Exact rate of convergence of k-nearest-neighbor classification rule

A binary classification problem is considered. The excess error probability of the k-nearest neighbor classification rule according to the error probability of the Bayes decision is revisited by a decomposition of the excess error probability into approximation and estimation error. Under a weak margin condition and under a modified Lipschitz condition, tight upper bounds are presented such that one avoids the condition that the feature vector is bounded

Aspirin, but Not Tirofiban Displays Protective Effects in Endotoxin Induced Lung Injury

Background Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Recruitment of neutrophils into the lungs, regarded as a key mechanism in progression of ALI, depends on signaling between neutrophils and platelets. Consequently we explored the effect of platelet-targeted aspirin and tirofiban treatment in endotoxin induced acute lung injury Methods C57Bl/6 mice were exposed to aerosolized LPS (500 mu g/ml) for 30min and treated with Aspirin (100 mu g/g bodyweight via intraperitoneal injection, 30 min before or 1 hour after LPS inhalation) or Tirofiban (0.5 mu g/g bodyweight via tail vein injection 30 min before or 1 hour after LPS inhalation). The count of alveolar, interstitial, and intravascular neutrophils was assessed 4h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and protein content in the BAL fluid. Results Aspirin both before and after LPS inhalation reduced neutrophil influx into the lung and lung permeability indicating the protective role of Aspirin in ALI. Tirofiban, however, did not alter neutrophil recruitment after LPS inhalation. Release of platelet-derived chemokines CCL5 and PF4 and neutrophil extracellular traps was reduced by Aspirin but not by Tirofiban. Conclusion Aspirin, but not Tirofiban reduces neutrophil recruitment and displays protective effects during endotoxin induced lung injury

High-Intensity Interval Training Decreases Resting Urinary Hypoxanthine Concentration in Young Active Men—A Metabolomic Approach

High-intensity interval training (HIIT) is known to improve performance and skeletal muscle energy metabolism. However, whether the body’s adaptation to an exhausting short-term HIIT is reflected in the resting human metabolome has not been examined so far. Therefore, a randomized controlled intervention study was performed to investigate the effect of a ten-day HIIT on the resting urinary metabolome of young active men. Fasting spot urine was collected before (−1 day) and after (+1 day; +4 days) the training intervention and 65 urinary metabolites were identified by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Metabolite concentrations were normalized to urinary creatinine and subjected to univariate statistical analysis. One day after HIIT, no overall change in resting urinary metabolome, except a significant difference with decreasing means in urinary hypoxanthine concentration, was documented in the experimental group. As hypoxanthine is related to purine degradation, lower resting urinary hypoxanthine levels may indicate a training-induced adaptation in purine nucleotide metabolism

Vascular CXCR4 Limits Atherosclerosis by Maintaining Arterial Integrity Evidence From Mouse and Human Studies

BACKGROUND: The CXCL12/CXCR4 chemokine ligand/receptor axis controls (progenitor) cell homeostasis and trafficking. So far, an atheroprotective role of CXCL12/CXCR4 has only been implied through pharmacological intervention, in particular, because the somatic deletion of the CXCR4 gene in mice is embryonically lethal. Moreover, cell-specific effects of CXCR4 in the arterial wall and underlying mechanisms remain elusive, prompting us to investigate the relevance of CXCR4 in vascular cell types for atheroprotection. METHODS: We examined the role of vascular CXCR4 in atherosclerosis and plaque composition by inducing an endothelial cell (BmxCreERT2-driven)-specific or smooth muscle cell (SMC, SmmhcCreERT2-or TaglnCre-driven)-specific deficiency of CXCR4 in an apolipoprotein E-deficient mouse model. To identify underlying mechanisms for effects of CXCR4, we studied endothelial permeability, intravital leukocyte adhesion, involvement of the Akt/WNT/beta-catenin signaling pathway and relevant phosphatases in VE-cadherin expression and function, vascular tone in aortic rings, cholesterol efflux from macrophages, and expression of SMC phenotypic markers. Finally, we analyzed associations of common genetic variants at the CXCR4 locus with the risk for coronary heart disease, along with CXCR4 transcript expression in human atherosclerotic plaques. RESULTS: The cell-specific deletion of CXCR4 in arterial endothelial cells (n=1215) or SMCs (n=13-24) markedly increased atherosclerotic lesion formation in hyperlipidemic mice. Endothelial barrier function was promoted by CXCL12/\CXCR4, which triggered Akt/WNT/beta-catenin signaling to drive VE-cadherin expression and stabilized junctional VE-cadherin complexes through associated phosphatases. Conversely, endothelial CXCR4 deficiency caused arterial leakage and inflammatory leukocyte recruitment during atherogenesis. In arterial SMCs, CXCR4 sustained normal vascular reactivity and contractile responses, whereas CXCR4 deficiency favored a synthetic phenotype, the occurrence of macrophage-like SMCs in the lesions, and impaired cholesterol efflux. Regression analyses in humans (n=259 796) identified the C-allele at rs2322864 within the CXCR4 locus to be associated with increased risk for coronary heart disease. In line, C/C risk genotype carriers showed reduced CXCR4 expression in carotid artery plaques (n=188), which was furthermore associated with symptomatic disease. CONCLUSIONS: Our data clearly establish that vascular CXCR4 limits atherosclerosis by maintaining arterial integrity, preserving endothelial barrier function, and a normal contractile SMC phenotype. Enhancing these beneficial functions of arterial CXCR4 by selective modulators might open novel therapeutic options in atherosclerosis

