bluuebunny/crossref_metadata_2025 huggingface dataset:
Ortho‐carboxylate Effects in Copper‐mediated Nucleophilic Substitution of Halothiophenecarboxylic Acids and Halobenzoic Acids with Sodium Bisulphite
Authors: Ramaswamy Govindarajan K. , Mohanasundaram Thanigaiarasu , Velayutham Murugesan , Kuppuswamy Balasubramanian K.
Published: December 2011

Ortho‐carboxylate effects in Ullmann type nucleophilic substitution reactions were found to be much more pronounced as compared to those of other substituent and steric factors. In this study, we propose an ortho halogen assisted intramolecular oxidative addition‐reductive elimination mechanism that fits our experimental observations. Experimental data has been generated with halothiophenecarboxylic acids and halobenzoic acids by performing copper‐mediated nucleophilic substitution with scant referred sodium bisulphite as nucleophile under aqueous conditions. The novel mechanism was used to establish a new and improved process for preparation of monopotassium salts of 3‐sulphothiophene‐2‐carboxylic acid, 2‐sulphobenzoic acid, and 5‐sulphothiophene‐2‐carboxylic acid. These monopotassium salts are critical intermediates and building blocks in the preparation of several therapeutically valuable drugs. The differences in reactivity between the halogens, chlorine and bromine was utilized to prepare aryl ethers including 2‐acetyl‐3‐phenoxythiophene and 2‐acetyl‐3‐(m‐tolyloxy)thiophene that have not been reported in literature so far.
Sterols from the Stems of Momordica charantia
Authors: Liao Yun‐Wen , Chen Chiy‐Rong , Hsu Jue‐Liang , Cheng Hsueh‐Ling , Shih Wen‐Ling , Kuo Yueh‐Hsiung , Huang Tzou‐Chi , Chang Chi‐I
Published: December 2011

A new sterol, 5α,6α‐epoxy‐3β‐hydroxy‐(22E,24R)‐ergosta‐8,22‐dien‐7‐one (1), together with eight known sterols, 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7α‐diol (2), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8,22‐diene‐3β,7β‐diol (3), 5α,6α‐epoxy‐(22E,24R)‐ergosta‐8(14),22‐diene‐3β,7α‐diol (4), 3β‐hydroxy‐(22E,24R)‐ergosta‐5,8,22‐trien‐7‐one (5), ergosterol peroxide (6), clerosterol (7), decortinol (8), and decortinone (9), were isolated from the stems of Momordica charantia. Their structures were elucidated by mean of extensive spectroscopic methods, including 1H, 13C, 2D‐NMR and HR‐EI‐MS, as well as comparison with the literature data. Compounds 1, 4, 5, 8, and 91 were not cytotoxic against the SK‐Hep 1 cell line.
An Easy and Efficient Synthesis of Bisindolylmethanes and Tetraindolylmethane Tröger's Base Catatlyzed by AgBF4
Authors: Shaikh Ajam C. , Chen Chinpiao
Published: December 2011

This work presents a highly efficient and simple method for the synthesis of bisindolylmethanes, catalyzed by AgBF4, with excellent yields. Various substituted aldehydes and ketones with indole under this reaction condition is elucidated. This reaction occurs efficiently under mild reaction conditions, such as are applied with methoxy or furfural, which commonly undergoes cleavage under strongly acidic reaction conditions. The presented approach was suitable for the synthesis of complex systems, such as tetraindolylmethane Tröger's Base.
The Isolation and Determination of Sulforaphane from Broccoli Tissues by Reverse Phase‐High Performance Liquid Chromatography
Authors: Azizi Naser Seyed , Amiri‐Besheli Behnam , Sharifi‐Mehr Salman
Published: December 2011

Sulforaphane is a cognate isothiocyanate of glucoraphanin, released by degradation of glucosinolate through myrosinase enzyme, when Brassica tissues are crushed or chewed. C8 analytical column and mixture of water/acetonitrile 65/35 (ν/ν) as mobile phase were used to separate sulforaphane in broccoli tissues (e.g., 7‐day‐seedling, seed, floret and leave). Confirmation of sulforaphane in crude extract of broccoli tissues was monitored using gas chromatography‐mass spectroscopy (GC‐MS). The highest amount of sulforaphane (1216 μg/g dry weight) found in 7‐day‐seedling. This method is suitable for routine screening of plant materials and proposes a low cost and robust technique for the analysis of sulforaphane.
Direct Electrochemistry and Electrocatalysis of Myoglobin with Ionic Liquid through Multilayers Film on Carbon Ionic Liquid Electrode
Authors: Ruan Chengxiang , Lou Jin , Wang Yan , Guo Yaqing , Gao Weimin , Sun Wei
Published: December 2011

