Objectives: Negative energy balance can impair regeneration of the respiratory epithelium and limit the functionality of respiratory muscles, which can prolong mechanical ventilation. The present study sought to quantify and identify deviation in energy requirements of patients with septic shock during and upon liberation from mechanical ventilation. Methods: Patients admitted into intensive care with initial diagnosis of septic shock and mechanical ventilation-dependent were recruited. Their metabolic requirements before and after liberation from mechanical ventilation were measured by indirect calorimetry. Paired t-test was used to examine the variance between the two modes of breathing and Spearman rho correlation coefficient to examine relationship of selected indicators. Results: Thirty-five patients, 20 males and 15 females mean age 69 ±10 years, body height of 1.58 ±0.08 meters, and ideal body weight 59.01 ±7.63 kg were recruited. Median APACHEII score was 22, length of stay in the intensive care was 45 ±65 days and duration on mechanical ventilation was 24 ±25 days. Measured energy expenditure during ventilation was 2090 ±489 kcal∙d-1 upon liberation from ventilation was 1910 ±579 kcal∙d-1, and actual caloric intake was 1148 ±495 kcal∙d-1. Paired-t test showed that measured energy expenditure (p=0.02), actual calories provision and energy expenditure with (p=0.00) and without (p=0.00) ventilator support were all significantly different. Mean carbohydrate oxidation was 0.17 ±0.09 g·min-1 when patients were on mechanical ventilation compared to 0.14 ±0.08 g·min-1 upon liberalization from it, however, the results were not statistically significant. Furthermore, mean lipid oxidation was 0.08 ±0.05 g·min-1 during mechanical ventilation and 0.09±0.07 g·min-1 upon liberalization from it and the mean difference was not statistically significant. Spearman correlation coefficient showed a positive relationship between actual calorie provision and duration of stay in intensive care (r=0.41 and p=0.01) and duration on mechanical ventilation (r=0.55 and p=0.00). Oxygen consumption (r=0.49 and p=0.00) and carbon dioxide production (r=0.4 and p=0.02) were moderately strong and positive during and upon liberation from mechanical ventilation. Correlation between lipid oxidation and oxygen consumption during ventilation (r=0.74, p=0.00) and after ventilation (r=0.82, p=0.00) as well as lipid oxidation and carbon dioxide production during ventilation (r=0.37, p=0.03) and liberation from ventilator (r=0.91, p=0.00) were significantly correlated with each other in grams per minute only. Conclusions: This is a pioneering study to examine energy expenditure and substrate utilization and oxidation within a single cohort of patients. The lower measured energy expenditure upon liberation from mechanical ventilation among critically ill patients could result from positive pressure support from ventilation, the repeated cycle of “rest” and “work” during weaning from ventilators and the asynchronization between self-initiated breathing effort and the ventilatory support. The positive relationship in duration on mechanical ventilation and length of stay with calorie consumption could be longer stay led to more time for progression to reach nutrition targets. . Any discrepancy in energy expenditure and substrate utilization with and without ventilatory support should be monitored. Future studies are important to examine whether matching energy expenditure with energy intake could promote positive clinical outcomes.

