• MeSH
• ekonomické modely MeSH
• ekonomika lékařská MeSH
• obchod MeSH
• poskytování zdravotní péče MeSH
• sektor zdravotní péče MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Ekonomie
• NLK Obory
• ekonomie, ekonomika, ekonomika zdravotnictví

OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

• MeSH
• alkoholdehydrogenasa genetika   MeSH
• biologické markery krev   MeSH
• cévní mozková příhoda krev   etiologie   genetika   MeSH
• dospělí MeSH
• genetické markery MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus * MeSH
• koronární nemoc krev   etiologie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• pití alkoholu škodlivé účinky   genetika   MeSH
• senioři MeSH
• statistické modely MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH

The purpose of the present study was to examine and contrast emotional experiences of rugby and wheelchair rugby players by utilizing the Individual Zones of Optimal Functioning (IZOF) model. The IZOF questionnaire was completed by 26 male rugby and 11 wheelchair rugby players. The content of emotions was studied as a) frequency of separate adjectives from the emotion profiles, b) frequency of adjectives clustered in groups of synonyms, and c) displaying frequency of helpful and harmful effect of the adjectives. To compare the contents of emotions between rugby and wheelchair rugby players the Chi-Square test was used. To compare the intensities of emotions on the inter-group level we utilized Mann-Whitney U Test. The data revealed several significant differences (p < 0,05) between the two teams in selected emotion content (in 6 out of 48 groups of synonyms) and in indicated emotion intensities (during the best ever performance in 6 cases and during the worst ever performance in 1 case out of 48 groups). The analysis also demonstrated that wheelchair rugby players perceived harmful negative emotions during their worst ever performance at significantly higher intensity compared to the rugby players. The results support utilizing an individual approach in studies of performance-related emotional experiences and suggest that the IZOF model was applicable to research in emotional experiences of athletes with disabilities.

• Klíčová slova
• výkon, dotazník IZOF, srovnání, týmový sport,
• MeSH
• americký fotbal MeSH
• emoce fyziologie   MeSH
• financování organizované MeSH
• lidé MeSH
• postižení MeSH
• průzkumy a dotazníky MeSH
• psychologické modely MeSH
• sportovní výkon psychologie   MeSH
• sporty MeSH
• statistika jako téma MeSH
• Check Tag
• lidé MeSH

Game theoretic models of evolution such as the Hawk-Dove game assume that individuals gain fitness (which is a proxy of the per capita population growth rate) in pair-wise contests only. These models assume that the equilibrium distribution of phenotypes involved (e.g., Hawks and Doves) in the population is given by the Hardy-Weinberg law, which is based on instantaneous, random pair formation. On the other hand, models of population dynamics do not consider pairs, newborns are produced by singles, and interactions between phenotypes or species are described by the mass action principle. This article links game theoretic and population approaches. It shows that combining distribution dynamics with population dynamics can lead to stable coexistence of Hawk and Dove population numbers in models that do not assume a priori that fitness is negative density dependent. Our analysis shows clearly that the interior Nash equilibrium of the Hawk and Dove model depends both on population size and on interaction times between different phenotypes in the population. This raises the question of the applicability of classic evolutionary game theory that requires all interactions take the same amount of time and that all single individuals have the same payoff per unit of time, to real populations. Furthermore, by separating individual fitness into birth and death effects on singles and pairs, it is shown that stable coexistence in these models depends on the time-scale of the distribution dynamics relative to the population dynamics. When explicit density-dependent fitness is included through competition over a limited resource, the combined dynamics of the Hawk-Dove model often lead to Dove extinction no matter how costly fighting is for Hawk pairs.

