bluuebunny/crossref_metadata_2025 huggingface dataset:
The geomagnetic storm time response of GPS total electron content in the North American sector
Authors: Thomas E. G. , Baker J. B. H. , Ruohoniemi J. M. , Coster A. J. , Zhang S.‐R.
Published: February 2016

Over the last two decades, maps of GPS total electron content (TEC) have improved our understanding of the large perturbations in ionospheric electron density which occur during geomagnetic storms. However, previous regional and global studies of ionospheric storms have performed only a limited separation of storm time, local time, longitudinal, and seasonal effects. Using 13 years of GPS TEC data, we present a complete statistical characterization of the ionospheric response to geomagnetic storms for midlatitudes in the North American sector where dense ground receiver coverage is available. The rapid onset of a positive phase is observed across much of the dayside and evening ionosphere followed by a longer‐lasting negative phase across all latitudes and local times. Our results show clear seasonal variations in the storm time TEC, such that summer events tend to be dominated by the negative storm response while winter events exhibit a stronger initial positive phase with minimal negative storm effects. We find no discernable difference between spring and fall equinox events with both being equivalent to the average storm time response across all seasons. We also identify a prominent magnetic declination effect such that stronger dayside positive storm effects are observed in regions of negative declination (i.e., eastern North America). On the nightside, asymmetries in the TEC response are observed near the auroral oval and midlatitude trough which may be attributed to thermospheric zonal winds pushing plasma upward/downward along field lines of opposite declination.
Assessment of calibration assumptions under strong climate changes
Authors: Van Schaeybroeck Bert , Vannitsem Stéphane
Published: February 2016

Climate model calibration relies on different working hypotheses. The simplest bias correction or delta change methods assume the invariance of bias under climate change. Recent works have questioned this hypothesis and proposed linear bias changes with respect to the forcing. However, when the system experiences larger forcings, these schemes could fail. Calibration assumptions are tested within a simplified framework in the context of an intermediate complexity model for which the reference (or “reality”) differs from the model by a single parametric model error and climate change is emulated by largely different CO2 forcings. It appears that calibration does not add value since the variation of bias under climate change is nonmonotonous for almost all variables and large compared to the climate change and the bias, except for the global temperature and sea ice area. For precipitation, calibration provides added value both globally and regionally. The calibration methods used fail to correct climate variability.
What to Expect When Expecting With Systemic Lupus Erythematosus (SLE): A Population‐Based Study of Maternal and Fetal Outcomes in SLE and Pre‐SLE
Authors: Arkema Elizabeth V. , Palmsten Kristin , Sjöwall Christopher , Svenungsson Elisabet , Salmon Jane E. , Simard Julia F.
Published: February 2016

Objective

To assess maternal and fetal outcomes associated with subclinical (pre‐systemic lupus erythematosus [SLE] and SLE presenting up to 5 years postpartum) and prevalent maternal SLE during pregnancy compared with the general population.

Methods

This prospective cohort study used population‐based Swedish registers to identify 13,598 women with first singleton pregnancies registered in the Medical Birth Register (551 prevalent SLE, 65 pre‐SLE within 0–2 years, 133 pre‐SLE within 2–5 years, and 12,847 general population). SLE was defined as ≥2 SLE‐coded discharge diagnoses in the patient register with ≥1 diagnosis from a specialist. Unadjusted risks of adverse pregnancy or birth outcomes were calculated by SLE status, and Cochran‐Armitage tests evaluated trend across exposure groups.

Results

Maternal outcomes such as preeclampsia, hypothyroidism, stroke, and infection were more common among women with SLE. Sixteen percent of prevalent‐SLE pregnancies were diagnosed with preeclampsia compared with 5% of those from the general population. Among the pre‐SLE women, preeclampsia was found in 26% of those with SLE within 2 years postpartum and 13% in those with SLE within 2–5 years postpartum. Similarly, infant outcomes, such as preterm birth, infection, and mortality, were worse among those born to mothers with prevalent SLE and pre‐SLE during pregnancy. The test for trend was significant for most outcomes.

Conclusion

Our data demonstrate that adverse maternal and fetal outcomes are more common in SLE pregnancies. Furthermore, these unfavorable outcomes are observed in pregnancies occurring prior to the diagnosis of SLE. Thus, the underlying immunologic profile of SLE and alterations preceding clinical SLE may contribute to these pregnancy complications.
Combining Sensor and Protective Functionalities in Ferromagnetic Nanocomposite Thin Films for Applications in Harsh Environments
Authors: Seemann Klaus , Leiste Harald , Stüber Michael , Krüger Kathrin , Brunken Hayo , Ludwig Alfred , Thede Claas , Quandt Eckhard
Published: February 2016

The present paper discusses the development of Fe48Co52/TiN, Fe32Co44Hf12N12/TiN, Fe–Co/Al–N multilayer, and Fe2B single layer films produced by magnetron sputtering processes. These films combine appropriate magnetic and wear resistant multifunctional properties for the employment as sensor components for monitoring the actual state of stress and/or temperature of cutting tools used in the metal processing industry. At this point, the ferromagnetic layers enable the sensor function, whereas the TiN or Al–N layers support mechanical features. Being exposed to stress and/or temperature, the change of polarization or permeability can be utilized as a response for reading‐out the sensor component.
Embedded Sensor Networks for Textile‐Reinforced Thermoplastics: Sensor Network Design and Mechanical Composite Performance
Authors: Weck Daniel , Sauer Sebastian , Adam Frank , Starke Eric , Böhm Robert , Modler Niels
Published: February 2016

