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1.
Lancet ; 395(10225): 689-697, 2020 02 29.
Artículo en Inglés | MEDLINE | ID: mdl-32014114

RESUMEN

BACKGROUND: Since Dec 31, 2019, the Chinese city of Wuhan has reported an outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV). Cases have been exported to other Chinese cities, as well as internationally, threatening to trigger a global outbreak. Here, we provide an estimate of the size of the epidemic in Wuhan on the basis of the number of cases exported from Wuhan to cities outside mainland China and forecast the extent of the domestic and global public health risks of epidemics, accounting for social and non-pharmaceutical prevention interventions. METHODS: We used data from Dec 31, 2019, to Jan 28, 2020, on the number of cases exported from Wuhan internationally (known days of symptom onset from Dec 25, 2019, to Jan 19, 2020) to infer the number of infections in Wuhan from Dec 1, 2019, to Jan 25, 2020. Cases exported domestically were then estimated. We forecasted the national and global spread of 2019-nCoV, accounting for the effect of the metropolitan-wide quarantine of Wuhan and surrounding cities, which began Jan 23-24, 2020. We used data on monthly flight bookings from the Official Aviation Guide and data on human mobility across more than 300 prefecture-level cities in mainland China from the Tencent database. Data on confirmed cases were obtained from the reports published by the Chinese Center for Disease Control and Prevention. Serial interval estimates were based on previous studies of severe acute respiratory syndrome coronavirus (SARS-CoV). A susceptible-exposed-infectious-recovered metapopulation model was used to simulate the epidemics across all major cities in China. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credibile interval (CrI). FINDINGS: In our baseline scenario, we estimated that the basic reproductive number for 2019-nCoV was 2·68 (95% CrI 2·47-2·86) and that 75 815 individuals (95% CrI 37 304-130 330) have been infected in Wuhan as of Jan 25, 2020. The epidemic doubling time was 6·4 days (95% CrI 5·8-7·1). We estimated that in the baseline scenario, Chongqing, Beijing, Shanghai, Guangzhou, and Shenzhen had imported 461 (95% CrI 227-805), 113 (57-193), 98 (49-168), 111 (56-191), and 80 (40-139) infections from Wuhan, respectively. If the transmissibility of 2019-nCoV were similar everywhere domestically and over time, we inferred that epidemics are already growing exponentially in multiple major cities of China with a lag time behind the Wuhan outbreak of about 1-2 weeks. INTERPRETATION: Given that 2019-nCoV is no longer contained within Wuhan, other major Chinese cities are probably sustaining localised outbreaks. Large cities overseas with close transport links to China could also become outbreak epicentres, unless substantial public health interventions at both the population and personal levels are implemented immediately. Independent self-sustaining outbreaks in major cities globally could become inevitable because of substantial exportation of presymptomatic cases and in the absence of large-scale public health interventions. Preparedness plans and mitigation interventions should be readied for quick deployment globally. FUNDING: Health and Medical Research Fund (Hong Kong, China).


Asunto(s)
Simulación por Computador , Infecciones por Coronavirus/epidemiología , Epidemias , China/epidemiología , Infecciones por Coronavirus/transmisión , Predicción , Hospitalización/estadística & datos numéricos , Humanos , Periodo de Incubación de Enfermedades Infecciosas , Internacionalidad , Cadenas de Markov , Método de Montecarlo , Prevalencia
2.
Environ Monit Assess ; 192(2): 100, 2020 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-31912242

RESUMEN

Water temperature is a key characteristic defining chemical, physical, and biologic conditions in riverine systems. Models of riverine water quality require many inputs, which are commonly beset by uncertainty. This study presents an uncertainty analysis of inputs to the stream-temperature simulation model HFLUX. This paper's assessment relies on a Markov chain Monte Carlo (MCMC) analysis with the DREAM algorithm, which has fast convergence rate and good accuracy. The inputs herein considered are the river width and depth, percent shade, view to sky, streamflow, and the minimum and maximum values of inputs required for uncertainty analysis. The results are presented as histograms for each input specifying the input's uncertainty. A comparison of the observational data with the DREAM algorithm estimates yielded a maximum error equal to 7.5%, which indicates excellent performance of the DREAM algorithm in ascertaining the effect of uncertainty in riverine water quality assessment.


