bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Heterocyclic Analogs of α‐aminoadipic Acid and its Esters Based on Imidazo[2,1‐b][1,3]Thiazole
Authors: Šačkus Algirdas , Bričkutė Diana , Paliulis Osvaldas , Sløk Frank Abildgaard
Published: June 2014

A method for the preparation of heterocyclic analogs of α‐aminoadipic acid and its esters based on the imidazo[2,1‐b][1,3]thiazole ring system was developed. In this method, free‐radical bromination of ethyl 6‐methylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate with NBS afforded a versatile building block, ethyl 6‐bromomethylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate. Coupling of ethyl 6‐bromomethylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate with Schöllkopf's chiral auxiliary followed by acidic hydrolysis generated ethyl 6‐[(2S)‐2‐amino‐3‐methoxy‐3‐oxopropyl]imidazo[2,1‐b][1,3]thiazole‐5‐carboxylate. A similar procedure using diethyl (Boc‐amino)malonate yielded racemic 2‐amino‐3‐[(5‐ethoxycarbonyl)imidazo[2,1‐b][1,3]thiazol‐6‐yl]propanoic acid.
Using A3 thinking to improve the STAT medication process
Authors: Manojlovich Milisa , Chase Valerie J. , Mack Megan , Conroy Meghan K. , Belanger Karen , Zawol Debbie , Corr Karen M. , Fowler Karen E. , Viglianti Elizabeth
Published: June 2014

BACKGROUND

Although the term STAT conveys a sense of urgency, it is sometimes used to circumvent a system that may be too slow to accomplish tasks in a timely manner. We describe a quality‐improvement project undertaken by a US Department of Veterans Affairs (VA) hospital to improve the STAT medication process.

METHODS

We adapted A3 Thinking, a problem‐solving process common in Lean organizations, to our problem. In the discovery phase, a color‐coded flow map of the existing process was constructed, and a real‐time STAT order was followed in a modified “Go to the Gemba” exercise. In the envisioning phase, the team brainstormed to come up with as many improvement ideas as possible, which were then prioritized based on the anticipated effort and impact. The team then identified initial experiments to be carried out in the experimentation phase; each experiment followed a standard Plan‐Do‐Study‐Act cycle.

RESULTS

On average, the number of STAT medications ordered per month decreased by 9.5%. The average time from STAT order entry to administration decreased by 21%, and time from medication delivery to administration decreased by 26%. Improvements were also made in technician awareness of STAT medications and nurse notification of STAT medication delivery.

CONCLUSIONS

Adapting A3 Thinking for process improvement was a low‐cost/low‐tech option for a VA facility. The A3 Thinking process led to a better understanding of the meaning of STAT across disciplines, and promoted a collaborative culture in which other hospital‐wide problems may be addressed in the future. Journal of Hospital Medicine 2014;9:540–544. 2014 Society of Hospital Medicine
Acute anti‐hyperglycaemic effects of an unripe apple preparation containing phlorizin in healthy volunteers: a preliminary study
Authors: Makarova Elina , Górnaś Paweł , Konrade Ilze , Tirzite Dace , Cirule Helena , Gulbe Anita , Pugajeva Iveta , Seglina Dalija , Dambrova Maija
Published: June 2014

BACKGROUND

The health‐promoting properties of apples are directly related to the biologically active compounds that they contain, such as polyphenols. The objective of this study was to prepare a low‐sugar, fibre‐ and phlorizin‐enriched powder from unripe apples and to gain insight regarding its anti‐hyperglycaemic activity in healthy volunteers.

RESULTS

The unripe apples (Malus domestica Borkh.) were collected 30 days after the full bloom day; blanched and pressed to obtain apple pomace which was then processed with a food cutter, oven‐dried and milled to prepare apple powder. The concentrations of total sugars, water‐soluble pectin and phlorizin in the apple preparation were 153.44 ± 2.46, 27.73 ± 0.51 and 12.61 ± 0.15 g kg−1, respectively. Acute ingestion of the apple preparation improved glucose metabolism in the oral glucose tolerance test (OGTT) in six healthy volunteers by reducing the postprandial glucose response at 15 to 30 min by approximately two‐fold (P < 0.05) and by increasing urinary glucose excretion during the 2‐ to 4‐h interval of the OGTT by five‐fold (P < 0.05).

CONCLUSION

The results obtained indicate that the dried and powdered pomace of unripe apples can be used as a health‐promoting natural product for the reduction of postprandial glycaemia and to improve the health of patients with diabetes. © 2014 Society of Chemical Industry
Determination of synthetic dyes in bean and meat products by liquid chromatography with tandem mass spectrometry
Authors: Li Juan , Ding Xiaoming , Zheng Jiaxin , Liu Dandan , Guo Fei , Liu Hongmin , Zhang Yanbing
Published: June 2014

A sensitive and efficient method was developed for the simultaneous determination of eight synthetic dyes (Chrysoidin, Auramine O, Sudan(I–IV), Para Red, and Rhodamine B) in bean and meat products using high‐performance liquid chromatography with tandem mass spectrometry. A simple extraction procedure using acetonitrile has been applied for the extraction of these dyes from spiked bean and meat samples. Chromatographic separation was achieved on a Waters XTerra C18 column (2.1 × 150 mm, 5 μm) with a multistep gradient elution. Detection and quantification were performed using mass spectrometry in multiple reaction monitoring mode. Linear calibrations were obtained with correlation coefficients R2 > 0.99. The limits of detection and quantification for the eight dyes were in the ranges of 0.03–0.75 and 0.1–2.0 μg/kg depending on matrices, respectively. The recoveries of these dyes in different food matrices were between 71.2 and 116.9% with relative standard deviations <15.2%, suggesting that the developed method is promising for the accurate quantification of the eight dyes at trace levels in bean and meat products.
Rapid analysis of three β‐agonist residues in food of animal origin by automated on‐line solid‐phase extraction coupled to liquid chromatography and tandem mass spectrometry
Authors: Mi Jiebo , Li Shujing , Xu Hong , Liang Wei , Sun Tao
Published: June 2014

