bluuebunny/crossref_metadata_2025 huggingface dataset:
Residual nodal disease in patients with advanced‐stage oropharyngeal squamous cell carcinoma treated with definitive radiation therapy and posttreatment neck dissection: Association with locoregional recurrence, distant metastasis, and decreased survival
Authors: Sandulache Vlad C. , Ow Thomas J. , Daram Shiva P. , Hamilton Jackson , Skinner Heath , Bell Diana , Rosenthal David I. , Beadle Beth M. , Ang K. Kian , Kies Merrill S. , Johnson Faye M. , El‐Naggar Adel K. , Myers Jeffrey N.
Published: September 2012

Background

Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in frequency. We reviewed patients with advanced‐stage OPSCC treated with chemoradiation to assess the impact of residual neck disease on survival.

Methods

We reviewed 202 patients with OPSCC between 1990 and 2010 treated with primary chemoradiation followed by neck dissection. Imaging was analyzed using RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria. Survival was evaluated using both univariate and multivariate analyses.

Results

Overall survival at 5 years was 89%. Forty‐two patients (21%) had residual disease in the neck (pN+). pN+ was associated with greater locoregional recurrence (LRR) and distant metastasis (DM) and decreased survival. No clinicopathologic factors were predictive of pN+. Contrasted posttreatment CT had low sensitivity and specificity.

Conclusions

In advanced OPSCC pN+, patients have higher rates of LRR and DM. Neither clinicopathologic factors nor posttreatment imaging was predictive of pN+, although increased use of modern imaging may reduce the rate of negative neck dissections. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1454–1460, 2013
Enhanced catalytic activity from proteinoid microspheres
Authors: Quirk Stephen
Published: September 2012

Creating materials that are capable of catalyzing enzymatic reactions could be important to the treatment of both acute and chronic wounds, as well as other topical diseases. As a first step in the design of catalytic biomaterials, a new class of proteinoid microsphere (PM), that includes amino acids found in phosphatase enzyme active sites, has been constructed. This material can significantly enhance catalytic activity for phosphoester hydrolysis, with observed specific activity increases between 35‐ and 55‐fold. Further specific activity increases occur when metal cations, notably iron or zinc, are added to the PMs. Specific activity increases between 140‐ and 300‐fold for these metal modified systems are measured. The phosphatase activity increase is demonstrated for both aromatic phosphate esters as well as the high‐energy phosphate bond of adenosine triphosphate. PMs bind substrate heterogeneously on their surfaces in an enthalpically driven reaction that is defined by an overall favorable free energy, but unfavorable entropy. The catalytic PMs have been successfully blended with polyolefin foam and extruded with PLA. These materials remain fully active. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Effects of chemical and thermochemical pretreatments on sunflower oil cake in biochemical methane potential assays
Authors: Fernández‐Cegrí V. , Raposo F. , de la Rubia M.A. , Borja R.
Published: September 2012

BACKGROUND: The effects of chemical and thermochemical pretreatments on the composition and anaerobic biodegradability of sunflower oil cake were studied to compare these pretreatments and to assess their effectiveness. Four reagents (lime, sodium hydroxide, sulphuric acid, and sodium bicarbonate) at concentrations of 25% (w/w) of dry weight of substrate and 20 g L−1 substrate concentration were used for the chemical pretreatment for 4 h. The same conditions were used for thermochemical pretreatment with heating at 75°C. After the pretreatments, the solid and liquid fractions were separated and subjected to biochemical methane potential tests.

RESULTS: The methane yields of the solid fraction obtained with lime, sodium hydroxide, sulphuric acid and bicarbonate were 130±9, 54±4, 61±6 and 88±7 mL CH4 g‐1CODadded, respectively, and after thermochemical pretreatment were 26±2, 84±7, 74±7, and 77±6 mL CH4 g‐1CODadded, respectively. The methane yields for liquids were 152±13, 2±0, 0±0, 249±19 mL CH4 g‐1CODadded, for the chemical pre‐treatment, respectively, and after the thermochemical pretreatment were 273±13, 58±5, 0±0 and 145±12 mL CH4 g‐1CODadded, respectively.

CONCLUSION: Only the solid fraction obtained after the chemical pretreatment with lime gave a methane yield higher (130 mL CH4 g‐1CODadded) than the obtained for the untreated solid material (114 mL CH4 g‐1CODadd). No thermochemical pretreatment enhanced the methane yield of the solid or liquid fractions of the untreated material. © 2012 Society of Chemical Industry
Therapeutic hypothermia for cardiac arrest: Real‐world utilization trends and hospital mortality
Authors: Jena Anupam B. , Romley John A. , Newton‐Cheh Christopher , Noseworthy Peter
Published: September 2012

BACKGROUND:

Therapeutic hypothermia (TH) improves outcomes following cardiac arrest in small clinical trials.

OBJECTIVE:

To study real‐world utilization and outcomes in US hospitals.

DESIGN:

Retrospective cohort study.

SETTING:

California hospitals.

PATIENTS:

Patients eligible for therapeutic hypothermia after cardiac arrest.

INTERVENTIONS:

We analyzed all discharges from California (1999–2008) to identify patients eligible for TH after cardiac arrest. Patients were considered eligible for TH if both cardiac arrest and anoxic brain injury were among the administrative diagnoses (n = 46,833). Patients undergoing TH (n = 204) were identified through billing codes.

MEASUREMENTS:

TH utilization and in‐hospital mortality.

