Purpose: To evaluate the incidence of central hole-induced ring-shaped dysphotopsia after posterior chamber phakic implantable collamer lens (ICL) with central hole (hole ICL) implantation and to investigate the causes of central hole-induced dysphotopsia. MethodsThe clinical study enrolled 29 eyes of 15 consecutive myopic patients implanted with hole ICL. The incidence of ring-shaped dysphotopsia after hole ICL implantation was evaluated. In the experimental simulation study, non-sequential ray tracing was used to construct myopic human eye models with hole ICL and ICL without a central hole (conventional ICL). Simulated retinal images measured in log-scale irradiance were compared between the two ICLs for an extended Lambertian light-emitting disc object 20cm in diameter placed 2m from the corneal vertex. To investigate the causes of hole-induced dysphotopsia, a series of retinal images were simulated using point sources at infinity with well-defined field angles (0 to -20 degrees) and multiple ICL models. ResultsOf 29 eyes, 15 experienced ring-shaped dysphotopsia after hole ICL implantation. The simulation study using an extended Lambertian source showed that hole ICL-evoked ring-shaped dysphotopsia was formed at a retinal field angle of 40 degrees. Component-level analysis using a well-defined off-axis point source from infinity revealed that ring-shaped dysphotopsia was generated by stray light refraction from the inner wall of the hole and the posterior ICL surface. ConclusionHole ICL-evoked ring-shaped dysphotopsia was related to light refraction at the central hole structure. Surgeons are advised to explain to patients the possibility of ring-shaped dysphotopsia after hole ICL implantation.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Adolescent Idiopathic Scoliosis (AIS) is typically treated surgically by Posterior Spinal Fusion (PSF) surgery. Intravenous analgesics and oral opioids are commonly used for pain management. Several adjunct therapies are used in addition to the standard treatments. One of these therapies is the use of dexmedetomidine (dex). Though dex has been found to be an effective sedative for post‐operative patients, there are also several adverse effects that are associated with its use. The purpose of this study was to investigate the effectiveness and overall benefit of using dex for pain control for patients undergoing PSF for AIS. IRB approval was obtained. A group of 43 patients with AIS undergoing PSF and using Dex for adjunctive pain control were matched with 43 patients who did not use Dex. The groups were matched based on gender, age, height, weight, and level of spinal fusion. During the patients’ post‐operative hospital stay, the total opioid use and clinical pain scores were compared between the two groups using t‐tests, with significance set at p<0.05. Total opiate use was 239.6 morphine equivalent doses in the non‐Dex (control) group and 246.2 in the group that received Dex (p=0.72). The average pain score in the control group was 2.3, and the group that received Dex was 2.6 (p =0.43). There were no differences in the complication rate between the two groups, specifically the oversedation rates and pulmonary complications. Lastly, the average length of stay for the control group was 4.8 days compared to the dex group, which was 5.0 days (p=0.35). Although adjunctive pain modalities may be very useful in the treatment of postoperative pain after PSF in patients with AIS, the use of Dex in this cohort did not improve pain scores, lower opioid use, or lower the LOS. Based on these results, we do not recommend the routine use of dexmedetomidine as an adjunctive pain control modality. Adjunctive modalities are important in pain control in patients with AIS undergoing PSF, but the use of dexmedotomidine was not effective in improving pain control.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Surgical correction of Adolescent Idiopathic Scoliosis (AIS) carries a substantial risk of complication. The literature supports improved perioperative outcomes through the two surgeon strategy in other complex orthopedic procedures. Does the presence of 2 versus 1 attending surgeons affect the perioperative morbidity of posterior spinal fusion (PSF) in patients with AIS curves greater than 70°? We reviewed the database from a large regional children’s hospital of all patients with AIS curves greater than 70° who underwent PSF from 2009‐2014 and divided the cohort into single versus 2‐surgeon groups (28 vs. 19 cases, respectively). We analyzed cases for length of surgery, estimated blood loss, and length of stay. The groups were identical when comparing age, gender, spinal levels fused, and average ASA score. However, the average Cobb angle in the single surgeon group was significantly less than in the 2 surgeon group at 78.4 vs 84.0 degrees, respectively (p=0.049). Mean operative time for single versus 2 surgeons was 238 (SD 48) vs 212 (SD 46) minutes (p=0.078). Mean percent estimated blood loss was 26% (SD 14.1) for single surgeon vs 31% (SD 14.9) for 2 surgeons (p=0.236), and mean estimated blood loss for single surgeon vs 2 surgeons was 830ml (SD 361) vs 1045ml (SD 346) (p=0.052). Mean length of stay was significantly decreased in the 2 surgeon group at 5.16 days (SD 1.7) versus the single surgeon group at 6.82 days (SD 6.82) (p=0.002). The use of 2 surgeons in AIS deformity correction at an experienced regional children’s hospital did not improve clinical outcomes. The average length of stay was reduced in the two‐surgeon group, but there was no significant impact on blood loss or operative time. However, this study does not rule out the potential for positive impact with a two‐surgeon strategy, and given previous supportive data in the literature, this approach should further evaluated to determine its effect on improving perioperative outcomes.

