The dose-effect relationship in psychotherapy has been examined extensively, but few studies have included session frequency as a component of psychotherapy "dose." Those studies that have examined the effects of session frequency have indicated that it may affect both the total amount of recovery and the speed of recovery. No studies were found examining the clinical significance of this construct in a naturalistic setting. The change trajectories of 16,003 clients were examined using multi-level modeling and including session frequency as a fixed effect. Of these clients, subgroups were identified that were scheduled approximately once a week or approximately once every two weeks. These groups were compared to each other for differences in speed of recovery and clinically significant change. Results indicated that more frequent therapy was associated with steeper recovery curves. When comparing groups scheduled once a week to those scheduled once every two weeks, more clinically significant gains were identified in those attending once a week, and more significant deterioration was identified in those attending once every two weeks. These findings are discussed in light of the existing literature and the implications for future psychotherapy research and clinical practice.

La radiothérapie interne sélective (RTIS), en plein développement ces dernières années, constitue une alternative thérapeutique pour les cancers primaires et secondaires inopérables du foie. Le principe repose sur l’administration intra-artérielle de microsphères chargées d’yttrium-90 avec pour objectif la destruction des cellules tumorales par l’irradiation.L’activité d’yttrium-90 à administrer au patient est actuellement généralement prescrite à partir d’approches semi-empiriques ou peu personnalisées, faciles à mettre en place cliniquement. De nouveaux outils sont aujourd'hui disponibles semblables à ceux utilisés en radiothérapie externe. Leur utilisation encore peu répandue nécessite un retour d'expérience clinique pour mettre en avant leurs bénéfices et guider l'application clinique. Par ailleurs, le traitement RTIS est précédé d'une étape de simulation. Des différences inhérentes à cette procédure en deux temps (type de particules utilisées, modalité d’imagerie, modifications de flux vasculaires, etc.) existent et pourraient potentiellement conduire à des écarts dosimétriques entre la planification et le traitement. C’est dans ce contexte que s’inscrit le projet de cette thèse qui porte sur l'optimisation de la dosimétrie pour le traitement du carcinome hépatocellulaire par RTIS.Les doses délivrées au cours de 42 traitements par microsphères de résine réalisés entre 2012 et 2015 au CHU de Montpellier, ont été rétrospectivement calculées à l’échelle du voxel sur un logiciel de dosimétrie dédié (PLANET Dose, DOSIsoft, Cachan). Les doses délivrées ont été calculées pour le volume tumoral et le volume de foie sain définis anatomiquement, à partir de l’imagerie post-traitement TEP aux microsphères d’yttrium-90. Ce travail a mené à deux études complémentaires. La première analyse a consisté à confronter les données dosimétriques recueillies (doses moyennes, histogrammes dose-volume) à la réponse tumorale, la toxicité hépatique et la survie du patient. Les résultats obtenus, en accord avec ceux de la littérature, ont confirmé l’existence d’une relation dose-effet en RTIS. La deuxième étude a mis en évidence les limites du modèle BSA (body surface area pour surface corporelle) qui avait été utilisé pour planifier l’activité à administrer, à prédire la dose délivrée et par conséquent l’efficacité du traitement. L’absence de considérations dosimétriques et de prise en compte de l’hétérogénéité de distribution, de ce modèle ont notamment été discutées. Ces deux études ont ainsi souligné l'intérêt de planifier l'activité d'yttrium-90 à administrer en se basant sur des données dosimétriques individualisées.Une troisième étude a été conduite sur une population de 23 patients atteints de CHC, traités par microsphères de verre traités entre 2015 et 2018 au CHU de Montpellier. L’objectif a été de comparer les dosimétries prédictives et post-traitement calculées à l’échelle du voxel. Les résultats cliniques obtenus ont été appuyés par des expérimentations sur fantômes physiques (simple et anthropomorphique). Une bonne corrélation a été montrée, mettant en avant la valeur prédictive de la dosimétrie de planification. En revanche, un écart significatif a été observé et semble lié en partie à la quantification de l’imagerie TEP à l’yttrium-90. De plus, il a été montré que le geste radiologique peut influencer la distribution de particules et donc de dose, d’où la nécessité d’une reproductibilité aussi parfaite que possible entre les deux étapes. / Selective internal radiation