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The aim of this study was to evaluate the influence of model (alcohol, sugar, salt, protein and acid) and real foods and beverages on the viability of probiotics during incubation and artificial digestion. Viability of monocultures Lactobacillus acidophilus CCM4833 and Bifidobacterium breve CCM7825T, and a commercial mixture of 9 probiotic bacterial strains, was tested by cultivation assay and flow cytometry. In model foods, the best viability was determined in the presence of 0.2 g/L glucose, 10% albumin and 10% ethanol. As the most suitable real food for probiotic survival, complex protein and carbohydrate substrates were found, such as beef broth, potato salad with pork, chicken with rice, chocolate spread, porridge and yoghurt. The best liquid was milk and meat broth, followed by Coca-Cola, beer and coffee. Viability of probiotics was higher when consumed with meals than with beverages only. Addition of prebiotics increased the viability of probiotics, especially in presence of instant and fast foods. Generally, the highest viability of probiotics during artificial digestion was observed in mixed culture in the presence of protein, sugar and fat, or their combination. The increase of cell viability observed in such foods during model digestion may further contribute to the positive effect of probiotics on human health.

Abstract Background Overdoses due to non-medical use of prescription opioids and other opiates have become the leading cause of accidental deaths in the USA. Buprenorphine and extended-release naltrexone are key evidence-based pharmacotherapies available to addiction treatment providers to address opioid use disorder (OUD) and prevent overdose deaths. Treatment organizations’ efforts to provide these pharmacotherapies have, however, been stymied by limited success in recruiting providers (physicians, nurse practitioners, and physician assistants) to prescribe these medications. Historically, the addiction treatment field has not attracted physicians, and many barriers to implementing OUD pharmacotherapy exist, ranging from lack of confidence in treating OUD patients to concerns regarding reimbursement. Throughout the USA, the prevalence of OUD far exceeds the capacity of the OUD pharmacotherapy treatment system. Poor access to OUD pharmacotherapy prescribers has become a workforce development need for the addiction treatment field and a significant health issue. Methods This cluster randomized controlled trial (RCT) is designed to increase buprenorphine and extended-release naltrexone treatment capacity for OUD. The implementation intervention to be tested is a bundle of OUD pharmacotherapy capacity building practices called the Prescriber Recruitment Bundle (PRB), which was developed and piloted in a previous statewide buprenorphine implementation study. For this cluster RCT, organizational sites will be recruited and then randomized into one of two arms: (1) control, with treatment as usual and access to a website with PRB resources, or (2) intervention, with organizations implementing the PRB using the Network for the Improvement of Addiction Treatment organizational change model over a 24-month intervention period and a 10-month sustainability period. The primary treatment outcomes for each organizational site are self-reported monthly counts of buprenorphine slots, extended-release naltrexone capacity, number of buprenorphine patients, and number of extended-release naltrexone patients. This trial will be conducted in Florida, Ohio, and Wisconsin, resulting in 35 sites in each arm, for a total sample size of 70 organizations. Discussion This study addresses three issues of substantial public health significance: (1) the pressing opioid misuse epidemic, (2) the low uptake of OUD treatment pharmacotherapies, and (3) the need to increase prescriber participation in the addiction treatment workforce. Trial registration ClinicalTrials.gov NCT02926482 ,

Business travel is nowadays a key component of tourism industry and an important instrument for reducing seasonality. Literature has identified several attributes that affect the decision-making process when choosing a destination to hold an event. The main objective of this research is to determine their importance and how they influence the decision-making process. Vilamoura in Portugal and Marbella in Spain are the destinations under analysis, as they are important seaside destinations where business travel has contributed to a successful meeting industry. In order to achieve the study’s aim, a qualitative methodology based on semi-structured interviews both to event organisers and suppliers has been conducted. The findings confirm the hypothesis that underpinned the study, demonstrating that destination image is the main determining site-selection factor. This investigation, proposed as an exploratory examination for further research, could constitute a useful resource for event professionals to improve their destination promotion and their positioning.

Recently, the electron transport through a quasi-one dimensional (quasi-1D) electron gas was investigated experimentally as a function of the confining potential. We present a physical model for quantum ballistic transport of electrons through a short conduction channel, and investigate the role played by the Coulomb interaction in modifying the energy levels of two-electron states at low temperatures as the width of the channel is increased. In this regime, the effect of the Coulomb interaction on the two-electron states has been shown to lead to four split energy levels, including two anticrossings and two crossing-level states. Due to the interplay between the anticrossing and crossing of the energy levels, the ground state for the two-electron model switches from one anticrossing state for strong confinement to a crossing state for intermediate confinement as the channel width is first increased, and then returned to its original anticrossing state. This switching behavior is related to the triplet spin degeneracy as well as the Coulomb repulsion and reflected in the ballistic conductance. Here, many-body effects can still affect electron occupations in the calculation of quantum ballistic conductance although it cannot vary the center-of-mass velocity.

A fast track “Hot Start” process was implemented to launch the European Bank for Induced Pluripotent Stem Cells (EBiSC) to provide early release of a range of established control and disease linked human induced pluripotent stem cell (hiPSC) lines. Established practice amongst consortium members was surveyed to arrive at harmonised and publically accessible Standard Operations Procedures (SOPs) for tissue procurement, bio-sample tracking, iPSC expansion, cryopreservation, qualification and distribution to the research community. These were implemented to create a quality managed foundational collection of lines and associated data made available for distribution. Here we report on the successful outcome of this experience and work flow for banking and facilitating access to an otherwise disparate European resource, with lessons to benefit the international research community. eTOC: The report focuses on the EBiSC experience of rapidly establishing an operational capacity to procure, bank and distribute a foundational collection of established hiPSC lines. It validates the feasibility and defines the challenges of harnessing and integrating the capability and productivity of centres across Europe using commonly available resources currently in the field.

