Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis.

INTRODUCTION: The dichotomization of non-small cell carcinoma (NSCLC) subtype into squamous (SQCC) and adenocarcinoma (ADC) has become important in recent years and is increasingly required with regard to management. The aim of this study was to determine the utility of a panel of commercially available antibodies in refining the diagnosis on small biopsies and also to determine whether cytologic material is suitable for somatic EGFR genotyping in a prospectively analyzed series of patients undergoing investigation for suspected lung cancer. METHODS: Thirty-two consecutive cases of NSCLC were first tested using a panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, 34betaE12, and a D-PAS stain for mucin, to determine their value in refining diagnosis of NSCLC. After this test phase, two further pathologists independently reviewed the cases using a refined panel that excluded 34betaE12 because of its low specificity for SQCC, and refinement of diagnosis and concordance were assessed. Ten cases of ADC, including eight derived from cytologic samples, were sent for EGFR mutation analysis. RESULTS: There was refinement of diagnosis in 65% of cases of NSCLC to either SQCC or ADC in the test phase. This included 10 of 13 cases where cell pellets had been prepared from transbronchial needle aspirates. Validation by two further pathologists with varying expertise in lung pathology confirmed increased refinement and concordance of diagnosis. All samples were adequate for analysis, and they all showed a wild-type EGFR genotype. CONCLUSION: A panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, and a D-PAS stain for mucin increases diagnostic accuracy and agreement between pathologists when faced with refining a diagnosis of NSCLC to SQCC or ADC. These small samples, even cell pellets derived from transbronchial needle aspirates, seem to be adequate for EGFR mutation analysis.

A Validation Study for the Use of ROS1 Immunohistochemical Staining in Screening for ROS1 Translocations in Lung Cancer

INTRODUCTION: The presence of ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) rearrangements in lung cancers confers sensitivity to ROS kinase inhibitors, including crizotinib. However, they are rare abnormalities (in ∼1% of non-small cell lung carcinomas) that are typically identified by fluorescence in situ hybridization (FISH), and so screening using immunohistochemical (IHC) staining would be both cost- and time-efficient.

METHODS: A cohort of lung tumors negative for other common mutations related to targeted therapies were screened to assess the sensitivity and specificity of IHC staining in detecting ROS1 gene rearrangements, enriched by four other cases first identified by FISH. A review of published data was also undertaken.

RESULTS: IHC staining was 100% sensitive (95% confidence interval: 48-100) and 83% specific (95% confidence interval: 86-100) overall when an h-score higher than 100 was used. Patients with ROS1 gene rearrangements were younger and typically never-smokers, with the tumors all being adenocarcinomas with higher-grade architectural features and focal signet ring morphologic features (two of five). Four patients treated with crizotinib showed a partial response, with three also showing a partial response to pemetrexed. Three of four patients remain alive at 13, 27, and 31 months, respectively.

CONCLUSION: IHC staining can be used to screen for ROS1 gene rearrangements, with patients herein showing a response to crizotinib. Patients with tumors that test positive according to IHC staining but negative according to FISH were also identified, which may have implications for treatment selection.

Assessing microvascular function with breathing maneuvers : an oxygenation-sensitive CMR study

