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1.
Bone Joint J ; 101-B(9): 1063-1070, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31474149

RESUMO

AIMS: The primary aim of the study was to perform an analysis to identify the cost per quality-adjusted life-year (QALY) of robot-assisted unicompartmental knee arthroplasty (rUKA) relative to manual total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) for patients with isolated medial compartment osteoarthritis (OA) of the knee. Secondary aims were to assess how case volume and length of hospital stay influenced the relative cost per QALY. PATIENTS AND METHODS: A Markov decision analysis was performed, using known parameters for costs, outcomes, implant survival, and mortality, to assess the cost-effectiveness of rUKA relative to manual TKA and UKA for patients with isolated medial compartment OA of the knee with a mean age of 65 years. The influence of case volume and shorter hospital stay were assessed. RESULTS: Using a model with an annual case volume of 100 patients, the cost per QALY of rUKA was £1395 and £1170 relative to TKA and UKA, respectively. The cost per QALY was influenced by case volume: a low-volume centre performing ten cases per year would achieve a cost per QALY of £7170 and £8604 relative to TKA and UKA. For a high-volume centre performing 200 rUKAs per year with a mean two-day length of stay, the cost per QALY would be £648; if performed as day-cases, the cost would be reduced to £364 relative to TKA. For a high-volume centre performing 200 rUKAs per year with a shorter length of stay of one day relative to manual UKA, the cost per QALY would be £574. CONCLUSION: rUKA is a cost-effective alternative to manual TKA and UKA for patients with isolated medial compartment OA of the knee. The cost per QALY of rUKA decreased with reducing length of hospital stay and with increasing case volume, compared with TKA and UKA. Cite this article: Bone Joint J 2019;101-B:1063-1070.


Assuntos
Artroplastia do Joelho/economia , Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Idoso , Artroplastia do Joelho/estatística & dados numéricos , Análise Custo-Benefício , Feminino , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Cadeias de Markov , Osteoartrite do Joelho/economia , Osteoartrite do Joelho/epidemiologia , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Reino Unido/epidemiologia
2.
Medicine (Baltimore) ; 98(33): e16843, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415409

RESUMO

BACKGROUND: The aim of this study was, from the Chinese healthcare perspective, to assess the cost-effectiveness of positron-emission tomography-computed tomography (PET-CT) with F-fluorodeoxyglucose (F-FDG) in preoperation staging for nonsmall-cell lung cancer (NSCLC) with resected monometastatic disease based on a retrospective study. This study was conducted from January 2017 to February 2019 at an academic hospital. METHODS: A Markov model and 3 decision-tree models were designed to calculate the long-term medical costs, outcomes, and incremental cost-effectiveness ratios (ICERs) of the 2 diagnostic strategies (PET-CT and conventional CT). Model robustness was assessed in sensitivity analyses. RESULTS: For the base-case analysis, preoperative PET-CT evaluation for NSCLC with resected monometastatic disease provided an additional 1.475, 2.129, and 2.412 life-years (LYs), in the time horizon of 10-, 20-, and 30-year, respectively, and the ICERs for the PET-CT group compared with the conventional CT group were $1153, $1393, and $1430 per LY, separately. The acceptability curves demonstrated that when the willingness-to-pay (WTP) thresholds ranged from $500 to $3000/LY, the probability of cost-effectiveness changed varied dramatically, and at WTP > $3000, the probability that the PET-CT group achieved cost-effectiveness was 100%. Sensitivity analyses suggested that the models we designed were robust. CONCLUSION: Compared with conventional CT scan, preoperative F-FDG PET-CT evaluation for patients with resected monometastatic NSCLC is cost-effective from the Chinese healthcare perspective. Preoperative F-FDG PET-CT evaluation should be popularized for patients with resected monometastatic NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/economia , China , Análise Custo-Benefício , Árvores de Decisões , Humanos , Linfonodos/diagnóstico por imagem , Cadeias de Markov , Estadiamento de Neoplasias/instrumentação , Cuidados Pré-Operatórios/economia , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos
3.
Pan Afr Med J ; 33: 26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384341