An automated online solid‐phase extraction with liquid chromatography and tandem mass spectrometry method was developed and validated for the detection of clenbuterol, salbutamol, and ractopamine in food of animal origin. The samples from the food matrix were pretreated with an online solid‐phase extraction cartridge by Oasis MCX for <5 min after acid hydrolysis for 30 min. The peak focusing mode was used to elute the target compounds directly onto a C18 column. Chromatographic separation was achieved under gradient conditions using a mobile phase composed of acetonitrile/0.1% formic acid in aqueous solution. Each analyte was detected in two multiple reaction monitoring transitions via an electrospray ionization source in a positive mode. The relative standard deviations ranged from 2.6 to 10.5%, and recovery was between 76.7 and 107.2% at all quality control levels. The limits of quantification of three β‐agonists were in the range of 0.024–0.29 μg/kg in pork, sausage, and milk powder, respectively. This newly developed method offers high sensitivity and minimum sample pretreatment for the high‐throughput analysis of β‐agonist residues.
Acetone‐Based Cellulose Solvent
Authors: Kostag Marc , Liebert Tim , Heinze Thomas
Published: June 2014

Acetone containing tetraalkylammonium chloride is found to be an efficient solvent for cellulose. The addition of an amount of 10 mol% (based on acetone) of well‐soluble salt triethyloctylammonium chloride (Et3OctN Cl) adjusts the solvent's properties (increases the polarity) to promote cellulose dissolution. Cellulose solutions in acetone/Et3OctN Cl have the lowest viscosity reported for comparable aprotic solutions making it a promising system for shaping processes and homogeneous chemical modification of the biopolymer. Recovery of the polymer and recycling of the solvent components can be easily achieved.

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Increased intracortical inhibition in hyperglycemic hemichorea‐hemiballism
Authors: Li Jie‐Yuan , Chen Robert
Published: June 2014

Hemichorea‐hemiballism (HC‐HB) in uncontrolled diabetes mellitus is an uncommon manifestation of hyperglycemia. The pathophysiology of hyperglycemic HC‐HB is not well understood. A previous report showed increased intracortical inhibition in the motor cortex in a patient with diabetes with HC‐HB. The objective of this study is to investigate motor cortex excitability in patients with hyperglycemic HC‐HB. We hypothesized that intracortical inhibition measured with transcranial magnetic stimulation, which likely reflects the excitability of cortical γ‐aminobutyric acid (GABA)ergic circuits, would be impaired in patients with hyperglycemic HC‐HB. We studied 15 patients with mean age 71.5 years (range, 48‐94 y) and 12 age‐matched healthy subjects. The motor cortex contralateral to the hemichorea was tested. Transcranial magnetic stimulation measures included motor evoked potential, recruitment curve, GABAA mediated short interval intracortical inhibition, intracortical facilitation, and GABAB mediated silent period duration and long interval intracortical inhibition. No significant difference was found in motor threshold, recruitment curve response, short interval intracortical inhibition, or intracortical facilitation in both rest and active conditions between patients with hyperglycemic HC‐HB and normal subjects. However, long interval intracortical inhibition was significantly increased during muscle activation but not at rest in patients with hyperglycemic HC‐HB. The silent period duration is also increased in patients with hyperglycemic HC‐HB. We concluded that long interval intracortical inhibition and silent period are increased in the motor cortex contralateral to the hemichorea in hyperglycemic HC‐HB, but only during muscle activation. Hemichorea‐hemiballism may be associated with increased GABAB receptor‐mediated inhibitory activity in the motor cortex. © 2014 International Parkinson and Movement Disorder Society
Conformational equilibrium and dynamic behavior of bis‐N‐triflyl substituted 3,8‐diazabicyclo[3.2.1]octane
Authors: Shainyan Bagrat A. , Moskalik Mikhail Yu. , Heydenreich Matthias , Kleinpeter Erich
Published: June 2014

Restricted rotation about the N–S partial double bonds in a bis‐N‐triflyl substituted 3,8‐diazabicyclo[3.2.1]octane derivative 1 has been frozen at low temperature (ΔG≠ = 11.6 kcal mol−1), and the existence of all four rotamers about the two N–S bonds, 3‐in,8‐in, 3‐in,8‐out, 3‐out,8‐in, and 3‐out,8‐out, respectively, proved experimentally by NMR spectroscopy and theoretically by DFT and MP2 calculations. Copyright © 2014 John Wiley & Sons, Ltd.
Systematic review of screening for trisomy 21 in twin pregnancies in first trimester combining nuchal translucency and biochemical markers: a meta‐analysis
Authors: Prats Pilar , Rodríguez Ignacio , Comas Carmina , Puerto Bienvenido
Published: June 2014

Aim

This article is a systematic review of the literature to establish the detection rate and false‐positive rate of the combined test for the screening of trisomy 21 in twins.

Material and methods

We conducted a literature search (MEDLINE, EMBASE and ScienceDirect and Cochrane) to identify studies between 1995 and 2013 that provided data on the combined test in twins. Selected studies included data on maternal age, number of fetuses affected by Down syndrome, test strategy, sensitivity and specificity of the test.

Results

The combined test in twins had a pooled sensitivity of 0.893 [95% confidence interval (CI) 0.797–0.947] and a pooled specificity of 0.946 (95% CI 0.933–0.957). The performance of the test was good (summary receiver operating characteristic area under the curve: 0.817). In dichorionic twins, sensitivity and specificity were 0.862 (95% CI 0.728–0.936) and 0.952 (95% CI 0.942–0.96), respectively. In monochorionic twins, the sensitivity and specificity were 0.874% (95% CI 0.526–0.977) and 0.954% (95% CI 0.943–0.963), respectively.

