Dissertations / Theses on the topic 'Spasm'

The major objective of this project was to examine the potential for mediators of IgE-mediated allergic reactions to alter neural activity. The project was divided into three parts. In Part I, the ability of endogenously released chemical mediators to alter neural activity in vitro was assessed by measuring isometric contractile responses to electrical field stimulation (EFS) (2-128 Hz, 20 V, 0.5 msec. duration) of sensitized rabbit bronchi before and after exposure to the antigen horseradish peroxidase (HRP). Antigen enhanced bronchial responses to EFS with low frequencies: mean log (± S.E.) frequency which produced 20% of maximum response decreased from 1.04 (± 0.05) to 0.90 (± 0.07) Hz (p < 0.05). Responses of unsensitized bronchi were not enhanced by antigen. Chlorpheniramine, an H₁ antagonist, abolished the antigen effect. Antigen did not enhance the responses to exogenous acetylcholine. Hence, the antigen is apparently modulating neural activity and not smooth muscle per se. In Part II, the capacity for histamine to modulate vagally-induced bronchoconstriction in anesthetized, vagotomized, mechanically-ventilated rabbits was examined in vivo. Changes in pulmonary resistance induced by electrically stimulating the cut ends of the vagi (2-32 Hz, 20 V, 0.5 msec. duration) were assessed before and 10 minutes after histamine aerosolization (10 breaths of 10 mg/ml). Histamine inhalation potentiated vagally-induced bronchoconstriction at low frequencies: mean log (± S.E.) frequency producing a 20% change in pulmonary resistance decreased from 0.88 (± 0.09) to 0.56 (± 0.15) (p < 0.05). Chlorpheniramine abolished this effect. In Part III, the dependence on IgE antibodies of the in vitro modulation of neurally-induced contraction of sensitized bronchi was investigated. Rabbits were passively immunized with fractions enriched with HRP-specific IgE, IgG, or IgM antibodies. After 72 hours, rabbits were sacrificed and the responses of bronchi to EFS were assessed before and after antigen challenge. Antigen enhanced the responses to EFS only of bronchi passively sensitized with IgE. Therefore, antigen enhancement of neural activity was dependent on IgE. These studies demonstrate that the interaction between antigen and IgE antibodies can induce the release of chemical mediators which can alter neural activity.

Aims: The purpose of the research presented in this thesis is to elucidate the mechanism of the stimulation of oxidative metabolism and contractile function that occurs in vascular smooth muscle during cerebral vasospasm (CV) after subarachnoid haemorrhage (SAH). The biochemical mechanisms leading to CV were investigated using an in vitro model of CV developed for this research. CSF (cerebrospinal fluid) from SAH patients at risk of vasospasm which stimulated oxygen consumption (CSF S ) was used to model vasospasm. The hypothesis is CSF_S contains a substance which stimulates tension generation over that of CSF_N ,(non-stimulatory cerebrospinal fluid) and also inhibits the myosin light chain phosphatase. Methods: The porcine carotid artery was used as a model for the human basilar artery. The rate of oxygen consumption (JO₂) was measured in response to CSF_S and tension generation was also examined. Various agents were used to treat or pretreat the tissue such as magnesium and andalpha;₁-adrenergic receptor agonists. Their effects on the CSF_S-induced stimulation were measured to study the mechanism of vasospasm. A myosin light chain phosphatase (MLCP) assay was developed to study the mechanisms leading to CV. Results and conclusion: Addition of CSF_S to the porcine carotid artery is a reliable and reproducible in vitro model of CV. Using this model, it was found that Mg⁺⁺ loading and andalpha;₁-adrenergic receptor agonists attenuated the vasospasm, but a non-specific endothelin antagonist had no effect. Acute addition of 12mM Mg⁺⁺ relaxed the tissue from a CSF_S induced contraction significantly and rendered the contraction rinsible. Okadaic acid (InM), a phosphatase inhibitor, had very similar effects to CSF_S because it stimulated JO₂ and slowed relaxation after a stretch. There was also significant inhibition of phosphatase caused by the CSF_S. Vasospasm appears to be caused by a combination of a contractile stimulus, and inhibition of MLCP activity.

Vaginismus is a sexual dysfunction that has received insufficient empirical attention. The first chapter of this thesis consists of a critical review of the literature and demonstrates the overall paucity of research studies and their poor methodological quality. The second and third chapter are based on the results of an experimental study comparing 87 women, matched on age, relationship status, and parity and assigned to 3 groups, vaginismus, dyspareunia/vulvar vestibulitis syndrome (VVS), and no pain. A structured interview evaluating pain with intercourse and history of gynecological problems as well as psychometric measures; evaluating sexual and physical abuse, sexual knowledge and schema, sexual functioning, relationship adjustment and psychological distress were administered. The reliability of vaginal muscle spasm as the main diagnostic criterion, differential diagnosis, and the role of pain were assessed via by 2 separate gynecological and, 2 separate physical therapist examination, 2 EMG evaluations, and a review of the interview data by 2 separate psychologists. Findings suggest that the spasm-based definition and resulting diagnostic reliability of vaginismus are not adequate. Both, women in the vaginismus and VVS groups exhibited higher levels of pelvic floor hypertonicity compared to women with no pain; however, women in the vaginismus group demonstrated the highest levels. Measures of pain did not distinguish between women with vaginismus and VVS. The only dependent measure clearly differentiating women with vaginismus was defensive and avoidant reactions during the physical exams. A re-conceptualization based on a multidimensional diagnostic framework including pelvic floor hypertonicity, avoidance and defensive reactions to vaginal penetration, and genital pain was suggested. The third paper was based on the results of questionnaires investigating etiological correlates of vaginismus, sexual and physical abuse, sexual self-schema, sexual knowled

Children with cerebral palsy and powerful whole body extensor spasms find sitting in a rigid seat uncomfortable and sometimes painful due to the large forces they apply to their constraints. They are usually unable to speak and communication is difficult. The spasms affect every aspect of their lives. This thesis describes the genesis of a new functional dynamic seat for children with severe whole body extensor spasms, and the novel method used to design it. This novel seat technology is known as ‘Whole Body Dynamic Seating’. The thesis describes the clinical need this seat addresses, and the design and technology context in which this research takes place. The user evaluation, observation, measurement, analysis and reasoning that led to a successful seat design are described in detail. Children with cerebral palsy sometimes have whole body spasms that mean they cannot be seated in conventional static seating that positions a child in a fixed posture. For this research the children were classified as functioning at Chailey Sitting Ability Level 1 and Gross Motor Functional Classification System Level V. Such children spend much of their time being held by a person, or lying on a mat, bed or pad. This results in difficulty with social engagement and physical functioning, particularly in school. This research created a seat that such children could sit in, providing a comfortable and functional seat for use in a home or school classroom environment. This seat was designed with the direct and essential involvement of disabled children, their parents, therapists, teachers and carers. The work is part of a larger programme of research into seating and support technology that will enhance a child’s ability to gain functional movement and communication skills that can be employed to enable the child’s free self expression and social participation. The research investigated means of supporting children with whole body extensor spasms through a progressive iterative method utilizing direct user evaluation of a series of prototypes incrementing in complexity and fidelity towards a fully functional physical seat. An iterative method was used to design, build and evaluate three dynamic seats. This method incorporated two new approaches to prototyping developed for the research programme in response to difficulties encountered in designing dynamic systems for children with highly complex neuromotor disability. Soft and Semi-soft prototyping and evaluation methods provided essential feedback on dynamic seating concepts that guided proposed solutions, without requiring costly and time-consuming manufacture. Video was used to create a record of the children’s movements and responses for subsequent analysis. Instrumentation was built into the seats to enable direct objective measurement of the reaction forces and seat movement caused by extensor spasms. This thesis presents several unique features created through this research programme: 1. Independent and virtually hinged anatomical dynamic thigh supports; 2. Independent anatomical dynamic foot supports; 3. A virtually hinged dynamic back support; 4. An anatomical dynamic head support concept. The final Whole Body Dynamic Seat was child-centred in its functionality and aesthetic design, and was favourably commented upon by parents, children and school staff. Use of the new dynamic seating by three children (including one from a previous work programme) showed that children with severe whole body extensor spasms can be seated comfortably. The children also demonstrated gains in physical and social function as a result of using the dynamic seats. The two fully independent dynamic seats made advances in comfort over static seating for children with whole body extensor spasms. One of the children especially liked the seat and resisted being put back into his usual seating. An adult with severe cerebral palsy and extensor spasms evaluated a dynamic foot support concept and reported very significant reductions in spasticity and pain, and gains in physical function. The Whole Body Dynamic Seats showed gains in postural symmetry and in hand and head function over the usual static seats when used by the children with spasms. These gains were reported by staff during long term evaluations and measured specifically during the final evaluation. Two children learned to control the movement of seats in which they were sat, and were able to control their posture and use that control to carry out functions such as switch pressing. Such learning through the use of dynamic seating by children with severe dystonic cerebral palsy and whole body extensor spasms has not previously been documented. The seats did not just affect the children - school staff were affected too. School staff working around the children in the dynamic seats were observed to be more inclusive towards the children, and to expect more interaction from them. The ability of the children to move altered staff expectations of their ability to participate and communicate. This new seating has improved the quality of life of the children that use it. Future implementation of this technology in commercially produced seating offers the possibility of similar gains to many more severely disabled children who are currently less comfortable and less functional than they need to be.

Вступ. За даними низки експериментальних досліджень та клінічних спостережень висунуто припущення про патогенетичну роль цитокін-індукованого запалення, а також широкої групи представників цитокінів та факторів росту у формуванні судомного синдрому. Ці ствердження підсилювалися через виявлені просудомні ефекти цитокінів, які спричиняють прозапальну та просудомні дію. З цього приводу логічним постає інше припущення стосовно можливої реалізації протисудомної дії за умов блокади активності прозапальних цитокінів. Метою серії наших дослідів було визначення ефектів блокування активності рецепторів інтерлейкін-1 (ІЛ-1) при різних формах експериментального судомного синдрому.