Multilayers of myoglobin (Mb) with ionic liquid 1‐ethyl‐3‐methylimidazolium tetrafluoroborate ([EMIM]BF4) was assembled on carbon ionic liquid electrode (CILE) based on the electrostatic attraction between the negatively charged Mb and the positively charged imidazolium ion of IL. The CILE was fabricated with 1‐ethyl‐3‐methylimidazolium ethylsulfate ([EMIM]EtOSO3) as the modifier, which exhibited imidazolium ion on the electrode surface. Then Mb molecules were assembled on the surface of CILE step‐by‐step to get a {IL/Mb}n multilayer film modified electrode. UV‐Vis adsorption and FT‐IR spectra indicated that Mb remained its native structure in the IL matrix. In deaerated phosphate buffer solution (pH 7.0) a pair of well‐defined quasi‐reversible redox peaks appeared with the apparent formal potential (E0′) as ‐0.212 V (vs. SCE), which was the characteristic of Mb heme Fe(III)/Fe(II) redox couples. The results indicated that the direct electron transfer of Mb was realized on the modified electrode. The {IL/Mb}n/CILE displayed excellent electrocatalytic ability to the trichloroacetic acid reduction in the concentration range from 2.0 to 22.0 mmol/L with the detection limit of 0.6 mmol/L (3σ). The proposed method provides a new platform to fabricate the third generation biosensor based on the self‐assembly of redox protein with ILs.
Regular Graphs, Eigenvalues and Regular Factors
Authors: Lu Hongliang
Published: December 2011

In this article, we obtain a sufficient condition for the existence of regular factors in a regular graph in terms of its third largest eigenvalue. We also determine all values of k such that every r‐regular graph with the third largest eigenvalue at most has a k‐factor.
Novel synthesis of 1,2,4‐triazolophanes and 1,3,4‐oxadiazolophanes: A dieckmann condensation approach
Authors: Chande Madhukar S. , Sajithkumar C. , Mondkar Hemant S. , Barve Pravin A. , Diwan Sachin
Published: December 2011

The Dieckmann condensation has been used for the first time for the syntheses of novel 1,2,4‐triazolophanes and 1,3,4‐oxadiazolophanes. The bis‐1,3,4‐oxadiazol‐2‐thiols1aand1bwere reacted with ethyl bromoacetate to give the diesters2aand2b. Diesters2aand2bwere treated under dry conditions with sodium methoxide in methanol to afford desired symmetrical 1,3,4‐oxadiazolophanes3aand3b. Similarly, diesters of macrocycle precursors containing 1,2,4‐triazole moiety, that is,6a,6b,10,13a,13b, and13cwere synthesized from5a,5b,9,12a,12b, and12c, respectively. Dieckmann condensation of these diesters afforded symmetrical ketones7a,7b,11,14a,14b, and14c. Extrusion of CO2was observed afterin situhydrolysis of the conventional Dieckmann product during neutralization by dilute mineral acids to afford highly symmetrical ketone in good yields. Further, the ketones14a,14b, and14cwere converted into their respective thiones by the reaction with Lawesson's reagent. All the products were synthesized with good yields, and structures were confirmed by various spectroscopic tools and elemental analyses. J. Heterocyclic Chem.,, (2012).
Enhancing concentration and mass sensitivities for liquid chromatography trace analysis of clopyralid in drinking water
Authors: Gu Binghe , Meldrum Brian , McCabe Terry , Phillips Scott
Published: December 2011

A theoretical treatment was developed and validated that relates analyte concentration and mass sensitivities to injection volume, retention factor, particle diameter, column length, column inner diameter and detection wavelength in liquid chromatography, and sample volume and extracted volume in solid‐phase extraction (SPE). The principles were applied to improve sensitivity for trace analysis of clopyralid in drinking water. It was demonstrated that a concentration limit of detection of 0.02 ppb (μg/L) for clopyralid could be achieved with the use of simple UV detection and 100 mL of a spiked drinking water sample. This enabled reliable quantitation of clopyralid at the targeted 0.1 ppb level. Using a buffered solution as the elution solvent (potassium acetate buffer, pH 4.5, containing 10% of methanol) in the SPE procedures was found superior to using 100% methanol, as it provided better extraction recovery (70–90%) and precision (5% for a concentration at 0.1 ppb level). In addition, the eluted sample was in a weaker solvent than the mobile phase, permitting the direct injection of the extracted sample, which enabled a faster cycle time of the overall analysis. Excluding the preparation of calibration standards, the analysis of a single sample, including acidification, extraction, elution and LC run, could be completed in 1 h. The method was used successfully for the determination of clopyralid in over 200 clopyralid monoethanolamine‐fortified drinking water samples, which were treated with various water treatment resins.
Tracheotomy outcomes and complications: A national perspective
Authors: Shah Rahul K. , Lander Lina , Berry Jay G. , Nussenbaum Brian , Merati Albert , Roberson David W.
Published: December 2011

Objectives/Hypothesis:

To provide national level data on frequency of tracheotomy and complication rate and in‐hospital mortality following tracheotomy.

Study Design:

Retrospective cohort study.

Methods:

Retrospective cohort study using a public national database, the Nationwide Inpatient Sample, 2006.

Results:

There were 113,653 tracheotomies performed in patients 18 years or older in 2006. The overall complication rate was 3.2%, and the in‐hospital mortality rate was 19.2%. The data suggest that in‐hospital mortality is usually due to the underlying illness rather than the tracheotomy. Mortality was higher in patients older than 50 years, those with cardiac conditions, particularly congestive heart failure, those with public insurance, and patients in Northeast hospitals. Patients with neurologic conditions, trauma, and upper airway infection are more likely to survive to discharge. In‐hospital mortality is slightly higher in nonteaching hospitals.