Asunto(s)
Monitoreo del Ambiente/métodos , Hidrodinámica , Ríos , Algoritmos , Teorema de Bayes , Cadenas de Markov , Método de Montecarlo , Temperatura Ambiental , Incertidumbre , Agua/química , Calidad del Agua
3.
Plast Reconstr Surg ; 145(2): 401e-406e, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31985655

RESUMEN

BACKGROUND: Chronic migraines affect approximately 2 percent of the U.S. population and cost an estimated $17 billion per year. OnabotulinumtoxinA (botulinum toxin type A) is a U.S. Food and Drug Administration-approved prophylactic medication for chronic migraine headaches and is best injected in a targeted fashion into specific trigger sites. The purpose of this study was to determine the cost-effectiveness of long-term, targeted botulinum toxin type A versus peripheral trigger site deactivation surgery for the treatment of migraine headaches. METHODS: A Markov model was constructed to examine long-term, targeted botulinum toxin type A versus peripheral trigger site deactivation surgery. Costs, utilities, and other model inputs were identified from the literature. One-way and probabilistic sensitivity analyses were performed. An incremental cost-effectiveness ratio under $50,000 per quality-adjusted life-year was considered cost-effective. RESULTS: The mean cost of peripheral trigger site deactivation surgery was $10,303, with an effectiveness of 7.06; whereas the mean cost of long-term, targeted botulinum toxin type A was $36,071, with an effectiveness of 6.34. Trigger-site deactivation surgery is more effective and less costly over the time horizon of the model. One-way sensitivity analysis revealed that surgery is the most cost-effective treatment in patients requiring treatment for greater than 6.75 years. CONCLUSIONS: Based on this model, peripheral trigger site deactivation surgery is the more cost-effective option for treating refractory migraine headaches requiring treatment beyond 6.75 years. The model reveals that peripheral trigger-site deactivation surgery is more effective and less costly than long-term, targeted botulinum toxin type A over the course of a patient's lifetime.


Asunto(s)
Inhibidores de la Liberación de Acetilcolina , Toxinas Botulínicas Tipo A , Trastornos Migrañosos , Procedimientos Neuroquirúrgicos , Inhibidores de la Liberación de Acetilcolina/economía , Inhibidores de la Liberación de Acetilcolina/uso terapéutico , Adulto , Toxinas Botulínicas Tipo A/economía , Toxinas Botulínicas Tipo A/uso terapéutico , Análisis Costo-Beneficio , Humanos , Cadenas de Markov , Persona de Mediana Edad , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/economía , Trastornos Migrañosos/cirugía , Procedimientos Neuroquirúrgicos/economía , Procedimientos Neuroquirúrgicos/métodos
4.
J Chem Theory Comput ; 16(2): 1333-1348, 2020 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-31917926

RESUMEN

Hydrogen/deuterium exchange (HDX) is a powerful technique to investigate protein conformational dynamics at amino acid resolution. Because HDX provides a measurement of solvent exposure of backbone hydrogens, ensemble-averaged over potentially slow kinetic processes, it has been challenging to use HDX protection factors to refine structural ensembles obtained from molecular dynamics simulations. This entails dual challenges: (1) identifying structural observables that best correlate with backbone amide protection from exchange and (2) restraining these observables in molecular simulations to model ensembles consistent with experimental measurements. Here, we make significant progress on both fronts. First, we describe an improved predictor of HDX protection factors from structural observables in simulated ensembles, parametrized from ultralong molecular dynamics simulation trajectory data, with a Bayesian inference approach used to retain the full posterior distribution of model parameters. We next present a new method for obtaining simulated ensembles in agreement with experimental HDX protection factors, in which molecular simulations are performed at various temperatures and restraint biases and used to construct multiensemble Markov State Models (MSMs). Finally, the BICePs (Bayesian Inference of Conformational Populations) algorithm is then used with our HDX protection factor predictor to infer which thermodynamic ensemble agrees best with the experiment and estimate populations of each conformational state in the MSM. To illustrate the approach, we use a combination of HDX protection factor restraints and chemical shift restraints to model the conformational ensemble of apomyoglobin at pH 6. The resulting ensemble agrees well with the experiment and gives insight into the all-atom structure of disordered helices F and H in the absence of heme.