Background People diagnosed with cancer are living longer and whilst cancer survival is improving for many cancers, there is not the same parity for all social groups - older people and people living in more deprived areas often have more chronic health conditions. We examined the association between those other health conditions and cancer incidence, prevalence and survival for all Welsh patients, for the four most common cancers and all malignant cancer cases (excluding non-melanoma skin cancer). Methods We extracted data on all malignant cancer cases from the WCISU’s population-based cancer registry for diagnosis periods 1995-2015. Cases were linked to a Cluster Network and to Patient Episode Database for Wales hospital data for the preceding year to establish pre-existing health conditions. From this, a Charlson score was calculated for each case - this is a validated score to predict risk of death and disease burden. For incidence and prevalence, we calculated the proportion of patients with Charlson score 0, 1 and 2+, and proportions with each health condition examined. We calculated one-year net survival by Charlson score or condition. Where possible, analysis was by cancer type, age-band, area deprivation, rurality, sex and stage at diagnosis. Results One in four people were already living with another serious condition. Patients diagnosed in more deprived areas of Wales were more likely to have an existing condition at diagnosis. Survival worsened as the severity or number of existing conditions increased. Conclusion Patients diagnosed with cancer in more deprived areas of Wales were more likely to be already living with another serious condition, showing a significant decrease in their projected survival at Charlson score 1 and 2+ compared to the least deprived areas. This work will enable acute, primary and community care, and other organisations to understand the overall burden of ill health in the cancer population in Wales.

Ali came to Denmark in 2011 to seek asylum. After two and a half years in asylum camps his case was rejected, and since then he has lived 'underground' as undocumented migrant in Copenhagen. The film explores Ali's experience of life as 'illegal migrant’ in Denmark. It deals with the conditions of ‘rightlessness’ and ‘deportability’ and how these conditions influence Ali’s general experience of time, place and belonging. Because of the threat of deportation Ali's face and identity is not shown in the film, and the story is carried by Ali's voice and images of Copenhagen city.

Introduction Over 30% of Canadians between the ages of 16 and 24 years attend university. This period of life coincides with the onset of common mental illnesses. Yet, data to inform university-based mental health prevention and early intervention initiatives are limited. The U-Flourish longitudinal study based out of Queen’s University, Canada and involving Oxford University in the UK, is a student informed study funded by the Canadian Institute for Health Research Strategy for Patient Oriented Research (CIHR-SPOR). The primary goal of U-Flourish research is to examine the contribution of risk and resiliency factors to outcomes of well-being and academic success in first year students transitioning to university.Methods and analysis The study is a longitudinal survey of all first-year undergraduate students entering Queen’s University in the fall term of 2018 (and will launch at Oxford University in fall of 2019). In accordance with the CIHR-SPOR definitions, students represent the target population (ie, patient equivalent). Student peer health educators were recruited to inform the design, content and implementation of the study. Baseline surveys of Queen’s first year students were completed in the fall of 2018, and follow-up surveys at the end of first year in the spring of 2019. Extensive student-led engagement campaigns were used to maximise participation rates. The baseline survey included measures of personal factors, family factors, environmental factors, psychological and emotional health, and lifestyle factors. Main outcomes include self-reported indicators of mental health at follow-up and mental health service access, as well as objective measures of academic success through linkage to university administrative and academic databases. A combination of mixed effects regression techniques will be employed to determine associations between baseline predictive factors and mental health and academic outcomes.Ethics and dissemination Ethical approval was obtained by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (HSREB) (#6023126) at Queen’s University. Findings will be disseminated through international and national peer-reviewed scientific articles and other channels including student-driven support and advocacy groups, newsletters and social media.

ABC exporters mediate the translocation of cytotoxic compounds to the cell exterior via ATP hydrolysis. Here, the authors show that the bacterial transporter MsbA requires additional energy from the transmembrane electrochemical proton gradient to facilitate drug transport.

Caloric vestibular stimulation (CVS) can temporarily reduce visuospatial neglect and related symptoms. The present study examined the effect of CVS on representational neglect during free exploration of the map of France. We asked patients to name cities they could mentally “see” on the map of France, without giving them any directional instructions related to the left or right sides of the map. In right brain damaged patients with left visuospatial neglect, the mental representation of the map was asymmetrical (favoring the right side). After stimulation, neglect patients named more towns on the left side of the map, leading to a significant reduction in map representation asymmetry. Our findings are consistent with previous studies on visuospatial neglect and are in favor of a central effect of vestibular stimulation on mechanisms involved in space representation.

Our study seeks to assess the effects of an initiation to research on the development of early career schoolteacher practices. This initiation, included in schoolteacher education in France, represents, in the particular case of Creteil, 120 hours spread over the two years of a master's degree. The thematic offer allows students to engage in different fields of research according to their choice. In our study, these fields concern the didactics of a discipline (mathematics, sports) or the transversal question of gender equality and sexuality, approached from a socio-didactic point of view. We are interested in the teaching practices of novice teachers during the first two years of practice after their tenure. Our ambition is to link certain professional gestures to the training offered in the initiation to research and the writing of a research essay, for each of our different fields.