Conclusions:

This database study determined baseline data for the rate of complications (3.2%) for patients undergoing tracheotomy; it showed that only 80% of adult patients who underwent tracheotomy in the United States survived to discharge. Patients located in the Northeast, patients more than 50 years old, and patients with cardiac conditions were at particularly high risk for mortality. This study provides normative data for these outcomes for patient counseling and planning future quality improvement initiatives in this patient population.Laryngoscope, 122:25–29, 2012
Infiltrating lymphocytes and human papillomavirus‐16–associated oropharyngeal cancer
Authors: Wansom Derrick , Light Emily , Thomas Dafydd , Worden Francis , Prince Mark , Urba Susan , Chepeha Douglas , Kumar Bhavna , Cordell Kitrina , Eisbruch Avraham , Taylor Jeremy , Moyer Jeffrey , Bradford Carol , D'Silva Nisha , Carey Thomas , McHugh Jonathan , Wolf Gregory ,   UM Head Neck SPORE Program
Published: December 2011

Objectives/Hypothesis:

Human papillomavirus‐16 (HPV‐16)–associated carcinoma of the oropharynx has a favorable prognosis. Such patients have elevated CD8+ T‐lymphocyte levels that correlate with response to chemotherapy and survival. Tumor‐infiltrating lymphocyte (TIL) subpopulations were assessed in pretreatment biopsies from a prospective patient cohort to determine if TIL subsets differed by HPV status, clinical factors, or patient outcome or correlated with peripheral blood T‐cell levels.

Study Design:

Retrospective immunological correlative study of patients entered in a prospective Phase 2 clinical trial.

Methods:

Measured were CD8, CD4, CD68, and Treg (FoxP3) lymphocytes by immunohistochemistry in a tissue microarray created from patients (n = 46) with advanced oropharyngeal cancer. Correlations with peripheral blood levels, HPV status, expression of epidermal growth factor receptor (EGFR), clinical tumor, and patient characteristics and outcome were determined. Median follow‐up was 6.6 years.

Results:

HPV‐16–positive patients had improved survival (P = .016). Degree of T‐cell infiltration did not differ by HPV status but was significantly related to disease‐specific survival (DSS) and overall survival (OS). Even after adjusting for HPV status, we found that CD8, FoxP3, and total T cells were significantly associated with DSS (P = .0236, P = .0040, and P = .0197, respectively) and OS (P = .0137, P = .0158, and P = .0115, respectively). Less T‐cell infiltration (P = .0130) and CD4 cells in particular (P = .0792) were associated with higher EGFR expression.

Conclusions:

Improved outcomes are associated with increased TILs independent of HPV status and suggest the local immune response may be more related to factors such as tumor size, EGFR expression, or performance status than HPV status. Further study of larger numbers of patients and infiltrates combined with functional analysis of individual subsets may be necessary to detect significant differences in local immunity in HPV‐16–related cancers.Laryngoscope, 122:121–127, 2012
The role of preoperative, intratympanic glucocorticoids for hearing preservation in cochlear implantation: A prospective clinical study
Authors: Rajan Gunesh P. , Kuthubutheen Jafri , Hedne Naveen , Krishnaswamy Jay
Published: December 2011

Background:

Hearing Preservation is becoming increasingly important in cochlear implantation as there is growing evidence that preserving the residual hearing, especially in the low frequencies in combination with the electric stimulation can significantly improve hearing and speech outcomes in noise. Besides the ongoing development of atraumatic implant electrodes and insertion techniques, the implementation of pharmacologic hair cell protection is thought to increase hearing preservation. This study investigates the effects of preoperative intratympanic glucocorticoid application on hearing preservation rates in cochlear implantation.

Study Design:

Prospective interventional study.

Setting:

Tertiary neurotology referral center.

Patients:

Patients undergoing cochlear implantation with measurable preoperative hearing thresholds using either a Flex soft electrode or a Flex EAS electrode depending on the degree of residual low frequency hearing.

Intervention:

Preoperative intratympanic steroid application during cochlear implantation via round window insertion.

Main Outcome Measures:

Level of hearing preservation after cochlear implantation; electrode‐ and frequency‐specific hearing preservation rates.

Results:

Preoperative hearing thresholds were comparable in the control group and the interventional Flex soft group (70.5 db ± 12.5 dB vs. 73.5 dB ± 10.5 dB, P = .27). As per selection criteria the low‐frequency hearing thresholds were significantly lower in interventional Flex EAS groups when compared to the control group. Hearing preservation was significantly better in the interventional group with no case of complete hearing loss in this group (11 dB ± 2.5 dB vs. 19.5 dB 3.5 dB, P < .05). The interventional group displayed a higher stability of hearing preservation after implantation (r = .8, P = .03). Level of hearing preservation was higher when a specific hearing preservation electrode was used (r = .85, P < .05). Hearing preservation in the low frequencies was significantly higher than in the high frequencies.

Conclusions:

Our study suggests that the additional preoperative use of intratympanic glucocorticoids improves and stabilizes hearing preservations rates in round window cochlear implantation for adults and children with residual hearing.Laryngoscope, 122:190–195, 2012
The price paid: Manipulation of otolaryngologists by the tobacco industry to obfuscate the emerging truth that smoking causes cancer
Authors: Jackler Robert K. , Samji Hussein A.
Published: December 2011

Objectives/Hypothesis:

Our objectives were to explore the multifaceted campaign by the tobacco industry to enlist otolaryngologists in support of their efforts to reassure consumers that cigarettes were safe, and to elucidate the incentives that led so many leading otolaryngologists to give testimony denying a causal linkage between tobacco use and head and neck cancer.

Study Design:

Historical analyses.