Aceitando que existe um tempo lingüístico distinto do tempo físico ou do tempo cronológico, este trabalho visa o estudo do sistema temporal no español utilizando como modelo teórico as propostas de José Luiz Fiorin em As astúcias da enunciação. Desde o ponto de vista da teoria semiótica, adotada no presente trabalho, o sentido constrói-se por um percurso gerativo em três níveis: fundamental, narrativo e discursivo. A enunciação, como ato produtor de um enunciado, é a instância encarregada de instaurar no nível discursivo as categorias de pessoa, tempo e espaço. A partir do momento da enunciação estabelecem-se três momentos de referência, um momento de referência concomitante e dois não concomitantes com o momento da enunciação, o momento de referência da anterioridade e o momento de referência da posterioridade. Por sua vez cada um desses momentos de referência desdobram-se em momentos do acontecimento, igualmente concomitantes e não concomitantes (anteriores e posteriores). Os tempos verbais que exprimem a relação de concomitância configuram o sistema enunciativo e os tempos que explicam a relação de não concomitância com o momento da enunciação conformam o sistema enuncivo. São estudadas as relações dos tempos verbais do español a respeito do momento da enunciação e as diferentes posições que ocupam nos sistemas tanto enuncivo quanto enunciativo, os usos fundamentais e as possíveis neutralizações em determinados contextos ou em função da intenção do enunciador. A verificação do modelo teórico se faz extensiva às mudanças ocorridas tanto no estilo direto, o narrador delega a voz a um interlocutor, quanto no estilo indireto, na passagem de dois momentos de enunciação para um só. Não serão esquecidas as correlações temporais e as relações que os tempos do subjuntivo estabelecem com o verbo principal e, portanto, com o momento de referência dele. / Accepting there is a linguistic tense different from physical or chronological time, this work aims the studying of Spanish time system by using the theoretical model proposed by José Luiz Fiorin in his As astúcias da enunciação. From the point of view of Semiotic theory, adopted in this work, the meaning is constructed by a generative process in several levels, fundamental, narrative and discursive. Enunciation, as a producer fact of a statement, is the instance in charge to initiate in a discursive level the categories of person, time and space. From the moment of enunciation they are created three moments of reference: one moment of concomitance reference and two non-concomitance with the moment of enunciation, the moment of anterior reference and the moment of posterior reference. At the same time, each one of these moments of reference is separated into moments of occurrence, equally concomitance and nonconcomitance (anterior and posterior). The verbal tenses that express the relationship of concomitance configure the enunciative system and verbal times express the relationship of not-concomitance configure the enuncive system. First, they will be studied the relationship of Spanish verbal tenses regarding the moment of the enunciation and different positions they occupy in the systems both enuncive and enunciative. Second, they will be also studied the fundamental uses and possible verbal neutralizations in specific contexts or depending of the writer´s intention. Finally, the verification of Fiorin model is extended to the changes done in the direct style, when the narrator delegates the voice to one interlocutor, as much as in the indirect style, when the two moments of enunciation become just one. They will not been forgotten time correlations and the relationship of the subjunctive tenses establish with the main verb; therefore, with the moment of its reference.

