Search

Purpose: This study aimed to evaluate the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in patients with multiple sclerosis (MS)., Material and Methods: From November 2009 to February 2010, 74 participants (40 MS patients and 34 healthy controls) were enrolled in a randomised singleblind prospective study. All participants underwent ultrasonography (US) to detect signs of CCSVI., Results: CCSVI was detected in 55% of patients in the MS group and 35% in the control group; the difference was not statistically significant (p=0.089)., Conclusions: In our experience, a slight difference exists in the prevalence of CCSVI between MS and healthy controls, but it is not as yet clear which parameters may be most significant. This preliminary study failed to show a statistically significant difference in the prevalence of CCSVI among patients affected by MS. It did, however, reveal a tendency that requires a larger number of patients to achieve statistically significant results.

A series of Biginelli adducts bearing different substituents at C-4 position were synthesized by using p-sulfonic acid calix[4]arene as a catalyst. The in vitro potential to scavenge reactive nitrogen/oxygen species (RNS and ROS) and the ability to inhibit cancer cells growth were then investigated. Four adducts were found to be potent scavengers of 2,2-diphenyl-1-picrylhydrazyl (RNS) and/or superoxide anion (ROS) radicals. The antiproliferative activity against cancer cells was disclosed for the first time for 16 monastrol analogs. The capacity of all compounds to inhibit cancer cells growth was dependent on the histological origin of cells, except for BA24, which was highly active against all cell lines. BA20 and BA33 were as potent as the reference drug doxorubicin against adriamycin-resistant ovarian and prostate cancer cells, respectively. These results highlight some monastrol analogs as lead compounds for the design of new free radical scavengers and anticancer agents., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Monolayer field-effect transistors based on a high-mobility n-type polymer are demonstrated. The accurate control of the long-range order by Langmuir-Schäfer (LS) deposition yields dense polymer packing exhibiting good injection properties, relevant current on/off ratio and carrier mobility in a staggered configuration. Layer-by-layer LS film transistors of increasing thickness are fabricated and their performance compared to those of spin-coated films., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gliadin is a constituent of the cereal protein gluten, responsible for the intolerance generated in celiac disease. Its detection is of high interest for food safety of celiac patients, since the only treatment known until now is a lifelong avoidance of this protein in the diet. Therefore, it is essential to have an easy and reliable method of analysis to control the contents in gluten-free foods. An electrochemical magneto immunosensor for the quantification of gliadin or small gliadin fragments in natural or pretreated food samples is described for the first time and compared to a novel magneto-ELISA system based on optical detection. The immunological reaction was performed on magnetic beads as solid support by the oriented covalent immobilization, of the protein gliadin on tosyl-activated beads. Direct, as well as indirect competitive immunoassays were optimized, achieving the best analytical performance with the direct competitive format. Excellent detection limits (in the order of μg L(-1)) were achieved, according to the legislation for gluten-free products. The matrix effect, as well as the performance of the assays was successfully evaluated using spiked gluten-free foodstuffs (skimmed milk and beer), obtaining excellent recovery values in the results., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: It is still unclear whether chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS), because substantial methodological differences have been claimed by Zamboni to account for the lack of results of other groups. Furthermore, the potential role of venous malformations in influencing MS severity has not been fully explored. This information is particularly relevant, because uncontrolled surgical procedures are increasingly offered to MS patients to treat their venous stenoses., Methods: In the present study, CCSVI was studied in 84 MS patients and in 56 healthy subjects by applying the Zamboni method for CCSVI identification., Results: We found no significant differences (p = 0.12) in CCSVI frequency between MS and control subjects. Furthermore, no differences were found between CCSVI-positive and CCSVI-negative patients in terms of relevant clinical variables such as disease duration, time between onset and first relapse, relapsing or progressive disease course, and risk of secondary progression course. Statistically significant differences were not found between CCSVI-positive and CCSVI-negative MS subjects by analyzing direct measures of disability such as mean Expanded Disability Status Scale (EDSS) (p = 0.07), mean progression index (p > 0.1), and mean MS severity score (p > 0.1). The percentage of subjects who reached EDSS 4.0 and 6.0 milestones was not different among CCSVI-negative and CCSVI-positive subjects, and no significant correlation was found between severity of disability and number of positive CCSVI criteria., Interpretation: Our results indicate that CCSVI has no role in either MS risk or MS severity., (Copyright © 2011 American Neurological Association.)