Conclusions

The results of this meta‐analysis show that the accumulative evidence on the performance of the combined test in twin pregnancies is good. Nowadays, it seems to be the best first‐trimester screening test available for twin pregnancies. © 2014 John Wiley & Sons, Ltd.
Hydrolytic fitness of N‐glycosyl bonds: comparing the deglycosylation kinetics of modified, alternative, and native nucleosides
Authors: Rios Andro C. , Yu Hiu T. , Tor Yitzhak
Published: June 2014

Nature's selection of the contemporary nucleobases in RNA and DNA continues to intrigue the origin of life community. While the prebiotic synthesis of the N‐glycosyl bond has historically been a central area of investigation, variations in hydrolytic stability among the N‐glycosyl bonds may have presented an additional selection pressure that contributed to nucleobase and nucleoside evolution. To experimentally probe this hypothesis, a systematic kinetic analysis of the hydrolytic deglycosylation reactions of modified, alternative, and native nucleosides was undertaken. Rate constants were measured as a function of temperature (at pH 1) to produce Arrhenius and Eyring plots for extrapolation to 37°C and determination of thermodynamic activation parameters. Rate enhancements based on the differences in reaction rates of deoxyriboglycosidic and riboglycosidic bonds were found to vary under the same conditions. Rate constants of deoxynucleosides were also measured across the pH range of 1–3 (at 50°C), which highlighted how simple changes to the heterocycle alone can lead to a significant variation in deglycosylation rates. The contemporary nucleosides exhibited the slowest deglycosylation rates in comparison with the nonnative/alternative nucleosides, which we suggest as experimental support for nature's selection of the fittest N‐glycosyl bonds. Copyright © 2014 John Wiley & Sons, Ltd.
The role of zinc in the stability of the marginally stable IscU scaffold protein
Authors: Iannuzzi Clara , Adrover Miquel , Puglisi Rita , Yan Robert , Temussi Piero Andrea , Pastore Annalisa
Published: June 2014

Understanding the factors that determine protein stability is interesting because it directly reflects the evolutionary pressure coming from function and environment. Here, we have combined experimental and computational methods to study the stability of IscU, a bacterial scaffold protein highly conserved in most organisms and an essential component of the iron–sulfur cluster biogenesis pathway. We demonstrate that the effect of zinc and its consequence strongly depend on the sample history. IscU is a marginally stable protein at low ionic strength to the point that undergoes cold denaturation at around −8°C with a corresponding dramatic decrease of enthalpy, which is consistent with the fluxional nature of the protein. Presence of constitutively bound zinc appreciably stabilizes the IscU fold, whereas it may cause protein aggregation when zinc is added back posthumously. We discuss how zinc coordination can be achieved by different side chains spatially available and all competent for tetrahedral coordination. The individual absence of some of these residues can be largely compensated by small local rearrangements of the others. We discuss the potential importance of our findingsin vitrofor the functionin vivoof the protein.
The in vivo efficacy and side effect pharmacology of GS‐5759, a novel bifunctional phosphodiesterase 4 inhibitor and long‐acting β2‐adrenoceptor agonist in preclinical animal species
Authors: Salmon Michael , Tannheimer Stacey L. , Gentzler Terry T. , Cui Zhi‐Hua , Sorensen Eric A. , Hartsough Kimberly C. , Kim Musong , Purvis Lafe J. , Barrett Edward G. , McDonald Jacob D. , Rudolph Karin , Doyle‐Eisele Melanie , Kuehl Philip J. , Royer Christopher M. , Baker William R. , Phillips Gary B. , Wright Clifford D.
Published: June 2014

Bronchodilators are a central therapy for symptom relief in respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma, with inhaled β2‐adrenoceptor agonists and anticholinergics being the primary treatments available. The present studies evaluated the in vivo pharmacology of (R)‐6‐[[3‐[[4‐[5‐[[2‐Hydroxy‐2‐(8‐hydroxy‐2‐oxo‐1,2‐dihydroquinolin‐5‐yl)ethyl]amino]pent‐1‐ynyl]phenyl]carbamoyl]phenyl]sulfonyl]‐4‐[(3‐methoxyphenyl)amino]‐8‐methylquinoline‐3‐carboxamide (GS‐5759), a novel bifunctional compound with both phosphodiesterase 4 (PDE4) inhibitor and long‐acting β2‐adrenoceptor agonist (LABA) activity, which has been optimized for inhalation delivery. GS‐5759 dose‐dependently inhibited pulmonary neutrophilia in a lipopolysaccharide (LPS) aerosol challenge model of inflammation in rats with an ED50 ≤ 10 μg/kg. GS‐5759 was also a potent bronchodilator with an ED50 of 0.09 μg/kg in guinea pigs and 3.4 μg/kg in dogs after methylcholine (MCh) and ragweed challenges respectively. In cynomolgus monkeys, GS‐5759 was dosed as a fine‐particle dry powder and was efficacious in the same dose range in both MCh and LPS challenge models, with an ED50 = 70 μg/kg for bronchodilation and ED50 = 4.9 μg/kg for inhibition of LPS‐induced pulmonary neutrophilia. In models to determine therapeutic index (T.I.), efficacy for bronchodilation was evaluated against increased heart rate and GS‐5759 had a T.I. of 700 in guinea pigs and >31 in dogs. In a ferret model of emesis, no emesis was seen at doses several orders of magnitude greater than the ED50 observed in the rat LPS inflammation model. GS‐5759 is a bifunctional molecule developed for the treatment of COPD, which has both bronchodilator and anti‐inflammatory activity and has the potential for combination as a triple therapy with a second compound, within a single inhalation device.
Characterization of a novel brain barrier ex vivo insect‐based P‐glycoprotein screening model
Authors: Andersson Olga , Badisco Liesbeth , Hansen Ane Håkansson , Hansen Steen Honoré , Hellman Karin , Nielsen Peter Aadal , Olsen Line Rørbæk , Verdonck Rik , Abbott N. Joan , Vanden Broeck Jozef , Andersson Gunnar
Published: June 2014