INTRODUÇÃO: A instabilidade multiligamentar do joelho, normalmente, é provocada por um trauma que determina sua luxação, um evento pouco frequente, mas, que pode trazer sequelas devastadoras. Mesmo com o tratamento cirúrgico preconizado é alto o índice de complicações. A mobilização precoce no pósoperatório provoca afrouxamento dos ligamentos reconstruídos, o que leva à instabilidade residual. A imobilização melhora a estabilidade, mas provoca dor e rigidez. Este trabalho tem o objetivo de avaliar se o uso do fixador externo articulado proporciona melhora na mobilidade, estabilidade e na função subjetiva de pacientes submetidos à reconstrução ligamentar. MÉTODOS: Neste ensaio clínico randomizado com grupos paralelos, 33 pacientes do ambulatório do Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Universidade de São Paulo com mais que 3 semanas de lesão dos ligamentos cruzados anterior e posterior associado à lesão de ligamento colateral fibular e/ ou ligamento colateral tibial foram submetidos à cirurgia de reconstrução multiligamentar, após alocação cega aleatória ao grupo 0 - controle (18 pacientes), com órtese rígida ou ao grupo 1 - fixador externo articulado por 6 semanas (15 pacientes), no período entre novembro de 2010 e novembro de 2013. Após seguimento mínimo de um ano de pós-operatório, a estabilidade dos ligamentos reconstruídos foi avaliada ao exame físico, foram mensurados os déficits de extensão e de flexão residual em relação ao joelho contralateral não acometido e foi aplicado o questionário específico para sintomas do joelho de Lysholm. RESULTADOS: Não houve diferença na avaliação da estabilidade articular nem na extensão entre os grupos. No grupo 1, o déficit de flexão passiva foi menor (4,8º +- 5,4º contra 18,2 +- 14,8º, p < 0,05) com mais pacientes, obtendo déficit de flexão considerado normal, de até 5º (64% contra 18%, p < 0,05) e com classificação excelente ou boa no questionário de Lysholm (73% contra 35%, p < 0,05). CONCLUSÕES: Comparado ao protocolo de reabilitação com órtese rígida removível, o uso do fixador externo articulado no tratamento cirúrgico das lesões multiligamentares do joelho proporciona os mesmos resultados de estabilidade ligamentar, aumenta a amplitude de movimento final, com manutenção da extensão e redução do déficit de flexão e proporciona melhores resultados funcionais / INTRODUCTION: Multiligament knee instability is normally caused by a trauma which results in its dislocation, an infrequent event, but one which can have devastating aftereffects. Even with the recommended surgical treatment the rate of complications is high. Early post-operative mobilization provokes loosening of the reconstructed ligaments, which leads to residual instability. Immobilization improves the stability, but causes pain and stiffness. This study aims to assess whether the use of an articulated external fixator provides improvements in the mobility, stability and the subjective function of the patients submitted to ligament reconstruction. METHODS: In this randomized clinical trial with parallel groups, 33 patients of the outpatient clinic of the Institute of Orthopaedics and Traumatology of the Hospital das Clínicas of the University of Sao Paulo with more than 3 weeks of injury to the anterior cruciate ligaments and the posterior cruciate ligaments associated with injury to the fibular collateral ligament and/or medial collateral ligament, were submitted to multiligament reconstruction surgery, after blind random allocation to either: Group 0 - control (18 patients), with rigid bracing, or to Group 1 - articulated external fixator for 6 weeks (15 patients), in the period from November, 2010 to November 2013. The stability of the reconstructed ligaments were assessed after 1 year postoperatively by physical examination, the deficit of residual extension and flexion was measured in relation to the unaffected contralateral knee and the Lysholm knee scoring scale questionnaire was applied. RESULTS: There was no difference in the assessment of joint stability or of the extension between the groups. In group 1 the passive flexion deficit was less (4.8º +- 5.4º versus 18.2 +- 14.8º, p<0.05) with more patients obtaining a flexion deficit considered normal, or up to 5º (64% versus 18%, p<0.05) and with excellent or good classification in the Lysholm knee scoring scale questionnaire (73% versus 35%, p<0.05). CONCLUSIONS: Compared to the rehabilitation protocol with removable rigid bracing, the use of an articulated external fixator in the treatment of multiligament knee injuries provides equal results for ligament stability, increases the amplitude of the Range of Motion, maintains the extension and reduces the flexion deficit, and provides better functional result

