Lateral intraparietal area (LIP) neurons are thought to compute the decision of where to look. Specifically, their firing rate is thought to represent accumulated evidence for a decision by ramping up to a high level, the putative decision bound, before an eye movement to a given location. However, LIP neurons are also highly responsive to visual stimuli. Because all previous research put a visual stimulus (a saccadic target) in the response field (RF) location of a neuron during decision formation, it is unknown if LIP neurons can still show decision computation without this visual drive. We therefore recorded the spiking activity of LIP neurons in a conventional decision task where a monkey decides the direction of a noisy motion stimulus and indicates his decision with a saccade. On half the trials, the Choice Targets remained on for the whole trial, as is conventionally done. On the remaining trials, targets were flashed at the beginning of the trial and absent during motion-viewing. Furthermore, we recorded the activity of any neuron with an RF, instead of only neurons exhibiting persistent memory activity before an instructed saccade. This enabled us to also test the long-held assumption that only cells with persistent memory activity show decision signals. Our results show that 1) cells without persistent activity indeed show decision signals, 2) population response drops without RF stimulation (although individual neurons were affected in diverse ways), 3) distinct, repeating response “motifs” exist among cells, 4) a signal exists where neural response is lower for stronger motion strength stimuli, regardless of direction. These results prove that contrary to dogma, a neuron’s ability to show a long “memory” response is not related to an ability to accumulate evidence over time for a decision. Also, LIP firing rate cannot be interpreted as a pure decision variable because it simultaneously represents decision-irrelevant, visual stimuli. Finally, diverse, but repeating responses among cells suggest the existence of cell types in LIP. These results demonstrate that LIP acts as a bank of potentially useful signals, and raises the question of how they might be used for a decision. / text

Posterior capsule opacification (PCO) is a major component of secondary cataract, a complication of current cataract surgery practice. This iatrogenic condition occurs in virtually all pediatric cases and to a lesser extent in adults. PCO correlates with the development in the latter half of the 20th Century of extracapsular cataract extraction (ECCE). In these surgeries, the lens capsule is left intact. During ECCE surgery a circular capsulotomy opening is created in the anterior lens capsule, and the cataractous, proteinaceous lens is removed, often via ultrasonic lens liquefaction i.e. phacoemulsification. The posterior, equatorial and remaining anterior portions of the sac-like capsule are left intact, permitting the insertion of an artificial lens into the emptied capsule. However, cells from the monolayer of epithelium on the inner surface of the capsule often begin to proliferate and migrate onto the normally cell-free inner surface of the posterior capsule, and may obscure the central axis of vision. Subsequently, a second surgery is necessary to create a small capsulotomy in the centre of the posterior capsule, usually employing an Nd:YAG laser. However, up to 5% of patients who have capsulotomies may then develop further serious, vision-threatening complications such as macular edema and retinal detachments. This thesis reports the photodynamic therapy (PDT) conditions required to prevent lens epithelial (LE) cell de novo proliferation and migration onto posterior lens capsules in a euthanized rabbit surgical model in order to predict parameters required to prevent PCO in humans. Experiments with primary in vitro cultures of human LE cells have shown rapid delivery of the photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA) and efficient killing with low light doses of 690 nm red light. Additional studies have shown the efficacy of various viscous agents in protecting the comeal endothelium. During model phacoemulsification ECCE surgeries, the use of hyaluronate viscoelastic carriers addressed the need for containment necessary for localized delivery of photosensitizer in the emptied capsule. Long-term monitoring of PDT-treated rabbit lens capsules in vitro has demonstrated a phototoxic effect including complete cell kill in this surgical model employing the prophylactic use of PDT.