Ce projet illustre cinq études, mettant l'emphase sur le développement d'une nouvelle approche diagnostique cardiovasculaire afin d'évaluer le niveau d’oxygène contenu dans le myocarde ainsi que sa fonction microvasculaire. En combinant une séquence de résonance magnétique cardiovasculaire (RMC) pouvant détecter le niveau d’oxygène (OS), des manœuvres respiratoires ainsi que des analyses de gaz artériels peuvent être utilisés comme procédure non invasive destinée à induire une réponse vasoactive afin d’évaluer la réserve d'oxygénation, une mesure clé de la fonction vasculaire. Le nombre de tests diagnostiques cardiaques prescrits ainsi que les interventions, sont en pleine expansion. L'imagerie et tests non invasifs sont souvent effectués avant l’utilisation de procédures invasives. L'imagerie cardiaque permet d’évaluer la présence ou absence de sténoses coronaires, un important facteur économique dans notre système de soins de santé. Les techniques d'imagerie non invasives fournissent de l’information précise afin d’identifier la présence et l’emplacement du déficit de perfusion chez les patients présentant des symptômes d'ischémie myocardique. Néanmoins, plusieurs techniques actuelles requièrent la nécessité de radiation, d’agents de contraste ou traceurs, sans oublier des protocoles de stress pharmacologiques ou physiques. L’imagerie RMC peut identifier une sténose coronaire significative sans radiation. De nouvelles tendances d’utilisation de RMC visent à développer des techniques diagnostiques qui ne requièrent aucun facteur de stress pharmacologiques ou d’agents de contraste. L'objectif principal de ce projet était de développer et tester une nouvelle technique diagnostique afin d’évaluer la fonction vasculaire coronarienne en utilisant l' OS-RMC, en combinaison avec des manœuvres respiratoires comme stimulus vasoactif. Ensuite, les objectifs, secondaires étaient d’utilisés l’OS-RMC pour évaluer l'oxygénation du myocarde et la réponse coronaire en présence de gaz artériels altérés. Suite aux manœuvres respiratoires la réponse vasculaire a été validée chez un modèle animal pour ensuite être utilisé chez deux volontaires sains et finalement dans une population de patients atteints de maladies cardiovasculaires. Chez le modèle animal, les manœuvres respiratoires ont pu induire un changement significatif, mesuré intrusivement par débit sanguin coronaire. Il a été démontré qu’en présence d'une sténose coronarienne hémodynamiquement significative, l’OS-RMC pouvait détecter un déficit en oxygène du myocarde. Chez l’homme sain, l'application de cette technique en comparaison avec l'adénosine (l’agent standard) pour induire une vasodilatation coronarienne et les manœuvres respiratoires ont pu induire une réponse plus significative en oxygénation dans un myocarde sain. Finalement, nous avons utilisé les manœuvres respiratoires parmi un groupe de patients atteint de maladies coronariennes. Leurs myocardes étant altérées par une sténose coronaire, en conséquence modifiant ainsi leur réponse en oxygénation. Par la suite nous avons évalué les effets des gaz artériels sanguins sur l'oxygénation du myocarde. Ils démontrent que la réponse coronarienne est atténuée au cours de l’hyperoxie, suite à un stimuli d’apnée. Ce phénomène provoque une réduction globale du débit sanguin coronaire et un déficit d'oxygénation dans le modèle animal ayant une sténose lorsqu’un supplément en oxygène est donné. En conclusion, ce travail a permis d'améliorer notre compréhension des nouvelles techniques diagnostiques en imagerie cardiovasculaire. Par ailleurs, nous avons démontré que la combinaison de manœuvres respiratoires et l’imagerie OS-RMC peut fournir une méthode non-invasive et rentable pour évaluer la fonction vasculaire coronarienne régionale et globale.

Influence of Splenectomy on the Biodistribution of Technetium-99m Dimercaptosuccinic Acid (99mTc-DMSA) in Rats

This study aimed to evaluate if the splenectomy alters the biodistribution of 99mTc-DMSA and renal function in Wistar rats. The animals were separated in the groups: splenectomy (n = 6) and control (n = 6). After splenectomy (15 days), the administration of 0.1ml of 99mTc-DMSA IV (0.48 MBq) was carried out. Thirty minutes later, kidney, heart, lung, thyroid, stomach, bladder and femur and samples of blood were isolated. The organs were weighed, counted and the percentage of radioactivity -g (%ATI-g) determined. Serum urea and creatinine, hematocrit, leukocytes and platelets were measured. Statistics by t test (p<0.05) was done. There was a significant reduction in %ATI-g in kidney and blood (p<0.05) of splenectomized animals, a significant increase (p<0.05) of urea (88.8 ± 18.6 mg-dL) and creatinine (0.56 ± 0.08 mg-dL), compared to the controls (51.5±1.6, 0.37±0.02mg-dL, respectively), as well as increase in platelets and leucocytes, and hematocrit reduction. The analysis of the results indicates that in rats, splenectomy seems to alter the renal function and the uptake of 99mTc-DMSA

Bonnette de test d’optique adaptative pour l'Observatoire du Mont Mégantic

Les télescopes de grande envergure requièrent des nouvelles technologies ayant un haut niveau de maturité technologique. Le projet implique la création d’un banc de test d’optique adaptative pour l’évaluation de la performance sur le ciel de dispositifs connexes. Le banc a été intégré avec succès à l’observatoire du Mont Mégantic, et a été utilisé pour évaluer la performance d’un senseur pyramidal de front d’onde. Le système a permis la réduction effective de la fonction d’étalement du point d’un facteur deux. Plusieurs améliorations sont possibles pour augmenter la performance du système.

