Exploring views of members of the public and policymakers on the acceptability of population level dietary and active-travel policies: a qualitative study.

BACKGROUND: There is limited evidence on what shapes the acceptability of population level dietary and active-travel policies in England. This information would be useful in the decision-making process about which policies should be implemented and how to increase their effectiveness and sustainability. To fill this gap, we explored public and policymakers' views about factors that influence public acceptability of dietary and active-travel policies and how to increase public acceptability for these policies. METHODS: We conducted online, semi-structured interviews with 20 members of the public and 20 policymakers in England. A purposive sampling frame was used to recruit members of the public via a recruitment agency, based on age, sex, socioeconomic status and ethnicity. Policymakers were recruited from existing contacts within our research collaborations and via snowball sampling. We explored different dietary and active-travel policies that varied in their scope and focus. Interviews were transcribed verbatim and analysed using thematic reflexive analysis with both inductive and deductive coding. RESULTS: We identified four themes that informed public acceptability of dietary and active-travel policies: (1) perceived policy effectiveness, i.e., policies that included believable mechanisms of action, addressed valued co-benefits and barriers to engage in the behaviour; (2) perceived policy fairness, i.e., policies that provided everyone with an opportunity to benefit (mentioned only by the public), equally considered the needs of various population subgroups and rewarded 'healthy' behaviours rather than only penalising 'unhealthy' behaviours; (3) communication of policies, i.e., policies that were visible and had consistent and positive messages from the media (mentioned only by policymakers) and (4) how to improve policy support, with the main suggestion being an integrated strategy addressing multiple aspects of these behaviours, inclusive policies that consider everyone's needs and use of appropriate channels and messages in policy communication. CONCLUSIONS: Our findings highlight that members' of the public and policymakers' support for dietary and active-travel policies can be shaped by the perceived effectiveness, fairness and communication of policies and provide suggestions on how to improve policy support. This information can inform the design of acceptable policies but can also be used to help communicate existing and future policies to maximise their adoption and sustainability.

Development and Interrogation of a Transcriptomic Resource for the Giant Triton Snail (Charonia tritonis).

Gastropod molluscs are among the most abundant species that inhabit coral reef ecosystems. Many are specialist predators, along with the giant triton snail Charonia tritonis (Linnaeus, 1758) whose diet consists of Acanthaster planci (crown-of-thorns starfish), a corallivore known to consume enormous quantities of reef-building coral. C. tritonis are considered vulnerable due to overexploitation, and a decline in their populations is believed to have contributed to recurring A. planci population outbreaks. Aquaculture is considered one approach that could help restore natural populations of C. tritonis and mitigate coral loss; however, numerous questions remain unanswered regarding their life cycle, including the molecular factors that regulate their reproduction and development. In this study, we have established a reference C. tritonis transcriptome derived from developmental stages (embryo and veliger) and adult tissues. This was used to identify genes associated with cell signalling, such as neuropeptides and G protein-coupled receptors (GPCRs), involved in endocrine and olfactory signalling. A comparison of developmental stages showed that several neuropeptide precursors are exclusively expressed in post-hatch veligers and functional analysis found that FFamide stimulated a significant (20.3%) increase in larval heart rate. GPCRs unique to veligers, and a diversity of rhodopsin-like GPCRs located within adult cephalic tentacles, all represent candidate olfactory receptors. In addition, the cytochrome P450 superfamily, which participates in the biosynthesis and degradation of steroid hormones and lipids, was also found to be expanded with at least 91 genes annotated, mostly in gill tissue. These findings further progress our understanding of C. tritonis with possible application in developing aquaculture methods.

Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma.

BACKGROUND: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. METHODS: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. RESULTS: In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47-0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65-1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13-0.70). CONCLUSIONS: SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. CLINICAL TRIAL REGISTRATION: ISRCTN71070888; ClinialTrials.gov (NCT03529175).

Genetic merit for fertility traits in Holstein cows: VI. Oocyte developmental competence and embryo development.