When viewing a face, healthy individuals tend to fixate on upper regions, particularly the eyes, which provide important configural information about the spatial layout of the face. In contrast, individuals with face blindness (prosopagnosia) rely more on local features – particularly the mouth. Presented here is an examination of face perception deficits in individuals with Posterior Cortical Atrophy (PCA). PCA is a rare progressive neurodegenerative disorder that is characterized by atrophy in occipito-parietal and occipito-temporal areas. PCA primarily affects higher visual processing, while memory, reasoning, and insight remain relatively intact. Common among individuals with PCA is simultanagnosia, an inability to perceive more than one object or detail simultaneously. One might consider simultanagnosia the most extreme form of a feature-based approach. In a series of investigations, individuals with PCA and their healthy control participants completed a same/different discrimination task in which images of faces were presented as cue-target pairs. Eye-tracking equipment (Experiment 1) and the newly developed Viewing window paradigm (Experiment 2) were used to investigate scanning patterns when faces were presented in full view, and through a restricted viewing aperture, respectively. In contrast to previous prosopagnosia research, individuals with PCA each produced unique scan paths that focused on one aspect of the face. Individuals with PCA tended to focus on areas of high-contrast but many of these areas were not diagnostically useful, suggesting that they were having difficulty processing the face even at a featural level. These results suggest a role of simultanagnosia in the scan patterns of PCA patients that is not reflective of ‘typical’ prosopagnosia, and instead points to simultanagnosia, sometimes matched with basic perceptual impairments, as a significant contributor to the face perception deficits seen in PCA.

When viewing a face, healthy individuals tend to fixate on upper regions, particularly the eyes, which provide important configural information about the spatial layout of the face. In contrast, individuals with face blindness (prosopagnosia) rely more on local features – particularly the mouth. Presented here is an examination of face perception deficits in individuals with Posterior Cortical Atrophy (PCA). PCA is a rare progressive neurodegenerative disorder that is characterized by atrophy in occipito-parietal and occipito-temporal areas. PCA primarily affects higher visual processing, while memory, reasoning, and insight remain relatively intact. Common among individuals with PCA is simultanagnosia, an inability to perceive more than one object or detail simultaneously. One might consider simultanagnosia the most extreme form of a feature-based approach. In a series of investigations, individuals with PCA and their healthy control participants completed a same/different discrimination task in which images of faces were presented as cue-target pairs. Eye-tracking equipment (Experiment 1) and the newly developed Viewing window paradigm (Experiment 2) were used to investigate scanning patterns when faces were presented in full view, and through a restricted viewing aperture, respectively. In contrast to previous prosopagnosia research, individuals with PCA each produced unique scan paths that focused on one aspect of the face. Individuals with PCA tended to focus on areas of high-contrast but many of these areas were not diagnostically useful, suggesting that they were having difficulty processing the face even at a featural level. These results suggest a role of simultanagnosia in the scan patterns of PCA patients that is not reflective of ‘typical’ prosopagnosia, and instead points to simultanagnosia, sometimes matched with basic perceptual impairments, as a significant contributor to the face perception deficits seen in PCA.