Apresentamos nesta tese a primeira geração direta de emaranhamento tripartite entre feixes intensos de luz. Medimos o emaranhamento entre os feixes sinal, complementar e bombeio refletido, produzidos por um Oscilador Paramétrico Ótico (OPO) operando acima do limiar de oscilação. A principal característica do nosso sistema é a diferença entre os comprimentos de onda dos campos (l0 = 532.251 nm, l1 = 1062.102 nm, e l2 = 1066.915 nm). Esta é a primeira medida de emaranhamento entre mais de dois subsistemas produzidos por uma única fonte no âmbito de variáveis contínuas. Para investigar a existência emaranhamento, utilizamos o critério de positividade sob transposição parcial (PPT). Este critério, aplicado a sistemas compostos por estados gaussianos, dispostos em bipartições do tipo 1×(N 1), torna-se necessário e suficiente na demonstração do emaranhamento. Realizamos também a caracterização do emaranhamento produzido quando submetemos os campos a perdas, identificando regiões de parâmetros onde os estados apresentam emaranhamento frágil ou robusto. A fim de garantir que estamos lidando com estados gaussianos, investigamos a estatística das flutuações dos campos, mostrando excelente acordo entre os valores dos momentos de ordem mais alta da fotocorrente medida e os valores esperados para uma distribuição gaussiana. O estudo que apresentamos é um passo importante para a elaboração de uma rede de informação quântica que possibilitará a comunicação entre diferentes sistemas físicos. / We present in this thesis the first direct generation of tripartite entanglement among bright beams of light. We measured the entanglement among signal, idler and reflected pump beams, produced by an Optical Parametric Oscillator (OPO) operating above the threshold. The main feature of our system is the difference between the wavelengths of the fields (l0 = 532.251 nm, l1 = 1062.102 nm, e l2 = 1066.915 nm). This is the first measurement of entanglement among more than two subsystems produced by a single source, in a continuous variable system. In order to investigate the existence of entanglement, we applied the criterion of positivity under partial transposition (PPT). This criterion, applied to systems composed of Gaussian states, arranged in 1×(N1) bipartition, becomes necessary and sufficient to demonstrate entanglement. We also characterized the entanglement when the fields are submitted to losses, identifying regions of parameters where the states have fragile or robust entanglement. To ensure that we are dealing with Gaussian states, we investigate the statistics of the fields, showing excelent agreement among values of higher order moments of the photocurrent measured and expected values for a Gaussian distribution. The present study is an important step in the development of a quantum information network formed by different physical systems.

A surdez neurossensorial imunomediada (SNIM) é uma das formas reversíveis de surdez neurossensorial, justificando a necessidade de identificação de marcadores mais específicos que ajudem na sua abordagem. O Western blot com antígenos de tecidos bovinos detecta um anticorpo contra a proteína de 68kD (hsp-70) em SNIM. Entretanto, anticorpos antihsp- 70 são comumente encontrados em indivíduos sadios. O objetivo do estudo foi determinar a reatividade de soros de pacientes com doenças otológicas freqüentemente relacionadas à etiologia auto-imune contra antígeno celular de linhagem humana (HeLa) através do Western blot, comparando com outros marcadores sorológicos de auto-imunidade. Soros de 81 pacientes com surdez neurossensorial (25 surdez súbita, 35 rapidamente progressiva e 21 doença Ménière) foram testados por Western blot utilizando extrato total de célula HeLa como antígeno alvo. Os pacientes com surdez foram comparados com indivíduos com audição normal e sem queixas otológicas ou história de doença sistêmica auto-imune (n=48). Observou-se reatividade contra célula HeLa principalmente nas regiões de 42, 48 and 62kD no grupo com surdez. O padrão de reatividade foi diferente entre os diferentes subgrupos de surdez. A reatividade contra as bandas de 48 and 62kD foi observada em surdez súbita e surdez rapidamente progressiva. A proteína de 48kD proveniente da surdez rapidamente progressiva parece ser diferente daquela encontrada em