Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.

Task assignment algorithms for two-type heterogeneous multiprocessors

Consider the problem of assigning implicit-deadline sporadic tasks on a heterogeneous multiprocessor platform comprising two different types of processors—such a platform is referred to as two-type platform. We present two low degree polynomial time-complexity algorithms, SA and SA-P, each providing the following guarantee. For a given two-type platform and a task set, if there exists a task assignment such that tasks can be scheduled to meet deadlines by allowing them to migrate only between processors of the same type (intra-migrative), then (i) using SA, it is guaranteed to find such an assignment where the same restriction on task migration applies but given a platform in which processors are 1+α/2 times faster and (ii) SA-P succeeds in finding a task assignment where tasks are not allowed to migrate between processors (non-migrative) but given a platform in which processors are 1+α times faster. The parameter 0<α≤1 is a property of the task set; it is the maximum of all the task utilizations that are no greater than 1. We evaluate average-case performance of both the algorithms by generating task sets randomly and measuring how much faster processors the algorithms need (which is upper bounded by 1+α/2 for SA and 1+α for SA-P) in order to output a feasible task assignment (intra-migrative for SA and non-migrative for SA-P). In our evaluations, for the vast majority of task sets, these algorithms require significantly smaller processor speedup than indicated by their theoretical bounds. Finally, we consider a special case where no task utilization in the given task set can exceed one and for this case, we (re-)prove the performance guarantees of SA and SA-P. We show, for both of the algorithms, that changing the adversary from intra-migrative to a more powerful one, namely fully-migrative, in which tasks can migrate between processors of any type, does not deteriorate the performance guarantees. For this special case, we compare the average-case performance of SA-P and a state-of-the-art algorithm by generating task sets randomly. In our evaluations, SA-P outperforms the state-of-the-art by requiring much smaller processor speedup and by running orders of magnitude faster.

Task Assignment Algorithms for Heterogeneous Multiprocessors

Consider the problem of assigning implicit-deadline sporadic tasks on a heterogeneous multiprocessor platform comprising a constant number (denoted by t) of distinct types of processors—such a platform is referred to as a t-type platform. We present two algorithms, LPGIM and LPGNM, each providing the following guarantee. For a given t-type platform and a task set, if there exists a task assignment such that tasks can be scheduled to meet their deadlines by allowing them to migrate only between processors of the same type (intra-migrative), then: (i) LPGIM succeeds in finding such an assignment where the same restriction on task migration applies (intra-migrative) but given a platform in which only one processor of each type is 1 + α × t-1/t times faster and (ii) LPGNM succeeds in finding a task assignment where tasks are not allowed to migrate between processors (non-migrative) but given a platform in which every processor is 1 + α times faster. The parameter α is a property of the task set; it is the maximum of all the task utilizations that are no greater than one. To the best of our knowledge, for t-type heterogeneous multiprocessors: (i) for the problem of intra-migrative task assignment, no previous algorithm exists with a proven bound and hence our algorithm, LPGIM, is the first of its kind and (ii) for the problem of non-migrative task assignment, our algorithm, LPGNM, has superior performance compared to state-of-the-art.

CPMD-mindful task assignment for NPS-F

The multiprocessor scheduling scheme NPS-F for sporadic tasks has a high utilisation bound and an overall number of preemptions bounded at design time. NPS-F binpacks tasks offline to as many servers as needed. At runtime, the scheduler ensures that each server is mapped to at most one of the m processors, at any instant. When scheduled, servers use EDF to select which of their tasks to run. Yet, unlike the overall number of preemptions, the migrations per se are not tightly bounded. Moreover, we cannot know a priori which task a server will be currently executing at the instant when it migrates. This uncertainty complicates the estimation of cache-related preemption and migration costs (CPMD), potentially resulting in their overestimation. Therefore, to simplify the CPMD estimation, we propose an amended bin-packing scheme for NPS-F allowing us (i) to identify at design time, which task migrates at which instant and (ii) bound a priori the number of migrating tasks, while preserving the utilisation bound of NPS-F.