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-06-01T19:34:33Z No. of bitstreams: 1 Ana Claudia Silva. Estudo Clínico e Molecular em uma Coorte de Portadores....pdf: 2715219 bytes, checksum: 4103002ffbaa5c81df61ae344016cbb9 (MD5) / Made available in DSpace on 2012-06-01T19:34:33Z (GMT). No. of bitstreams: 1 Ana Claudia Silva. Estudo Clínico e Molecular em uma Coorte de Portadores....pdf: 2715219 bytes, checksum: 4103002ffbaa5c81df61ae344016cbb9 (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / A deficiência de hormônio do crescimento (DGH) tem incidência estimada entre 1/4.000 a 1/10.000 nascidos vivos e pode ser isolada ou associar-se a outras deficiências hormonais. Como não há exame “padrão-ouro”, o seu diagnóstico baseia-se em critérios antropométricos associados a pico diminuído de GH após testes de estímulos farmacológicos. Mais recentemente, a presença de ectopia do lobo posterior hipofisário (ELP) à ressonância nuclear magnética de hipófise (RNMH) tem sido considerada marcador de DGH e mutações em genes associados à embriogênese hipofisária têm sido descritas nesse pacientes. O objetivo do trabalho foi descrever as características clínicas, moleculares e radiológicas de uma coorte de portadores de DGH, acompanhada num mesmo centro de referência (Centro de Diabetes e Endocrinologia da Bahia), entre dezembro de 1998 e dezembro de 2009. Métodos: todos os pacientes realizaram avaliação da função hipofisária e RNMH. O estudo foi dividido em duas partes. Na primeira, foram incluídos apenas pacientes com DGH e ELP (n=130), sendo realizada a caracterização fenotípica da população. Além disso, mutações nos genes HESX1, LHX4 e OTX2 foram avaliadas em 104 pacientes, pelos métodos de PCR e SSCP ou PCR e sequenciamento. Na segunda parte do estudo, foi comparada a resposta terapêutica no primeiro ano de tratamento com hormônio do crescimento nos pacientes com (n=58) e sem (n=26) ELP. Resultados: No subgrupo de pacientes com ELP observou-se grande variabilidade fenotípica. Deficiência hormonal hipofisária combinada foi descrita em 61,5% dos pacientes, sendo mais frequente naqueles nos quais a haste hipofisária não foi visualizada. Malformações cerebrais ocorreram em 9,2% dos pacientes. Trinta pacientes apresentaram mutações, não descritas anteriormente, em genes associados à embriogênese hipofisária, sendo 26 no LHX4 e cinco no HESX1. Mutações no OTX2 não foram identificadas nessa população. A segunda parte do estudo evidenciou que a velocidade de crescimento durante o tratamento com GH foi similar nos pacientes com e sem ELP. Conclusões: o estudo, que avaliou a maior casuística de pacientes com DGH associada à ELP já descrita, confirma a heterogeneidade fenotípica da população, além da baixa prevalência de mutações na mesma. Além disso, ao contrário de estudos prévios, demonstra que a presença de ELP não se associou a melhor resposta ao tratamento com GH. / The estimated incidence of growth hormone deficiency (GHD) is between 1/4.000 and 1/10.000 among live births. It may be isolated or associated with other hormone deficiencies. As there is no gold standard test, the diagnosis of GHD relies on anthropometric criteria associated with decreased GH peak after pharmacological stimulation tests. More recently, the description of ectopic posterior pituitary lobe (EPPL) on magnetic resonance imaging (MRI) has been considered a marker of GHD and mutations in genes involved in pituitary gland organogenesis have been described in these patients. The aim of this study was to describe clinical, molecular and radiological characteristics of a cohort of GHD patients followed, in a single reference center (Diabetes and Endocrinology Center or Bahia), between December 1998 and December 2009. Methods: all patients underwent pituitary function evaluation and MRI. The study was divided in two parts. In the first one, only patients with GHD and EPL were included (=130) and phenotypic characterization of the population was performed. In addition, mutations in HESX1, LHX4 and OTX2 genes were investigated in 104 patients using polymerase chain reaction (PCR) plus single strand conformation polymorphism (SSCP) or PCR and automatic sequencing. In the second part of the study, the growth pattern in the first year of GH treatment was compared in patients with (n=58) and without (n=26) EPPL. Results: Large phenotypic variability was observed in the subgroup of patients with EPPL. Combined pituitary deficiency was described in 61.5% of the patients, more frequent in those with no visible pituitary stalk. Cerebral malformations were described in 9.2% of the patients. Thirty patients have mutations, not described in previous studies, 26 in LHX4 and five in HESX1. OTX2 mutations were not identified in this population. The second part of the study showed similar growth pattern in patients with and without EPPL. Conclusions: The study, with the largest cohort of GHD patients associated with EPPL already described, confirms the phenotypic heterogeneity of the population and the low prevalence of mutations in genes involved in pituitary embryogenesis. Furthermore, unlike previous studies, the presence of EPPL was not associated with a better growth response to human growth hormone therapy.

