Otimização da anisotropia fronto-calosa e ressonância magnética [1,5T] no idoso normal e com risco cérebro-vascular

RESUMO: Os mais recentes métodos de neuro imagem tal como a Ressonância Magnética (RM) permitiram obter imagens detalhadas do cérebro humano in vivo. Essas imagens revelam, muitas vezes, achados imprevistos face ao padrão normal, com elevada propensão para os indivíduos idosos e franca coexistência com fatores de risco vascular, como característica dum processo de envelhecimento normal. Embora na última década tenham surgido várias publicações sobre este assunto, ele continua ainda pouco explicado. Um pouco por todo o mundo têm emergido os programas de prevenção da doença e promoção da saúde desenvolvidos pela Saúde Pública suportadas sobretudo pelo avanço das tecnologias médicas que resultaram, entre outros impactos, num crescimento da população idosa. Estima-se, em 2030, uma composição demográfica com 20% de indivíduos acima dos 65 anos. Neste contexto, a doença microvascular cerebral é a causa mais frequente de comprometimento cognitivo vascular no idoso sendo as características senescentes na imagem por RM do tipo lesões isquémicas da Substância Branca (Leukoaraiosis) e enfartes lacunares (Status lacunar), atrofia cerebral, gliose e acumulação excessiva de ferro nos núcleos da base. Esta tese, considerando a linha de investigação de que deriva – Ciências da Vida - especialização em Medicina Clinica - Biotecnologia, reúne e reflete sobre três vertentes ligadas à RM e interdependentes em relação a uma problemática comum. A primeira trata da caracterização da Tecnologia por Ressonância Magnética existente em Portugal, a qual inclui uma avaliação exploratória da aplicação da técnica de Difusão Anisotrópica nos estudos cerebrais. As dimensões analíticas estudadas foram a Tecnológica, Sociodemográfica e Económica. Na recolha de dados recorreu-se a várias fontes de informação e a uma metodologia exploratória faseada, validada pela triangulação dos resultados. A sua análise obedeceu a critérios de estratificação e agrupamento segundo as mesmas dimensões analíticas. Otimização da anisotropia fronto-calosa e [RM 1,5T] no idoso normal e com risco cérebro-vascular A segunda descreve o estudo anátomo – radiológico que recaiu sobre parâmetros de quantificação assente na temática do cérebro do idoso em cadáver segundo uma metodologia experimental aplicada às métricas da difusão por RM. Na terceira, e última, é apresentado o estudo técnico - radiológico para avaliação e otimização da imagem ponderada em difusão em estudos clínicos associados ao cérebro do idoso “The Usual Brain Aging” ou Envelhecimento Cerebral Normal, com base metodológica assente nos critérios e indicadores estabelecidos pelo Estudo de Imagem de Roterdão (Rotterdam Scan Study - RSS). Como principais resultados obteve-se que não existem em Portugal estruturas para avaliação dos equipamentos pesados ou Agência de Avaliação das Tecnologias da Saúde para desenvolver o importante papel da produção de estudos comparativos entre os equipamentos disponíveis no mercado, a relação preço-qualidade e a sua afetação às necessidades clínico-epidemiológicas. Constatou-se que a implementação de equipamentos de RM está fortemente assente em critérios económicos carecendo de recomendações e diretivas para o uso racionalizado destas tecnologias. Quanto a dados quantitativos concluímos que a maioria dos equipamentos está instalada em instituições privadas (80,2%); a intensidade de campo magnético mais frequente é [1,5T] com 119 equipamentos; os equipamentos estão instalados maioritariamente nos distritos de Lisboa (55 unidades) e do Porto (39 unidades); o rácio médio de equipamentos por habitante em Portugal é de 1 para 65 195 habitantes; a amplitude de gradientes com maior expressão na amostra é 30-39mT/m; a maioria dos equipamentos foi instalada no intervalo temporal [2009-2012] com 59 equipamentos; apenas 6 instituições desenvolvem investigação clinica e a maioria das bobinas para estudos de crânio são do tipo Array. O estudo de otimização da técnica da difusão revelou, quanto à avaliação dos valoresb, que os mais baixos (b=500 s/mm2 e b=1000 s/mm2), apresentam maior IS e SNR sendo esta uma boa medida referente à qualidade de imagem, no entanto, os valores-b mais elevados (b=2000 s/mm2) apresentam maior CNR e CR, face aos anteriores, o Otimização da anisotropia fronto-calosa e [RM 1,5T] no idoso normal e com risco cérebro-vascular que apesar de proporcionar inferior detalhe anatómico e consequentemente inferior qualidade de imagem, num encéfalo normal, pode auxiliar na interpretação e apresentar vantagens na identificação de lesões microvasculares sempre que persistirem dúvidas em relação ao diagnóstico diferencial de doença microvascular do tipo status lacunar ou Hiperintensidades da Substância Branca. As alterações deste parâmetro são particularmente refletidas nas diferenças da avaliação da qualidade de imagem na região fronto-calos Concluímos da avaliação quantitativa da concentração média de ferro (26Fe) em todas as faixas etárias que os núcleos da base que apresentam maior concentração são, por ordem decrescente: Substância Nigra, Globus Pallidus, Putamen, Tálamo, Núcleo Rubro e Núcleo Caudado; que existe uma predominância na concentração de ferro (26Fe) no hemisfério esquerdo e que os indivíduos do género masculino apresentam mais ferro (26Fe) que os do género feminino nas faixas etárias [30-40[, [40-50[ e [50-60[. Como principal conclusão do estudo da concentração média de ferro em relação à idade destacamos que a concentração média de ferro (26Fe) é superior nos grupos etários superiores, logo aumenta com a idade, sobretudo