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We developed a synthesis strategy involving a diazo transfer reaction and subsequent click reaction to conjugate a murine cathelicidin-related antimicrobial peptide (CRAMP18–35) to chitosan and hydroxypropyl chitosan (HPC), confirmed the structure, and investigated the antimicrobial activity. Chitosan azide and HPC-azide were prepared with a low degree of azidation by reacting the parent chitosan and HPC with imidazole sulfonyl azide hydrochloride. CRAMP18–35 carrying an N-terminal pentynoyl group was successfully grafted onto chitosan and HPC via copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. The chitosan–peptide conjugates were characterized by IR spectroscopy and proton NMR to confirm the conversion of the azide to 1,2,3-triazole and to determine the degree of substitution (DS). The DS of the chitosan and HPC CRAMP18–35 conjugates was 0.20 and 0.13, respectively. The antibacterial activity of chitosan–peptide conjugates was evaluated for activity against two species of Gram-positive bacteria, Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis), and two species of Gram-negative bacteria, Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). The antimicrobial peptide conjugates were selectively active against the Gram-negative bacteria and lacking activity against Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

Mass spectrometry imaging has advanced from a niche technique to a widely applied spatial biology tool operating at the forefront of numerous fields, most notably making a significant impact in biomedical pharmacological research. The growth of the field has gone hand in hand with an increase in publications and usage of the technique by new laboratories, and consequently this has led to a shift from general MSI reviews to topic-specific reviews. Given this development, we see the need to recapitulate the strengths of MSI by providing a more holistic overview of state-of-the-art MSI studies to provide the new generation of researchers with an up-to-date reference framework. Here we review scientific advances for the six largest biomedical fields of MSI application (oncology, pharmacology, neurology, cardiovascular diseases, endocrinology, and rheumatology). These publications thereby give examples for at least one of the following categories: they provide novel mechanistic insights, use an exceptionally large cohort size, establish a workflow that has the potential to become a high-impact methodology, or are highly cited in their field. We finally have a look into new emerging fields and trends in MSI (immunology, microbiology, infectious diseases, and aging), as applied MSI is continuously broadening as a result of technological breakthroughs. [ABSTRACT FROM AUTHOR]

Bacteremia with anaerobic bacteria is generally a marker of severe prognosis. However, population-based data is lacking. Our aim was to describe the epidemiology and the 30-day mortality rate of anaerobic bacteremia in a Danish population-based setting. In this population-based cohort study, all first-time episodes of anaerobic bacteremia from the North Denmark Bacteremia Research Database during 1994–2019 were identified. Information on comorbidities, discharge diagnoses, and mortality was retrieved. 30-day mortality rates were calculated and a multivariate logistic regression analysis to identify risk factors for death was performed. 1750 episodes with anaerobic bacteremia were identified, corresponding to an incidence rate of 12.5 per 100,000 inhabitants (increasing from 11.2 in 1994–2014 to 17.7 in 2015–2019). Of these episodes, a third were polymicrobial, and the majority (70 %) of patients had one or more comorbid conditions. Abdominal infection was the source of bacteremia in 61 % of patients, while it was unknown for 15 %. The most frequently isolated genera were Bacteroides (45 %), Clostridium (20 %) and Fusobacterium (6 %). The overall crude 30-day mortality rate was 27 %, but rates were even higher for patients of high age, with liver disease, and solid tumors. The odds ratio (OR) for 30-day mortality was 1.32 for Clostridium species, and 1.27 for polymicrobial bacteremia with aerobic bacteria. The incidence rate of anaerobic bacteremia increased, and the 30-day mortality rate remained high during the study period. Multiple factors influence 30-day mortality rates, including high age, liver disease, solid tumor, polymicrobial bacteremia, and bacteremia with Clostridium species. • 1750 episodes of anaerobic bacteremia during 1994–2019 are described. • Most common isolated genera were Bacteroides, Clostridium and Fusobacterium. • 30-day mortality rate for anaerobic bacteremia was 27 %, with no trend over time. • Liver disease, solid tumor and high age were associated with higher mortality rates. • The 30-day mortality rate in patients with Clostridium species was 38%. [ABSTRACT FROM AUTHOR]

Background: Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination.Methods: In this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial, individuals aged 18-55 years with a body-mass index 27·0-39·9 kg/m2 and who were otherwise healthy were recruited from a single centre in the USA. The trial included six sequential overlapping cohorts, and in each cohort eligible participants were randomly assigned (3:1) to once-weekly subcutaneous cagrilintide (0·16, 0·30, 0·60, 1·2, 2·4, or 4·5 mg) or matched placebo, in combination with once-weekly subcutaneous semaglutide 2·4 mg, without lifestyle interventions. In each cohort, the doses of cagrilintide and semaglutide were co-escalated in 4-week intervals to the desired dose over 16 weeks, participants were treated at the target dose for 4 weeks, and then followed up for 5 weeks. Participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was number of treatment-emergent adverse events from baseline to end of follow-up. Secondary pharmacokinetic endpoints assessed from day of last dose (week 19) to end of treatment (week 20) were area under the plasma concentration-time curve from 0 to 168 h (AUC0-168 h) and maximum concentration [Cmax] of cagrilintide and semaglutide; exploratory pharmacokinetic endpoints were half-life, time to Cmax [tmax], plasma clearance, and volume of distribution of cagrilintide and semaglutide; and exploratory pharmacodynamic endpoints were changes in bodyweight, glycaemic parameters, and hormones. Safety, pharmacokinetic, and pharmacodynamic endpoints were assessed in all participants who were exposed to at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03600480, and is now complete.Findings: Between July 25, 2018, and Dec 17, 2019, 285 individuals were screened and 96 were randomly assigned to cagrilintide (0·16-2·4 mg group n=12; 4·5 mg group n=11) or placebo (n=24), in combination with semaglutide 2·4 mg, of whom 95 were exposed to treatment (one patient in 0·60 mg cagrilintide group was not exposed) and included in the safety and full analysis datasets. The mean age was 40·6 years (SD 9·2), 56 (59%) of 95 participants were men and 51 (54%) were Black or African American. Of 566 adverse events reported in 92 participants (69 [97%] of 71 participants assigned to 0·16-4·5 mg cagrilintide and 23 [96%] of 24 assigned to placebo), 207 (37%) were gastrointestinal disorders. Most adverse events were mild to moderate in severity and the proportion of participants with one or more adverse event was similar across treatment groups. Exposure was proportional to cagrilintide dose and did not affect semaglutide exposure or elimination. AUC0-168 h ranged from 926 nmol × h/L to 24 271 nmol × h/L, and Cmax ranged from 6·14 nmol/L to 170 nmol/L with cagrilintide 0·16-4·5 mg. AUC0-168 h ranged from 12 757 nmol × h/L to 15 305 nmol × h/L, and Cmax ranged from 96·4 nmol/L to 120 nmol/L with semaglutide 2·4 mg. Cagrilintide 0·16-4·5 mg had a half-life of 159-195 h, with a median tmax of 24-72 h. Semaglutide 2·4 mg had a half-life of 145-165 h, with a median tmax of 12-24 h. Plasma clearance and volume of distribution for both cagrilintide and semaglutide were similar across treatment groups. At week 20, mean percentage bodyweight reductions were greater with cagrilintide 1·2 and 2·4 mg than with placebo (15·7% [SE 1·6] for cagrilintide 1·2 mg and 17·1% [1·5] for cagrilintide 2·4 mg vs 9·8% [1·2] for pooled placebo cohorts 1-5; estimated treatment difference of -6·0% [95% CI -9·9 to -2·0] for cagrilintide 1·2 mg and -7·4% [-11·2 to -3·5] for cagrilintide 2·4 mg vs pooled placebo), and with cagrilintide 4·5 mg than with matched placebo (15·4% [1·3] vs 8·0% [2·2]; estimated treatment difference -7·4% [-12·8 to -2·1]), all in combination with semaglutide 2·4 mg. Glycaemic parameters improved in all treatment groups, independently of cagrilintide dose. Changes in hormones were similar across treatment groups.Interpretation: Concomitant treatment with cagrilintide and semaglutide 2·4 mg was well tolerated with an acceptable safety profile. Future larger and longer trials are needed to fully assess the efficacy and safety of this treatment combination.Funding: Novo Nordisk A/S. [ABSTRACT FROM AUTHOR]