In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P‐glycoprotein (Pgp) efflux transporter in the brain barrier of the desert locust (Schistocerca gregaria). In an in vivo study on the locust, we found an increased uptake of the two well‐known Pgp substrates, rhodamine 123 and loperamide after co‐administration with the Pgp inhibitors cyclosporine A or verapamil. Furthermore, ex vivo studies on isolated locust brains demonstrated differences in permeation of high and low permeability compounds. The vertebrate Pgp inhibitor verapamil did not affect the uptake of passively diffusing compounds but significantly increased the brain uptake of Pgp substrates in the ex vivo model. In addition, studies at 2°C and 30°C showed differences in brain uptake between Pgp‐effluxed and passively diffusing compounds. The transcriptome data show a high degree of sequence identity of the locust Pgp transporter protein sequences to the human Pgp sequence (37%), as well as the presence of conserved domains. As in vertebrates, the locust brain–barrier function is morphologically confined to one specific cell layer and by using a whole‐brain ex vivo drug exposure technique our locust model may retain the major cues that maintain and modulate the physiological function of the brain barrier. We show that the locust model has the potential to act as a robust and convenient model for assessing BBB permeability in early drug discovery.
Directing peptide crystallization through curvature control of nanotubes
Authors: Gobeaux Frédéric , Tarabout Christophe , Fay Nicolas , Meriadec Cristelle , Ligeti Melinda , Buisson David‐Alexandre , Cintrat Jean‐Christophe , Artzner Franck , Paternostre Maïté
Published: June 2014

In the absence of efficient crystallization methods, the molecular structures of fibrous assemblies have so far remained rather elusive. In this paper, we present a rational method to crystallize the lanreotide octapeptide by modification of a residue involved in a close contact.

Indeed, we show that it is possible to modify the curvature of the lanreotide nanotubes and hence their diameter. This fine tuning leads to crystallization because the radius of curvature of the initially bidimensional peptide wall can be increased up to a point where the wall is essentially flat and a crystal is allowed to grow along a third dimension. By comparing X‐ray diffraction data and Fourier transform Raman spectra, we show that the nanotubes and the crystals share similar cell parameters and molecular conformations, proving that there is indeed a structural continuum between these two morphologies. These results illustrate a novel approach to crystallization and represent the first step towards the acquisition of an Å‐resolution structure of the lanreotide nanotubes β‐sheet assembly. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
Modulating Effects of Pycnogenol® on Oxidative Stress and DNA Damage Induced by Sepsis in Rats
Authors: Taner Gökçe , Aydın Sevtap , Bacanlı Merve , Sarıgöl Zehra , Şahin Tolga , Başaran A. Ahmet , Başaran Nurşen
Published: June 2014

The aim of this study was to evaluate the protective effects of Pycnogenol® (Pyc), a complex plant extract from the bark of French maritime pine, on oxidative stress parameters (superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and total glutathione (GSH) and malondialdehyde (MDA) levels), an inflammatory cytokine (tumor necrosis factor alpha (TNF‐α) level) and also DNA damage in Wistar albino rats. Rats were treated with 100 mg/kg intraperitonally Pyc following the induction of sepsis by cecal ligation and puncture. The decreases in MDA levels and increases in GSH levels, and SOD and GPx activities were observed in the livers and kidneys of Pyc‐treated septic rats. Plasma TNF‐α level was found to be decreased in the Pyc‐treated septic rats. In the lymphocytes, kidney, and liver tissue cells of the sepsis‐induced rats, Pyc treatment significantly decreased the DNA damage and oxidative base damage using standard alkaline assay and formamidopyrimidine DNA glycosylase‐modified comet assay, respectively. In conclusion, Pyc treatment might have a role in the prevention of sepsis‐induced oxidative damage not only by decreasing DNA damage but also increasing the antioxidant status and DNA repair capacity in rats. Copyright © 2014 John Wiley & Sons, Ltd.
A pre‐emption framework for UMTS compatible satellite system supporting multimedia traffic
Authors: Pillai Anju , Hu Yim‐Fun , Halliwell Rosemary
Published: June 2014

The pre‐emption procedure is an important part of the radio resource management when dealing with the emergency traffic. It allows resources to be allocated to higher priority connections by pre‐empting lower priority connections. The provision of the pre‐emption mechanism becomes much more important in the case of satellite systems such as the Inmarsat Broadband Global Area Network system, which aids in providing the communication during a catastrophe. This paper focuses on the pre‐emption framework for a Universal Mobile Telecommunications System‐based satellite systems. Three algorithms have been proposed, Greedy, SubSetSum and Fuzzy pre‐emption algorithm. Extensive simulations are carried out for the three algorithms, and their performances are compared against each other. Simulation results show that the Fuzzy pre‐emption algorithm performs better than the other two algorithms. Copyright © 2014 John Wiley & Sons, Ltd.
A dynamic key management scheme for dynamic wireless sensor networks
Authors: Erfani Seyed Hossein , Javadi Hamid H.S. , Rahmani Amir Masoud
Published: June 2014

