A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression

Preliminary findings suggest that transcranial direct current stimulation (tDCS) can have antidepressant effects. We sought to test this further in a parallel-group, double-blind clinical trial with 40 patients with major depression, medication-free randomized into three groups of treatment: anodal tDCS of the left dorsolateral prefrontal cortex (active group-`DLPFC`); anodal tDCS of the occipital cortex (active control group-`occipital`) and sham tDCS (placebo control group-`sham`). tDCS was applied for 10 sessions during a 2-wk period. Mood was evaluated by a blinded rater using the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The treatment was well tolerated with minimal side-effects that were distributed equally across all treatment groups. We found significantly larger reductions in depression scores after DLPFC tDCS [HDRS reduction of 40.4 % (+/-25.8%)] compared to occipital [HDRS reduction of 21.3 % ( +/-12.9%)] and sham tDCS [HDRS reduction of 10.4 % (+/-36.6%)]. The beneficial effects of tDCS in the DLPFC group persisted for 1 month after the end of treatment. Our findings support further investigation on the effects of this novel potential therapeutic approach - tDCS - for the treatment of major depression.

Analysis of Piezoelectric sensor to detect flexural waves

The electromechanical transfer characteristics of adhesively bonded piezoelectric sensors are investigated. By the use of dynamic piezoelectricity theory, Mindlin plate theory for flexural wave propagation, and a multiple integral transform method, the frequency-response functions of piezoelectric sensors with and without backing materials are developed and the pressure-voltage transduction functions of the sensors calculated. The corresponding simulation results show that the sensitivity of the sensors is not only dependent on the sensors' inherent features, such as piezoelectric properties and geometry, but also on local characteristics of the tested structures and the admittance and impedance of the attached electrical circuit. It is also demonstrated that the simplified rigid mass sensor model can be used to analyze successfully the sensitivity of the sensor at low frequencies, but that the dynamic piezoelectric continuum model has to be used for higher frequencies, especially around the resonance frequency of the coupled sensor-structure vibration system.

Flexural waves transmitted by rectangular piezoceramic transducers

Rectangular piezoceramic transducers are widely used in ultrasonic evaluation and health monitoring techniques and structural vibration control applications. In this paper the flexural waves excited by rectangular transducers adhesively attached to isotropic plates are investigated. In view of the difficulties in developing accurate analytical models describing the transfer characteristics of the transducer due to the complex electromechanical transduction processes and transducer-structure interactions involved, a combined theoretical-experimental approach is developed. A multiple integral transform method is used to describe the propagation behaviour of the waves in the plates, while a heterodyne Doppler laser vibrometer is employed as a non-contact receiver device. This combined theoretical-experimental approach enables the efficient characterization of the electromechanical transfer properties of the piezoelectric transducer which is essential for the development of optimized non-destructive evaluation systems. The results show that the assumption of a uniform contact pressure distribution between the transducer and the plate can accurately predict the frequency spectrum and time domain response signals of the propagating waves along the main axes of the rectangular transmitter element.

STRATEGIC DECISIONS OF FAMILY FIRMS ON CASH ACCUMULATION

ABSTRACTGiven the particular strengths, weaknesses, and peculiarities of family firms as well as the importance of liquidity in today’s marketplace, we analyze the distinct characteristics and strategies of family businesses related to the amount of cash a firm holds. We look beyond the traditional factors that influence decisions related to cash management to examine factors that are particularly important for family firms. Specifically, we outline the relevance of strategic decisions guided by family firms’ conservatism, flexibility, long-term view, and the active control that they have over family members. To our knowledge, no prior studies exist regarding family firms and their strategic adjustment of cash holding. Therefore, we investigate whether the ownership structure of the firm (through the presence of a controlling family) moderates decisions on cash holding. We found that family firms tend to accumulate cash for strategic reasons and as a result of their own idiosyncrasies. Thus, family firms can achieve optimal cash accumulation more efficiently than non-family firms.

Observação e controlo da segurança estrutural de barragens de betão: utilização integrada de modelos numéricos e de modelos de separação de efeitos

Dissertação de Natureza Científica elabora da no âmbito do protocolo de cooperação entre o ISEL e o LNEC para obtenção do grau de Mestre em Engenharia Civil

Análise do comportamento sísmico da barragem de Luzzone: desenvolvimento de um programa de EF3D utilizando uma formulação em deslocamentos e pressões

Trabalho Final de Mestrado elaborado no Laboratório Nacional de Engenharia Civil (LNEC) para a obtenção do grau de Mestre em Engenharia Civil pelo Instituto Superior de Engenharia de Lisboa no âmbito do protocolo entre o ISEL e o LNEC

