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Perturbation of lipid homoeostasis is a major risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. We aimed to identify genetic variants affecting lipid levels, and thereby risk of CVD, in Greenlanders. Genome-wide association studies (GWAS) of six blood lipids, triglycerides, LDL-cholesterol, HDL-cholesterol, total cholesterol, as well as apolipoproteins A1 and B, were performed in up to 4473 Greenlanders. For genome-wide significant variants, we also tested for associations with additional traits, including CVD events. We identified 11 genome-wide significant loci associated with lipid traits. Most of these loci were already known in Europeans, however, we found a potential causal variant near PCSK9(rs12117661), which was independent of the known PCSK9loss-of-function variant (rs11491147). rs12117661 was associated with lower LDL-cholesterol (βSD(SE) = −0.22 (0.03), p= 6.5 × 10−12) and total cholesterol (−0.17 (0.03), p= 1.1 × 10−8) in the Greenlandic study population. Similar associations were observed in Europeans from the UK Biobank, where the variant was also associated with a lower risk of CVD outcomes. Moreover, rs12117661 was a top eQTL for PCSK9across tissues in European data from the GTEx portal, and was located in a predicted regulatory element, supporting a possible causal impact on PCSK9expression. Combined, the 11 GWAS signals explained up to 16.3% of the variance of the lipid traits. This suggests that the genetic architecture of lipid levels in Greenlanders is different from Europeans, with fewer variants explaining the variance.

The combination of decreasing food intake and increasing energy expenditure represents a powerful strategy for counteracting cardiometabolic diseases such as obesity and type 2 diabetes1. Yet current pharmacological approaches require conjugation of multiple receptor agonists to achieve both effects2–4, and so far, no safe energy-expending option has reached the clinic. Here we show that activation of neurokinin 2 receptor (NK2R) is sufficient to suppress appetite centrally and increase energy expenditure peripherally. We focused on NK2R after revealing its genetic links to obesity and glucose control. However, therapeutically exploiting NK2R signalling has previously been unattainable because its endogenous ligand, neurokinin A, is short-lived and lacks receptor specificity5,6. Therefore, we developed selective, long-acting NK2R agonists with potential for once-weekly administration in humans. In mice, these agonists elicit weight loss by inducing energy expenditure and non-aversive appetite suppression that circumvents canonical leptin signalling. Additionally, a hyperinsulinaemic–euglycaemic clamp reveals that NK2R agonism acutely enhances insulin sensitization. In diabetic, obese macaques, NK2R activation significantly decreases body weight, blood glucose, triglycerides and cholesterol, and ameliorates insulin resistance. These findings identify a single receptor target that leverages both energy-expending and appetite-suppressing programmes to improve energy homeostasis and reverse cardiometabolic dysfunction across species.

Solvation is a ubiquitous phenomenon in the natural sciences. At the macroscopic level, it is well understood through thermodynamics and chemical reaction kinetics1,2. At the atomic level, the primary steps of solvation are the attraction and binding of individual molecules or atoms of a solvent to molecules or ions of a solute1. These steps have, however, never been observed in real time. Here we instantly create a single sodium ion at the surface of a liquid helium nanodroplet3,4, and measure the number of solvent atoms that successively attach to the ion as a function of time. We found that the binding dynamics of the first five helium atoms is well described by a Poissonian process with a binding rate of 2.0 atoms per picosecond. This rate is consistent with time-dependent density-functional-theory simulations of the solvation process. Furthermore, our measurements enable an estimate of the energy removed from the region around the sodium ion as a function of time, revealing that half of the total solvation energy is dissipated after four picoseconds. Our experimental method opens possibilities for benchmarking theoretical models of ion solvation and for time-resolved measurements of cation–molecule complex formation.

Radiotherapy is one of the most common cancer treatments, yet, some patients require high doses to respond. Therefore, the development of new strategies leans toward personalizing therapy to avoid unnecessary burden on cancer patients. This approach prevents the administration of ineffective treatments or uses combination strategies to increase the sensitivity of cancer cells. ADAM12 has been shown to be upregulated in many cancers and correlate with poor survival and chemoresistance, thus making it a potential candidate responsible for radioresistance. Here, we show that ADAM12 expression is upregulated in response to irradiation in both mouse and human cancer cells in vitro, as well as in tumor tissues from rectal cancer patients. Interestingly, the expression of ADAM12 following radiotherapy correlates with the initial disease stage and predicts the response of rectal cancer patients to the treatment. While we found no cell-autonomous effects of ADAM12 on the response of colon cancer cells to irradiation in vitro, depletion of ADAM12 expression markedly reduced the tumor growth of irradiated cancer cells when subcutaneously transplanted in syngeneic mice. Interestingly, loss of cancer cell-derived ADAM12 expression increased the number of CD31+FAP−cells in murine tumors. Moreover, conditioned medium from ADAM12−/−colon cancer cells led to increased tube formation when added to endothelial cell cultures. Thus, it is tempting to speculate that altered tumor vascularity may be implicated in the observed effect of ADAM12 on response to radiotherapy in rectal cancer. We conclude that ADAM12 represents a promising prognostic factor for stratification of rectal cancer patients receiving radiotherapy and suggest that targeting ADAM12 in combination with radiotherapy could potentially improve the treatment response.