RESUMO: A operação de Nissen, por laparoscopia, é considerada a cirurgia antirefluxo mais adequada por ser a que melhor replica a fisiologia normal da válvula gastresofágica na maioria dos doentes com sintomas típicos de doença do refluxo gastresofágico (DRGE). São critérios técnicos o encerramento seguro dos pilares do diafragma e a criação de fundoplicatura completa (360 graus), curta (inferior a dois centímetros), lassa e sem tensão – desiderando para o qual a laqueação proximal dos vasos curtos gástricos é crucial. Realizei a operação de Nissen, por laparoscopia, em sessenta mulheres e quarenta homens com DRGE, sem mortalidade operatória, no Serviço de Cirurgia 6 do Hospital dos Capuchos, CHLC, EPE. Os cem doentes apresentavam média etária de 46 anos e queixas, com tempo de evolução entre 1 e 43 anos, de pirose (90%), regurgitação (80%), azia (73%), epigastralgias (54%). A endoscopia alta revelou esofagite de grau Savary-Miller 0-I (62%), II (23%), III (8%), IV (7%); hérnia de deslizamento (71%), hérnia paraesofágica (8%), sem hérnia (21%); a pHmetria de 24h diagnosticou padrão misto (38%), levantado (20%), deitado (20%), inconclusiva (22%) e a manometria diagnosticou EEI hipotónico (35%), peristálise esofágica normal (88%), hipomotilidade ligeira (5%) e foi omissa (7%). Hérnia hiatal, esofagite grave, ineficácia do controlo sintomático com inibidor da bomba de protões e desejo de descontinuidade terapêutica constituíram as indicações para tratamento cirúrgico. Por celioscopia, efetuei laqueação dos vasos curtos gástricos (70%), cruroplastia e fundoplicatura total (seda 2/0), curta (dimensão média 1,5-2 cm), lassa, sem tensão e sem calibração intraoperatória do esófago. A fundoplicatura de Nissen laparoscópica mostrou-se segura e eficaz no tratamento da DRGE. A sua idoneidade foi ainda comprovada pela normalização da pHmetria de 24 horas e da manometria pós-operatórias, com significado estatístico, num grupo de catorze voluntários assintomáticos. Em catamnese com recuo médio 30,7 meses 94% dos indivíduos persistem assintomáticos. Interrogando-me acerca das repercussões desta operação sobre a microcirculação do fundo gástrico coloquei, como premissa, a possibilidade de na operação de Nissen a laqueação dos vasos curtos poder induzir modificação no diâmetro arteriolar da parede do fundo gástrico. Para pesquisar a influência da laqueação dos vasos curtos gástricos e da fundoplicatura total sobre o calibre arteriolar da parede do estômago no cárdia, no fundo e na região dos vasos curtos gástricos, idealizei um Projeto de investigação experimental em cobaias. O Projeto foi desenvolvido no Centro de Investigação do Departamento de Anatomia da FCM-UNL. Para a sua realização obtive autorização da Comissão Científica e Pedagógica da FCM-UNL, requeri a acreditação como investigador à Direção Geral de Veterinária e, por recorrer à utilização de animais, submeti-o à Comissão de Ética da FCM-UNL, que o aprovou por unanimidade. Para limitar o número de animais utilizados ao mínimo necessário, calculei, por método estatístico, a quantidade de cobaias necessárias. Subdividindo-as num grupo de ensaio (GE), onde realizei a operação de Nissen, e num grupo de controlo (GC), onde apenas procedi a tração gástrica, defini e apliquei protocolos de anestesia, de cirurgia e de eutanásia, segundo os princípios dos 3R – Replacement, Reduction, Refinement da técnica de experimentação humana de Russell e Burch (1959) – uma estrutura ética amplamente aceite para a realização de experimentação científica humanizada com animais. A utilização das técnicas de estudo angiomorfológico permitiu-me analisar e descrever a anatomia normal, a vascularização arterial macroscópica, a microangioarquitetura, por microscopia eletrónica de varrimento de moldes de corrosão vascular, e a histologia da parede do estômago da cobaia. Procedi, também, à definição dos critérios morfológicos que considerei suscetíveis de validação deste modelo animal para o estudo proposto. Por razões académicas, foi necessário abreviar o Projeto encurtando, em cerca de dois anos, o prazo disponível para conclusão do estudo. Apreciando-o com o Gabinete de Análise Epidemiológica e Estatística do Centro de Investigação do CHLC, EPE, optou-se, perante a escassez de elementos após já terem sido recrutados 46 animais, por uma amostra, suplementar, de dimensão de conveniência de oito cobaias (quatro em cada grupo), condicionada pelo limite temporal universitário e pelo respeito pela dignidade dos animais. Neste subgrupo procedi, por microscopia eletrónica de varrimento, à medição dos calibres arteriolares nos moldes vasculares do cárdia, do fundo e da zona dos vasos curtos gástricos tanto no GC como no GE efetuando 469 medições no primeiro e 461 no último. Os dados foram enviados ao Centro de Investigação do CHLC, EPE que procedeu à sua análise estatística (ANOVA). A referida análise revelou que as arteríolas do plexo mucoso e as do plexo submucoso do cárdia, do fundo e da região dos vasos curtos gástricos, mostraram aumento de calibre no GE. O aumento foi, estatisticamente, significativo por ser superior a 50% do calibre do GC. Nos vasos curtos, a diferença foi mais pequena, mas persistiu sendo, estatisticamente, significativa. Os vasos retos dilataram na base, na sua emergência do plexo seroso, apenas no fundo gástrico. Na cobaia a operação de Nissen – fundoplicatura total com laqueação dos vasos curtos gástricos –, provocou vasodilatação arteriolar do fundo gástrico. Considero que essa vasodilatação constituiu acomodação à modificação introduzida e infiro que o mesmo possa acontecer no ser humano. Admito, assim, que também ocorra vasodilatação no ser humano, na sequência da laqueação dos vasos curtos gástricos, pela analogia microvascular entre as duas espécies e que essa vasodilatação corresponda, igualmente, a um mecanismo de adaptação arteriolar visando, por exemplo, suprir a perda incorrida pela laqueação. A associação experimental entre laqueação dos vasos curtos gástricos e realização de fundoplicatura total, que exerce aumento inerente de pressão sobre a JEG, não só não provocou défice da microcirculação do esófago distal ou do estômago proximal como desencadeou um mecanismo de vasodilatação fúndica que reforça o conceito de segurança da operação de Nissen para tratamento da DRGE. -------------- ABSTRACT: The laparoscopic Nissen operation is considered to be the most appropriate antirefluxsurgery because it suitably replicates the standard physiology of the gastroesophageal valve in most patients with typical symptoms of gastroesophageal reflux disease (GERD). The technical criteria includes the safe shutdown of the diafragmatic crura(cruroplasty) and the creation of a complete fundoplication (360 degrees), short (lesser than two inches), floppy and without tension – a goal for which the proximal ligation of the gastric short vessels is crucial. The laparoscopic Nissen operation was performed in sixty women and forty men with GERD, without any operative mortality, at the Surgical Department of the Hospital dos Capuchos, CHLC, EPE. The one hundred patients, averaged 46 years old, complained of heartburn (90%), regurgitation (80%) and upper abdominal pain (54 %). The endoscopy process revealed Savary-Miller esophagitis of grade 0-I (62%), II (23%), III (8%), IV (7%), sliding hernia (71%), paraesophageal hernia (8%) or no herniation (21%). The pHmetry/24h diagnosed mixed pattern (38%), raised (20%), lying (20%) or inconclusive (22%). The manometry diagnosed hypotensive LES (35%), normal esophageal peristalsis (88%), mild hypomotility (5%) and was absent (7%). Hiatal hernia, severe esophagitis, ineffective symptomatic control with proton pump inhibitor and request for treatment discontinuation were the signs for surgical action. A laparoscopic ligation of short gastric vessels (70%), cruroplasty and fundoplication (silk 2/0), short (average size 1.5–2 cm) and floppy, without tension and without intraoperative calibration of the esophagus were thus performed. The laparoscopic Nissen fundoplication behaved safe and effective in treating GERD. In a group of 14 asymptomatic volunteers its reputation was confirmed with statistical significance by normalization of postoperative pHmetry/24h and manometry. 94% of the individuals remained asymptomatic up to 30.7 months (average) in the follow-up. Interrogating myself about the impact of this operation on the microcirculation of the gastric fundus I put premised on the possibility of the ligation of the short gastric vessels in the Nissen procedure can induce changes in the arteriolar diameter in the Wall of the gastric fundus. To explore the influence of ligation of the short gastric vessels and the fundoplication at the arteriolar caliber of the cardia, the fundus and the region of the short vessels of the gastric wall, I designed a project of experimental research in guinea pigs with two interdependent components: one veterinary and another technical where I applied angiomorphological studies. The project was developed at the Research Centre of the Department of Anatomy FCMUNL. For its accomplishment I got permission from the Scientific and Pedagogical Committee of the FCM-UNL, I requested for accreditation as a researcher at the General Directorate of Veterinary and, by resorting to the use of animals I submitted it to the Ethics Committee of the FCM-UNL, which approved it unanimously. The guinea pigs were divided into two experimental groups: an experimental group (EG), in which the Nissen procedure was performed and a control group (CG) in which only a gastric traction was done. Protocols of anesthesia, surgery and euthanasia were applied according to the 3Rs – Replacement, Reduction, Refinement of the technique of human experimentation of Burch and Russell (1959) – a widely accepted ethical framework for conducting scientific experiments using animals humanely. Using histological and angiomorphological techniques, I performed the analysis and the description of the normal, macro and microvascular, anatomy of the guinea pig stomach and I defined the morphological criteria that I considered susceptible for validation of this animal model for the proposed study. By means of scanning electron microscopy I measured the arteriolar calibers of the vascular casts of the cardia, of the fundus and of the short gastric vessels in both CG and EG, making 469 measurements in the former and 461 in the latter. The data were sent to the Research Center of the CHLC which conducted the statistical analysis (ANOVA). The data were sent to the Centre for Research of the CHLC, EPE which proceeded to statistical analysis (ANOVA). This analysis revealed that the arterioles plexus of the mucosal and submucosal plexus of the cardia, fundus and region of the short gastric vessels, showed increased caliber in EG. The increase was statistically significant for being greater than 50% CG gauge. In the short gastric vessels, the difference was smaller, but persisted and statistically significant. Straight vessels were dilated at the base, on its emergence of the plexus serous only in the fundus. In the guinea pig, the Nissen procedure - complete fundoplication with ligation of the short gastric vessels - caused arteriolar vasodilation on the gastric fundus. I believe that this vasodilation constituted some accommodation to the modification introduced and infer that the same might happen in humans. I admit therefore that vasodilation also occurs in humans following the ligation of the short gastric vessels by microvascular analogy between the two species and that this vasodilation corresponds also to na adaptation mechanism arteriolar, for example, to compensate the loss incurred by ligation. The association of experimental ligation of the short gastric vessels with conducting complete fundoplication, which exerts increased pressure on the EGJ, not only did not cause a microcirculation deficit of the distal esophagus or proximal stomach as triggered a mechanism of fundic vasodilation which reinforces the security concept of the Nissen procedure for treatment of GERD.