therapy (SIRT) is a growing therapeutic alternative for unresectable primary and secondary liver cancer. The principle is based on the intra-arterial administration of yttrium-90 loaded microspheres for tumor cell destruction through irradiation.Yttrium-90 activity to be administered to the patient is, at the moment, usually prescribed using semi-empirical or barely personalized approaches that can be easily clinically implemented. New tools, similar to the ones used in external beam radiotherapy, are available today. These tools, which are not yet widely spread, require clinical feedback to show their benefits and guide the clinical application. Besides, a simulation stage is always performed before SIRT treatment itself. This two-step procedure implies differences (in terms of particles used, imaging modality, vascular flow modifications, etc.) that could potentially lead to dose deviations between planning and treatment. The thesis project comes within this scope, dealing with dosimetry optimization for hepatocellular carcinoma SIRT.Delivered doses during 42 treatment procedures performed between 2012 and 2015 at Montpellier University Hospital, were retrospectively calculated at the voxel level using a dosimetry dedicated software (PLANET Dose, DOSIsoft, Cachan). Two complementary studies were carried out from this work. The first one analyzed dose data (average dose, dose volume histograms) versus patient follow-up including tumor response, liver toxicity and patient survival. The results obtained are consistent with the other teams, confirming the dose-effect relationship in SIRT. The second study highlighted the limitations of the BSA (body surface area) model that was used for activity planning. In particular, the limitations of this model to predict delivered dose and consequently treatment efficiency were quantitatively demonstrated. The lack of dosimetry and heterogeneity distribution considerations were also discussed. These two studies emphasized the interest for yttrium-90 activity planning based on individualized dose data.A third study was conducted on a population of 23 patients treated between 2015 and 2018 at Montpellier University Hospital. The aim was to compare predictive and post-treatment dosimetry calculated at the voxel level. The clinical results were supported by phantom (simple and anthropomorphic) experimentations. A good correlation was observed highlighting the predictive value of dosimetry planning. However, a significant deviation was noticed and seems to be partly related to yttrium-90 TEP quantification. In addition, it was also noted that the radiological gesture can affect particle distribution and consequently dose distribution, this is why reproducibility as perfect as possible is required between the two stages.

Intensive Care Units (ICUs) account for over 10 percent of all US hospital beds, have over 4.4 million patient admissions yearly, approximately 360,000 deaths, and account for close to 30% of acute care hospital costs. The need for critical care services has increased due to an aging population and medical advances that extend life. The result is efforts to improve patient outcomes, optimize financial performance, and implement models of ICU care that enhance quality of care and reduce health care costs. This retrospective chart review study examined the dose effect of APN Intensivists in a surgical intensive care unit (SICU) on differences in patient outcomes, healthcare charges, SICU length of stay, charges for APN intensivist services, and frequency of APNs special initiatives when the SICU was staffed by differing levels of APN Intensivist staffing over four time periods (T1-T4) between 2009 and 2011. The sample consisted of 816 randomly selected (204 per T1-T4) patient chart data. Study findings indicated reported ventilator associated pneumonia (VAP) rates, ventilator days, catheter days and catheter associated urinary tract infection (CAUTI) rates increased at T4 (when there was the lowest number of APN Intensivists), and there was increased pressure ulcer incidence in first two quarters of T4. There was no statistically significant difference in post-surgical glycemic control (M = 142.84, SD= 40.00), t (223) = 1.40, p = .17, and no statistically significant difference in the SICU length of stay among the time-periods (M= 3.27, SD = 3.32), t (202) = 1.02, p= .31. Charges for APN services increased over the 4 time periods from $11,268 at T1 to $51,727 at T4 when a system to capture APN billing was put into place. The number of new APN initiatives declined in T4 as the number of APN Intensivists declined. Study results suggest a dose effect of APN Intensivists on important patient health outcomes and on the number of APNs initiatives to prevent health complications in the SICU.

