A near-miss management system architecture for the forensic investigation of software failures.

Digital forensics has been proposed as a methodology for doing root-cause analysis of major software failures for quite a while. Despite this, similar software failures still occur repeatedly. A reason for this is the difficulty of obtaining detailed evidence of software failures. Acquiring such evidence can be challenging, as the relevant data may be lost or corrupt following a software system's crash. This paper proposes the use of near-miss analysis to improve on the collection of evidence for software failures. Near-miss analysis is an incident investigation technique that detects and subsequently analyses indicators of failures. The results of a near-miss analysis investigation are then used to detect an upcoming failure before the failure unfolds. The detection of these indicators - known as near misses - therefore provides an opportunity to proactively collect relevant data that can be used as digital evidence, pertaining to software failures. A Near Miss Management System (NMS) architecture for the forensic investigation of software failures is proposed. The viability of the proposed architecture is demonstrated through a prototype.

Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone.

Ondansetron (OND) is a new 5-HT3 receptor antagonist that give complete protection from emesis/nausea in approximately 50% of cisplatin (CDDP)-treated patients. To evaluate if dexamethasone (DEX) added to OND increases antiemetic efficacy, we carried out a double-blind randomized crossover study to compare the antiemetic activity of OND with OND plus DEX. One hundred two chemotherapy-naive patients (44 women and 58 men) scheduled to receive CDDP chemotherapy at doses greater than or equal to 50 mg/m2 entered the study. Eighty-nine patients completed both cycles with the following results: complete protection from emesis/nausea was obtained in 57/59 patients (64.0%/66.3%) with OND and in 81/79 (91.0%/88.8%) with OND plus DEX (P = .0005/P = .0021). At the end of the study, 53% of the patients expressed a treatment preference, and of these, 74% chose OND plus DEX compared with 26% who preferred OND alone, a statistically significant difference (P less than .003). Side effects were very mild and not significantly different between the two treatments. We conclude that OND plus DEX is more efficacious than OND in protecting patients from CDDP-induced emesis and nausea.

Double-blind, multicenter, randomized trial to compare the effect of two doses of adrenocorticotropic hormone versus placebo in controlling delayed emesis after high-dose cisplatin in adult patients with cancer.

PURPOSE: To compare, in a double-blind, placebo-controlled, randomized trial, the efficacy of two different doses of the depot formulation of adrenocorticotropic hormone (ACTH) in controlling delayed emesis after cisplatin. PATIENTS AND METHODS: One hundred fifty-two patients were enrolled onto the study. On day 1, all patients received cisplatin (60 to 120 mg/m2) and a combination of dexamethasone 20 mg plus ondansetron or metoclopramide to prevent acute emesis. On day 2 (24 hours after cisplatin administration), patients were randomized to receive placebo, or ACTH 1 mg intramuscularly (I.M.), or ACTH 2 mg I.M. plus one additional dose of 1 mg on day 4. Details of vomiting, nausea, and adverse effects were recorded daily for every 24-hour period from day 2 to day 6. In a subset of patients, serum cortisol levels were measured between 20 and 72 hours after cisplatin administration. RESULTS: One hundred fifty patients were assessable. Over the 5 days of the study, delayed vomiting occurred less frequently in the patients treated with ACTH 2 mg plus 1 mg than in those treated with ACTH 1 mg or placebo (28%, 38%, and 65%, respectively; P = .001). The greatest observed differences were seen on days 2 (24 to 48 hours; P = .01) and 3 (48 to 72 hours; P = .01). On days 4, 5, and 6 (96 to 144 hours), no significant differences were observed among the three arms. The severity of delayed emesis expressed as the mean number of emetic episodes per day was 0.48, 0.70, and 0.80, respectively (P = .002). Patients treated with the higher dose of ACTH had the least nausea on day 3 (P = .02) and day 4 (P = .03). Adrenal cortisol secretion rapidly increased after ACTH injection, but was suppressed for approximately 44 hours in the placebo group. Toxicity was mild and transient in all groups. CONCLUSION: ACTH reduces the incidence and severity of delayed vomiting and nausea after cisplatin. A dose of 2 mg 24 hours after cisplatin is better than one of 1 mg. Whether the activity of ACTH is mediated only by adrenal corticosteroids needs to be verified.