Asunto(s)
Apoproteínas/química , Simulación por Computador , Mioglobina/química , Teorema de Bayes , Hidrógeno , Cadenas de Markov , Modelos Químicos , Modelos Moleculares , Conformación Proteica
5.
PLoS One ; 15(1): e0225301, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31978044

RESUMEN

OBJECTIVE: The objective was to assess the real-world cost-effectiveness of rivaroxaban, versus vitamin K antagonists (VKAs), for stroke prevention in patients with atrial fibrillation (AF) from a French national health insurance perspective. METHODS: A Markov model was developed with a lifetime horizon and cycle length of 3 months. All inputs were drawn from real-world evidence (RWE) studies: data on baseline patient characteristics at model entry were obtained from a French RWE study, clinical event rates as well as persistence rates for the VKA treatment arm were estimated from a variety of RWE studies, and a meta-analysis provided comparative effectiveness for rivaroxaban compared to VKA. Model outcomes included costs (drug costs, clinical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers. RESULTS: In the base-case analysis, the incremental total cost was €714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The resulting incremental cost/QALY and incremental cost/LY were €6,006 and €4,586, respectively. The results were more sensitive to the inclusion of treatment-specific utility decrements and clinical event rates. CONCLUSIONS: Although there is no official willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French patients with AF from a national insurance perspective.


Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Rivaroxabán/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Vitamina K/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Fibrilación Atrial/economía , Fibrilación Atrial/patología , Análisis Costo-Beneficio , Femenino , Francia/epidemiología , Humanos , Masculino , Cadenas de Markov , Persona de Mediana Edad , Infarto del Miocardio/economía , Infarto del Miocardio/patología , Infarto del Miocardio/prevención & control , Años de Vida Ajustados por Calidad de Vida , Rivaroxabán/economía , Accidente Cerebrovascular/economía , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/prevención & control , Warfarina/uso terapéutico
6.
J Stroke Cerebrovasc Dis ; 29(1): 104465, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31704123

RESUMEN

BACKGROUND: The Kingdom of Saudi Arabia has a young but ageing population, leading to concerns for planning for future growth in the number of strokes to provide necessary care. An understanding of the expected evolution of stroke incidence is therefore necessary to plan infrastructure changes. Our aim was to predict the number of first strokes occurring in Saudi Arabia over a 10-year period. METHODS: An epidemiological model was developed, using local mortality and population data to model changes in the population. Gender- and age-specific stroke rates were then applied to the population projections to estimate the number of first strokes occurring over a 10-year period. Stroke incidence data from a range of sources were applied to obtain a plausible range for the change in expected number of first strokes. RESULTS: The model predicted population growth of 12.8% over the 10-year period. Depending on the stroke incidence data applied, the number of first strokes occurring during this time was predicted to increase within the range 57%-67%. CONCLUSIONS: A growing and ageing population is expected to lead to a substantial increase in the number of first strokes occurring in Saudi Arabia in the coming decade. Our results suggest that stroke care services will need to be expanded to continue to ensure high quality care, and that strategies for stroke prevention will play an important role in reducing the overall burden. This type of analysis can be applied to other countries' stroke policy planning.


Asunto(s)
Accidente Cerebrovascular/epidemiología , Distribución por Edad , Femenino , Predicción , Necesidades y Demandas de Servicios de Salud/tendencias , Humanos , Incidencia , Masculino , Cadenas de Markov , Evaluación de Necesidades/tendencias , Formulación de Políticas , Dinámica Poblacional , Arabia Saudita/epidemiología , Distribución por Sexo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/terapia , Factores de Tiempo
7.
J Chem Theory Comput ; 16(1): 80-87, 2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31809040

RESUMEN

By using an approach that allows computing the free energy in high-dimensional spaces together with a clustering technique capable of identifying kinetic attractors stabilized by conformational disorder, we analyze a molecular dynamics trajectory of the Villin headpiece from Lindorff-Larsen, K.; et al. How fast-folding proteins fold. Science 2011, 334, 517-520. We compute its free-energy landscape in the space of all its Cα carbons. This landscape has the shape of a 12-dimensional funnel with the free energy decreasing monotonically as a function of the native contacts. There are no significant folding barriers. The funnel can be partitioned in five regions, three mainly folded and two unfolded, which behave as Markov states. The slowest relaxation time among these states corresponds to the folding transition. The second slowest time is only twice smaller and corresponds to a transition within the unfolded state. This indicates that the unfolded part of the funnel has a nontrivial shape, which induces a sizable kinetic barrier between disordered states.