An optimal boundary fair scheduling

Nowadays, many real-time operating systems discretize the time relying on a system time unit. To take this behavior into account, real-time scheduling algorithms must adopt a discrete-time model in which both timing requirements of tasks and their time allocations have to be integer multiples of the system time unit. That is, tasks cannot be executed for less than one time unit, which implies that they always have to achieve a minimum amount of work before they can be preempted. Assuming such a discrete-time model, the authors of Zhu et al. (Proceedings of the 24th IEEE international real-time systems symposium (RTSS 2003), 2003, J Parallel Distrib Comput 71(10):1411–1425, 2011) proposed an efficient “boundary fair” algorithm (named BF) and proved its optimality for the scheduling of periodic tasks while achieving full system utilization. However, BF cannot handle sporadic tasks due to their inherent irregular and unpredictable job release patterns. In this paper, we propose an optimal boundary-fair scheduling algorithm for sporadic tasks (named BF TeX ), which follows the same principle as BF by making scheduling decisions only at the job arrival times and (expected) task deadlines. This new algorithm was implemented in Linux and we show through experiments conducted upon a multicore machine that BF TeX outperforms the state-of-the-art discrete-time optimal scheduler (PD TeX ), benefiting from much less scheduling overheads. Furthermore, it appears from these experimental results that BF TeX is barely dependent on the length of the system time unit while PD TeX —the only other existing solution for the scheduling of sporadic tasks in discrete-time systems—sees its number of preemptions, migrations and the time spent to take scheduling decisions increasing linearly when improving the time resolution of the system.

Provably Good Task Assignment for Two-Type Heterogeneous Multiprocessors Using Cutting Planes

Consider scheduling of real-time tasks on a multiprocessor where migration is forbidden. Specifically, consider the problem of determining a task-to-processor assignment for a given collection of implicit-deadline sporadic tasks upon a multiprocessor platform in which there are two distinct types of processors. For this problem, we propose a new algorithm, LPC (task assignment based on solving a Linear Program with Cutting planes). The algorithm offers the following guarantee: for a given task set and a platform, if there exists a feasible task-to-processor assignment, then LPC succeeds in finding such a feasible task-to-processor assignment as well but on a platform in which each processor is 1.5 × faster and has three additional processors. For systems with a large number of processors, LPC has a better approximation ratio than state-of-the-art algorithms. To the best of our knowledge, this is the first work that develops a provably good real-time task assignment algorithm using cutting planes.

Real-time scheduling with resource sharing on heterogeneous multiprocessors

Consider the problem of scheduling a task set τ of implicit-deadline sporadic tasks to meet all deadlines on a t-type heterogeneous multiprocessor platform where tasks may access multiple shared resources. The multiprocessor platform has m k processors of type-k, where k∈{1,2,…,t}. The execution time of a task depends on the type of processor on which it executes. The set of shared resources is denoted by R. For each task τ i , there is a resource set R i ⊆R such that for each job of τ i , during one phase of its execution, the job requests to hold the resource set R i exclusively with the interpretation that (i) the job makes a single request to hold all the resources in the resource set R i and (ii) at all times, when a job of τ i holds R i , no other job holds any resource in R i . Each job of task τ i may request the resource set R i at most once during its execution. A job is allowed to migrate when it requests a resource set and when it releases the resource set but a job is not allowed to migrate at other times. Our goal is to design a scheduling algorithm for this problem and prove its performance. We propose an algorithm, LP-EE-vpr, which offers the guarantee that if an implicit-deadline sporadic task set is schedulable on a t-type heterogeneous multiprocessor platform by an optimal scheduling algorithm that allows a job to migrate only when it requests or releases a resource set, then our algorithm also meets the deadlines with the same restriction on job migration, if given processors 4×(1+MAXP×⌈|P|×MAXPmin{m1,m2,…,mt}⌉) times as fast. (Here MAXP and |P| are computed based on the resource sets that tasks request.) For the special case that each task requests at most one resource, the bound of LP-EE-vpr collapses to 4×(1+⌈|R|min{m1,m2,…,mt}⌉). To the best of our knowledge, LP-EE-vpr is the first algorithm with proven performance guarantee for real-time scheduling of sporadic tasks with resource sharing on t-type heterogeneous multiprocessors.