Dynamic wireless sensor network (DWSN) is a group of mobile sensor nodes deployed in an intended area. Secure communication in DWSNs depends on the existence of an efficient key management scheme. Because of the movements of sensor nodes and unknown mobility pattern, dynamic key management is an important issue in such networks. In this paper, we propose a new key management scheme, which uses key pre‐distribution and post‐deployment key establishment mechanisms for DWSNs. The proposed approach ensures that the two communicating nodes share at least one common key. It also provides efficient ways for key generation and revocation as well as addition or deletion of mobile sensor nodes. Compared with the other key management schemes, which are designed for DWSNs, our simulation and analytical results demonstrate the efficiency of the proposed approach in terms of confidentiality, resilience, memory usage, energy consumption and overhead. Copyright © 2014 John Wiley & Sons, Ltd.
Seismic collapse assessment of reinforced concrete moment frames using endurance time analysis
Authors: Tajmir Riahi Hossein , Amouzegar Hamed , Falsafioun Mehrdad
Published: June 2014

In this paper, seismic collapse of reinforced concrete moment frames is assessed using endurance time (ET) analysis. A set of 30 frames that incorporate deterioration of concrete components is used for this assessment. Application of ET method for collapse assessment of structures is explained, and its accuracy for this purpose is evaluated by comparing its results with incremental dynamic analysis results. Input motions for ET analysis are generated based on ASCE7‐05 design spectrum, and also accelerograms used for incremental dynamic analysis are spectrally matched to the same spectrum. Distribution of different engineering demand parameters over frames height and their values at collapse occurrence are compared for two methods. Results show that spectral accelerations in which collapse occurs in both analyses are very similar for most of the frames, and ET method can appropriately predict the collapse mechanisms of the structures especially for taller frames. Accuracy of ET method in collapse assessment of reinforced concrete moment frames is satisfactory, and this method can be used as a good estimator for study of collapse mechanisms with much less computational effort. Copyright © 2014 John Wiley & Sons, Ltd.
Quantitative ultrasound texture analysis of fetal lungs to predict neonatal respiratory morbidity
Authors: Bonet‐Carne E. , Palacio M. , Cobo T. , Perez‐Moreno A. , Lopez M. , Piraquive J. P. , Ramirez J. C. , Botet F. , Marques F. , Gratacos E.
Published: June 2014

Objective

To develop and evaluate the performance of a novel method for predicting neonatal respiratory morbidity based on quantitative analysis of the fetal lung by ultrasound.

Methods

More than 13 000 non‐clinical images and 900 fetal lung images were used to develop a computerized method based on texture analysis and machine learning algorithms, trained to predict neonatal respiratory morbidity risk on fetal lung ultrasound images. The method, termed ‘quantitative ultrasound fetal lung maturity analysis’ (quantusFLM™), was then validated blindly in 144 neonates, delivered at 28 + 0 to 39 + 0 weeks' gestation. Lung ultrasound images in DICOM format were obtained within 48 h of delivery and the ability of the software to predict neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, was determined.

Results

Mean (SD) gestational age at delivery was 36 + 1 (3 + 3) weeks. Among the 144 neonates, there were 29 (20.1%) cases of neonatal respiratory morbidity. Quantitative texture analysis predicted neonatal respiratory morbidity with a sensitivity, specificity, positive predictive value and negative predictive value of 86.2%, 87.0%, 62.5% and 96.2%, respectively.

Conclusions

Quantitative ultrasound fetal lung maturity analysis predicted neonatal respiratory morbidity with an accuracy comparable to that of current tests using amniotic fluid. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Adaptive randomization for balancing over covariates
Authors: Hu Feifang , Hu Yanqing , Ma Zhenjun , Rosenberger William F.
Published: June 2014

In controlled clinical trials, balanced allocation over covariates is often viewed as an essential component in ensuring valid treatment comparisons. Minimization, sometimes called ‘dynamic allocation’, or ‘covariate‐adaptive randomization’ has an advantage over stratified randomization, in that it is able to achieve balance over a large number of covariates when the sample size is small to medium. Despite its effectiveness, minimization has been questioned by regulatory agencies, mainly because of its increased complexity in practice and its potential impact on subsequent analysis. In recent years, however, with developments in clinical trials information technology, as well as advances in statistical theory, the attitudes toward minimization have evolved. In its 2013 draft guidelines, the European Medicines Agency (EMA) provided instructive guidelines for the implementation of minimization. In this paper we review the broad class of methods that belong to minimization, including its original forms for balancing over covariate margins and its generalization to balancing over other subgroups of interest or over continuous covariates. Moreover, we review the theoretical development in recent years, including the large‐sample properties of balance under minimization, the impact of minimization on inference for different data types, and on suitable randomization tests.WIREs Comput Stat2014, 6:288–303. doi: 10.1002/wics.1309

This article is categorized under:

Applications of Computational Statistics > Clinical Trials
Surveillance for Low‐Grade Dysplastic Barrett’s Oesophagus: One Size Fits All?
Authors: Zaninotto Giovanni , Bennett Cathy
Published: June 2014

This paper reviews the role of low‐grade dysplasia (LGD) as a marker of progression in Barrett’s oesophagus (BO). Albeit with its limits due to the difficulty of its diagnosis and the low agreement among pathologists, LGD remains the most relevant single prognostic factor of progression, and, when the diagnosis is confirmed by two or three pathologists, the chances of progression to high‐grade dysplasia or invasive adenocarcinoma are as high as 40 %. On the other hand, BO patients who remain dysplasia free at several follow‐up examinations seem to have a very low likelihood of progression. The diagnosis of LGD should be confirmed by two pathologists, and surveillance programs should be tailored depending on the presence or persistent absence of LGD. Ablative therapy should be also considered for cases where LGD persists in a series of follow‐ups.
Exomsequenzierung zur Identifizierung von Krankheitsgenen für seltene Syndrome
Authors: Kortüm F. , Abdollahpour H. , Alawi M. , Korenke G.C. , Seemanova E. , Tinschert S. , Zenker M. , Rosenberger G. , Kutsche K.
Published: June 2014

Hintergrund

Die Exomanalyse ist als Methode zur Identifizierung von pathogenen Sequenzvarianten bei Patienten mit einem nach den mendelschen Regeln vererbten Krankheitsbild nicht mehr wegzudenken. Sie bildet umfassend die codierenden Sequenzen eines Genoms ab und ist schnell und kostengünstig.