Introdução: A prevalência da obesidade infanto juvenil tem aumentado, sendo importante que mais profissionais estejam habilitados para o manejo. Objetivo: Comparar o efeito, após 12 meses, de três intervenções: programa de atividade física (AF), manejo dietoterápico (D) e atendimento ambulatório de referência em um hospital terciário (AMO) sobre o índice de massa corporal (IMC), composição corporal, taxa metabólica (TMB) e perfil metabólico de crianças e adolescentes com obesidade. Procedimentos Metodológicos: Ensaio clínico randomizado em 82 sujeitos de 8 a 15 anos, com obesidade. No grupo D, recebia dieta ajustada a partir da TMB por calorimetria indireta; no grupo AF, educador físico orientava prática de AF no domicílio e, no grupo AMO, orientações para introdução e manutenção de hábitos saudáveis. O acompanhamento foi mensal e os dados antropométricos, composição corporal, taxa metabólica basal e exames laboratoriais foram determinados no início, aos 6 e 12 meses de seguimento. O projeto foi aprovado pelo Comitê de Ética e Pesquisa do HCPA número 10-0011 e registrado www.clinicaltrials.gov NCT012973774. Resultados: Foram avaliados 82 sujeitos. A diferença (percentual) entre os grupos AF, D e AMO, respectivamente, foi de: escore Z do IMC -7,1% (-10,8 a -3,3), -5,0% (-8,4 a -1,5) e –15,2%(- 19,5 a -10,9); p=0,001; Peso (Kg) massa gorda 9,2% (4,3 a 14,2), 10,4% (4,8 a 15,9) e 4,3% (-1,7 a 10,4), p=0,248; Peso(Kg) massa livre de gordura 10,5%(7,5 a 13,4), 7,0% (4,1 a 10,0) e 6,7% (2,8 a 10,7) p=0,203; TMB 50,3%(2,2 a 232), 31,6%(-23,7 a 147), 38,6%(-17,3 a 232), p=0,669. As alterações laboratoriais mais frequentes no início do estudo nos grupos AMO, AF e D foram, respectivamente, valor HDL baixo (82,1%, 77,8%, 63%), insulina jejum 15 μUI/mL (71,4%, 81,5% e 66,7%) e homeostasis model assessment insulin resistence índex alterado (67,9%, 81,5%, 63%). O diagnóstico de síndrome metabólica (SM) foi feito em 20% das crianças obesas. No grupo AMO houve redução maior significativa do escore Z do IMC, da circunferência da cintura (CC), aumento do valor do HDL, redução da insulina de jejum e do HOMA-IR, redução da pressão sistólica e no número de componentes da SM. No grupo AF houve uma redução maior no colesterol total, no valor do LDL e dos triglicerídeos (TG). O grupo D também mostrou melhora no escore Z do IMC, redução do valor do colesterol total (CT), do LDL e dos TG. Apesar da redução dos indivíduos com diagnóstico de síndrome metabólica no grupo AMO (de 7 para 2) e AF (de 4 para 1) não houve diferença significativa quando comparados os 3 grupos. Conclusões: As três intervenções foram efetivas no tratamento da obesidade de crianças e adolescentes. Este estudo comprova a necessidade de estratégias combinadas e a longo prazo no manejo da obesidade na criança e adolescente para reduzir as alterações cardio metabólicas presentes nesta população e evitar a progressão dos fatores de risco para doenças cardiovasculares, metabólicas e morte prematura. Portanto, estas 3 estratégias podem ser utilizadas no manejo da obesidade infanto juvenil. / Background: The prevalence of paediatric obesity has increased in recent years, and health care workers must be trained to treat these conditions. Objective: To compare the effect of three year-long interventions: physical activity (PA) programme, dietary intervention (D) and treatment in an outpatient obesity clinic (OOC), on the body mass index (BMI), body composition, basal metabolic rate (BMR) and biochemical measurements of children and adolescents with obesity. Methodological Procedures: Randomized clinical trial of 82 participants aged between 8 and 15, diagnosed with obesity. Participants in the PA group received individualised home-based physical activity programmes from a physical education teacher. In the D group, participants received dietary counselling based on BMRs as measured by indirect calorimetry. In the OOC group, participants were given instructions on how to adopt and maintain healthy lifestyle habits. Participants had monthly appointments with physical educators, nutritionists or health care workers, depending on participant group. Anthropometric data, body composition, BMR and biochemical measurements were assessed at baseline, and after 6 and 12 months of treatment. Project approved by Comitê de Ética e Pesquisa do HCPA número 10-0011 and registred www.clinicaltrials.gov NCT012973774. Results: Differences between the PA, D and OOC groups over the course of the study were as follows: BMI Z score -7.1% (-10.8 to -3.3), -5.0% (-8.4 to -1.5) and –15.2%(-19.5 to -10.9); p=0.001; Fat mass (Kg) 9,2% (4,3 a 14,2), 10,4% (4,8 a 15,9) and 4,3% (-1,7 a 10,4), p=0,248; Fat-free mass weight(Kg) 10.5%(7.5 to 13.4), 7.0% (4.1 to 10.0) and 6.7% (2.8 to 10.7) p=0.203; BMR 50.3%(2.2 to 232), 31.6%(-23.7 to 147), 38.6%(-17.3 to 232), p=0.669. The most frequent laboratory anormalities at baseline in groups OOC, PA and D were, respectively, value low HDL (82.1%, 77.8%, 63%), fasting insulin 15 μUI / mL (71.4% , 81.5% and 66.7%) and high homeostasis model assessment insulin resistence index (67.9%, 81.5%, 63%). The diagnosis of metabolic syndrome was made in 20% of obese children. OOC group was significantly greater reduction in BMI Z score, waist circumference, total cholesterol, increasing the value of HDL, reduced fasting insulin and HOMA-IR, systolic blood pressure reduction and the number of metabolic syndrome components. In the PA group, there was a greater reduction in total cholesterol in the amount of LDL and TG. Group D also showed improvement in BMI Z score, reducing the value of total cholesterol, LDL and TG. Despite the reduction of individuals diagnosed with metabolic syndrome in the group OOC (7 to 2) and PA (4 to 1) no significant difference when comparing the three groups. Conclusions: All three interventions led to a reduction in BMI Z score, and increased fat free mass, BMR and biochemical measurements over the course of a year. This study demonstrates the need for combined strategies and long-term management of obesity in children and adolescents to reduce cardio metabolic changes present in this population and prevent the progression of risk factors for cardiovascular and metabolic diseases and premature death. Therefore, all three interventions are suitable treatments for paediatric obesity.

