148 research outputs found
Performance of networks of artificial neurons: The role of clustering
The performance of the Hopfield neural network model is numerically studied
on various complex networks, such as the Watts-Strogatz network, the
Barab{\'a}si-Albert network, and the neuronal network of the C. elegans.
Through the use of a systematic way of controlling the clustering coefficient,
with the degree of each neuron kept unchanged, we find that the networks with
the lower clustering exhibit much better performance. The results are discussed
in the practical viewpoint of application, and the biological implications are
also suggested.Comment: 4 pages, to appear in PRE as Rapid Com
Intermittent exploration on a scale-free network
We study an intermittent random walk on a random network of scale-free degree
distribution. The walk is a combination of simple random walks of duration
and random long-range jumps. While the time the walker needs to cover all
the nodes increases with , the corresponding time for the edges displays a
non monotonic behavior with a minimum for some nontrivial value of . This
is a heterogeneity-induced effect that is not observed in homogeneous
small-world networks. The optimal increases with the degree of
assortativity in the network. Depending on the nature of degree correlations
and the elapsed time the walker finds an over/under-estimate of the degree
distribution exponent.Comment: 12 pages, 3 figures, 1 table, published versio
Can the evolution of music be analyzed in a quantitative manner?
We propose a methodology to study music development by applying multivariate
statistics on composers characteristics. Seven representative composers were
considered in terms of eight main musical features. Grades were assigned to
each characteristic and their correlations were analyzed. A bootstrap method
was applied to simulate hundreds of artificial composers influenced by the
seven representatives chosen. Afterwards we quantify non-numeric relations like
dialectics, opposition and innovation. Composers differences on style and
technique were represented as geometrical distances in the feature space,
making it possible to quantify, for example, how much Bach and Stockhausen
differ from other composers or how much Beethoven influenced Brahms. In
addition, we compared the results with a prior investigation on philosophy.
Opposition, strong on philosophy, was not remarkable on music. Supporting an
observation already considered by music theorists, strong influences were
identified between composers by the quantification of dialectics, implying
inheritance and suggesting a stronger master-disciple evolution when compared
to the philosophy analysis.Comment: 8 pages, 6 figures, added references for sections 1 and 4.C, better
mathematical description on section 2. New values and interpretation, now
considering a bootstrap metho
Risdiplam in Type 1 Spinal Muscular Atrophy
BACKGROUND: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. METHODS: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. RESULTS: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. CONCLUSIONS: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.)
Automatic Network Fingerprinting through Single-Node Motifs
Complex networks have been characterised by their specific connectivity
patterns (network motifs), but their building blocks can also be identified and
described by node-motifs---a combination of local network features. One
technique to identify single node-motifs has been presented by Costa et al. (L.
D. F. Costa, F. A. Rodrigues, C. C. Hilgetag, and M. Kaiser, Europhys. Lett.,
87, 1, 2009). Here, we first suggest improvements to the method including how
its parameters can be determined automatically. Such automatic routines make
high-throughput studies of many networks feasible. Second, the new routines are
validated in different network-series. Third, we provide an example of how the
method can be used to analyse network time-series. In conclusion, we provide a
robust method for systematically discovering and classifying characteristic
nodes of a network. In contrast to classical motif analysis, our approach can
identify individual components (here: nodes) that are specific to a network.
Such special nodes, as hubs before, might be found to play critical roles in
real-world networks.Comment: 16 pages (4 figures) plus supporting information 8 pages (5 figures
InstalaçÔes rurais e prĂĄticas de bem-estar animal na produção de bovinos de corte em propriedades rurais do municĂpio de Dom Pedrito-RS.
O presente trabalho tem por objetivos analisar as instalaçÔes rurais e as prĂĄticas de manejo que favoreçam o bem-estar animal na produção de bovinos de corte implantadas em propriedades rurais no municĂpio de Dom Pedrito, Rio Grande do Sul. Foram coletados dados de dez propriedades com o auxĂlio de um formulĂĄrio de Boas PrĂĄticas AgropecuĂĄrias (BPA) da Empresa Brasileira de Pesquisa AgropecuĂĄria (EMBRAPA), adaptado aos propĂłsitos do trabalho. Considerou-se, para esta anĂĄlise, as caracterĂsticas estruturais das paredes do brete, seringa, embarcadouro e estado de conservação do curral. As prĂĄticas de manejo consideradas foram relacionadas aos aspectos sanitĂĄrios e de embarque dos animais. As instalaçÔes, manejo sanitĂĄrio e de embarque apresentaram, respectivamente, 58%, 62% e 47% de conformidade para o favorecimento do bem-estar dos animais. Constatou-se que as instalaçÔes, mesmo antigas, podem, com alguns ajustes, atender as necessidades bĂĄsicas para um bom manejo com os animais. Entretanto, as consequĂȘncias de prĂĄticas de manejo inadequadas no bem-estar animal e na qualidade do produto final devem ser melhor disseminadas nas propriedades rurais
Standardizing Clinical Trials Workflow Representation in UML for International Site Comparison
BACKGROUND: With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. METHODS: Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. RESULTS: Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. CONCLUSIONS: This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows
Production of HIV Particles Is Regulated by Altering Sub-Cellular Localization and Dynamics of Rev Induced by Double-Strand RNA Binding Protein
Human immunodeficiency virus (HIV)-1 encoded Rev is essential for export from the nucleus to the cytoplasm, of unspliced and singly spliced transcripts coding for structural and nonstructural viral proteins. This process is spatially and temporally coordinated resulting from the interactions between cellular and viral proteins. Here we examined the effects of the sub-cellular localization and dynamics of Rev on the efficiency of nucleocytoplasmic transport of HIV-1 Gag transcripts and virus particle production. Using confocal microscopy and fluorescence recovery after bleaching (FRAP), we report that NF90ctv, a cellular protein involved in Rev function, alters both the sub-cellular localization and dynamics of Rev in vivo, which drastically affects the accumulation of the viral protein p24. The CRM1âdependent nuclear export of Gag mRNA linked to the Rev Response Element (RRE) is dependent on specific domains of the NF90ctv protein. Taken together, our results demonstrate that the appropriate intracellular localization and dynamics of Rev could regulate Gag assembly and HIV-1 replication
Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).
Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and â„1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (nâ=â5069) or prospectively (nâ=â5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (â€6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; pâ=â0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)
Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.
BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362
- âŠ