RESUMO

Introduction: approximately eighty million people around the world are living with hepatitis C, and 700,000 people die every year, due to hepatitis C related complications. In Seychelles, a total of 777 cases of hepatitis C were reported from 2002 to 2016, but up to mid of 2016, the cases were not being treated. Treatment with Harvoni, a combination of sofosbuvir and ledipasvir (SOF/LDV), is now being offered on the condition that the patient does not, or has stopped, injecting drugs. This paper is the first to establish the cost effectiveness of treating all cases of hepatitis C in Seychelles with Harvoni, as compared to no treatment. Methods: data extracted from literature was used to populate an economic model to calculate cost-effectiveness from Seychelles' government perspective. The model structure was also informed by the systematic review and an accompanying grading of economic models using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. A Markov model was developed, employing a lifetime horizon and costs and benefits were analysed from a payer's perspective and combined into incremental cost effectiveness ratios (ICERs). Results: the direct-acting antiviral (DAA), Harvoni, was found to be cost-saving in Seychelles hepatitis C virus (HCV) cohort, as compared to no treatment, with an ICER of € 753.65/QALY. The treatment was also cost-saving when stratified by gender, with the ICER of male and female being € 783.74/QALY and € 635.20/QALY, respectively. Moreover, the results obtained from acceptability curves showed that treating patients with Harvoni is the most cost-effective option, even for low thresholds. Conclusion: treating hepatitis C cases in Seychelles is cost-saving. It is worth developing a treatment programme to include all cases of hepatitis C, regardless of status of drug injection.


Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Antivirais/economia , Benzimidazóis/economia , Análise Custo-Benefício , Feminino , Fluorenos/economia , Hepatite C Crônica/economia , Humanos , Masculino , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Fatores Sexuais , Seicheles , Abuso de Substâncias por Via Intravenosa/epidemiologia , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/economia
4.
J Chem Theory Comput ; 15(9): 4974-4981, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31402652

RESUMO

Predicting the costructure of small-molecule ligands and their respective target proteins has been a long-standing problem in drug discovery. For weak binding compounds typically identified in fragment-based screening (FBS) campaigns, determination of the correct binding site and correct binding mode is usually done experimentally via X-ray crystallography. For many targets of pharmaceutical interest, however, establishing an X-ray system which allows for sufficient throughput to support a drug discovery project is not possible. In this case, exploration of fragment hits becomes a very laborious and consequently slow process with the generation of protein/ligand cocrystal structures as the bottleneck of the entire process. In this work, we introduce a computational method which is able to reliably predict binding sites and binding modes of fragment-like small molecules using solely the structure of the apoprotein and the ligand's chemical structure as input information. The method is based on molecular dynamics simulations and Markov-state models and can be run as a fully automated protocol requiring minimal human intervention. We describe the application of the method to a representative subset of different target classes and fragments from historical FBS efforts at Boehringer Ingelheim and discuss its potential integration into the overall fragment-based drug discovery workflow.


Assuntos
Cadeias de Markov , Simulação de Dinâmica Molecular , Proteínas/química , Sítios de Ligação , Cristalografia por Raios X , Humanos , Ligantes
5.
Ecol Lett ; 22(10): 1680-1689, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31347244

RESUMO

Predicting connectivity, or how landscapes alter movement, is essential for understanding the scope for species persistence with environmental change. Although it is well known that movement is risky, connectivity modelling often conflates behavioural responses to the matrix through which animals disperse with mortality risk. We derive new connectivity models using random walk theory, based on the concept of spatial absorbing Markov chains. These models decompose the role of matrix on movement behaviour and mortality risk, can incorporate species distribution to predict the amount of flow, and provide both short- and long-term analytical solutions for multiple connectivity metrics. We validate the framework using data on movement of an insect herbivore in 15 experimental landscapes. Our results demonstrate that disentangling the roles of movement behaviour and mortality risk is fundamental to accurately interpreting landscape connectivity, and that spatial absorbing Markov chains provide a generalisable and powerful framework with which to do so.


Assuntos
Distribuição Animal , Ecossistema , Mortalidade , Movimento , Animais , Cadeias de Markov , Análise Espaço-Temporal
6.
J Chem Phys ; 150(24): 244120, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31255081

RESUMO

Recently derived steady-state differential rate laws for the catalytic turnover of molecules containing two substrate sites are reformulated as integrated rate laws. The analysis applies to a broad class of Markovian dynamic models, motivated by the varied and often complex mechanisms associated with DNA modifying enzymes. Analysis of experimental data for the methylation kinetics of DNA by Dam (DNA adenine methyltransferase) is drastically improved through the use of integrated rate laws. Data that are too noisy for fitting to differential predictions are reliably interpreted through the integrated rate laws.