A presente tese se ocupa da percepção fônica de línguas não nativas e tem como objetivo repensar as premissas básicas do PERCEPTUAL ASSIMILATION MODEL-L2 [PAM-L2 (BEST; TYLER, 2007)] no que diz respeito aos seus eixos cognitivo, fônico e filosófico. De acordo com os proponentes do modelo, (i) a percepção da fala não nativa dispensa mecanismos cognitivos no que se refere a representações mentais ou processos inferenciais; (ii) a unidade de análise do evento perceptual, em termos de fala, é o gesto articulatório; e (iii) o acesso às informações disponíveis no mundo é direto, garantido pela atuação dos sentidos como nossos próprios sistemas perceptuais. Julgamos que tais premissas são limitadas e incoerentes com o objeto de investigação dos autores e argumentamos, portanto, que os eixos cognitivo, fônico e filosófico do modelo devam ser vislumbrados sobre um ponto de vista alternativo. Quanto ao primeiro eixo, defendemos que o evento perceptual seja concebido essencialmente como um fenômeno cognitivo, criado e gerenciado pelo encéfalo, que envolve abstrações, representações mentais e inferências acerca dos objetos do mundo. Em relação ao segundo eixo, julgamos que o tratamento acústico-articulatório (ALBANO, 2001) à unidade gestual seja mais apropriado à percepção de elementos fônicos não nativos, diferindo do tratamento articulatório (BROWMAN; GOLDSTEIN, 1989, 1992) que reside originalmente no modelo. No que diz respeito ao terceiro eixo, adotamos a posição realista indireta (JACKSON, 1977, 2010) como sendo aquela que abarca de modo mais adequado a percepção das unidades fônicas não nativas, em detrimento do realismo direto (J. GIBSON, 1966, 1986). Decorrentes de nosso refinamento teórico, questões adicionais à percepção fônica não nativa são endereçadas, as quais concernem à falsa dicotomia L2 VS. LE, à influência do sistema grafêmico sobre a percepção fônica e à formação de novas categorias fônicas a serviço do idioma-alvo. Discutimos, também, os aspectos metodológicos de alguns estudos perceptuais, assim como suas implicações para uma nova caracterização do modelo, e ponderamos sobre o delineamento, o tipo de conhecimento de base testado (língua materna ou não nativa) e o objetivo de cada tarefa perceptual a ser empregada em ambiente laboratorial. / This Doctoral Dissertation addresses the phonic perception of non-native languages and aims to rethink the central tenets of the PERCEPTUAL ASSIMILATION MODEL-L2 [PAM-L2 (BEST; TYLER, 2007)] with respect to its cognitive, phonic and philosophical spheres. According to the proponents of the model, (i) the perception of non-native speech disregards any cognitive mechanisms related to mental representations or inferential processes; (ii) the unit for analyzing perceptual events, in terms of speech, corresponds to the articulatory gesture; and (iii) we have direct access to the information available in the world, since our senses act as our own perceptual systems. We argue that these premises are limited and inconsistent with the research object of the authors and, thus, we assume that the cognitive, phonic and philosophical spheres of the model should be glimpsed from an alternative point of view. As for the first sphere, we argue that the perceptual event is essentially a cognitive phenomenon, created and managed by the brain, which involves abstractions, mental representations and inferences about the objects of the world. Regarding the second sphere, we state that an acoustic-articulatory treatment (ALBANO, 2001) to the gestural unit is more appropriate to the perception of non-native phonic elements, differing from the articulatory treatment (BROWMAN; GOLDSTEIN, 1989, 1992) that is originally conveyed by the model. With respect to the third sphere, opposing direct realism (J. GIBSON, 1966, 1986), we adopt the indirect realist position (JACKSON, 1977, 2010) as the one that encompasses the perception of non-native phonic units more adequately. Due to our theoretical refinement, we address additional issues to the phonic perception, which concern the false L2 vs. LE dichotomy, the impact of graphical systems on phonic perception, and the formation of new phonic categories at the service of the target language. We discuss methodological aspects of perceptual studies, as well as their implications for a new characterization of the model, and we also consider the design, the type of knowledge tested (native or nonnative language) and the purpose of each perceptual task to be used in a laboratory environment.

