bluuebunny/crossref_metadata_2025 huggingface dataset:
Corneal confocal microscopy for the diagnosis of diabetic autonomic neuropathy
Authors: Tavakoli Mitra , Begum Piyara , McLaughlin John , Malik Rayaz A
Published: December 2014

Background

Diabetic autonomic neuropathy (DAN) results in increased morbidity and mortality. The early diagnosis of DAN can be difficult and is commonly evaluated using cardiac autonomic function tests as a surrogate. However, they are not widely available, have limited sensitivity and specificity, and can be confounded by concomitant cardiovascular disease and medications. Methods: The diagnostic utility of corneal confocal microscopy for diagnosis of DAN was assessed. Thirty‐four diabetic patients without [Composite Autonomic Scoring Scale (CASS)≤2] vs with (CASS>2) DAN and 18 healthy control subjects (HC) underwent detailed assessment of somatic and autonomic neuropathy, Composite Autonomic Symptom Scale (COMPASS), (CASS), and Corneal Confocal Microscopy (CCM). Results: Corneal nerve fiber density, branch density, and length showed a progressive and significant reduction in patients with DAN vs HC and those without DAN. CCM correlated highly significantly with COMPASS and CASS, and corneal nerve fiber parameters demonstrated a high sensitivity and specificity for diagnosis of DAN. Conclusions: This study demonstrates that corneal nerve damage detected using CCM can be deployed to diagnose subclinical and overt DAN. It therefore represents a rapid, non‐invasive, highly sensitive and specific diagnostic test for DAN. Muscle Nerve, 2015 Muscle Nerve 52:363–370, 2015
Structural basis for acceptor‐substrate recognition of UDP‐glucose: anthocyanidin 3‐O‐glucosyltransferase from Clitoria ternatea
Authors: Hiromoto Takeshi , Honjo Eijiro , Noda Naonobu , Tamada Taro , Kazuma Kohei , Suzuki Masahiko , Blaber Michael , Kuroki Ryota
Published: December 2014

UDP‐glucose: anthocyanidin 3‐O‐glucosyltransferase (UGT78K6) from Clitoria ternatea catalyzes the transfer of glucose from UDP‐glucose to anthocyanidins such as delphinidin. After the acylation of the 3‐O‐glucosyl residue, the 3′‐ and 5′‐hydroxyl groups of the product are further glucosylated by a glucosyltransferase in the biosynthesis of ternatins, which are anthocyanin pigments. To understand the acceptor‐recognition scheme of UGT78K6, the crystal structure of UGT78K6 and its complex forms with anthocyanidin delphinidin and petunidin, and flavonol kaempferol were determined to resolutions of 1.85 Å, 2.55 Å, 2.70 Å, and 1.75 Å, respectively. The enzyme recognition of unstable anthocyanidin aglycones was initially observed in this structural determination. The anthocyanidin‐ and flavonol‐acceptor binding details are almost identical in each complex structure, although the glucosylation activities against each acceptor were significantly different. The 3‐hydroxyl groups of the acceptor substrates were located at hydrogen‐bonding distances to the Nε2 atom of the His17 catalytic residue, supporting a role for glucosyl transfer to the 3‐hydroxyl groups of anthocyanidins and flavonols. However, the molecular orientations of these three acceptors are different from those of the known flavonoid glycosyltransferases, VvGT1 and UGT78G1. The acceptor substrates in UGT78K6 are reversely bound to its binding site by a 180° rotation about the O1–O3 axis of the flavonoid backbones observed in VvGT1 and UGT78G1; consequently, the 5‐ and 7‐hydroxyl groups are protected from glucosylation. These substrate recognition schemes are useful to understand the unique reaction mechanism of UGT78K6 for the ternatin biosynthesis, and suggest the potential for controlled synthesis of natural pigments.
NTChem: A high‐performance software package for quantum molecular simulation
Authors: Nakajima Takahito , Katouda Michio , Kamiya Muneaki , Nakatsuka Yutaka
Published: December 2014

In this Software News, the authors introduce NTChem, a new comprehensive software package developed in Japan, for ab initio quantum chemistry calculations. It includes various high‐performance computational methods and functions for quantum molecular simulations. Furthermore, it is designed for high‐performance calculations on a computer with numerous compute nodes. Therefore, it makes optimum use of the K computer's processing power. This Software News specifically examines the parallel performance of NTChem on the K computer. © 2014 Wiley Periodicals, Inc.
The development and validation of micro‐CT of large deep frozen specimens
Authors: Kampschulte Marian , Erdmann Georg , Sender Jonas , Martels Gunhild , Böcker Wolfgang , ElKhassawna Thaqif , Heiß Christian , Langheinrich Alexanders Claus , Roeb Elke , Roderfeld Martin , Krombach Gabriele Anja
Published: December 2014