Background: Childhood eczema is very common. Treatment often includes emollient bath additives, despite there being little evidence of their effectiveness. Objectives: To determine the clinical effectiveness and cost-effectiveness of emollient bath additives in the management of childhood eczema. Design: Pragmatic, randomised, open-label, multicentre superiority trial with two parallel groups. Setting: Ninety-six general practices in Wales, the west of England and southern England. Invitation by personal letter or opportunistically. Participants: Children aged between 12 months and 12 years fulfilling the UK Diagnostic Criteria for Atopic Eczema. Children with inactive or very mild eczema (a score of ≤ 5 on the Nottingham Eczema Severity Scale) were excluded, as were children who bathed less than once per week or whose parents/carers were not prepared to accept randomisation. Interventions: The intervention group were prescribed bath additives by their usual clinical team and were asked to use them regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued standard eczema management, including regular leave-on emollients and topical corticosteroids (TCSs) when required. Main outcome measures: The primary outcome was eczema control measured by Patient Oriented Eczema Measure [POEM, 0 (clear) to 28 (severe)] weekly for 16 weeks. The secondary outcomes were eczema severity over 1 year (4-weekly POEM), number of eczema exacerbations, disease-specific quality of life (QoL) (Dermatitis Family Impact Questionnaire), generic QoL (Child Health Utility-9 Dimensions) and type and quantity of topical steroid/calcineurin inhibitors prescribed. Children were randomised (1 : 1) using online software to either bath additives plus standard eczema care or standard eczema care alone, stratified by recruiting centre, and there was open-label blinding. Results: From December 2014 to May 2016, 482 children were randomised: 51% were female, 84% were white and the mean age was 5 years (n = 264 in the intervention group, n = 218 in the control group). Reported adherence to randomised treatment allocation was > 92% in both groups, with 76.7% of participants completing at least 12 (80%) of the first 16 weekly questionnaires for the primary outcome. Baseline POEM score was 9.5 [standard deviation (SD) 5.7] in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. Average POEM score over the first 16 weeks was 7.5 (SD 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group, with no statistically significant difference between the groups. After controlling for baseline severity and confounders (ethnicity, TCS use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additive group were 0.41 points higher than in the bath additive group (95% confidence interval –0.27 to 1.10), which is well below the published minimal clinically important difference of 3 points. There was no difference between groups in secondary outcomes or in adverse effects such as redness, stinging or slipping. Limitations: Simple randomisation resulted in an imbalance in baseline group size, although baseline characteristics were well balanced between groups. Conclusion: This trial found no evidence of clinical benefit of including emollient bath additives in the standard management of childhood eczema. Future work: Further research is required on optimal regimens of leave-on emollients and the use of emollients as soap substitutes. Trial registration: Current Controlled Trials ISRCTN84102309. Funding: This project was funded by the NIHR Health Technology Assessment Programme and will be published in full in Health Technology Assessment; Vol. 22, No. 57. See the NIHR Journals Library website for further project information.

Background Women with hypertensive pregnancy disorders have adverse levels of cardiovascular risk factors. It is unclear how this adverse risk factor profile evolves during adult life. We compared life course trajectories of cardiovascular risk factors in women with preeclampsia or gestational hypertension in their first pregnancy to normotensive women. Methods and Results We linked information on cardiovascular risk factors from the population‐based HUNT (Nord‐Trøndelag Health Study) surveys with pregnancy information from the Medical Birth Registry of Norway. Trajectories of cardiovascular risk factors were constructed for 22 308 women with a normotensive first pregnancy; 1092 with preeclampsia, and 478 with gestational hypertension in first pregnancy. Already before first pregnancy, women with preeclampsia in their first pregnancy had higher measures of adiposity, blood pressure, heart rate, and serum lipids and glucose compared with women with a normotensive first pregnancy. After first pregnancy, there was a parallel development in cardiovascular risk factor levels, but women with a normotensive first pregnancy had a time lag of >10 years compared with the preeclampsia group. There were no clear differences in risk factor trajectories between women with gestational hypertension and women with preeclampsia. Conclusions Women with hypertensive pregnancy disorders in their first pregnancy had an adverse cardiovascular risk factor profile before pregnancy compared with normotensive women, and the differences persisted beyond 50 years of age. Hypertensive disorders in pregnancy signal long‐term increases in modifiable cardiovascular risk factors, and may be used to identify women who would benefit from early prevention strategies.

INTRODUCTION: la prévalence de l’hépatite B est très variable à travers les espaces géographiques et semble influencée par l’infection à VIH. La présente étude vise à comparer la prévalence de l’hépatite B en fonction du statut sérologique VIH en milieu hospitalier à Parakou au Bénin.Méthodes: il s’agissait d’une étude transversale incluant les adultes de 18 ans et plus reçus au Centre Hospitalier Universitaire et Départemental de Parakou entre Mai 2011 et Juin 2012. Le diagnostic de l’hépatite B a été fait par la recherche de l’antigène HBs et celui du VIH par des tests rapides sur des prélèvements de sang veineux. Les données ont été analysées avec le logiciel EpiInfo. Un modèle de régression logistique multivariable a été développé pour explorer les facteurs associés à la présence de l’hépatite B.Résultats: sur un total de 1516 sujets inclus, 744 étaient séropositifs au VIH. L’âge moyen était de 31,3 +/- 11,1 ans et 65,1% étaient des femmes. La prévalence de l’hépatite B dans l’ensemble de l’échantillon a été estimée à 13,9% [IC95%: 12,2%-15,7%]. Cette prévalence était plus élevée chez les sujets séropositifs au VIH (16,9% vs 10,9%; p = 0,0006), mais la différence n’est cependant plus significative en analyse multivariée, en dehors du groupe des sujets originaires du Borgou/Alibori (p = 0,02). Une association constante a toutefois été observée entre la tranche d’âge de 24 à 44 ans (p = 0,03), le sexe masculin (p =0,01), le niveau d’étude primaire (p = 0,02) et une prévalence élevée de l’hépatite B.Conclusion: la prévalence de l’hépatite B était plus élevée chez les sujets séropositifs au VIH. Elle est influencée par l’âge, le sexe, le niveau d’instruction et l’origine géographique.

Isolated Hemihyperplasia (IHH) is a rare disorder that results in the enlargement of a portion of a limb, a complete limb or an entire half of an individual's body. We describe an 11 year-old girl with isolated hemihyperplasia of her right upper and lower extremities, breast, and vulvar region. A mass consisting of asymmetric enlargement and fatty infiltration of the right adductor compartment was first noticed at approximately 4 years of life and progressed dramatically to severely affect her gait. We surgically debulked the thigh and resected the excess skin to restore symmetry. The patient did well postoperatively, achieved excellent cosmesis, and restoration of gait.

For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and among alleles is poorly understood. Besides their fundamental biological significance, these questions have important implications for the interpretation of functional genetic analyses, for example, if these factors alter the ordering of allelic series or patterns of complementation. We examined the impact of genetic background and rearing environment for a series of mutations spanning the range of phenotypic effects for both the scalloped and vestigial genes, which influence wing development in Drosophila melanogaster. Genetic background and rearing environment influenced the phenotypic outcome of mutations, including intra-genic interactions, particularly for mutations of moderate expressivity. We examined whether cellular correlates (such as cell proliferation during development) of these phenotypic effects matched the observed phenotypic outcome. While cell proliferation decreased with mutations of increasingly severe effects, surprisingly it did not co-vary strongly with the degree of background dependence. We discuss these findings and propose a phenomenological model to aid in understanding the biology of genes, and how this influences our interpretation of allelic effects in genetic analysis.

