Exopolysaccharide (pullulan) production from sugarcane bagasse hydrolysate aiming to favor the development of biorefineries.

Pullulan is a biopolymer used in food industry produced by Aureobasidium pullulans from starch. In the present work, sugarcane bagasse (SCB) hydrolysate was evaluated as an alternative substrate in fermentation process assisted by blue LED lights. The best fermentation conditions in Erlenmeyer flasks were 25.3 °C, stirring speed of 232 rpm and yeast extract concentration of 1.88 g/L, yielding 25.19 g/L of pullulan, that corresponded to yield of 0.48 g/g and 0.28 g/(L·h) of volumetric productivity. By using a column bubble photobioreactor, similar yield values were obtained. Thermal properties of the produced pullulan as glass transition (Tg) and melting (Tm) temperatures were 38 °C and 160 °C, respectively, which were similar to the corresponding values of commercial food grade pullulan. Therefore, SCB hydrolysate is a promising substrate to produce good quality pullulan (86% of purity) with application in food industry, besides to represent a new alternative for biorefineries.

Evaluation of serum (1 → 3)-ß-D-glucan clinical performance: kinetic assessment, comparison with galactomannan and evaluation of confounding factors.

PURPOSE: We investigated the clinical performance of (1 → 3)-ß-D-glucan (BG), as an early marker of invasive fungal infections (IFI), in different clinical settings. METHODS: BG serum levels were assessed by Fungitell (Associates of Cape Cod, Inc), in parallel with galactomannan (GM) when requested by clinicians. By a prospective monocentric study, 270 episodes at risk or with suspect of IFI were enrolled, namely 58 proven-probable invasive aspergillosis (IA), 27 proven invasive candidiasis (IC), 11 possible IC, 16 P.jirovecii pneumonia (PJP), 4 episodes of other IFI and 154 non-IFI controls. RESULTS: We found that (a) the BG overall sensitivity, specificity, positive predictive value and negative predictive value (NPV) were 87.9, 80.5, 76.7 and 89.9 %, respectively; (b) the highest sensitivity was found in the IC groups, followed by PJP, IA and other IFI groups; (c) an association was observed between BG kinetics and patients outcome; (d) in the IA episodes, the combination of BG or GM vs GM alone increased sensitivity from 60.0 to 83.3 % in the haematological patients; (e) false-positive BG results were related to Gram-negative infections or infusion of polyclonal IgM-enriched immunoglobulins, where high levels of BG were indeed detected. CONCLUSION: Besides strengthening its overall good clinical performance, we provide evidence that serum BG correlates with clinical outcome and that, once used in combination with GM, BG allows to enhance IFI diagnosis rate. The high sensitivity and NPV, observed in the Intensive Care Unit setting, open to BG validation as a marker for assessment of antifungal treatment.

Clinical performance of a commercial real-time PCR assay for Aspergillus DNA detection in serum samples from high-risk patients: comparison with a galactomannan enzyme immunoassay.

We investigated the clinical performance of a polymerase chain reaction (PCR)-based commercial platform, the Myconostica MycAssay™ Aspergillus (MAP), for fungal DNA detection in the serum of patients at risk of invasive aspergillosis (IA). Sixty-four hospitalized patients were prospectively enrolled and a total of 71 different episodes were investigated (30 episodes were clinically/microbiologically classified as IA and 41 as control episodes). When MAP was compared to the galactomannan (GM) assay, no significant differences were found in terms of sensitivity (46.7% vs. 50.0%), specificity (97.6% vs. 95.1%), positive predictive value (PPV) (93.3% vs. 88.2%), and negative predictive value (NPV) (71.4% vs. 72.2%). The corresponding areas under the curve (AUC) of the receiver operating characteristic (ROC) curves were also superimposable. Overall, because of the good agreement between the two assays and considering the high specificity and PPV of the MAP, we suggest the use of this PCR-based platform as a second-level examination for the evaluation of clinically undefined cases where culture or GM have provided positive results.