Repetitive freeze/thaw cycles lead to a progressive loss of structural and molecular integrity in deep frozen specimens. The aim of this study was to evaluate a micro‐CT stage, which maintains the cryoconservation of large specimens throughout micro‐CT imaging. Deep frozen ovine vertebral segments (−20 °C) were fixed in a micro‐CT stage made of expanded polystyrene and cooled with dry ice (0 g, 60 g and 120 g). The temperature inside the stage was measured half‐hourly over a time span of three hours with subsequent measurement of surface temperature. The method was validated in a series of 30 deep frozen vertebral specimens and in liver tissue after repetitive micro‐CT scanning. Isolation without cooling resulted in defrosting. Cooling with 60 g of dry ice led to a temperature rise inside the stage (max. 5.1 °C) and on the specimen surfaces (max. −3 °C). Cooling with 120 g of dry ice resulted in a significant (p < 0.001) and sufficient lowering of the temperature inside the stage (max. −14 °C) and on the surface of the specimens (max. −13.9 °C). The surface temperature during the subsequent micro‐CT validation study did not exceed −16 °C (processing time 1 h 45 min). The resolution was 33 μm isotropic voxel side length, enabling a binarization of bone microstructures. Temperature can reliably be maintained below −10 °C during a micro‐CT scan by applying the described technique. The resulting spatial resolution and image quality permits a binarization of bone microstructure. SCANNING 37:63–72, 2015. © 2014 Wiley Periodicals, Inc.
Relationships between bat occupancy and habitat and landscape structure along a savanna, woodland, forest gradient in the Missouri Ozarks
Authors: Starbuck Clarissa A. , Amelon Sybill K. , Thompson Frank R.
Published: December 2014

Many land‐management agencies are restoring savannas and woodlands using prescribed fire and forest thinning, and information is needed on how wildlife species respond to these management activities. Our objectives were to evaluate support for relationships of bat site occupancy with vegetation structure and management and landscape composition and structure across a gradient of savanna to forest in the Missouri Ozark Highlands, USA. We selected study sites that were actively managed for savanna and woodland conditions and control areas on similar landforms that had succeeded to closed‐canopy forest. We used Anabat detectors to survey bats during the summers of 2010, 2011, and 2012. We fit single‐species site‐occupancy models to estimate detection probability and site occupancy. We evaluated a priori hypotheses in an information theoretic approach by evaluating support for candidate models that included habitat, landscape, and management effects. Site occupancy of evening bats (Nycticeius humeralis) was negatively related to poletimber and sawtimber density and positively related to fire frequency, while northern long‐eared bat (Myotis septentrionalis) site occupancy was positively related to poletimber density and negatively related to understory stem densities. Site occupancy of big brown bats (Eptesicus fuscus), eastern red bats (Lasiurus borealis), and tri‐colored bats (Perimyotis subflavus) were mostly not related to local vegetation structure and site occupancy was high across the savanna, woodland, forest gradient. We found more consistent and larger effect sizes for landscape‐scale than for habitat‐scale relationships; therefore, land managers should be cognizant of large‐scale patterns in land cover when making local management decisions for these species. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Noninvasive Prenatal Testing: The Indian Perspective
Authors: Verma Ishwar Chander
Published: December 2014

This article summarizes the Professor Kamal Buckshee Oration given by the author at the annual conference of the Society of Fetal Medicine in Kochi, August 2014. The contributions of Professor Buckshee to fetal medicine are briefly described. The article traces the development of fetal medicine in India. It discusses the application of noninvasive prenatal testing (NIPT) in India. It briefly calculates the cost benefits of sexing of the fetus for X-linked disease. It also describes the results of screening 320 pregnant women using NIPT for aneuploidies. The benefits and limitations of NIPT are presented.
Heart Rate Variability and Omega-3 Index in Euthymic Patients with Bipolar Disorders
Authors: Voggt A. , Berger M. , Obermeier M. , Löw A. , Seemueller F. , Riedel M. , Moeller H.J. , Zimmermann R. , Kirchberg F. , Von Schacky C. , Severus E.
Published: December 2014

Background:

Affective disorders are associated with an increased risk of cardiovascular disease, which, at least partly, appears to be independent of psychopharmacological treatments used to manage these disorders. Reduced heart rate variability (SDNN) and a low Omega-3 Index have been shown to be associated with increased risk for death after myocardial infarction. Therefore, we set out to investigate heart rate variability and the Omega-3 Index in euthymic patients with bipolar disorders.

Methods:

We assessed heart rate variability (SDNN) and the Omega-3 Index in 90 euthymic, mostly medicated patients with bipolar disorders (Bipolar-I, Bipolar-II) on stable psychotropic medication, free of significant medical comorbidity and in 62 healthy controls. Heart rate variability was measured from electrocardiography under a standardized 30 minutes resting state condition. Age, sex, BMI, smoking, alcohol consumption and caffeine consumption as potential confounders were also assessed.

Results:

Heart rate variability (SDNN) was significantly lower in patients with bipolar disorders compared to healthy controls (35.4 msec versus 60.7 msec; P < 0.0001), whereas the Omega-3 Index did not differ significantly between the groups (5.2% versus 5.3%). In a linear regression model, only group membership (patients with bipolar disorders versus healthy controls) and age significantly predicted heart rate variability (SDNN).