La sclérose tubéreuse de Bourneville (STB) est une maladie génétique et multi-systémique à transmission autosomique dominante due à des mutations d’un gène TSC1 ou TSC2 qui codent respectivement pour hamartine et tuberine ayant une action inhibitrice sur la voie de signalisation mTOR. L’épilepsie précoce et pharmacorésistante est la manifestation neurologique la plus fréquente et la plus délétère de la STB. Elle débute souvent dans la première année de vie par des spasmes infantiles qui évoluent avec l’âge et en absence de traitement vers des crises toniques ou tonico-cloniques. Bien que les crises soient supposées être générées dans des tubers corticaux, les mécanismes de l’épilepsie ne sont pas bien élucidés et le traitement reste souvent inefficace. Des études morphologiques ont montré une altération de l’expression ARNm des récepteurs au glutamate dans les cellules géantes et les neurones dysplasiques des tubers, mais leur implication fonctionnelle restait à montrer. Les différentes sous-unités NMDA ont une expression âge-dépendante et région-spécifique, les plus grands changements survenant au début de la vie quand l’épilepsie de la STB apparaît. Ce travail avait pour but d’étudier à l’aide de méthodes électrophysiologiques in vitro et in vivo l’expression fonctionnelle des sous-unités NMDA aberrantes et de déterminer leur rôle dans l’épileptogènese chez les souris hétérozygotes Tsc1+/- et sur le tissu humain STB post-opératoire. Nous avons pu démontrer que : i) Les souris hétérozygotes pour le gène Tsc1 sont spontanément épileptiques in vivo et in vitro dans une courte fenêtre dévelopmentale de P9 à P18. ii) Elles présentent une altération d’expression des récepteurs NMDA couche-spécifique et mTOR dépendante avec une surexpression des sous-unités GluN2C/D dans la couche 4 et 2/3 et GluN2B dans les couches 2/3. Cette expression anormale est prévenue par l’administration d’un inhibiteur de la voie mTOR, la rapamycine. iii) Les mêmes altérations d’expression des récepteurs NMDA, sont montrées sur les tissus post-opératoires, non seulement de tubers de STB mais aussi des dysplasies corticales focales (DCF), ces deux malformations ayant des similarités étiologiques et physiopathologiques. iv) La RT-PCR quantitative confirme une expression excessive de GluN2C dans le cortex de souris Tsc1+/- et sur le tissu humain des tubers et DCF. v) Les décharges épileptiques chez la souris Tsc1+/- sont générées dans la couche granulaire 4 du cortex avant de se propager vers les couches superficielles et les couches profondes, empruntant ainsi les microcircuits corticaux. vi) L’expression excessive de la sous-unité GluN2C dans le cortex contribue à l’hyperexcitabilité neuronale chez la souris Tsc1+/- et sur des tissus humains de tubers et de DCF puisque les crises et les décharges sont bloquées par les antagonistes sélectifs de GluN2C/D. vii) Les crises chez la souris Tsc1+/- suivent une séquence âge-dépendante évoluant du type «spasms-like» vers «tonic-clonic like», rappelant celle de l’épilepsie humaine, avec deux pics de haute incidence de crises à P13 et P16 correspondant chez l’homme respectivement l’âge des spasmes infantiles et celui des crises toniques. L’évolution avec l’âge du délai de propagation inter-hémisphérique pourrait contribuer à ce changement de types de crises. Ces résultats montrent donc pour la première fois qu’une happloinsuffisance pour le gène Tsc1 chez les souris Tsc1+/- sans tubers suffit à produire une altération de l’expression des récepteurs NMDA de manière mTOR dépendante et contribuer ainsi à l’épileptogènese dans la STB. La souris Tsc1+/- est le premier modèle génétique sans anomalies morphologiques présentant une épilepsie spontanée qui évolue des spasmes vers des crises toniques et tonico-cloniques. Néanmoins cette épilepsie diffère de l’épilepsie humaine de la STB par l’absence de crises focales et de pharmacorésistance, ce qui pourrait être expliqué par l’absence de tubers chez la souris Tsc1+/-. (...)
Tuberous sclerosis complex (TSC) is a genetic multisystemic disease with autosomal dominant transmission due to mutations in a gene TSC1 or TSC2 respectively which encode hamartin and tuberin proteins having an inhibitory action on the mTOR signaling pathway. Early refractory epilepsy is the most common and most deleterious neurological manifestation. The epilepsy often begins in the first year of life by infantile spasms that change in the lack of treatment to tonic or tonic-clonic seizures in age-dependent manner. Although seizures are thought to be generated in cortical tubers, epilepsy mechanisms are not well understood and treatment is often ineffective. Morphological studies showed the altered expression of glutamate receptor mRNA in the giant cells and dysplastic neurons of tubers, but their functional involvement remains unknown. The different NMDA subunits have an age-dependent and region-specific expression, the greatest changes occurring early in life when the TSC epilepsy appears. This work aimed to study the functional expression of aberrant NMDA subunits expression and their role in the epileptogenesis in heterozygous Tsc1+/- mice and post-surgical human tissue of TSC patients using in vitro and in vivo electrophysiological methods. The study reveal that: i) Heterozygous tuber-free Tsc1+/- mice show spontaneous epilepsy in vivo and in vitro in a short developmental window from P9 to P18. ii) These mice exhibit an altered NMDA receptor expression in mTOR dependent and layer-specific manner with GluN2C/D subunits overexpression in layers 4 and 2/3, and GluN2B ovexpression in layers 2/3. This abnormal NMDA receptors expression is prevented by the administration of an mTOR inhibitor, rapamycin. iii) The same alterations of NMDA receptors’ expression are shown in post-surgical tissues not only in tubers from TSC patients, but also in focal cortical dysplasia (FCD), these two malformations sharing etiological and pathophysiological similarities. iv) Quantitative RT-PCR confirms the excessive GluN2C subunit expression in Tsc1+/- mouse cortex and human tissue of tubers and DCF. v) Epileptic discharges in Tsc1+/- mice are generated in the granular layer 4 of the cortex before spreading to the superficial and then to deep layers, thus borrowing the cortical microcircuits. vi) Excessive expression of GluN2C subunit in the cortex contributes to neuronal hyperexcitability in Tsc1+/- mice, as well as in human tubers and DCF tissues, since epileptic discharges are blocked by selective GluN2C/D antagonists. vii) Seizures in Tsc1+/- mice follow the age-dependent sequence, evolving from "spasms-like" to "tonic-clonic like" thus reminding the human epilepsy, with two peaks of highest seizure incidence at P13 and P16 corresponding respectively to age of infantile spasms and of tonic seizures in human. The age-dependent evolution of interhemispheric propagation delay could contribute to this change in seizure type. These results show for the first time that TSC1 happloinsuffisancy in tuber-free Tsc1+/- mice is sufficient to produce an alteration in NMDA receptor expression in an mTOR dependent manner, and thus contributes to epileptogenesis in TSC. The Tsc1+/- mouse line is the first genetic model of TSC without morphological abnormalities presenting with early spontaneous seizures which evolves from “spasms-like” to “tonic-clonic like” seizures. However, the epilepsy in Tsc1+/- mice differs from human TSC epilepsy by the absence of focal seizures and of drug-resistance. Both could be explained by the lack of tubers in the Tsc1+/- mice. It remains to determine whether the expression of GluN2C subunit is also transitional in Tsc1+/- mice and whether other factors contribute to determine the age-dependent epilepsy. This study opens new therapeutic perspectives of TSC epilepsy targeting GluN2C subunit of NMDA receptors

Вступ. Епілепся є одним із найскладніших захворювань нервової системи. Неефективність лікування хворих з епілепсією є наслідком різнобічності її патогенетичних механізмів. В неврологічній практиці показані епізоди виникнення судомних проявів внаслідок судинних мальформацій головного мозку. Показано, що напади епілепсії у пацієнтів із судинними захворюваннями мозку погіршують перебіг основного захворювання, погіршують їх якість життя, уповільнюють процес відновлення після інсульту та обтяжують морфо-функціональні порушення, які виникли після обмеження кровопостачання до головного мозку. Проблемою в клініці є своєчасна діагностики ризику та/або можливості виникнення епілептиформних нападів у вказаного контингенту хворих, що є неможливим без ретельного дослідження патогенезу судомного синдрому. Показано, що епізоди ішемії мозку підвищують чутливість головного мозку щодо конвульсивних впливів. Мета роботи – вивчення патогенетичних механізмів хронічного судомного синдрому, який виник після ішемії мозку.

