Search

Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear. This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk. The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated. During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81). Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Fluorescent probes based on photoinduced electron transfer (PET) quenching of long lifetime triangulenium fluorophores have found multiple applications. For such probes a successful design relies on the right balance between the rate of PET quenching and fluorescence. In a series of ADOTA (A) and DAOTA (D) triangulenium fluorophores appended with aniline‐like quencher moieties, we have investigated the rate of quenching and its relation to thermodynamic driving force, distance, and conjugation within the quencher moiety. Three different quenchers, a short (1), a long (2), and a long twisted (3), 4‐aminophenyl, 4'‐aminobiphenyl, and 2,2'‐dimethyl‐4'‐aminobiphenyl, respectively were investigated. Steady‐state spectroscopy and electrochemistry confirms that the quencher moieties are electronically decoupled from the dyes and have similar oxidation potentials and thus driving force for PET quenching, irrespectively of their different length and conjugation. Time‐resolved fluorescence measurement was used to measure the fast PET quenching, with rate constant kPET ranging from >4×1011 to 2×109 s−1. Interestingly, PET quenching is equally efficient/fast from 1 and 2, even with increase in distance between the donor and the acceptor. However, when twisting the biphenyl in 3, a 20‐fold decrease in quenching is found. Even with this decrease in kPET, the quenching in 3 A/D is still highly efficient, with nearly 99 % quenching. The study show that long lifetime fluorophores can be efficiently switched even by relatively slow PET processes and that PET quencher moieties can be removed far from the fluorophore if conjugated linkers are applied. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Background: The sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors were developed as glucose‐lowering drugs to treat type 2 diabetes (T2D). However, significant reductions in clinical outcomes have now been demonstrated in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of the presence of T2D. Multiple hypotheses have been proposed for the underlying mechanisms, and the data to support these proposals are emerging. Objectives: To review the clinical outcome data with SGLT2 inhibitors in HFrEF and the data to support the mechanisms for these clinical effects. Methods: Literature review was supported by a PubMed search for relevant articles up to 19 April 2022. Findings: Current data support increased diuresis and reverse cardiac remodelling as important mechanisms for the reductions in heart failure hospitalizations and mortality observed with SGLT2 inhibitors (empagliflozin or dapagliflozin) in patients with HFrEF. Alteration in intrarenal haemodynamic is likely contributing to the observed renoprotective effect of SGLT2 inhibitors. Conclusions: Solid clinical data support the current recommendations to use empagliflozin or dapagliflozin in HFrEF. The underlying mechanisms likely include changes in cardiac and intrarenal haemodynamic. Yet, these mechanisms do not seem to solely explain the observed magnitude of clinical effect with SGLT2 inhibitors in HFrEF, and other mechanisms may contribute. [ABSTRACT FROM AUTHOR]

Area-based initiatives (ABIs) is a frequently used strategy within contemporary urban regeneration policies to tackle physical and social challenges in deprived neighbourhoods. A central characteristic of their approach is active involvement of local stakeholders as part of making robust and lasting improvements. The claim raised in this article is that urban regeneration mobilizes citizens through a narrow perception of "voluntarism" that tends to exclude vulnerable and socially marginalized citizens. The article presents a typology of voluntarism that makes a distinction between (a) social voluntarism, (b) civic voluntarism and (c) hybrid voluntarism, combining non-paid voluntarism with pro-profit activities. Empirically, we draw on studies from ABIs in Denmark where collaboration with charity organizations and hybrid organizations has been used to mobilize marginalized citizens in the urban regeneration areas. We find that collaborations with charity-based and hybrid organizations are sparse and small-scale so far, but appear promising with regards to involve socially vulnerable groups. [ABSTRACT FROM AUTHOR]

Background: Plasma growth differentiation factor-15 (GDF-15) biomarker levels increase in response to inflammation and tissue injury, and increased levels of GDF-15 are associated with increased risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve outcome in HFrEF, have been shown to increase plasma GDF-15 in diabetic patients. We aimed to investigate the effect of empagliflozin on GDF-15 in HFrEF patients. Methods: This Empire HF Biomarker substudy was from the multicentre, randomized, double-blind, placebo-controlled Empire HF trial that included 190 patients from June 29, 2017, to September 10, 2019. Stable ambulatory HFrEF patients with ejection fraction of ≤ 40% were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo for 12 weeks. Changes from baseline to 12 weeks in plasma levels of GDF-15, high-sensitive C-reactive protein (hsCRP), and high-sensitive troponin T (hsTNT) were assessed. Results: A total of 187 patients who were included in this study, mean age was 64 ± 11 years; 85% male, 12% with type 2 diabetes, mean ejection fraction 29 ± 8, with no differences between the groups. Baseline median plasma GDF-15 was 1189 (918–1720) pg/mL with empagliflozin, and 1299 (952–1823) pg/mL for placebo. Empagliflozin increased plasma GDF-15 compared to placebo (adjusted between-groups treatment effect; ratio of change (1·09 [95% confidence interval (CI), 1.03–1.15]: p = 0.0040). The increase in plasma GDF15 was inversely associated with a decrease in left ventricular end-systolic (R = – 0.23, p = 0.031), and end-diastolic volume (R = – 0.29, p = 0.0066). There was no change in plasma hsCRP (1.09 [95%CI, 0.86–1.38]: p = 0.48) or plasma hsTNT (1.07 [95%CI, 0.97–1.19]: p = 0.18) compared to placebo. Patients with diabetes and treated with metformin demonstrated no increase in plasma GDF-15 with empagliflozin, p for interaction = 0·01. Conclusion: Empagliflozin increased plasma levels of GDF-15 in patients with HFrEF, with no concomitant increase in hsTNT nor hsCRP. Trial registration: The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585. [ABSTRACT FROM AUTHOR]