Methods:

Recent litigation has exposed for public viewing a huge trove of internal tobacco industry documents. These documents include correspondence files, internal memoranda, research solicitations, grant agreements, records of payments, marketing plans, and testimony by otolaryngologists on behalf of tobacco interests in court proceedings, before congressional committees, and at U.S. Federal Trade Commission hearings.

Results:

Evidence shows that marketing divisions of major tobacco companies systematically sought to use the authority and prestige of otolaryngologists to support their promotional efforts. Industry documents reveal widespread collaboration by leaders in the field through conducting research and giving well‐compensated testimony favorable to tobacco interests. Invariably, industry‐funded research showed tobacco in a favorable light. The industry also sought to influence otolaryngologists with free cigarettes, elegant dinners, and hospitality booths at conventions.

Conclusions:

In revealing this unfortunate period in our history, we by no means intend to diminish the memory of distinguished leaders whose tobacco involvements were certainly more acceptable by the standards of their own time. Rather, by exposing the pervasive tobacco industry manipulation of scientific research for commercial purposes we seek to encourage vigilance by contemporary researchers who might consider seeking funding from an industry that places the pursuit of profits above the well‐being of its customers.Laryngoscope, 122:75–87, 2012
Hearing results and quality of life after streptomycin/dexamethasone perfusion for meniere's disease
Authors: Shea Paul F. , Richey Phyllis A. , Wan Jim Y. , Stevens Suzanne R.
Published: December 2011

Objectives/Hypothesis:

To evaluate the hearing changes and quality‐of‐life outcomes of 393 cases of streptomycin/dexamethasone inner ear perfusion performed by the primary author on 312 ears of 299 patients with Meniere's disease between July 2002 and May 2010.

Study Design:

Retrospective chart review.

Methods:

Objective arm: A database was used to compile pretreatment and post‐treatment audiograms as well as basic demographic information, dates of treatment, number of treatments, and which ear was treated. All patients met the 1995 American Academy of Otolaryngology–Head and Neck Surgery Committee on Hearing and Equilibrium Guidelines for the diagnosis and evaluation of therapy in Meniere's disease. All patients underwent one or more 3‐day treatments consisting of daily intratympanic injections of a low‐dose streptomycin/high‐dose dexamethasone mixture plus intravenous dexamethasone. The end point for treatment was adequate control of vertigo. Subjective arm: The Meniere's Disease Outcomes Questionnaire survey was used to assess patients' quality of life after receiving streptomycin/dexamethasone inner ear perfusion. All procedures were performed by the primary author at the Shea Ear Clinic, a tertiary‐referral otology clinic and outpatient surgery center.

Results:

After a single 3‐day treatment, the average change in pure tone average was 0.89 dB (±11). The average change in word recognition score was 0.49% (±17). The average number of days from treatment to follow‐up audiogram was 94 with a range of 8 to 1,603. Clinically significant hearing loss occurred after 62 of 393 (15.7%) treatments. Severe hearing loss occurred after 20 of 393 treatments (5.0%). The percentage of ears with clinically significant hearing loss after all treatments was 56 of 312 (17.9%). A total of 215 surveys were returned from 383 patients (56.1%) to whom they were mailed. There were 90% of patients who indicated improvement in quality of life after treatment and 88% who indicated improvement in their “vertigo subscore,” a domain within the survey that focuses on vertigo control.

Conclusions:

Streptomycin/dexamethasone inner ear perfusion is as safe to the hearing of patients with Meniere's disease as other aminoglycoside regimens and provides a significant improvement in quality of life.Laryngoscope, 122:204–211, 2012
A multi‐institutional analysis of tracheotomy complications
Authors: Halum Stacey L. , Ting Jonathan Y. , Plowman Emily K. , Belafsky Peter C. , Harbarger Claude F. , Postma Gregory N. , Pitman Michael J. , LaMonica Donna , Moscatello Augustine , Khosla Sid , Cauley Christy E. , Maronian Nicole C. , Melki Sami , Wick Cameron , Sinacori John T. , White Zrria , Younes Ahmed , Ekbom Dale C. , Sardesai Maya G. , Merati Albert L.
Published: December 2011

Objectives/Hypothesis:

To define the prevalence of tracheotomy tube complications and evaluate risk factors (RFs) associated with their occurrence.

Study Design:

Multi‐institution historical cohort.

Methods:

Data regarding tracheotomy tube complications from consecutive surgeries performed across eight participating institutions between January 1, 2008 and December 31, 2009 were retrospectively collected. Patient demographics, comorbidities, physician specialty, and surgical technique were recorded and statistically analyzed to identify the incidence of surgical complications following tracheotomy and associated RFs.

Results:

The charts of 1,175 tracheotomy procedures were reviewed from eight academic institutions. Otolaryngologists performed 66.2% of the tracheotomies. Intraoperative, early (<1 week), and late complication rates were 1.4%, 5.6%, and 7.1%, respectively. Postoperative bleeding was identified as the most common early complication (2.6%), whereas airway stenosis was the most common late complication (1.7%). The use of outer flange security sutures to anchor the tracheostomy tube was negatively associated with the incidence of early complication (P < .0001). The use of large endotracheal tubes (size >7.5) and obesity were associated with the development of airway stenosis (P < .05).Twenty‐two percent of patients undergoing tracheotomy died during hospitalization.