Autoimmune liver diseases include autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. They are chronic, heterogenous diseases affecting the liver which is a key metabolic organ that ensures glucose homeostasis. It is well known that patients with other chronic liver diseases such as cirrhosis and nonalcoholic fatty liver disease (NAFLD) display glucose disturbances like insulin resistance and have an increased risk of diabetes. Previous evidence on glucose disturbances in patients with autoimmune liver disease is scarce but does point towards a potentially increased risk of type 1 diabetes and type 2 diabetes. The underlying mechanisms are unknown but may reflect genetic predisposition, concurrent NAFLD and or cirrhosis development, and treatment (steroid) related impairment of glucose homeostasis. Therefore, increased awareness and surveillance of diabetes development in patients with autoimmune liver disease may be important. Overall, detection and treatment of diabetes generally follow the usual diabetes guidelines; however, in patients with advanced liver cirrhosis, HbA1c may not be a reliable marker of average glucose levels, and treatment with insulin is generally recommended. In addition, it has recently been suggested that sodium–glucose cotransporter 2 inhibitors may be beneficial in treating refractory ascites. Further research on diabetes risk in autoimmune liver disease is warranted.

The unique properties of light underpin the visions of photonic quantum technologies, optical interconnects and a wide range of novel sensors, but a key limiting factor today is losses due to either absorption or backscattering on defects. Recent developments in topological photonics have fostered the vision of backscattering-protected waveguides made from topological interface modes, but, surprisingly, measurements of their propagation losses were so far missing. Here we report on measurements of losses in the slow-light regime of valley-Hall topological waveguides and find no indications of topological protection against backscattering on ubiquitous structural defects. We image the light scattered out from the topological waveguides and find that the propagation losses are due to Anderson localization. The only photonic topological waveguides proposed for materials without intrinsic absorption in the optical domain are quantum spin-Hall and valley-Hall interface states, but the former exhibit strong out-of-plane losses, and our work, therefore, raises fundamental questions about the real-world value of topological protection in reciprocal photonics.

Principal component analysis (PCA) is widely used in statistics, machine learning, and genomics for dimensionality reduction and uncovering low-dimensional latent structure. To address the challenges posed by ever-growing data size, fast and memory-efficient PCA methods have gained prominence. In this paper, we propose a novel randomized singular value decomposition (RSVD) algorithm implemented in PCAone, featuring a window-based optimization scheme that enables accelerated convergence while improving the accuracy. Additionally, PCAone incorporates out-of-core and multithreaded implementations for the existing Implicitly Restarted Arnoldi Method (IRAM) and RSVD. Through comprehensive evaluations using multiple large-scale real-world data sets in different fields, we show the advantage of PCAone over existing methods. The new algorithm achieves significantly faster computation time while maintaining accuracy comparable to the slower IRAM method. Notably, our analyses of UK Biobank, comprising around 0.5 million individuals and 6.1 million common single nucleotide polymorphisms, show that PCAone accurately computes the top 40 principal components within 9 h. This analysis effectively captures population structure, signals of selection, structural variants, and low recombination regions, utilizing <20 GB of memory and 20 CPU threads. Furthermore, when applied to single-cell RNA sequencing data featuring 1.3 million cells, PCAone, accurately capturing the top 40 principal components in 49 min. This performance represents a 10-fold improvement over state-of-the-art tools.

Patients with inflammatory arthritis have a high risk of sleep disturbances and disorders. The objective was to evaluate the evidence of nonpharmacologic interventions targeting sleep disturbances or disorders in patients with inflammatory arthritis. A systematic search was undertaken from inception to September 8, 2020. We included randomized trials concerning nonpharmacologic interventions applied in adults with inflammatory arthritis and concomitant sleep disturbances or disorders. The primary outcome was the sleep domain, while secondary outcomes were core outcome domains for inflammatory arthritis trials and harms. The Cochrane Risk of Bias tool was applied, and the overall quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Effect sizes for continuous outcomes were based on the standardized mean difference, combined using random‐effects meta‐analysis. Six trials (308 patients) were included in the quantitative synthesis; 3 of these reported improvement in sleep in favor of the nonpharmacologic interventions. The meta‐analysis of the sleep domains indicated a large clinical effect of –0.80 (95% confidence interval –1.33, –0.28) in favor of nonpharmacologic interventions targeting sleep disturbances or disorders. The estimate was rated down twice for risk of bias and unexplained inconsistency; this risk was assessed as corresponding to low‐quality evidence. None of the secondary core outcomes used in contemporary inflammatory arthritis trials indicated a clinical benefit in favor of nonpharmacologic interventions targeting sleep. Nonpharmacologic interventions targeting sleep disturbances/disorders in patients with inflammatory arthritis indicated a promising effect on sleep outcomes, but not yet with convincing evidence.