Assuntos
DNA/química , DNA Metiltransferases Sítio Específica (Adenina-Específica)/química , Metilação de DNA , Cinética , Cadeias de Markov , Modelos Químicos
7.
BMC Bioinformatics ; 20(1): 394, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31311497

RESUMO

BACKGROUND: High-dimensional data of discrete and skewed nature is commonly encountered in high-throughput sequencing studies. Analyzing the network itself or the interplay between genes in this type of data continues to present many challenges. As data visualization techniques become cumbersome for higher dimensions and unconvincing when there is no clear separation between homogeneous subgroups within the data, cluster analysis provides an intuitive alternative. The aim of applying mixture model-based clustering in this context is to discover groups of co-expressed genes, which can shed light on biological functions and pathways of gene products. RESULTS: A mixture of multivariate Poisson-log normal (MPLN) model is developed for clustering of high-throughput transcriptome sequencing data. Parameter estimation is carried out using a Markov chain Monte Carlo expectation-maximization (MCMC-EM) algorithm, and information criteria are used for model selection. CONCLUSIONS: The mixture of MPLN model is able to fit a wide range of correlation and overdispersion situations, and is suited for modeling multivariate count data from RNA sequencing studies. All scripts used for implementing the method can be found at https://github.com/anjalisilva/MPLNClust .


Assuntos
Algoritmos , RNA/química , Análise por Conglomerados , Sequenciamento de Nucleotídeos em Larga Escala , Cadeias de Markov , Modelos Teóricos , Método de Monte Carlo , RNA/genética , RNA/metabolismo , Análise de Sequência de RNA , Interface Usuário-Computador
8.
BMC Bioinformatics ; 20(Suppl 13): 381, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31337329

RESUMO

BACKGROUND: How can we obtain fast and high-quality clusters in genome scale bio-networks? Graph clustering is a powerful tool applied on bio-networks to solve various biological problems such as protein complexes detection, disease module detection, and gene function prediction. Especially, MCL (Markov Clustering) has been spotlighted due to its superior performance on bio-networks. MCL, however, is skewed towards finding a large number of very small clusters (size 1-3) and fails to detect many larger clusters (size 10+). To resolve this fragmentation problem, MLR-MCL (Multi-level Regularized MCL) has been developed. MLR-MCL still suffers from the fragmentation and, in cases, unrealistically large clusters are generated. RESULTS: In this paper, we propose PS-MCL (Parallel Shotgun Coarsened MCL), a parallel graph clustering method outperforming MLR-MCL in terms of running time and cluster quality. PS-MCL adopts an efficient coarsening scheme, called SC (Shotgun Coarsening), to improve graph coarsening in MLR-MCL. SC allows merging multiple nodes at a time, which leads to improvement in quality, time and space usage. Also, PS-MCL parallelizes main operations used in MLR-MCL which includes matrix multiplication. CONCLUSIONS: Experiments show that PS-MCL dramatically alleviates the fragmentation problem, and outperforms MLR-MCL in quality and running time. We also show that the running time of PS-MCL is effectively reduced with parallelization.


Assuntos
Algoritmos , Proteínas/metabolismo , Análise por Conglomerados , Cadeias de Markov , Mapas de Interação de Proteínas , Proteínas/química
9.
Environ Sci Pollut Res Int ; 26(23): 24176-24189, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31228063

RESUMO

This paper develops the specific emission factors for buses in the real-world traffic conditions in the inner city of Hanoi, Vietnam. An engine stationary cycle consisting of 14 modes was developed based on the typical driving cycle of Hanoi buses which had been constructed with the application of Markov chain theory. This is the first engine stationary emissions test cycle constructed for heavy-duty engine in Vietnam. Based on this cycle, the country-specific emission factors (CSEFs) of air pollutants including CO, HC, NOx, CO2, and PM for buses in Hanoi have been developed using the emission measurements on the engine test bed. It is found that almost all developed emission factors are higher than those derived from the emission measurements to the ECE R49 on the same engine. These emission factors, therefore, can be used to improve the quality of the emission inventory of buses in Hanoi.


