Mixed effect models Dotaz Zobrazit nápovědu
Plants adapt to continual changes in environmental conditions throughout their life spans. High-throughput phenotyping methods have been developed to noninvasively monitor the physiological responses to abiotic/biotic stresses on a scale spanning a long time, covering most of the vegetative and reproductive stages. However, some of the physiological events comprise almost immediate and very fast responses towards the changing environment which might be overlooked in long-term observations. Additionally, there are certain technical difficulties and restrictions in analyzing phenotyping data, especially when dealing with repeated measurements. In this study, a method for comparing means at different time points using generalized linear mixed models combined with classical time series models is presented. As an example, we use multiple chlorophyll time series measurements from different genotypes. The use of additional time series models as random effects is essential as the residuals of the initial mixed model may contain autocorrelations that bias the result. The nature of mixed models offers a viable solution as these can incorporate time series models for residuals as random effects. The results from analyzing chlorophyll content time series show that the autocorrelation is successfully eliminated from the residuals and incorporated into the final model. This allows the use of statistical inference.
- Klíčová slova
- ARIMA, Arabidopsis, linear mixed models, time series analysis,
- Publikační typ
- časopisecké články MeSH
We have developed a method to longitudinally classify subjects into two or more prognostic groups using longitudinally observed values of markers related to the prognosis. We assume the availability of a training data set where the subjects' allocation into the prognostic group is known. The proposed method proceeds in two steps as described earlier in the literature. First, multivariate linear mixed models are fitted in each prognostic group from the training data set to model the dependence of markers on time and on possibly other covariates. Second, fitted mixed models are used to develop a discrimination rule for future subjects. Our method improves upon existing approaches by relaxing the normality assumption of random effects in the underlying mixed models. Namely, we assume a heteroscedastic multivariate normal mixture for random effects. Inference is performed in the Bayesian framework using the Markov chain Monte Carlo methodology. Software has been written for the proposed method and it is freely available. The methodology is applied to data from the Dutch Primary Biliary Cirrhosis Study.
- MeSH
- biliární cirhóza farmakoterapie MeSH
- biologické markery analýza MeSH
- cholagoga a choleretika terapeutické užití MeSH
- diskriminační analýza * MeSH
- interpretace statistických dat * MeSH
- kyselina ursodeoxycholová terapeutické užití MeSH
- lidé MeSH
- lineární modely * MeSH
- longitudinální studie MeSH
- počítačová simulace MeSH
- progrese nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- cholagoga a choleretika MeSH
- kyselina ursodeoxycholová MeSH
We studied haemosporidian parasites in the scarlet rosefinch Carpodacus erythrinus in a small isolated semicolony during an eight-year period using molecular methods of parasite detection. The scarlet rosefinch is an interesting model of parasite host species. It winters in South Asia which represents a rare exception among European passerines. Males express yellow to red carotenoid-based plumage ornament which is a good predictor of male reproductive success. In 240 blood samples originating from 199 adult individuals, the total parasite prevalence reached 60%. Prevalence varied among years from 36 to 81% in Haemoproteus, 8 to 22% in Plasmodium, and 0 to 14% in Leucocytozoon. Twenty parasite lineages were detected (Haemoproteus: 5 lineages, Plasmodium: 10 lineages, and Leucocytozoon: 5 lineages). Among them, the Haemoproteus ROFI2 lineage, which is a host-specific parasite lineage of the scarlet rosefinch, was the most frequently found. Parasite lineages showed varying degree of lineage specificity. While Haemoproteus lineages detected in the scarlet rosefinch have relatively narrow host breadth restricted mainly to Fringillidae family, Leucocytozoon and Plasmodium lineages generally showed wider host range. The presence of some parasite lineages hitherto detected in sedentary European passerines (SISKIN1, CCF3, BT2) or in Culicoides biting midges at the same locality (ROFI1) suggest local transmission. On the contrary, lineages LK05 and FANTAIL1 that were previously reported exclusively from Asian hosts imply parasite transmission at the scarlet rosefinch wintering sites in South Asia. Mixed infections were found in 17% of infected samples and comprised mainly the most frequent lineages. The pattern of concomitant infections seemed to be rather random and matched expected levels based on lineage frequencies. Between-year comparisons revealed that in a majority of the repeatedly captured individual hosts the infection status remained unchanged (individuals stayed uninfected or possessed the same parasite lineages). However, 16 gains and 8 losses of lineages were also reported. We have not found any effect of haemosporidians on male carotenoid ornament expression or host body mass.