Background: Plasma growth differentiation factor-15 (GDF-15) biomarker levels increase in response to inflammation and tissue injury, and increased levels of GDF-15 are associated with increased risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve outcome in HFrEF, have been shown to increase plasma GDF-15 in diabetic patients. We aimed to investigate the effect of empagliflozin on GDF-15 in HFrEF patients. Methods: This Empire HF Biomarker substudy was from the multicentre, randomized, double-blind, placebo-controlled Empire HF trial that included 190 patients from June 29, 2017, to September 10, 2019. Stable ambulatory HFrEF patients with ejection fraction of ≤ 40% were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo for 12 weeks. Changes from baseline to 12 weeks in plasma levels of GDF-15, high-sensitive C-reactive protein (hsCRP), and high-sensitive troponin T (hsTNT) were assessed. Results: A total of 187 patients who were included in this study, mean age was 64 ± 11 years; 85% male, 12% with type 2 diabetes, mean ejection fraction 29 ± 8, with no differences between the groups. Baseline median plasma GDF-15 was 1189 (918–1720) pg/mL with empagliflozin, and 1299 (952–1823) pg/mL for placebo. Empagliflozin increased plasma GDF-15 compared to placebo (adjusted between-groups treatment effect; ratio of change (1·09 [95% confidence interval (CI), 1.03–1.15]: p = 0.0040). The increase in plasma GDF15 was inversely associated with a decrease in left ventricular end-systolic (R = – 0.23, p = 0.031), and end-diastolic volume (R = – 0.29, p = 0.0066). There was no change in plasma hsCRP (1.09 [95%CI, 0.86–1.38]: p = 0.48) or plasma hsTNT (1.07 [95%CI, 0.97–1.19]: p = 0.18) compared to placebo. Patients with diabetes and treated with metformin demonstrated no increase in plasma GDF-15 with empagliflozin, p for interaction = 0·01. Conclusion: Empagliflozin increased plasma levels of GDF-15 in patients with HFrEF, with no concomitant increase in hsTNT nor hsCRP. Trial registration: The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585. [ABSTRACT FROM AUTHOR]

In this brief contribution, we are introduced to two of Erik Hansen's restoration works in Denmark, the Marble Bridge across Frederiksholm's Canal (erected 1739–1745) and his private house in Wildersgade (built ca. 1725), both in Copenhagen. These two examples demonstrate Hansen's unique approach to architecture, in which he literarily is "The Man Who Speaks with the Stones." [ABSTRACT FROM AUTHOR]

Purpose: Information seeking can be used to make sense of a situation or solve a problem. Information seeking can be considered a coping strategy when facing illness, crisis or other life-changing events. Cancer is a globally occurring, life-threatening disease, and this review aims to provide an overview of the existing literature on the active information seeking behaviour of cancer patients specifically focussing on how active information seeking serves as a coping strategy. Design/methodology/approach: This study adheres to current guidelines for conducting systematic reviews and consequently, thorough literature searches were conducted in four databases: Medline, Embase, CINAHL and Scopus which resulted in 7,179 publications. Following a careful screening process, this systematic review identifies 14 studies on the use of information seeking to cope with cancer. Findings: The included studies consist of both qualitative and quantitative approaches to analysing the use of information seeking to cope with cancer. The included studies have focussed primarily on demographic factors, the impact of affect, information needs, sources and coping strategies. Research limitations/implications: A number of research gaps within library and information science are identified. Bringing research in this field into information science could allow for a greater understanding of information literacy, the use of existing information and the process of information searching when using information seeking to cope with serious illness. Originality/value: This systematic review focusses on how information seeking serves as a coping strategy for cancer patients and provides an overview of the recent literature. [ABSTRACT FROM AUTHOR]

Interactive simulations and visualizations augment the teaching and learning of quantum mechanics by making equations and concepts come to life. However, graphical visualizations are nearly always limited to a set of hard-coded functionalities. Text-based codes can offer a higher degree of flexibility, but only at the expense of steep learning curves or time investments. We introduce Quantum Composer, which allows the user to build, expand, or explore quantum mechanical simulations by interacting with graphically connectable nodes, each corresponding to a physical concept, mathematical operation, or visualization. Quantum Composer eliminates numerical and programming details while retaining accessibility, emphasis on understanding, and rapid feedback mechanisms. We illustrate its open-ended applicability through a series of examples in introductory and advanced quantum mechanics courses, student projects, and research environments. [ABSTRACT FROM AUTHOR]

Background: Inhibition of the sodium-glucose cotransporter-2 (SGLT2i) improves outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF), but the mechanism by which they improve outcomes remains unclear.Objectives: This study aimed to investigate the effects of sodium-glucose cotransporter-2 inhibitor empagliflozin on central hemodynamics in patients with HF and HFrEF.Methods: This investigator-initiated, double-blinded, placebo-controlled, randomized trial enrolled 70 patients with HFrEF from March 6, 2018, to September 10, 2019. Patients were assigned to empagliflozin of 10 mg or matching placebo once daily on guideline-driven HF therapy for 12 weeks. The primary outcome was ratio of pulmonary capillary wedge pressure (PCWP) to cardiac index (CI) at peak exercise after 12 weeks. Patients underwent right-heart catheterization at rest and during exercise at baseline and 12-week follow-up.Results: Patients with HFrEF, mean age of 57 years, mean left-ventricular ejection fraction, 26%, and 12 (17%) with type 2 diabetes mellitus were randomized. There was no significant treatment effect on peak PCWP/CI (-0.13 mm Hg/l/min/m2; 95% confidence interval: -1.60 to 1.34 mm Hg/l/min/m2; p = 0.86). Considering hemodynamics over the full range of exercise loads, PCWP was significantly reduced (-2.40 mm Hg; 95% confidence interval: -3.96 to -0.84 mm Hg; p = 0.003), but not CI (-0.09 l/min/m2; 95% confidence interval: -0.14 to 0.32 l/min/m2; p = 0.448) by empagliflozin. This was consistent among patients with and without type 2 diabetes.Conclusions: Among patients with stable HFrEF, empagliflozin for 12 weeks reduced PCWP compared with placebo. There was no significant improvement in neither CI nor PCWP/CI at rest or exercise. [ABSTRACT FROM AUTHOR]

With the development of deep learning techniques, the field of direction of arrival (DOA) estimation has also made significant progress. However, the accuracy of DOA estimation using end-to-end neural networks (NNs) heavily relies on the classification step of the networks, which necessitates the use of large and representative datasets. Additionally, conventional speech presence probability (SPP) estimation methods based on the ideal ratio mask (IRM) may misclassify time-frequency (T-F) bins dominated by non-speech and noise, which hinders the accurate extraction of directional information. To improve the robustness of existing DOA estimation algorithms, this paper proposes a DOA estimation method with T-F bin selection. In terms of output, instead of using IRM-based SPP, our proposed approach focuses on the a posteriori SPP, a deliberate choice aimed at circumventing potential confusion. For input optimization, we construct features that encompass spatial, temporal, and directional information concurrently, and these are coupled with a frequency bin-wise recurrent neural network (RNN) model to attain precise multi-channel SPP estimation. Subsequently, these SPP estimates are utilized to extract local information for DOA estimation. Moreover, the cascaded structure ensures that the model has the ability to complete out-of-label tasks, effectively reducing the dataset requirements by training only a subset of direction information to achieve omnidirectional DOA estimation. Besides, this contributes to the algorithm's ability to eliminate its reliance on the step size, setting it apart from other end-to-end methods. Simulation results validate that the proposed method achieves higher accuracy and lower error compared to both NN-based end-to-end approaches and traditional full-band approaches under various conditions of reverberation and signal-to-noise ratio. [ABSTRACT FROM AUTHOR]

