Handgrip Strength Predicts Longitudinal Changes in Clock Drawing Test Performance. An Observational Study in a Sample of Older Non-Demented Adults.

OBJECTIVE: Impairment of physical performance might identify older people at higher risk of dementia over time. The present study evaluated handgrip strength as independent predictor of cognitive decline. DESIGN: Observational, prospective. Follow-up duration: 11.2 ± 0.8 months. SETTING AND PARTICIPANTS: Geriatric outpatients center. 104 consecutive stroke- and dementia-free older adults (44% men, ages 80.2 ± 5.4 years). METHODS: The Clinical Dementia Rating scale and the Clock Drawing Test (CDT) were administered. Handgrip strength was assessed using a Jamar hand dynamometer. Brain magnetic resonance imaging studies at 1.5 T were performed. White matter damage was expressed as severity of white matter hyperintensities (WMHs). Longitudinal changes in cognitive function were expressed as 1-year decline in CDT performance. RESULTS: A robust association was observed between baseline handgrip strength and 1-year cognitive decline after multiple adjustment. Of note, the strength of such association was only minimally attenuated after adjusting for deep WMHs extent (ß coefficient for handgrip strength = 0.183, SE= 0.038, p= 0.007, R2= 0.58). CONCLUSIONS: Handgrip strength predicted accelerated 1-year decline in cognitive function, assessed by CDT, in a sample of older adults. Future studies are needed to elucidate the causal mechanisms linking limitations in physical function with dementia risk.

Decision landscapes: visualizing mouse-tracking data.

Computerized paradigms have enabled gathering rich data on human behaviour, including information on motor execution of a decision, e.g. by tracking mouse cursor trajectories. These trajectories can reveal novel information about ongoing decision processes. As the number and complexity of mouse-tracking studies increase, more sophisticated methods are needed to analyse the decision trajectories. Here, we present a new computational approach to generating decision landscape visualizations based on mouse-tracking data. A decision landscape is an analogue of an energy potential field mathematically derived from the velocity of mouse movement during a decision. Visualized as a three-dimensional surface, it provides a comprehensive overview of decision dynamics. Employing the dynamical systems theory framework, we develop a new method for generating decision landscapes based on arbitrary number of trajectories. This approach not only generates three-dimensional illustration of decision landscapes, but also describes mouse trajectories by a number of interpretable parameters. These parameters characterize dynamics of decisions in more detail compared with conventional measures, and can be compared across experimental conditions, and even across individuals. The decision landscape visualization approach is a novel tool for analysing mouse trajectories during decision execution, which can provide new insights into individual differences in the dynamics of decision making.

An experimental approach to identify dynamical models of transcriptional regulation in living cells.

We describe an innovative experimental approach, and a proof of principle investigation, for the application of System Identification techniques to derive quantitative dynamical models of transcriptional regulation in living cells. Specifically, we constructed an experimental platform for System Identification based on a microfluidic device, a time-lapse microscope, and a set of automated syringes all controlled by a computer. The platform allows delivering a time-varying concentration of any molecule of interest to the cells trapped in the microfluidics device (input) and real-time monitoring of a fluorescent reporter protein (output) at a high sampling rate. We tested this platform on the GAL1 promoter in the yeast Saccharomyces cerevisiae driving expression of a green fluorescent protein (Gfp) fused to the GAL1 gene. We demonstrated that the System Identification platform enables accurate measurements of the input (sugars concentrations in the medium) and output (Gfp fluorescence intensity) signals, thus making it possible to apply System Identification techniques to obtain a quantitative dynamical model of the promoter. We explored and compared linear and nonlinear model structures in order to select the most appropriate to derive a quantitative model of the promoter dynamics. Our platform can be used to quickly obtain quantitative models of eukaryotic promoters, currently a complex and time-consuming process.

Pinning control of complex networks via edge snapping.

In this paper, we propose a hierarchy of novel decentralized adaptive pinning strategies for controlled synchronization of complex networks. This hierarchy addresses the fundamental need of selecting the sites to pin through a fully decentralized approach based on edge snapping. Specifically, we present three different strategies of increasing complexity which use a combination of network evolution and adaptation of the coupling and control gains. Theoretical results are complemented by extensive numerical investigations of the performance of the proposed strategies on a set of testbed examples.

Discontinuity-induced bifurcations of piecewise smooth dynamical systems.

This paper presents an overview of the current state of the art in the analysis of discontinuity-induced bifurcations (DIBs) of piecewise smooth dynamical systems, a particularly relevant class of hybrid dynamical systems. Firstly, we present a classification of the most common types of DIBs involving non-trivial interactions of fixed points and equilibria of maps and flows with the manifolds in phase space where the system is non-smooth. We then analyse the case of limit cycles interacting with such manifolds, presenting grazing and sliding bifurcations. A description of possible classification strategies to predict and analyse the scenarios following such bifurcations is also discussed, with particular attention to those methodologies that can be applied to generic n-dimensional systems.

Catastrophic sliding bifurcations and onset of oscillations in a superconducting resonator.

This paper presents a general analysis and a concrete example of the catastrophic case of a discontinuity-induced bifurcation in so-called Filippov nonsmooth dynamical systems. Such systems are characterized by discontinuous jumps in the right-hand sides of differential equations across a phase space boundary and are often used as physical models of stick-slip motion and relay control. Sliding bifurcations of periodic orbits have recently been shown to underlie the onset of complex dynamics including chaos. In contrast to previously analyzed cases, in this work a periodic orbit is assumed to graze the boundary of a repelling sliding region, resulting in its abrupt destruction without any precursive change in its stability or period. Necessary conditions for the occurrence of such catastrophic grazing-sliding bifurcations are derived. The analysis is illustrated in a piecewise-smooth model of a stripline resonator, where it can account for the abrupt onset of self-modulating current fluctuations. The resonator device is based around a ring of NbN containing a microbridge bottleneck, whose switching between normal and super conducting states can be modeled as discontinuous, and whose fast temperature versus slow current fluctuations are modeled by a slow-fast timescale separation in the dynamics. By approximating the slow component as Filippov sliding, explicit conditions are derived for catastrophic grazing-sliding bifurcations, which can be traced out as parameters vary. The results are shown to agree well with simulations of the slow-fast model and to offer a simple explanation of one of the key features of this experimental device.

Comparing different ODE modelling approaches for gene regulatory networks.

A fundamental step in synthetic biology and systems biology is to derive appropriate mathematical models for the purposes of analysis and design. For example, to synthesize a gene regulatory network, the derivation of a mathematical model is important in order to carry out in silico investigations of the network dynamics and to investigate parameter variations and robustness issues. Different mathematical frameworks have been proposed to derive such models. In particular, the use of sets of nonlinear ordinary differential equations (ODEs) has been proposed to model the dynamics of the concentrations of mRNAs and proteins. These models are usually characterized by the presence of highly nonlinear Hill function terms. A typical simplification is to reduce the number of equations by means of a quasi-steady-state assumption on the mRNA concentrations. This yields a class of simplified ODE models. A radically different approach is to replace the Hill functions by piecewise-linear approximations [Casey, R., de Jong, H., Gouze , J.-L., 2006. Piecewise-linear models of genetic regulatory networks: equilibria and their stability. J. Math. Biol. 52 (1), 27-56]. A further modelling approach is the use of discrete-time maps [Coutinho, R., Fernandez, B., Lima, R., Meyroneinc, A., 2006. Discrete time piecewise affine models of genetic regulatory networks. J. Math. Biol. 52, 524-570] where the evolution of the system is modelled in discrete, rather than continuous, time. The aim of this paper is to discuss and compare these different modelling approaches, using a representative gene regulatory network. We will show that different models often lead to conflicting conclusions concerning the existence and stability of equilibria and stable oscillatory behaviours. Moreover, we shall discuss, where possible, the viability of making certain modelling approximations (e.g. quasi-steady-state mRNA dynamics or piecewise-linear approximations of Hill functions) and their effects on the overall system dynamics.

How to synchronize biological clocks.

This paper is concerned with a novel algorithm to study networks of biological clocks. A new set of conditions is established that can be used to verify whether an existing network synchronizes or to give guidelines to construct a new synthetic network of biological oscillators that synchronize. The methodology uses the so-called contraction theory from dynamical system theory and Gershgorin disk theorem. The strategy is validated on two examples: a model of glycolisis in yeast cells and a synthetic network of Repressilators that synchronizes.

Minimal control synthesis adaptive control of nonlinear systems: utilizing the properties of chaos.

This paper discusses a novel approach to the control of chaos based on the use of the adaptive minimal control synthesis algorithm. The strategies presented are based on the explicit exploitation of different properties of chaotic systems including the boundedness of the chaotic attractors and their topological transitivity (or ergodicity). It is shown that chaos can be exploited to synthesize more efficient control techniques for nonlinear systems. For instance, by using the ergodicity of the chaotic trajectory, we show that a local adaptive control strategy can be used to synthesize a global controller. An application is to the swing-up control of a double inverted pendulum.

Efecto de la suplementación oral con sobre en el perfíl lipídico de pacientes venezolanos hiperlipémicos / Effect of copper suplementation in lipid profile of Venezuelan hiperlipemic patients

Se considera que la mayoría de las dietas occidentales satisfacen los requerimientos diarios de cobre debido a su presencia ubicua en los alimentos. Estudios recientes han demostrado que el cobre alimentario se encuentra a menudo por debajo de sus requerimientos diarios, lo que puede determinar una carencia de este elemento. Esta carencia está asociada con hipercolesterolemia e hipertrigliceridemia, tanto en humanos como en animales experimentales. En el presente estudio de intervención se examonó el efecto de la administración de 5mg de Cu/día, en 73 pacientes (grupo tratado), de ambos géneros, con edades entre 26y 48 años, con niveles séricos elevados de colesterol total y triglicéridos sin tratamiento con drogas hipolipémicas y se comparó con 73 pacientes hiperlipémicos no sometidos a tratamiento con Cu (grupo control), quienes fueron agrupados por género, edad, peso corporal, consumo de cigarrillos, ingesta de calorías y grasas y actividad física. Antes de administrar el cobre, se extrajo una muestra de sangre para las determinaciones de cobre, cinc y lípidos séricos. Al final del período experimental (45 días), se obtuvo una muestra de sangre para las determinaciones correspondientes. Los resultados sufieren la existencia de una cerencia marginal del elemento traza en el 38 por ciento de los sujetos y demuestran que el cobre disminuye significativamente (p<0.05) los nivles séricos del colesterol total (r=-0.976), de triglicéricos (r=-0.972), de LDL-colesterol (r=-0.961) y de cinc (r=-0.980) con un ligero incremento (r=-0.984) del HDL- colesterol. Estos hallazgos demuestran que el cobre se puede emplear en el tratamiento de los pacientes con hipercolesterolemia e hipertrigliceridemia; aunque los mecanismos, que explican como el cobre determina estos cambios, no se conocen exactamente

[Effect of copper supplementation on lipid profile of Venezuelan hyperlipemic patients]. / Efecto de la suplementación oral con cobre en el perfil lipídico de pacientes Venezolanos hiperlipémicos.

It has been assumed that most Western diets satisfy the requirement of copper/day because of ubiquitous presence of this element in most foods. Recent studies have shown that dietary copper (Cu) may often fall below the estimated daily requirements, what could determine a deficiency of this trace element. This deficiency is associated with hypercholesterolemia and hypertrigliceridemia, both in human and experimental animals. In the present intervention study was examined the effect of the administration of 5 mg of Cu/day in 73 patients (treated group), of both genders, with ages between 26 and 48 years, with high serum levels of total cholesterol and triglycerides without pharmacological treatment and compared with 73 hyperlipemic subjects non-treated with copper (control group) who were matched by gender, age, body weight, smoking habits, calories and fat intake, and physical activity. Before copper administration, a sample of blood was obtained for serum determinations of copper, zinc and lipids. At the end of the experimental period (45 days), a new sample of blood was taken for the corresponding determinations. The results suggest the existence of a marginal deficiency of the trace element in 38% of the subjects and demonstrate that copper supplementation decreases (p < 0.05) serum levels of total cholesterol (r = -0.976), triglycerides (r = -0.972), LDL-cholesterol (r = -0.961) and zinc (r = -0.980) with a slight increment (r = 0.894) of HDL-cholesterol. These findings demonstrate that copper can be used in the treatment of the patients with hypercholesterolemia and hypertriglyceridemia. The mechanisms by which Cu determines these changes are not known.

[Effect of cooper supplementation on blood pressure values in patients with stable moderate hypertension]. / Efecto de la suplementación con cobre sobre los valores de presión arterial en pacientes con hipertensión moderada estable.

Copper (Cu) deficiency is associated with changes in arterial pressure. The effect depends of the age of initiation of the copper-deficient diet. Copper deficiency started at a young age causes hypotension. When initiated in older or adult animals, copper deficiency can cause hypertension. A case-control study was carried out to investigate the effect of administrating 5 mg Cu/d in 60 subjects, both genders, with mild stable hypertension, pharmacologically untreated (treated group) and compared with 60 hypertensives (control group) who were matched by gender, age, body weight, smoking habits, calories, fat and salt intake (NaCl), and physical activity. Hypertension was diagnosed when the blood pressure was > 150/95 mm Hg. Mean age, mean corporal weight and risk factors were similar in both groups. The results suggested the existence of a marginal deficiency of the trace element in 62% of subjects and demonstrated that Cu decreases systolic (r = -0.963) and diastolic (r = -0.981) blood pressures in treated group (p < 0.05). Control patients did not show significant changes in their arterial pressures. These findings indicate a functional alteration in human blood pressure regulation during mild copper depletion and suggest that Cu could be used in the treatment of stable moderate arterial hypertension. Further investigation is needed to determine the extent of this influence.

Efecto de la suplementación con cobre sobre los valores de presión arterial en pacientes con hipertensión moderada estable / Effect of cooper supplementation on blood pressure values in patients with stable moderate hypertension

Copper (Cu) deficiency is associated with changes in arterial pressure. The effect depends of the age of initiation of the copper-deficient diet. Copper deficiency started at a young age causes hypotension. When initiated in older or adult animals, copper deficiency can cause hypertension. A case-control study was carried out to investigate the effect of administrating 5 mg Cu/d in 60 subjects, both genders, with mild stable hypertension, pharmacologically untreated (treated group) and compared with 60 hypertensives (control group) who were matched by gender, age, body weight, smoking habits, calories, fat and salt intake (NaCl), and physical activity. Hypertension was diagnosed when the blood pressure was > 150/95 mm Hg. Mean age, mean corporal weight and risk factors were similar in both groups. The results suggested the existence of a marginal deficiency of the trace element in 62 per cent of subjects and demonstrated that Cu decreases systolic (r = -0.963) and diastolic (r = -0.981) blood pressures in treated group (p < 0.05). Control patients did not show significant changes in their arterial pressures. These findings indicate a functional alteration in human blood pressure regulation during mild copper depletion and suggest that Cu could be used in the treatment of stable moderate arterial hypertension. Further investigation is needed to determine the extent of this influence.

Eating behavior in obese patients with and without type 2 diabetes mellitus.

OBJECTIVE: Aim of this study was the assessment of the prevalence of eating disorders, and of eating disorder symptoms, in obese patients with type 2 diabetes, compared to non-diabetic subjects. DESIGN: Three samples of individuals were studied: a series of 156 (76 male, 80 female) overweight and obese type 2 diabetic patients, aged 30-65 y, with a body mass index (BMI)>28 kg/m(2) (DM); a series of 192 (20 male, 172 female) obese (BMI>30 kg/m(2)) non-diabetic patients aged 30-65 y seeking treatment for weight loss (OC); and a non-clinical sample of 48 (22 male, 26 female) obese (BMI>30 kg/m(2)) subjects aged 30-65 y selected from the lists of two general practices (OP). Eating behavior was assessed using the Eating Disorder Examination (EDE 12.0D). RESULTS: The prevalence of Binge Eating Disorder was lower than 5% in all the three samples. Median EDE scores in females were significantly higher in OC (3.0) and OP (3.4) than in DM (1.7), while diabetic patients showed higher scores on Restraint than both non-diabetic samples. Among diabetic patients, a significant correlation of EDE scores with HbA(1)c was observed. CONCLUSIONS: Type 2 diabetes is unlikely to induce relevant eating disturbances in obese patients, apart from an increase in restraint. Abnormalities of eating attitudes and behavior are associated with an impairment of metabolic control.

The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres.

Several case-control association studies have raised the possibility that the A allele of a -1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa. However the absence of linkage and the existence of negative association studies raise the possibility of false positive findings, resulting from population stratification or lack of statistical power. To address this controversy we recruited a sample of 316 patients with anorexia nervosa from six European centres, and utilised a family-based transmission disequilibrium (TDT) approach to analyse the HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into consideration in order to detect clinical heterogeneity or a quantitative trait effect. The TDT approach showed that the A allele was transmitted 133 times and not transmitted 148 times (McNemar chi(2) = 0.29, df = 1, P = 0.59). Also, the haplotype-based haplotype relative risk method showed no evidence for association of the A allele, in samples from each centre (chi(2) < 2.15, df = 1, P > 0.14) and in the total sample (chi(2) = 0.55, df = 1; P = 0.46). Furthermore, we found no evidence for heterogeneity of the A allele frequency between samples (chi(2) = 2.54, df = 4, P = 0.64), either according to minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12). QTL-TDT analyses also showed no direct role of the A allele on these traits. We thus found no evidence for a significant role of the 5-HT(2A) gene in anorexia nervosa. Previous results may have been exposed to stratification bias (which we controlled by the TDT method) and/or the risk of type 1 error (from which we were less exposed because of the sample size).

Psychopathological and clinical features of outpatients with an eating disorder not otherwise specified.

In order to investigate similarities and differences between Eating Disorder Not Otherwise Specified (EDNOS) and Anorexia Nervosa (AN) and Bulimia Nervosa (BN), we studied a consecutive series of 189 female outpatients attending two Eating Disorder Units. The data were collected by means of interviews (Eating Disorder Examination, EDE 12.0D), the Structured Diagnostic Interview for DSM III-R, (SCID), and self-reported questionnaires (Beck Depression Inventory, BDI, and State and Trait Anxiety Inventory, STAI 1-2). The diagnosis of EDNOS was as frequent as that of AN and BN (43.8% versus 43.2%). There were no significant differences between EDNOS and AN/BN patients in terms of their general and specific psychopathological features, but significant differences were observed between bulimic-like and anorectic-like EDNOS patients, as well as between those with AN and BN. In conclusion, in our clinical setting, the patients with EDNOS and those with typical eating disorders have similar psychopathological features, thus suggesting that EDNOS patients should be further divided into two groups, anorectic-like (similar to AN) and bulimic-like (similar to BN) patients.

Fluoxetine and fluvoxamine combined with individual cognitive-behaviour therapy in binge eating disorder: a one-year follow-up study.

BACKGROUND: : The treatment of binge eating disorder (BED) is still the object of debate. In the present study, the effectiveness of antidepressant drugs (fluoxetine - FLX - 60 mg/day, fluvoxamine - FLV -300 mg/day), cognitive-behavioural therapy (CBT) and combined treatments (CBT + FLX, CBT + FLV) has been evaluated in a randomized, clinical trial. Results at the end of the active treatment (in the 24th week) and 1-year follow-up outcomes have been evaluated. METHODS: One hundred eight (44 M, 64 F) BED patients were randomly assigned to either CBT, FLX (60 mg/day), FLV (300 mg/day), CBT + FLX or CBT + FLV, for 24 weeks. At the beginning (T0), at the end (T1) of treatment and after 1 year (T2), body mass index (BMI) and eating attitude and behaviours (by EDE 12.0D) were assessed. RESULTS: At T1, BMI and EDE scores were significantly reduced in CBT, CBT + FLX and CBT + FLV, but not in the FLX and FLV treatment groups. In the CBT + FLV group, a greater (p < 0.05) reduction of EDE total scores was observed, when compared to CBT + FLX or CBT treatment groups. At T2, BMI was significantly higher than at T1, but still significantly lower than at T0 in the CBT, CBT + FLX and CBT + FLV groups, while EDE scores remained unchanged from T1 in all treatment groups. CONCLUSIONS: CBT was more effective than FLX or FLV in the treatment of BED. The addition of FLX to CBT does not seem to provide any clear advantage, while the addition of FLV could enhance the effects of CBT on eating behaviours. Modifications of eating behaviours are maintained at the 1-year follow-up, although the lost weight was partly regained.

Grazing and border-collision in piecewise-smooth systems: a unified analytical framework.

A comprehensive derivation is presented of normal form maps for grazing bifurcations in piecewise smooth models of physical processes. This links grazings with border-collisions in nonsmooth maps. Contrary to previous literature, piecewise linear maps correspond only to nonsmooth discontinuity boundaries. All other maps have either square-root or (3/2)-type singularities.