Textile‐reinforced thermoplastics enable lightweight components suitable for high volume production. Composite‐embedded sensor networks allow for additional functionalities like structural health monitoring. In this paper, the design of such embedded sensor networks is described and the necessity to adapt the existing composite manufacturing process is discussed. The impact of the embedded components on the mechanical behavior of textile‐reinforced thermoplastics is investigated by comparing the mechanical behavior of specimens with and without dummy inclusions for different load cases. Design suggestions for the electronic components, the network and the composite structure are formulated.
Terpolymerization of Carbon Dioxide with Propylene Oxide and γ‐Butyrolactone Catalyzed by SalenCoIII(2,4‐dinitrophenoxy) and Lewis‐Basic Cocatalyst
Authors: Niu Yongsheng , Li Hongchun
Published: February 2016

The terpolymerization of γ‐butyrolactone (GBL), propylene oxide (PO), and CO2 catalyzed by SalenCoIII(2,4‐dinitrophenoxy) (Salen = N,N‐bis(3,5‐di‐tert‐butylsalicylidene)‐ethylenediimine) (1) was studied in the presence of nBu4NBr. The reaction conditions, such as nBu4NBr/the 1 molar ratio, CO2 pressure, reaction temperature, reaction time, and GBL/PO molar ratios were optimized. A reasonably high viscosity‐average molar mass of 115.9 kg/mol and yield of 118.6 g/g of catalyst were achieved at an appropriate combination under the optimum conditions. The structure of as‐prepared product was characterized by the IR and 1H NMR spectra. Compared with a copolymer of PO/CO2, the thermal property of terpolymer has been evaluated largely. The reactivity ratios of CO2 and GBL (rCO2 = 5.62 and rGBL = 0.31) were experimentally evaluated by the Fineman–Ross methodology.
Clinical and pathologic features of Aicardi–Goutières syndrome due to an IFIH1 mutation: A pediatric case report
Authors: Marguet Florent , Laquerrière Annie , Goldenberg Alice , Guerrot Anne‐Marie , Quenez Olivier , Flahaut Philippe , Vanhulle Catherine , Dumant‐Forest Clémentine , Charbonnier Françoise , Vezain Myriam , Bekri Soumeya , Tournier Isabelle , Frébourg Thierry , Nicolas Gaël
Published: February 2016

We describe the case of a young patient with calcifying encephalopathy, born to asymptomatic parents. An extensive hypothesis‐driven etiological assessment was performed and failed to detect the precise etiology during many years. We therefore decided to perform whole exome sequencing of the child–unaffected parents trio. A de novo pathogenic variant in the IFIH1 gene which has recently been shown to cause autosomal dominant forms of Aicardi–Goutières syndrome was identified. This child presented with a severe form with neonatal thrombocytopenia and hepatomegaly, the latter having been detected during late gestation. Although first milestones were uneventful, he progressively lost motor skills from the age of 12 months and developed severe spastic paraplegia. Brain imaging revealed white matter abnormalities and extensive calcifications. He also presented atypical skin lesions, different from chilblains. His medical history was marked by two episodes of acute pancreatitis. We provide herein the results of pathological examination including detailed description of the neuropathological hallmarks. To our knowledge, this the first detailed clinico‐pathological description of a patient with an IFIH1 pathogenic variant. © 2016 Wiley Periodicals, Inc.
Deficient visuospatial working memory functions and neural correlates of the default‐mode network in adolescents with autism spectrum disorder
Authors: Chien Hsiang‐Yun , Gau Susan Shur‐Fen , Isaac Tseng Wen‐Yih
Published: February 2016

In addition to the essential features of autism spectrum disorder (ASD), namely social communication deficits and repetitive behaviors, individuals with ASD may suffer from working memory deficits and an altered default‐mode network (DMN). We hypothesized that an altered DMN is related to working memory deficits in those with ASD. A total of 37 adolescents with ASD and 36 age‐ and IQ‐matched typically developing (TD) controls were analyzed. Visuospatial working memory performance was assessed using pattern recognition memory (PRM), spatial recognition memory (SRM), and paired‐associates learning (PAL) tasks. The intrinsic functional connectivity (iFC) of the DMN was indexed by the temporal correlations between the resting‐state functional magnetic resonance imaging signals of pairs of DMN regions, including those between the posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) and between the PCC and parahippocampi (PHG). The corresponding structural connectivity of the DMN was indexed by the generalized fractional anisotropy (GFA) of the dorsal and ventral cingulum bundles on the basis of diffusion spectrum imaging data. The results showed that ASD adolescents exhibited delayed correct responses in PRM and SRM tasks and committed more errors in the PAL task than the TD controls did. The delayed responses during the PRM and SRM tasks were negatively correlated with bilateral PCC–mPFC iFCs, and PAL performance was negatively correlated with right PCC–PHG iFC in ASD adolescents. Furthermore, ASD adolescents showed significant lower GFA in the right cingulum bundles than the TD group did; the GFA value was negatively correlated with SRM performance in ASD. Our results provide empirical evidence for deficient visuospatial working memory and corresponding neural correlates within the DMN in adolescents with ASD. Autism Res 2016, 9: 1058–1072. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Die Verformungsberechnung der Lahntalbrücke Limburg
Authors: Sonnabend Stephan , Franz Stefan , Steinbrück Christina , Kerschensteiner Martin
Published: February 2016

Die Neue Lahntalbrücke bei Limburg ist ein semi‐integrales Spannbetonbauwerk, das aus einem Realisierungswettbewerb hervorgegangen ist. Es zeichnet sich durch seine schlanke, ansprechende Gestaltung aus. Das Bauwerk wird im Freivorbau hergestellt. Nachfolgend werden die Besonderheiten für die Verformungsberechnung der Lahntalbrücke vorgestellt. Dabei wird erläutert, welche Überlegungen zu der letztlich ausgeführten Bauabschnittseinteilung geführt haben. Es werden die einzelnen zu berücksichtigenden Verformungsanteile aufgezeigt und die daraus resultierende Verformungsberechnung erläutert. Abschließend wird die Verifizierung bzw. Verwertung der Verformungsberechnung auf der Baustelle über das Vermessungsprogramm dargelegt.