To our knowledge, this is the first study reporting the effect of sodium-glucose cotransporter 2 inhibitors on insulin resistance in patients who have HFrEF primarily without diabetes. In total, 120 patients were enrolled,[4] including 108 (90%) patients without a history of T2D, of whom 19 (18%) had new-onset T2D and 35 (32%) had impaired glucose tolerance based on the oral glucose tolerance testing. Keywords: body composition; diabetes mellitus, type 2; empagliflozin; heart failure; insulin resistance; sodium-glucose transporter 2 inhibitors EN body composition diabetes mellitus, type 2 empagliflozin heart failure insulin resistance sodium-glucose transporter 2 inhibitors 2208 2210 3 06/02/21 20210601 NES 210601 The general notion has been that the mechanisms behind the clinical benefits of sodium-glucose cotransporter 2 inhibitors in patients with heart failure and reduced ejection fraction (HFrEF) are related to effects beyond improved glycemic control.[1] However, insulin resistance is a common metabolic characteristic of heart failure, and improved insulin resistance may better the long-term prognosis,[2] for example, by preventing type 2 diabetes (T2D) or by reverse cardiac remodeling. [Extracted from the article]

This paper presents a systematic literature review of research focused on use of Semantic Web technologies in formal educational contexts. Through systematic search, the review has identified 199 research articles, which are examined with the intention of identifying prevalent themes within the body of research within the field of formal educational use of Semantic Web technologies. The themes identified by the review are: (1) Semantic Web ontologies; (2) Efficient distribution, accessibility, retrieval, reuse and combination of educational resources; (3) Linked Data; (4) Semantic Web enhanced virtual learning environments and personalization of learning environments; (5) Semantic Web learning objects; (6) Evaluation, feedback and assessment; (7) Semantic Web services; (8) Pedagogical tools for teachers and students. Furthermore, this review seeks to examine how these themes and the use of Semantic Web technologies in formal education reflects on the ongoing discussion of how pedagogy and technology should interact. The outset of this discussion is a previous study by Dirckinck‐Holmfeld, which establishes that there is a tendency to emphasize technology over pedagogy in educational design and development. [ABSTRACT FROM AUTHOR]

The prevalence of heart failure (HF) in patients with type 2 diabetes (T2DM) is debatable and no data exist concerning the diagnostic value of mid‐regional pro‐atrial natriuretic peptide (MR‐proANP). We aimed to identify HF prevalence and evaluate the diagnostic value of MR‐proANP in outpatients followed in two specialized diabetes clinics. HF was pre‐defined as HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). The prevalence of HFrEF and HFpEF was 2.4% and 17.5%, respectively. An MR‐proANP <60 pmol/L ruled out HFrEF in the total population (n = 806) and in patients reporting dyspnea (n = 311) with a sensitivity of 94.7% and 87.5%, a negative predictive value of 99.7% and 99.0%, a specificity of 39.5% and 33.0%, and a positive predictive value of 3.6% and 3.3%, respectively. In a multivariable model including age, sex, T2DM duration, albuminuria, uncontrolled systolic blood pressure, abnormal electrocardiogram and ischaemic heart disease for diagnosis of HF in patients reporting dyspnea, adding MR‐proANP increased the area under the curve from 0.69 to 0.78 (P < 0.001). In conclusion, HFrEF was rare among outpatients with T2DM. MR‐proANP rules out HFrEF and contributes independent information relevant to diagnosis of HF in patients reporting dyspnea. [ABSTRACT FROM AUTHOR]

Energy retrofitting of existing buildings is a central challenge for local, national, and international climate policies, and in several countries, single-family houses represent a major energy-saving potential. Although many municipalities are implementing local climate policies with initiatives to promote energy retrofitting of buildings, little research has been done regarding the role of single-family houses in local climate policies. Thus, we have little knowledge about specific initiatives to promote energy retrofitting amongst owners of single-family houses, we know little about experience from such initiatives, and we lack knowledge about the extent to which national and EU policies support local initiatives directed at homeowners. This article provides insights into these issues from an explorative study on local climate strategies in Danish front-runner municipalities where single-family housing is the dominating building segment. Based on a study of local governance strategies in 12 municipalities targeting homeowners' engagement in energy retrofitting, the paper finds that these municipalities have developed promising local network-based ways to engage homeowners in energy retrofitting, but finds simultaneously that the national policy mix is only partly supporting these local initiatives. The paper also points out that the local and regional context for the programmes, including the local economic situation, is of great importance, and this context creates both potentials and challenges for the local programmes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prevalence of dehydration in occupational settings and contextualize findings to effects on performance in cognitively dominated tasks, simple and complex motor tasks during moderate and high heat stress. Methods: The study included an occupational part with hydration assessed in five industries across Europe with urine samples collected from 139 workers and analyzed for urine specific gravity. In addition, laboratory experiments included eight male participants completing mild-intensity exercise once with full fluid replacement to maintain euhydration, and once with restricted water intake until the dehydration level corresponded to 2% bodyweight deficit. Following familiarization, euhydration and dehydration sessions were completed on separate days in random order (cross-over design) with assessment of simple motor (target pinch), complex motor (visuo-motor tracking), cognitive (math addition) and combined motor-cognitive (math and pinch) performance at baseline, at 1°C (MOD) and 2°C (HYPER) delta increase in body core temperature. Results: The field studies revealed that 70% of all workers had urine specific gravity values ≥1.020 corresponding to the urine specific gravity (1.020±0.001) at the end of the laboratory dehydration session. At this hydration level, HYPER was associated with reductions in simple motor task performance by 4±1%, math task by 4±1%, math and pinch by 9±3% and visuo-motor tracking by 16±4% (all P<0.05 compared to baseline), whereas no significant changes were observed when the heat stress was MOD (P>0.05). In the euhydration session, HYPER reduced complex (tracking) motor performance by 10±3% and simple pinch by 3±1% (both P<0.05, compared to baseline), while performance in the two cognitively dominated tasks were unaffected when dehydration was prevented (P>0.05). Conclusion: Dehydration at levels commonly observed across a range of occupational settings with environmental heat stress aggravates the impact of hyperthermia on performance in tasks relying on combinations of cognitive function and motor response accuracy. [ABSTRACT FROM AUTHOR]

