In order to understand this behavior, we present a statistical “”breakdown”" analysis performed P5091 on Cu doped Ge0.3Se0.7 based memory devices under elevated temperature and constant voltage stress conditions. Following the approach of electrochemical phase formation, the precursor of the “”ON resistance switching”" is considered to be nucleation – the emergence of small clusters of atoms carrying the basic properties of the new phase which forms the conducting filament. Within the framework of nucleation

theory, the observed fluctuations in the time required for “”ON resistance switching”" are found to be consistent with the stochastic nature of critical nucleus formation. (C) 2011 American Institute selleck kinase inhibitor of Physics. [doi:10.1063/1.3631013]“
“Purpose: in an attempt to overcome the potential long-term limitations observed with plasma-sprayed hydroxyapatite-coated implants, nanothickness bioceramic coatings have been processed onto previously grit-blasted/acid-etched

surfaces. Our objective was to evaluate the bone response to alumina-blasted/acid-etched and a thin ion beam-deposited bioceramic (rest) implant surfaces at 2 and 4 weeks in vivo with a dog tibia model.

Materials and Methods: Plateau root form implants (5 x 6 mm) were placed bilaterally along the proximal tibia of 6 Doberman dogs and remained for 2 and 4 weeks in vivo (n = 6 per implant type and time in vivo). After euthanization, the implants were processed in a nondecalcified form and reduced to similar to 30 mu m-thickness; plates. Transmitted light optical microscopy at various magnifications was used to qualitatively evaluate the bone healing patterns. Bone-to-implant contact (BIC) was determined and 1-way ANOVA at 95% level of significance with Tukey’s

post-hoc multiple comparisons was used for statistical analysis.

Results: Histomorphology showed GSK2126458 ic50 new bone formation filling the spaces between the plateaus at both in vivo time intervals through large quantities of woven bone formation. A higher degree of bone organization was observed between the plateaus of Test implants at 4 weeks in vivo than the alumina-blasted/acid-etched implants. No significant differences in BIC were observed for the different groups (P > .86).

Conclusion: Despite nonsignificant differences between BIC for the different implant surfaces and times in vivo, higher degrees of bone organization were observed for the Test implants at 4 weeks, and biomechanical testing is suggested to verify its biomechanical fixation effectiveness. (C) 2009 American Association of Oral and Maxillofacial Surgeons”
“Objective. We determined the effect of the angle of apical resection on apical leakage using a computerized fluid filtration meter with a laser system and a digital air pressure regulator in 46 extracted single-rooted human teeth.

Orthograde endodontic treatment was performed.

Patients in group C or D are at high risk of exacerbations and should receive a long-acting anticholinergic or a combination of an inhaled corticosteroid and a long-acting beta, agonist. For patients whose symptoms are not controlled with one of these regimens, triple therapy with an inhaled corticosteroid, long-acting beta, agonist, and anticholinergic should check details be considered. Prophylactic antibiotics and oral corticosteroids are not recommended for prevention of COPD exacerbations. Continuous oxygen therapy improves mortality rates in patients with severe hypoxemia and COPD. Lung volume reduction surgery can improve survival rates in patients with severe, upper lobe predominant COPD with heterogeneous emphysema

distribution. (Copyright (C) 2013 American Academy

of Family Physicians.)”
“This is the second part of a document describing a voluntary certification process based on Joint Commission International (JCI) criteria developed by the Italian Society of Nephrology (SIN) and JCI representatives. In the first part we discussed standards for clinical care delivery and performance measurements related to chronic kidney disease care. Herein (PartII), we complete the description of Performace measurements and CKD care by describing issues related to programme management and clinical information management.”
“gamma-Cystathionase (CTH, EC: 4.4.1.1), an enzyme widely distributed in the world of prokaryotic and eukaryotic organisms, catalyzes PFTα mw the formation and transformations of sulfane sulfur-containing compounds and plays a pivotal role in the L-cysteine desulfuration pathway.

