bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunohistochemical localization of OCT2 in the cochlea of various species
Authors: Hellberg Victoria , Gahm Caroline , Liu Wei , Ehrsson Hans , Rask‐Andersen Helge , Laurell Göran
Published: April 2015

Objective

To locate the organic cation transporter 2 (OCT2) in the cochlea of three different species and to modulate the ototoxicity of cisplatin in the guinea pig by pretreatment with phenformin, having a known affinity for OCT2.

Study Design

Immunohistochemical and in vivo study.

Methods

Sections from the auditory end organs were subjected to immunohistochemical staining in order to identify OCT2 in cochlea from untreated rats, guinea pigs, and a pig. In the in vivo study, guinea pigs were given phenformin intravenously 30 minutes before cisplatin administration. Electrophysiological hearing thresholds were determined, and hair cells loss was assessed 96 hours later. The total amount of platinum in cochlear tissue was determined using mass spectrometry.

Results

Organic cation transporter 2 was found in the supporting cells and in type I spiral ganglion cells in the cochlea of all species studied. Pretreatment with phenformin did not reduce the ototoxic side effect of cisplatin. Furthermore, the concentration of platinum in the cochlea was not affected by phenformin.

Conclusions

The localization of OCT2 in the supporting cells and type I spiral ganglion cells suggests that this transport protein is not primarily involved in cisplatin uptake from the systemic circulation. We hypothesize that OCT2 transport intensifies cisplatin ototoxicity via transport mechanisms in alternate compartments of the cochlea.

Level of Evidence

N/A. Laryngoscope, 125:E320–E325, 2015
Lateral skull base Inflammatory pseudotumor: A systematic review
Authors: Spinazzi Eleonora F. , Desai Stuti V. , Fang Christina H. , Jyung Robert W. , Liu James K. , Baredes Soly , Eloy Jean Anderson
Published: April 2015

Objective

Inflammatory pseudotumor (IPT) of the lateral skull base is a rare nonneoplastic inflammatory process of unknown cause often mistaken for malignancy or infection. This systematic review aims to analyze all reported cases of lateral skull base IPT to date in order to provide insight into the management of this uncommon lesion.

Data Sources

MEDLINE/PubMed database.

Review Methods

The MEDLINE/PubMed databases were searched for articles related to lateral skull base IPT. A bibliography review of the search results was then performed for additional articles. Demographics, presentation, radiographic findings, treatment, follow‐up, and outcome were analyzed.

Results

Thirty articles describing 39 patients were reviewed. The most common presenting symptom was hearing loss (53.8%). The mastoid bone had the highest incidence of IPT (61.5%). Computed tomography (CT) was the most utilized imaging modality. The lesion appeared isointense on T1‐weighted magnetic resonance imaging (MRI) (75.0%) and hypointense on T2‐weighted MRI (62.5%). Histopathological analysis showed fibrosis (96.9%) with inflammatory cell infiltration (100.0%). Surgical resection (alone or in combination with other treatments) was the most common treatment modality (92.3%), producing the greatest number of disease‐free patients overall (96.0%). The mean follow‐up time was 21.6 months, at which point 34.4% of patients showed improvement and 31.3% were completely disease‐free.

Conclusion

This review is the most comprehensive analysis of lateral skull base IPT to date. A thorough workup including clinical exam, imaging, and biopsy is essential for diagnosis. Surgical excision is the most common and most successful treatment modality, followed by surgery with corticosteroids. Laryngoscope, 125:2593–2600, 2015
Construct validity of cadaveric temporal bones for training and assessment in mastoidectomy
Authors: Awad Zaid , Tornari Chrysostomos , Ahmed Shahanaz , Tolley Neil S.
Published: April 2015

Objective

To determine the construct validity of cadaveric temporal bones in mastoidectomy training.

Study Design

A prospective observational study.

Methods

Trainees from the North London otolaryngology training program performed step‐wise modified radical mastoidectomy on cadaveric temporal bones under faculty supervision. Performance was assessed using a validated mastoidectomy assessment tool. A longitudinal assessment of nine trainees was also carried out over two sessions separated by 12 months. The main outcomes measures were task‐specific (TS) and global skills (GS).

Results

Twenty‐six intermediate and eight novice trainees participated and were assessed by a minimum of two assessors each. Intermediate trainees performed significantly better than novices in TS and GS (P < 0.001). Performance correlated well with training level using Spearman rank correlation coefficient (rs) (TS rs 0.265 and GS rs 0.503). The number of otological procedures performed, and in particular mastoidectomies, correlated well with performance (TS rs 0.327 and GS rs 0.528). Longitudinal assessment showed significant improvement with iteration (TS P = 0.008 and GS P = 0.008). Attending otological courses also improved performance significantly (TS rs 0.345 and GS rs 0.469).

Conclusions

The cadaveric temporal bone demonstrated construct validity and can be used to detect progress in performance of otolaryngology trainees. This is a keystone in moving toward a competency‐based training system.

Level of Evidence

N/A. Laryngoscope, 125:2376–2381, 2015
Value and discriminative power of the seven‐item eustachian tube dysfunction questionnaire
Authors: Van Roeyen Shari , Van de Heyning Paul , Van Rompaey Vincent
Published: April 2015

Objectives/Hypothesis

Obstructive eustachian tube (ET) dysfunction is a common condition associated with various otologic symptoms. The current lack of a diagnostic gold standard makes diagnosis and evaluation at follow‐up difficult. The aim of the study was to determine the value and discriminative power of the seven‐item Eustachian Tube Dysfunction Questionnaire (ETDQ‐7) in patients with obstructive ET dysfunction and patulous ET.