na Substância Nigra e no Núcleo Lenticular. No estudo técnico-radiológico encontrámos evidências do aumento da difusibilidade da água na substância branca subcortical dos sujeitos idosos comparativamente aos mais jovens. Uma relação idêntica foi avaliada nos tálamos. O aumento relacionado com a idade parece ser predominantemente observado em doentes com mais de 65 anos de idade o que pode refletir alterações estruturais ligeiras associados ao envelhecimento normal. Os resultados indicam que a análise quantitativa das imagens ponderadas em difusão fornece informações, sobre a estrutura do cérebro, as quai s não estão disponíveis apenas por inspeção visual, tanto nas imagens ponderadas em difusão como em outras sequências de aplicação clínica de rotina. Para fazer face às desvantagens dos sistemas de quantificação das HSB os quais são dispendiosos, complexos, requererem tecnologia e formação específicas, recomendamos que a aplicação automatizada GUIAL, desenvolvida ao longo do nosso trabalho é de utilização elementar e prática para que seja introduzida nos sistemas de aquisição de imagem por RM com o fim de integrar o processamento de imagem nos indivíduos portadores de fatores de risco vascular. A avaliação do ADC, nesta amostra, permitiu concluir que a variação desta variável é explicada estatisticamente pela existência da condição clínica de status lacunar em ambos os hemisférios ou por outras palavras, o status lacunar influencia o valor de ADC. Embora uma pequena percentagem da variação do ADC seja explicada pelo género, o ADC nos homens foi superior ao das mulheres o que não nos surpreende, pois são também os homens onde a frequência de doença microvascular se revelou mais expressiva. Os valores do ADC, globalmente, entre os hemisférios cerebrais não mostraram alterações exceto na SB entre os idosos e não idosos. A SB da região frontal mostrou valores diminuídos na anisotropia e isotropia face às restantes áreas anatómicas. Os estudos indicam que na idade avançada existe uma maior predisposição para suscetibilidades de estrutura com status de desconexão. A classificação das HSB foi superior em indivíduos mais velhos e com status lacunar, e em menor quantidade (inferior rating de classificação) nos indivíduos idosos sem status lacunar. As alterações volumétricas foram mais frequentes no homem do que na mulher, presumivelmente devido à associação com a elevada classificação de status lacunar. Um aumento do índice de Evan correspondeu, neste estudo, ao aumento das HSB, à diminuição do volume cerebral total, à expansão ventrículo-sulcal frontal e ao aumento da medida do ângulo caloso. Estes resultados foram agravados pela classificação elevada de status lacunar nos indivíduos que apresentaram indícios de doença de pequenos vasos, com manifesto aumento dos espaços de Virchow-Robin,enfartes lacunares ou HSB. Esses resultados foram mais expressivos no género masculino do que no feminino revelando uma maior vulnerabilidade sobretudo na atrofia frontal nos homens. Por sua vez as dimensões do Corpo Caloso tornaram-se reduzidas devido à compressão dos ventrículos laterais e terceiro ventrículo. Estes indicadores tiveram expressão particularmente nos indivíduos com mais de 65 anos. ---------------------------------------------------------------------------------------------ABSTRACT: The latest neuroimaging methods, such as Magnetic Resonance Imaging (MRI), have enabled detailed images of in vivo human brain. These images reveal often unexpected findings related to the normal pattern, with high predisposition for the elderly people with forthright coexistence with vascular risk factors such as characteristics of a normal aging process. Although it has been, in the last decade, several publications on this subject, it is still little explained. All over the world have emerged disease prevention programs and health promotion developed by the Public Health sector, supported mainly by the advancement of medical technologies that have resulted, among other impacts, in a growing of the elderly population. It is estimated, in 2030, a demographic composition with 20% o people over 65 years. In this context, microvascular disease is the most common cause of cognitive vascular impairment in the elderly and senescent characteristics in the MRI trough ischemic lesions of the white matter (Leukoaraiosis) and lacunar infarcts (lacunar status), cerebral atrophy, gliosis and iron accumulation in the basal ganglia in excess.This thesis, considering the research line that stems - Life Sciences - specialization in Clinical Medicine, Biotechnology, gathers and reflects on three aspects linked to MR, interdependent and related to a common problem. The first deals with the Magnetic Resonance Technology characterization in Portugal, which includes an exploratory evaluation of the implementation of Anisotropic Diffusion technique in brain studies. The analytical dimensions studied were the Technologic, Socio-demographic and Economics. Collecting data was supported by different sources of information and was applied an exploratory methodology whose results were validated by triangulation. The research method was grouped and stratified criteria under the same analytical dimensions. The second describes the anatomical study - which was focused on radiological measurement parameters, based on the brain’s specimen under an experimental methodology applied to MRI diffusion metrics. Radiological evaluation and optimization of the weighted image diffusion in clinical studies were associated with the brain of the elderly "The Usual Brain Aging" with methodological basis based on established criteria and indicators by