Individuals with Down syndrome (DS) have impaired general motor skills compared to typically developed (TD) individuals. To gain knowledge on how young adults with DS learn and retain new motor skills. A DS-group (mean age = 23.9 ± 3 years, N = 11), and an age-matched TD-group (mean age 22.8 ± 1.8, N = 14) were recruited. The participants practiced a visuomotor accuracy tracking task (VATT) in seven blocks (10.6 min). Online and offline effects of practice were assessed based on tests of motor performance at baseline immediate and 7-day retention. The TD-group performed better than the DS-group on all blocks (all P < 0.001). Both groups improved VATT-performance online from baseline to immediate retention, (all P < 0.001) with no difference in online effect between groups. A significant between-group difference was observed in the offline effect (∆TD - ∆DS, P = 0.04), as the DS-group's performance at 7-day retention was equal to their performance at immediate retention (∆DS, P > 0.05), whereas an offline decrease in performance was found in the TD-group (∆TD, P < 0.001). Visuomotor pinch force accuracy is lower for adults with DS compared to TD. However, adults with DS display significant online improvements in performance with motor practice similar to changes observed for TD. Additionally, adults with DS demonstrate offline consolidation following motor learning leading to significant retention effects. • A visuomotor learning task was applied to study motor learning in adults with DS. • The DS-group had lower motor performance compared to typically developed controls. • The DS-group learned the new skill at the same rate as the TD-group. • A difference in offline effects were observed between the groups. [ABSTRACT FROM AUTHOR]

The demand for energy in Southeast Asia and the Pacific region has resulted in vast growth in gas exploration across the continent of Australia. With the approval for a number of liquefied natural gas (LNG) export facilities across the Australian seaboard, Arup Australasia has put its multi-disciplinary capabilities to full use in the delivery of a number of LNG jetties in Gladstone, Queensland in a design and construct collaboration with the contractor John Holland Group (JHG). This paper presents the design and construction of the dolphin structures, which were the result of close collaboration between JHG and Arup. The goal of this paper is to describe the importance of early constructability considerations and the complex interface between maritime, geotechnical and structural disciplines. The paper outlines the inputs and the consideration of both berthing and mooring dolphins designed to accommodate berthing and mooring of vessels of up to 220 000 m3 capacity. The approach of the paper is to describe the design solution in broad terms and selected key aspects in detail. [ABSTRACT FROM AUTHOR]

Human and animal studies have documented that neural circuitries in the spinal cord show adaptive changes caused by altered supraspinal and/or afferent input to the spinal circuitry in relation to learning, immobilization, injury and neurorehabilitation. Reversible adaptations following, e.g. the acquisition or refinement of a motor skill rely heavily on the functional integration between supraspinal and sensory inputs to the spinal cord networks. Accordingly, what is frequently conceived as a change in the spinal circuitry may be a change in either descending or afferent input or in the relative integration of these, i.e. a change in the neuronal weighting. This is evident from findings documenting only task-specific functional changes after periods of altered inputs whereas resting responses remain unaffected. In fact, the proximity of the spinal circuitry to the outer world may demand a more rigid organization compared to the highly flexible cortical circuits. The understanding of all of this is important for the planning and execution of neurorehabilitation. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses articles in the issue on topics including construction and design of ancient Greek temples and buildings, the spatial aspects of Greek cult, and the design, use, and significance of Greek cult objects.

Abstract: Background: While patients with coronary artery disease (CAD) and cerebrovascular disease share similar risk factor profiles, data on whether IS can be considered a “CAD equivalent” are limited. We aimed to determine whether ischemic stroke is an independent predictor of CAD by using cardiac computed tomography angiography (CTA). Methods: We analyzed the CTA in 392 patients with no history of CAD (24 patients with acute IS and 368 patients with acute chest pain). Extent of plaque burden was additionally dichotomized into 0–4 versus >4 segments. Results: Patients with IS had a near 5-fold increase odds of having coronary artery plaque (odds ratio [OR] 4.9, P <0.01) as compared to those without IS. After adjustment for age, gender, and traditional cardiac risk factors, there remained a near 4-fold increase odds for coronary plaque (adjusted OR 3.7, P =0.04). When stratified by extent of plaque, patients with IS had over 18-fold increase odds of having >4 segments of plaque than 0–4 segments as compared to patients without stroke (OR 18.3, P <0.01), which remained significantly associated in adjusted analysis (adjusted OR 12.1, P <0.001). Conclusion: Acute IS is independently associated with higher risk and greater extent of CAD compared to patients with acute chest pain at low-to-intermediate risk for acute coronary syndrome. [Copyright &y& Elsevier]

In this article, we provide a conceptual and argumentative framework for studying how Area-based Initiatives (ABIs) can facilitate contact between networks in deprived neighbourhoods and external forms of power (linking social capital). These relations provide the residents and other members of civil society with crucial access to leveraging resources, ideas and information. Although few studies on linking social capital have been carried out in relation to urban regeneration, there is empirical evidence that suggests that it can play a positive role in establishing trust and relations between civil society and a municipality. We set out with a review of how social capital literature has been applied in an urban context, and then demonstrate empirical examples from Denmark of how, in different contexts (village, town and city), ABIs have facilitated processes that generated different forms of social capital (bridging, bonding and linking). The article concludes that ABIs contribute to creating linking social capital, but the extent of the contribution depends on the level of bonding and bridging social capital in the area. We argue that public planners as well as evaluators of the ABIs should increase their awareness about the potentials of an ABI to create linking social capital in deprived neighbourhoods. [ABSTRACT FROM AUTHOR]

The article explores the information-seeking behavior of cancer patients, and mentions that cancer patients actively seek information about their health and illness, but may also consciously and cautiously avoid information that does not meet their needs. It mentions different patterns of information-seeking behavior among cancer patients, from intensive seeking to avoiding information, and how avoidance can be an approach used as part of seeking activities.

Enzymatic coagulation of bovine milk can be divided in 2 steps: an enzymatic step, in which the Phe105-Met106 bond of the milk protein bovine κ-casein is cleaved, and an aggregation step. The aspartic peptidases bovine and camel chymosin (EC 3.4.23.4) are typically used to catalyze the enzymatic step. The most commonly used method to study chymosin activity is the relative milk-clotting activity test that measures the end point of the enzymatic and aggregation step. This method showed that camel chymosin has a 2-fold higher milk-clotting activity toward bovine milk than bovine chymosin. To enable a study of the enzymatic step independent of the aggregation step, a fluorescence resonance energy transfer assay has been developed using a peptide substrate derived from the 98-108 sequence of bovine κ-casein. This assay and Michaelis-Menten kinetics were employed to determine the enzymatic activity of camel and bovine chymosin under milk clotting-like conditions (pH 6.65, ionic strength 80 mM). The results obtained show that the catalytic efficiency of camel chymosin is 3-fold higher than bovine chymosin. The substrate affinity and catalytic activity of bovine and camel chymosin increase at lower pH (6.00 and 5.50). The glycosylation of bovine and camel chymosin did not affect binding of the fluorescence resonance energy transfer substrate, but doubly glycosylated camel chymosin seems to have slightly higher catalytic efficiency. In the characterization of the enzymes, the developed assay is easier and faster to use than the traditionally used relative milk-clotting activity test method. [ABSTRACT FROM AUTHOR]