O objetivo desse trabalho foi avaliar a biocompatibilidade de diferentes agentes cimentantes (Ketac Cem Easy Mix 3M ESPE e RelyX Unicem 3M ESPE) microscopicamente, por meio de implantes em tecido conjuntivo subcutâneo de camundongos isogênicos; microscópica e radiograficamente, após aplicação em cavidades profundas, próximas à polpa, em dentes de cães. No estudo em tecido conjuntivo subcutâneo foram utilizados quarenta camundongos isogênicos da linhagem BALB/c divididos em 9 grupos com 3 períodos experimentais: Grupo I: Ketac Cem Easy Mix (7 dias), Grupo II: RelyX Unicem (7 dias), Grupo III: tubo de polietileno vazio (7 dias), Grupo IV: Ketac Cem Easy Mix (21 dias) Grupo V: RelyX Unicem (21 dias), Grupo VI: tubo de polietileno vazio (21 dias), Grupo VII: Ketac Cem Easy Mix (63 dias), Grupo VIII: RelyX Unicem (63 dias), Grupo IX: tubo de polietileno vazio (63 dias). No estudo em dentes de cães foram utilizados quarenta dentes (80 raízes) de 4 cães, distribuídos em 6 grupos: Grupo I: Ketac Cem Easy Mix (7 dias), Grupo II: RelyX Unicem (7 dias), Grupo III: Cimento de óxido de zinco e eugenol (7 dias), Grupo IV: Ketac Cem Easy Mix (70 dias) Grupo V: RelyX Unicem (70 dias), Grupo VI: Cimento de óxido de zinco e eugenol (70 dias). A análise microscópica no tecido conjuntivo subcutâneo foi realizada em microscópio de luz comum, baseada nos seguintes parâmetros: infiltrado inflamatório (celularidade e tipo de célula) e reparo tecidual. Na análise microscópica em dentes de cães, foi registrada a descrição completa das características da dentina, polpa e tecidos periapicais de acordo com os seguintes aspectos: Presença de polpa normal; Presença de dentina reacional; Presença de ulceração; Pulpite e Presença de necrose pulpar, sendo os resultados submetidos à análise estatística utilizando-se o teste exato de Fisher (p<0,05). A avaliação radiográfica foi realizada por meio de radiografias periapicais obtidas previamente à execução dos atos operatórios e após os períodos experimentais, com relação à integridade da lâmina dura, presença ou ausência de reabsorções radiculares e áreas de rarefação óssea periapical. Os resultados da análise microscópica evidenciaram que, quando empregados sobre a dentina, ambos os cimentos não ocasionaram reações pulpares insatisfatórias. No entanto, quando colocados diretamente sobre o tecido pulpar, desencadearam reação inflamatória intensa, com necrose pulpar e desenvolvimento de reação periapical. No tecido conjuntivo subcutâneo de camundongos, o Ketac Cem Easymix apresentou resposta inflamatória e fenômenos reacionais intensos em todos os períodos analisados. Já o RelyX Unicem apresentou resposta inflamatória discreta com reparo tecidual nos períodos mais tardios. Podemos concluir que os cimentos RelyX Unicem e Ketac Cem Easymix apresentaram resultados satisfatórios, quando empregados na dentina de cavidades profundas, sem exposição pulpar. No entanto, quando em contato com o tecido conjuntivo subcutâneo e com o tecido pulpar em microexposições apresentaram resultados insatisfatórios. / The purpose of this study was to evaluate the biocompatibility of different luting agents (Ketac Cem Easy Mix 3M ESPE and RelyX Unicem 3M ESPE), microscopically, by means of implants in the subcutaneous connective tissue of isogenic mice; microscopically and radiographically, after application to deep cavities, close to the pulp, in dogs teeth. In the study in subcutaneous connective tissue, 40 isogenic BALB/c mice were allocated in 9 groups with 3 experimental periods: Group I: Ketac Cem Easy Mix® (7 days), Group II: RelyX Unicem (7 days), Group III: empty polyethylene tube (7 days), Group IV: Ketac Cem Easy Mix (21 days) Group V: RelyX? Unicem (21 days), Group VI: empty polyethylene tube (21 days), Group VII: Ketac Cem Easy Mix (63 days), Group VIII: RelyX Unicem (63 days), Group IX: empty polyethylene tube (63 days). In the study in the pulp tissue of dogs teeth, 40 teeth (80 roots) of 4 dogs were used and assigned to 6 groups: Group I: Ketac Cem Easy Mix (7 days), Group II: RelyX Unicem (7 days), Group III: zinc oxide and eugenol cement (7 days), Group IV: Ketac Cem Easy Mix (70 days) Group V: RelyX Unicem (70 days), Group VI: zinc oxide and eugenol cement (70 days). The microscopic analysis of the subcutaneous connective tissue was performed under standard ligth microscopy, according to the following parameters: presence of inflammatory infiltrate (cellularity and cell type) and tissue repair. In the microscopic analysis in dogs teeth, a comprehensive description of dentin, pulp and periapical tissue characteristics