Cellular components and tunic architecture of the solitary ascidian Styela canopus (Stolidobranchiata, Styelidae).

Cell distribution and tunic morphology in the ascidian Styela canopus were examined by electron microscopy. The observations showed that the outer covering is composed of a thin sinuous cuticle with several protrusions and a deep layer of ground substance. The fibrous component and its arrangement in the tunic were demonstrated: elementary fibrils exhibit a 'microtubular' structure and an elliptical cross-sectional shape. Four types of cells were described: clear vesicular tunic granulocytes, tunic microgranulocytes, unilocular tunic granulocytes, and globular tunic granulocytes. Morphofunctional aspects of the tunic tissue and certain phylogenetic relationships are discussed.

Localization of antimicrobial peptides in the tunic of Ciona intestinalis (Ascidiacea, Tunicata) and their involvement in local inflammatory-like reactions.

Tunicates comprising a wide variety of different species synthesize antimicrobial peptides as important effector molecules of the innate immune system. Recently, two putative gene families coding for antimicrobial peptides were identified in the expressed sequence tag database of the tunicate Ciona intestinalis. Two synthetic peptides representing the cationic core region of one member of each of the families displayed potent antibacterial and antifungal activities. Moreover, the natural peptides were demonstrated to be synthesized and stored in distinct hemocyte types. Here, we investigated the presence of these natural peptides, namely Ci-MAM-A and Ci-PAP-A, in the tunic of C. intestinalis considering that the ascidian tunic is a body surface barrier exposed to constant microbial assault. Furthermore, as the tunic may represent a major route of entry for pathogen invasion after its damage we monitored the location of these peptides upon a local inflammatory-like reaction induced by injection of foreign cells. Using immunocytochemistry and electron microscopy both peptides were localized to the tunic and were massively present in granulocytes of inflamed tissue. Conclusively, antimicrobial peptides may constitute a chemical barrier within the tunic of urochordates.

A fraud management system architecture for next-generation networks.

This paper proposes an original architecture for a fraud management system (FMS) for convergent. Next-generation networks (NGNs), which are based on the Internet protocol (IP). The architecture has the potential to satisfy the requirements of flexibility and application-independency for effective fraud detection in NGNs that cannot be met by traditional FMSs. The proposed architecture has a thorough four-stage detection process that analyses billing records in IP detail record (IPDR) format - an emerging IP-based billing standard - for signs of fraud. Its key feature is its usage of neural networks in the form of self-organising maps (SOMs) to help uncover unknown NGN fraud scenarios. A prototype was implemented to test the effectiveness of using a SOM for fraud detection and is also described in the paper.

Primary chemotherapy in operable breast carcinoma comparing CMF (cyclophosphamide, methotrexate, 5-fluorouracil) with an anthracycline-containing regimen: short-term responses translated into long-term outcomes.

BACKGROUND: The role of anthracyclines has been extensively studied in adjuvant chemotherapy, but much less in the primary chemotherapy of early breast carcinoma. This study, comparing CMF (cyclophosphamide, methotrexate, 5-fluorouracil) with the rotational anthracycline-containing regimen CMFEV (CMF plus epirubicin and vincristine) administered as primary chemotherapy, demonstrated a significant increase in clinical complete response in premenopausal women. We report the long-term results. PATIENTS AND METHODS: Two hundred and eleven patients with stage I or II palpable breast carcinoma and a tumour diameter of >2.5 cm were randomised to receive CMF or CMFEV for four cycles before surgery. After surgery, the patients in both arms received adjuvant CMF for three cycles. RESULTS: In the study population as a whole, there was a non-significant 20% reduction in mortality and relapse rates in the CMFEV arm. However, the effect of the experimental regimen was only found in premenopausal patients, especially in terms of relapse-free survival (P=0.07) and locoregional relapse-free survival (P=0.0009), thus mirroring the effect on response rates. After 10 years, the proportions of premenopausal patients free from locoregional relapse as a first event in the CMF and CMFEV groups were 68% and 97%, respectively. No relevant differences were found in postmenopausal patients. CONCLUSION: The overall results of this study showed that the greater activity of the experimental anthracycline-containing combination over CMF as primary chemotherapy in premenopausal patients translated into long-term effects in the same subgroup.