Pyoderma gangrenosum is rarely seen in the surgical disciplines. In the described case the patient was initially diagnosed with necrotizing fasciitis and admitted to the intensive care unit suffering from septic shock. The automated implantable cardioverter defibrillator (AICD), the suspected focus for infection, had already been removed. Following weeks of broad spectrum antibiotics and wound debridement without clinical improvement the alternative diagnosis of pyoderma gangrenosum was reached. Consequently the patient was treated with immunosuppressive therapy and his condition improved rapidly such that he was ultimately discharged to rehabilitation. [ABSTRACT FROM AUTHOR]

Here we report that grafting of a short antimicrobial peptide, anoplin, to chitosan polymers is a strategy for abolishing the hemolytic propensity, and at the same time increasing the activity of the parent peptide. Anoplin–chitosan conjugates were synthesized by CuAAC reaction of multiple peptides through 2-azidoacetyl groups on chitosan. [ABSTRACT FROM AUTHOR]

Abstract: A quencher-free molecular beacon capable of generating pyrene excimer fluorescence has been constructed using strategically positioned pyrene-UNA monomers. Hybridization of a fully complementary RNA target was accompanied by a pyrene excimer emission increase of more than 900%, and detection of RNA in living cells was demonstrated. [Copyright &y& Elsevier]

Men and women are known to react differently to stress. Thus, stress cardiomyopathy almost solely strikes women. Stress cardiomyopathy is suggested to relate to sex differences in catecholamine reaction. Left heart function during dobutamine stress is well described, but sex-specific inotropic and lusitropic response to abrupt termination of dobutamine stress is not. We aimed to investigate sex differences in left ventricular (LV) and atrial (LA) function during and after dobutamine stress. We enrolled 20 healthy elderly subjects (60-70 yr, 10 females) and measured their LV and LA volumes throughout the cardiac cycle by cardiac magnetic resonance imaging at rest, during dobutamine stress (15 μg·kg-1·min-1), 15 min after termination (T15), and 30 min after termination (T30) of dobutamine stress. We calculated LV ejection fractions, LV stroke volumes, LV peak filling rates, and LA passive, active, and conduit volumes. Sex differences were not observed at rest or during dobutamine stress. Compared with prestress values, at T15 a rebound decrease in LV peak filling rate was observed in women (-22 ± 3%, P < 0.001) but not in men. This was reflected in reduced LA passive emptying volume (-40 ± 3%, P < 0.001) and a corresponding increase in LA active emptying volume (36 ± 2%, P < 0.001). At T30 there were no differences between the sexes. We conclude that dobutamine causes greater stress to the female heart. This is revealed after termination of dobutamine stress where the left heart recovers in men, whereas women experience rebound LV stiffening with reduced diastolic relaxation. This is the first report of a sex-specific transient rebound phenomenon in cardiovascular response to catecholamines. [ABSTRACT FROM AUTHOR]

The aim of this study is to describe phasic volume changes of the left atrium (LA) in healthy young and elderly subjects at rest and during pharmacological stress (PS). LA maximum size is related to cardiovascular mortality. LA has passive, active, and conduit function for left ventricular (LV) filling. We hypothesized that changes in LV compliance from normal aging are reflected in LA volume changes and that PS will augment these differences. We enrolled twenty young (20-30 yr) and twenty elderly (60-70 yr) healthy subjects and measured their LV and LA volumes by cardiac magnetic resonance imaging at rest and during dobutamine and glycopyrrolate stress. We identified LA minimum, maximum, and middiastolic volumes and the volume before atrial contraction. LA emptying volumes were calculated as LA passive and active emptying volumes and LA conduit volume. We also calculated LV peak filling rates (LVPFRs). Both at rest and during PS, LA maximum and minimum volumes were similar in the groups, whereas middiastolic volume was higher in the elderly. During PS, a marked decrease in LA passive emptying function and a corresponding increase in LA active emptying function were seen in the elderly but not in the young. At rest, LVPFR was lower in the elderly, and during PS this difference was augmented. The aging heart has reduced LVPFR, which is reflected in reduced LA passive and compensatory increased LA active volumetric contribution to LV stroke volume. These age-related differences are evident at rest and highly augmented during both dobutamine and glycopyrrolate stress. [ABSTRACT FROM AUTHOR]

The article discusses the therapeutic use of locked nucleic acid (LNA)-containing aptamers. One challenge in the use of aptamers as therapeutic agents is the intracellular delivery limits imposed by their size and polyanionic character. A study on the development and evolution of LNA-containing aptamers to obtain increased biostability, structural stability and biological function is described.

