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Focused lung ultrasound (FLUS) has high diagnostic accuracy in many common conditions seen in a variety of emergency settings. Competencies are essential for diagnostic success and patient safety but can be challenging to acquire in clinical environments. Immersive virtual reality (IVR) offers an interactive risk-free learning environment and is progressing as an educational tool. First, this study explored the educational impact of novice FLUS users participating in a gamified or non-gamified IVR training module in FLUS by comparing test scores using a test with proven validity evidence. Second, the learning effect was assessed by comparing scores of each group with known test scores of novices, intermediates and experienced users in FLUS. A total of 48 participants were included: 24 received gamified and 24 received non-gamified IVR training. No significant difference was found between gamified (mean = 15.5 points) and non-gamified (mean = 15.2 points), indicating that chosen gamification elements for our setup did not affect learning outcome (p = 0.66). The mean scores of both groups did not significantly differ from those of known intermediate users in FLUS (gamified p = 0.63, non-gamified p = 0.24), indicating that both IVR modules could be used as unsupervised out-of-hospital training for novice trainees in FLUS.

BACKGROUND: Thrombosis is common among patients with cancer. Primary thromboprophylaxis guided by the Khorana score is endorsed by guidelines but recommendations rely mainly on data from patients treated with chemotherapy.OBJECTIVES: To explore if the Khorana score could risk stratify patients with cancer treated with immune checkpoint inhibitors according to risk of venous and arterial thrombosis.PATIENTS/METHODS: The study population and Khorana score were defined using administrative Danish health registries. The primary outcome was 6-month risk of venous thromboembolism after initiation of checkpoint inhibitor treatment. Secondary outcomes were arterial thrombosis and any thromboembolic event. Death was considered a competing risk event.RESULTS: Among 3946 patients with cancer initiating checkpoint inhibitor treatment without other indications for anticoagulation, the overall 6-month incidence of venous thromboembolism was 2.6% (95% confidence interval [CI]: 2.1-3.1). Risks were 2.1% (95% CI: 1.5-3.0), 2.6% (95% CI: 2.0-3.4), and 3.7% (95% CI: 2.1-5.9) in low (score 0), intermediate (score 1-2), and high risk (score ≥3) Khorana categories, respectively. Among patients eligible for primary thromboprophylaxis according to guidelines (Khorana score ≥2), risk of venous thromboembolism was 4.1% (95% CI: 3.1-5.4). Higher Khorana risk category was also associated with higher 6-month risk of both arterial thrombosis and any thromboembolic events.CONCLUSIONS: The Khorana score was able to risk stratify patients with cancer treated with immune checkpoint inhibitors according to 6-month risk of thromboembolic events. Risks of venous thromboembolism were lower than in randomized thromboprophylaxis trials, thus questioning the absolute benefit of routine primary thromboprophylaxis in an unselected population of patients treated with immune checkpoint inhibitors.

BackgroundElectrocardiographic T-wave morphology is used in drug safety studies as an adjunct to the QT c interval, but few measurements of T-wave morphology can be interpreted in clinical practice. Morphology combination score (MCS) is a combination of T-wave flatness/peakedness, asymmetry, and notching, enabling easy visual assessment of T-wave morphology. We aimed to test the association between T-wave morphology, quantified by MCS, and mortality.MethodsWe included electrocardiograms recorded in 2001–2011 from 342,294 primary care patients. Using Cox regression, we evaluated the association between MCS, cardiovascular death, and all-cause mortality, adjusting for heart rate, QT c, QT-prolonging drugs, diabetes, ischemic heart disease, hypertension, and congestive heart failure.Results270,039 individuals (44% men, median age 55 [inter-quartile range: 42–67 years]) were included and followed for a median of 9.3 years, during which time 13,489 (5.0%) died from cardiovascular causes and 50,481 (18.7%) from any cause. High values of MCS (i.e. asymmetric, flattened, and/or notched T waves) were associated with an adjusted mortality Hazard Ratio of 1.75 (95% CI 1.62–1.89) and 1.61 (1.43–1.92) for women and men, respectively. Low values of MCS (i.e. peaked and symmetric T waves) were associated with a Hazard Ratio of 1.18 (1.08–1.28) and 1.71 (1.48–1.98) for women and men, respectively.ConclusionsIn a large primary care population, we found that T-wave asymmetry, flatness, and notching provided prognostic information on mortality independent of heart rate, QTc, and baseline comorbidities.

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AIMS: Potassium disturbances are common and associated with increased morbidity and mortality, even in patients without prior cardiovascular disease. We examined six electrocardiographic (ECG) measures and their association to serum potassium levels.METHODS AND RESULTS: From the Copenhagen General Practitioners' Laboratory, we identified 163,547 individuals aged ≥16 years with a first available ECG and a concomitant serum potassium measurement during 2001-2011. Restricted cubic splines curves showed a non-linear relationship between potassium and the Fridericia corrected QT (QTcF) interval, T-wave amplitude, morphology combination score (MCS), PR interval, P-wave amplitude and duration. Therefore, potassium was stratified in two intervals K: 2.0-4.1 mmol/L and 4.2-6.0 mmol/L for further analyses. Within the low potassium range, we observed: QTcF was 12.8 ms longer for each mmol/L decrease in potassium (p