surdez súbita devido a sua resistência à tripsina. Este estudo demonstrou a existência de autorreatividade contra células HeLa na surdez súbita, surdez rapidamente progressiva e doença de Ménière, sugerindo a presença de novos autoanticorpos. O seu papel é ainda desconhecido. Estudos detalhados são necessários para avaliar a real relevância clínica desta autorreatividade na patologia de orelha interna ou como marcador prognóstico ou diagnóstico / Immune-mediated sensorineural hearing loss (SNHL) is one of few forms of reversible SNHL, justifying the need to define more specific markers to help clinical approach. Western blot with bovine tissues detect an autoantibody against the 68kD protein (hsp70) in immune-mediated SNHL. However, antihsp70 antibodies are also common in healthy individuals. The objective of this study was to determinate the reactivity of serum from patients with otologic entities often related to autoimmune etiology against human cell line antigen (HeLa) by Western blot, comparing to other serological markers. Sera of 81 patients with SNHL (25 sudden SNHL, 35 rapidly progressive SNHL and 21 Ménière\'s disease patients) were tested by Western blot using HeLa cell total extract as target. Western blot outcome was compared with detection of other current autoimmune markers. Experimental group data were compared to normal-hearing subjects (n=48) without otologic or systemic autoimmune disease. Reactivity to HeLa cells was observed mostly at 42, 48 and 62kD region which pattern was different among different groups. Binding to 48 and 62kD HeLa cell antigen was observed in sudden SNHL and rapidly progressive SNHL. The 48kD protein from rapidly progressive SNHL seems to be different from sudden SNHL\'s according to resistance to trypsin. This study detected autoreactivity to HeLa cells in sudden SNHL, rapidly progressive SNHL and Ménière\'s disease, suggesting the presence of new autoantibodies. Their role is still unknown and further studies should evaluate their relevance on pathology in the inner ear or as diagnostic or prognostic marker

Wong Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1999. / Includes bibliographical references (leaves [110]-126). / Abstracts in English and Chinese. / ABSTRACT --- p.VI / ACKNOWLEDGEMENTS --- p.X / GLOSSARY --- p.XI / Chapter CHAPTER 1 --- INTRODUCTION AND LITERATURE REVIEW --- p.1 / Chapter 1.1 --- Sudden infant death syndrome --- p.1 / Chapter 1.1.1 --- Definition --- p.1 / Chapter 1.1.2 --- Epidemiology of sudden infant death syndrome --- p.1 / Chapter 1.1.3 --- Pathologic findings --- p.5 / Chapter 1.1.4 --- Theories of causation --- p.6 / Chapter 1.1.5 --- Associations of SIDS with temperature and hyperthermia --- p.8 / Chapter 1.1.6 --- Associations of sudden infant death syndrome with infection --- p.11 / Chapter 1.1.7 --- Association of sudden infant death syndrome with sleep state --- p.13 / Chapter 1.2 --- Overview of cytokines --- p.15 / Chapter 1.2.1 --- Definition --- p.15 / Chapter 1.2.2 --- Classification of cytokines --- p.15 / Chapter 1.2.3 --- Biological activities --- p.16 / Chapter 1.2.4 --- Cytokines and temperature --- p.20 / Chapter 1.2.5 --- Cytokines and infection --- p.22 / Chapter 1.2.6 --- Cytokines and smoking --- p.23 / Chapter 1.2.7 --- Cytokines and sleep/arousal --- p.23 / Chapter 1.3 --- Hypothesis and aims of the study --- p.27 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.28 / Chapter 2.1 --- Overview of methods in piglet experiments --- p.28 / Chapter 2.2 --- Pilot study design --- p.30 / Chapter 2.2.1 --- Study Groups --- p.30 / Chapter 2.2.2 --- Temperature controller --- p.33 / Chapter 2.2.3 --- PowerLab system --- p.34 / Chapter 2.2.4 --- Experimental set up --- p.36 / Chapter 2.2.5 --- Provisional ethical approval --- p.36 / Chapter 2.3 --- Problems and results of pilot experiments --- p.37 / Chapter 2.3.1 --- What is baseline body temperature of neonatal rat? --- p.38 / Chapter 2.3.2 --- What type of anaesthesic agent to use? --- p.39 / Chapter 2.3.3 --- What dose of ketamine to use? --- p.40 / Chapter 2.3.4 --- Dilution of ketamine --- p.41 / Chapter 2.3.5 --- Temperature calibration --- p.41 / Chapter 2.3.6 --- What is optimal neonatal rat age to use? --- p.44 / Chapter 2.3.7 --- Which method of blood collection to use? --- p.45 / Chapter 2.3.8 --- What method to raise body temperature? --- p.47 / Chapter 2.3.9 --- Summary results --- p.48 / Chapter 2.4 --- Final study design --- p.49 / Chapter 2.4.1 --- Study animal --- p.49 / Chapter 2.4.2 --- Final Study Groups --- p.50 / Chapter 2.4.3 --- Final ethical approval --- p.56 / Chapter 2.4.4 --- Muramyl dipeptide --- p.56 / Chapter 2.4.5 --- Recalibration of Temperature Controller --- p.57 / Chapter 2.4.6 --- Data collection --- p.58 / Chapter 2.4.7 --- Blood collection and Storage --- p.58 / Chapter 2.4.8 --- Study timetable --- p.59 / Chapter 2.5 --- Cytokines analysis --- p.59 / Chapter 2.5.1. --- Methods of Quantitative Enzyme Immunoassay --- p.59 / Chapter 2.5.2 --- Base theories of Enzyme-linked immunosorbent assay (ELISA) --- p.60 / Chapter 2.5.3 --- Procedure for cytokines assay --- p.61 / Chapter 2.6 --- Histology --- p.65 / Chapter 2.6.1. --- Macroscopic --- p.65 / Chapter 2.6.2. --- Microscopic --- p.65 / Chapter 2.7 --- Data handling and statistical analysis --- p.66 / Chapter CHAPTER 3 --- RESULTS --- p.67 / Chapter 3.1 --- Group (body weight) characteristics --- p.67 / Chapter 3.2 --- Serum concentration of IL- 6，IL-1 β --- p.69 / Chapter 3.3 --- Temperature --- p.78 / Chapter 3.4 --- Mortality rate --- p.80 / Chapter 3.5 --- Cardio-respiratory parameters --- p.85 / Chapter 3.6 --- Macroscopic findings at postmortem --- p.87 / Chapter 3.7 --- Histology --- p.91 / Chapter CHAPTER 4 --- DISCUSSION --- p.96 / Chapter 4.1 --- Study Model --- p.96 / Chapter 4.11 --- Core temperature of newborn rat --- p.95 / Chapter 4.12 --- Temperature calibration --- p.97 / Chapter 4.13 --- Respiratory and pulse rate measurements --- p.93 / Chapter 4.14 --- Measurement of sleep state --- p.99 / Chapter 4.2 --- Animal age and weight --- p.99 / Chapter 4.3 --- Cytokines response to heating --- p.101 / Chapter 4.4 --- Cytokine response to MDP --- p.104 / Chapter 4.5 --- "Hyperthermia, MDP and mortality" --- p.106 / Chapter 4.6 --- Further study --- p.107 / Chapter CHAPTER 5 --- CONCLUSION --- p.109 / Chapter 5.1 --- Small animal model of hyperthermia --- p.109 / Chapter 5.2 --- Hyperthermia and MDP elicit cytokine response --- p.109 / Chapter 5.3 --- Hyperthermia and MDP increase mortality rate --- p.109 / REFERENCES --- p.110 / APPENDICES --- p.A / Appendix 1: Experimental record --- p.A / Appendix 2 : Planned Study Timetable --- p.C / Appendix 3: PowerLab System --- p.E

A surdez neurossensorial imunomediada (SNIM) é uma das formas reversíveis de surdez neurossensorial, justificando a necessidade de identificação de marcadores mais específicos que ajudem na sua abordagem. O Western blot com antígenos de tecidos bovinos detecta um anticorpo contra a proteína de 68kD (hsp-70) em SNIM. Entretanto, anticorpos antihsp- 70 são comumente encontrados em indivíduos sadios. O objetivo do estudo foi determinar a reatividade de soros de pacientes com doenças otológicas freqüentemente relacionadas à etiologia auto-imune contra antígeno celular de linhagem humana (HeLa) através do Western blot, comparando com outros marcadores sorológicos de auto-imunidade. Soros de 81 pacientes com surdez neurossensorial (25 surdez súbita, 35 rapidamente progressiva e 21 doença Ménière) foram testados por Western blot utilizando extrato total de célula HeLa como antígeno alvo. Os pacientes com surdez foram comparados com indivíduos com audição normal e sem queixas otológicas ou história de doença sistêmica auto-imune (n=48). Observou-se reatividade contra célula HeLa principalmente nas regiões de 42, 48 and 62kD no grupo com surdez. O padrão de reatividade foi diferente entre os diferentes subgrupos de surdez. A reatividade contra as bandas de 48 and 62kD foi observada em surdez súbita e surdez rapidamente progressiva. A proteína de 48kD proveniente da surdez rapidamente progressiva parece ser diferente daquela encontrada em surdez súbita devido a sua resistência à tripsina. Este estudo demonstrou a existência de autorreatividade contra células HeLa na surdez súbita, surdez rapidamente progressiva e doença de Ménière, sugerindo a presença de novos autoanticorpos. O seu papel é ainda desconhecido. Estudos detalhados são necessários para avaliar a real relevância clínica desta autorreatividade na patologia de orelha interna ou como marcador prognóstico ou diagnóstico / Immune-mediated