- MeSH
- Haemosporida izolace a purifikace MeSH
- koinfekce epidemiologie parazitologie veterinární MeSH
- krev parazitologie MeSH
- nemoci ptáků epidemiologie parazitologie MeSH
- Passeriformes MeSH
- prevalence MeSH
- protozoální infekce zvířat epidemiologie parazitologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Asie MeSH
- Evropa MeSH
A series of gold(I) triphenylphosphine (PPh3) complexes (1-9) involving 2-chloro-N6-(substituted-benzyl)adenine derivatives as N-donor ligands was synthesized and thoroughly characterized by relevant methods, including electrospray-ionization (ESI) mass spectrometry and multinuclear NMR spectroscopy. The anti-inflammatory and antiedematous effects of three representatives 1, 5 and 9 were evaluated by means of in vitro model based on the expression of pro- and anti-inflammatory cytokines and influence of the complexes on selected forms of matrix metalloproteinases secreted by LPS-activated THP-1 monocytes and in vivo model evaluating the antiedematous effect of the complexes in the carrageenan-induced rat hind-paw edema model. In addition to the pharmacological observations, the affected hind paws were post mortem subjected to histological and immunohistochemical evaluations. The results of both in vivo and ex vivo methods revealed low antiedematous and anti-inflammatory effects of the complexes, even though the in vitro model identified them as promising anti-inflammatory acting compounds. The reason for this discrepancy lies probably in low stability of the studied complexes in biological environment, as demonstrated by the solution interaction studies with sulfur-containing biomolecules (cysteine and reduced glutathione) using the ESI mass spectrometry.
- MeSH
- adenin chemie MeSH
- antiflogistika chemie farmakologie terapeutické užití MeSH
- buněčné linie MeSH
- cytokiny metabolismus MeSH
- edém farmakoterapie MeSH
- ELISA MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- krysa rodu Rattus MeSH
- ligandy MeSH
- organofosforové sloučeniny chemie farmakologie terapeutické užití MeSH
- potkani Wistar MeSH
- techniky in vitro MeSH
- zlato chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenin MeSH
- antiflogistika MeSH
- cytokiny MeSH
- ligandy MeSH
- organofosforové sloučeniny MeSH
- triphenylphosphine MeSH Prohlížeč
- zlato MeSH
Infrared absorption and vibrational circular dichroism (IR and VCD) spectra of model fragments of TrpZip-style beta-hairpin structures are simulated using density functional theory (DFT) methods to estimate the influence of fragment size, end effects, conformational irregularities, peptide side chains, and solvent. Different fragmentation schemes, computing the strands and turn segments separately, were tested by varying the sizes of each and their respective overlaps. For suitably overlapping fragments, atomic property tensors were found to be reliably transferable, as tested by their ability to generate simulated spectra in good agreement with results from ab initio DFT computations for the entire peptide. This fragment approach significantly reduces computational times and opens up a wider range of systems that can be studied with a DFT-based approach as compared to previous methods based on uniform repeating sequences. However, vacuum calculations do not adequately represent the frequency dispersion of solvated molecules, and thus, some alternate strategies for solvation correction are explored for improving the simulation accuracy. Unlike for regular periodic secondary structure, the solvent significantly impacts the spectral shapes of hairpins, due to the different degrees of hydration of individual amide groups, which can be exposed to or shielded from water due to external vs internal hydrogen bonding. This is amplified by the shielding of selected amides from the solvent due to bulky side chains. The peptide plus solvent was structurally modeled with molecular dynamics methods, and then an electrostatic field-based parametrization correction was added to the force field and intensity tensors to compensate for the solvent dipolar field. The effect of the shielding and subsequent reordering of modes has a larger impact on VCD than IR band shapes.