RESULTS:

Use of TH increased over the study period with 87.3% (178/204) of TH occurring between 2006 and 2008. Few hospitals appeared to perform TH over the study period (47/419, 11.2%). Utilization of TH was concentrated in a few centers, with the top 3 of 419 centers accounting for 31.4% (64/204) of cases. Patients undergoing TH were younger, less likely to be male, more likely to be treated at teaching centers, and had similar comorbidities compared to eligible individuals who did not undergo TH. The adjusted odds ratio for hospital mortality among patients undergoing TH was 0.80 (95% confidence interval [CI] 0.60–1.06, P = 0.11).

CONCLUSIONS:

TH utilization appears low, but implementation is increasing. Case selection and referral biases limit the analysis of the relationship between center TH volume and in‐hospital mortality. Journal of Hospital Medicine 2012. © 2012 Society of Hospital Medicine.
Impact of proactive rounding by a rapid response team on patient outcomes at an academic medical center
Authors: Butcher Brad W. , Vittinghoff Eric , Maselli Judith , Auerbach Andrew D.
Published: September 2012

BACKGROUND:

The impact of rapid response teams (RRT) on patient outcomes remains uncertain.

OBJECTIVE:

To examine the effect of proactive rounding by an RRT on outcomes of hospitalized adults discharged from intensive care.

DESIGN:

Retrospective, observational study.

SETTING:

Academic medical center.

PATIENTS:

All adult patients discharged alive from the intensive care unit (ICU) at the University of California San Francisco Medical Center between January 2006 and June 2009.

INTERVENTION:

Introduction of proactive rounding by an RRT.

MEASUREMENTS:

Outcomes included the ICU readmission rate, ICU average length of stay (LOS), and in‐hospital mortality of patients discharged from the ICU. Data were obtained from administrative billing databases and analyzed using an interrupted time series (ITS) model.

RESULTS:

We analyzed 17 months of preintervention data and 25 months of postintervention data. Introduction of proactive rounding by the RRT did not change the ICU readmission rate (6.7% before vs 7.3% after; P = 0.24), the ICU LOS (5.1 days vs 4.9 days; P = 0.24), or the in‐hospital mortality of patients discharged from the ICU (6.0% vs 5.5%; P = 0.24). ITS models testing the impact of proactive rounding on secular trends found no improvement in any of the 3 clinical outcomes relative to their preintervention trends.

CONCLUSIONS:

Proactive rounding by an RRT did not improve patient outcomes, raising further questions about RRT benefits. Journal of Hospital Medicine 2013. © 2012 Society of Hospital Medicine
Causes of sudden unexpected death of adult hospital patients
Authors: Nichols Larry , Chew Brandon
Published: September 2012

The sudden unexpected death of a hospitalized patient is distressing to the family and the healthcare team. It is also common. Assessment of the causes without autopsy is frequently incorrect. To elucidate the causes of death, 175 cases of adult hospital patients in the University of Pittsburgh Medical Center Health System, who died suddenly and unexpectedly, were investigated with autopsies. The most common cause was judged to be a cardiac arrhythmia, in 58 (33%) of cases, presumptive in 46 cases, because only 12 of these patients were on cardiac monitoring. Of the arrhythmia patients, 36 (62%) had ≥75% coronary artery stenosis and 31 (53%) had histological evidence of myocardial infarction, with 15 (26%) of those with subacute or old myocardial infarction lacking a history of myocardial infarction. Hemorrhage was judged the cause of death in 38 (22%) of cases, including 31 (82%) with endogenous coagulopathy, anticoagulation, or antiplatelet therapy. Pulmonary thromboembolism was judged the cause of death in 27 (15%) of cases. Overall, hemorrhage deserves better appreciation as a cause of sudden unexpected death of hospitalized adults. Journal of Hospital Medicine 2012. © 2012 Society of Hospital Medicine
Effect of fever on hospital presentation, diagnosis, and treatment in patients with H1N1/09 influenza
Authors: Sopirala Madhuri M. , Haas Douglas M. , Ali Naeem A. , Mangino Julie E. , Pan Xueliang , Turner Abigail Norris
Published: September 2012

OBJECTIVE:

Fever is typically considered part of the influenza‐like illness in hemagglutinin type 1 and neuraminidase type 1 (H1N1/09) influenza. We assessed the proportion of patients that did not have fever as part of their illness prior to hospital presentation. We assessed the role of fever on the delay in hospital presentation, diagnosis, and treatment of these patients.

METHODS:

We performed a retrospective analysis of all hospitalized adult patients with laboratory‐confirmed pandemic H1N1/09 at a tertiary care center in the United States from June 1 to December 31, 2009.

RESULTS:

Fifty‐six of 135 study patients (42%) had no fever; 31 (23%) required intensive care unit (ICU) admission, and 9 (7%) died. Those without fever had higher Charlson index (P = 0.01), significantly longer time to hospital presentation (median 4 vs 2 days, P < 0.001), longer time to treatment since the onset of illness (median 5 vs 2 days, P = 0.001), and were more frequently in an ICU (P = 0.01). After adjustment for age (<40 vs ≥40) and Charlson index (0, 1–2, ≥3), patients without fever had significantly increased likelihood of late hospital presentation (>2 days from the onset of illness) (P = 0.001) and also had increased likelihood of ICU stay (P = 0.05).

