Linguistically responsive learning and teaching for non-native speakers in undergraduate nursing education: a scoping review protocol.

INTRODUCTION: Non-native-speaking nursing students as well as faculty, preceptors and mentors face specific issues related to language in undergraduate nursing education. A better understanding of the language experiences, needs, requirements, assessments and support activities will guide linguistically responsive learning and teaching and will direct future curriculum development. This scoping review aims to examine and map the extent of literature related to linguistically responsive learning and teaching for non-native speakers in undergraduate nursing education and to describe the lived experiences, barriers and facilitators, language needs, assessment tools and supportive interventions. METHODS AND ANALYSIS: This scoping review will follow the Joanna Briggs Institute (JBI) methodology for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). In May 2023, a preliminary search was conducted. The comprehensive search will include MEDLINE (PubMed), CINAHL (EBSCO), ERIC (EBSCO) and MLA (EBSCO). OpenGrey (DANS) and reference lists of the included articles will be searched for grey literature and additional articles. Two independent reviewers will screen titles and abstracts, then review the full texts of articles. Data will be extracted using a data extraction form and will be presented in figures, tables and narrative syntheses, in line with the review questions. This review will include articles that describe the experiences of non-native-speaking nursing students, faculty or preceptors in undergraduate nursing education and clinical practice environment. Articles that report on language requirements, needs and assessment tools will also be considered as well as articles reporting on supportive activities and interventions within the study programmes. Articles related to exchange students or programmes will be excluded. ETHICS AND DISSEMINATION: No ethical approval is required. The findings of the review will be disseminated through peer-review publication as well as oral and poster presentations at scientific conferences.

Health promotion intervention among women with recent gestational diabetes mellitus: penetration, participation, and baseline findings from the Face-it randomized controlled trial.

INTRODUCTION: Face-it is a randomized controlled trial for women with recent gestational diabetes mellitus (GDM) and their families designed to evaluate the effect of a health promotion intervention on type 2 diabetes mellitus (T2DM) risk and quality of life. This study examined (1) the penetration and participation rates for the Face-it trial, (2) the characteristics of the participating women and the potential differences in characteristics according to partner participation status, and (3) representativity of the women at baseline. RESEARCH DESIGN AND METHODS: We identified women with GDM during pregnancy and invited them and their partners to a baseline examination 10-14 weeks after delivery. Representativity was assessed by comparing the baseline participants with non-participating women, the general population of women with GDM delivering in Denmark, and populations from other intervention trials. RESULTS: The penetration rate was 38.0% (867/2279) and the participation rate was 32.9% (285/867). The 285 women who attended baseline had a mean age of 32.7 (±4.8) years and body mass index (BMI) of 28.1 (±5.4) kg/m2, and 69.8% had a partner who participated. The women participating with a partner were more often primiparous, born in Denmark (82.8% vs 68.2%), were younger, and more often had a BMI ≤24.9 kg/m2 (35.7% vs 21.2%) compared with women without a partner. Compared with the general population of women with GDM in Denmark, these women broadly had similar degree of heterogeneity, but had higher rates of primiparity and singleton deliveries, and lower rates of preterm delivery and prepregnancy obesity. CONCLUSIONS: The penetration and participation rates were acceptable. We found a high rate of partner participation. Overall, women participating with a partner were comparable with those participating without a partner. Participating women were broadly similar to the general national GDM population, however with prepregnancy obesity, multiparity, preterm delivery, and multiple pregnancy being less represented. TRIAL REGISTRATION NUMBER: NCT03997773.

The experience of women with recent gestational diabetes during the COVID-19 lockdown: a qualitative study from Denmark.