Conclusion:

Heart rate variability (SDNN) may provide a useful tool to study the impact of interventions aimed at reducing the increased risk of cardiovascular disease in euthymic patients with bipolar disorders. The difference in SDNN between cases and controls cannot be explained by a difference in the Omega-3 Index.
The functions of Runx family transcription factors and Cbfb in skeletal development
Authors: Komori Toshihisa
Published: December 2014

Runx family transcription factors consist of Runx1, Runx2, and Runx3. Runx1 is involved in chondrocyte differentiation at an early stage. Runx2 is a major transcription factor for chondrocyte maturation, and Runx3 has a redundant function with Runx2 and it is partly involved in chondrocyte maturation. Runx2 directly regulates Ihh expression and enhances chondrocyte proliferation. Runx2 is an essential transcription factor for osteoblast differentiation. Heterozygous mutation of RUNX2 causes cleidocranial dysplasia, which is characterized by hypoplastic clavicles, open fontanelles, and supernumerary teeth. Runx2 directly regulates Sp7 expression, and Runx2 together with Sp7 and canonical Wnt signaling completes determination of the lineage of mesenchymal cells into osteoblasts. Runx2 expression in osteoblasts is regulated by a 343‐bp enhancer. Dlx5/6 and Mef2 directly bind this enhancer; form an enhanceosome with Tcf7, β‐catenin, Sox5/6, Smad1, and Sp7; and activate this enhancer. Msx2 inhibits this enhancer, and switching of the binding of Msx2 to Dlx5 is important for this activation. Core binding factor β (Cbfb) forms a heterodimer with Runx family proteins and enhances their DNA‐binding capacity. In Cbfb conditional knockout mice in osteoblast and chondrocyte lineages, the differentiation of chondrocytes and osteoblasts is inhibited. All of the Runx family proteins are reduced in the cartilaginous limb skeletons and calvariae in Cbfb conditional knockout mice, although the reduction of Runx2 protein in calvariae is much milder than that in cartilaginous limb skeletons. Therefore, Cbfb regulates skeletal development by stabilizing Runx family proteins, and Runx2 protein stability is less dependent on Cbfb in calvariae than in cartilaginous limb skeletons.
MODEL THEORETIC STABILITY AND DEFINABILITY OF TYPES, AFTER A. GROTHENDIECK
Authors: YAACOV ITAÏ BEN
Published: December 2014

We point out how the “Fundamental Theorem of Stability Theory”, namely the equivalence between the “non order property” and definability of types, proved by Shelah in the 1970s, is in fact an immediate consequence of Grothendieck’s “Critères de compacité” from 1952. The familiar forms for the defining formulae then follow using Mazur’s Lemma regarding weak convergence in Banach spaces.
Boundary layer stabilization using free-stream vortices
Authors: Siconolfi L. , Camarri S. , Fransson J. H. M.
Published: December 2014

In this numerical investigation we explore the possibility of applying free-stream vortices as a passive flow control method for delaying the transition to turbulence. The work is motivated by previous experimental studies demonstrating that stable streamwise boundary layer (BL) streaks can attenuate both two- and three-dimensional disturbances inside the BL, leading to transition delay, with the implication of reducing skin-friction drag. To date, successful control has been obtained using physical BL modulators mounted on the surface in order to generate stable streaks. However, surface mounted BL modulators are doomed to failure when the BL is subject to free-stream turbulence (FST), since a destructive interaction between the two is inevitable. In order to tackle free-stream disturbances, such as FST, a smooth surface is desired, which has motivated us to seek new methods to induce streamwise streaks inside the BL. A first step, in a systematic order, is taken in the present paper to prove the control idea of generating free-stream vortices for the attenuation of ordinary Tollmien–Schlichting waves inside the BL. In this proof-of-concept study we show that, by applying a spanwise array of counter-rotating free-stream vortices, inducing streamwise BL streaks further downstream, it is possible to alter the BL stability characteristics to such a degree that transition delay may be accomplished. For the demonstration we use direct numerical simulations along with stability analysis.
Reproductive biology of the silky shark Carcharhinus falciformis in the southern Mexican Pacific
Authors: Galván-Tirado C. , Galván-Magaña F. , Ochoa-Báez R.I.
Published: December 2014

Despite being one of the most abundant and highly exploited species in the Mexican Pacific Ocean, information on the biology of the silky shark, Carcharhinus falciformis is limited. The objective of the present study was to describe the reproductive biology of this species, based on 262 sharks (117 females and 145 males) caught from September 2004 to May 2006 in the Gulf of Tehuantepec, Mexico. The size of females ranged from 70 to 229 cm total length (TL); males measured from 69 to 220 cm TL. Female reproductive organ measurements showed that between 175 and 190 cm TL there was an increase in oviducal gland width (19–45 mm), as well as in uterus size (20–220 mm width). Mature males over 180 cm had calcified claspers, well-developed testes (184–282 mm) and presence of sperm in the seminal vesicles. The estimated length of males at first maturity was 180 cm, and that of females was 190 cm. Ovarian fecundity varied from 4 to 11 oocytes, and uterine fecundity varied from 2 to 14 embryos. We infer that mating occurs between May and June. We did not find sperm storage in the oviducal glands. Birth size was observed to be between 60 and 69 cm TL. No defined gestation period was observed.
Experiences of Older Adults in Transition from Hospital to Community
Authors: Neiterman Elena , Wodchis Walter P. , Bourgeault Ivy Lynn
Published: December 2014