Tesis por compendio / [ES] La obesidad representa un importante reto para la salud pública debido a su elevada prevalencia y a las comorbilidades asociadas. Las dietas hipercalóricas activan el sistema inmunitario intestinal y alteran la microbiota intestinal causando daños metabólicos en el organismo. De hecho, la pérdida de homeostasis inmunológica intestinal se considera un evento que precede a la aparición de la inflamación sistémica de bajo grado asociada a la obesidad. Dado que la microbiota intestinal es un factor modificable, su modulación puede convertirse en una oportunidad para reducir el impacto de la obesidad. Por ello la identificación de los factores que participan en la respuesta inflamatoria a las dietas obesogénicas y la búsqueda de alternativas terapéuticas basadas en la microbiota constituyen una vía de investigación prometedora para combatir la obesidad. Esta Tesis Doctoral evalúa el potencial de nuevos probióticos y estrategias dietéticas para combatir la obesidad basadas en sus propiedades inmunomoduladoras. En el Primer Capítulo investigamos el potencial anti-obesogénico del propil propano tiosulfinato (PTS), un compuesto organosulfurado derivado de la especie Allium, en dos dosis diferentes (0,1 o 1 mg/kg/día) utilizando un modelo murino de obesidad inducida por la dieta (DIO). Nuestros hallazgos demostraron los efectos protectores de PTS frente a la obesidad, ya que su administración redujo el peso corporal y mejoró la homeostasis de glucosa. En el tejido adiposo y el hígado, PTS redujo la inflamación y el metabolismo lipídico aberrante causado por la dieta obesogénica. Además, PTS incrementó la actividad termogénica en el tejido adiposo marrón y reforzó la función barrera intestinal. En vista de los modestos cambios en el ecosistema microbiano intestinal, concluimos que estos efectos no eran mediados por la microbiota. En el Segundo Capítulo evaluamos el potencial anti-obesogénico y el mecanismo de acción de una nueva bacteria llamada Phascolarctobacterium faecium DSM 32890. Para ello, realizamos diferentes experimentos in vitro e in vivo usando diferentes cultivos celulares (macrófagos derivados de médula ósea y células linfoides innatas intestinales del grupo 1 (LC1s)) y modelos murinos DIO (ratones C57BL/6J y Rag1-/-). El tratamiento de ratones alimentados con una dieta hipercalórica con P. faecium incrementó la proporción de los macrófagos M2 en el intestino, lo que contrarrestó el aumento de ILC1s y, en última instancia, mitigó la intolerancia a la glucosa y el aumento de peso corporal, independientemente de la viabilidad de la bacteria. Además, P. faecium reforzó la función barrera intestinal y evitó la inflamación sistémica causada por la dieta hipercalórica. Estos beneficios metabólicos se mantuvieron en ausencia de inmunidad adaptativa, pero se perdieron cuando la bacteria se coadministró con un inhibidor (GW2580) de la polarización de macrófagos M2. Por último, realizamos un amplio estudio con datos metagenómicos de 6.361 personas que mostró una relación inversa entre P. faecium y la obesidad, independientemente de la nacionalidad, el sexo o la edad, lo que sugiere la asociación de esta bacteria con la salud metabólica. En el Tercer Capítulo, investigamos la implicación de las ILC1s intestinales en la progresión de la obesidad y las alteraciones metabólicas asociadas. Para ello, evaluamos longitudinalmente la respuesta de las ILC1s y las consecuencias su depleción de ILC1s en un modelo murino DIO. En el intestino, el bloqueo de ILC1s evitó el aumento de macrófagos M1 e ILC2s y promovió la activación de la vía ILC3-IL22, aumentando la producción de mucina, la expresión de péptidos antimicrobianos y el número de células neuroendocrinas. Además, el bloqueo de ILC1s restableció el perfil microbiano y el metaboloma, acercándose al perfil asociado con la salud metabólica. En última instancia, estas mejoras se asociaron con una mayor secreción de hormonas intestinales, y una reducción de la insulinemia y la adiposidad. / [CA] L'obesitat és un repte per a la salut pública degut a la elevada prevalença i les comorbiditats. Les dietes hipercalòriques activen el sistema immunitari intestinal i alteren la microbiota intestinal causant danys metabòlics en l'organisme. De fet, la pèrdua d'homeòstasi immunològica a escala intestinal es considera un esdeveniment primerenc que precedeix l'aparició de la inflamació sistèmica de baix grau associada a l'obesitat. Atés que la microbiota intestinal és un factor modificable, la seua modulació pot convertir-se en una oportunitat per a reduir l'impacte de l'obesitat. Per això, la identificació dels factors que participen en la resposta inflamatòria a les dietes obesogèniques i la recerca d'alternatives terapèutiques basades en la microbiota son una via d'investigació prometedora per a combatre