bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement
Authors: Barazzoni Rocco , Short Kevin R. , Asmann Yan , Coenen-Schimke Jill M. , Robinson Matthew M. , Sreekumaran Nair K.
Published: September 2012

Systemic insulin administration causes hypoaminoacidemia by inhibiting protein degradation, which may in turn inhibit muscle protein synthesis (PS). Insulin enhances muscle mitochondrial PS and ATP production when hypoaminoacidemia is prevented by exogenous amino acid (AA) replacement. We determined whether insulin would stimulate mitochondrial PS and ATP production in the absence of AA replacement. Using l-[1,2-13C]leucine as a tracer, we measured the fractional synthetic rate of mitochondrial as well as sarcoplasmic and mixed muscle proteins in 18 participants during sustained (7-h) insulin or saline infusion ( n = 9 each). We also measured muscle ATP production, mitochondrial enzyme activities, mRNA levels of mitochondrial genes, and phosphorylation of signaling proteins regulating protein synthesis. The concentration of circulating essential AA decreased during insulin infusion. Mitochondrial, sarcoplasmic, and mixed muscle PS rates were also lower during insulin (2–7 h) than during saline infusions despite increased mRNA levels of selected mitochondrial genes. Under these conditions, insulin did not alter mitochondrial enzyme activities and ATP production. These effects were associated with enhanced phosphorylation of Akt but not of protein synthesis activators mTOR, p70S6K, and 4EBP1. In conclusion, sustained physiological hyperinsulinemia without AA replacement did not stimulate PS of mixed muscle or protein subfractions and did not alter muscle mitochondrial ATP production in healthy humans. These results support that insulin and AA act in conjunction to stimulate muscle mitochondrial function and mitochondrial protein synthesis.
A Nonparametric Shewhart-Type Quality Control Chart for Monitoring Broad Changes in a Process Distribution
Authors: Bakir Saad T.
Published: September 2012

This paper develops a distribution-free (or nonparametric) Shewhart-type statistical quality control chart for detecting a broad change in the probability distribution of a process. The proposed chart is designed for grouped observations, and it requires the availability of a reference (or training) sample of observations taken when the process was operating in-control. The charting statistic is a modified version of the two-sample Kolmogorov-Smirnov test statistic that allows the exact calculation of the conditional average run length using the binomial distribution. Unlike the traditional distribution-based control charts (such as the Shewhart X-Bar), the proposed chart maintains the same control limits and the in-control average run length over the class of all (symmetric or asymmetric) continuous probability distributions. The proposed chart aims at monitoring a broad, rather than a one-parameter, change in a process distribution. Simulation studies show that the chart is more robust against increased skewness and/or outliers in the process output. Further, the proposed chart is shown to be more efficient than the Shewhart X-Bar chart when the underlying process distribution has tails heavier than those of the normal distribution.
The FlatwormMacrostomum lignanoIs a Powerful Model Organism for Ion Channel and Stem Cell Research
Authors: Simanov Daniil , Mellaart-Straver Imre , Sormacheva Irina , Berezikov Eugene
Published: September 2012

Bioelectrical signals generated by ion channels play crucial roles in many cellular processes in both excitable and nonexcitable cells. Some ion channels are directly implemented in chemical signaling pathways, the others are involved in regulation of cytoplasmic or vesicular ion concentrations, pH, cell volume, and membrane potentials. Together with ion transporters and gap junction complexes, ion channels form steady-state voltage gradients across the cell membranes in nonexcitable cells. These membrane potentials are involved in regulation of such processes as migration guidance, cell proliferation, and body axis patterning during development and regeneration. While the importance of membrane potential in stem cell maintenance, proliferation, and differentiation is evident, the mechanisms of this bioelectric control of stem cell activity are still not well understood, and the role of specific ion channels in these processes remains unclear. Here we introduce the flatwormMacrostomum lignanoas a versatile model organism for addressing these topics. We discuss biological and experimental properties ofM. lignano, provide an overview of the recently developed experimental tools for this animal model, and demonstrate how manipulation of membrane potential influences regeneration inM. lignano.
Simple Cystatin C Formula for Estimation of Glomerular Filtration Rate in Overweight Patients with Diabetes Mellitus Type 2 and Chronic Kidney Disease
Authors: Bevc Sebastjan , Hojs Radovan , Ekart Robert , Završnik Matej , Gorenjak Maksimiljan , Puklavec Ludvik
Published: September 2012

In clinical practice the glomerular filtration rate (GFR) is estimated from serum creatinine-based equations like the Cockcroft-Gault formula (C&G) and Modification of Diet in Renal Disease formula (MDRD). Recently, serum cystatin C-based equations, the newer creatinine formula (The Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)), and equation that use both serum creatinine and cystatin C (CKD-EPI creatinine & cystatin formula) were proposed as new GFR markers. Present study compares serum creatinine-based equations, combined (including both serum creatinine and cystatin C) equation, and serum simple cystatin C formula (100/serum cystatin C) against 51CrEDTA clearance in 113 adult overweight Caucasians with diabetes mellitus type 2 (DM2) and chronic kidney disease (CKD). The results of present study demonstrated that the simple cystatin C formula could be a useful tool for the evaluation of renal function in overweight patients with DM2 and impaired kidney function in daily clinical practice in hospital and especially in outpatients. Despite the advantages of the simple cystatin C formula, cystatin C-based equations cannot completely replace the “gold standard” for estimation of the GFR in a population of DM2 patients with CKD, but may contribute to a more accurate selection of patients requiring such invasive and costly procedures.
Modified Hybrid Block Iterative Algorithm for Uniformly Quasi‐ϕ‐Asymptotically Nonexpansive Mappings
Authors: Feng Qiansheng , Su Yongfu , Yan Fangfang
Published: September 2012