BACKGROUND: Following COVID-19 and the lockdowns, maternity care and support for women after delivery have been temporary restructured. Studies show that COVID-19 adversely impacts pregnant and peripartum women in the general population, but experiences among women in the first year after delivery/in the wider postpartum period remain unexplored. Moreover, experiences among women with recent gestational diabetes mellitus (GDM) are lacking; though it is a group with a potential high need for support after delivery. The aim of our study was to investigate (i) how women with recent GDM experienced COVID-19 and the first lockdown in Denmark, and (ii) the women's risk perception and health literacy in terms of interaction with the healthcare system in relation to COVID-19. METHODS: We performed a qualitative study among 11 women with recent GDM (infants aged 2-11 months old). Semi-structured interviews were conducted in April-May 2020 by telephone or Skype for Business, when Denmark was under lockdown. We analysed data using a thematic qualitative content analysis. RESULTS: Three themes emerged: i) Everyday life and family well-being, ii) Worries about COVID-19 and iii) Health literacy: Health information and access to healthcare. The women were generally not worried about their own or their infant's risk of COVID-19. The lockdown had a negative impact on everyday life e.g. routines, loneliness, breastfeeding uncertainties and worries for the infant's social well-being; but better family dynamics were also described. It was challenging to maintain healthy behaviours and thus the women described worries for the risk of type 2 diabetes and GDM in subsequent pregnancies. The women missed peer support and face-to-face visits from health visitors and found it difficult to navigate the restructured care with online/telephone set-ups. CONCLUSIONS: COVID-19 and the lockdown affected everyday life among women with recent GDM both positively and negatively. Our findings suggest a need for care that are responsive to psychological and social aspects of health throughout the COVID-19 pandemic and support to limit worries about adaptation to motherhood and the infant's social well-being. Communication focusing on the importance and relevance of contacting healthcare providers should also be strengthened.

Loss of Sucrase-Isomaltase Function Increases Acetate Levels and Improves Metabolic Health in Greenlandic Cohorts.

BACKGROUND & AIMS: The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency. METHODS: The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings. RESULTS: Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (ß [standard error], -2.0 [0.5] kg/m2; P = 3.1 × 10-5), body weight (-4.8 [1.4] kg; P = 5.1 × 10-4), fat percentage (-3.3% [1.0%]; P = 3.7 × 10-4), fasting triglyceride (-0.27 [0.07] mmol/L; P = 2.3 × 10-6), and remnant cholesterol (-0.11 [0.03] mmol/L; P = 4.2 × 10-5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (ß [standard error], 0.056 [0.002] mmol/L; P = 2.1 × 10-26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test. CONCLUSIONS: These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate.

Systematically developing a family-based health promotion intervention for women with prior gestational diabetes based on evidence, theory and co-production: the Face-it study.

BACKGROUND: Women with prior gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes; however, this risk can be reduced by engaging in positive health behaviours e.g. healthy diet and regular physical activity. As such behaviours are difficult to obtain and maintain there is a need to develop sustainable behavioural interventions following GDM. We aimed to report the process of systematically developing a health promotion intervention to increase quality of life and reduce diabetes risk among women with prior GDM and their families. We distil general lessons about developing complex interventions through co-production and discuss our extensions to intervention development frameworks. METHODS: The development process draws on the Medical Research Council UK Development of complex interventions in primary care framework and an adaptation of a three-stage framework proposed by Hawkins et al. From May 2017 to May 2019, we iteratively developed the Face-it intervention in four stages: 1) Evidence review, qualitative research and stakeholder consultations; 2) Co-production of the intervention content; 3) Prototyping, feasibility- and pilot-testing and 4) Core outcome development. In all stages, we involved stakeholders from three study sites. RESULTS: During stage 1, we identified the target areas for health promotion in families where the mother had prior GDM, including applying a broad understanding of health and a multilevel and multi-determinant approach. We pinpointed municipal health visitors as deliverers and the potential of using digital technology. In stage 2, we tested intervention content and delivery methods. A health pedagogic dialogue tool and a digital health app were co-adapted as the main intervention components. In stage 3, the intervention content and delivery were further adapted in the local context of the three study sites. Suggestions for intervention manuals were refined to optimise flexibility, delivery, sequencing of activities and from this, specific training manuals were developed. Finally, at stage 4, all stakeholders were involved in developing realistic and relevant evaluation outcomes. CONCLUSIONS: This comprehensive description of the development of the Face-it intervention provides an example of how to co-produce and prototype a complex intervention balancing evidence and local conditions. The thorough, four-stage development is expected to create ownership and feasibility among intervention participants, deliverers and local stakeholders. TRIAL REGISTRATION: ClinicalTrials.gov NCT03997773 , registered retrospectively on 25 June 2019.