Conclusions:

Perioperative tracheotomy complications are rare; however, the rate of death for all causes is high (22%) in this population. Obesity and the use of endotracheal tubes over 7.5 in size are major risk factors for the development of airway stenosis. Although percutaneous tracheotomy resulted in a significantly higher rate of postoperative bleeding (6.6%) than the open method (1.9%) (P < .05), the use of outer flange tracheostomy tube sutures may reduce this complication.Laryngoscope, 122:38–45, 2012
Surveillance and management practices in tracheotomy patients
Authors: Zhu Hannah , Das Preety , Brereton Jean , Roberson David , Shah Rahul K.
Published: December 2011

Objectives/Hypothesis:

To ascertain the surveillance and management practices for tracheotomy patients.

Study Design:

Survey of tracheotomy management.

Methods:

An electronically distributed 26‐question survey was distributed under the auspices of the American Academy of Otolaryngology–Head and Neck Surgery Foundation.

Results:

There were 478 responses. The mean number of years in practice was 21.2 years (standard deviation [SD], 11.0 years). Sixty‐five percent of respondents perform mainly adult tracheotomy. There is variation in surveillance patterns of immediate, postoperative, intermediate, and long‐term surveillance. On average, respondents follow a fresh tracheotomy daily for about 6 days, monthly for about 3 months, and long‐term surveillance every 4 months on average. Almost all respondents perform long‐term surveillance during routine tracheotomy changes; 61.4% perform this surveillance with an endoscope, and a minority rely on history and examination. The mean frequency of tracheotomy tube changes was 2 months (SD, 2.2 months; median, 1.1 month; range, 0.06–12 months). Two hundred sixty‐one respondents have or have used a decannulation algorithm. The vast majority, 96.2%, are comfortable with their current management practices. Over half of the respondents perceive value in a clinical practice guideline to help them with standardizing care, and 80% of respondents feel that it would assist other specialties in the care and surveillance of tracheotomy patients.

Conclusions:

There is marked variability in the surveillance and management of tracheotomy patients. There exists opportunity to improve care through standardization of surveillance and management of these patients. Laryngoscope, 122:46–50, 2012
Screening for head and neck cancer in liver transplant candidates: A review of 11 years of experience at the University of Pittsburgh
Authors: Dedhia Raj C. , Grandis Jennifer R. , Fontes Paulo A. , Johnson Jonas T. , Weissfeld Joel
Published: December 2011

Objectives/Hypothesis:

At our institution, any liver transplant candidate with a recent history of smoking combined with daily use of alcohol prior to a 6‐month sobriety period warrants formal evaluation by otolaryngology. Given the significant resource consumption and lack of evidence in support of this strategy, we sought to determine the effectiveness of these guidelines in detecting head and neck cancer.

Study Design:

Retrospective review of clinical database and patient billing records.

Methods:

Under an institutional review board‐approved protocol, a search was performed for patients seen at our institution's otolaryngology office from 1999 to 2010. This patient list was cross‐matched with the patients evaluated for transplant at the University of Pittsburgh Starzl Transplantation Institute during the same timeframe. A search for the diagnosis of head and neck squamous cell carcinoma of the head and neck (HNC) among these patients was carried out through both a National Cancer Institute‐affiliated clinical research registry and ICD‐9 codes from billing records. Otolaryngology attending physicians were also asked to recall detection of HNC upon screening of this patient population.

Results:

Of 581 patient evaluations performed by the otolaryngologist for HNC screening prior to liver transplantation from 1999 to 2009, one (0.17% of evaluations) case of HNC was detected.

Conclusions:

Given the consumption of resources required for this screening strategy and the limited yield, it appears that current screening guidelines are ineffective and need to be reconsidered.
Is otitis media with effusion almost always accompanying cleft palate in children?: The experience of 319 Asian patients
Authors: Chen Yi‐Wei , Philip Chen Kuo‐Ting , Chang Po‐Hung , Su Jen‐Liang , Huang Chi‐Che , Lee Ta‐Jen
Published: December 2011

Objectives/Hypothesis:

To evaluate the incidence of concomitant otitis media with effusion (OME) in children with cleft palate in Taiwan and the reliability of preoperative tympanometry.

Study Design:

Individual prospective cohort study.

Methods:

We included 319 patients who underwent palatoplasty for cleft palate from 2005 to 2010. All received tympanometry 1 day before surgery, and myringotomy was performed before palatoplasty. Grommet was inserted if there was OME, the amount and content of which were graded and recorded. All data, including the tympanometry results, were analyzed for statistical significance.

Results:

The incidence of OME accompanying cleft palate during palatoplasty was 71.92% in Asian patients, which was lower than in previous studies. The content of OME was serous fluid in 47.8%, mucoid in 33.1%, and mucopus in 19.1%. Type‐B tympanogram had high sensitivity (0.956) in all age groups. However, its specificity was poor in children younger than 9 months (0.375), fair in children aged 9 to 14 months (0.582), and good in children older than 14 months (0.857).