Needle probe measurements are used in a wide variety of fields for measuring the thermal conductivity of materials. It is most common to extract the thermal conductivity from the temperature rise data using the asymptotic solution to the heat equation. With special reference to, but not limited to Earth materials, this study presents an inversion procedure using pulsed needle probe data to determine both thermal conductivity and thermal diffusivity. The measured temperature response data are interpreted using a finite element forward model and a Markov Chain Monte Carlo inversion algorithm. The thermal properties of the needle probe are part of the forward model and determined by measurements on calibration standards. We examine several factors by synthetic modelling and quantify their effects by Monte Carlo inversions. This include (1) the heat production rate of the probe in order to produce similar temperature increases in materials of different thermal properties, (2) the contact resistance between needle probe and sample, (3) the limitations imposed by sample diameter and the thermal properties of the surrounding medium, and (4) the duration of heating period required to obtain good results. Laboratory test measurements on selected materials (water, glycerol, ceramic standard, clay) demonstrate good agreement with expected values obtained from literature. We demonstrate that the combination of numerical forward modelling and Monte Carlo inversion, applied to the pulsed needle, is a flexible and powerful methodology for accurate laboratory measurements of material thermal properties and with well-defined estimates of uncertainty. With the given equipment and laboratory setup, thermal conductivity is measured to within few percent, while thermal diffusivity generally has a somewhat higher degree of uncertainty, up to about five percent.

Thermoelectric effect is a physical phenomenon which intricately relates the thermal energy of charge carriers to their charge transport. Understanding the mechanism of this interaction in different systems lies at the heart of inventing novel materials which can revolutionize thermoelectric power generation technology. Despite the recent surge of interest in organic thermoelectric materials, the community has had difficulties in formulating the charge transport mechanism in the presence of a significant degree of disorder. Here, we analyze the thermoelectric properties of various conducting polymers doped by solid-state diffusion of dopant molecules based on a transport model with a power law energy dependence of transport function. A fine control of the degree of doping via postdoping annealing provides an accurate empirical evidence of a strong energy dependence of the carrier mobility in the conducting polymers. A superior thermoelectric power factor of conducting polymers doped by solid-state diffusion to that of other doping methods can be attributed to a resulting higher intrinsic mobility and higher free carrier concentration.

Background Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS.

Producing entire male pigs entails a risk of boar taint in the meat due to increased levels of the compounds skatole and androstenone in the carcass. Allowing meat from entire male pigs to be marketed and sold together with meat from castrates and female pigs increases the risk of consumers being dissatisfied due to boar tainted samples. To reduce this risk, it is necessary to set sorting limits for androstenone and skatole preventing meat from the most boar-tainted entire males from reaching the market. This paper presents a model framework in which the risk of consumer expressions of dislike is modelled as a function of the concentrations of skatole and androstenone. A bivariate log-normal model of skatole and androstenone concentrations is estimated from a representative sample of entire male pigs, and, by combining these two models, the expected risk of dislike and the number of discarded carcasses is estimated as a function of sorting limits. If the risk of dislike of meat from entire male pigs equals the risk of dislike of meat from castrates, up to 80% of the carcasses should be discarded. However, there is a huge variation in consumer response. This new analytical approach allows the industry to set appropriate sorting limits by balancing the risk of dissatisfied consumers with the proportion of discarded entire male carcasses.

Dispersions of whey protein isolate (WPI), microparticulated whey protein (MWP), nanoparticulated whey protein (NWP) and micellar casein isolate (MCI) were characterised in terms of protein denaturation and particle size. WPI exhibited high native whey protein content, while MWP and NWP showed low native whey protein content. The acid gelation behaviour of milk protein ingredients and mixtures thereof (5% protein) in different ionic environments (deionised water, whey permeate and dialysed against skimmed milk) was also investigated. The gelation curves of NWP showed no significant difference for in the three different ionic environments, and high gel strength after acidification was observed. WPI, MWP and MCI dispersed in deionised water gelled faster than in the other two ionic environments. MCI in whey permeate showed slower gelation and lower G’ than their dialysed samples.

This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂, 5♀) were randomly assigned single-blinded to normoxic (21% O2) and hypoxic (10% O2) trials with measurements taken at rest and 30 min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH) and low density lipoprotein (LDL) oxidation (spectrophotometry). Cerebral and femoral venous blood flow was evaluated by transcranial Doppler ultrasound (CBF) and constant infusion thermodilution (FBF). With 3 participants lost to follow up (final n = 4♂, 3♀), hypoxia increased CBF and FBF (P = 0.041 vs. normoxia) with further elevations in FBF during exercise (P = 0.002 vs. rest). Cerebral and femoral ascorbate and α-tocopherol consumption (v a) and increased LDL oxidation during hypoxia (P < 0.043-0.049 vs. normoxia) implying free radical-mediated lipid peroxidation subsequent to inadequate antioxidant defense. This was pronounced during exercise across the femoral circulation in proportion to the increase in local O2 uptake (r = -0.397 to -0.459, P = 0.037-0.045) but unrelated to any reduction in PO2. These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O2 flux than to O2 tension.

Purpose In this cadaveric study, we aim to define the basic anatomy of the anterior glenoid with attention to the relationships of calcified cartilage, capsulolabral complex, and osseous morphology of the anterior glenoid. Methods Seventeen cadaveric glenoid specimens (14 male, 3 female, mean age 53.9 ± 10) were imaged with micro-computed tomography (CT) and embedded in poly-methyl-methacrylate. Specimens were included for final analysis only if the entire glenoid articular cartilage, labrum, capsule, and biceps insertion were pristine and without evidence of injury, degeneration, or damage during the preparation process. Group 1 members (n = 9) were axially sectioned through 3 to 9 o'clock and 4 to 8 o'clock; group 2 members (n = 8) were radially sectioned through 3, 4, 5, and 9 o'clock. A scanning electron microscope (SEM) analysis quantified the percentage of bone within a 5 × 2.5 mm region at the glenoid rim. Micro-CT, SEM, and light microscopy evaluated the capsulolabral complex and calcified fibrocartilage. Results A 7 ± 2.1 mm region of calcified fibrocartilage at 4 o'clock was identified from the articular face to the medial glenoid neck supporting the overlying capsulolabral footprint and was >3× thicker at the articular attachment (316 ± 153 μm) versus the glenoid neck (92 ± 66 μm). At 3 to 9 o'clock and 4 to 8 o'clock 79.2% ± 5.4% and 75.2% ± 7.8% of the glenoid osseous width was covered with articular cartilage. The labrum accounted for 13.1% ± 3.4% of the glenoid width at 4 o'clock. SEM analysis demonstrated decreased glenoid bone density at 3, 4, and 5 o'clock (P ≤ .015) and no difference (P = .448) at 9 o'clock versus central subchondral bone. Conclusions The capsulolabral footprint contributes significantly to the glenoid face, inserts directly adjacent to the articular cartilage, and extends medially along the glenoid neck. A layer of calcified fibrocartilage lies immediately beneath the capsulolabral footprint and is 3× thicker at the articular insertion compared with the glenoid neck. Lastly, there is a bone density gradient at the anterior-inferior rim versus the central subchondral bone. Clinical Relevance Arthroscopic Bankart repair has been reported to have a significant failure rate in many settings. It is felt that reproducing anatomy with the repair could help improve outcomes. Based on this study's findings, an arthroscopic Bankart technique that most closely reproduces native anatomy and potentially optimizes soft-tissue healing could be performed. This includes removal of 1 to 2 mm of articular cartilage from the glenoid face with anchor placement at this location to appropriately reposition the capsulolabral complex.

α-Lactalbumin (α-LA) is a key commercial whey protein for nutritional purposes. The holo protein (calcium saturated) is considered the most heat stable whey protein, capable of refolding from unfolded states under many conditions. This is due to the absence of free thiols (cysteine residues) that are typically involved in thermal aggregation and thiol–disulphide exchange reactions of other whey proteins. Heating (0–120 min at 90 °C, pH 7.0) holo α-LA generates free thiols through thermal cleavage of disulphide bonds, resulting in aggregates comprising unfolded α-LA species. The addition of free cysteine promotes the formation of soluble aggregates, effectively decreasing the holding time required to reach a particular aggregate size in a dose-dependent manner (0.35–1.4 m m cysteine). Excess cysteine (≥14 m m ) causes a destabilisation of α-LA, shown by decreased denaturation temperature and gel formation. These data indicate that low doses of cysteine can be used to control α-LA aggregation.

To better understand the interactions between nanoparticulated whey protein (NWP) and other milk proteins during acidification, milk model systems were diluted to 0.5% protein concentration and adjusted to pH of 6.0–4.5 following homogenisation and heat treatment. The diluted systems with different concentrations of NWP (0–0.5%) were characterised in terms of particle size, viscosity, surface charge and hydrophobicity. When pH was adjusted to 5.5, aggregation was initiated at levels of NWP (0.25–0.5%) leading to significant increase in particle size and viscosity. Pure NWP (0.5%) showed largest initial surface charge (−27 mv) and higher surface hydrophobicity than the other systems. The results indicated that NWP could self-associate above pH 5.5 and not only the decrease of electrostatic repulsion but also other interactions, such as hydrophobic interaction, play an important role in contributing to the early self-association of NWP.

Protein modifications in liquid infant formula (IF) have been widely studied, but distinguishing between heat- and storage-induced structural changes remains challenging. A generic liquid IF was subjected to direct or indirect UHT treatment and stored at 40 °C up to 180 days. Colour and pH were monitored and structural changes were characterised by dynamic light scattering, SDS-PAGE and centrifugal field-flow fractionation (FFF) coupled with multi-angle light scattering (MALS) and UV detectors to evaluate whether heat-induced differences would level out during storage. Both direct- and indirect UHT treatment led to structural changes, where the higher heat load of the indirect UHT treatment caused more pronounced changes. Indications were that storage-induced changes in pH, browning and non-reducible cross-links were not dependent on UHT treatment. However, FFF-MALS-UV analysis allowed characterisation of complex aggregates, where structural changes continued to be most pronounced in indirect UHT treated samples, and different storage-induced aggregation behaviour was observed.

