bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic differences among never, occasional and moderate alcohol users in southern China, and its use in alcohol research: a cross-sectional study
Authors: Yeung S L Au , Jiang C Q , Zhang W S , Lam T H , Cheng K K , Leung G M , Schooling C M
Published: August 2013

Background

Western observational studies show moderate alcohol use, compared with never use, positively associated with health. Moderate users differ systematically from others, making these observations vulnerable to confounding. Observations from other contexts may help distinguish whether these associations are confounded. To assess whether southern Chinese would provide a more suitable setting to examine the association of moderate alcohol use with health, we compared never alcohol users with moderate alcohol users and occasional users in this setting.

Methods

We used age-adjusted multinomial regression to assess sex-stratified associations of alcohol use (never, occasional (<1 occasion/week), moderate (≤140 g ethanol/week for women and ≤210 g for men)) with health attributes and indicators in the Guangzhou Biobank Cohort Study (2003–2008) (n=26 361).

Results

Among men, moderate alcohol users, when compared with never users, had slightly lower socioeconomic position and unhealthier lifestyle. Conversely, occasional alcohol users, when compared with never users, had higher socioeconomic position and healthier lifestyle. Among women, when compared with never users, both occasional and moderate users had higher socioeconomic position and healthier lifestyle. However, all alcohol users for both sexes, when compared with never users, were more likely to be ever smokers and to be exposed to secondhand smoke.

Conclusions

Observations in alcohol epidemiology may be affected by confounding due to contextually specific systematic differences. Results from a particular setting should not be interpreted as causal unless they are verified in different populations and, preferably, in non-observational studies.
Embryological studies in Taraxacum udum Jordan (sect. Palustria)
Authors: Musiał Krystyna , Górka Patrycja , Kościńska-Pająk Maria , Marciniuk Paweł
Published: August 2013

The present paper reports our observations on the mode of reproduction in Taraxacum udum (sect. Palustria), a very rare species in Poland, known only from a single locality. Based on the analysis of the developmental processes in the ovules, it can be concluded that this bog dandelion is an obligate and autonomous apomict. Its reproduction involves (i) restitutional diplospory, also known as Taraxacum type; (ii) parthenogenesis; and (iii) autonomous endosperm formation. Moreover, observations on the anatomy of ovules confirmed the occurrence of a special storage tissue around the embryo sac, which is considered to be an additional source of nutrition for the embryo. An examination of the anthers showed that, in spite of highly disturbed meiosis, apomictic T. udum produces pollen but pollen grains are heterogeneous in size and stainable using an acetocarmine test.
JOINT MAINTENANCE AND SPARE COMPONENT PROVISIONING POLICY FOR k-OUT-OF-n SYSTEMS
Authors: CHEN LIANGPENG , YE ZHI-SHENG , XIE MIN
Published: August 2013

This study develops an analytic framework for joint modeling of age-based preventive maintenance and (s, Q) spare component provisioning policy for k-out-of-n:G systems with i.i.d. nonrepairable components. We assume that during system maintenance, instead of discarding the whole system, only failed components are replaced by spares if the on-handspares are sufficient. The objective is to determine a proper preventive maintenance interval and the ordering parameters to minimize the undiscounted long run average cost under a system availability constraint. Our study sheds light on the lumpy demand scenario in the problems of joint modeling of preventive maintenance and spare provisioning.
CALABI–YAU GEOMETRIES: ALGORITHMS, DATABASES AND PHYSICS
Authors: HE YANG-HUI
Published: August 2013

With a bird's-eye view, we survey the landscape of Calabi–Yau threefolds, compact and noncompact, smooth and singular. Emphasis will be placed on the algorithms and databases which have been established over the years, and how they have been useful in the interaction between the physics and the mathematics, especially in string and gauge theories. A skein which runs through this review will be algorithmic and computational algebraic geometry and how, implementing its principles on powerful computers and experimenting with the vast mathematical data, new physics can be learnt. It is hoped that this interdisciplinary glimpse will be of some use to the beginning student.
AN L1-REGULARIZED NAÏVE BAYES-INSPIRED CLASSIFIER FOR DISCARDING REDUNDANT AND IRRELEVANT PREDICTORS
Authors: VIDAURRE DIEGO , BIELZA CONCHA , LARRAÑAGA PEDRO
Published: August 2013

The naïve Bayes model is a simple but often satisfactory supervised classification method. The original naïve Bayes scheme, does, however, have a serious weakness, namely, the harmful effect of redundant predictors. In this paper, we study how to apply a regularization technique to learn a computationally efficient classifier that is inspired by naïve Bayes. The proposed formulation, combined with an L1-penalty, is capable of discarding harmful, redundant predictors. A modification of the LARS algorithm is devised to solve this problem. We tackle both real-valued and discrete predictors, assuring that our method is applicable to a wide range of data. In the experimental section, we empirically study the effect of redundant and irrelevant predictors. We also test the method on a high dimensional data set from the neuroscience field, where there are many more predictors than data cases. Finally, we run the method on a real data set than combines categorical with numeric predictors. Our approach is compared with several naïve Bayes variants and other classification algorithms (SVM and kNN), and is shown to be competitive.
A THEORETICAL FRAMEWORK FOR TRUST-BASED NEWS RECOMMENDER SYSTEMS AND ITS IMPLEMENTATION USING DEFEASIBLE ARGUMENTATION
Authors: BRIGUEZ CRISTIAN E. , CAPOBIANCO MARCELA , MAGUITMAN ANA G.
Published: August 2013

