bluuebunny/crossref_metadata_2025 huggingface dataset:
L-arginine uptake by cationic amino acid transporter 2 is essential for colonic epithelial cell restitution
Authors: Singh Kshipra , Coburn Lori A. , Barry Daniel P. , Boucher Jean-Luc , Chaturvedi Rupesh , Wilson Keith T.
Published: February 2012

Restoration of the colonic epithelial barrier is an important response during colitis. L-arginine (L-Arg) is a semiessential amino acid that reduces murine colitis induced by Citrobacter rodentium . Cationic amino acid transporter (CAT) proteins increase L-Arg uptake into cells. L-Arg is utilized to produce nitric oxide (NO), by inducible NO synthase (iNOS), or L-ornithine (L-Orn) by arginase (Arg) enzymes. The latter is followed by generation of polyamines by ornithine decarboxylase (ODC) and L-proline (L-Pro) by ornithine aminotransferase (OAT). We show that L-Arg enhanced epithelial restitution in conditionally immortalized young adult mouse colon (YAMC) cells in a wound repair model, and in isolated mouse colonic epithelial cells (CECs), using a cell migration assay. Restitution was impaired by C. rodentium . Wounding induced CAT2, and inhibition of L-Arg uptake by the competitive inhibitor L-lysine (L-Lys) or by CAT2 shRNA, but not CAT1 shRNA, decreased restitution. Migration was impaired in CECs treated with L-Lys or from CAT2−/− mice. Wounding increased Arg1 expression, and inhibition of arginase with S-(2-boronoethyl)-L-cysteine (BEC) or Arg1 shRNA inhibited restitution in YAMC cells; cell migration in CECs was also impaired by BEC. Inhibition of ODC or iNOS did not alter restitution. L-Orn or L-Pro restored restitution in cells treated with BEC or Arg1 shRNA, whereas the polyamine putrescine had no benefit. Wounding increased OAT levels, OAT shRNA inhibited restitution, and L-Pro restored restitution in cells with OAT knockdown. Uptake of L-Arg, and its metabolism by Arg1 to L-Orn and conversion to L-Pro by OAT is essential for colonic epithelial wound repair.
Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise
Authors: Gundermann David M. , Fry Christopher S. , Dickinson Jared M. , Walker Dillon K. , Timmerman Kyle L. , Drummond Micah J. , Volpi Elena , Rasmussen Blake B.
Published: February 2012

Blood flow restriction (BFR) to contracting skeletal muscle during low-intensity resistance exercise training increases muscle strength and size in humans. However, the mechanism(s) underlying these effects are largely unknown. We have previously shown that mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis (MPS) are stimulated following an acute bout of BFR exercise. The purpose of this study was to test the hypothesis that reactive hyperemia is the mechanism responsible for stimulating mTORC1 signaling and MPS following BFR exercise. Six young men (24 ± 2 yr) were used in a randomized crossover study consisting of two exercise trials: low-intensity resistance exercise with BFR (BFR trial) and low-intensity resistance exercise with sodium nitroprusside (SNP), a pharmacological vasodilator infusion into the femoral artery immediately after exercise to simulate the reactive hyperemia response after BFR exercise (SNP trial). Postexercise mixed-muscle fractional synthetic rate from the vastus lateralis increased by 49% in the BFR trial ( P < 0.05) with no change in the SNP trial ( P > 0.05). BFR exercise increased the phosphorylation of mTOR, S6 kinase 1, ribosomal protein S6, ERK1/2, and Mnk1-interacting kinase 1 ( P < 0.05) with no changes in mTORC1 signaling in the SNP trial ( P > 0.05). We conclude that reactive hyperemia is not a primary mechanism for BFR exercise-induced mTORC1 signaling and MPS. Further research is necessary to elucidate the cellular mechanism(s) responsible for the increase in mTOR signaling, MPS, and hypertrophy following acute and chronic BFR exercise.
Oreocnide integrifoliaFlavonoids Augment Reprogramming for Islet Neogenesis andβ-Cell Regeneration in Pancreatectomized BALB/c Mice
Authors: Ansarullah  , Bharucha Bhavna , Umarani Malati , Dwivedi Mitesh , Laddha Naresh C. , Begum Rasheedunnisa , Hardikar Anandwardhan A. , Ramachandran A. V.
Published: February 2012

Agents which can either trigger proliferation ofβ-cells or induce neogenesis ofβ-cells from precursors would be of pivotal role in reversing diabetic manifestations. We examined the role of flavonoid rich fraction (FRF) ofOreocnide integrifolialeaves using a mice model of experimental regeneration. BALB/c mice were subjected to ~70% pancreatectomy (Px) and supplemented with FRF for 7, 14, and 21 days after pancreatectomy. Px animals displayed increased blood glucose levels and decreased insulin titres which were ameliorated by FRF supplementation. FRF-treated mice demonstrated prominent newly formed islets budding off from ducts and depicting increased BrdU incorporation. Additionally, transcripts levels of Ins1/2, Reg-3α/γ, Ngn-3, and Pdx-1 were upregulated during the initial 1 week. The present study provides evidence of a nutraceutical contributing to islet neogenesis from ductal cells as the mode ofβ-cell regeneration and a potential therapeutic for clinical trials in management of diabetic manifestations.
Modal Experiment on Structural Condition Monitoring Using Cumulative Harmonic Analysis
Authors: Takahashi Yoshinori , Goto Satoru , Tohyama Mikio
Published: February 2012