This perspective aims to report on experimental preparation and investigation tools for engineering molecular thin films with a three-dimensional (3D) nanoscale control that is of relevant interest for different emerging applications as well as for the development of calibration standards. Such thin films may be obtained by man-made methods, self-assembly or spatio-temporal self-organization and/or by the combination of these last approaches with external tools. Understanding the main features and the physical-chemistry underlying the related ordering phenomena is in due course and a theoretical framework is under development. In this respect it is of fundamental importance to achieve the ability to get 3D structural images with a nanoscale detail. This issue is at the early stage and novel techniques like electron tomography and scanning transmission X-ray microscopy are very promising.

We report on the application of three-coordinate organoboron polymers, inherently strong electron acceptors, in flexible photovoltaic (PV) cells. Poly[(1,4-divinylenephenylene)(2,4,6-triisopropylphenylborane)] (PDB) has been blended with poly(3-hexylthiophene-2,5-diyl) (P3HT) to form a thin film bulk heterojunction (BHJ) on PET/ITO substrates. Morphology may be modulated to give a high percentage of domains (10-20 nm in size) allowing exciton separation. The photoelectric properties of the BHJs in devices with aluminium back electrodes were imaged by light beam induced current (LBIC) and light beam induced voltage (LBIV) techniques. Open circuit voltages, short circuit currents and overall external quantum efficiencies obtained are among the highest reported for all-polymer PV cells., (Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Summary: A highly sensitive assay for rapidly screening-out Mycobacterium bovis in contaminated samples was developed based on electrochemical genosensing. The assay consists of specific amplification and double-tagging of the IS6110 fragment, highly related to M. bovis, followed by electrochemical detection of the amplified product. PCR amplification was carried out using a labeled set of primers and resulted in a amplicon tagged at each terminus with both biotin and digoxigenin. Two different electrochemical platforms for the detection of the double-tagged amplicon were evaluated: (i) an avidin biocomposite (Av-GEB) and (ii) a magneto sensor (m-GEC) combined with streptavidin magnetic beads. In both cases, the double- tagged amplicon was immobilized through its biotinylated end and electrochemically detected, using an antiDig-HRP conjugate, through its digoxigenin end. The assay was determined to be highly sensitive, based on the detection of 620 and 10 fmol of PCR amplicon using the Av-GEB and m-GEC strategies, respectively. Moreover, the m-GEC assay showed promising features for the detection of M. bovis on dairy farms by screening for the presence of the bacterium's DNA in milk samples. The obtained results are discussed and compared with respect to those of inter-laboratory PCR assays and tuberculin skin testing.

Objective: We describe the long-term outcomes of 510 diabetic patients with critical limb ischemia (CLI) and an active foot ulcer or gangrene, seen at the University Hospital of Rome Tor Vergata, a tertiary care clinic., Research Design and Methods: These patients were seen between November 2002 and November 2007 (mean follow-up 20 +/- 13 months [range 1-66 months]). The Texas Wound Classification was used to grade these wounds that were either class C (ischemia) and D (ischemia+infection) and grade 2-3 (deep-very deep). This comprehensive treatment protocol includes rapid and extensive initial debridement, aggressive use of peripheral percutaneous angioplasty, empirical intravenous antibiotic therapy, and strict follow-up., Results: The protocol was totally applied (with percutaneous angioplasty [PA+]) in 456 (89.4%) patients and partially (without percutaneous angioplasty [PA-]) in 54 (10.6%) patients. Outcomes for the whole group and PA+ and PA- patients are, respectively: healing, n = 310 (60.8%), n = 284 (62.3%), and n = 26 (48.1%); major amputation, n = 80 (15.7%), n = 67 (14.7%), and n = 13 (24.1%); death, n = 83 (16.25%), n = 68 (14.9%), and n = 15 (27.8%); and nonhealing, n = 37 (7.25%), n = 37 (8.1%), and n = 0 (0%) (chi(2) <0.0009). Predicting variables at multivariate analysis were the following: for healing, ulcer dimension, infection, and ischemic heart disease; and for major amputation, ulcer dimension, number of minor amputations, and age. Additional predicting variables for PA+ patients were the following: for healing, transcutaneous oxygen tension [DeltaTcPo(2)]; and for major amputation, basal TcPo(2), basal A1C, DeltaTcPo(2), and percutaneous angioplasty technical failure., Conclusions: Early diagnosis of CLI, aggressive treatment of infection, and extensive use of percutaneous angioplasty in ischemic affected ulcers offers improved outcome for many previously at-risk limbs. Ulcer size >5 cm(2) indicates a reduced chance of healing and increased risk of major amputation. It was thought that all ulcers warrant aggressive treatment including percutaneous angioplasty and that treatment should be considered even for small ischemic ulcers.