- MeSH
- algoritmy MeSH
- chemické modely * MeSH
- cirkulární dichroismus MeSH
- molekulární sekvence - údaje MeSH
- peptidy chemie MeSH
- počítačová simulace MeSH
- sekundární struktura proteinů MeSH
- sekvence aminokyselin MeSH
- spektrofotometrie infračervená MeSH
- voda chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- srovnávací studie MeSH
- Názvy látek
- peptidy MeSH
- voda MeSH
Knowledge of population exposure to phthalates based on the urinary metabolite levels is of the highest importance for health risk assessment. Such data are scarce in the Czech population. In the study conducted in 2016, six urinary phthalate metabolites were analysed in a total of 370 first morning urine samples of healthy children aged 5 and 9 years, namely mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-benzyl phthalate (MBzP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP). The two latter mono-butyl phthalate isoforms dominated among all samples with geometric means of 63.0 µg/L (MnBP) and 44.1 µg/L (MiBP), followed by 5OH-MEHP (20.6 µg/L), 5oxo-MEHP (12.9 µg/L), MBzP (3.65 µg/L), and MEHP (2.31 µg/L). Daily intake (DI) of the parent phthalates was estimated using the creatinine-based model. The highest DI values were found for di-n-butyl phthalate (DnBP) (median 2.5 µg/kg bw/day; 95th percentile 7.8 µg/kg bw/day) and di-2-ethylhexyl phthalate (DEHP) (median 2.3 µg/kg bw/day; 95th percentile 8.9 µg/kg bw/day) in 5-year-old children. The tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA) was exceeded in case of DnBP (in 1% of 9-year-olds and in 3% of 5-year-olds). Exposure risk was assessed based on hazard quotients calculation and cumulative approach for similar health effect. The combined exposure to four phthalates expressed by hazard index (HI) for reprotoxicity revealed exceeding of HI threshold in 14% of 5-year-olds and in 9% of 9-year-olds. These findings strongly support the need to reduce the burden of children by phthalates.
- MeSH
- dávka bez pozorovaného nepříznivého účinku MeSH
- diethylhexylftalát aplikace a dávkování analogy a deriváty moč MeSH
- dítě MeSH
- hodnocení rizik MeSH
- kreatinin moč MeSH
- kyseliny ftalové aplikace a dávkování moč MeSH
- látky znečišťující životní prostředí aplikace a dávkování moč MeSH
- lidé MeSH
- předškolní dítě MeSH
- školy MeSH
- vystavení vlivu životního prostředí analýza MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- diethylhexylftalát MeSH
- kreatinin MeSH
- kyseliny ftalové MeSH
- látky znečišťující životní prostředí MeSH
- mono-(2-ethylhexyl)phthalate MeSH Prohlížeč
- mono-benzyl phthalate MeSH Prohlížeč
- mono-isobutyl phthalate MeSH Prohlížeč
- monobutyl phthalate MeSH Prohlížeč
INTRODUCTION: Recent research indicated that cognitive speed of processing training (SPT) improved Useful Field of View (UFOV) among individuals with Parkinson's disease (PD). The effects of SPT in PD have not been further examined. The objectives of the current study were to investigate use, maintenance and dose effects of SPT among individuals with PD. METHODS: Participants who were randomized to SPT or a delayed control group completed the UFOV at a six-month follow-up visit. Use of SPT was monitored across the six-month study period. Regression explored factors affecting SPT use. Mixed effect models were conducted to examine the durability of training gains among those randomized to SPT (n = 44), and training dose effects among the entire sample (n = 87). RESULTS: The majority of participants chose to continue to use SPT (52%). Those randomized to SPT maintained improvements in UFOV performance. A significant dose effect of SPT was evident such that more hours of training were associated with greater UFOV performance improvements. The cognitive benefits derived from SPT in PD may be maintained for up to three months. CONCLUSION: Future research should determine how long gains endure and explore if such training gains transfer.
- Klíčová slova
- Mixed effect models, cognitive training, non-pharmacological intervention,
- MeSH
- činnosti denního života psychologie MeSH
- kognice * MeSH
- kognitivní poruchy komplikace psychologie terapie MeSH
- lidé MeSH
- Parkinsonova nemoc komplikace psychologie terapie MeSH
- praxe (psychologie) * MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
We introduce and study a multicomponent lipid film mimicking lipid composition of the human lung surfactant. It consists of phospholipids with various lipid headgroups and tail saturation. Furthermore, it includes cholesterol and oxidized lipids. Langmuir trough and fluorescence microscopy experiments are combined with fully atomistic molecular dynamics simulations. The considered lipid mixtures form complex interfacial films with properties modulated by lateral compression. Cholesterol laterally condenses, and oxidized lipids laterally expand the films; both types of molecules increase film miscibility. Oxidized lipids also alter the lipid-water interface enhancing film hydration; this effect can be partially reversed by cholesterol. Regarding presentation of different chemical moieties toward the aqueous subphase, the zwitterionic phosphatidylcholine groups dominate at the lipid-water interface, while both the negatively charged phosphatidylglycerol and hydroxyl group of cholesterol are less exposed. The investigated synthetic lipid-only mimic of the lung surfactant may serve as a basis for further studies involving nonlipid pulmonary surfactant components.
