bluuebunny/crossref_metadata_2025 huggingface dataset:
Draft Genome Sequence of a Metronidazole-Susceptible Atopobium vaginae Isolate
Authors: Schuyler Jessica A. , Mordechai Eli , Adelson Martin E. , Gygax Scott E. , Hilbert David W.
Published: September 2015

We report the draft genome sequence of a vaginal isolate of
Atopobium vaginae
vaginae
(strain 44061), an organism linked to bacterial vaginosis (BV), the most common gynecological infection in the United States. This species is often highly resistant to metronidazole, which is a front-line therapy for BV. Strain 44061 is a metronidazole-susceptible isolate (MIC, 16 µg/ml), and its genome sequence will be useful for comparative studies to elucidate the molecular basis of metronidazole resistance in this species.
Complete Genome Sequence of Bacillus megaterium Podophage Pavlov
Authors: Burgos Roberto W. , Mash Scott J. , Cahill Jesse L. , Rasche Eric S. , Kuty Everett Gabriel F.
Published: September 2015

Bacillus megaterium
is a large spore-forming bacterium found widely in the environment. Phages infecting
B. megaterium
can be used as genetic tools to expand the array of uses of
B. megaterium
in research and industry. Here, we present the complete genome of Pavlov, a podophage infecting
B. megaterium
.
Complete Genome Sequence of an
Edwardsiella piscicida
-Like Species, Recovered from Tilapia in the United States
Authors: Reichley Stephen R. , Waldbieser Geoffrey C. , Lawrence Mark L. , Griffin Matt J.
Published: September 2015

An
Edwardsiella piscicida
-like species is a Gram-negative facultative anaerobe that causes disease in some fish species. In this report, we present the complete and annotated genome of isolate LADL05-105, recovered from cultured tilapia reared in Louisiana, which contains a chromosome of 4,142,037 bp and no plasmids.
Theorising and testing environmental pathways to behaviour change: natural experimental study of the perception and use of new infrastructure to promote walking and cycling in local communities
Authors: Panter Jenna , Ogilvie David
Published: September 2015

Objective

Some studies have assessed the effectiveness of environmental interventions to promote physical activity, but few have examined how such interventions work. We investigated the environmental mechanisms linking an infrastructural intervention with behaviour change.

Design

Natural experimental study.

Setting

Three UK municipalities (Southampton, Cardiff and Kenilworth).

Participants

Adults living within 5 km of new walking and cycling infrastructure.

Intervention

Construction or improvement of walking and cycling routes. Exposure to the intervention was defined in terms of residential proximity.

Outcome measures

Questionnaires at baseline and 2-year follow-up assessed perceptions of the supportiveness of the environment, use of the new infrastructure, and walking and cycling behaviours. Analysis proceeded via factor analysis of perceptions of the physical environment (step 1) and regression analysis to identify plausible pathways involving physical and social environmental mediators and refine the intervention theory (step 2) to a final path analysis to test the model (step 3).

Results

Participants who lived near and used the new routes reported improvements in their perceptions of provision and safety. However, path analysis (step 3, n=967) showed that the effects of the intervention on changes in time spent walking and cycling were largely (90%) explained by a simple causal pathway involving use of the new routes, and other pathways involving changes in environmental cognitions explained only a small proportion of the effect.

Conclusions

Physical improvement of the environment itself was the key to the effectiveness of the intervention, and seeking to change people's perceptions may be of limited value. Studies of how interventions lead to population behaviour change should complement those concerned with estimating their effects in supporting valid causal inference.
Teachers’ experiences of adolescents’ pain in everyday life: a qualitative study
Authors: Rohde Gudrun , Westergren Thomas , Haraldstad Kristin , Johannessen Berit , Høie Magnhild , Helseth Sølvi , Fegran Liv , Slettebø Åshild
Published: September 2015

Objectives

More adolescents report pain now than previously. In Norway, episodic pain problems have been reported by 60% of children and adolescents aged 8–18 years, with 21% reporting duration of pain of more than 3 months. Since adolescents spend much time at school, the attitude and behaviour of teachers play important roles regarding the experience of pain felt by adolescents in everyday life. Yet research on how teachers perceive the pain experienced by adolescents in a school setting is limited. We therefore seek to gain insight to teachers’ classroom experiences with (1) adolescent's self-reported pain symptoms; (2) adolescents management of their pain and (3) how to help adolescents manage their pain.

Setting

Teachers in 5 junior high schools in Norway representing municipalities in 3 rural areas and 2 cities.

Research design

A qualitative study with an explorative design comprising 5 focus group interviews. Each group consisted of 3–8 junior high school teachers. A semistructured interview guide was used to cover the issues. The transcribed text was analysed with qualitative content analysis.

Participants

22 teachers participated (5 men, 17 women; age range 29–62 years) with teaching experience ranging from 3 to nearly 40 years.

Results

The main theme describing the experience of teachers with adolescents’ pain in everyday life is that pain and management of pain is a social, physical and psychological interwoven phenomenon. Through empirical analyses, 3 subcategories emerged: (1) everyday pain—expressing strenuous life; (2) managing pain—escaping struggle and (3) strategies of teachers—support and normalisation.