Saewan and Kumam (2010) have proved the convergence theorems for finding the set of solutions of a general equilibrium problems and the common fixed point set of a family of closed and uniformly quasi‐ϕ‐asymptotically nonexpansive mappings in a uniformly smooth and strictly convex Banach space E with Kadec‐Klee property. In this paper, authors prove the convergence theorems and do not need the Kadec‐Klee property of Banach space and some other conditions used in the paper of S. Saewan and P. Kumam. Therefore, the results presented in this paper improve and extend some recent results.
A Case of Respiratory Syncytial Virus Infection in an HIV-Positive Adult
Authors: Gupta Aakriti , Mody Purav , Gupta Shefali
Published: September 2012

Respiratory syncytial virus (RSV) is commonly known to cause an influenza-like illness. However, it can also cause more severe disease in young children and older adults comprising of organ transplant patients with immunocompromised status. Till date, only four cases of RSV infections have been reported in HIV-positive adults. We describe here a case of HIV-positive female with relatively preserved immune function who presented with RSV infection requiring ventilation and showed improvement after prompt treatment with intravenous immunoglobulin.
Nonsmooth Modeling of Vibro-Impacting Euler-Bernoulli Beam
Authors: Vyasarayani C. P. , Sandhu Sukhpreet Singh , McPhee John
Published: September 2012

A new technique to simulate nonsmooth motions occurring in vibro-impacting continuous systems is proposed. Sticking motions that are encountered during vibro-impact simulation are imposed exactly using a Lagrange multiplier, which represents the normal reaction force between the continuous system and the obstacle. The expression for the Lagrange multiplier is developed in closed form. The developed theory is demonstrated by numerically simulating the forced response of a pinned-pinned beam impacting a point-like rigid obstacle.
On Sumudu Transform Method in Discrete Fractional Calculus
Authors: Jarad Fahd , Taş Kenan
Published: September 2012

In this paper, starting from the definition of the Sumudu transform on a general time scale, we define the generalized discrete Sumudu transform and present some of its basic properties. We obtain the discrete Sumudu transform of Taylor monomials, fractional sums, and fractional differences. We apply this transform to solve some fractional difference initial value problems.
A Comparison of Parametric and Sample-Based Message Representation in Cooperative Localization
Authors: Lien Jaime , Ferner Ulric J. , Srichavengsup Warakorn , Wymeersch Henk , Win Moe Z.
Published: September 2012

Location awareness is a key enabling feature and fundamental challenge in present and future wireless networks.
Most existing localization methods rely on existing infrastructure and thus lack the flexibility and robustness necessary for large ad hoc networks. In this paper, we build upon SPAWN (sum-product algorithm over a wireless network), which determines node locations through iterative message passing, but does so at a high computational cost. We compare different message representations for SPAWN in terms of performance and complexity and investigate several types of cooperation based on censoring. Our results, based on experimental data with ultra-wideband (UWB) nodes, indicate that parametric message representation combined with simple censoring can give excellent performance at relatively low complexity.
Bevacizumab and Breast Cancer: A Meta-Analysis of First-Line Phase III Studies and a Critical Reappraisal of Available Evidence
Authors: Rossari José R. , Metzger-Filho Otto , Paesmans Marianne , Saini Kamal S. , Gennari Alessandra , de Azambuja Evandro , Piccart-Gebhart Martine
Published: September 2012

Background. Randomized studies have shown different magnitude of bevacizumab benefit in the treatment of advanced breast cancer. Regulatory agencies have modified bevacizumab treatment indications across different regions. In this study, we perform a meta-analysis of phase III studies aiming to interrogate the magnitude of bevacizumab benefit for the treatment of first-line HER2-negative metastatic breast cancer (MBC).Methods. Data from studies E2100, AVADO and RIBBON-1 were used to calculate the benefit of bevacizumab in terms of tumor overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicities. Combined statistical estimates of hazard ratios (HR) and odds ratios were calculated using fixed-effects or random-effects models.Results. A total of 2,695 patients were evaluated. Combining bevacizumab with different chemotherapy backbones resulted in a 30% risk reduction of PFS events (HR = 0.70; 95% confidence interval [CI], 0.57–0.86) and increased ORR (odds ratio 1.81; 95% CI, 1.53–2.14). No OS benefit could be demonstrated (HR = 0.95; 95% CI, 0.85–1.06). Bevacizumab significantly increased the incidence of adverse events such as proteinuria, hypertension and cardiovascular events.Conclusions. Bevacizumab combined with chemotherapy in the first-line treatment of MBC significantly improved ORR and PFS, but also increased grade 3-4 toxicities. No significant OS advantage was observed.
Characterization of the Phosphoproteome in Human Bronchoalveolar Lavage Fluid
Authors: Giorgianni Francesco , Mileo Valentina , Desiderio Dominic M. , Catinella Silvia , Beranova-Giorgianni Sarka
Published: September 2012