Diet and physical activity in Greenland: genetic interactions and associations with obesity and diabetes.

The Inuit in Greenland have gone through dramatic lifestyle changes during the last half century. More time is spent being sedentary and imported foods replaces traditional foods like seal and whale. The population has also experienced a rapid growth in obesity and metabolic disturbances and diabetes is today common despite being almost unknown few decades ago. In this paper, we describe and discuss the role of lifestyle changes and genetics for Inuit metabolic health. Novelty: Cardiometabolic disease risk has increased in Greenland. Lifestyle changes and possibly gene-lifestyle interactions play a role.

Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers.

AIMS/HYPOTHESIS: The common muscle-specific TBC1D4 p.Arg684Ter loss-of-function variant defines a subtype of non-autoimmune diabetes in Arctic populations. Homozygous carriers are characterised by elevated postprandial glucose and insulin levels. Because 3.8% of the Greenlandic population are homozygous carriers, it is important to explore possibilities for precision medicine. We aimed to investigate whether physical activity attenuates the effect of this variant on 2 h plasma glucose levels after an oral glucose load. METHODS: In a Greenlandic population cohort (n = 2655), 2 h plasma glucose levels were obtained after an OGTT, physical activity was estimated as physical activity energy expenditure and TBC1D4 genotype was determined. We performed TBC1D4-physical activity interaction analysis, applying a linear mixed model to correct for genetic admixture and relatedness. RESULTS: Physical activity was inversely associated with 2 h plasma glucose levels (ß[main effect of physical activity] -0.0033 [mmol/l] / [kJ kg-1 day-1], p = 6.5 × 10-5), and significantly more so among homozygous carriers of the TBC1D4 risk variant compared with heterozygous carriers and non-carriers (ß[interaction] -0.015 [mmol/l] / [kJ kg-1 day-1], p = 0.0085). The estimated effect size suggests that 1 h of vigorous physical activity per day (compared with resting) reduces 2 h plasma glucose levels by an additional ~0.7 mmol/l in homozygous carriers of the risk variant. CONCLUSIONS/INTERPRETATION: Physical activity improves glucose homeostasis particularly in homozygous TBC1D4 risk variant carriers via a skeletal muscle TBC1 domain family member 4-independent pathway. This provides a rationale to implement physical activity as lifestyle precision medicine in Arctic populations. DATA REPOSITORY: The Greenlandic Cardio-Metabochip data for the Inuit Health in Transition study has been deposited at the European Genome-phenome Archive ( https://www.ebi.ac.uk/ega/dacs/EGAC00001000736 ) under accession EGAD00010001428.

Digestive tract morphology and enzyme activities of juvenile diploid and triploid Atlantic salmon (Salmo salar) fed fishmeal-based diets with or without fish protein hydrolysates.

Triploid, sterile Atlantic salmon (Salmo salar) could make a contribution to the development of the farming industry, but uncertainties about the performance and welfare of triploids have limited their adoption by farmers. In this study, we compared the ontogeny of digestive tract morphology and enzyme activities (pepsin, trypsin, chymotrypsin, alkaline phosphatase and aminopeptidase) of diploid and triploid Atlantic salmon. Fish were fed diets based on fishmeal (STD) or a mix of fishmeal and hydrolysed fish proteins (HFM) whilst being reared at low temperature from start-feeding to completion of the parr-smolt transformation. Fish weights for each ploidy and feed combination were used to calculate thermal growth coefficients (TGCs) that spanned this developmental period, and the data were used to examine possible relationships between enzyme activities and growth. At the end of the experiment, faeces were collected and analyzed to determine the apparent digestibility coefficients (ADCs) of the dietary amino acids (AAs). Digestive tract histo-morphology did not differ substantially between ploidies and generally reflected organ maturation and functionality. There were no consistent differences in proteolytic enzyme activities resulting from the inclusion of HFM in the diet, nor was there improved digestibility and AA bioavailability of the HFM feed in either diploid or triploid fish. The triploid salmon had lower ADCs than diploids for most essential and non-essential AAs in both diets (STD and HFM), but without there being any indication of lower intestinal protease activity in triploid fish. When trypsin-to-chymotrypsin activity and trypsin and alkaline phosphatase (ALP) ratios (T:C and T:ALP, respectively) were considered in combination with growth data (TGC) low T:C and T:ALP values coincided with times of reduced fish growth, and vice versa, suggesting that T:C and T:ALP may be used to predict recent growth history and possible growth potential.