This paper describes a cumulative harmonic analysis (CHA) that replaces the stepwise time window function of Berman and Fincham's cumulative spectral analysis with a spectral accumulation function, thereby enabling a new structural health monitoring method. CHA estimates and visualizes system damping conditions without the need of transient-vibration records. The damping conditions are closely related to the spectral distribution around the dominant spectral peaks due to structural resonance. This type of spectral distribution can be visualized with CHA even within a short interval of random vibration samples. The effect of CHA on monitoring the damping conditions was reported by the authors in a previous study. In the current study, the authors confirmed the usefulness of CHA for structural condition monitoring by conducting scale-model experiments.
Preparation of Folate‐Conjugated Pluronic F127/Chitosan Core‐Shell Nanoparticles Encapsulating Doxorubicin for Breast Cancer Treatment
Authors: Manaspon Chawan , Viravaidya-Pasuwat Kwanchanok , Pimpha Nuttaporn
Published: February 2012

A targeting drug delivery system using folate‐conjugated pluronic F127/chitosan core‐shell nanoparticles was developed to deliver doxorubicin (DOX) to the target cancer cells. First, DOX was encapsulated in pluronic F127 micelle cores in the presence of sodium dodecyl sulfate (SDS) by a self‐assembly method. To form a shell, a layer of either chitosan or folate‐conjugated chitosan was deposited onto the pluronic micelles. The encapsulation efficiency was approximately 58.1 ± 4.7%. The average size of the core‐shell nanoparticles was 37.4 ± 2.0 nm, while the zeta potential was 12.9 ± 2.3 mV, indicating the presence of a shell layer and more stable particles. In an in vitro DOX release study, an initial burst release, followed by a sustained release, was observed within 24 hours. In addition, the core‐shell nanoparticles showed greater cytotoxicity towards MCF‐7 cells than free DOX, suggesting a better therapeutic efficacy in treating cancer.
Simulation and Experimental Studies on Perfect Tracking Optimal Control of an Electrohydraulic Actuator System
Authors: Ghazali R. , Sam Y. M. , Rahmat M. F. , Zulfatman  , Hashim A. W. I. M.
Published: February 2012

This paper presents a perfect tracking optimal control for discrete-time nonminimum phase of electrohydraulic actuator (EHA) system by adopting a combination of feedback and feedforward controller. A linear-quadratic regulator (LQR) is firstly designed as a feedback controller, and a feedforward controller is then proposed to eliminate the phase error emerged by the LQR controller during the tracking control. The feedforward controller is developed by implementing the zero phase error tracking control (ZPETC) technique in which the main difficulty arises from the nonminimum phase system with no stable inverse. Subsequently, the proposed controller is performed in simulation and experimental studies where the EHA system is represented in discrete-time model that has been obtained using system identification technique. It also shows that the controller offers better performance as compared to conventional PID controller in reducing phase and gain error that typically occurred in positioning or tracking systems.
Photosensitized Oxidation of 9,10-Dimethylanthracene on Dye-Doped Silica Composites
Authors: Albiter Elim , Alfaro Salvador , Valenzuela Miguel A.
Published: February 2012

A series of cationic dyes, methylene blue (MB), safranin O (SF), toluidine blue (TB), and neutral red (NR), were successfully incorporated into a silica matrix by using ultrasound irradiation during the Stöber process. Several analyses were performed, including scanning dynamic light scattering (DLS), electron microscopy (SEM), nitrogen physisorption, FTIR spectroscopy, UV-vis, and diffuse reflectance spectroscopy. The entrapped dyes on silica were evaluated in singlet oxygen (1O2) generation under visible light irradiation, by means of the photosensitized oxidation of 9,10-dimethylanthracene (DMA). According to the results, the photocatalytic performance of the silica composites was improved, and the leakage of the dye from the particles was suppressed. Among these four different types of dye-doped silica composites, the SiO2-SF composite showed the most efficient delivery of1O2.
Multiple Biomarkers for Risk Prediction in Chronic Heart Failure
Authors: Ky Bonnie , French Benjamin , Levy Wayne C. , Sweitzer Nancy K. , Fang James C. , Wu Alan H.B. , Goldberg Lee R. , Jessup Mariell , Cappola Thomas P.
Published: February 2012

Background—

Prior studies have suggested using a panel of biomarkers that measure diverse biological processes as a prognostic tool in chronic heart failure. Whether this approach improves risk prediction beyond clinical evaluation is unknown.

Methods and Results—

In a multicenter cohort of 1513 chronic systolic heart failure patients, we measured a contemporary biomarker panel consisting of high-sensitivity C-reactive protein, myeloperoxidase, B-type natriuretic peptide, soluble fms-like tyrosine kinase receptor-1, troponin I, soluble toll-like receptor-2, creatinine, and uric acid. From this panel, we calculated a parsimonious multimarker score and assessed its performance in predicting risk of death, cardiac transplantation, or ventricular assist device placement in comparison to an established clinical risk score, the Seattle Heart Failure Model (SHFM). During a median follow-up of 2.5 years, there were 317 outcomes: 187 patients died; 99 were transplanted; and 31 had a ventricular assist device placed. In unadjusted Cox models, patients in the highest tertile of the multimarker score had a 13.7-fold increased risk of adverse outcomes compared with the lowest tertile (95% confidence interval, 8.75–21.5). These effects were independent of the SHFM (adjusted hazard ratio, 6.80; 95% confidence interval, 4.18–11.1). Addition of the multimarker score to the SHFM led to a significantly improved area under the receiver operating characteristic curve of 0.803 versus 0.756 (
P
=0.003) and appropriately reclassified a significant number of patients who had the outcome into a higher risk category (net reclassification improvement, 25.2%; 95% confidence interval, 14.2–36.2%;
P
<0.001).