Conclusions

Teachers have a biopsychosocial understanding and approach to pain experienced by adolescents. This understanding influences the role of teachers as significant others in the lives of adolescents with regard to pain and management of their pain in a school setting.
What is the influence of randomisation sequence generation and allocation concealment on treatment effects of physical therapy trials? A meta-epidemiological study
Authors: Armijo-Olivo Susan , Saltaji Humam , da Costa Bruno R , Fuentes Jorge , Ha Christine , Cummings Greta G
Published: September 2015

Objective

To determine if adequacy of randomisation and allocation concealment is associated with changes in effect sizes (ES) when comparing physical therapy (PT) trials with and without these methodological characteristics.

Design

Meta-epidemiological study.

Participants

A random sample of randomised controlled trials (RCTs) included in meta-analyses in the PT discipline were identified.

Intervention

Data extraction including assessments of random sequence generation and allocation concealment was conducted independently by two reviewers. To determine the association between sequence generation, and allocation concealment and ES, a two-level analysis was conducted using a meta-meta-analytic approach.

Primary and secondary outcome measures

association between random sequence generation and allocation concealment and ES in PT trials.

Results

393 trials included in 43 meta-analyses, analysing 44 622 patients contributed to this study. Adequate random sequence generation and appropriate allocation concealment were accomplished in only 39.7% and 11.5% of PT trials, respectively. Although trials with inappropriate allocation concealment tended to have an overestimate treatment effect when compared with trials with adequate concealment of allocation, the difference was non-statistically significant (ES=0.12; 95% CI −0.06 to 0.30). When pooling our results with those of Nueschet al, we obtained a pooled statistically significant value (ES=0.14; 95% CI 0.02 to 0.26). There was no difference in ES in trials with appropriate or inappropriate random sequence generation (ES=0.02; 95% CI −0.12 to 0.15).

Conclusions

Our results suggest that when evaluating risk of bias of primary RCTs in PT area, systematic reviewers and clinicians implementing research into practice should pay attention to these biases since they could exaggerate treatment effects. Systematic reviewers should perform sensitivity analysis including trials with low risk of bias in these domains as primary analysis and/or in combination with less restrictive analyses. Authors and editors should make sure that allocation concealment and random sequence generation are properly reported in trial reports.
Superiority trials: raising the bar of null hypothesis statistical testing
Authors: Shafiq Nusrat , Malhotra Samir
Published: September 2015

We propose a ‘superiority margin’, akin to the non-inferiority margin used in non-inferiority trials. This would overcome several drawbacks of null hypothesis statistical testing and can be applicable to other types of analyses as well.
GLOBALIZATION AND ECONOMIC GROWTH IN CAMBODIA
Authors: MAH JAI S.
Published: September 2015

For the past two decades, since the political situation became stable, Cambodia has recorded a very rapid economic growth rate. In the meantime, globalization has progressed both in terms of the expansion of international trade and foreign direct investment (FDI) inflows. This paper applies small sample cointegration tests and error correction models to reveal the determinants of Cambodia’s rapid economic growth. The cointegration test results support the existence of a long-run equilibrium relationship among the variables concerned. The error-correction models show that expansion of international trade values has caused the rapid economic growth in Cambodia, regardless of the measure of international trade used.
PATTERNS AND DETERMINANTS OF INTRA-INDUSTRY TRADE IN SOUTHEAST ASIA: EVIDENCE FROM THE AUTOMOTIVE AND ELECTRICAL APPLIANCES SECTORS
Authors: SALIM RUHUL , ISLAM AMIRUL , BLOCH HARRY
Published: September 2015

Using finely disaggregated data at six-digit harmonized code classification level, this paper examines the patterns and determinants of horizontal and vertical intra-industry trade in the automobile and electrical appliances sectors during the past few decades among the six major Southeast Asian countries. It is found from the analysis of the data that intra-industry trade is much higher than the inter-industry trade in each of these two sectors. Further, the determinants of these two types of trade are found to differ somewhat in terms of sign and magnitude across the sectors, implying the importance of sector-specific factors as influences on the pattern of trade.
Lock-On Vortex Shedding Patterns and Bifurcation Analysis of the Forced Streamwise Oscillation of the Cylinder Wake
Authors: Nabatian N. , Mureithi N. W.
Published: September 2015

The two-dimensional numerical simulation of the flow over a cylinder forced to oscillate in the streamwise direction for Re = 200 is performed in CFX ANSYS. The controlled-vibration comprises of prescribed inline vibration from displacement amplitude-to-cylinder diameter A/D = 0.05 up to 0.5 with the excitation frequency ratios of 1, 1.5 and 2 including the harmonic and superharmonic excitation regions. The immersed boundary method is used to model the cylinder oscillation. Modal decomposition of the transverse velocity field via the proper orthogonal decomposition (POD) method is applied to uncover the interaction of symmetric and antisymmetric modes of the near wake. A model using the first two POD modes is developed based on symmetry group equivariance. The model predicts the mode interactions and bifurcated solution branches for all cases, and is shown to be in good agreement with numerical as well as previous experimental results. Lock-on is determined for a range of values of the oscillation amplitudes and frequency ratios. It is shown that the lock-on range widens with increasing nondimensional oscillation amplitude. The asymmetric 2S, P + S and symmetric pattern S with symbol S for a single vortex and P for a vortex pair shed per cycle, as well as a regime in which vortex formation is not synchronized with cylinder motion are observed in the cylinder wake depending on the combination of oscillation amplitude and frequency ratio. The frequency ratio variation from 1 to 2 leads to the switching from asymmetric to symmetric modes. The symmetric flow pattern corresponds to a near zero lift coefficient on the cylinder.
On the Inherent Self-Excited Macroscopic Randomness of Chaotic Three-Body Systems
Authors: Liao Shijun , Li Xiaoming
Published: September 2015