The deformation calculation of the Lahntalbrücke Limburg

The new Lahntalbrücke in Limburg is a semi‐integral prestressed concrete structure that has emerged from a design competition. It is distinguished by its slender, attractive design. The superstructure is currently erected as balanced cantilever construction. Subsequently, the peculiarities of the deformation calculation of the Lahntalbrücke are presented. The considerations about the allocation of the construction sections are discussed. The individual amounts of deflection to be considered are shown and the resulting deformation calculation is explained. Finally, the implementation of the deformation calculation regarding deflection measurements on the construction site is presented.
Disrupted functional brain network organization in patients with obstructive sleep apnea
Authors: Park Bumhee , Palomares Jose A. , Woo Mary A. , Kang Daniel W. , Macey Paul M. , Yan‐Go Frisca L. , Harper Ronald M. , Kumar Rajesh
Published: February 2016

Introduction

Obstructive sleep apnea (OSA) subjects show impaired autonomic, affective, executive, sensorimotor, and cognitive functions. Brain injury in OSA subjects appears in multiple sites regulating these functions, but the integrity of functional networks within the regulatory sites remains unclear. Our aim was to examine the functional interactions and the complex network organization of these interactions across the whole brain in OSA, using regional functional connectivity (FC) and brain network topological properties.

Methods

We collected resting‐state functional magnetic resonance imaging (MRI) data, using a 3.0‐Tesla MRI scanner, from 69 newly diagnosed, treatment‐naïve, moderate‐to‐severe OSA (age, 48.3 ± 9.2 years; body mass index, 31 ± 6.2 kg/m2; apnea–hypopnea index (AHI), 35.6 ± 23.3 events/h) and 82 control subjects (47.6 ± 9.1 years; body mass index, 25.1 ± 3.5 kg/m2). Data were analyzed to examine FC in OSA over controls as interregional correlations and brain network topological properties.

Results

Obstructive sleep apnea subjects showed significantly altered FC in the cerebellar, frontal, parietal, temporal, occipital, limbic, and basal ganglia regions (FDR, P < 0.05). Entire functional brain networks in OSA subjects showed significantly less efficient integration, and their regional topological properties of functional integration and specialization characteristics also showed declined trends in areas showing altered FC, an outcome which would interfere with brain network organization (P < 0.05; 10,000 permutations). Brain sites with abnormal topological properties in OSA showed significant relationships with AHI scores.

Conclusions

Our findings suggest that the dysfunction extends to resting conditions, and the altered FC and impaired network organization may underlie the impaired responses in autonomic, cognitive, and sensorimotor functions. The outcomes likely result from the prominent structural changes in both axons and nuclear structures, which occur in the condition.
FGF2 regulates proliferation, migration, and invasion of ECA109 cells through PI3K/Akt signalling pathway in vitro
Authors: Shi Hui , Xu Jingjing , Zhao Rui , Wu Huiqun , Gu Luo , Chen Yijiang
Published: February 2016

Esophageal cancer is one of the most common malignant cancers that arise from esophagus tissues. Fibroblast growth factor 2 (FGF2) has been implicated in multiple biological functions and was considered as an oncogenic factor in tumorigenesis. However, the effects of FGF2 in esophageal carcinoma are yet to be fully elucidated. To better understand the function of FGF2 in esophageal cancer, we used the esophageal cancer cell line ECA109 as a cell model and downregulated FGF2 expression using RNAi; the results showed that insufficient expression of FGF2 inhibited cells proliferation, migration, and invasion of ECA109 cells. Meanwhile, the proliferation, migration, and invasion abilities were stimulated after treatment of exogenous FGF2. In addition, a PI3K/Akt signalling pathway inhibitor (LY294002) alleviated the tumorigenic effects of FGF2. These findings implied that the oncogenic effects of FGF2 was mediated, at least in part, through the PI3K/Akt signalling pathway and FGF2 may be a potential therapeutic target to constrain the tumorigenesis of esophageal cancer.
Efficacy and safety of catheter‐based rheolytic and aspiration thrombectomy in children
Authors: Qureshi Athar M. , Petit Christopher J. , Crystal Matthew A. , Liou Aimee , Khan Asra , Justino Henri
Published: February 2016