Comprehensive treatments for social cognitive deficits in schizophrenia: A critical review and effect-size analysis of controlled studies

Recent advances in psychosocial treatments for schizophrenia have targeted social cognitive deficits. A critical literature review and effect-size (ES) analysis was conducted to investigate the efficacy of comprehensive programs of social cognitive training in schizophrenia. Results revealed 16 controlled studies consisting of seven models of comprehensive treatment with only three of these treatment models investigated in more than one study. The effects of social cognitive training were reported in 11/15 studies that included facial affect recognition skills (ES=.84) and 10/13 studies that included theory-of-mind (ES=.70) as outcomes. Less than half (4/9) of studies that measured attributional style as an outcome reported effects of treatment, but effect sizes across studies were significant (ESs=.30-.52). The effect sizes for symptoms were modest, but, with the exception of positive symptoms, significant (ESs=.32-.40). The majority of trials were randomized (13/16), selected active control conditions (11/16) and included at least 30 participants (12/16). Concerns for this area of research include the absence of blinded outcome raters in more than 50% of trials and low rates of utilization of procedures for maintaining treatment fidelity. These findings provide preliminary support for the broader use of comprehensive social cognitive training procedures as a psychosocial intervention for schizophrenia.

Acompanhamento das Técnicas de Construção na Obra do Aproveitamento Hidroelétrico de Foz Tua

O presente trabalho foi desenvolvido na obra do Aproveitamento Hidroelétrico de Foz Tua onde a autora teve oportunidade de realizar o estágio curricular junto da equipa da Fiscalização no período de 2 de Fevereiro de 2015 a 31 de Julho de 2015. A elaboração do presente trabalho pretende transmitir conhecimentos adquiridos relacionados com a constituição de um Aproveitamento Hidroelétrico, os tipos de barragens existentes, monitorização e controlo da segurança da estrutura da Barragem, controlo de qualidade de betão e o processo construtivo de uma Barragem. A construção da Barragem do Aproveitamento Hidroelétrico de Foz Tua tem sido realizada através do método tradicional, que consiste na aplicação de betão convencional compactado por vibração interna. Ao longo deste processo, foram aplicadas diversas técnicas construtivas, nomeadamente: escavação, betonagem, refrigeração artificial, injeção de juntas e tratamento de fundações. Neste trabalho foram ainda analisados os cuidados de segurança necessários neste tipo de estruturas, tendo como base o Regulamento de Segurança de Barragens. Este regulamento define as regras a seguir durante a execução da barragem e a monotorização que deve ser efetuada à mesma, permitindo assim o controlo da segurança da estrutura na sua construção e vida útil. É necessário ainda existir um controlo da qualidade, produção e aplicação do betão na estrutura de modo a aumentar a segurança, qualidade e durabilidade da mesma.

Development of a poly(L-Lactic acid) based drug release system

Dissertação de mestrado em Biofísica e Bionanossistemas

A look through the new therapeutic window: irbesartan

Although an impressive array of efficacious antihypertensive agents are available to treat hypertension, the optimal use of these agents is limited by dose-related side-effect profiles. This is particularly the case for widely used first-line antihypertensive agents such as diuretics, beta-blockers, calcium antagonists, and alpha1-blockers; this represents a major therapeutic dilemma in treating hypertension. With the development of the angiotensin II receptor antagonists (AIIRAs), this dilemma might have been solved. Irbesartan is a long-acting AIIRA that provides dose-related efficacy with placebo-like tolerability at all clinical doses. The results of placebo and active-control trials of irbesartan have demonstrated that the agent is as effective as the leading members of major antihypertensive classes with respect to blood pressure control, while having superior tolerability. Pooled data from nine multicenter, randomized, placebo-controlled trials with irbesartan have documented no adverse events caused by dose-response. This feature could widen the traditionally narrow therapeutic window in the treatment of hypertension and point to the use of AIIRAs such as irbesartan as first-line therapy in the management of hypertension.

NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality.