What is the origin of macroscopic randomness (uncertainty)? This is one of the most fundamental open questions for human beings. In this paper, 10 000 samples of reliable (convergent), multiple-scale (from 10-60 to 102) numerical simulations of a chaotic three-body system indicate that, without any external disturbance, the microscopic inherent uncertainty (in the level of 10-60) due to physical fluctuation of initial positions of the three-body system enlarges exponentially into macroscopic randomness (at the level O(1)) until t = T*, the so-called physical limit time of prediction, but propagates algebraically thereafter when accurate prediction of orbit is impossible. Note that these 10 000 samples use micro-level, inherent physical fluctuations of initial position, which have nothing to do with human beings. Especially, the differences of these 10 000 fluctuations are mathematically so small (in the level of 10-60) that they are physically the same since a distance shorter than a Planck length does not make physical sense according to the string theory. This indicates that the macroscopic randomness of the chaotic three-body system is self-excited, say, without any external force or disturbances, from the inherent micro-level uncertainty. It provides us the new concept "self-excited macroscopic randomness (uncertainty)". The macroscopic randomness is found to be dependent upon microscopic uncertainty, from the statistical viewpoint. In addition, it is found that, without any external disturbance, the chaotic three-body system might randomly disrupt with symmetry-breaking at t = 1000 in about 25% probability, which provides us new concepts "self-excited random disruption", "self-excited random escape" and "self-excited symmetry breaking" of the chaotic three-body system. Hence, it suggests that a chaotic three-body system might randomly evolve by itself, without any external forces or disturbance. Thus, the world is essentially uncertain, since such kind of self-excited macroscopic randomness (uncertainty) is inherent and unavailable. This work also implies that an universe could randomly evolve by itself into complicated structures, without any external forces. To emphasize this point, the so-called "molecule-effect" (or "nonbutterfly effect") of chaos is suggested in this paper. All of these reliable computations could deepen our understandings of chaos from physical viewpoints, and reveal a kind of origin of macroscopic randomness/uncertainty.
Controlling Chaos for Fractional Order Loss Type of Coupled Dynamos Systems via Feedback
Authors: Hao Jianhong , Xiong Xueyan , Bin Hong , Sun Nayan
Published: September 2015

This paper studies the problem of chaos control for the fractional order modified coupled dynamos system that involves mechanical damping loss. Based on the Routh–Hurwitz criterion generalized to the fractional order stability theory, the stability conditions of the controlled system are discussed. We adopt a simple single-variable linear feedback method to suppress chaos to the unstable equilibrium point and limit cycle. Then, a modified feedback control method is developed in light of the sliding mode variable structure, namely exerting the controller only when the system trajectory is close to the target orbit. This method not only maintains the dynamics of the system, but provides the optimal control time and adjustable limit cycles radius. Numerical simulation proves the validity of this method.
Weakly Almost Periodic Points and Some Chaotic Properties of Dynamical Systems
Authors: Yin Jiandong , Zhou Zuoling
Published: September 2015

Let X be a compact metric space and f : X → X be a continuous map. In this paper, ergodic chaos and strongly ergodic chaos are introduced, and it is proven that f is strongly ergodically chaotic if f is transitive but not minimal and has a full measure center. In addition, some sufficient conditions for f to be Ruelle–Takens chaotic are presented. For instance, we prove that f is Ruelle–Takens chaotic if f is transitive and there exists a countable base [Formula: see text] of X such that for each i > 0, the meeting time set N(Ui, Ui) for Ui with respect to itself has lower density larger than [Formula: see text].
A New Method for Suppressing Periodic Narrowband Interference Based on the Chaotic van der Pol Oscillator
Authors: Lu Jia , Zhang Xiaoxing , Xiong Hao
Published: September 2015

The chaotic van der Pol oscillator is a powerful tool for detecting defects in electric systems by using online partial discharge (PD) monitoring. This paper focuses on realizing weak PD signal detection in the strong periodic narrowband interference by using high sensitivity to the periodic narrowband interference signals and immunity to white noise and PD signals of chaotic systems. A new approach to removing the periodic narrowband interference by using a van der Pol chaotic oscillator is described by analyzing the motion characteristic of the chaotic oscillator on the basis of the van der Pol equation. Furthermore, the Floquet index for measuring the amplitude of periodic narrowband signals is redefined. The denoising signal processed by the chaotic van der Pol oscillators is further processed by wavelet analysis. Finally, the denoising results verify that the periodic narrowband and white noise interference can be removed efficiently by combining the theory of the chaotic van der Pol oscillator and wavelet analysis.
A combinatorial algorithm for visualizing representatives with minimal self-intersection
Authors: Arettines Chris
Published: September 2015