Conclusions—

In ambulatory chronic heart failure patients, a score derived from multiple biomarkers integrating diverse biological pathways substantially improves prediction of adverse events beyond current metrics.
Are Myocardial Infarction–Associated Single-Nucleotide Polymorphisms Associated With Ischemic Stroke?
Authors: Cheng Yu-Ching , Anderson Christopher D. , Bione Silvia , Keene Keith , Maguire Jane M. , Nalls Michael , Rasheed Asif , Zeginigg Marion , Attia John , Baker Ross , Barlera Simona , Biffi Alessandro , Bookman Ebony , Brott Thomas G. , Brown Robert D. , Chen Fang , Chen Wei-Min , Ciusani Emilio , Cole John W. , Cortellini Lynelle , Danesh John , Doheny Kimberly , Ferrucci Luigi , Grazia Franzosi Maria , Frossard Philippe , Furie Karen L. , Golledge Jonathan , Hankey Graeme J. , Hernandez Dena , Holliday Elizabeth G. , Hsu Fang-Chi , Jannes Jim , Kamal Ayeesha , Khan Muhammad Saleem , Kittner Steven J. , Koblar Simon A. , Lewis Martin , Lincz Lisa , Lisa Antonella , Matarin Mar , Moscato Pablo , Mychaleckyj Josyf C. , Parati Eugenio A. , Parolo Silvia , Pugh Elizabeth , Rost Natalia S. , Schallert Michael , Schmidt Helena , Scott Rodney J. , Sturm Jonathan W. , Yadav Sunaina , Zaidi Moazzam , Boncoraglio Giorgio B. , Levi Christopher Royce , Meschia James F. , Rosand Jonathan , Sale Michele , Saleheen Danish , Schmidt Reinhold , Sharma Pankaj , Worrall Bradford , Mitchell Braxton D.
Published: February 2012

Background and Purpose—

Ischemic stroke (IS) shares many common risk factors with coronary artery disease (CAD). We hypothesized that genetic variants associated with myocardial infarction (MI) or CAD may be similarly involved in the etiology of IS. To test this hypothesis, we evaluated whether single-nucleotide polymorphisms (SNPs) at 11 different loci recently associated with MI or CAD through genome-wide association studies were associated with IS.

Methods—

Meta-analyses of the associations between the 11 MI-associated SNPs and IS were performed using 6865 cases and 11 395 control subjects recruited from 9 studies. SNPs were either genotyped directly or imputed; in a few cases a surrogate SNP in high linkage disequilibrium was chosen. Logistic regression was performed within each study to obtain study-specific βs and standard errors. Meta-analysis was conducted using an inverse variance weighted approach assuming a random effect model.

Results—

Despite having power to detect odds ratio of 1.09–1.14 for overall IS and 1.20–1.32 for major stroke subtypes, none of the SNPs were significantly associated with overall IS and/or stroke subtypes after adjusting for multiple comparisons.

Conclusions—

Our results suggest that the major common loci associated with MI risk do not have effects of similar magnitude on overall IS but do not preclude moderate associations restricted to specific IS subtypes. Disparate mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events.
Alternatively-Spliced Extra Domain A of Fibronectin Promotes Acute Inflammation and Brain Injury After Cerebral Ischemia in Mice
Authors: Khan Mohammad Moshahid , Gandhi Chintan , Chauhan Neelam , Stevens Jeff W. , Motto David G. , Lentz Steven R. , Chauhan Anil K.
Published: February 2012

Background and Purpose—

The fibronectin isoform containing the alternatively spliced extra domain A (EDA
+
-FN) is normally absent from the circulation, but plasma levels of EDA
+
-FN can become markedly elevated in several human pathological conditions associated with inflammation including ischemic stroke. It remains unknown whether EDA
+
-FN contributes to stroke pathogenesis or is simply an associative marker. Several in vitro studies suggest that EDA
+
-FN can activate Toll-like receptor 4, an innate immune receptor that triggers proinflammatory responses. We undertook a genetic approach in mice to investigate the ability of EDA
+
-FN to mediate inflammatory brain damage in a focal cerebral ischemia/reperfusion injury model.

Methods—

We used genetically modified EDA
+/+
mice, which constitutively express EDA
+
-FN. Extent of injury, neurological outcome, and inflammatory mechanisms were assessed after 1-hour cerebral ischemia/23-hour reperfusion injury and compared with wild-type mice.

Results—

We found that EDA
+/+
mice developed significantly larger infarcts and severe neurological deficits that were associated with significant increased neutrophil and macrophage infiltration as quantitated by immunohistochemistry. Additionally, we found upregulation of nuclear factor-κB, cyclo-oxygenase-2, and inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the EDA
+/+
mice compared with wild-type mice. Interestingly, increased brain injury and neurological deficits were largely abrogated in EDA
+/+
mice by treatment with a specific Toll-like receptor 4 inhibitor.