Background

Vascular thromboses are a significant cause of morbidity and mortality in children. Data in children regarding catheter‐based rheolytic and aspiration thrombectomy systems are limited. We sought to review the safety and efficacy of catheter‐based rheolytic and aspiration thrombectomy systems in children. Methods: Data of all children having undergone thrombectomy using specialized rheolytic or aspiration systems were reviewed. Results: Thrombectomy was performed in 50 vessels in 21 patients, median age 1.9 months (8 days–18 yrs), median weight 4.3 (1.1–67.9) kg. Thrombectomy was performed using AngioJet in 16, Helix Clot Buster in 5, Fetch catheter in 8, Pronto catheter in 1, and a combination of other systems in 20 vessels (with AngioJet in 16). Thrombectomy was successful in 47/50 (94%) vessels in 18/21 (86%) patients with additional balloon/stent therapy or tPA administration performed in 16/18 (89%) of these patients. There were 2 (9.5%) major complications (both with AngioJet) consisting of asystole when thrombectomy was performed using activation times of >5 sec. At a median follow‐up of 10 months (2 weeks–7 years), all 47 successfully treated vessels are patent, with 8/18 (44%) patients requiring reintervention with angioplasty/stent placement or repeat thrombectomy. Conclusions: Catheter‐based thrombectomy systems are an important adjunctive tool in the treatment of children with thrombotic vessel occlusions. Significant hemodynamic compromise seen when using AngioJet may be minimized by using activation times of ≤5 sec. © 2016 Wiley Periodicals, Inc.
Microfungi Potentially Pathogenic for Humans Reported in Surface Waters Utilized for Recreation
Authors: Biedunkiewicz Anna , Góralska Katarzyna
Published: February 2016

Fungal infections are commonly reported among outdoor bathers. Recreational water reservoirs are an important element of the mycosis epidemiological chain in the biosphere because they can be a source of fungi from municipal wastes, of asymptomatic carriers or bathers carrying mycoses. Yeast‐like fungi and moulds were isolated from samples of four surface water baths and five swimming pools in 2011–2012. Membrane filters and standard laboratory‐based protocols were used to identify the isolated fungi. In total, 51 saprotrophic and potentially pathogenic species classified in the biosafety level‐2 group were found. In one of the eutrophic lakes, a positive correlation was observed between the frequency of trading and the presence of coliform yeasts, while in the second, a correlation was found between the number of species of fungi and the presence of faecal streptococci. In swimming pool waters, the key factors that determined higher numbers of fungi were increased temperature, followed by low concentrations of chlorine ions. Together with the bacteriological and physicochemical analysis, constant mycological monitoring of recreational water (lake pools and swimming pools) should be a standard inspection element to reduce sanitary and epidemiologic risks to people using these water reservoirs for recreational purposes.
A systematic review of the cost and cost‐effectiveness studies of proton radiotherapy
Authors: Verma Vivek , Mishra Mark V. , Mehta Minesh P.
Published: February 2016

BACKGROUND

Economic analyses of new technologies, such as proton‐beam radiotherapy (PBT), are a public health priority. To date, no systematic review of the cost‐effectiveness of PBT has been performed.

METHODS

Systematic searches of PubMed, EMBASE, abstracts from American Society for Radiation Oncology and American Society of Clinical Oncology meetings, and the Cost‐Effectiveness Analysis Registry were conducted (2000‐2015) along with abstracts from the Particle Therapy Co‐Operative Group of North America for both years of existence (2014‐2015). Eighteen original investigations were analyzed.

RESULTS

The cost‐effectiveness for prostate cancer—the single most common diagnosis currently treated with PBT—was suboptimal. PBT was the most cost‐effective option for several pediatric brain tumors. PBT costs for breast cancer were increased but were favorable for appropriately selected patients with left‐sided cancers at high risk of cardiac toxicity and compared with brachytherapy for accelerated partial breast irradiation. For non‐small cell lung cancer (NSCLC), the greatest cost‐effectiveness benefits using PBT were observed for locoregionally advanced—but not early stage—tumors. PBT offered superior cost‐effectiveness in selected head/neck cancer patients at higher risk of acute mucosal toxicities. Similar cost‐effectiveness was observed for PBT, enucleation, and plaque brachytherapy in patients with uveal melanoma.

CONCLUSIONS

With greatly limited amounts of data, PBT offers promising cost‐effectiveness for pediatric brain tumors, well‐selected breast cancers, locoregionally advanced NSCLC, and high‐risk head/neck cancers. Heretofore, it has not been demonstrated that PBT is cost‐effective for prostate cancer or early stage NSCLC. Careful patient selection is absolutely critical to assess cost‐effectiveness. Together with increasing PBT availability, clinical trial evidence, and ongoing major technological improvements, cost‐effectiveness data and conclusions from this analysis could change rapidly. Cancer 2016;122:1483–501. © 2016 American Cancer Society.
Conflict Narratives from the Health Care Frontline: A Conceptual Model
Authors: Kim Sara , Buttrick Elizabeth , Bohannon Isaac , Fehr Ryan , Frans Elise , Shannon Sarah E.
Published: February 2016

We examined health care conflicts through interviews with health care leaders, providers, and patients. Ninety‐two medical providers, nurses, technologists, hospital leaders, and patients/families shared 156 conflict stories. We identified individual, interpersonal, and organizational factors contributing to interprofessional conflicts. Individual contributors included resource depletion (i.e., stress and fatigue), perceptions of others’ seemingly selfish motives, and judgment toward colleagues’ competence. Interpersonal conflicts involved prior unresolved conflicts, dehumanization, power differentials, or communication breakdown. Organizational factors included navigating within complex organizational structures and noncompliance with group norms. Conflicts resulted in negative consequences for patients (safety, satisfaction), providers (career, relationships, satisfaction, morale), and organizations (performance, staff turnover).
Direct Instruction and Guided Practice Matter in Conflict Resolution and Social‐Emotional Learning
Authors: DeVoogd Karen , Lane‐Garon Pamela , Kralowec Charles A.
Published: February 2016