• MeSH
• biologická evoluce * MeSH
• biologické modely * MeSH
• populační dynamika MeSH
• teorie her MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Synoptický přehled sleduje dvě linie ústředního tématu: cesta životem a strategie jejího zkoumání. Aktuální úkol představuje vypracování teorie celoživotního vývoje směřující k rozpoznání a specifikaci dynamiky individuálního vývoje ve spojení s alokací zdrojů růstu, resilience a zvládání ztrát. Probíhající empirická zkoumání svědčí o tom, jak se tento obecný koncept ověřuje ve specifických oblastech, jako jsou kognitivní procesy, motorika nebo emocionalita. Je psychologie celoživotního vývoje, life span developmental psychology, speciální vývojovou psychologií, je obecnou integrativní vývojovou koncepcí ontogeneze nebo je pouze jednou z orientací při zkoumání vývoje? Naznačují se argumenty v probíhajících diskusích. K hlavním aspiracím teorie celoživotního vývoje patří vypracování profilu relativní alokace biologicky a kulturně zakotvených zdrojů pro funkce růstu, resilience a zvládání ztrát. Pluralismus se jeví jako obecná charakteristika změn postmoderny v koncepcích diverzity. Konstatuje se nárůst prací o pozitivních i rizikových faktorech v celoživotní perspektivě.

The synoptic overview follows two lines of the core topic: life span development and the strategy of its research. The actual task is to design a life span development theory leading to the recognition and specification of individual development dynamics together with allocation of resources for growth, resilience and coping with losses. Ongoing empirical research point out how this general concept is tested in specific areas, such as cognitive processes, motor activity and emotionality. Is lifespan developmental psychology a special kind of developmental psychology, a general integrative ontogenetic concept, or is, is just one of the orientations in the current research of development? Arguments in current discussions are hinted. One of the main pretensions of life span development theory is to allocate a profile of biology- and culture-based sources of growth, resilience and coping with losses. Pluralism appears to be a general characteristic for changes of postmodernism in the concepts of diversity. The number of papers dealing with both positive and risk factors in the lifespan development context is increasing.

• MeSH
• kvalita života * psychologie   MeSH
• lidé MeSH
• psychologie * metody   MeSH
• životní změny * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Celiac disease (CD) is a disorder that affects both children and adults. Over the few last decades, several new atypical cases have been identified through improved diagnostic tools. On the other hand, the onset of CD at a later age, including atypical CD forms whose clinical picture overlaps with other autoimmune diseases, shows that currently there are several unknown gene mutations, which could be responsible for the disease development. Non-celiac gluten sensitivity (NCGS) is entity included by the ingestion of gluten leading to intestinal, or extraintestinal symptoms that improve once the gluten is removed from the nutrition. In this article relationships between genetically modified rodent animals with previously unknown multiple organ changes and CD, respectively NCGS are reviewed. Relationships between the small bowel histological changes and other organs pathology are discussed. Results of research document that changes have similar genetic background and can develop to serious autoimmune systematic diseases, including small bowel inflammation resembling atypical CD or NCGS. These may have extra-intestinal symptomatology but without a clear explanation of causes and differences in their manifestations. Research on animal models helps to discover links between several disorders associated with gastrointestinal damage. New methods based on individual gene mutations can help in atypical adult CD and NCGS recognitions in the future.