was undertaken, based on the following aspects: presence of normal pulp; presence of reparative dentin; presence of ulceration; presence of pulpitis; and presence of pulp necrosis. The radiographic evaluation was performed by means of the analysis of periapical radiographs taken before the operative procedures and at the experimental periods, with respect to the integrity of the lamina dura, presence or absence of root resorptions and areas of periapical bone rarefaction. The results of the microscopic analysis demonstrated that, when applied to dentin, both cements did not cause adverse pulp reactions. Nevertheless, when applied directly to the pulp tissue, the luting agents triggered an intense inflammatory response, with pulp necrosis and development of periapical reaction. In the subcutaneous connective tissue of mice, Ketac Cem Easymix induced an inflammatory response and intense reactive phenomena at all analyzed periods. On the other hand, RelyX Unicem induced a discrete inflammatory response with tissue repair at the later periods. It may be concluded that RelyX Unicem and Ketac Cem Easymix luting agents presented satisfactory results when applied to the dentin of deep cavities without pulp exposure. However, when placed in contact with the subcutaneous connective tissue and pulp tissue in areas of micro-exposures, these materials presented unsatisfactory results.

<div>Previous studies have shown that implementing trajectory optimization can reduce state estimations errors. These navigation based path planning problems are often diffcult to solve being computationally burdensome and exhibiting other numerical issues, so former studies have often used lower-delity methods or lacked explanatory power.</div><div><br></div><div><div>This work utilizes indirect optimization methods, particularly optimal control theory, to obtain high-quality solutions minimizing state estimation errors approximated by a continuous-time extended Kalman lter. Indirect methods are well-suited to this because necessary conditions of optimality are found prior to discretization and numerical computation. They are also highly parallelizable enabling application to increasingly larger problems.</div></div><div><br></div><div><div>A simple one dimensional problem shows some potential obstacles to solving problems of this type including regions of the trajectory where the control is unimportant. Indirect trajectory optimization is applied to a more complex scenario to minimize location estimation errors of a single cart traveling in a 2-D plane to a goal location and measuring range from a xed beacon. This resulted in a 96% reduction of the location error variance when compared to the minimum time solution. The single cart problem also highlights the importance of the matrix that encodes the linearization of the vehicle's measurement with respect to state. It is shown in this case that the vehicle roughly attempts to maximize the magnitude of its elements. Additionally, the cart problem further illustrates problematic regions of a design space where the objective is not signicantly affected by the trajectory.</div></div><div><br></div><div><div>An aircraft descent problem demonstrates the applicability of these methods to aerospace problems. In this case, estimation error variance is reduced 28.6% relative to the maximum terminal energy trajectory. Results are shown from two formulations of this problem, one with control constraints and one with control energy cost, to show the benets and disadvantages of the two methods. Furthermore, the ability to perform trade studies on vehicle and trajectory parameters is shown with this problem by solving for dierent terminal velocities and different initial locations.</div></div>

A obesidade tem aumentado de maneira epidêmica em todo mundo. Independente da sua causa básica, um desequilíbrio no balanço energético está sempre envolvido. Sendo assim, o cálculo adequado das necessidades energéticas do paciente é de grande importância. Diversos estudos evidenciam que as fórmulas comuns para estimativa do gasto metabólico de repouso (GMR), principal componente do gasto energético total, tendem a superestimar seus valores o que prejudica o tratamento clínico da obesidade. O objetivo do estudo foi avaliar o GMR de uma coorte feminina adulta brasileira, através dos resultados dos exames de calorimetria indireta (CI). Para tanto foram utilizados 760 exames de CI de mulheres com idade entre 18 e 65 anos. Os resultados foram tabulados, a população foi dividida em quintis de peso e então foram realizadas