PURPOSE: NovoTTF-100A is a portable device delivering low-intensity, intermediate frequency electric fields via non-invasive, transducer arrays. Tumour Treatment Fields (TTF), a completely new therapeutic modality in cancer treatment, physically interfere with cell division. METHODS: Phase III trial of chemotherapy-free treatment of NovoTTF (20-24h/day) versus active chemotherapy in the treatment of patients with recurrent glioblastoma. Primary end-point was improvement of overall survival. RESULTS: Patients (median age 54years (range 23-80), Karnofsky performance status 80% (range 50-100) were randomised to TTF alone (n=120) or active chemotherapy control (n=117). Number of prior treatments was two (range 1-6). Median survival was 6.6 versus 6.0months (hazard ratio 0.86 [95% CI 0.66-1.12]; p=0.27), 1-year survival rate was 20% and 20%, progression-free survival rate at 6months was 21.4% and 15.1% (p=0.13), respectively in TTF and active control patients. Responses were more common in the TTF arm (14% versus 9.6%, p=0.19). The TTF-related adverse events were mild (14%) to moderate (2%) skin rash beneath the transducer arrays. Severe adverse events occurred in 6% and 16% (p=0.022) of patients treated with TTF and chemotherapy, respectively. Quality of life analyses favoured TTF therapy in most domains. CONCLUSIONS: This is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to chemotherapy regimens that are commonly used for recurrent glioblastoma. Toxicity and quality of life clearly favoured TTF.

Aktiivinen jännitteensäätö hajautetussa sähköntuotannossa

Hajautetun tuotannon määrä kasvaa jakeluverkossa tulevaisuudessa ja siksi jakeluverkon toiminta tulee muuttumaan aktiivisempaan suuntaan. Nykyisin tuotannon aiheuttamaa jännitteennousua rajoitetaan yleensä passiivisilla menetelmillä kuten vahvistamalla verkkoa. Tuotantolaitos ei tällöin osallistu jakeluverkon jännitteensäätöön. Tämä saattaa nostaa kapasiteetiltaan suurehkon tuotannon liittymiskustannukset niin korkeiksi, ettei tuotantolaitosta kannata rakentaa. Aktiivisella jännitteensäädöllä tuotantokapasiteettia voitaisiin merkittävästi kasvattaa nykyisissä jakeluverkoissa. Aktiivinen jännitteensäätö voi perustua joko paikalliseen säätöön, jolloin esim. tuotantolaitosta säädetään paikallisen jännitteen perusteella tai koordinoituun säätöön, jolloin verkon komponentteja säädetään kokonaisuutena. Työssä tutustutaan hajautettuun tuotantoon ja sen vaikutuksiin jakeluverkon jännitetasoissa sekä jännitteensäädössä. Työssä edetään passiivisesta jännitteensäädöstä aktiiviseen jännitteensäätöön. Aktiivisessa jännitteensäädössä tutustutaan muutamaan kirjallisuudessa esitettyyn algoritmiin ja käytännön toteutukseen. Työssä keskitytään vain verkon jännitetasoon, eikä muita jännitteen laadun ominaisuuksia oteta huomioon.

Vuotasapainon hallinta kokosiltasyötetyssä muuntajassa

Keskitaajuudella toimivia muuntajia käytetään laajalti tehoelektroniikkasovelluksissa kuten DC/DC-konverttereissa ja muissa hakkuriteholähteissä. Muuntaja on induktiivinen komponentti, jonka magneettisen tasapainon säilyttäminen hakkuriteholähteissä on laitteen virheettömän toiminnan kannalta tärkeää. Muuntajaa syöttävän virtapiirin on muodostettava symmetrinen syöttöjännite, jotta muuntajan vuo ei ajaudu positiiviseen tai negatiiviseen kyllästykseen. Tässä diplomityössä esitetään muuntajan sähkömagneettinen toimintaperiaate, kyllästymisen syyt hakkuriteholähteissä sekä kehitetään aktiivinen ohjaus vuotasapainon säilyttämiseksi. Hakkuriteholähteissä käytettävissä muuntajissa on monesti useampi kuin kaksi käämiä. Tässä työssä tutkittavassa muuntajassa on useita ensiöitä ja useita toisioita ja muuntajaa syötetään keskitaajuudella. Tämä tuo uusia ongelmia verrattuna perinteiseen yksivaiheiseen DC/DC-konvertteriin. Näihin ongelmiin esitetään ratkaisut diplomityön tutkimuksessa.

Single axis controlled attraction type magnetic bearing

This paper presents a new type of magnetic bearing with active control only in axial direction. The bearing uses two pairs of permanent magnets working in attraction mode to restrict the radial motion and a control system composed of two electromagnets, a gap sensor and a controller to keep the axis in a fixed axial position. The principle, the dynamic model for axial motion and the control system for this bearing are presented. Finally, by experiments conducted in a prototype, the effectiveness of the presented concept is shown.