Although the importance of trust in recommender systems is widely recognized, the actual mechanisms of trust propagation and trust preservation are poorly understood. This is partly due to the fact that trust is a complex notion, which is typically context dependent, subjective, dynamic and not always transitive or symmetrical. This paper presents a theoretical analysis of the notion of trust in news recommendation and discusses the advantages of modeling this notion using Defeasible Logic Programming, a general-purpose defeasible argumentation formalism based on logic programming. In the proposed framework, users can express explicit trust statements on news reports, news sources and other users. Trust is then modeled and propagated using a dialectical process supported by a Defeasible Logic Programming interpreter. A set of basic postulates for trust and their representation by means of defeasible rules is presented. The suitability of the approach is investigated with a set of illustrative examples and then analyzed from a formal perspective. The obtained results indicate that the proposed framework provides a solid foundation for building trust-based news recommendation services.
A MEASUREMENT APPROACH FOR OVERCOMING UNBALANCED OVERWORK IN MULTI-AGENT SYSTEMS
Authors: GUTIÉRREZ CELIA , GARCÍA-MAGARIÑO IVÁN
Published: August 2013

Overworking behaviors appear in multi-agent systems specially when there are unbalanced communication patterns. This occurs when an agent receives many messages in a short period of time in comparison to other agents. As the agent pays attention to the large amount of messages, it worsens its performance, causing the system's performance to worsen as well, while other agents with similar services can be idle. The reasons for these behaviors are varied and depend on the nature of the messages. This article presents a measurement approach that detects unbalanced overworking situations in multi-agent systems with a new metric. Moreover, this approach includes a set of recommendations that determine possible common causes of this defective behavior depending on the relations of different measurement values. These recommendations also propose a solution for repairing each cause, suppressing these unbalanced overworking situations. A tool has been developed for allowing designers to measure the agents' communications, to obtain the diagnosis, and to know the recommended solutions. The current work has been applied in two case studies, whose results advocate that the suppression of unbalanced overworking situations is strongly related to the improvement of performance in multi-agent systems. Furthermore, the experience of this approach in nine different problem domains is presented as support for the causes and solutions of the set of recommendations.
QUANTUM RAINBOW COSMOLOGICAL MODEL WITH PERFECT FLUID
Authors: MAJUMDER BARUN
Published: August 2013

Isotropic quantum cosmological perfect fluid model is studied in the formalism of Rainbow gravity. It is found that the only surviving matter degree of freedom played the role of cosmic time. With the suitable choice of the Rainbow functions it is possible to find the wave packet naturally from the superposition of the wave functions of the Schrödinger–Wheeler–deWitt equation. The many-worlds interpretation of quantum mechanics is applied to investigate the behavior of the scale factor and the behavior is found to depend on the operator ordering. It is shown that the model in the Rainbow framework may avoid singularity yielding a bouncing nonsingular universe.
APPLICATION OF THE FINITE STRIP METHOD TO MODELING OF VIBRATIONS OF COLLECTING ELECTRODES
Authors: ADAMIEC-WÓJCIK IWONA , NOWAK ANDRZEJ , WOJCIECH STANISŁAW
Published: August 2013

The paper presents an application of the finite strip method to modeling of vibrations of the collecting electrodes, which are shells with large length (up to 16 m), width of 0.5 m and thickness of 0.002 m. The models and computer programs have been worked out and validated. Comparison of results obtained from numerical simulations and experimental measurements are presented and discussed. The equations of motion have been solved using methods for solution of sparse algebraic equations and Newmark method. The strip method has proved to be numerically effective. The programs enable us to carry out calculations for a system with several hundred thousands of degrees of freedom with time of analysis requiring thousand integration steps during less than 90 min on a PC computer. High numerical efficiency enables the geometrical parameters of the collecting electrodes to be selected in order to ensure large accelerations caused by a beater to be spread evenly over the surface of the electrodes. Conclusions concerning the influence of length of the collecting electrodes on the normal and tangentz accelerations are formulated.
INTER-QUARTILE RANGE APPROACH TO LENGTH–INTERVAL ADJUSTMENT OF ENROLLMENT DATA IN FUZZY TIME SERIES FORECASTING
Authors: ISMAIL ZUHAIMY , EFENDI RISWAN , DERIS MUSTAFA MAT
Published: August 2013

Various methods have been presented to investigate the length of data interval and partition number of universe of discourse in fuzzy time series to achieve high level forecasting accuracy. However, the interval length is still an issue and thus, influencing the forecasting accuracy. This paper proposes a new approach using the average inter-quartile range to improve the interval length and subsequently the partition number of universe of discourse. Moreover, in forecasting method, the first-differencing data is also considered to obtain better forecast. The enrollment data of Alabama University is used as an example and the efficiency of the proposed method is compared with the previous methods. The result shows that the proposed method improves the accuracy and efficiency of the yearly enrollment forecasting opportunities.
The Making of the 18th Party Central Committee: Progress and Problems of Institutionalisation
Authors: GORE Lance L P
Published: August 2013