l'obesitat. Aquesta Tesi Doctoral avalua el potencial de nous probiòtics i estratègies dietètiques per a combatre l'obesitat basada en propietats immunomoduladores. En el Primer Capítol investiguem el potencial anti-obesogènic del propil propà tiosulfat (PTS), un compost organosulfurat derivat de l'espècie Allium, en dues dosis diferents (0,1 o 1 mg/kg/dia) utilitzant un model murí d'obesitat induïda per la dieta. Els resultats demostren els efectes protectors de PTS enfront a l'obesitat, ja que la seua administració va reduir el pes corporal i va millorar l'homeòstasi de glucosa. En el teixit adipós i el fetge, PTS va prevenir l'augment de la resposta inflamatòria i les alteracions del metabolisme lipídic causades per la dieta hipercalòrica. A més, PTS va incrementar l'activitat termogènica en el teixit adipós marró i millorà la funció barrera intestinal alterats per la dieta. Observàrem canvis modestos en la microbiota intestinal, concloent que els efectes no estan mediats de manera significativa per la microbiota. En el Segon Capítol avaluem el potencial anti-obesogènic i el mecanisme d'acció d'un nou bacteri Phascolarctobacterium faecium DSM 32890. Hem realitzat experiments in vitro i in vivo utilitzant diferents cultius cel·lulars (macròfags derivats de medul·la òssia i de cèl·lules limfoides innates intestinals del grup 1 (LC1s) i models murins d'obesitat induïda per la dieta (ratolins C57BL/6J, i Rag1-/- ). El tractament de ratolins alimentats amb una dieta hipercalòrica amb P. faecium incrementà la proporció dels macròfags M2 a l'intestí, contrarestant l'augment d'ILC1s i en última instància, mitigà la intolerància a la glucosa i l'augment del pes corporal, independentment de la viabilitat del bacteri. A més, P. faecium reforçà la funció bacterial intestinal i evità la inflamació sistèmica causada per la dieta hipercalòrica. Aquests beneficis metabòlics es mantenien en absència d'immunitat adaptativa, però es perderen quan el bacteri es coadministrà amb un inhibidor (GW2580) de la polarització de macròfags M2. Finalment, realitzàrem un ampli estudi amb dades metagenòmiques de 6.361 persones que mostrà una relació inversa entre P. faecium i l'obesitat, independentment de la nacionalitat, el sexe o l'edat, suggerint l'associació d'aquest bacteri amb la salut metabòlica. En el Tercer Capítol, investiguem la implicació de les ILC1s residents en l'intestí en la progressió de l'obesitat i les alteracions metabòliques associades. Evaluàrem longitudinalment la resposta de les ILC1s i les conseqüències de la depleció de ILC1s en un model murí d'obesitat. A l'intestí, el bloqueig de ILC1s va evitar l'augment de macròfags M1 i ILC2s, i va promoure l'activació de la via ILC3-IL22, augmentant la producció de mucina, l'expressió de pèptids antimicrobians i el nombre de cèl·lules neuroendocrines. El bloqueig de ILC1s va restablir la microbiota i el seu metaboloma, similar a l'estat saludable. Aquestes millores es van associar amb una major secreció d'hormones intestinals, i una reducció de la insulinèmia i l'adipositat. / [EN] Obesity is a major public health challenge due to its high prevalence, and association with metabolic comorbidities. Hypercaloric diets are known to overactivate the intestinal immune system and disrupt the microbiome, ultimately causing detrimental metabolic effects. The loss of intestinal immune homeostasis is considered an early step preceding the development of systemic low-grade inflammation associated with obesity and metabolic complications. In this regard, extensive evidence supports that the gut microbiome may be modified favorable and, thus, help to ameliorate these conditions. Hence, identifying factors triggering the low-grade inflammation and microbiome-base solutions to reduce the obesity burden represent promising avenues of research. This Doctoral Thesis aims to advance the knowledge and provide novel probiotics and dietary strategies to combat the burden of obesity based on their immunomodulatory properties to shape the metabolic response to the diet. In the First Chapter, we have investigated the anti-obesogenic potential of propyl propane thiosulfinate (PTS), an organo-sulfur compound derived from Allium species, at two different doses (0.1 or 1 mg/kg/day) using a murine model of diet-induced obesity (DIO). Our preclinical findings showed the protective effects of PTS against obesity, reducing body weight gain and maintaining glucose homeostasis, thus suggesting its potential to ameliorate the impact of the HFHSD. In the adipose tissue and the liver, PTS reduced inflammation and the aberrant lipid metabolism caused by the obesogenic diet. Additionally, PTS promoted thermogenic activity in the brown adipose tissue and enhance intestinal gut barrier defense. In view of the modest changes in the microbial ecosystem, we