as análises estatísticas. A média do GMR variou entre 1226 calorias/dia a 1775 calorias/dia. A fórmula de Harris-Benedict (HB) superestimou o GMR em torno de 7%. Concluímos a partir da correlação entre as variáveis que o peso possui correlação positiva com o GMR e a idade uma correlação negativa. O GMR assim como o quociente respiratório (QR) pode ser usado como preditor de obesidade. Este trabalho trouxe duas novas propostas de equações para cálculo do GMR, uma para população com IMC < 35 kg/m2 e outra para população com IMC 35 kg/m2 / Obesity has increased epidemically in all world. Independently on the primary cause, an imbalance in the energy balance is always involved. Thus, the precise calculation of the energy requirements of the patient is of great importance. Several studies show that commonly used equations for estimation of resting metabolic rate (RMR), the main component of total energy expenditure, tend to overestimate its value, which could impair the clinical treatment of obesity. The goal of this study is to standardize the RMR of a Brazilian adult female cohort, with results of tests of indirect calorimetry (IC). In order to do so, 760 tests of IC performed in Brazilian females patients aged between 18 and 65 years old, were used. The results were charted, the population distributed according to quintiles of weight and the statistical analyses applied. The RMR average fluctuated between 1226 and 1775 calories. Harris-Benedict equation overestimated the RMR by 7%. From the correlation between the variables, we conclude that weight has a positive correlation with RMR and age a negative correlation. RMR and respiratory quotient (QR) can be use as obesity predictors. Two new equations were proposed in our study, one for population with BMI < 35kg/m2 and another for population with BMI 35 kg/m2

This essay is a narratological analysis of Stephen King’s ​The Shining, ​and​ ​employs Mieke Bal’s categorization of focalization, description and discourse with the intent of establishing their function in representing the concept of the uncanny in the narrative. By analyzing these narratological functions and their interplay, several manifestations of the ordinarily elusive uncanny become evident. The novel, through the structuring of the narrative and use of forthright descriptions as well as the insight into the characters’ minds, continually manages to represent the disturbances of the familiar that characterize the uncanny.

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For biomedical research to improve clinical practice, and for funding levels to be sustained, it is increasingly important to understand the pathways from research to clinical practice and to assess the societal impact of research. Approaches to research evaluation through traditional study of journals, journal articles and standard citation analysis, have played comparatively small roles in these developments. In this thesis I critically review how I applied existing methods, and developed a new approach, to study two pathways from research to clinical practice. For Pathway 1, questionnaire surveys of clinicians' views on journals read to inform their clinical practice, and comparisons with impact factors, revealed that a few journals were read widely and considered important by clinicians. Relationships between journal importance and impact factor were complex. For Pathway 2, I applied a novel methodology to identify important citations to four key research papers in an attempt to trace important citations through numerous citing generations. My findings included: few cited papers were important to the citing papers; the number of citation occasions within the citing paper correlated strongly with a cited paper's importance; self-citations were also important; and it was feasible to trace through a series of generations of citations. Evidence of societal impact of the four key research papers examined in my studies included important papers in subsequent generations cited in clinical guidelines, many of which were international. In assessing the impact of my own studies, I found Pathway 1 papers had societal impact on research evaluation methodology; journal editorial policy; and medical library provision policy and practice. Societal impacts of the new methodology, Pathway 2, included informing further methodological development and research evaluation. My portfolio, together with my critical review, adds understanding and provides additional data to current assessment methods of wider impacts of research, and bases for further studies.