Study design

Diagnostic test study.

Methods

The ETDQ‐7 was completed by 39 patients with obstructive ET dysfunction, eight patients with patulous ET, and 22 healthy controls. The internal consistency was evaluated using the Cronbach α coefficient. Receiver operating characteristic (ROC) was determined as an accuracy measure.

Results

The mean ETDQ‐7 total score was 9.91 in the control group, 25.77 in the patients with obstructive ET dysfunction, and 27 in the patulous ET group. The Cronbach α coefficient was 0.795 in the obstructive ET group and 0.72 in the patulous ET group, demonstrating adequate reliability. The area under the curve in ROC analysis for the obstructive ET group was 95% and 96% for the patulous ET dysfunction group, which confirms its excellent discriminant validity toward the healthy control group. However, the ETDQ‐7 cannot discriminate between obstructive ET dysfunction and patulous ET.

Conclusions

The ETDQ‐7 can be a useful disease‐specific rating scale for ET dysfunction but is unable to discriminate between patients with obstructive ET dysfunction and patulous ET.

Level of Evidence

3b Laryngoscope, 125:2553–2556, 2015
Psychological effects of dysphonia in voice professionals
Authors: Salturk Ziya , Kumral Tolgar Lutfi , Aydoğdu Imran , Arslanoğlu Ahmet , Berkiten Güler , Yildirim Güven , Uyar Yavuz
Published: April 2015

Objectives/Hypothesis

To evaluate the psychological effects of dysphonia in voice professionals compared to non–voice professionals and in both genders.

Study Design

Cross‐sectional analysis.

Methods

Forty‐eight 48 voice professionals and 52 non–voice professionals with dysphonia were included in this study. All participants underwent a complete ear, nose, and throat examination and an evaluation for pathologies that might affect vocal quality. Participants were asked to complete the Turkish versions of the Voice Handicap Index‐30 (VHI‐30), Perceived Stress Scale (PSS), and the Hospital Anxiety and Depression Scale (HADS). HADS scores were evaluated as HADS‐A (anxiety) and HADS‐D (depression). Dysphonia status was evaluated by grade, roughness, breathiness, asthenia, and strain (GRBAS) scale perceptually. The results were compared statistically.

Results

Significant differences between the two groups were evident when the VHI‐30 and PSS data were compared (P = .00001 and P = .00001, respectively). However, neither HADS score (HADS‐A and HADS‐D) differed between groups. An analysis of the scores in terms of sex revealed that females had significantly higher PSS scores (P = .006). The GRBAS scale revealed no difference between groups (P = .819, .931, .803, .655, and .803, respectively). No between‐sex differences in the VHI‐30 or HADS scores were evident

Conclusions

We found that voice professionals and females experienced more stress and were more dissatisfied with their voices.

Level of Evidence

4. Laryngoscope, 125:1908–1910, 2015
The travails of setting up a living donor liver transplant program: Experience from Pakistan and lessons learned
Authors: Dar Faisal Saud , Bhatti Abu Bakar Hafeez , Dogar Abdul‐Wahab , Zia Haseeb , Amin Sadaf , Rana Atif , Nazer Rashid , Khan Nasir Ayub , Khan Etizaz‐ud‐din , Rajput Muhammad Zameer , Salih Muhammad , Shah Najmul Hassan
Published: April 2015

Living donor liver transplantation (LDLT) is the only treatment option for patients with end‐stage liver disease (ESLD) where cadaveric donors are not available. In developing countries, the inception of LDLT programs remains a challenge. The first successful liver transplantation program in Pakistan started transplantation in 2012. The objective of this study was to report outcomes of 100 LDLT recipients in a developing country and to highlight the challenges encountered by a new LDLT program in a resource‐limited setting. We retrospectively reviewed recipients who underwent LDLT between April 2012 and August 2014. Demographics, etiology, graft characteristics, and operative variables were assessed. Outcome was assessed on the basis of morbidity and mortality. All complications of ≥ 3 on the Clavien‐Dindo grading system were included as morbidity. Estimated 1‐year survival was calculated using Kaplan‐Meier curves, and a Log‐rank test was used to determine the significance. Outcomes between the first 50 LDLTs (group 1) and latter 50 LDLTs (group 2) were also compared. Median age was 46.5 (0.5‐72) years, whereas the median MELD score was 15.5 (7‐37). The male to female ratio was 4:1. ESLD secondary to hepatitis C virus was the most common indication (73% patients). There were 52 (52%) significant (≥ grade 3) complications. The most common morbidities were bile leaks in 9 (9%) and biliary strictures in 14 (14%) patients. Overall mortality in patients who underwent LDLT for ESLD was 10.6%. Estimated 1‐year survival was 87%. Patients who underwent transplantation in the latter period had a significantly lower overall complication rate (36% versus 68%; P = 0.01). Comparable outcomes can be achieved in a new LDLT program in a developing country. Outcomes improve as experience increases. Liver Transpl 21:982‐990, 2015. © 2015 AASLD.
Slowing Down of Ring Polymer Diffusion Caused by Inter‐Ring Threading
Authors: Lee Eunsang , Kim Soree , Jung YounJoon
Published: April 2015

Diffusion of long ring polymers in a melt is much slower than the reorganization of their internal structures. While direct evidence for entanglements has not been observed in the long ring polymers unlike linear polymer melts, threading between the rings is suspected to be the main reason for slowing down of ring polymer diffusion. It is, however, difficult to define the threading configuration between two rings because the rings have no chain end. In this work, evidence for threading dynamics of ring polymers is presented by using molecular dynamics simulation and applying a novel analysis method. The simulation results are analyzed in terms of the statistics of persistence and exchange times that have proved useful in studying heterogeneous dynamics of glassy systems. It is found that the threading time of ring polymer melts increases more rapidly with the degree of polymerization than that of linear polymer melts. This indicates that threaded ring polymers cannot diffuse until an unthreading event occurs, which results in the slowing down of ring polymer diffusion.