The hypothesis of this study was that cows with good genetic merit for fertility traits (Fert+) would produce oocytes and embryos of greater quality than cows with poor genetic merit for fertility traits (Fert-) and that mRNA expression of candidate genes would reflect the observed differences in quality. The aim of the study, therefore, was to determine the effect of genetic merit for fertility traits on morphological classification and mRNA abundance of key genes in immature oocytes and cumulus cells following ovum pick-up and in embryos following superovulation, artificial insemination (AI), and uterine flushing. In experiment 1, 17 Fert+ and 11 Fert- cows, ranging from 54 to 84 d in milk, were submitted to ovum pick-up on 4 occasions during a 2-wk period. Recovered cumulus-oocyte complexes (COC) were morphologically graded. Oocytes and cumulus cells were separated, and mRNA abundance of genes associated with oocyte developmental competence was measured. There was no effect of genotype on the distribution of COC grades or on the mRNA abundance of the candidate genes in grade 1 COC. In experiment 2, 20 Fert+ and 19 Fert- cows, ranging from 71 to 189 d in milk, were submitted to superovulation and AI. The uteri of cows that responded to the superovulation protocol (17 Fert+ and 16 Fert- cows) were nonsurgically flushed 7 d postovulation. Recovered embryos were morphologically graded, and mRNA abundance of genes associated with embryo development was measured in grade 1 blastocysts. The response to the superovulation protocol was assessed by counting the number of codominant follicles on the day of AI, which was similar for both genotypes (22.0 ± 9.7 and 19.8 ± 8.2 for Fert+ and Fert- cows, respectively). There was no effect of genotype on the proportion of transferable embryos recovered or on the mRNA abundance of the candidate genes tested in the grade 1 blastocysts. Of the total embryos classified as blastocysts, however, the Fert+ cows tended to have a greater proportion of grade 1 blastocysts compared with Fert- cows (90% vs. 64%, respectively). In conclusion, genetic merit for fertility traits had a no effect on mRNA abundance of the candidate genes that were examined in immature oocytes and cumulus cells and in embryos recovered after superovulation. The observed differences in morphological blastocyst quality following superovulation would suggest that the superior reproductive performance of Fert+ cows could arise during the later stages of embryo development from d 7 until maternal recognition of pregnancy.

Putative chemosensory receptors are differentially expressed in the sensory organs of male and female crown-of-thorns starfish, Acanthaster planci.

BACKGROUND: Chemosensation is a critical signalling process for all organisms and is achieved through the interaction between chemosensory receptors and their ligands. The Crown-of-thorns starfish, Acanthaster planci species complex (COTS), is a predator of coral polyps and Acanthaster cf. solaris is currently considered to be one of the main drivers of coral loss on the Great Barrier Reef in Queensland, Australia. RESULTS: This study reveals the presence of putative variant Ionotropic Receptors (IRs) which are differentially expressed in the olfactory organs of COTS. Several other types of G protein-coupled receptors such as adrenergic, metabotropic glutamate, cholecystokinin, trace-amine associated, GRL101 and GPCR52 receptors have also been identified. Several receptors display male-biased expression within the sensory tentacles, indicating possible reproductive significance. CONCLUSIONS: Many of the receptors identified in this study may have a role in reproduction and are therefore key targets for further investigation. Based on their differential expression within the olfactory organs and presence in multiple tissues, it is possible that several of these receptor types have expanded within the Echinoderm lineage. Many are likely to be species-specific with novel ligand-binding affinity and a diverse range of functions. This study is the first to describe the presence of variant Ionotropic Glutamate Receptors in any Echinoderm, and is only the second study to investigate chemosensory receptors in any starfish or marine pest. These results represent a significant step forward in understanding the chemosensory abilities of COTS.

Understanding the health and wellbeing challenges of the food banking system: A qualitative study of food bank users, providers and referrers in London.