We have studied self-assembled molecular monolayers (SAMs) of several 3′-C3-SH conjugated single-strand (ss) and double-strand (ds) 20-base oligonucleotides (ONs) immobilized on single-crystal, atomically planar Au(111)-electrode surfaces in the presence of the triply positively charged base spermidine (Spd). This cation binds strongly to the polyanionic ON backbone and stabilizes the ds-form relative to the ss-form. A combination of chemical ON synthesis, melting temperature measurements, cyclic voltammetry (CV), and in situ scanning tunneling microscopy (STM) in aqueous biological buffer under electrochemical potential control was used. Spd binding was found to increase notably the ds-ON melting temperature. CV displays capacitive features associated with ss- and ds-ON. A robust capacitive peak around -0.35 V versus saturated calomel electrode (SCE), specific to ds-ON and highly sensitive to base pair mismatches, was consistently observed. The peak is likely to be caused by surface structural reorganization around the peak potential and located close to reported peak potentials of several DNA intercalating or covalently tethered redox molecules reported as probes for long-range electron transfer. [ABSTRACT FROM AUTHOR]

Abstract: Fluorescent labeling of chitosan and its derivatives is widely used for in vitro visualization and is accomplished by random introduction of the fluorophore to the polymer backbone, conceivably altering the bioactivity of the polymer. Here, we report for the first time the regioselective conjugation of a fluorophore to the reducing end of a fully N,N,N-trimethylated chitosan (TMC) by oxime formation. End-labeled conjugation of 5-(2-((aminooxyacetyl)amino)ethylamino)naphthalene-1-sulfonic acid (EDANS-O-NH2) fluorophore to TMC to form TMC-oxime-EDANS (f-TMC) was confirmed by 1H NMR and fluorescence spectroscopy. Average molecular weight calculations of f-TMC with 1H NMR and fluorescence spectroscopy gave similar results or ∼7.7kDa. f-TMC in human bronchial epithelial cells was both cell membrane bound as well as intracellularly localized. This demonstrates the proof-of-concept for selective oxime formation at the reducing end of a chitosan derivative, which can be used for tracking chitosan in gene and drug delivery purposes and gives rise to further modifications with other functional groups. [Copyright &y& Elsevier]

Pyoderma gangrenosum is rarely seen in the surgical disciplines. In the described case the patient was initially diagnosed with necrotizing fasciitis and admitted to the intensive care unit suffering from septic shock. The automated implantable cardioverter defibrillator (AICD), the suspected focus for infection, had already been removed. Following weeks of broad spectrum antibiotics and wound debridement without clinical improvement the alternative diagnosis of pyoderma gangrenosum was reached. Consequently the patient was treated with immunosuppressive therapy and his condition improved rapidly such that he was ultimately discharged to rehabilitation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Pregnancy associated plasma protein-A (PAPP-A) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease (CAD) in patients undergoing coronary angiography. Here we address the prognostic value of serum PAPP-A in unselected stable CAD patients. Method: Blood samples were drawn at study entry. Serum PAPP-A values ≥4mIU/L were considered elevated. Mortality and non-fatal myocardial infarction was prospectively registered. The primary outcome was the composite outcome of myocardial infarction and all-cause mortality, secondary outcomes were all-cause mortality and myocardial infarction. Results: Patients (n =4243) were followed for a median of 2.8 years. In a Cox analysis, elevated PAPP-A was significantly related to the composite outcome of myocardial infarction and death (HR 1.99, 95% CI 1.62–2.45, p <0.0005), all-cause mortality (HR 2.42, 1.92–3.06, p <0.0005), and myocardial infarction (HR 1.40, 1.01–1.94, p =0.046). After Holm''s correction, the latter significance disappeared. After adjustment for risk factors and medication at entry, elevated PAPP-A remained significantly related to the composite outcome (HR 1.51, 1.22–1.86, p <0.0005) and all-cause mortality (HR 1.68, 1.32–2.13, p <0.0005). Conclusion: In patients with stable CAD elevated serum PAPP-A seems promising as aid in identifying patients at high risk for death. [Copyright &y& Elsevier]

Introduction: Pulmonary regurgitation (PR) following repair of right ventricular (RV) outflow obstruction is related to slowly progressive RV dilatation and heart failure and will eventually require surgical intervention, but optimal timing of pulmonary valve replacement is challenging. Tissue Doppler based quantification of RV contractility may offer additional information in the management of these patients. Methods: In a porcine animal model free PR was induced by percutaneous stenting of the pulmonary valve orifice (N = 23). After 1, 2, or 3 months of free PR percutaneous pulmonary valve replacement (PPVR) was performed. Tissue Doppler derived measures of global and regional myocardial contractility were obtained by transthoracic echocardiography, and compared to a sham-operated control group (N = 9). Results: Free PR is associated with RV dilatation (RV end-diastolic area increased from 15 ± 3 to 23 ± 7 cm2/m2, P < 0.0001) and a decrease in RV fractional area change from 62 ± 10% to 57 ± 12%, P = 0.08, with no impact of duration of free PR. The isovolumic acceleration, regional strain, and strain rate were unchanged after free PR and after PPVR. No consistent relation of echocardiographic measures of contractility and response to PPVR could be identified. Conclusion: Echocardiographic measures of RV contractility remained unchanged, despite significant RV remodeling following chronic PR and PPVR persistently induced significant recovery in the majority of the animals. These results may imply that Tissue Doppler based measures of RV contractility may not be sufficiently sensitive to be a suitable adjunct to conventional echocardiography in the follow-up of patients with free PR in order to optimize timing of valve replacement. (Echocardiography 2010;27:854-863) [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To examine if pregnancy-associated plasma protein-A (PAPP-A) in patients with chest pain, could identify patients at risk for death or myocardial infarction. Design and methods: Patients admitted with chest pain and both normal ECG and normal biomarkers were evaluated by serial measurement of PAPP-A. Main outcome measures were mortality and non-fatal myocardial infarction. Results: Median age of patients included (415) was 67years and 43% were women. The risk of death or non-fatal myocardial infarction after 3 months was 15% in the highest quartile of circulating PAPP-A compared with 3% in the lowest quartile (relative risk 3.7, p <0.01). Corresponding numbers after 1 year were 24% and 10% (relative risk 2.4, p =0.01). Conclusion: In patients admitted with chest pain and both normal ECG and normal biomarkers PAPP-A seems to be valuable for predicting patients at high risk of death or non-fatal myocardial infarction. [Copyright &y& Elsevier]

To investigate whether pregnancy-associated plasma protein-A (PAPP-A) is a prognostic marker in patients admitted with high-risk acute coronary syndrome. In patients admitted with high-risk non–ST-segment elevation acute coronary syndrome (NSTE-ACS) and ST-segment elevation myocardial infarction (STEMI), risk stratification is primarily determined by the markers of myocardial necrosis and known demographic risk profiles. However, it has recently been proposed that the presence and extent of vulnerable plaques might influence the prognosis significantly. A marker for the vulnerable plaque could identify patients at high risk who would potentially benefit from intensive treatment and surveillance. Two populations of consecutive patients admitted with high-risk NSTE-ACS (n = 123) and STEMI (n = 314) were evaluated with serial measurements of PAPP-A. The incidence of mortality and nonfatal myocardial infarction was prospectively registered for 2.66 to 3.47 years. In the patients with high-risk NSTE-ACS, PAPP-A was related to the risk of nonfatal myocardial infarction (p = 0.02) and death (p = 0.03). This result was consistent on multivariate analysis of the combination of mortality or nonfatal myocardial infarction (odds ratio 2.65, 95% confidence interval 1.40 to 5.03) but not for mortality alone (p = NS). In patients with STEMI, PAPP-A was related to the risk of death (p = 0.01) but not the composite outcome of myocardial infarction and death. This was also true after adjustment for other univariate predictors of death (odds ratio 2.19, 95% confidence interval 1.16 to 4.16). In conclusion, PAPP-A seems to be valuable in predicting the outcomes of patients admitted with high-risk NSTE-ACS or STEMI. [Copyright &y& Elsevier]