Rotterdam Scan Study (RSS). The main results obtained reveal the inexistence frameworks in Portugal for evaluation of equipments or Agency of Health Technology to produce studies comparing the equipment available on the market, the value for money and its allocation to clinical and epidemiological needs. It was found that the implementation of MRI equipment is strongly based on economic criteria lacking recommendations and guidelines for the rationalized use of these technologies. As the quantitative data we conclude that most of the scanners are located in private clinical institutions (80,2%); the most frequent magnetic field intensity is [1.5T] with 119 scanners; the scanners are mainly installed in Lisbon (55 units) and Porto (39 units) districts; the average ratio of equipment per capita in Portugal is 1 to 65 195 people; the gradient power with higher expression in the sample is 30-39mT / m;most of the scanners were installed in the years range [2009-2012 years] with 59 equipment; only 6 clinical placements develop clinical research and the most coils for brain studies are of Array type. The optimization study of diffusion technique revealed, as the assessment of the bvalues, the lower (b = 500 s / mm2 and b = 1000 s / mm 2), promotes an increase in the SI and SNR being this measure related to a higher image quality, however the highest b values (b = 2000 s / mm 2) have a higher CNR (Contrast to Noise-Ratio) and CR (Contrast Ratio), compared to the previous ones. This may provide less anatomical details and, thus, ower image quality, of a normal brain, however can help the interpretation and have advantages in identifying microvascular injuries when doubts persist regarding the differential diagnosis of microvascular disease of lacunar or WMH (White Matter Hyperintensities) status type. Changes on this parameter are Otimização da anisotropia fronto-calosa e [RM 1,5T] no idoso normal e com risco cérebro-vascular particularly reflected in the differences of image quality evaluation in the frontocallosum anatomical area. We conclude from the quantitative assessment of the average concentration of iron (26Fe), in all age groups to the basal ganglia, that the higher concentrations are, in descending order: Nigral Substantia, Globus pallidus, Putamen, Thalamus, Rubio nucleus and Caudate nucleus; that there is a predominance in the concentration of iron (26Fe) in the left hemisphere and that male gender show higher iron (26Fe) level tha females, in the age groups [30-40 [[40-50 [and [50- 60 [. Regarding a main conclusion of the mean concentration study of iron, in terms of age we point out that the average concentration of iron (26Fe) is higher among older groups and increases with age, especially in Nigral Substantia and Lenticular Nucleus. On the technical and radiological study we found evidence of an increased in water /diffusivity in the ubcortical white matter of the elderly compared with younger subjects. A similar relationship was assessed in the Thalamus. The increase agerelated seems to be predominantly observed in patients over 65 years which may reflect minor structural changes associated with normal aging. The results indicate that quantitative analysis of diffusion weighted imaging can provide information about the structure of the brain which is not reached only by visual inspection or standard sequences applied in clinical routine. To address the disadvantages the systems of quantification of WMH which the authors state that are costly, complex, require specific technology and training, we recommend that the automated application GUIAL, developed over our work is basic and practical to use and to be introduced in MR image systems acquisition in order to integrate image processing in patients with vascular risk factors. The evaluation of the ADC showed that its variation is statistically explained by the existence of the medical condition of lacunar status, in both hemispheres, or in other words, the lacunar status influences the ADC value. Although a small percentage of the ADC variation is explained by gender, the ADC in men was higher than women which Otimização da anisotropia fronto-calosa e [RM 1,5T] no idoso normal e com risco cérebro-vascular do not surprise us, since they are also men where the frequency of microvasculardisease has proved more significant. The values of ADC, overall, between the cerebral hemispheres showed no changes but were different in WM among the elderly and non-elderly subjects.The WM's forehead showed decreased values in anisotropy and isotropy face the other anatomical areas. The studies indicate that in old age there is a greater tendency to higher susceptibility to disconnection- status framework. The classification of WMH was higher in elderly people and lacunar status, and fewer (lower classification rating) in the elderly without lacunar status. volumetric changes were more frequent in men than in women, most probably because of its association with high lacunar status rating. An increase of Evan index corresponded, in this study, to an increase in WMH, to a decreased of total brain volume, to a ventricle sulcal frontal and callous angle expansion. These results were wound up by high ranking of lacunar status in subjects who had small vessel disease, clear increase in spaces of Virchow-Robin, lacunar infarctions or WMH. These results were more significant in males than in females revealing vulnerability particularly in the frontal atrophy in men. In turn the size of Corpus Callosum because reduced due to the compression of the lateral and third ventricles. These indicators had expression particularly in individuals over 65 years.