Conclusions—

These findings provide the first evidence that EDA
+
-FN promotes inflammatory brain injury after ischemic stroke and suggest that the elevated levels of plasma EDA
+
-FN observed in chronic inflammatory conditions could worsen injury and outcome in patients after acute stroke.
Endovascular Therapy of 623 Patients With Anterior Circulation Stroke
Authors: Galimanis Aekaterini , Jung Simon , Mono Marie-Luise , Fischer Urs , Findling Oliver , Weck Anja , Meier Niklaus , Marco De Marchis Gian , Brekenfeld Caspar , El-Koussy Marwan , Mattle Heinrich P. , Arnold Marcel , Schroth Gerhard , Gralla Jan
Published: February 2012

Background and Purpose—

Endovascular therapy of acute ischemic stroke has been shown to be beneficial for selected patients. The purpose of this study is to determine predictors of outcome in a large cohort of patients treated with intra-arterial thrombolysis, mechanical revascularization techniques, or both.

Methods—

We prospectively acquired data for 623 patients with acute cerebral infarcts in the carotid artery territory who received endovascular treatment at a single center. Logistic regression analysis was performed to determine predictors of outcome.

Results—

Median National Institutes of Health Stroke Scale (NIHSS) at admission was 15. Partial or complete recanalization was achieved in 70.3% of patients; it was independently associated with hypercholesterolemia (
P
=0.02), absence of coronary artery disease (
P
=0.023), and more proximal occlusion site (
P
<0.0001). After 3 months, 80.5% of patients had survived, and 48.9% of patients reached favorable outcome (modified Rankin scale score 0–2). Good collaterals (
P
<0.0001), recanalization (
P
=0.023), hypercholesterolemia (
P
=0.03), lower NIHSS at admission (
P
=0.001), and younger age (
P
<0.0001) were independent predictors for survival. More peripheral occlusion site (
P
<0.0001), recanalization (
P
<0.0001), hypercholesterolemia (
P
=0.002), good collaterals (
P
=0.002), lower NIHSS (
P
<0.0001), younger age (
P
<0.0001), absence of diabetes (
P
=0.002), and no previous antithrombotic therapy (
P
=0.036) predicted favorable outcome. Time to treatment was only a predictor of outcome, when collaterals were excluded from the model. Symptomatic intracerebral hemorrhage occurred in 5.5% and was independently predicted by poor collaterals (
P
=0.004).

Conclusions—

Several independent predictors for outcome and complications were identified. Unlike in intravenous thrombolysis trials, time to treatment was a predictor of outcome only when collaterals were excluded from the model, indicating the important role of collaterals for the time window.
Contrast Delay on Perfusion CT as a Predictor of New, Incident Infarct
Authors: Keedy Alexander W. , Fischette W. Scott , Soares Bruno P. , Arora Sandeep , Lau Benison C. , Magge Rajiv , Bredno Joerg , Cheng SuChun , Wintermark Max
Published: February 2012

Background and Purpose—

The purpose of this study was to determine if the assessment of intracranial collateral circulation by CT angiography and/or perfusion CT (PCT) can predict the risk of future ischemic stroke in a large, retrospective cohort study.

Methods—

We identified 135 consecutive patients who underwent CT angiography of the head and neck and PCT of the brain at baseline and with subsequent follow-up brain imaging. Clinical and demographic information and carotid wall features were collected. Collateral circulation was assessed anatomically at CT angiography and functionally by measuring the mean transit time delay at PCT. The clinical, carotid, CT angiography, and PCT variables were compared between those with and without new incident infarct at follow-up imaging using mixed effect logistic statistical models.

Results—

During the follow-up period, 15 patients developed a new infarct and 120 patients did not. Clinical features associated with the stroke risk were age, hypertension, hyperlipidemia, and atrial fibrillation. The carotid features associated with stroke risk were wall thickness. Anatomic assessment of collaterals on CT angiography was not associated with stroke risk, whereas the functional assessment of collaterals (mean transit time delay on PCT) was associated with stroke risk. In a multivariate model, age, atrial fibrillation, and mean transit time delay (OR, 22.8;
P
<0.001) were the only covariates that were independent predictors of future ischemic stroke.

Conclusions—

The mean transit time delay on PCT contains important physiological information and should not be discarded. Along with age and atrial fibrillation, this functional assessment of intracranial collateral circulation predicts the risk of future hemispheric infarct.
Discrepancy Between Cardiac and Physical Functional Reserves in Stroke
Authors: Jakovljevic Djordje G. , Moore Sarah A. , Tan Lip-Bun , Rochester Lynn , Ford Gary A. , Trenell Michael I.
Published: February 2012

Background and Purpose—

Understanding the physiological limitations to exercise after stroke will assist the development of targeted therapies to improve everyday function. This study defines (1) whether exercise capacity is limited by the cardiovascular system (oxygen supply) or skeletal muscles (oxygen utilization); and (2) cardiac function and pumping capability in people with stroke.

Methods—

Twenty-eight male participants with mild ischemic stroke (70±6 years of age, 18±20 months poststroke) and 25 male, age-matched healthy control subjects performed a graded cardiopulmonary exercise test with gas exchange and noninvasive hemodynamic measurements. Maximal oxygen extraction was calculated as the ratio between peak oxygen consumption and peak cardiac output. Cardiac function and pumping capability were assessed by peak exercise cardiac power output (expressed in watts) and cardiac output.