Given an orientable surface with boundary and a free homotopy class of a closed curve on this surface, we present a purely combinatorial algorithm which produces a representative of that homotopy class with minimal self-intersection.
On permutation polynomials over finite fields of characteristic 2
Authors: Gupta Rohit , Sharma R. K.
Published: September 2015

Let [Formula: see text] denotes the finite field of order [Formula: see text] where [Formula: see text] A permutation polynomial [Formula: see text] over [Formula: see text] with [Formula: see text] and [Formula: see text] such that for each [Formula: see text] is a permutation polynomial satisfying [Formula: see text] is called a o-polynomial. In this paper, we determine all o-polynomials up to degree [Formula: see text].
On graded Brown–McCoy radicals of graded rings
Authors: Ilić-Georgijević Emil
Published: September 2015

We investigate the graded Brown–McCoy and the classical Brown–McCoy radical of a graded ring, which is the direct sum of a family of its additive subgroups indexed by a nonempty set, under the assumption that the product of homogeneous elements is again homogeneous. There are two kinds of the graded Brown–McCoy radical, the graded Brown–McCoy and the large graded Brown–McCoy radical of a graded ring. Several characterizations of the graded Brown–McCoy radical are given, and it is proved that the large graded Brown–McCoy radical of a graded ring is the largest homogeneous ideal contained in the classical Brown–McCoy radical of that ring.
First cohomology of 𝔞𝔣𝔣(1) and 𝔞𝔣𝔣(1|1) acting on linear differential operators
Authors: Basdouri Imed , Boujelben Maha , Derbali Ammar
Published: September 2015

We consider the [Formula: see text]-module structure on the spaces of differential operators acting on the spaces of weighted densities. We compute the first differential cohomology of the Lie superalgebra [Formula: see text] with coefficients in differential operators acting on the spaces of weighted densities. We study also the super analogue of this problem getting the same results.
A survey of corneal changes caused by daily wear silicone hydrogel contact lenses
Authors: Kettesy Beata , Vardai Julianna , Berta Andras , Modis Laszlo , Kemeny-Beke Adam
Published: September 2015

Purpose: The examination of the effects of second generation lotrafilcon B silicone hydrogel (SiH) lenses on the cornea when worn for three years of daily wear. Material and Methods: 55 healthy patients were divided into two groups: current hydrogel contact lens wearers refitted with lotrafilcon B lenses (Group 1; 28 patients) and neophyte contact lens wearers (Group 2; 27 patients). Each patient's subjective eye comfort was measured with a self-administered questionnaire. The corneas were analyzed using contact specular microscope to measure corneal thickness and the endothelium before the SiH lenses were fitted after four weeks, one month, six months, one year, two years, and three years of lens wear. Results: Subjective complaints of patients in Group 1 were reduced; however patients in Group 2 experienced discomfort during the first two to four weeks of use. In Group 1, objective examinations identified a decrease in endothelial cell density. In Group 2, the endothelial cell density increased slightly in the first two years but decreased after three years. The results indicate that lotrafilcon B slows down the deleterious effects of contact lenses. The coefficient of variation significantly decreased after six months in Group 1 (0.47 vs 0.44; p = 0.049), whereas, in Group 2, the hexagonal cells improved significantly after one month (27.78 vs 28.25; p = 0.025). Conclusion: Based on the subjects involved and the period of time under examination, it can be concluded that high-Dk SiH lenses support the physiological metabolism and functions of the cornea by improving oxygen provision.
Blood-brain barrier and cerebral blood flow: Age differences in hemorrhagic stroke
Authors: Oxana Semyachkina-Glushkovskaya , Olga Sindeeva , Arkady Abdurashitov , Sergey Sindeev , Ekaterina Zinchenko , Artem Gekaluk , Maria Ulanova , Kassim Mohanad , Ludmila Yankovskaya , Valery Tuchin
Published: September 2015

Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits. There are important differences in the factors, clinical events and outcomes associated with the stroke in infants and adults. However, mechanisms underlying age differences in the stroke development remain largely unknown. Therefore, treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children. The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke. Here, we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats. Using histological methods and magnetic resonance imaging, we found age differences in the type of intracranial hemorrhages. Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum. Using Doppler optical coherent tomography, we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs. adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs. adult brain in rats. However, adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier (BBB) permeability. The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB (occludin and claudin-5) in neonatal vs. mature brain in rats.
Anode property of carbon coated LiFePO4 nanocrystals
Authors: Ni Jiangfeng , Jiang Jiaxing , Savilov S. V. , Aldoshin S. M.
Published: September 2015