Asunto(s)
Carbono/química , Proteínas de Microfilamentos/química , Pliegue de Proteína , Termodinámica , Animales , Pollos , Análisis por Conglomerados , Cinética , Cadenas de Markov , Simulación de Dinámica Molecular , Conformación Proteica
8.
Neural Netw ; 121: 10-20, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31522021

RESUMEN

This paper studies the synchronous problem of Markovian switching complex networks associated with partly unknown transitional rates, stochastic noise, and randomly coupling strength. In order to achieve the synchronization for these array networks, event-triggered pinning control is established and developed, in which the pinning node undergoes a self-adapted switch, governed by a Markov chain. Two types of event-triggered sampling controls, centralized and decentralized event-triggered sampling, respectively, are established. Sufficient conditions for synchronization are developed by constructing a desirable stochastic Lyapunov functional as well as by employing the properties of Markov chain and Itoˆ integration. Numerical simulations are provided to demonstrate the effectiveness of the proposed approach.


Asunto(s)
Cadenas de Markov , Procesos Estocásticos
9.
Syst Biol ; 69(1): 76-90, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31125064

RESUMEN

A statistical framework to infer areas of endemism from geographic distributions is proposed. This novel method is based on hidden Markov random fields (HMRFs), a type of undirected graph model commonly used in computer vision. This framework assumes areas of endemism are the states of the hidden layer of the model, whereas taxon distributions are emitted values in the observed layer. Taxon distributions are associated to the observed layer through a clustering procedure based on the extent of overlap. Observations are emitted by the hidden layer according to a Gaussian distribution, whereas the joint distribution of the hidden layer follows a Potts model. State and parameter inference of the maximum a posteriori configuration is performed through a modified version of the expectation-maximization algorithm. The optimal number of areas of endemism in the data set is estimated through the pseudolikelihood information criterion, a model selection procedure that uses an approximation to likelihood. The performance of the new algorithm was assessed on simulated data, and compared with the most popular methods for delimitation of areas of endemism: biotic element analysis, parsimony analysis of endemism, and endemicity analysis. HMRFs efficiently recovered the true pattern across a wide range of uncertainty values. The performance was also examined on empirical data: South African weevils (Sciobius) and Central American ground beetles and funnel-web tarantulas (Carabidae and Dipluridae, respectively). HMRFs uncovered six areas of endemism from the weevil data set, whereas eight were estimated for the Central American arthropods (compared with 3-5 and 3-14 from the other methods, respectively).


Asunto(s)
Distribución Animal , Modelos Estadísticos , Algoritmos , Animales , Simulación por Computador , Cadenas de Markov
10.
Food Microbiol ; 85: 103285, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31500704

RESUMEN

The objective of this study was to determine the kinetic parameters and apply Markov Chain Monte Carlo (MCMC) simulation to predict the growth of Clostridium perfringens from spores in cooked ground chicken meat during dynamic cooling. Inoculated samples were exposed to various cooling conditions to observe dynamic growth. A combination of 4 cooling profiles was used in one-step inverse analysis with the Baranyi model as the primary model and the cardinal parameters model as the secondary model. Six kinetic parameters of the Baranyi model and the cardinal parameters model, including Q0, Ymax, µopt, Tmin, Topt, and Tmax, were estimated. The estimated Tmin, Topt, and Tmax were 14.8, 42.9, and 50.5 °C, respectively, with a µopt of 5.25 h-1 and maximum cell density of 8.4 log CFU/g. Correlation analysis showed that both Q0 and Ymax are weakly correlated to other parameters, while the remaining parameters are mostly mildly to strongly correlated with each other. Although it may be difficult to estimate highly correlated parameters using a single temperature profile, one-step analysis with multiple different temperature profiles helped estimate them successfully. The estimated parameters were used as the prior information to construct the posterior distribution for Bayesian analysis. MCMC simulation was used to predict the bacterial growth using different dynamic temperature profiles for validation of the accuracy of the predictive models. The MCMC simulation results showed that the Bayesian analysis produced more accurate predictions of bacterial growth during cooling than the deterministic method. With Bayesian analysis, the root-mean-square-error (RMSE) of prediction was only 0.1 log CFU/g with all residual errors within ±0.25 log CFU/g. Therefore, Bayesian analysis is recommended for predicting the growth of C. perfringens in cooked meat during cooling.