Cette étude a examiné comment les patients éprouvent des transitions à la communauté des hôpitaux, y compris les problèmes de la vie quotidienne et les préoccupations médicales. Grâce à l'analyse de données qualitatives à partir d'entretiens avec 36 personnes, y compris 17 adultes âgées à haut risque avec des problèmes multiples de santé chroniques, récemment sortis de l'hôpital, et 19 membres de la famille qui ont fourni les patients avec des soins continus, nous avons demandé (1) quels sont les défis que les patients éprouvent dans la transition de l'hôpital, et (2) quelles sont les solutions de systèmes et politiques qui peuvent répondre aux défis que ces patients éprouvent? Nos résultats révèlent des défis à court et a long terme associés aux transitions à la maison. Les défis à court terme comprennent la préparation de l'habitation pour le patient et la compréhension de l'organisation des soins à la maison. Les défis à long terme sont associés à des problèmes pratiques et émotionnels. Réfléchissant sur nos résultats, nous suggérons que les besoins sociaux des patients peuvent être d'une importance égale à leurs besoins médicaux lors de la récupération post-décharge, et nous discutons les implications pour la politique.
Optical properties of SiO2@M (M = Au, Pd, Pt) core–shell nanoparticles: material dependence and damping mechanisms
Authors: Zhang Xuemin , Ye Shunsheng , Zhang Xun , Wu Lianpeng
Published: December 2014

Optical properties of SiO2@M (M = Au, Pd, Pt) NPs are investigated. Both the plasmon hybridization effect and the retardation effect influence the plasmon band position, causing an initial blue shift, and then a red shift, with the increase of shell thickness.
Cultural and Linguistic Considerations in Language Assessment and Intervention for Levantine Arabic Speaking Children
Authors: Khamis-Dakwar Reem , Khattab Ghada
Published: December 2014

Working with multilingual children requires knowledge of their home/heritage culture and language(s), norms for development of these languages in monolingual and multilingual settings, and access to assessments and clinical resources. In the case of Arabic, all three requirements are normally missing due to the paucity of research on language development in Arabic. In the face of a steady increase in the Arab-American population and limited related linguistic and cultural knowledge, Arab-Americans run the same risk of over- and under-identification of language impairment as do many minority groups in the United States. This paper aims to provide foundational knowledge of the diversity of the Arab culture and language(s), and of the prevalence of multilingualism in the Arab world. We also present some background on the Arab population in the United States, while highlighting potential vulnerable areas of service delivery. A brief account of some of the main linguistic features of Levantine Arabic (LA) is then provided, followed by implications for language interaction in the perception and production patterns of heritage language speakers. We hope that this paper will enhance speech-language pathologists (SLPs') ability to implement best practices in bilingual assessment when working with children from a Levantine background and to raise their awareness of implicit bias.
Turkish: Linguistic and Cultural Considerations for SLPs in Multilingual Contexts
Authors: Topbaş Seyhun
Published: December 2014

Speech-language pathologists (SLPs) around the world are likely to provide clinical services to Turkish speaking people with communication disorders. Most non-Turkish SLPs are not fluent in Turkish as a second language to serve bilingual or minority clients. This paper introduces the reader to basic information about the Turkish language and culture, followed by considerations for clinicians working with Turkish-speaking clients and their families.
Inherent point defects at the thermal higher-Miller index (211)Si/SiO2 interface
Authors: Iacovo S. , Stesmans A.
Published: December 2014

Electron spin resonance (ESR) studies were carried out on the higher-Miller index (211)Si/SiO2 interface thermally grown in the temperature range Tox = 400–1066 °C to assess interface quality in terms of inherently incorporated point defects. This reveals the presence predominantly of two species of a Pb-type interface defect (interfacial Si dangling bond), which, based on pertinent ESR parameters, is typified as Pb0(211) variant, close to the Pb0 center observed in standard (100)Si/SiO2—known as utmost detrimental interface trap. Tox ≳ 750 °C is required to minimize the Pb0(211) defect density (∼4.2 × 1012 cm−2; optimized interface). The data clearly reflect the non-elemental nature of the (211)Si face as an average of (100) and (111) surfaces. It is found that in oxidizing (211)Si at Tox ≳ 750 °C, the optimum Si/SiO2 interface quality is retained for the two constituent low-index (100) and (111) faces separately, indicating firm anticipating power for higher-index Si/SiO2 interfaces in general. It implies that, as a whole, the quality of a thermal higher-index Si/SiO2 interface can never surmount that of the low-index (100)Si/SiO2 structure.
Protein and cell patterning in closed polymer channels by photoimmobilizing proteins on photografted poly(ethylene glycol) diacrylate
Authors: Larsen Esben Kjær Unmack , Mikkelsen Morten Bo Lindholm , Larsen Niels B.
Published: December 2014

Definable surface chemistry is essential for many applications of microfluidic polymer systems. However, small cross-section channels with a high surface to volume ratio enhance passive adsorption of molecules that depletes active molecules in solution and contaminates the channel surface. Here, we present a one-step photochemical process to coat the inner surfaces of closed microfluidic channels with a nanometer thick layer of poly(ethylene glycol) (PEG), well known to strongly reduce non-specific adsorption, using only commercially available reagents in an aqueous environment. The coating consists of PEG diacrylate (PEGDA) covalently grafted to polymer surfaces via UV light activation of the water soluble photoinitiator benzoyl benzylamine, a benzophenone derivative. The PEGDA coating was shown to efficiently limit the adsorption of antibodies and other proteins to <5% of the adsorbed amount on uncoated polymer surfaces. The coating could also efficiently suppress the adhesion of mammalian cells as demonstrated using the HT-29 cancer cell line. In a subsequent equivalent process step, protein in aqueous solution could be anchored onto the PEGDA coating in spatially defined patterns with a resolution of <15 μm using an inverted microscope as a projection lithography system. Surface patterns of the cell binding protein fibronectin were photochemically defined inside a closed microfluidic device that was initially homogeneously coated by PEGDA. The resulting fibronectin patterns were shown to greatly improve cell adhesion compared to unexposed areas. This method opens for easy surface modification of closed microfluidic systems through combining a low protein binding PEG-based coating with spatially defined protein patterns of interest.
The influence of carbon doping on the performance of Gd2O3 as high-k gate dielectric
Authors: Shekhter P. , Chaudhuri A. R. , Laha A. , Yehezkel S. , Shriki A. , Osten H. J. , Eizenberg M.
Published: December 2014