Fine structural observations of the granulocytes involved in the tunic inflammatory-like reaction of Ciona intestinalis (Tunicata).

Erythrocytes injected into the tunic of Ciona intestinalis induced an inflammatory-like reaction which can cause lysis of the neighboring tissue. Electron microscopy observations of the granulocytes of the injured tunic show lysosomic figures and degranulations features suggesting granulocyte involvement in the destructive process.

Cryptosporidiosis among children attending the Maternity and Paediatrics Teaching Hospital, Wad Medani, Central Region, Sudan.

Modified Ziehl Neelson staining technique was used to identify Cryptosporidium species oocysts in stool specimens. Faecal samples from 166 children with diarrhoea and from a control of 95 children, were submitted for examination. 13 children from among those with diarrhoea and none from the control group were found to have Cryptosporidium species oocysts. The majority of these 13 positive children presented with abdominal pain, nausea, low grade fever and anorexia.

Hemocyte migration during inflammatory-like reaction of Ciona intestinalis (Tunicata, ascidiacea).

Following an injuring factor such as the injection of erythrocytes into the tunic of Ciona intestinalis, an inflammatory-like response occurs and blood cells are massively involved in these mechanisms. Electron microscope observations illustrate the infiltration and migration of blood cells throughout the mantle epithelium into the tunic and show several prominent morphological changes.

Encapsulation response of Ciona intestinalis (Ascidiacea) to intratunical erythrocyte injection. I. The inner capsular architecture.

Previous studies on the ascidian Ciona intestinalis have shown that an encapsulation response is experimentally induced by inserting vertebrate erythrocytes into the tunic, which initiates a massive inflammatory cell infiltration to isolate the injured area. Several hemocytes contribute to capsule formation, destruction of the foreign cells, tunic regeneration, and wound healing. The fine features of some inflammatory cell types are described although the complete capsular structure is not yet reported. Accordingly, the present investigation further examines various aspects of this cellular reaction against erythrocytes and, for the first time, presents the involvement of extratunical circulating hemocytes and mantle epithelium in capsule formation.

Different phenotypes of colon carcinoma cells interacting with endothelial cells: role of E-selectin and ultrastructural data.

Adhesion molecules are intimately involved in the process of tumour progression. Among them, E-selectin is an inducible endothelial cell adhesion molecule that plays a role in the interactions of neoplastic cells with the endothelium. These interactions are required for the trans-endothelial migration of tumour cells that leads to the growth at the new sites. Since the detailed events in the early phase of metastasis still remain poorly defined, our study has undertaken an electron-microscopic analysis of the interactions of human colon carcinoma cells with endothelial cells as well as an analysis of the effect of recombinant purified E-selectin in the cell signalling involved in colon cancer cell malignant phenotype. Results revealed that SW480 and T84 colon cancer cell lines show different features, different adhesion kinetics, a different cytoskeletal organization, and a different tyrosine phosphorylation pattern when seeded on an endothelial cell monolayer or recombinant E-selectin. In particular T84 cancer cells adhere more efficiently to the E-selectin and this interaction is associated with pronounced morphological changes, actin redistribution and filopodial processes, and an increase in tyrosine phosphorylation of different proteins. These data support the hypothesis that E-selectin ligand is not only a cell-cell adhesion molecule but also initiates a signalling transduction pathway inside the cells.

Encapsulation response of Ciona intestinalis (Ascidiacea) to intratunical erythrocyte injection.

Electron microscopic studies on the encapsulation induced by erythrocyte injection into the tunic of the ascidian Ciona intestinalis were carried out. The observations reported in the present paper complete the description previously given of capsule architecture and contribute to the characterization of the cells involved in the inflammatory reaction. The inflamed area is surrounded by an ample and peculiar "three-layered coat" respectively composed of flattened and packed extratunical hemocytes, the monolayered epithelium, and a layer of intratunical electron-dense particles. The latter are also clustered, variously arranged, and distributed in the tunic ground substance. The epithelial cells appear to be undergoing an active secretory phase; in several regions they also show discontinuities and organule and surface changes. The infiltrating hemocytes, mainly globular and unilocular granulocytes, appear frequently to be degranulating and in relation with electron-dense particles, net-like fibrous materials, and fine membranes. The involvement of morula-shaped granulocytes is discussed, as well as possible relationships with the melanization process, and finally analogies in the structural organization with the inflammatory reactions induced in other invertebrates. A schematic drawing, based on all available observations of the capsule architecture, is presented in order to reconstruct the entire inflamed area and illustrate the relative fine features.

Vinorelbine combined with paclitaxel infused over 96 hours (VI-TA-96) for patients with metastatic breast carcinoma.

BACKGROUND: Vinorelbine (VI) and paclitaxel (TA) are among the most active single agents in the treatment of patients with breast carcinoma, and both have microtubules as their cytotoxic target. This Phase I-II study combined these 2 agents and used a 96-hour intravenous (i.v.) infusion of paclitaxel to maximize their cytotoxic activities. METHODS: Patients with metastatic breast carcinoma who were previously treated with chemotherapy were administered increasing doses of a 96-hour paclitaxel i.v. infusion from Days 1 to 5, with a first fixed dose of vinorelbine (12.5 mg/m(2) on Days 1 and 5) every 3 weeks. The dose of paclitaxel was then decreased starting from the previously established tolerated dose, and a second fixed dose of vinorelbine (15 mg/m(2) on Days 1 and 5) was given. This identified 2 acceptable doses of paclitaxel (110 mg/m(2) with VI 12.5 mg/m(2) and 90 mg/m(2) with VI 15 mg/m(2)). The latter was used in the subsequent Phase II study. RESULTS: For the 50 patients treated with any dose, the complete response (CR) and the CR plus partial response (PR) rates were, respectively, 14% and 48% (95% confidence interval [CI], 34-67%). When only the 27 patients treated with the Phase II dose were considered, the figures were, respectively, 11% and 52% (95% CI, 42-62%). The median time to progression was 26 weeks, and the median survival 51 weeks. The dose-limiting toxicity was febrile neutropenia. CONCLUSIONS: At the dose schedule identified for the Phase II study, the VI-TA-96 combination has considerable antitumor activity; pharmacoeconomic interest (it requires about half the doses of the agents administered singly); no major toxicity, except G4 neutropenia; and no need for premedication. This combination may be recommended as one of the most effective therapeutic options for patients with metastatic breast carcinoma who were pretreated mainly with anthracycline-containing chemotherapy.

Bcl-2 expression on fine-needle aspirates from primary breast carcinoma: correlation with other biologic factors.