OBJECTIVE--Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes. RESEARCH DESIGN AND METHODS--In this study we investigate the combined effect of these variants and their ability to discriminate between normal weight and overweight/obese individuals. We applied receiver operating characteristics (ROC) curves, and estimated the area under the ROC curve (AUC) as a measure of the discriminatory ability. The analyses were performed cross-sectionally in the population-based Inter99 cohort where 1,725 normal weight, 1,519 overweight, and 681 obese individuals were successfully genotyped for all 20 variants. RESULTS--When combining all variants, the 10% of the study participants who carried more than 22 risk-alleles showed a significant increase in probability of being both overweight with an odds ratio of 2.00 (1.47-2.72), P = 4.0 x [10.sup.-5], and obese with an OR of 2.62 (1.76-3.92), P = 6.4 x [10.sup.-7], compared with the 10% of the study participants who carried less than 14 risk-alleles. Discrimination ability for overweight and obesity, using the 20 single nucleotide polymorphisms (SNPs), was determined to AUCs of 0.53 and 0.58, respectively. When combining SNP data with conventional nongenetic risk factors of obesity, the discrimination ability increased to 0.64 for overweight and 0.69 for obesity. The latter is significantly higher (P < 0.001) than for the nongenetic factors alone (AUC = 0.67). CONCLUSIONS--The discriminative value of the 20 validated common obesity variants is at present time sparse and too weak for clinical utility, however, they add to increase the discrimination ability of conventional nongenetic risk factors. Diabetes 59:1667-1673, 2010, The prevalence of obesity is increasing rapidly in all parts of the world. The primary cause of the current epidemic development is likely an unhealthy lifestyle, especially high calorie intake [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cose.2009.01.003 Byline: Eirik Albrechtsen (a)(b), Jan Hovden (a) Abstract: Empirical findings from surveys and in-depth interviews with information security managers and users indicate that a digital divide exists between these groups in terms of their views on and experience of information security practices. Information security professionals mainly regard users as an information security threat, whereas users believe themselves that they are an untapped resource for security work. The limited interaction between users and information security managers results in a lack of understanding for the other's point of view. These divergent views on and interpretations of information security mean that managers tend to base their practical method on unrealistic assumptions, resulting in management approaches that are poorly aligned with the dynamics of the users' working day. Author Affiliation: (a) Department of Industrial Economics and Technology Management, Norwegian University of Science and Technology, N-7491 Trondheim, Norway (b) Department of Safety Research, SINTEF Technology and Society, N-7465 Trondheim, Norway Article History: Received 3 May 2007; Revised 1 December 2008; Accepted 5 January 2009

OBJECTIVE--We evaluated the impact on diabetes-related intermediary traits of common novel type 2 diabetes-associated variants in the JAZF1 (rs864745), CDC123/CAMK1D (rs12779790), TSPAN8 (rs7961581), THADA (rs7578597), AD AMTS9 (rs4607103), and NOTCH2 (rs10923931) loci, which were recently identified by meta-analysis of genome-wide association data. RESEARCH DESIGN AND METHODS--We genotyped the six variants in 4,516 middle-aged glucose-tolerant individuals of the population-based Inter99 cohort who were all characterized by an oral glucose tolerance test (OGTT). RESULTS--Homozygous carriers of the minor diabetes risk G-allele of the CDC123/CAMK1D rs12779790 showed an 18% decrease in insulinogenic index (95% CI 10-27%; P = 4 x [10.sup.-5]), an 18% decrease in corrected insulin response (CIR) (8.1-29%; P = 4 x [10.sup.-4]), and a 13% decrease in the ratio of area under the serum-insulin and plasma-glucose curves during an OGTT (AUC-insulin/AUC-glucose) (5.8-20%; P = 4 x [10.sup.-4]). Carriers of the diabetes-associated T-allele of JAZF1 rs864745 had an allele-dependent 3% decrease in BIGTT-AIR (0.9-4.3%; P = 0.003). Furthermore, the diabetes-associated C-allele of TSPAN8 rs7961581 associated with decreased levels of CIR (4.5% [0.5-8.4]; P = 0.03), of AUC-insulin/AUC-glucose ratio (3.9% [1.2-6.7]; P = 0.005), and of the insulinogenic index (5.2% [1.9-8.6]; P = 0.002). No association with traits of insulin release or insulin action was observed for the THADA, ADAMTS9, or NOTCH2 variants. CONCLUSIONS--If replicated, our data suggest that type 2 diabetes at-risk alleles in the JAZF1, CDC123/CAMK1D, and TSPAN8 loci associate with various OGTT-based surrogate measures of insulin release, emphasizing the contribution of abnormal pancreatic β-cell function in the pathogenesis of type 2 diabetes., Recent discoveries using genome-wide association (GWA) studies have led to progression in the understanding of the molecular genetic background of type 2 diabetes, dramatically increasing the number of common validated [...]

OBJECTIVE--Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on [...]

OBJECTIVE--In the present study, we aimed to validate the type 2 diabetes susceptibility alleles identified in six recent genome-wide association studies in the HHEX/KIF11/IDE (rs1111875), CDKN2A/B (rs10811661), and IGF2BP2 (rs4402960) [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cose.2006.11.004 Byline: Eirik Albrechtsen Abstract: Users play an important role in the information security performance of organisations by their security awareness and cautious behaviour. Interviews of users at an IT-company and a bank were qualitatively analyzed in order to explore users' experience of information security and their personal role in the information security work. The main patterns of the study were: (1) users state to be motivated for information security work, but do not perform many individual security actions; (2) high information security workload creates a conflict of interest between functionality and information security; and (3) documented requirements of expected information security behaviour and general awareness campaigns have little effect alone on user behaviour and awareness. The users consider a user-involving approach to be much more effective for influencing user awareness and behaviour. Author Affiliation: Department of Industrial Economics and Technology Management, Norwegian University of Science and Technology, N-7491 Trondheim, Norway Article History: Received 10 January 2006; Revised 30 October 2006; Accepted 6 November 2006