Alterações da substância branca cerebral relacionadas com o envelhecimento

INTRODUÇÃO: Estudos prévios, com técnicas de imagem, documentam de forma consistente a existência de alterações da substância branca cerebral relacionadas com o envelhecimento (ASBRE). Tais alterações poderão ter um papel importante no declínio funcional do idoso, reflectindo‐se sobretudo no desempenho motor e cognitivo, com repercussão evidente na prática clínica. Apesar disso, a caracterização em definitivo dos fenótipos clínicos e da evolução das ASBRE continua por esclarecer, possivelmente pelas dificuldades metodológicas de que se reveste o seu estudo, incluindo: a adequação das baterias neuropsicológicas, a utilização de amostras de doentes com diferentes graus de severidade e de envolvimento regional, as limitações das diferentes escalas e a sensibilidade dos diferentes métodos de imagem. A Ressonância Magnética (RM) de difusão tem revelado grande sensibilidade para as alterações isquémicas, admitindo‐se que poderá permitir uma melhor caracterização das ASBRE e deste modo possibilitar uma correlação mais precisa com as variáveis cognitivas e motoras, permitindo avaliar ainda a substância branca aparentemente normal (SBAN). OBJECTIVOS: Descrever a evolução imagiológica das ASBRE no intervalo de um ano e analisar a sua expressão clínica e impacto funcional; identificar factores preditivos de progressão das ASBRE e de declínio funcional associado. Descrever a expressão clínica e perfil evolutivo dos doentes com ASBRE com envolvimento preferencial da região parieto‐occipital; comparar este grupo de doentes com os doentes com ASBRE, sem envolvimento preferencial desta região. Medir os coeficientes de difusão aparente (CDA), utilizando regiões de interesse (RDI), em diferentes localizações da substância branca, incluindo substância branca lesada e SBAN, descrever sua evolução temporal no intervalo de um ano e determinar suas correlações clínicas e imagiológicas. MÉTODOS: Utilizando uma amostra de conveniência, foram estudados 30 doentes, com mais de 65 anos, sem incapacidade funcional ou com incapacidade mínima, avaliada pela escala de actividades instrumentais da vida diária (IADL), apresentando ASBRE em TC. Foi utilizado um protocolo exaustivo de avaliação clínica (com particular destaque para as funções motoras e cognitivas) e imagiológica, em dois momentos de avaliação separados por um ano de intervalo (t0 e t1). As ASBRE foram avaliadas com escalas visuais, escala ARWMC e escala de Fazekas, e os doentes foram estudados em função do grau de severidade (ligeiro versus moderado a grave na escala de Fazekas) e de um envolvimento preferencial posterior (definido como 2 ou mais pontos na escala ARWMC na região parieto‐occipital por comparação com a região frontal). Os CDA foram avaliados mediante estudo de RDI, na substância branca frontal lesada (SBFL) e SBAN frontal, parieto‐occipital e dos pedúnculos cerebelosos. Para verificar diferenças na ordem de distribuição das variáveis foi usado o teste de Mann‐Whitney e para comparação de proporções, o teste exacto de Fisher. Na comparação entre a avaliação em t0 e t1 foi usado o teste Wilcoxon Signed Ranks na comparação da distribuição da ordem das variáveis e o teste McNemar na análise de frequências. Na análise correlacional foram utilizados os testes de T para variáveis emparelhadas e as correlações entre estas foram efectuadas com o coeficiente de correlação de Spearman ou de Pearson. O trabalho foi aprovado pela Comissão de Ética do hospital onde foi realizado e todos os doentes incluídos assinaram um consentimento informado. RESULTADOS: A idade média da população estudada foi 72,5 anos (17 doentes eram do sexo masculino). No final de um ano, 1 doente tinha falecido e 3 doentes não completaram a avaliação imagiológica. Registou‐se uma progressão significativa das ASBRE segundo a escala ARWMC (t0: 8,37 / t1: 9,65 ; p<0,001). Na análise funcional, motora e cognitiva, não houve um agravamento significativo. Avaliando os doentes em t0 e t1 segundo o grau de severidade das ASBRE, o grupo com atingimento moderado a grave (ASBRE2) comparado com o grupo com atingimento ligeiro (ASBRE1) apresentava: maior extensão de lesão da substância branca (ARWMC t0: 11,9 / 4,8 ; p<0.001 ; t1: 14,0 / 5,9 ; p<0,001); tendência a pior desempenho funcional (IADL t0: 90,7 / 99,2 ; p=0,023; t1: 86,4 / 96,7 ; p=n.s.) e motor (SPPB t0: 9,8 / 10,3 ; p=n.s. ; t1: 9,5 / 10,5 ; p=0,058); tendência a maior compromisso do humor (Escala Cornell t0: 6,7 / 3,5 ; p=0,037; t1: 6,2 / 4,5 ; p=n.s.). Analisando a evolução, de t0 para t1, de cada um dos grupos (ASBRE2 e ASBRE1) registou‐se: aumento da extensão da lesão da substância branca em ambos (ASBRE2: 12,0 / 14,0;z=‐2,687 ; p=0,007; ASBR1: 4,8 / 5,9 ; z=‐2,724 ; p=0,006); variação não significativa funcional e motora; tendência ao agravamento em ambos na prova de Cancelamento de dígitos (ASBRE2: 17,5 / 17,4 ; p=n.s. ; ASBRE1: 19,9 / 16,9 ; z=‐2,096 ; p=0,036);tendência à melhoria em ambos no MMS (ASBRE2: 25,7 / 27,5 ; z=‐2,155 ; p=0,031; ASBRE1: 