There has been limited success with blood-based biomarkers of neurodegeneration. One perceived reason is that blood has no direct contact to the brain. Recently developed blood-based biomarkers of tau-degradation have shown promise as potential tools for peripheral assessment of neurodegeneration; however, factors contributing to the levels of these in blood are poorly understood. Using multiple linear regression analysis in cross-sectional data from an observational cohort (n = 5626), the aim was to examine which factors correlate to the serological levels of two novel biomarkers measuring truncated tau fragments (Tau-A and Tau-C) in serum. Platelets, albumin and several modifiable risk factors, including Body Mass Index, high density lipoprotein and white blood cell count were associated with the serum level of tau fragments. The factors associated with tau in serum may promote neurodegeneration and alter the permeability of the Blood Brain Barrier through chronic inflammation and vascular dysfunction. These data are of key importance for understanding the mechanism of release and subsequent peripheral processing of tau from the brain and will assist in the development of future blood-based biomarkers.

Non-fat milk model systems containing 5% total protein were investigated with addition of micro- or nanoparticulated whey protein at two levels of casein (2.5% and 3.5%, w/w). The systems were subjected to homogenisation (20 MPa), heat treatment (90 °C for 5 min) and chemical (glucono-delta-lactone) acidification to pH 4.6 and characterised in terms of denaturation degree of whey protein, particle size, textural properties, rheology and microstructure. The model systems with nanoparticulated whey protein exhibited significant larger particle size after heating and provided acid gels with higher firmness and viscosity, faster gelation and lower syneresis and a denser microstructure. In contrast, microparticulated whey protein appeared to only weakly interact with other proteins present and resulted in a protein network with low connectivity in the resulting gels. Increasing the casein/whey protein ratio did not decrease the gel strength in the acidified milk model systems with added whey protein aggregates.

Aim Type 1 diabetes requires extensive self-management to avoid complications and may have negative effects on the everyday life of people with the disease. The aim of this study was to compare adults with type 1 diabetes to the general population in terms of health-related quality of life, occupational status (level of employment, working hours and sick leave) and education level. Methods 2415 adults (aged 18–98years) with type 1 diabetes were compared to 48,511 adults (aged 18–103years) from the general population. Data were obtained from two cross-sectional surveys conducted in 2010 and 2011 of adults living or treated in the Capital Region in Denmark. Differences between adults with type 1 diabetes and the general population were standardised for age and sex and analyzed using linear probability models and negative binomial regression. Differences were further analyzed in subgroups. Results Compared to the general population, adults with type 1 diabetes experienced lower health-related quality of life, were more frequently unemployed, had more sick leave per year and were slightly better educated. Differences in health-related quality of life and employment increased with age and were larger among women, as compared to men. No significant differences were found with regard to working hours. Conclusion Our findings suggest that type 1 diabetes is associated with lower health-related quality of life, higher unemployment and additional sick leave. The negative association with type 1 diabetes is more pronounced in women and older adults.

Decarbonization of the maritime transportation fuels is a primary objective of the shipping industry. Ammonia is an attractive option because of its relatively low greenhouse gas (GHG) emissions, high energy density, competitive cost, and ubiquitous infrastructure for manufacturing, storage, and distribution. The environmental benefits are enhanced when the manufacture of ammonia is assisted by renewable energy and feedstocks. This paper evaluates the potential usage of ammonia, especially renewable ammonia, as a maritime transportation fuel. The assessment covers manufacturing approaches, energy and feedstock sources, economics, and environmental impact based on well-to-tank and tank-to-propeller bases. Comparison is also made with conventional fuels that are currently used in the shipping industry. Finally, the paper discusses future directions and impact of technological advances on the potential use of renewable ammonia as a transportation fuel.

There is growing pressure to reduce greenhouse gas (GHG) emissions from maritime transportation. One of the most effective strategies for reducing GHG emissions is to switch from conventional fuels such as heavy fuel oil to alternative fuels. Green hydrogen is a promising alternative for the shipping industry. Nonetheless, its potential usage will depend on more than its environmental friendliness. Economic, technical, and safety factors must be assessed. This paper provides a critical assessment of the potential usage of green hydrogen in the shipping industry with an evaluation of production routes, techno-economic performance, storage, and safety. Benchmarking is also carried out compared to existing ‘grey’ and ‘blue’ production routes specific to shipping industry applications. Important metrics for liquid hydrogen are analyzed to evaluate production cost and GHG emissions for various routes. Furthermore, a comparison is made for the safety and health issues of hydrogen compared to conventional and emerging maritime shipping fuels.