Results—

Peak oxygen consumption (18.4±4.6 versus 26.8±5.5 mL/kg/min,
P
<0.01) and arterial–venous O
2
difference (9.3±2.5 versus 12.6±1.9 mlO
2
/100 mL of blood,
P
<0.01) were both reduced in stroke participants compared with healthy control subjects. In contrast, peak exercise cardiac power output (4.79±0.79 versus 4.51±0.96 W,
P
=0.49), cardiac output (16.4±3.1 versus 17.1±2.5 L/min,
P
=0.41), and the pressure-generating capacity of the heart (127±11 versus 125±14 mm Hg,
P
=0.97) were similar between stroke participants and healthy control subjects.

Conclusions—

The ability of skeletal muscles to extract oxygen is diminished after stroke. However, cardiac function and pumping capability are maintained. Appropriate therapies targeting muscle oxygen uptake such as exercise rehabilitation may improve exercise capacity after stroke.
The Successor Representation and Temporal Context
Authors: Gershman Samuel J. , Moore Christopher D. , Todd Michael T. , Norman Kenneth A. , Sederberg Per B.
Published: February 2012

The successor representation was introduced into reinforcement learning by Dayan ( 1993 ) as a means of facilitating generalization between states with similar successors. Although reinforcement learning in general has been used extensively as a model of psychological and neural processes, the psychological validity of the successor representation has yet to be explored. An interesting possibility is that the successor representation can be used not only for reinforcement learning but for episodic learning as well. Our main contribution is to show that a variant of the temporal context model (TCM; Howard & Kahana, 2002 ), an influential model of episodic memory, can be understood as directly estimating the successor representation using the temporal difference learning algorithm (Sutton & Barto, 1998 ). This insight leads to a generalization of TCM and new experimental predictions. In addition to casting a new normative light on TCM, this equivalence suggests a previously unexplored point of contact between different learning systems.
Influence of the Subgrid Variability of the Raindrop Size Distribution on Radar Rainfall Estimators
Authors: Jaffrain Joël , Berne Alexis
Published: February 2012

This work aims at quantifying the variability of the parameters of the power laws used for rain-rate estimation from radar data, on the basis of raindrop size distribution measurements over a typical weather radar pixel. Power laws between the rain rate and the reflectivity or the specific differential phase shift are fitted to the measured values, and the variability of the parameters is analyzed. At the point scale, the variability within this radar pixel cannot be solely explained by the sampling uncertainty associated with disdrometer measurements. When parameters derived from point measurements are applied at the radar pixel scale, the resulting error in the rain amount varies between −2% and +15%.
Diurnal Characteristics of Rainfall over the Contiguous United States and Northern Mexico in the Dynamically Downscaled Reanalysis Dataset (US10)
Authors: Yamada Tomohito J. , Lee Myong-In , Kanamitsu Masao , Kanamaru Hideki
Published: February 2012

The diurnal characteristics of summer rainfall in the contiguous United States and northern Mexico were examined with the United States reanalysis for 5 years in 10-km horizontal resolution (US10), which is dynamically downscaled from the National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) Global Reanalysis 1 using the Regional Spectral Model (RSM). The hourly precipitation outputs demonstrate a realistic structure in the temporal evolution of the observed rainfall episodes and their magnitudes across the United States without any prescriptions of the observed rainfall to the global reanalysis and the downscaled regional reanalysis. Nighttime rainfall over the Great Plains associated with eastward-propagating, mesoscale convective systems originating from the Rocky Mountains is also represented realistically in US10, while the original reanalysis and most general circulation models (GCMs) have difficulties in capturing the series of nocturnal precipitation events in summer over the Plains. The results suggest an important role of the horizontal resolution of the model in resolving small-scale, propagating convective systems to improve the diurnal cycle of summer rainfall.
Practice Analysis of Nutrition Support Professionals
Authors: Matarese Laura E. , Chinn Roberta N. , Hertz Norman R. , Callahan Phila , Harvey‐Banchik Lillian , Strang Brian
Published: February 2012

Background: The National Board of Nutrition Support Certification (NBNSC) is an independent credentialing board responsible for administering the multidisciplinary certification examination in nutrition support. For an exam to be legally and practically defensible, it must represent practice. Validation is by practice audit, the highest level of supporting evidence. Objectives: To define the role of the nutrition support professional (NSP) and the current elements (knowledge and functions) required for competent NSP practice. Methods: A survey instrument was constructed using a content validation strategy to establish the link between job tasks and the content of the examination. Internet‐based surveys were made available to 5100 NSPs. NSP duties performed and knowledge required for patient safety and welfare were analyzed for the group as a whole and for each profession separately. Results: A total of 765 surveys were completed (return rate of 15%). The results of the practice audit demonstrate a common core of practice across the nutrition support disciplines as well as a universal core of elements believed to be important for competent nutrition support practice. Conclusion: The results of this survey continue to support a common core of practice across nutrition support disciplines as well as a common core of elements believed to be important for competent nutrition support practice. Accordingly, the NBNSC will continue to offer one examination to all disciplines both nationally and internationally and confer the Certified Nutrition Support Clinician (CNSC) credential to all individuals who successfully pass this validated examination.
ADHD Medication Vacations and Parent–Child Interactions by Gender
Authors: Barnard-Brak Lucy , Schmidt Marcelo , Sulak Tracey
Published: February 2012

Objective: The purpose of the current study was to examine medication vacations among children with ADHD according to parent–child dyads (e.g., mother–son, father–daughter, mother–daughter, and father–son). Method: In a survey study of 259 parents of children with ADHD, the use of medication vacations according to parent–child sex dyads was examined. Results: Results of the current study suggest that fathers seem to report endorsing medication vacations more with their sons with ADHD as opposed to their daughters with ADHD. There did not seem to be any significant differences among mothers. Conclusion: Results of the current study conclude with directions for future research and practice.
Effect of weld conditions on microstructures and mechanical properties of friction stir welded joints on AZ31B magnesium alloys
Authors: Fu R D , Ji H S , Li Y J , Liu L
Published: February 2012