Global-scale examination of protein phosphorylation in human biological fluids by phosphoproteomics approaches is an emerging area of research with potential for significant contributions towards discovery of novel biomarkers. In this pilot work, we analyzed the phosphoproteome in human bronchoalveolar lavage fluid (BAL) from nondiseased subjects. The main objectives were to assess the feasibility to probe phosphorylated proteins in human BAL and to obtain the initial catalog of BAL phosphoproteins, including protein identities and exact description of their phosphorylation sites. We used a gel-free bioanalytical workflow that included whole-proteome digestion of depleted BAL proteins, enrichment of phosphopeptides by immobilized metal ion affinity chromatography (IMAC), LC-MS/MS analyses with a linear ion trap mass spectrometer, and searches of a protein sequence database to generate a panel of BAL phosphoproteins and their sites of phosphorylation. Based on sequence-diagnostic MS/MS fragmentation patterns, we identified a collection of 36 phosphopeptides that contained 26 different phosphorylation sites. These phosphopeptides mapped to 21 phosphoproteins including, for example, vimentin, plastin-2, ferritin heavy chain, kininogen-1, and others. The characterized phosphoproteins have diverse characteristics in terms of cellular origin and biological function. To the best of our knowledge, results of this study represent the first description of the human BAL phosphoproteome.
Sparse Signal Recovery via ECME Thresholding Pursuits
Authors: Song Heping , Wang Guoli
Published: September 2012

The emerging theory of compressive sensing (CS) provides a new sparse signal processing paradigm for reconstructing sparse signals from the undersampled linear measurements. Recently, numerous algorithms have been developed to solve convex optimization problems for CS sparse signal recovery. However, in some certain circumstances, greedy algorithms exhibit superior performance than convex methods. This paper is a followup to the recent paper of Wang and Yin (2010), who refine BP reconstructions via iterative support detection (ISD). The heuristic idea of ISD was applied to greedy algorithms. We developed two approaches for accelerating the ECME iteration. The described algorithms, named ECME thresholding pursuits (EMTP), introduced two greedy strategies that each iteration detects a support set I by thresholding the result of the ECME iteration and estimates the reconstructed signal by solving a truncated least‐squares problem on the support set I. Two effective support detection strategies are devised for the sparse signals with components having a fast decaying distribution of nonzero components. The experimental studies are presented to demonstrate that EMTP offers an appealing alternative to state‐of‐the‐art algorithms for sparse signal recovery.
A Survey of Methods for Gas-Lift Optimization
Authors: Rashid Kashif , Bailey William , Couët Benoît
Published: September 2012

This paper presents a survey of methods and techniques developed for the solution of the continuous gas-lift optimization problem over the last two decades. These range from isolated single-well analysis all the way to real-time multivariate optimization schemes encompassing all wells in a field. While some methods are clearly limited due to their neglect of treating the effects of inter-dependent wells with common flow lines, other methods are limited due to the efficacy and quality of the solution obtained when dealing with large-scale networks comprising hundreds of difficult to produce wells. The aim of this paper is to provide an insight into the approaches developed and to highlight the challenges that remain.
Inhibition of Advanced Glycation End-Product Formation byOriganum majoranaL.In Vitroand in Streptozotocin-Induced Diabetic Rats
Authors: Perez Gutierrez Rosa Martha
Published: September 2012

The development of AGE inhibitors is considered to have therapeutic potential in patients with diabetes diseases. The aim of the present study was investigate the effect of methanolic extract of the leaves ofOriganum majorana(OM) used as spice in many countries on AGEs formation.In vitrostudies indicated a significant inhibitory effects on the formation of AGEs. Their antiglycation activities were not only brought about by their antioxidant activities but also related to their trapping abilities of reactive carbonyl species such as methylglyoxal, an intermediate reactive carbonyl of AGE formation. The results demonstrate that OM have significant effects onin vitroAGE formation, and the glycation inhibitory activity was more effectively than those obtained using as standard antiglycation agent aminoguanidine. OM is a potent agent for protecting LDL against oxidation and glycation. Treatment of streptozotocin-diabetic mice with OM and glibenclamide for 28 days had beneficial effects on renal metabolic abnormalities including glucose level and AGEs formation. Diabetic mice showed increase in tail tendon collagen, glycated collagen linked fluorescence and reduction in pepsin digestion. Treatment with OM improved these parameters when compared to diabetic control and glibenclamide.
Nurse Managers’ Leadership Styles in Finland
Authors: Vesterinen Soili , Suhonen Marjo , Isola Arja , Paasivaara Leena
Published: September 2012

Nurse managers who can observe their own behaviour and its effects on employees can adjust to a better leadership style. The intention of this study was to explore nurses’ and supervisors’ perceptions of nurse managers’ leadership styles. Open-ended interviews were conducted with 11 nurses and 10 superiors. The data were analysed by content analysis. In the study, six leadership styles were identified: visionary, coaching, affiliate, democratic, commanding, and isolating. Job satisfaction and commitment as well as operation and development work, cooperation, and organizational climate in the work unit were the factors, affected by leadership styles. The nurse managers should consider their leadership style from the point of view of employees, situation factors, and goals of the organization. Leadership styles where employees are seen in a participatory role have become more common.
Two Positive Periodic Solutions for a Neutral Delay Model of Single‐Species Population Growth with Harvesting
Authors: Fang Hui
Published: September 2012