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Size‐Controlled Fabrication of Polyaniline Microfibers Based on 3D Hydrodynamic Focusing Approach
Authors: Yoo Imsung , Song Simon , Uh Kyungchan , Lee Chan Woo , Kim Jong‐Man
Published: April 2015

Owing to the relatively high conductivity and unique redox behavior, polyaniline (PANI) has been one of the most technologically promising conducting polymers. Although various methodologies have been developed, fabrication of PANI microfibers has been a challenging task owing to the poor solubility in most organic solvents. By taking advantage of a microfluidic technology and organic soluble acid labile t‐Boc‐protected PANI (t‐Boc‐PANI) as the conducting polymer precursor, fabrication of PANI microfibers in a size‐controlled manner is possible. Introduction of a THF solution containing t‐Boc‐PANI, and dodecylbenzenesulfonic acid (DBSA) as a core flow, and water as a sheath flow into a microfluidic channel with a 3D hydrodynamic focusing effect results in crystallization of the polymer fiber. By changing the flow rate, linear PANI microfibers that range from 16.2 to 39.4 μm in diameter are readily obtained.

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Water‐Assisted Vapor Deposition of PEDOT Thin Film
Authors: Goktas Hilal , Wang Xiaoxue , Ugur Asli , Gleason Karen K.
Published: April 2015

The synthesis and characterization of poly(3,4‐ethylenedioxythiophene) (PEDOT) using water‐assisted vapor phase polymerization (VPP) and oxidative chemical vapor deposition (oCVD) are reported. For the VPP PEDOT, the oxidant, FeCl3, is sublimated onto the substrate from a heated crucible in the reactor chamber and subsequently exposed to 3,4‐ethylenedioxythiophene (EDOT) monomer and water vapor in the same reactor. The oCVD PEDOT was produced by introducing the oxidant, EDOT monomer, and water vapor simultaneously to the reactor. The enhancement of doping and crystallinity is observed in the water‐assisted oCVD thin films. The high doping level observed at UV–vis–NIR spectra for the oCVD PEDOT, suggests that water acts as a solubilizing agent for oxidant and its byproducts. Although the VPP produced PEDOT thin films are fully amorphous, their conductivities are comparable with that of the oCVD produced ones.

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SAXS Analysis of Shell Formation During Nanocapsule Synthesis via Inverse Miniemulsion Periphery RAFT Polymerization
Authors: Utama Robert H. , Dulle Martin , Förster Stephan , Stenzel Martina H. , Zetterlund Per B.
Published: April 2015

Currently available methods for synthesis of polymeric nanocapsules only offer limited control over the shell thickness, even though it is an important parameter for various applications. Furthermore, suitable methods to critically measure this parameter in a facile way are still nonexistent. Here, lab‐scale small‐angle X‐ray scattering (SAXS) is utilized to in situ measure the evolution of shell thickness during nanocapsule synthesis via inverse miniemulsion periphery reversible addition–fragmentation chain transfer (RAFT) polymerization (IMEPP). The measured shell thickness is consistent with estimates from the commonly used transmission electron microscopy (TEM) technique. Moreover, the individual thicknesses of two concentric shells comprising different polymeric materials (the outer shell formed via IMEPP chain extension of the inner shell) can be determined, thus further demonstrating the versatility of this approach.

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Development of an NMR microprobe procedure for high‐throughput environmental metabolomics of Daphnia magna
Authors: Nagato Edward G. , Lankadurai Brian P. , Soong Ronald , Simpson André J. , Simpson Myrna J.
Published: April 2015

Nuclear magnetic resonance (NMR) is the primary platform used in high‐throughput environmental metabolomics studies because its non‐selectivity is well suited for non‐targeted approaches. However, standard NMR probes may limit the use of NMR‐based metabolomics for tiny organisms because of the sample volumes required for routine metabolic profiling. Because of this, keystone ecological species, such as the water flea Daphnia magna, are not commonly studied because of the analytical challenges associated with NMR‐based approaches. Here, the use of a 1.7‐mm NMR microprobe in analyzing tissue extracts from D. magna is tested. Three different extraction procedures (D2O‐based buffer, Bligh and Dyer, and acetonitrile : methanol : water) were compared in terms of the yields and breadth of polar metabolites. The D2O buffer extraction yielded the most metabolites and resulted in the best reproducibility. Varying amounts of D. magna dry mass were extracted to optimize metabolite isolation from D. magna tissues. A ratio of 1–1.5‐mg dry mass to 40 µl of extraction solvent provided excellent signal‐to‐noise and spectral resolution using 1H NMR. The metabolite profile of a single daphnid was also investigated (approximately 0.2 mg). However, the signal‐to‐noise of the 1H NMR was considerably lower, and while feasible for select applications would likely not be appropriate for high‐throughput NMR‐based metabolomics. Two‐dimensional NMR experiments on D. magna extracts were also performed using the 1.7‐mm NMR probe to confirm 1H NMR metabolite assignments. This study provides an NMR‐based analytical framework for future metabolomics studies that use D. magna in ecological and ecotoxicity studies. Copyright © 2015 John Wiley & Sons, Ltd.
Comparison of muscle BOLD responses to arterial occlusion at 3 and 7 Tesla
Authors: Towse Theodore F. , Childs Benjamin T. , Sabin Shea A. , Bush Emily C. , Elder Christopher P. , Damon Bruce M.
Published: April 2015

Purpose

The purpose of this study was to determine the feasibility of muscle BOLD (mBOLD) imaging at 7 Tesla (T) by comparing the changes in R2* of muscle at 3 and 7T in response to a brief period of tourniquet‐induced ischemia.