27,5 / 28,2 ; p=n.s). Avaliando os doentes em t0 e t1 em função do padrão de distribuição das ASBRE, os doentes com um envolvimento preferencial posterior (ASBREP) comparados com os restantes (ASBREnP), apresentavam: maior extensão da lesão (ARWMC t0: 10,8 / 6,9 ; p=0,025; t1: 12,9 / 7,6 ; p=0,011); diferenças não significativas no desempenho motor; tendência a melhor desempenho na prova dos Labirintos (t0: 8,1 / 11,8 ; p=0,06; t1: 8,7 / 9,5 ; p=n.s.) e Cancelamento de dígitos (t0: 20,9 / 17,4 ; p=0,045; t1: 18,5 / 16,3 ; p=n.s.); tendência a maior compromisso depressivo na GDS (t0: 5,0 / 3,68 ; p=n.s. ; t1: 5,7 / 3,3 p=0,033). Analisando o perfil evolutivo de t0 para t1, registou‐se: aumento da extensão da lesão nos dois grupos (ASBREP: 10,8 / 12,9 ; z=‐2,555 ; P=0,011; ASBREnP: 6,4 / 7,6 ; z=‐2,877 ; p=0,04); variação em sentidos diferentes com melhoria funcional no grupo ASBREP (91,0 / 95,5 ; z=‐0,926 ; p=0,036) e agravamento no grupo ASBREnP (96,7 / 89,8 ; z=‐2,032 ; p=0,042); variação sem sentidos diferentes, com agravamento significativo no grupo ASBREnP no item estação de pé do SPPB (ASBREP 3,8/3,9 p=n.s.; ASBREnP 3,9/3,6; z=‐2,236 ; p=0,025); tendência à melhoria nos dois grupos no MMS (ASBREP: 27,2 / 28,2 ; p=n.s.; ASBREnP: 26,3 / 27,7 ; z=‐2,413 ; p=0,016) e tendência em sentidos diferentes no Trail Making, com eventual melhoria no grupo ASBREP (113,9 / 91,6 ; p=n.s.) e agravamento no grupo ASBREnP (113,7 / 152,0 ; z=‐2,155 ; p=0,031). Na análise da imagem, utilizando a escala ARWMC e o estudo dos CDA, na avaliação transversal na inclusão, a comparação entre as pontuações médias da escala ARWML nas diferentes regiões mostrava diferenças significativas (F=39,54 , p<0,0001). A análise comparativa post‐hoc de Bonferroni mostrou valores significativamente mais altos para as regiões frontais e parieto‐occipitais (p<0,0001). Os valores médios dos CDA eram significativamente diferentes entre regiões (F=44,56; p<0,0001), sendo mais altos na SBFL (p<0,0001). Não existia diferença significativa entre os valores registados na SBAN nas regiões frontais e parieto‐occipitais. As pontuações regionais da escala ARWMC e os valores médios dos CDA correlacionavam‐se todos de forma positiva. A pontuação da escala ARWMC na região frontal correlacionava‐se significativamente com os valores do CDA da SBFL (r=0,467 ; p=0,012). Existia tendência para uma correlação positiva entre as pontuações da escala ARWMC na região frontal e os valores médios dos CDA na SBAN frontal (r=0,276 ; p=0,155). As pontuações da escala ARWMC e os CDA correlacionavam‐se de forma positiva com a idade e com a tensão arterial (TA). Foram encontradas correlações significativas entre: idade e SBAN frontal (r=0,440 ; p=0,019); TA diastólica e SBFL (r=0,386 ; p=0,034); TA sistólica e SBAN Parieto‐occipital (r=0,407 ; P=0,032). Na avaliação motora e cognitiva, dado elevado número de variáveis, foi efectuada uma análise de factor principal. Registou‐se uma tendência global negativa na correlação entre as pontuações da escala visual na região frontal, os valores dos CDA, e o desempenho motor e cognitivo. Na análise evolutiva, (n=19), registou‐se variação significativa dos CDA, com aumento na SBFL (Direita: z=‐2,875 ; p=0,004 ; Esquerda: z=‐2,113 ; p=0,035) e diminuição na SBAN dos pedúnculos cerebelosos (Direita: z=‐2,094 ; p=0,036 ; Esquerda: z=‐1,989 ; p=0,047). Foi observada uma correlação negativa entre a variação do CDA na SBAN dos pedúnculos cerebelosos e na SBFL contralateral (SBAN pedúnculo cerebeloso Esquerdo / SBFL Direita: r=‐0,133 ; p=n.s.; SBAN pedúnculo cerebeloso Direito / SBFL Esquerda: r=‐0,561 ; p=0,012). Os valores dos CDA à direita correlacionavam‐se de forma positiva com a velocidade da marcha (r=0,562 ; p=0,012). CONCLUSÕES: A progressão das ASBRE pode ser observada com uma escala visual detalhada no intervalo de um ano. Contudo, o eventual agravamento da incapacidade funcional, motora e cognitiva, não parece ser apreciável em igual intervalo de tempo. A maior severidade das ASBRE associa‐se a uma tendência para um maior compromisso funcional, motor e possivelmente do humor. A questão da progressão em escalas simplificadas, de um estádio ligeiro para um estádio moderado a grave, não é elucidada pelos resultados do presente trabalho. Os doentes com um envolvimento preferencial da região parieto‐occipital poderão constituir um subgrupo distinto que, apesar de ter maior extensão de lesão, parece ter um melhor desempenho motor e cognitivo. O perfil evolutivo destes doentes parece igualmente ser distinto, não se observando a tendência ao agravamento funcional, motor e cognitivo (sobretudo em provas de função executiva) que se encontra nos restantes doentes. A análise transversal na inclusão, utilizando uma escala visual e o estudo dos CDA, sugere que a severidade das ASBRE se correlaciona com o compromisso motor e cognitivo, bem como com a idade e com a TA. Uma maior vulnerabilidade da substância branca frontal à lesão vascular parece ter um papel importante no compromisso motor e na disfunção executiva, (essencialmente à custa do compromisso da atenção), possivelmente associada à desconexão dos circuitos fronto‐subcorticais. A análise dos CDA sugere que isso é válido igualmente para a SBAN e sublinha que, as imagens de RM convencional poderão não traduzir a verdadeira extensão da lesão e consequentemente do compromisso motor e cognitivo. A relação entre a progressão da doença vascular em lesões frontais constituídas e a redução do CDA no pedúnculo cerebeloso contralateral poderá estar associada a um pior desempenho motor. A disrupção dos circuitos fronto‐cerebelosos, determinando hipometabolismo e diminuição da perfusão no cerebelo, poderá ser responsável pela diminuição do CDA no cerebelo. ABSTRACT INTRODUCTION: Previous studies, with new imaging techniques, have consistently documented the presence of age‐related white matter lesions (ARWML), emphasizing their role in agerelated functional decline, mainly related to motor and cognitive impairment, and inherent consequences in clinical practice. However clinical significance of ARWML remains to be elucidated, probably on account of methodological difficulties such as: specific neuropsychological batteries, utilization of samples with different degrees of severity and regional involvement, utilization of different imaging scales and different sensitivity of imaging techniques. Recently, Diffusion Weighted Magnetic Ressonance imaging (DWI) has shown a higher sensitivity to ischemic lesions, suggesting it might be superior for characterization of ARWML, allowing more precise correlation with motor and cognitive variables, and evaluating also normal appearing white matter (NAWM). OBJECTIVES: To describe imagiologic evolution of ARWML within one year interval and to analyse its clinical and functional significance. To identify predictors of ARWML progression and associated functional impairment. To describe clinical characteristics and evolution profile of patients with predominantly posterior lesions; to compare this group of patients with patients without predominantly posterior lesions. To study average Apparent Diffusion Coeficcients (ADC) in different white matter regions using regions of interest (ROI); to analyse their evolution profile and to determine their clinical and imagiologic correlations. METHODS: A sample of 30 patients older than 65 years, without functional impairment or with minimal impairment, according to the Instrumental Activities of Daily Lliving scale, with ARWML on CT scan, were studied in a cross‐sectional design. An extensive clinical(with detailed motor and cognitive evaluation) and imagiologic protocol was applied in two one‐year interval separate moments (t0 and t1). ARWML were studied using visual scales, ARWMC and Fazekas’s scale, and patients were studied according to degree of severity (Fazekas scale mild versus moderate / severe) and preferential involvement of the posterior region (defined as 2 or more points in the ARWMC scale in the parietooccipital region compared with frontal region). Evaluation of ADC was performed using ROI in frontal lesioned white matter (FLWM) and NAWM (frontal, parieto‐occipital and cerebellar regions). To study differences in the distribution of variables the Mann‐Whitney test was used and to compare proportions the exact Fisher Test was used. To compare temporal evolution profile between t0 and t1, the Wilcoxon Signed ranks Test was used to analyse the distribution of variables and the Mc Nemar Test to analyse frequencies. Correlation analysis was performed using Spearman or Pearson tests. The study was approved by the local Ethics Committee and all patients signed an informed consent. RESULTS: Mean age was 72.5 years (17 patients were male). By the end of the study, one patient was dead and 3 patients did not undergo brain imaging. There was a higher extent of ARWML evaluated with the ARWMC scale (t0: 8.37 / t1: 9.65 ; p<0.001). Functional, motor and cognitive performance did not progress significantly. Evaluating patients in t0 and t1 according to the degree of severity (Fazekas scale), the moderate / severe group of patients (WML2), compared with the mild group (WML1), showed: higher extent of lesion (ARWMC scale t0: 11.9 / 4.8 ; p<0.001 ; t1: 14.0 / 5.9 ; p<0.001); tendency to worse functional (IADL t0: 90.7 / 99.2 ; p=0.023; t1: 86.4 / 96.7 ; p=n.s.) and motor (SPPB t0: 9.8 / 10.3 ; p=n.s. ; t1: 9.5 / 10.5 ; p=0.058) performance; tendency to higher depressive scores (Cornell Scale t0: 6.7 / 3.5 ; p=0.037; t1: 6.2 / 4.5; p=n.s.). Analysing the evolution profile from t0 to t1 of each group (WML2 and WML1), there was a higher extent of lesion (ARWMC scale) in both (WML2: 12.0 / 14.0; z=‐2.687 ; p=0.007; WML1: 4.8 / 5.9 ; z=‐2.724 ; p=0.006); non‐significant variation in functional and motor performances; tendency to worse performance on the Digit Cancelling (WML2: 17.5 / 17.4 ; p=n.s. ; WML1: 19.9 / 16.9 ; z=‐2.096 ; p=0,036) and to better performance on the MMS (WML2: 25.7 / 27.5 ; z=‐2.155 ; p=0.031; WML1: 27.5/ 28.2 ; p=n.s). Evaluating patients in t0 and t1 