Nanostructured LiFePO4 is appealing cathode material for rechargeable lithium batteries. Herein, however, we report the intriguing anode properties of carbon coated LiFePO4 nanocrystals. In the potential range of 0–3.0 V, the LiFePO4 nanocrystal electrodes afford high reversible capacity of 373 mAh[Formula: see text]g[Formula: see text] at a current rate of 0.05 A[Formula: see text]g[Formula: see text] and retains 239 mAh[Formula: see text]g[Formula: see text] at a much higher rate of 1.25 A[Formula: see text]g[Formula: see text]. In addition, it is capable of sustaining 1000 cycles at 1.25 A[Formula: see text]g[Formula: see text] without any capacity fading. Such superior properties indicate that nanostructured LiFePO4 could also be promising anode for rechargeable battery applications.
Chronic high-fat feeding increases GIP and GLP-1 secretion without altering body weight
Authors: Wang Fei , Yoder Stephanie M. , Yang Qing , Kohan Alison B. , Kindel Tammy L. , Wang Jacob , Tso Patrick
Published: September 2015

The incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), enhance postprandial insulin secretion, promote adipogenesis, and regulate gastrointestinal motility and food intake. To date, a consensus on how the incretin response is altered in obesity is lacking. We investigated the effects of chronic high-fat (HF) feeding on incretin secretion in the lymph fistula rat model. Male Sprague-Dawley rats (8 wk) were provided a semipurified AIN93M HF or low-fat (LF) diet ad libitum for 3 or 13 wk; a HF pair-fed (HF-PF) group was included as a control during the 3-wk feeding trial. Energy intake, body weight, and body composition were regularly monitored. At the culmination of the feeding period, an intestinal lymphatic duct cannula and duodenal infusion tube were installed. All animals were challenged with a 3-ml Ensure bolus (3.125 kcal/animal) to measure lymphatic incretin secretion. Despite a significantly higher energy intake, both the 3-wk and 13-wk HF-fed animals did not have an increase in body weight and only a slight increase in body fat compared with LF-fed rats. Following the duodenal Ensure challenge, the 3-wk and 13-wk HF-fed rats had significantly greater lymphatic GIP and GLP-1 secretion than the LF-fed animals. Additionally, the HF-PF group displayed a secretion profile similar to the HF-fed animals for GIP but a similar pattern to the LF-fed animals for GLP-1. The HF-PF data suggest that the increased GIP secretion is driven by the greater percentage of fat intake, whereas the increased GLP-1 secretion is driven by the excess caloric intake.
Tumors and Mitochondrial Respiration: A Neglected Connection
Authors: Viale Andrea , Corti Denise , Draetta Giulio F.
Published: September 2015

For decades, tumor cells have been considered defective in mitochondrial respiration due to their dominant glycolytic metabolism. However, a growing body of evidence is now challenging this assumption, and also implying that tumors are metabolically less homogeneous than previously supposed. A small subpopulation of slow-cycling cells endowed with tumorigenic potential and multidrug resistance has been isolated from different tumors. Deep metabolic characterization of these tumorigenic cells revealed their dependency on mitochondrial respiration versus glycolysis, suggesting the existence of a common metabolic program active in slow-cycling cells across different tumors. These findings change our understanding of tumor metabolism and also highlight new vulnerabilities that can be exploited to eradicate cancer cells responsible for tumor relapse. Cancer Res; 75(18); 3687–91. ©2015 AACR.
Effect of a Three-Week Inpatient Rehabilitation Program on 544 Consecutive Patients with Very Severe COPD: A Retrospective Analysis
Authors: Greulich Timm , Koczulla Andreas Rembert , Nell Christoph , Kehr Katharina , Vogelmeier Claus F. , Stojanovic Dragan , Wittmann Michael , Schultz Konrad
Published: September 2015

Background: Pulmonary rehabilitation improves exercise capacity, symptoms, and quality of life in chronic obstructive pulmonary disease (COPD) patients, and is therefore recommended in all stages of the disease. However, there are insufficient data on patients with very severe disease. Objective: To describe the effect of an in-house multidisciplinary pulmonary rehabilitation program on patients with very severe COPD. Methods: We performed a retrospective analysis of 544 consecutive patients with very severe COPD (FEV1 0.97 ± 0.26 l) that underwent an in-house pulmonary rehabilitation program (23.44 ± 4.97 days). The studied outcome parameters were the 6-min walk test (6-MWT), health-related quality of life as analyzed by the COPD Assessment Test (CAT) and a dyspnea score [modified Medical Research Council (mMRC) scale], and lung function [forced expiratory volume in 1 s (FEV1) and residual volume (RV)]. Results: We found significant improvements regarding 6-MWT scores (from 321.93 ± 115.67 to 365.82 ± 111.79 m; p < 0.001), CAT scores (from 23.21 ± 6.75 to 19.57 ± 7.35; p < 0.001), mMRC scale scores (from 3.17 ± 1.14 to 2.81 ± 1.22; p < 0.001), and FEV1 (from 0.97 ± 0.26 to 1.08 ± 0.33 l; p < 0.001). A number of baseline variables were significantly correlated with the improvements that occurred during the program (Δ): baseline 6-MWT with Δ6-MWT (r = -0.316; p < 0.001), baseline CAT with ΔCAT (r = -0.302; p < 0.001), baseline mMRC with ΔmMRC (r = -0.444; p < 0.001), and baseline RV with ΔRV (r = -0.284; p < 0.001), demonstrating that improvements were more pronounced in patients with worse baseline characteristics. Patients on long-term oxygen therapy (LTOT) exhibited significantly greater improvements regarding CAT than patients not on LTOT. Conclusion: Patients with very severe COPD exhibit clinically meaningful improvements when undergoing pulmonary rehabilitation.
Comparing Clinical Outcomes in Upper versus Lower Lobe Endobronchial Valve Treatment in Severe Emphysema
Authors: Eberhardt Ralf , Herth Felix J.F. , Radhakrishnan Sri , Gompelmann Daniela
Published: September 2015