sensorineural hearing loss (SNHL) is one of few forms of reversible SNHL, justifying the need to define more specific markers to help clinical approach. Western blot with bovine tissues detect an autoantibody against the 68kD protein (hsp70) in immune-mediated SNHL. However, antihsp70 antibodies are also common in healthy individuals. The objective of this study was to determinate the reactivity of serum from patients with otologic entities often related to autoimmune etiology against human cell line antigen (HeLa) by Western blot, comparing to other serological markers. Sera of 81 patients with SNHL (25 sudden SNHL, 35 rapidly progressive SNHL and 21 Ménière\'s disease patients) were tested by Western blot using HeLa cell total extract as target. Western blot outcome was compared with detection of other current autoimmune markers. Experimental group data were compared to normal-hearing subjects (n=48) without otologic or systemic autoimmune disease. Reactivity to HeLa cells was observed mostly at 42, 48 and 62kD region which pattern was different among different groups. Binding to 48 and 62kD HeLa cell antigen was observed in sudden SNHL and rapidly progressive SNHL. The 48kD protein from rapidly progressive SNHL seems to be different from sudden SNHL\'s according to resistance to trypsin. This study detected autoreactivity to HeLa cells in sudden SNHL, rapidly progressive SNHL and Ménière\'s disease, suggesting the presence of new autoantibodies. Their role is still unknown and further studies should evaluate their relevance on pathology in the inner ear or as diagnostic or prognostic marker

Background: Parents of children with epilepsy have been shown to have higher rates of depression, anxiety and stress in comparison to parents of children without epilepsy due to the impact of caring for a child with a chronic condition. A systematic review of existing literature aimed to identify qualitative research that examined parents' experiences of caring for their children with epilepsy. Methods: The systematic review explored the experiences that parents have in caring for their child with epilepsy. A search of electronic databases for qualitative literature was completed. The quality of all eligible articles papers was assessed, and findings from studies were synthesised. Results: Twelve studies met inclusion criteria for the review; findings suggest that parents need time to process their child's diagnosis of epilepsy; they cope with this in differing ways and are motivated to learn how to adapt and cope with parenting their child with epilepsy. Conclusions: Parents of children with epilepsy may experience symptoms of stress, this may motivate them to learn how best to care for their child. Empirical Paper Abstract Background: Parents' experiences of being told about sudden unexpected death in epilepsy (SUDEP) may be particularly challenging to cope with. As little is known about how mothers understand and make sense of SUDEP, a qualitative research project aimed to explore mothers' experiences. It was hoped this would be helpful for clinicians to understand in order to assist them in providing information to parents in a way that minimises distress. Methods: The empirical article explored mother's experiences of being told about SUDEP and the subsequent impact of this for 11 mothers of children with epilepsy. Interpretative Phenomenological Analysis methodology was utilised, with themes derived from interpretation of interview transcripts, in order to describe the experiences of the participants. Results: Within the empirical study, five themes emerged. The way in which mothers found out about SUDEP seemed to have a link to their perception of risk and how they subsequently managed feelings of uncertainty and the psychological impact of knowing about SUDEP. Mothers' recommendations to clinicians included when, how and what to tell other parents, and were based on their own helpful and unhelpful experiences of being informed about SUDEP. Conclusions: In being told about SUDEP, mothers may struggle to make sense of it and this can be associated with an increase in anxiety. However, clinicians can reduce potential distress by carefully timing when and how they tell parents, and by making sure information is clear and relevant for the child in question.