In the UK, food poverty has been associated with conditions such as obesity, malnutrition, hypertension, iron deficiency, and impaired liver function. Food banks, the primary response to food poverty on the ground, typically rely on community referral and distribution systems that involve health and social care professionals and local authority public health teams. The perspectives of these key stakeholders remain underexplored. This paper reports on a qualitative study of the health and wellbeing challenges of food poverty and food banking in London. An ethnographic investigation of food bank staff and users was carried out alongside a series of healthcare stakeholder interviews. A total of 42 participants were interviewed. A Critical Grounded Theory (CGT) analysis revealed that contemporary lived experiences of food poverty are embedded within and symptomatic of extreme marginalisation, which in turn impacts upon health. Specifically, food poverty was conceptualised by participants to: firstly, be a barrier to providing adequate care and nutrition for young children; secondly, be exacerbated by lack of access to adequate fresh food, food storage and cooking facilities; and thirdly, amplify existing health and social problems. Further investigation of the local government structures and professional roles that both rely upon and serve to further embed the food banking system is necessary in order to understand the politics of changing welfare landscapes.

A Sperm Spawn-Inducing Pheromone in the Silver Lip Pearl Oyster (Pinctada maxima).

Pheromones are considered to play an important role in broadcast spawning in aquatic animals, facilitating synchronous release of gametes. In oysters, the sperm has been implicated as a carrier for the spawn-inducing pheromone (SIP). In hatchery conditions, male pearl oysters (Pinctata maxima) can be stimulated to spawn through a variety of approaches (e.g. rapid temperature change), while females can only be induced to spawn through exposure to conspecific sperm, thus limiting development of targeted pairing, required for genetic research and management. The capacity for commercial production and improvement of genetic lines of pearl oysters could be greatly improved with access to a SIP. In this study, we prepared and sequenced crude and semi-purified P. maxima sperm extracts that were used in bioassays to localise the female SIP. We report that the P. maxima SIP is proteinaceous and extrinsically associated with the sperm membrane. Bioactivity from pooled RP-HPLC fractions, but not individual fractions, suggests that the SIP is multi-component. We conclude that crude sperm preparations, as described in this study, can be used as a sperm-free inducer of female P. maxima spawning, which enables for a more efficient approach to genetic breeding.

Multiomics analysis of the giant triton snail salivary gland, a crown-of-thorns starfish predator.

The giant triton snail (Charonia tritonis) is one of the few natural predators of the adult Crown-of-Thorns starfish (COTS), a corallivore that has been damaging to many reefs in the Indo-Pacific. Charonia species have large salivary glands (SGs) that are suspected to produce either a venom and/or sulphuric acid which can immobilize their prey and neutralize the intrinsic toxic properties of COTS. To date, there is little information on the types of toxins produced by tritons. In this paper, the predatory behaviour of the C. tritonis is described. Then, the C. tritonis SG, which itself is made up of an anterior lobe (AL) and posterior lobe (PL), was analyzed using an integrated transcriptomics and proteomics approach, to identify putative toxin- and feeding-related proteins. A de novo transcriptome database and in silico protein analysis predicts that ~3800 proteins have features consistent with being secreted. A gland-specific proteomics analysis confirmed the presence of numerous SG-AL and SG-PL proteins, including those with similarity to cysteine-rich venom proteins. Sulfuric acid biosynthesis enzymes were identified, specific to the SG-PL. Our analysis of the C. tritonis SG (AL and PL) has provided a deeper insight into the biomolecular toolkit used for predation and feeding by C. tritonis.

"I don't know how I'm still standing" a Bakhtinian analysis of social housing and health narratives in East London.