The primary purpose of this paper is to estimate the carbon footprint of conventional rye bread produced on an industrial scale and consumed in Denmark by identifying the stages that contribute significantly to the carbon footprint (hotspots) of production. The results are then interpreted by comparing and discussing the results of this study with the results of other studies identified in the extant body of literature. To estimate the carbon footprint, we considered an industrial bakery supply chain in a single in-depth quantitative case study. Using an attributional approach, we estimated the carbon footprint of 1 kg of rye bread to be 731 g CO2 equivalents (CO2eq). As in previous studies, the primary hotspot was found to be the raw material stage, especially agricultural production (cultivation), with processing and distribution stages as secondary hotspots. The waste management stage was determined to be an important and previously overlooked opportunity for improvement. [ABSTRACT FROM AUTHOR]

In this work, we present a framework for constructing a spatial map of an indoor environment using the concept of echolocation. More specifically, we propose a non-linear least squares (NLS) estimator which is combined with a spatial filtering technique, e.g., beamforming, to estimate both the time-of-arrival (TOA) and direction-of-arrival (DOA) of the acoustic echoes. The proposed framework is complemented with an echo detector to classify a spurious estimate and an acoustic reflector, i.e., a wall. Based on these estimators, we propose two algorithms that complement existing range sensors and aid robotic platforms in acoustic reflector localization and mapping: single-channel localization and mapping (ScLAM) and a multi-channel localization and mapping (McLAM). Compared to commonly used sensors, such as lidar, cameras and ultrasonic sensors, our proposed model-based approach can detect transparent surfaces that are typically found in an office environment and could work in audible frequency ranges. A proof-of-concept robotic platform was built to test our algorithms. According to our evaluation, both qualitative and quantitative experiments reveal that the proposed methods can detect an acoustic reflector up to a distance of 1.5 m at a signal-to-diffuse-noise ratio (SDNR) of 0 dB in a simulated environment and 10 dB in a real environment with an accuracy of 80%. • A framework for constructing a spatial map of an indoor environment is proposed using echolocation intended for robotic platform. • A general model of the early reflections that takes ego-noise, interfering sound and background noise within the signal model. • A non-linear least squares (NLS) estimator is used to estimate acoustic reflectors for time of arrival (TOA) estimates and beamforming technique was used for direction of arrival (DOA) estimates. • A novel echo detector is proposed to classify an acoustic echoes belonging to a wall from empty space. • Two methods are proposed ScLAM and McLAM. [ABSTRACT FROM AUTHOR]

The article discusses the study conducted by L. Kaasenbrood and colleagues on the risk of recurrent vascular disease events in patients who have varied manifestations of cardiovascular disease. The author states that risk prediction researches in primary prevention of cardiovascular disease need to consistently include the evaluation and validation of the existing models in varied settings.

Hip adduction strength is important for kicking and acceleration in soccer players. Changes in hip adduction strength may therefore have an effect on soccer players’ athletic performance. The purpose of this study was to investigate the acute and sub-acute effects of a kicking drill session on hip strength, concerning isometric hip adduction, abduction and flexion torque of the kicking leg and the supporting leg. Ten injury-free male elite soccer players, mean ±sage of 15.8 ± 0.4 years participated. All players underwent a specific 20 min kicking drill session, comprising 45 kicks. The players were tested the day before, 15 min after and 24 h after the kicking drill session by a blinded tester using a reliable test procedure. The isometric hip-action and leg-order were randomized. For the kicking leg, hip adduction torque increased from 2.45 (2.19–2.65) Nm ∙ kg−1, median (25th–75th percentiles), at pre-kicking to 2.65 (2.55–2.81) Nm ∙ kg−1(P= 0.024) 24 h post-kicking. This may have implications for the soccer player’s ability to maximally activate the hip adductors during kicking and acceleration, and thereby improve performance the day after a kicking drill session. [ABSTRACT FROM AUTHOR]

In this article, the author argues that the design process should move away from a traditional problem-solving approach to one that is more profoundly grounded in the everyday experiences of humans. It is argued that the goal of design should be to make everyday experiences more meaningful and even happier. The author suggests that experience-based designing (XbD) can lead to an exploration of new possibilities in design, rather than a focus of merely finding solutions to problems. The author explores the notion of designing for everyday but profound experiences.

Abstract: The purpose of this paper is to assess the financial impact as well as greenhouse gas emissions of bioenergy application in a food-processing company. The assessment of bioenergy comprises collection and handling of organic waste and conversion of these biomasses through anaerobic digestion into biogas. In order to validate the proposed options of bioenergy application, we considered a food processing company in Denmark as a case company in a single in-depth case study. In the case studied, the produced biogas is to be utilized in one of two options at a bakery site: To substitute natural gas in combined heat and power (CHP) production (option 1) or substitute natural gas for production processes (ovens) and boilers (heat in form of water and steam production). The financial and environmental assessment is undertaken using the proposed bioenergy application, and indicates that it is possible to realize financial benefits in terms of additional profits and cost savings, but that challenging conditions can be problematic from a company perspective and provide challenges for the promotion of bioenergy investments. Specifically, substituting natural gas for processes and boilers is identified as the scenario providing the best financial result. The results also indicate that bioenergy application results in reduced greenhouse gas emissions in both options compared with the base scenario, however with no significant differences between the two options. [Copyright &y& Elsevier]

Background Soccer players with weak hip-adductor muscles are at increased risk of sustaining groin injuries. Therefore, a simple hip-adductor strengthening programme for prevention of groin injuries is needed. Objective We aimed to investigate the effect of an 8-week hip-adductor strengthening programme, including one hip-adduction exercise, on eccentric and isometric hip-adduction strength, using elastic bands as external load. Methods Thirty-four healthy, sub-elite soccer players, mean (±SD) age of 22.1 (±3.3) years, were randomised to either training or control. During the mid-season break, the training group performed 8 weeks of supervised, progressive hip-adduction strength training using elastic bands. The participants performed two training sessions per week (weeks 1-2) with 3x15 repetition maximum loading (RM), three training sessions per week (weeks 3-6) with 3x10 RM and three training sessions per week (weeks 7-8) with 3x8 RM. Eccentric hip-adduction (EHAD), isometric hip-adduction (IHAD) and isometric hip-abduction (IHAB) strength, and the IHAD/IHAB ratio were measured assessor-blinded preintervention and postintervention, using reliable hand-held dynamometry procedures. Results In the training group, EHAD strength increased by 30% (p<0.001). In the control group, EHAD strength increased by 17% (p<0.001), but the increase was significantly larger in the training group compared with the control group (p=0.044). No other significant between-group strength-differences in IHAD, IHAB or the IHAD/IHAB ratio existed (p>0.05). Conclusions 8 weeks of hip-adduction strength training, using elastic bands, induce a relevant increase in eccentric hip-adduction strength in soccer players, and thus may have implications as a promising approach towards prevention of groin injuries in soccer. [ABSTRACT FROM AUTHOR]