INTRODUÇÃO: Pacientes com vias aéres hiperresponsivas têm uma resposta exarcebada das vias aéreas a vários estímulos. Nestes pacientes, a simples intubação é a causa mais freqüente do broncoespasmo, levando a complicações no peri-operatório. O óxido nítrico está envolvido na regulação da função fisiológica bem como em doenças das vias aéreas e nos últimos anos seu papel vem sendo constantemente estudado na modulação da broncoconstrição. OBJETIVO: Estudar a possibilidade da medida de óxido nítrico exalado (NOex) ser um marcador de episódios de broncoespasmo no intra-operatório. MÉTODOS: 146.358 fichas anestésicas foram analisadas no período de 1999/2004. Ocorreram registros de broncoespasmos em 863 pacientes neste período. Destas, nove sujeitos foram identificados como não asmáticos (grupo broncoespasmo), 12 sujeitos foram diagnosticados como asmáticos (grupo asma) e 10 indivíduos sem história prévia de doença foram selecionados aleatoriamente como grupo controle. Todos os sujeitos foram submetidos à medida de óxido nítrico exalado (partes/bilhão), espirometria e coleta de escarro induzido com salina hipertônica. Os dados foram comparados utilizando ANOVA seguido do teste de Tukey e Kruskal-Wallis seguido do teste de Dunn\'s. RESULTADOS: Os grupos broncoespasmo e controle apresentaram espirometria normal, com medidas estatísticamente diferentes do grupo asma (p <0,05). As porcentagens de eosinófilos (mediana) no escarro induzido foram maiores no grupo asma [2,5 (0,4-6,8)], menores no grupo broncoespasmo [0,5 (0-1,3), e grupo controle [0,0 (0)]. A medida de óxido nítrico exalado foi maior no grupo dos asmáticos [81,5 (57,6-86,8)] em relação aos controles [18,7 (16,0-24,7)] (p=0,001). Não houve diferença entre grupos broncoespasmo e asma, ambos significantemente diferentes do grupo controle (p <0,05). CONCLUSÃO: Pacientes não asmáticos que apresentaram broncoespasmo no intra-operatório durante a anestesia e manipulação da traquéia, possuem níveis de óxido nítrico no ar expirado exalado elevado.
INTRODUCTION: Airways of patients with bronchial hyperreactivity are characterized by exaggerated bronchoconstriction in response to a variety of stimuli. Henceforth, bronchospasm may occur during induction of anaesthesia. Nitric Oxide is part of either physiologic or pathophysiologic airway regulation and its role has been investigated as a bronchoconstrictior modulator. OBJECTIVE: to address the possibility of exhaled nitric oxide measurement (NOex) as a marker of intraoperative bronchospasm. METHODS: 146.358 anesthesia registered forms were revised (period: 1999/2004). Bronchospasm occurrence appeared registered in 863. From those, nine were identified as non-asthmatics patients (Bronchospasm group). Also, 12 asthmatics constituted one additional group (Asthma group) and 10 subjects with no previous airway disease or symptoms were randomly selected as control group. All subjects were submitted to exhaled nitric oxide measurements (parts/billion), spirometry and induced sputum. The data were compared by ANOVA followed by the Tukey test and Kruskal- Wallis followed by Dunn\'s test. RESULTS: Both bronchospasm and control groups had normal lung function test, different from asthma group (p <0.05). The percentage of eosinophils (median) in induced sputum was higher for asthma [2.5 (0.4-6.8)] lower for bronchospasm [0.5 (0-1.3)] and control group [0.0 (0)]. Exhaled Nitric Oxide was higher for asthmatic patients [81.5 (57.6-86.8)], compared to control group [18.7 (16.0-24.7)] (p=0.001). There was no difference between bronchospasm and asthma groups both different from control (p <0.05). CONCLUSION: non-asthmatics patients with intraoperative bronchospasm detected during anesthesia after airway manipulation showed higher nitric oxide expired levels.

O espasmo hemifacial (EHF) é caracterizado por movimentos involuntários que acometem músculos inervados pelo nervo facial. O EHF primário é mais comum, e ocorre geralmente devido o contato entre o nervo facial e um vaso da fossa posterior do crânio. Os espasmos faciais causam embaraço social e podem comprometer funções da vida diária. Situações de ansiedade são descritas com frequência como fator de piora da gravidade dos espasmos faciais. Apesar disso, não há estudos que tenham avaliado de forma objetiva a influência da ansiedade aguda no EHF. Objetivos: Avaliar se há aumento na gravidade dos espasmos faciais, quando pacientes com EHF primário são submetidos a uma situação experimental que induz ansiedade. Casuística e Métodos: Foram avaliados 60 pacientes com EHF primário, de um serviço terciário de distúrbio de movimento. Inicialmente, foi realizada a caracterização clínica e epidemiológica, incluindo investigação da presença de sintomas psiquiátricos como ansiedade não específica e ansiedade social. Posteriormente, os pacientes foram submetidos a uma situação experimental que induz ansiedade de forma controlada, o teste de simulação ao falar em público (TSFP), com filmagem da face durante o procedimento, para avaliação dos espasmos faciais. Resultados: O TSFP foi um instrumento eficiente para indução de ansiedade na amostra de indivíduos com EHF primário. Os maiores níveis de ansiedade foram observados durante o desempenho do discurso. Os participantes relataram piora subjetiva dos espasmos faciais com o teste, e esse desconforto se manteve mesmo após o fim do discurso. A avaliação objetiva dos espasmos demonstrou aumento significativo na intensidade dos movimentos involuntários, sobretudo na primeira fase do discurso. Conclusões: Pacientes com EHF primário apresentam aumento na gravidade dos espasmos faciais em situações agudas de ansiedade. Ademais, esse comportamento ocorre independente das características psíquicas de base dos pacientes que apresentam a patologia
Hemifacial Spasm (HFS) is an involuntary movement disorder that affects muscles innervated by the facial nerve. Primary HFS is more common and usually occurs due to the conflict between facial nerve and a vessel of the posterior fossa of the skull. Facial spasms cause social embarrassment and may compromise functions of daily living. HFS patients often describe an increase in facial spasms during anxiety situations. Nevertheless, previous studies have not assessed the influence of acute anxiety on HFS. Objectives: To evaluate if facial spasms worse when patients with primary HFS take part in an experimental situation that induces controlled anxiety. Casuistic and Methods: The research evaluated sixty patients with primary HFS from a tertiary movement disorder service. First, we performed a clinical and epidemiological description of patients, including the investigation of psychiatric symptoms such as nonspecific anxiety and social anxiety. After that, we submitted patients to an experimental situation that induces anxiety in a controlled way, the simulated public speaking test. We filmed the face of de patients during the procedure to evaluate facial spasms. Results: The simulated public speaking test efficiently induces anxiety in the sample individuals with primary HFS. There were higher levels of anxiety during the speech performance. Patients reported a subjective worsening of facial spasms during the test, and the symptoms remained severe even after the end of the speech. There was a significant increase in the degree of involuntary movements in objective evaluation of spasms, especially in the first phase of speech. Conclusions: Patients with primary HFS show worsening of facial spasms in acute anxiety situations. In addition, the increase in involuntary movements does not depend on psychic features of the subjects with HFS

O espasmo hemifacial (EHF) é um distúrbio de movimento caracterizado por contrações tônico ou clônicas involuntárias, unilaterais, intermitentes e irregulares dos músculos inervados pelo nervo facial ipsilateral. Apesar de considerado como um transtorno benígno, promove influência significativa na qualidade de vida dos portadores através do comprometimento funcional físico e emocional que promove, englobando, desde o prejuízo na leitura e outras funções visuais, até o constrangimento social e distúrbios psiquiátricos associados, como depressão e ansiedade. Objetivo.: Descrever as características clínicas e demográficas, assim como a frequência de sintomas psiquiátricos de ansiedade generalizada, social e depressão, e a relação destes sintomas com a qualidade de vida nesta amostra de pacientes. Métodos.: 111 pacientes portadores de EHF primário foram avaliados. Foi aplicado questionário geral para coleta de dados demográficos e clínicos associados a evolução e tratamento do distúrbio de movimento com toxina botulínica. Os sintomas psiquiátricos foram avaliados através de escalas validadas para a população brasileira. A avaliação de qualidade de vida foi através de escala específica validada para avaliação funcional nos portadores de EHF. Resultados.: A idade média de início foi de 49±13,1 (intervalo: 12 -77) e tempo de evolução até o diagnóstico de 3±1,5 anos, com predomínio no sexo feminino (2,08:1). O lado esquerdo foi afetado em 61 (54,9%) pacientes e o músculo orbicular dos olhos foi o primeiro acometido na maioria dos casos (85,5%). Grande parte (n=87) referiu início insidioso e evolução gradual. Nervosismo, estresse e ansiedade são importantes contribuintes de piora do espasmo, relatado por mais de 82% (n=92) dos portadores de EHF, e momentos de relaxamento, tranquilidade, descanso e atividades de lazer foram responsáveis por aliviar o espasmo em 57 entrevistados. Mais de 90% (n=96) perceberam melhora importante do espasmo após aplicação de TXB, e 24,5% (n=26) relataram algum efeito adverso em última aplicação, sendo assimetria labial e ressecamento ocular os mais frequentes. Sobre os sintomas psiquiátricos, 41,7% (n=45) apresentavam pontuações que sugerem algum grau de depressão, até 56,4% (n=57) ansiedade generalizada e 34,2% (n=38) ansiedade ou fobia social. A leitura como domínio funcional físico e a vergonha, a tristeza e a preocupação com reação de outras pessoas foram os maiores prejuízos funcionais descritos nesses pacientes. Conclusão.: As características clínicas e demográficas nos pacientes com EHF se assemelham a outras evidências descritas na literatura, assim como uma maior frequência de sintomas de depressão, ansiedade generalizada e fobia social nesta população. Os sintomas psiquiátricos, mais do que a gravidade do espasmo, apresentaram uma maior correlação com a qualidade de vida nesta amostra de pacientes.
Hemifacial spasm (HFS) is a movement disorder characterized by involuntary, unilateral, intermittent, tonic or clonic contractions of muscles innervated by the ipsilateral facial nerve. Although considered as a benign disorder, it promotes a significant influence on the quality of life of the patients through the physical and emotional impairment it promotes, ranging from impairment in reading and other visual functions to social embarrassment, and associated psychiatric disorders, such as depression and anxiety. Objective.: To describe the clinical and demographic characteristics, as well as the frequency of psychiatric symptoms of generalized anxiety, social anxiety and depression, and the relation of these symptoms with quality of life in this sample of patients. Methods.: 111 patients with primary HFS were evaluated. A general questionnaire was used to collect demographic and clinical data associated with the evolution and treatment of the movement disorder with botulinum toxin (BTX). The psychiatric symptoms were evaluated through scales validated for the Brazilian population. The quality of life assessment was based on a specific validated scale for functional evaluation in patients with HFS. Results.: The mean age at onset was 49 ± 13.1 (range: 12-77) and time to diagnosis of 3 ± 1.5 years, with a predominance of females (2.08 :1). The left side was affected in 61 (54.9%) patients and the orbicularis oculi muscles were the first affected in the majority of cases (85.5%). A large part (n = 87) reported insidious onset and gradual evolution. Nervousness, stress, and anxiety are important contributors to worsening spasm, reported by more than 82% (n = 92) of HFS patients, and moments of relaxation, tranquility, rest, and leisure activities were responsible for relieving spasm in 57 interviewees. More than 90% (n = 96) reported significant improvement of spasm after BTX application, and 24.5% (n = 26) reported some adverse effects in the last application, with lip asymmetry and ocular dryness being the most frequent. On the psychiatric symptoms, 41,7% (n = 45) presented scores that suggest some degree of depression, up to 56.4% (n = 57) generalized anxiety and 34.2% (n = 38) anxiety or social phobia. Reading as a physical functional domain and shame, sadness and concern for other people\'s reactions were the major functional losses described in these patients