Housing is a significant determinant of health and substandard housing is a public health issue. East London has long had a shortage of social and affordable housing, worsened in recent years by a combination of stressors. In one of East London's most deprived boroughs, Newham, changes brought about by the 2011 Localism Act and the unique demands of being the host Olympic borough in 2012 have brought considerable pressures to bear on social infrastructure. This paper examines how these pressures were experienced by local residents via their narratives of social housing and health. The data reported here are from a qualitative study comprising two waves of data collection. Narrative family interviews and go-along interviews were conducted with 40 Newham residents at wave one and 28 at wave two. A narrative analysis with a Bakhtinian interpretation was undertaken. This revealed that residents framed experiences of social housing in terms of an inherent system-level ideology based on notions of need and waiting. A particularly striking feature of this ideology was the extent to which descriptions of ill health and impairment were implicated in constructions of housing need; participants directly attributed a range of health complaints to their housing predicaments, including stress, depression, cancer scares, panic attacks and loss of sleep. Understanding the contested ideology of social housing can illuminate both the dynamic processes of social exclusion and the ways in which its subjects seek to resist it.

Neuropeptides encoded within a neural transcriptome of the giant triton snail Charonia tritonis, a Crown-of-Thorns Starfish predator.

Neuropeptides represent a diverse class of signaling molecules originating from neural tissues. These chemical modulators orchestrate complex physiological events including those associated with growth and reproduction. De novo transcriptome sequencing of a cerebral ganglion library of the endangered giant triton snail (Charonia tritonis) was undertaken in an effort to identify key neuropeptides that control or influence its physiology. The giant triton snail is considered a primary predator of the corallivore Acanthaster planci (Crown-of-Thorns Starfish) that is responsible for a significant loss in coral cover on reefs in the Indo-Pacific. The transcriptome library was assembled into contigs, and then bioinformatic analysis was used to identify a repertoire of 38 giant triton snail neuropeptide precursor genes, and various isoforms, that encode conserved molluscan neuropeptides. C. tritonis neuropeptides show overall precursor organisation consistent with those of other molluscs. These include those neuropeptides associated with mollusc reproduction such as the APGWamide, buccalin, conopressin, gonadotropin-releasing hormone (GnRH), NKY and egg-laying hormone. These data provide a foundation for further studies targeted towards the functional characterisation of neuropeptides to further understand aspects of the biology of the giant triton snail, such as elucidating its reproductive neuroendocrine pathway to allow the development of knowledge based captive breeding programs.

Genes and associated peptides involved with aestivation in a land snail.

Some animals can undergo a remarkable transition from active normal life to a dormant state called aestivation; entry into this hypometabolic state ensures that life continues even during long periods of environmental hardship. In this study, we aimed to identify those central nervous system (CNS) peptides that may regulate metabolic suppression leading to aestivation in land snails. Mass spectral-based neuropeptidome analysis of the CNS comparing active and aestivating states, revealed 19 differentially produced peptides; 2 were upregulated in active animals and 17 were upregulated in aestivated animals. Of those, the buccalin neuropeptide was further investigated since there is existing evidence in molluscs that buccalin modulates physiology by muscle contraction. The Theba pisana CNS contains two buccalin transcripts that encode precursor proteins that are capable of releasing numerous buccalin peptides. Of these, Tpi-buccalin-2 is most highly expressed within our CNS transcriptome derived from multiple metabolic states. No significant difference was observed at the level of gene expression levels for Tpi-buccalin-2 between active and aestivated animals, suggesting that regulation may reside at the level of post-translational control of peptide abundance. Spatial gene and peptide expression analysis of aestivated snail CNS demonstrated that buccalin-2 has widespread distribution within regions that control several physiological roles. In conclusion, we provide the first detailed molecular analysis of the peptides and associated genes that are related to hypometabolism in a gastropod snail known to undergo extended periods of aestivation.

Global metabolite analysis of the land snail Theba pisana hemolymph during active and aestivated states.