Conclusions:

The incidence of OME accompanying cleft palate has decreased in Asian patients in the past 5 years. Tympanometry is not a very reliable tool for evaluating OME in children with cleft palate younger than 14 months, especially those younger than 9 months. Meticulous examination of the middle ear during palatoplasty is necessary for making a definite diagnosis and deciding on the use of a grommet.Laryngoscope, 122:220–224, 2012
Casting defects and fatigue behaviour of ductile cast iron for wind turbine components: A comprehensive study
Authors: Shirani M. , Härkegård G.
Published: December 2011

Two types of EN‐GJS‐400‐18‐LT ductile cast iron were investigated in this research, clean baseline material in the shape of castings with different thicknesses and also defective material from a rejected wind turbine hub. P‐S‐N curves for baseline EN‐GJS‐400‐18‐LT specimens with different dimensions and from castings with different thicknesses at different load ratios were established. Geometrical size effect, technological size effects and mean stress effect on fatigue strength of baseline EN‐GJS‐400‐18‐LT were evaluated. Fatigue strength of baseline EN‐GJS‐400‐18‐LT was compared with that of defective material from the rejected hub. The effect of defects type, shape, size and position on fatigue strength of this material was evaluated. The hypothesis that the endurance observed in an S‐N test can be predicted based on the analysis of crack growth from casting defects through defect‐free ‘base’ material was tested for the analyzed defective material. 3D X‐ray computed tomography was use to detect defects in defective specimens and find the defect size distribution. The obtained defect size distribution for the defective material was used in random defect analysis to establish the scatter of fatigue life for defective specimens. Finally both safe‐life design and damage tolerant design of wind turbine castings were analyzed and compared.
Special fatigue aspects in support structures of offshore wind turbines
Authors: Schaumann P. , Lochte‐Holtgreven S. , Steppeler S.
Published: December 2011

Support structures of offshore wind turbines are exposed to high dynamic loads caused by wind, waves and operation. The support structures have to resist an extreme number of load cycles during their design life. Therefore, fatigue resistance becomes relevant for providing secure service time and economic design. As a result of growing turbine capacity and adverse offshore conditions, components which are involved in the load transfer need to be checked for fatigue in detail. This paper gives an overview of actual types of support structures, particular character of dynamic loads and fatigue resistances of specific constructional details.
Characterization of hydrogen embrittlement in automotive advanced high strength steels
Authors: Loidl M. , Kolk O. , Veith S. , Göbel T.
Published: December 2011

Hydrogen embrittlement is the limiting factor when it comes to the utilization of advanced highest strength steels in a car body frame. Steels with a tensile strength of greater than 1000 MPa are deemed to be susceptible to hydrogen induced delayed fracture and therefore are not yet widely used. To characterize the deleterious effects of hydrogen embrittlement in advanced highest strength steels the slow strain rate testing in gaseous hydrogen atmosphere is a suitable method for investigating the effect of hydrogen on the materials ductility. Additionally the hydrogen content after slow strain rate testing was measured by means of thermal desorption spectroscopy. By using this technique it is possible to differentiate between diffusible and trapped hydrogen. Diffusible hydrogen may interact with dislocations and therefore changes the fracture behaviour of metals. This was also documented by analysing the fracture surface of the tensile specimen by optical and scanning electron microscopy. The investigations yield a comprehensive view on the susceptibility towards hydrogen induced cracking and allow a comparative view among different steel grades.
Initial Financial Conditions, Unobserved Heterogeneity and the Survival of Nascent Canadian Manufacturing Firms
Authors: Huynh Kim P. , Petrunia Robert J. , Voia Marcel
Published: December 2011

The firm dynamics literature has stressed productivity, size, and age effects in firm duration. Understanding the implications of financial state has largely been unexplored because of the lack of quality data on private entrant firms. This paper investigates the role of start‐up financial conditions (debt‐to‐asset ratio) on the duration of entrant manufacturing firms using a unique administrative firm‐level database called T2LEAP. The debt‐to‐asset ratio has an economically and statistically significant effect on firm hazard after controlling for usual covariates and unobserved heterogeneity. Further, a non‐monotonic relationship between firm hazard and leverage appears. Firm hazard varies positively with leverage for firms in the top two leverage quintiles, whereas hazard rates fall with leverage in the lower quintiles. Copyright © 2011 John Wiley & Sons, Ltd.
Apathy in essential tremor, dystonia, and Parkinson's disease: A comparison with normal controls
Authors: Louis Elan D. , Huey Edward D. , Gerbin Marina , Viner Amanda S.
Published: December 2011

Background:

Apathy, defined as decreased goal‐directed activity, has been observed in Parkinson's disease. A number of cognitive/psychiatric features have been documented in essential tremor, yet we are unaware of studies of apathy.

Methods:

Using the Apathy Evaluation Scale (range = 18–72 [more apathy]), we compared 79 essential tremor cases, 20 dystonia cases, and 39 Parkinson's disease cases with 80 normal controls.

Results:

The score of the Apathy Evaluation Scale was higher in essential tremor, dystonia, and Parkinson's disease cases than controls (all P ≤ .04). Parkinson's disease cases had the highest scores. Analyses stratified by presence/absence of depressive symptoms indicated the presence of a group of apathetic but nondepressed cases.