Methods

Eight subjects (three male), aged 29.5 ± 6.1 years (mean ± standard deviation, SD), 167.0 ± 10.6 cm tall with a body mass of 62.0 ± 18.0 kg, participated in the study. Subjects reported to the lab on four separate occasions including a habituation session, two MRI scans, and in a subset of subjects, a session during which changes in blood flow and blood oxygenation were quantified using Doppler ultrasound (U/S) and near‐infrared spectroscopy (NIRS) respectively. For statistical comparisons between 3 and 7T, R2* rate constants were calculated as R2* = 1/T2*.

Results

The mean preocclusion R2* value was greater at 7T than at 3T (60.16 ± 2.95 vs. 35.17 ± 0.35 s−1, respectively, P < 0.001). Also, the mean ΔR2*END and ΔR2*POST values were greater for 7T than for 3T (−2.36 ± 0.25 vs. −1.24 ± 0.39 s−1, respectively, Table 1).

Conclusion

Muscle BOLD contrast at 7T is as much as six‐fold greater than at 3T. In addition to providing greater SNR and CNR, 7T mBOLD studies may offer further advantages in the form of greater sensitivity to pathological changes in the muscle microcirculation. Magn Reson Med 75:1333–1340, 2016. © 2015 Wiley Periodicals, Inc.
MPnRAGE: A technique to simultaneously acquire hundreds of differently contrasted MPRAGE images with applications to quantitative T1 mapping
Authors: Kecskemeti Steven , Samsonov Alexey , Hurley Samuel A. , Dean Douglas C. , Field Aaron , Alexander Andrew L.
Published: April 2015

Purpose

To introduce a new technique called MPnRAGE, which produces hundreds of images with different T1 contrasts and a B1 corrected T1 map.

Theory and Methods

An interleaved three‐dimensional radial k‐space trajectory with a sliding window reconstruction is used in conjunction with magnetization preparation pulses. This work modifies the SNAPSHOT‐FLASH T1 fitting equations for radial imaging with view‐sharing and develops a new rapid B1 correction procedure. MPnRAGE is demonstrated in phantoms and volunteers, including two volunteers with eight scans each and eight volunteers with two scans each. T1 values from MPnRAGE were compared with those from fast spin echo inversion recovery (FSE‐IR) in phantoms and a healthy human brain at 3 Tesla (T).

Results

The T1 fit for human white and gray matter was T1MPnRAGE = 1.00 · T1FSE‐IR + 24 ms, r2 = 0.990. Voxel‐wise coefficient of variation in T1 measurements across eight time points was between 0.02 and 0.08. Region of interest‐based T1 values were reproducible to within 2% and agree well with literature values.

Conclusion

In the same amount of time as a traditional MPRAGE exam (7.5 min), MPnRAGE was shown to produce hundreds of images with alternate T1 contrasts as well as an accurate and reproducible T1 map that is robust to B1 errors. Magn Reson Med 75:1040–1053, 2016. © 2015 Wiley Periodicals, Inc.
Instrumentation of UL‐94 test: understanding of mechanisms involved in fire retardancy of polymers
Authors: Dupretz Renaud , Fontaine Gaëlle , Duquesne Sophie , Bourbigot Serge
Published: April 2015

A quantitative approach of phenomena occurring in UL‐94 test setting up selected instrumentation was developed in this work. The instrumentation permits to measure the weight of droplets, the weight loss of the sample as well as the temperature gradients during the fire test. Three flame retardant formulations of PA6 exhibiting different modes of action (melamine cyanurate, melamine pyrophosphate, and guanidine sulfamate/melamine polyphosphate) were compared with the neat matrix and the corresponding formulations reinforced with 20 wt% glass fibers. It was shown that depending on the mode of action of the flame retardant, the heat propagation, the volatilization and the release of drops are significantly different with or without glass fibers. The measured parameters include the endothermic effect of MCA, the volatilization of guanidine sulfamate/melamine polyphosphate, the formation of an intumescent barrier with melamine pyrophosphate and the measurement ex situ of the thermal diffusivity of the drops. From this approach, the behavior of the samples and the influence of glass fibers are understood. Copyright © 2015 John Wiley & Sons, Ltd.
Ionic liquids and microwave irradiation in polymer synthesis
Authors: Tarasova Natalia , Zanin Alexey , Burdakov Kirill , Sobolev Pavel
Published: April 2015