CONCLUSIONS:

Forty‐two percent of patients with laboratory‐confirmed H1N1/09 did not have fever as part of their illness prior to hospital presentation. Patients without fever had delayed presentation to the hospital and thus experienced delayed treatment. Journal of Hospital Medicine 2013. © 2012 Society of Hospital Medicine
Does it Pay to Invest in Potable Water in the Developing World? Relationships Between External Financing and Economic Development in Sustainable Community‐Run Integrated Projects
Authors: Sauer Michael , Smith Stuart , Clemens Bruce
Published: September 2012

This paper quantifies the impact of external aid channelled through a support agency that practises a participatory approach to development. Researchers compiled completed project data collected from the non‐governmental organisation (NGO) Agua del Pueblo and discovered a positive relationship between external funding for water development projects and resulting economic development. This paper discusses the importance of water development as a channel for achieving overall economic development and the importance of the participatory approach for community development projects. Copyright © 2012 John Wiley & Sons, Ltd.
Recovery of chemical estimates by field inhomogeneity neighborhood error detection (REFINED): Fat/Water separation at 7 tesla
Authors: Narayan Sreenath , Kalhan Satish C. , Wilson David L.
Published: September 2012

Purpose:

To reduce swaps in fat–water separation methods, a particular issue on 7 Tesla (T) small animal scanners due to field inhomogeneity, using image postprocessing innovations that detect and correct errors in the B0 field map.

Materials and Methods:

Fat–water decompositions and B0 field maps were computed for images of mice acquired on a 7T Bruker BioSpec scanner, using a computationally efficient method for solving the Markov Random Field formulation of the multi‐point Dixon model. The B0 field maps were processed with a novel hole‐filling method, based on edge strength between regions, and a novel k‐means method, based on field‐map intensities, which were iteratively applied to automatically detect and reinitialize error regions in the B0 field maps. Errors were manually assessed in the B0 field maps and chemical parameter maps both before and after error correction.

Results:

Partial swaps were found in 6% of images when processed with FLAWLESS. After REFINED correction, only 0.7% of images contained partial swaps, resulting in an 88% decrease in error rate. Complete swaps were not problematic.

Conclusion:

Ex post facto error correction is a viable supplement to a priori techniques for producing globally smooth B0 field maps, without partial swaps. With our processing pipeline, it is possible to process image volumes rapidly, robustly, and almost automatically. J. Magn. Reson. Imaging 2013;37:1247–1253. © 2012 Wiley Periodicals, Inc.
Automatic segmentation of white matter hyperintensities by an extended FitzHugh & nagumo reaction diffusion model
Authors: Ji Shuangxi , Ye Changqing , Li Fan , Sun Wei , Zhang Jue , Huang Yining , Fang Jing
Published: September 2012

Purpose:

To evaluate the efficiency and reproducibility of the extended FitzHugh & Nagumo (FHN) reaction‐diffusion model proposed in this study for white matter hyperintensities (WMH) segmentation.

Materials and Methods:

Five types of magnetic resonance T2‐weighted fluid‐attenuated inversion‐recovery (T2FLAIR) images of 127 patients with different scanning parameters from five clinical scanner systems were selected for this study. After skull and scalp removal and denoise, the T2FLAIR images were processed by the proposed extended FHN model to obtain WMH. This new technique replaced the global threshold constant with a local threshold matrix.

Results:

There was no significant difference between the segmentation results of the training set and the manual contouring against those between the test set and the manual contouring based on similarity index (SI) values (P = 0.5217). The SI values of the five types of T2FLAIR images were 86.0% ± 15.4%, 85.8% ± 10.5%, 84.1% ± 14.8%, 87.2% ± 14.6%, 86.3% ± 12.7%, respectively, comparing the segmentation results using the proposed method to the manual delineations. The overall SI value of the images was 86.5% ± 14.5%. This approach also demonstrated a better WMH segmentation performance over its classic form (P < 0.001).

Conclusion:

The proposed approach is efficient and could provide a more effective and convenient tool for clinical quantitative WMH analysis. J. Magn. Reson. Imaging 2013;37:343–350. © 2012 Wiley Periodicals, Inc.
Correlation of apparent diffusion coefficient values measured by diffusion MRI and MGMT promoter methylation semiquantitatively analyzed with MS‐MLPA in patients with glioblastoma multiforme
Authors: Sunwoo Leonard , Choi Seung Hong , Park Chul‐Kee , Kim Jin Wook , Yi Kyung Sik , Lee Woong Jae , Yoon Tae Jin , Song Sang Woo , Kim Ja Eun , Kim Ji Young , Kim Tae Min , Lee Se‐Hoon , Kim Ji‐Hoon , Sohn Chul‐Ho , Park Sung‐Hye , Kim Il Han , Chang Kee‐Hyun
Published: September 2012

Purpose:

To retrospectively determine whether the apparent diffusion coefficient (ADC) values correlate with O6‐methylguanine DNA methyltransferase (MGMT) promoter methylation semiquantitatively analyzed by methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) in patients with glioblastoma.

Materials and Methods:

The study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability Act (HIPAA) compliant. Newly diagnosed patients with glioblastoma (n = 26) were analyzed with an ADC histogram approach based on enhancing solid portion. The methylation status of MGMT promoter was assessed by methylation‐specific polymerase chain reaction (MSP) and by MS‐MLPA. MS‐MLPA is a semiquantitative method that determines the methylation ratio. The Ki‐67 labeling index was also analyzed. The mean and 5th percentile ADC values were correlated with MGMT promoter methylation status and Ki‐67 labeling index using a linear regression model. Progression‐free survival (PFS) was also correlated with the ADC values using Kaplan–Meier survival analysis.

