Detection of parametric changes in the Peyrard-Bishop- Dauxois model of DNA using nonlinear Kalman filtering.

The derivative-free nonlinear Kalman filter is proposed for state estimation and fault diagnosis in distributed parameter systems of the wave-type and particularly in the Peyrard-Bishop-Dauxois model of DNA dynamics. At a first stage, a nonlinear filtering approach is introduced for estimating the dynamics of the Peyrard-Bishop-Dauxois 1D nonlinear wave equation, through the processing of a small number of measurements. It is shown that the numerical solution of the associated partial differential equation results in a set of nonlinear ordinary differential equations. With the application of a diffeomorphism that is based on differential flatness theory it is shown that an equivalent description of the system is obtained in the linear canonical (Brunovsky) form. This transformation enables to obtain local estimates about the state vector of the DNA model through the application us of the standard Kalman filter recursion. At a second stage, the local statistical approach to fault diagnosis is used to perform fault diagnosis for this distributed parameter system by processing with statistical tools the differences (residuals) between the output of the Kalman filter and the measurements obtained from the distributed parameter system. Optimal selection of the fault threshold is succeeded by using the local statistical approach to fault diagnosis. The efficiency of the proposed filtering approach in the problem of fault diagnosis for parametric change detection, in nonlinear wave-type models of DNA dynamics, is confirmed through simulation experiments.

Nonlinear optimal control for the multi-variable tumor-growth dynamics.

The multivariable tumor-growth dynamic model has been widely used to describe the inhibition of tumor-cells proliferation under the simultaneous infusion of multiple chemotherapeutic drugs. In this article, a nonlinear optimal (H-infinity) control method is developed for the multi-variable tumor-growth model. First, differential flatness properties are proven for the associated state-space description. Next, the state-space description undergoes approximate linearization with the use of first-order Taylor series expansion and through the computation of the associated Jacobian matrices. The linearization process takes place at each sampling instant around a time-varying operating point which is defined by the present value of the system's state vector and by the last sampled value of the control inputs vector. For the approximately linearized model of the system a stabilizing H-infinity feedback controller is designed. To compute the controller's gains an algebraic Riccati equation has to be repetitively solved at each time-step of the control algorithm. The global stability properties of the control scheme are proven through Lyapunov analysis. Finally, the performance of the nonlinear optimal control method is compared against a flatness-based control approach.

Nonlinear optimal control for the synchronization of biological neurons under time-delays.

The article proposes a nonlinear optimal control method for synchronization of neurons that exhibit nonlinear dynamics and are subject to time-delays. The model of the Hindmarsh-Rose (HR) neurons is used as a case study. The dynamic model of the coupled HR neurons undergoes approximate linearization around a temporary operating point which is recomputed at each iteration of the control method. The linearization procedure relies on Taylor series expansion of the model and on computation of the associated Jacobian matrices. For the approximately linearized model of the coupled HR neurons an H-infinity controller is designed. For the selection of the controller's feedback gain an algebraic Riccati equation is repetitively solved at each time-step of the control algorithm. The stability properties of the control loop are proven through Lyapunov analysis. First, it is shown that the H-infinity tracking performance criterion is satisfied. Moreover, it is proven that the control loop is globally asymptotically stable.

Low-dose capecitabine in breast cancer patients with symptomatic bone marrow infiltration: a case study.

BACKGROUND: The prognosis of patients with metastatic breast cancer and symptomatic bone marrow involvement is poor. The aim of treatment to these patients is palliation. In this study, we sought to determine the efficacy of therapy with low doses of capecitabine in this subgroup of patients. PATIENTS AND METHODS: Five consecutive breast cancer patients with overt bone marrow involvement were treated by low doses of capecitabine in our department. Four out of five patients also received bisphosphonates to palliate skeletal symptoms. The influence of this therapeutic regimen on tumor response, blood count normalization and overall survival was analysed. RESULTS: All patients except one responded in terms of their haematological profile within two months of the initiation of treatment. Duration of haematological response was 8+ months for all patients. In two of them, tumor response in other sites was evaluated as stable disease, in one as partial remission and in one as progressive disease. Two patients survived more than 22 months without bone marrow failure. CONCLUSION: These initial results are very encouraging for this subset of patients with poor prognosis and limited life expectancy. The administration of capecitabine might be an efficient alternative treatment option. Our results merit further investigation.

Sarcomatoid differentiation of renal cell carcinoma: a clinical case with literature review.

A small percentage (1-10%) of renal cell carcinomas (RCC) belongs to the sarcomatoid variant. These malignancies are aggressive with worse prognosis and unfortunately the results following immuno- and/or chemotherapy administration are discouraging. A 62-year-old Caucasian male with advanced renal cell cancer and sarcomatoid component treated with sunitinib is presented. Better understanding of prognostic and molecular markers might help the selection of patients with a chance of benefiting from administration of new targeted drugs.