Has Chinese elite politics attained a level of institutionalisation that long-term stability can be expected? This article explains the six-phased cadre performance evaluation system widely adopted at local power succession process and analyses the ways in which this system was selectively used in the making of the 18th Party Central Committee. Despite the various loopholes, the system does impose some constraints on arbitrary power; its wide adoption at the lower levels and the flatter power distribution enhance its legitimacy and promotes its institutionalisation.
Political Economy of Japanese Free Trade Network with ASEAN: Implications for Sino-Japanese Rivalry in East Asia
Authors: YAMAMOTO Chika
Published: August 2013

Many scholars have argued that Japanese involvement in free trade agreements (FTA) with the Association of Southeast Asian Nations (ASEAN) is part of a regional competition with China over leadership in East Asia. However, this paper redefines the vigorous Japanese pursuit of FTA policies with ASEAN as an essential agenda to serve various economic and political domestic interests of Japan.
The 2012 Diaoyu Islands Contretemps
Authors: TSENG Katherine Hui-yi
Published: August 2013

The Diaoyu Islands issue had again stirred up diplomatic rows between China and Japan and has further cast a shadow over structural issues like US-Japan alliance and China's foreign and security policies. The 2012 rows were caused by Japan's nationalisation of the islands. Ensuing miscalculation further exacerbated the dispute which has entered a new stage that requires new perceptions, efficient measures and firmer political wills for conflict management and peaceful resolution.
Magnetic diversion for electronic switches
Authors: Edwards Chris
Published: August 2013

'Chameleon processors' could function as programmable logic or nonvolatile memory.
Software-defined networking
Authors: Kirkpatrick Keith
Published: August 2013

Novel architecture allows programmers to quickly reconfigure network resource usage.
Ephemeral data
Authors: Shein Esther
Published: August 2013

Privacy issues can evaporate when embarrassing content does likewise.
20 obstacles to scalability
Authors: Hull Sean
Published: August 2013

Watch out for these pitfalls that can prevent Web application scaling.
The balancing act of choosing nonblocking features
Authors: Michael Maged M.
Published: August 2013

Design requirements of nonblocking systems.
Puzzled: Solutions and sources
Authors: Winkler Peter
Published: August 2013

Last month (Aug. 2013) you needed to win several chess games in a row, alternately playing white and black, and had to decide with which color you should start.
Uncomfortable user experience
Authors: Benford Steve , Greenhalgh Chris , Giannachi Gabriella , Walker Brendan , Marshall Joe , Rodden Tom
Published: August 2013

How to create and resolve discomfort for a thrilling and memorable experience.
Advancing theory through the conceptualization and development of causal attributions for computer performance histories
Authors: Kelley Helen , Compeau Deborah , Higgins Christopher A. , Parent Michael
Published: August 2013

Attribution theory, advanced by Bernard Weiner and his colleagues is an important, though sometimes controversial, theory that has demonstrated vitality and longevity. The cross-disciplinary application of attribution theory to, for example, organizational behavior, marketing, and education, has stimulated the interests of researchers and contributed to its theoretical validity and reliability. Compared to other disciplines, the application and theoretical testing of attribution theory are in the "spring" of their existence in the field of Information Systems (IS). This paper proposes that conceptualization and measurement of the causal attributions individuals make for their computer performance and performance histories, positive and negative, are critical to understanding computer adoption and post-adoption behaviors. We first identify the causal attributions that enterprise resource planning (ERP) users make for their computer performance histories. We then describe the conceptualization and development of multi-item scales to capture these causal attributions. This work contributes to theory and practice through (1) the development and psychometric testing of several attributional scales for advancing our understanding of the multi-theoretical stream of research investigating technology adoption at the individual level, and (2) by providing a description of a theoretical multi-method approach for the rigorous scale development of causal attributions. Our work suggests that researchers must consider several fundamental principles of attribution theory when investigating IS artifacts during various adoption phases.
Aspirin augments carotid-cardiac baroreflex sensitivity during muscle mechanoreflex and metaboreflex activation in humans
Authors: Drew Rachel C. , Muller Matthew D. , Blaha Cheryl A. , Mast Jessica L. , Herr Michael D. , Stocker Sean D. , Sinoway Lawrence I.
Published: August 2013

Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined. Twelve young subjects performed two trials during two visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean arterial pressure (Finometer) were recorded. CBR function was assessed using rapid neck pressures ranging from +40 to −80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 84 ± 4% ( P < 0.05) but did not affect 6-keto prostaglandin F1α. Following aspirin, stretch with metabolite accumulation significantly augmented maximal gain (GMAX) and operating point gain (GOP) of CBR-HR (GMAX; −0.71 ± 0.14 vs. −0.37 ± 0.08 and GOP; −0.69 ± 0.13 vs. −0.35 ± 0.12 beats·min-1·mmHg−1 for aspirin and placebo, respectively; P < 0.05). CBR-HR function curves were reset similarly with aspirin and placebo during stretch with metabolite accumulation. In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in humans. This increased sensitivity appears linked to reduced TXA2 production, which likely plays a role in metabolite sensitization of muscle mechanoreceptors.
No independent, but an interactive, role of calcium-activated potassium channels in human cutaneous active vasodilation
Authors: Brunt Vienna E. , Fujii Naoto , Minson Christopher T.
Published: August 2013