Results:

The mean methylation ratio was 0.21 ± 0.20. By MSP, there were 5 methylated and 21 unmethylated tumors. The mean ADC revealed a positive relationship with MGMT promoter methylation ratio (P = 0.015) and was also significantly different according to MSP‐determined methylation status (P = 0.011). Median PFS was significantly related with methylation ratio (P = 0.017) and MSP‐derived methylation status (P = 0.025). A positive relationship was demonstrated between PFS and the mean ADC value (P = 0.001). The 5th percentile ADC values showed a significant negative relationship with Ki‐67 labeling index (P = 0.036).

Conclusion:

We found that ADC values were significantly correlated with PFS as well as with MGMT promoter methylation status. We believe that ADC values may merit further investigation as a noninvasive biomarker for predicting treatment response. J. Magn. Reson. Imaging 2013;37:351–358. © 2012 Wiley Periodicals, Inc.
Study of the fragmentation of arginine isobutyl ester applied to arginine quantification in Aedes aegypti mosquito excreta
Authors: Bush David R. , Wysocki Vicki H. , Scaraffia Patricia Y.
Published: September 2012

It has been demonstrated that argininolysis and uricolysis are involved in the synthesis and excretion of urea in Aedes aegypti female mosquitoes. To further investigate the metabolic regulation of urea in female mosquitoes, it is desirable to have a rapid and efficient method to monitor arginine (Arg) concentration in mosquito excreta. Thus, a procedure currently used for the identification of Arg in urea cycle disorders in newborn babies was adapted to analyze Arg in A. aegypti excreta. The fragmentation patterns of the isobutyl esters of Arg and 15N2‐Arg (labeled at the guanidino group) were explored by electrospray ionization (ESI)‐tandem mass spectrometry and fragmentation pathways not described before were characterized. In addition, Arg, 18O2‐Arg, 15N2‐Arg and 15N2‐18O2‐Arg were also analyzed to elucidate some of the minor fragments in greater detail. Mosquito excreta from individual females were collected before and at different times after feeding a blood meal, mixed with 15N2‐Arg, an internal standard, and then derivatized as isobutyl esters. Based on the fragmentation mechanisms of Arg standards, studied by MS2 and MS3, Arg in the mosquito excreta was successfully analyzed by ESI‐multiple reaction monitoring in a triple‐quadrupole mass spectrometer. Arg excretion was monitored over a 120 h window before and after feeding female mosquitoes with a blood meal, with the maximum level of Arg excretion observed at 36–48 h post blood feeding. This method provides an efficient and rapid tool to quantify Arg in individual blood‐fed mosquitoes, and can be applied to other organisms, whose small size severally limits the use of conventional biochemical analysis. Copyright © 2012 John Wiley & Sons, Ltd.
Cytosine to uracil conversion through hydrolytic deamination of cytidine monophosphate hydroxy‐alkylated on the amino group: a liquid chromatography – electrospray ionization – mass spectrometry investigation
Authors: Losito I. , Angelico R. , Introna B. , Ceglie A. , Palmisano F.
Published: September 2012

A novel pathway for cytosine to uracil conversion performed in a micellar environment, leading to the generation of uridine monophosphate (UMP), was evidenced during the alkylation reaction of cytidine monophosphate (CMP) by dodecyl epoxide. Liquid chromatography‐electrospray ionization – ion trap ‐ mass spectrometry was used to separate and identify the reaction products and to follow their formation over time. The detection of hydroxy‐amino‐dodecane, concurrently with free UMP, in the reaction mixture suggested that, among the various alkyl‐derivatives formed, CMP alkylated on the amino group of cytosine could undergo tautomerization to an imine and hydrolytic deamination, generating UMP. Interestingly, no evidence for this peculiar conversion pathway was obtained when guanosine monophosphate (GMP), the complementary ribonucleotide of CMP, was also present in the reaction mixture, due to the fact that NH2‐alkylated CMP was not formed in this case. The last finding emphasized the role played by CMP–GMP molecular interactions, mediated by a micellar environment, in hindering the alkylation reaction at the level of the cytosine amino group. Copyright © 2012 John Wiley & Sons, Ltd.
In‐situ enrichment of phosphopeptides on MALDI plates modified by ambient ion landing
Authors: Krásný Lukáš , Pompach Petr , Strohalm Martin , Obsilova Veronika , Strnadová Marcela , Novák Petr , Volný Michael
Published: September 2012

We report substantial in‐situ enrichment of phosphopeptides in peptide mixtures using titanium and zirconium dioxide‐coated matrix assisted laser desorption‐ionization (MALDI) plates prepared by recently reported ambient ion landing deposition technique. The technique was able to modify four common materials currently used for MALDI targets (stainless steel, aluminum, indium‐tin oxide glass and polymeric anchor chip). The structure of the deposited dioxide was investigated by electron microscopy, and different surfaces were compared and discussed in this study. Two standard proteins were used to test the enrichment capabilities of modified MALDI plates: casein and in‐vitro phosphorylated trehalase. The enrichment of casein tryptic digest resulted in identification of 20 phosphopeptides (including miscleavages). Trehalase was used as a suitable model of larger protein that provided more complex peptide mixture after the trypsin digestion. All four possible phosphorylation sites in trehalase were identified and up to seven phosphopetides were found (including methionine oxidations and miscleavages). Two different mass spectrometers, MALDI‐Fourier transform ion cyclotron resonance (FTICR) and MALDI‐time of flight, were used to detect the phosphopeptides from modified MALDI plates after the enrichment procedure. It was observed that the desorption‐ionization phenomena on the modified surfaces are not critically influenced by the parameters of the different MALDI ion sources (e.g. different pressure, different extraction voltages), and thus the presence of dioxide layer on the standard MALDI plate does not significantly interfere with the main MALDI processes. The detection of phosphopeptides after the enrichment could be done by both instruments. Desorption electrospray ionization coupled to the FTICR was also tested, but, unlike MALDI, it did not provide satisfactory results. Copyright © 2012 John Wiley & Sons, Ltd.
Application of the ETD/PTR reactions in top‐down proteomics as a faster alternative to bottom‐up nanoLC‐MS/MS protein identification
Authors: Drabik A. , Bodzon‐Kulakowska A. , Suder P.
Published: September 2012