The rotational direction of the friction stir welding (FSW) tool plays a role as important as the weld parameters in FSW processes for magnesium alloys. The formation quality of the weld joints strongly relies on the rotational direction of the stir tool. Based on the present results the better tensile properties of the weld joints are achieved by welding at a higher rotational speed no matter what direction the stir tool rotates. The face bend properties are superior to the root bend properties of the joints. The optimal weld parameters are 1500 rev min−1/90 mm min−1 and 1200 rev min−1/60 mm min−1 for the clockwise and counterclockwise directions of the stir tool respectively. Regardless of the direction which the tool rotates in, fractures of the tensile specimens are mostly located at the boundary between the thermal mechanical affect zone and the nugget zone.
Effect of post-weld heat treatment on microstructure and property of linear friction welded Ti17 titanium alloy joint
Authors: Ma T J , Li W Y , Zhong B , Zhang Y , Li J L
Published: February 2012

In this study, post-weld heat treatment of linear friction welded Ti17 (Ti–5Al–2Sn–2Zr–4Mo–4Cr) titanium alloy joints was performed at 530, 610 and 670°C for 4 h followed by air cooling. Results show that with increasing treatment temperature, the recrystallisation extent of the α and β phases in the weld and deformation zones increases significantly. The overall property of the joint is remarkably improved, and the fracture behaviour of the tensile and impact samples changes from brittle failure to a ductile one. After treatment at 670°C, the impact toughness of the joint is 93·3% of the parent metal, and the failure of the tensile samples occurs in the parent metal far away from the weld. According to these findings, a treatment temperature slightly lower than 670°C but higher than 610°C would be a good value for linear friction welding Ti17 joints.
Study on rapid thermal cycling by inducted heating for microstructure of single SnAgCu solder joint
Authors: Chen J B , Li C , Wu Y P
Published: February 2012

This paper reports in detail the experimental investigation of the effect of rapid thermal cycling on microstructure and growth of the intermetallic compound (IMC) layer at the interface between Sn–3·0Ag–0·5Cu solder and Cu substrate. With the application of electromagnetic induced heating, the specimen was rapidly heated and cooled based on a control system that employs a fuzzy logic algorithm. The temperature distribution in the solder joint was simulated and analysed. The experimental results showed that the predicted temperature profile approximates the results of measurement. It was found that the rapid thermal cycling had an evident influence on the microstructure of a single solder joint. The thickness of the IMC layer grew gradually with the cycling temperature during the test period. In addition, heterogeneous coarsening occurred between the IMC and Cu substrate. The growth characteristics of the IMC layer showed a sawtooth-like profile along the subplate's sides from 60 to 200°C.
Effect of electron beam welding on fracture behaviour of thick TC4-DT alloy
Authors: Lu W , Lei Y P , Li X Y , Shi Y W
Published: February 2012

Fracture toughness of a damage tolerant Ti6Al4V (TC4-DT) alloy and its electron beam welded joint was investigated using compact tension specimens. Moreover, tensile test, microhardness test and microstructure examination were carried out. The result indicates that the weld metal is strength overmatching. The tensile strength and microhardness of the weld metal are higher than those of the base metal, but the ductility and the energy absorbed before fracture are lower. In addition, the fracture toughness K1c of the base metal is relatively high. The fracture toughness of the weld metal decreases compared with the base metal. It is expected that the toughness reduction of the weld metal is mainly related to the as solidified coarse β columnar grain structure containing martensite in comparison with the bimodal structure of the base metal. Moreover, fractographic observation shows that the fracture mode of both weld and base metals is found to be ductile.
Unique dual targeting of thymidylate synthase and topoisomerase1 by FdUMP[10] results in high efficacy against AML and low toxicity
Authors: Pardee Timothy S. , Gomes Evan , Jennings-Gee Jamie , Caudell David , Gmeiner William H.
Published: February 2012

Acute myeloid leukemia (AML) is an aggressive malignancy that leads to marrow failure and death. There is a desperate need for new therapies. The novel fluoropyrimidine, FdUMP[10], was highly active against both human AML cell lines, (IC50 values, 3.4nM-21.5nM) and murine lines (IC50 values, 123.8pM-131.4pM). In all cases, the IC50 of FdUMP[10] was lower than for cytarabine and ∼ 1000 times lower than 5-fluorouracil (5-FU). FdUMP[10] remained effective against cells expressing the Flt3 internal tandem duplication, BCR-ABL, MN1, and an shRNA against p53. It had activity against patient samples at concentrations that did not affect normal hematopoietic cells. FdUMP[10] inhibited thymidylate synthase (TS) and trapped topoisomerase I cleavage complexes (Top1CCs), leading to DNA damage and apoptosis. All cell lines and nearly all primary AML samples examined expressed both TS and Top1. In vivo, FdUMP[10] was active against a syngeneic AML model with a survival advantage equivalent to doxorubicin plus cytarabine. 5-FU treatment was toxic and did not improve survival. FdUMP[10] was better tolerated than 5-FU or cytarabine plus doxorubicin and did not affect normal HSCs, while 5-FU dramatically impaired their ability to engraft. In summary, FdUMP[10] was highly efficacious and better tolerated than standard therapies.
Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry
Authors: Vlachos Adrianna , Rosenberg Philip S. , Atsidaftos Eva , Alter Blanche P. , Lipton Jeffrey M.
Published: February 2012

Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by red cell aplasia and congenital anomalies. A predisposition to cancer has been suggested but not quantified by case reports. The DBA Registry of North America (DBAR) is the largest established DBA patient cohort, with prospective follow-up since 1991. This report presents the first quantitative assessment of cancer incidence in DBA. Among 608 patients with 9458 person-years of follow-up, 15 solid tumors, 2 acute myeloid leukemias, and 2 cases of myelodysplastic syndrome were diagnosed at a median age of 41 years in patients who had not received a bone marrow transplant. Cancer incidence in DBA was significantly elevated. The observed-to- expected ratio for all cancers combined was 5.4 (P < .05); significant observed-to-expected ratios were 287 for myelodysplastic syndrome, 28 for acute myeloid leukemia, 36 for colon carcinoma, 33 for osteogenic sarcoma, and 12 for female genital cancers. The median survival was 56 years, and the cumulative incidence of solid tumor/leukemia was approximately 20% by age 46 years. As in Fanconi anemia and dyskeratosis congenita, DBA is both an inherited bone marrow failure syndrome and a cancer predisposition syndrome; cancer risks appear lower in DBA than in Fanconi anemia or dyskeratosis congenita. This trial was registered at www.clinicaltrials.gov as #NCT00106015.
Lung transplantation in children and young adults: a 20-year single-centre experience
Authors: Gruber Saskia , Eiwegger Thomas , Nachbaur Edith , Tiringer Kerstin , Aigner Clemens , Jaksch Peter , Keplinger Maya , Klepetko Walter , Lang György , Taghavi Shahrokh , Graf Alexandra , Eichler Irmgard , Frischer Thomas , Szépfalusi Zsolt
Published: February 2012

Lung transplantation in adults is an accepted therapeutic option, whereas there is ongoing debate on its positive impact on survival in children. We report our experience of the first 20 yrs of paediatric lung transplantation at a single centre in Austria.

Patient survival, organ survival and freedom from bronchiolitis obliterans were estimated by Kaplan–Meier curves. Pre- and post-transplant parameters were assessed and their influence on patient and organ survival evaluated by univariate tests and stepwise multivariate analyses.

A total of 55 transplantations were performed in 43 patients. 1- and 5-yr patient survival rates were 72.1% and 60.6%, respectively, and 52.6% of patients were found to be free from bronchiolitis obliterans syndrome at 5 yrs post-transplant. Analysing different eras of transplantation suggests an improvement over the years with a 5-yr survival rate of 70.6% in the second decade. A positive effect of pre-transplant diabetes mellitus and immunosuppression was found with the newer drug tacrolimus, and a negative effect of pre-transplant in-hospital admission was reported. A high rate of successful re-transplantation prolonged total patient survival.
Survival in pulmonary hypertension in Spain: insights from the Spanish registry
Authors: Escribano-Subias Pilar , Blanco Isabel , López-Meseguer Manuel , Lopez-Guarch Carmen Jimenez , Roman Antonio , Morales Pilar , Castillo-Palma María Jesús , Segovia Javier , Gómez-Sanchez Miguel A. , Barberà Joan Albert
Published: February 2012

A pulmonary hypertension (PH) registry (Spanish Registry of Pulmonary Arterial Hypertension) was undertaken to analyse prevalence, incidence and survival of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Spain, and to assess the applicability of recent survival prediction equations.

Voluntary reporting of previously diagnosed and incident PAH or CTEPH cases (July 2007–June 2008) was performed. Demographic, functional and haemodynamic variables were evaluated.

866 patients with PAH and 162 with CTEPH were included. PAH associated with toxic oil syndrome and pulmonary veno-occlusive disease were reported for the first time in a PAH registry. Estimated prevalences were as follows: PAH, 16 and CTEPH, 3.2 cases per million adult inhabitants (MAI). Estimated incidences were as follows: PAH, 3.7 and CTEPH, 0.9 cases per MAI per yr. 1-, 3- and 5-yr survival was 87%, 75% and 65%, respectively, with no differences between PAH and CTEPH. Male sex, right atrial pressure and cardiac index were independent predictors of death. Matching between observed survival and that predicted by different equations was closer when the characteristics of the cohorts were similar.

Epidemiology and survival of PAH patients in the Spanish registry are similar to recent registries. Characteristics of the population from which survival prediction equations are derived influence their applicability to a different cohort. CTEPH is much less prevalent than PAH, although has a similar survival rate.
Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension
Authors: Simonneau Gérald , Torbicki Adam , Hoeper Marius M. , Delcroix Marion , Karlócai Kristóf , Galiè Nazzareno , Degano Bruno , Bonderman Diana , Kurzyna Marcin , Efficace Michela , Giorgino Ruben , Lang Irene M.
Published: February 2012

In this phase 2 proof-of-concept study we examined the safety and efficacy of selexipag, an orally available, selective prostacyclin receptor (IP receptor) agonist, as a treatment for pulmonary arterial hypertension (PAH).

43 adult patients with symptomatic PAH (receiving stable endothelin receptor antagonist and/or a phosphodiesterase type-5 inhibitor therapy) were randomised three to one to receive either selexipag or placebo. Dosage was up-titrated in 200-μg increments from 200 μg twice daily on day 1 to the maximum tolerated dose by day 35 (maximum allowed dose of 800 μg twice daily). Change in pulmonary vascular resistance at week 17 expressed as a percentage of the baseline value was the primary efficacy end-point, and was analysed in the per protocol set first and then in the all-treated set to assess robustness of results.