Gemcitabine and oral vinorelbine as salvage treatment in patients with advanced anthracycline- and taxane-pretreated breast cancer.

BACKGROUND: Despite progress achieved with new chemotherapeutic and endocrine agents, advanced breast cancer (ABC) remains a disease with poor prognosis. We sought to determine the efficacy of gemcitabine (GC) and oral vinorelbine (VB) in heavily preatreated ABC. PATIENTS AND METHODS: Patients previously treated with anthracyclines and taxanes in the metastatic setting with progressive disease were eligible. Treatment consisted of VB (60 mg/m2, orally) and GC (1000 mg/m2, intravenous infusion), every two weeks of a 28- day cycle. RESULTS: Thirty-one patients with ABC were enrolled. Toxicity was acceptable, mainly haematological. Three and 8 patients achieved a complete (9.6%) and partial (25.8%) response, respectively; ten patients (32.2%) had stable disease. Median time-to-progression was 5.3 months, while in responders 8.6 months. Median overall survival was 14 months. CONCLUSION: Oral VB and GC is an active and well-tolerated combination in anthracycline/taxane-pretreated ABC, representing an interesting option in this poor prognosis group of patients.

Urachal mucinous adenocarcinoma: a case report.

Adenocarcinomas account for 0.5-2% of all bladder cancers. Urachal carcinoma is a rare neoplasm which represents 0.01% of all cancers in adults and account for one third of bladder adenocarcinomas. A 65-year-old white man with an urachal mucinous adenocarcinoma is reported. None of the known predisposing risk factors for bladder cancer -such as tobacco use and professional exposure to chemicals -were identified in his past medical history. The patient suffered from multiple sclerosis for almost 11 years and in the last 6 years he was treated with low doses of mitoxantrone. He underwent a partial cystectomy and en block excision of the umbilical ligament and remains disease-free after one year. The development of this rare neoplasm should not be clearly dissociated from multiple sclerosis, either aetiologically sharing an unidentified common causative factor or due to its treatment with mitoxantrone.

First-line chemotherapy with fluorouracil-epirubicin-navelbine (FEN) combination in advanced breast cancer.

BACKGROUND: A phase II study was carried out to determine the safety and efficacy of the combination of vinorelbine, epirubicin and 5-fluorouracil (FEN) as first-line chemotherapy in advanced breast cancer (BC). PATIENTS AND METHODS: Thirty-four women with advanced BC, aged 32-75 years (median 59), previously untreated for recurrence, were enrolled in the study. The treatment consisted of fluorouracil 600 mg/m2 on day 1, epirubicin 75 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, every 3 weeks, up to a maximum of 9 cycles. RESULTS: The efficacy appeared favourable with 18 objective responses (3 complete and 15 partial) and 9 disease stabilizations, giving an overall response rate of 53% (95% CI: 36-70). The median progression-free and overall survival was 6 and 18 months, respectively (95% CI: 4.8-7.8 and 16.2-22.2, respectively). Toxicity was acceptable; the main grade 3/4 toxicity was alopecia in 94% of patients, neutropenia in 44% and less frequently gastrointestinal toxicity (9%), anaemia (6%), mucositis (6%), thrombocytopenia (3%) and diarrhoea (3%). No treatment-related death occurred, CONCLUSION: Our results suggest that FEN, as first-line chemotherapy, is an active and well-tolerated treatment for patients with advanced breast cancer.

Simultaneous endometrioid ovarian and uterine carcinoma diagnosed after an in vitro fertilization procedure--case report and review of the literature.

BACKGROUND: The presence of simultaneous carcinomas involving both the ovary and uterus is relatively uncommon, while the possible link between fertility drugs and carcinogenesis still remains controversial. CASE: The case of a 40-year-old patient with simultaneous aggressive endometrioid carcinoma of the ovary and uterus a few months after the sixth attempt of in vitro fertilization is presented. The patient had de novo lung disease at surgery and diffuse metastatic spread to adjacent bone, subcutaneous tissue and the central nervous system (CNS) soon after a spectacular response to the primary paclitaxel/carboplatinum chemotherapy and while on maintenance and second-line chemotherapy, respectively. CONCLUSION: The fulminating course of our patient might in part be attributed to the existence of advanced disease at presentation. Definite conclusions about the possible association with the previously performed assisted reproduction cannot be drawn but close clinical surveillance of such patients before, during and after infertility treatment is strongly warranted.

In vivo synergism between docetaxel and gemcitabine in patients with metastatic breast cancer: general concepts and future perspectives.

The docetaxel and gemcitabine combination is an active regimen as salvage therapy in taxane-resistant or taxane-refractory patients with metastatic breast cancer (MBC). We recently conducted a phase II study administering this combination to patients with MBC after docetaxel failure, with remarkably high response rates that could be attributed to an in vivo synergism between the two drugs. Women with MBC who were refractory or resistant to docetaxel monotherapy as first- or second-line treatment were recruited. Patients with progressive or stable disease after receiving a minimum of four cycles of docetaxel received gemcitabine 900 mg/m(2) on days 1 and 8 plus docetaxel 100 mg/m(2)on day 8, every 3 weeks. Forty-six percent of patients responded (three complete responses, 20 partial responses), while 28% had stable disease and 26% had progressive disease. Median duration of response was 6.07 +/- 2.43 months. Neutropenia was the only grade 4 toxicity, and reported in seven patients. Other grade 3 toxicities included neutropenia (12 patients), thrombocytopenia (seven patients), and anemia (one patient), while nonhematologic toxicities were easily manageable. These data outline the importance of a rational combination of existing, active chemotherapeutic agents for MBC, and broadens our perspectives for more effective combination regimens in various solid tumors in the future.

A phase II study of the effectiveness of docetaxel (Taxotere) in women with advanced breast cancer previously treated with polychemotherapy. Hellenic Cooperative Interhospital Group in Oncology.

PURPOSE: The aim was to study the effectiveness of docetaxel (Taxotere) in patients with advanced breast cancer treated previously with polychemotherapy. PATIENTS AND METHODS: Forty-nine patients received docetaxel (100 mg/m2; 1-h i.v. infusion) and corticosteroid premedication. Forty-one patients who had received previous anthracycline treatment were divided into anthracycline-refractory and anthracycline-resistant (early and late) groups. RESULTS: Of 45 evaluable patients, 66.7% had a partial response (PR) and 2.2% a complete response (CR), giving an overall response rate (ORR) of 68.9%. The ORR in anthracycline-refractory patients was 60% versus 82.6% in anthracycline-resistant patients; the difference was not significant. The ORR in early-resistance patients was 62.5% versus 93.4% in late-resistance patients (0.05 < P < 0.1). The median response duration and overall survival was 8 months (range, 4-23 + months) and 11.5 months (range, 4-31 + months), respectively, in 39 patients treated previously for metastatic disease. For 295 courses, grade 3/4 neutropenia developed in 28.6% of patients (12.5% of courses) and was febrile in 26.5% of patients (6.1% of courses), including one septic death. Hypersensitivity reactions (HSR) developed in 16.3% of patients, and fluid retention developed in 34.7% of patients (11.9% of courses). CONCLUSIONS: Docetaxel is an active second-line drug in advanced breast cancer. The time of relapse after cessation of anthracycline treatment may be a significant prognostic factor.

Cathepsin D concentration in tumor cytosols improves the accuracy of prognostic evaluation of primary breast cancer.

One hundred and seventy three women were followed-up for a median of 62 months after surgery for Stage I-III breast cancer. The concentration of cathepsin D (CD) in tumor cytosols was compared to the standard prognostic factors for the disease and related to relapse free and overall survival and type of relapse. Three groups were identified with different prognostic profile. High CD levels significantly shorten DFS in both node-negative and node-positive patients; a correlation between high cathepsin D levels and locoregional relapse should also be noted. This marker should be included in the initial evaluation of breast cancer as an indicator of invasiveness.

[The clinical features of brucellosis in an endemic area (author's transl)]. / Das klinische Erscheinungsbild der Brucellose in einem endemischen Gebiet

Brucellosis remains a problem in many rural areas of Greece. A case report is given of 50 patients with brucellosis treated at the regional hospital of an endemic area. Various forms of fever were observed; a raised temperature was universal. Sweating and joint pains were prominent general symptoms. The most common local findings were arthritis, orcheoepididymitis and osteomyelitis. More rarely, rashes, bronchitis, difficulty in micturition and paraesthesiae were found. Routine laboratory investigations were of no diagnostic help, but the serum agglutination reaction according to Wright is diagnostic of brucellosis at high titres. An equally successful therapeutic result was achieved with streptomycin in conjunction with tetracyclines or with the combined preparation of sulphamethoxiazole and trimethoprim.

Fuzzy reinforcement learning control for compliance tasks of robotic manipulators.

A fuzzy reinforcement learning (FRL) scheme which is based on the principles of sliding-mode control and fuzzy logic is proposed. The FRL uses only immediate reward. Sufficient conditions for the convergence of the FRL to the optimal task performance are studied. The validity of the method is tested through simulation examples of a robot which deburrs a metal surface.