INTRODUÇÃO: O hipopituitarismo está associado, em cerca de 40% dos casos, à ectopia da neuro-hipófise observada em imagem por ressonância magnética (RM). Nestes pacientes a visualização da haste ocorre predominantemente nos que têm deficiência isolada de GH (DIGH), enquanto a não visualização da mesma está mais associada à deficiência hipofisária múltipla (DHM). A etiologia deste quadro, no entanto, permanece indeterminada na maioria dos pacientes. A elevada freqüência de parto pélvico e de complicações neonatais sugere uma causa traumática, enquanto que relatos de casos familiares, associação com outras patologias do SNC e descrição de mutações nos genes HESX1, LHX4 e SOX3 apontam para uma causa genética. O LHX4 é um fator de transcrição envolvido na embriogênese hipofisária fundamental para a formação da bolsa de Rathke definitiva. O LHX4 está localizado no cromossomo 1q 25, possui 6 éxons e estende-se por mais de 45 kb de DNA genômico. A única mutação publicada neste gene em humanos é a IVS4-1G>C, associada a um fenótipo caracterizado por baixa estatura, deficiências de GH, TSH e ACTH, neuro-hipófise ectópica e malformação Arnold-Chiari tipo I. O objetivo do estudo é analisar as regiões exônicas e éxon-íntron do LHX4 e caracterizar o perfil hormonal, correlacionando com os achados de RM, em 63 pacientes com hipopituitarismo associado a neurohipófise ectópica. MÉTODOS: Os pacientes foram submetidos à avaliação hormonal e por imagem através de ressonância magnética. A análise molecular incluiu amplificação do gene por PCR, seqüenciamento automático e uso de enzima de restrição. RESULTADOS: A visualização da haste ocorreu em 21 pacientes; destes, 10 (48%) apresentaram DIGH. A não visualização da haste foi mais associada a DHM, o que ocorreu em 40 (95%) dos 42 pacientes. Não encontramos diferença significativa quando comparamos pacientes com haste visualizada e não visualizada quanto à freqüência de partos vaginais em apresentação pélvica, à freqüência de malformações do SNC e à posição precisa da neuro-hipófise ectópica. Identificamos 6 variações alélicas no gene LHX4 em nossos pacientes: GGT>GGC, no códon 21; GAC>GAT, no códon 128; AAC>AAT, no códon 150; AGC>AGT, no códon 230; GGA>GGT, no códon 283 e AAT>AGT no códon 329 (N329S), esta já descrita como polimorfismo no GenBank. Nenhuma das outras variações determina troca de aminoácidos, altera o sítio de \"splice\" ou se correlaciona com um padrão de deficiência hormonal característico. As variações alélicas nos códons 21, 128 e 150 foram caracterizadas como polimorfismos. Não foi possível estabelecer uma relação entre as variações alélicas e o fenótipo dos pacientes. CONCLUSÃO: Mutações no LHX4 são causas raras de hipopituitarismo / INTRODUCTION: Ectopic posterior pituitary lobe (EPL) is observed using magnetic resonance imaging (MRI) scans in about 40% of patients with hypopituitarism. In these patients, the pituitary stalk is visualized mainly in patients with isolated GH deficiency (IGHD), whilst it is not visualized predominantly in patients with combined pituitary hormone deficiency (CPHD). Nevertheless, the etiology of EPL remains undetermined in most of the patients. A traumatic etiology is proposed for this figure, which presents a high frequency of breech delivery and perinatal damages. On the other hand, a genetic cause is suggested by associations to other CNS abnormalities and reports of gene mutations in HESX1, LHX4 and SOX3, as well as familial cases. LHX4 is a transcription factor implicated in pituitary embryogenesis which is essential to definitive Rathke\'s pouch development. It is located in chromosome 1q25, has 6 exons and is stretched out for more than 45 kb of genomic DNA. The only documented human mutation in this gene, IVS4-1G>C, is associated to a phenotype characterized by short stature, GH, TSH and ACTH deficiencies, EPL and Arnold-Chiari type I malformation. The aim of this study is to analyze exonic and exon-intron regions of LHX4 gene and characterize the hormonal deficiency profiles, establishing relationships to MRI findings in 63 patients with hypopituitarism associated to EPL. METHODS: All patients were submitted to hormonal evaluation and MRI scans. The molecular analysis included amplification of the gene using PCR, direct automatic sequencer and digestion with restriction enzymes. RESULTS: The pituitary stalk was visualized in 21 patients; of these, 10 (48%) exhibited IGHD. The stalk was not visualized in 42 