Recently, it has been shown that mutations in the P2 promoter of the hepatocyte nuclear factor (HNF)-4α gene (HNF4A) cause maturity-onset diabetes of the young (MODY), while single nucleotide polymorphisms in this locus are associated with type 2 diabetes. In this study, we examined 1,189 bp of the P2 promoter and the associated exon 1D of HNF4A for variations associated with diabetes in 114 patients with type 2 diabetes, 72 MODYX probands, and 85 women with previous gestational diabetes mellitus. A -192c/g mutation was found in five patients. We screened 1,587 diabetic subjects and 4,812 glucose-tolerant subjects for the -192c/g mutation and identified 5 diabetic and 1 glucose-tolerant mutation carriers (P = 0.004). Examination of the families showed that carriers of the -192c/g mutation had a significantly impaired glucose-stimulated insulin release and lower levels of serum total cholesterol compared with matched control subjects. Furthermore, the mutation disrupted the binding of an unidentiffed sequence-specific DNA binding complex present in human islet extracts. Also, two novel linked polymorphisms in the P2 promoter at positions -1107g/t and -858c/t were identified. These variants were not significantly associated with type 2 diabetes or any pre-diabetic traits. In conclusion, a rare, novel mutation that disrupts a protein binding site in the pancreatic HNF4A promoter associates with late-onset diabetes., Mutations in the coding region and the P2 promoter of the hepatocyte nuclear factor (HNF)-4α gene (HNF4A) cause maturity-onset diabetes of the young (MODY) (1-3). Interestingly, studies in Caucasian populations [...]

ABSTRACT Constructing and administering lineups is a necessary and important part of police practice. Guidelines for outlining proper procedures have been put forth by the U. S. Department of Justice, [...]

The maintenance of physical distance, the absence of relatives and the relocation of registered nurses to COVID-19 units presumably affects nursing care at non-COVID-19 units. Using a qualitative design, this study explored registered nurses’ experiences of how COVID-19 influenced nursing care in non-COVID-19 units at a Danish university hospital during the first wave of the virus. The study is reported using the COREQ checklist. The analysis offered two findings: (1) the challenge of an increased workload for registered nurses remaining in non-COVID-19 units and (2) the difficulty of navigating the contradictory needs for both closeness to and distance from patients. The study concluded that several factors challenged nursing care in non-COVID-19 units during the COVID-19 pandemic. These may have decreased the amount of contact between patients and registered nurses, which may have contributed to a task-oriented approach to nursing care, leading to missed nursing care.

AN EMPTY CRADLE sits in the middle of the cobbled courtyard of a grand old building on Madison Avenue in New York City. Girls 'who had done the unthinkable, unmarried [...]

Accurate inference of population structure is important in many studies of population genetics. Here we present HaploNet, a method for performing dimensionality reduction and clustering of genetic data. The method is based on local clustering of phased haplotypes using neural networks from whole-genome sequencing or dense genotype data. By using Gaussian mixtures in a variational autoencoder framework, we are able to learn a low-dimensional latent space in which we cluster haplotypes along the genome in a highly scalable manner. We show that we can use haplotype clusters in the latent space to infer global population structure using haplotype information by exploiting the generative properties of our framework. Based on fitted neural networks and their latent haplotype clusters, we can perform principal component analysis and estimate ancestry proportions based on a maximum likelihood framework. Using sequencing data from simulations and closely related human populations, we show that our approach is better at distinguishing closely related populations than standard admixture and principal component analysis software. We further show that HaploNet is fast and highly scalable by applying it to genotype array data of the UK Biobank.

Controlling vibrations in solids is crucial to tailor their elastic properties and interaction with light. Thermal vibrations represent a source of noise and dephasing for many physical processes at the quantum level. One strategy to avoid these vibrations is to structure a solid such that it possesses a phononic stop band, that is, a frequency range over which there are no available elastic waves. Here we demonstrate the complete absence of thermal vibrations in a nanostructured silicon membrane at room temperature over a broad spectral window, with a 5.3-GHz-wide bandgap centred at 8.4 GHz. By constructing a line-defect waveguide, we directly measure gigahertz guided modes without any external excitation using Brillouin light scattering spectroscopy. Our experimental results show that the shamrock crystal geometry can be used as an efficient platform for phonon manipulation with possible applications in optomechanics and signal processing transduction.

It appears that many infants can be safely delivered vaginally if they are in the breech position. Medical records were analyzed of 1,212 infants in the breech position delivered between 1984 and 1992. The percentage of infants in the breech position delivered vaginally increased from 45% to 57% with a corresponding decrease in cesarean deliveries for similar infants during this time period. Slightly more infants delivered vaginally in the breech position were admitted to the neonatal intensive care unit or had birth complications compared to matched infants in the head down position.