By coincidence degree theory for k‐set‐contractive mapping, this paper establishes a new criterion for the existence of at least two positive periodic solutions for a neutral delay model of single‐species population growth with harvesting. An example is given to illustrate the effectiveness of the result.
An Economical High-Throughput Protocol for Multidimensional Fractionation of Proteins
Authors: Tooth David John , Gopala Krishna Varun , Layfield Robert
Published: September 2012

A sequential protocol of multidimensional fractionation was optimised to enable the comparative profiling of fractions of proteomes from cultured human cells. Differential detergent fractionation was employed as a first step to obtain fractions enriched for cytosolic, membrane/organelle, nuclear, and cytoskeletal proteins. Following buffer exchange using gel-permeation chromatography, cytosolic proteins were further fractionated by 2-dimensional chromatography employing anion-exchange followed by reversed-phase steps. Chromatographic fractions were shown to be readily compatible with 1- and 2-dimensional gel electrophoresis or with direct analysis by mass spectrometry using linear-MALDI-TOF-MS. Precision of extraction was confirmed by reproducible SDS-PAGE profiles, MALDI-TOF-MS spectra, and quantitation of trypsinolytic peptides using LC-MS/MS (MRM) analyses. Solid phases were immobilised in disposable cartridges and mobile-phase flow was achieved using a combination of centrifugation and vacuum pumping. These approaches yielded parallel sample handling which was limited only by the capacities of the employed devices and which enabled both high-throughput and experimentally precise procedures, as demonstrated by the processing of experimental replicates. Protocols were employed at 10 mg scale of extracted cell protein, but these approaches would be directly applicable to both smaller and larger quantities merely by adjusting the employed solid- and mobile-phase volumes. Additional potential applications of the fractionation protocol are briefly described.
Management of Venous Thromboembolism in Patients with Advanced Gastrointestinal Cancers: What Is the Role of Novel Oral Anticoagulants?
Authors: Martin Ludmila Katherine , Bekaii-Saab Tanios
Published: September 2012

Venous thromboembolism (VTE) is a frequent complication of gastrointestinal cancers that increases morbidity and may impact mortality. Low-molecular-weight heparins (LMWHs) and vitamin K antagonists (VKAs) are standard anticoagulation options for the ambulatory gastrointestinal cancer patient with VTE, but both of these agents are challenging to use for various reasons. Novel oral anticoagulants (NOAs) are new, orally available anticoagulants designed to be easier to administer with more reliable pharmacokinetics that eliminate the need for frequent monitoring of various laboratory parameters. This paper reviews the existing efficacy and safety data for the use of NOAs dabigatran etexilate, rivaroxaban, and apixaban and discusses the potential role of these agents in the management of gastrointestinal cancer-related VTE.
Oral HIV-Associated Kaposi Sarcoma: A Clinical Study from the Ga-Rankuwa Area, South Africa
Authors: Khammissa Razia A. G. , Pantanowitz Liron , Feller Liviu
Published: September 2012

Background. Kaposi sarcoma (KS) is one of the most common neoplasms diagnosed in HIV-seropositive subjects. Oral involvement is frequent and is associated with a poor prognosis. The aim of this study was to characterize the features of oral HIV-KS in patients from Ga-Rankuwa, South Africa.Methods. All cases with confirmed oral HIV-KS treated at the oral medicine clinic in Ga-Rankuwa from 2004 to 2010 were included in this retrospective study. Differences between males and females with oral HIV-KS in relation to HIV infection status, to oral KS presentation and to survival rates were statistically analysed.Results. Twenty (54%) of the 37 patients in the study were females and 17 (46%) were males. In 21 patients (57%), the initial presentation of HIV-KS was in the mouth. Other than the fact that females presented with larger (≥10 mm) oral KS lesions(P=0.0004), there were no statistically significant gender differences. Significantly more patients presented with multiple oral HIV-KS lesions than with single lesions(P=0.0003). Nine patients (24%) developed concomitant facial lymphoedema, and these patients had a significantly lower CD4+ T-cell count (28 cells/mm3) compared to the rest of the group (130 cells/mm3) (P=0.01). The average CD4+ T-cell count of the patients who died (64 cells/mm3) was significantly lower(P=0.0004), there were no statistically significant gender differences. Significantly more patients presented with multiple oral HIV-KS lesions than with single lesions(P=0.016)at the time of oral-KS presentation than of those who survived (166  cells/mm3). Conclusions: In Ga-Rankuwa, South Africa where HIV-KS is prevalent, oral KS affects similarly males and females. A low CD4+ T-cell count at the time of oral HIV-KS diagnosis and the development of facial lymphoedema during the course of HIV-KS disease portends a poor prognosis.
Current Understanding of Lifestyle and Environmental Factors and Risk of Non-Hodgkin Lymphoma: An Epidemiological Update
Authors: Bassig Bryan A. , Lan Qing , Rothman Nathaniel , Zhang Yawei , Zheng Tongzhang
Published: September 2012