Self-rated physical fitness and measured cardiorespiratory fitness, muscular strength, and body composition.

The purpose was to examine the correlation and association between a single-item question of self-rated physical fitness and objective measures of fitness and cardiometabolic risk factors in a large population-based study. Participants were 3441 men and women aged 18-85 years who filled in a questionnaire and participated in a clinical health examination in the Danish Health Examination Survey 2007-2008. Cardiorespiratory fitness was estimated by an indirect maximal exercise test. Muscle strength was measured by (a) sit-to-stand test, (b) handgrip strength, and (c) bent arm strength. Body mass index and fat percentage were used as measures for body composition. Associations were derived from regression analyses, correlations were calculated using Spearman's correlation test, and agreement was tested by kappa statistics. Within categories of self-rated physical fitness moving from lowest to highest, objectively measured cardiorespiratory fitness increased. Self-rated physical fitness was strongly correlated to cardiorespiratory fitness (rmen  = 0.69 and rwomen  = 0.65) and moderately correlated to the sit-to-stand test (rmen  = 0.49 and rwomen  = 0.48), bent arm strength (r = 0.45) and fat percentage (r = 0.46) among men, and handgrip strength among women (r =0.41). Mutually adjusted analysis showed a significant association between self-reported physical fitness and cardiorespiratory fitness for men and women and bent arm strength for women. The single-item question of physical fitness was correlated to cardiorespiratory fitness, muscle strength, and body composition. However, this study suggests that it mainly captures cardiorespiratory fitness. At the population level, the single-item question could be a useful tool to identify and monitor variation in fitness levels.

Transcriptome sequencing and histology reveal dosage compensation in the liver of triploid pre-smolt Atlantic salmon.

Triploid Atlantic salmon (Salmo salar L.) is seen as one of the best solutions to solve key issues in the salmon farming industry, such as the impact of escapees on wild stocks and pre-harvest sexual maturation. However, the effects of triploidy on salmon smoltification are poorly understood at the molecular level, even though smoltification is a very sensitive period that has a major influence on survival rate and performance of farmed salmon. In this study, we have compared the liver transcriptomes of diploid and triploid Atlantic salmon at three ontogeny stages: fry, parr and smolt. In diploid fish, a total of 2,655 genes were differentially expressed between fry and parr, whereas 506 genes had significantly different transcript levels between parr and smolts. In triploids, 1,507 and 974 genes were differentially expressed between fry and parr, and between parr and smolts, respectively. Most of these genes were down-regulated and 34 genes were differentially expressed between ploidies at the same stage. In both ploidy groups, the top differentially expressed genes with ontogeny stage belonged to common functional categories that can be related to smoltification. Nucleotide and energy metabolism were significantly down-regulated in fry when compared to parr, while immune system processes were significantly down-regulated in parr when compared to smolts. The close resemblance of enriched biological processes and pathways between ploidy groups suggests that triploidy is regulated by genome dosage compensation in Atlantic salmon. Histological analysis revealed that areas of vacuolization (steatosis) were present only in fry and parr stages, in contrast to a compact cellular histology with glycogen granules after smoltification. There was no significant difference in vacuolization between ploidy groups at the fry stage but the liver of diploid parr had a 33.5% higher vacuolization area compared to their triploid counterparts. Taken together, our data provide novel insights into the changes that occur at the molecular and histological level in the liver of both diploid and triploid Atlantic salmon prior to and during smoltification.