Abstract: We previously reported that the investigational multimodal antidepressant, vortioxetine, reversed 5-HT depletion-induced memory deficits while escitalopram and duloxetine did not. The present report studied the effects of vortioxetine and the potential impact of its 5-HT1A receptor agonist and 5-HT3 receptor antagonist properties on 5-HT depletion-induced memory deficits. Recognition and spatial working memory were assessed in the object recognition (OR) and Y-maze spontaneous alternation (SA) tests, respectively. 5-HT depletion was induced in female Long-Evans rats using 4-cholro-DL-phenylalanine methyl ester HCl (PCPA) and receptor occupancies were determined by ex vivo autoradiography. Rats were acutely dosed with vortioxetine, ondansetron (5-HT3 receptor antagonist) or flesinoxan (5-HT1A receptor agonist). The effects of chronic vortioxetine administration on 5-HT depletion-induced memory deficits were also assessed. 5-HT depletion reliably impaired memory performance in both the tests. Vortioxetine reversed PCPA-induced memory deficits dose-dependently with a minimal effective dose (MED) ≤0.1mg/kg (∼80% 5-HT3 receptor occupancy; OR) and ≤3.0mg/kg (5-HT1A, 5-HT1B, 5-HT3 receptor occupancy: ∼15%, 60%, 95%) in SA. Ondansetron exhibited a MED ≤3.0μg/kg (∼25% 5-HT3 receptor occupancy; OR), but was inactive in the SA test. Flesinoxan had a MED ≤1.0mg/kg (∼25% 5-HT1A receptor occupancy; SA); only 1.0mg/kg ameliorated deficits in the NOR. Chronic p.o. vortioxetine administration significantly improved memory performance in OR and occupied 95%, 66%, and 9.5% of 5-HT3, 5-HT1B, and 5-HT1A receptors, respectively. Vortioxetine′s effects on SA performance may involve 5-HT1A receptor agonism, but not 5-HT3 receptor antagonism, whereas the effects on OR performance may involve 5-HT3 receptor antagonism and 5-HT1A receptor agonism. [Copyright &y& Elsevier]

Abstract: Depressed patients suffer from cognitive dysfunction, including memory deficits. Acute serotonin (5-HT) depletion impairs memory and mood in vulnerable patients. The investigational multimodal acting antidepressant vortioxetine is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and 5-HT transporter (SERT) inhibitor that enhances memory in normal rats in novel object recognition (NOR) and conditioned fear (Mørk et al., 2013). We hypothesized that vortioxetine's 5-HT receptor mechanisms are involved in its memory effects, and therefore investigated these effects in 5-HT depleted rats. Four injections of the irreversible tryptophan hydroxylase inhibitor 4-chloro-dl-phenylalanine methyl ester hydrochloride (PCPA, 86mg/kg, s.c.) induced 5-HT depletion, as measured in hippocampal homogenate and microdialysate. The effects of acute challenge with vortioxetine or the 5-HT releaser fenfluramine on extracellular 5-HT were measured in PCPA-treated and control rats. PCPA's effects on NOR and spontaneous alternation (SA) performance were assessed along with the effects of acute treatment with 5-hydroxy-l-tryptophan (5-HTP), vortioxetine, the selective 5-HT reuptake inhibitor escitalopram, or the 5-HT norepinephrine reuptake inhibitor duloxetine. SERT occupancies were estimated by ex vivo autoradiography. PCPA depleted central 5-HT by >90% in tissue and microdialysate, and impaired NOR and SA performance. Restoring central 5-HT with 5-HTP reversed these deficits. At similar SERT occupancies (>90%) vortioxetine, but not escitalopram or duloxetine, restored memory performance. Acute fenfluramine significantly increased extracellular 5-HT in control and PCPA-treated rats, while vortioxetine did so only in control rats. Thus, vortioxetine restores 5-HT depletion impaired memory performance in rats through one or more of its receptor activities. [Copyright &y& Elsevier]

It is well known that following skill learning, improvements in motor performance may transfer to the untrained contralateral limb. It is also well known that retention of a newly learned task A can be degraded when learning a competing task B that takes place directly after learning A. Here we investigate if this interference effect can also be observed in the limb contralateral to the trained one. Therefore, five different groups practiced a ballistic finger flexion task followed by an interfering visuomotor accuracy task with the same limb. Performance in the ballistic task was tested before the training, after the training and in an immediate retention test after the practice of the interference task for both the trained and the untrained hand. After training, subjects showed not only significant learning and interference effects for the trained limb but also for the contralateral untrained limb. Importantly, the interference effect in the untrained limb was dependent on the level of skill acquisition in the interfering motor task. These behavioural results of the untrained limb were accompanied by training specific changes in corticospinal excitability, which increased for the hemisphere ipsilateral to the trained hand following ballistic training and decreased during accuracy training of the ipsilateral hand. The results demonstrate that contralateral interference effects may occur, and that interference depends on the level of skill acquisition in the interfering motor task. This finding might be particularly relevant for rehabilitation. [ABSTRACT FROM AUTHOR]

The sense of force is critical in the control of movement and posture. Multiple factors influence our perception of exerted force, including inputs from cutaneous afferents, muscle afferents and central commands. Here, we studied the influence of cutaneous feedback on the control of ankle force output. We used repetitive electrical stimulation of the superficial peroneal (foot dorsum) and medial plantar nerves (foot sole) to disrupt cutaneous afferent input in 8 healthy subjects. We measured the effects of repetitive nerve stimulation on (1) tactile thresholds, (2) performance in an ankle force-matching and (3) an ankle position-matching task. Additional force-matching experiments were done to compare the effects of transient versus continuous stimulation in 6 subjects and to determine the effects of foot anesthesia using lidocaine in another 6 subjects. The results showed that stimulation decreased cutaneous sensory function as evidenced by increased touch threshold. Absolute dorsiflexion force error increased without visual feedback during peroneal nerve stimulation. This was not a general effect of stimulation because force error did not increase during plantar nerve stimulation. The effects of transient stimulation on force error were greater when compared to continuous stimulation and lidocaine injection. Position-matching performance was unaffected by peroneal nerve or plantar nerve stimulation. Our results show that cutaneous feedback plays a role in the control of force output at the ankle joint. Understanding how the nervous system normally uses cutaneous feedback in motor control will help us identify which functional aspects are impaired in aging and neurological diseases. [ABSTRACT FROM AUTHOR]

