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  • Journal article
    Goiana-Da-Silva F, Nunes AM, Miraldo M, Bento A, Breda J, Araujo FFet al., 2018,

    Taxation in Public Health Service: The Experience in Taxation of Sugary Drinks in Portugal (vol 4, pg 233, 2018)

    , ACTA MEDICA PORTUGUESA, Vol: 31, Pages: 233-233, ISSN: 1646-0758
  • Journal article
    Grmai L, Hudry B, Miguel-Aliaga I, Bach EAet al., 2018,

    Chinmo prevents transformer alternative splicing to maintain male sex identity

    , PLoS Genetics, Vol: 14, Pages: 1-27, ISSN: 1553-7390

    Reproduction in sexually dimorphic animals relies on successful gamete production, executed by the germline and aided by somatic support cells. Somatic sex identity in Drosophila is instructed by sex-specific isoforms of the DMRT1 ortholog Doublesex (Dsx). Female-specific expression of Sex-lethal (Sxl) causes alternative splicing of transformer (tra) to the female isoform traF. In turn, TraF alternatively splices dsx to the female isoform dsxF. Loss of the transcriptional repressor Chinmo in male somatic stem cells (CySCs) of the testis causes them to “feminize”, resembling female somatic stem cells in the ovary. This somatic sex transformation causes a collapse of germline differentiation and male infertility. We demonstrate this feminization occurs by transcriptional and post-transcriptional regulation of traF. We find that chinmo-deficient CySCs upregulate tra mRNA as well as transcripts encoding tra-splice factors Virilizer (Vir) and Female lethal (2)d (Fl(2)d). traF splicing in chinmo-deficient CySCs leads to the production of DsxF at the expense of the male isoform DsxM, and both TraF and DsxF are required for CySC sex transformation. Surprisingly, CySC feminization upon loss of chinmo does not require Sxl but does require Vir and Fl(2)d. Consistent with this, we show that both Vir and Fl(2)d are required for tra alternative splicing in the female somatic gonad. Our work reveals the need for transcriptional regulation of tra in adult male stem cells and highlights a previously unobserved Sxl-independent mechanism of traF production in vivo. In sum, transcriptional control of the sex determination hierarchy by Chinmo is critical for sex maintenance in sexually dimorphic tissues and is vital in the preservation of fertility.

  • Journal article
    Viner RM, Kinra S, Nicholls D, Cole T, Kessel A, Christie D, White B, Croker H, Wong ICK, Saxena Set al., 2018,

    Burden of child and adolescent obesity on health services in England

    , Arch Dis Child, Vol: 103, Pages: 247-254, ISSN: 0003-9888

    OBJECTIVE: To assess the numbers of obese children and young people (CYP) eligible for assessment and management at each stage of the childhood obesity pathway in England. DESIGN: Pathway modelling study, operationalising the UK National Institute for Health and Care Excellence guidance on childhood obesity management against national survey data. SETTING: Data on CYP aged 2-18 years from the Health Survey for England 2006 to 2013. MAIN OUTCOME MEASURES: Clinical obesity (body mass index (BMI) >98th centile), extreme obesity (BMI >/=99.86th centile); family history of cardiovascular disease or type 2 diabetes; obesity comorbidities defined as primary care detectable (hypertension, orthopaedic or mobility problems, bullying or psychological distress) or secondary care detectable (dyslipidaemia, hyperinsulinaemia, high glycated haemoglobin, abnormal liver function). RESULTS: 11.2% (1.22 million) of CYP in England were eligible for primary care assessment and for community lifestyle modification. 2.6% (n=283 500) CYP were estimated to be likely to attend primary care. 5.1% (n=556 000) were eligible for secondary care referral. Among those aged 13-18 years, 8.2% (n=309 000) were eligible for antiobesity drug therapy and 2.4% (90 500) of English CYP were eligible for bariatric surgery. CYP from the most deprived quintile were 1.5-fold to 3-fold more likely to be eligible for obesity management. CONCLUSIONS: There is a mismatch between population burden and available data on service use for obesity in CYP in England, particularly among deprived young people. There is a need for consistent evidence-based commissioning of services across the childhood obesity pathway based on population burden.