Enterotoxigenic Escherichia coli (ETEC), being the major cause of post-weaning diarrhoea (PWD) in newlyweaned piglets, induces poor performance and economic losses in pig production. This functional in vitroscreening study investigated probiotic strains for use in suckling piglets as a prophylactic strategy towards PWD.Nine strains were evaluated based on their ability to: enhance intestinal epithelial barrier function, reduceadherence of ETEC F18 to intestinal cells, inhibit growth of ETEC F18, and grow on porcine milk oligosaccharides.Strains included in the screening were of the species Lactobacillus, Enterococcus, Bifidobacterium and Bacillus.Our in vitro screening demonstrated genus-, species and strain-specific differences in the mode of action ofthe tested probiotic strains. Some of the tested bifidobacteria were able to grow on the two porcine milk oligosaccharides,3′ -sialyllactose sodium salt (3’SL) and Lacto-N-neotetraose (LNnT), whereas most lactic acidbacteria strains and both Bacillus subtilis strains failed to do so. All probiotic strains inhibited growth of ETEC F18on agar plates. All but the bifidobacteria reduced binding of ETEC F18 to Caco-2 cell monolayers, with theEnterococcus faecium strain having the most profound effect. All three lactic acid bacteria and Bifidobacteriumanimalis subsp. lactis counteracted the ETEC F18-induced permeability across Caco-2 cell monolayers with theE. faecium strain exhibiting the most pronounced protective effect. The findings from this in vitro screening studyindicate that, when selecting probiotic strains for suckling piglets as a prophylactic strategy towards PWD, itwould be advantageous to choose a multi-species product including strains with different modes of action inorder to increase the likelihood of achieving beneficial effects in vivo.

The ability to understand and possibly even predict the productivity of wells across a field is an important accomplishment in a production setting. In the tight Lower Cretaceous chalk field Valdemar, 5 wells have been observed to produce significantly larger oil volumes compared to nearby wells. This study was conducted to map the inter-well differences in the oil composition to better understand the productivity differences. This was done by analyzing any chemical differences of 21 samples from 16 different wells by GC-MS and principal component analysis of summed extracted ion chromatograms (SICs) using the chemometric analysis of selected ion chromatograms (CHEMSIC) method. The sterane (m/z 217 and m/z 218) and C4 (m/z 234) biomarker SICs were found to have chemically meaningful features described by principal component 1 (PC1). The association between these markers and the relative production was modeled to provide a better understanding of the productivity of the different wells. A correlation between oil saturation and productivity was established in the sense that the more mature and thus less viscous oil seem to have charged certain favorably placed reservoir sections first; these locations coincide with the location of the 5 wells in question.

Formation of insoluble aggregates in acidic whey protein isolate (WPI) beverages during storage is a quality concern. Earlier studies showed that changes in processing methods from 95 °C for 180 s–120 °C for 20 s could prevent it. In the present study, WPI drinks were stored for up to 12 months and insoluble aggregates formed in re-solubilised WPI and its liquid phase analysed by proteomics. Insoluble aggregates were found to be enriched in caseinomacropeptides (CMP). Increased peptide formation by weak acid hydrolysis, especially of CMP, was found at 120 °C. Further enhanced hydrolysis of CMP was obtained by deamidation as well as by the presence of the genetic variant A of CMP. Batch variations may therefore be assigned to variations in CMP as well as variations in the distribution of genetic variants of A and B in different WPI batches used for the production of the WPI products.

Micro- and nanoparticulated whey protein (MWP, NWP) were added to non-fat milk model systems and processed into chemically (glucono-delta-lactone) acidified milk gels. Model systems contained 5% protein in total and were made at two levels of casein (2.5% and 3.5%, w/w) with and without the thiol-blocking agent N-ethylmaleimide. The systems were characterised in terms of thiol groups, gel electrophoresis, particle size, and rheology during processing (homogenisation, heat treatment and acidification). The results showed that the formation of disulphide-linked structures in milk model systems was closely related to the increased particle size and rheological behaviour of the gels. MWP enriched systems produced, upon acidification, weak protein networks and required the addition of whey protein isolate (WPI) to increase gel strength. However, systems containing NWP exhibited pronounced increase in particle size and higher firmness of acidified gels through both covalent and non-covalent interactions.

Objectives The aim of the CATCH (CArdiac cT in the treatment of acute CHest pain) trial was to investigate the long-term clinical impact of a coronary computed tomographic angiography (CTA)-guided treatment strategy in patients with recent acute-onset chest pain compared to standard care. Background The prognostic implications of a coronary CTA-guided treatment strategy have not been compared in a randomized fashion to standard care in patients referred for acute-onset chest pain. Methods Patients with acute chest pain but normal electrocardiograms and troponin values were randomized to treatment guided by either coronary CTA or standard care (bicycle exercise electrocardiogram or myocardial perfusion imaging). In the coronary CTA-guided group, a functional test was included in cases of nondiagnostic coronary CTA images or coronary stenoses of borderline severity. The primary endpoint was a composite of cardiac death, myocardial infarction (MI), hospitalization for unstable angina pectoris (UAP), late symptom-driven revascularizations, and readmission for chest pain. Results We randomized 299 patients to coronary CTA-guided strategy and 301 to standard care. After inclusion, 24 patients withdrew their consent. The median (interquartile range) follow-up duration was 18.7 (range 16.8 to 20.1) months. In the coronary CTA-guided group, 30 patients (11%) had a primary endpoint versus 47 patients (16%) in the standard care group (p = 0.04; hazard ratio [HR]: 0.62 [95% confidence interval: 0.40 to 0.98]). A major adverse cardiac event (cardiac death, MI, hospitalization for UAP, and late symptom-driven revascularization) was observed in 5 patients (2 MIs, 3 UAPs) in the coronary CTA-guided group versus 14 patients (1 cardiac death, 7 MIs, 5 UAPs, 1 late symptom-driven revascularization) in the standard care group (p = 0.04; HR: 0.36 [95% CI: 0.16 to 0.95]). Differences in cardiac death and MI (8 vs. 2) were insignificant (p = 0.06). Conclusions A coronary CTA-guided treatment strategy appears to improve clinical outcome in patients with recent acute-onset chest pain and normal electrocardiograms and troponin values compared to standard care with a functional test. (Cardiac-CT in the Treatment of Acute Chest Pain [CATCH]; NCT01534000 )