Our goal was to compare two popular analytical techniques used nowadays in proteomic investigations for proteins/peptides sequencing and identification, a widely used nanoLC‐MS/MS approach applied in the bottom‐up proteomics and electron transfer dissociation/proton transfer reaction fragmentation preferably used when top‐down strategy is applied. Comparison was carried out with the aid of the ESI‐quadrupole ion‐trap instrument using the following criteria: total time of analysis including sample preparation, sequence coverage, Mascot scoring, capability to detect modifications, quality of the results as a function of protein molecular weight and sample consumption. Copyright © 2012 John Wiley & Sons, Ltd.
Do different lamivudine‐resistant hepatitis B genotypes carry the same risk of entecavir resistance?
Authors: Lee Guan Huei , Aung Myat Oo , Dan Yock Young , Lee Yin Mei , Mak Belinda , Low How Cheng , Lim Kieron , Thwin Maung Aye , Tan Poh Seng , Lim Seng Gee
Published: September 2012

Entecavir switch is one of the treatment options for lamivudine‐resistant hepatitis B (HBV) patients in Asia. This study examined the outcome of patients with different baseline resistance genotypes in a cohort study. In this study, 14 patients with chronic HBV were treated with entecavir 1 mg/day for 5 years. Enrolment criteria include: documented lamivudine resistant mutations, treatment with adefovir 10 mg/day for at least 24 weeks, and Child‐Pugh score <7. Most had previous failed adefovir therapy and compensated cirrhosis of the liver. Clinical outcomes, liver biochemistries, and HBV DNA were monitored regularly. Patients with virologic breakthrough were rescued with add‐on adefovir. At the end of the treatment period, the mean HBV DNA fell from 5.92 × 106 (baseline) to 3.67 × 101 IU/ml. The presence of a HBV polymerase rtM204V mutation at the baseline was found to be the major risk factor for adverse outcomes. Compared to the patients with the rtM204I mutant, patients with the rtM204V mutant had increased risk of virologic breakthrough (80% vs. 0%, P = 0.010) requiring add‐on adefovir, slower virologic responses (log rank test, P = 0.0011), failure to reach undetectable HBV DNA levels (60% vs. 0%, P = 0.045), and higher risk of entecavir‐resistance (60% vs. 0%, P = 0.045). All the patients with rtM204I and rtA181 mutants had undetectable HBV DNA from 18th month. In summary, lamivudine‐resistant HBV patients with the rtM204V mutation have the highest risk of developing entecavir resistance, and entecavir monotherapy should be avoided. Those with the rtM204I and rtA181V mutations may have lower risks, but regular surveillance for viral breakthrough is required. J. Med. Virol. 85:26–33, 2012. © 2012 Wiley Periodicals, Inc.
Gastroesophageal reflux evaluation in patients affected by chronic cough: Restech versus multichannel intraluminal impedance/pH metry
Authors: Ummarino Dario , Vandermeulen Liv , Roosens Bart , Urbain Daniel , Hauser Bruno , Vandenplas Yvan
Published: September 2012

Objectives/Hypothesis:

Oropharyngeal (OP) pH monitoring has been developed to detect supra‐esophageal gastric reflux (SEGR). The results obtained with OP pH‐metry and multichannel intraluminal impedance/pH monitoring (MII/pH) were compared.

Study Design:

Diagnostic study.

Methods:

Ten patients (age 46.33 ± 9.86 years) presenting with chronic coughing underwent simultaneous OP and MII/pH recording. A 2‐minute interval was allowed between events detected with both techniques to be considered simultaneous.

Results:

A total of 515 reflux episodes were recorded with MII/pH (acid: 181; weakly acid: 310; weakly alkaline: 24); 180 (35%) reached the highest impedance channel (hypo‐pharynx); 74/180 (41%) were not related to a change in pH, according to the antimony electrode of the MII/pH catheter located at the upper esophageal sphincter. The OP monitoring measured 39 acid events; 17 (43.6%) were swallows according to MII, and 15 (38.5%) were not associated with MII or pH change. Only seven episodes were detected simultaneously with both techniques (1.3% for MII vs. 18% for OP; P = 0.0002). We found 49 pH‐only refluxes at the pH sensor in the hypo‐pharynx with MII/pH; only three (6.1%) correlated with OP reflux. Correlation in time between cough and reflux events was positive in 5/10 patients for MII (symptom index 5/10, symptom association probability 4/10), but in 0/10 patients according to OP pH metry.

Conclusion:

OP pH metry detected less reflux episodes than MII/pH; 35% of the OP events were swallows according to impedance. Time correlation between cough and reflux could not be demonstrated with OP pH metry.
Evaluating the utility of non–echo‐planar diffusion‐weighted imaging in the preoperative evaluation of cholesteatoma: A meta‐analysis
Authors: Li Peter M. M. C. , Linos Eleni , Gurgel Richard K. , Fischbein Nancy J. , Blevins Nikolas H.
Published: September 2012

Objectives/Hypothesis

To describe the accuracy of non–echo‐planar diffusion‐weighted magnetic resonance imaging (DW MRI) in identifying middle ear cholesteatoma.

Study Design

A meta‐analysis of the published literature.

Methods

A systematic review of the literature was performed to identify studies in which patients suspected of having middle ear cholesteatoma underwent DW MRI scans prior to surgery. A meta‐analysis of the included studies was performed.

Results

Ten published articles (342 patients) met inclusion criteria. Cholesteatoma was confirmed in 234 patients, of which 204 were detected by DW MRI (true positives) and 30 were not (false negatives). One hundred eight patients did not have cholesteatoma on surgical examination, and of these 100 were correctly identified by MRI (true negatives) whereas eight were not (false positives). The overall sensitivity of DW MRI in detecting cholesteatoma was 0.94 (confidence interval, 0.80–0.98) and specificity 0.94 (confidence interval, 0.85–0.98). DW MRI sequences could not reliably detect cholesteatomas under 3 mm in size.

Conclusions

Non–echo‐planar DW MRI is highly sensitive and specific in identifying middle ear cholesteatoma. DW MRI may help to stratify patients into groups of who would benefit from early second‐look surgery and those who could be closely observed.

Level of Evidence

2a.
Synthesis and Fluorescence Properties of Chiral Near‐Infrared Emissive Polymers Incorporating BODIPY Derivatives and (S)‐Binaphthyl
Authors: Wu Yuanzhao , Mao Xuerong , Ma Xiao , Huang Xiaobo , Cheng Yixiang , Zhu Chengjian
Published: September 2012

A new series of π‐conjugated chiroptical polymers consisting of styryl BODIPYs moieties and (S)‐binaphthyl units has been firstly synthesized via Sonogashira polymerization. The resulting polymers were characterized by 1H NMR spectroscopy, gel permeation chromatography (GPC), UV–Vis absorption spectroscopy, cyclic voltammetry (CV), circular dichroism (CD), and density functional theory (DFT) calculations. The chiral polymers have moderate molecular weights, high solubility in commonly solvents and stable chiroptical conformation. And more importantly, the four chiral polymers can exhibit near‐infrared (NIR) emissive and good anisotropic fluorescence. We anticipate these chiral NIR polymers will be useful in biological measurements and cellular imaging where NIR emission is beneficial.
Facile Soap‐Free Miniemulsion Polymerization of Methyl Methacrylate via Reverse Atom Transfer Radical Polymerization
Authors: Zhu Gaohua , Zhang Lifen , Pan Xiangqiang , Zhang Wei , Cheng Zhenping , Zhu Xiulin
Published: September 2012

A facile soap‐free miniemulsion polymerization of methyl methacrylate (MMA) was successfully carried out via a reverse ATRP technique, using a water‐soluble potassium persulfate (KPS) or 2,2′‐azobis(2‐methylpropionamidine) dihydrochloride (V‐50) both as the initiator and the stabilizer, and using an oil‐soluble N,N‐n‐butyldithiocarbamate copper (Cu(S2CN(C4H9)2)2) as the catalyst without adding any additional ligand. Polymerization results demonstrated the “living”/controlled characteristics of ATRP and the resultant latexes showed good colloidal stability with average particle size around 300–700 nm in diameter. The monomer droplet nucleation mechanism was proposed. NMR spectroscopy and chain‐extension experiments under UV light irradiation confirmed the attachment and livingness of UV light sensitive SC(S)N(C4H9)2 group in the chain end.
New Design of Thiol‐Responsive Degradable Polylactide‐Based Block Copolymer Micelles
Authors: Cunningham Alexander , Oh Jung Kwon
Published: September 2012

A new design to synthesize thiol‐responsive degradable polylactide (PLA)‐based micelles having a disulfide linkage in the middle of triblock copolymers is reported. They were synthesized by a new method that centers on the use of a disulfide‐labeled diol as an initiator for ring‐opening polymerization, followed by controlled radical polymerization. These well‐controlled copolymers with monomodal and narrow molecular weight distribution (Mw/Mn < 1.15) self‐assembled to form aqueous micellar aggregates with disulfide‐containing PLA cores, which is not toxic to cells. Central disulfide linkages were cleaved in response to thiols; such thiol‐triggered degradation enhanced the release of encapsulated anticancer drugs.
Toward a Universal Behavior of Linear Athermal Model Chains in the Limit of Infinite Chain‐length
Authors: Olaj Oskar Friedrich , Zifferer Gerhard
Published: September 2012

Athermal chains of various stiffness embedded in several types of lattices were analyzed with respect to their pair distribution function G(R). Extrapolation to infinite chain‐length on a reduced distance scale made all the G(R) data coincide within extremely narrow limits, thus suggesting the existence of a universal pair distribution function for polymers in good solvents in the long‐chain limit. The ratio –ln(G(R))/Z(R) with Z(R) being the reduced distribution of overlaps is also universal in type and varies only little with distance R. Further, a likewise universal function could be established that allows the construction of Z(R) from the Flory–Krigbaum expression taking into account not only the deviations from Gaussian behavior but also the effect of intramolecular repulsion present in athermal chains.

magnified image
Noise amplification in parallel whole‐head ultra‐low‐field magnetic resonance imaging using 306 detectors
Authors: Lin Fa‐Hsuan , Vesanen Panu T. , Nieminen Jaakko O. , Hsu Yi‐Cheng , Zevenhoven Koos C.J. , Dabek Juhani , Parkkonen Lauri T. , Zhdanov Andrey , Ilmoniemi Risto J.
Published: September 2012