Quantitative evaluation of visual function 12 months after bilateral implantation of a diffractive trifocal IOL

PURPOSE: To quantitatively evaluate visual function 12 months after bilateral implantation of the Physiol FineVision® trifocal intraocular lens (IOL) and to compare these results with those obtained in the first postoperative month. METHODS: In this prospective case series, 20 eyes of 10 consecutive patients were included. Monocular and binocular, uncorrected and corrected visual acuities (distance, near, and intermediate) were measured. Metrovision® was used to test contrast sensitivity under static and dynamic conditions, both in photopic and low-mesopic settings. The same software was used for pupillometry and glare evaluation. Motion, achromatic, and chromatic contrast discrimination were tested using 2 innovative psychophysical tests. A complete ophthalmologic examination was performed preoperatively and at 1, 3, 6, and 12 months postoperatively. Psychophysical tests were performed 1 month after surgery and repeated 12 months postoperatively. RESULTS: Final distance uncorrected visual acuity (VA) was 0.00 ± 0.08 and distance corrected VA was 0.00 ± 0.05 logMAR. Distance corrected near VA was 0.00 ± 0.09 and distance corrected intermediate VA was 0.00 ± 0.06 logMAR. Glare testing, pupillometry, contrast sensitivity, motion, and chromatic and achromatic contrast discrimination did not differ significantly between the first and last visit (p>0.05) or when compared to an age-matched control group (p>0.05). CONCLUSIONS: The Physiol FineVision® trifocal IOL provided satisfactory full range of vision and quality of vision parameters 12 months after surgery. Visual acuity and psychophysical tests did not vary significantly between the first and last visit.

Modelling and Verification of a Correction Factor to Evaluate the Efficiency of Solar Thermal Collectors with the Rapid Test Method

A new method for the evaluation of the efficiency of parabolic trough collectors, called Rapid Test Method, is investigated at the Solar Institut Jülich. The basic concept is to carry out measurements under stagnation conditions. This allows a fast and inexpensive process due to the fact that no working fluid is required. With this approach, the temperature reached by the inner wall of the receiver is assumed to be the stagnation temperature and hence the average temperature inside the collector. This leads to a systematic error which can be rectified through the introduction of a correction factor. A model of the collector is simulated with COMSOL Multipyisics to study the size of the correction factor depending on collector geometry and working conditions. The resulting values are compared with experimental data obtained at a test rig at the Solar Institut Jülich. These results do not match with the simulated ones. Consequentially, it was not pos-sible to verify the model. The reliability of both the model with COMSOL Multiphysics and of the measurements are analysed. The influence of the correction factor on the rapid test method is also studied, as well as the possibility of neglecting it by measuring the receiver’s inner wall temperature where it receives the least amount of solar rays. The last two chapters analyse the specific heat capacity as a function of pressure and tem-perature and present some considerations about the uncertainties on the efficiency curve obtained with the Rapid Test Method.

Hmx1 Function In Lateral Facial Development

Thesis (Master's)--University of Washington, 2016-08

The Effect of Carbohydrate Mouth Rinsing On Skill Specific Performance and Cognitive Function Following a Fatigue Inducing Bout of Fencing

The aim of this study was to investigate whether rinsing the mouth with a carbohydrate solution could improve skill-specific fencing performance and cognitive function following a fatigue inducing simulated bout of fencing in epee fencers. Eleven healthy, competitive epee fencers (three female; eight male; 33.9 ± 14.7 years; body mass 79 ± 16 kg; height 162 ± 54 cm) volunteered to participant in a single-blind crossover design study. During visit 1 participants completed a 1-minute lunge test and stroop test pre and post fatigue inducing fencing protocol. A 30 second electroencephalography (EEG) recording was taken pre-protocol participants were instructed stay in a seated stationary position with their eyes closed. Heart rate and ratings of perceived exertion were recorded following each fight during the fatiguing protocol. Participants mouth rinsed (10 seconds) either 25ml of a 6.7% maltodextrin solution (CHO) or 25ml of water (placebo) between fights and during the EEG recording. Blood lactate and glucose measurements were taken at baseline, pre and post protocol. All measurements and tests were repeated during a 2nd visit to the laboratory, except participants were given a different solution to mouth rinse, separated by a minimum of 5 days. The results showed an increase in heart rate (P < 0.05) and overall RPE (P < 0.001) over time in both trials. There were no recorded differences in blood glucose (F(1,8) = 0.634, P = 0.4, ηp 0.07) or blood lactate levels (F(1,8) = 0.123, P = 0.7, ηp 0.01) between trials. There was a significant improvement in lunge test accuracy in the CHO trial (F(1,8) = 5.214, P = 0.05, ηp 0.40). However, there was no recorded difference in response time to congruent (F(1,8) = 0.326, P = 0.58, ηp 0.04) or incongruent (F(1,8) = 0.189, P = 0.68, ηp 0.02) stimuli between trials. In conclusion mouth rinsing a CHO solution significantly improves accuracy of skill-specific fencing performance but does not affect cognitive function following a fatigue inducing fencing protocol in epee fencers.

The effect of carbohydrate mouth rinsing on fencing performance and cognitive function following fatigue-inducing fencing

This study investigated the impact that mouth rinsing carbohydrate solution has on skill-specific performance and reaction time following a fatigue inducing bout of fencing in epee fencers. Nine healthy, national level epee fencers visited a laboratory on 2 occasions, separated by a minimum of 5 days, to complete a 1-minute lunge test and Stroop test pre and post fatigue. Heart rate and ratings of perceived exertion (RPE) were recorded during completion of the fatiguing protocol. Between fights the participants mouth rinsed for 10 seconds, either 25ml of 6.7% maltodextrin solution (MALT) or water (PLAC). Blood lactate and glucose were recorded at baseline, pre- and post-testing. Results showed an increase in heart rate and overall RPE over time in both conditions. There were no differences in blood glucose (F(1,8)=.63, P=.4, ηp=.07) or blood lactate levels (F(1,8)=.12, P=.70, ηp=.01) between conditions as a function of time. There was a significant improvement in lunge test accuracy during the MALT trial (F(1,8)=5.21, P=.05, ηp=.40) with an increase from pre (81.2 ±8.3%) to post (87.6 ±9.4%), whereas there was no significant change during the placebo (pre 82.1 ±8.8%, post 78.8 ±6.4%). There were no recorded differences between conditions in response time to congruent (F(1,8)=.33, P=.58, ηp=.04) or incongruent stimuli (F(1,8)=.19, P=.68, ηp=.02). The study indicates that when fatigued mouth rinsing MALT significantly improves accuracy of skill-specific fencing performance but no corresponding influence on reaction time was observed.

Measuring function and mobility among clients with diabetes in Samoa

The aim of the thesis was to collect baseline data and to investigating suitable physical tests and a self-rapport questionnaire. Collected data was used to find a routine measurement when investigating foot health, function and mobility among clients suffering from diabetes in Samoa. Twenty-one participants suffering from diabetes were included in the study. Clients answered the Foot function index (FFI) questionnaire and performed physical tests, consisting of Bergs balance scale (BBS) and Time up and go (TUG). Results from the physical tests revealed a great balance disturbance and mobility limitations among the majority of the clients. General high weight and BMI was measured among both genders. Subjects with the highest BMI performed lowest time during TUG test. The statistic analyze revealed a strong correlation between the two physical tests, indicating that one of the tests could be applied as a routine measurement in the future, when evaluating function and mobility in Samoa. The compilation of self-report questionnaires indicated a general good foot health with a low amount of pain, disabilities and activity limitations.

Does the 6-minute walk test predicts functional capacity in a sample of elderly women? A pilot study

Introduction: Functional capacity is the capacity to conduct daily activities in an independent way. It can be estimated with the 6-minutes’ walk test (6MWT) and other validated functional tests. Objectives: Verify associations between functional capacity measured with two different instruments (6MWT and Composite Physical Function (CPF) scale) and levels of physical activity and between those and characterization variables. Methods: This sample consisted of 30 apparently healthy elderly women from Loures municipality. Essentially they should be independent and community-dwelling. Characterization data were collected, containing characterization of physical activity levels and anthropometric data. Functional capacity was assessed with CPF scale and distance walked by the 6MWT. Results were analysed using a SPSS v21.0 through correlation tests. Results: The walked distance in 6MWT was positively associated with height (r = 0.406; p = 0.026), physical activity level (r = 0.594; p = 0.001) and functional capacity (r = 0.682; p = 0.000). For each point more obtained in CPF, the distance walked increases on average by 7.5 meters. Relatively to sedentary participants, being insufficiently active increases, on average, the distance walked in 85.8 meters; and being active increases, on average, the distance walked in 108.8 meters. No other associations were observed in our sample. Conclusion: Based on the collected sample, walked distance in 6MWT has a high correlation with results in CPF scale, so this test can be used to predict functional capacity. More attention should be taken to promote strategies to increase walking in older adults.

Síndrome de Sjögren Primário

A Síndrome de Sjögren (SS) é uma das três patologias autoimunes mais frequentes na população mundial, ainda assim frequentemente infradiagnosticada. Esta síndrome é uma doença autoimune crónica que afeta as glândulas exócrinas, particularmente as glândulas salivares e lacrimais. A SS primária (SSp) afeta especificamente as glândulas exócrinas, enquanto que a SS secundária (SSs) aparece associada a outras patologias autoimunes sistémicas. A SS é caracterizada, histopatologicamente, por um infiltrado inflamatório linfocitário que interfere com a função glandular normal. Afeta 0,5% da população mundial, sendo claramente mais predominante em mulheres (9:1 versus homens), principalmente por volta dos 50 anos (após a menopausa), ainda que também possa aparecer depois da menarca (entre os 20 e os 30 anos). Considera se que a etiologia da SS é multifatorial. Fatores genéticos, ambientais, hormonais e virais estão implicados na sua etiopatogénese. É muito importante o papel dos Médicos Dentistas no diagnóstico da SSp, uma vez que na maior parte dos casos são eles quem detetam os primeiros sintomas, mais propriamente a boca seca. Diversos testes auxiliares são utilizados para o diagnóstico desta doença, tais como: o teste de Schimer, o teste de Rosa Bengala, a Sialometria, a Sialografia, a Biópsia das glândulas salivares, entre outros. A SSp, regra geral, tem um curso não doloroso, sendo a boca seca e a secura ocular as suas duas características clínicas mais salientes. A maior parte das manifestações orais que se apresentam nestes pacientes são resultado de hipofunção das glândulas salivares (da boca seca), tais como: a cárie dentária, a doença periodontal, as infeções fúngicas, entre outras. Esta doença também se pode associar a problemas a nível sistémico, que podem ser subdivididos em não viscerais (pele, artralgia, mialgia) e viscerais (pulmão, coração, rim, sistema gastrointestinal, sistema endócrino e sistema nervoso central e periférico). O tratamento é empírico, sintomático e direcionado a tratar as complicações da doença mais inicial, que consiste em limitar os danos da xerostomia e da queratoconjuntivite. A prevenção dos sintomas a nível oral e ocular é fundamental em pacientes com SSp, para assim terem maior qualidade de vida.

Angiogenesis in the pathogenesis of inflammatory joint and lung diseases

This paper reviews hypotheses about roles of angiogenesis in the pathogenesis of inflammatory disease in two organs, the synovial joint and the lung. Neovascularisation is a fundamental process for growth and tissue repair after injury. Nevertheless, it may contribute to a variety of chronic inflammatory diseases, including rheumatoid arthritis, osteoarthritis, asthma, and pulmonary fibrosis. Inflammation can promote angiogenesis, and new vessels may enhance tissue inflammation. Angiogenesis in inflammatory disease may also contribute to tissue growth, disordered tissue perfusion, abnormal ossification, and enhanced responses to normal or pathological stimuli. Angiogenesis inhibitors may reduce inflammation and may also help to restore appropriate tissue structure and function

Quantitative evaluation of visual function 12 months after bilateral implantation of a diffractive trifocal IOL

PURPOSE: To quantitatively evaluate visual function 12 months after bilateral implantation of the Physiol FineVision® trifocal intraocular lens (IOL) and to compare these results with those obtained in the first postoperative month. METHODS: In this prospective case series, 20 eyes of 10 consecutive patients were included. Monocular and binocular, uncorrected and corrected visual acuities (distance, near, and intermediate) were measured. Metrovision® was used to test contrast sensitivity under static and dynamic conditions, both in photopic and low-mesopic settings. The same software was used for pupillometry and glare evaluation. Motion, achromatic, and chromatic contrast discrimination were tested using 2 innovative psychophysical tests. A complete ophthalmologic examination was performed preoperatively and at 1, 3, 6, and 12 months postoperatively. Psychophysical tests were performed 1 month after surgery and repeated 12 months postoperatively. RESULTS: Final distance uncorrected visual acuity (VA) was 0.00 ± 0.08 and distance corrected VA was 0.00 ± 0.05 logMAR. Distance corrected near VA was 0.00 ± 0.09 and distance corrected intermediate VA was 0.00 ± 0.06 logMAR. Glare testing, pupillometry, contrast sensitivity, motion, and chromatic and achromatic contrast discrimination did not differ significantly between the first and last visit (p>0.05) or when compared to an age-matched control group (p>0.05). CONCLUSIONS: The Physiol FineVision® trifocal IOL provided satisfactory full range of vision and quality of vision parameters 12 months after surgery. Visual acuity and psychophysical tests did not vary significantly between the first and last visit.