The Longitudinal Association Between a Discrepancy Measure of Anosognosia in Patients with Dementia, Caregiver Burden and Depression

Anosognòsia; Cuidadors; Estudis longitudinalsAnosognosia; Cuidadores; Estudios longitudinalesAnosognosia; Caregivers; Longitudinal studiesBackground: According to cross-sectional studies, there is an association between anosognosia in people with dementia and caregiver’s burden and depression. Anosognosia in patients may be a cause of caregiver burden and depression. However, variability in caregiver anosognosia ratings may exist as caregivers with burden and depression may have a more pessimistic view of the patients’ health. Objective: To assess the variability of caregiver anosognosia ratings of patients with dementia using a widely used anosognosia scale and its longitudinal relationship with caregiver burden and depression. Methods: A convenience cohort of 221 consecutive dementia outpatient and caregiver dyads was followed up at 12 and 24 months. The main instruments used were the Anosognosia Questionnaire-Dementia (AQ-D), Caregiver Burden Interview, and Geriatric Depression Scale. Linear mixed models were used including time as a factor in every model. Multivariate analyses controlled for caregiver’s socio-demographic and possible confounding factors. Results: Attrition at 12 and 24 months was 24.9% and 42.5% respectively. Patients at baseline were on average 77.8 years of age, 63.3% were women, and 63.3% had < 5 years of education. In the bivariate analyses, caregiver burden, depression, and gender were associated with caregiver ratings of total, cognitive, and personality AQ-D of the patient at different time points. Multivariate analyses revealed burden as the caregiver variable most consistently associated with total, cognitive, and personality caregiver AQ-D ratings of the patient. Conclusion: Some caregiver characteristics, especially burden, are associated with caregiver ratings of AQ-D with regard to the patientPSI 2010-1901

Is Our Universe Natural?

It goes without saying that we are stuck with the universe we have. Nevertheless, we would like to go beyond simply describing our observed universe, and try to understand why it is that way rather than some other way. Physicists and cosmologists have been exploring increasingly ambitious ideas that attempt to explain why certain features of our universe aren't as surprising as they might first appear.Comment: Invited review for Nature, 11 page

Evolutionary-game-based dynamical tuning for multi-objective model predictive control

Model predictive control (MPC) is one of the most used optimization-based control strategies for large-scale systems, since this strategy allows to consider a large number of states and multi-objective cost functions in a straightforward way. One of the main issues in the design of multi-objective MPC controllers, which is the tuning of the weights associated to each objective in the cost function, is treated in this work. All the possible combinations of weights within the cost function affect the optimal result in a given Pareto front. Furthermore, when the system has time-varying parameters, e.g., periodic disturbances, the appropriate weight tuning might also vary over time. Moreover, taking into account the computational burden and the selected sampling time in the MPC controller design, the computation time to find a suitable tuning is limited. In this regard, the development of strategies to perform a dynamical tuning in function of the system conditions potentially improves the closed-loop performance. In order to adapt in a dynamical way the weights in the MPC multi-objective cost function, an evolutionary-game approach is proposed. This approach allows to vary the prioritization weights in the proper direction taking as a reference a desired region within the Pareto front. The proper direction for the prioritization is computed by only using the current system values, i.e., the current optimal control action and the measurement of the current states, which establish the system cost function over a certain point in the Pareto front. Finally, some simulations of a multi-objective MPC for a real multi-variable case study show a comparison between the system performance obtained with static and dynamical tuning.Peer ReviewedPostprint (author's final draft

DR_SEQAN: a PC/Windows-based software to evaluate drug resistance using human immunodeficiency virus type 1 genotypes

BACKGROUND: Genotypic assays based on DNA sequencing of part or the whole reverse transcriptase (RT)- and protease (PR)-coding regions of the human immunodeficiency virus type 1 (HIV-1) genome have become part of the routine clinical management of HIV-infected individuals. However, the results are difficult to interpret due to complex interactions between mutations found in viral genes. RESULTS: DR_SEQAN is a tool to analyze RT and PR sequences. The program output includes a list containing all of the amino acid changes found in the query sequence in comparison with the sequence of a wild-type HIV-1 strain. Translation of codons containing nucleotide mixtures can result in potential ambiguities or heterogeneities in the amino acid sequence. The program identifies all possible combinations of 2 or 3 amino acids that derive from translation of triplets containing nucleotide mixtures. In addition, when ambiguities affect codons relevant for drug resistance, DR_SEQAN allows the user to select the appropriate mutation to be considered by the program's drug resistance interpretation algorithm. Resistance is predicted using a rule-based algorithm, whose efficiency and accuracy has been tested with a large set of drug susceptibility data. Drug resistance predictions given by DR_SEQAN were consistent with phenotypic data and coherent with predictions provided by other publicly available algorithms. In addition, the program output provides two tables showing published drug susceptibility data and references for mutations and combinations of mutations found in the analyzed sequence. These data are retrieved from an integrated relational database, implemented in Microsoft Access, which includes two sets of non-redundant core tables (one for combinations of mutations in the PR and the other for combinations in the RT). CONCLUSION: DR_SEQAN is an easy to use off-line application that provides expert advice on HIV genotypic resistance interpretation. It is coded in Visual Basic for use in PC/Windows-based platforms. The program is freely available under the General Public License. The program (including the integrated database), documentation and a sample sequence can be downloaded fro

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit

Machine Learning Approach for Prescriptive Plant Breeding

We explored the capability of fusing high dimensional phenotypic trait (phenomic) data with a machine learning (ML) approach to provide plant breeders the tools to do both in-season seed yield (SY) prediction and prescriptive cultivar development for targeted agro-management practices (e.g., row spacing and seeding density). We phenotyped 32 SoyNAM parent genotypes in two independent studies each with contrasting agro-management treatments (two row spacing, three seeding densities). Phenotypic trait data (canopy temperature, chlorophyll content, hyperspectral reflectance, leaf area index, and light interception) were generated using an array of sensors at three growth stages during the growing season and seed yield (SY) determined by machine harvest. Random forest (RF) was used to train models for SY prediction using phenotypic traits (predictor variables) to identify the optimal temporal combination of variables to maximize accuracy and resource allocation. RF models were trained using data from both experiments and individually for each agro-management treatment. We report the most important traits agnostic of agro-management practices. Several predictor variables showed conditional importance dependent on the agro-management system. We assembled predictive models to enable in-season SY prediction, enabling the development of a framework to integrate phenomics information with powerful ML for prediction enabled prescriptive plant breeding

Cyclin-Dependent Kinase 9 Activity Regulates Neutrophil Spontaneous Apoptosis

Neutrophils are the most abundant leukocyte and play a central role in the immune defense against rapidly dividing bacteria. However, they are also the shortest lived cell in the blood with a lifespan in the circulation of 5.4 days. The mechanisms underlying their short lifespan and spontaneous entry into apoptosis are poorly understood. Recently, the broad range cyclin-dependent kinase (CDK) inhibitor R-roscovitine was shown to increase neutrophil apoptosis, implicating CDKs in the regulation of neutrophil lifespan. To determine which CDKs were involved in regulating neutrophil lifespan we first examined CDK expression in human neutrophils and found that only three CDKs: CDK5, CDK7 and CDK9 were expressed in these cells. The use of CDK inhibitors with differing selectivity towards the various CDKs suggested that CDK9 activity regulates neutrophil lifespan. Furthermore CDK9 activity and the expression of its activating partner cyclin T1 both declined as neutrophils aged and entered apoptosis spontaneously. CDK9 is a component of the P-TEFb complex involved in transcriptional regulation and its inhibition will preferentially affect proteins with short half-lives. Treatment of neutrophils with flavopiridol, a potent CDK9 inhibitor, increased apoptosis and caused a rapid decline in the level of the anti-apoptotic protein Mcl-1, whilst Bcl2A was unaffected. We propose that CDK9 activity is a key regulator of neutrophil lifespan, preventing apoptosis by maintaining levels of short lived anti-apoptotic proteins such as Mcl-1. Furthermore, as inappropriate inhibition of neutrophil apoptosis contributes to chronic inflammatory diseases such as Rheumatoid Arthritis, CDK9 represents a novel therapeutic target in such diseases

Temporal dynamics of microbiota before and after host death

The habitats that animals, humans and plants provide for microbial communities are inevitably transient, changing drastically when these hosts die. Because microbes associated with living hosts are ensured prime access to the deceased host's organic matter, it is feasible that opportunistic, adaptable lifestyles are widespread among host-associated microbes. Here we investigate the temporal dynamics of microbiota by starving to death a host-the planktonic Crustacean Daphnia magna-and tracking the changes in its microbial community as it approaches death, dies and decomposes. Along with obligate host-associated microbes that vanished after the host's death and decomposers that appeared after the host's death, we also detected microbes with opportunistic lifestyles, seemingly capable of exploiting the host even before its death. We suggest that the period around host death plays an important role for host-microbiota ecology and for the evolution of hosts and their microbes

Tandem E2F Binding Sites in the Promoter of the p107 Cell Cycle Regulator Control p107 Expression and Its Cellular Functions

The retinoblastoma tumor suppressor (Rb) is a potent and ubiquitously expressed cell cycle regulator, but patients with a germline Rb mutation develop a very specific tumor spectrum. This surprising observation raises the possibility that mechanisms that compensate for loss of Rb function are present or activated in many cell types. In particular, p107, a protein related to Rb, has been shown to functionally overlap for loss of Rb in several cellular contexts. To investigate the mechanisms underlying this functional redundancy between Rb and p107 in vivo, we used gene targeting in embryonic stem cells to engineer point mutations in two consensus E2F binding sites in the endogenous p107 promoter. Analysis of normal and mutant cells by gene expression and chromatin immunoprecipitation assays showed that members of the Rb and E2F families directly bound these two sites. Furthermore, we found that these two E2F sites controlled both the repression of p107 in quiescent cells and also its activation in cycling cells, as well as in Rb mutant cells. Cell cycle assays further indicated that activation of p107 transcription during S phase through the two E2F binding sites was critical for controlled cell cycle progression, uncovering a specific role for p107 to slow proliferation in mammalian cells. Direct transcriptional repression of p107 by Rb and E2F family members provides a molecular mechanism for a critical negative feedback loop during cell cycle progression and tumorigenesis. These experiments also suggest novel therapeutic strategies to increase the p107 levels in tumor cells

CSR and related terms in SME owner-managers' mental models in six European countries: national context matters

As a contribution to the emerging field of corporate social responsibility (CSR) cognition, this article reports on the findings of an exploratory study that compares SME owner–managers’ mental models with regard to CSR and related concepts across six European countries (Belgium, Italy, Norway, France, UK, Spain). Utilising Repertory Grid Technique, we found that the SME owner–managers’ mental models show a few commonalities as well as a number of differences across the different country samples. We interpret those differences by linking individual cognition to macro-environmental variables, such as language, national traditions and dissemination mechanisms. The results of our exploratory study show that nationality matters but that classifications of countries as found in the comparative capitalism literature do not exactly mirror national differences in CSR cognition and that these classifications need further differentiation. The findings from our study raise questions on the universality of cognition of academic management concepts and warn that promotion of responsible business practice should not rely on the use of unmediated US American management terminology