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype.

Seabird aggregations at sea have been shown to be associated with concentrations of prey. Previous research identified Central California as a highly used foraging area for seabirds, with locally breeding seabirds foraging close to their colonies on Southeast Farallon Island. Herein, we focus on nonresident (i.e. non-locally breeding) seabird species off of Central California. We hypothesized that high-use foraging areas for nonresident seabirds would be influenced by oceanographic and bathymetric factors and that spatial and temporal distributions would be similar within planktivorous and generalist foraging guilds but would differ between them. With data collected by the Applied California Current Ecosystem Studies (ACCESS) partnership during cruises between April and October from 2004-2013, we developed generalized linear models to identify high-use foraging areas for each of six nonresident seabird species. The four generalist species are Phoebastria nigripes (black-footed albatross), Ardenna griseus (sooty shearwater), Ardenna creatopus (pink-footed shearwater), and Fulmarus glacialis (northern fulmar). The two planktivorous species are Phalaropus lobatus (red-necked phalarope) and Phalaropus fulicarius (red phalarope). Sea surface temperature was significant for generalist species and sea surface salinity was important for planktivorous species. The distance to the 200-m isobath was significant in five of six models, Pacific Decadal Oscillation with a 3-month lag in four models, and sea surface fluorescence, the distance to Cordell Bank, and depth in three models. We did not find statistically significant differences between distributions of individual seabird species within a foraging guild or between guilds, with the exception of the sooty shearwater. Model results for a multi-use seabird foraging area highlighted the continental shelf break, particularly within the vicinity of Cordell Bank, as the highest use areas as did Marxan prioritization. Our research methods can be implemented elsewhere to identify critical habitat that needs protection as human development pressures continue to expand to the ocean.

Background: Behavioural counselling with intensive follow-up for obesity is effective, but in resource-constrained primary care settings briefer approaches are needed. Objectives: To estimate the clinical effectiveness and cost-effectiveness of an internet-based behavioural intervention with regular face-to-face or remote support in primary care, compared with brief advice. Design: Individually randomised three-arm parallel trial with health economic evaluation and nested qualitative interviews. Setting: Primary care general practices in the UK. Participants: Patients with a body mass index of ≥ 30 kg/m2 (or ≥ 28 kg/m2 with risk factors) identified from general practice records, recruited by postal invitation. Interventions: Positive Online Weight Reduction (POWeR+) is a 24-session, web-based weight management intervention completed over 6 months. Following online registration, the website randomly allocated participants using computer-generated random numbers to (1) the control intervention (n = 279), which had previously been demonstrated to be clinically effective (brief web-based information that minimised pressure to cut down foods, instead encouraging swaps to healthier choices and increasing fruit and vegetables, plus 6-monthly nurse weighing); (2) POWeR+F (n = 269), POWeR+ supplemented by face-to-face nurse support (up to seven contacts); or (3) POWeR+R (n = 270), POWeR+ supplemented by remote nurse support (up to five e-mails or brief telephone calls). Main outcome measures: The primary outcome was a modelled estimate of average weight reduction over 12 months, assessed blind to group where possible, using multiple imputation for missing data. The secondary outcome was the number of participants maintaining a 5% weight reduction at 12 months. Results: A total of 818 eligible individuals were randomised using computer-generated random numbers. Weight change, averaged over 12 months, was documented in 666 out of 818 participants (81%; control, n = 227; POWeR+F, n = 221; POWeR+R, n = 218). The control group maintained nearly 3 kg of weight loss per person (mean weight per person: baseline, 104.4 kg; 6 months, 101.9 kg; 12 months, 101.7 kg). Compared with the control group, the estimated additional weight reduction with POWeR+F was 1.5 kg [95% confidence interval (CI) 0.6 to 2.4 kg; p = 0.001] and with POWeR+R was 1.3 kg (95% CI 0.34 to 2.2 kg; p = 0.007). By 12 months the mean weight loss was not statistically significantly different between groups, but 20.8% of control participants, 29.2% of POWeR+F participants (risk ratio 1.56, 95% CI 0.96 to 2.51; p = 0.070) and 32.4% of POWeR+R participants (risk ratio 1.82, 95% CI 1.31 to 2.74; p = 0.004) maintained a clinically significant 5% weight reduction. The POWeR+R group had fewer individuals who reported doing another activity to help lose weight [control, 47.1% (64/136); POWeR+F, 37.2% (51/137); POWeR+R, 26.7% (40/150)]. The incremental cost to the health service per kilogram weight lost, compared with the control group, was £18 (95% CI –£129 to £195) for POWeR+F and –£25 (95% CI –£268 to £157) for POWeR+R. The probability of being cost-effective at a threshold of £100 per kilogram was 88% and 98% for POWeR+F and POWeR+R, respectively. POWeR+R was dominant compared with the control group. No harms were reported and participants using POWeR+ felt more enabled in managing their weight. The qualitative studies documented that POWeR+ was viewed positively by patients and that health-care professionals generally enjoyed supporting patients using POWeR+. Study limitations: Maintenance of weight loss after 1 year is unknown. Future work: Identifying strategies for longer-term engagement, impact in community settings and increasing physical activity. Conclusion: Clinically valuable weight loss (> 5%) is maintained in 20% of individuals using novel written materials with brief follow-up. A web-based behavioural programme and brief support results in greater mean weight loss and 10% more participants maintain valuable weight loss; it achieves greater enablement and fewer participants undertaking other weight-loss activities; and it is likely to be cost-effective. Trial registration: Current Controlled Trials ISRCTN21244703. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 4. See the NIHR Journals Library website for further project information.