The incidence rates of non-Hodgkin lymphoma (NHL) have steadily increased over the last several decades in the United States, and the temporal trends in incidence can only be partially explained by the HIV epidemic. In 1992, an international workshop sponsored by the United States National Cancer Institute concluded that there was an “emerging epidemic” of NHL and emphasized the need to investigate the factors responsible for the increasing incidence of this disease. Over the past two decades, numerous epidemiological studies have examined the risk factors for NHL, particularly for putative environmental and lifestyle risk factors, and international consortia have been established in order to investigate rare exposures and NHL subtype-specific associations. While few consistent risk factors for NHL aside from immunosuppression and certain infectious agents have emerged, suggestive associations with several lifestyle and environmental factors have been reported in epidemiologic studies. Further, increasing evidence has suggested that the effects of these and other exposures may be limited to or stronger for particular NHL subtypes. This paper examines the progress that has been made over the last twenty years in elucidating the etiology of NHL, with a primary emphasis on lifestyle factors and environmental exposures.
Exploration of Newer Possibilities to the Synthesis of Diazepine and Quinoline Carboxylic Acid Derivatives
Authors: Soni Vatsala , Sharma Meenakshi , Agarwal Anshu , Kishore Dharma
Published: September 2012

Heterocyclic systems containing benzothiazoles, carbazole (and azacarbazole) moieties have attracted the attention of chemists owing to these nuclei having been identified in the literature as most promising pharmacophores in drug design and synthesis. Based on these observations, it could be anticipated that incorporation of the bioactive azepine moiety and quinoline moiety into the molecular framework of benzothiazoles fused to carbazole (and azacarbazoles) could produce interesting series of compounds 9–12 with enhanced biological activities, whose structure was unequivocally established from its microanalyses and spectral data.
Evaluation of NaCl Effect on Vibration-Delaminated Metal-Polymer Composites by Improved Micro-Raman Methodology
Authors: Zumelzu E. , Asomavich I. , Rull F. , Cabezas C.
Published: September 2012

Polyethylene terephthalate (PET) is a polymer coating that protects the electrolytic chromium coated steel (ECCS) against aggressive electrolytes like NaCl. It is widely accepted by manufacturers that NaCl has no effect on the PET coating, which is inert. However, we showed that there are some effects at the structural level, caused by vibrations, and facilitated by defects on the layers. The vibrations occurring during the transportation of food containers produce delaminations at given points of the metal-polymer interface, known as antinodes, which in turn may produce PET degradation affecting food quality. The former can be determined by electrochemical measurements, and the changes in composition or structural order can be characterized by Raman. The present work applied this latter technique in experimental samples of PET-coated ECCS sheets by performing perpendicular and parallel analyses to the surface, and determined that it constitutes a new potential methodology to determine the behavior of the composite under the above conditions. The results demonstrated that the delamination areas on the PET facilitated polymer degradation by the electrolyte. Moreover, the Raman characterization evidenced the presence of multilayers and crystalline orderings, which limited its functionality as a protective coating.
Mature Teratoma in Association with Neural Tube Defect (Occipital Encephalocele): Series of Four Cases and Review of the Literature
Authors: Goyal Nishant , Singh Pankaj Kumar , Kakkar Aanchal , Sharma Meher Chand , Mahapatra Ashok Kumar
Published: September 2012

Both occipital encephalocele and teratomas are midline congenital malformations. Encephalocele is a form of neural tube defect in which there is a congenital defect of the cranium through which occurs a protrusion of brain matter or meninges, while teratoma is a tumor derived from all three germ layers. The association between occipital encephalocele and teratoma has not been reported to date. In the present study, the authors present a series of four such cases.
Postprandial Hyperglycemia Corrected by IGF-I (Increlex®) in Laron Syndrome
Authors: Latrech Hanane , Simon Albane , Beltrand Jacques , Souberbielle Jean-Claude , Belmejdoub Ghizlane , Polak Michel
Published: September 2012

Background: Laron syndrome is caused by a mutation in the growth hormone (GH) receptor and manifests as insulin-like growth factor-I (IGF-I) deficiency, severe short stature, and early hypoglycemia. We report a case with postprandial hyperglycemia, an abnormality not reported previously. Postprandial hyperglycemia was due to chronic IGF-I deficiency, and was reversed by IGF-I replacement therapy. Methods: A Moroccan girl referred for short stature at 7 years and 8 months of age had dwarfism [height, 78 cm (–9 SDs); weight, 10 kg (–4 SDs)], hypoglycemia, and truncal obesity. Her serum IGF-I level was very low, and her baseline serum GH level was elevated to 47 mIU/l. Molecular analysis showed a homozygous mutation in the GH receptor gene. Results: Continuous glucose monitoring before treatment showed asymptomatic hypoglycemia with postprandial hyperglycemia (2.5 g/l, 13.75 mmol/l). Treatment with recombinant human IGF-I (mecasermin, Increlex®) was started. The blood glucose profile improved with 0.04 µg/kg/day and returned to normal with 0.12 µg/kg/day. Conclusion: Postprandial hyperglycemia is a metabolic consequence of chronic IGF-I deficiency. The beneficial effect of IGF-I replacement therapy may be ascribable to improved postprandial transfer of glucose.
Development and Regeneration Potential of the Mammalian Intervertebral Disc
Authors: Henriksson Helena Barreto , Brisby Helena
Published: September 2012