Assuntos
Poluentes Atmosféricos/análise , Veículos Automotores , Emissões de Veículos/análise , Dióxido de Carbono/análise , Monóxido de Carbono/análise , Cidades , Cadeias de Markov , Óxidos de Nitrogênio/análise , Material Particulado/análise , Vietnã
10.
Dis Colon Rectum ; 62(7): 872-881, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31188189

RESUMO

BACKGROUND: Intensive surveillance strategies are currently recommended for patients after curative treatment of colon cancer, with the aim of secondary prevention of recurrence. Yet, intensive surveillance has not yielded improvements in overall patient survival compared with minimal follow-up, and more intensive surveillance may be costlier. OBJECTIVE: The purpose of this study was to estimate the quality-adjusted life-years, economic costs, and cost-effectiveness of various surveillance strategies after curative treatment of colon cancer. DESIGN: A Markov model was calibrated to reflect the natural history of colon cancer recurrence and used to estimate surveillance costs and outcomes. SETTINGS: This was a decision-analytic model. PATIENTS: Individuals entered the model at age 60 years after curative treatment for stage I, II, or III colon cancer. Other initial age groups were assessed in secondary analyses. MAIN OUTCOME MEASURES: We estimated the gains in quality-adjusted life-years achieved by early detection and treatment of recurrence, as well as the economic costs of surveillance under various strategies. RESULTS: Cost-effective strategies for patients with stage I colon cancer improved quality-adjusted life-expectancy by 0.02 to 0.06 quality-adjusted life-years at an incremental cost of $1702 to $13,019. For stage II, they improved quality-adjusted life expectancy by 0.03 to 0.09 quality-adjusted life-years at a cost of $2300 to $14,363. For stage III, they improved quality-adjusted life expectancy by 0.03 to 0.17 quality-adjusted life-years for a cost of $1416 to $17,631. At a commonly cited willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the most cost-effective strategy for patients with a history of stage I or II colon cancer was liver ultrasound and chest x-ray annually. For those with a history of stage III colon cancer, the optimal strategy was liver ultrasound and chest x-ray every 6 months with CEA measurement every 6 months. LIMITATIONS: The study was limited by model structure assumptions and uncertainty around the values of the model's parameters. CONCLUSIONS: Given currently available data and within the limitations of a model-based decision-analytic approach, the effectiveness of routine intensive surveillance for patients after treatment of colon cancer appears, on average, to be small. Compared with testing using lower cost imaging, currently recommended strategies are associated with cost-effectiveness ratios that indicate low value according to well-accepted willingness-to-pay thresholds in the United States. See Video Abstract at http://links.lww.com/DCR/A921.


Assuntos
Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Modelos Teóricos , Vigilância da População/métodos , Idoso , Antígeno Carcinoembrionário/sangue , Neoplasias do Colo/sangue , Neoplasias do Colo/economia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Humanos , Cadeias de Markov , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Anos de Vida Ajustados por Qualidade de Vida , Prevenção Secundária/economia , Taxa de Sobrevida
11.
Chem Biol Interact ; 309: 108699, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31202688

RESUMO

The crystal structures of truncated forms of cholinesterases provide good models for assessing the role of non-covalent interactions in dimer assembly in the absence of cross-linking disulfide bonds. These structures identify the four-helix bundle that serves as the interface for formation of acetylcholinesterase and butyrylcholinesterase dimers. Here we performed a theoretical comparison of the structural and energetic factors governing dimerization. This included identification of inter-subunit and intra-subunit hydrogen bonds and hydrophobic interactions, evaluation of solvent-accessible surfaces, and estimation of electrostatic contributions to dimerization. To reveal the contribution to dimerization of individual amino acids within the contact area, free energy perturbation alanine screening was performed. Markov state modelling shows that the loop between the α13 and α14 helices in BChE is unstable, and occupies 4 macro-states. The order of magnitude of mean first passage times between these macrostates is ~10-8 s. Replica exchange molecular dynamics umbrella sampling calculations revealed that the free energy of human BChE dimerization is -15.5 kcal/mol, while that for human AChE is -26.4 kcal/mol. Thus, the C-terminally truncated human butyrylcholinesterase dimer is substantially less stable than that of human acetylcholinesterase. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:CHEMBIOINT:1.