concluded that the effects of PTS were not mediated by the gut microbiota. In the Second Chapter, we have evaluated the anti-obesogenic potential and the mechanism of action of the new intestinal strain, Phascolarctobacterium faecium DSM 32890, isolated in our laboratory from a healthy volunteer. To that aim, we have performed different in vitro and in vivo experiments, including the use of different types of cell cultures (bone marrow-derived macrophages and group 1 of innate lymphoid cells (ILC1s)) and DIO murine models (wild-type C57BL/6J and Rag1-/- mice). Treatment of HFHSD-fed mice with P. faecium, regardless of its viability, shifted the macrophage phenotype towards an M2-type, which counteracted the obesity-induced increase in gut-resident ILC1s and ultimately mitigated glucose intolerance and body weight gain. Moreover, P. faecium treatment prevented systemic inflammation, boosted secretory immunoglobulin A production and induced antimicrobial peptide and interleukin 22 expression. These metabolic benefits were maintained in the absence of an adaptive immune system but were lost when the bacterium was co-administered with an inhibitor (GW2580) of M2 macrophage polarization. We confirmed that P. faecium was more prevalent in the gut metagenomes of non-obese adults regardless of nationality, sex or age, suggesting that it might contribute to safeguard metabolic health in humans. In the Third Chapter, we have investigated the involvement of gut-resident ILC1s in obesity progression and metabolic disruption. To address this goal, we evaluated longitudinally, in a DIO murine model, the ILC1s response to an obesogenic diet and the consequences of the ILC1s depletion. In the intestine, ILC1s depletion blunted the increases in M1 macrophages and ILC2s. Additionally, ILC1s depletion promoted the ILC3-IL22 pathway, increasing mucin production, the expression of antimicrobial gut peptides, and the number of neuroendocrine cells. Moreover, ILC1s depletion restored microbial and metabolomic profiles, resembling those associated with a healthy symbiotic state. The improvements in gut homeostasis were linked to a higher gut hormone secretion, and reduced insulinemia and adiposity. / Rebeca Liébana García has been beneficiary of an FPU contract (FPU 18/02026) and a mobility grant (EST22/00430) from Spanish Ministry of Universities. The experimental work conduced in this Doctoral Thesis has been funded by the Spanish Ministry of Science and Innovation (MICINN AGL2017-88801-P, PID2020-119536RB-I00), the Centre for the Development of Industrial Technology (CDTI, Ref 20170847), and the EU H2020 Marie Sklodowska Curie Actions (MSCA-IF “MicroILCs, GA: 8905454). / Liébana García, R. (2023). Effect and Mechanisms of Action of Intestinal Bacteria and Bioactive Compounds on the Immune System and Metabolism in Obesity Models [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/201910 / Compendio

The model used as the basis for regulation of human radiation exposures in the United States has been a source of controversy for decades because human health consequences have not been determined with statistically meaningful certainty for the dose levels allowed for radiation workers and the general public. This dissertation evaluates the evolution of the science and regulation of radiation health effects in the United States since the early 1900s using actor-network theory and the concept of co-production of science and social order. This approach elucidated the ordering instruments that operated at the nexus of the social and the natural in making institutions, identities, discourses, and representations, and the sociotechnical imaginaries animating the use of those instruments, that culminated in a regulatory system centered on the linear no-threshold dose-response model and the As Low As Reasonably Achievable philosophy. The science of radiation health effects evolved in parallel with the development of radiation-related technologies and the associated regulatory system. History shows the principle of using the least amount of radiation exposure needed to achieve the desired effect became established as a social convention to help avoid inadvertent harm long before there was a linear no-threshold dose-response model. Because of the practical need to accept some level of occupational radiation exposure, exposures from medical applications of radiation, and some de minimis exposure to the general public, the ALARA principle emerged as an important ordering instrument even before the linear no-threshold model had gained wide support. Even before ALARA became the law, it had taken hold in a manner that allowed the nuclear industry to rationalize its operations as representing acceptable levels of risk, even though it could not be proven that the established exposure limits