Human, tetrameric CTH is composed of two dimers and each monomer binds pyridoxal phosphate (PLP). The gene, located on the short arm of chromosome 1, consists of 13 exons and 12 introns. As a result of alternative splicing, three isoforms of human CTH arise. Analysis of genetic variations of the CTH encoding gene showed a large number of polymorphisms. A decrease of the expression of CTH entails a drop in the level of cysteine, glutathione (GSH), taurine JNJ-26481585 cost and hydrogen sulfide (H2S) in the cells and, more importantly, leads to cystathioninuria. H2S, endogenously formed by CTH, affects the vasodilation and regulation of blood pressure. CTH knockout mice have decreased levels of H2S, hypertension, and reduced capacity for vascular endothelium relaxation. Overexpression of the gene encoding CTH in the cells leads to increased production of H2S. H2S plays a role in protection of neurons against oxidative stress, and stimulates an increase in gamma-glutamylcysteine synthetase and thereby an increase in the level of GSH. Sulfurtransferases, including CTH, can locally prevent oxidative stress due to reversible oxidation of – SH groups in the presence of increased levels of reactive oxygen species, and reduction in the presence of GSH and/or reduced thioredoxin.

We aimed to assess the protective effect of inactivated influenza vaccination in these children.

Methods: We conducted a prospective case-control study in PARP inhibitor general practices and a hospital emergency department, testing all eligible patients for influenza and a range of other common respiratory viruses. Influenza vaccine effectiveness (VE) against laboratory-confirmed influenza was estimated with cases defined as children with an influenza-like illness who tested positive and controls as those with an influenza-like illness who tested negative for influenza virus. We calculated VE using the adjusted odds ratio from multivariate logistic regression. As a surrogate

marker for adequate specimen collection, we explored the difference in VE point estimates defining controls as children in whom another respiratory virus was detected.

Results: A total of 75 children were enrolled from general practices and 214 through the emergency department, with 12 (27%) and 36 (17%), respectively, having laboratory-confirmed influenza. Using all the influenza-negative controls, the adjusted VE was 58% (95% confidence interval, 9-81). When controls were limited to those with another virus present, the adjusted VE was 68% (95%

confidence interval, 26-86).

Conclusions: VE estimates were higher when controls included only those children with another respiratory virus detected. Testing for other common respiratory viruses enables the control group to be restricted to those for whom an adequate MK-2206 sample is likely.”
“Deuterium permeation during ion bombardment through tungsten membranes coated by amorphous carbon films was investigated and compared with the permeation through bare tungsten. The membrane was bombarded by D(3)(+) ions with energies of 200 and 1200 eV/D at a temperature of 873 K. The thickness of the amorphous carbon film was 120-170 nm. Detailed characterization of the carbon films were performed using AFM, NRA, RBS, FIB/SEM and Selleck SBI-0206965 XPS. The influence of the carbon films on permeation were strong for both ion energies,

but different for each energy. In the case of 200 eV/D ions, the film was completely removed by the end of permeation due to intensive chemical sputtering, the lag time of permeation was much longer than for the bare membrane, and the permeation rate rose to a maximum value close to the bare membrane and then decreased to lower values. In the case of 1200 eV/D, the films were sputtered only very slowly, the lag time was much longer than in the case of the bare membrane but shorter than at 200 eV/D, and the permeation rate increased steadily up to several percents of the incident flux. (C) 2011 American Institute of Physics. [doi:10.1063/1.3611386]“
“Polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified, mainly in respiratory specimens from children.

Moreover, our collection of insertion homozygotes provides a powerful tool to accelerate the functional analysis of nuclear-encoded chloroplast proteins in Arabidopsis. The Chloroplast Function Database is freely available at http://rarge.psc.riken.jp/chloroplast/. The homozygous lines generated in this project are also available from

the various Arabidopsis stock centers. Crenigacestat We have donated the insertion homozygotes to their originating seed stock centers.”
“Anopheles darlingi is the most important malaria vector in Central and South America. After a dramatic reduction of malaria cases in the whole Brazilian territory, with the lowest abundance being attained by 1970, the disease resurged in the Amazon region, where it is now a great public health concern. Consequently, better knowledge about vector species became urgent. We examined the genetic diversity and population structure of A. darlingi, sampled in

four localities in the State of Rondonia, Brazil, using 139 amplified fragment length polymorphism marker loci. In each locality, samples were collected in two environments: a peri-domicile one (in the balconies of houses) and an extra-domicile environment (about 15 m from the house). Estimates of expected heterozygosity, Shannon diversity index and percentage of polymorphic loci showed medium to high values, with the samples from the areas closer to Porto Velho exhibiting the smallest values. There was evidence of small population differences,

evaluated by F-st, genetic distance and analysis of molecular variance. Comparison between peri- and extra-domicile samples showed greater https://www.selleckchem.com/products/BMS-777607.html values of F-st and genetic distance than between pairs of localities, indicating influence of environmental conditions on the genetics of populations.”
“Background: The anabolic effect of resistance exercise is enhanced by the provision of dietary protein.