Cross-cultural understanding has been identified as an important graduate capability crucial for global citizenry, and most universities now include cultural skills or competence within their generic graduate capabilities. However, cross-cultural education and pedagogy are specialised areas and few academics are equipped, or have the confidence, to teach in this area. As a consequence, cross-cultural graduate capabilities are rarely effectively measured or assured. Despite these challenges, the Australian higher education sector is increasingly being called upon to Indigenise its curriculum and develop graduates with Indigenous cultural competence (Australian Universities Guiding Principles for Developing Indigenous Cultural Competency, 2011). This paper describes the approach used to introduce a unit into Curtin University's School of Nursing and Midwifery, in partnership with Curtin's Centre for Aboriginal Studies, with the aim of developing graduate Indigenous Australian cultural competence. Pedagogical approaches are discussed and an analysis of quantitative and qualitative data from the University's online student feedback mechanism provided. Results show that although the unit has provided the majority of students with a strong start on their journey to developing Indigenous cultural competence a single course is not sufficient and, consistent with the literature in the field, resistance to compulsory Indigenous content is evident. The paper considers some of the complexities of teaching Indigenous Australian content within a contemporary Australian university. In doing so, the paper explores what Indigenous cultural competency might be and how it might be achieved providing a useful model with application to other disciplines.

Policies that state dogs and cats should not be adopted as gifts are prevalent at animal welfare organizations, despite the fact that this belief is unfounded. Denying adopters who intend to give the animals as gifts may unnecessarily impede the overarching goal of increasing the rate of live-releases of dogs and cats from our nations’ shelter system. The results of this brief survey show that receiving a dog or cat as a gift was neither significantly associated with impact on self-perceived love/attachment, nor was it associated with whether or not respondents still had the dog or cat in the home. The results from this survey add to a growing body of literature that suggests there is no increased risk of relinquishment for dogs and cats received as a gift.

Eyewitness memories are malleable and can be influenced by many factors. This study focuses on how construal of the self can influence the memory and create the post-event misinformation effect. It is hypothesised that individuals with interdependent self-construal are more influenced by an authoritative source than individuals with independent self-construal. After watching a short clip showing a theft, participants were presented with a co-witness testimony including some misinformation, which came either from a police officer off-duty or an anonymous passer-by. Participants, aged 18-35, were recruited in Belgium, Germany, Norway, Slovakia, Switzerland and the UK. They were evaluated regarding their independence/interdependence with the Self-Construal Scale.

This Practice Report offers a strategic approach to making research and learning skills explicit within the curriculum of first year core units, by enabling a systematic process of pedagogical conversations between teaching faculty, learning skills advisers and librarians. It reports on a collaborative project between staff of Monash Library and academic staff of the faculties of Business and Economics and Information Technology. It offers tools and protocols for the review and renewal of curricula and co-curricula practice within a partnership model, informed by the Research Skills Development (RSD) Framework. It takes into account teaching and learning approaches, intervention and support strategies, assessment, and feedback mechanisms. It also responds to emerging trends in higher education delivery such as blended learning and the flipped classroom model (Baker, 2000).

Dansk Vi beskriver, hvordan virtuelle eksperimenter kan udnyttes i et læringsdesign ved at forberede de studerende til hands-on-eksperimenter ved storskalafaciliteter. Vi illustrerer designet ved at vise, hvordan virtuelle eksperimenter bruges på Niels Bohr Institutets kandidatkursus om neutronspredning. I den sidste uge af kurset, rejser studerende til et storskala neutronspredningsfacilitet for at udføre neutronspredningseksperimenter. Vi bruger studerendes udsagn om deres oplevelser til at argumentere for, at arbejdet med virtuelle experimenter forbereder de studerende til at engagere sig mere frugtbart med eksperimenter ved at lade dem fokusere på fysikken og relevante data i stedet for instrumenternes funktion. Vi hævder, at det er, fordi de kan overføre deres erfaringer med virtuelle eksperimenter til rigtige eksperimenter. Vi finder dog, at læring stadig er situeret i den forstand, at kun kendskab til bestemte eksperimenter overføres. Vi afslutter med at diskutere de muligheder, som virtuelle eksperimenter giver. English We describe how virtual experiments can be utilized in a learning design that prepares students for hands-on experiments at large-scale facilities. We illustrate the design by showing how virtual experiments are used at the Niels Bohr Institute in a master level course on neutron scattering. In the last week of the course, students travel to a large-scale neutron scattering facility to perform real neutron scattering experiments. Through student interviews and survey answers, we argue, that the virtual training prepares the students to engage more fruitfully with experiments by letting them focus on physics and data rather than the overwhelming instrumentation. We argue that this is because they can transfer their virtual experimental experience to the real-life situation. However, we also find that learning is still situated in the sense that only knowledge of particular experiments is transferred. We proceed to discuss the affordances of virtual experiments.

Progress has been slow in improving health disparities between Aboriginal and Torres Strait Islander (Indigenous) Australians and other Australians. While reasons for this are complex, delivering healthcare respectful of cultural differences is one approach to improving Indigenous health outcomes. This paper presents and evaluates an intercultural academic leadership programme developed to support tertiary educators teaching Indigenous health and culture prepare interdisciplinary students to work respectfully and appropriately as health professionals with Indigenous peoples. The programme acknowledges the impact of colonisation on Indigenous Australians and draws on theories of the intercultural space to inform reflection and discussion on Indigenous/non-Indigenous relations and their impact on healthcare. Furthermore, the programme encourages establishing a community of practice as a resource for educators. Evaluation indicated participants’ confidence to teach Indigenous content increased following the programme. Participants felt more able to create intercultural, interdisciplinary and interactive learning spaces that were inclusive and safe for students from all cultures. Participants learned skills to effectively facilitate and encourage students to grapple with the complexity of the intercultural space, often tense, uncertain and risky, to enable new understandings and positions to emerge that could better prepare graduates to work in Indigenous health contexts.

The nonsense-mediated mRNA decay (NMD) pathway functions to degrade both abnormal and wild-type mRNAs. NMD is essential for viability in most organisms, but the molecular basis for this requirement is unknown. Here we show that a single, conserved NMD target, the mRNA coding for the stress response factor growth arrest and DNA-damage inducible 45 (GADD45) can account for lethality in Drosophila lacking core NMD genes. Moreover, depletion of Gadd45 in mammalian cells rescues the cell survival defects associated with NMD knockdown. Our findings demonstrate that degradation of Gadd45 mRNA is the essential NMD function and, surprisingly, that the surveillance of abnormal mRNAs by this pathway is not necessarily required for viability.