Protocol for a randomised controlled trial of a co-produced, complex, health promotion intervention for women with prior gestational diabetes and their families: the Face-it study.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with an increased risk of future diabetes in both mother, father and offspring. More knowledge is needed about how to effectively reduce the risk of diabetes through sustained behavioural interventions in these families. The Face-it intervention is a complex health promotion intervention embedded in multi-level supportive environments. The aim of the intervention is to reduce type 2 diabetes risk and increase quality of life among families in the first year following a GDM-affected pregnancy by promoting physical activity, healthy dietary behaviours and breastfeeding through a focus on social support, motivation, self-efficacy, risk perception and health literacy. METHODS: This national multicentre study is a two-arm randomised controlled trial including 460 women with GDM in a ratio of 2 (intervention):1 (usual care). The Face-it intervention consists of three main components: 1) additional visits from municipal health visitors, 2) digital health coaching tailored to family needs and 3) a structured cross-sectoral communication system in the health care system. The intervention runs from 3 to 12 months after delivery. The primary outcome is maternal body mass index at 12 months after delivery as a proxy for diabetes risk. The women will be examined at baseline and at follow-up, and this examination will include blood tests, oral glucose tolerance test (OGTT), anthropometrics, blood pressure, self-reported diet and physical activity, breastfeeding, quality of life, health literacy, physical and mental health status, risk perception and social support. Aside from those data collected for OGTT and breastfeeding and offspring parameters, the same data will be collected for partners. Data on offspring anthropometry will also be collected. Information on pregnancy- and birth-related outcomes will be derived from the medical records of the woman and child. DISCUSSION: This randomised controlled trial seeks to demonstrate whether the Face-it intervention, addressing the individual, family and health care system levels, is superior to usual care in reducing diabetes risk for mothers and their families. Coupled with a process evaluation and an economic analysis, the study will provide evidence for policymakers and health services about health promotion among families affected by GDM and the potential for reducing risk of type 2 diabetes and associated conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03997773. Registered June 25, 2019 - Retrospectively registered.

The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders.

The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biological mechanisms underlying obesity. Stage 1 BMI-association analyses were performed in 4,626 Greenlanders. Stage 2 replication and meta-analysis were performed in additional cohorts comprising 1,058 Yup'ik Alaska Native people, and 1,529 Greenlanders. Obesity-related traits were assessed in the stage 1 study population. We identified a common variant on chromosome 11, rs4936356, where the derived G-allele had a frequency of 24% in the stage 1 study population. The derived allele was genome-wide significantly associated with lower BMI (beta (SE), -0.14 SD (0.03), p = 3.2x10-8), corresponding to 0.64 kg/m2 lower BMI per G allele in the stage 1 study population. We observed a similar effect in the Yup'ik cohort (-0.09 SD, p = 0.038), and a non-significant effect in the same direction in the independent Greenlandic stage 2 cohort (-0.03 SD, p = 0.514). The association remained genome-wide significant in meta-analysis of the Arctic cohorts (-0.10 SD (0.02), p = 4.7x10-8). Moreover, the variant was associated with a leaner body type (weight, -1.68 (0.37) kg; waist circumference, -1.52 (0.33) cm; hip circumference, -0.85 (0.24) cm; lean mass, -0.84 (0.19) kg; fat mass and percent, -1.66 (0.33) kg and -1.39 (0.27) %; visceral adipose tissue, -0.30 (0.07) cm; subcutaneous adipose tissue, -0.16 (0.05) cm, all p<0.0002), lower insulin resistance (HOMA-IR, -0.12 (0.04), p = 0.00021), and favorable lipid levels (triglyceride, -0.05 (0.02) mmol/l, p = 0.025; HDL-cholesterol, 0.04 (0.01) mmol/l, p = 0.0015). In conclusion, we identified a novel variant, where the derived G-allele possibly associated with lower BMI in Arctic populations, and as a consequence also leaner body type, lower insulin resistance, and a favorable lipid profile.