Radiation therapy (RT) and intrathecal drug delivery systems (IDDS) are often used concurrently to optimize pain management in patients with cancer. Concern remains among clinicians regarding the potential for IDDS malfunction in the setting of RT. Here we assessed the frequency of IDDS malfunction in a large cohort of patients treated with RT. Cancer patients with IDDS and subsequent RT at our institution from 2011 to 2019 were eligible for this study. Patients were excluded in the rare event that their IDDS was managed by an outside clinic and follow‐up documentation was unavailable. Eighty‐eight patients aged 22–88 years old (43% female, 57% male) representing 106 separate courses of RT were retrospectively identified. Patients received varying levels of radiation for treatment of cancer and cumulative dose to the IDDS was calculated. IDDS interrogation was subsequently performed by a pain specialist. Malfunction was recorded as deviation from the expected drug volume and/or device errors reported upon interrogation as defined by the manufacturer. Total measured RT dose to the IDDS ranged from 0 to 18.0 Gy (median = 0.2 Gy) with median dose of 0.04 Gy/fraction (range, 0–3.2 Gy/fraction). Ten pumps received a total dose >2 Gy and three received ≥5 Gy. Eighty‐two percentage of patients had follow‐up with a pain specialist for IDDS interrogation and all patients underwent follow‐up with a healthcare provider following RT. There were zero incidences of IDDS malfunction related to RT. No patient had clinical evidence of radiation related pump malfunction at subsequent encounters. We found no evidence that RT in patients with IDDS led to device failure or dysfunction. While radiation oncologists and pain specialists should coordinate patient care, it does not appear that RT dose impacts the function of the IDDS to warrant significant clinical concern.

In the present paper, we discuss three challenges with the Norwegian Child Protective System (CPS) that might have contributed to the recent criticism from the European Court of Human Rights (ECtHR). First, how to balance the rights of the child with those of the parents. Second, the psychological field’s influence on the interpretation of what constitutes the best interest of the child, and third we describe several missing links in the CPS work. Throughout the paper, we find indications of a well-developed Act, but a less optional CPS practice. Likewise, we find evidence for a narrow interpretation of the best interest of the child related to CPS and expert psychologists’ application of attachment theory, and several organizational and educational shortcomings in the area of CPS. We conclude that the child is not fully seen as a legal subject in the eyes of the ECtHR, and that more research into CPS measures and organization are needed to better deliver adequate assistance to vulnerable families.

A better understanding of the biological factors underlying antidepressant treatment in patients with major depressive disorder (MDD) is needed. We perform gene expression analyses and explore sources of variability in peripheral blood related to antidepressant treatment and treatment response in patients suffering from recurrent MDD at baseline and after 8 weeks of treatment. The study includes 281 patients, which were randomized to 8 weeks of treatment with vortioxetine (N= 184) or placebo (N= 97). To our knowledge, this is the largest dataset including both gene expression in blood and placebo-controlled treatment response measured by a clinical scale in a randomized clinical trial. We identified three novel genes whose RNA expression levels at baseline and week 8 are significantly (FDR < 0.05) associated with treatment response after 8 weeks of treatment. Among these genes were SOCS3(FDR = 0.0039) and PROK2(FDR = 0.0028), which have previously both been linked to depression. Downregulation of these genes was associated with poorer treatment response. We did not identify any genes that were differentially expressed between placebo and vortioxetine groups at week 8 or between baseline and week 8 of treatment. Nor did we replicate any genes identified in previous peripheral blood gene expression studies examining treatment response. Analysis of genome-wide expression variability showed that type of treatment and treatment response explains very little of the variance, a median of <0.0001% and 0.05% in gene expression across all genes, respectively. Given the relatively large size of the study, the limited findings suggest that peripheral blood gene expression might not be the best approach to explore the biological factors underlying antidepressant treatment.

ABSTRACTThe lack of interest among pre-university students to choose STEM subjects for their higher education is a heavily debated issue in many western-world countries. To boost Danish students’ interest in biology, a study event on artificial reefs was introduced when teaching marine biology in lower secondary school and upper secondary school (student age 13–20 years). The purpose was to investigate if the focus on artificial reefs could generate an increased interest in natural science and marine biology among the students. The students’ interest in science was evaluated using electronic questionnaires before and after they had completed the teaching programme. The students were significantly more interested in natural sciences and marine biology after than before the teaching program. The development in situational interest in science and in the oceans was different for males and females with females being most interested. Thus, it is possible to trigger a situational interest for science and marine biology by teaching about artificial reefs, but the way interest is triggered differs between different age groups and sexes.

Glucagon and glucagon-like peptide-1 (GLP-1) originate from the common precursor, proglucagon, and their plasma concentrations have been reported to be increased during inflammatory conditions. Increased blood glucose levels are frequently observed in septic patients, and therefore we hypothesized that glucagon, but not GLP-1, is increased in individuals with inflammation.Prospective longitudinal cohort study.We measured glucagon and GLP-1 in plasma sampled consecutively in three cohorts consisting of patients with infective endocarditis (n= 16), urosepsis (n= 28) and post-operative inflammation following percutaneous aortic valve implantation or thoracic endovascular aortic repair (n= 5). Correlations between C-reactive protein (CRP), a marker of systemic inflammation, and glucagon and GLP-1 concentrations were investigated. Additionally, glucagon and GLP-1 concentrations were measured after a bolus infusion of lipopolysaccharide (LPS, 1 ng/kg) in nine healthy young males.Glucagon and CRP were positively and significantly correlated (r = 0.27; P= 0.0003), whereas no significant association between GLP-1 and CRP was found (r = 0.08, P= 0.30). LPS infusion resulted in acute systemic inflammation reflected by increased temperature, pulse, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and concomitantly increased concentrations of glucagon (P< 0.05) but not GLP-1.Systemic inflammation caused by bacterial infections or developed as a non-infected condition is associated with increased plasma concentration of glucagon, but not GLP-1. Hyperglucagonemia may contribute to the impaired glucose control in patients with systemic inflammatory diseases.