In human cutaneous microvasculature, endothelium-derived hyperpolarizing factors (EDHFs) account for a large portion of vasodilation associated with local stimuli. Thus we sought to determine the role of EDHFs in active vasodilation (AVD) to passive heating in two protocols. Whole body heating was achieved using water-perfused suits (core temperature increase of 0.8–1.0°C), and skin blood flow was measured using laser-Doppler flowmetry. In the first protocol, four sites were perfused continuously via microdialysis with: 1) control; 2) tetraethylammonium (TEA) to block calcium-activated potassium (KCa) channels, and thus the actions of EDHFs; 3) N-nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase (NOS); and 4) TEA + l-NAME ( n = 8). Data are presented as percent maximal cutaneous vascular conductance (CVC). TEA had no effect on AVD (CVC during heated plateau: control 57.4 ± 4.9% vs. TEA 63.2 ± 5.2%, P = 0.27), indicating EDHFs are not obligatory. l-NAME attenuated plateau CVC to 33.7 ± 5.4% ( P < 0.01 vs. control); while TEA + l-NAME augmented plateau CVC compared with l-NAME alone (49.7 ± 5.3%, P = 0.02). From these data, it appears combined blockade of EDHFs and NOS necessitates dilation through other means, possibly through inward rectifier (KIR) and/or ATP-sensitive (KATP) potassium channels. To test this second hypothesis, we measured AVD at the following sites ( n = 8): 1) control, 2) l-NAME, 3) l-NAME + TEA, and 4) l-NAME + TEA + barium chloride (BaCl2; KIR and KATP blocker). The addition of BaCl2 to l-NAME + TEA reduced plateau CVC to 32.7 ± 6.6% ( P = 0.02 vs. l-NAME + TEA), which did not differ from the l-NAME site. These data combined demonstrate a complex interplay between vasodilatory pathways, with cross-talk between NO, KCa channels, and KIR and/or KATP channels.
Resistance training improves indices of muscle insulin sensitivity and β-cell function in overweight/obese, sedentary young men
Authors: Croymans Daniel M. , Paparisto Ergit , Lee Mary M. , Brandt Nina , Le Brian K. , Lohan Derek , Lee Cathy C. , Roberts Christian K.
Published: August 2013

We examined the effects of RT on oral glucose tolerance test (OGTT)-derived indices of muscle insulin sensitivity, hepatic insulin resistance, β-cell function, and skeletal muscle proteins related to glucose transport in overweight/obese, sedentary young men. Twenty-eight participants [median body mass index (BMI) 30.9 kg/m2; age 22 yr] completed 12 wk of RT (3 sessions/wk) and were assessed for changes in OGTT-derived indices, resting metabolic rate, body composition, serum adipokines, and skeletal muscle protein content [hexokinase 2 (HK2), glucose transporter type 4 (GLUT4), RAC-β serine/threonine-protein kinase (AKT2), glycogen synthase kinase 3β, and insulin receptor substrate 1]. Individualized responses to RT were also evaluated. RT significantly improved insulin and glucose area under the curve (both P < 0.03). With the use of OGTT indices of insulin action, we noted improved muscle insulin sensitivity index (mISI; P = 0.03) and oral disposition index ( P = 0.03). BMI, lean body mass (LBM), and relative strength also increased (all P < 0.03), as did skeletal muscle protein content of HK2, GLUT4, and AKT2 (26–33%; all P < 0.02). Hepatic insulin resistance index, adiponectin, leptin, and total amylin did not change. Further analysis demonstrated the presence of highly individualized responsiveness to RT for glucose tolerance and other outcomes. RT improved oral indices of muscle insulin sensitivity and β-cell function but not hepatic insulin resistance in overweight/obese young men. In addition to the increase in LBM, the improvements in insulin action may be due, in part, to increases in key insulin signaling proteins.
Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats
Authors: Hansen M. B. , Olsen N. V. , Hyldegaard O.
Published: August 2013

Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication.
Unilateral nasal allergic reactions increase bilateral sinus eosinophil infiltration
Authors: Baroody Fuad M. , deTineo Marcella , Naclerio Robert M.
Published: August 2013