Conclusions:

Patients with Parkinson's disease, essential tremor, and dystonia had elevated apathy scores. Features of apathy seemed to occur in these conditions independent of depressive symptoms. The mechanistic basis for the apparent increased features of apathy in essential tremor and dystonia deserves further study. © 2011 Movement Disorder Society
Reorientation of fiber orientation distributions using apodized point spread functions
Authors: Raffelt David , Tournier J‐Donald , Crozier Stuart , Connelly Alan , Salvado Olivier
Published: December 2011

Using high angular resolution diffusion‐weighted images, spherical deconvolution enables multiple white matter fiber populations to be resolved within a single voxel by computing the fiber orientation distribution (FOD). Higher order information provided by FODs could improve several methods for investigating population differences in white matter, including image registration, voxel‐based analysis, atlas‐based segmentation and labeling, and group average fiber tractography. All of these methods require spatial normalization of FODs. In this article, a novel method to reorient the FOD is presented, which is an important step required for FOD spatial normalization. The proposed method was assessed using both qualitative and quantitative experiments, with numerical simulations and in vivo human data. Results demonstrate that the proposed method improves FOD reorientation accuracy, removes undesired artefacts, and decreases computation time compared to a previous approach. The utility of the proposed method is illustrated by nonlinear FOD spatial normalization of 10 human subjects. Accurate reorientation and normalization of FODs is a critical step toward investigating white matter tissue in the context of multiple fiber orientations. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Motion correction and registration of high b‐value diffusion weighted images
Authors: Ben‐Amitay Shani , Jones Derek K. , Assaf Yaniv
Published: December 2011

It has been suggested that, high b‐value diffusion weighted MRI improves the sensitivity and specificity of these images to tissue microstructure when compared with “clinical” b‐value diffusion weighted MRI (b ≈ 1000 s/mm2). However, it suffers from poor signal to noise ratio ‐ leading to longer acquisition times and therefore more motion artifacts. Together with the orientational sensitivity of the diffusion weighted MRI signal, the contrast at different b‐values and different gradient directions is significantly different. These features of high b‐value diffusion images preclude the ability to perform conventional image‐registration‐based motion/distortion correction. Here, we suggest a framework based on both experimental data (diffusion tensor MRI) and simulations (using the composite hindered and restricted model of diffusion framework) to correct the motion induced misalignments and artifacts of high b‐value diffusion weighted MRI. This approach was evaluated using visual assessment of the registered diffusion weighted MRI and the composite hindered and restricted model of diffusion analysis results, as well as residual analysis to assess the quality of the composite hindered and restricted model of diffusion fitting. Both qualitative and quantitative results demonstrate an improvement in fitting the data to the composite hindered and restricted model of diffusion model following the suggested registration framework, thereby, addressing a long‐standing problem and making the correction of motion/distortions in data collected at high b‐values feasible for the first time. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.
Pharmacological MRI of the choroid and retina: Blood flow and BOLD responses during nitroprusside infusion
Authors: Shih Yen‐Yu I. , Li Guang , Muir Eric R. , De La Garza Bryan H. , Kiel Jeffrey W. , Duong Timothy Q.
Published: December 2011

Nitroprusside, a vasodilatory nitric oxide donor, is clinically used during vascular surgery and to lower blood pressure in acute hypertension. This article reports a novel application of blood flow (BF) and blood oxygenation level dependent (BOLD) MRI on an 11.7T scanner to image the rat chorioretinal BF and BOLD changes associated with graded nitroprusside infusion. At low doses (1 or 2 μg/kg/min), nitroprusside increased BF as expected but decreased BOLD signals, showing an intriguing BF–BOLD uncoupling. At high doses (3−5 μg/kg/min), nitroprusside decreased BF and markedly decreased BOLD signals. To our knowledge, this is the first pharmacological MRI application of the retina. This approach has potential to open up new avenues to study the drug‐related hemodynamic functions and to evaluate the effects of novel therapeutic interventions on BOLD and BF in the normal and diseased retinas. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Real‐time phase‐contrast MRI of cardiovascular blood flow using undersampled radial fast low‐angle shot and nonlinear inverse reconstruction
Authors: Joseph Arun A. , Merboldt Klaus‐Dietmar , Voit Dirk , Zhang Shuo , Uecker Martin , Lotz Joachim , Frahm Jens
Published: December 2011

Velocity‐encoded phase‐contrast MRI of cardiovascular blood flow commonly relies on electrocardiogram‐synchronized cine acquisitions of multiple heartbeats to quantitatively determine the flow of an averaged cardiac cycle. Here, we present a new method for real‐time phase‐contrast MRI that combines flow‐encoding gradients with highly undersampled radial fast low‐angle shot acquisitions and phase‐sensitive image reconstructions by regularized nonlinear inversion. Apart from calibration studies using steady and pulsatile flow, preliminary in vivo applications focused on through‐plane flow in the ascending aorta of healthy subjects. With bipolar velocity‐encoding gradients of alternating polarity that overlap the slice‐refocusing gradient, the method yields flow‐encoded images with an in‐plane resolution of 1.8 mm, section thickness of 6 mm and measuring time at 3 T of 24 ms (TR/TE = 3.44/2.76 ms; flip angle, 10º; seven radial spokes per image). Accordingly, phase‐contrast maps and corresponding velocity profiles achieve a temporal resolution of 48 ms. The evaluated peak velocities, stroke volumes, flow rates and respective variances over at least 20 consecutive heartbeats are in general agreement with literature data. Copyright © 2011 John Wiley & Sons, Ltd.
The role of tandem duplicator phenotype in tumour evolution in high‐grade serous ovarian cancer
Authors: Ng Charlotte KY , Cooke Susanna L , Howe Kevin , Newman Scott , Xian Jian , Temple Jillian , Batty Elizabeth M , Pole Jessica CM , Langdon Simon P , Edwards Paul AW , Brenton James D
Published: December 2011