INTRODUÇÃO: A doença de Gaucher (DG) é um erro inato do metabolismo, do grupo das doenças lisossômicas, causado pela atividade deficiente da enzima glicocerebrosidase. Os tipos mais comuns da DG são o tipo I, que é o mais freqüente e não apresenta comprometimento neurológico; o II, agudo e neuropático; e o III, subagudo e neuropático. Todos os tipos caracterizam-se pela heterogeneidade clínica, com manifestações sintomáticas e de intensidade distintas, tais como hepatoesplenomegalia, alterações ósseas e hematológicas. Alguns estudos descrevem alterações metabólicas como gasto energético basal (GEB) aumentado – hipermetabolismo - em pacientes sem tratamento. A terapia de escolha para a DG é a reposição enzimática (TRE), a qual consegue reverter muitas das manifestações da doença. OBJETIVOS: 1) Avaliar o GEB por meio de calorimetria indireta em pacientes com DG do Centro de Referência do Rio Grande do Sul; 2) Avaliar o estado nutricional dos pacientes incluídos no estudo; 3) Relacionar o GEB com as condições clínicas dos pacientes. METODOLOGIA: Estudo transversal, prospectivo, controlado. Os pacientes atendidos no CRDG foram convidados a participar do estudo (n= 29), sendo que 17 concordaram (média de idade= 30,0 ± 17,2 anos, sexo masculino= 8; DG tipo III= 3 pacientes). Os pacientes com DG tipo I (n= 14; sexo masculino= 6) foram pareados por sexo, idade e índice de massa corporal (IMC) com controles hígidos para avaliação do GEB. Para determinação dos valores de VO2 e VCO2 foi utilizado um ergoespirômetro (MedGraphics Cardiorespiratory Diagnostic Systems, modelo CPX-D). Os pacientes e os controles receberam orientação prévia quanto ao jejum e o repouso e no dia da calorimetria foram pesados e medidos, sendo então calculado o IMC. Os pacientes não apresentavam outras morbidades, nem estavam em uso de medicamentos que poderiam interferir no GEB. Nas análises estatísticas, foi utilizado o GEB em kcal/kg/dia. RESULTADOS: A avaliação do estado nutricional revelou que, no grupo dos pacientes com DG tipo I, cinco estavam com sobrepeso e os demais eutróficos; no grupo com DG tipo III, dois pacientes encontravam-se desnutridos e um eutrófico. Foram realizadas 19 avaliações do GEB em 17 pacientes: dois pacientes a realizaram no período pré e após 6 meses de TRE. A média de idade e de IMC dos pacientes com DG tipo I e dos controles foi de 32,8 ± 17,6 e 32,1 ± 16,6 anos e 23,3 ± 3,1 e 22,4 ± 3,1kg/m2, respectivamente. A idade dos pacientes com DG tipo III foi, respectivamente, 12, 17 e 20 anos. Quatorze pacientes estavam recebendo TRE (média de tempo de TRE= 6,6 ± 5,3 anos; média de dose de enzima= 27,1 ± 11,7 UI/kg/inf. de imiglucerase). A média de GEB dos pacientes com DG tipo I em TRE (n= 12) foi 27,1% maior do que a dos controles (p= 0,007). O GEB de pacientes em TRE (n=12) comparado aos sem TRE (n= 4) não apresentou diferença (p= 0,92). Comparando o GEB dos pacientes em TRE e o de seus controles com o GEB estimado pela equação de Harris-Benedict, observou-se que os pacientes apresentaram GEB 6,3% maior do que o estimado (p= 0,1), enquanto que seus controles tiveram GEB 17,0% menor do que o estimado (p= 0,001). O GEB medido dos pacientes com DG tipo III foi, respectivamente, 14%, 72% e 16% maior do que o estimado pela equação de Harris e Benedict. Não foi encontrada associação significativa entre GEB e as seguintes variáveis: idade, peso, estatura, escore de gravidade, quantidade de enzima recebida, idade de início de TRE, tempo de tratamento e presença ou ausência de megalias. A correlação do GEB com o IMC foi negativa e significativa, conforme esperado. DISCUSSÃO/CONCLUSÕES: O estado nutricional classificado pelo IMC mostrou que a maior parte dos pacientes com DG tipo I estava eutrófica; no entanto, um terço apresentou pré-obesidade. Dois dos três pacientes com DG tipo III encontravam-se desnutridos. Todos os pacientes, mesmo em TRE, apresentaram um GEB significativamente maior do que os controles. A TRE não consegue normalizar o hipermetabolismo desses pacientes. / INTRODUCTION: Gaucher disease (GD) is an inborn error of metabolism of the group of lysosomal diseases, caused by the deficient activity of the glucocerebrosidase enzyme. The most common types of GD are: type I, which is the most frequent and does not present neurological compromise; type II, which is acute and neuropathic; and type III, which is subacute and neuropathic. All types are characterized by clinical heterogeneity and symptomatic manifestations of various intensity, such as hepatoesplenomegaly and bone and hematological alterations. Some studies have described metabolic alterations, such as increased basal metabolic rate (BMR), that is, hypermetabolism, in untreated patients. The therapy of choice for GD is enzyme replacement therapy (ERT), which can stop many manifestations of the disease. OBJECTIVES: 1) To evaluate BMR by means of indirect calorimetry in patients with GD seen at the Reference Center for Gaucher Disease of Rio Grande do Sul (RCGD); 2) To evaluate the nutritional status of patients included in the study; 3) To relate BMR with clinical conditions presented by patients. METHODS: The present was a prospective, controlled, cross-over study. Patients seen at the RCGD were invited to participate in the study (n=29); of these, 17 agreed to participate (mean age=30.0 ± 17.2 years, male= 8; GD type III=3 patients). Patients with GD type I (n=14; male= 6) were paired by gender, age, and body mass index (BMI) to healthy controls to evaluate BMR. To determine the values of VO2 and VCO2 an ergospirometer was used (MedGraphics Cardiorespiratory Diagnostic Systems, model CPX-D). Patients and controls received previous orientation as to fasting and resting and, on the day of the calorimetry, were weighed and measured in order for the BMI to be calculated. Patients did not present any other morbidity, neither were they making use of any medication that could interfere with BMR. In the statistical analyses, BMR in kcal/kg/day was used. RESULTS: The evaluation of the nutritional status showed that, in the group of patients with GD type I, five patients were overweight; the other were eutrophic; in the group of patients with GD type III, two patients were malnourished; one was eutrophic. Nineteen evaluations of BMR were conducted in 17 patients; two patients conducted the evaluation in the period pre-ERT and after 6 months of ERT. Mean age and mean BMI of patients with GD type I and controls were 32.8 ± 17.6 and 32.1 ± 16.6 years and 23.3 ± 3.1 and 22.4 ± 3.1kg/m2, respectively. The age of patients with GD type III was, respectively, 12, 17 and 20 years. Fourteen patients were receiving ERT (mean time of ERT=6.6 ± 5.3 years; mean enzyme dose=27.1 ± 11.7 UI/kg/inf of imiglucerase). The mean BMR of patients with GD type I on TRE (n=12) was 27.1% higher when compared to controls (p=0.007). When compared to patients not on ERT (n=4), the BMR of patients on ERT (n=12) did not show any difference (p=0.92). Comparing the BMR of patients on ERT and that of their controls with the BMR estimated by the Harris-Benedict equation, we observed that patients showed a 6.3% higher BMR than the estimated (p=0.1), while the BMR of their controls was 17.0% lower than the estimated (p=0.001). The BMR of patients with GD type III was, respectively, 14%, 72% and 16% higher than the estimated by the Harris-Benedict equation. No significant association was found between BMR and the following variables: age; weight; height; severity score; amount of enzyme received; age at beginning of ERT; time of treatment; and presence or absence of megalies. The correlation between BMR and BMI was negative and significant, as expected. DISCUSSION/CONCLUSIONS: The nutritional status classified by BMI showed that most patients with GD type I were eutrophic; however, one third of the patients showed pre-obesity. Two of the three patients with GD type III were malnourished. All patients, even on ERT, showed a significantly higher BMR when compared to controls. In conclusion, ERT was not able to normalize the hypermetabolism of these patients.