One of the approaches for overcoming the issue of leakage current in modern metal-oxide-semiconductor devices is utilizing the high dielectric constants of lanthanide based oxides. We investigated the effect of carbon doping directly into Gd2O3 layers on the performance of such devices. It was found that the amount of carbon introduced into the dielectric is above the solubility limit; carbon atoms enrich the oxide-semiconductor interface and cause a significant shift in the flat band voltage of the stack. Although the carbon atoms slightly degrade this interface, this method has a potential for tuning the flat band voltage of such structures.
Whole-transcriptome analysis of endothelial to hematopoietic stem cell transition reveals a requirement for Gpr56 in HSC generation
Authors: Solaimani Kartalaei Parham , Yamada-Inagawa Tomoko , Vink Chris S. , de Pater Emma , van der Linden Reinier , Marks-Bluth Jonathon , van der Sloot Anthon , van den Hout Mirjam , Yokomizo Tomomasa , van Schaick-Solernó M. Lucila , Delwel Ruud , Pimanda John E. , van IJcken Wilfred F.J. , Dzierzak Elaine
Published: December 2014

Hematopoietic stem cells (HSCs) are generated via a natural transdifferentiation process known as endothelial to hematopoietic cell transition (EHT). Because of small numbers of embryonal arterial cells undergoing EHT and the paucity of markers to enrich for hemogenic endothelial cells (ECs [HECs]), the genetic program driving HSC emergence is largely unknown. Here, we use a highly sensitive RNAseq method to examine the whole transcriptome of small numbers of enriched aortic HSCs, HECs, and ECs. Gpr56, a G-coupled protein receptor, is one of the most highly up-regulated of the 530 differentially expressed genes. Also, highly up-regulated are hematopoietic transcription factors, including the “heptad” complex of factors. We show that Gpr56 (mouse and human) is a target of the heptad complex and is required for hematopoietic cluster formation during EHT. Our results identify the processes and regulators involved in EHT and reveal the surprising requirement for Gpr56 in generating the first HSCs.
Correlation of Central Blood Pressure to Hypertensive Target Organ Damages During Antihypertensive Treatment: The J-TOP Study
Authors: Shimizu Motohiro , Hoshide Satoshi , Ishikawa Joji , Yano Yuichiro , Eguchi Kazuo , Kario Kazuomi
Published: December 2014

BACKGROUND

Some previous studies have shown that central blood pressure (BP) is more closely related to cardiovascular risks than brachial BP. This study compared the correlations between asymptomatic organ damages and each of central BP, brachial clinic BP, and home BP during antihypertensive treatment.

METHODS

In the Japan Morning Surge-Target Organ Protection (J-TOP) study, which compared bedtime or awakening dosing of candesartan (+diuretics as needed) among subjects with home systolic BP (SBP) higher than 135mm Hg, we evaluated 180 hypertensive patients who successfully underwent pulse wave analysis by HEM-9000AI and measured their urinary albumin/creatinine ratio (UACR) and left ventricular mass index (LVMI) (n = 144) at baseline and after 6 months of treatment.

RESULTS

During antihypertensive treatment, significant reductions were found in central SBP, UACR, and LVMI (all P < 0.001). Multiple regression analyses showed that the decrease in central SBP was associated with those of log-transformed UACR (β = 0.24, P < 0.01) and LVMI (β = 0.23, P = 0.04), independently of the decrease in both clinic and home SBP. The goodness-of-fit of the association between the reduction in SBP and the UACR (P < 0.01) or LVMI (P = 0.04) was improved by adding central SBP to the SBP measurement.

CONCLUSION

These findings suggest that the change in central BP could be an important therapeutic target during antihypertensive treatment, in addition to peripheral clinic and home BP.
Capecitabine-Induced Takotsubo Cardiomyopathy: A Case Report and Literature Review
Authors: Qasem Abdulraheem , Bin Abdulhak Aref A. , Aly Abdelrahman , Moormeier Jill
Published: December 2014

Capecitabine is an orally administered chemotherapeutic agent that is metabolized at the tumor site to 5-fluorouracil and thought to be without significant cardiac toxicity. We report a rare case of takotsubo cardiomyopathy that is thought to be related to capecitabine where the patient presented with chest pain, and ST elevation within 48 hours of capecitabine therapy. Workup included cardiac catheterization and coronary angiogram that showed nonobstructive coronary artery disease and anteroapical left ventricular wall motion abnormality with left ventricular ejection fraction of 35%. The drug was stopped, and the patient was treated with beta-blocker and angiotensin-converting enzymes inhibitor. Six weeks later, she had a repeat echocardiogram that was normal. Capecitabine-related cardiomyopathy seems to be very rare because only 5 cases have been reported in the literature (including our case). The condition has to be anticipated and treated to prevent the serious consequence of cardiac dysfunction. All reported cases have eventually recovered after stopping capecitabine.
Strategies of symbolization in cardiovascular time series to test individual gestational development in the fetus
Authors: Cysarz Dirk , Edelhäuser Friedrich , Van Leeuwen Peter
Published: December 2014