patients, most of them with CPHD (95%). We did not find a statistical difference, when patients with and without visualized pituitary stalk were compared, regarding breech deliveries, CNS malformations and exact position of EPL. We identified 6 allelic variations in LHX4 gene: GGT>GGC in codon 21, GAC>GAT in codon 128, AAC>AAT in codon 150, AGC>AGT in codon 230, GGA>GGT in codon 283 and AAT>AGT in codon 329 (N329S), this already related as a polymorphism in GenBank. None of the former variations determine amino acid changes, nor splicing site changes, not even are related to a typical profile of hormonal deficiency. The allelic variations in codons 21, 128 and 150 were described as polymorphisms. It was not possible to establish a relationship between the allelic variations and the phenotype. CONCLUSION: LHX4 gene mutations are rare causes of hypopituitarism

Posterior capsule opacification (PCO) is a major component of secondary cataract, a complication of current cataract surgery practice. This iatrogenic condition occurs in virtually all pediatric cases and to a lesser extent in adults. PCO correlates with the development in the latter half of the 20th Century of extracapsular cataract extraction (ECCE). In these surgeries, the lens capsule is left intact. During ECCE surgery a circular capsulotomy opening is created in the anterior lens capsule, and the cataractous, proteinaceous lens is removed, often via ultrasonic lens liquefaction i.e. phacoemulsification. The posterior, equatorial and remaining anterior portions of the sac-like capsule are left intact, permitting the insertion of an artificial lens into the emptied capsule. However, cells from the monolayer of epithelium on the inner surface of the capsule often begin to proliferate and migrate onto the normally cell-free inner surface of the posterior capsule, and may obscure the central axis of vision. Subsequently, a second surgery is necessary to create a small capsulotomy in the centre of the posterior capsule, usually employing an Nd:YAG laser. However, up to 5% of patients who have capsulotomies may then develop further serious, vision-threatening complications such as macular edema and retinal detachments. This thesis reports the photodynamic therapy (PDT) conditions required to prevent lens epithelial (LE) cell de novo proliferation and migration onto posterior lens capsules in a euthanized rabbit surgical model in order to predict parameters required to prevent PCO in humans. Experiments with primary in vitro cultures of human LE cells have shown rapid delivery of the photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA) and efficient killing with low light doses of 690 nm red light. Additional studies have shown the efficacy of various viscous agents in protecting the comeal endothelium. During model phacoemulsification ECCE surgeries, the use of hyaluronate viscoelastic carriers addressed the need for containment necessary for localized delivery of photosensitizer in the emptied capsule. Long-term monitoring of PDT-treated rabbit lens capsules in vitro has demonstrated a phototoxic effect including complete cell kill in this surgical model employing the prophylactic use of PDT. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Pharmacologic and chromatographic methods were employed to identify the neurohypophysial peptides present in, two species of cyslostomes, the western brook lamprey, Lampetra richardsoni, and the Pacific hagfish, Polistotrema stoutii. The evidence obtained indicated the presence of low amounts of 8-arginine -oxytocin or arginine vasotocin in both animals. No evidence was provided to suggest the existence of a second biologically active posterior pituitary principle in either species, and with the lamprey, it appeared unlikely that more than one percent of the total activity extracted from the neurohypophysial tissues could have been due to a second peptide without being detected. The results of the study thus supported previous claims that cyclo-stomes were unique amoung vertebrates in the possession of a single active neurohypophysial principle. The evolutionary significance of this feature of lamprey and hagfish is discussed, as well as the possibility of the existence, in the pituitary of lower vertebrates, of "intermediate" neurohypophysial peptides with low biological activity. Pharmacologic and chromatographic investigations of midbrain and hind-brain "control" material from the western brook