The state of metabolic dormancy has fascinated people for hundreds of years, leading to research exploring the identity of natural molecular components that may induce and maintain this state. Many animals lower their metabolism in response to high temperatures and/or arid conditions, a phenomenon called aestivation. The biological significance for this is clear; by strongly suppressing metabolic rate to low levels, animals minimize their exposure to stressful conditions. Understanding blood or hemolymph metabolite changes that occur between active and aestivated animals can provide valuable insights relating to those molecular components that regulate hypometabolism in animals, and how they afford adaptation to their different environmental conditions. In this study, we have investigated the hemolymph metabolite composition from the land snail Theba pisana, a remarkably resilient mollusc that displays an annual aestivation period. Using LC-MS-based metabolomics analysis, we have identified those hemolymph metabolites that show significant changes in relative abundance between active and aestivated states. We show that certain metabolites, including some phospholipids [e.g. LysoPC(14:0)], and amino acids such as l-arginine and l-tyrosine, are present at high levels within aestivated snails. Further investigation of our T. pisana RNA-sequencing data elucidated the entire repertoire of phospholipid-synthesis genes in the snail digestive gland, as a precursor towards future comparative investigation between the genetic components of aestivating and non-aestivating species. In summary, we have identified a large number of metabolites that are elevated in the hemolymph of aestivating snails, supporting their role in protecting against heat or desiccation.

[Same words, different meanings: How epidemiological terminology struggles with population health intervention research]. / À mêmes mots, sens différents--les difficultés de la terminologie épidémiologique avec la recherche en interventions en santé des populations.

Public health research differs from clinical epidemiological research in that its focus is primarily on the population level social and structural determinants of individual health and the interventions that might ameliorate them, rather than having a primary focus on individual-level risks. It is typically concerned with the proximal and distal causes of health problems, and their location within complex systems, more than with single exposures. Thus, epidemiological terms and concepts may have very different implications when used in the context of population health. This paper considers some key differences in relation to terms like 'population', 'baseline', 'control group' 'outcome' and 'adverse effects'. Even the concept of an 'intervention' often needs careful handling. The paper concludes that there is a need for an expanded, and more realistic use of these terms in the population health intervention research context.

REGene: a literature-based knowledgebase of animal regeneration that bridge tissue regeneration and cancer.

Regeneration is a common phenomenon across multiple animal phyla. Regeneration-related genes (REGs) are critical for fundamental cellular processes such as proliferation and differentiation. Identification of REGs and elucidating their functions may help to further develop effective treatment strategies in regenerative medicine. So far, REGs have been largely identified by small-scale experimental studies and a comprehensive characterization of the diverse biological processes regulated by REGs is lacking. Therefore, there is an ever-growing need to integrate REGs at the genomics, epigenetics, and transcriptome level to provide a reference list of REGs for regeneration and regenerative medicine research. Towards achieving this, we developed the first literature-based database called REGene (REgeneration Gene database). In the current release, REGene contains 948 human (929 protein-coding and 19 non-coding genes) and 8445 homologous genes curated from gene ontology and extensive literature examination. Additionally, the REGene database provides detailed annotations for each REG, including: gene expression, methylation sites, upstream transcription factors, and protein-protein interactions. An analysis of the collected REGs reveals strong links to a variety of cancers in terms of genetic mutation, protein domains, and cellular pathways. We have prepared a web interface to share these regeneration genes, supported by refined browsing and searching functions at http://REGene.bioinfo-minzhao.org/.

Multi-tissue transcriptomics for construction of a comprehensive gene resource for the terrestrial snail Theba pisana.

The land snail Theba pisana is native to the Mediterranean region but has become one of the most abundant invasive species worldwide. Here, we present three transcriptomes of this agriculture pest derived from three tissues: the central nervous system, hepatopancreas (digestive gland), and foot muscle. Sequencing of the three tissues produced 339,479,092 high quality reads and a global de novo assembly generated a total of 250,848 unique transcripts (unigenes). BLAST analysis mapped 52,590 unigenes to NCBI non-redundant protein databases and further functional analysis annotated 21,849 unigenes with gene ontology. We report that T. pisana transcripts have representatives in all functional classes and a comparison of differentially expressed transcripts amongst all three tissues demonstrates enormous differences in their potential metabolic activities. The genes differentially expressed include those with sequence similarity to those genes associated with multiple bacterial diseases and neurological diseases. To provide a valuable resource that will assist functional genomics study, we have implemented a user-friendly web interface, ThebaDB (http://thebadb.bioinfo-minzhao.org/). This online database allows for complex text queries, sequence searches, and data browsing by enriched functional terms and KEGG mapping.