The analysis of symbolic dynamics applied to physiological time series retrieves dynamical properties of the underlying regulation which are robust against the symbolic transformation. In this study, three different transformations to produce a symbolic series were applied to fetal RR interval series to test whether they reflect individual changes of fetal heart rate variability in the course of pregnancy. Each transformation was applied to 215 heartbeat datasets obtained from 11 fetuses during the second and the third trimester of pregnancy (at least 10 datasets per fetus, median 17). In the symbolic series, the occurrence of symbolic sequences of length 3 was categorized according to the amount of variations in the sequence: no variation of the symbols, one variation, two variations. Linear regression with respect to gestational age showed that the individual course during pregnancy performed best using a binary transformation reflecting whether the RR interval differences are below or above a threshold. The median goodness of fit of the individual regression lines was 0.73 and also the variability among the individual slopes was low. Other transformations to symbolic dynamics performed worse but were still able to reflect the individual progress of fetal cardiovascular regulation.
Characterizing dilute combustion instabilities in a multi-cylinder spark-ignited engine using symbolic analysis
Authors: Daw C. S. , Finney C. E. A. , Kaul B. C. , Edwards K. D. , Wagner R. M.
Published: December 2014

Spark-ignited internal combustion engines have evolved considerably in recent years in response to increasingly stringent regulations for emissions and fuel economy. One new advanced engine strategy ustilizes high levels of exhaust gas recirculation (EGR) to reduce combustion temperatures, thereby increasing thermodynamic efficiency and reducing nitrogen oxide emissions. While this strategy can be highly effective, it also poses major control and design challenges due to the large combustion oscillations that develop at sufficiently high EGR levels. Previous research has documented that combustion instabilities can propagate between successive engine cycles in individual cylinders via self-generated feedback of reactive species and thermal energy in the retained residual exhaust gases. In this work, we use symbolic analysis to characterize multi-cylinder combustion oscillations in an experimental engine operating with external EGR. At low levels of EGR, intra-cylinder oscillations are clearly visible and appear to be associated with brief, intermittent coupling among cylinders. As EGR is increased further, a point is reached where all four cylinders lock almost completely in phase and alternate simultaneously between two distinct bi-stable combustion states. From a practical perspective, it is important to understand the causes of this phenomenon and develop diagnostics that might be applied to ameliorate its effects. We demonstrate here that two approaches for symbolizing the engine combustion measurements can provide useful probes for characterizing these instabilities.
Ordinal symbolic analysis and its application to biomedical recordings
Authors: Amigó José M. , Keller Karsten , Unakafova Valentina A.
Published: December 2014

Ordinal symbolic analysis opens an interesting and powerful perspective on time-series analysis. Here, we review this relatively new approach and highlight its relation to symbolic dynamics and representations. Our exposition reaches from the general ideas up to recent developments, with special emphasis on its applications to biomedical recordings. The latter will be illustrated with epilepsy data.
Assessing directionality and strength of coupling through symbolic analysis: an application to epilepsy patients
Authors: Lehnertz Klaus , Dickten Henning
Published: December 2014

Inferring strength and direction of interactions from electroencephalographic (EEG) recordings is of crucial importance to improve our understanding of dynamical interdependencies underlying various physiological and pathophysiological conditions in the human epileptic brain. We here use approaches from symbolic analysis to investigate—in a time-resolved manner—weighted and directed, short- to long-ranged interactions between various brain regions constituting the epileptic network. Our observations point to complex spatial–temporal interdependencies underlying the epileptic process and their role in the generation of epileptic seizures, despite the massive reduction of the complex information content of multi-day, multi-channel EEG recordings through symbolization. We discuss limitations and potential future improvements of this approach.
Joint symbolic dynamics for the assessment of cardiovascular and cardiorespiratory interactions
Authors: Baumert Mathias , Javorka Michal , Kabir Muammar
Published: December 2014

Beat-to-beat variations in heart period provide information on cardiovascular control and are closely linked to variations in arterial pressure and respiration. Joint symbolic analysis of heart period, systolic arterial pressure and respiration allows for a simple description of their shared short-term dynamics that are governed by cardiac baroreflex control and cardiorespiratory coupling. In this review, we discuss methodology and research applications. Studies suggest that analysis of joint symbolic dynamics provides a powerful tool for identifying physiological and pathophysiological changes in cardiovascular and cardiorespiratory control.
Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth
Authors: Li Nan , Zhang Yajie , Han Xin , Liang Ke , Wang Jiadong , Feng Lin , Wang Wenqi , Songyang Zhou , Lin Chunru , Yang Liuqing , Yu Yonghao , Chen Junjie
Published: December 2014