Objectives: Selleck MK-8931 We aimed to determine the ingested protein dose response of muscle (MPS) and albumin protein synthesis (APS) after resistance exercise. In addition, we measured the phosphorylation of candidate signaling proteins thought to regulate acute changes in MPS.

Design: Six healthy young men reported to the laboratory on 5 separate occasions to perform an intense bout of leg-based resistance exercise. After exercise, participants consumed, in a randomized order, drinks containing 0, 5, 10, 20, or 40 g whole egg protein. Protein synthesis and whole-body leucine oxidation were measured over 4 h after exercise by a primed constant infusion of [1-(13)C] leucine.

Results: MPS displayed a dose response to dietary protein ingestion and was maximally stimulated at 20 g. The phosphorylation of ribosomal protein S6 kinase (Thr(389)), ribosomal protein S6 (Ser(240/244)), and the epsilon-subunit of eukaryotic initiation factor 2B (Ser(539)) were unaffected by protein ingestion.

Data were compared with those of the previous study in which the same pathology protocol, based on axial slicing and extensive tissue sampling from the circumferential margin, had

been used.

Results: The R1 rate was high in pancreatic (82%) and bile duct (72%) cancer and significantly lower in ampullary cancer (25%). Margin positivity was often multifocal, the posterior margin being most frequently involved. Margin status correlated with survival in the entire cohort (P = 0.006) and the pancreatic subgroup (P = 0.046). These findings were consistent with observations in our previous study.

Conclusions: Margin involvement in pancreatic cancer is a frequent DZNeP mw and prognostically significant finding when specimens are assessed using the LEEPP.”
“The response of seed production to CO2 concentration ([CO2]) is known to vary considerably among C-3 annual species. Here we analyse the interspecific variation in CO2 responses selleck compound of seed production per plant with particular attention to nitrogen use. Provided that seed production is limited by nitrogen availability, an increase in seed mass per plant results

from increase in seed nitrogen per plant and/or from decrease in seed nitrogen concentration ([N]). Meta-analysis reveals that the increase in seed mass per plant under elevated [CO2] is mainly due to increase in seed nitrogen per plant rather than seed [N] dilution. Nitrogen-fixing legumes enhanced nitrogen acquisition more than non-nitrogen-fixers, resulting in a large increase in seed mass per plant. In Poaceae, an increase in seed mass per plant was also caused by a decrease in seed [N]. Greater carbon allocation to albumen (endosperm and/or perisperm) than the embryo may account for [N] reduction in grass seeds. These differences in CO2 response of seed production among functional groups may affect their fitness, leading to changes in species composition in the future high-[CO2] ecosystem.”
“Single-crystal Cu(001)

layers, 4-1400 nm thick, were deposited on MgO(001) with and without a 2.5-nm-thick TiN(001) buffer layer. X-ray diffraction and reflection indicate that the TiN(001) surface suppresses Cu-dewetting, yielding TPCA-1 clinical trial a 4 x lower defect density and a 9 x smaller surface roughness than if grown on MgO(001) at 25 degrees C. In situ and low temperature electron transport measurements indicate that ultra-thin (4 nm) Cu(001) remains continuous and exhibits partial specular scattering at the Cu-vacuum boundary with a Fuchs-Sondheimer specularity parameter p = 0.6 +/- 0.2, suggesting that the use of epitaxial wetting layers is a promising approach to create low-resistivity single-crystal Cu nanoelectronic interconnects. (C) 2011 American Institute of Physics. [doi: 10.1063/1.

Seven

patients with superior semicircular canal dehiscence underwent plugging procedure via middle fossa approach, and VEMP thresholds became normalized after the surgery in 3 of them. VEMP test failed to provide accurate diagnosis in only 3 cases.