Characterisation of two conopressin precursor isoforms in the land snail, Theba pisana.

Increased understanding of the molecular components involved in mollusc reproduction may assist in understanding the evolutionary adaptations used by animals, including hermaphrodites, to produce offspring. The neuropeptide conopressin, a member of the vasopressin/oxytocin-like peptide family, can modulate various reproductive activities in invertebrates. In this study, we used the hermaphroditic land snail, Theba pisana, to investigate the presence and tissue-specific distribution of a conopressin gene. Our transcriptomic analysis of T. pisana CNS sheath tissue has revealed two conopressin gene transcripts (Tpi-conopressin-1 and Tpi-conopressin-2), each encoding for precursors containing an identical conopressin nonapeptide and a variable neurophysin. T. pisana conopressins share high identity with other land snails and slugs, as well as other mollusc and vertebrate vasopressin/oxytocin, supported by phylogenetic analysis. Conserved residues in the T. pisana neurophysin are important for peptide binding, and we present molecular dynamic models demonstrating the most likely stable structure of the Tpi-conopressin-1 peptide when associated with neurophysin. RT-PCR shows that Tpi-conopressin-1 is additionally expressed in reproductive tissues, including the dart sac, where abundant spatial expression throughout the sac region is found; this implies a role in 'love' dart synthesis or dart injection during mating. The presence of a conopressin receptor in the CNS sheath indicates CNS neural excitation. In summary, this study represents a detailed molecular analysis of conopressin in a land snail.

Differential peptide expression in the central nervous system of the land snail Theba pisana, between active and aestivated.

Hypometabolism is a physiological state of dormancy entered by many animals in times of environmental stress. There are gaps in our understanding of the molecular components used by animals to achieve this metabolic state. The availability of genomic and transcriptome data can be useful to study the process of hypometabolism at the molecular level. In this study, we use the land snail Theba pisana to identify peptides that may be involved in the hypometabolic state known as aestivation. We found a total of 22 neuropeptides in the central nervous system (CNS) that were differentially produced during activity and aestivation based on mass spectral-based neuropeptidome analysis. Of these, 4 were upregulated in active animals and 18 were upregulated in aestivation. A neuropeptide known to regulate muscle contractions in a variety of molluscs, the small cardioactive peptide A (sCAPA), and a peptide of yet unknown function (termed Aestivation Associated Peptide 12) were chosen for further investigation using temporal and spatial expression analysis of the precursor gene and peptide. Both peptides share expression within regions of the CNS cerebral ganglia and suboesophageal ganglia. Relative transcript abundance suggests that regulation of peptide synthesis and secretion is post-transcriptional. In summary, we provide new insights into the molecular basis of the regulation of aestivation in land snails through CNS peptide control.

"Everyone was looking at you smiling": East London residents' experiences of the 2012 Olympics and its legacy on the social determinants of health.

Mega-sporting event regeneration, as a specific approach to urban renewal, uses impending host-city status as a catalyst for revitalisation and has the potential to improve health both through addressing deprivation and by promoting increased sport and physical activity among the host-city's population. This qualitative study explored how hosting of the London 2012 Games impacted upon the way East London residents perceived and experienced the social determinants of health in their local neighbourhood. We conducted narrative family interviews, go-along interviews and video focus group workshops with 66 Newham residents, aged 12-55 years, immediately after the Games. A narrative analytic approach examined accounts of health and wellbeing experiences in terms of neighbourhood change and the spectacle of the Games. Participants of this qualitative study generally welcomed the respite and the unexpected chance to live in a cleaner, safer and more unified environment. However, this positivity was underscored by an acute awareness that this was a very temporary situation and one that was intended to support the event rather than residents.

Primordial germ cell migration in the yellowtail kingfish (Seriola lalandi) and identification of stromal cell-derived factor 1.