Several recent studies have found signs of recent selection on the carnitine palmitoyl-transferase 1A (CPT1A) gene in the ancestors of Arctic populations likely as a result of their traditional diet. CPT1A is involved in fatty acid transportation and is known to affect circulating fatty acid profiles in Inuit as does the unique traditional diet rich in marine animals. We aimed to assess which fatty acids may have driven the selection of rs80356779, a c.1436C>T (p.(Pro479Leu)) variant in CPT1A, by analyzing a potential interaction between the variant and traditional Inuit diet. We included 3005 genome-wide genotyped individuals living in Greenland, who had blood cell membrane fatty acid levels measured. Consumption of 25 traditional food items was expressed as percentage of total energy intake. We tested for CPT1A× traditional diet interaction while taking relatedness and admixture into account. Increasing intakes of traditional diet was estimated to attenuate the effect of 479L on 20:3 omega-6 levels (p= 0.000399), but increase the effect of the variant on 22:5 omega-3 levels (p= 0.000963). The 479L effect on 22:5 omega-3 more than doubled in individuals with a high intake of traditional diet (90% percentile) compared with individuals with a low intake (10% percentile). Similar results were found when assessing interactions with marine foods. Our results suggest that the association between traditional diet and blood cell fatty acid composition is affected by the CPT1Agenotype, or other variants in linkage disequilibrium, and support the hypothesis that omega-3 fatty acids may have been important for adaptation to the Arctic diet.

Background: Bariatric surgery leads to a substantial weight loss (WL), however, a subset of patients undergoing surgery fails to achieve adequate WL. The reason for the individual variation in WL remains unexplained. Using an exploratory cross-disciplinary approach, we aimed to identify preoperative and early postoperative factors explaining the variation in WL after bariatric surgery. Methods: Sixty-one subjects were recruited. Eighteen subjects did not receive surgery and three subjects dropped out, leaving a total sample of 40 subjects. Physiological, social, and psychological data were collected before and 6 months after surgery. All variables were analyzed in combination using a least absolute shrinkage and selection operator (LASSO) regression to explain the variation in WL 18 months after Roux-en-Y gastric bypass (n= 30) and sleeve gastrectomy (n= 10). Results: Mean WL was 31% (range: 10–52%). The following preoperative factors predicted 59% of the variation in WL: type of surgery (14%), diabetes status (12%), economic resources (9%), sex (7%), binge eating disorder (7%), degree of depression (5%), household type (3%), and physical activity (1%). Including information on early responses after surgery increased the ability to predict WL to 78% and was explained by early WL (47%), changes in energy density of food consumed from a buffet meal (9%), changes in glicentin (5%), degree of depression (5%), sex (5%), type of surgery (2%), economic resources (2%), and changes in drive for thinness (1%). Conclusions: Using a cross-disciplinary approach, a substantial part of the individual variation in WL was explained by a combination of basic patient characteristics, psychological profile, and social conditions as well as physiological, psychological and behavioral responses to surgery. These results suggest that patient characteristics collected in a cross-disciplinary approach may help determine predictors for less successful WL after bariatric surgery. If verified in larger cohorts this may form the basis for individualized postoperative support to optimize WL outcome.

Aspirin is considered critical lifelong therapy for patients with established cardiovascular (CV) disease (including coronary artery, cerebrovascular, and peripheral arterial diseases) and is consequently one of the most widely used medications worldwide. However, the indications for aspirin use continue to evolve and recent trials question its efficacy for primary prevention. Although one third of patients undergoing noncardiac surgery and at risk for a major adverse CV event receive aspirin perioperatively, uncertainty still exists about how aspirin should be optimally managed in this context, and significant practice variability remains. Recent trials suggest that the risks of continuing aspirin during the perioperative period outweigh the benefits in many cases, but data on patients with high CV risk remain limited. We performed a comprehensive PubMed and Medline literature search using the following keywords: aspirin, aspirin withdrawal, perioperative, coronary artery disease, cerebrovascular disease, peripheral artery disease, and CV disease; we manually reviewed all relevant citations for inclusion. Patients taking aspirin for the primary prevention of CV disease should likely discontinue it during the perioperative period, especially when there is a high risk of bleeding. Patients with established CV disease but without a coronary stent should likely continue aspirin during the perioperative period unless undergoing closed-space surgery. Patients with a history of coronary stenting also likely need aspirin continuation throughout the perioperative period for nonclosed space procedures. Perioperative clinicians need to balance the risks of ceasing aspirin before surgery against its continuation during the perioperative interval using a patient-specific strategy. The guidance on decision-making with regard to perioperative aspirin cessation or continuation using currently available clinical data from studies in high-risk patients along with nonclinical aspirin studies is conflicting and does not enable a simplified or unified answer. However, pertinent guidelines on CV disease management provide a basic framework for aspirin management, and large trial findings provide some insight into the safety of perioperative aspirin cessation in some contexts, although uncertainty on perioperative aspirin still exists. This review provides an evidence-based update on perioperative aspirin management in patients undergoing noncardiac surgery with a focus on recommendations for perioperative clinicians on continuing versus holding aspirin during this context.