Conclusion: Air-bone gaps may be a result of various otologic pathologies, and the VEMP test is useful during clinical evaluation, better than tympanometry and acoustic reflexes. To avoid unnecessary middle ear surgery for air-bone gaps with unknown or unsure cause, VEMP test should be used in the differential diagnosis before an expensive imaging study.”
“Objective: This study investigated a novel approach to induce chondrogenic differentiation of human mesenchymal stem cells (hMSC). We hypothesized that a structured buy DAPT three-dimensional co-culture using hMSC and chondrocytes would provide chondroinductive cues to hMSC without inducing hypertrophy.

Method: In an effort to promote optimal chondrogenic differentiation of hMSC, we created bilaminar cell pellets (BCPs), which consist of a spherical population of hMSC encased within a layer of juvenile chondrocytes (JC). In addition Selleckchem ON-01910 to histologic

analyses, we examined proteoglycan content and expression of chondrogenic and hypertrophic genes in BCPs, JC pellets, and hMSC pellets grown in the presence or absence of transforming growth factor-beta (TGF beta) following 21 days of culture in either growth or chondrogenic media.

Results: In either growth or chondrogenic media, we observed that BCPs and JC pellets produced more proteoglycan than hMSC pellets treated with TGF beta. BCPs and JC pellets also exhibited higher expression of the chondrogenic genes Sox9, aggrecan, and collagen 2A1, and lower expression of the hypertrophic genes matrix metalloproteinase-13, Runx2, collagen 1A1, and collagen 10A1 than hMSC pellets. Histologic analyses suggest that JC promote chondrogenic differentiation

of cells in BCPs without hypertrophy. Furthermore, Adriamycin when cultured in hypoxic and inflammatory conditions intended to mimic the injured joint microenvironment, BCPs produced significantly more proteoglycan than either JC pellets or hMSC pellets.

Conclusion: The BCP co-culture promotes a chondrogenic phenotype without hypertrophy and, relative to pellet cultures of hMSCs or JCs alone, is more resistant to the adverse conditions anticipated at the site of articular cartilage repair. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.”
“In recent years, transoral robotic surgery has been introduced as an efficient and a reliable method for excision of selected oral cavity, tongue base, and supraglottic tumors in otolaryngology. In this case report, a 39-year-old woman with a history of hoarseness and dysphagia for approximately 6 months is presented.

In vivo, increased chondroitin-4-sulphation may reduce the attachment of P. falciparum-infected erythrocytes to human cells. Extra-lysosomal localization of ASB and reduced impact of chloroquine when baseline ASB activity is less suggest possible mechanisms of resistance to the effects of chloroquine.”
“Novel citric acid-based polyesters were synthesized by condensation of citric acid,

1,8-octanediol, and unsaturated monomers such as glycerol 1,3-diglycerolate diacrylate and bis(hydroxypropylfumarate). Under the synthesis BI 2536 nmr conditions used, the crosslinked elastomeric network exhibited a wide range of mechanical properties. The mechanical properties of acrylated elastomers ranged from 7.4 to 75.9 MPa for Young’s modulus, 2.8 to 15.7 MPa for ultimate tensile stress, and 86 to 733% for elongation at break. The mechanical properties of fumarate-containing elastomers ranged from 16.4 to 38.3 MPa for Young’s modulus, 5.5 to 10.2 MPa for ultimate tensile stress, and 278 to

260% for elongation at break, which depended on the content of 1-vinyl-2-pyrrolidinone. Addition of a secondary crosslink network is a viable method to increase the range of mechanical properties of citric acid-based biodegradable elastomers. Selleckchem PR 171 The glass transition temperature (T(g)) of the elastomers is between -12.7 and -1.6 degrees C, confirming that all the elastomers are in a rubbery state at room temperature. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 114: 1464-1470, 2009″
“Background: The aim of this study was to compare the effectiveness of an educational strategy (advice to withdraw the overused medication/s) with that of two structured pharmacological detoxification programmes in patients with complicated medication overuse

headache (MOH) plus migraine.