We have previously shown that unilateral nasal challenge with antigen causes an increase in the number of eosinophils in the ipsilateral maxillary sinus. Here we aimed to determine whether there was an eosinophil response in the contralateral maxillary sinus after unilateral nasal challenge with antigen. Twenty subjects with a history of seasonal allergic rhinitis and a positive nasal challenge to ragweed or grass allergens were studied outside of their allergy season. Catheters were placed in both maxillary sinuses and the subjects were challenged with antigen via the left nostril. The subjects recorded nasal symptoms before and after each allergen challenge and hourly for 8 h afterward. We performed nasal lavages of the nose and sinuses at the same time as symptoms were recorded. The lavages were analyzed for the number of eosinophils and levels of albumin. Subjects showed a symptomatic response to challenge accompanied by an influx of eosinophils into the nose and increased vascular permeability. The number of eosinophils increased in both maxillary sinuses. The total change from diluent in eosinophils during the late phase response was higher in the ipsilateral maxillary sinus (median = 8,505; range = 0–100,360) compared with the contralateral sinus (median = 1,596; range = −13,527–93,373; P = 0.03). We conclude that eosinophils increase in both maxillary sinuses after unilateral nasal challenge. We speculate that a central neurologic reflex initiated in the nose by the nasal challenge contributes to the bilateral eosinophil response in the maxillary sinuses. We further speculate that, since there are more eosinophils in the ipsilateral compared with the contralateral maxillary sinus, there is also an axonal reflex into the ipsilateral maxillary sinus that contributed to the eosinophil response.
Visualization and stereological characterization of individual rat lung acini by high-resolution X-ray tomographic microscopy
Authors: Haberthür David , Barré Sébastien F. , Tschanz Stefan A. , Yao Eveline , Stampanoni Marco , Schittny Johannes C.
Published: August 2013

The small trees of gas-exchanging pulmonary airways, which are fed by the most distal purely conducting airways, are called acini and represent the functional gas-exchanging units. The three-dimensional architecture of the acini has a strong influence on ventilation and particle deposition. Due to the difficulty in identifying individual acini on microscopic lung sections, the knowledge about the number of acini and their biological parameters, like volume, surface area, and number of alveoli per acinus, are limited. We developed a method to extract individual acini from lungs imaged by high-resolution synchrotron radiation-based X-ray tomographic microscopy and estimated their volume, surface area, and number of alveoli. Rat acini were isolated by semiautomatically closing the airways at the transition from conducting to gas-exchanging airways. We estimated a mean internal acinar volume of 1.148 mm3, a mean acinar surface area of 73.9 mm2, and a mean of 8,470 alveoli/acinus. Assuming that the acini are similarly sized throughout different regions of the lung, we calculated that a rat lung contains 5,470 ± 833 acini. We conclude that our novel approach is well suited for the fast and reliable characterization of a large number of individual acini in healthy, diseased, or transgenic lungs of different species, including humans.
Episodic ventilation lowers the efficiency of pulmonary CO2excretion
Authors: Malte Christian Lind , Malte Hans , Wang Tobias
Published: August 2013

The ventilation pattern of many ectothermic vertebrates, as well as hibernating and diving endotherms, is episodic where breaths are clustered in bouts interspersed among apneas of varying duration. Using mechanically ventilated, anesthetized freshwater turtles ( Trachemys scripta), a species that normally exhibits this episodic ventilation pattern, we investigated whether episodic ventilation affects pulmonary gas exchange compared with evenly spaced breaths. In two separate series of experiments (a noninvasive and an invasive), ventilation pattern was switched from a steady state, with evenly spaced breaths, to episodic ventilation while maintaining overall minute ventilation (30 ml·min−1·kg−1). On switching to an episodic ventilation pattern of 10 clustered breaths, mean CO2excretion rate was reduced by 6 ± 5% (noninvasive protocol) or 20 ± 8% (invasive protocol) in the first ventilation pattern cycle, along with a reduction in the respiratory exchange ratio. O2uptake was either not affected or increased in the first ventilation pattern cycle, while neither heart rate nor overall pulmonary blood flow was significantly affected by the ventilation patterns. The results confirm that, for a given minute ventilation, episodic ventilation is intrinsically less efficient for CO2excretion, thereby indicating an increase in the total bodily CO2store in the protocol. Despite the apparent CO2retention, mean arterial Pco2only increased 1 Torr during the episodic ventilation pattern, which was concomitant with a possible reduction of respiratory quotient. This would indicate a shift in metabolism such that less CO2is produced when the efficiency of excretion is reduced.
Muscle immobilization and remobilization downregulates PGC-1α signaling and the mitochondrial biogenesis pathway
Authors: Kang Chounghun , Ji Li Li
Published: August 2013