Seven schools in an economically challenged area of an urban school district in central California implemented mentored peer mediation programs under the guidance of a university–K‐12 partnership project, Mediator Mentors. Individual student outcomes for social‐cognitive dispositions, perceptions of school climate, conflict strategy choices, and standardized testing results in language arts were analyzed on the basis of assessments administered after one year of program implementation and compared to pretest values generated by student mediators and nonmediators. Attendance and student perceptions of school safety were also examined after a year of peer mediation at the schools. Overall school climate was analyzed with respect to bullying incidence and suspension and expulsion rates before and after one year of program implementation.
67 GHz three‐spiral transformer CMOS oscillator
Authors: Pepe Domenico , Chlis Ilias , Zito Domenico
Published: February 2016

This paper presents a 67GHz LC oscillator exploiting a three‐spiral transformer and implemented in 65nm bulk complementary metal–oxide–semiconductor technology by STMicroelectronics. The three‐spiral transformer allows operating with a lower voltage supply, still obtaining good phase noise performance, and achieving a compact design. Measured performances when supplied with 1.2 V are: oscillation frequency of 67 GHz, phase noise (PN) equal to −96 dBc/Hz at 1 MHz frequency offset from the carrier, power consumption (PC) equal to 19.2 mW and figure of merit (FOM) equal to −179.7 dB/Hz. Measured performances when supplied with 0.6 V are: oscillation frequency of 67 GHz; PN equal to −88.7 dBc/Hz at a 1 MHz frequency offset from the carrier; PC equal to 3.6 mW and FOM equal to −179.7 dB/Hz. Copyright © 2016 John Wiley & Sons, Ltd.
Dynamic Phosphonic Bridges in Aqueous Uranyl Clusters
Authors: Oliveri Anna F. , Pilgrim Corey D. , Qiu Jie , Colla Christopher A. , Burns Peter C. , Casey William H.
Published: February 2016

The uranyl cage clusters (UO2)22(O2)15(PHO3)20(H2O)1026– (U22) and (UO2)28(O2)20(PHO3)24(H2O)1232– (U28) can be probed in aqueous solutions by using a combination of 1H Diffusion‐Ordered Spectroscopy (DOSY) and 1H‐31P Heteronuclear‐Single Quantum Coherence (HSQC) spectroscopy. This class of clusters is ideal for 1H NMR analysis in D2O because of the covalent character of the H–P bond in the phosphonic bridges. 1H DOSY indicates that the clusters are stable in solution and provides hydrodynamic radii of 9.8 ± 0.4 Å for the U22 and 12.3 ± 0.5 Å for the U28 clusters. Furthermore, 1H‐31P HSQC delivers unequivocal signal assignment for both nuclei, which enables solution dynamics to be monitored by variable‐temperature experiments, and reveals the presence of phosphonic‐bridge conformers. The results provide some of the first dynamic information about steady conformational changes in these enormous actinide macroions.
(Imidazol‐2‐yl)methyl‐1,3‐propanediones: Regioselective C–H Functionalization of the Imidazole Ring by Acylacetylene/Aldehyde Pairs
Authors: Trofimov Boris A. , Andriyankova Ludmila V. , Nikitina Lina P. , Belyaeva Kseniya V. , Mal'kina Anastasiya G. , Bagryanskaya Irina Yu. , Afonin Andrei V. , Ushakov Igor A.
Published: February 2016

The metal‐free regioselective C‐2–H functionalization of 1‐substituted imidazoles has been effected by a cascade reaction with aromatic or heteroaromatic aldehydes and acylacetylenes under mild conditions (55–60 °C, MeCN) to give (imidazol‐2‐yl)methyl‐1,3‐propanediones in 22–77 %, mainly 40–70 % yields.
State‐of‐the‐art technologies for rapid and high‐throughput sample preparation and analysis of N‐glycans from antibodies
Authors: Aich Udayanath , Lakbub Jude , Liu Aston
Published: February 2016

Glycosylation is a PTM that occurs during production of many protein‐based biologic drugs and can have a profound impact on their biological, clinical, and pharmacological properties. Quality by design, process optimization, and advance in manufacturing technology create a demand for robust, sensitive, and accurate profiling and quantification of antibody glycosylation. Potential drawbacks in antibody glycosylation profiling include the high hands‐on time required for sample preparation and several hours for data acquisition and analysis. Rapid and high‐throughput (HTP) N‐glycan profiling and characterization along with automation for sample preparation and analysis are essential for extensive antibody glycosylation analysis due to the substantial improvement of turnaround time. The first part of this review article will focus on the recent progress in rapid and HTP sample preparation and analysis of antibody glycosylation. Subsequently, the article will cover a brief overview of various separation and mass spectrometric methods for the rapid and HTP analysis of N‐glycans in antibodies. Finally, we will discuss the recent developments in process analytical technologies for the screening and quantification of N‐glycans in antibodies.
Secreted expression of an active human interferon‐beta (HuIFNβ) in Kluyveromyces lactis
Authors: Madhavan Aravind , Sukumaran Rajeev Kumar
Published: February 2016