Data on various specific aspects of the synthesis of polymeric materials under microwave irradiation and on the use of such specific class of solvents as ionic liquids as the reaction medium, are analyzed in this review. Chemistry and chemical technology should be considered as a powerful means to achieve sustainable development goals, so the characteristics of microwave‐induced processes and processes using ionic liquids have been discussed in relation to the 12 principles of green chemistry. These processes are shown to possess high resource efficiency and energy efficiency potential. Copyright © 2015 John Wiley & Sons, Ltd.
Beneficial Effects of a Point‐of‐Care Bleeding Risk Calculator on Anticoagulant Selection in the Coronary Catheterization Laboratory
Authors: Kerl Jocelyn J. , Spexarth Frank C. , Pedersen Rachel , Stone Mia , Allaqaband Suhail Q. , Schulgit James L. , Bajwa Tanvir K. , Gupta Anjan N. , DeFranco Anthony C.
Published: April 2015

Study Objectives

To estimate periprocedural bleeding risk before elective percutaneous coronary intervention (PCI) by using a point‐of‐care bleeding risk calculator and to document changes in anticoagulant use and bleeding complications after implementation of use of this calculator.

Design

Prospective observational pilot study with a historical control cohort.

Setting

Tertiary care medical center.

Patients

The pilot cohort consisted of 100 patients undergoing ad hoc PCI during elective cardiac catheterization procedures between January and May 2013, whose bleeding risk and accompanying PCI anticoagulant recommendations were determined by the use of a pre‐PCI point‐of‐care bleeding risk calculator. The historical control cohort consisted of all patients who underwent elective PCI at the same facility between April 1, 2011, and March 31, 2012, before implementation of use of the bleeding risk calculator.

Measurements and Main Results

The pre‐PCI bleeding risk calculator distinguished patients in the pilot cohort as high risk (score 12 or higher) or low risk (lower than 12) for bleeding after a PCI procedure. The primary outcome was bivalirudin use in the pilot cohort compared with its use in the historical control cohort. Implementation of the bleeding risk calculator significantly decreased bivalirudin use compared with bivalirudin use in the historical control cohort (87% in the control cohort vs 60% in the pilot cohort, p<0.01). Bivalirudin use remained high in patients at high bleeding risk (82.2% in the pilot cohort vs 87.4% in the control cohort, p=0.3) and its use was decreased in patients at low bleeding risk (41.8% in the pilot cohort vs 87.1% in the control cohort, p<0.01). The incidence of bleeding complications in the pilot cohort was comparable with that in the control cohort (1% vs. 0.4%, p=0.37), although this pilot study was underpowered to potentially detect a significant change in the incidence of bleeding complications.

Conclusion

A simple bleeding risk calculator can substantially reduce overall bivalirudin use by specifically decreasing its use among patients at low bleeding risk while maintaining its use among patients at high bleeding risk. The incidence of bleeding complications remained unchanged despite decreasing bivalirudin use among patients undergoing elective coronary catheterization who were at low risk for bleeding.
Autoinduction of Voriconazole Metabolism in a Child with Invasive Pulmonary Aspergillosis
Authors: Hsu Alice Jenh , Dabb Alix , Arav‐Boger Ravit
Published: April 2015

Inter‐ and intra‐patient variability in voriconazole pharmacokinetics has been described in children as the result of age‐specific differences in hepatic metabolism, saturable nonlinear pharmacokinetics, CYP450 2C19 polymorphisms, decreased bioavailability compared with adults, and drug–drug interactions. We introduce dose‐dependent autoinduction of metabolism as another cause for altered voriconazole pharmacokinetics in children and summarize previously published literature on this phenomenon. A 10‐year‐old girl with severe aplastic anemia developed invasive pulmonary aspergillosis after high‐dose cyclophosphamide therapy and required high doses of voriconazole for longer than 2 months. She initially achieved a therapeutic trough of 1.4 μg/ml on voriconazole 11 mg/kg/dose orally every 12 hours but required dose escalations to 9.3 mg/kg/dose orally every 8 hours to maintain a trough above 1 μg/ml. Because there were no changes in concomitant medications, route of administration, adherence, or oral intake, we conclude that the only plausible explanation for the precipitous drop in voriconazole troughs was autoinduction of metabolism, a phenomenon previously reported in adults receiving higher than usual doses or prolonged courses (longer than 2 months). These data highlight the need for continued therapeutic drug monitoring of voriconazole after initial therapeutic troughs are achieved because autoinduction of metabolism can lead to significant declines in subsequent voriconazole troughs, potentially leading to treatment failure.
Rectal Propranolol Controls Paroxysmal Sympathetic Hyperactivity: A Case Report
Authors: May Casey C. , Oyler Douglas R. , Parli Sara E. , Talley Cynthia L.
Published: April 2015

Paroxysmal sympathetic hyperactivity (PSH) affects approximately 10% of survivors of acquired brain injury and is associated with substantial morbidity. The most effective maintenance therapies include oral β‐blockers and α‐2 antagonists. We report the use of rectal propranolol for symptomatic control of PSH in a critically ill patient with an altered gastrointestinal tract for whom oral intake was contraindicated. A 15‐year‐old Caucasian male with no past medical history was admitted status post all‐terrain vehicle rollover with multiple intra‐abdominal injuries. On hospital day 40, the patient experienced cardiac arrest with a subsequent anoxic brain injury, which was complicated by the development of PSH on post‐arrest day 1. Because of his altered gastrointestinal tract, he was symptomatically managed with propranolol 40 mg per rectum every 6 hours in the form of specially prepared suppositories, intravenously infused morphine and dexmedetomidine, and a transdermal clonidine patch. The patient improved clinically during this treatment and was transferred to a rehabilitation facility. This is the first case report to describe successful use of propranolol suppositories in a clinical environment. This case supports the use of propranolol suppositories as a potential alternative route when oral administration is not possible.
Approach to Addressing Missing Data for Electronic Medical Records and Pharmacy Claims Data Research
Authors: Bounthavong Mark , Watanabe Jonathan H. , Sullivan Kevin M.
Published: April 2015

Objective

The complete capture of all values for each variable of interest in pharmacy research studies remains aspirational. The absence of these possibly influential values is a common problem for pharmacist investigators. Failure to account for missing data may translate to biased study findings and conclusions. Our goal in this analysis was to apply validated statistical methods for missing data to a previously analyzed data set and compare results when missing data methods were implemented versus standard analytics that ignore missing data effects.