Prolonged immobilization (IM) results in skeletal muscle atrophy accompanied by increased reactive oxygen species (ROS) generation, inflammation, and protein degradation. However, the biological consequence of remobilizing such muscle has been studied only sparsely. In this study, we examined the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)-controlled mitochondrial biogenesis pathway and inflammatory response in mice subjected to 2 wk of hindlimb IM followed by 5 days of remobilization (RM). We hypothesized that ROS generation and activation of redox-sensitive signaling pathways play important roles in the etiology of muscle injury. FVB/N mice (age 2 mo) were randomly assigned to either 14 days of IM by casting one of the hindlimbs ( n = 7), IM followed by 5 days of RM with casting removed ( n = 7), or to a control group (Con; n = 7). Muscle to body weight ratios of three major leg muscles were significantly decreased as a result of IM. Two ubiquitin-proteasome pathway enzymes, muscle atrophy F-box (MAFb or atrogin-1) and muscle ring finger-1 (MuRF-1), were upregulated with IM and maintained at high levels during RM. Protein contents of PGC-1α and nuclear respiratory factors 1 and 2 in tibialis anterior (TA) muscle were reduced by 50% ( P < 0.01) in IM vs. Con, with no recovery observed during RM. IM suppressed mitochondrial transcription factor A and cytochrome- c content by 57% and 63% ( P < 0.01), respectively, and cytochrome- c oxidase activity by 58% ( P < 0.05). Furthermore, mitochondrial DNA content was reduced by 71% ( P < 0.01) with IM. None of these changes were reversed after RM. With RM, TA muscle showed a 2.3-fold ( P < 0.05) higher H2O2 content and a 4-fold ( P < 0.01) higher 8-isoprostane content compared with Con, indicating oxidative stress. Tumor necrosis factor-α and interleukin-6 levels in TA muscle were 4- and 3-fold higher ( P < 0.05), respectively, in IM and RM vs. CON. The nuclear factor-κB (NF-κB) pathway activation was observed only after RM, but not after IM alone. These data indicate an increase in ROS generation during the initial phase of muscle RM that could activate the NF-κB pathway, and elicit inflammation and oxidative stress. These events may hinder muscle recovery from IM-induced mitochondrial deterioration and protein loss.
Characterization and Clinical Relevance of ALDHbright Populations in Prostate Cancer
Authors: Le Magnen Clémentine , Bubendorf Lukas , Rentsch Cyrill A. , Mengus Chantal , Gsponer Joel , Zellweger Tobias , Rieken Malte , Thalmann George N. , Cecchini Marco G. , Germann Markus , Bachmann Alexander , Wyler Stephen , Heberer Michael , Spagnoli Giulio C.
Published: August 2013

Purpose: High aldehyde dehydrogenase (ALDH) has been suggested to selectively mark cells with high tumorigenic potential in established prostate cancer cell lines. However, the existence of cells with high ALDH activity (ALDHbright) in primary prostate cancer specimens has not been shown so far. We investigated the presence, phenotype, and clinical significance of ALDHbright populations in clinical prostate cancer specimens.

Experimental Design: We used ALDEFLUOR technology and fluorescence-activated cell-sorting (FACS) staining to identify and characterize ALDHbright populations in cells freshly isolated from clinical prostate cancer specimens. Expression of genes encoding ALDH-specific isoforms was evaluated by quantitative real-time PCR in normal prostate, benign prostatic hyperplasia (BPH), and prostate cancer tissues. ALDH1A1-specific expression and prognostic significance were assessed by staining two tissue microarrays that included more than 500 samples of BPH, prostatic intraepithelial neoplasia (PIN), and multistage prostate cancer.

Results: ALDHbright cells were detectable in freshly excised prostate cancer specimens (n = 39) and were mainly included within the EpCAM(+) and Trop2(+) cell populations. Although several ALDH isoforms were expressed to high extents in prostate cancer, only ALDH1A1 gene expression significantly correlated with ALDH activity (P < 0.01) and was increased in cancers with high Gleason scores (P = 0.03). Most importantly, ALDH1A1 protein was expressed significantly more frequently and at higher levels in advanced-stage than in low-stage prostate cancer and BPH. Notably, ALDH1A1 positivity was associated with poor survival (P = 0.02) in hormone-naïve patients.

Conclusions: Our data indicate that ALDH contributes to the identification of subsets of prostate cancer cells of potentially high clinical relevance. Clin Cancer Res; 19(19); 5361–71. ©2013 AACR.
Emergence of Polyclonal FLT3 Tyrosine Kinase Domain Mutations during Sequential Therapy with Sorafenib and Sunitinib in FLT3-ITD–Positive Acute Myeloid Leukemia
Authors: Baker Sharyn D. , Zimmerman Eric I. , Wang Yong-Dong , Orwick Shelley , Zatechka Douglas S. , Buaboonnam Jassada , Neale Geoffrey A. , Olsen Scott R. , Enemark Eric J. , Shurtleff Sheila , Rubnitz Jeffrey E. , Mullighan Charles G. , Inaba Hiroto
Published: August 2013

Purpose: To evaluate the clinical activity of sequential therapy with sorafenib and sunitinib in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD)-positive acute myelogenous leukemia (AML) and monitor the emergence of secondary FLT3 tyrosine kinase domain (TKD) mutations during treatment.

Experimental Design: Six children with relapsed/refractory AML were treated with sorafenib in combination with clofarabine and cytarabine, followed by single-agent sorafenib if not a candidate for transplantation. Sunitinib was initiated after sorafenib relapse. Bone marrow samples were obtained for assessment of FLT3 TKD mutations by deep amplicon sequencing. The phase of secondary mutations with ITD alleles was assessed by cloning and sequencing of FLT3 exons 14 through 20. Identified mutations were modeled in Ba/F3 cells, and the effect of kinase inhibitors on FLT3 signaling and cell viability was assessed.

Results: Four patients achieved complete remission, but 3 receiving maintenance therapy with sorafenib relapsed after 14 to 37 weeks. Sunitinib reduced circulating blasts in two patients and marrow blasts in one. Two patients did not respond to sorafenib combination therapy or sunitinib. FLT3 mutations at residues D835 and F691 were observed in sorafenib resistance samples on both ITD-positive and -negative alleles. Deep sequencing revealed low-level mutations and their evolution during sorafenib treatment. Sunitinib suppressed leukemic clones with D835H and F691L mutations, but not D835Y. Cells expressing sorafenib-resistant FLT3 mutations were sensitive to sunitinib in vitro.