Mehrdimensionale Change-Point-Schätzung mit U-Statistiken

Wir betrachten ein mehrdimensionales Change-Point-Problem. Seien X1;n; : : : ;Xn;n unabhängige Zufallselemente bei denen q, q 2 N, Verteilungswechsel auftreten. Dass heisst, es existiert ein Vektor µ = (µ1; : : : ; µq) 2 Rq mit 0 = µ0 < µ1 < ¢ ¢ ¢ < µq < µq+1 = 1 sowie Verteilungen º0;n; : : : ; ºq;n, so dass Xj;n für [nµi] < j · [nµi+1] die Verteilung ºi;n besitzt. Wir führen eine Klasse von Schätzer ^µn für den unbekannten Change-Point µ ein. Diese sind Maximalstellen von gewichteten q + 1-Stichproben U-Statistiken. Das Ziel der Arbeit ist die Un- tersuchung des asymptotischen Verhalten der Schätzer

Planning a market exit strategy for manufacturers of consumer goods when entering foreign markets

Aim: The internal market for manufacturers of consumer products companies is often too small in order to grant long-term success. Therefore, companies expand and enter foreign markets. This paper presents a planning process for market penetration for the selected foreign market, which will show the possibility of a withdrawal and shows also whether an exit scenario is planned by manufacturers of consumer products and when companies tend to think about a market exit. Design / Research methods: First, the literature was studied. Based on this, hypothesis were prepared. This was followed by a telephone survey of decision-makers from German manufacturers of the consumer products companies.  Conclusions / findings: A planning process for market penetration was developed, which shows next to the market entry also the market exit. Additional this paper shows that manufacturers of consumer products companies can be better prepared for a market exit than companies without an exit strategy, in particular, if the manufacturer sets out relevant economic parameters for the foreign market which determine whether to remain in the market or leave. Originality / value of the article: When analysing literature on planning processes for market entry, it becomes clear that an exit strategy is not planned. This may indicate that the authors did not consider a market exit and/or anticipate this as a worst case in their market entry assumption. Implications of the research: The last market entry of the surveyed companies usually occurred recently. For market exit results to be determined, a further consultation of the companies examined should be undertaken over a longer period of time

Mehrdimensionale Change-Point-Schätzung mit U-Statistiken

Wir betrachten ein mehrdimensionales Change-Point-Problem. Seien X1;n; : : : ;Xn;n unabhängige Zufallselemente bei denen q, q 2 N, Verteilungswechsel auftreten. Dass heisst, es existiert ein Vektor µ = (µ1; : : : ; µq) 2 Rq mit 0 = µ0 < µ1 < ¢ ¢ ¢ < µq < µq+1 = 1 sowie Verteilungen º0;n; : : : ; ºq;n, so dass Xj;n für [nµi] < j · [nµi+1] die Verteilung ºi;n besitzt. Wir führen eine Klasse von Schätzer ^µn für den unbekannten Change-Point µ ein. Diese sind Maximalstellen von gewichteten q + 1-Stichproben U-Statistiken. Das Ziel der Arbeit ist die Un- tersuchung des asymptotischen Verhalten der Schätzer

Neutrophils in atherosclerosis: from mice to man

Infiltration of leukocyte subsets is a driving force of atherosclerotic lesion growth, and during the past decade, neutrophils have received growing attention in chronic inflammatory processes, such as atherosclerosis. Equipped with various ready to be released mediators, evolved to fight invading pathogens, neutrophils may also hold key functions in affecting sterile inflammation, such as in atherosclerosis. Many of their secretion products might instruct or activate other immune cells (particularly monocytes) to, for example, enter atherosclerotic lesions or release proinflammatory mediators. Despite the emerging evidence for the mechanistic contribution of neutrophils to early atherosclerosis in mice, their role in human atherogenesis, atheroprogression, and atherosclerotic plaque destabilization is still poorly understood. This brief review will summarize latest findings on the role of neutrophils in atherosclerosis and will pay special attention to studies describing a translation approach by combining measurements in mouse and huma

An NMR-Based Approach to Identify Urinary Metabolites Associated with Acute Physical Exercise and Cardiorespiratory Fitness in Healthy Humans—Results of the KarMeN Study

Knowledge on metabolites distinguishing the metabolic response to acute physical exercise between fit and less fit individuals could clarify mechanisms and metabolic pathways contributing to the beneficial adaptations to exercise. By analyzing data from the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study, we characterized the acute effects of a standardized exercise tolerance test on urinary metabolites of 255 healthy women and men. In a second step, we aimed to detect a urinary metabolite pattern associated with the cardiorespiratory fitness (CRF), which was determined by measuring the peak oxygen uptake (VO2peak) during incremental exercise. Spot urine samples were collected pre- and post-exercise and 47 urinary metabolites were identified by nuclear magnetic resonance (NMR) spectroscopy. While the univariate analysis of pre-to-post-exercise differences revealed significant alterations in 37 urinary metabolites, principal component analysis (PCA) did not show a clear separation of the pre- and post-exercise urine samples. Moreover, both bivariate correlation and multiple linear regression analyses revealed only weak relationships between the VO2peak and single urinary metabolites or urinary metabolic pattern, when adjusting for covariates like age, sex, menopausal status, and lean body mass (LBM). Taken as a whole, our results show that several urinary metabolites (e.g., lactate, pyruvate, alanine, and acetate) reflect acute exercise-induced alterations in the human metabolism. However, as neither pre- and post-exercise levels nor the fold changes of urinary metabolites substantially accounted for the variation of the covariate-adjusted VO2peak, our results furthermore indicate that the urinary metabolites identified in this study do not allow to draw conclusions on the individual’s physical fitness status. Studies investigating the relationship between the human metabolome and functional variables like the CRF should adjust for confounders like age, sex, menopausal status, and LBM