Problemstellung

Da die technischen Schwierigkeiten bei der Durchführung der Exomsequenzierung inzwischen weitgehend gelöst sind, stellt die Auswertung der großen Datenmenge und somit das Finden der pathogenen Sequenzvariante inmitten 10.000er Sequenzabweichungen die eigentliche Herausforderung dar. Dies kann nur mithilfe einer bioinformatischen Filterung der Daten erfolgen, die jeweils unter Berücksichtigung der in die Analyse einbezogenen Patienten und Familienmitglieder sowie des wahrscheinlichsten Erbganges angepasst werden muss.

Lösungsansätze

Anhand von 4 Fallbeispielen werden verschiedene Priorisierungsstrategien für die Filterung der Sequenzvarianten vorgestellt, die jeweils zur Identifikation der wahrscheinlich pathogenen Veränderung bei dem jeweiligen Indexpatienten geführt haben.
Einführung in die Grundlagen der Hochdurchsatzsequenzierung
Authors: Neveling K. , Hoischen A.
Published: June 2014

Hintergrund

Next Generation Sequencing ist die neue Sequenziermethode für DNA. Aber was verbirgt sich eigentlich dahinter und was ist der Unterschied zur Sanger-Sequenzierung? In dieser Übersicht wird die neue Technologie ein wenig näher erläutert, und es wird erklärt, dass es sich hierbei nicht um eine einzige, sondern um viele neue Techniken handelt.

Technologie und Anwendung

Die momentan bekanntesten Sequenziergeräte und -techniken werden im Detail erklärt und die Gemeinsamkeiten der Maschinen, aber gerade auch die Unterschiede sowie Vor- und Nachteile dargestellt. Auf diese Weise soll der Leser erkennen, dass es nicht die perfekte Maschine für alle Applikationen gibt, sondern dass man für die jeweilige Fragestellung die Maschine aussuchen sollte, deren Spezifikationen sich hierfür am ehesten eignen. Auch die Möglichkeit des Outsourcings wird besprochen, die sicherlich für einige Laboratorien interessant sein könnte. Desweiteren wird kurz erklärt, dass, analog zur Polymerase-Kettenreaktion bei der Sanger-Sequenzierung, auch beim Next Generation Sequencing zuvor oft die zu untersuchenden Regionen anreichert werden. Hierfür existieren verschiedene Methoden, deren Wahl i. d. R. von der Anzahl der zu untersuchenden Patienten und Gene abhängt.

Ausblick

Es wird ein Ausblick auf neueste Entwicklungen gegeben, die deutlich anzeigen, dass das Ende der genetischen Revolution noch nicht in Sicht ist.
NGS Datenanalyse und Qualitätskontrolle
Authors: Weißmann R. , Gilissen C.
Published: June 2014

Next Generation Sequencing (NGS) wird immer häufiger in der Humangenetik eingesetzt. Die Analyse der anfallenden Datenmengen birgt allerdings andere und größere Herausforderungen als bisher eingesetzte Verfahren. In diesem Artikel werden einige Grundlagen, die dem Verständnis der anfallenden Daten und Analyseschritte beim NGS dienen sollen, beschrieben. Ein besonderer Schwerpunkt ist dabei die Qualitätskontrolle.
Moldova on the Path to Europe: Not Yet Irreversible
Authors: Secrieru Stanislav
Published: June 2014

EU–Moldova relations have improved dramatically over the last four years. A new legal framework to reflect Moldova's more ambitious European agenda has been negotiated and sectoral integration in various fields has gathered rapid pace. Despite impressive progress, however, the path has not been smooth, and Moldova's European integration is not yet irreversible. Moldova's pluralism is still weak, institutions need time for consolidation and anti-corruption efforts are yet to demonstrate results. Russia has also often been a complicating factor. As Moldova is about to embark on the implementation of an Association Agreement agenda, the EU has to reassess recent policy on Moldova, identify potential pitfalls along the road and attune its approach in order to circumvent probable obstacles and thus maximise the effects of its transformative power in the coming years.
The Impact of an Ultramarathon on Hormonal and Biochemical Parameters in Men
Authors: Kupchak Brian R. , Kraemer William J. , Hoffman Martin D. , Phinney Stephen D. , Volek Jeff S.
Published: June 2014

Objective

To examine circulating hormonal responses in men competing in the Western States Endurance Run (WSER, June 23 to 24, 2012): a 161-km trail run that starts in Squaw Valley, CA, and concludes in Auburn, CA.

Methods

We examined 12 men who completed the WSER. Blood samples were obtained the morning before the race, immediately postrace (IP), and 1 (D1) and 2 (D2) days after the conclusion of the WSER. The hypothalamic-pituitary-testicular (HPT) axis was assessed by measuring testosterone and luteinizing hormone (LH). We also examined sex hormone-binding globulin (SHBG) and cortisol. Biochemical and muscle damage markers were also measured.

Results

Relative to prerace, there were significant ( P ≤ .05) decreases in testosterone, LH, and SHBG, whereas cortisol showed a significantly marked elevation at IP. Testosterone, LH, SHBG, and cortisol remained significantly different from prerace at D1. Additionally, the testosterone to cortisol (T:C) ratio, a marker of anabolism, was decreased at IP and D1. Serum total protein, albumin, and globulin significantly decreased at IP, and remained decreased at D1 and D2. Bilirubin increased significantly IP and D1, whereas alkaline phosphatase decreased at D1 and D2. Creatine kinase, myoglobin, aspartate aminotransferase, and alanine aminotransferase increased at IP, and continued to be significantly elevated at D1 and D2.