Background: Lung volume reduction surgery has been recommended for patients with upper lobe predominant emphysema and was associated with less favorable outcomes in patients with non-upper lobe predominant emphysema. The value of endobronchial valve (EBV) treatment in lower lobe predominant emphysema has not been studied. Objectives: To confirm the equivalence of upper and lower lobe valve treatments in patients with heterogeneous emphysema. Methods: A retrospective analysis from the Endobronchial Valve for Emphysema Palliation Trial (VENT), where patients with heterogeneous emphysema received Zephyr® EBV (Pulmonx Corp., Redwood City, Calif., USA) or medical treatment, was performed. Patients with low interlobar collateral ventilation and accurate placement of valves in the target lobes were identified. Safety and efficacy were compared between patients who underwent upper versus lower lobe treatment. Results: Of the 331 patients, 60 had low interlobar collateral ventilation and successful lobar exclusion (45 patients with upper lobe treatment and 15 patients with lower lobe treatment). There was no difference in baseline characteristics between the groups except for a higher destruction score (70.3 vs. 60.7%; p = 0.0010) and a higher heterogeneity index (24 vs. 13%; p = 0.0005) for the upper lobe cohort. At 180 days, both groups had improved clinically. There were no significant differences in mean changes or responder rates of forced expiratory volume in 1 s (+23.8 vs. +22.9%), the St. Georges Respiratory Questionnaire (-6.50 vs. -7.53 points), the 6-min walk test (+24.1 vs. +44.0 m), target lobe volume reduction (-1,199 vs. -1,042 ml), or in the adverse event rate between both cohorts. Conclusion: Patients with lower and upper lobe predominant emphysema benefit equally from EBV therapy when interlobar collateral ventilation is low and lobar exclusion is achieved. Patients with lower lobe disease did not have increased adverse events compared to patients with upper lobe emphysema.
Increased Urinary Excretion of Podocyte Markers in Normoalbuminuric Patients with Diabetes
Authors: Lioudaki Eirini , Stylianou Konstantinos G. , Petrakis Ioannis , Kokologiannakis Georgios , Passam Andreas , Mikhailidis Dimitri P. , Daphnis Eugene K. , Ganotakis Emmanouil S.
Published: September 2015

Background: Podocyte injury plays a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). We investigated whether patients with diabetes mellitus (DM) without overt DN present podocyte markers in urine suggestive of early podocyte injury. Methods: We studied 71 patients with DM type 2 and normal urine albumin excretion (UAE) and 39 non-diabetic controls. The mRNA abundance of 3 podocyte-specific markers in urinary sediment (nephrin, podocin and synaptopodin) was measured with real-time quantitative PCR. All the subjects were categorized according to their urinary podocyte marker profile into 2 groups, those with only synaptopodin mRNA presence (synaptopodin only group) and those with nephrin and/or podocin mRNA presence in addition to synaptopodin in their urine (nephrin and/or podocin group). Results: Synaptopodin mRNA was detected in the urine of all the diabetics and controls. The presence of nephrin and/or podocin mRNA in urine was more frequent among DM patients compared to controls (53.5 vs. 30.8%, respectively; p = 0.022). Binary logistic regression analysis revealed that the only significant predictor of the presence of nephrin and/or podocin mRNA in urine was the presence of DM (OR 2.59, 95% CI 1.14-5.91, p = 0.024, adjusted for all risk factors). A strong correlation between nephrin and podocin urinary mRNA levels was noted (r = +0.796, p < 0.001). Conclusion: This study demonstrated that urinary podocyte markers are more prevalent in diabetic patients with normal UAE compared to controls, and this may reflect early podocyte injury. DM is the only significant determinant of the presence of nephrin and/or podocin mRNA in urine in this population. Therefore, urinary podocyte markers may emerge as a valuable tool in the early diagnosis of DN.
Applying Genomics and Proteomics in Translational Surgical Oncology Research
Authors: Gemoll Timo , Meyer Rüdiger , Habermann Jens K.
Published: September 2015

Background: Translational surgical research can range from investigating clinically oriented basic pathophysiological research via the correlation of molecular findings with a patient's clinical outcome to conducting treatment response studies. Herein, the specialist's opinion as a ‘surgeon scientist' plays a pivotal role, e.g. in planning experimental setups focusing on the clinically most relevant needs. Summary and Key Messages: This review provides a survey of genomic and proteomic technologies and gives an up-to-date overview of those studies applying these technologies exemplarily in colorectal cancer-based biomarker research. Although current results are promising, future validation studies within multicenter networks are required to promote the translation of ‘omics' from bench to bedside. In this endeavor, departments of surgery and institutes of experimental surgery together should play a fundamental role. The program for ‘clinician scientists' recently launched by the German Research Society (DFG) could be one tool to promote interdisciplinary networks and surgeons' impact on translational research.
Two Novel HOGA1 Splicing Mutations Identified in a Chinese Patient with Primary Hyperoxaluria Type 3
Authors: Wang Xinsheng , Zhao Xiangzhong , Wang Xiaoling , Yao Jian , Zhang Feifei , Lang Yanhua , Tuffery-Giraud Sylvie , Bottillo Irene , Shao Leping
Published: September 2015