- MeSH
- cholesterol chemie MeSH
- fluorescenční mikroskopie MeSH
- lidé MeSH
- lipidy chemie MeSH
- oxidace-redukce MeSH
- plicní surfaktanty chemie MeSH
- simulace molekulární dynamiky * MeSH
- voda chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cholesterol MeSH
- lipidy MeSH
- plicní surfaktanty MeSH
- voda MeSH
BACKGROUND AND PURPOSE: The relationship between lesion formation and brain atrophy development in the early phase of multiple sclerosis is unclear. We investigated the association between new lesion accumulation and brain atrophy progression in patients with clinically isolated syndrome over 48 months. MATERIALS AND METHODS: Patients with clinically isolated syndrome (n = 210) were evaluated with 1.5T MR imaging at baseline and at 6, 12, 24, 36, and 48 months as part of a multicenter observational study of early administration of intramuscular interferon β-1a. Mixed-effect model analyses, adjusted for age, sex, and treatment status, investigated the association between accumulation of contrast-enhancing and T2 lesions and brain-volume percent changes in a 48-month period. RESULTS: In patients with clinically isolated syndrome, the average whole-brain volume decreased 2.5%, the mean lateral ventricle volume increased 16.9%, and a mean of 7.7 new/enlarging T2 lesions accumulated over the follow-up period. Patients with clinically isolated syndrome who showed greater percentages of change in whole-brain, white and gray matter, cortical, and lateral ventricle volumes over the follow-up period had more severe lesion outcomes at baseline (all P < .007). There were significant associations between decreased individual brain-volume measures at baseline and greater percentages of change during follow-up (P < .05). We found a significant association between the total cumulative number of new/enlarging T2 lesions and the evolution of whole-brain (P < .001), lateral ventricle (P = .007), gray matter and thalamic (P = .013), subcortical deep gray matter (P = .015), and cortical (P = .036) volumes over the follow-up period. CONCLUSIONS: Lesion accumulation and brain-volume changes occur simultaneously in the early phase of clinically isolated syndrome. More severe lesion and brain-volume outcomes at baseline were associated with greater development of brain atrophy over the follow-up period in patients with clinically isolated syndrome.
- MeSH
- adjuvancia imunologická terapeutické užití MeSH
- atrofie patologie MeSH
- demyelinizační nemoci farmakoterapie patologie MeSH
- dospělí MeSH
- interferon beta 1a terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nemoci mozku farmakoterapie patologie MeSH
- progrese nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adjuvancia imunologická MeSH
- interferon beta 1a MeSH
Acute orofacial pain is associated with significant disability and has a detrimental impact on quality of life. Although various origins of the pain in trigeminal territory can be identified an odontogenic pathology is the most common cause of acute orofacial pain in patients. Due to complex pathophysiology drugs with multitarget action might provide beneficial effect in pain management. The aim of the present study was to experimentally examine the anti-nociceptive effects of tapentadol, an opioid agonist and a norepinephrine reuptake inhibitor (MOR/NRI), in our animal model of orofacial pain. We tested the effect of tapentadol at gradual doses of 1, 2 and 5 mg/kg during thermal and mechanical stimulation in the trigeminal area of adult rats. We observed that tapentadol exhibits antinociceptive effect at dosages of 2 mg/kg and 5 mg/kg and only in association with mechanical stimulation.
- MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech MeSH
- obličejová bolest farmakoterapie patologie MeSH
- opioidní analgetika farmakologie MeSH
- pilotní projekty MeSH
- potkani Wistar MeSH
- tapentadol farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- opioidní analgetika MeSH
- tapentadol MeSH