Bovine and camel chymosin are aspartic peptidases that are used industrially in cheese production. They cleave the Phe105-Met106 bond of the milk protein κ-casein, releasing its predominantly negatively charged C-terminus, which leads to the separation of the milk into curds and whey. Despite having 85% sequence identity, camel chymosin shows a 70% higher milk-clotting activity than bovine chymosin towards bovine milk. The activities, structures, thermal stabilities and glycosylation patterns of bovine and camel chymosin obtained by fermentation in Aspergillus niger have been examined. Different variants of the enzymes were isolated by hydrophobic interaction chromatography and showed variations in their glycosylation, N-terminal sequences and activities. Glycosylation at Asn291 and the loss of the first three residues of camel chymosin significantly decreased its activity. Thermal differential scanning calorimetry revealed a slightly higher thermal stability of camel chymosin compared with bovine chymosin. The crystal structure of a doubly glycosylated variant of camel chymosin was determined at a resolution of 1.6 Å and the crystal structure of unglycosylated bovine chymosin was redetermined at a slightly higher resolution (1.8 Å) than previously determined structures. Camel and bovine chymosin share the same overall fold, except for the antiparallel central β-sheet that connects the N-terminal and C-terminal domains. In bovine chymosin the N-terminus forms one of the strands which is lacking in camel chymosin. This difference leads to an increase in the flexibility of the relative orientation of the two domains in the camel enzyme. Variations in the amino acids delineating the substrate-binding cleft suggest a greater flexibility in the ability to accommodate the substrate in camel chymosin. Both enzymes possess local positively charged patches on their surface that can play a role in interactions with the overall negatively charged C-terminus of κ-casein. Camel chymosin contains two additional positive patches that favour interaction with the substrate. The improved electrostatic interactions arising from variation in the surface charges and the greater malleability both in domain movements and substrate binding contribute to the better milk-clotting activity of camel chymosin towards bovine milk. [ABSTRACT FROM AUTHOR]

This paper presents current research on Danish municipalities' use of Energy Service Companies (ESCO) as a way to improve the standard of public buildings and to increase energy efficiency. In recent years more and more municipalities have used ESCO-contracts to retrofit existing public buildings, and to make them more energy efficient. At the moment 30 municipalities (of the 98 municipalities in Denmark) are involved in, or preparing, ESCO contracts. Nevertheless, ESCO-contracting still faces many challenges on the Danish market, as there is a widespread skepticism towards the concept amongst many stakeholders. The purpose of this paper is to discuss the various experience gained so far by municipalities use of ESCO-contracting, the different approached to ESCO-contracting being used in practice, as well as the different viewpoints drivers and barriers behind the development. The strong growth in ESCO-contracts reflects that the ESCO-concept fits well with a number of present problems that municipalities are facing, as well as a flexible adaptation to the local context in different municipalities. [ABSTRACT FROM AUTHOR]

Part of the sensory information is processed by our central nervous system without conscious perception. Subconscious processing has been shown to be capable of triggering motor reactions. In the present study, we asked the question whether visual information, which is not consciously perceived, could influence decision-making in a choice reaction task. Ten healthy subjects (28±5 years) executed two different experimental protocols. In the Motor reaction protocol, a visual target cue was shown on a computer screen. Depending on the displayed cue, subjects had to either complete a reaching movement (go-condition) or had to abort the movement (stop-condition). The cue was presented with different display durations (20-160 ms). In the second Verbalization protocol, subjects verbalized what they experienced on the screen. Again, the cue was presented with different display durations. This second protocol tested for conscious perception of the visual cue. The results of this study show that subjects achieved significantly more correct responses in the Motor reaction protocol than in the Verbalization protocol. This difference was only observed at the very short display durations of the visual cue. Since correct responses in the Verbalization protocol required conscious perception of the visual information, our findings imply that the subjects performed correct motor responses to visual cues, which they were not conscious about. It is therefore concluded that humans may reach decisions based on subconscious visual information in a choice reaction task. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the performance of five risk models (Diamond–Forrester, the updated Diamond–Forrester, Morise, Duke, and a new model designated COronary Risk SCORE (CORSCORE) in predicting significant coronary artery disease (CAD) in patients with chest pain suggestive of stable angina pectoris. Methods: Retrospective cohort for creation of CORSCORE by means of logistic regression analysis. Prospective cohort for validation of the five risk models using receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Significant CAD was defined as lumen area diameter reduction ≥50% at coronary angiography. All risk models include information on age, sex, and symptoms. In addition the Duke, Morise, and CORSCORE models include information on tobacco use and hypercholesterolemia. Duke and Morise also include information on diabetes. History of myocardial infarction is used by the Duke and CORSCORE models whereas hypertension is included in the Morise and CORSCORE models. The Duke model includes information on electrocardiogram (ECG) changes and the Morise model includes information on family history, body mass index, obesity, and oestrogen status. Results: 4781 retrospective and 633 prospective consecutive patients referred for coronary angiography were included. The area under the ROC for the updated Diamond–Forrester, Duke, and CORSCORE was significantly larger than for the Diamond–Forrester (p ≤0.001). The IDI was significantly higher for the Duke as compared to all other models (p ≤0.006). Conclusion: The Duke, updated Diamond–Forrester, and CORSCORE risk models are most efficient in predicting CAD in a contemporary cohort of patients with symptoms suggestive of angina. The updated Diamond–Forrester may most operational in daily clinical practice since it is calculated from the lowest number of clinical variables. [Copyright &y& Elsevier]

An experimental magnetic refrigeration test device has been built at Risø DTU. The device is designed to be modular, and thus all parts of the device can easily be replaced depending on the experiment. This makes the device highly versatile, with the possibility of performing a wide variety of different experiments. The test device is of the reciprocating type, and the magnetic field source is provided by a permanent Halbach magnet assembly with an average flux density of 1.03 Tesla. This work presents experimental results for flat plate regenerators made of gadolinium and sintered compounds of La(Fe,Co,Si)13 and experimentally investigates the effect of thermal conduction through the regenerator housing walls. Each regenerator was tested over a range of hot reservoir temperatures under no load conditions for a regenerator comprised of gadolinium. The test machine was also tested with two different compositions of La(Fe,Co,Si)13 compounds. Test results are presented for a regenerator made of a single La(Fe,Co,Si)13 material and a two-material regenerator, and the results are compared to the same system using gadolinium. [ABSTRACT FROM AUTHOR]