In ultra‐low‐field magnetic resonance imaging, arrays of up to hundreds of highly sensitive superconducting quantum interference devices (SQUIDs) can be used to detect the weak magnetic fields emitted by the precessing magnetization. Here, we investigate the noise amplification in sensitivity‐encoded ultra‐low‐field MRI at various acceleration rates using a SQUID array consisting of 102 magnetometers, 102 gradiometers, or 306 magnetometers and gradiometers, to cover the whole head. Our results suggest that SQUID arrays consisting of 102 magnetometers and 102 gradiometers are similar in g‐factor distribution. A SQUID array of 306 sensors (102 magnetometers and 204 gradiometers) only marginally improves the g‐factor. Corroborating with previous studies, the g‐factor in 2D sensitivity‐encoded ultra‐low‐field MRI with 9 to 16‐fold 2D accelerations using the SQUID array studied here may be acceptable. Magn Reson Med 70:595–600, 2013. © 2012 Wiley Periodicals, Inc.
Turboprop+: Enhanced turboprop diffusion‐weighted imaging with a new phase correction
Authors: Lee Chu‐Yu , Li Zhiqiang , Pipe James G. , Debbins Josef P.
Published: September 2012

Faster periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) diffusion‐weighted imaging acquisitions, such as Turboprop and X‐prop, remain subject to phase errors inherent to a gradient echo readout, which ultimately limits the applied turbo factor (number of gradient echoes between each pair of radiofrequency refocusing pulses) and, thus, scan time reductions. This study introduces a new phase correction to Turboprop, called Turboprop+. This technique employs calibration blades, which generate 2‐D phase error maps and are rotated in accordance with the data blades, to correct phase errors arising from off‐resonance and system imperfections. The results demonstrate that with a small increase in scan time for collecting calibration blades, Turboprop+ had a superior immunity to the off‐resonance‐related artifacts when compared to standard Turboprop and recently proposed X‐prop with the high turbo factor (turbo factor = 7). Thus, low specific absorption rate and short scan time can be achieved in Turboprop+ using a high turbo factor, whereas off‐resonance related artifacts are minimized. Magn Reson Med 70:497–503, 2013. © 2012 Wiley Periodicals, Inc.
MRI biosensor for protein kinase A encoded by a single synthetic gene
Authors: Airan Raag D. , Bar‐Shir Amnon , Liu Guanshu , Pelled Galit , McMahon Michael T. , van Zijl Peter C. M. , Bulte Jeff W. M. , Gilad Assaf A.
Published: September 2012

Purpose:

Protein kinases including protein kinase A (PKA) underlie myriad important signaling pathways. The ability to monitor kinase activity in vivo and in real‐time with high spatial resolution in genetically specified cellular populations is a yet unmet need, crucial for understanding complex biological systems as well as for preclinical development and screening of novel therapeutics.

Methods:

Using the hypothesis that the natural recognition sequences of protein kinases may be detected using chemical exchange saturation transfer magnetic resonance imaging, we designed a genetically encoded biosensor composed of eight tandem repeats of the peptide LRRASLG, a natural target of PKA.

Results:

This sensor displays a measurable change in chemical exchange saturation transfer signal following phosphorylation by PKA. The natural PKA substrate LRRASLG exhibits a chemical exchange saturation transfer‐magnetic resonance imaging contrast at +1.8 and +3.6 ppm, with a >50% change after phosphorylation with minutes‐scale temporal resolution. Expression of a synthetic gene encoding eight monomers of LRRASLG yielded two peaks at these chemical exchange saturation transfer frequencies.

Conclusion:

Taken together, these results suggest that this gene may be used to assay PKA levels in a biologically relevant system. Importantly, the design strategy used for this specific sensor may be adapted for a host of clinically interesting protein kinases. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Model‐based reconstruction of undersampled diffusion tensor k‐space data
Authors: Welsh Christopher L. , DiBella Edward V. R. , Adluru Ganesh , Hsu Edward W.
Published: September 2012

The practical utility of diffusion tensor imaging, especially for 3D high‐resolution spin warp experiments of ex vivo specimens, has been hampered by long acquisition times. To accelerate the acquisition, a compressed sensing framework that uses a model‐based formulation to reconstruct diffusion tensor fields from undersampled k‐space data was presented and evaluated. Accuracies in brain specimen white matter fiber orientation, fractional anisotropy, and mean diffusivity mapping were compared with alternative methods achievable using the same scan time via reduced image resolution, fewer diffusion encoding directions, standard compressed sensing, or asymmetrical sampling reconstruction. The efficiency of the proposed approach was also compared with fully sampled cases across a range of the number of diffusion encoding directions. In general, the proposed approach was found to reduce the image blurring and noise and to provide more accurate fiber orientation, fractional anisotropy, and mean diffusivity measurements compared with the alternative methods. Moreover, depending on the degree of undersampling used and the diffusion tensor imaging parameter examined, the measurement accuracy of the proposed scheme was equivalent to fully sampled diffusion tensor imaging datasets that consist of 33–67% more encoding directions and require proportionally longer scan times. The findings show model‐based compressed sensing to be promising for improving the resolution, accuracy, or scan time of diffusion tensor imaging. Magn Reson Med 70:429–440, 2013. © 2012 Wiley Periodicals, Inc.
Is there correlation between electromyography and digital palpation as means of measuring pelvic floor muscle contractility in nulliparous, pregnant, and postpartum women?
Authors: Botelho Simone , Pereira Larissa Carvalho , Marques Joseane , Lanza Ana Helena , Amorim Cesar Ferreira , Palma Paulo , Riccetto Cassio
Published: September 2012

Aims

The continence mechanisms depend on the integrity of the pelvic floor muscles. It is therefore important to find simple, reliable, and safe methods to assess its contractility in a clinical setting. This study aims to investigate if digital palpation of the pelvic floor muscles presents correlation with its electromyographic activity.