Clubroot disease affects all Brassicaceae spp. and is caused by the obligate biotroph pathogen Plasmodiophora brassicae. The development of galls on the root system is associated with the establishment of a new carbon metabolic sink. Here, we aimed to deepen our knowledge of the involvement of primary metabolism in the Brassica napus response to clubroot infection. We studied the dynamics and the diversity of the metabolic responses to the infection. Root system metabotyping was carried out for 18 rapeseed genotypes displaying different degrees of symptom severity, under inoculated and noninoculated conditions at 42 days postinoculation (dpi). Clubroot susceptibility was positively correlated with clubroot-induced accumulation of several amino acids. Although glucose and fructose accumulated in some genotypes with minor symptoms, their levels were negatively correlated to the disease index across the whole set of genotypes. The dynamics of the metabolic response were studied for the susceptible genotype ‘Yudal,’ which allowed an “early” metabolic response (established from 14 to 28 dpi) to be differentiated from a “late” response (from 35 dpi). We discuss the early accumulation of amino acids in the context of the establishment of a nitrogen metabolic sink and the hypothetical biological role of the accumulation of glutathione and S-methylcysteine.

The surveillance programme of work-related diseases (WRD) is based on a network of occupational physicians who notify all WRD diagnosed during a two-week observation period. The aims are mainly to estimate the prevalence of non-compensated WRD in the working population according to socio economic factors; to determine new indicators of occupational health; to update the lists of compensable occupational diseases; to understand and assess undercompensation and under-notification. The participation rate for occupational physicians is around 33% in 2008. The main WRD are the musculoskeletal disorders, followed by the mental disorders. This 2-week protocol, repeated regularly, provides useful data on frequency of pathologies linked to employment as well as an estimate of unreported WRD subject to compensation or non-compensated WRDs, and the trends of WRDs over the time.

With an apparent increase of harmful algal blooms (HABs) worldwide,healthcare providers, public health personnel and coastal managers are struggling toprovide scientifically-based appropriately-targeted HAB outreach and education. Since1998, the Florida Poison Information Center-Miami, with its 24 hour/365 day/year freeAquatic Toxins Hotline (1-888-232-8635) available in several languages, has received over 25,000 HAB-related calls. As part of HAB surveillance, all possible cases of HAB-relatedillness among callers are reported to the Florida Health Department. This pilot studyevaluated an automated call processing menu system that allows callers to access bilingualHAB information, and to speak directly with a trained Poison Information Specialist. Themajority (68%) of callers reported satisfaction with the information, and many provided specific suggestions for improvement. This pilot study, the first known evaluation of use and satisfaction with HAB educational outreach materials, demonstrated that the automated system provided useful HAB-related information for the majority of callers, and decreased the routine informational call workload for the Poison Information Specialists, allowing them to focus on callers needing immediate assistance and their healthcare providers. These results will lead to improvement of this valuable HAB outreach, education and surveillance tool. Formal evaluation is recommended for future HAB outreach and educational materials.

We previously reported enzymatic activity assays for the base excision repair (BER) enzymes DNA polymerase β (pol β), aprataxin (APTX), and flap endonuclease 1 (FEN1) in cell extracts from Saccharomyces cerevisiae (Çağlayan and Wilson, 2014). Here, we describe a method to prepare cell extracts from vertebrate cells to investigate these enzymatic activities for the processing of the 5´-adenylated-sugar phosphate-containing BER intermediate. This new protocol complements our previous publication. The cell lines used are wild-type and APTX-deficient human lymphoblast cells from an Ataxia with Oculomotor Apraxia Type 1 (AOA1) disease patient, wild-type and APTX-null DT40 chicken B cells, and mouse embryonic fibroblast (MEF) cells. This protocol is a quick and efficient way to make vertebrate cell extracts without using commercial kits.

Krill (Euphausiids) play a vital ecosystem role in many of the world's most productive marine regions, providing an important trophic linkage. We introduce a robust modeling approach to link Cassin's auklet (Ptychoramphus aleuticus) abundance and distribution to large-scale and local oceanic and atmospheric conditions and relate these patterns to similarly modeled distributions of an important prey resource, krill. We carried out at-sea strip transect bird surveys and hydroacoustic assessments of euphausiids (2004-2013). Data informed separate, spatially-explicit predictive models of Cassin's auklet abundance (zero-inflated negative binomial regression) and krill biomass (two-part model) based on these surveys. We established the type of prey responsible for acoustic backscatter by conducting net tows of the upper 50 m during surveys. We determined the types of prey fed to Cassin's auklet chicks by collecting diet samples from provisioning adults. Using time-depth-recorders, we found Cassin's auklets utilized consistent areas in the upper water column, less than 30 m, where krill could be found (99.5% of dives were less than 30 m). Birds primarily preyed upon two species of euphausiids, Euphausia pacifica and Thysanoessa spinifera, which were available in the upper water column. Cassin's auklet abundance was best predicted by both large scale and localized oceanic processes (upwelling) while krill biomass was best predicted by local factors (temperature, salinity, and fluorescence) and both large scale and localized oceanic processes (upwelling). Models predicted varying krill and bird distribution by month and year. Our work informs the use of Cassin's auklet as a valuable indicator or krill abundance and distribution and strengthens our understanding of the link between Cassin's auklet and its primary prey. We expect future increases in frequency and magnitude of anomalous ocean conditions will result in decreased availability of krill leading to declines in the Farallon Islands population of Cassin's auklets.