Aceitando que existe um tempo lingüístico distinto do tempo físico ou do tempo cronológico, este trabalho visa o estudo do sistema temporal no español utilizando como modelo teórico as propostas de José Luiz Fiorin em As astúcias da enunciação. Desde o ponto de vista da teoria semiótica, adotada no presente trabalho, o sentido constrói-se por um percurso gerativo em três níveis: fundamental, narrativo e discursivo. A enunciação, como ato produtor de um enunciado, é a instância encarregada de instaurar no nível discursivo as categorias de pessoa, tempo e espaço. A partir do momento da enunciação estabelecem-se três momentos de referência, um momento de referência concomitante e dois não concomitantes com o momento da enunciação, o momento de referência da anterioridade e o momento de referência da posterioridade. Por sua vez cada um desses momentos de referência desdobram-se em momentos do acontecimento, igualmente concomitantes e não concomitantes (anteriores e posteriores). Os tempos verbais que exprimem a relação de concomitância configuram o sistema enunciativo e os tempos que explicam a relação de não concomitância com o momento da enunciação conformam o sistema enuncivo. São estudadas as relações dos tempos verbais do español a respeito do momento da enunciação e as diferentes posições que ocupam nos sistemas tanto enuncivo quanto enunciativo, os usos fundamentais e as possíveis neutralizações em determinados contextos ou em função da intenção do enunciador. A verificação do modelo teórico se faz extensiva às mudanças ocorridas tanto no estilo direto, o narrador delega a voz a um interlocutor, quanto no estilo indireto, na passagem de dois momentos de enunciação para um só. Não serão esquecidas as correlações temporais e as relações que os tempos do subjuntivo estabelecem com o verbo principal e, portanto, com o momento de referência dele. / Accepting there is a linguistic tense different from physical or chronological time, this work aims the studying of Spanish time system by using the theoretical model proposed by José Luiz Fiorin in his As astúcias da enunciação. From the point of view of Semiotic theory, adopted in this work, the meaning is constructed by a generative process in several levels, fundamental, narrative and discursive. Enunciation, as a producer fact of a statement, is the instance in charge to initiate in a discursive level the categories of person, time and space. From the moment of enunciation they are created three moments of reference: one moment of concomitance reference and two non-concomitance with the moment of enunciation, the moment of anterior reference and the moment of posterior reference. At the same time, each one of these moments of reference is separated into moments of occurrence, equally concomitance and nonconcomitance (anterior and posterior). The verbal tenses that express the relationship of concomitance configure the enunciative system and verbal times express the relationship of not-concomitance configure the enuncive system. First, they will be studied the relationship of Spanish verbal tenses regarding the moment of the enunciation and different positions they occupy in the systems both enuncive and enunciative. Second, they will be also studied the fundamental uses and possible verbal neutralizations in specific contexts or depending of the writer´s intention. Finally, the verification of Fiorin model is extended to the changes done in the direct style, when the narrator delegates the voice to one interlocutor, as much as in the indirect style, when the two moments of enunciation become just one. They will not been forgotten time correlations and the relationship of the subjunctive tenses establish with the main verb; therefore, with the moment of its reference.

Posterior urethral valves cause bladder outflow obstruction and damage to the developing fetal kidney. Posterior urethral valves affect 1 in 8000 new-born males. A third of these children develop end stage renal failure by adolescence, despite valve ablation in the early post-natal period, implying that majority of the damage to the kidneys occurs in utero. How does this damage occur, and should we intervene in utero? The answers to these questions require further research, and are the basis to this thesis. This thesis focused on the effect bladder outflow obstruction has on morphology and apoptosis in the fetal kidney in a fetal lamb model. It also looked at the effect of bladder outflow obstruction on fetal stress hormone levels. Bladder outflow obstruction was created surgically in fetal lambs at day 70 of gestation, and fetal kidneys were analysed at day 2, 5, 10, 20 and 30 after creation of obstruction. Controls undergoing sham surgery were used for comparison. Four aspects were investigated: - effects of bladder outflow obstruction on renal histology effects of bladder outflow obstruction on expression of pro-apoptosis gene Bax and anti-apoptosis gene Bcl-X - effects of bladder outflow obstruction on renal regional apoptosis effects of bladder outflow obstruction on serum fetal ACTH and cortisol levels. Bladder outflow obstruction resulted in sequential morphological change in the fetal kidney over time. By 2 days post-obstruction, cystic change was noted. In addition, patchy attenuation of the nephrogenic blastema was evident by 5 days post-obstruction, with more confluent blastemal attenuation as well as generalized renal architectural