To evaluate the efficacy of transcatheter foam sclerotherapy (TCFS) in pelvic varicocele using sodium-tetradecyl-sulfate foam (STSF), we conducted a retrospective study in 38 patients (mean age, 36.9 years; range, 22-44 years) with pelvic congestion syndrome (PCS) treated between January 2000 and June 2005 by TCFS. Pelvic pain was associated with dyspareunia in 23 (60.5%) patients, urinary urgency in 9 (23.7%) patients, and worsening of pain during menstruation and at the end of a day of work in 7 (18.4%) and 38 (100%) patients, respectively. Diagnosis was made by pelvic and transvaginal color Doppler ultrasound examination, demonstrating ovarian or pelvic varices with a diameter >5 mm presenting venous reflux. TCFS was performed in all patients, using 3% STSF. Follow-up was performed by physical examination, pelvic and transvaginal Doppler ultrasound examination and by a questionnaire-based assessment of pain at 1, 3, 6, and 12 months after the procedure. Technical success was achieved in all patients (100%). In three patients a pelvic colic-like pain occurred immediately after sclerotic agent injection, disappearing spontaneously after a few minutes. No recurrent varicoceles were observed during a 12-month follow-up. A statistically significant improvement in each category of specific symptoms was observed at 1, 3, 6, and 12 months after the procedure. We conclude that TCFS of female varicocele using a 3% STSF is safe and effective for the treatment of PCS. It is associated with a significant reduction of symptoms and can be regarded as a valid alternative to other endovascular and surgical techniques.

Pelvic haemorrhage is a rare but important complication that may follow sacrospinous fixation of the vaginal vault. When such complication occurs, packing and clipping of the involved artery is often suggested as the first-line treatment, while arterial embolization is considered only after failure of surgery. In this report, we describe the successful super-selective embolization of a variant of the superior vesical artery in a patient who underwent Endo-Stitch sacrospinous colpopexy. Based on our experience, we suggest that when a well-trained radiological staff is available, endovascular embolization is an effective and less invasive option.

Automated software for cancer registration, called Open Registry and developed by ourselves was adopted by the Varese (population-based) Cancer Registry starting from 1997. Since the use of automated cancer registration is increasing, it is important to assess the quality and completeness of the automated data being produced. In this study, we assessed the completeness of the automatically generated data by comparison with a gold standard of all cases identified by manual and automatic systems for the year 1997 when the automated system was introduced, and the manual system was still in operation. We also evaluated the efficiency of the automated system. 5027 cases were generated automatically; 2959 (59%) were accepted automatically and 2068 (41%) were flagged for manual checking. Sixty-nine cases (1.3%) were not recorded automatically, the most common reason (0.8%) being that the incidence record was dated 1998, even though the case was incident in 1997. A total of 98.7% of all cases found were picked up by the automated system. A completeness figure of 98.7% indicates that the automatic procedure is a valid alternative to manual methods for routine case generation. The fact that 59% of cases were registered automatically indicates that the system can speed up data production and enhance registry efficiency.