Herein we present the synthesis and thermal stability studies of modified oligonucleotides containing an unlocked nucleic acid (UNA) terpyridine monomer. Incorporation of this monomer into both strands of a DNA duplex allowed reversible thermal stability modulation upon addition or withdrawal of divalent metal ions. A likely explanation of this phenomenon is interstrand complexation between two terpyridine units and a metal ion. This system could be useful in the development of nanoscale devices based on DNA hybridization. [ABSTRACT FROM AUTHOR]

Staphylococcal enterotoxin B (SEB) is a pyrogenic exotoxin and a potent superantigen which causes massive T cell activation and cytokine secretion, leading to profound immunosuppression and morbidity. The inhibition of SEB-induced responses is thus considered a goal in the management of certain types of staphylococcal infections. Lactoferrin (LF) is a multi-functional glycoprotein with both bacteriostatic and bactericidal activities. In addition, LF is known to have potent immunomodulatory properties. Given the anti-microbial and anti-inflammatory properties of this protein, we hypothesized that LF can modulate T cell responses to SEB. Here, we report that bovine LF (bLF) was indeed able to attenuate SEB-induced proliferation, interleukin-2 production and CD25 expression by human leucocyte antigen (HLA)-DR4 transgenic mouse T cells. This inhibition was not due to bLF's iron-binding capacity, and could be mimicked by the bLF-derived peptide lactoferricin. Cytokine secretion by an engineered SEB-responsive human Jurkat T cell line and by peripheral blood mononuclear cells from healthy donors was also inhibited by bLF. These findings reveal a previously unrecognized property of LF in modulation of SEB-triggered immune activation and suggest a therapeutic potential for this naturally occurring protein during toxic shock syndrome. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To describe the presence and time-related pattern of circulating pregnancy associated plasma protein A (PAPP-A) levels in patients with non ST-segment elevation acute coronary syndrome (NSTE-ACS). Design and methods: Consecutively admitted patients (N =573) with clinical signs of NSTE-ACS were included. Blood samples for analysis of PAPP-A were drawn at admission and every 6–8 h until levels of biomarkers of myocardial necrosis showed a consistent decrease. Results: High-risk NSTE-ACS was diagnosed in 123 patients (23%). Significantly more patients with high-risk NSTE-ACS (63%) had detectable PAPP-A than did those with low-risk NSTE-ACS (49%) (P <0.001). PAPP-A concentrations were significantly associated with typical angina at admission, significant ST-depressions on the ECG, multivessel disease and presence of high-risk NSTE-ACS. Conclusion: PAPP-A seems to be a marker ischaemia both in patients with low- and high-risk NSTE-ACS, possibly due to the release of PAPP-A from the vulnerable plaque. [Copyright &y& Elsevier]

In this paper, we completely classify which graded polynomial R-algebras in finitely many even degree variables can occur as the singular cohomology of a space with coefficients in R, a 1960 question of N. E. Steenrod, for a commutative ring R satisfying mild conditions. In the fundamental case , our result states that the only polynomial cohomology rings over that can occur are tensor products of copies of , , and , confirming an old conjecture. Our classification extends Notbohm's solution for , p odd. Odd degree generators, excluded above, only occur if R is an -algebra and in that case the recent classification of 2-compact groups by the authors can be used instead of the present paper. Our proofs are short and rely on the general theory of p-compact groups, but not on classification results for these. [ABSTRACT FROM PUBLISHER]

With reference to a specific dataset, we consider how to perform a flexible non-parametric Bayesian analysis of an inhomogeneous point pattern modelled by a Markov point process, with a location-dependent first-order term and pairwise interaction only. A priori we assume that the first-order term is a shot noise process, and that the interaction function for a pair of points depends only on the distance between the two points and is a piecewise linear function modelled by a marked Poisson process. Simulation of the resulting posterior distribution using a Metropolis–Hastings algorithm in the ‘conventional’ way involves evaluating ratios of unknown normalizing constants. We avoid this problem by applying a recently introduced auxiliary variable technique. In the present setting, the auxiliary variable used is an example of a partially ordered Markov point process model. [ABSTRACT FROM AUTHOR]

Traditional biomarkers in acute coronary syndromes reflect myocardial necrosis but not the underlying arteriosclerotic disease. Pregnancy-associated plasma protein A (PAPP-A) is a new biomarker in acute coronary syndromes that detects vulnerable plaques in arteriosclerotic disease and identifies acute coronary syndromes earlier than traditionally used biomarkers. Information regarding circulating PAPP-A levels in patients with ST elevation myocardial infarctions (STEMIs) is limited and contradictory. The aim of the present study was to describe the presence and time-related pattern of circulating PAPP-A levels in patients with STEMIs. Consecutive patients (n = 354) referred for primary percutaneous intervention because of STEMI were included in the study. Blood samples for the analysis of PAPP-A, creatine kinase-MB (CKMB), and troponin T were drawn at admission and every 6 to 8 hours until biomarkers of myocardial necrosis were consistently decreasing. PAPP-A was measured using a newly developed sandwich enzyme-linked immunosorbent assay technique based on 2 monoclonal antibodies. In total, 1,091 PAPP-A, 1,049 troponin T, and 1,016 CKMB samples were analyzed. Mean PAPP-A values at admission were significantly higher in patients with STEMIs than in those with non–ST elevation myocardial infarctions or unstable angina pectoris (27.6 vs 12.2 mIU/L, p <0.01). In samples drawn <2 hours after admission, the sensitivity of PAPP-A was superior (93%) to that of CKMB (60%) and troponin T (61%). In conclusion, PAPP-A levels are elevated in >90% of patients presenting with STEMIs if measured <6 hours after the onset of symptoms or <2 hours of primary percutaneous coronary intervention. In the early stages of STEMI, PAPP-A seems to be a more sensitive marker of myocardial infarction than CKMB and troponin T. [Copyright &y& Elsevier]

Abstract: Thermodynamic inhibitors can be used in avoiding gas hydrate problems in natural gas and oil production and transportation. A new correlation for predicting the suppression of the hydrate dissociation temperature of various petroleum fluids in the presence of different thermodynamic inhibitors (e.g., electrolytes and organic inhibitors) is presented. The correlation, which can be applied to drilling and reservoir fluids, requires inhibitor concentration, pressure of the system and, if known, the dissociation pressure of the fluid in the presence of distilled water at 273.15 K. The correlation has been developed using hydrate phase boundaries for methane and seven natural gases in the presence of various single inhibitors generated by a well-proven comprehensive thermodynamic model. It covers nine electrolyte solutions and six organic inhibitors, which may be available and/or added to the reservoir and drilling fluids. The developed correlation is generic and could be easily extended to other salts and organic inhibitors. [Copyright &y& Elsevier]