Assuntos
Acetilcolinesterase/química , Butirilcolinesterase/química , Acetilcolinesterase/metabolismo , Sequência de Aminoácidos , Butirilcolinesterase/metabolismo , Dimerização , Humanos , Interações Hidrofóbicas e Hidrofílicas , Cadeias de Markov , Simulação de Dinâmica Molecular , Conformação Proteica em alfa-Hélice , Alinhamento de Sequência , Eletricidade Estática , Termodinâmica
12.
Value Health ; 22(6): 693-703, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31198187

RESUMO

BACKGROUND: Direct-acting antivirals are successful in curing hepatitis C virus infection in more than 95% of patients treated for 12 weeks, but they are expensive. Shortened treatment durations, which may have lower cure rates, have been proposed to reduce costs. OBJECTIVES: To evaluate the lifetime cost-effectiveness of different shortened treatment durations for genotype 1 noncirrhotic treatment-naive patients. METHODS: Assuming a UK National Health Service perspective, we used a probabilistic decision tree and Markov model to compare 3 unstratified shortened treatment durations (8, 6, and 4 weeks) against a standard 12-week treatment duration. Patients failing shortened first-line treatment were re-treated with a 12-week treatment regimen. Parameter inputs were taken from published studies. RESULTS: The 8-week treatment duration had an expected incremental net monetary benefit of £7737 (95% confidence interval £3242-£11 819) versus the standard 12-week treatment, per 1000 patients. The 6-week treatment had a positive incremental net monetary benefit, although some uncertainty was observed. The probability that the 8- and 6-week treatments were the most cost-effective was 56% and 25%, respectively, whereas that for the 4-week treatment was 17%. Results were generally robust to sensitivity analyses, including a threshold analysis that showed that the 8-week treatment was the most cost-effective at all drug prices lower than £40 000 per 12-week course. CONCLUSIONS: Shortening treatments licensed for 12 weeks to 8 weeks is cost-effective in genotype 1 noncirrhotic treatment-naive patients. There was considerable uncertainty in the estimates for 6- and 4-week treatments, with some indication that the 6-week treatment may be cost-effective.


Assuntos
Antivirais/economia , Hepatite C Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Carbamatos/economia , Carbamatos/uso terapêutico , Análise Custo-Benefício , Árvores de Decisões , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Compostos Heterocíclicos de 4 ou mais Anéis/economia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Compostos Macrocíclicos/economia , Compostos Macrocíclicos/uso terapêutico , Cadeias de Markov , Sofosbuvir/economia , Sofosbuvir/uso terapêutico , Medicina Estatal/organização & administração , Medicina Estatal/estatística & dados numéricos , Sulfonamidas/economia , Sulfonamidas/uso terapêutico , Reino Unido
13.
Environ Monit Assess ; 191(7): 422, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31177407

RESUMO

Modeling spatial-temporal dynamic of land use change is of great necessity for understanding the status of the past, causes of the change, and prediction of the future. This study aims to objectify three topics which include identifying the past land use changes, modeling the future changes, and subsequently considering their driving forces. The change detection analysis has shown that about 12,081.8 ha of the study area has changed since 1984 to 2014. Moreover, the models of cellular automata (CA) and Markov chain were applied in order to predict the land use changes of 2024 and 2034. The simulated transition matrix showed that about 6780 ha and 10,835 ha would change during the periods of 2014-2024 and 2014-2034, respectively. Furthermore, the results of the logistic regression model showed that the human driving forces of distance to roads, distance to wells, distance to streams, and distance to residential areas have had a negative effect on the process land use changes. Additionally, a questionnaire was used to obtain information considering the management factors of preventing land use changes, the perception of the natural resources' experts and in turn finding some socioeconomic and policy forces on land use changes. The Friedman's test analysis indicates that the factors of the official rules of government, economy, weakness of regulatory systems, and development activities, e.g., infrastructure and industrial projects, were identified as the leading causes of converting natural ecosystems to other land uses, particularly to cropland. Therefore, the decision-makers and managers should be assigned comprehensive planning for the protection, restoration, and development of natural resources, especially in this region.