Interferon‐beta (IFNβ) is a cytokine involved in the antiviral, anti‐proliferative and immunomodulatory responses of cells, and a potent drug for multiple sclerosis. Human interferon beta (HuIFNβ) gene fused with the glucoamylase signal sequence in the N‐terminus and 6 His Tag in the C‐terminus was cloned into pKlac1 vector and introduced in Kluyveromyces lactis to allow secreted expression and one‐step purification of the protein. Recombinant yeast transformant with the highest level of HuIFNβ production was identified, and this secreted up to 1 mg/L of the cytokine after 72 h of incubation. Glycosylated and non‐glycosylated forms of the cytokine were elaborated by the yeast, the latter in higher quantities. His tag of the protein allowed easy one‐step purification by nickel‐nitriloacetic acid affinity chromatography, yielding close to 100% purity. SDS‐PAGE, western blot and MALDI‐TOF‐TOF confirmed the identity of the protein. The biological activity of the recombinant HuIFNβ was confirmed by its anti cell proliferative activity on HeLa cells. Expression of HuIFNβ in K. lactis is advantageous since it is a very safe organism to produce proteins for therapeutic applications, allows glycosylation and offers a cost effective method for large scale production as it can be grown in cheap carbon sources.
Cardiac arrest with vagal stimulation during intraoperative nerve monitoring
Authors: Almquist Martin , Thier Mark , Salem Farhad
Published: February 2016

Background

Intraoperative neuromonitoring (IONM) is widely used during thyroid surgery. During both intermittent and continuous IONM stimulation of the vagus nerve is performed. This has previously been reported to be safe.

Methods

We present our findings based on the case reports of 2 patients.

Results

IONM of the recurrent laryngeal nerve (RLN), following the standards of the International Neuromonitoring Study Group, was conducted in 2 patients, one undergoing thyroid surgery and the second parathyroid surgery. In both cases, after dissection and stimulation of the vagus nerve on 1 mAmp, the patients became asystolic. Resuscitation efforts were successful in both patients.

Conclusion

These 2 cases demonstrate that stimulation of the vagus nerve during IONM can lead to profound cardiac events. Consideration should be given to these potential complications when utilizing IONM. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2419–E2420, 2016
Oncocytic carcinoma of the major salivary glands: A population‐based study of 278 cases
Authors: Zhan Kevin Y. , Lentsch Eric J.
Published: February 2016

Background

Oncocytic carcinomas of the major salivary glands are extremely rare, with <100 cases reported.

Methods

A retrospective review of the National Cancer Database was performed from 1998 to 2012.

Results

We found 278 cases of major salivary oncocytic carcinoma. Most patients were men (61.9%), white (84.8%), with parotid disease (88.5%). Median age was 67 years (range, 16–90 years). Regional and distant metastases were found in 36.4% and 4.7% of cases. Overall survival at 5 and 10‐years was 64% and 39%, respectively. Distant metastasis (hazard ratio [HR] = 13.87; 95% confidence interval [CI] = 2.98–64.52; p = .0010) and regional metastasis (HR = 3.01; 95% CI = 1.20–7.55; p = .019) are significant negative predictors, whereas positive margins approached significance (HR = 3.01; 95% CI = 1.20–7.55; p = .074).

Conclusion

Oncocytic carcinoma has a poor long‐term prognosis and lymph node metastases are common. Distant and regional metastases are significant predictors of decreased survival. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1981–E1986, 2016
Ketoconazole‐Associated Liver Injury in Drug‐Drug Interaction Studies in Healthy Volunteers
Authors: Banankhah Peymaan S. , Garnick Kyle A. , Greenblatt David J.
Published: February 2016

Ketoconazole is a potent CYP3A inhibitor in vivo, and frequently serves as an index CYP3A inhibitor in drug‐drug interaction (DDI) studies with healthy volunteers. Limitations restricting the use of systemic ketoconazole in such studies have been recently imposed by regulatory agencies in the United States, the European Union, and elsewhere. A risk of ketoconazole‐associated liver injury in the context of DDI studies was cited as the primary justification for these measures. To evaluate the basis for these restrictions, we analyzed a series of published DDI studies identified from a review of existing literature. The study set consisted of 53 DDI studies, and included 971 healthy volunteers with systemic ketoconazole exposure in addition to the victim drug under study. Ketoconazole‐associated abnormalities in serum chemistry values indicative of liver injury were observed in 4 subjects, representing a prevalence of 0.41% within the study population. There were no major adverse reactions or instances of hepatic failure. All abnormalities indicative of liver injury resolved upon discontinuation of ketoconazole treatment. The findings from this review do not support restriction of ketoconazole as an index CYP3A inhibitor in DDI studies involving healthy volunteers.
Diagnosis of neonatal ovarian torsion: Emphasis on prenatal and postnatal sonographic findings
Authors: Kim Hyun Su , Yoo So‐Young , Cha Min Jae , Kim Ji Hye , Jeon Tae Yeon , Kim Wee Kyoung
Published: February 2016

Purpose

Our aim was to retrospectively review the imaging findings of patients with neonatal ovarian torsion, emphasizing prenatal and postnatal sonographic findings.

Methods

Eleven patients who had had neonatal ovarian torsion diagnosed surgically (n = 9) or clinicoradiologically (n = 2) were enrolled. Prenatal and postnatal sonographic features, including sequential postnatal change, were reviewed. Clinical and pathologic features were also investigated.

Results

All patients except one had a fetal ovarian cyst (mean, 5.3 cm) detected on third‐trimester sonography, either simple (n = 6) or complex (n = 4). In all 11 patients, initial postnatal sonography had revealed a complex cyst (mean, 4.7 cm) with intracystic clot or debris, the double‐wall sign, a fluid–fluid level, and multiple septation. None of the patients had had symptoms or signs related to the ovarian torsion. Follow‐up sonography in seven patients had revealed increased echogenicity of the cyst wall with frequent calcification and a decrease in size of the cyst. In two patients, the interval of the change in cyst position was noted, and autoamputation of the torsed ovary had been surgically confirmed. Serous cystadenoma had been identified in one patient.