Inhibitory effects of different lactobacilli on Candida albicans hyphal formation and biofilm development.

The aim of this study was to investigate the effects of different species of Lactobacilli on hyphal formation and biofilm development by the opportunistic fungal pathogen Candida albicans. We employed 4 different Lactobacillus species, namely L. rhamnosus, L. acidophilus, L. plantarum and L. reuteri, and 2 C. albicans strains, the reference DAY286 and its isogenic hwp1/hwp1 mutant, the FJS24 strain. As assessed by morphological analysis and quantitative colorimetric assays, Lactobacillus crude filtrate supernatant fluids (CFSF) affected Candida, impairing both hyphal formation and biofilm production. The CFSF-mediated phenomenon occurred in a dilution- and time-dependent manner and was consistently observed, irrespective of the C. albicans HWP1 genotype.

Motorcycle riders' perception of helmet use: complaints and dissatisfaction.

In accidents which involve two-wheeled vehicles the helmet plays a life-saving role, but very little is known about the motorcycle rider's perception of the helmet. We evaluated the relationships between having been involved in an accident and dissatisfaction with the helmet, and between the perception of motorcycle riders and the objective features of the helmet. This was a case-control study: riders of motorized two-wheelers who had been involved in accidents (accident cases) were compared against a similarly interviewed sample of riders that had not been in accidents (control cases). Information about the driver, the vehicle and the helmet was collected in all interviews. To evaluate the relationships, logistic regressions were carried out. The majority of drivers were dissatisfied with their helmets, but no evidence was found to link this dissatisfaction with having been involved in an accident. The two most common complaints related to noisiness, followed by the helmet visor. Complaints did not seem to be statistically associated with physical features of the helmet.

A protein microarray immunoassay for the serological evaluation of the antibody response in vertically transmitted infections.

The detection of specific serum antibodies is mainly achieved by enzyme-linked immunosorbent assay (ELISA). Here, we describe the setting up of a microarray-based serological assay to screen for IgG and IgM against vertically transmitted pathogens (Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus types 1 and 2, varicella zoster virus, Chlamydia trachomatis). The test, accommodated onto a restricted area of a microscope slide, consists of: (a) the immobilization of antigens and human IgG and IgM antibody dilution curves, laid down in an orderly manner; (b) addition of serum samples; (c) detection of antigen-serum antibodies complexes by indirect immunofluorescence. The IgG and IgM curves provide an internal calibration system for the interpolation of the signals from the single antigens. The test was optimized in terms of spotting conditions and processing protocol. The detection limit was 400 fg for the IgG assay and 40 fg for the IgM assay; the analytical specificity was >98%. The clinical sensitivity returned an average value of 78%, the clinical specificity was >96%, the predictive values were >73%, and the efficiency was >88%. The results obtained make this test a promising tool, suitable for introduction in the clinical diagnostic routine of vertically transmitted infections, in parallel (and in future as an alternative) to ELISA.

Event-free survival and cost-effectiveness in adult acute lymphoblastic leukaemia in first remission treated with allogeneic transplantation.

Allogeneic transplantation in patients with acute lymphoblastic leukaemia in first remission (ALL-CR1) has been studied in several clinical trials. However, no pooled survival analysis has yet been done. We conducted a survival meta-analysis to compare allogeneic transplantation vs chemotherapy or autologous transplantation using an intention-to-treat approach. Our study included the controlled clinical trials, wherein allocation to allogeneic transplant was based on donor availability. The event-free individual survival data were reconstructed on the basis of published information and Kaplan-Meier graphs. We then generated the meta-analytic event-free survival curves for the two treatments. The mean survival gain per patient was estimated and a simplified cost-effectiveness assessment was carried out. In the allogeneic transplantation group, 293 patients were examined and 479 as controls (four trials). The event-free survival difference was statistically significant (P=0.011). The relative risk for event occurrence was 0.79 for the experimental group vs the controls (95% CI: 0.66-0.96; P=0.017). The mean survival gain was 1 year per patient. The cost per life-year gained was less than the conventional threshold of 50,000 euros. Allogeneic transplantation in ALL-CR1 improves event-free survival as compared to chemotherapy or autologous transplantation. Its cost-effectiveness profile is acceptable.