  • Journal article
    White B, Hsia Y, Kinra S, Saxena S, Christie D, Viner RM, Wong ICKet al., 2017,

    Survey of anti-obesity drug prescribing for obese children and young people in UK primary care.

    , BMJ Paediatrics Open, Vol: 1, ISSN: 2399-9772

    Objectives Antiobesity drug (AOD) prescribing in childrenand young people (CYP) in primary care is rising with highrates of discontinuation. Little is known about prescribingin this group in terms of patient demographics andcomorbidities, reasons for initiation and discontinuation, oradherence to national guidelines.Design Questionnaire survey to general practitioners(GPs) identified using a nationally representative primarycare database covering 6% of UK population.Setting UK-wide primary care.Participants Patients were eligible if prescribed anAOD aged ≤18 years between 2010 and 2012. A total of151 patients from 108 unique practices were identifiedvia national prescribing database, with responses for 119patients (79%) from 84 practices; 94 of 119 (79%) wereeligible for inclusion.Primary and secondary outcomes Survey of GPprescribing habits of AODs to CYP. We audited orlistatusage against the National Institute for Health and CareExcellence (NICE) guidance.Results 47% were prescribed metformin, 59% orlistatand 5% both drugs. Orlistat was largely prescribed by GPsindependently (49/55 prescriptions, 89%) and metforminby GPs on specialist recommendation (12/44, 27%).Orlistat was largely prescribed in those over 16 yearsof age without physical comorbidities. Metformin wasinitiated for treatment of polycystic ovarian syndrome(70%), insulin resistance (25%) and impaired glucosecontrol (9%). Median supply of metformin was 10.5months (IQR 4–18.5 months) and 2.0 months (1.0–4.0) fororlistat (p≤0.001). Drug terminations were largely due tofamilies not requesting repeat prescriptions. NICE guidanceadherence was low; 17% of orlistat prescriptions wereinitiated by specialists, and 56% had evidence of obesityrelatedcomorbidity. GPs reported lower confidence inprescribing AOD to CYP compared with adults (10-pointLikert score median 3 vs 8, p<0.001).Conclusions Prescribing of AOD in primary care ischallenging with low adherence to NICE guidance. Furtherwork is

  • Journal article
    Perea D, Guiu J, Hudry B, Konstantinidou C, Milona A, Hadjieconomou D, Carroll T, Hoyer N, Natarajan D, Kallijärvi J, Walker JA, Soba P, Thapar N, Burns AJ, Jensen KB, Miguel-Aliaga Iet al., 2017,

    Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia.

    , EMBO Journal, Vol: 36, Pages: 3029-3045, ISSN: 0261-4189

    Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homoeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders such as Hirschsprung disease.

  • Journal article
    Miguel-Aliaga I, 2017,

    Irene Miguel-Aliaga

    , Current Biology, Vol: 27, Pages: R286-R287, ISSN: 1879-0445
  • Journal article
    Finnamore H, Silva BM, Hickson BM, Whelan K, Shovlin CLet al., 2017,

    7-day weighed food diaries suggest patients with hereditary hemorrhagic telangiectasia may spontaneously modify their diet to avoid nosebleed precipitants

    , ORPHANET JOURNAL OF RARE DISEASES, Vol: 12, ISSN: 1750-1172

    Hereditary hemorrhagic telangiectasia (HHT) poses substantial burdens due to nosebleeds and iron deficiency resulting from recurrent hemorrhagic iron losses. Recent studies by our group found surprising links between HHT nosebleeds and certain food groups. In this letter, we report 7-day weighed food diary assessments of an unselected group of 25 UK patients with HHT whose nosebleeds ranged from mild to severe (median epistaxis severity score 4.66, range 0.89– 9.11). The diaries provide evidence that food items most commonly reported to provoke nosebleeds were ingested by fewer HHT patients, compared to food items less commonly reported to provoke nosebleeds (chi-squared p <0.001).