Introdução: A morte súbita é a principal causa de morte na doença de Chagas, correspondendo de 55 a 65% dos casos. Observa-se que parte destas, ocorre em pacientes com função ventricular esquerda (FEVE) preservada, levando a acreditar que fatores desestabilizadores do substrato arritmogênico exercem um importante papel nestes eventos. Evidências já demonstraram a depressão parassimpática como fator contribuinte na gênese de arritmias diversas em presença de cardiopatia isquêmica. Assim, insiste-se na necessidade de se identificar precocemente quais os pacientes, no contexto da cardiopatia chagásica crônica, apresentam risco aumentado para o desenvolvimento de eventos arrítmicos complexos. Acredita-se que a avaliação autonômica identifique subgrupos distintos de risco. O presente estudo teve como objetivo determinar a sensibilidade do barorreflexo (SBR) em pacientes com doença de Chagas, nas formas indeterminada (GI) e arritmogênica com taquicardia ventricular não sustentada (GII) e com taquicardia ventricular sustentada (GIII) e, secundariamente, avaliar a associação entre a severidade da arritmia ventricular com o grau de comprometimento da SBR. Métodos: 42 pacientes foram submetidos à monitorização cardiovascular não invasiva pelo sistema Task Force ® onde foi determinada a SBR, utilizando o método da fenilefrina e analisada a variabilidade da frequência cardíaca (VFC) no domínio do tempo por meio da eletrocardiografia dinâmica de 24horas e a FEVE, por meio da ecocardiografia. Resultados: Observou-se diferença estatística significativa entre os grupos em relação à SBR em resposta à fenilefrina. O GIII apresentou o menor valor de SBR (6,09 ms/mmHg) quando comparado aos GII (11,84ms/mmHg) e GI (15,23ms/mmHg). Após comparação múltipla entre os grupos, verificou-se diferença significativa entre GI e GIII (p= 0,01). Quando se correlacionou SBR e densidade de extra-sístoles ventriculares (EV), observou-se que todos os pacientes portadores de baixa densidade de EV (< 10/hora) apresentavam SBR preservada (6,1ms/mmHg).Em contrapartida, entre aqueles com alta densidade de EV (>10/hora) somente 59% tinham SBR preservada (p=0,003). Nos pacientes com SBR deprimida (3,0-6,0 ms/mmHg) houve maior densidade de EV (p=0,01). Pacientes com SBR preservada apresentaram tanto função ventricular normal como moderadamente comprometida (66,7% com FEVE<40% e 79,5% com FEVE40%; p=0,62). O mesmo observou-se em pacientes com SBR moderadamente deprimida, (15,4% com FEVE<40% e 33,3% com FEVE40%; p=0,46). Não foi verificada correlação entre SBR e VFC. Ao se aplicar o modelo de regressão logística, observou-se que somente a SBR influenciou o aparecimento da taquicardia ventricular sustentada (p=0.028). Conclusão: A SBR está preservada na forma indeterminada da doença de Chagas e diminuída na forma arritmogênica. O comprometimento da SBR é progressivo e acompanha a evolução da doença, sendo mais intenso nos pacientes com arritmias ventriculares mais complexas. O grau de disfunção autonômica não se correlacionou com a função ventricular, mas, sim, com a densidade e a complexidade das arritmias / Introduction: Sudden death is the main cause of death in Chagas disease, corresponding to 55 to 65% of the cases. Some of these occur in patients with normal or almost normal left ventricular function (LVF), leading us to believe that factors that destabilize the arrhythmogenic substrate play an important role in these events. Evidences show parasympathetic depression to be a contributing factor in the genesis of diverse arrhythmias in the presence of ischemic heart disease. Thus, we insist on the need of an early identification of the patients, in the context of chronic Chagas heart disease, that are at increased risk of developing complex arrhythmic events. It is possible that autonomic assessment allows the identification of distinct risk subgroups. The objective of this study was to determine the baroreflex sensitivity (BRS) in patients with the indeterminate form of Chagas disease, (GI), and with the arrhythmogenic form of Chagas disease with nonsustained