Conclusions

Neonatal ovarian torsion most commonly manifests as an asymptomatic complex cyst on sonography due to torsion of a fetal ovarian cyst. Serial monitoring of a fetal ovarian cyst for its resolution or changes in its appearance is mandatory for making an early diagnosis of torsion. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:290–297, 2016
The path(s) to employee trust in direct supervisor in nascent and established relationships: A fuzzy set analysis
Authors: Frazier M. Lance , Tupper Christina , Fainshmidt Stav
Published: February 2016

While many of the propositions advanced by Mayer, Davis, and Schoorman's (1995) integrative model of interpersonal trust have been supported empirically, we still know little about how time impacts the relative importance of the model's elements. In addition, there may be situations in which trust can develop with lesser degrees of any of the trustworthiness facets or propensity to trust. Hence, we apply a configurational set‐theoretic perspective to examine what combinations will be sufficient to produce the presence of trust in a direct supervisor across nascent and established relationships. We find three distinct configurations associated with trust in supervisor, which allows us to elaborate theory and provide novel insights to trust research. In particular, we find that in both nascent and established relationships, perceptions of high supervisor ability, benevolence, and integrity constitute a sufficient configuration for high trust in supervisor. In established relationships, however, there were two paths to high trust in supervisor: (i) perceptions of high supervisor ability and integrity, or (ii) perceptions of high supervisor ability and benevolence, accompanied by high propensity to trust. As such, in established relationships, perceptions of high supervisor benevolence and high propensity to trust may be substitutable with perceptions of high supervisor integrity. Copyright © 2016 John Wiley & Sons, Ltd.
Effects of biogas and raw slurries on grass growth and soil microbial indices
Authors: Wentzel Stefanie , Joergensen Rainer Georg
Published: February 2016

Biogas slurry is increasingly used as fertilizer. Earlier research was focused on plant growth and soil chemical properties, with only little information available regarding the effects of biogas slurry on soil and root microbial indices. For this reason, a 70 d pot experiment was conducted in which biogas and raw slurries obtained from six biodynamic farms were added to a soil. Italian ryegrass (Lolium multiflorum Lam.) was cultivated to investigate the effects on plant yield, N uptake (two harvests), soil microbial biomass, soil fungi, and root‐colonizing microorganisms. Biogas slurries increased the mean total above‐ground plant biomass by 66% and raw slurries by 35% in comparison to the control. The mean plant N‐uptake increased under biogas and raw slurry application by 166% and 65%, respectively, compared with the unfertilized pots. The effects of biogas and raw slurry application on soil microbial indices were similar except for the lower fungal biomass after biogas slurry amendment. In contrast to biogas slurries, the raw slurries significantly increased microbial biomass C and N by roughly 25% in comparison to the control. The application of biogas slurries significantly decreased the soil ergosterol content in comparison with raw slurry and control treatment, leading to a significantly lower ergosterol : microbial biomass C ratio. In the roots, biogas and raw slurry application significantly decreased the concentrations of the amino sugars galactosamine and glucosamine by 39 and 27%, respectively, but not that of ergosterol in comparison with the control. This was most likely due to a reduced colonization with arbuscular mycorrhizal fungi in the presence of highly available plant nutrients.
Harvest date effects on aroma compounds in aged Riesling icewines
Authors: Khairallah Ramsey , Reynolds Andrew G , Bowen Amy J
Published: February 2016

Background

Riesling icewine is an important product of the Ontario wine industry. The objective of this study was to characterize concentrations in aroma compounds in aged icewines associated with three harvest dates (H1, H2, H3) using stir bar sorptive extraction–gas chromatography–mass spectrometry and to make inferences, where appropriate, with respect to their roles in potential wine quality.

Results

Delaying harvest decreased concentrations of many odorants, but increased many critical odor‐active compounds; e.g. 1‐octen‐3‐ol, ethyl benzoate, ethyl octanoate, cis‐rose oxide, and β‐ionone. H1 wines had higher concentrations of four aldehydes, three alcohols, nine esters, seven terpenes, γ‐nonalactone, p‐vinylguaiacol, β‐damascenone, and 2‐furanmethanol. However, many of these compounds, with some exceptions, have relatively high odor thresholds. Fourteen compounds were above their odor thresholds, including decanal, 1‐octen‐3‐ol, phenylethyl alcohol, four ethyl esters, cis‐rose oxide, linalool, γ‐nonalactone, p‐vinylguaiacol, ethyl cinnamate, β‐damascenone, and 1,1,6‐trimethyl‐1,2‐dihydronaphthalene. H3 wines contained higher concentrations of highly odor‐active compounds, e.g. 1‐octen‐3‐ol, cis‐rose oxide, and β‐ionone. Only phenylethyl alcohol [H3 odor activity value (OAV) = 0.33 (honey, spice, rose)] and linalool [H3 OAV = 0.92 (floral, lavender)] had H3 OAVs < 1.

Conclusions

Early harvest increased many esters and aliphatic compounds, but delayed harvest appeared to substantially increase concentrations of several highly odor‐active compounds. © 2016 Society of Chemical Industry
In vivo assessment of iron bioavailability from fortified pearl millet based weaning food
Authors: Sihag Manvesh Kumar , Sharma Vivek , Goyal Ankit , Arora Sumit , Kapila Rajeev
Published: February 2016

BACKGROUND

Iron is an essential micronutrient required for normal growth and development of the body. Infants are more vulnerable to develop iron‐deficiency anaemia due to inadequate iron supply in early stages. The objective of the study was in vivo assessment of iron bioavailability from pearl millet based weaning food fortified with iron and vitamin A, and to investigate the role of vitamin A in iron absorption in animal models.