according to the regional distribution of ARWML, patients with predominantly posterior lesions (WMLP) compared with the rest of the group (WMLnP), showed: higher extent of lesion (ARWMC scale t0: 10.8 / 6.9 ; p=0.025; t1:12.9 / 7.6 ; p=0.011); non significant differences on motor evaluation; tendency to a better performance on Maze (t0: 8.1 / 11.8 ; p=0.06; t1: 8.7 / 9.5 ; p=n.s.) and Digit cancelling (t0: 20.9 / 17.4 ; p=0.045; t1: 18.5 / 16.3 ; p=n.s.) tests;tendency to higher scores on GDS (t0: 5.0 / 3.68 ; p=n.s. ; t1: 5.7 / 3.3 p=0.033). Analysing the evolution profile from t0 to t1 of each group (WMLP and WMLnP), there was: higher extent of lesion (ARWMC scale) in both groups (WMLP: 10.8 / 12.9 ;z=‐2,555 ; P=0,011; WMLnP: 6.4 / 7.6 ; z=‐2.877; p=0.04); variation in different directions with better functional performance in the group WMLP (91.0 / 95.5 ;z=‐0.926 ; p=0.036) and worse in WMLnP (96.7 / 89.8 ; z=‐2.032 ; p=0.042); variation in different directions with worse motor performance in one SPPB item (total stands) in the group WMLnP (WMLP 3.8/3.9 p=n.s.; ASBREnP 3.9/3.6; z=‐2.236 ; p=0.025);tendency to improvement in both groups in MMS (WMLP: 27.2 / 28.2 ; p=n.s.; WMLnP:26.3 / 27.7 ; z=‐2.413 ; p=0.016); tendency to a variation in different directions in the Trail Making Test, with possible improvement in the group WMLP (113.9 / 91.6 ;p=n.s.) and worsening in the group WMLnP (113.7 / 152.0 ; z=‐2.155 ; p=0.031). Imaging analysis in the inclusion, using the ARWMC scale and ADC evaluation, showed significant differences in different regions (F=39.54, p<0.0001). Comparative post‐hoc Bonferroni analysis showed significantly higher scores in the frontal and parieto‐occipital regions (p<0.0001. ADC values were significantly different between regions (F=44.56; p<0.0001), being higher in FLWM (p<0‐0001). There was no significant difference between ADC in NAWM in frontal and parieto‐occipital regions. ARWMC scores and ADC values correlated positively. Significant correlations were found between frontal ARWMC score and FLWM ADC values (r=0.467 ; p=0.012). ARWMC scores and ADC values correlated positively with age and blood pressure. Significant correlations were: age and frontal NAWM (r=0.440 ; p=0.019); Diastolic blood pressure and FLWM (r=0.386 ; p=0.034); sistolic blood pressure and parietooccipital NAWM (r=0.407 ; P=0.032). Due to the higher number of motor and cognitive variables a preliminary study was done, using principal component analysis. A global tendency to a negative correlation was found between ARWMC scores, ADC values and motor and cognitive performances. Evolutive analysis of ADC (n=19), showed a significant variation, with higher values in t1 in FLWM (Right: z=‐2.875 ; p=0.004 ; Left: z=‐2.113 ; p=0.035) and lower values in t1 in cerebellar NAWM (Right: z=‐2.094 ; p=0.036 ; Left: z=‐1.989 ; p=0.047). A negative correlation was found between ADC variation in cerebellar NAWM and contralateral FLWM (Left cerebellar NAWM / Right FLWM: r=‐0.133 ; p=n.s.; Right cerebellar NAWM/ Left FLWM: r=‐0.561 ; p=0.012). ADC values on the right correlated positively with walking speed (r=0,562 ; p=0,012). CONCLUSIONS: Progression of ARWML can be documented with a detailed visual scale in a one year interval. However, functional, motor and cognitive impairment, do not seem to progress significantly within the same period. A higher severity of ARWML is associated with a tendency to a worse functional and motor performance (and possibly to higher scores in depression scales). The issue of progression in a simplified visual scale from a mild to a moderate / severe degree of ARWML is not further elucidated. Patients with predominantly posterior lesions may be a subset of ARWML patients, with a different profile, that despite higher extent of lesion, seem to fair better than the rest of the group, namely with better performance on motor and cognitive tests. Evolution profile of this subset of patients also seems to be different, without a clearcut tendency to worsening functional, motor and cognitive (particularly for executive function tests) performance that is observed in the rest of the group. Imaging analysis, with a visual scale and ADC evaluation, suggests that severity of ARWML correlates negatively with cognitive and motor performance and positively with age and blood pressure. A higher vulnerability of frontal white matter to vascular disease seems to play an important role in motor and cognitive dysfunction, mainly determined by impairment of attention skills associated with frontal‐subcortical disconnection. DWI results, suggest that this may also be true for NAWM, underlining that conventional MR images may not represent the true extent of cognitive decline. The relation between vascular disease progression inside frontal lesions and ADC reduction in contralateral cerebellar peduncles, may be associated with a worse motor performance. Disruption of fronto‐cerebellar cicuits, with associated regional hypometabolism, may be responsible for the reduction of cerebellar ADC.