A statistically significant 30.3% reduction in geometric mean pulmonary vascular resistance was observed after 17 weeks' treatment with selexipag compared with placebo (95% confidence limits -44.7– -12.2; p=0.0045, Wilcoxon rank sum test). This was supported by a similar result from the all-treated set. Selexipag was well tolerated with a safety profile in line with the expected pharmacological effect.

Our results encourage the further investigation of selexipag for the treatment of PAH.
The effect of airway pressure and oscillation amplitude on ventilation in pre-term infants
Authors: Miedema Martijn , de Jongh Frans H. , Frerichs Inez , van Veenendaal Mariette B. , van Kaam Anton H.
Published: February 2012

We determined the effect of lung recruitment and oscillation amplitude on regional oscillation volume and functional residual capacity (FRC) in high-frequency oscillatory ventilation (HFOV) used in pre-term infants with respiratory distress syndrome (RDS).

Changes in lung volume, oscillation volume and carbon dioxide levels were recorded in 10 infants during a stepwise recruitment procedure, and an increase in pressure amplitude of 5 cmH2O was measured using electrical impedance tomography and transcutaneous monitoring. The pressures at maximal respiratory system compliance, maximal oscillation volume and minimal carbon dioxide levels were determined. Impedance data were analysed for the chest cross-section and predefined regions of interest.

Despite the fixed pressure amplitude, the oscillation volume changed during the incremental pressure steps following a parabolic pattern, with an inverse relationship to the carbon dioxide pressures. The pressures corresponding with maximal compliance, maximal oscillation volume and minimal carbon dioxide were similar and highly correlated. Regional analysis showed similar findings. The increase in pressure amplitude resulted in increased oscillation volumes and decreased carbon dioxide levels, while FRC remained unchanged.

In HFV pre-term infants with RDS, oscillation volumes are closely related to the position of ventilation in the pressure–volume envelope and the applied pressure amplitude. Changes in pressure amplitude do not seem to affect FRC.
Quadriceps wasting and physical inactivity in patients with COPD
Authors: Shrikrishna Dinesh , Patel Mehul , Tanner Rebecca J. , Seymour John M. , Connolly Bronwen A. , Puthucheary Zudin A. , Walsh Simon L.F. , Bloch Susannah A. , Sidhu Paul S. , Hart Nicholas , Kemp Paul R. , Moxham John , Polkey Michael I. , Hopkinson Nicholas S.
Published: February 2012

Quadriceps weakness is an important complication of advanced chronic obstructive pulmonary disease (COPD) but few data exist concerning muscle bulk in early disease. We hypothesised that quadriceps bulk, measured by ultrasound rectus femoris cross-sectional area (USRFCSA), would be reduced in mild, as well as advanced, COPD compared with controls, and would correlate with physical activity.

161 patients with stable COPD and 40 healthy subjects had a measurement of USRFCSAand wore a multisensor armband to record physical activity.

USRFCSAwas reduced in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I patients compared with healthy subjects (p=0.0002). Stage II–IV patients had reduced USRFCSA(p<0.0001) compared with controls but were not significantly different from those with stage I disease. Physical activity level was reduced in stage I (p=0.002) and stage II–IV disease compared with controls. Using regression analysis, physical activity level was independently associated with USRFCSAin stage I (p=0.01) but not stage II–IV disease, where residual volume to total lung capacity ratio was the only independent predictor of physical activity level.

Quadriceps wasting exists in patients with mild, as well as advanced, COPD, and is independently associated with physical inactivity in GOLD stage I disease. The identification of these patients may guide early lifestyle and therapeutic interventions.
Sleep-disordered breathing in deep vein thrombosis and acute pulmonary embolism
Authors: Arzt Michael , Luigart Ruth , Schum Carola , Lüthje Lars , Stein Annika , Koper Iris , Hecker Cornelia , Dumitrascu Rio , Schulz Richard ,   for the “Circulation and Sleep” working group of the German Society of Sleep Research and Sleep Medicine (DGSM)
Published: February 2012

Sleep-disordered breathing (SDB) may trigger thromboembolic events by enhancing intravascular clot formation. The primary objective of the present nested case–control study was to investigate whether the prevalence of SDB is increased in patients with deep vein thrombosis (DVT) and/or acute pulmonary embolism (PE).

82 consecutive patients with DVT and/or PE (cases) were prospectively enrolled irrespective of SDB-related symptoms and formed matched pairs with patients without DVT and/or PE (controls) according to sex and pre-defined categories of age and body mass index.

The prevalence of SDB (respiratory disturbance index assessed by polygraphy ≥15 events·h−1) was significantly greater in the cases with DVT and/or PE than in controls (40versus26%, p=0.046) and was predominantly obstructive in nature. Multiple regression analysis revealed that SDB was significantly associated with DVT and/or PE (OR 2.28, 95% CI 1.08–4.85; p=0.032) independent of established risk factors for thrombosis. In the sex-specific analyses this association was significant in females (OR 4.14, 95% CI 1.05–16.36; p=0.042), but not in males (OR 1.55, 95% CI 0.57–4.21; p=0.391).

SDB occurs more frequently in females with DVT and/or PE than in controls matched for anthropometric variables, and is independently associated with the occurrence of these thromboembolic events.