Background Despite the significance of firearm safety, we need additional data to understand the prevalence and context surrounding firearm-related problems within the child welfare system. Objective Estimate proportion of cases reporting a firearm-related problem during case initiation and the contexts in which these problems exist. Sample and Setting 75,809 caseworker-written investigation summaries that represented all substantiated referrals of maltreatment in Michigan from 2015 to 2017. Methods We developed an expert dictionary of firearm-related terms to search investigation summaries. We retrieved summaries that contained any of the terms to confirm whether a firearm was present (construct accurate) and whether it posed a threat to the child. Finally, we coded summaries that contained firearm-related problems to identify contexts in which problems exist. Results Of the 75,809 substantiated cases, the dictionary flagged 2397 cases that used a firearm term (3.2 %), with a construct accuracy rate of 96 %. Among construct accurate cases, 79 % contained a firearm-related problem. The most common intent for a firearm-related problem was violence against a person (45 %). The co-occurrence of domestic violence and/or substance use with a firearm-related problem was high (41 % and 48 %, respectively). 49 % of summaries that contained a firearm-related problem did not provide information regarding storage. Conclusion When caseworkers document a firearm within investigative summaries, a firearm-related risk to the child likely exists. Improved documentation of firearms and storage practices among investigated families may better identify families needing firearm-related services.

BACKGROUND: The Fourth Universal Definition of Myocardial Infarction defines electrocardiographic Q waves as duration ≥30 ms and amplitude ≥1 mm or QS complex in 2 contiguous leads. However, current taskforce criteria may be overly restrictive. Therefore, we investigated the association of isolated, lenient, or strict Q waves with long-term outcome.METHODS: From 2001 to 2015, we included Danish primary care patients with digital electrocardiograms (ECGs) that were evaluated for Q waves. If none occurred, patients had no Q waves. If no other contiguous Q wave occurred, patients had isolated Q waves. If another contiguous Q wave occurred meeting only 1 criterion (≥30 ms and RESULTS: Of 365,206 patients, 87,957 had isolated, lenient, or strict Q waves (24%; median age, 61 years; male, 48%), and 277,249 had no Q waves (76%; median age, 53 years; male, 42%). Mortality risk was increased with isolated (all-cause adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 1.29-1.37; cardiovascular-cause aHR, 1.78; 95% CI, 1.70-1.87), lenient (all-cause aHR, 1.41; 95% CI, 1.33-1.50; cardiovascular-cause aHR, 1.78; 95% CI, 1.63-1.94), or strict (all-cause aHR, 1.64; 95% CI, 1.57-1.72; cardiovascular-cause aHR, 2.70; 95% CI, 2.52-2.89) Q waves compared with no Q waves. Highest mortality risk was associated with lenient or strict Q waves in anteroseptal leads.CONCLUSIONS: This large contemporary analysis suggests that less-stringent Q-wave criteria carry prognostic value in predicting adverse outcome among primary care patients.

Whey protein isolate (WPI) is widely used as a protein ingredient in foods, but undergoes thermal treatment before and during application to make the final product. The aim of the present study was to determine the temperature dependency of formation of volatiles that potentially act as off-flavours in reconstituted WPI solutions (3%, w/v) heated for different temperature–time combinations (50–90 °C for 5–10 min). Differences in orthonasal aroma were evaluated by triangle tests by a sensory panel. The panel could distinguish between samples heated for 10 min at 60 °C and 70 °C. Analysis by headspace gas chromatography-mass spectrometry (GC-MS) showed that heating the samples at 90 °C for 10 min significantly increased the concentration of dimethyl disulphide and dimethyl trisulphide compared with heating at 80 °C for 10 min or below, which suggests that sulphur-derived odour could be decreased by decreasing the heating temperature by 10 °C.

This study finds that the production profile (temperature and longevity) of low enthalpy geothermal reservoirs depends significantly on the thermal conductivity of the confining beds, which recharge the reservoir by conduction. The thermal recharge furthermore is proportional to the production rate and increases dramatically in thin reservoirs, while impermeable reservoir sections have little effect on the production profile. For the Margretheholm geothermal plant, Copenhagen, Denmark, production temperatures are modelled to decrease by only 7 °C–14 °C after 300 years of production due to thermal recharge. The study emphasizes the huge potential of geothermal energy in the development of environmentally sustainable cities.

We propose 1D and 2D lattice wave functions constructed from the SU(n)1 Wess–Zumino–Witten (WZW) model and derive their parent Hamiltonians. When all spins in the lattice transform under SU(n) fundamental representations, we obtain a two-body Hamiltonian in 1D, including the SU(n) Haldane– Shastry model as a special case. In 2D, we show that the wave function converges to a class of Halperin’s multilayer fractional quantum Hall states and belongs to chiral spin liquids. Our result reveals a hidden SU(n) symmetry for this class of Halperin states. When the spins sit on bipartite lattices with alternating fundamental and conjugate representations, we provide numerical evidence that the state in 1D exhibits quantum criticality deviating from the expected behaviors of the SU(n)1 WZW model, while in 2D they are chiral spin liquids being consistent with the prediction of the SU(n)1 WZW model. © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). Funded by SCOAP 3 .