A Percepção dos Cuidadores Informais Relativamente ao Centro de Dia Para Pessoas com Doença de Alzheimer

A sobrecarga familiar provocada pela doença de Alzheimer é reconhecida como um problema de saúde pública: há cada vez menos cuidadores jovens para cada vez mais doentes idosos e as insuficientes respostas de suporte social são uma realidade. O acto de cuidar no domícilio afecta de forma significativa os padrões ocupacionais dos prestadores de cuidados, levando-os a situações de desiquilíbrio ocupacional e a grande desgaste fisico e emocional. Assim, este trabalho pretende compreender a percepção dos cuidadores informais relativamente à integração destas pessoas em centros de dia, como estratégia de melhoria da estabilidade emocional e equilíbrio ocupacional dos seus familiares. Em termos da recolha da informação empírica, recorremos a uma metodologia mista, constituída por procedimentos mais de natureza quantitativa e outros de carácter mais qualitativo. Nesse enquadramento foram administrados a cerca de 10 cuidadores informais, antes e depois do seu familiar ter sido integrado no centro de dia, os instrumentos “Entrevista de Zarit para a sobrecarga do cuidador” e o “Teste abreviado da qualidade de vida” (WHOQOL-Bref), no sentido de se avaliar o impacto desta medida no equilíbrio emocional e percepção subjectiva da qualidade de vida. Concomitantemente, foram realizadas entrevistas também antes e depois da integração no sentido de compreender de que forma a frequência no centro de dia potencia um equilíbrio ocupacional mais adaptado. Os resultados obtidos mostram que ocorreu uma diminuição da sobrecarga emocional e uma melhoria da percepção subjectiva de qualidade de vida por parte dos cuidadores, bem como, um padrão de equilíbrio ocupacional mais ajustado e equilibrado e potenciador de bem-estar, após a frequência de seis meses do familiar com doença de Alzheimer no centro de dia “Memória de Mim”. Ainda que tratando-se de um estudo exploratório, estas conclusões parecem apontar para a importância destas respostas sociais no suporte às pessoas com demências e aos seus familiares.