Defense of breast cancer malpractice claims.

The goal of this study was to determine whether factors associated with the successful defense and cost of malpractice cases involving the failure to diagnose breast cancer could be identified in medical and legal records. Secondary goals were to develop a multidisciplinary clinical algorithm utilizing National Comprehensive Cancer Network (NCCN) practice guidelines with practitioner risk management strategies. Physician deviations from these guidelines were tracked to identify high-risk areas in the diagnosis of breast cancer. A multidisciplinary clinical algorithm was introduced and practitioner risk management issues were addressed. In this study specific medical, legal, and cost factors were retrospectively abstracted and analyzed to identify associations between medical and legal factors and medicolegal outcome. ProMutual handled 156 malpractice cases involving breast cancer between January 22, 1986, and November 20, 1997. Of the total, 124 cases involving 212 defendants were closed. The closed cases were analyzed, using multivariable stepwise logistic and linear regression, to identify associations between clinical factors and case outcome. Women's health practitioners (WHPs), including obstetrician-gynecologists (OB-GYNs), family medicine, and internal medicine clinicians, were the largest group of defendants (97). Others included radiologists (43), surgeons (33), and pathologists (3). OB-GYNs accounted for 31% of these defendants, with a cost of more than $16 million. The greatest number of specialists represented in the open cases were radiologists, with 38% of the total. The defense model predicts that the probability of successful defense is lessened with inadequate record keeping, a patient that has metastasis and is alive, and a delay in diagnosis of 12 months or more. The overall indemnity model predicts a higher indemnity with the spread of disease at the time of evaluation, a patient who has metastasis and is alive, and a date of occurrence closer to the present. Indemnity is less in patients who have had a lymph node dissection, who have died, or who are alive without metastasis. The WHP model predicts an increased overall indemnity with the spread of disease at the time of evaluation and the presence of a mass without pain. Indemnity decreases with a history of pregnancy, absence of presenting symptoms, or presentation with pain with or without a mass, and the performance of a lymph node dissection.

Evaluation of linear and nonlinear tomosynthetic reconstruction methods in digital mammography.

RATIONALE AND OBJECTIVES: The purpose of this study was to comparatively evaluate digital planar mammography and both linear and nonlinear tomosynthetic reconstruction methods. MATERIALS AND METHODS: A "disk" (ie, target) identification study was conducted to compare planar and reconstruction methods. Projective data using a composite phantom with circular disks were acquired in both planar and tomographic modes by using a full-field, digital mammographic system. Two-dimensional projections were reconstructed with both linear (ie, backprojection) and nonlinear (ie, maximization and minimization) tuned-aperture computed tomographic (TACT) methods to produce three-dimensional data sets. Four board-certified radiologists and one 4th-year radiology resident participated as observers. All images were compared by these observers in terms of the number of disks identified. RESULTS: Significant differences (P < .05, Bonferroni adjusted) were observed between all reconstruction and planar methods. No significant difference, however, was observed between the planar methods, and only a marginally significant difference (P < .054, Bonferroni adjusted) was observed between TACT-backprojection and TACT-minimization. CONCLUSION: A combination of linear and nonlinear reconstruction schemes may have potential implications in terms of enhancing image visualization to provide radiologists with valuable diagnostic information.

Comparison of full-field digital mammography with screen-film mammography for cancer detection: results of 4,945 paired examinations.