At the present time, the normal cell proliferation rate and regeneration processes in the intervertebral disc (IVD) are not fully known. Historically, the IVD has been considered an organ with little or no regenerative capacity. However, several studies have identified the presence of cells expressing progenitor/stem cell markers in adult cartilage tissue and recent data suggest that adult mammalian IVDs have regenerative capacity, albeit slow. The aim of this review is to give an overview of the present knowledge regarding IVD development, regeneration and repair mechanisms in mammals, with a special focus on human discs. At a time when regenerative medicine is making progress and biological treatment options, such as stem cell therapy, are suggested for patients with degenerated discs causing chronic low back pain, basic knowledge about disc cells and their regenerative capacity form a useful basis for the exploration of new treatment options.
Different Mechanisms of Intestinal Calcium Absorption at Different Life Stages: Therapeutic Implications and Long-Term Responses to Treatment in Patients with Hereditary Vitamin D-Resistant Rickets
Authors: Chaturvedi Deepti , Garabedian Michèle , Carel Jean-Claude , Léger Juliane
Published: September 2012

Background: Intestinal calcium absorption is regulated principally by 1,25-dihydroxyvitamin D, but other regulators are also involved. Case Report: The 3 children studied were born with unaffected bones. Two were referred at 21 months of age, with clinical features of severe vitamin D-resistant rickets. They were treated with intravenous calcium for 12–18 months, following an initial lack of response to oral calcium and vitamin D. The third patient, who was exclusively breast-fed, was diagnosed at 4 months of age, due to alopecia. His condition was successfully managed with high doses of oral calcium and vitamin D. All 3 patients were homozygous for a mutation in the DNA-binding domain of vitamin D receptor. At the most recent evaluation of these patients, currently maintained on oral calcium and vitamin D, clinical findings were normal. Conclusion: During gestation, calcium flux across the placenta is normal, preventing bone diseases in affected fetuses. High calcium intake early in life and, perhaps, the maintenance of breastfeeding for several months may constitute an effective approach to ensuring adequate absorption and preventing severe rickets. During childhood, after parenteral calcium treatment to bypass intestinal calcium absorption, it is possible to maintain normal bone through long-term oral calcium supplementation.
The Quality of 5-Aminolevulinic Acid-Induced Photodynamic Diagnosis and Transurethral Resection of Bladder Tumors: Does the Urologist Play a Role?
Authors: Draga Ronald O.P. , Grimbergen Matthijs C.M. , Kok Esther T. , Jonges Trudy N. , van Swol Christiaan F.P. , Bosch Ruud J.L.H.
Published: September 2012

Introduction: The aim of this study is to evaluate the quality of photodynamic diagnosis (PDD) and transurethral resection of bladder tumors (TURBT) among different urologists. Patients and Methods: The selected data consists of 194 patients, 268 5-aminolevulinic acid (5-ALA)-induced PDD procedures and 934 biopsies. Tumors were resected and biopsies were taken from suspicious areas under guidance of white light endoscopy and 5-ALA-induced fluorescence cystoscopy. The quality of PDD was determined by evaluating the mean number of tumors resected by 5 urologists and, thereafter, assessing the time to recurrence between groups. Results: Urologist 1 took 37% more biopsies (p < 0.001) and diagnosed 42% more tumors (p = 0.005) and 46% more false positives (p < 0.001) from bladders compared to urologists 2, 3, 4 and 5 together. The mean time to bladder cancer recurrence for all recurrences within 0–18 months was 11.0 months for operator 1 and 8.3 months for the other urologists (p = 0.01). Conclusions: The resecting urologist appears to be an important factor for the quality of standard and PDD-assisted TURBT. Learning curve programs may be required with experienced surgeons accompanying those with less experience.
Feasibility of Noninvasive Single-Channel Automated Differentiation of Obstructive and Central Hypopneas with Nasal Airflow
Authors: Morgenstern C. , Randerath W.J. , Schwaibold M. , Bolz A. , Jané R.
Published: September 2012

Background: The identification of obstructive and central hypopneas is considered challenging in clinical practice. Presently, obstructive and central hypopneas are usually not differentiated or scores lack reliability due to the technical limitations of standard polysomnography. Esophageal pressure measurement is the gold-standard for identifying these events but its invasiveness deters its usage in daily practice. Objectives: To determine the feasibility and efficacy of an automatic noninvasive analysis method for the differentiation of obstructive and central hypopneas based solely on a single-channel nasal airflow signal. The obtained results are compared with gold-standard esophageal pressure scores. Methods: A total of 41 patients underwent full night polysomnography with systematic esophageal pressure recording. Two experts in sleep medicine independently differentiated hypopneas with the gold-standard esophageal pressure signal. Features were automatically extracted from the nasal airflow signal of each annotated hypopnea to train and test the automatic analysis method. Interscorer agreement between automatic and visual scorers was measured with Cohen's kappa statistic (ĸ). Results: A total of 1,237 hypopneas were visually differentiated. The automatic analysis achieved an interscorer agreement of ĸ = 0.37 and an accuracy of 69% for scorer A, ĸ = 0.40 and 70% for scorer B and ĸ = 0.41 and 71% for the agreed scores of scorers A and B. Conclusions: The promising results obtained in this pilot study demonstrate the feasibility of noninvasive single-channel hypopnea differentiation. Further development of this method may help improving initial diagnosis with home screening devices and offering a means of therapy selection and/or control.
Genetic Control of Testis Development
Authors: Sekido R. , Lovell-Badge R.
Published: September 2012