Conclusions

Training for and completing the WSER produced a significant suppression in the HPT axis as seen by decreased levels of testosterone and LH. Additionally, running the WSER continued to influence endocrine function until 2 days after the race. Furthermore, the stress caused by the WSER produced severe muscle damage.
AN EXISTENCE RESULT FOR A VARIATIONAL-LIKE INEQUALITY
Authors: INOAN DANIELA
Published: June 2014

In this paper we establish an existence result for a class of generalised variational-like inequalities, when the functions used in their definition are of type ql and satisfy some general continuity assumptions. We use a Brézis–Nirenberg–Stampacchia type result.
Older adults’ perceptions of adherence to community physical activity groups
Authors: HARTLEY SANDRA ELAINE , YEOWELL GILLIAN
Published: June 2014

Community physical activity (PA) groups have come in to being worldwide to inspire older adults to engage in PA. However, there is limited evidence that older adults adhere to these groups, particularly those of a lower socio-economic status, with health conditions, from black and minority ethnic (BME) groups and men. This study aimed to explore experiences of attending PA groups from the viewpoint of community-living older adults, including those sub-groups of the population highlighted above. The purpose was to gain an understanding of what would influence long-term adherence to community PA groups. Eighteen participants aged 65 and above took part in three focus groups carried out in North West England. Thematic network analysis was used for theme generation and interpretation. Low-cost, universal locations are essential to enable older adults to engage regularly in PA, however, it is the social space that is created within these physical settings that is most influential in fostering their long-term adherence. Facilitating cross-cultural relationships and supporting older adults to have more control in shaping the PA environment will ensure that these settings are more conducive to the long-term adherence of diverse groups of older adults.
A REVISION OF AMOMUM (ZINGIBERACEAE) IN SUMATRA
Authors: Droop A. J. , Newman M. F.
Published: June 2014

Amomum Roxb. (Zingiberaceae) in Sumatra, Indonesia is revised. Twenty-four species are recognised, most names are typified, detailed descriptions of species are provided and a key to these species is given. Provisional IUCN conservation assessments are supplied for all species. Two new species are described: Amomum mentawaiense A.J.Droop and Amomum oligophyllum A.J.Droop.
TREND IN CYCLE OR CYCLE IN TREND? NEW STRUCTURAL IDENTIFICATIONS FOR UNOBSERVED-COMPONENTS MODELS OF U.S. REAL GDP
Authors: Dungey Mardi , Jacobs Jan P.A.M. , Tian Jing , van Norden Simon
Published: June 2014

A well-documented property of the Beveridge–Nelson trend–cycle decomposition is the perfect negative correlation between trend and cycle innovations. We show how this may be consistent with a structural model where permanent innovations enter the cycle or transitory innovations enter the trend, and that identification restrictions are necessary to make this structural distinction. A reduced-form unrestricted version is compatible with either option, but cannot distinguish which is relevant. We discuss economic interpretations and implications using U.S. real GDP data.
ON WEAK-FRAGMENTABILITY OF BANACH SPACES
Authors: HEYDARI F. , BEHMARDI D. , BEHROOZI F.
Published: June 2014

Many characterizations of fragmentability of topological spaces have been investigated. In this paper we deal with some properties of weak-fragmentability of Banach spaces.
Hyponatraemic seizures following prostate brachytherapy
Authors: Slevin Finbar , Rodda Sree Lakshmi , Bosomworth Mike , Bottomley David
Published: June 2014

Aim

To demonstrate the importance of fluid management in the perioperative period by presenting a case of hyponatraemic seizures following prostate brachytherapy.

Case

A 61-year-old gentleman, who had prostate cancer but was otherwise well, developed confusion and word-finding difficulties the day after prostate brachytherapy. This was followed by tonic–clonic seizures that necessitated treatment, intubation and ventilation, and admission to the intensive care unit. Investigations revealed serum sodium of 116 mmol/L. Fluid balance was inadequately recorded, but the patient had drank more than 3 L of water before he developed hyponatraemia.

Discussion

Postoperative severe hyponatraemia and hyponatraemic encephalopathy develop because of anti-diuretic hormone release and hypotonic fluid administration. These are medical emergencies and should be managed in an intensive care unit. Symptoms range from headache, nausea and confusion to seizures, respiratory arrest and death, and are related to cerebral oedema. Treatment is done using hypertonic sodium chloride to increase the serum sodium to safe levels. Care should be taken to avoid overly rapid correction of serum sodium. Complete documentation of fluid balance is essential to allow proper assessment of fluid status. Patients should be advised on appropriate oral fluids in the postoperative period.
Synthesis of thinned planar antenna arrays using teaching–learning-based optimization
Authors: Dib Nihad I.
Published: June 2014

In this paper, the design of thinned planar antenna arrays of isotropic radiators with optimum side lobe level reduction is studied. The teaching–learning-based optimization (TLBO) method, a newly proposed global evolutionary optimization method, is used to determine an optimum set of turned-ON elements of thinned planar antenna arrays that provides a radiation pattern with optimum side lobe level reduction. The TLBO represents a new algorithm for optimization problems in antenna arrays design. It is shown that the TLBO provides results that are better than (or the same as) those obtained using other evolutionary algorithms.
An Introduction to the History of America
Authors: Palit Chittabrata , Mukherjee Jenia
Published: June 2014

This textbook comprehensively captures the historical sojourn of America from pre-colonial to present times, covering every important aspect with detailed historiography. It also sheds light on new evolving themes like American environmental history and American 'exceptionalism', to familiarize students and readers with the current emerging trends and approaches in American History.