ventricular tachycardia (GII) and sustained ventricular tachycardia (GIII) and to assess the correlation between the severity of ventricular arrhythmia and the degree of BRS impairment. Methods: Forty-two patients were subjected to noninvasive cardiovascular monitoring using the Task Force® system. The phenylephrine method was used to determine BRS, 24- hour dynamic electrocardiography was used to analyze heart rate variability (HRV) over time and echocardiography was used to determine LVF. Results: A statistical difference was observed between the groups regarding their BRS to phenylephrine. GIII presented the lowest BRS value (6.09 ms/mmHg) when compared with GII (11.84ms/mmHg) and GI (15.23ms/mmHg). After multiple comparisons among the groups, a significant difference was found between GI and GIII (p=0.01). When BRS was correlated with ventricular extrasystole (VE) density, all patients who had low VE density (<10/hour) had preserved BRS (6.1ms/mmHg). On the other hand, only 59% of those with high EV density (>10/hour) had preserved BRS (p=0.003). In patients with moderately depressed BRS (3.0-6.0 ms/mmHg) there was a greater density of EV (p=0.01). Patients with preserved BRS had preserved or moderately compromised LVF (66.7% with LVF<40% and 79.5% with LVF40%; p=0.62) as had patients with moderately depressed BRS (15.4% with LVF<40% and 33.3% with LVF40%; p=0.46). There was no correlation between BRS and LVF. When the logistic regression model was applied, only BRS influenced the presence of sustained ventricular tachycardia (p=0.028). Conclusion: BRS is preserved in indeterminate Chagas disease and diminished in the arrhythmogenic form. The BRS impairment is progressive as the disease progresses, being more evident in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with ventricular function but with the density and complexity of the arrhythmias

Epilepsy is a neurological disorder that is characterized by aberrant electrical activity in the brain resulting in at least two unprovoked seizures over a period longer than 24 hours. Approximately 60% of individuals with epilepsy are diagnosed with temporal lobe epilepsy (TLE) and about one third of those individuals do not respond well to anti-seizure medications. This places those individuals at high risk for sudden unexpected death in epilepsy (SUDEP). SUDEP is defined as when an individual with epilepsy, who is otherwise healthy, dies suddenly and unexpectedly for unknown reasons. SUDEP is one of the leading causes of death in individuals with acquired epilepsies (i.e. not due to genetic mutations), such as TLE. Previous studies utilizing genetic models of epilepsy have suggested that circuitry within the vagal complex of the brainstem may play a role in SUDEP risk. Gamma-aminobutyric acid (GABA) neurons of the nucleus tractus solitarius (NTS) within the vagal complex receive, filter, and modulate cardiorespiratory information from the vagus nerve. GABAergic NTS neurons then project to cardiac vagal motor neurons, eventually effecting parasympathetic output to the periphery. In this study, a mouse model of TLE was used to assess the effect of epileptogenesis on GABAergic NTS neuron function and determine if functional alterations in these neurons impact SUDEP risk. It was discovered that mice with TLE (i.e. TLE mice) have significantly increased mortality rates compared to control animals, suggesting that SUDEP occurs in this model. Using whole cell electrophysiology synaptic and intrinsic properties of GABAergic NTS neurons were investigated in TLE and control mice. Results suggest that during epileptogenesis, GABAergic NTS neurons become hyperexcitable, potentially due to a reduction in A-type potassium channel current and increased excitatory synaptic input. Increases in hyperexcitability have been shown to be associated with an increased risk of spreading depolarization and action potential inactivation leading to neuronal quiescence. This may lead to a decreased inhibition of parasympathetic tone, causing cardiorespiratory collapse and SUDEP in TLE.