Conclusions: Sunitinib has activity in patients that are resistant to sorafenib and harbor secondary FLT3 TKD mutations. The use of sensitive methods to monitor FLT3 mutations during therapy may allow individualized treatment with the currently available kinase inhibitors. Clin Cancer Res; 19(20); 5758–68. ©2013 AACR.
Second Transurethral Resection after Ta High-Grade Bladder Tumor: A 4.5-Year Period at a Single University Center
Authors: Lazica David A. , Roth Stephan , Brandt Alexander S. , Böttcher Stefanie , Mathers Michael J. , Ubrig Burkhard
Published: August 2013

Purpose: We evaluated the results of second transurethral resections of the bladder (TURB) after pTa high-grade bladder cancer over a 4.5-year period. Patients and Methods: From July 2007 to December 2011, 2,159 TURBs were performed at our institution, of which 1,143 were initial resections for primary bladder tumor or recurrence. Of these, 142 revealed pTa high-grade bladder cancer, and here we investigated tumor characteristics of initial TURB and results of second resection. Results: The incidence of pTa high-grade tumor was 12.4% (n = 142). Of 87 patients who underwent a second resection, tumor was found in 36 (41.4%); tumors were multifocal in 25 (69.4%) and <3 cm in 29 (80.6%). Tumor was detected at the primary site in 38.9%, at other locations in 22.2%, and at both in 38.9%. Histology revealed pTa low-grade in 13 (14.9% of 87), pTa high-grade in 15 (17.2%), and pT1 in 5 (5.7%) patients. No muscle-invasive tumor was detected. A significant association was found for the number of tumors at initial TURB: in patients with tumor at second resection, 55.1% had had multiple tumors at first resection, more than twice those with solitary tumor (23.7%) (0.004). Conclusions: In our study, Ta high-grade tumors show a relevant rate of persistent tumor at second resection, most of them located at the primary tumor site. As recommended by the American and European clinical guidelines, patients with Ta high-grade tumor should undergo second resection.
Surgical Management of Benign Idiopathic Osteonecrosis of the External Auditory Canal
Authors: Saxby Alexander J. , Linder Thomas E.
Published: August 2013

Background/Aims: Benign idiopathic osteonecrosis of the external ear canal remains a challenging management problem, with many patients experiencing a prolonged chronic course requiring frequent debridement. The technique of bony sequestrectomy, followed by rotation of a vascularized fascial flap and then a free full-thickness skin graft is presented. Methods: Success with this technique is described in a retrospective case series format in addition to a review of the existing literature on surgical techniques for the treatment of this condition. Results: The described technique was performed on 5 patients following prolonged periods of failed medical therapy (minimum 8 months). All 5 patients achieved a healed external auditory canal, with no ongoing skin ulceration or bony sequestration. Follow-up data (median 22 months) suggests that the technique provides a robust and long-lasting therapy. Conclusion: Symptomatic benign idiopathic osteonecrosis of the tympanic bone is well treated by provision of vascularized tissue to maximize the chance of bone healing and subsequent cure. It should be considered early in the management protocol to avoid lengthy symptomatic periods, the symptoms of which ultimately may not heal with medical therapy alone.
Agreement between Time-Domain and Spectral-Domain Optical Coherence Tomography in the Assessment of Macular Thickness in Patients with Idiopathic Macular Telangiectasia Type 2
Authors: Mathew Raeba , Sivaprasad Sobha , Florea Daniela , Leung Irene , Sallo Ferenc , Clemons Traci , Bird Alan C. , Peto Tunde ,   on behalf of the MacTel Study Group
Published: August 2013

Purpose: To estimate the conversion factors to transpose macular thickness measurements on time-domain (TD) to various spectral-domain (SD) optical coherence tomography (OCT) machines in patients with macular telangiectasia type 2a (MacTel). Procedures: Macular scans on TD- and SD-OCT were performed on patients at the same visit. The retinal thickness values in various ETDRS subfields and macular volume were compared between different OCT machines. Results: The macular thickness and volume were significantly greater (p < 0.0001, r = 0.678-0.822) on SD-OCT. The mean differences in macular thickness between TD Stratus and SD-OCT by Spectralis, Cirrus and Topcon were 62, 41 and 20 μm, respectively. The conversion factor of macular thickness from TD-OCT to Spectralis, Cirrus and Topcon were +65, +39 and +25 μm, respectively. Conclusion and Message: The estimates of conversion of macular thickness from TD- to SD-OCT using simple mean differences between machines and those by linear regression were similar suggesting that the former may be used for the longitudinal follow-up of MacTel patients.
Nutrient Composition of Cirina forda (Westwood)-Enriched Complementary Foods
Authors: Adepoju Oladejo Thomas , Daboh Oladele Olatunji
Published: August 2013