The authors have attempted to radically explore the development of America as a 'Global Hegemon' at the cost of the underdevelopment of her non-western/ non-American counterparts. A detailed politico-economic and social narrative of the American nation is given with facts and interpretations, raising a number of conceptual and methodological questions. This textbook also brings out the often unaddressed tension between America's self-perception and the actual reality which can be mapped through crisis in the domestic front as well as its impact on other peoples, nations and cultures. The historiography provided at the end of every relevant theme would be immensely helpful for students and readers pursuing further research.
Effects of IL‐1β–Blocking Therapies in Type 2 Diabetes Mellitus: A Quantitative Systems Pharmacology Modeling Approach to Explore Underlying Mechanisms
Authors: Palmér R , Nyman E , Penney M , Marley A , Cedersund G , Agoram B
Published: June 2014

Recent clinical studies suggest sustained treatment effects of interleukin‐1β (IL‐1β)–blocking therapies in type 2 diabetes mellitus. The underlying mechanisms of these effects, however, remain underexplored. Using a quantitative systems pharmacology modeling approach, we combined ex vivo data of IL‐1β effects on β‐cell function and turnover with a disease progression model of the long‐term interactions between insulin, glucose, and β‐cell mass in type 2 diabetes mellitus. We then simulated treatment effects of the IL‐1 receptor antagonist anakinra. The result was a substantial and partly sustained symptomatic improvement in β‐cell function, and hence also in HbA1C, fasting plasma glucose, and proinsulin–insulin ratio, and a small increase in β‐cell mass. We propose that improved β‐cell function, rather than mass, is likely to explain the main IL‐1β–blocking effects seen in current clinical data, but that improved β‐cell mass might result in disease‐modifying effects not clearly distinguishable until >1 year after treatment.

CPT: Pharmacometrics & Systems Pharmacology (2014) 3, e118; doi:10.1038/psp.2014.16; advance online publication 11 June 2014
Do voltammetry electrodes modified with MIPs really work? The role of large molecules: folic acid as a probe
Authors: Pereira Abigail Vasconcelos , Cervini Priscila , Gomes Cavalheiro Éder Tadeu
Published: June 2014

There are many uncertainties concerning the use of molecularly imprinted polymers (MIPs) as electrode modifiers.
Flexible and practical synthesis of 3-oxyindoles through gold-catalyzed intermolecular oxidation of o-ethynylanilines
Authors: Shu Chao , Li Long , Xiao Xin-Yu , Yu Yong-Fei , Ping Yi-Fan , Zhou Jin-Mei , Ye Long-Wu
Published: June 2014

A novel gold-catalyzed intermolecular oxidation of o-ethynylanilines has been developed, which provides a reliable access to synthetically useful 3-oxyindoles. Importantly, this gold-catalyzed oxidative process outcompetes the typical indole formation.
An Escherichia coli trap in human serum albumin microtubes
Authors: Yuge S. , Akiyama M. , Komatsu T.
Published: June 2014

Human serum albumin microtubes captured Escherichia coli (E. coli) into their one-dimensional pore space interior with a high efficiency. Similar MTs including an Fe3O4 layer also captured E. coli and were manipulated by a magnetic field.
Zinc-catalyzed synthesis of 2-alkenylfurans via cross-coupling of enynones and diazo compounds
Authors: González Jesús , López Luis A. , Vicente Rubén
Published: June 2014

A ZnCl2 catalyzed selective cross-coupling of enynones and diazo compounds, leading to a variety of 2-alkenylfurans, is reported.
Mechanochemical synthesis of crystalline and amorphous digold(i) helicates exhibiting anion- and phase-switchable luminescence properties
Authors: Jobbágy Csaba , Molnár Miklós , Baranyai Péter , Deák Andrea
Published: June 2014

For the first time, mechanochemical synthesis has been used for the preparation of anion- and phase-switchable luminescent dinuclear gold(i) helicates.
The road to nowhere: equilibrium partition coefficients for nanoparticles
Authors: Praetorius Antonia , Tufenkji Nathalie , Goss Kai-Uwe , Scheringer Martin , von der Kammer Frank , Elimelech Menachem
Published: June 2014

This perspective demonstrates the inapplicability of equilibrium partition coefficients as fate descriptors for nanoparticles.
Role of salivary and candidal proteins in denture stomatitis: an exploratory proteomic analysis
Authors: Byrd Warren C. , Schwartz-Baxter Sarah , Carlson Jim , Barros Silvana , Offenbacher Steven , Bencharit Sompop
Published: June 2014

Denture stomatitis is an interaction between host and candidal organisms modifying by proteins from serum, tissue, and saliva as well as microbial environment of the denture.
One-step synthesis of diazaspiro[4.5]decane scaffolds with exocyclic double bonds
Authors: Li Lidong , Hu Qiong , Zhou Pingping , Xie Haifeng , Zhang Xiaorong , Zhang Hao , Hu Yadong , Yin Fei , Hu Yimin
Published: June 2014

Unactivated yne-en-ynes reacted with a range of substituted aryl halides in the presence of Pd(OAc)2–PPh3to afford diazaspiro[4.5]decane with exocyclic double bonds.
Copper-catalyzed nucleophilic trifluoromethylation of benzylic chlorides
Authors: Miyake Yoshihiro , Ota Shin-ichi , Shibata Masashi , Nakajima Kazunari , Nishibayashi Yoshiaki
Published: June 2014

The reactions of primary and secondary benzylic chlorides with trifluoromethyltrimethylsilane in the presence of a catalytic amount of copper(i) thiophene-2-carboxylate (CuTC) have been found to give the corresponding benzylic trifluoromethylated products in good to high yields.