RESULTS

Results revealed that anaemic group showed significantly (P < 0.05) higher bioavailability than that of normal rat models. Animals fed vitamin A supplemented pearl‐millet diet exhibited comparable results with a sub‐group provided commercially available weaning diet in both normal and anaemic groups, but significantly (P < 0.05) higher values for studied biological indices than that of a sub‐group provided iron fortified pearl‐millet or synthetic diet. When the anaemic rats were provided iron + vitamin A fortified diet, iron bioavailability increased and liver iron stores returned to the normal levels after 30 days, indicating a promoter role of vitamin A in intestinal iron absorption.

CONCLUSIONS

Overall, bioavailability of electrolytic iron could be improved by supplementation of vitamin A, and this mixture can be considered as a useful fortificant for pearl millet based complementary foods fortification designed to prevent iron deficiency. © 2016 Society of Chemical Industry
Coupled Orientation and Stretching of Chains in Mesoscale Models of Polydisperse Linear Polymers in Startup of Steady Shear Flow Simulations
Authors: Gooneie Ali , Schuschnigg Stephan , Holzer Clemens
Published: February 2016

Polydisperse linear polymers are studied in startup of steady shear flow simulations using dissipative particle dynamics. The results show that with an increase in polydispersity the stress overshoot declines while the steady‐state stress increases. Various physical characteristics of the systems are studied including frequency of nonbonded interactions, gyration radius data, flow alignment angles, and average bond lengths. The patterns in the data suggest higher forces are necessary to orient and stretch long chain fractions in the flow direction. Relaxation modulus data prove the broad range of relaxation mechanisms in polydisperse systems. Linear viscoelasticity theory is used to quantify the relaxation spectrum. The results indicate an increase in the longest relaxation time in systems with higher polydispersity. The steady‐state shear viscosity results show higher viscosities with an increase in polydispersity at all shear‐rates. The good agreement of the characteristic behaviors of modeled polydisperse polymers with experiments is encouraging for future work.

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Stimulation latency and comparison of cycling regimens in women using sacral neuromodulation
Authors: Cadish Lauren A. , Osann Kathryn E. , Noblett Karen L.
Published: February 2016

Aims

In this two‐part study, we sought to define how long sacral neuromodulation users with overactive bladder should trial a new setting before attributing symptoms to that setting. Subsequently, we evaluated patient preferences of variable stimulation regimens.

Methods

In the initial phase of this prospective pilot study, participants' devices were turned off and later reactivated; time to symptom recurrence and resolution were recorded. In phase two, participants trialed four settings in a masked fashion with random order. After unmasking, participants chose their preferred setting and were followed 1 year.

Results

Twelve subjects completed phase one. With the device off, the mean time to symptom recurrence was 11.25 days. Mean time to symptom regression following reactivation was 6.42 days. Combined, the 90th percentile was 15 days for symptoms to reflect the device's new setting. Among 23 women completing part two, the most popular setting at the time of unmasking was a 1‐hr on, 2‐hr off cycled setting chosen by 7 (30%) participants. According to published estimates of battery longevity, 14 (61%) participants chose a more energy‐conserving setting at the time of unmasking. The mean difference in estimated battery longevity between the chosen and baseline regimens was 14.5 months. These gains diminished in the following year with clinical changes in device settings by patients and providers.

Conclusions

Sacral neuromodulation patients should allow a 2‐week trial before attributing symptoms to a new setting. With additional information, many opt for energy‐conserving settings. A 1‐hr on, 2‐hr off regimen warrants further study. Neurourol. Urodynam. 36:486–489, 2017. © 2016 Wiley Periodicals, Inc.
Treatment of fecal retention is important in the management of overactive bladder in children
Authors: Choi You Jin , Seo Bo Seon , Lee Jun Ho , Jeong Su Jin
Published: February 2016

Aims

The investigation of fecal retention using objective and patient‐friendly tools, rather than the diagnosis of constipation, might be important in the management of overactive bladder (OAB) in children. The present study aimed to evaluate the incidence and grade of fecal retention in children with OAB and to determine the effectiveness of laxative treatment for fecal retention in the management of OAB in children.

Methods

This study included 88 children with OAB aged 5–15 years. Fecal retention was defined as type 1/2 feces (Bristol stool form scale) or a Leech score above eight points, and constipation was determined according to the ROME III criteria. Among the 88 children, 71 with fecal retention or constipation were treated with oral laxatives (polyethylene glycol 3,350/4,000 or lactulose) for 2 weeks, and the responses to the treatment were assessed.

Results

Among the 88 children, 63 (71.6%) had a Leech score above eight points as assessed by plain abdominal radiography, 52 (59.1%) had type 1/2 feces (Bristol stool form scale), 24 (27.3%) had functional constipation and only 6 (6.8%) had none of either. Among the 71 children who received laxative treatment for 2 weeks, 58 (81.7%) reported an improvement in OAB symptoms. Additionally, the number of children with a Leech score above eight points was significantly higher in the good response group than in the poor response group (P = 0.014).

Conclusion

Investigation of fecal retention with the Leech scoring system and laxative treatment might be helpful in the management of OAB in children. Neurourol. Urodynam. 36:490–494, 2017. © 2016 Wiley Periodicals, Inc.