Asunto(s)
Clostridium perfringens/crecimiento & desarrollo , Culinaria , Manipulación de Alimentos , Productos de la Carne/microbiología , Temperatura Ambiental , Animales , Teorema de Bayes , Pollos , Recuento de Colonia Microbiana , Simulación por Computador , Cinética , Cadenas de Markov , Modelos Biológicos , Método de Montecarlo , Esporas Bacterianas/crecimiento & desarrollo
11.
Zhonghua Fu Chan Ke Za Zhi ; 54(12): 840-847, 2019 Dec 25.
Artículo en Chino | MEDLINE | ID: mdl-31874474

RESUMEN

Objective: To evaluate the feasible cervical cancer screening strategies in rural China. Methods: The study was based on the health industry scientific research project of National Health Commission in 2015, cervical cancer screening technology and demonstration research suitable for rural areas in China, we collected health economics and epidemiological parameters and established the unscreening model and screening model with Treeage Pro 2011 software. Combining with the data acquired from site investigation, including population screening, treatment-related clinical materials and cost data, we simulated the occurrence and the development of cervical cancer of rural women in China under different screening and intervention programs and predicted the screening effects [cumulative incidence, cumulative risk of disease, life years and quality adjusted life years (QALY) , gains] and costs after 20 years, and using health economic evaluation analysis (cost-effectiveness analysis, cost-utility analysis, cost-benefit analysis). Screening programs included five screening strategies [visual inspection with acetic acid/lugol's iodine (VIA/VILI), careHPV, ThinPrep cytology test (TCT), careHPV+TCT, careHPV+VIA/VILI] and three screening intervals (1-year, 3-year, 5-year), a total of fifteen screening programs. Results: Compared with no screening, fifteen screening programs reduced the cumulative incidence by 22.65%-51.76%. Compared with TCT or VIA/VILI, for the same screening interval, the reduced cumulative incidence, the amounts of life-year saved and QALY and benefits gained of careHPV were the highest. The cost-effectiveness ratios of these screening programs ranged (0.44-3.24)×10(4) Yuan per life-year saved, cost-utility ratios ranged (0.15- 1.01)×10(4) Yuan per QALY, benefit-cost ratios ranged 7.73-59.10. The results of incremental costeffectiveness ratios showed that VIA/VILI every five years, VIA/VILI every three years, careHPV every five years, careHPV every three years and careHPV every year were dominant programs. Conclusions: VIA/VILI screening is cost-effective, careHPV is slightly more expensive but more effective. In rural China, careHPV screening every five years could be recommended. This study provides a basis for the determination of cervical cancer screening methods feasible for rural areas in China.


Asunto(s)
Detección Precóz del Cáncer/economía , Tamizaje Masivo/economía , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , China , Análisis Costo-Beneficio , Detección Precóz del Cáncer/métodos , Femenino , Humanos , Cadenas de Markov , Tamizaje Masivo/métodos , Salud Rural , Neoplasias del Cuello Uterino/economía
12.
BMC Evol Biol ; 19(1): 232, 2019 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-31878875

RESUMEN

BACKGROUND: Inexpensive pathogen genome sequencing has had a transformative effect on the field of phylodynamics, where ever increasing volumes of data have promised real-time insight into outbreaks of infectious disease. As well as the sheer volume of pathogen isolates being sequenced, the sequencing of whole pathogen genomes, rather than select loci, has allowed phylogenetic analyses to be carried out at finer time scales, often approaching serial intervals for infections caused by rapidly evolving RNA viruses. Despite its utility, whole genome sequencing of pathogens has not been adopted universally and targeted sequencing of loci is common in some pathogen-specific fields. RESULTS: In this study we highlighted the utility of sequencing whole genomes of pathogens by re-analysing a well-characterised collection of Ebola virus sequences in the form of complete viral genomes (≈19 kb long) or the rapidly evolving glycoprotein (GP, ≈2 kb long) gene. We have quantified changes in phylogenetic, temporal, and spatial inference resolution as a result of this reduction in data and compared these to theoretical expectations. CONCLUSIONS: We propose a simple intuitive metric for quantifying temporal resolution, i.e. the time scale over which sequence data might be informative of various processes as a quick back-of-the-envelope calculation of statistical power available to molecular clock analyses.