Modelo in vitro de ateroesclerosis: Efecto de la infección con Trypanosoma cruzi, lípidos y lipoproteínas sobre la expresión de receptores Toll-like y scavengers en la formación de células espumosas derivadas de macrófagos

Los receptores Toll-like (TLRs) son receptores ancestrales que reconocen modelos moleculares asociados a patógenos y nos defienden de los microorganismos. Su activación por vías de señalización que involucran al factor de transcripción NF-kB, estimula la producción de citoquinas inflamatorias, quimioquinas, moléculas de adhesión y procoagulantes. Recientemente se ha documentado la participación de TLR 2 y 4 en el desarrollo /progresión del ateroma en modelos experimentales in vivo, siendo postulados como nexo entre inflamación, infecciones y ateroesclerosis. Infecciones bacterianas y virales han demostrado jugar un papel en su desarrollo. Sin embargo, el rol de parásitos intracelulares obligados -Trypanosoma cruzi- ha sido escasamente explorado. Los macrófagos, células claves del sistema inmune innato, que pueden ser infectadas in vivo e in vitro por este parásito, expresan en su superficie receptores multiligando scavenger (SR) clase B. Entre ellos, CD 36, capta lipoproteínas de baja densidad (LDL) oxidadas y este mecanismo endocítico no controlado por feedback favorecería la formación de células espumosas, la lesión más temprana de ateroesclerosis. El objetivo general de este proyecto es contribuir a esclarecer el conocimiento de los mecanismos bioquímicos, celulares y moleculares que participan en la formación de células espumosas derivadas de macrófagos. Determinar el efecto de potenciales factores aterogénicos sobre receptores Toll-like and SR-CD 36, permitiría diseñar terapias alternativas tendientes a modular su actividad con la finalidad de disminuir la elevada morbilidad/mortalidad que ocasiona la ateroesclerosis en la sociedad occidental. En nuestro modelo proponemos los siguientes objetivos específicos: -Dilucidar el compromiso de TLRs y SR-clase B en el proceso de aterogenésis, específicamente en la formación de células espumosas.-Investigar la influencia de la infección por T. cruzi, ácidos grasos y LDL modificadas como factores aditivos en la formación de estas células. -Evaluar el efecto de ligandos agonistas de TLR2/4 y SR-CD 36. -Determinar el perfil de citoquinas inflamatorias liberadas en el sobrenadante de los cultivos celulares. -Estudiar el efecto metabólico de las hormonas insulina y adipoquinas en el proceso bioquímico y celular que permite la formación de células espumosas.