Design

Using data from a retrospective cohort study, the statistical method of multiple imputation was used to provide regression‐based estimates of the missing values to improve available data usable for study outcomes measurement. These findings were then contrasted with a complete‐case analysis that restricted estimation to subjects in the cohort that had no missing values. Odds ratios were compared to assess differences in findings of the analyses. A nonadjusted regression analysis (“crude analysis”) was also performed as a reference for potential bias.

Setting

Veterans Integrated Systems Network that includes VA facilities in the Southern California and Nevada regions.

Patients

New statin users between November 30, 2006, and December 2, 2007, with a diagnosis of dyslipidemia.

Main outcome measure

We compared the odds ratios (ORs) and 95% confidence intervals (CIs) for the crude, complete‐case, and multiple imputation analyses for the end points of a 25% or greater reduction in atherogenic lipids.

Results

Data were missing for 21.5% of identified patients (1665 subjects of 7739). Regression model results were similar for the crude, complete‐case, and multiple imputation analyses with overlap of 95% confidence limits at each end point. The crude, complete‐case, and multiple imputation ORs (95% CIs) for a 25% or greater reduction in low‐density lipoprotein cholesterol were 3.5 (95% CI 3.1–3.9), 4.3 (95% CI 3.8–4.9), and 4.1 (95% CI 3.7–4.6), respectively. The crude, complete‐case, and multiple imputation ORs (95% CIs) for a 25% or greater reduction in non–high‐density lipoprotein cholesterol were 3.5 (95% CI 3.1–3.9), 4.5 (95% CI 4.0–5.2), and 4.4 (95% CI 3.9–4.9), respectively. The crude, complete‐case, and multiple imputation ORs (95% CIs) for 25% or greater reduction in TGs were 3.1 (95% CI 2.8–3.6), 4.0 (95% CI 3.5–4.6), and 4.1 (95% CI 3.6–4.6), respectively.

Conclusion

The use of the multiple imputation method to account for missing data did not alter conclusions based on a complete‐case analysis. Given the frequency of missing data in research using electronic health records and pharmacy claims data, multiple imputation may play an important role in the validation of study findings.
Combination Therapy with Monoamine Oxidase Inhibitors and Other Antidepressants or Stimulants: Strategies for the Management of Treatment‐Resistant Depression
Authors: Thomas Samantha J. , Shin Mirae , McInnis Melvin G. , Bostwick Jolene R.
Published: April 2015

Treatment‐resistant depression (TRD) is a major health concern. More than 40% of patients treated for major depressive disorder with an appropriate antidepressant dose for an adequate duration fail to respond. Further, approximately half of adults with major depressive disorder fail to achieve sustained remission despite various medication trials. The utilization of monoamine oxidase inhibitors (MAOIs) for the treatment of depression in clinical practice today is low due to their widely known adverse effects, some of which may be life threatening, and the risk for dietary and drug interactions. For these reasons, MAOIs are not recommended to be prescribed along with other antidepressants or certain prescription or nonprescription drugs. Pharmacologic options are limited for individuals with TRD, however, and there is a paucity of data on the efficacy of MAOIs in combination with other antidepressants for the management of TRD. We performed a search of the PubMed database (inception through January 25, 2015) to identify cases that illustrate the potential utility, as well as risks, of combination treatment with MAOIs and other antidepressants for the management of TRD; 18 articles met the criteria for our search. In addition, we performed a retrospective case series by reviewing the medical records of 29 adults treated for depression with an MAOI plus another psychotropic agent (an antidepressant or stimulant medication) between 2003 and 2012 at a large Midwestern teaching hospital. We compared the findings of the published experience with our local experience to allow for more informed decisions regarding pharmacotherapy in patients with TRD. We separated the local experience into two groups: 15 cases with the selective MAO type B inhibitor selegiline combined with medications presumed to increase the risk of serotonin syndrome and 14 cases with nonselective MAOIs (phenelzine and tranylcypromine) combined with other contraindicated medications. Although risks of combination treatment certainly exist with selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, or clomipramine, the current literature supports cautious use of combining MAOIs with other antidepressants in patients with TRD who have failed multiple treatment modalities. In addition, the data from the 29 patients receiving combination therapy with an MAOI and another antidepressant or stimulant medication revealed that 21% improved significantly, with no complications. This case series and literature review suggest that when used under close supervision and under the care of an experienced clinician in psychiatry, combination therapy may be a consideration for the management of TRD in patients not responding to monotherapy or other combinations of antidepressants.
Clinical Implications of Vancomycin Heteroresistant and Intermediately Susceptible Staphylococcus aureus
Authors: Gomes Diane M. , Ward Kristina E. , LaPlante Kerry L.
Published: April 2015