Asunto(s)
Ebolavirus/genética , Genes Virales , Genoma Viral , Fiebre Hemorrágica Ebola/epidemiología , Mapeo Cromosómico , Brotes de Enfermedades , Fiebre Hemorrágica Ebola/transmisión , Fiebre Hemorrágica Ebola/virología , Humanos , Cadenas de Markov , Filogenia , Secuenciación Completa del Genoma
13.
BMC Bioinformatics ; 20(Suppl 20): 640, 2019 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-31842741

RESUMEN

BACKGROUND: It is now well established that eukaryotic coding genes have the ability to produce more than one type of transcript thanks to the mechanisms of alternative splicing and alternative transcription. Because of the lack of gold standard real data on alternative splicing, simulated data constitute a good option for evaluating the accuracy and the efficiency of methods developed for splice-aware sequence analysis. However, existing sequence evolution simulation methods do not model alternative splicing, and so they can not be used to test spliced sequence analysis methods. RESULTS: We propose a new method called SimSpliceEvol for simulating the evolution of sets of alternative transcripts along the branches of an input gene tree. In addition to traditional sequence evolution events, the simulation also includes gene exon-intron structure evolution events and alternative splicing events that modify the sets of transcripts produced from genes. SimSpliceEvol was implemented in Python. The source code is freely available at https://github.com/UdeS-CoBIUS/SimSpliceEvol. CONCLUSIONS: Data generated using SimSpliceEvol are useful for testing spliced RNA sequence analysis methods such as methods for spliced alignment of cDNA and genomic sequences, multiple cDNA alignment, orthologous exons identification, splicing orthology inference, transcript phylogeny inference, which requires to know the real evolutionary relationships between the sequences.


Asunto(s)
Empalme Alternativo/genética , Simulación por Computador , Evolución Molecular , Programas Informáticos , Animales , Secuencia de Bases , ADN Complementario/genética , Exones/genética , Humanos , Intrones/genética , Cadenas de Markov , Probabilidad , ARN Mensajero/genética , ARN Mensajero/metabolismo
14.
Parasit Vectors ; 12(1): 512, 2019 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-31666097

RESUMEN

BACKGROUND: Parasites of deep-sea fishes from the South-East Pacific (SPO) are poorly known. Of c.1030 species of fish found in this area, 100-150 inhabit the deep-sea (deeper than 200 m). Only six articles concerning metazoan parasites of fish from deep-waters of SOP are known, and nine monogenean species have been reported. Currently, ten species are known in Acanthocotyle Monticelli, 1888 (Monogenea) and when stated, all of them are found in shallow waters (10-100 m). Acanthocotyle gurgesiella Ñacari, Sepulveda, Escribano & Oliva, 2018 is the only known species parasitizing deep-sea skates (350-450 m) in the SPO. The aim of this study was the description of two new species of Acanthocotyle from two Rajiformes. METHODS: In September 2017, we examined specimens of two species of deep-sea skates (Rajiformes), Amblyraja frerichsi (Krefft) and Bathyraja peruana McEachran & Myyake, caught at c.1500 m depth off Tocopilla, northern Chile, as a by-catch of the Patagonian tooth fish Dissostichus eleginoides Smitt fishery. Specimens of Acanthocotyle were collected from the skin of the skates. Morphometric (including multivariate analysis of proportional measurements, standardized by total length), morphological and molecular analyses (LSU rRNA and cox1 genes) were performed in order to identify the collected specimens. RESULTS: The three approaches used in this study strongly suggest the presence of two new species in the genus Acanthocotyle: Acanthocotyle imo n. sp. and Acanthocotyle atacamensis n. sp. parasitizing the skin of the thickbody skate Amblyraja frerichsi and the Peruvian skate Bathyraja peruana, respectively. The main morphological differences from the closely related species Acanthocotyle verrilli Goto, 1899 include the number of radial rows of sclerites, the non-discrete vitelline follicles and the number of testes. CONCLUSIONS: The two species of monogeneans described here are the only recorded parasites from their respective host species in the SPO. Assessing host specificity for members of Acanthocotyle requires clarifying the systematics of Rajiformes.