Sex determination refers to the decision of the bipotential early gonads to develop as either testes or ovaries during embryogenesis. In mammals, a single genetic trigger involved in this pivotal decision has been identified on the Y chromosome: the testis-determining gene SRY/Sry. During embryogenesis, SRY triggers the differentiation of Sertoli cells from the supporting cell precursor lineage which would otherwise give granulosa cells in ovaries. Several testis-specific events occur after SRY expression and the onset of Sertoli cell differentiation, notably Leydig cell differentiation, testis cord formation, and development of testis-specific vasculature. Although a number of genes involved in these events have been identified, how they relate to Sry action is poorly understood. Furthermore, even at the adult stage, some of these genes retain a key role in maintaining the testicular fate because conditional ablation of the genes leads to adult testis dysgenesis or transdifferentiation into an ovary. This sheds light on mammalian sex-reprogramming, despite the prevailing dogma that postnatal sex change does not occur in mammals. In this review, we summarize our current understanding of genetic pathways of testis determination and differentiation in mammals, particularly in the mouse and the human.
National Trends in Utilization and Outcomes of Endovascular Treatment of Acute Ischemic Stroke Patients in the Mechanical Thrombectomy Era
Authors: Hassan Ameer E. , Chaudhry Saqib A. , Grigoryan Mikayel , Tekle Wondwossen G. , Qureshi Adnan I.
Published: September 2012

Background and Purpose—

Because several new devices for mechanical thrombectomy have become available, the outcomes of patients undergoing endovascular treatment for acute ischemic stroke are expected to improve in the United States. We performed this analysis to evaluate trends in utilization of endovascular treatment and associated rates of death and disability among acute ischemic stroke patients over a 6-year period, including further assessment within age strata.

Methods—

We obtained data for patients admitted to hospitals in the United States from 2004 to 2009 with a primary diagnosis of ischemic stroke using a large national database. We determined the rate and pattern of utilization, and associated in-hospital outcomes of endovascular treatment among ischemic stroke patients and further analyzed trends within age strata. Outcomes were classified as minimal disability, moderate to severe disability, and death based on discharge disposition and compared between 2 time periods: 2004 to 2007 (post-MERCI) and 2008 to 2009 (post-Penumbra) approvals

Results—

Of the 3 292 842 patients admitted with ischemic stroke, 72 342 (2.2%) received intravenous thrombolytic treatment and 13 799 (0.4%) underwent endovascular treatment. There was a 6-fold increase in patients who underwent endovascular treatment (0.1% of ischemic strokes in 2004 vs 0.6% in 2009;
P
<0.001), with the patients aged ≥85 years having the lowest rate of utilization (0.2%). The rates of intracranial hemorrhage remained unchanged throughout the 6 years. In multivariate logistic regression analysis, after adjusting for age, gender, presence of hypertension, congestive heart failure, renal failure, and secondary intracranial hemorrhages, there was no difference in the rate of minimal disability between the 2 study intervals (2004–2007 vs 2008–2009; odds ratio, 0.8; 95% confidence interval, 0.7–1.04;
P
=0.11). Mortality decreased while moderate to severe disability increased for patients treated during 2008 to 2009 (odds ratio, 0.7; 95% confidence interval, 0.6–0.9;
P
=0.007; and odds ratio, 1.4; 95% confidence interval, 1.2–1.7;
P
=0.0002).

Conclusion—

There has been a significant increase in the proportion of acute ischemic stroke patients receiving endovascular treatment over the 6 years and reduction in in-hospital mortality. Our results highlight the need to implement endovascular techniques in a balanced manner across various age groups that also results in the reduction of disability in addition to mortality.
Smartphone Teleradiology Application Is Successfully Incorporated Into a Telestroke Network Environment
Authors: Demaerschalk Bart M. , Vargas Jason E. , Channer Dwight D. , Noble Brie N. , Kiernan Terri-Ellen J. , Gleason Elizabeth A. , Vargas Bert B. , Ingall Timothy J. , Aguilar Maria I. , Dodick David W. , Bobrow Bentley J.
Published: September 2012

Background and Purpose—

ResolutionMD mobile application runs on a Smartphone and affords vascular neurologists access to radiological images of patients with stroke from remote sites in the context of a telemedicine evaluation. Although reliability studies using this technology have been conducted in a controlled environment, this study is the first to incorporate it into a real-world hub and spoke telestroke network. The study objective was to assess the level of agreement of brain CT scan interpretation in a telestroke network between hub vascular neurologists using ResolutionMD, spoke radiologists using a Picture Archiving and Communications System, and independent adjudicators.

Methods—

Fifty-three patients with stroke at the spoke hospital consented to receive a telemedicine consultation and participate in a registry. Each CT was evaluated by a hub vascular neurologist, a spoke radiologist, and by blinded telestroke adjudicators, and agreement over clinically important radiological features was calculated.

Results—

Agreement (
κ
and 95% CI) between hub vascular neurologists using ResolutionMD and (1) the spoke radiologist; and (2) independent adjudicators, respectively, were: identification of intracranial hemorrhage 1.0 (0.92–1.0), 1.0 (0.93–1.0), neoplasm 1.0 (0.92–1.0), 1.0 (0.93–1.0), any radiological contraindication to thrombolysis 1.0 (0.92–1.0), 0.85 (0.65–1.0), early ischemic changes 0.62 (0.28–0.96), 0.58 (0.30–0.86), and hyperdense artery sign 0.40 (0.01–0.80), 0.44 (0.06–0.81).

