The paper describes a novel control strategy for simultaneous manipulation of several microscale particles over a planar microelectrode array using dielectrophoresis. The approach is based on a combination of numerical nonlinear optimization, which gives a systematic computational procedure for finding the voltages applied to the individual electrodes, and exploitation of the intrinsic noise, which compensates for the loss of controllability when two identical particles are exposed to identical forces. Although interesting on its own, the proposed functionality can also be seen as a preliminary achievement in a quest for a technique for separation of two particles. The approach is tested experimentally with polystyrene beads (50 microns in diameter) immersed in deionized water on a flat microelectrode array with parallel electrodes. A digital camera and computer vision algorithm are used to measure the positions. Two distinguishing features of the proposed control strategy are that the range of motion is not limited to interelectrode gaps and that independent manipulation of several particles simultaneously is feasible even on a simple microelectrode array.

• MeSH
• algoritmy MeSH
• design vybavení MeSH
• elektrody MeSH
• elektroforéza metody   MeSH
• hluk MeSH
• mikromanipulace přístrojové vybavení   metody   MeSH
• mikrosféry MeSH
• počítačové zpracování signálu přístrojové vybavení   MeSH
• teoretické modely MeSH
• zpětná vazba * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma. The Neuroblastoma New Drug Development Strategy (NDDS) has: 1) established a group with expertise in drug development; 2) prioritised targets and drugs according to tumour biology (target expression, dependency, pre-clinical data; potential combinations; biomarkers), identifying as priority targets ALK, MEK, CDK4/6, MDM2, MYCN (druggable by BET bromodomain, aurora kinase, mTORC1/2) BIRC5 and checkpoint kinase 1; 3) promoted clinical trials with target-prioritised drugs. Drugs showing activity can be rapidly transitioned via parallel randomised trials into front-line studies. Expert opinion: The Neuroblastoma NDDS is based on the premise that optimal drug development is reliant on knowledge of tumour biology and prioritisation. This approach will accelerate neuroblastoma drug development and other poor prognosis childhood malignancies.

• MeSH
• časové faktory MeSH
• cílená molekulární terapie MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• neuroblastom farmakoterapie   patologie   MeSH
• preklinické hodnocení léčiv metody   MeSH
• prognóza MeSH
• protinádorové látky škodlivé účinky   farmakologie   MeSH
• racionální návrh léčiv * MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Pharmacotherapy during pregnancy is often inevitable for medical treatment of the mother, the fetus or both. The knowledge of drug transport across placenta is, therefore, an important topic to bear in mind when deciding treatment in pregnant women. Several drug transporters of the ABC and SLC families have been discovered in the placenta, such as P-glycoprotein, breast cancer resistance protein, or organic anion/cation transporters. It is thus evident that the passage of drugs across the placenta can no longer be predicted simply on the basis of their physical-chemical properties. Functional expression of placental drug transporters in the trophoblast and the possibility of drug-drug interactions must be considered to optimize pharmacotherapy during pregnancy. In this review we summarize current knowledge on the expression and function of ABC and SLC transporters in the trophoblast. Furthermore, we put this data into context with medical conditions that require maternal and/or fetal treatment during pregnancy, such as gestational diabetes, HIV infection, fetal arrhythmias and epilepsy. Proper understanding of the role of placental transporters should be of great interest not only to clinicians but also to pharmaceutical industry for future drug design and development to control the degree of fetal exposure.

• MeSH
• ABC transportéry metabolismus   MeSH
• biologický transport MeSH
• komplikace těhotenství farmakoterapie   patofyziologie   MeSH
• léčivé přípravky aplikace a dávkování   metabolismus   MeSH
• lékové interakce MeSH
• lidé MeSH
• maternofetální výměna látek fyziologie   MeSH
• membránové transportní proteiny metabolismus   MeSH
• placenta metabolismus   MeSH
• racionální návrh léčiv MeSH
• těhotenství MeSH
• trofoblasty metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Clinical procedure for mild cognitive impairment (MCI) is mainly based on clinical records and short cognitive tests. However, low suspicion and difficulties in understanding test cut-offs make diagnostic accuracy being low, particularly in primary care. Artificial neural networks (ANNs) are suitable to design computed aided diagnostic systems because of their features of generating relationships between variables and their learning capability. The main aim pursued in that work is to explore the ability of a hybrid ANN-based system in order to provide a tool to assist in the clinical decision-making that facilitates a reliable MCI estimate. The model is designed to work with variables usually available in primary care, including Minimental Status Examination (MMSE), Functional Assessment Questionnaire (FAQ), Geriatric Depression Scale (GDS), age, and years of education. It will be useful in any clinical setting. Other important goal of our study is to compare the diagnostic rendering of ANN-based system and clinical physicians. A sample of 128 MCI subjects and 203 controls was selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The ANN-based system found the optimal variable combination, being AUC, sensitivity, specificity, and clinical utility index (CUI) calculated. The ANN results were compared with those from medical experts which include two family physicians, a neurologist, and a geriatrician. The optimal ANN model reached an AUC of 95.2%, with a sensitivity of 90.0% and a specificity of 84.78% and was based on MMSE, FAQ, and age inputs. As a whole, physician performance achieved a sensitivity of 46.66% and a specificity of 91.3%. CUIs were also better for the ANN model. The proposed ANN system reaches excellent diagnostic accuracy although it is based only on common clinical tests. These results suggest that the system is especially suitable for primary care implementation, aiding physicians work with cognitive impairment suspicions.

• MeSH
• databáze faktografické statistika a číselné údaje   MeSH
• diagnóza počítačová metody   statistika a číselné údaje   MeSH
• kognitivní dysfunkce diagnóza   psychologie   MeSH
• lidé MeSH
• neuronové sítě * MeSH
• neuropsychologické testy * statistika a číselné údaje   MeSH
• plocha pod křivkou MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• studie případů a kontrol MeSH
• systémy pro podporu klinického rozhodování * statistika a číselné údaje   MeSH
• výpočetní biologie MeSH
• Check Tag
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• lékařská informatika MeSH
• Publikační typ
• kongresy MeSH
• sborníky MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• lékařská informatika

• MeSH
• ekonomika a organizace zdravotní péče MeSH
• lékařská informatika MeSH
• průzkumy zdravotní péče MeSH
• reforma zdravotní péče MeSH
• zajištění kvality zdravotní péče MeSH
• Publikační typ
• kongresy MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• veřejné zdravotnictví

• MeSH
• Evropská unie MeSH
• výzkum MeSH
• Publikační typ
• abstrakty MeSH
• Geografické názvy
• Evropa MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• veřejné zdravotnictví
• politologie, politika, zdravotní politika

• O autorovi
• Commission of the European Communities. Biomedical and Health Research Programme Autorita