Background/Aims: Dried Cirina forda (Westwood) larva is widely marketed, cheap, and commonly consumed in Southwestern Nigeria. Its powder was used in enriching two commonly used complementary food staples (maize and sorghum) as a source of protein and essential micronutrients in complementary foods for infants and young children. Methods: Samples of soaked and dried sorghum and maize flours and C. forda powder were prepared, and C. forda powder was added to the dried soaked maize and sorghum flours at 5, 10, and 15% (w/w) inclusion levels and analyzed for proximate, mineral, and antinutrient compositions using standard methods of AOAC. Results: One hundred grams of C. forda larva contained 52.6 g of protein, 16.8 g of lipids, 2.6 g of ash, 268.67 mg of calcium, 5.64 mg of iron, and 15.00 mg of zinc, and yielded 458.40 kcal energy with 4.40 mg of trypsin inhibitor. Sorghum and maize flours contained 9.2 and 8.3 g of protein, respectively. Addition of C. forda at 5, 10, and 15% levels to fermented sorghum and maize flours significantly increased both micro- and macronutrients of the complementary foods (p < 0.05), and the nutrient density and trypsin inhibitor increased with the inclusion level (p < 0.05). Conclusion: The trypsin inhibitor level was very low and cannot cause protein malabsorption. C. forda can serve as a good source of nutrients such as protein, fat, calcium, phosphorus, iron, and zinc in formulating nutrient-dense complementary foods.
Tenc1-Deficient Mice Develop Glomerular Disease in a Strain-Specific Manner
Authors: Uchio-Yamada Kozue , Sawada Kyoko , Tamura Kotaro , Katayama Sumie , Monobe Youko , Yamamoto Yoshie , Ogura Atsuo , Manabe Noboru
Published: August 2013

Background/Aims: Tenc1 (also known as tensin2) is an integrin-associated focal adhesion molecule that is broadly expressed in mouse tissues including the liver, muscle, heart and kidney. A mouse strain carrying mutated Tenc1, the ICR-derived glomerulonephritis (ICGN) strain, develops severe nephrotic syndrome. Methods: To elucidate the function of Tenc1 in the kidney, Tenc1ICGN was introduced into 2 genetic backgrounds, i.e. DBA/2J (D2) and C57BL/6J (B6), strains that are respectively susceptible and resistant to chronic kidney disease. Results: Biochemical and histological analysis revealed that homozygous Tenc1ICGN mice develop nephrotic syndrome on the D2 background (D2GN) but not on the B6 background (B6GN). Initially, abnormal assembly and maturation of glomerular basement membrane (GBM) were observed, and subsequently effacement of podocyte foot processes was noted in the kidneys of D2GN but not B6GN mice. These defects are likely to be involved in the integrin signaling pathway. Conclusion: This study suggests that Tenc1 contributes to the maintenance of GBM structures and that the genetic background influences the severity of nephrotic syndrome.
The Localized Inflammatory Response to Bronchoscopic Thermal Vapor Ablation
Authors: Gompelmann Daniela , Eberhardt Ralf , Ernst Armin , Hopkins Peter , Egan Jim , Stanzel Franz , Valipour Arschang , Wagner Manfred , Witt Christian , Baker Kimberly M. , Gotfried Mark H. , Kesten Steven , Snell Gregory , Herth Felix J.F.
Published: August 2013

Background: Bronchoscopic thermal vapor ablation (BTVA) reduces lung volumes in emphysema patients by inducing a localized inflammatory response (LIR) leading to a healing process of fibrosis, but may also increase symptoms. Objectives: We sought to evaluate whether the clinical manifestation of LIR correlated with patient outcome. Methods: Respiratory adverse events and inflammatory markers were analyzed from a multicenter trial of BTVA in patients with upper-lobe-predominant emphysema. End points including changes in forced expiratory flow (FEV1), lobar volume, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) and 6-minute-walk distance (6-MWD) were analyzed according to the presence or absence of a respiratory adverse event requiring treatment with an antibiotic or steroid. Results: Forty-four patients received BTVA. Increases of inflammatory markers were observed with a peak between the second and fourth week. Eighteen respiratory adverse events occurred in 16 patients within 30 days of BTVA, requiring antibiotics and/or steroids. These patients had significantly greater lobar volume reduction (65.3 vs. 33.4%, p = 0.007) and a change in residual volume at 12 months (-933 vs. 13 ml, p < 0.001) associated with a greater improvement of exercise capacity and health-related quality of life than patients without respiratory adverse events. Conclusion: Patients with more prominent respiratory symptoms in the first 30 days following BTVA experience greater efficacy. The clinical manifestations of the LIR are predictive of long-term clinical benefits.
Peritoneal Carcinomatosis: Registry and Centers in Germany
Authors: Pelz Jörg O. W.
Published: August 2013

Background: At present, there are only few objective quality criteria for the treatment of peritoneal carcinomatosis using cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion (HIPEC). Method and Results: However, because this therapy is associated with significant morbidity and mortality, such quality criteria are quite important. Accreditation of peritoneal carcinomatosis centers by the German Society for General and Visceral Surgery was a first step towards establishing these clinics. Conclusion: One key requirement for accreditation is membership in the German Peritoneal Carcinomatosis Registry. This prospective database provides a collation and evaluation of the epidemiological and therapeutic factors relating to this disease.