The maritime expansion of Scandinavian populations during the Viking Age (about ad750–1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci—including the lactase-persistence allele of LCTand alleles of ANKAthat are associated with the immune response—in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.

Background/objectives: Bile acids in plasma are elevated after bariatric surgery and may contribute to metabolic improvements, but underlying changes in bile flow are poorly understood. We assessed bilio-enteric flow of bile and plasma bile concentrations in individuals with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with matched non-surgical controls (CON). Subjects/methods: Fifteen RYGB, 10 SG and 15 CON underwent 99Tc-mebrofenin cholescintigraphy combined with intake of a high-fat 111In-DTPA-labelled meal and frequent blood sampling. A 75Se-HCAT test was used to assess bile acid retention. Results: After RYGB, gallbladder filling was decreased (p= 0.045 versus CON), basal flow of bile into the small intestine increased (p= 0.005), bile acid retention augmented (p= 0.021) and basal bile acid plasma concentrations elevated (p= 0.009). During the meal, foods passed unimpeded through the gastric pouch resulting in almost instant postprandial mixing of bile and foods, but the postprandial rise in plasma bile acids was brief and associated with decreased overall release of fibroblast growth factor-19 (FGF-19) compared with CON (p= 0.033). After SG, bile flow and retention were largely unaltered (p> 0.05 versus CON), but gastric emptying was accelerated (p&lt; 0.001) causing earlier mixture of bile and foods also in this group. Neither basal nor postprandial bile acid concentrations differed between SG and CON. Conclusions: Bilio-enteric bile flow is markedly altered after RYGB resulting in changes in plasma concentrations of bile acids and FGF-19, whereas bile flow and plasma concentrations are largely unaltered after SG.

Objectives: Gastrointestinal hormones contribute to the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB) on glycemic control. Secretin is secreted from duodenal S cells in response to low luminal pH, but it is unknown whether its secretion is altered after RYGB and if secretin contributes to the postoperative improvement in glycemic control. We hypothesized that secretin secretion increases after RYGB as a result of the diversion of nutrients to more distal parts of the small intestine, and thereby affects islet hormone release. Methods: A specific secretin radioimmunoassay was developed, evaluated biochemically, and used to quantify plasma concentrations of secretin in 13 obese individuals before, 1 week after, and 3 months after RYGB. Distribution of secretin and its receptor was assessed by RNA sequencing, mass-spectrometry and in situ hybridization in human and rat tissues. Isolated, perfused rat intestine and pancreas were used to explore the molecular mechanism underlying glucose-induced secretin secretion and to study direct effects of secretin on glucagon, insulin, and somatostatin secretion. Secretin was administered alone or in combination with GLP-1 to non-sedated rats to evaluate effects on glucose regulation. Results: Plasma postprandial secretin was more than doubled in humans after RYGB (P&lt; 0.001). The distal small intestine harbored secretin expressing cells in both rats and humans. Glucose increased the secretion of secretin in a sodium-glucose cotransporter dependent manner when administered to the distal part but not into the proximal part of the rat small intestine. Secretin stimulated somatostatin secretion (fold change: 1.59, P&lt; 0.05) from the perfused rat pancreas but affected neither insulin (P= 0.2) nor glucagon (P= 0.97) secretion. When administered to rats in vivo, insulin secretion was attenuated and glucagon secretion increased (P= 0.04), while blood glucose peak time was delayed (from 15 to 45 min) and gastric emptying time prolonged (P= 0.004). Conclusions: Glucose-sensing secretin cells located in the distal part of the small intestine may contribute to increased plasma concentrations observed after RYGB. The metabolic role of the distal S cells warrants further studies.

Parathyroid hormone (PTH) is a key hormone in regulation of calcium homeostasis and its secretion is regulated by calcium. Secretion of PTH is attenuated during intake of nutrients, but the underlying mechanism(s) are unknown. We hypothesized that insulin acts as an acute regulator of PTH secretion.Intact PTH was measured in plasma from patients with T1D and matched healthy individuals during 4-h oral glucose tolerance tests (OGTT) and isoglycemic i.v. glucose infusions on 2 separate days. In addition, expression of insulin receptors on surgical specimens of parathyroid glands was assessed by immunochemistry (IHC) and quantitative PCR (qPCR).The inhibition of PTH secretion was more pronounced in healthy individuals compared to patients with T1D during an OGTT (decrementalAUC0–240min: −5256 ± 3954 min × ng/L and −2408 ± 1435 min × ng/L, P= 0.030). Insulin levels correlated significantly and inversely with PTH levels, also after adjusting for levels of several gut hormones and BMI (P= 0.002). Expression of insulin receptors in human parathyroid glands was detected by both IHC and qPCR.Our study suggests that insulin may act as an acute regulator of PTH secretion in humans.

Estimating total narrow-sense heritability in admixed populations remains an open question. In this work, we used extensive simulations to evaluate existing linear mixed-model frameworks for estimating total narrow-sense heritability in two population-based cohorts from Greenland, and compared the results with data from unadmixed individuals from Denmark. When our analysis focused on Greenlandic sib pairs, and under the assumption that shared environment among siblings has a negligible effect, the model with two relationship matrices, one capturing identity by descent and one capturing identity by state, returned heritability estimates close to the true simulated value, while using each of the two matrices alone led to downward biases. When phenotypes correlated with ancestry, heritability estimates were inflated. Based on these observations, we propose a PCA-based adjustment that recovers the true simulated heritability. We use this knowledge to estimate the heritability of ten quantitative traits from the two Greenlandic cohorts, and report differences such as lower heritability for height in Greenlanders compared with Europeans. In conclusion, narrow-sense heritability in admixed populations is best estimated when using a mixture of genetic relationship matrices on individuals with at least one first-degree relative included in the sample.

Neprilysin degrades natriuretic peptides in circulation and is also suggested to degrade the gut hormones gastrin and cholecystokinin. Neprilysin inhibition has become a therapeutic strategy and thus a regimen in need of further testing in terms of other hormonal axes besides natriuretic peptides. The aim of this study was to examine whether acute inhibition of neprilysin affects meal-induced responses in gastrin and cholecystokinin concentrations in healthy individuals.Nine healthy young men were included in an open-labelled, randomized cross-over clinical trial. The participants received a standardized meal (25 g fat, 26 g protein, 42 g carbohydrate) on two separate days with or without a one-time dosage of sacubitril ((194 mg)/valsartan (206 mg)). Blood pressure, heart rate and blood samples were measured and collected during the experiment. Statistical differences between groups were assessed using area under the curve together with an ANOVA with a Bonferronipost hoctest. Sacubitril/valsartan increased the postprandial plasma concentrations of both gastrin and cholecystokinin (80% (AUC0-270 min, P= 0.004) and 60% (AUC0-270 min, P= 0.003), respectively) compared with the control meal. No significant hemodynamic effects were noted (blood pressure, AUC0-270 min, P= 0.86, heart rate, AUC0-270 min, P= 0.96).Our study demonstrates that sacubitril/valsartan increases the postprandial plasma concentrations of gastrin and cholecystokinin in healthy individuals. The results thus suggest that neprilysin-mediated degradation of gastrin and cholecystokinin is physiologically relevant and may have a role in heart failure patients treated with sacubitril/valsartan.

In type 2 diabetes, long-acting GLP-1 receptor agonists lower fasting plasma glucose and improve glycaemic control via their insulinotropic and glucagonostatic effects. In type 1 diabetes, their efficacy as an add-on treatment to insulin therapy is modest. Short-acting GLP-1 receptor agonists also lower postprandial glucose excursions in type 2 diabetes by decelerating gastric emptying rate. We aimed to test the efficacy of a short-acting GLP-1 receptor agonist in type 1 diabetes.

The 68th Benzon Foundation Symposium brought together leading experts to explore the integration of mass spectrometry (MS)-based proteomics and artificial intelligence in revolutionizing personalized medicine. This report highlights key discussions on recent technological advances in MS-based proteomics, including improvements in sensitivity, throughput, and data analysis. Particular emphasis was placed on plasma proteomics and its potential for biomarker discovery across various diseases. The symposium addressed critical challenges in translating proteomic discoveries to clinical practice, including standardization, regulatory considerations and the need for robust ‘business cases’ to motivate adoption. Promising applications were presented in areas such as cancer diagnostics, neurodegenerative diseases, and cardiovascular health. The integration of proteomics with other omics technologies and imaging methods was explored, showcasing the power of multi-modal approaches in understanding complex biological systems. Artificial intelligence emerged as a crucial tool for the acquisition of large-scale proteomic datasets, extracting meaningful insights, and enhancing clinical decision-making. By fostering dialogue between academic researchers, industry leaders in proteomics technology, and clinicians, the symposium illuminated potential pathways for proteomics to transform personalized medicine, advancing the cause of more precise diagnostics and targeted therapies.

COVID-19 restrictions prevented relatives from visiting and accompanying patients to hospital and required that nurses wore personal protective equipment. These changes affected patients’ relationships with relatives and challenged their ability to connect with nurses. Individual, semi-structured interviews with 15 patients were carried out to explore patients’ experiences of their relationships with relatives and their collaboration with nurses during in- and outpatient contacts in non-COVID-19 hospital wards. The analysis of data was guided by phenomenological hermeneutic frame of reference and the study was reported according to the COREQ checklist. The findings illustrated that patients felt lonely and insecure when separated from relatives, caught between relatives and professionals during information exchange, and experienced the absence of relatives as both beneficial and burdening. Visitor restrictions provided patients with time to heal but prevented provision of informal care. Patients had to take responsibility for maintaining contact with relatives independent of their health condition. COVID-19 restrictions created distance with nurses, which potentially led to insufficient physical and psychosocial care.

Intrahepatic triacylglycerol (liver TG) content is associated with hepatic insulin resistance and dyslipidemia. Liver TG content can be modulated within days under hypocaloric conditions.

Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in β cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo.We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion.