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.

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.

Flatness-based control approach to drug infusion for cardiac function regulation.

A new control method based on differential flatness theory is developed in this study, aiming at solving the problem of regulation of haemodynamic parameters. Actually control of the cardiac output (volume of blood pumped out by heart per unit of time) and of the arterial blood pressure is achieved through the administered infusion of cardiovascular drugs such as dopamine and sodium nitroprusside. Time delays between the control inputs and the system's outputs are taken into account.

Non-linear feedback control of the p53 protein-mdm2 inhibitor system using the derivative-free non-linear Kalman filter.

It is proven that the model of the p53-mdm2 protein synthesis loop is a differentially flat one and using a diffeomorphism (change of state variables) that is proposed by differential flatness theory it is shown that the protein synthesis model can be transformed into the canonical (Brunovsky) form. This enables the design of a feedback control law that maintains the concentration of the p53 protein at the desirable levels. To estimate the non-measurable elements of the state vector describing the p53-mdm2 system dynamics, the derivative-free non-linear Kalman filter is used.

Robust synchronization of coupled neural oscillators using the derivative-free nonlinear Kalman Filter.

A synchronizing control scheme for coupled neural oscillators of the FitzHugh-Nagumo type is proposed. Using differential flatness theory the dynamical model of two coupled neural oscillators is transformed into an equivalent model in the linear canonical (Brunovsky) form. A similar linearized description is succeeded using differential geometry methods and the computation of Lie derivatives.

Change detection in the dynamics of an intracellular protein synthesis model using nonlinear Kalman filtering.

A method for early diagnosis of parametric changes in intracellular protein synthesis models (e.g. the p53 protein - mdm2 inhibitor model) is developed with the use of a nonlinear Kalman Filtering approach (Derivative-free nonlinear Kalman Filter) and of statistical change detection methods.

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.

Fixed-point bifurcation analysis in biological models using interval polynomials theory.

The paper proposes a systematic method for fixed-point bifurcation analysis in circadian cells and similar biological models using interval polynomials theory. The stages for performing fixed-point bifurcation analysis in such biological systems comprise (i) the computation of fixed points as functions of the bifurcation parameter and (ii) the evaluation of the type of stability for each fixed point through the computation of the eigenvalues of the Jacobian matrix that is associated with the system's nonlinear dynamics model. Stage (ii) requires the computation of the roots of the characteristic polynomial of the Jacobian matrix.

A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer.

HLA-mismatched natural killer (NK) cells have shown efficacy in acute myeloid leukemia, and their adoptive transfer in patients with other malignancies has been proven safe. This phase I clinical trial was designed to evaluate safety (primary endpoint) and possible clinical efficacy (secondary endpoint) of repetitive administrations of allogeneic, in vitro activated and expanded NK cells along with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients with unresectable, locally advanced/metastatic NSCLC receiving 1st/2nd line chemotherapy were eligible to receive 2-4 doses of activated NK cells from two relative donors.

Biweekly gemcitabine (GEM) in combination with erlotinib (ERL): an active and convenient regimen for advanced pancreatic cancer.

Background: Pancreatic cancer remains a disease of high mortality and one of the most frustrating, resistant solid neoplasms to treat. The aim of this study was to evaluate a biweekly gemcitabine plus daily erlotinib regimen in patients with advanced (stage III-IV) pancreatic cancer in terms of overall survival and time to progression of the disease. The secondary aim was to record treatment related toxicities.

Paraneoplastic cerebellar degeneration in a patient with pseudomyxoma peritonei and breast cancer: case report and literature review.

The case of a 31-year-old woman with progressive cerebellar degeneration preceding by several months the diagnosis and treatment of breast cancer initially and pseudomyxoma peritonei (PMP) with evidence of causative association with the latter is presented. Despite various chemotherapeutic and surgical manipulations, the patient did not substantially improve and succumbed 20 months following initial diagnosis of the neurological disorder. Interestingly, neurological symptoms partially regressed transiently only after surgical debulking of the PMP and not after the remission of breast cancer after various chemotherapeutic regimens suggesting an etiological relationship of the former and the cerebellar degeneration.

Salvage therapy of pretreated advanced breast cancer with bevacizumab and paclitaxel every two weeks: a retrospective case review study.

Background: Targeting angiogenesis is nowadays one of the most promising approaches for breast cancer. Bevacizumab (BEV), a VEGF-trap monoclonal antibody, was recently approved in combination with paclitaxel (PAC) for the first line treatment of advanced breast cancer (ABC). The activity of this combination in pretreated patients is not known.

A Phase II trial of the combination of vinorelbine and capecitabine as second-line treatment in metastatic breast cancer previously treated with taxanes and/or anthracyclines.

Purpose: Survival time for metastatic breast cancer (MBC) can be substantially improved by combination chemotherapy in the adjuvant setting. Capecitabine and vinorelbine have shown considerable efficacy and favourable toxicity as single agents. The aim of this study is to evaluate the response to the combination of capecitabine and vinorelbine as second-line treatment in patients previously treated with taxanes and/or anthracyclines.

Systemic sclerosis associated with rectal cancer. Case report and a brief review of the literature.

Autoimmune diseases may appear as paraneoplastic syndromes during the course of a neoplastic disease, the most common being dermatomyositis/ polymyositis. The association of systemic sclerosis and cancer is not clear. The case of a 56-year-old male with rectal cancer and systemic sclerosis where the coexistence of the two diseases was closely related, so that scleroderma was considered a paraneoplastic syndrome rather than a concomitant morbid condition, is presented.

Concomitant gastric adenocarcinoma and stromal tumor in a woman with polymyalgia rheumatica.

Gastrointestinal stromal tumors (GISTs) are rare neoplasms (1%) of the gastrointestinal tract and to our knowledge only rare cases of synchronous presentation of gastric carcinomas and GISTs are reported in the literature. A 72-year-old female with a simultaneous presentation of gastric adenocarcinoma and GIST is presented. Moreover, due to polymyalgia rheumatica the patient received corticosteroids as treatment for the last 3 years.

Bevacizumab added to the irinotecan and capecitabine combination for advanced colorectal cancer: a well-tolerated, active and convenient regimen.

Objectives: The literature data regarding bevacizumab (BEV) administered together with capecitabine (CAP) and irinotecan (IRI) in patients with advanced colorectal cancer (CRC) are limited. The safety and efficacy of the addition of BEV to the IRI and CAP (XELIRI) regimen were retrospectively analyzed and reported.

Patients And Methods: Adult patients 18 years or older with advanced CRC, Eastern Cooperative Oncology Group performance status (ECOG PS) < or =2, exposed to < or =1 chemotherapy (CT) regimen not including IRI or CAP, received BEV 7.

Particle and Kalman filtering for state estimation and control of DC motors.

State estimation is a major problem in industrial systems. To this end, Gaussian and nonparametric filters have been developed. In this paper the Kalman Filter, which assumes Gaussian measurement noise, is compared to the Particle Filter, which does not make any assumption on the measurement noise distribution.

Adaptive fuzzy control with output feedback for H infinity tracking of SISO nonlinear systems.

Observer-based adaptive fuzzy H(infinity) control is proposed to achieve H(infinity) tracking performance for a class of nonlinear systems, which are subject to model uncertainty and external disturbances and in which only a measurement of the output is available. The key ideas in the design of the proposed controller are (i) to transform the nonlinear control problem into a regulation problem through suitable output feedback, (ii) to design a state observer for the estimation of the non-measurable elements of the system's state vector, (iii) to design neuro-fuzzy approximators that receive as inputs the parameters of the reconstructed state vector and give as output an estimation of the system's unknown dynamics, (iv) to use an H(infinity) control term for the compensation of external disturbances and modelling errors, (v) to use Lyapunov stability analysis in order to find the learning law for the neuro-fuzzy approximators, and a supervisory control term for disturbance and modelling error rejection. The control scheme is tested in the cart-pole balancing problem and in a DC-motor model.

Erlotinib monotherapy in patients with advanced non-small cell lung cancer: an effective approach with low toxicity.

Background: Treatment of non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) and particularly erlotinib (Tarceva) has been a field of intense research. This retrospective study was conducted to assess the efficacy of erlotinib and its impact on survival.

Patients And Methods: Patients with stage IIIB or IV, advanced or recurrent metastatic NSCLC were included in the study and were administered erlotinib 150 mg daily, at different lines of treatment.

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.

Trastuzumab plus paclitaxel or docetaxel in HER-2-negative/HER-2 ECD-positive anthracycline- and taxane-refractory advanced breast cancer.

Trastuzumab is considered effective against human epidermal growth factor receptor (HER)-2-positive breast cancer as assessed by immunohistochemistry (IHC) and fluorescence or chromogenic in situ hybridization (FISH/CISH) on biopsy material. Trastuzumab is now approved in both the adjuvant and metastatic settings for this patient population. Because HER-2 extracellular domain (ECD) levels have been correlated with disease progression in the metastatic setting, we considered trastuzumab salvage therapy plus a taxane in heavily pretreated trastuzumab-naive relapsed breast cancer patients with high serum levels of HER-2 ECD (> or =15 ng/ml).

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.

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.