Methods

The sample consisted of 307 women with mean age of 23.93 years, including 39 nulliparous, 117 primigravid pregnant, 64 primiparous, in post‐vaginal delivery, and 87 primiparous women, in post‐cesarean section delivery. The assessment consisted of both digital palpation and surface electromyography. One, and the same, highly skilled and experienced physiotherapist, who was able to classify the different grades of contractility accurately, performed digital palpation using the Modified Oxford Grading Scale. Surface electromyography was performed using an intravaginal probe. For electromyography evaluation, three contractions of 5 sec each were recorded, and an average of three Root Mean squares was considered for analysis. Spearman's Coefficient, Jonckheere–Terpstra Test, Kruskal–Wallis as well as Dunn Test were used for statistical analysis.

Results

The strong correlation found between the two methods (P < 0.001) indicates that both digital palpation and electromyography can be used in everyday practice, both for clinical use and scientific research, although both have their specific limitations and requirements to avoid the risk of biases.

Conclusion

There was a correlation between pelvic floor muscle contractility measured by surface electromyography and by digital palpation. Both methods can be used to validate data in research and clinical setting. Neurourol. Urodynam. 32: 420–423, 2013. © 2012 Wiley Periodicals, Inc.
Evaluation of a new disposable “tampon like” electrostimulation technology (Pelviva®) for the treatment of urinary incontinence in women: A 12‐week single blind randomized controlled trial
Authors: Oldham Jackie , Herbert Julia , McBride Kathryn
Published: September 2012

Aims

To test the null hypothesis that a novel disposable “tampon like” electrostimulation device (Pelviva®) is no better than unsupervised pelvic floor muscle exercise for treatment of urinary incontinence in women.

Methods

Pre/post‐intervention assessor blinded, single center RCT. A total of 123 community dwelling self referred women with symptoms of stress, urge, or mixed incontinence were randomly assigned to one of two 12‐week duration treatments: Pelviva® used for 30 min a day plus unsupervised pelvic floor muscle exercise or unsupervised exercises alone. Outcome measures included ICIQ‐UI (primary), ICIQ FLUTSex and global impression of severity and improvement (secondary) completed at recruitment, after 4 weeks of unsupervised exercise and immediately post‐treatment. Diary of exercise frequency/type, overall impression, and usage of device was completed mid‐ and post‐treatment.

Results

Pelviva® plus exercise produced significantly better outcome than unsupervised exercise alone: 5 points (45%) versus 1 point (10%) for ICIQ‐UI (P = 0.014); 67% versus 33% for leak frequency (P = 0.005); 40% versus 20% for leak interference with life (P = 0.018). Incontinence was less bothersome during sex to a greater extent in the Pelviva® group (P = 0.026). Women were enthusiastic about the device, found it comfortable/easy to use and experienced no adverse events.

Conclusions

The Pelviva® device plus unsupervised exercise is more successful than unsupervised pelvic floor muscle exercise alone in treating urinary incontinence. The device is easy/comfortable to use, there are no apparent adverse incidents, and women can manage their incontinence in the privacy of their own home. The product will be launched 2013. Neurourol. Urodynam. 32: 460–466, 2013. © 2012 Wiley Periodicals, Inc.
Urinary incontinence after surgery for pelvic organ prolapse
Authors: Lensen Ellen J.M. , Withagen Mariella I.J. , Kluivers Kirsten B. , Milani Alfredo L. , Vierhout Mark E.
Published: September 2012

Aims

This study focused on the changes in urinary incontinence (UI) rates pre‐ and postoperatively and identified risk factors which predict the presence of symptoms of urgency urinary incontinence (UUI) or stress urinary incontinence (SUI) after surgery for pelvic organ prolapse (POP) without concomitant or previous anti‐incontinence surgery.

Methods

All consecutive women who underwent POP surgery without concomitant or previous anti‐incontinence surgery in the years 2004–2010 were included. Assessments were performed preoperatively and at 1‐year follow‐up, including pelvic organ prolapse quantification score and a standardized urogynecological questionnaire (Urogenital Distress Inventory, UDI). Primary outcome of this study was stress and/or urgency UI postoperatively. Furthermore, this study measured the improvement or worsening of UI following surgery using the UDI. Univariable‐ and multivariable logistic regression with forward selection procedure was used to identify the risk factors.

Results

Nine hundred seven patients were included. De novo SUI appeared in 22% and de novo UUI occurred in 21% of the women. At 1‐year 42% were cured for UUI and 39% were recovered from SUI by POP surgery alone. The best predictor for the occurrence of postoperative SUI or UUI was the presence of preoperative SUI or UUI. BMI and chronic obstructive pulmonary disease (COPD) were identified as independent risk factors for postoperative SUI. A recurrence in the anterior compartment protected against SUI postoperatively.

Conclusions

Preoperative SUI or UUI is the most important predictor of SUI and UUI postoperatively. BMI and COPD were identified as important risk factors for SUI. Neurourol. Urodynam. 32: 455–459, 2013. © 2012 Wiley Periodicals, Inc.