Chagasic megaesophagus and megacolon diagnosed in childhood and probably caused by vertical transmission

Reports on children presenting symptoms compatible with the chronic phase of Chagas disease are sporadic. We report a case of a 7-year-old boy who had megaesophagus and megacolon, both of them a consequence of the trypanosomiasis. The etiology was established by means of laboratory and histological features. Based on epidemiological data, the authors concluded that vertical transmission was the most probable route of acquisition. This diagnosis should be considered in children presenting similar complaints, even those living away from endemic areas.

Mixomas Cardíacos, 13 Anos de Experiência no seu Diagnóstico Ecocardiográfico

INTRODUCTION: Transthoracic echocardiography is the method of choice for the diagnosis of cardiac myxomas, but the transesophageal approach provides a better definition of the location and characteristics of the tumor. The authors review their thirteen years' experience on the echocardiographic diagnosis of this pathology. METHODS: From 1994 to 2007, 41 cardiac tumors were diagnosed in our echocardiographic laboratory, of which 27 (65.85%) were cardiac myxomas. The exams and the patients' clinical files were retrospectively reviewed. RESULTS: Of the 27 patients, 22 (81.5%) were female, with a mean age of 62.1 +/- 13.6 years (25-84 years). The predominant clinical features were due to the obstruction caused by the tumor in more than two thirds of the patients, followed by constitutional symptoms in one third and embolic events in 30%. In the lab results, anemia was found in three patients and elevated sedimentation rate and CRP in two. In two patients the myxoma was found by chance. All the cases were of the sporadic type, although we found a prevalence of thyroid disease of 14% (4 patients). All patients underwent urgent surgical resection except one, in whom surgery was refused due to advanced age and comorbidities. The myxomas followed a typical distribution with 24 (88.8%) located in the left atrium, 18 of them attached to the atrial septum (AS) and two to the mitral valve. In one patient, the tumor involved both atria. The other two cases originated in the right atrium at the AS. Embolic phenomena were more frequent in small tumors (p = 0.027) and in those with a villous appearance (p = 0.032). Obstructive manifestations were associated with larger tumors (p = 0.046) and larger left atria (p = 0.048). In our series, there were no deaths during hospitalization or in the follow-up period of 5.2 +/- 3.7 years in 19 patients. There were two recurrences, both patients being successfully reoperated. CONCLUSION: Myxoma is the most common cardiac tumor. Transesophageal echocardiography provides excellent morphologic definition, aiding in diagnosis and follow-up. Most clinical manifestations are obstructive and are associated with larger tumors. Small tumors with a friable appearance have a higher chance of embolization. Surgical resection is usually curative and the long-term prognosis is excellent.

A Papillary Fibroelastoma of the Tricuspid Valve

Primary cardiac tumours are rare in children. Of these, papillary fibroelastomas are unusual but benign, usually being found in adults. There are only sporadic cases reported in children. We diagnosed such a papillary fibroelastoma involving the tricuspid valve in an asymptomatic child during a routine cardiac investigation.

Complexo Demencial Relacionado com SIDA

O complexo demencial relacionado com SIDA, ou mais recentemente classificado como demência associada ao VIH, manifesta-se clinicamente como uma demência subcortical. Surge em estadios avançados da infecção pelo VIH, evoluindo num período de tempo que pode variar entre semanas a meses. Os autores revêem a fisiopatologia, quadro clínico, diagnóstico diferencial e abordagem terapêutica desta situação.

An Exact Schedulability Test for Global FP Using State Space Pruning

Presented at 23rd International Conference on Real-Time Networks and Systems (RTNS 2015). 4 to 6, Nov, 2015, Main Track. Lille, France.

Neurotoxocarosis

Infection of humans with embryonated eggs of Toxocara canis (larva migrans) remains asymptomatic, or results in covert or common toxocarosis, visceral larva migrans syndrome, or ophthalmologic and neurologic impairment. Though neurological manifestations of Toxocara canis larvae are rare, toxocarosis remains an important differential diagnosis of various neurological disorders. Manifestations of the central nervous system are dementia, meningo-encephalitis, myelitis, cerebral vasculitis, epilepsy, or optic neuritis. Manifestations of the peripheral nervous system comprise radiculitis, affection of cranial nerves, or musculo-skeletal involvement. If toxocarosis is neglected, ignored, or refused as a differential of these abnormalities, it may be easily overlooked for years. Early recognition and treatment of the infection is, however, of paramount importance since it reduces morbidity and mortality and the risk of secondary superinfection. Like the visceral manifestations, neurological manifestations of toxocarosis are treated by benzimidazole components, most frequently albendazole, corticosteroids, or diethylcarbamazine. If detected and treated early, the prognosis of neurological manifestations of toxocarosis is favourable.