• MeSH
• celiakie * genetika   MeSH
• gluteny MeSH
• hlodavci * MeSH
• modely u zvířat MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Před 40 lety vyšel v lékařském časopise Annual Review of Physiology přehledový článek A. Guytona a dvou spoluautorů o regulaci krevního oběhu, jehož obsahem byl formalizovaný popis fyziologických vztahů v oběhovém systému, včetně všech jeho návazností na ostatní fyziologické subsystémy pomocí graficky vyjádřeného matematického modelu. Tento článek byl jitým mezníkem, který otevřel novou oblast fyziologického výzkumu nazývanou „integrativní fyziologie“. Obdobně jako se teoretická fyzika formálními prostředky snaží popsat fyzikální realitu a vysvětlit výsledky experimentálního výzkumu, tak se „integrativní fyziologie“ na základě experimentálních výsledků snaží vytvořit formalizovaný popis vzájemného propojení fyziologických regulací a vysvětlit jejich funkci v rozvoji nejrůznějších onemocnění. V sedmdesátých letech byla tato doména oblastí čistě teoretického výzkumu několika ojedinělých pracovišť. S rozvojem informačních technologií se modelování fyziologických systémů stalo běžnou součástí fyziologického výzkumu, kde začala převládat spíše tvorba menších, snadněji identifikovatelných modelů jednotlivých fyziologických subsystémů. V posledních letech však tvorba rozsáhlých modelů fyziologických systémů zažívá určitou renesanci, zejména v souvislosti s možností uplatnění těchto modelů jako teoretického podkladu pro lékařské trenažéry. Rozvoji rozsáhlých integrovaných modelů fyziologických systémů napomáhá i nová generace (tzv. equation–based) simulačních prostředí. Problematika modelování integrativní fyziologie se stala součástí řady mezinárodních projektů (např. programy „Physiome“, nebo program EU „Virtual Physiological Human“), uplatnění těchto modelů pro vysvětlení kauzálních souvislostí patogenez řady onemocnění i jejich vy- užití v lékařských trenažérech.

A review article of A. Guyton and two co-authors was published in the medical journal Annual Review of Physiology 40 years ago, which focused on blood circulation control, and which contained formalized description of physiological relationships in the circulatory system including all its connections to other physiological subsystems using a graphic mathematical model. This article was a certain milestone that opened a new area of physiological research called “integrative physiology“. Similarly as theoretic physics, this new area seeks to describe physical reality and to explain experimental research results using formal means; thus based on experimental results, “integrative physiology seeks to create a formalized description of mutual connections of physiological control systems and to explain their functions in the development of various diseases. In the 70ies, this was a domain of purely theoretic research of a few sporadic departments. However, physiological system modelling has become a common part of physiological research with the continued development of information technologies, while it was rather the design of smaller, more easily identifiable models of individual physiological subsystems that started to predominate. However, the design of extensive models of physiological systems has seen certain rebirth in recent years, particularly in connection with potential application of such models as a theoretic foundation for medical simulators. The development of extensive integrated models of physiological systems has been assisted also by the new generation of (the so called equation-based) simulation environments. The issues of integrative physiology modelling have become part of many international projects (for example, “Physiome“ programs or the EU program “Virtual Physiological Human“), application of such models in explaining causal relationships of the pathogenesis of numerous diseases as well as their use in medical simulators.

• MeSH
• biologické modely MeSH
• design vybavení MeSH
• fyziologie MeSH
• počítačová simulace MeSH
• robotika MeSH
• studium lékařství metody   MeSH
• teoretické modely MeSH
• uživatelské rozhraní počítače MeSH

The aim of this study was a comparison of risk stratification for death in patients after myocardial infarction (MI) and of risk stratification for malignant arrhythmias in patients with implantable cardioverter-defibrillator (ICD). The individual risk factors and more complex approaches were used, which take into account that a borderline between a risky and non-risky value of each predictor is not clear-cut (fuzzification of a critical value) and that individual risk factors have different weight (area under receiver operating curve – AUC or Sommers´ D – Dxy). The risk factors were baroreflex sensitivity, ejection fraction and the number of ventricular premature complexes/hour on Holter monitoring. Those factors were evaluated separately and they were involved into logit model and fuzzy models (Fuzzy, Fuzzy- AUC, and Fuzzy-Dxy). Two groups of patients were examined: a) 308 patients 7-21 days after MI (23 patients died within period of 24 month); b) 53 patients with left ventricular dysfunction examined before implantation of ICD (7 patients with malignant arrhythmia and electric discharge within 11 month after implantation). Our results obtained in MI patients demonstrated that the application of logit and fuzzy models was superior over the risk stratification based on algorithm where the decision making is dependent on one parameter. In patients with implanted defibrillator only logit method yielded statistically significant result, but its reliability was doubtful because all other tests were statistically insignificant. We recommend evaluating the data not only by tests based on logit model but also by tests based on fuzzy models.