Assuntos
Conservação dos Recursos Naturais/métodos , Conservação dos Recursos Naturais/tendências , Monitoramento Ambiental/métodos , Política Ambiental/tendências , Modelos Teóricos , Recursos Naturais , Ecossistema , Humanos , Modelos Logísticos , Cadeias de Markov , Fatores Socioeconômicos
14.
BMC Bioinformatics ; 20(1): 327, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31195954

RESUMO

BACKGROUND: The gap gene system controls the early cascade of the segmentation pathway in Drosophila melanogaster as well as other insects. Owing to its tractability and key role in embryo patterning, this system has been the focus for both computational modelers and experimentalists. The gap gene expression dynamics can be considered strictly as a one-dimensional process and modeled as a system of reaction-diffusion equations. While substantial progress has been made in modeling this phenomenon, there still remains a deficit of approaches to evaluate competing hypotheses. Most of the model development has happened in isolation and there has been little attempt to compare candidate models. RESULTS: The Bayesian framework offers a means of doing formal model evaluation. Here, we demonstrate how this framework can be used to compare different models of gene expression. We focus on the Papatsenko-Levine formalism, which exploits a fractional occupancy based approach to incorporate activation of the gap genes by the maternal genes and cross-regulation by the gap genes themselves. The Bayesian approach provides insight about relationship between system parameters. In the regulatory pathway of segmentation, the parameters for number of binding sites and binding affinity have a negative correlation. The model selection analysis supports a stronger binding affinity for Bicoid compared to other regulatory edges, as shown by a larger posterior mean. The procedure doesn't show support for activation of Kruppel by Bicoid. CONCLUSIONS: We provide an efficient solver for the general representation of the Papatsenko-Levine model. We also demonstrate the utility of Bayes factor for evaluating candidate models for spatial pattering models. In addition, by using the parallel tempering sampler, the convergence of Markov chains can be remarkably improved and robust estimates of Bayes factors obtained.


Assuntos
Drosophila melanogaster/genética , Redes Reguladoras de Genes , Animais , Teorema de Bayes , Proteínas de Drosophila/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Funções Verossimilhança , Cadeias de Markov , Modelos Genéticos , Método de Monte Carlo
15.
Artigo em Alemão | MEDLINE | ID: mdl-31243489

RESUMO

Dementia is one of the most frequent diseases of people aged 65 and older. As a result of the upcoming demographic transition, a significant increase is expected to the current number of around 1.7 million dementia patients. A precise estimate of this increase is especially important for decision-makers and payers to the health-care system. This study examined the effects of different assumptions on the future frequency of disease using a time-discrete Markov model with population-related and disease-specific components. Based on health insurers' administrative data from AOK Baden-Württemberg, we determined age- and gender-specific prevalence rates, incidence rates, and mortality differences of dementia patients and combined them with demographic components from German population statistics. As a result, our Markov model showed a 20 to 25% higher number of dementia patients in 2030, compared to the results of the status quo projection applied in most previous studies, with the assumption of constant prevalence rates over time. Hence, our results indicate that even in the medium term payers will have to face significant increases in dementia-related health expenditures. By 2060, the number of dementia patients in Germany would rise to 3.3 million assuming a further increase to life expectancy and constant incidence rates over time. The assumption of a compression of the morbidity would reduce this number to 2.6 million.


Assuntos
Demência/epidemiologia , Previsões/métodos , Gastos em Saúde/tendências , Formulário de Reclamação de Seguro/estatística & dados numéricos , Assistência de Longa Duração/economia , Idoso , Efeitos Psicossociais da Doença , Alemanha/epidemiologia , Gastos em Saúde/estatística & dados numéricos , Humanos , Incidência , Expectativa de Vida , Assistência de Longa Duração/estatística & dados numéricos , Cadeias de Markov , Prevalência
16.
Plant Physiol Biochem ; 141: 388-397, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31226508