PTEN [phosphatidylinositol (3,4,5)-trisphosphate phosphatase and tensin homolog deleted from chromosome 10], a phosphatase and critical tumor suppressor, is regulated by numerous post-translational modifications, including phosphorylation, ubiquitination, acetylation, and SUMOylation, which affect PTEN localization and protein stability. Here we report ADP-ribosylation as a new post-translational modification of PTEN. We identified PTEN as a novel substrate of tankyrases, which are members of the poly(ADP-ribose) polymerases (PARPs). We showed that tankyrases interact with and ribosylate PTEN, which promotes the recognition of PTEN by a PAR-binding E3 ubiquitin ligase, RNF146, leading to PTEN ubiquitination and degradation. Double knockdown of tankyrase1/2 stabilized PTEN, resulting in the subsequent down-regulation of AKT phosphorylation and thus suppressed cell proliferation and glycolysis in vitro and tumor growth in vivo. Furthermore, tankyrases were up-regulated and negatively correlated with PTEN expression in human colon carcinomas. Together, our study revealed a new regulation of PTEN and highlighted a role for tankyrases in the PTEN–AKT pathway that can be explored further for cancer treatment.
Tumor thickness as a prognostic factor in extramammary Paget's disease
Authors: Ito Takamichi , Kaku Yumiko , Nagae Konosuke , Nakano‐Nakamura Misa , Nakahara Takeshi , Oda Yoshinao , Hagihara Akihito , Furue Masutaka , Uchi Hiroshi
Published: December 2014

Extramammary Paget's disease (EMPD) is a rare tumor and a widely accepted classification system specific for the disease has not been established. To elucidate prognostic factors of EMPD, we conducted a retrospective review of 145 patients with 155 EMPD lesions and investigated clinicopathological factors using univariate and multivariate analyses. We also explored tumor thickness and metastatic lymph nodes using detection analysis to determine cut‐off points for survival. All patients were Japanese (88 men and 57 women), with EMPD in the genital (82.8%), perianal (3.4%) and axillary regions (1.4%). In the remaining cases (12.4%), there were lesions at two or more regions. Univariate analysis revealed the following prognostic factors: perianal location, presence of nodules, invasion depth, tumor thickness, number of metastatic nodes and serum carcinoembryonic antigen level. Both tumor thickness and perianal location retained statistical significance in multivariate analysis (hazard ratio, 1.39; 95% confidence interval, 1.12–1.72; P = 0.0024; hazard ratio, 50.72; 95% confidence interval, 4.20–612.63; P = 0.0020; respectively). The signal detection analysis indicated tumor thickness of more than 3 mm and three or more metastatic lymph nodes as cut‐off points for survival. In conclusion, tumor thickness and the number of metastatic lymph nodes closely correlated with patient outcome and these factors could be suitable for the tumor and node classification.
Effect of inhibition proliferation in human lung adenocarcinoma A549 cells by cytokine‐induced killer cells
Authors: Li Dengrui , Guo Sumin , Li Hui , Zhu Guiyun , Gao Li , Xin Xin , Yan Dandan , Li Xiuwu , Geng Shujun , Hou Hongwei , Yang Yonghui
Published: December 2014

Background

Adenocarcinoma, the most common form of lung cancer, is one of main human malignant tumors. In this paper, we focus on the effect of antitumor activity of cytokine‐induced killer (CIK) cells on human lung adenocarcinoma cell line A549.

Methods

CIK cells were obtained by inducing peripheral blood mononuclear cells with recombinant human (rh) interferon‐gamma, monoclonal anti‐CD3 antibody, rh interleukin (IL)‐1alpha, and rhIL‐2, which were added into the culture. A549 cell viability of CIK cells was determined using MTS assay. Flow cytometry (FCM) experiments were performed to detect cell cycle changes. The expression of P27 in A549 cells treated by CIK cells was evaluated by Western blot.

Result

The percentage of CD3+CD16+CD56+ T cells in a representative peripheral blood mononucleated cell sample was 33.7 ± 1.3%. CIK cells, in dose and time dependent manners, inhibited the proliferation of A549. FCM demonstrated that A549 cells were accumulated in G2/M and G0/G1 phases when treated with CIK cells. FCM was used to analyze whether A549 cells treated with CIK cells induced apotosis or necrosis at 10:1 or 20:1. Compared to the control group, P27 was prominently upregulated in the CIK treated group.

Conclusion

We propose that the pharmacological mechanisms of A549 cells inhibited by CIK cells can be estimated to possibly elicit different biological significance, which, in part, can be ascribed to a different mass transport rate in vitro.
The Determinants and Consequences of Information Acquisition via EDGAR
Authors: Drake Michael S. , Roulstone Darren T. , Thornock Jacob R.
Published: December 2014

Using a novel data set that tracks all web traffic on the SEC's EDGAR servers from 2008 to 2011, we examine the determinants and capital market consequences of investor information acquisition of SEC filings. The average user employs the database very few times per quarter and most users target specific filing types such as periodic accounting reports; a small subset of users employ EDGAR almost daily and access many filings. EDGAR activity is positively related with corporate events (particularly restatements, earnings announcements, and acquisition announcements), poor stock performance, and the strength of a firm's information environment. EDGAR activity is related to, but distinct from, other proxies of investor interest such as trading volume, business press articles, and Google searches. Finally, information acquisition via EDGAR, both to obtain earnings news and to provide context for it, has a positive influence on market efficiency with respect to earnings news. Overall, our results are important because they provide a unique, user‐based perspective on investor access of mandatory disclosures and its impact on price formation.
Transrectal ultrasound‐guided biopsy sepsis and the rise in carbapenem antibiotic use
Authors: Leahy Olivia R. , O'Reilly Mary , Dyer David R. , Phillips David , Grummet Jeremy P.
Published: December 2014

Background

This study sought to determine the number of hospital admissions for sepsis following transrectal ultrasound‐guided (TRUS) biopsy, and the rate of both prophylactic and therapeutic use of carbapenem antibiotics for TRUS biopsy, at a single institution.