Associations between birth weight and glucose intolerance in adulthood among Greenlandic Inuit.

AIMS: To examine the association between birth weight and glucose intolerance in adult Greenlandic Inuit. METHODS: We examined 1429 participants aged 18-56 years from two population-based, cross-sectional studies in Greenland with information on birth weight. Oral glucose tolerance tests, anthropometric measures and ultrasound of abdominal tissue were performed. Associations of birth weight with glucose markers were analysed using linear or logistic regressions. Spline analyses were conducted to examine u-shaped associations. Adjustments were done for age, sex, birth place, family history of diabetes, genetic admixture, TBC1D4 p.Arg684Ter carrier status, BMI and visceral adipose tissue. RESULTS: The median birthweight was 3300 g and 3.9% had type 2 diabetes, T2DM. Spline analyses indicated overall linear associations. In fully adjusted analyses, an increase in birth weight of 1 kg was associated with a change in fasting plasma glucose of -0.06 mmol/L (95%CI: -0.11, -0.01), 2-h plasma glucose of -0.16 mmol/L (95%CI: -0.35, 0.02), HOMA-IR of -5.45% (95%CI: -10.34, -0.29), insulin sensitivity index of 7.04% (95%CI: 1.88, 12.45) and a trend towards a reduced risk of hyperglycaemia and T2DM, although statistically insignificant. CONCLUSIONS: Birth weight was inversely associated with hepatic and peripheral insulin resistance independently of adult adiposity. Thus, the findings support low birth weight as a contributing factor for glucose intolerance in adult Inuit in Greenland.

Divergent responses of Atlantic cod to ocean acidification and food limitation.

In order to understand the effect of global change on marine fishes, it is imperative to quantify the effects on fundamental parameters such as survival and growth. Larval survival and recruitment of the Atlantic cod (Gadus morhua) were found to be heavily impaired by end-of-century levels of ocean acidification. Here, we analysed larval growth among 35-36 days old surviving larvae, along with organ development and ossification of the skeleton. We combined CO2 treatments (ambient: 503 µatm, elevated: 1,179 µatm) with food availability in order to evaluate the effect of energy limitation in addition to the ocean acidification stressor. As expected, larval size (as a proxy for growth) and skeletogenesis were positively affected by high food availability. We found significant interactions between acidification and food availability. Larvae fed ad libitum showed little difference in growth and skeletogenesis due to the CO2 treatment. Larvae under energy limitation were significantly larger and had further developed skeletal structures in the elevated CO2 treatment compared to the ambient CO2 treatment. However, the elevated CO2 group revealed impairments in critically important organs, such as the liver, and had comparatively smaller functional gills indicating a mismatch between size and function. It is therefore likely that individual larvae that had survived acidification treatments will suffer from impairments later during ontogeny. Our study highlights important allocation trade-off between growth and organ development, which is critically important to interpret acidification effects on early life stages of fish.

Measuring social inequality in health amongst indigenous peoples in the Arctic. A comparison of different indicators of social disparity among the Inuit in Greenland.

The purpose of the article is to compare different indicators of social position as measures of social inequality in health in a population sample from an indigenous arctic people, the Inuit in Greenland. Data was collected during 2005-2015 and consisted of information from 3967 adult Inuit from towns and villages in all parts of Greenland. Social inequalities for smoking and central obesity were analysed in relation to seven indicators of social disparity in four dimensions, i.e. education and employment, economic status, sociocultural position, and place of residence. For each indicator we calculated age-adjusted prevalence by social group, rate ratio and the concentration index. The indicators were correlated with Pearson's r ranging from 0.24 to 0.82. Concentration indices ranged from 0.01 to 0.17. We could not conclude that one indicator was superior to others. Most of the indicators were traditional socioeconomic indicators used extensively in research in western countries and these seemed to be useful among the Inuit too, in particular household assets and job. Two sociocultural indicators developed for use among the Inuit and which included parameters specific to the indigenous peoples in the transition from a traditional to a modern life style proved to be equally useful but not superior to the traditional socioeconomic indicators. The choice of indicator must depend on what it is realistic to collect in the actual research setting and the use of more than one indicator is recommended. It is suggested to further develop culture specific indicators of social position for indigenous peoples.

Identification of novel high-impact recessively inherited type 2 diabetes risk variants in the Greenlandic population.

AIMS/HYPOTHESIS: In a recent study using a standard additive genetic model, we identified a TBC1D4 loss-of-function variant with a large recessive impact on risk of type 2 diabetes in Greenlanders. The aim of the current study was to identify additional genetic variation underlying type 2 diabetes using a recessive genetic model, thereby increasing the power to detect variants with recessive effects. METHODS: We investigated three cohorts of Greenlanders (B99, n = 1401; IHIT, n = 3115; and BBH, n = 547), which were genotyped using Illumina MetaboChip. Of the 4674 genotyped individuals passing quality control, 4648 had phenotype data available, and type 2 diabetes association analyses were performed for 317 individuals with type 2 diabetes and 2631 participants with normal glucose tolerance. Statistical association analyses were performed using a linear mixed model. RESULTS: Using a recessive genetic model, we identified two novel loci associated with type 2 diabetes in Greenlanders, namely rs870992 in ITGA1 on chromosome 5 (OR 2.79, p = 1.8 × 10-8), and rs16993330 upstream of LARGE1 on chromosome 22 (OR 3.52, p = 1.3 × 10-7). The LARGE1 variant did not reach the conventional threshold for genome-wide significance (p < 5 × 10-8) but did withstand a study-wide Bonferroni-corrected significance threshold. Both variants were common in Greenlanders, with minor allele frequencies of 23% and 16%, respectively, and were estimated to have large recessive effects on risk of type 2 diabetes in Greenlanders, compared with additively inherited variants previously observed in European populations. CONCLUSIONS/INTERPRETATION: We demonstrate the value of using a recessive genetic model in a historically small and isolated population to identify genetic risk variants. Our findings give new insights into the genetic architecture of type 2 diabetes, and further support the existence of high-effect genetic risk factors of potential clinical relevance, particularly in isolated populations. DATA AVAILABILITY: The Greenlandic MetaboChip-genotype data are available at European Genome-Phenome Archive (EGA; https://ega-archive.org/ ) under the accession EGAS00001002641.

Growth and development of skeletal anomalies in diploid and triploid Atlantic salmon (Salmo salar) fed phosphorus-rich diets with fish meal and hydrolyzed fish protein.

Diploid and triploid Atlantic salmon, Salmo salar were fed high-protein, phosphorus-rich diets (56-60% protein; ca 18g phosphorus kg-1 diet) whilst being reared at low temperature from start-feeding until parr-smolt transformation. Performances of salmon fed diets based on fish meal (STD) or a mix of fishmeal and hydrolysed fish proteins (HFM) as the major protein sources were compared in terms of mortality, diet digestibility, growth and skeletal deformities. Separate groups of diploids and triploids were reared in triplicate tanks (initially 3000 fish per tank; tank biomass ca. 620 g) from 0-2745 degree-days post-start feeding (ddPSF). Growth metrics (weight, length, condition factor) were recorded at ca. 4 week intervals, external signs of deformities to the operculum, jaws and spinal column were examined in parr sampled at 1390 ddPSF, and external signs of deformity and vertebral anomalies (by radiography) were examined in fish sampled at the end of the trial (2745 ddPSF). The triploid salmon generally had a lower mass per unit length, i.e. lower condition factor, throughout the trial, but this did not seem to reflect any consistent dietary or ploidy effects on either dietary digestibility or the growth of the fish. By the end of the trial fish in all treatment groups had achieved a weight of 50+ g, and had completed the parr-smolt transformation. The triploids had slightly, but significantly, fewer vertebrae (Triploids STD 58.74 ± 0.10; HFM 58.68 ± 0.05) than the diploids (Diploids STD 58.97 ± 0.14; HFM 58.89 ± 0.01), and the incidence of skeletal (vertebral) abnormalities was higher in triploids (Triploids STD 31 ± 0.90%; HFM 15 ± 1.44%) than in diploids (Diploids STD 4 ± 0.80%; HFM 4 ± 0.83%). The HFM diet gave a significant reduction in the numbers of triploid salmon with vertebral anomalies in comparison with the triploids fed the STD diet possibly as a result of differences in phosphorus bioavailability between the two diets. Overall, the incidence of skeletal deformities was lower than reported in previous studies (Diploids 20+%, Triploids 40+%), possibly as a result of the combination of rearing at low-temperature and phosphorus-rich diets being used in the present study.