Background: Twenty-six HOGA1 mutations have been reported in primary hyperoxaluria (PH) type 3 (PH3) patients with c.700 + 5G>T accounting for about 50% of the total alleles. However, PH3 has never been described in Asians. Methods: A Chinese child with early-onset nephrolithiasis was suspected of having PH. We searched for AGXT, GRHPR and HOGA1 gene mutations in this patient and his parents. All coding regions, including intron-exon boundaries, were analyzed using PCR followed by direct sequence analysis. Results: Two heterozygous mutations not previously described in the literature about HOGA1 were identified (compound heterozygous). One mutation was a successive 2 bp substitution at the last nucleotide of exon 6 and at the first nucleotide of intron 6, respectively (c.834_834 + 1GG>TT), while the other one was a guanine to adenine substitution of the last nucleotide of exon 6 (c.834G>A). Direct sequencing analysis failed to find these mutations in 100 unrelated healthy subjects and the functional role on splicing of both variants found in this study was confirmed by a minigene assay based on the pSPL3 exon trapping vector. In addition, we found a SNP in this family (c.715G>A, p.V239I). There were no mutations detected in AGXT and GRHPR. Conclusion: Two novel HOGA1 mutations were identified in association with PH3. This is the first description and investigation on mutant gene analysis of PH3 in an Asian.
Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Reversed Flow Direction
Authors: Heuslein Joshua L. , Meisner Joshua K. , Li Xuanyue , Song Ji , Vincentelli Helena , Leiphart Ryan J. , Ames Elizabeth G. , Blackman Brett R. , Price Richard J.
Published: September 2015

Objective—

Collateral arteriogenesis, the growth of existing arterial vessels to a larger diameter, is a fundamental adaptive response that is often critical for the perfusion and survival of tissues downstream of chronic arterial occlusion(s). Shear stress regulates arteriogenesis; however, the arteriogenic significance of reversed flow direction, occurring in numerous collateral artery segments after femoral artery ligation, is unknown. Our objective was to determine if reversed flow direction in collateral artery segments differentially regulates endothelial cell signaling and arteriogenesis.

Approach and Results—

Collateral segments experiencing reversed flow direction after femoral artery ligation in C57BL/6 mice exhibit increased pericollateral macrophage recruitment, amplified arteriogenesis (30% diameter and 2.8-fold conductance increases), and remarkably permanent (12 weeks post femoral artery ligation) remodeling. Genome-wide transcriptional analyses on human umbilical vein endothelial cells exposed to reversed flow conditions mimicking those occurring in vivo yielded 10-fold more significantly regulated transcripts, as well as enhanced activation of upstream regulators (nuclear factor κB [NFκB], vascular endothelial growth factor, fibroblast growth factor-2, and transforming growth factor-β) and arteriogenic canonical pathways (protein kinase A, phosphodiesterase, and mitogen-activated protein kinase). Augmented expression of key proarteriogenic molecules (Kruppel-like factor 2 [KLF2], intercellular adhesion molecule 1, and endothelial nitric oxide synthase) was also verified by quantitative real-time polymerase chain reaction, leading us to test whether intercellular adhesion molecule 1 or endothelial nitric oxide synthase regulate amplified arteriogenesis in flow-reversed collateral segments in vivo. Interestingly, enhanced pericollateral macrophage recruitment and amplified arteriogenesis was attenuated in flow-reversed collateral segments after femoral artery ligation in intercellular adhesion molecule 1
−/−
mice; however, endothelial nitric oxide synthase
−/−
mice showed no such differences.

Conclusions—

Reversed flow leads to a broad amplification of proarteriogenic endothelial signaling and a sustained intercellular adhesion molecule 1–dependent augmentation of arteriogenesis. Further investigation of the endothelial mechanotransduction pathways activated by reversed flow may lead to more effective and durable therapeutic options for arterial occlusive diseases.
Clinical and Prognostic Impact of a New Left Ventricular Ejection Index in Primary Mitral Regurgitation Because of Mitral Valve Prolapse
Authors: Magne Julien , Szymanski Catherine , Fournier Alexandre , Malaquin Dorothée , Avierinos Jean François , Tribouilloy Christophe
Published: September 2015

Background—

To prevent left ventricular dysfunction (LVD), surgery is recommended in patients with severe primary mitral regurgitation as soon as ejection fraction (EF) ≤60% or LV end-systolic diameter ≥40 mm. However, LVD may be concealed behind preoperative normal LVEF and LV end-systolic diameter. We sought to identify whether a new composite echocardiographic Doppler marker of the LV ejection according to the LV dilatation may predict postoperative LVD and outcome after mitral valve repair in patients with primary mitral regurgitation.

