La representación de la comunicación social a través de la noción de "armonía"

Desde las épocas más remotas, el concepto de "armonía" ocupa un lugar central y determinante en la cultura china. Pero no es un concepto extático sino todo lo contrario: un término siempre en construcción al que a lo largo de la historia de la civilización china se le han agregado numerosos elementos. En un momento determinado, por presiones políticas se "realza exclusivamente el Confucianismo suprimiendo otras corrientes ideológicas"1. Este cambio se realizó en la era del emperador Wu de la dinastía Han (147-87), en donde la noción de 'armonía', que representa la arteria la dicha ideología, alcanzó una prosperidad sin precedentes. Desde ese momento, y a lo largo de dos mil años, la "armonía" se convirtió en el eje en la vida cotidiana, la sociedad y la cultura de China hasta el momento actual. A continuación, vamos a aclarar este concepto del que tenemos en cuenta su extraordinaria complejidad y riqueza de significados, explicándolo en cinco partes: el estudio del propio término "armonía", su inclusión en la tradición religiosa china, las formas de representación que adopta en la cultura oriental, su inserción y su presencia en la vida cotidiana y una reflexión acerca de la actual "Sociedad Armoniosa"

A mechanistic pharmacokinetic model for intrathecal administration of antisense oligonucleotides

Intrathecal administration is an important mode for delivering biological agents targeting central nervous system (CNS) diseases. However, current clinical practices lack a sound theorical basis for a quantitative understanding of the variables and conditions that govern the delivery efficiency and specific tissue targeting especially in the brain. This work presents a distributed mechanistic pharmacokinetic model (DMPK) for predictive analysis of intrathecal drug delivery to CNS. The proposed DMPK model captures the spatiotemporal dispersion of antisense oligonucleotides (ASO) along the neuraxis over clinically relevant time scales of days and weeks as a function of infusion, physiological and molecular properties. We demonstrate its prediction capability using biodistribution data of antisense oligonucleotide (ASO) administration in non-human primates. The results are in close agreement with the observed ASO pharmacokinetics in all key compartments of the central nervous system. The model enables determination of optimal injection parameters such as intrathecal infusion volume and duration for maximum ASO delivery to the brain. Our quantitative model-guided analysis is suitable for identifying optimal parameter settings to target specific brain regions with therapeutic drugs such as ASOs

Pharmacokinetics and Pharmacodynamics of Once-Daily versus Twice-Daily Raltegravir in Treatment-Naïve HIV-Infected Patients

ABSTRACT QDMRK was a phase III clinical trial of raltegravir given once daily (QD) (800-mg dose) versus twice daily (BID) (400 mg per dose), each in combination with once-daily coformulated tenofovir-emtricitabine, in treatment-naive HIV-infected patients. Pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) analyses were conducted using a 2-step approach: individual non-model-based PK parameters from observed sparse concentration data were determined, followed by statistical analysis of potential relationships between PK and efficacy response parameters after 48 weeks of treatment. Sparse PK sampling was performed for all patients (QD, n = 380; BID, n = 384); selected sites performed an intensive PK evaluation at week 4 (QD, n = 22; BID, n = 20). In the intensive PK subgroup, daily exposures (area under the concentration-time curve from 0 to 24 h [AUC 0–24 ]) were similar between the two regimens, but patients on 800 mg QD experienced ∼4-fold-higher maximum drug concentration in plasma ( C max ) values and ∼6-fold-lower trough drug concentration ( C trough ) values than those on 400 mg BID. Geometric mean (GM) C trough values were similarly lower in the sparse PK analysis. With BID dosing, there was no indication of any significant PK/PD association over the range of tested PK parameters. With QD dosing, C trough values correlated with the likelihood of virologic response. Failure to achieve an HIV RNA level of <50 copies/ml appeared predominantly at high baseline HIV RNA levels in both treatment arms and was associated with lower values of GM C trough in the 800-mg-QD arm, though other possible drivers of efficacy, such as time above a threshold concentration, could not be evaluated due to the sparse sampling scheme. Together, these findings emphasize the importance of the shape of the plasma concentration-versus-time curve for long-term efficacy

La representación de la comunicación social a través de la noción de "armonía"

Desde las épocas más remotas, el concepto de "armonía" ocupa un lugar central y determinante en la cultura china. Pero no es un concepto extático sino todo lo contrario: un término siempre en construcción al que a lo largo de la historia de la civilización china se le han agregado numerosos elementos. En un momento determinado, por presiones políticas se "realza exclusivamente el Confucianismo suprimiendo otras corrientes ideológicas"1. Este cambio se realizó en la era del emperador Wu de la dinastía Han (147-87), en donde la noción de 'armonía', que representa la arteria la dicha ideología, alcanzó una prosperidad sin precedentes. Desde ese momento, y a lo largo de dos mil años, la "armonía" se convirtió en el eje en la vida cotidiana, la sociedad y la cultura de China hasta el momento actual. A continuación, vamos a aclarar este concepto del que tenemos en cuenta su extraordinaria complejidad y riqueza de significados, explicándolo en cinco partes: el estudio del propio término "armonía", su inclusión en la tradición religiosa china, las formas de representación que adopta en la cultura oriental, su inserción y su presencia en la vida cotidiana y una reflexión acerca de la actual "Sociedad Armoniosa"