Background: Birth defects are a leading cause of neonatal and infant mortality in Italy, however little is known of the etiology of most defects. Improvements in diagnosis have revealed increasing numbers of clinically insignificant defects, while improvements in treatment have increased the survival of those with more serious and complex defects. For etiological studies, prevention, and management, it is important to have population-based monitoring which provides reliable data on the prevalence at birth of such defects., Methods: We recently initiated population-based birth defect monitoring in the Provinces of Mantova, Sondrio and Varese of the Region of Lombardy, northern Italy, and report data for the first year of operation (1999). The registry uses all-electronic source files (hospital discharge files, death certificates, regional health files, and pathology reports) and a proven case-generation methodology, which is described. The data were checked manually by consulting clinical records in hospitals. Completeness was checked against birth certificates by capture-recapture. Data on cases were coded according to the four-digit malformation codes of the International Classification of Diseases, Ninth Revision (ICD-9). We present data only on selected defects., Results: We found 246 selected birth defects in 12,008 live births in 1999, 148 among boys and 98 among girls. Congenital heart defects (particularly septal defects) were the most common (90.8/10,000), followed by defects of the genitourinary tract (34.1/10, 000) (particularly hypospadias in boys), digestive system (23.3/10,000) and central nervous system (14.9/10,000), orofacial clefts (10.8/10,000) and Down syndrome (8.3/10,000). Completeness was satisfactory: analysis of birth certificates resulted in the addition of two birth defect cases to the registry., Conclusion: This is the first population-based analysis on selected major birth defects in the Region. The high birth prevalences for septal heart defect and hypospadias are probably due to the inclusion of minor defects and lack of coding standardization; the latter problem also seems important for other defects. However the data produced are useful for estimating the demands made on the health system by babies with birth defects.

Purpose: The spine is an important source of pain and disability, affecting two thirds of adults at some time in their lives. Treatment in these patients is mainly conservative medical management, based on medication, physical therapy, behavioral management, and psychotherapy, surgery being limited to elective cases with neurologic deficits. This study was carried out to evaluate the efficacy of percutaneous nucleoplasty in patients affected by painful diskal protrusions and contained herniations., Methods: From February 2004 to October 2005, 72 patients (48 men, 24 women; mean age 48 years) affected by lumbar disk herniation were treated with nucleoplasty coblation. All patients were evaluated clinically and with radiography and MRI in order to confirm the presence of lumbalgic and/or sciatalgic pain, in the absence of major neurologic deficit and with lack of response after 6 weeks of conservative management., Results: Average preprocedural pain level for all patients was 8.2 (on a visual analog scale of 1 to 10), while the average pain level at 12 months follow-up was 4.1. At the 1 year evaluation, 79% of patients demonstrated a statistically significant improvement in numeric pain scores (p < 0.01): 17% (12 patients) were completely satisfied with complete resolution of symptoms, and 62% (43 patients) obtained a good result., Conclusion: Our data indicate that nucleoplasty coblation is a promising treatment option for patients with symptomatic disk protrusion and herniation who present with lumbalgic and/or sciatalgic pain, have failed conservative therapies, and are not considered candidates for open surgery.

Background: Automated procedures are increasingly used in cancer registration, and it is important that the data produced are systematically checked for consistency and accuracy. We evaluated an automated procedure for cancer registration adopted by the Lombardy Cancer Registry in 1997, comparing automatically-generated diagnostic codes with those produced manually over one year (1997)., Methods: The automatically generated cancer cases were produced by Open Registry algorithms. For manual registration, trained staff consulted clinical records, pathology reports and death certificates. The social security code, present and checked in both databases in all cases, was used to match the files in the automatic and manual databases. The cancer cases generated by the two methods were compared by manual revision., Results: The automated procedure generated 5027 cases: 2959 (59%) were accepted automatically and 2068 (41%) were flagged for manual checking. Among the cases accepted automatically, discrepancies in data items (surname, first name, sex and date of birth) constituted 8.5% of cases, and discrepancies in the first three digits of the ICD-9 code constituted 1.6%. Among flagged cases, cancers of female genital tract, hematopoietic system, metastatic and ill-defined sites, and oropharynx predominated. The usual reasons were use of specific vs. generic codes, presence of multiple primaries, and use of extranodal vs. nodal codes for lymphomas. The percentage of automatically accepted cases ranged from 83% for breast and thyroid cancers to 13% for metastatic and ill-defined cancer sites., Conclusion: Since 59% of cases were accepted automatically and contained relatively few, mostly trivial discrepancies, the automatic procedure is efficient for routine case generation effectively cutting the workload required for routine case checking by this amount. Among cases not accepted automatically, discrepancies were mainly due to variations in coding practice.