We construct a connected finite loop space of rank 66 and dimension 1254 whose rational cohomology is not isomorphic as a graded vector space to the rational cohomology of any compact Lie group, hence providing a counterexample to a classical conjecture. Aided by machine calculation we verify that our counterexample is minimal, i.e., that any finite loop space of rank less than 66 is in fact rationally equivalent to a compact Lie group, extending the classical known bound of 5. [ABSTRACT FROM AUTHOR]

Abstract We consider the combination of path sampling and perfect simulation in the context of both likelihood inference and non-parametric Bayesian inference for pairwise interaction point processes. Several empirical results based on simulations and analysis of a data set are presented, and the merits of using perfect simulation are discussed. [ABSTRACT FROM AUTHOR]

This primer provides a self-contained exposition of the case where spatial birth-and-death processes are used for perfect simulation of locally stable point processes. Particularly, a simple dominating coupling from the past (CFTP) algorithm and the CFTP algorithms introduced in [13], [14], and [5] are studied. Some empirical results for the algorithms are discussed. [ABSTRACT FROM AUTHOR]

ABSTRACT Considering the ever-increasing importance of marine gas hydrates, it is crucial to gain a better understanding of clathrate formation and decomposition in porous media. It is well established that, due to capillary effects, small-diameter pores – similar to those found in natural sediments – act to inhibit hydrate stability. However, accurate data constraining these effects are still lacking. Here, we present experimental methane clathrate dissociation data for 3.5 mass% methanol aqueous solutions in confined silica glass pores of narrow distribution (30.6, 15.8, and 9.2 nm mean diameters). These data have been used to validate a thermodynamic model for clathrate stability porous media. Experimental data show a marked improvement on literature data – which we attribute to the experimental and interpretative methods used – and are in good agreement with the model predictions. Results suggest that mass transfer of inhibitors (methanol) and dissolved gas during clathrate formation/dissociation within the porous network plays an important role in controlling gas hydrate equilibria. [ABSTRACT FROM AUTHOR]

Presents a study that proposed an image analysis system that does not require an expensive image analysis programming tool but should be optimized for routine tasks of analyzing large numbers of samples. Description of the components and features of the system; Validation using D-squames® covering a wide range of desquamation; Comparison of two image analysis algorithms and visual grading; Implications for the objective determination of desquamation levels.

Herein, we describe the design and synthesis of 16 neo‐glycolipids that are potential permeation enhancers for oral drug delivery of peptide therapeutics. These amphiphilic neo‐glycolipids are composed of fatty acids and various carbohydrates (d‐glucose, lactose, cellobiose, maltose) via an oxime linker. The ability of the synthesized neo‐glycolipids to enhance permeation of fluorescein‐labelled dextran (4 kDa) or 3H‐mannitol across intestinal epithelium was investigated in vitro using monolayers of human epithelial Caco‐2 cells. Their effects were compared with (pre‐)clinically known enhancers as reference compounds; sodium salts of octanoic, decanoic, and dodecanoic acid, and sodium salcaprozate (SNAC). Most neo‐glycolipids increased the permeation of the model compounds, proving that neo‐glycolipids, which possess vastly different properties from the reference compounds, e. g. in terms of clogD and polar surface area, are effective permeation enhancers. The neo‐glycolipid based on decanoic acid and glucose was more potent than related compounds based on disaccharides. Significant differences in solubility and cellular compatibility were found for neo‐glyolipids based on different carbohydrates. Finally, neo‐glycolipids were evaluated as permeation enhancers for the peptide hormone PYY3‐36. Glucose‐ and maltose‐derived neo‐glycolipids based on decanoic and dodecanoic acid showed promising enhancements in PYY3‐36 permeation in vitro while maintaining good cellular compatibility, relevant for oral delivery of obesity treatments. [ABSTRACT FROM AUTHOR]

Aims: The combination of cagrilintide and semaglutide (CagriSema) is being developed for the treatment of obesity and type 2 diabetes. The objective of this thorough QT study was to confirm that cagrilintide does not result in a clinically relevant prolongation in cardiac repolarization compared with placebo. Materials and Methods: This was a double‐blind study (NCT05804162) in which healthy participants were randomized to cagrilintide, administered as a once‐weekly subcutaneous injection dose escalated to 4.5 mg, or a placebo. The primary end point was the time‐matched change from baseline in Fridericia heart rate–corrected QT interval (QTcF) at 12‐, 24‐, 48‐ and 72 h after the last cagrilintide 4.5‐mg dose. To conclude that cagrilintide does not induce a clinically relevant prolongation, the upper limit of the two‐sided 90% confidence interval (CI) for the treatment difference at each of the four time points must fall below 10 ms. To establish QT assay sensitivity, participants in the placebo arms received a single 400‐mg oral moxifloxacin dose as a positive control and moxifloxacin placebo in a nested cross‐over fashion. Results: A total of 105 participants received cagrilintide (n = 53) or placebo (n = 52). No clinically relevant QTcF prolongation occurred after the last cagrilintide 4.5‐mg dose; the upper limits of the two‐sided 90% CIs of the placebo‐adjusted QTcF changes from baseline were below 10 ms at all time points. QT assay sensitivity was demonstrated with moxifloxacin as a positive control. Conclusions: Cagrilintide did not result in clinically relevant QTcF prolongation, indicating no increased risk of ventricular tachyarrhythmias. [ABSTRACT FROM AUTHOR]

Purpose: Purpose of this study was to investigate Dual-energy CT (DECT) derived virtual non-calcium (VNCa) values for absolute quantification of the bone marrow composition in the wrist.Materials and Methods: We prospectively included consecutive adult participants and examined their wrists with DECT. Ranges of VNCa and calcium values were measured in the carpal bones, radius and ulna using a semi-automatic method. Bones with bone marrow edema, assessed by two blinded radiologists, were excluded. After determining optimum parameters for the three-material decomposition, the influence of calcium values, age and sex on VNCa values was assessed using multiple linear regression.Results: 41 participants (Median age 53 years, range 20 years - 88 years, 51 % men) were enrolled and 399 bones assessed. At participant level mean VNCa values were -143 HU (SD 14 HU) using the current parameters for three-material decomposition and -104HU (SD 11 HU) with optimized parameters. There was a strong and significant influence of calcium values on VNCa values with the current parameters (p < 0.001, -0.137 HU[VNCa] / HU[Calcium]). With optimized parameters the calcium values and sex were not statistically significant predictors of VNCa values. Age was a significant, but clinically negligible, predictor (p = 0.03, -0.225 HU / year).Conclusions: After optimizing three-material decomposition parameters, calcium values, age and sex do not substantially influence virtual non-calcium values, and DECT may therefore be used for absolute quantification of the bone marrow composition - alleviating the need for reference bones or groups. [ABSTRACT FROM AUTHOR]