La restitution du patrimoine culturel bâti présentée sur Internet, sur cédéroms interactifs ou sur bornes muséales, ... est une préoccupation constante de la médiation culturelle. Grâce aux qualités des hypermédias, à savoir l'hypertexte et le multimédia, il semble que ces produits existants ont des capacités à restituer des informations patrimoniales aux publics, mais finalement ils n'ont pas l'efficacité cognitive et pédagogique que nous pourrions en attendre. En exploitant les possibilités offertes par les outils numériques, l'objectif est de proposer aux non-experts désireux d'apprendre, un espace de navigation hypermédia basé sur des hypothèses systémiques, fonctionnelles et graphiques, afin de concevoir un outil complet de visualisation et d'immersion comme aide à la compréhension des connaissances archéologiques et architecturales. D'un point de vue expérimental, nous identifions parmi les caractéristiques des jeux vidéo et de la cartographie, celles qui seraient susceptibles de rendre compte des environnements sémiologiques et cognitifs utiles à la re-présentation et à l'apprentissage. L'espace de navigation proposé, met en correspondance des activités d'exploration et de création. Au fur et à mesure de sa déambulation en temps réel, l'apprenant est guidé et motivé en suivant des parcours topographique, cognitif et scénarisé. Parallèlement, il crée sa propre « carte mémorielle » qui va l'aider à s'orienter, à construire ses connaissances et à les mémoriser. Le travail conduit à un modèle conceptuel applicable à tous types de bâtis. Il débouche sur un prototype qui utilise la Pyramide de Khéops comme support d'expérimentation.

Workshop Mensch-Computer-Vernetzung Derzeitige Spam-Erkennung weist eklatante Mängel auf. Die Zunahme des Spam-Aufkommens erfordet neue Ansätze, um der Plage Herr zu werden. Der Vortrag erläutert, wie mit Hilfe des Satzes von Bayes die Spam-Erkennung deutlich verbessert werden kann.

The internet has matured into the focal point of our era. Its ecosystem is vast, complex, and in many regards unaccounted for. One of the most prevalent aspects of the internet is spam. Similar to the rest of the internet, spam has evolved from simply meaning ‘unwanted emails’ to a blanket term that encompasses any unsolicited or illegitimate content that appears in the wide range of media that exists on the internet. Many forms of spam permeate the internet, and spam architects continue to develop tools and methods to avoid detection. On the other side, cyber security engineers continue to develop more sophisticated detection tools to curb the harmful effects that come with spam. This virtual arms race has no end in sight. Most efforts thus far have been toward accurately detecting spam from ham, and rightfully so since initial detection is essential. However, research is lacking in understanding the current ecosystem of spam, spam campaigns, and the behavior of the botnets that drive the majority of spam traffic. This thesis focuses on characterizing spam, particularly the spam that appears in forums, where the spam is delivered by bots posing as legitimate users. Forum spam is used primarily to push advertisements or to boost other websites’ perceived popularity by including HTTP links in the content of the post. We conduct an experiment to collect a sample of the blog posts and network activity of the spambots that exist in the internet. We then present a corpora available to conduct analysis on and proceed with our own analysis. We cluster associated groups of users and IP addresses into entities, which we accept as a model of the underlying botnets that interact with our honeypots. We use Natural Language Processing (NLP) and Machine Learning (ML) to determine that creating semantic-based models of botnets are sufficient for distinguishing them from one another. We also find that the syntactic structure of posts has little variation from botnet to botnet. Finally we confirm that to a large degree botnet behavior and content hold across different domains.

As the massive increase of electronic mail (email) usage continues, SPAM (unsolicited bulk email), has continued to grow because it is a very inexpensive method of advertising. These unwanted emails can cause a serious problem by filling up the email inbox and thereby leaving no space for legitimate emails to pass through. Currently the only defense against SPAM is the use of SPAM filters. A novel SPAM filter GetEmail5 along with the design rationale, is described in this thesis. To test the efficacy of GetEmail5 SPAM filter, an experimental setup was created and a commercial bulk email program was used to send SPAM and non-SPAM emails to test the new SPAM filter. GetEmail5’s efficiency and ability to detect SPAM was compared against two highly ranked commercial SPAM filters on different sets of emails, these included all SPAM, non-SPAM, and mixed emails, also text and HTML emails. The results showed the superiority of GetEmail5 compared to the two commercial SPAM filters in detecting SPAM emails and reducing the user’s involvement in categorizing the incoming emails. This thesis demonstrates the design rationale for GetEmail5 and also its greater effectiveness in comparison with the commercial SPAM filters tested.

As the massive increase of electronic mail (email) usage continues, SPAM (unsolicited bulk email), has continued to grow because it is a very inexpensive method of advertising. These unwanted emails can cause a serious problem by filling up the email inbox and thereby leaving no space for legitimate emails to pass through. Currently the only defense against SPAM is the use of SPAM filters. A novel SPAM filter GetEmail5 along with the design rationale, is described in this thesis. To test the efficacy of GetEmail5 SPAM filter, an experimental setup was created and a commercial bulk email program was used to send SPAM and non-SPAM emails to test the new SPAM filter. GetEmail5's efficiency and ability to detect SPAM was compared against two highly ranked commercial SPAM filters on different sets of emails, these included all SPAM, non-SPAM, and mixed emails, also text and HTML emails. The results showed the superiority of GetEmail5 compared to the two commercial SPAM filters in detecting SPAM emails and reducing the user's involvement in categorizing the incoming emails. This thesis demonstrates the design rationale for GetEmail5 and also its greater effectiveness in comparison with the commercial SPAM filters tested.

As the massive increase of electronic mail (email) usage continues, SPAM (unsolicited bulk email), has continued to grow because it is a very inexpensive method of advertising. These unwanted emails can cause a serious problem by filling up the email inbox and thereby leaving no space for legitimate emails to pass through. Currently the only defense against SPAM is the use of SPAM filters. A novel SPAM filter GetEmail5 along with the design rationale, is described in this thesis. To test the efficacy of GetEmail5 SPAM filter, an experimental setup was created and a commercial bulk email program was used to send SPAM and non-SPAM emails to test the new SPAM filter. GetEmail5's efficiency and ability to detect SPAM was compared against two highly ranked commercial SPAM filters on different sets of emails, these included all SPAM, non-SPAM, and mixed emails, also text and HTML emails. The results showed the superiority of GetEmail5 compared to the two commercial SPAM filters in detecting SPAM emails and reducing the user's involvement in categorizing the incoming emails. This thesis demonstrates the design rationale for GetEmail5 and also its greater effectiveness in comparison with the commercial SPAM filters tested.