Methods: One hundred and thirty-seven complicated MOH patients participated in the GDC-0941 manufacturer study. MOH was defined as complicated in patients presenting at least one of the following: a) a diagnosis of co-existent and complicating medical illnesses; b) a current diagnosis of mood disorder, anxiety disorder, eating disorder, or substance addiction disorder; c) relapse after previous detoxification treatment; d) social and environmental problems; e) daily use of multiple doses of symptomatic medications. Group A (46 patients) received only intensive advice to withdraw the overused medication/s. Group B (46 patients) underwent a standard detoxification programme as outpatients (advice + steroids + preventive treatment). Group C (45 patients) underwent a standard inpatient withdrawal programme (advice + steroids + fluid replacement and antiemetics preventive treatment).

Methods: The modulatory effects of phytoestrogens and curcumin on the induction ofANXA1 were investigated via sandwich ELISA method, while their effects on the activity of sPLA(2)-V were determined by photometric assays. Besides, the cell viability of these compounds was determined by standard trypan blue exclusion method using PBMCs.

Results: The results indicate a significant increase (p < 0.05) in the total content ofANXA1, particularly by coumestrol (p < 0.01), in both inflammatory and non-inflammatory

cells. Besides, the compounds also exhibited a dose-dependent inhibition selleck chemical of sPLA(2)-V activity; however, among these compounds, curcumin and genistein were the strongest inhibitors with an IC50 value of 11.1 +/- 0.3 mu M and 13.6 +/- 0.6 mu M respectively.

Conclusion: The investigated compounds have a potential to induce synthesis and secretion ofANXA1 as well as inhibitory activity of sPLA(2)-V, suggesting

their inhibitory role in phospholipid metabolism and inflammation.”
“Dejerine-Sottas disease is classified as hereditary motor sensory neuropathy (HMSN) type III and shows Ion Channel Ligand Library cost evidence of Friedreich’s ataxia, significant reduction in nerve conduction velocity (NCV), hypomyelination and demyelination of the nerve fibers.

In this study, a 10-years-old girl with Dejerine-Sottas disease is presented in which routine clinical signs (ataxia and reduced NCV) seem with significant impairments of auditory brainstem pathway. It is indicated that pure tone audiometry, standard tympanometry (tympanometry and acoustic reflex), and otoacoustic emissions (OAEs) showed normal results

in both ears (normal peripheral auditory system). In contrast, auditory brainstem responses (ABRs) indicated DNA Damage inhibitor abnormal findings in absolute latencies of I, III, and V and inter-peak latencies of I-III and I-V. These findings suggested auditory brainstem involvement especially in low and mid regions. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“The spectrum of orbital inflammatory diseases ranges broadly from specific diseases as connective tissue disorders, thyroid ophthalmopathy to non-specific inflammations, which may involve one or multiple structures of the orbit and/ or the surrounding sinus. Idiopathic orbital myositis (IOM) may be a localized process or it can be secondary to systemic diseases. We report 4 patients affected by IOM; in all relapsing diplopia was the main complaint, associated with orbital pain in 3 and with abnormal visual evoked responses in 2. Computed tomography (CT), magnetic resonance imaging (MRI) supported the diagnosis revealing enlargement, altered signal intensity of affected muscles. Repeated MRI scans and extensive laboratory examinations comprising of the search for a remote malignacy, lymproliferative, connective tissue diseases, thyroid ophthalmopathy were necessary to confirm the diagnosis.

METHODS The following four methods were tested: cryoEMBEDDER, float, heat sink, and slide. Standardized specimens of porcine skin were used to ensure uniformity. We measured the time required for a technician to flatten, embed, and cut to the first complete section of PF-6463922 cell line each specimen. Additionally, we measured the depth in microns required to cut into an embedded specimen to achieve a complete

section.

RESULTS There were advantages and disadvantages of each method, and our findings suggest that the heat sink and float methods are more time efficient but that the slide and cryoEMBEDDER methods require less cutting into the specimen to obtain a complete section.”
“Preliminary investigation of a number of plant extracts for allelopathic activity

using seed germination inhibition bioassay showed a promising activity of the water extract of the aerial parts of Mikania scandens. Activity-guided fractionation of the M. scandens extract led to the isolation of the highly allelopathic active compound mikanolide, GSK1120212 with minimum inhibitory concentration of 0.083?mu M?mL-1. As M. scandens is a highly abundant invasive plant in Sri Lanka and other South Asian countries, this plant could be developed as an environment friendly natural herbicide, either in crude form as shredded plant material or as pure mikanolide, which is the major constituent (similar to 0.02%) in the plant.”
“BACKGROUND Unprotected hydrodynamic debridement can produce

aerosols, with the risk of cross-contamination and infection for patients and medical staff.