Chemoselective oxime coupling was used for facile conjugation of unprotected, reducing glycans and glycopeptide aldehydes with core?shell gold nanoparticles carrying reactive aminooxy groups on the organic shell. [ABSTRACT FROM AUTHOR]

It is not well investigated whether exposure to specific drug classes is associated with COVID-19. We investigated the risk of SARS-CoV-2 infection and severe COVID-19 among healthcare workers according to prescription drug use. We conducted an observational study among Danish healthcare workers. SARS-CoV-2 positivity was defined as a positive PCR/ELISA test throughout 2020 and severe COVID-19 as any above 48-hour hospitalization within 14 days after infection. Patient characteristics came from online surveys while data on SARS-CoV-2, drugs and hospitalizations came from Danish Health Registers. Infected individuals were matched with uninfected controls based on age, sex, and chronic diseases. Drug exposure was defined as any prescription redemption in the past six and one month(s) before infection for each drug class. Models assessing the risk of infection (conditional logistic regression) and severe COVID-19 (logistic regressions) versus drug usage were adjusted for BMI, smoking, alcohol, education, region, and patient contact when possible. We matched 5,710 SARS-CoV-2-infected cases with 57,021 controls. The odds of infection were reduced by calcium channel blocker (adjusted odds ratio (aOR) 0.81, 95% Confidence Interval (CI): 0.66–1.00) and vasoprotective drug (aOR 0.77, CI: 0.62–0.95) usage during the six months before infection compared to no usage. Exposure to antibacterials in the past month increased the odds of infection (aOR 1.27, CI: 1.09–1.48). Among infected participants, the odds of severe COVID-19 were higher with usage of almost any investigated drug, especially, diuretics (crude odds radio (OR) 4.82, CI:2.15–10.83), obstructive airway disease drugs (OR 4.49, CI: 2.49–8.08), and antibacterials (OR 2.74 CI:1.62–4.61). In conclusion, antibacterials were associated with more SARS-CoV-2 infections and calcium channel blockers with less. Once infected, users of prescription drugs had higher odds of developing severe COVID-19. These findings suggest a need for studies to clarify interactions between specific drug groups, behaviour, known risk factors, and disease susceptibility/severity. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Maternal preeclampsia is associated with both congenital heart defects and changes in left ventricular structure and function in the offspring. Whether preeclampsia and gestational hypertension also affect the offspring's cardiac conduction system is unknown.This study assesses whether infants exposed to maternal hypertensive disorders of pregnancy (HDPs) exhibit changes in their electrocardiogram (ECG) compared with infants unexposed to HDPs.This population‐based cohort study included newborns from the Copenhagen Baby Heart Study who had an ECG performed within 30 days of birth and had available obstetric information. ECG parameters of newborns exposed to maternal HDPs were compared with those of unexposed newborns using linear regression.Our study cohort included 11,826 newborns, including 441 exposed to maternal preeclampsia and 320 exposed to gestational hypertension. Infants exposed to preeclampsia had prolonged QRS durations (adjusted mean difference 0.6 ms, 95% confidence interval [CI] 0.04, 1.16) and lower maximum amplitudes of the R‐wave in V1 (adjusted mean difference, linear scale 0.95, 95% CI 0.90, 1.00), compared with unexposed infants. Exposure to maternal preeclampsia was not associated with changes in other ECG parameters. Exposure to gestational hypertension was associated with increased QT interval durations (QTc Bazett, adjusted mean difference 2.48 ms, 95% CI −0.23, 5.20; QTc Fridericia, adjusted mean difference 2.32 ms, 95% CI −0.19, 4.83).Our findings suggest that the newborn cardiac conduction system is affected by exposure to maternal preeclampsia. This could reflect the previously described thickening of the left ventricular myocardium in infants exposed to preeclampsia. [ABSTRACT FROM AUTHOR]

Chemical modification of proteins has numerous applications, but it has been challenging to achieve the required high degree of selectivity on lysine amino groups. Recently, we described the highly selective acylation of proteins with an N‐terminal Gly‐His6 segment. This tag promoted acylation of the N‐terminal Nα‐amine resulting in stable conjugates. Herein, we report the peptide sequences Hisn‐Lys‐Hism, which we term Lys‐His tags. In combination with simple acylating agents, they facilitate the acylation of the designated Lys Nϵ‐amine under mild conditions and with high selectivity over native Lys residues. We show that the Lys‐His tags, which are 7 to 10 amino acids in length and still act as conventional His tags, can be inserted in proteins at the C‐terminus or in loops, thus providing high flexibility regarding the site of modification. Finally, the selective and efficient acylation of the therapeutic antibody Rituximab, pure or mixed with other proteins, demonstrates the scope of the Lys‐His tag acylation method. [ABSTRACT FROM AUTHOR]

The wolf (Canis lupus) is arguably the most successful species at recolonizing its now human‐dominated former ranges in Europe and North America. Over the centuries while the wolf was absent, humans have transformed ecosystems to a large extent. In this paper, we highlight key aspects of these human‐modified ecosystems that include changes to (meso)carnivore communities, wolves themselves (genetics, behaviour), woody plant communities and the playing field for predator–prey interactions (landscape structure).We argue that the recognition of the novelty of human‐modified ecosystems logically leads to novel pathways of how wolves can influence ecosystem functioning. Thus far, the ecological impacts of wolves in human‐dominated systems have largely been predicted based on the documented effects they have on prey species or lower trophic levels in well‐preserved systems with low human impact. However, wolves in human‐modified ecosystems will engage in an array of novel interactions and potential novel trophic cascades that do not occur in more natural ecosystems with lower human impact.This should encourage us to re‐assess the questions we ask about wolf impacts in novel systems. A promising direction for future studies is exploring what novel interactions establish and under what conditions wolves can exert their ecosystem impacts (context dependence) in the human‐modified ecosystems wolves are recolonizing.Policy implications. Understanding these novel interactions and the context dependence of ecosystem impacts could guide us to act to improve conditions to enable wolves to exert their ecosystem impacts again. These novel interactions may be the true ecological and societal value of having wolves returning to human‐modified landscapes. [ABSTRACT FROM AUTHOR]