Differential effect of long versus short wavelength light exposure on pupillary re-dilation in patients with outer retinal disease.

BACKGROUND: In patients with outer retinal degeneration, a differential pupil response to long wavelength (red) versus short wavelength (blue) light stimulation has been previously observed. The goal of this study was to quantify differences in the pupillary re-dilation following exposure to red versus blue light in patients with outer retinal disease and compare them with patients with optic neuropathy and with healthy subjects. DESIGN: Prospective comparative cohort study. PARTICIPANTS: Twenty-three patients with outer retinal disease, 13 patients with optic neuropathy and 14 normal subjects. METHODS: Subjects were tested using continuous red and blue light stimulation at three intensities (1, 10 and 100 cd/m2) for 13 s per intensity. Pupillary re-dilation dynamics following the brightest intensity was analysed and compared between the three groups. MAIN OUTCOME MEASURES: The parameters of pupil re-dilation used in this study were: time to recover 90% of baseline size; mean pupil size at early and late phases of re-dilation; and differential re-dilation time for blue versus red light. RESULTS: Patients with outer retinal disease showed a pupil that tended to stay smaller after light termination and thus had a longer time to recovery. The differential re-dilation time was significantly greater in patients with outer retinal disease (median = 28.0 s, P < 0.0001) compared with controls and patients with optic neuropathy. CONCLUSIONS: A differential response of pupil re-dilation following red versus blue light stimulation is present in patients with outer retinal disease but is not found in normal eyes or among patients with visual loss from optic neuropathy.

Els cultius in vitro i el desenvolupament vegetal

Biotecnologia Vegetal de materials de treball que incorporin les TICs. El material elaborat ha estat un llibre electrònic utilitzable tant on-line (web) com off-line (CD). Els materials generats com a resultes d’aquest projecte han estat situats en un servidor de la UdL accessible des de l’exterior de la Universitat. Aquest llibre electrònic és d’accés obert i es pot consultar on-line a l’URL (http://sakai.udl.es/cursos/76304/indexC.htm). El llibre electrònic conté un total de 98 Mb d’informació hipermèdia i hipertexual distribuïda en més de 380 arxius dels quals 50 són pàgines html, 10 arxius doc, 10 arxius pdf, 258 imatges fixes i 8 arxius de vídeo en format flash (swf). L’accés al llibre electrònic es realitza a través d’una pantalla inicial que dóna pas a un menú que distribueix els materials en 7 apartats. Els textos estan acompanyats de gran quantitat d’imatges fotogràfiques, gràfics, esquemes, imatges infogràfiques i videoclips generats de novo per aquest projecte. En dissenyar la web s’han tingut en compte criteris de confiabilitat, accessibilitat i usabilitat. El primer disseny de la web ha estat validat per un panel d’usuaris i utilitzat posteriorment amb alumnes durant el curs 2007-2008. Les observacions i suggeriments fets per aquests ja han estat incorporats en aquest document final. Una primera enquesta de satisfacció realitzada amb aquest alumnat permet concloure, a títol provisional donat lo reduït de la població enquestada, que l’alumnat mostra un grau de coneixement de les eines TIC suficient i que consideren positiva la incorporació de materials multimèdia com a recurs educatiu. A més a més, la realització d’aquest projecte i la seva aplicació a l’aula ha estat presentada en dues ponències al “Congreso Internacional de Docencia y Innovación Universitaria”.

Intrinsically photosensitive retinal ganglion cell function in relation to age: a pupillometric study in humans with special reference to the age-related optic properties of the lens.

BACKGROUND: The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC) can be assessed by a means of pupil responses to bright blue (appr.480 nm) light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC. METHODS: Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red) or 470 nm (blue) both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively). Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC) over two time-windows: early (0-10 s after light termination) and late (10-30 s after light termination). Lens transmission was measured with an ocular fluorometer. RESULTS: The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p=0.02, p=0.0014, respectively) for the blue light stimulus condition only.The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions.Lens transmission decreased linearly with age (p<0.0001). The pupil response was stable or increased with decreasing transmission, though only significantly for the early poststimulus AUC to 300 cd/m2 light (p=0.02). CONCLUSIONS: Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led to similar results, however, the effect of age was greater on these pupil responses than that of the lens transmission. Thus there must be other age related factors such as lens scatter and/or adaptive processes influencing the ipRGC mediated pupil response enhancement observed with advancing age.