  • Book chapter
    Baxter WL, childs PRN, 2017,

    Designing Circular Possessions

    , The Routledge Handbook of Sustainable Product Design, Editors: Chapman

    The notion of possession is one of the most fundamental concepts that guide everyday behaviour. Paradoxically, it is often poorly understood. This is particularly true in a circular context where consumer interactions with possessions are being altered and in some cases redefined. Thus, an understanding of possession serves as a useful, if not necessary, prerequisite to designing circular products, services and systems. This chapter explores the idea of possession: what it is, how an object becomes one and why it is important for the circular economy. Possession is understood through a human-centred lens that considers the consumer’s state of mind towards and relationship with an object. A state of possessiveness can be attained for material or immaterial objects and for objects that may or may not legally belong to the person. The discussion is presented within a design framework that discusses the motives and routes that lead to the state of possession. This framework is substantiated by looking at affordance principles and paths associated with possession. Each section includes a theoretical discussion as well as practical examples and insights that can be incorporated into the product design process itself. This chapter aids in understanding interactions relevant to the circular economy such as the maintenance and care that comes with object attachment and adoption of access-based consumption models. Understanding and designing for these desired interactions should be the first priority of designers followed by an establishment of laws, regulations and policies to support them.

  • Journal article
    Sassi F, 2017,

    COUNTING THE COSTS OF ALCOHOL: HOW USEFUL AN AID TO POLICYMAKING?

    , ADDICTION, Vol: 112, Pages: 569-570, ISSN: 0965-2140
  • Journal article
    Garcia Perez I, Posma JM, Gibson R, Chambers ES, Hansen TH, Vestergaard H, Hansen T, Beckmann M, Pedersen O, Elliott P, Stamler J, Nicholson JK, Draper J, Mathers JC, Holmes E, Frost Get al., 2017,

    Objective assessment of dietary patterns using metabolic phenotyping: a randomized, controlled, crossover trial

    , The Lancet Diabetes & Endocrinology, Vol: 5, Pages: 184-195, ISSN: 2213-8587

    Background: The burden of non-communicable diseases, such as obesity, diabetes, coronary heart disease and cancer, can be reduced by the consumption of healthy diets. Accurate monitoring of changes in dietary patterns in response to food policy implementation is challenging. Metabolic profiling allows simultaneous measurement of hundreds of metabolites in urine, many of them influenced by food intake. We aim to classify people according to dietary behaviour and enhance dietary reporting using metabolic profiling of urine.Methods: To develop metabolite models from 19 healthy volunteers who attended a clinical research unit for four day periods on four occasions. We used the World Health Organisation’s healthy eating guidelines (increase fruits, vegetables, wholegrains, dietary fibre and decrease fats, sugars, and salt) to develop four dietary interventions lasting for four days each that ranged from a diet associated with a low to high risk of developing non-communicable disease. Urine samples were measured by 1H-NMR spectroscopy. This study is registered as an International Standard Randomized Controlled Trial, number ISRCTN 43087333. INTERMAP U.K. (n=225) and a healthy-eating Danish cohort (n=66) were used as free-living validation datasets.Findings: There was clear separation between the urinary metabolite profiles of the four diets. We also demonstrated significant stepwise differences in metabolite levels between the lowest and highest metabolic risk diets and developed metabolite models for each diet. Application of the derived metabolite models to independent cohorts confirmed the association between urinary metabolic and dietary profiles in INTERMAP (P<0•001) and the Danish cohort (P<0•001).Interpretation: Urinary metabolite models, developed in a highly controlled environment, can classify groups of free-living people into consumers of dietary profiles associated with lower or higher non-communicable disease risk based on multivariate m

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