High‐grade serous ovarian carcinoma (HGSOC) is characterized by genomic instability, ubiquitous TP53 loss, and frequent development of platinum resistance. Loss of homologous recombination (HR) is a mutator phenotype present in 50% of HGSOCs and confers hypersensitivity to platinum treatment. We asked which other mutator phenotypes are present in HGSOC and how they drive the emergence of platinum resistance. We performed whole‐genome paired‐end sequencing on a model of two HGSOC cases, each consisting of a pair of cell lines established before and after clinical resistance emerged, to describe their structural variants (SVs) and to infer their ancestral genomes as the SVs present within each pair. The first case (PEO1/PEO4), with HR deficiency, acquired translocations and small deletions through its early evolution, but a revertant BRCA2 mutation restoring HR function in the resistant lineage re‐stabilized its genome and reduced platinum sensitivity. The second case (PEO14/PEO23) had 216 tandem duplications and did not show evidence of HR or mismatch repair deficiency. By comparing the cell lines to the tissues from which they originated, we showed that the tandem duplicator mutator phenotype arose early in progression in vivo and persisted throughout evolution in vivo and in vitro, which may have enabled continual evolution. From the analysis of SNP array data from 454 HGSOC cases in The Cancer Genome Atlas series, we estimate that 12.8% of cases show patterns of aberrations similar to the tandem duplicator, and this phenotype is mutually exclusive with BRCA1/2 carrier mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Health‐related quality of life (HRQL) in children with sickle cell disease and thalassemia following hematopoietic stem cell transplant (HSCT)
Authors: Kelly Michael J. , Pennarola Brian W. , Rodday Angie Mae , Parsons Susan K. ,   on behalf of the Journeys to Recovery Study, the HSCT‐CHESS™ Study
Published: December 2011

Background

Little is known regarding the health‐related quality of life (HRQL) trajectory of children with sickle cell disease or thalassemia (“hemoglobinopathies”) following hematopoietic stem cell transplantation (HSCT).

Procedures

We serially evaluated the HRQL of 13 children with hemoglobinopathies who received HSCT during two prospective multi‐center studies using the Child Health Ratings Inventories (CHRIs). The HRQL scores among children with hemoglobinopathies, as reported separately by the children and their parents were compared using repeated measures models to scores of a comparison group of children receiving HSCT for malignancies or severe aplastic anemia.

Results

The sample included 13 children with hemoglobinopathies (median age: 8 years, range 5–18) and 268 children in the comparison group (median age: 11 years, range 5–18). There were similar rates of early infection, chronic graft versus host disease, and all‐cause mortality between the two groups. There was no significant difference in recovery to baseline scores for physical, emotional, and role functioning by 3 months for either group. Children with hemoglobinopathies had higher HRQL scores for physical (beta = 12, se = 5.5, P = 0.01) and baseline emotional functioning (beta = 11.6, se = 5.5, P = 0.03) than the comparison group. For all domains for both groups, parent reports demonstrated a nadir at 45 days with recovery to baseline by 3 months following transplant. Children's ratings were higher than those of their parents in both diagnostic groups.

Conclusions

Children with hemoglobinopathies had higher physical and emotional functioning scores prior to HSCT and experienced a similar pattern of recovery to their baseline functioning by 3 months post‐HSCT when compared to children receiving HSCT for acquired conditions. Pediatr Blood Cancer 2012;59:725–731. © 2011 Wiley Periodicals, Inc.
Treatment choice of immunotherapy or further chemotherapy for Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis
Authors: Shiraishi Akira , Ohga Shouichi , Doi Takehiko , Ishimura Masataka , Takimoto Tomohito , Takada Hidetoshi , Miyamoto Toshihiro , Abe Yasunobu , Hara Toshiro
Published: December 2011

Background

Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis (EBV‐HLH) leads to an aggressive and often fatal course without appropriate treatment. Etoposide therapy is crucial for the better prognosis, although it remains unknown what patients need cytotoxic agents. Since we have complied with step‐up strategy in a tertiary center, treatment outcomes were studied to search predictors for disease course.

Methods

The study enrolled 22 EBV‐HLH patients treated between 1999 and 2010 in Kyushu University. Immunotherapy, chemotherapy and stem cell transplantation (SCT) proceeded in stages unless patients attained a consecutive >21 days‐afebrile remission. Clinical and laboratory data and outcomes were retrospectively analyzed.

Results

Median age of 9 males and 13 females was 5 years (range: 9 months–41 years). Sixteen patients (73%) presented at age <15 years. Two patients remitted spontaneously, 12 attained remissions after immunotherapy, 5 after chemotherapy, and 1 after successful SCT. The remaining two patients died after chemotherapy and SCT, respectively. Median EBV load was 1 × 105 copies/ml of peripheral blood (range: 200–5 × 107). T‐cells were exclusively targeted (94%; 15/16 examined) often with EBV/T‐cell receptor clonality. EBV status indicated 19 primary infections and 3 reactivations. Either death occurred in EBV‐reactivated patients who underwent chemotherapy ± SCT. Age at primary infection in pediatric patients increased in the last 5 years. Patients having prolonged fever (P = 0.017) or high soluble CD25 levels (P = 0.017) at diagnosis were at higher risk for requiring chemotherapy assessed by multivariate analyses.

Conclusions

No cytotoxic agents were needed for >60% of EBV‐HLH patients. Early immunotherapy may modulate T‐cell activation and reduce the chance of unnecessary chemotherapy. Pediatr Blood Cancer 2012;59:265–270. © 2011 Wiley Periodicals, Inc.