At the onset of dynamic movements excitation of the motor cortex (M1) is spatially restricted to areas representing the involved muscles whereas adjacent areas are inhibited. The current study elucidates whether the cortical motor command for dynamic contractions is also restricted to a certain population of cortical neurons responsible for the fast corticospinal projections. Therefore, corticospinal transmission was assessed with high temporal resolution during dynamic contractions after both, magnetic stimulation over M1 and the brainstem. The high temporal resolution could be obtained by conditioning the soleus H-reflex with different interstimulus intervals by cervicomedullary stimulation (CMS-conditioning) and transcranial magnetic stimulation (TMS) of M1 (M1-conditioning). This technique provides a precise time course of facilitation and inhibition. CMS- and M1-conditioning produced an 'early facilitation' of the H-reflex, which occurred around 3 ms earlier with CMS-conditioning. The early facilitation is believed to be caused by activation of direct monosynaptic projections to the spinal motoneurons. CMS-conditioning resulted in a subsequent 'late facilitation', which is considered to reflect activity of slow-conducting and/or indirect corticospinal pathways. In contrast, M1-conditioning produced a 'late disfacilitation' or even 'late inhibition'. As the late dis-facilitation was only seen following M1- but not CMS-conditioning, it is argued that cortical activation during dynamic tasks is restricted to fast, direct corticospinal projections whereas corticomotoneurons responsible for slow and/or indirectly projecting corticospinal pathways are inhibited. The functional significance of restricting the descending cortical drive to fast corticospinal pathways may be to ensure a temporally focused motor command during the execution of dynamic movements. [ABSTRACT FROM AUTHOR]

Antispastic medication is often used in the clinic together with physiotherapy. However, some of the antispastic drugs, e.g., baclofen and diazepam, may influence the plastic mechanisms that are necessary for motor learning and hence efficient physiotherapy. In the present study, we consequently investigated the influence of baclofen and diazepam on acquisition of a visuomotor skill. The study was designed as a semi-randomized, double-blinded, placebo-controlled, crossover study in 16 healthy human subjects. The motor skill task required the subjects to match a given force trajectory by increasing or decreasing ankle dorsiflexor torque. Subjects trained for a total of 30 min. Transcranial magnetic stimulation of the primary motor cortex leg area was applied to elicit motor evoked potentials in the anterior tibial muscle (TA). Coupling between populations of TA motor units was calculated in the frequency (coherence) domain during isometric dorsiflexion. Subjects receiving placebo showed statistically significant improvement in motor performance ( q = 34.1, P = 0.014) accompanied by a statistically significant reduction in intramuscular coherence. Subjects receiving baclofen and diazepam conversely showed no progression in motor performance ( P > 0.05), and the training was not accompanied by a decrease in intramuscular coherence. TA motor evoked potentials had significantly lower threshold following the training in the placebo group, whereas this was not the case in the treatment groups. These data indicate that diazepam and baclofen interfere with the acquisition of a motor skill by disrupting some of the neuroplastic changes that are involved in improved motor performance. This suggests that antispastic treatment should be used with caution in subjects receiving concomitant physiotherapy. [ABSTRACT FROM AUTHOR]

Background: Presence of microvascular obstruction (MVO) following primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) confers higher risk of left-ventricular remodelling and dysfunction. Measurement of cardiac troponin I (cTnI) after STEMI reflects the extent of myocardial destruction. We aimed to explore whether cTnI values were associated with presence of MVO independently of infarct size in STEMI patients receiving pPCI. Methods: 175 patients with STEMI were included. cTnI was sampled at 24 and 48 h. MVO and infarct size was determined by delayed enhancement with cardiac magnetic resonance at five to seven days post index event. Results: The presence of MVO following STEMI was associated with larger infarct size and higher values of cTnI at 24 and 48 h. For any given infarct size or cTnI value, there was a greater risk of MVO development in non-anterior infarctions. cTnI was strongly associated with MVO in both anterior and non-anterior infarctions ( P < 0.01) after adjustment for covariates (including infarct size); and was reasonably effective in predicting MVO in individual patients (area-under-the-curve ≥≥0.81). Conclusion: Presence of MVO is reflected in levels of cTnI sampled at an early time-point following STEMI and this association persists after adjustment for infarct size. [ABSTRACT FROM AUTHOR]

Humans are capable of learning numerous motor skills, but newly acquired skills may be abolished by subsequent learning. Here we ask what factors determine whether interference occurs in motor learning. We speculated that interference requires competing processes of synaptic plasticity in overlapping circuits and predicted specificity. To test this, subjects learned a ballistic motor task. Interference was observed following subsequent learning of an accuracy-tracking task, but only if the competing task involved the same muscles and movement direction. Interference was not observed from a nonlearning task suggesting that interference requires competing learning. Subsequent learning of the competing task 4 h after initial learning did not cause interference suggesting disruption of early motor memory consolidation as one possible mechanism underlying interference. Repeated transcranial magnetic stimulation (rTMS) of corticospinal motor output at intensities below movement threshold did not cause interference, whereas suprathreshold rTMS evoking motor responses and (re)afferent activation did. Finally, the experiments revealed that suprathreshold repetitive electrical stimulation of the agonist (but not antagonist) peripheral nerve caused interference. The present study is, to our knowledge, the first to demonstrate that peripheral nerve stimulation may cause interference. The finding underscores the importance of sensory feedback as error signals in motor learning. We conclude that interference requires competing plasticity in overlapping circuits. Interference is remarkably specific for circuits involved in a specific movement and it may relate to sensory error signals. [ABSTRACT FROM AUTHOR]

Background. Although troponin is a cornerstone biomarker in the assessment and management of patients with acute coronary syndrome, much remains to be learned about the biology of this widely used biomarker, including its post-release modification. Degradation of troponin following release in patients with acute coronary syndrome has been described; however whether such post-release modification occurs in other non-acute coronary syndrome states remains unknown. The aim of this study was to define troponin degradation in patients with acute ischemic stroke. Materials and methods. Troponin I (cTnI) was measured daily during the first 5 days of admission in 244 patients with acute ischemic stroke. Western blot analysis was performed using anti-cTnI antibodies and compared with serum concentrations of cTnI in seven patients and one patient with myocardial infarction (positive control). Results. Elevated levels of troponin were detected in 25 (10 %) patients; in all, both intact cTnI and cTnI degradation products were detected, with up to seven degradation fragments found. Samples with the highest total cTnI levels gave the strongest and most numerous western-blotting bands. All fragments were comparable with the degradation pattern of the positive control in terms of position. Conclusions. Immunoblotting of blood samples from patients with acute ischemic stroke reveals similar degradation patterns of cTnI as has been described in patients with acute myocardial infarction. The biological ramification and potential clinical impact of this finding bears further scrutiny. [ABSTRACT FROM AUTHOR]