BACKGROUND: The bcl-2 gene encodes for a protein that is involved in cell death regulation. It frequently is expressed in breast tumors, in which it is associated with favorable prognostic factors. It has been suggested that bcl-2 also may act as a modulator of response to chemotherapy and/or endocrine therapy. Because fine-needle aspiration (FNA) biopsy has been established as a reliable method for the diagnosis and biologic characterization of breast carcinoma, we assessed Bcl-2 expression on FNAs from primary breast carcinoma and evaluated its correlations with other prognostic variables. METHODS: Bcl-2, estrogen receptor (ER), progesterone receptor (PgR), p53 protein expression, and Ki-67 growth fraction were evaluated by immunocytochemistry on FNAs from 130 patients with primary breast carcinoma. Nuclear cytologic grade was assessed on FNA smears. RESULTS: Bcl-2 was expressed in 99 of 130 FNAs (76%). Bcl-2 expression was correlated with positive ER (P < 0.001) and PgR (P < 0.001) status and inversely correlated with p53 (P = 0.0036), Ki-67 (P = 0.0073), and nuclear cytologic grade (P < 0.001). CONCLUSIONS: Bcl-2 expression, evaluated by immunocytochemistry on FNAs from primary breast carcinoma, correlates with favorable prognostic features such as ER and PgR expression, p53 negativity, a low Ki-67 index, and high tumor differentiation. These results are in agreement with those found on histologic samples. As FNA biopsy is used increasingly as a primary tool in the diagnosis of breast carcinoma, Bcl-2 evaluation by immunocytochemistry on FNA may provide, in addition to other biologic variables, useful information for prognostic and predictive purposes, particularly in patients considered to be candidates for neoadjuvant treatments. Cancer (Cancer Cytopathol)

Retinyl ester hydrolases in retinal pigment epithelium.

In bovine retinal pigment epithelium membranes we have found three hydrolases which were active against trans-retinyl palmitate. This was possible by assaying different subcellular fractions as a function of pH in the range 3-9. Detection of these activities has been favored by the use in the enzyme assay of Triton X-100, which has an activating effect up to a concentration of 0.03% at a detergent-protein ratio of about 1.5-3.0. Apparent kinetic parameters for the retinyl ester hydrolases have been determined after a study of the optimization of assay conditions. Vmax values for hydrolases acting at pH 4.5, 6.0, and 7.0 were, respectively, 156, 55, and 70 nmol/h/mg. To identify the subcellular site for these hydrolytic activities, assays of marker enzymes from various organelles in each subcellular preparation were carried out, demonstrating the lysosomal origin of the pH 4.5 retinyl ester hydrolase and the microsomal origin of the pH 6.0 retinyl ester hydrolase and suggesting that the pH 7.0 retinyl ester hydrolase originates from the Golgi complex.

Activation of the acrosome reaction after treatment with human follicular fluid. A morphofunctional evaluation useful for in vitro fertilization.

Studies aided by transmission electron microscopy were made in order to evaluate the occurrence and efficiency of the human follicular fluid in the activation of the processes leading to the acrosome reaction; quantitative, qualitative and morphological data and relative evaluations are here presented. The effects of the human follicular fluid were compared with those determined by other types of treatment, semen untreated, Pellet-Swim-up, and Centrifugation on Discontinuous Percoll Gradient. The transmission electron microscope observations permitted to evaluate the percentage of sperm with an activation of the acrosome reaction in the different groups. The analysis of the data showed a statistically relevant difference (P < 0.001) among the first group (Control group) and the SU group, the MP group and the hFF group, regarding the sperm with AR activation. The sperm treatment with 50% diluted hFF represents an important option to the preparation protocols of the semen samples useful for ART.

E-selectin modulates the malignant properties of T84 colon carcinoma cells.

The extravasation of metastatic cells is regulated by molecular events involving the initial adhesion of tumor cells to the endothelium and subsequently the migration of cells in the host connective tissue. E-selectin on endothelial cells and sialyl Lewis X carbohydrate component on tumor cells are mainly involved in the adhesion of colon carcinoma cells to the endothelium of target organ. Interaction of T84 colon cancer cells to purified E-selectin in vitro caused an increase in the tyrosine phosphorylation of a number of proteins as well as the modulation of cellular properties correlated to the metastatic phenotype. Specifically, E-selectin-stimulated actin reorganization, increased collagenase secretion, and induced cell migration. Treatment of T84 cells with herbimycin A inhibited cell adhesion as well as selectin-induced increase of cell migration, and cytoskeleton assembly. Our data demonstrate that binding of cancer cells to E-selectin starts signal transduction pathways which may affect the tumor metastatic abilities.