PURPOSE: To prospectively compare full-field digital mammography (FFDM) with screen-film mammography (SFM) for cancer detection in a screening population. MATERIALS AND METHODS: At two institutions, 4,945 FFDM examinations were performed in women aged 40 years and older presenting for SFM. Two views of each breast were acquired with each modality. SFM and FFDM images were interpreted independently. Findings detected with either SFM or FFDM were evaluated with additional imaging and, if warranted, biopsy. RESULTS: Patients in the study underwent 152 biopsies, which resulted in the diagnosis of 35 breast cancers. Twenty-two cancers were detected with SFM and 21 with FFDM. Four were interval cancers that became palpable within 1 year of screening and were considered false-negative findings with both modalities. The difference in cancer detection rate was not significant. FFDM had a significantly lower recall rate (11.5%; 568 of 4,945) than SFM (13.8%; 685 of 4,945) (P <.001, McNemar chi(2) model; P <.03, generalized estimating equations model). The positive biopsy rate for findings detected with FFDM (30%; 21 of 69) was higher than that for findings detected with SFM (19%; 22 of 114), but this difference was not significant. CONCLUSION: No difference in cancer detection rate has yet been observed between FFDM and SFM. FFDM has so far led to fewer recalls than SFM.

Breast imaging using an amorphous silicon-based full-field digital mammographic system: stability of a clinical prototype.

An amorphous silicon-based full-breast imager for digital mammography was evaluated for detector stability over a period of 1 year. This imager uses a structured CsI:TI scintillator coupled to an amorphous silicon layer with a 100-micron pixel pitch and read out by special purpose electronics. The stability of the system was characterized using the following quantifiable metrics: conversion factor (mean number of electrons generated per incident x-ray), presampling modulation transfer function (MTF), detector linearity and sensitivity, detector signal-to-noise ratio (SNR), and American College of Radiology (ACR) accreditation phantom scores. Qualitative metrics such as flat field uniformity, geometric distortion, and Society of Motion Picture and Television Engineers (SMPTE) test pattern image quality were also used to study the stability of the system. Observations made over this 1-year period indicated that the maximum variation from the average of the measurements were less than 0.5% for conversion factor, 3% for presampling MTF over all spatial frequencies, 5% for signal response, linearity and sensitivity, 12% for SNR over seven locations for all 3 target-filter combinations, and 0% for ACR accreditation phantom scores. ACR mammographic accreditation phantom images indicated the ability to resolve 5 fibers, 4 speck groups, and 5 masses at a mean glandular dose of 1.23 mGy. The SMPTE pattern image quality test for the display monitors used for image viewing indicated ability to discern all contrast steps and ability to distinguish line-pair images at the center and corners of the image. No bleeding effects were observed in the image. Flat field uniformity for all 3 target-filter combinations displayed no artifacts such as gridlines, bad detector rows or columns, horizontal or vertical streaks, or bad pixels. Wire mesh screen images indicated uniform resolution and no geometric distortion.

Comparison of tomosynthesis methods used with digital mammography.

RATIONALE AND OBJECTIVES: The authors performed this study to investigate the potential applicability of tomosynthesis to digital mammography. Four methods of tomosynthesis-tuned aperture computed tomography (TACT)-backprojection, TACT-iterative restoration, iterative reconstruction with expectation maximization, and Bayesian smoothing-were compared to planar mammography and analyzed in terms of their contrast-detail characteristics. Specific comparisons between the tomosynthesis methods were not attempted in this study. MATERIALS AND METHODS: A full-field, amorphous, silicon-based, flat-panel digital mammographic system was used to obtain planar and tomosynthesis projection images. A composite tomosynthesis phantom with a centrally located contrast-detail insert was used as the object of interest. The total exposure for multiple views with tomosynthesis was always equal to or less than that for the planar technique. Algorithms were used to reconstruct the object from the acquired projections. RESULTS: Threshold contrast characteristics with all tomosynthesis reconstruction methods were significantly better than those with planar mammography, even when planar mammography was performed at more than twice the exposure level. Reduction of out-of-plane structural components was observed in all the tomosynthesis methods analyzed. CONCLUSION: The contrast-detail trends of all the tomosynthesis methods analyzed in this study were better than those of planar mammography. Further optimization of the algorithms could lead to better image reconstruction, which would improve visualization of valuable diagnostic information.

