set of trial data was collated from national and recommended list trials from the period 1988 to 2016. This data was used to estimate variety means for 20 quality related traits in 451 spring barley cultivars, and 407 winter cultivars. Genotypes for these cultivars were generated using iSelect 9k and 50k genotyping platforms, and a genome wide association scan performed to identify malting quality quantitative trait loci (QTL). 24 QTL were identified in spring barley cultivars, and 2 from the winter set. A number of these correspond to known malting quality related genes but the remainder represents novel genetic variation that is accessible to breeders for the genetic improvement of new cultivars.Mark E. Looseley, Luke Ramsay, Hazel Bull, J. Stuart Swanston, Paul D. Shaw, Malcolm Macaulay, Allan Booth, Joanne R. Russell, Robbie Waugh, on behalf of the IMPROMALT Consortium, William T.B. Thoma