Association entre les dérégulations des cellules dendritiques et les altérations des lymphocytes B présentes chez les patients infectés par le VIH

La dérégulation du compartiment B est une conséquence importante de l’infection par le virus de l’immunodéficience humaine (VIH), qui peut mener à des manifestations autoimmunes et ultimement à des lymphomes B. Parmi les premières anomalies détectées, on dénote l’activation polyclonale, reflétée par la présence d’hyperglobulinémie (hyper-Ig) et des titres élevés d’autoanticorps chez les patients. On observe également une altération des dynamiques des populations, notamment une expansion de la population des cellules matures activées. De plus, les patients évoluent vers l’incapacité de générer une réponse humorale efficace, et sont sujets à une perte de la mémoire immunologique en phase chronique, caractérisée par une diminution de la population des cellules mémoires et par l’épuisement cellulaire. Toutefois, on connaît très peu les mécanismes impliqués dans de telles altérations. Les cellules dendritiques (DC) sont parmi les premières populations cellulaires à rencontrer et à propager le VIH lors d’une infection, et s’en trouvent affectées directement et indirectement, par le virus et ses composantes. On retrouve en effet une diminution des fréquences de DC dans le sang, les muqueuses et les organes lymphoïdes de patients infectés par le VIH, ainsi qu’un blocage au niveau de la maturation cellulaire. Toutefois, un débat perdure quant à l’apparition de ces altérations durant la phase aigüe de l’infection, et à la restauration des fréquences et des fonctions des DC chez les patients sous traitement. Cette controverse est due à la rareté des études longitudinales incluant des suivis qui s’échelonnent de la phase aigüe à la phase chronique de l’infection. Les DC jouent un rôle important dans le développement, la survie et l’activation des lymphocytes B, de façon T-dépendante et T-indépendante, notamment via des facteurs de croissance tel que BLyS (B lymphocyte stimulator). Par conséquent, nous formulons l’hypothèse que dans le cadre d’une infection VIH, les altérations observées au niveau des cellules B sont modulées par les DC. L’objectif majeur de cette étude est donc d’évaluer l’implication potentielle des DC dans les altérations des cellules B au cours de l’infection par le VIH. Pour ce faire, nous avons d’abord caractérisé de façon longitudinale le statut des populations de DC du sang périphérique de patients infectés au VIH et présentant différents types de progression de la maladie. Cela nous a permis d’évaluer la présence d’une corrélation entre les dynamiques de DC et le type de progression. Par la suite, nous avons évalué la capacité des DC à exprimer BLyS, puis mesuré sa concentration ainsi que celles d’autres facteurs de croissance des cellules B dans le plasma des patients. Enfin, nous avons caractérisé le statut des lymphocytes B, en fonction du stade de l’infection et du taux de progression clinique des patients. Cette étude démontre une diminution de la fréquence des populations de DC myéloïdes (mDC) dans le sang de patients infectés par le VIH sujets à une progression clinique. Cette diminution est observée dès le stade aigu de l’infection et au-delà du traitement antirétroviral (ART). Des concentrations élevées de MCP-1 (monocyte chemotactic protein), MIP (macrophage inflammatory protein) -3α et MIP-3β suggèrent la possibilité d’un drainage vers des sites périphériques. Nous observons également des niveaux supérieurs à la normale de précurseurs CD11c+CD14+CD16- en phase chronique, possiblement liés à une tendence de régénération des DC. Les patients en phase chronique présentent de hautes concentrations plasmatiques de BLyS, reflétée par un haut taux d’expression de cette cytokine par les mDC et leurs précurseurs. Parallèlement, nous observons une expansion des cellules B matures activées ainsi que des taux élevés d’IgG et IgA dans le sang de ces patients. De plus, nous constatons l’expansion d’une population de cellules B qui présente à la fois des caractéristiques de cellules B immatures transitionnelles (TI, transitional immature), et de cellules B recirculantes activées de la zone marginale (MZ, marginal zone), considérées ici comme des «précurseurs/activées de la MZ». Cette étude démontre aussi, chez les progresseurs lents, une meilleure préservation du compartiment des DC du sang périphérique, accompagnée d’une augmentation de précurseurs des DC de phénotype CD11c+CD14+CD16+, ainsi que des concentrations plasmatiques et niveaux d’expression normaux de BLyS. Conséquemment, nous n’avons pas observé d’augmentation des cellules B matures activées et des cellules B précurseurs/activées de la MZ. Toutefois, la fréquence des cellules B matures de la MZ est diminuée, reflétant possiblement leur recrutement vers des sites périphériques et leur contribution à un mécanisme actif de contrôle de la progression de la maladie. L’ensemble de ce travail suggère que dans le cadre d’une infection au VIH, les altérations observées au niveau des DC modulent les anomalies des cellules B. Par conséquent, le maintien de l’équilibre des fonctions DC, notamment les fonctions noninflammatoires, pourrait avoir un impact important dans la prévention de la progression de maladies associées aux altérations du compartiment des cellules B.