Methods

A retrospective review of prospectively collected data from the medical records electronic database of Cabrini Health, a private metropolitan hospital, was queried for coding of admissions under any admitting urologist for sepsis and prostate‐related infections from 2009 to 2012. Records were examined for whether a TRUS biopsy had been performed within 14 days prior and if a therapeutic carbapenem was required. The database also queried the use of carbapenems as prophylaxis in patients undergoing TRUS biopsy.

Results

Of the 63 admissions for TRUS biopsy sepsis, multi‐drug‐resistant organisms were isolated from 26 (41%). Twenty‐three admissions were from the 1937 patients who underwent a TRUS biopsy at Cabrini (a sepsis rate of 1.2%) and 40 were following TRUS biopsies at other centres. Thirty‐seven (58.7%) patients received therapeutic carbapenems either empirically, or after culture results. Of the 1937 Cabrini TRUS biopsy patients, 154 (8%) were given a carbapenem as prophylaxis, with a rapid increase in prophylactic use over the 4 years studied from 0.25% to 13%.

Conclusion

This study did not show evidence of an increasing rate of hospital admissions for TRUS biopsy sepsis at this institution. However, there was a dramatic uptake in prophylactic administration of carbapenems. Increasing carbapenem use may contribute to development of carbapenem‐resistant bacteria. Alternative methods of prostate biopsy that avoid sepsis should be considered.
A workshop report on the development of the Cow's Milk‐related Symptom Score awareness tool for young children
Authors: Vandenplas Yvan , Dupont Christophe , Eigenmann Philippe , Host Arne , Kuitunen Mikael , Ribes‐Koninckx Carmen , Shah Neil , Shamir Raanan , Staiano Annamaria , Szajewska Hania , Von Berg Andrea
Published: December 2014

Clinicians with expertise in managing children with gastrointestinal problems and/or atopic diseases attended a workshop in Brussels in September 2014 to review the literature and determine whether a clinical score derived from symptoms associated with the ingestion of cow's milk proteins could help primary healthcare providers. The Cow's Milk‐related Symptom Score (CoMiSS), which considers general manifestations, dermatological, gastrointestinal and respiratory symptoms, was developed as an awareness tool for cow's milk‐related symptoms. It can also be used to evaluate and quantify the evolution of symptoms during therapeutic interventions, but does not diagnose cow's milk protein allergy and does not replace a food challenge. Its usefulness needs to be evaluated by a prospective randomised study.

Conclusion

The CoMiSS provides primary healthcare clinicians with a simple, fast and easy‐to‐use awareness tool for cow's milk‐related symptoms.
Methadone dose in heroin‐dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity
Authors: Mouly Stéphane , Bloch Vanessa , Peoc'h Katell , Houze Pascal , Labat Laurence , Ksouda Kamilia , Simoneau Guy , Declèves Xavier , Bergmann Jean Francois , Scherrmann Jean‐Michel , Laplanche Jean‐Louis , Lepine Jean‐Pierre , Vorspan Florence
Published: December 2014

Aims

Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid‐dependent responder patients.

Methods

Eighty‐one stable patients (60 men and 21 women, 43.7 ± 8.1 years old, 63.1 ± 50.9 mg day−1 methadone), divided into quartiles with respect to the median daily dose, were enrolled and underwent clinical examination, treatment history and determination of liver/intestinal cytochrome P450 (CYP) 3A4 activity measured by the midazolam test, R,S‐methadone trough concentration and clinically significant polymorphisms of the OPRM1, DRD2, COMT, ABCB1, CYP2B6, CYP3A5, CYP2C19 and CYP2D6 genes.

Results

Methadone maintenance dose was correlated to the highest dose ever used (r2 = 0.57, P < 0.0001). Fractioned methadone intake (odds ratio 4.87, 95% confidence interval 1.27–18.6, P = 0.02), bodyweight (odds ratio 1.57, 95% confidence interval 1.01–2.44, P = 0.04), history of cocaine dependence (80 vs. 44 mg day−1 in never‐addict patients, P = 0.005) and ethnicity (Asian > Caucasian > African, P = 0.04) were independently associated with high‐dose methadone in multiple regression analysis. A modest correlation was observed between liver/intestinal CYP3A4 activity and methadone dose at steady state (Spearman rank correlation coefficient [rs] = 0.21, P = 0.06) but not with highest dose ever used (rs = 0.15, P = 0.18) or dose‐normalized R,S‐methadone trough concentrations (rs = −0.05, P = 0.64). Concomitant CYP3A4 inhibitors only affected the relationship between methadone dose and R,S‐methadone trough concentration. None of the genetic polymorphisms explored was predictive of the methadone maintenance dose.

Conclusions

Methadone maintenance dose was predicted by sociodemographic and clinical variables rather than genetic polymorphisms or liver/intestinal CYP3A4 activity in stable patients.