disorganization by 10 days post-obstruction. By 20 and 30 days post-obstruction, cystic renal dysplasia had developed. Bladder outflow obstruction resulted in an increase in the ratio of renal expression of pro-apoptosis gene Bax to anti-apoptosis gene Bcl-X. Regional apoptosis counts showed increased tubular apoptosis compared to controls at 2 days post-obstruction, and increased blastemal apoptosis compared to controls at 5 days post-obstruction. By 10 days post-obstruction, blastemal apoptosis counts were reduced compared to controls. There were no significant differences in fetal serum ACTH and cortisol levels between fetal lambs with bladder outflow obstruction and controls. In conclusion, the results of this thesis outline the spectrum of morphological change in the fetal kidney over 30 days of bladder outflow obstruction. They show that detectable changes in morphology occur within two days of bladder outflow obstruction. Likewise, detectable changes in gene expression occur within 2 days of bladder outflow obstruction. The increased ratio of expression of Bax to Bcl-X suggests a swing towards increased apoptosis in response to bladder outflow obstruction. Further research is required to ascertain if these changes are reversible. However, the early onset of these changes as shown in this thesis suggests that any fetal intervention to protect the fetal kidney from the effects of bladder outflow obstruction may need to be instituted very early in gestation

Vertebrate wnt8a occupies a position at a crossroads linking anteroposterior and dorsoventral axis patterning. While functional aspects of wnt8a are beginning to be understood, the regulation of wnt8a expression and its relationship to mesoderm induction and maintenance pathways are unclear. Three inputs that control wnt8a expression in the zebrafish embryonic margin have been identified: the Brachyury-related T-box transcription factors No tail a (Ntla) and No tail b (Ntlb, previously called Bra) and the maternal zinc-finger transcription factor Zbtb4 (previously called Kzp) are known direct regulators, and Nodal signaling is genetically upstream of wnt8a expression. The transcriptional mechanisms by which the wnt8a locus integrates these diverse temporal inputs are not yet known. We have generated zebrafish transgenic for a modified genomic PAC clone that expresses EGFP from the wnt8a locus. The EGFP reporter transgene is expressed in a pattern nearly identical to wnt8a, including maternal deposition, expression in the ventrolateral mesoderm and in the yolk syncytial layer. Using this transgenic line, we identified two phases of wnt8a transcriptional regulation in zebrafish: phase I comprises Nodal-dependent activation during early gastrulation and phase II comprises No tail (Ntl)-dependent regulation from mid to late gastrula stages onwards. These phases mirror the transition from Nodal-dependent mesoderm induction to Ntl-dependent mesoderm maintenance. To further understand how the wnt8a locus integrates these signals to achieve its transcriptional output, we analyzed upstream cis-regulatory regions through transgenic reporter assays. We identified three promoters in the bicistronic wnt8a locus, two of which drive expression of the upstream coding region (wnt8a.1). We identified two regulatory regions, proximal and distal: the proximal regulatory region contains a mesodermal enhancer with potential binding sites for FoxH1 and Ntl that is required for both the Nodal and Ntl responses. Phase I expression requires Nodal signaling through the mesoderm enhancer in combination with the distal regulatory region, which bears a Zbtb4 consensus binding site. Phase II expression requires Ntl regulation of the mesoderm enhancer in the context of the proximal regulatory region. The distal regulatory region negatively impacts phase II expression driven by the proximal regulatory region, indicating a complex relationship of regulatory elements.

No description available.

We consider the problem of testing the equality of two sample means, when the number of tests performed is large. Applying this problem to the context of gene expression data, our goal is to detect a set of genes differentially expressed under two treatments or two biological conditions. A null hypothesis of no difference in the gene expression under the two conditions is constructed. Since such a hypothesis is tested for each gene, it follows that thousands of tests are performed simultaneously, and multiple testing issues then arise. The aim of our research is to make a connection between Bayesian analysis and frequentist theory in the context of multiple comparisons by deriving some properties shared by both p-values and posterior probabilities. The ultimate goal of this work is to use the posterior probability of the one-sided alternative hypothesis (or equivalently, posterior probability of the half-space) in the same spirit as a p-value. We show for instance that such a Bayesian probability can be used as an input in some standard multiple testing procedures controlling for the False Discovery rate.