First-line therapies in inflammatory bowel disease.

Background and Aims: Medical therapy of inflammatory bowel disease (IBD) is becoming more complex, given the increasing choice of drugs to treat Crohn's disease (CD) and ulcerative colitis (UC). We aimed to summarize the current guidelines for first-line treatments in IBD. Methods: An extensive literature search with focus on the guidelines of the European Crohn's and Colitis Organisation for the diagnosis and treatment of CD and UC was performed. First-line treatments were defined as the following drug categories: 5-aminosalicylates, budesonide, systemic steroids, azathioprine, 6-mercaptopurine, methotrexate, infliximab, adalimumab and certolizumab pegol. The following drug categories were not included: cyclosporine and tacrolimus (not yet approved by Swissmedic for IBD treatment). Results: Treatment recommendations for the following clinically frequent situations are presented according to disease severity: ileocecal CD, colonic CD, proximal small bowel CD and perianal CD. For UC the following situations are presented: ulcerative proctitis, left-sided colitis and pancolitis. Conclusions: We provide a summary on the use of first-line therapies for clinically frequent situations in patients with CD and UC.

Chromatic pupillometry in patients with retinitis pigmentosa.

OBJECTIVE:: To evaluate the chromatic pupillary response as a means of assessing outer and inner retinal function in patients with retinitis pigmentosa (RP). DESIGN:: Evaluation of diagnostic technology. PARTICIPANTS:: Thirty-two patients with RP and visual loss and 43 normal subjects. METHODS:: Patients were tested with a chromatic pupillometer using red and blue lights (1, 10, and 100 cd/m(2)), and their pupil responses were compared with those from 43 normal subjects (reported previously). Visual field and electroretinography (ERG) results were examined and compared with the pupil responses. MAIN OUTCOME MEASURES:: The percent pupil contraction of the transient response to a low-intensity (1 cd/m(2)) blue light and high-intensity (100 cd/m(2)) red light and the sustained response to a high-intensity blue light was calculated for 1 eye of each subject. RESULTS:: The pupil responses to red and blue light at all intensities were recordable in all patients except 1, whose pupil responded only to bright blue light. There was a significant difference of the pupil response between patients with RP and normal subjects in testing conditions that emphasized rod (1 cd/m(2) blue light) or cone (100 cd/m(2) red light) contribution (P<0.001). Patients with a non-recordable scotopic ERG showed significantly reduced pupil responses (P<0.001) to low-intensity blue light (1 cd/m(2)). Patients with a non-recordable or abnormal photopic ERG showed significantly reduced pupil responses (P<0.05) to high-intensity red light (100 cd/m(2)). Patients with a nonrecordable ERG had the most visual field loss and reduced pupil responses. Unexpectedly, patients with RP showed a slower re-dilation of the pupil after termination of bright blue light compared with red light, a pattern not observed in normal subjects. CONCLUSIONS:: Pupil responses to red and blue light stimuli weighted to favor cone or rod input are significantly reduced in patients with RP but are still recordable in patients having a non-recordable ERG. In addition, outer photoreceptor disease appears to unmask a post-illumination pupillary constriction to bright blue light, most likely mediated by intrinsic activation of melanopsin ganglion cells. Chromatic pupillometry provides a novel, noninvasive method for following retinal functional status, particularly in patients with severe RP and non-recordable ERG. FINANCIAL DISCLOSURE(S):: Proprietary or commercial disclosure may be found after the references.

Soil water dynamics related to the degree of compaction of two brazilian oxisols under no-tillage