• MeSH
• algoritmy MeSH
• baroreflex MeSH
• časové faktory MeSH
• defibrilátory implantabilní MeSH
• elektrická defibrilace přístrojové vybavení   MeSH
• elektrokardiografie ambulantní MeSH
• financování organizované MeSH
• fuzzy logika MeSH
• hodnocení rizik MeSH
• infarkt myokardu mortalita   patofyziologie   MeSH
• komorové extrasystoly patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• prognóza MeSH
• reprodukovatelnost výsledků MeSH
• rizikové faktory MeSH
• ROC křivka MeSH
• senioři MeSH
• srdeční arytmie patofyziologie   prevence a kontrola   MeSH
• tepový objem MeSH
• ukazatele zdravotního stavu MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• srovnávací studie MeSH

Models based on ordinary differential equations (ODE) are widespread tools for describing dynamical systems. In biomedical sciences, data from each subject can be sparse making difficult to precisely estimate individual parameters by standard non-linear regression but information can often be gained from between-subjects variability. This makes natural the use of mixed-effects models to estimate population parameters. Although the maximum likelihood approach is a valuable option, identifiability issues favour Bayesian approaches which can incorporate prior knowledge in a flexible way. However, the combination of difficulties coming from the ODE system and from the presence of random effects raises a major numerical challenge. Computations can be simplified by making a normal approximation of the posterior to find the maximum of the posterior distribution (MAP). Here we present the NIMROD program (normal approximation inference in models with random effects based on ordinary differential equations) devoted to the MAP estimation in ODE models. We describe the specific implemented features such as convergence criteria and an approximation of the leave-one-out cross-validation to assess the model quality of fit. In pharmacokinetics models, first, we evaluate the properties of this algorithm and compare it with FOCE and MCMC algorithms in simulations. Then, we illustrate NIMROD use on Amprenavir pharmacokinetics data from the PUZZLE clinical trial in HIV infected patients.

• MeSH
• algoritmy MeSH
• Bayesova věta MeSH
• HIV infekce farmakoterapie   MeSH
• karbamáty farmakokinetika   MeSH
• klinické zkoušky jako téma MeSH
• látky proti HIV farmakokinetika   MeSH
• lidé MeSH
• monitorování léčiv přístrojové vybavení   metody   MeSH
• pravděpodobnostní funkce MeSH
• reprodukovatelnost výsledků MeSH
• software * MeSH
• statistické modely MeSH
• sulfonamidy farmakokinetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Effective treatment options for advanced colorectal cancer (CRC) are limited, survival rates are poor and this disease continues to be a leading cause of cancer-related deaths worldwide. Despite being a highly heterogeneous disease, a large subset of individuals with sporadic CRC typically harbor relatively few established 'driver' lesions. Here, we describe a collection of genetically engineered mouse models (GEMMs) of sporadic CRC that combine lesions frequently altered in human patients, including well-characterized tumor suppressors and activators of MAPK signaling. Primary tumors from these models were profiled, and individual GEMM tumors segregated into groups based on their genotypes. Unique allelic and genotypic expression signatures were generated from these GEMMs and applied to clinically annotated human CRC patient samples. We provide evidence that a Kras signature derived from these GEMMs is capable of distinguishing human tumors harboring KRAS mutation, and tracks with poor prognosis in two independent human patient cohorts. Furthermore, the analysis of a panel of human CRC cell lines suggests that high expression of the GEMM Kras signature correlates with sensitivity to targeted pathway inhibitors. Together, these findings implicate GEMMs as powerful preclinical tools with the capacity to recapitulate relevant human disease biology, and support the use of genetic signatures generated in these models to facilitate future drug discovery and validation efforts.

• MeSH
• alely MeSH
• druhová specificita MeSH
• geny ras MeSH
• kolorektální nádory enzymologie   genetika   patologie   MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• protoonkogenní proteiny B-raf genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH