Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.

BACKGROUND Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. METHODS AND FINDINGS The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction  = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction  = 1.50×10-3) and waist circumference (p for interaction  = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Correlations between motor and intellectual functions in normally developing children between 7 and 18 years.

The relationship between motor and intellectual functions was examined in 252 healthy children from 7 to 18 years using the Zurich Neuromotor Assessment and standardized intelligence tests. The magnitude of Spearman correlations between neuromotor and intellectual scores was generally weak (r = 0.15-0.37). The strongest correlations were found between performance in the pegboard task and visuomotor intelligence (r = 0.35) and between contralateral associated movements and intelligence in boys (r = 0.37). We conclude that specific connections between motor and intellectual functions may exist. However, because the magnitude of correlations is generally weak, we suggest that motor and intellectual domains in healthy children are largely independent.

The Franco-German motor before the eastern enlargement: the causes of its decline

The Franco-German axis has been a transcendent force behind the European integration ever since the early years of the EEC. Nevertheless, since the fall of the Berlin Wall in November 1989, the perception of a progressive distancing between France and Germany as far as the EU politics is concerned, has increased. There has not been a definitive break in Franco-German relations. However, the influence of the Franco-German axis in the EU has been reduced in the 90s. Finally, in the Nice IGC (December 2000), the misunderstandings of these two “big” states about their weight in the Council, almost caused the failure to conclude the Treaty of Nice, clearing the way for the Eastern enlargement. The traditional balance between France and Germany has been eroded. Germany has consolidated its role of leadership in the EU, and above all towards the candidate countries. The purpose of this paper is to analyse the fifth enlargement as one of the causes of the decline of the Franco-German axis as the motor of the process of European integration.

Modelització i simulació del motor d'inducció en règim transitori amb PSIM

El present treball pretén modelitzar i simular el motor d’inducció trifàsic en règim transitori amb PSIM 6.0 Demo(la versió del programa que s’utilitza actualment a l’Escola Politècnica Superior de la UdG), però també s’estudia el model en règim permanent, per tal de comparar a nivell teòric els resultats dels dos règims. Primer cal entendre i implementar el model del motor d’inducció, i així obtenir l'esquema equivalent en règim transitori, per després poder-lo simular. Abans de dur a terme la simulació, cal obtenir els paràmetres del circuit equivalent del motor real per introduir-los al programa informàtic, amb la finalitat de tenir precisió en les respostes. Aquests valors s’obtindran mitjançant assajos necessaris al laboratori. Posteriorment, es fan simulacions i pràctiques reals amb el motor treballen en diferents condicions per veure el seu comportament, i així poder comparar els resultats de la simulació amb els valors reals. També s’implementa un estudi de la influencia dels paràmetres interns en el funcionament del motor. Així es podrà visualitzar i comparar les respostes de diferents variables en cadascunes de les simulacions que es duguin a terme. Finalment, seria interessant la introducció de la màquina d’inducció trifàsica actuant com a generador en la simulació.Aquest és un estudi en el qual se simula la màquina d'inducció trifàsic en règim transitori i en règim permanent mitjançant l'ús del PSIM, que és el programa informàtic de simulació

Millora d'un motor monocilíndric de 4T

En el nostre treball final de carrera tindrem com objecte la millora de les prestacions d’un motor de 4T per a una motocicleta d’enduro. L’augment de potència s’aconseguirà des de diferents perspectives, variant el sistema d’admissió, el canvi de la distribució de les vàlvules de la culata o variant la lubrificació del pistó. Per realitzar l’objecte d’aquest treball utilitzarem com a base de l’estudi el motor de 4T de la FSE 450 del 2004 de GASGAS Motos SA. El motor de 4T utilitzat està orientat cap a una utilització d’enduro, per tant amb unes característiques de parell determinades. Partirem de l’anàlisi d’un motor amb sistema d’admissió per depressió (carburador convencional) idesprés instal·larem el sistema d’injecció indirecta monopunt. La millora també afectarà a l’estil de conducció de la motocicleta, per tant comentarem els resultats obtinguts des de dues perspectives: d’una conducció estàndard i una d’esportiva

Primary motor cortex involvement in Alzheimer disease.

In Alzheimer disease (AD) the involvement of entorhinal cortex, hippocampus, and associative cortical areas is well established. Regarding the involvement of the primary motor cortex the reported data are contradictory. In order to determine whether the primary motor cortex is involved in AD, the brains of 29 autopsy cases were studied, including, 17 cases with severe cortical AD-type changes with definite diagnoses of AD, 7 age-matched cases with discrete to moderate cortical AD-type changes, and 5 control cases without any AD-type cortical changes. Morphometric analysis of the cortical surface occupied by senile plaques (SPs) on beta-amyloid-immunostained sections and quantitative analysis of neurofibrillary tangles (NFTs) on Gallyas-stained sections was performed in 5 different cortical areas including the primary motor cortex. The percentage of cortical surface occupied by SPs was similar in all cortical areas, without significant difference and corresponded to 16.7% in entorhinal cortex, 21.3% in frontal associative, 16% in parietal associative, and 15.8% in primary motor cortex. The number of NFTs in the entorhinal cortex was significantly higher (41 per 0.4 mm2), compared with those in other cortical areas (20.5 in frontal, 17.9 in parietal and 11.5 in the primary motor cortex). Our findings indicate that the primary motor cortex is significantly involved in AD and suggest the appearance of motor dysfunction in late and terminal stages of the disease.

Natureza e gravidade das lesões em vítimas de acidente de trânsito de veículo a motor

Trata-se de um estudo retrospectivo que teve por objetivo caracterizar a natureza e gravidade da lesão de pacientes hospitalizados, vítimas de acidente de trânsito de veículo a motor através da Abbreviated Injury Scale (AIS). Foram analisadas 220 vítimas internadas em uma Instituição referência para trauma em São Paulo, Brasil. Do total de pacientes, 111 eram pedestres, 83 ocupantes de auto e 26 ocupantes de moto. As lesões mais frequentes localizaram se em membros/cintura pélvica e cabeça/pescoço para toda população do estudo com gravidade de lesão AIS £ 3. Faleceram 45 vítimas, sendo dois terços de pedestres.

Dynamic diagnosis based on interval analytical redundancy relations and signs of the symptoms

A model-based approach for fault diagnosis is proposed, where the fault detection is based on checking the consistencyof the Analytical Redundancy Relations (ARRs) using an interval tool. The tool takes into account the uncertainty in theparameters and the measurements using intervals. Faults are explicitly included in the model, which allows for the exploitation of additional information. This information is obtained from partial derivatives computed from the ARRs. The signs in the residuals are used to prune the candidate space when performing the fault diagnosis task. The method is illustrated using a two-tank example, in which these aspects are shown to have an impact on the diagnosis and fault discrimination, since the proposed method goes beyond the structural methods

Interregional compensatory mechanisms of motor functioning in progressing preclinical neurodegeneration.

Understanding brain reserve in preclinical stages of neurodegenerative disorders allows determination of which brain regions contribute to normal functioning despite accelerated neuronal loss. Besides the recruitment of additional regions, a reorganisation and shift of relevance between normally engaged regions are a suggested key mechanism. Thus, network analysis methods seem critical for investigation of changes in directed causal interactions between such candidate brain regions. To identify core compensatory regions, fifteen preclinical patients carrying the genetic mutation leading to Huntington's disease and twelve controls underwent fMRI scanning. They accomplished an auditory paced finger sequence tapping task, which challenged cognitive as well as executive aspects of motor functioning by varying speed and complexity of movements. To investigate causal interactions among brain regions a single Dynamic Causal Model (DCM) was constructed and fitted to the data from each subject. The DCM parameters were analysed using statistical methods to assess group differences in connectivity, and the relationship between connectivity patterns and predicted years to clinical onset was assessed in gene carriers. In preclinical patients, we found indications for neural reserve mechanisms predominantly driven by bilateral dorsal premotor cortex, which increasingly activated superior parietal cortices the closer individuals were to estimated clinical onset. This compensatory mechanism was restricted to complex movements characterised by high cognitive demand. Additionally, we identified task-induced connectivity changes in both groups of subjects towards pre- and caudal supplementary motor areas, which were linked to either faster or more complex task conditions. Interestingly, coupling of dorsal premotor cortex and supplementary motor area was more negative in controls compared to gene mutation carriers. Furthermore, changes in the connectivity pattern of gene carriers allowed prediction of the years to estimated disease onset in individuals. Our study characterises the connectivity pattern of core cortical regions maintaining motor function in relation to varying task demand. We identified connections of bilateral dorsal premotor cortex as critical for compensation as well as task-dependent recruitment of pre- and caudal supplementary motor area. The latter finding nicely mirrors a previously published general linear model-based analysis of the same data. Such knowledge about disease specific inter-regional effective connectivity may help identify foci for interventions based on transcranial magnetic stimulation designed to stimulate functioning and also to predict their impact on other regions in motor-associated networks.

Autologous adult cortical cell transplantation enhances functional recovery following unilateral lesion of motor cortex in primates: a pilot study.

BACKGROUND:: Although cell therapy is a promising approach after cerebral cortex lesion, few studies assess quantitatively its behavioral gain in non-human primates. Furthermore, implantations of fetal grafts of exogenous stem cells are limited by safety and ethical issues. OBJECTIVE:: To test in non-human primates the transplantation of autologous adult neural progenitor cortical cells with assessment of functional outcome. METHODS:: Seven adult macaque monkeys were trained to perform a manual dexterity task, before the hand representation in motor cortex was chemically lesioned unilaterally. Five monkeys were used as control, compared to two monkeys subjected to different autologous cells transplantation protocols performed at different time intervals. RESULTS:: After lesion, there was a complete loss of manual dexterity in the contralesional hand. The five "control" monkeys recovered progressively and spontaneously part of their manual dexterity, reaching a unique and definitive plateau of recovery, ranging from 38% to 98% of pre-lesion score after 10 to 120 days. The two "treated" monkeys reached a first spontaneous recovery plateau at about 25 and 40 days post-lesion, representing 35% and 61% of the pre-lesion performance, respectively. In contrast to the controls, a second recovery plateau took place 2-3 months after cell transplantation, corresponding to an additional enhancement of functional recovery, representing 24 and 37% improvement, respectively. CONCLUSIONS:: These pilot data, derived from two monkeys treated differently, suggest that, in the present experimental conditions, autologous adult brain progenitor cell transplantation in non-human primate is safe and promotes enhancement of functional recovery.

Brain tissue properties differentiate between motor and limbic basal ganglia circuits.

Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome.

The Lausanne cohort Lc65+: a population-based prospective study of the manifestations, determinants and outcomes of frailty

BACKGROUND: Frailty is a relatively new geriatric concept referring to an increased vulnerability to stressors. Various definitions have been proposed, as well as a range of multidimensional instruments for its measurement. More recently, a frailty phenotype that predicts a range of adverse outcomes has been described. Understanding frailty is a particular challenge both from a clinical and a public health perspective because it may be a reversible precursor of functional dependence. The Lausanne cohort Lc65+ is a longitudinal study specifically designed to investigate the manifestations of frailty from its first signs in the youngest old, identify medical and psychosocial determinants, and describe its evolution and related outcomes. METHODS/DESIGN: The Lc65+ cohort was launched in 2004 with the random selection of 3054 eligible individuals aged 65 to 70 (birth year 1934-1938) in the non-institutionalized population of Lausanne (Switzerland). The baseline data collection was completed among 1422 participants in 2004-2005 through questionnaires, examination and performance tests. It comprised a wide range of medical and psychosocial dimensions, including a life course history of adverse events. Outcomes measures comprise subjective health, limitations in activities of daily living, mobility impairments, development of medical conditions or chronic health problems, falls, institutionalization, health services utilization, and death. Two additional random samples of 65-70 years old subjects will be surveyed in 2009 (birth year 1939-1943) and in 2014 (birth year 1944-1948). DISCUSSION: The Lc65+ study focuses on the sequence "Determinants --> Components --> Consequences" of frailty. It currently provides information on health in the youngest old and will allow comparisons to be made between the profiles of aging individuals born before, during and at the end of the Second World War.

Integració del motor APIS de qüestionaris on-line en una plataforma d'eLearning basada en serveis

El projecte Integració del motor APIS de qüestionaris on-line en una plataformad'eLearning basada en serveis descriu el procés d'anàlisi i implementació del codi necessari per integrar dins de la plataforma d'eLearning SLeD tot el motor d'APIS de manera que SLeD pugui reproduir preguntes o items i exàmens complets o tests dins d'una UOL o unitat d'aprenentatge. Això permetrà dotar a APIS d'un control de sessió d'usuari i permetrà una utilitat que fins ara no tenia, la possibilitat de entrar al món online mitjançant SLeD. Tot aixòs’implementa gràcies a la connexió WebServices amb el mòdul CCSI de CopperCore i SLeD que s'encarrega de donar facilitats al programador de cara a ampliar el ventall d'eines que ofereix aquesta plataforma i fomentar encara més la idea del codi lliure (open source) i la utilitat globalitzadora d'e-Learning.