OBJECTIVE To evaluate the hygienic safety and the role of aerosol prevention QNZ inhibitor of a pulsatile debridement.

METHODS & MATERIALS Bacterial emissions during debridement of chronic ulcer wounds of seven patients using the Debri-Jet hydrodynamic in different modifications were analyzed.

RESULTS Only a special aerosol prevention system (vacuum sensor, flexible cuff applicator) was able to effectively avoid the emission of infection relevant pathogens. The emitted pathogenic spectrum reflects the wound colonization of the individual patient wound; the most mobilized and emitted species were Staphylococcus aureus and Pseudomonas aeruginosa.

CONCLUSION Unprotected pulsatile debridement can produce highly relevant bacterial emissions. Equipped with an elaborate aerosol prevention technique, the Debri-Jet is a hygienically safe and effective debridement system and poses no more hygienic risks than conventional debridement. Because even conventional nonhydrodynamic debridement can produce cross-contamination, basic hygienic precautions, including the wearing of masks, gloves, and eye-shield, and performance of the procedure by trained staff must be used during debridement.”
“Nine secondary metabolites, including four steroids, four phenolics and one cerebroside, were isolated from the methanol extract of the fruiting bodies of the basidiomycete Sarcodon joedes.

Opioid selleck chemicals usage was calculated at day 7 and 3 months posttreatment.

Results.

Compared with pretreatment, VAS pain scores decreased at day 7 and 3 months posttreatment in all three groups (P < 0.01). However, the VAS pain

scores of the BTX-A group decreased more significantly compared with lidocaine and placebo groups at day 7 and 3 months posttreatment (P < 0.01). Sleep time (hours) had improved at day 7 and at 3 months compared with pretreatment in all three groups, but the BTX-A group improved more significantly compared with lidocaine and placebo groups (P < 0.01). The percent of subjects using opioids posttreatment in the BTX-A group was the lowest (21.1%) compared with the lidocaine (52.6%) and placebo (66.7%) groups (P < 0.01).

Conclusions.

Subcutaneous administration of BTX-A significantly decreased pain in PHN and reduced opioid use compared with lidocaine and placebo at day 7 and 3 months post-treatment. It also increased subjects’ sleep times.”
“Objective To

establish a regenerative treatment for soft tissue defects of the external auditory meatus (EAM) without conventional surgical therapy.

Study Design Controlled clinical pilot study.

Setting General Ferroptosis inhibitor hospitals.

Patients Sixty-five patients with new or old EAM defects without active inflammation were selected. Ages ranged from 12 to 87 years (average age of 58 yr).

Intervention Therapeutic nonsurgical treatment of EAM defects. Gelatin sponge, basic fibroblast growth factor (b-FGF), fibrin glue, and water proof transparent dressing were used in the repair procedure. Patients were divided into 2 groups: treatment with (n = 54) and without

(n = 11) b-FGF. After Daporinad in vivo mechanically disrupting the edge of the EAM defect, gelatin sponge immersed in b-FGF was placed over the defect and covered with fibrin glue. In cases of extensive EAM defects, the EAM was filled with gelatin sponge/b-FGF, and the auricle was wrapped in water proof dressing. Two or 3 weeks postprocedure, crust over the defect was removed. If complete defect closure was not achieved after 1 treatment course, the treatment was repeated.

Main Outcome Measure Evaluation of complete closure of EAM defects 3 months posttreatment.

Results Complete closure of the EAM defect was achieved within 3 treatment courses in 92.6% (50/54) and 18.2% (2/11) of the patients with or without b-FGF, respectively. No inflammation/infection or severe sequelae were observed.

Conclusion This study demonstrated the effectiveness of combining gelatin sponge, b-FGF, and fibrin glue for EAM defect regeneration. This innovative regenerative therapy is an easy, simple, cost-effective and minimally invasive method for treating EAM defects.”
“Tumors arising from the proximal biliary tree remain particularly challenging with respect to their evaluation and treatment. Complete resection with negative histologic margins is the most effective treatment modality.

However, the majority of patients are not candidates for surgery.