Methods and Results—

Between 1991 and 2010, patients who underwent mitral valve repair for primary mitral regurgitation were studied. From preoperative echocardiography, we calculated LV ejection index (LVEI) using following formula: LVEI=indexed LV end-systolic diameter/LV outflow tract time–velocity integral. In the 278 patients included, the best correlation with postoperative LVEF was found with LVEI (
r
=−0.40;
P
<0.0001), even in patients with preoperative LVEF≥60% (
r
=−0.46;
P
<0.0001). In multivariable analysis, LCEI>1.13 was an independent predictor of postoperative LVD (
P
<0.0001). During a mean follow-up of 10±4.6 years, 67 (29%) deaths occurred. When compared with patients with preserved LVEI, those with LVEI>1.13 had significantly lower both survival and cardiac death–free survival (
P
=0.017 and
P
=0.008, respectively). Similar results were found in patients with preoperative LVEF≥60% (
P
=0.049 and
P
=0.016, respectively). In Cox proportional hazard model, after meticulous adjustment for cofactors, LVEI>1.13 remains independently associated with death (hazard ratio, 1.64;
P
=0.039) and cardiac-related death (hazard ratio, 3.27;
P
=0.026).

Conclusions—

After mitral valve repair for primary mitral regurgitation, the preoperative LVEI is a new and simple composite parameter of both LV dilatation and LV forward flow able to accurately predict postoperative LVD and outcome.
Biological Effects of Cardiac Magnetic Resonance on Human Blood Cells
Authors: Lancellotti Patrizio , Nchimi Alain , Delierneux Céline , Hego Alexandre , Gosset Christian , Gothot André , Jean-Flory Tshibanda Luaba , Oury Cécile
Published: September 2015

Background—

Cardiac magnetic resonance (CMR) is increasingly used for the diagnosis and management of cardiac diseases. Recent studies have reported immediate post-CMR DNA double-strand breaks in T lymphocytes. We sought to evaluate CMR-induced DNA damage in lymphocytes, alterations of blood cells, and their temporal persistence.

Methods and Results—

In 20 prospectively enrolled healthy men (31.4±7.9 years), blood was drawn before and after (1–2 hours, 2 days, 1 month, and 1 year) unenhanced 1.5T CMR. Blood cell counts, cell death, and activation status of lymphocytes, monocytes, neutrophils, and platelets were evaluated. The first 2-hour post-CMR were characterized by a small increase of lymphocyte B and neutrophil counts and a transient drop of total lymphocytes because of a decrease in natural killer cells. Among blood cells, only neutrophils and monocytes displayed slight and transient activation. DNA double-strand breaks in lymphocytes were quantified through flow cytometric analysis of H2AX phosphorylation (γ-H2AX). γ-H2AX intensity in T lymphocytes did not change early after CMR but increased significantly at day 2 ≤1 month before returning to baseline levels of 1-year post-CMR.

Conclusions—

Unenhanced CMR is associated with minor but significant immediate blood cell alterations or activations figuring inflammatory response, as well as DNA damage in T lymphocytes observed from day 2 until the first month but disappearing at 1-year follow-up. Although further studies are required to definitely state whether CMR can be used safely, our findings already call for caution when it comes to repeat this examination within a month.
Direct Transfer From the Referring Hospitals to the Catheterization Laboratory to Minimize Reperfusion Delays for Primary Percutaneous Coronary Intervention
Authors: Anderson Lindsay L , French William J , Peng S. Andrew , Vora Amit N , Henry Timothy D , Roe Matthew T , Kontos Michael C , Granger Christopher B , Bates Eric R , Hellkamp Anne , Wang Tracy Y
Published: September 2015

Background—

For patients with ST-segment–elevation myocardial infarction (STEMI) requiring interhospital transfer for primary percutaneous coronary intervention, direct transfer from the STEMI referral hospital to the catheterization laboratory (cath lab) at the STEMI receiving hospital may expedite reperfusion, but can be logistically challenging.

Methods and Results—

We studied 33 901 STEMI patients transferred for primary percutaneous coronary intervention in the Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines from July 2008 to December 2012. The majority of patients were transferred directly to the cath lab (26 510 [78.2%]), and 7391 patients (21.8%) were transferred first to the hospital emergency department/ward. We observed significant interhospital variation in transfer patterns; only 21% of STEMI receiving hospitals routinely transferred >90% of STEMI patients to the cath lab directly. Compared with patients transferred first to the emergency department/ward, STEMI patients transferred to the cath lab had significantly lower first door-to-balloon times (median 191 versus 116 minutes,
P
<0.0001). After multivariable logistic regression, patients transferred directly to the cath lab also had lower adjusted mortality risk (odds ratio 0.58, 95% confidence interval 0.51–0.66,
P
<0.0001). Cardiogenic shock, heart failure signs/symptoms, and nonsystem reasons for reperfusion delay were present in 11%, 15%, and 28% of patients transferred first to the emergency department/ward, respectively. The association of direct cath lab transfer with lower mortality persisted after excluding patients with these reasons for delay to primary percutaneous coronary intervention (adjusted odds ratio 0.62, 95% confidence interval 0.46–0.84,
P
=0.002).

Conclusions—

Direct transfer of STEMI patients to the cath lab for primary percutaneous coronary intervention was associated with significantly faster reperfusion and lower mortality risk compared with transfer first to the emergency department/ward.