Whole blood mercury and the risk of cardiovascular disease among the Greenlandic population.

BACKGROUND: Studies have found mercury to be associated with cardiovascular disease (CVD), however, primarily in populations with low exposure. The highest levels, and variations in the levels, of whole blood mercury (WBM) worldwide have been found in Greenland. We prospectively assessed the association between WBM and the risk of developing CVD in the Greenlandic population. METHODS: We assessed the effects of WBM levels on incident CVD among 3083 Greenlandic Inuit, participating in a population-based cohort study conducted from 2005 to 2010. WBM was measured at baseline. Participants were followed in the National Patient Registries for Denmark and Greenland and in the causes of death register for CVD events from inclusion in the study until CVD event, emigration, death or end of follow-up (30/9-2013). Using Cox regression analyses, we calculated the incidence rates and the hazard ratio of CVD events according to WBM levels. Potential interactions with sex were also investigated. RESULTS: The highest levels of WBM were found in men, who had a significantly higher median level (19 µg/L (IQR:1-44)), compared with women (15 µg/L (IQR: 1-32), (p < 0.001)). The crude hazard ratio (HR) for incident CVD was 1.00 (95% CI 1.00-1.00) for 5 µg/l increase in WBM. After adjusting for several potential confounders, there was still no association between WBM and incident CVD (HR 0.99; 95%CI:0.99-1.00). We found no interactions with sex. CONCLUSIONS: In a population with high levels of WBM, we found no association between WBM and the risk of developing CVD in Greenland.

Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes.

We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe an enrichment of rare ADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. These findings provide new information on disease etiology relevant for future treatment strategies.

Associations between vitamin D status and atherosclerosis among Inuit in Greenland.

BACKGROUND AND AIMS: Low levels of vitamin D are suspected to be a risk factor for cardiovascular disease and atherosclerosis. The aim of this study was to assess the prevalence of subclinical atherosclerosis among Inuit in Greenland, and to evaluate the association with vitamin D status. We hypothesized that low vitamin D status could be associated with higher carotid intima-media thickness (IMT) as a marker of atherosclerosis. METHODS: 756 adults from the Inuit Health in Transition (IHIT) study carried out in Greenland in the period 2005-2010 were included. A blood sample donated in 1987 was available for a sub-sample of 102 individuals. Serum 25(OH)D3 from the IHIT study and the 1987 survey was used as a measure of vitamin D status. IMT measurements were conducted by ultrasound scanning. The prevalence of atherosclerosis was estimated, and the association between serum 25(OH)D3 and IMT measurements was examined by linear regression. RESULTS: The overall prevalence of subclinical atherosclerosis was 20.1% (n = 152). The linear regression analyses indicated a weak positive association between serum 25(OH)D3 level and IMT measurements from the IHIT study, though not statistically significant after adjustment for potential confounders (ß = 0.35% per 10 nmoL/L 25(OH)D3, p = 0.06). Linear regression analyses of the association between serum 25(OH)D3 level in the 1987 survey and IMT measurements also indicated a positive, though not statistically significant, association after adjustment (ß = 0.07% per 10 nmoL/L 25(OH)D3, p = 0.86). CONCLUSIONS: Our findings did not support the hypothesis of an association between low vitamin D levels and risk of atherosclerosis.