RESUMO

Members of the Jasmonate ZIM domain (JAZ) proteins act as transcriptional repressors in the jasmonate (JA) hormonal response. To characterize the potential roles of JAZ gene family in plant development and abiotic stress response, fifteen JAZs were identified based on the genome of Nicotiana tabacum. Structural analysis confirmed the presence of single Jas and TIFY motif. Tissue expression pattern analysis indicated that NtJAZ-2, -3, -5, and -10 were highly expressed in roots and NtJAZ-11 was expressed only in the cotyledons. The transcript level of NtJAZ-3, -5, -9, and -10 in the stem epidermis was higher than that in the stem without epidermis. Dynamic expression of NtJAZs exposed to abiotic stress and phytohormone indicated that the expression of most NtJAZs was activated by salicylic acid, methyl jasmonate, gibberellic acid, cold, salt, and heat stresses. With abscisic acid treatment, NtJAZ-1, -2, and -3 were not activated; NtJAZ-4, -5, and -6 were up-regulated; and the remaining NtJAZ genes were inhibited. With drought stress, the expression of NtJAZ-1, -2, -3, -4, -5, -6, -7, and -8 was up-regulated, whereas the transcript of the remaining genes was inhibited. Moreover, high concentration MeJA (more than 1 mM MeJA) had an effect on secreting trichome induction, but inhabited the plant growth. Nine NtJAZs may play important role in secreting trichome induction. These results indicate that the JAZ proteins are convergence points for various phytohormone signal networks, which are involved in abiotic stress responses.


Assuntos
Proteínas de Plantas/metabolismo , Proteínas Repressoras/metabolismo , Estresse Fisiológico , Tabaco/genética , Tabaco/metabolismo , Tricomas/metabolismo , Acetatos/metabolismo , Motivos de Aminoácidos , Arabidopsis/metabolismo , Cromossomos/metabolismo , Ciclopentanos/metabolismo , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Cadeias de Markov , Oxilipinas/metabolismo , Filogenia , Reguladores de Crescimento de Planta/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Proteínas Repressoras/genética , Transdução de Sinais , Fatores de Transcrição/genética
17.
Nat Commun ; 10(1): 2648, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201322

RESUMO

Polarization affects many forms of social organization. A key issue focuses on which affective relationships are prone to change and how their change relates to performance. In this study, we analyze a financial institutional over a two-year period that employed 66 day traders, focusing on links between changes in affective relations and trading performance. Traders' affective relations were inferred from their IMs (>2 million messages) and trading performance was measured from profit and loss statements (>1 million trades). Here, we find that triads of relationships, the building blocks of larger social structures, have a propensity towards affective balance, but one unbalanced configuration resists change. Further, balance is positively related to performance. Traders with balanced networks have the "hot hand", showing streaks of high performance. Research implications focus on how changes in polarization relate to performance and polarized states can depolarize.


Assuntos
Comércio , Tomada de Decisões/fisiologia , Modelos Psicológicos , Assunção de Riscos , Rede Social , Humanos , Cadeias de Markov , Mensagem de Texto/estatística & dados numéricos
18.
J Chem Phys ; 150(22): 225102, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31202237

RESUMO

A majority of cellular proteins function as part of multimeric complexes of two or more subunits. Multimer formation requires interactions between protein surfaces that lead to closed structures, such as dimers and tetramers. If proteins interact in an open-ended way, uncontrolled growth of fibrils can occur, which is likely to be detrimental in most cases. We present a statistical physics model that allows aggregation of proteins as either closed dimers or open fibrils of all lengths. We use pairwise amino-acid contact energies to calculate the energies of interacting protein surfaces. The probabilities of all possible aggregate configurations can be calculated for any given sequence of surface amino acids. We link the statistical physics model to a population genetics model that describes the evolution of the surface residues. When proteins evolve neutrally, without selection for or against multimer formation, we find that a majority of proteins remain as monomers at moderate concentrations, but strong dimer-forming or fibril-forming sequences are also possible. If selection is applied in favor of dimers or in favor of fibrils, then it is easy to select either dimer-forming or fibril-forming sequences. It is also possible to select for oriented fibrils with protein subunits all aligned in the same direction. We measure the propensities of amino acids to occur at interfaces relative to noninteracting surfaces and show that the propensities in our model are strongly correlated with those that have been measured in real protein structures. We also show that there are significant differences between amino acid frequencies at isologous and heterologous interfaces in our model, and we observe that similar effects occur in real protein structures.