Staphylococcus aureus (S. aureus) has proven to be a major pathogen with the emergence of methicillin‐resistant S. aureus (MRSA) infections and recently with heteroresistant vancomycin‐intermediate S. aureus (hVISA) and vancomycin‐intermediate S. aureus (VISA) infections. Although vancomycin is traditionally a first‐line and relatively effective antibiotic, its continued use is under question because reports of heteroresistance in S. aureus isolates are increasing. Both hVISA and VISA infections are associated with complicated clinical courses and treatment failures. The prevalence, mechanism of resistance, clinical significance, and laboratory detection of hVISA and VISA infections are not conclusive, making it difficult to apply research findings to clinical situations. We provide an evidence‐based review of S. aureus isolates expressing heterogenic and reduced susceptibility to vancomycin.
Nationwide Evaluation of Day‐to‐Day Clinical Pharmacists’ Interventions in German Hospitals
Authors: Langebrake Claudia , Ihbe‐Heffinger Angela , Leichenberg Katja , Kaden Sandra , Kunkel Mareike , Lueb Michael , Hilgarth Heike , Hohmann Carina
Published: April 2015

Study Objective

To describe and evaluate the extent and diversity of nationwide data from clinical pharmacists’ interventions (PIs) in German hospitals.

Design

Retrospective analysis.

Data Source

The ADKA‐DokuPIK German database, a national anonymous self‐reported Internet‐based documentation system for routine PIs as well as for medication errors reported by German hospital pharmacists.

Measurements and Main Results

Data sets from ADKA‐DokuPIK entered between January 2009 and December 2012 were analyzed descriptively. A total of 27,610 PIs were entered, mainly by ward‐based clinical pharmacists (82.5%). Most of the PIs were performed on surgical wards (37.8%), followed by anesthesiology/intensive care unit/intermediate care unit and internal medicine. The most prevalent therapeutic subgroup that was the trigger for the PIs was antibacterials for systemic use (13.9%), followed by antithrombotic agents, analgesics, drugs for acid‐related disorders, and agents acting on the renin‐angiotensin system. About a quarter of interventions (23.4%) were performed due to inappropriate use of drugs, followed by use of a wrong dose or administration interval (22.1%), resulting in the most frequently taken actions of change of dose, change of drug, and drug stopped/paused (withheld). Altogether, the implementation rate of the PIs was 85.5%. Underlying medication errors were predominantly classified as “error, no harm” according to the National Coordinating Council for Medication Error Reporting and Prevention.

Conclusion

For the first time in a European country, our findings show the scope of clinical pharmacist involvement in patient care in daily clinical practice and demonstrate the usefulness and importance of their proactive interventions in the prevention of hazards and risks for hospital inpatients.
A new route to atactic polypropylene: The second life of premetallocene homogeneous polymerization catalyst
Authors: Kissin Yury V. , Rishina Laura A. , Lalayan Svetlana S. , Krasheninnikov Vadim G.
Published: April 2015

Amorphous atactic polypropylene (PP) with an average molecular weight of 50,000–100,000 is produced by polymerizing propylene with a ternary Ti(Oiso‐Pr)4 ‐ AlEt2Cl/MgBu2 catalyst at 30–50 °С. Main advantages of this catalyst compared with other catalysts capable of nearly exclusively producing atactic PP (such as some heterogeneous Ziegler‐Natta, metallocene and postmetallocene catalysts) are high activity, low cost and the ease of use: the catalyst is prepared in situ from three commercially available compounds readily soluble in aliphatic and aromatic hydrocarbons. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 2124–2131
Pediatric Pulmonology year in review 2014: Part 1
Authors: Noah Terry L. , Yilmaz Ozge , Nicolai Thomas , Birnkrant David , Praud Jean‐Paul
Published: April 2015

Our discipline and our journal cover an extremely broad range of research and scholarly topics related to children's respiratory disorders. To better meet the needs of our readership for updated perspectives on the rapidly expanding knowledge in our field, we here summarize the past year's publications in our major topic areas, as well as selected publications in these areas from the core clinical journal literature outside our own pages. Pediatr Pulmonol. 2015; 50:621–629. © 2015 Wiley Periodicals, Inc.
Interplay of strain and interdiffusion in Heusler alloy bilayers
Authors: Dutta Biswanath , Hickel Tilmann , Neugebauer Jörg , Behler Christian , Fähler Sebastian , Behler Anna , Waske Anja , Teichert Niclas , Schmalhorst Jan‐Michael , Hütten Andreas
Published: April 2015

Combining conventional and inverse magnetocaloric materials promises to enhance solid state refrigeration. As a first step here we present epitaxial Ni–Mn–Ga/Ni–Mn–Sn bilayer films. We examine the dependence of the lateral and normal lattice constants on the deposition sequence by combining experimental and ab initio techniques. Structural properties are determined with X‐ray diffraction as well as highresolution transmission electron microscopy, while ab initio calculations explain the interplay of strain, local relaxations and the interdiffusion of atoms. The latter is confirmed by Auger electron spectroscopy and is expected to have a noticeable impact on the functional properties of the Heusler materials. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
The Potential for Plant Derivatives against Acrylamide Neurotoxicity
Authors: Adewale O. O. , Brimson J. M. , Odunola O. A. , Gbadegesin M. A. , Owumi S. E. , Isidoro C. , Tencomnao T.
Published: April 2015