truly precluded harm to the exposed individuals. Laboratory experiments and epidemiology indicated that a linear dose-response model appeared suitable as a "cautious assumption" by the 1950s. The linear no-threshold model proved useful to both the nuclear establishment and its detractors. In the hands of proponents of nuclear technologies, the model predicted that occupational exposures and exposures to the public represented small risks compared to naturally occurring levels of radiation and other risks that society deemed acceptable. Conversely, opponents of nuclear technologies used the model to advance their causes by predicting health impacts for undesirable numbers of people if large populations received small radiation exposures from sources such as fallout from nuclear weapon testing or effluents from nuclear reactor operations. In terms of sociotechnical imaginaries, the linear no-threshold model was compatible with both of the dominant imaginaries involved in the actor-network. In the technocratic imaginary of institutions such as the Atomic Energy Commission, the model served as a tool for qualified experts to make risk-informed decisions about applications of nuclear technologies. In the socially progressive imaginary of the citizen activist groups, the model empowered citizens to formulate arguments informed by science and rooted in the precautionary principle to challenge decisions and actions by the technocratic institutions. This enduring dynamic tension has led to the model retaining the status of "unproven but useful" even as the underlying science has remained contested. / Doctor of Philosophy / This dissertation provides a social science perspective on an enduring paradox of the nuclear industry: why is regulation of radiation exposure based on a model that everyone involved agrees is wrong? To answer that question, it was necessary to delve into the history of radiation science to establish how safety regulation began and evolved along with the understanding of radiation's health effects. History shows the philosophy of keeping radiation exposures as small as possible for any given application developed long ago when the health effects of radiation were very uncertain. This practice turned out to be essential as science started to indicate that there may not be a safe threshold dose below which radiation exposure had no potential for health consequences. By the 1950s, a combination of theory, experiments, health studies of the survivors of the World War II atomic bombings, and other evidence suggested that the risk of cancer was proportional to the amount of radiation a person received (i.e., linear). Although this "linear no-threshold" model was far from proven, both sides used it in debates over nuclear weapon testing and safety standards for nuclear reactors in the 1950s through the early 1970s. Since the model predicted small health risks for the levels of radiation experienced by radiation workers and the public, nuclear advocates used it to argue that the risks were smaller than many other risks that people accept every day. At the same time, opposing activists used the model to argue that small cancer likelihoods added up to a lot of cancers when large populations were exposed. This decades-long discourse effectively institutionalized the model. The model's "unproven but useful" status was strengthened in the early 1970s when the Atomic Energy Commission supplemented its numeric exposure limits by turning the longtime practice of dose minimization into a requirement. This "As Low As Reasonably Achievable" requirement plays a vital role in rationalizing why a non-zero exposure limit is safe enough despite the fact that the linear no-threshold model treats any amount of radiation as harmful.

Studies on relations between number of sessions and effect of psychotherapy have usually assumed a constant rate of change across different lengths of therapy, explained by a model called the dose-effect model. This assumption has been challenged by the good-enough level (GEL) model, which makes the prediction that the rate of change will vary as a function of total number of sessions. This study aimed to compare these models. We also assessed the relationship between reliable and clinically significant change (RCSI) and total dose of therapy. Participants were drawn from two datasets in the Swedish primary care (n = 640) and adult psychiatric care (n = 249). The participants made session-wise ratings on the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM). Multilevel analyses indicated a better fit using the GEL-model, with some reservations concerning RCSI and patterns of change. The results may indicate a general lawful relationship that may have implications for future research, as well as psychotherapy practice and policy making.

Nesta dissertação é apresentado o estudo da célula SRAM estática de 6 transistores, com tecnologia CMOS, sendo utilizada em ambiente exposto à radiação. Foi verificado, através de simulação com o Hspice (HSPICE, 2009; KIME, 1998) e com a análise de Monte Carlo, o seu comportamento com relação à dose de ionização total (Total Ionization Dose, TID), a qual altera a tensão de limiar (threshold voltage, Vth) e a corrente de fuga, não sendo utilizada nenhuma técnica de fabricação especial para tolerância à radiação. Na simulação foi observado o comportamento da célula com relação ao tempo de atraso de escrita, à margem de ruído de leitura e ao consumo de energia. As simulações incluem as tecnologias de 130nm e 350nm sendo, portanto, possível comparar os efeitos de radiação citados em ambas, para verificar qual é a mais naturalmente resistente a radiação, verificando se está coerente com resultados divulgados na literatura. Para simular o efeito de dose, altera-se a tensão de limiar (threshold voltage, Vth) com a análise de Monte Carlo e, para a corrente de fuga, adiciona-se uma fonte de corrente entre o dreno e fonte de cada transistor. Os valores de Vth e corrente de fuga foram obtidos nas referências (HAUGERUD, 2005) para a tecnologia 130nm e (LACOE, 1998) para a tecnologia 350 nm. As simulações mostram que o comportamento foi coerente com resultados já conhecidos, em que a tecnologia mais antiga (350nm) tem alterações mais significativas do que a tecnologia mais atual, em relação à TID. / This work presents the study of the static RAM (SRAM) cell with 6 transistor, using CMOS technology, under radiation environment. The electrical behavior of the cell is evaluated using SPICE simulation (HSPICE, 2009; KIME, 1998) and applying Monte Carlo analysis. The effect of total ionization dose is analyzed through the modeling of threshold voltage shifts and leakage currents. The case study processes of this work do not use any special fabrication steps to make the circuit tolerant to radiation. The behavior of the cell related to write propagation time, read noise margin and energy consumption is evaluated through scripts written to support the simulation campaign. The simulations were performed for both 130nm and 350nm technologies, making possible to compare which one is more resistant to radiation. To further explore the dose effect in the case where the radiation does not affect all transistors in exactly the same way, the threshold voltage (Vth) of the transistors is varied randomly in the Monte Carlo analysis. To consider the leakage current, it is added a current source between drain and source of each transistor. The values of Vth and leakage current were obtained in reference (HAUGERUD, 2005) for the 130nm and in reference (LACOE, 1998) for the 350nm technology. The simulations show that the behavior was consistent with results already known, in which the older technology (350nm) is more significant changes then the most current technology, for the TID.

Nesta dissertação é apresentado o estudo da célula SRAM estática de 6 transistores, com tecnologia CMOS, sendo utilizada em ambiente exposto à radiação. Foi verificado, através de simulação com o Hspice (HSPICE, 2009; KIME, 1998) e com a análise de Monte Carlo, o seu comportamento com relação à dose de ionização total (Total Ionization Dose, TID), a qual altera a tensão de limiar (threshold voltage, Vth) e a corrente de fuga, não sendo utilizada nenhuma técnica de fabricação especial para tolerância à radiação. Na simulação foi observado o comportamento da célula com relação ao tempo de atraso de escrita, à margem de ruído de leitura e ao consumo de energia. As simulações incluem as tecnologias de 130nm e 350nm sendo, portanto, possível comparar os efeitos de radiação citados em ambas, para verificar qual é a mais naturalmente resistente a radiação, verificando se está coerente com resultados divulgados na literatura. Para simular o efeito de dose, altera-se a tensão de limiar (threshold voltage, Vth) com a análise de Monte Carlo e, para a corrente de fuga, adiciona-se uma fonte de corrente entre o dreno e fonte de cada transistor. Os valores de Vth e corrente de fuga foram obtidos nas referências (HAUGERUD, 2005) para a tecnologia 130nm e (LACOE, 1998) para a tecnologia 350 nm. As simulações mostram que o comportamento foi coerente com resultados já conhecidos, em que a tecnologia mais antiga (350nm) tem alterações mais significativas do que a tecnologia mais atual, em relação à TID. / This work presents the study of the static RAM (SRAM) cell with 6 transistor, using CMOS technology, under radiation environment. The electrical behavior of the cell is evaluated using SPICE simulation (HSPICE, 2009; KIME, 1998) and applying Monte Carlo analysis. The effect of total ionization dose is analyzed through the modeling of threshold voltage shifts and leakage currents. The case study processes of this work do not use any special fabrication steps to make the circuit tolerant to radiation. The behavior of the cell related to write propagation time, read noise margin and energy consumption is evaluated through scripts written to support the simulation campaign. The simulations were performed for both 130nm and 350nm technologies, making possible to compare which one is more resistant to radiation. To further explore the dose effect in the case where the radiation does not affect all transistors in exactly the same way, the threshold voltage (Vth) of the transistors is varied randomly in the Monte Carlo analysis. To consider the leakage current, it is added a current source between drain and source of each transistor. The values of Vth and leakage current were obtained in reference (HAUGERUD, 2005) for the 130nm and in reference (LACOE, 1998) for the 350nm technology. The simulations show that the behavior was consistent with results already known, in which the older technology (350nm) is more significant changes then the most current technology, for the TID.

Nesta dissertação é apresentado o estudo da célula SRAM estática de 6 transistores, com tecnologia CMOS, sendo utilizada em ambiente exposto à radiação. Foi verificado, através de simulação com o Hspice (HSPICE, 2009; KIME, 1998) e com a análise de Monte Carlo, o seu comportamento com relação à dose de ionização total (Total Ionization Dose, TID), a qual altera a tensão de limiar (threshold voltage, Vth) e a corrente de fuga, não sendo utilizada nenhuma técnica de fabricação especial para tolerância à radiação. Na simulação foi observado o comportamento da célula com relação ao tempo de atraso de escrita, à margem de ruído de leitura e ao consumo de energia. As simulações incluem as tecnologias de 130nm e 350nm sendo, portanto, possível comparar os efeitos de radiação citados em ambas, para verificar qual é a mais naturalmente resistente a radiação, verificando se está coerente com resultados divulgados na literatura. Para simular o efeito de dose, altera-se a tensão de limiar (threshold voltage, Vth) com a análise de Monte Carlo e, para a corrente de fuga, adiciona-se uma fonte de corrente entre o dreno e fonte de cada transistor. Os valores de Vth e corrente de fuga foram obtidos nas referências (HAUGERUD, 2005) para a tecnologia 130nm e (LACOE, 1998) para a tecnologia 350 nm. As simulações mostram que o comportamento foi coerente com resultados já conhecidos, em que a tecnologia mais antiga (350nm) tem alterações mais significativas do que a tecnologia mais atual, em relação à TID. / This work presents the study of the static RAM (SRAM) cell with 6 transistor, using CMOS technology, under radiation environment. The electrical behavior of the cell is evaluated using SPICE simulation (HSPICE, 2009; KIME, 1998) and applying Monte Carlo analysis. The effect of total ionization dose is analyzed through the modeling of threshold voltage shifts and leakage currents. The case study processes of this work do not use any special fabrication steps to make the circuit tolerant to radiation. The behavior of the cell related to write propagation time, read noise margin and energy consumption is evaluated through scripts written to support the simulation campaign. The simulations were performed for both 130nm and 350nm technologies, making possible to compare which one is more resistant to radiation. To further explore the dose effect in the case where the radiation does not affect all transistors in exactly the same way, the threshold voltage (Vth) of the transistors is varied randomly in the Monte Carlo analysis. To consider the leakage current, it is added a current source between drain and source of each transistor. The values of Vth and leakage current were obtained in reference (HAUGERUD, 2005) for the 130nm and in reference (LACOE, 1998) for the 350nm technology. The simulations show that the behavior was consistent with results already known, in which the older technology (350nm) is more significant changes then the most current technology, for the TID.

This study examines psychotherapy response in connection to treatment duration and maintenance of treatment gains. The dose-effect perspective (Howard et al. 1986) first proposed applying medical terminology to investigate a level of exposure to a dose of psychotherapy (in number of sessions) where individuals can expect to receive sufficient benefit (i.e., 48 -- 58% of clients can be expected to sufficiently benefit from therapy by 8 sessions). The proponents of the Good Enough Level (Barkham et at. 2006) argued that mere exposure to therapy is not an effective measure for client benefit, but rather that client responses to therapy vary. They contend that instead of recommendations for attending a certain number of sessions (dose-effect) that individuals who attend psychotherapy will discontinue attending therapy when they have obtained sufficient benefit (good enough level). Archival data of university students who previously attended individual therapy were obtained and subjects were contacted via email to take a survey and follow up measure of general well being. Those individuals who completed the Outcome Questionnaire-45 were selected for the study and their treatment response was analyzed in connection to treatment duration measured in number of sessions attended. 288 met criteria for the current study, consisting of 197 women and 91 men ranging in age from 17 to 52 (M= 21). Conclusions obtained from this study indicate that treatment duration is not a factor in subjects having positive outcomes to psychotherapy. Additionally, there was not a significant difference among subjects who were able to maintain treatment gains and the number of session attended in treatment. These results offer support for the Good Enough Level model of treatment response suggesting that individuals respond to therapy differently and discontinue when they have received sufficient benefit. Implications for these findings are discussed along with limitations of the current study.