Assuntos
Evolução Molecular , Modelos Biológicos , Agregados Proteicos , Multimerização Proteica , Proteínas/química , Aminoácidos/química , Cadeias de Markov , Método de Monte Carlo , Termodinâmica
19.
BMC Infect Dis ; 19(1): 474, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138129

RESUMO

BACKGROUND: Tuberculosis (TB) is the leading cause of death from an infectious disease in Ethiopia, killing more than 30 thousand people every year. This study aimed to determine whether the rates of poor TB treatment outcome varied geographically across Ethiopia at district and zone levels and whether such variability was associated with socioeconomic, behavioural, health care access, or climatic conditions. METHODS: A geospatial analysis was conducted using national TB data reported to the health management information system (HMIS), for the period 2015-2017. The prevalence of poor TB treatment outcomes was calculated by dividing the sum of treatment failure, death and loss to follow-up by the total number of TB patients. Binomial logistic regression models were computed and a spatial analysis was performed using a Bayesian framework. Estimates of parameters were generated using Markov chain Monte Carlo (MCMC) simulation. Geographic clustering was assessed using the Getis-Ord Gi* statistic, and global and local Moran's I statistics. RESULTS: A total of 223,244 TB patients were reported from 722 districts in Ethiopia during the study period. Of these, 63,556 (28.5%) were cured, 139,633 (62.4%) completed treatment, 6716 (3.0%) died, 1459 (0.7%) had treatment failure, and 12,200 (5.5%) were lost to follow-up. The overall prevalence of a poor TB treatment outcome was 9.0% (range, 1-58%). Hot-spots and clustering of poor TB treatment outcomes were detected in districts near the international borders in Afar, Gambelia, and Somali regions and cold spots were detected in Oromia and Amhara regions. Spatial clustering of poor TB treatment outcomes was positively associated with the proportion of the population with low wealth index (OR: 1.01; 95%CI: 1.0, 1.01), the proportion of the population with poor knowledge about TB (OR: 1.02; 95%CI: 1.01, 1.03), and higher annual mean temperature per degree Celsius (OR: 1.15; 95% CI: 1.08, 1.21). CONCLUSIONS: This study showed significant spatial variation in poor TB treatment outcomes in Ethiopia that was related to underlying socioeconomic status, knowledge about TB, and climatic conditions. Clinical and public health interventions should be targeted in hot spot areas to reduce poor TB treatment outcomes and to achieve the national End-TB Strategy targets.


Assuntos
Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Teorema de Bayes , Análise por Conglomerados , Etiópia/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Acesso aos Serviços de Saúde , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Método de Monte Carlo , Prevalência , Fatores Socioeconômicos , Análise Espacial , Resultado do Tratamento
20.
Environ Sci Pollut Res Int ; 26(20): 20669-20688, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104240

RESUMO

The construction of The Three Gorges Reservoir has changed land use structure and reconstituted landscape pattern as imparts significant influence upon the land use structure and ecological environment of Three Gorges Reservoir Regions. The ecological safety of reservoir area is extremely dependent on unique location and special geological conditions of Zhongxian County, the center of Three Gorges Reservoir Regions in Chongqing, and therefore, ecological environment of reservoir area will be changed with the transition of land use in Zhongxian County. Based on land use data in 2000, 2005, 2010, this paper chooses influencing factors from aspects of natural topographic and geomorphological conditions, accessibility to economic development and land use expansion, and then establishes Logistic-CA-Markov (Logistic-Cellular Automata-Markov) and WLC-CA-Markov (Weighted Linear Combination- Cellular Automata- Markov) models so as to simulate spatial pattern of land use of Zhongxian County. The results demonstrate that WLC-CA-Markov model established here has better controllability and higher simulation precision (the kappa coefficient is 0.9295). In the future development of Zhongxian County, the area of grassland and plow land will be reduced continuously, the area of construction land will be expanded obviously mostly because of the added area both near the water and in the north of Zhongxian county, the area of woodland will be increased to a little extent, the area of water area and unused land has gentle change. In the sustainable scenario, the area of grassland will be reduced slightly, the area of water area keeps steady, the area of plow land is reduced but higher than red line of plow land, the area of construction land is increased with significantly smaller increase amplitude than that in the natural development scenario, and the woodland is increased. This scenario coordinates ecological environment with economic development of regional society and turns out to be the best development scenario of land use.


Assuntos
Conservação dos Recursos Naturais/tendências , Ecossistema , Modelos Estatísticos , China , Simulação por Computador , Conservação dos Recursos Naturais/estatística & dados numéricos , Desenvolvimento Econômico , Cadeias de Markov , Desenvolvimento Vegetal , Rios , Urbanização
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