Psychometric properties of the Chinese version of the Gudjonsson compliance scale: scale validation and associations with mental health

Abstract Background Trait compliance involves people reacting favorably to demands made by others across different situations. This may lead to susceptibility to external pressures, exploitation, and manipulation. Moreover, trait compliance was found to correlate with various mental health outcomes, such as depression and anxiety. The Gudjonsson Compliance Scale (GCS) is an efficient tool for assessing trait compliance in Western contexts. To date, no study has validated the psychometric properties of the GCS in Chinese populations. Methods Two college student samples from China were recruited. The first sample (N = 4,276) was used to conduct exploratory factor analysis. The second (N = 4,356) was used to perform a confirmatory factor analysis. The reliability, measurement invariance, and correlational tests were conducted on the two combined samples. Results The Chinese GCS showed a 3-factor structure, with two items deleted. Reliability was supported by moderate-to-good internal consistency of the three-factor scales and good internal consistency on the full scale. Strong measurement invariance across sex, ethnicity, and group recruitment was supported. Scores of the total scale and factor scales were found to significantly associated with several mental health problems. Conclusions The Chinese version of the GCS appears to be a valid and reliable instrument for measuring trait compliance and could promote both the assessment and research on compliance in Chinese population

Protein image alignment via piecewise affine transformations

Abstract We present a new approach for aligning families of 2D gels. Instead of choosing one of the gels as reference and performing pairwise alignment, we construct an ideal gel that is representative for the entire family and obtain a set of piecewise affine transformations that optimally align each gel of the family to the ideal gel. The coefficients defining the transformations as well as the ideal landmarks are obtained as the solution of a large-scale quadratic programming problem that can be solved efficiently by interiorpoint methods. 1 Proteomics and 2-D PAGE Proteome analysis involves the separation, visualization and analysis of complex mixtures containing as many as several thousand proteins obtained from whole cells, tissues or organisms. Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), first introduced by O’Farrell [9] and Klose [8] in 1975, remains a core technology for separating complex protein mixtures in the majority of proteome projects. The main goal of protein separation methods is to detect differentially expressed proteins across treatment groups. However, a major bottleneck toward that goal is the misalignment of gels due to warping and thus confounding biological variation with non-biologically relevant distortions. This paper provides a computationally feasible gel alignment methods based on powerful optimization techniques such as interior point methods. With 2D-PAGE technique, proteins are separated orthogonally according to their charge and size. The separated proteins are then stained so that they are readily detectable, and the gels are digitally scanned into a database for storage. Gel images ar

A Disease Progression Model to Quantify the Nonmotor Symptoms of Parkinson's Disease in Participants With Leucine-Rich Repeat Kinase 2 Mutation.

Leucine-rich repeat kinase 2 (LRRK2) inhibitors are currently in clinical development as interventions to slow progression of Parkinson's disease (PD). Understanding the rate of progression in PD as measured by both motor and nonmotor features is particularly important in assessing the potential therapeutic effect of LRRK2 inhibitors in clinical development. Using standardized data from the Critical Path for Parkinson's Unified Clinical Database, we quantified the rate of progression of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I (nonmotor aspects of experiences of daily living) in 158 participants with PD who were carriers and 598 participants with PD who were noncarriers of at least one of three different LRRK2 gene mutations (G2019S, R1441C/G, or R1628P). Age and disease duration were found to predict baseline disease severity, while presence of at least one of these three LRRK2 mutations was a predictor of the rate of MDS-UPDRS Part I progression. The estimated progression rate in MDS-UPDRS Part I was 0.648 (95% confidence interval: 0.544, 0.739) points per year in noncarriers of a LRRK2 mutation and 0.259 (95% confidence interval: 0.217, 0.295) points per year in carriers of a LRRK2 mutation. This analysis demonstrates that the rate of progression based on MDS-UPDRS Part I is ~ 60% lower in carriers as compared with noncarriers of LRRK2 gene mutations

A Disease Progression Model to Quantify the Nonmotor Symptoms of Parkinson’s Disease in Participants With Leucine‐Rich Repeat Kinase 2 Mutation

Leucine-rich repeat kinase 2 (LRRK2) inhibitors are currently in clinical development as interventions to slow progression of Parkinson's disease (PD). Understanding the rate of progression in PD as measured by both motor and nonmotor features is particularly important in assessing the potential therapeutic effect of LRRK2 inhibitors in clinical development. Using standardized data from the Critical Path for Parkinson's Unified Clinical Database, we quantified the rate of progression of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I (nonmotor aspects of experiences of daily living) in 158 participants with PD who were carriers and 598 participants with PD who were noncarriers of at least one of three different LRRK2 gene mutations (G2019S, R1441C/G, or R1628P). Age and disease duration were found to predict baseline disease severity, while presence of at least one of these three LRRK2 mutations was a predictor of the rate of MDS-UPDRS Part I progression. The estimated progression rate in MDS-UPDRS Part I was 0.648 (95% confidence interval: 0.544, 0.739) points per year in noncarriers of a LRRK2 mutation and 0.259 (95% confidence interval: 0.217, 0.295) points per year in carriers of a LRRK2 mutation. This analysis demonstrates that the rate of progression based on MDS-UPDRS Part I is ~ 60% lower in carriers as compared with noncarriers of LRRK2 gene mutations