Soil water properties are related to crop growth and environmental aspects and are influenced by the degree of soil compaction. The objective of this study was to determine the water infiltration and hydraulic conductivity of saturated soil under field conditions in terms of the compaction degree of two Oxisols under a no-tillage (NT). Two commercial fields were studied in the state of Rio Grande do Sul, Brazil: one a Haplortox after 14 years under NT; the other a Hapludox after seven years under NT. Maps (50 x 30 m) of the levels of mechanical penetration resistance (PR) were drawn based on the kriging method, differentiating three compaction degrees (CD): high, intermediate and low. In each CD area, the infiltration rate (initial and steady-state) and cumulative water infiltration were measured using concentric rings, with six replications, and the saturated hydraulic conductivity (K(θs)) was determined using the Guelph permeameter. Statistical evaluation was performed based on a randomized design, using the least significant difference (LSD) test and regression analysis. The steady-state infiltration rate was not influenced by the compaction degree, with mean values of 3 and 0.39 cm h-1 in the Haplortox and the Hapludox, respectively. In the Haplortox, saturated soil hydraulic conductivity was 26.76 cm h-1 at a low CD and 9.18 cm h-1 at a high CD, whereas in the Hapludox, this value was 5.16 cm h-1 and 1.19 cm h-1 for the low and high CD, respectively. The compaction degree did not affect the initial and steady-state water infiltration rate, nor the cumulative water infiltration for either soil type, although the values were higher for the Haplortox than the Hapludox.

Evaluation of Dowel Bar Retrofits for Local Road Pavements, TR-520, 2008

As truck traffic on Iowa secondary roads has increased, engineers have moved to concrete pavements of greater depths. Early designs included thickened edge pavements and depths of seven inches or greater. The designs typically did not have load transfer devices installed in the transverse joints and relied on aggregate interlock for this purpose. In some cases, aggregate interlock was not adequate to deal with the soils and traffic conditions and faulting of the joints has begun to appear. Engineers are now faced with the need to install or retrofit load transfer in the joints to preserve the pavements. Questions associated with this decision range from the type of dowel material to dowel diameter, spacing, number of bars, placement method, and construction techniques to be used to assure reduction or elimination of faulting. Buena Vista County constructed a dowel bar retrofit project on one mile of road. The plan called for addition of the dowels (2, 3, or 4) in the outer wheel path only and surface grinding in lieu of asphalt overlay. The project included the application of elliptical- and round-shaped dowels in a rehabilitation project. Dowel material types included conventional epoxy-coated steel and fiber-reinforced polymer (FRP). This work involved the determination of relative costs in materials to be used in this type of work and performance of FRP and elliptical-shaped steel dowels in the retrofit work. The results indicate good performance from each of the bar configurations and use the results of ride and deflection testing over the research period to project the benefits that can be gained from each configuration vs. the anticipated construction costs. The reader is cautioned that this project could not relate the number of dowels required to the level of anticipated truck traffic for other roads that might be considered.

Kuivatuksen hallintaparametrien vaikutus sellun paperiteknisiin ominaisuuksiin

Sellun kuivatuksesta ei löydy paljoa tutkimustietoa. Työn tarkoituksena on antaa lyhyt teoriakuvaus sellun kuivatuksesta, kuivatukseen vaikuttavista tekijöistä jasellun kuivatuksen vaikutuksesta sellun laatuun. Käytännön osassa tutkittiin kuivauskoneen poikkiradan hienoainepitoisuuden ja vetolujuussuhteiden vaihtelua, suihkusuhteiden, kenkäpuristimen viivakuorman sekä paalipuristimen puristusvoimanvaikutusta sellun paperiteknisiin ominaisuuksiin. Sellun kuivauskone koostuu perälaatikosta, viiraosasta, puristinosasta sekä kuivausosasta.Perälaatikon tehtävä on syöttää massa tasaisesti viiraosalle. Viiraosalla poistuu suurin osa vedestä (noin 94 %) ja viiraosalla tapahtuu pohjan muodostus. Tässä työssä tutkittu suihkusuhde on yksi rainan muodostukseen vaikuttava tekijä. Puristinosalla voidaan sellun ominaisuuksiin vaikuttaa puristuksen voimalla ja kestolla ja tätä työssä tutkittiin kenkäpuristimen viivakuormaa muuttamalla. Varsinainen kuivatus voi tapahtua joko kuumia sylinteripintoja tai ilmaa hyödyntäen. Kuivauskoneen jälkeen on leikkuri, paalauspöytä ja paalipuristin. Paalipuristuksen vaikutusta sellun ominaisuuksiin tutkittiin keventämällä paalipuristusta nykyisestä.

Comparison of accelerated T1-weighted whole-brain structural-imaging protocols.