A prevalência de sintomas de asma, broncoespasmo induzido pelo exercício (BIE), hiperresponsividade brônquica (HRB) e alergia em atletas que praticam modalidades de alto rendimento e longa duração tem aumentado nas últimas décadas e tem sido estudada principalmente em atletas de inverno e nadadores. No entanto, a prevalência de sintomas de asma e alergia e os mecanismos inflamatórios envolvidos no BIE que ocorre em corredores de longa distância permanecem pouco conhecidos. Objetivos: O presente estudo tem como objetivo avaliar a prevalência de sintomas de asma e alergia em corredores de longa distância de elite e investigar os mecanismos inflamatórios envolvidos no BIE nos atletas sem histórico de asma. Casuística e Métodos: Este estudo foi realizado em duas fases: na Fase I, foi avaliada a prevalência de sintomas de asma e alergia em 201 corredores de longa distância, através da aplicação dos questionários ISAAC e AQUA©. Na Fase II, foram avaliados os mecanismos inflamatórios envolvidos no BIE de 40 corredores que não apresentaram sintomas de asma na Fase I e que foram selecionados aleatoriamente. Nesta fase, os atletas compareceram ao laboratório em três momentos, com intervalo máximo de duas semanas entre cada visita, e foram submetidos às seguintes avaliações 1º) escarro induzido e teste cardiopulmonar máximo, 2º) broncoprovocação por metacolina e, 3º) óxido nítrico no ar exalado (FeNO), metabólitos LTE4 e 9alfa, 11beta-PGF2 e teste de hiperventilação eucápnica voluntária (HEV). Resultados: A prevalência de sintomas de asma e alergia foi de 6,5% e 60,5%, respectivamente. Ao analisar as questões do AQUA©, observou-se alta frequência de sintomas de BIE (62,3%) e rinite (56,6%). Os sintomas de alergia não foram associados a variáveis como gênero, idade, experiência em corridas de longa distância, volume de treinamento semanal e desempenho em provas de meia maratona e maratona. Verificou-se ainda que a prevalência de BIE foi de 27,5%. Quando comparados os atletas BIE+ e BIE- não foram observadas diferenças nos valores de VEF1 absoluto, nas medidas antropométricas, nas características de treinamento e também no desempenho. Os atletas BIE+ relataram mais sintomas de alergia (p=0,03), se mostraram mais responsivos à metacolina (p=0,01), apresentaram maior porcentagem de eosinófilos no escarro (p=0,03) e níveis mais elevados de FeNO (p < 0,001*) quando comparados aos atletas BIE-. Os níveis urinários de LTE4 e 9alfa, 11beta-PGF2 basais e após 60 minutos do teste de HEV foram similares entre os grupos BIE+ e BIE-, no entanto, ao comparar os níveis destes mediadores antes e após o teste de HEV, observou-se uma diminuição nos níveis de LTE4, apenas nos atletas BIE- (p=0,04). Conclusões: Corredores de longa distância apresentam elevada prevalência de sintomas de alergia e BIE e baixa prevalência de sintomas de asma. Além disto, os atletas BIE+ referem mais sintomas de alergia, são mais hiperresponsivos à metacolina, apresentam um padrão inflamatório eosinofílico e elevados níveis de FeNO embora sem diferenças nos níveis basais dos metabólitos do mastócito
An increased prevalence of asthma and allergic symptoms, exercise-induced bronchoconstriction (EIB) and bronchial hyperresponsiveness (BHR) has been observed in elite and endurance athletes, especially winter sports athletes and swimmers. However, the occurrence of allergy symptoms and the inflammatory mechanisms involved in the EIB that occurs in long distance runners remains poorly known. Objectives: the aims of the present study were to assess the prevalence of symptoms of asthma and allergy in long distance runners and to investigate possible inflammatory mediators involved in the EIB that occurs in those without asthma history. Methods: This cross sectional study was performed in two phases. In Phase I, the prevalence of symptoms of asthma and allergy was assessed in 201 long distance runners using ISAAC and AQUA© questionnaires. In Phase II, 40 athletes were randomly selected among those who did not present asthma history and they performed the following measurements: induced sputum, cardiopulmonary exercise testing, methacholine bronchoprovocation challenge, exhaled nitric oxide (FeNO), urinary collection to quantify LTE4 and 9alfa, 11beta-PGF2 metabolites and eucapnic voluntary hyperventilation test (EVH). Results: The prevalence of asthma and allergy symptoms was 6.5% and 60.5%, respectively. In addition, we observed a high frequency of EIB symptoms (62.3%) and rhinitis (56.6%). Allergy symptoms were not associated with anthropometric characteristics, running experience, weekly training volume and best half-marathon and marathon performance. The prevalence of EIB was 27.5% and no difference in baseline lung function, anthropometric data as well as training and performance characteristics was observed between athletes with (EIB+) and without (EIB-) EIB. EIB+ athletes reported more allergy symptoms (p=0.03) and were more resposive to methacholine (p=0.01) than EIB- athletes. A higher percentage of eosinophils in the induced sputum (p=0.03) and levels of FeNO (p < 0.001*) were observed in EIB+ athletes. However, there was no difference in the urinary levels of LTE4 and 9alfa, 11beta-PGF2 either at baseline or after EVH test. Conclusions: Long distance runners have a high prevalence of allergy symptoms and EIB and a low prevalence of asthma symptoms. Moreover, EIB+ athletes report more symptoms of allergy and present airway hyperresponsiveness, eosinophilic inflammation and increased levels of exhaled nitric oxide, without difference in the baseline levels of mast cell metabolites

Myofascial a pain syndrome is widely widespread in sport practice. For him a muscular spasm and presence of trigger points are characteristic, at palpation of that strengthening of pain is marked. Basic principles over of renewal of sportsmen are brought with myofascial by a pain syndrome.
Myofascial zespół bólowy jest szeroko rozpowszechniony w praktyce sportowej. Dla niego ma charakterystyczny skurcz mięśni i obecność punktów spustowych charakterystycznych, na palpacji tego wzmocnienia bólu jest zaznaczone. Podstawowe zasady odnowy sportowców przynoszą myofascial przez zespół bólu.
В настоящее время одним из наиболее приоритетных направлений физической терапии является комплексная реабилитация. Разработка научно обоснованных, эффективных нелекарственных методов при миофасциальном болевом синдроме является одной из приоритетных задач реабилитации спортсменов. Технологии реабилитации включают в себя большой арсенал традиционных и нетрадиционных оздоровительных методов, среди которых широко используются природные и преформированные физические факторы. Одним из наиболее перспективных методов, на сегодняшний день, является метод динамической электростимуляции (ДЭНС). Простота применения, неинвазивность, высокая эффективность метода дает возможность использовать ДЭНС в комплексной реабилитации спортсменов

New Internet collaborative media introduce new ways of communicating that are not immune to abuse. A fake eye-catching profile in social networking websites, a promotional review, a response to a thread in online forums with unsolicited content or a manipulated Wiki page, are examples of new the generation of spam on the web, referred to as Web 2.0 Spam or Spam 2.0. Spam 2.0 is defined as the propagation of unsolicited, anonymous, mass content to infiltrate legitimate Web 2.0 applications.The current literature does not address Spam 2.0 in depth and the outcome of efforts to date are inadequate. The aim of this research is to formalise a definition for Spam 2.0 and provide Spam 2.0 filtering solutions. Early-detection, extendibility, robustness and adaptability are key factors in the design of the proposed method.This dissertation provides a comprehensive survey of the state-of-the-art web spam and Spam 2.0 filtering methods to highlight the unresolved issues and open problems, while at the same time effectively capturing the knowledge in the domain of spam filtering.This dissertation proposes three solutions in the area of Spam 2.0 filtering including: (1) characterising and profiling Spam 2.0, (2) Early-Detection based Spam 2.0 Filtering (EDSF) approach, and (3) On-the-Fly Spam 2.0 Filtering (OFSF) approach. All the proposed solutions are tested against real-world datasets and their performance is compared with that of existing Spam 2.0 filtering methods.This work has coined the term ‘Spam 2.0’, provided insight into the nature of Spam 2.0, and proposed filtering mechanisms to address this new and rapidly evolving problem.

Workshop "Netz- und Service-Infrastrukturen" Dieser Beitrag zum Workshop "Netz- und Service-Infrastrukturen" 2004 analysiert den Stand der Anti-Spam-Maßnahmen an der TU Chemnitz und zeigt neue Techniken auf.

Twitter generates the majority of its revenue from advertising. Third parties pay to have their products advertised on Twitter through: tweets, accounts and trends. However, spammers can use Sybil accounts (fake accounts) [21] to advertise and avoid paying for it. Sybil accounts are highly active on Twitter performing advertising campaigns to serve their clients [5]. They aggressively try to reach a large audience to maximize their influence. These accounts have similar behavior if controlled by the same master. Most of their spam tweets include a shortened URL to trick users into clicking on it. Also, since they share resources with each other, they tend to tweet similar trending topics to attract a larger audience. However, some Sybil accounts do not spam aggressively to avoid being detected [22], rendering it difficult for traditional spam detectors to be effective in detecting low spamming Sybil accounts. In this paper, I investigate additional criteria to measure the similarity between accounts on Twitter. I propose an algorithm to define the correlation among accounts by investigating their tweeting habits and content. Given known labeled accounts by spam detectors, this approach can detect hidden accounts that are closely related to labeled accounts but are not detected by traditional spam detection approaches.

Communication through text messaging, SMS (Short Message Service), is nowadays a huge industry with billions of active users. Because of the huge userbase it has attracted many companies trying to market themselves through unsolicited messages in this medium in the same way as was previously done through email. This is such a common phenomenon that SMS spam has now become a plague in many countries. This report evaluates several established machine learning algorithms to see how well they can be applied to the problem of filtering unsolicited SMS messages. Each filter is mainly evaluated by analyzing the accuracy of the filters on stored message data. The report also discusses and compares requirements for hardware versus performance measured by how many messages that can be evaluated in a fixed amount of time. The results from the evaluation shows that a decision tree filter is the best choice of the filters evaluated. It has the highest accuracy as well as a high enough process rate of messages to be applicable. The decision tree filter which was found to be the most suitable for the task in this environment has been implemented. The accuracy in this new implementation is shown to be as high as the implementation used for the evaluation of this filter. Though the decision tree filter is shown to be the best choice of the filters evaluated it turned out the accuracy is not high enough to meet the specified requirements. It however shows promising results for further testing in this area by using improved methods on the best performing algorithms.