Primordial germ cells (PGCs) are progenitors of the germ cell lineage, giving rise to either spermatogonia or oogonia after the completion of gonadal differentiation. Currently, there is little information on the mechanism of PGCs migration leading to the formation of the primordial gonad in perciform fish. Yellowtail kingfish (Seriola lalandi) (YTK) (order Perciforms) inhabit tropical and temperate waters in the southern hemisphere. Fundamental details into the molecular basis of larval development in this species can be easily studied in Australia, as they are commercially cultured and readily available. In this study, histological analysis of YTK larvae revealed critical time points for the migration of PGCs to the genital ridge, resulting in the subsequent development of the primordial gonad. In YTK larvae at 3, 5, 7 and 10 days post hatch (DPH), PGCs were not yet enclosed by somatic cells, indicating the primordial gonad had not yet started to form. While at 15, 18 and 20 DPH PGCs had already settled at the genital ridge and started to become enclosed by somatic cells indicating the primordial gonad had started to develop. A higher number of PGCs were observed in the larvae at 15 and 18 DPH indicating PGCs proliferation, which corresponds with them becoming enclosed by the somatic cells. Directional migration of PGCs toward the genital ridge is a critical event in the subsequent development of a gonad. In zebrafish, mouse and chicken, stromal-cell derived factor (SDF1) signalling is one of the key molecules for PGC migration. We subsequently isolated from YTK the SDF1 (Slal-SDF1) gene, which encodes for a 98-residue precursor protein with a signal peptide at the N-terminus. There is spatial conservation between fish species of four cysteine residues at positions C9, C11, C34 and C49, expected to form disulphide bonds and stabilize the SDF structure. In YTK, Slal-SDF1 gene expression analyses shows that this gene is expressed in larvae from 1 to 22 DPH and demonstrates distinct spatial localisation in the larvae at 7 DPH. These results provide a platform for further studies into the molecular machinery of PGC migration in yellowtail kingfish, as well as other perciform fish species.

From trial to population: a study of a family-based community intervention for childhood overweight implemented at scale.

OBJECTIVES: To assess how outcomes associated with participation in a family-based weight management intervention (MEND 7-13, Mind, Exercise, Nutrition..Do it!) for childhood overweight or obesity implemented at scale in the community vary by child, family, neighbourhood and MEND programme characteristics. METHODS/SUBJECTS: Intervention evaluation using prospective service level data. Families (N=21,132) with overweight children are referred, or self-refer, to MEND. Families (participating child and one parent/carer) attend two sessions/week for 10 weeks (N=13,998; N=9563 with complete data from 1788 programmes across England). Sessions address diet and physical activity through education, skills training and motivational enhancement. MEND was shown to be effective in obese children in a randomised controlled trial (RCT). Outcomes were mean change in body mass index (BMI), age- and sex-standardised BMI (zBMI), self-esteem (Rosenberg scale) and psychological distress (Strengths and Difficulties Questionnaire) after the 10-week programme. Relationships between the outcome and covariates were tested in multilevel models adjusted for the outcome at baseline. RESULTS: After adjustment for covariates, BMI reduced by mean 0.76 kg m(-2) (s.e.=0.021, P<0.0001), zBMI reduced by mean 0.18 (s.e.=0.0038, P<0.0001), self-esteem score increased by 3.53 U (s.e.=0.13, P<0.0001) and psychological distress score decreased by 2.65 U (s.e.=0.31, P<0.0001). Change in outcomes varied by participant, family, neighbourhood and programme factors. Generally, outcomes improved less among children from less advantaged backgrounds and in Asian compared with white children. BMI reduction under service conditions was slightly but not statistically significantly less than in the earlier RCT. CONCLUSIONS: The MEND intervention, when delivered at scale, is associated with improved BMI and psychosocial outcomes on average, but may work less well for some groups of children, and so has the potential to widen inequalities in these outcomes. Such public health interventions should be implemented to achieve sustained impact for all groups.