Oligomeric species of various proteins are linked to the pathogenesis of different neurodegenerative disorders. Consequently, there is intense focus on the discovery of novel inhibitors, e.g. small molecules and antibodies, to inhibit the formation and block the toxicity of oligomers. In Parkinson disease, the protein α-synuclein (αSN) forms cytotoxic oligomers. The flavonoid epigallocatechin gallate (EGCG) has previously been shown to redirect the aggregation of αSN monomers and remodel αSN amyloid fibrils into disordered oligomers. Here, we dissect EGCG's mechanism of action. EGCG inhibits the ability of preformed oligomers to permeabilize vesicles and induce cytotoxicity in a rat brain cell line. However, EGCG does not affect oligomer size distribution or secondary structure. Rather, EGCG immobilizes the C-terminal region and moderately reduces the degree of binding of oligomers to membranes. We interpret our data to mean that the oligomer acts by destabilizing the membrane rather than by direct pore formation. This suggests that reduction (but not complete abolition) of the membrane affinity of the oligomer is sufficient to prevent cytotoxicity.

The Wernecke igneous clasts consist of blocks of plutonic and volcanic rock that range up to hundreds of metres in size. These clasts occur exclusively within zones of hydrothermal breccia (Wernecke Breccia) which are widespread in central and northern Yukon. The breccia zones are hosted by the Wernecke Supergroup and have been dated by U–Pb titanite at 1599 Ma. Four U–Pb zircon ages on the Wernecke igneous clasts (1714–1706 Ma) demonstrate that the clasts are older than the Wernecke Supergroup (

Objectives In patients admitted on suspicion of acute coronary syndrome, with normal electrocardiogram and troponines, we evaluated the clinical impact of a Coronary CT angiography (CCTA)-strategy on referral rate for invasive coronary angiography (ICA), detection of significant coronary stenoses (positive predictive value [PPV]) and subsequent revascularisations, as compared to a function-based strategy (standard care). Secondarily we assessed intermediate term clinical events. Methods and results We randomised 600 patients to a CCTA-guided strategy (299 patients) or standard care (301 patients). In the CCTA-guided group referral for ICA required a coronary stenosis >70% or >50% in the left main, and for intermediate stenoses (50–70%), a stress test was used. A significant stenosis on ICA was defined as a stenosis ≥70% or reduced FFR ≤0.75 in intermediate stenoses (50–70%). Referral rate for ICA was 17% with CCTA vs. 12% with standard care (p=0.1). ICA confirmed significant coronary artery stenoses in 12% vs. 4% (p=0.001), and 10% vs. 4% were subsequently revascularised (p=0.005). PPV for the detection of significant stenoses was 71% with CCTA vs 36% with standard care (p=0.001). Clinical events (cardiac death, myocardial infarction, unstable angina pectoris, revascularisation and readmission for chest pain), during 120days of follow-up, were recorded in 8 patients (3%) in the CCTA-guided group vs. 15 patients (5%) in the standard care group (p=0.1). Conclusion In patients with recent acute-onset chest pain, a CCTA-guided diagnostic strategy improves PPV for the detection of significant coronary stenoses, and increases the frequency of revascularisations, when compared to a conventional functional approach.

The presence of Cenozoic deposits along the Norwegian Atlantic margin required extensive erosion of the Scandinavian Mountains in a generally cooling climate from the Oligocene to the present. The volume of the deposits implies that the transfer of mass from the inland area to the offshore shelf induced isostatic displacements on a kilometer scale. However, except for glacial excavation of the deep fjords, little is known about the distribution of Cenozoic inland erosion. A long-lasting paradigm incorporates remnants of peneplains at high elevation and assumes very little Cenozoic erosion on these surfaces through time. This scenario has recently been challenged by quantitative geomorphological studies indicating that the matrix of Cenozoic sediments deposited offshore must have been sourced from these surfaces. An alternative explanation for the present-day high-elevation low-relief surfaces is therefore that they evolved throughout the Cenozoic because of glacial and periglacial erosion processes that are known to vary strongly with altitude. Here we explore the implications of the latter scenario by reconstructing a pre-Cenozoic fluvial landscape without elevated low-relief surfaces. We use the present-day offshore sediment volumes for constraining the total Cenozoic erosion, and we find that a likely pre-Cenozoic fluvial landscape is only in few places more than 1 km higher than today. The rock mass of the offshore sediments is generally used for filling the fjords created during the Quaternary glaciations and for restoring concave river profiles from sea level to the peaks. Our reconstruction is based on a fluvial landscape algorithm and considers the isostatic response to the transfer of rock mass – from the basins onto the onshore area. A comparison between the reconstructed and the present-day topography demonstrates that offshore tilting of pre-Cenozoic strata can be partly explained by flexural isostatic compensation in response to the Cenozoic erosion and deposition. Locations of future thermochronometry studies for testing Scandinavian landscape evolution models are suggested based on temperature estimates of the present-day surface buried beneath the erosion products restored from the offshore basins.