This thesis takes on a broader perspective of the modern age phenomenon we call spam. One of the aims of this thesis is to present and to compare the variety of methods used in the day-to-day fight against spam, as far they have evolved today, but also to present and discuss some alternative methods for suggested future use. The properties of a common e-mail spam are analyzed to show how the components that make up the structure in an e-mail can be used to classify spam. Furthermore I explain the naïve Bayesian classification methods, the signature-based method, the commonly used rule-based method and the challenge and response method and discuss these. The widespread use of blacklists is also explained and a close new variant to blacklisting, Turntide is presented and discussed. This is followed by a brief presentation and discussion of proposed countermeasure methods, including FFBs and Captcha. PHEmail is then shown, a new proposed method which takes advantage of already established social relations, in the fight against spam. Next important step is to present the new legislative bills in USA and in the EC, the criticism regarding these laws is also discussed. The thesis finally presents two suggested methods to fight spam, both initiated by Microsoft: Caller ID and the use of electronic stamps. The thesis rounds off with an open discussion regarding how well this broad variety of methods may interact with each others.
Uppsatsnivå: D

Orientador: Akedo Yamakami
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de Computação
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Resumo: Nos últimos anos, spams têm se tornado um importante problema com enorme impacto na sociedade. A filtragem automática de tais mensagens impõem um desafio especial em categorização de textos, no qual a característica mais marcante é que os filtros enfrentam um adversário ativo, que constantemente procura evadir as técnicas de filtragem. Esta tese apresenta um estudo abrangente sobre o problema do spamming. Dentre as contribuições oferecidas, destacam-se: o levantamento histórico e estatístico do fenômeno do spamming e as suas consequências, o estudo sobre a legalidade do spam e os recursos jurídicos adotados por alguns países, a análise de medidas de desempenho utilizadas na avaliação dos filtros de spams, o estudo dos métodos mais empregados para realizar a filtragem de spams, a proposta de melhorias dos filtros Bayesianos através da adoção de técnicas de redução de dimensionalidade e, principalmente, a proposta de um novo método de classificação baseado no princípio da descrição mais simples auxiliado por fatores de confidência. Vários experimentos são apresentados e os resultados indicam que a técnica proposta 'e superior aos melhores filtros anti-spams presentes tanto comercialmente quanto na literatura.
Abstract: Spam has become an increasingly important problem with a big economic impact in society. Spam filtering poses a special problem in text categorization, in which the defining characteristic is that filters face an active adversary, which constantly attempts to evade filtering. In this thesis, we present a comprehensive study of the spamming problem. Among many offered contributions we present: the statistical and historical survey of spamming and its consequences, a study regarding the legality of spams and the main juridic methods adopted by some countries, the study and proposal of new performance measures used for the evaluation of the spam classifiers, the proposals for improving the accuracy of Naive Bayes filters by using dimensionality reduction techniques and a novel approach to spam filtering based on the minimum description length principle and confidence factors. Furthermore, we have conducted an empirical experiments which indicate that the proposed classifier outperforms the state-of-the-art spam filters.
Doutorado
Automação
Doutor em Engenharia Elétrica

The arrival of any piece of unsolicited and unwanted email, commonly referred to as spam, is a source of annoyance to many email users. It results in real costs to individuals and organisations. Spam also contributes to a reluctance to use email by some individuals. Currently most spam prevention techniques rely on methods that examine the whole email message at the mail server. This thesis details research that aims to deny spam entry into the internal network, stopping it ever reaching the mail server. A system is described that can identify current potential spammer IP addresses in real-time and then inform all network gateways to block emails from those addresses. Various tests of the system's timeliness and efficiency are then illustrated, leading to a final conclusion of the system's viability and overall usefulness. This is followed by a discussion of various areas in which future research could be carried out.

Spam is becoming a more and more severe problem for individuals, networks, organisations and businesses. The losses caused by spam are billions of dollars every year. Research shows that spam contributes more than 80% of e-mails with an increased in its growth rate every year. Spam is not limited to emails; it has started affecting other technologies like VoIP, cellular and traditional telephony, and instant messaging services. None of the approaches (including legislative, collaborative, social awareness and technological) separately or in combination with other approaches, can prevent sufficient of the spam to be deemed a solution to the spam problem. The severity of the spam problem and the limitations of the state-of-the-Art solutions create a strong need for an efficient anti-spam mechanism that can prevent significant volumes of spam without showing any false positives. This can be achieved by an efficient anti-spam mechanism such as the proposed anti-spam mechanism known as "Spam Prevention using Access Codes", SPAC. SPAC targets spam from two angles i.e. to prevent/block spam and to discourage spammers by making the infrastructure environment very unpleasant for them. In addition to the idea of Access Codes, SPAC combines the ideas behind some of the key current technological anti-spam measures to increase effectiveness. The difference in this work is that SPAC uses those ideas effectively and combines them in a unique way which enables SPAC to acquire the good features of a number of technological anti-spam approaches without showing any of the drawbacks of these approaches. Sybil attacks, Dictionary attacks and address spoofing have no impact on the performance of SPAC. In fact SPAC functions in a similar way (i.e. as for unknown persons) for these sorts of attacks. An application known as the "SPAC application" has been developed to test the performance of the SPAC mechanism. The results obtained from various tests on the SPAC application show that SPAC has a clear edge over the existing anti-spam technological approaches.

This thesis examines several aspects of the debate on the choice of best firstline treatment for infantile spasms. The first part of the thesis describes, analyses and interprets outcomes from the United Kingdom Infantile Spasms Study (UKISS), a multicentre randomised controlled trial that compares treatment with prednisolone or tetracosactide (hormonal treatments) against vigabatrin. This study was coordinated from the Bath Unit for Research in Paediatrics at the Royal United Hospital, Bath, and showed that the early primary clinical response, cessation of spasms, was significantly more likely in infants who were allocated hormonal treatments. However, the overall proportions with relapse-free response at the end of the study period, when the child reached the age of 12 to 14 months, were similar in all three treatment groups. In a group of infants of a priori interest who had no identified underlying aetiology, neurodevelopmental outcomes were significantly better in children who had been allocated hormonal treatments, although this finding was not robust within a sensitivity analysis. The second part of the thesis examines problems with case definitions and outcome measures in epidemiological and interventional studies of infantile spasms, and describes the development of West Delphi, a consensus elicitation process that has produced published proposals for standardised case definitions and outcome measures for such studies. Its most novel proposals were: (1) that the primary clinical outcome cessation of spasms should be defined by the absence of observed spasms for at least 28 days from the time of the last observed spasms, with the last spasms being observed within 14 days of treatment allocation; and (2) that there should be a standardised primary electroclinical response that studies should also report as a primary outcome.

Spam is an increasing menace in email: 90% of email is spam, and over 90% of spam is sent by botnets---networks of compromised computers under the control of miscreants. In this dissertation, we introduce email spam filtering using network-level features of spammers. Network-level features are based on lightweight measurements that can be made in the network, often without processing or storing a message. These features stay relevant for longer periods, are harder for criminals to alter at will (e.g., a bot cannot act independently of other bots in the botnet), and afford the unique opportunity to observe the coordinated behavior of spammers. We find that widely-used IP address-based reputation systems (e.g., IP blacklists) cannot keep up with the threats of spam from previously unseen IP addresses, and from new and stealthy attacks---to thwart IP-based reputation systems, spammers are reconnoitering IP Blacklists and sending spam from hijacked IP address space. Finally, spammers are "gaming" collaborative filtering by users in Web-based email by casting fraudulent "Not Spam" votes on spam email. We present three systems that detect each attack that uses spammer behavior rather than their IP address. First, we present IP blacklist counter-intelligence, a system that can passively enumerate spammers performing IP blacklist reconnaissance. Second, we present SpamTracker, a system that distinguishes spammers from legitimate senders by applying clustering on the set of domains to which email is sent. Third, we analyze vote-gaming attacks in large Web-based email systems that pollutes user feedback on spam emails, and present an efficient clustering-based method to mitigate such attacks.

Spam, the distribution of unsolicited bulk email, is a big security threat on the Internet. Recent studies show approximately 70-90% of the worldwide email traffic—about 70 billion messages a day—is spam. Spam consumes resources on the network and at mail servers, and it is also used to launch other attacks on users, such as distributing malware or phishing. Spammers have increased their virulence and resilience by sending spam from large collections of compromised machines (“botnets”). Spammers also make heavy use of URLs and domains to direct victims to point-of-sale Web sites, and miscreants register large number of domains to evade blacklisting efforts. To mitigate the threat of spam, users and network administrators need proactive techniques to distinguish spammers from legitimate senders and to take down online spam-advertised sites. In this dissertation, we focus on characterizing spam-related activities and developing systems to detect them early. Our work builds on the observation that spammers need to acquire attack agility to be profitable, which presents differences in how spammers and legitimate users interact with Internet services and exposes detectable during early period of attack. We examine several important components across the spam life cycle, including spam dissemination that aims to reach users' inboxes, the hosting process during which spammers set DNS servers and Web servers, and the naming process to acquire domain names via registration services. We first develop a new spam-detection system based on network-level features of spamming bots. These lightweight features allow the system to scale better and to be more robust. Next, we analyze DNS resource records and lookups from top-level domain servers during the initial stage after domain registrations, which provides a global view across the Internet to characterize spam hosting infrastructure. We further examine the domain registration process and present the unique registration behavior of spammers. Finally, we build an early-warning system to identify spammer domains at time-of-registration rather than later at time-of-use. We have demonstrated that our detection systems are effective by using real-world datasets. Our work has also had practical impact. Some of the network-level features that we identified have since been incorporated into spam filtering products at Yahoo! and McAfee, and our work on detecting spammer domains at time-of-registration has directly influenced new projects at Verisign to investigate domain registrations.