Asunto(s)
Enfermedades de los Peces/parasitología , Platelmintos/clasificación , Infecciones por Trematodos/veterinaria , Animales , Teorema de Bayes , Chile , ADN de Helmintos/química , ADN de Helmintos/aislamiento & purificación , Complejo IV de Transporte de Electrones/genética , Genes Mitocondriales , Especificidad del Huésped , Funciones de Verosimilitud , Cadenas de Markov , Método de Montecarlo , Análisis Multivariante , Océano Pacífico , Filogenia , Platelmintos/anatomía & histología , Platelmintos/genética , Análisis de Componente Principal , ARN Ribosómico/genética , Piel/parasitología , Infecciones por Trematodos/parasitología
15.
PLoS Genet ; 15(11): e1008449, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31725722

RESUMEN

Understanding the causes and consequences of recombination landscape evolution is a fundamental goal in genetics that requires recombination maps from across the tree of life. Such maps can be obtained from population genomic datasets, but require large sample sizes. Alternative methods are therefore necessary to research organisms where such datasets cannot be generated easily, such as non-model or ancient species. Here we extend the sequentially Markovian coalescent model to jointly infer demography and the spatial variation in recombination rate. Using extensive simulations and sequence data from humans, fruit-flies and a fungal pathogen, we demonstrate that iSMC accurately infers recombination maps under a wide range of scenarios-remarkably, even from a single pair of unphased genomes. We exploit this possibility and reconstruct the recombination maps of ancient hominins. We report that the ancient and modern maps are correlated in a manner that reflects the established phylogeny of Neanderthals, Denisovans, and modern human populations.


Asunto(s)
Genoma Humano/genética , Hominidae/genética , Metagenómica , Recombinación Genética/genética , Animales , Mapeo Cromosómico , Variación Genética/genética , Humanos , Cadenas de Markov , Hombre de Neandertal/genética , Paleontología/tendencias , Filogenia
16.
BMC Bioinformatics ; 20(Suppl 18): 573, 2019 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-31760933

RESUMEN

BACKGROUND: During procedures for conducting multiple sequence alignment, that is so essential to use the substitution score of pairwise alignment. To compute adaptive scores for alignment, researchers usually use Hidden Markov Model or probabilistic consistency methods such as partition function. Recent studies show that optimizing the parameters for hidden Markov model, as well as integrating hidden Markov model with partition function can raise the accuracy of alignment. The combination of partition function and optimized HMM, which could further improve the alignment's accuracy, however, was ignored by these researches. RESULTS: A novel algorithm for MSA called ProbPFP is presented in this paper. It intergrate optimized HMM by particle swarm with partition function. The algorithm of PSO was applied to optimize HMM's parameters. After that, the posterior probability obtained by the HMM was combined with the one obtained by partition function, and thus to calculate an integrated substitution score for alignment. In order to evaluate the effectiveness of ProbPFP, we compared it with 13 outstanding or classic MSA methods. The results demonstrate that the alignments obtained by ProbPFP got the maximum mean TC scores and mean SP scores on these two benchmark datasets: SABmark and OXBench, and it got the second highest mean TC scores and mean SP scores on the benchmark dataset BAliBASE. ProbPFP is also compared with 4 other outstanding methods, by reconstructing the phylogenetic trees for six protein families extracted from the database TreeFam, based on the alignments obtained by these 5 methods. The result indicates that the reference trees are closer to the phylogenetic trees reconstructed from the alignments obtained by ProbPFP than the other methods. CONCLUSIONS: We propose a new multiple sequence alignment method combining optimized HMM and partition function in this paper. The performance validates this method could make a great improvement of the alignment's accuracy.


Asunto(s)
Biología Computacional/métodos , Proteínas/genética , Alineación de Secuencia/métodos , Algoritmos , Animales , Humanos , Cadenas de Markov , Familia de Multigenes , Filogenia , Proteínas/química , Programas Informáticos
17.
J Chem Phys ; 151(18): 185105, 2019 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-31731855

RESUMEN

Force spectroscopy techniques are often used to learn about the free energy landscape of single biomolecules, typically by recovering free energy quantities that, extrapolated to zero force, are compared to those measured in bulk experiments. However, it is not always clear how the information obtained from a mechanically perturbed system can be related to the information obtained using other denaturants since tensioned molecules unfold and refold along a reaction coordinate imposed by the force, which is not likely to be meaningful in its absence. Here, we explore this dichotomy by investigating the unfolding landscape of a model protein, which is unfolded first mechanically through typical force spectroscopy-like protocols and next thermally. When unfolded by nonequilibrium force extension and constant force protocols, we recover a simple two-barrier landscape as the protein reaches the extended conformation through a metastable intermediate. Interestingly, folding-unfolding equilibrium simulations at low forces suggested a totally different scenario, where this metastable state plays little role in the unfolding mechanism, and the protein unfolds through two competing pathways [R. Tapia-Rojo et al., J. Chem. Phys. 141, 135102 (2014)]. Finally, we use Markov state models to describe the configurational space of the unperturbed protein close to the critical temperature. The thermal dynamics is well understood by a one-dimensional landscape along an appropriate reaction coordinate, however it is very different from the mechanical picture. In this sense, the results of our protein model for the mechanical and thermal descriptions provide incompatible views of the folding/unfolding landscape of the system, and the estimated quantities to zero force result are hard to interpret.