Oligomers assembled from designed building blocks to fold in novel ways have emerged as tools and allow the creation of new structures and molecular properties. Herein, we describe the use of a highly constrained adamantane moiety with one amino group and three carboxylic acids as a monomer. It can be viewed as a constrained, α,α‐dialkylated γ‐amino tri‐acid with side‐chains that mimic glutamic acid. We alternated this amino acid with glycine to synthesize a heteropeptide adamantane‐based oligomer. An N‐terminal l‐ or d‐tyrosine was included to investigate possible chirality induction. The oligomer was assembled by solid‐phase peptide synthesis using Fmoc‐ and Boc‐protection strategies. This novel oligomer was characterized by circular dichroism spectroscopy, which revealed a clear effect from the chirality of the N‐terminal tyrosine. Molecular dynamics simulation indicated that the adamantane oligomers populated compact conformations, with a subset forming cyclic geometries by hydrogen bonding. Through these interactions the chirality of Tyr induced an overall chirality in the cyclic conformations, which is in agreement with the spectroscopic data. This points to the use of adamantane building blocks in novel chirality switches. [ABSTRACT FROM AUTHOR]

Background Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. Methods In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Results Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05–7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09–1.57) and BA.3 (1.32, 1.09–1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76–0.98), BA.4 (0.85, 0.75–0.97), and BA.5 (0.87, 0.76–0.99) antigens in individuals with a prior infection. Conclusions Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of Omicron variants. [ABSTRACT FROM AUTHOR]

In pediatric echocardiography, reference intervals are required to distinguish normal variation from pathology. Left ventricular (LV) parameters are particularly important predictors of clinical outcome. However, data from healthy newborns are limited, and current reference intervals provide an inadequate approximation of normal reference ranges. Normative reference intervals and z -scores for 2-dimensional echocardiographic measurements of LV structure and function based on a large group of healthy newborns were developed. The study population included 13,454 healthy newborns from the Copenhagen Baby Heart Study who were born at term to healthy mothers, had an echocardiogram performed within 30 days of birth, and did not have congenital heart disease. To develop normative reference intervals, this study modeled 10 LV parameters as a function of body surface area through joint modeling of 4 statistical components. Infants in the study population (48.5% were female) had a median body surface area of 0.23 m2 (IQR: 0.22-0.25 m2) and median age of 12.0 days (IQR: 8.0-15.0 days) at examination. All normative reference intervals performed well in both sexes without stratification on infant sex. In contrast, creation of separate reference models for infants examined at <7 days of age and those examined at 7-30 days of age was necessary to optimize the performance of the reference intervals. This study provides normative reference intervals and z -scores for 10 clinical, widely used echocardiographic measures of LV structure and function based on a large cohort of newborns. These results provide highly needed reference material for clinical application by pediatric cardiologists. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: To explore and describe how the National Early Warning Score (NEWS) and Individual Early Warning Score (I‐EWS) are used and how they support nurses' patient risk assessment practice. Design: A qualitative observational fieldwork study drawing on ethnographical principles was performed in six hospitals in two regions of Denmark in 2019. Methods: Data were generated from participant observations and informal interviews with 32 nurses across 15 different wards in the hospitals. A total of 180 h of participant observation was performed. The observations lasted between 1.5 and 8 h and were conducted during day or evening shifts. Results: NEWS and I‐EWS supported nurses' observations of patients, providing useful knowledge for planning patient care, and prompting critical thinking. However, the risk assessment task was sometimes delegated to less experienced staff members, such as nursing students and healthcare assistants. The Early Warning Score (EWS) systems were often adapted by nurses according to contextual aspects, such as the culture of the speciality in which the nurses worked and their levels of competency. In some situations, I‐EWS had the effect of enhancing nurse autonomy and responsibility for decision‐making in relation to patient care. Conclusions: EWS systems support nurses' patient risk assessment practice, providing useful information. I‐EWS makes it easier to factor the heterogeneity of patients and the clinical situation into the risk assessments. The delegation of risk assessment to other, less experienced staff members pose a risk to patient safety, which needs to be addressed in the ongoing debate regarding the shortage of nurses. Impact The findings of this study can help ward nurses, hospital managers and policymakers to develop and improve strategies for improved person‐centred nursing care. [ABSTRACT FROM AUTHOR]

Objective: Patients with diabetes are at increased risk of experiencing myocardial infarction. The influence of the prevailing plasma glucose level on infarction and mortality after acute ischaemia is however unknown. The aim was to study the effect of the acute plasma glucose level on the myocardial infarction size in a closed-chest pig model.Design: 38 non-diabetic pigs were randomised to hypoglycaemic (1.8-2.2 mmol/l; n = 15), normoglycaemic (5-7 mmol/l; n = 12) or hyperglycaemic glucose clamping (22-23 mmol/l; n = 11). After 30 min within glucose target myocardial infarction was induced for 30 min followed by reperfusion for 120 min. Hereafter the heart was double-stained to delineate infarction from viable tissue within the area at risk.Results: Mean infarction size was 201 ± 35 mm(2) (mean ± SEM) in the hypoglycaemic group, 154 ± 40 mm(2) in the normoglycaemic group and 134 ± 40 mm(2) in the hyperglycaemic group, with no differences in infarction size, infarct/area at risk ratio or troponin T levels between the groups. There was no difference in incidence of ventricular fibrillation or mortality between the groups.Conclusion: No statistically significant associations were observed between the acute glycaemic level and measures of myocardial infarction, rates of ventricular fibrillation and subsequent premature death in the setting of acute ischaemia and reperfusion. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study was to describe the changes in the axis of the knee joint in both radiologically osteoarthritic and non-osteoarthritic knees, on the basis of angles measurable in standardized clinical short knee radiographs, in a cross sectional study of an epidemiological cohort.Design: From the third inclusion of the Copenhagen City Heart Study, 4,151 subjects were selected for standardized radiography of the knees. After censuring the inclusion, the resulting cohort was comprised of 3,488 individuals. Images were analyzed for radiological knee joint osteoarthritis (OA) and the anatomical femorotibial axis of the knee joint was measured.Results: The prevalence of knee joint OA in males was 27.9% and 27.5%, for the left and right knees respectively. In females this was 32.8% and 36.4%. The mean knee joint angles were 4.11° in males; and 5.45° in females. A difference of 1.3° was found between the genders. In non-osteoarthritic knees the increase in valgus orientation in relationship to increasing age was found to be 0.03° and 0.04° per year, respectively, for males and females. Likewise, Kellgren and Lawrence found that OA was seen to influence a shift towards varus of 0.55°-0.76° per level of OA.Conclusion: Stratification in accordance with morphological severity of OA documented a clear tendency for the axis of the diseased knees to depart from the mean, primarily in the direction of varus. In knees exhibiting no signs of radiographic osteoarthritis we found a significant relationship between increasing age and a shift in the anatomical axis in the direction of valgus. [ABSTRACT FROM AUTHOR]