Conclusions—

CT head interpretations of telestroke network patients by vascular neurologists using ResolutionMD on Smartphones were in excellent agreement with interpretations by spoke radiologists using a Picture Archiving and Communications System and those of independent telestroke adjudicators using a desktop viewer.

Clinical Trial Registration Information—

www.clinicaltrials.gov
unique identifier NCT00829361.
Relationship Between Asian Dust and Ischemic Stroke
Authors: Kamouchi Masahiro , Ueda Kayo , Ago Tetsuro , Nitta Hiroshi , Kitazono Takanari ,   for the Fukuoka Stroke Registry Investigators
Published: September 2012

Background and Purpose–

Particulate matter is increasingly recognized as a cause of human diseases, including cardiovascular diseases. However, the association between Asian dust (AD), a windblown sand dust originating from mineral soil in the deserts of China and Mongolia, and the incidence of cardiovascular diseases is unclear. The aim of the present study was to elucidate whether AD is associated with the incidence of ischemic stroke.

Methods–

This study investigated the onset time of 7429 consecutive patients with ischemic stroke who were admitted to seven stroke centers in Fukuoka, Japan, between June 1999 and March 2010. Meteorologic variables and air pollutants, including AD and suspended particulate matters, were investigated during the identical period. A time-stratified case-crossover study was conducted to assess the association between AD and stroke incidence using a conditional logistic regression analysis.

Results–

Although AD was not significantly associated with the overall incidence of ischemic stroke, there was a relationship specific to the stroke subtypes. AD was significantly associated with the incidence of atherothrombotic brain infarction after adjusting for expected confounders, including meteorologic variables and other air pollutants. No association was detected in other types of ischemic stroke.

Conclusion–

These data suggest that AD does not increase the overall incidence of ischemic stroke, but it is specifically associated with the risk of atherothrombotic brain infarction.
The Shape of Phase-Resetting Curves in Oscillators with a Saddle Node on an Invariant Circle Bifurcation
Authors: Ermentrout G. Bard , Glass Leon , Oldeman Bart E.
Published: September 2012

We introduce a simple two-dimensional model that extends the Poincaré oscillator so that the attracting limit cycle undergoes a saddle node bifurcation on an invariant circle (SNIC) for certain parameter values. Arbitrarily close to this bifurcation, the phase-resetting curve (PRC) continuously depends on parameters, where its shape can be not only primarily positive or primarily negative but also nearly sinusoidal. This example system shows that one must be careful inferring anything about the bifurcation structure of the oscillator from the shape of its PRC.
Time Constant Estimates for Radiosonde Temperature Sensors
Authors: Tschudin Marcel E. , Schroeder Steven R.
Published: September 2012

To correct time lag errors in radiosonde temperatures the sensor time constant has to be known. Time constants are not published for some widely used sensors and, in some cases, available time constants disagree. This study focuses on ML-405, ML-419, VIZ/Sippican Mark II Microsonde and B2, Russian MMT-1, and Chinese GZZ-7 rod thermistors. It measures still air time constants and heat capacities and derives theoretical still air and aerated time constants based on heat transfer involving nonuniform cylinders. With low aeration, such as in the stratosphere, heat conduction by lead wires from the thermistor noticeably shortens the time constant. Some discrepancies in published time constants are explained by researchers not considering the temperature dependence of all relevant variables. Empirical formulas are derived to estimate the aerated time constant of cylindrical temperature sensors based on dimensions. The aerated time constant in soundings is found to be about 6 times as long at 10 hPa as near sea level.
Use of Multiple Verification Methods to Evaluate Forecasts of Convection from Hot- and Cold-Start Convection-Allowing Models
Authors: Stratman Derek R. , Coniglio Michael C. , Koch Steven E. , Xue Ming
Published: September 2012

This study uses both traditional and newer verification methods to evaluate two 4-km grid-spacing Weather Research and Forecasting Model (WRF) forecasts: a “cold start” forecast that uses the 12-km North American Mesoscale Model (NAM) analysis and forecast cycle to derive the initial and boundary conditions (C0) and a “hot start” forecast that adds radar data into the initial conditions using a three-dimensional variational data assimilation (3DVAR)/cloud analysis technique (CN). These forecasts were evaluated as part of 2009 and 2010 NOAA Hazardous Weather Test Bed (HWT) Spring Forecasting Experiments. The Spring Forecasting Experiment participants noted that the skill of CN’s explicit forecasts of convection estimated by some traditional objective metrics often seemed large compared to the subjectively determined skill. The Gilbert skill score (GSS) reveals CN scores higher than C0 at lower thresholds likely due to CN having higher-frequency biases than C0, but the difference is negligible at higher thresholds, where CN’s and C0’s frequency biases are similar. This suggests that if traditional skill scores are used to quantify convective forecasts, then higher (>35 dBZ) reflectivity thresholds should be used to be consistent with expert’s subjective assessments of the lack of forecast skill for individual convective cells. The spatial verification methods show that both CN and C0 generally have little to no skill at scales <8–12Δx starting at forecast hour 1, but CN has more skill at larger spatial scales (40–320 km) than C0 for the majority of the forecasting period. This indicates that the hot start provides little to no benefit for forecasts of convective cells, but that it has some benefit for larger mesoscale precipitation systems.