Two consanguineous Qatari siblings presented for evaluation: a 17-4/12-year-old male with hypogonadotropic hypogonadism, alopecia, intellectual disability, and microcephaly and his 19-year-old sister with primary amenorrhea, alopecia, and normal cognition. Both required hormone treatment to produce secondary sex characteristics and pubertal development beyond Tanner 1. SNP array analysis of both probands was performed to detect shared regions of homozygosity which may harbor homozygous mutations in a gene causing their common features of abnormal pubertal development, alopecia, and variable cognitive delay. Our patients shared multiple homozygous genomic regions; ten shared regions were >1 Mb in length and constituted 0.99% of the genome. DCAF17, encoding a transmembrane nuclear protein of uncertain function, was the only gene identified in a homozygous region known to cause hypogonadotropic hypogonadism. DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Sequencing of the coding exons and flanking intronic regions of DCAF17 in the proband revealed homozygosity for a previously described founder mutation (c.436delC). Targeted DCAF17 sequencing of his affected sibling revealed the same homozygous mutation. This family illustrates the utility of SNP array testing in consanguineous families to efficiently and inexpensively identify regions of genomic homozygosity in which genetic candidates for recessive conditions can be identified.

This article details reflections of an interdisciplinary team of educators working with groups of health sciences students in preparing them for working with Aboriginal and Torres Strait Islander peoples. The first-year common core unit discussed here is one attempt to equip future health practitioners with skills and knowledges to work adequately in this complex area. Processes of engagement, central to critical reflection and learning that is iterative and cyclical, are emphasised here using the authors’/educators’ experiences of teaching in the unit. Within this first-year unit, the content delivered — its underlying processes and principles, and assessment design using reflective journalling — coalesces into what is a valued unit of study in preparing students for practising in this field. While the content of the unit is political, provocative and powerful, which presents challenges for students and teaching staff alike, we maintain here that processes of critical reflection and action learning are central to its success and significantly contribute to enhancing students’ learning and to changing students’ perspectives.

Understanding seabird habitat preferences is critical to future wildlife conservation and threat mitigation in California. The objective of this study was to investigate drivers of seabird habitat selection within the Gulf of the Farallones and Cordell Bank National Marine Sanctuaries to identify areas for targeted conservation planning. We used seabird abundance data collected by the Applied California Current Ecosystem Studies Program (ACCESS) from 2004-2011. We used zero-inflated negative binomial regression to model species abundance and distribution as a function of near surface ocean water properties, distances to geographic features and oceanographic climate indices to identify patterns in foraging habitat selection. We evaluated seasonal, inter-annual and species-specific variability of at-sea distributions for the five most abundant seabirds nesting on the Farallon Islands: western gull (Larus occidentalis), common murre (Uria aalge), Cassin's auklet (Ptychorampus aleuticus), rhinoceros auklet (Cerorhinca monocerata) and Brandt's cormorant (Phalacrocorax penicillatus). The waters in the vicinity of Cordell Bank and the continental shelf east of the Farallon Islands emerged as persistent and highly selected foraging areas across all species. Further, we conducted a spatial prioritization exercise to optimize seabird conservation areas with and without considering impacts of current human activities. We explored three conservation scenarios where 10, 30 and 50 percent of highly selected, species-specific foraging areas would be conserved. We compared and contrasted results in relation to existing marine protected areas (MPAs) and the future alternative energy footprint identified by the California Ocean Uses Atlas. Our results show that the majority of highly selected seabird habitat lies outside of state MPAs where threats from shipping, oil spills, and offshore energy development remain. This analysis accentuates the need for innovative marine spatial planning efforts and provides a foundation on which to build more comprehensive zoning and management in California's National Marine Sanctuaries.

Glucose sensing (eg. glucokinase activity) becomes impaired in the development of type 2 diabetes, the etiology of which is unclear. Estrogen can stimulate glucokinase activity, whereas the pervasive environmental pollutant bisphenol A (BPA) can inhibit estrogen action, hence we aimed to determine the effect of BPA on glucokinase activity directly.To evaluate a potential acute effect on hepatic glucokinase activity, BPA in water (n = 5) vs. water alone (n = 5) was administered at the EPA's purported "safe dose" (50 µg/kg) by gavage to lean 6-month old male C57BL/6 mice. Two hours later, animals were euthanized and hepatic glucokinase activity measured over glucose levels from 1-20 mmol/l in liver homogenate. To determine the effect of chronic BPA exposure on hepatic glucokinase activity, lean 6-month old male C57BL/6 mice were provided with water (n = 15) or water with 1.75 mM BPA (∼50 µg/kg/day; n = 14) for 2 weeks. Following the 2-week exposure, animals were euthanized and glucokinase activity measured as above.Hepatic glucokinase activity was signficantly suppressed after 2 hours in animals given an oral BPA bolus compared to those who received only water (p = 0.002-0.029 at glucose 5-20 mmol/l; overall treatment effect p

The unfolded protein response (UPR) is a collection of pathways that maintains the protein secretory pathway during the many physiological and pathological conditions that cause stress in the endoplasmic reticulum (ER). The UPR is mediated in part by Ire1, an ER transmembrane kinase and endoribonuclease that is activated when misfolded proteins accumulate in the ER. Ire1's nuclease initiates the cytosolic splicing of the mRNA encoding X-box binding protein (Xbp1), a potent transcription factor that then upregulates genes responsible for restoring ER function. This same nuclease is responsible for the degradation of many other mRNAs that are localized to the ER, through Regulated Ire1 Dependent Decay (RIDD). Here we show that Smt3, a homolog of small ubiquitin-like modifier (sumo), is a non-canonical RIDD target in Drosophila S2 cells. Unlike other RIDD targets, the sumo transcript does not stably associate with the ER membrane, but instead relies on an Xbp1-like stem loop and a second UPR mediator, Perk, for its degradation during stress.

Root-knot nematodes (RKN) are obligatory plant parasitic worms that establish and maintain an intimate relationship with their host plants. During a compatible interaction, RKN induce the redifferentiation of root cells into multinucleate and hypertrophied giant cells essential for nematode growth and reproduction. These metabolically active feeding cells constitute the exclusive source of nutrients for the nematode. Detailed analysis of glutathione (GSH) and homoglutathione (hGSH) metabolism demonstrated the importance of these compounds for the success of nematode infection in Medicago truncatula. We reported quantification of GSH and hGSH and gene expression analysis showing that (h)GSH metabolism in neoformed gall organs differs from that in uninfected roots. Depletion of (h)GSH content impaired nematode egg mass formation and modified the sex ratio. In addition, gene expression and metabolomic analyses showed a substantial modification of starch and γ-aminobutyrate metabolism and of malate and glucose content in (h)GSH-depleted galls. Interestingly, these modifications did not occur in (h)GSH-depleted roots. These various results suggest that (h)GSH have a key role in the regulation of giant cell metabolism. The discovery of these specific plant regulatory elements could lead to the development of new pest management strategies against nematodes.