Asunto(s)
Desplegamiento Proteico , Proteínas/química , Temperatura Ambiental , Cadenas de Markov , Fenómenos Mecánicos , Modelos Moleculares , Conformación Proteica
18.
BMC Health Serv Res ; 19(1): 874, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31752849

RESUMEN

BACKGROUND: Breast cancer is the leading malignancy among Filipino women, with about 23.50% of cases characterized by human epidermal growth factor receptor-2 (HER2) overexpression. Trastuzumab, in addition to standard chemotherapy, is currently recommended as primary treatment for HER2-positive early-stage breast cancer (EBC) in the adjuvant settings, and has been listed in the Philippine National Formulary (PNF) since 2008, but with no current evidence yet on its value for money, to date. Hence, despite several policy enablers, its accessibility remains to be limited in the Philippines. We performed an economic evaluation to assess the cost-effectiveness and budget impact of adjuvant trastuzumab therapy for HER2-positive EBC in the Philippines, using healthcare system and societal perspectives, in aid of guiding coverage decisions. METHODS: A Markov model-based cost-utility and budget impact analyses were conducted to estimate the total costs incurred and outcomes gained in using 1 year of adjuvant trastuzumab added to standard chemotherapy versus standard chemotherapy alone, over a lifetime horizon. We discounted both costs and outcomes at 3.5% per annum. Parameters were estimated using country survival data, systematic review and meta-analysis of the relative treatment effect, local and international cost data, and published utility data. Univariate and probabilistic sensitivity analyses were used to account for parameter uncertainty. RESULTS: Trastuzumab therapy was dominated with an incremental cost-effectiveness ratio (ICER) at PHP 453,505 per QALY gained from a healthcare system perspective or PHP 458,686 per QALY gained from a societal perspective, with 10% cost-effectiveness probability at the country cost-effectiveness threshold of PHP 120,000 per QALY gained. National implementation will cost an additional amount of PHP 13,909 million in year one alone, plus about PHP 2000 to 3000 million annually for the succeeding fiscal years. CONCLUSION: At its current cost, 1 year of adjuvant trastuzumab therapy compared to standard chemotherapy alone for HER2-positive EBC does not represent value for money in the Philippines. Its current cost will have to significantly lower down by one-half to achieve cost-effectiveness.


Asunto(s)
Antineoplásicos Inmunológicos/economía , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/economía , Trastuzumab/economía , Anticuerpos Monoclonales Humanizados/economía , Antineoplásicos/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/economía , Terapia Combinada , Análisis Costo-Beneficio , Costos de los Medicamentos , Femenino , Humanos , Cadenas de Markov , Persona de Mediana Edad , Filipinas , Años de Vida Ajustados por Calidad de Vida , Receptor ErbB-2 , Trastuzumab/uso terapéutico
20.
Phys Chem Chem Phys ; 21(44): 24527-24534, 2019 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-31663550

RESUMEN

Folding is generally assumed to be a Markov process, without memory. When the molecular motion is coupled to that of a probe as in single-molecule force spectroscopy (SMFS) experiments, however, theory predicts that the coupling to a second Markov process should induce memory when monitoring a projection of the full multi-dimensional motion onto a reduced coordinate. We developed a method to evaluate the time constant of the induced memory from its effects on the autocorrelation function, which can be readily determined from experimental data. Applying this method to both simulated SMFS measurements and experimental trajectories of DNA hairpin folding measured by optical tweezers as a model system, we validated the prediction that the linker induces memory. For these measurements, the timescale of the induced memory was found to be similar to the time required for the force probe to respond to changes in the molecule, and in the regime where the experimentally observed dynamics were not significantly perturbed by probe-molecule coupling artifacts. Memory effects are thus a general feature of SMFS measurements induced by the mechanical connection between the molecule and force probe that should be considered when interpreting experimental data.


Asunto(s)
ADN/química , Imagen Individual de Molécula , ADN/metabolismo , Secuencias Invertidas Repetidas , Cinética , Cadenas de Markov , Conformación de Ácido Nucleico , Pinzas Ópticas
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