Orientador: Paulo Licio de Geus
Dissertação (mestrado profissional) - Universidade Estadual de Campinas, Instituto de Computação
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Resumo: As tecnologias tradicionais para filtragem de spam apresentam algumas limitações que dificultam a precisão na classificação das mensagens, que neste trabalho são denominadas de ¿falso-negativos¿ e ¿falso-positivos¿. Em geral, as taxas de falso-positivos são mais graves do que as taxas de falso-negativos, ou seja, visualizar um spam é melhor do que não ver uma mensagem importante. Portanto, um grande número de ferramentas anti-spam têm surgido rapidamente para minimizar a ocorrência de falso-positivos e os problemas ocasionados pelo recebimento de mensagens não solicitadas. Este trabalho tem o objetivo de estudar técnicas variadas no combate ao spam, em especial, os filtros Bayesianos anti-spam. Os resultados obtidos apontam os filtros Bayesianos anti-spam como uma excelente solução para controlar o recebimento de spam
Abstract: Traditional technologies to filter out spam present some limitations that impact the accuracy in the message classification process, that is, the rates of false-negatives and falsepositives. As a rule, false-positives are much worse than false-negatives; in other words, visualizing a spam is better than missing an important message. Therefore, a large number of anti-spam tools have arisen lately to try and minimize false-positives rates while reducing the high unsolicited mail volume. The goal of this work is to study a variety of anti-spam techniques, especially the Bayesian filters. The results obtained indicate that Bayesian anti-spam filters are an excellent solution to control spam reception
Mestrado
Redes de Computadores
Mestre em Computação

Spam se typicky nevyskytuje ve formě samostatných zpráv, ale často bývá sdružován do takzvaných kampaní. Ty bývají automaticky generovány pomocí šablon. Díky tomu jsou jednotlivé zprávy sémanticky, ale ne syntakticky, ekvivalentní. Cílem práce je navrhnout algoritmus schopný z množiny zpráv jedné kampaně zpětně extrahovat šablonu, ze které tyto zprávy byly generovány. Práce se zaměřuje na spam v SMS komunikaci, ale navržené postupy jsou dostatečně obecné pro širší použití. Algoritmus je postaven na metodě zarovnávání dvou sekvencí, používané v bioinformatice pro nalezení podobných oblastí proteinových řetězců. Výstupem je regulární výraz popisující šablonu dané kampaně. Součástí řešení je také nástroj pro vizualizaci šablony pomocí HTML.Řešení bylo ověřeno na přibližně třech stovkách skutečných kampaní z celého světa. V naprosté většině případů je poskytnutý výsledek postačující pro identifikaci kampaně.

Tableau d'honneur de la Faculté des études supérieures et postdoctorales, 2016-2017
Les courriels Spams (courriels indésirables ou pourriels) imposent des coûts annuels extrêmement lourds en termes de temps, d’espace de stockage et d’argent aux utilisateurs privés et aux entreprises. Afin de lutter efficacement contre le problème des spams, il ne suffit pas d’arrêter les messages de spam qui sont livrés à la boîte de réception de l’utilisateur. Il est obligatoire, soit d’essayer de trouver et de persécuter les spammeurs qui, généralement, se cachent derrière des réseaux complexes de dispositifs infectés, ou d’analyser le comportement des spammeurs afin de trouver des stratégies de défense appropriées. Cependant, une telle tâche est difficile en raison des techniques de camouflage, ce qui nécessite une analyse manuelle des spams corrélés pour trouver les spammeurs. Pour faciliter une telle analyse, qui doit être effectuée sur de grandes quantités des courriels non classés, nous proposons une méthodologie de regroupement catégorique, nommé CCTree, permettant de diviser un grand volume de spams en des campagnes, et ce, en se basant sur leur similarité structurale. Nous montrons l’efficacité et l’efficience de notre algorithme de clustering proposé par plusieurs expériences. Ensuite, une approche d’auto-apprentissage est proposée pour étiqueter les campagnes de spam en se basant sur le but des spammeur, par exemple, phishing. Les campagnes de spam marquées sont utilisées afin de former un classificateur, qui peut être appliqué dans la classification des nouveaux courriels de spam. En outre, les campagnes marquées, avec un ensemble de quatre autres critères de classement, sont ordonnées selon les priorités des enquêteurs. Finalement, une structure basée sur le semiring est proposée pour la représentation abstraite de CCTree. Le schéma abstrait de CCTree, nommé CCTree terme, est appliqué pour formaliser la parallélisation du CCTree. Grâce à un certain nombre d’analyses mathématiques et de résultats expérimentaux, nous montrons l’efficience et l’efficacité du cadre proposé.
Spam emails yearly impose extremely heavy costs in terms of time, storage space, and money to both private users and companies. To effectively fight the problem of spam emails, it is not enough to stop spam messages to be delivered to end user inbox or be collected in spam box. It is mandatory either to try to find and persecute the spammers, generally hiding behind complex networks of infected devices, which send spam emails against their user will, i.e. botnets; or analyze the spammer behavior to find appropriate strategies against it. However, such a task is difficult due to the camouflage techniques, which makes necessary a manual analysis of correlated spam emails to find the spammers. To facilitate such an analysis, which should be performed on large amounts of unclassified raw emails, we propose a categorical clustering methodology, named CCTree, to divide large amount of spam emails into spam campaigns by structural similarity. We show the effectiveness and efficiency of our proposed clustering algorithm through several experiments. Afterwards, a self-learning approach is proposed to label spam campaigns based on the goal of spammer, e.g. phishing. The labeled spam campaigns are used to train a classifier, which can be applied in classifying new spam emails. Furthermore, the labeled campaigns, with the set of four more ranking features, are ordered according to investigators priorities. A semiring-based structure is proposed to abstract CCTree representation. Through several theorems we show under some conditions the proposed approach fully abstracts the tree representation. The abstract schema of CCTree, named CCTree term, is applied to formalize CCTree parallelism. Through a number of mathematical analysis and experimental results, we show the efficiency and effectiveness of our proposed framework as an automatic tool for spam campaign detection, labeling, ranking, and formalization.

Unsolicited messages affects virtually every popular social media website, and spammers have become increasingly proficient at bypassing conventional filters, prompting a stronger effort to develop new methods. First, we build an independent model using features that capture the cases where spam is obvious. Second, a relational model is built, taking advantage of the interconnected nature of users and their comments. By feeding our initial predictions from the independent model into the relational model, we can propagate and jointly infer the labels of all comments at the same time. This allows us to capture the obfuscated spam comments missed by the independent model that are only found by looking at the relational structure of the social network. The results from our experiments shows that models utilizing the underlying structure of the social network are more effective at detecting spam than ones that do not. This thesis includes previously published coauthored material.

Email spam has steadily grown and has become a major problem for users, email service providers, and many other organizations. Many adversarial methods have been proposed to combat spam and various studies have been made on the evolution of email spam, by finding evolution patterns and trends based on historical spam data and by incorporating spam filters. In this thesis, we try to understand the evolution of email spam and how we can build better classifiers that will remain effective against adaptive adversaries like spammers. We compare various methods for analyzing the evolution of spam emails by incorporating spam filters along with a spam dataset. We explore the trends based on the weights of the features learned by the classifiers and the accuracies of the classifiers trained and tested in different settings. We also evaluate the effectiveness of the classifier trained in adversarial settings on synthetic data.

Functional Electrical Stimulation (FES) can be used to assist patients with complete paraplegia arising from a traumatic spinal cord injury to stand. In clinical practice the take-up of this technology is poor. It was hypothesised that one potential reason was that the posture during standing was difficult to predict from non-standing biomechanical measures because of the spinal cord's motor responses to standing. In six patients biomecharrical and electrophysiological recordings were made to test whether motor activity arising as a result of standing affected their standing posture. Recordings were made using surface EMG electrodes, force plates and instrumented handles a motion analysis system. No motor activity that affected the posture of the patients was recorded during standing or when the patients changed their hip or ankle angles. The act of standing with FES assistance affected spasms in two of the six patients. In one patient his spasms became regularised to a 16s pattern when standing with FES but when standing without FES and in the second patient his spasms were stopped for periods of up to 7 hours. This prolonged cessation only occurred when standing with FES. Mechanically supported standing produced a short (5 minute) cessation in the activity. The neural activity during the sit-to-stand or steady state standing did not change with increasing experience of standing in one naive subject studied over 6 weeks. The patient used the same strategy for the sit-to-stand as other patients. He improved his performance of this strategy by shortening the phases and the intervals between the phases as well as reducing the safety margin for knee buckling. The spinal cord when removed from descending inputs is capable of generating rhythmical motor outputs in response to changes in sensory inputs. FES may interact with some of this oscillatory activity.

The early onset epileptic encephalopathy of infantile spasms is frequently associated with acute cognitive regression, long-term learning disability and autistic spectrum disorder. Although there may be a structural basis to the epilepsy, it appears that seizure activity is directly implicated in the process associated with the above disabilities. There are strong indications of the crucial role of temporal lobe dysfunction in children within this and related epileptic regressions including the site of lesions in tuberous sclerosis and the EEG localisation in a later onset epileptic encephalopathy, the Landau-Kleffner-syndrome. Thus the hypothesis for this study was that the temporal lobe is functionally abnormal in children with infantile spasms. This was tested by recording event related potentials, the electrical indicators of the brain's perception and processing of auditory stimuli. The aims of the current study were to describe the normal developmental changes of mismatch-negativity (MMN) and novelty P3 in the first year of life and to identify whether these ERPs are abnormal in children with infantile spasms. The developmental status of infants with infantile spasms was assessed at presentation. The MMN was only shown in a group mean average in control infants. All obligatory and the endogenous P250, P500, Ncl and Nc2 ERP components of the control infants showed age dependent latencies and differed in latency between wakefulness and stage 2 sleep. Using nonparametric calculations infants with infantile spasms had prolonged latencies of the obligatory and endogenous components during both wakefulness and sleep compared to controls. The results of this study support the hypothesis that the auditory processing is interrupted in infants with infantile spasms. As the auditory cortex is very immature during the first year of life it is therefore suggested that infantile spasms may interfere with crucial maturational processes during the first year of life.