Certain industrial chemicals and food contaminants have been demonstrated to possess neurotoxic activity and have been suspected to cause brain‐related disorders in humans. Acrylamide (ACR), a confirmed neurotoxicant, can be found in trace amount in commonly consumed human aliments as a result of food processing or cooking. This discovery aroused a great concern in the public, and increasing efforts are continuously geared towards the resolution of this serious threat. The broad chemical diversity of plants may offer the resources for novel antidotes against neurotoxicants. With the goal of attenuating neurotoxicity of ACR, several plants extracts or derivatives have been employed. This review presents the plants and their derivatives that have been shown most active against ACR‐induced neurotoxicity, with a focus on their origin, pharmacological activity, and antidote effects. Copyright © 2015 John Wiley & Sons, Ltd.
Degradation‐shock‐based Reliability Models for Fault‐tolerant Systems
Authors: Liu Zhenyu , Ma Xiaobing , Shen Lijuan , Zhao Yu
Published: April 2015

Reliability modeling of fault‐tolerant systems subject to shocks and natural degradation is important yet difficult for engineers, because the two external stressors are often positively correlated. Motivated by the fact that most radiation‐induced failures are contributed from these two external stressors, a degradation‐shock‐based approach is proposed to model the failure process. The proposed model accommodates two kinds of failure modes: hard failure caused by shocks and soft failure caused by degradation. We consider a generalized m–δ shock model for systems with fault‐tolerant design: failure occurs if the time lag between m sequential shocks is less than δ hours or degradation crosses a critical threshold. An example concerning memory chips used in space is presented to demonstrate the applicability of the proposed model. Copyright © 2015 John Wiley & Sons, Ltd.
The Performance of the Multivariate Adaptive Exponentially Weighted Moving Average Control Chart with Estimated Parameters
Authors: Aly Aya A. , Mahmoud Mahmoud A. , Hamed Ramadan
Published: April 2015

The multivariate adaptive exponentially weighted moving average control chart (MAEWMA) can detect shifts of different sizes while diminishing the inertia problem to a large extent. Although it has several advantages compared to various multivariate charts, previous literature has not considered its performance when the parameters are estimated. In this study, the performance of the MAEWMA chart with estimated parameters is studied while considering the practitioner‐to‐practitioner variation. This kind of variation occurs due to using different Phase I samples by different practitioners in estimating the unknown parameters. The simulation results in this paper show that estimating the parameters results in extensively excessive false alarms and as a result a large number of Phase I samples is needed to achieve the desired in‐control performance. Using small number of Phase I samples in estimating the parameters may result in an in‐control ARL distribution that almost completely lies below the desired value. To handle this problem, we strongly recommend the use of a bootstrap‐based algorithm to adjust the control limit of the MAEWMA chart. This algorithm enables practitioners to achieve, with a certain probability, an in‐control ARL that is greater than or equal to the desired value while using the available number of Phase I samples. Copyright © 2015 John Wiley & Sons, Ltd.
Combining field observations and laboratory experiments to assess the ecological preferences ofTanymastix stagnalis(L., 1758) (Crustacea, Branchiopoda) in Mediterranean temporary ponds
Authors: Olmo Carla , Fandos Déborah , Armengol Xavier , Ortells Raquel
Published: April 2015

Malladas de El Saler is a mosaic of dune slacks scattered along a coastal sand bar in the Mediterranean region. Active populations of the fairy shrimpT. stagnalisare exclusively present in one of these ponds. We combined field observations and laboratory experiments to find the ecological requirements ofT. stagnalisthat determine this habitat exclusiveness and the possibility of future establishment in nearby ponds. Conductivity revealed as a determinant ecological constraint. In the field, the species was restricted to conductivity levels below 1.28 mS cm−1and in experimental microcosms, hatchability, survival and reproductive potential were detrimental from 2.9 mS cm−1. The observation of life history characteristics from the experimental individuals confirmed the importance of the unpredictable character of Mediterranean temporary ponds in shaping life history strategies, as they hatched early, matured rapidly and produced a high number of cysts. We discuss the essential steps during colonization that may explain the presence or absence in our ponds, and revealed a harsh future for the species if the current conditions of habitat deterioration persist. We suggest several conservation measures, including a cyst bank storage or/and adult translocations to nearby suitable ponds. These measures will ensure (1) the preservation of genetic diversity and (2) healthy metapopulation dynamics with recolonization rates compensating for local extinctions.
Improvement of Palm Oil Biodiesel Filterability by Adsorption Methods
Authors: Plata Vladimir , Haagenson Darrin , Dağdelen Ayhan , Wiesenborn Dennis , Kafarov Viatcheslav
Published: April 2015

Palm oil biodiesel (POB) is characterized by a very high cold soak filtration time (CSFT), which places the acceptability of this biofuel at risk. Therefore, the effect of four adsorbents, namely diatomaceous earth, natural silicate (NS), neutral bleaching earth (NBE), and acid activated bleaching earth (AABE), at two levels of addition (1 and 5 wt%) or two temperatures (25 and 110 °C) on the precipitate content and CSFT of POB was investigated. The impact on total glycerin content, moisture content, and oxidative stability was also examined. All treatments significantly decreased the precipitate content, total glycerin content, and moisture content, but only treatments with NS, NBE, and AABE at 5 wt% and 25 °C achieved acceptable filterability. The OSI value was also decreased; however, it remained above the ASTM limit. Operational conditions of treatment with AABE were further optimized in a two‐factor, five‐level center composite design. The combination of 0.65 wt% AABE and 10 min at 25 °C decreased CSFT to below the ASTM limit. Lower adsorbent concentrations could be effective down to 0.44 wt%, given a corresponding increase in the contact time up to 30 min.