This paper presents test results of a new motor-integrated permanent-magnet gear and clarifies a path for future optimizations. The demonstrator, whose fabrication is also described, is initially targeting electrical traction for vehicles. Basic measured parameters in the forms of back electromotive force, stall torque, and inductances are all in line with finite-element calculations. However, very high rotational losses are present in the demonstrator, and these losses are higher than the calculations. Some of the losses are present due to poor aspects in the fabrication of the demonstrator, while others are identified to be caused by a nonoptimal diameter/length aspect ratio. The torque density is superior, and the copper losses are only a fraction of the copper losses in other traction motors. With the proposed changes to reduce the rotational losses, it is believed that the unit has a great potential for traction applications. [ABSTRACT FROM AUTHOR]

A core loss model for switched reluctance motor (SRM) is introduced in which flux waveforms in different parts of the motor are predicted by carrying out a two-dimensional (2D) finite-element (FE) transient analysis using ANSYS FE software. Since the predicted flux waveforms are non-sinusoidal, the improved Steinmetz equation is used for core loss calculation. The core loss model is developed totally in ANSYS parametric design language as a parametric model and it can be used easily for different types of SRM. The developed core loss model is applied to an 8/6 SRM and the experimental results are presented for validation of the model. [ABSTRACT FROM AUTHOR]

Several cardiovascular, structural, and functional abnormalities have been considered as potential causes of cardioembolic ischemic strokes. Beyond atrial fibrillation, other sources of embolism clearly exist and may warrant urgent action, but they are only a minor part of the many stroke mechanisms and strokes that seem to be of embolic origin remain without a determined source. The associations between stroke and findings like atrial fibrillation, valve calcification, or heart failure are confounded by co-existing risk factors for atherosclerosis and vascular disease. In addition, a patent foramen ovale which is a common abnormality in the general population is mostly an innocent bystander in patients with ischemic stroke. For these reasons, experts from the national Danish societies of cardiology, neurology, stroke, and neuroradiology sought to develop a consensus document to provide national recommendations on how to manage patients with a suspected cardioembolic stroke. Design: Comprehensive literature search and analyses were done by a panel of experts and presented at a consensus meeting. Evidence supporting each subject was vetted by open discussion and statements were adjusted thereafter. Results: The most common sources of embolic stroke were identified, and the statement provides advise on how neurologist can identify cases that need referral, and what is expected by the cardiologist. Conclusions: A primary neurological and neuroradiological assessment is mandatory and neurovascular specialists should manage the initiation of secondary prophylactic treatment. If a cardioembolic stroke is suspected, a dedicated cardiologist experienced in the management of cardioembolism should provide a tailored clinical and echocardiographic assessment. [ABSTRACT FROM AUTHOR]

We have explored and compared interfacial electrochemical electron transfer (ET) of three organic aromatic redox molecules, methylene blue (MB), resorufin (RSF), and anthraquinone monosulfonate (AQMS), non-covalently bound to single- and double-strand (ss and ds) DNA- and LNA-based ("locked nucleic acids") oligonucleotides (ONs). The redox probes were chosen for their equilibrium potentials and particularly for their different electrostatic charges. The ONs were linked to Au(111)-surfaces via Au S bonds, diluted by mercaptohexanol (MCH) which blocks direct redox probe electrochemical electron transfer and ensures that space is left for in situ ds formation. The study combines nucleic acid synthesis, electrochemistry at single-crystal electrode surfaces, and scanning tunnelling microscopy under electrochemical control (in situ STM). The three redox molecules bind differently to the ONs. Electrostatic binding dominates for positively charged MB. ET through the MB-marked LNA ONs appears but no ss/ds LNA ON difference could be distinguished. Electrostatically neutral RSF binds in π-π stacking or other non-electrostatic, non-covalent modes onto both DNA and LNA ONs. RSF voltammetric signals on MCH-diluted ON adlayers could be associated with "long-range" ET. There is no electrochemical RSF ss/ds difference on LNA ONs, but clear ss/ds distinction on RSF binding to DNA ONs with a strong RSF signal for ds and no signal for ss. Negatively charged AQMS also binds in intercalating, non-electrostatic modes with clear ds voltammetric signals of both DNA and LNA but no ss signal. We have explored the electrochemical behavior of three electrostatically differently charged aromatic redox molecules intercalated in single- and double-strand DNA- and LNA-based oligonucleotides. We also recorded single-molecule in situ STM imaging of intercalated AQMS. Unlabelled Image • Voltammetry of DNA-intercalation on atomically planar Au(111)-electrode surfaces • Comparison of three electrostatically differently charged intercalators • Comparison of intercalation in DNA- and LNA-based oligonucleotides • Single-molecule in situ scanning tunnelling microscopy of DNA intercalation [ABSTRACT FROM AUTHOR]

DNA nanostructures have been designed and used in many different applications. However, the use of nucleic acid scaffolds to promote the self‐assembly of artificial protein mimics is only starting to emerge. Herein five coiled‐coil peptide structures were templated by the hybridization of a d‐DNA triplex or its mirror‐image counterpart, an l‐DNA triplex. The self‐assembly of the desired trimeric structures in solution was confirmed by gel electrophoresis and small‐angle X‐ray scattering, and the stabilizing synergy between the two domains was found to be chirality‐independent but orientation‐dependent. This is the first example of using a nucleic acid scaffold of l‐DNA to template the formation of artificial protein mimics. The results may advance the emerging POC‐based nanotechnology field by adding two extra dimensions, that is, chirality and polarity, to provide innovative molecular tools for rational design and bottom‐up construction of artificial protein mimics, programmable materials and responsive nanodevices. [ABSTRACT FROM AUTHOR]

Background The present study aimed to investigate the long-term risk of hemorrhagic stroke (HS) in patients with infective endocarditis (IE). Methods Using a register-based nationwide cohort of 9 million Danes, we performed propensity score matching between patients with left-sided IE from 1977 to mid-2015 and IE-free individuals (1:10). Follow-up started 1 year after the IE diagnosis. Hazard ratios (HRs) for HS in patients with IE compared with the matched cohort were estimated using Cox regression. Results During follow-up of 5735 patients with left-sided IE from 1 year after IE diagnosis and up to 37.5 years (median, 6.3 years), 103 cases of HS were observed. Compared with the matched cohort, patients with IE had a higher long-term risk of HS (HR, 1.47; 95% confidence interval, 1.20–1.80; P <.001). The risk of HS was particularly increased in patients within the lowest propensity score quartile (HR, 2.60; 95% confidence interval, 1.89–3.58). Mediation analyses suggested that the increased HS risk could be explained by an indirect effect of mechanical heart valve insertion, atrial fibrillation, or treatment with anticoagulants. The cumulative risk of HS 30 years after start of follow-up was 3.0% in patients with IE. Conclusions IE does not directly increase the long-term risk of HS. The apparent excess risk of HS in patients with previous IE was explained by mediating factors, including mechanical heart valve insertion, atrial fibrillation, and anticoagulation medication. [ABSTRACT FROM AUTHOR]