Two patients with posttraumatic priapism underwent transcatheter embolization using microcoils, resulting in temporary penile detumescence and an apparent resolution of the artero-venous fistula. In both cases, priapism recurred 24 hours after the procedure and was successfully treated through selective transcatheter embolization of the nidus using acrylic glue (Glubran 2). The patients showed complete recovery of sexual activity within 30 days from the procedure and persistent exclusion of the artero-venous fistula after a 12-month follow-up.

Background: The aim of the present study was to evaluate the role of non-invasive methods in the early detection of pulmonary and cardiac involvement in Systemic sclerosis (SSc) and to identify clinical and/or instrumental patterns of prognostic value., Patients and Methods: Twenty female patients affected by SSc (8 with diffuse cutaneous SSc and 12 with limited cutaneous SSc) were enrolled in our study. Cardiac and pulmonary involvement (respiratory function tests and carbon monoxide lung diffusion [DLCO], chest radiography, high resolution computed tomography [HRCT] and lung perfusion magnetic resonance) were evaluated., Results: All 18 patients studied with respiratory function tests showed a significant reduction of DLCO. HRCT was considerably more sensitive than traditional chest radiography (59% versus 28%; p<0.05). Lung perfusion MRI revealed normal findings in 15 patients. Abnormal lung perfusion MRI results were found only in 3 patients. Angina pectoris with electrocardiographic and scintigraphic ischemic changes, severe regional wall motion abnormalities and complex arrhythmias seemed to be associated with poor prognosis., Conclusion: Taken together these results indicate that a pulmonary involvement occurs both in limited and in diffuse cutaneous SSc patients and develops, in 83% of the cases, without any regional lung perfusion abnormality. Furthermore, cardiac involvement is detected in 65% of the cases as a consequence of a range of noxious events including myocardial ischemia, fibrosis and pressure overload which may result in ventricular dysfunction and arrhythmias. Lung perfusion MRI should be considered as a complementary diagnostic method for the functional evaluation of these symptoms in systemic sclerosis.

Morton's neuroma (MN) is a frequent cause of metatarsalgia. The aim of our study was to evaluate the efficacy of neuroma alcohol-sclerosing therapy (NAST) under US guide in MN after a 10-month follow-up. Forty intermetatarsal neuromas underwent alcohol-sclerosing therapy after sonographic evaluation of their dimensions and echotexture. After subcutaneous anesthesia, a sclerosing solution composed of anesthetic (carbocaine-adrenaline 70%) and ethylic alcohol (30%) was injected inside the mass under US guidance. The procedure was repeated at intervals of 15 days until the resolution of the symptoms. A total or partial symptomatic relief was obtained in 36 cases (90%). No procedure-related complications were observed. Transitory plantar pain, due to the flogistic reaction induced by the sclerosing solution, occurred in 6 cases (15%). The 10-month follow-up revealed a 20-30% mass volume reduction and an adiposus-like change in echotexture. In the 4 cases (10%) of therapeutic failure, the preliminary sonography demonstrated a hypoechoic echotexture with a strong US beam attenuation corresponding to a highly fibrous neuroma after surgical resection. The NAST is a feasible and cost-efficient procedure with high rates of therapeutic success.

Background: Our aim was to prospectively evaluate a semi-quantitative pulmonary perfusion MR technique using a breath-hold 2D dynamic sequence in patients with severe pulmonary emphysema., Materials and Methods: Thirty patients with severe emphysema were studied with pulmonary perfusion MRI. Results were compared with those obtained through lung scintigraphy, considered as the gold standard technique. We used Fast Field Echo (FFE) pulse sequences in the coronal and sagittal planes, with paramagnetic contrast agent administration. Ten healthy volunteers were studied as the control group. Three thoracic radiologists independently reviewed all the subjects, evaluating the site and entity of perfusional defects. Peak intensity and apparent mean transit time were calculated., Results: MRI showed high sensitivity (86.7%) and good specifity (80.0%) in detecting perfusional defects. We observed lower peak signal intensities in emphysematous regions., Conclusion: Lung perfusion MR is a potential alternative to Nuclear Medicine in the evaluation of severe pulmonary emphysema.