Mammographic imaging with a small format CCD-based digital cassette: physical characteristics of a clinical system.

The physical characteristics of a clinical charge coupled device (CCD)-based imager (Senovision, GE Medical Systems, Milwaukee, WI) for small-field digital mammography have been investigated. The imager employs a MinR 2000 (Eastman Kodak Company, Rochester, NY) scintillator coupled by a 1:1 optical fiber to a front-illuminated 61 x 61 mm CCD operating at a pixel pitch of 30 microns. Objective criteria such as modulation transfer function (MTF), noise power spectrum (NPS), detective quantum efficiency (DQE), and noise equivalent quanta (NEQ) were employed for this evaluation. The results demonstrated a limiting spatial resolution (10% MTF) of 10 cy/mm. The measured DQE of the current prototype utilizing a 28 kVp, Mo-Mo spectrum beam hardened with 4.5 cm Lucite is approximately 40% at close to zero spatial frequency at an exposure of 8.2 mR, and decreases to approximately 28% at a low exposure of 1.1 mR. Detector element nonuniformity and electronic gain variations were not significant after appropriate calibration and software corrections. The response of the imager was linear and did not exhibit signal saturation under tested exposure conditions.

Potential contribution of computer-aided detection to the sensitivity of screening mammography.

PURPOSE: To determine the false-negative rate in screening mammography, the capability of computer-aided detection (CAD) to identify these missed lesions, and whether or not CAD increases the radiologists' recall rate. MATERIALS AND METHODS: All available screening mammograms that led to the detection of biopsy-proved cancer (n = 1,083) and the most recent corresponding prior mammograms (n = 427) were collected from 13 facilities. Panels of radiologists evaluated the retrospectively visible prior mammograms by means of blinded review. All mammograms were analyzed by a CAD system that marks features associated with cancer. The recall rates of 14 radiologists were prospectively measured before and after installation of the CAD system. RESULTS: At retrospective review, 67% (286 of 427) of screening mammography-detected breast cancers were visible on the prior mammograms. At independent, blinded review by panels of radiologists, 27% (115 of 427) were interpreted as warranting recall on the basis of a statistical evaluation index; and the CAD system correctly marked 77% (89 of 115) of these cases. The original attending radiologists' sensitivity was 79% (427 of [427 + 115]). There was no statistically significant increase in the radiologists' recall rate when comparing the values before (8.3%) with those after (7.6%) installation of the CAD system. CONCLUSION: The original attending radiologists had a false-negative rate of 21% (115 of [427 + 115]). CAD prompting could have potentially helped reduce this false-negative rate by 77% (89 of 115) without an increase in the recall rate.

Full breast digital mammography with an amorphous silicon-based flat panel detector: physical characteristics of a clinical prototype.

The physical characteristics of a clinical prototype amorphous silicon-based flat panel imager for full-breast digital mammography have been investigated. The imager employs a thin thallium doped CsI scintillator on an amorphous silicon matrix of detector elements with a pixel pitch of 100 microm. Objective criteria such as modulation transfer function (MTF), noise power spectrum, detective quantum efficiency (DQE), and noise equivalent quanta were employed for this evaluation. The presampling MTF was found to be 0.73, 0.42, and 0.28 at 2, 4, and 5 cycles/mm, respectively. The measured DQE of the current prototype utilizing a 28 kVp, Mo-Mo spectrum beam hardened with 4.5 cm Lucite is approximately 55% at close to zero spatial frequency at an exposure of 32.8 mR, and decreases to approximately 40% at a low exposure of 1.3 mR. Detector element nonuniformity and electronic gain variations were not significant after appropriate calibration and software corrections. The response of the imager was linear and did not exhibit signal saturation under tested exposure conditions.