Objectives The aim of this study was to investigate whether the heart rate-corrected QT (QTc) interval on the electrocardiogram (ECG) is associated with the onset of atrial fibrillation (AF). Background Patients with hereditary short-QT or long-QT syndromes, representing the very extremes of the QT interval, both seem to have a high prevalence of AF. Methods A total of 281,277 subjects were included, corresponding to one-third of the population of the greater region of Copenhagen. These subjects underwent digital ECG recordings in a general practitioner’s core facility from 2001 to 2010. Data on drug use, comorbidities, and outcomes were collected from Danish registries. Results After a median follow-up period of 5.7 years, 10,766 subjects had developed AF, of whom 1,467 (14%) developed lone AF. Having a QTc interval lower than the first percentile (≤372 ms) was associated with a multivariate-adjusted hazard ratio of 1.45 (95% confidence interval: 1.14 to 1.84; p = 0.002) of AF, compared with the reference group (411 to 419 ms). From the reference group and upward, the risk of AF increased with QTc interval duration in a dose-response manner, reaching a hazard ratio of 1.44 (95% confidence interval: 1.24 to 1.66, p l 0.001) for those with QTc intervals ≥99th percentile (≥464 ms). The association with respect to longer QTc intervals was stronger for the outcome of lone AF, as evidenced by a hazard ratio of 2.32 (95% confidence interval: 1.52 to 3.54, p l 0.001) for having a QTc interval ≥99th percentile (≥458 ms). Conclusions In this large ECG study, a J-shaped association was found between QTc interval duration and risk of AF. This association was strongest with respect to the development of lone AF.

International audience; In this reply, we comment on the issues raised by Japsen, Chalmers, and Green [Japsen et al. (2013). The mountains of North-East Greenland are not remnants of the Caledonian topography. A comment on Pedersen et al. (2012): Tectonophysics]. We find that new vitrinite reflectance measurements from one location in the region may suggest a more complicated post-Caledonian evolution than proposed by Pedersen et al. (2012) for the southernmost part of the studied area. Overall, however, we cannot reconcile our AFT data set with a complete obliteration of the topography in late Paleozoic times, followed by episodic post-Caledonian exhumation and re-burial, as suggested by Japsen et al. (2013).

Classical hereditary hemochromatosis involves the HFE -gene and diagnostic analysis of the DNA variants HFE p.C282Y (c.845G > A; rs1800562) and HFE p.H63D (c.187C > G; rs1799945). The affected protein alters the iron homeostasis resulting in iron overload in various tissues. The aim of this study was to validate the TaqMan-based Sample-to-SNP protocol for the analysis of the HFE -p.C282Y and p.H63D variants with regard to accuracy, usefulness and reproducibility compared to an existing SNP protocol. The Sample-to-SNP protocol uses an approach where the DNA template is made accessible from a cell lysate followed by TaqMan analysis. Besides the HFE -SNPs other eight SNPs were used as well. These SNPs were: Coagulation factor II-gene F2 c.20210G > A, Coagulation factor V-gene F5 p.R506Q (c.1517G > A; rs121917732), Mitochondria SNP: mt7028 G > A, Mitochondria SNP: mt12308 A > G, Proprotein convertase subtilisin/kexin type 9-gene PCSK9 p.R46L (c.137G > T), Plutathione S-transferase pi 1-gene GSTP1 p.I105V (c313A > G; rs1695), LXR g.-171 A > G, ZNF202 g.-118 G > T. In conclusion the Sample-to-SNP kit proved to be an accurate, reliable, robust, easy to use and rapid TaqMan-based SNP detection protocol, which could be quickly implemented in a routine diagnostic or research facility.

Anthracycline-based regimens are a mainstay of early breast cancer therapy, however their use is limited by cardiac toxicity. The potential for cardiotoxicity is a major consideration in the design and development of combinatorial therapies incorporating anthracyclines and agents that target the HER2-mediated signaling pathway, such as trastuzumab. In this regard, HER2-targeted liposomal doxorubicin was developed to provide clinical benefit by both reducing the cardiotoxicity observed with anthracyclines and enhancing the therapeutic potential of HER2-based therapies that are currently available for HER2-overexpressing cancers. While documenting the enhanced therapeutic potential of HER2-targeted liposomal doxorubicin can be done with existing models, there has been no validated human cardiac cell-based assay system to rigorously assess the cardiotoxicity of anthracyclines. To understand if HER2-targeting of liposomal doxorubicin is possible with a favorable cardiac safety profile, we applied a human stem cell-derived cardiomyocyte platform to evaluate the doxorubicin exposure of human cardiac cells to HER2-targeted liposomal doxorubicin. To the best of our knowledge, this is the first known application of a stem cell-derived system for evaluating preclinical cardiotoxicity of an investigational agent. We demonstrate that HER2-targeted liposomal doxorubicin has little or no uptake into human cardiomyocytes, does not inhibit HER2-mediated signaling, results in little or no evidence of cardiomyocyte cell death or dysfunction, and retains the low penetration into heart tissue of liposomal doxorubicin. Taken together, this data ultimately led to the clinical decision to advance this drug to Phase I clinical testing, which is now ongoing as a single agent in HER2-expressing cancers.