An amperometric enzyme sensor using tyrosinase, also called polyphenol oxidase (PPO), was constructed for determination of phenolic compounds and herbicides. The enzyme was entrapped in a conducting polymer, poly 3,4-ethylenedioxythiophene (PEDT), electrochemically generated on a glassy carbon electrode. Several experimental parameters in the electropolymerisation process and working conditions were determined to optimise biosensor performances. Mono-phenol and di-phenol were tested in oxygenated solutions, by amperometric measurements at -200 mV (vs. SCE) in a batch system. The limit of detection of these molecules ranges from 5 to 500 nM. Detection of herbicides was obtained from the inhibition of tyrosinase electrode responses. The limit of detection for atrazine and diuron was 1 and 0.5 mgl(-1) respectively. These data suggest that PEDT film is a promising PPO immobilisation method.

Purpose: To report our preliminary experience with multi-slice spiral CT coronary angiography of the coronary arteries., Materials and Methods: 50 volunteers (mean age 61 years, range 45-72) with baseline heart rates below 70 bpm underwent multi-detector row CT coronary angiography (GE Light Speed Plus, 140 kVp, 270 mA, 1.25-mm collimation, 0.5-second rotation time, high quality pitch) with retrospective ECG gating after receiving 140-150 ml of iodinated contrast medium (Iopamiro 300 mg-dl, Bracco, Italy) at a flow rate of 4 ml/sec. Three of the 50 patients had previously undergone coronary procedures (1 anterior descending artery stent, 1 left circumflex artery stent and 1 anterior descending artery percutaneous angioplasty) and three were undergoing follow-up examinations after by-pass surgery. The remaining 44 patients were asymptomatic and had no history of coronary artery disease. All CT angiograms were back-reconstructed from 20 to 80% of the diastolic cycle with 10% increments to establish the phase with fewer "stair-step" motion artefacts for each artery. Patients with heart rates above 70 bpm were administered beta-blockers during the five days preceding the examination in doses appropriate for the patient's clinical characteristics., Results: The CT room occupation time ranged from 25 to 35 minutes (mean time 27') and the post-processing time from 30 to 60 minutes (mean time 40'). The left anterior descending artery was best visualised in middle diastole (70% of cardiac cycle), the circumflex artery at 60% of the cardiac cycle, and the right coronary artery at 40%. Out of 132 arteries, 19 (14.4%) were considered non-assessable due to "stair-step" motion artefacts, whereas 2 (1.5%) were only partially visualised owing to the presence of extensive wall calcifications. Among the 113 assessable arteries, we observed: 72 normal coronary arteries without stenosis or wall calcifications (54.5%); 28 arteries with minimal wall irregularities and stenoses below 50% (21.2%); 7 stenoses >50% involving the right coronary artery (no. 2), the anterior descending arteries (no. 4) and the left circumflex artery (no. 1) (5.3%). In the remaining 6 patients, optimal visualisation of the stents and venous and arterial surgical by-passes was obtained., Conclusions: Although further larger-scale studies are required to compare MSCT coronary angiography with CT coronary angiography, the application of MSCT technology to the study of the coronary arteries is a promising technique with a good potential for use in routine clinical practice. In selected patients (with baseline heart rates <70 bpm, or after beta-blocker therapy) it is able to provide very interesting results and could be used as a method of choice for following patients after interventional procedures or as a mass-screening tool to select patients to be referred for coronary angiography.

Until recently, MR examinations of the pancreas were limited by motion artifacts, vascular pulsatility and poor spatial resolution. Today, new techniques have been developed, which allow to overcome these problems and provide additional information such as selective images of biliary and pancreatic ducts and vascular structures. MR examinations of the pancreas need to include either breath-hold or nonbreath-hold morphological T1- and T2-weighted images; a contrast agent is required when the study is performed with fast imaging which allow the acquisition of dynamic images in arterial and portal venous phases. Recently, a new liver-specific contrast agent (Mn-DPDP) has been demonstrated to provide selective pancreatic enhancement. As a complement to baseline sequences, MR cholangiopancreatography images can be acquired, possibly integrated by functional examination after secretin administration. Finally, contrast-enhanced MR angiography opens new perspectives for vascular studies, particularly for the locoregional staging of pancreatic cancer.