Transforming growth factor (TGF) β has diverse and sometimes paradoxical effects on cell proliferation and differentiation, presumably reflecting a fundamental but incompletely-understood role in regulating tissue homeostasis. It is generally considered that downstream activity is modulated at the ligand:receptor axis, but microarray analysis of proliferative versus differentiating normal human bladder epithelial cell cultures identified unexpected transcriptional changes in key components of the canonical TGFβ R/activin signalling pathway associated with cytodifferentiation. Changes included upregulation of the transcriptional modulator SMAD3 and downregulation of inhibitory modulators SMURF2 and SMAD7. Functional analysis of the signalling pathway revealed that non-differentiated normal human urothelial cells responded in paracrine mode to TGFβ by growth inhibition, and that exogenous TGFβ inhibited rather than promoted differentiation. By contrast, in differentiated cell cultures, SMAD3 was activated upon scratch-wounding and was involved in promoting tissue repair. Exogenous TGFβ enhanced the repair and resulted in hyperplastic scarring, indicating a feedback loop implicit in an autocrine pathway. Thus, the machinery for autocrine activation of the SMAD3-mediated TGFβR pathway is established during urothelial differentiation, but signalling occurs only in response to a trigger, such as wounding. Our study demonstrates that the circuitry of the TGFβR pathway is defined transcriptionally within a tissue-specific differentiation programme. The findings provide evidence for re-evaluating the role of TGFβR signalling in epithelial homeostasis as an autocrine-regulated pathway that suppresses differentiation and promotes tissue repair. This provides a new paradigm to help unravel the apparently diverse and paradoxical effect of TGFβ signalling on cell proliferation and differentiation.

In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination.

BACKGROUND:Candida albicans is a low level commensal organism in normal human populations with the continuous potential to expand and cause a spectrum of clinical conditions. METHODOLOGY/PRINCIPAL FINDINGS:Using ex vivo human organ cultures and populations of primary human cells, we have developed several related experimental systems to examine early-stage interactions between C. albicans and mucosal surfaces. Experiments have been conducted both with exogenously added C. albicans and with overtly normal human mucosal surfaces supporting pre-existing infections with natural isolates of Candida. Under different culture conditions, we have demonstrated the formation of C. albicans colonies on human target cells and filament formation, equivalent to tissue invasion. CONCLUSIONS/SIGNIFICANCE:These organ culture systems provide a valuable new resource to examine the molecular and cellular basis for Candida colonization of human mucosal surfaces.

Introduction Women with a history of gestational diabetes mellitus (GDM) are at increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Recommendations for postpartum follow-up include targeted lifestyle advice to lower the risk.The aim of this study was to compare postpartum lifestyle behaviours and perceptions among women with and without a history of GDM. In addition, we examined whether lifestyle behaviours of women with a history of GDM participating in a lifestyle intervention study differed from lifestyle behaviours of women with a history of GDM in the general population.Research design and methods We linked data from the fourth survey of the population-based Trøndelag Health Study (HUNT4) to information from the Medical Birth Registry of Norway for women with registered births between 2000 and 2019. Using logistic regression, we compared lifestyle behaviours in women with and without GDM. In secondary analyses, lifestyle behaviours in women with GDM participating in a postpartum lifestyle intervention study were compared with HUNT participants with GDM using Fisher’s exact tests/t-tests.Results A high proportion of the women in our population, regardless of GDM history, reported several unhealthy lifestyle behaviours. We found no significant association between history of GDM and lifestyle behaviours. The lifestyle intervention study for women with a history of GDM appeared to recruit women with more favourable lifestyle behaviours.Conclusions Women, regardless of GDM history, could potentially benefit from further support for lifestyle improvement, but it may be especially important in women with a history of GDM given their increased risk of T2DM and CVD. Interventions targeting women with GDM might not reach the women with the unhealthiest lifestyle behaviours, and measures to reach out to all women should be further investigated.

Background: We have demonstrated that 6-month urinary CCL2: Cr is a predictor of interstitial fibrosis and tubular atrophy (IFTA) on 24-month biopsy and death-censored graft loss. However, IFTA is no longer considered prognostically significant, whereas patients with graft loss frequently have interstitial fibrosis and inflammation (IF+i=ci>0+i>0). As early CCL2: Cr predicts late graft loss, the goal of this study was to determine if 6-month urinary CCL2: Cr was a predictor of IF+i at 24 months., Methods: Urinary CCL2 at 6 months was measured with ELISA and correlated with IF+i on 24-month surveillance biopsies from a prospective, multicenter adult renal transplant cohort (n=111)., Results: Six-month urinary CCL2: Cr was significantly higher in IF+i and transplant glomerulopathy patients compared with normal histology at 24 months. By multivariate analysis, 6-month urinary CCL2: Cr was independently correlated with IF+i at 24 months (OR 2.78, 95% CI 1.38-6.12, AUC 0.695, P=0.003). Six-month urinary CCL2: Cr was also an independent correlate of 6-month IF+i (OR 1.99, 95% CI 1.03-4.18, AUC 0.63, P=0.04). Six-month urinary CCL2: Cr distinguished noninflamed renal tissue (normal, fibrosis) from IF+i with a sensitivity/specificity of 0.71/0.62 at a cutoff of 15 ng CCL2/mmol Cr (AUC 0.695, P=0.003, n=91)., Conclusions: Urinary CCL2: Cr may be useful for the noninvasive identification of patients with or at risk for IF+i. These patients may benefit from avoidance of drug minimization/withdrawal protocols and more intensive post-transplant surveillance. Furthermore, urinary CCL2: Cr may also identify individuals who may benefit from novel interventional trials targeting IF+i.