lamprey suggested that small amounts of arginine vasotocin may have been present in these tissues. The possible explanations for this extra-hypothalamic location of a neurohypophysial peptide are discussed, in light of similar findings in other vertebrates. Subsequent to the demonstration of the presence of arginine vasotocin in Lampetra richardsoni, the levels of the peptide were studied in animals of various ages and in larvae kept under various photoperiods. Determinations of the amounts of AVT present in the lamprey during its life history were made in an attempt to corroborate published histological observations which suggested that in Lampetra planeri a marked depletion of the principle occurred at metamorphosis. Although the interpretation of results was complicated by the presence of substantial amounts of contaminating substances in the pituitary extracts, it appeared unlikely that the levels of AVT were drastically reduced at transformation in L. richardsoni. Rather, the data indicated that the amounts of the peptide, as well as the quantities of other active substances in both pituitary and hindbrain tissues, were augmented when larvae transformed into adults. This increase in rat uterus activity extracted from the tissues was correlated with an increase in dry weight of the brain, and it appeared likely that the two occurrences were causally linked. No significant deviations were noted in the rat uterus activity extracted from groups of larval lamprey kept under different photoperiods. The variations that occurred amoung the neurohypophysial tissues were paralleled by differences amoung the control tissues; this suggested that photoperiod had effects on other biologically active subatances in the central nervous system besides AVT. / Science, Faculty of / Zoology, Department of / Graduate

This diploma thesis is about Bayesian approach in managerial decision making process. The goal is not only to quantify the principals used by managers during decision making in real situations but also the application of Bayesian methods on given examples. The mentioned principals are the probability updates after gaining a new information. In thesis are also described the computer systems which work with Bayesian calculations and a chosen system is described in detail. In a practical part of this thesis is demonstrated the use of Bayesian principals in real decision making situations -- there is demonstrated the use of Bayesian games, Bayesian networks (both classic and dynamic) and risk decision making process.

Bakgrund Droppfot är vanligt vid många sjukdomar och tillstånd, och resulterar i en oförmåga att dorsalextendera fotleden. I vissa fall måste en sentransferering av tibialis posterior utföras för att återställa förmågan att dorsalextendera. Operationen utförs på olika sätt, är väldokumenterad och väl beforskad. För att operationen ska ge önskat resultat krävs god rehabilitering postoperativt. Rehabiliteringen är mindre dokumenterad och saknar tydliga direktiv att förhålla sig till.  Syfte Syftet med denna scoping review var att sammanställa och granska den tillgängliga kunskapen angående rehabiliteringen efter en sentransferering av tibialis posterior.   Metod En scoping review valdes som studiedesign då artikelutbudet är begränsat. Studien utfördes enligt riktlinjer av Arksey & O’Malley (2005), samt Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA).  Resultat Resultatet av sökningen och artikelurvalet på 28 artiklar visade på en stor inkonsekvens i hur rehabiliteringen utförs. De data som extraherades var; antal deltagare, typ av operation, belastning postoperativt, immobiliseringstid, samt beskrivning av fysioterapeutiska insatser. Vissa studier vittnar om 11-12 veckors immobilisering i gips, medan andra mobiliserar inom en vecka postoperativt och undviker att gipsa. Den stora inkonsekvensen kan delvis förklaras med att deltagarnas grunddiagnoser varierar mellan de inkluderade studierna, samt att de kirurgiska tillvägagångssätten skilde sig åt, samt inkluderade andra operationer. Endast två studier behandlade rehabiliteringen som sitt huvudsyfte. Slutsats Bristfällig forskning finns för att kunna dra några vetenskapliga slutsatser. Mer forskning behövs, både som adresserar fysioterapeutiska interventioner och rehabiliteringsfasen i helhet. Mer specifik forskning gällande rehabiliteringen vid sentransferering av tibialis posterior med beaktande av de enskilda diagnoserna behövs också.