Abstract not available

This thesis tests the hypothesis that increased neuronal cell death in SIDS infants is related to the ability of risk factors, such as prone sleeping, to expose infants to intermittent hypercapnic hypoxia (IHH). Based on the hypothesis that the NMDA system is linked to neuronal death, by way of excitotoxicity, correlations were also sought between cell death and changes in NMDA receptor (NR1) expression in brainstem nuclei controlling cardiorespiratory function. The first aim of this study was to verify that increased neuronal cell death occurs in SIDS infants. To verify a piglet model of SIDS risk factors, brainstem changes were examined in piglets exposed to IHH, and comparisons were made to changes seen in SIDS infants. The NMDA receptor was characterised in controls for both the human infant and the piglet groups. Comparisons of neuronal changes were made with SIDS infants, and piglets exposed to IHH. Non-radioactive in-situ hybridisation and immunohistochemistry were performed on formalin fixed and paraffin embedded brainstem tissue to identify markers of cell death (caspase-3, active caspase-3, and TUNEL), and to examine NR1 mRNA and protein expressions. Staining was quantified using computerised image analysis software. Eight nuclei from the brainstem medulla (caudal in piglets, and mid in infants), and two nuclei from the rostral pons (infants) were studied. The first dataset included human infants aged 1-6 months with a diagnosis of SIDS (n=15) or non-SIDS (n=10). The second dataset comprised developing piglets aged 13-14 days, with controls (n=6), against those exposed to IHH for 2 (n=6) or 4 (n=5) days. Increased neuronal cell death was not verified in the SIDS infants, but abnormalities in NR1 expression were present in selected nuclei of the medulla. Piglets exposed to IHH had increased neuronal cell death and changes in NR1 in selected nuclei of the medulla. There was also a positive correlation between increased cell death and high NR1 levels. Preliminary data showed that SIDS infants who usually slept prone had some differences in NR1 compared to those who did not usually sleep prone. From these findings, it was concluded that IHH may underlie the abnormalities in NMDA receptor expression that are present in the brainstem of SIDS infants. Although IHH can induce an increase in neuronal cell death, its significance in the aetiology of SIDS is not known. In piglets, IHH induced cell death correlated with high NMDA expression in some brainstem nuclei, supporting the hypothesis that excitotoxicity may be involved in the mechanism for cell death. Moreover, this thesis presents for the first time, �preliminary pathological proof� of an association between prone sleeping and abnormal NMDA receptor expression in SIDS infants.

<p>Egentlig depression är en folksjukdom, men i dagsläget är kognitiv beteendeterapi, som fått mest stöd i depressionsforskning, en bristvara. Därav finns ett behov av att med begränsade resurser kunna hjälpa så många patienter som möjligt och då är Internetbaserad självhjälpsbehandling i ett alternativ vid mild till måttlig depression. Denna behandlingsform kan dock inte hjälpa alla, varför de som inte svarat på den inledande behandlingen som ett andra steg bör erbjudas mer intensiv och individualiserad vård; så kallad. stepped care. Vid depression uppvisar vissa patienter sudden gains, det vill säga relativt stora, snabba och stabila minskningar av symptom, som ofta bibehålls på lång sikt.</p><p>Syftet med studien var att undersöka effekten av stepped care vid mild till måttlig depression, vinna ökade kunskaper om sudden gains samt se om överlappningar mellan sudden gains och stepped care fanns.</p><p>85 deltagare inkluderades i studien, varav 69 randomiserades till Internetbaserad självhjälpsbehandling eller live gruppbehandling. Övriga deltagare utgjorde en preferensgrupp där de själva valt Internetbehandling. Båda behandlingsalternativen utgick från samma KBT-baserade behandlingsmoduler, som administrerades under åtta veckor samtidigt som veckovisa självskattningar med MADRS-S hämtades in. Efter avslutad behandling bedömdes vilka deltagare, bland dem som fått Internetbehandling, som var i behov av fortsatt vård och därmed skulle erbjudas ytterligare åtta sessioner med telefonterapi.</p><p>Efter de första åtta veckorna var 70 % av samtliga deltagare utan diagnos och 40 % av deltagarna hade uppvisat sudden gains. Endast 22 % visade sig vid eftermätningen behöva gå vidare till telefonterapi, varav 60 % tackade ja och 40 % fullföljde. Efter avslutad telefonterapi var 75 % av dessa deltagare utan diagnos. En begränsning med studien är att den endast är partiellt randomiserad. Slutsatsen är att den Internetbaserade självhjälpsbehandlingen var så effektiv att få deltagare behövde ytterligare vård i stepped care. De deltagare som uppvisade sudden gains mådde bättre än övriga vid behandlingens slut och fortsatte att må bättre vid enmånadsuppföljning.</p>