Imaging in neuroscience, clinical research and pharmaceutical trials often employs the 3D magnetisation-prepared rapid gradient-echo (MPRAGE) sequence to obtain structural T1-weighted images with high spatial resolution of the human brain. Typical research and clinical routine MPRAGE protocols with ~1mm isotropic resolution require data acquisition time in the range of 5-10min and often use only moderate two-fold acceleration factor for parallel imaging. Recent advances in MRI hardware and acquisition methodology promise improved leverage of the MR signal and more benign artefact properties in particular when employing increased acceleration factors in clinical routine and research. In this study, we examined four variants of a four-fold-accelerated MPRAGE protocol (2D-GRAPPA, CAIPIRINHA, CAIPIRINHA elliptical, and segmented MPRAGE) and compared clinical readings, basic image quality metrics (SNR, CNR), and automated brain tissue segmentation for morphological assessments of brain structures. The results were benchmarked against a widely-used two-fold-accelerated 3T ADNI MPRAGE protocol that served as reference in this study. 22 healthy subjects (age=20-44yrs.) were imaged with all MPRAGE variants in a single session. An experienced reader rated all images of clinically useful image quality. CAIPIRINHA MPRAGE scans were perceived on average to be of identical value for reading as the reference ADNI-2 protocol. SNR and CNR measurements exhibited the theoretically expected performance at the four-fold acceleration. The results of this study demonstrate that the four-fold accelerated protocols introduce systematic biases in the segmentation results of some brain structures compared to the reference ADNI-2 protocol. Furthermore, results suggest that the increased noise levels in the accelerated protocols play an important role in introducing these biases, at least under the present study conditions.

Fate of cadmium in rat renal tubules: a microinjection study.

109Cd was injected into the lumen of superficial proximal or distal tubules of rat kidneys, and recovery in the pelvic urine from the ipsilateral kidney was measured. Fractional recovery of labeled inulin always exceeded 90%. About 70% of injected inorganic Cd (CdCl2) was taken up by the epithelium of proximal tubules, while more than 90% of the injected amount was recovered after distal microinjection. The proximal fractional Cd uptake of a 1:1 (molar) Cd-L-cysteine complex was 82%, but was below 60% for a 5-10:1 molar ratio of cysteine:Cd. The chelate Cd-pentetic acid was recovered in final urine nearly quantitatively after proximal or distal microinjection. Fractional uptake of 109Cd from a Cd-metallothionein (Mt) complex, following proximal microinjection, ranged between 17 (Cd-Mt 0.19 mM) and 8% (Cd-Mt 1.5 mM). It is concluded that luminal Cd uptake by the tubular epithelium depends markedly on the chemical form of Cd and, when present, occurs mostly or exclusively in proximal tubules.

Análise estrutural de ciclodextrinas: um estudo comparativo entre métodos teóricos clássicos e quânticos

In the present work, we analyzed the accuracy of distinct theoretical methods to reproduce the solid state structures of cyclodextrins. The a, b and g-cyclodextrins (CD) were considered and also their hydrates with included water molecules: a-CD.2H2O, b-CD.10H2O and g-CD.12H2O. The geometries were fully optimized using Molecular Mechanics (MM2), semiempirical (AM1 and PM3) and ab initio (HF/3-21G) methods and quantitatively compared with experimental data from X ray diffraction. The results obtained from the classical MM2 method were in best agreement with the experiment. The semiempirical and ab initio structures were also in satisfactory accordance with the experimental data. In general, the PM3 method was found to be more suitable than the AM1 to describe the CD geometries, mainly when the intramolecular hydrogen bonds are considered.

Improving Cross Direction Basis Weight Profile in a Fourdrinier Paper Machine

The purpose of this study was to improve PM7’s basis weight CD profile in Stora Enso’s Berghuizer mill and to search mechanical defects which affect to the formation of the basis weight CD profile. In the theoretical part PM7’s structure was presented and the formation of the basis weight and caliper CD profiles was examined as well as disturbances which are affecting to the formation. The function of the control system was scrutinised for the side of CD profiles as well as the formation of the measured CD profiles. Tuning of the control system was examined through the response model and filtering. Specification of the response model and filtering was explained and how to determine 2sigma statistical number. In the end of the theoretical part ATPA hardware and a new profile browser were introduced. In the experimental part focus was in the beginning to search and remove mechanical defects which are affecting to CD profiles. The next step was to verify the reliability of the online measurements, to study the stability of the basis weight CD profile and to find out so called fingerprint, a basis weight CD profile which is unique for each paper machine. New response model and filtering value for basis weight CD profile was determined by bump tests. After a follow up period the affect of the new response model and filtering was analysed.