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INTRODUCTION: A growing interest in using proton pencil beam scanning in combination with collimators for the treatment of small, shallow targets, such as ocular melanoma or pre-clinical research emerged recently. This study aims at demonstrating that the dose of a synchrotron-based PBS system with a dedicated small, shallow field nozzle can be accurately predicted by a commercial treatment planning system (TPS) following appropriate tuning of both, nozzle and TPS. MATERIALS: A removable extension to the clinical nozzle was developed to modify the beam shape passively. Five circular apertures with diameters between 5 to 34mm, mounted 72cm downstream of a range shifter were used. For each collimator treatment plans with spread-out Bragg peaks (SOBP) with a modulation of 3 to 30mm were measured and calculated with GATE/Geant4 and the research TPS RayStation (RS11B-R). The dose grid, multiple coulomb scattering and block discretization resolution were varied to find the optimal balance between accuracy and performance. RESULTS: For SOBPs deeper than 10mm, the dose in the target agreed within 1% between RS11B-R, GATE/Geant4 and measurements for aperture diameters between 8 to 34mm, but deviated up to 5% for smaller apertures. A plastic taper was introduced reducing scatter contributions to the patient (from the pipe) and improving the dose calculation accuracy of the TPS to a 5% level in the entrance region for large apertures. CONCLUSION: The commercial TPS and GATE/Geant4 can accurately calculate the dose for shallow, small proton fields using a collimator and pencil beam scanning.
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Neoplasias Oculares , Terapia com Prótons , Humanos , Prótons , Síncrotrons , PlásticosRESUMO
For this research, the properties of the logistic growth model for independent and coexisting species were used to set definitions for the possible regulation of one or two growth variables through their coupling parameters. The present analysis is done for the single-species Verhulst model without coupling, the single-species Verhulst model coupled with an exogenous signal, and the two-species Verhulst coexistence growth model which represents six different ecological regimes of interaction. The models' parameters, such as the intrinsic growth rate and the coupling, are defined. Finally, the control results are expressed as lemmas for regulation, and they are shown using a simulation example of a fish population growing independent of human interaction (no harvesting, no fishing) and the simulation of the regulation of said population when the coupling of fish and humans is involved (harvesting, fishing).
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Modelos Biológicos , Crescimento Demográfico , Animais , Humanos , Dinâmica Populacional , Simulação por ComputadorRESUMO
Introducción: El reflujo de enzimas pancreáticas hacia la vía biliar extra-hepática y la vesícula biliar es un fenómeno anormal que tiene un rol en la litogénesis y carcinogénesis. Debido a que la presión de la vía biliar depende entre otros factores, de las presiones del esfínter de Oddi. La disfunción de éste se vería reflejada en presiones elevadas de la vía biliar en pacientes con colelitiasis. Objetivo: El objetivo de este estudio es el de medir las presiones de la vía biliar extra-hepática en pacientes con y sin colelitiasis y relacionarlas con la presencia de reflujo pancreáticobiliar. Material y Método: Se diseñó un estudio pros-pectivo de casos y controles. La muestra está constituida por todos los pacientes operados con gastrectomía total por cáncer gástrico estadios I y II durante 30 meses. La medida de resultado primaria fue establecer diferencias en las presiones de la vía biliar entre pacientes con y sin colelitiasis. Resultados: Las presiones de la vía biliar extra-hepática en pacientes con colelitiasis fueron más elevadas (16,9 mmHg) que en los pacientes sin colelitiasis (3,3 mmHg) (p < 0,0001). Estas presiones se correlacionan con la presencia de amilasa y lipasa en la bilis de la vesícula; se encontraron niveles elevados de enzimas pancreáticas en pacientes con colelitiasis (p < 0,0001). Conclusiones: Las presiones de la vía biliar en pacientes con colelitiasis fueron, significativamente, mayores comparadas con las presiones de la vía biliar en pacientes sin colelitiasis. En los pacientes con colelitiasis, la presión elevada de la vía biliar se asocia a la presencia de reflujo pancreáticobiliar.
Background: The reflux of pancreatic enzymes into the bile duct and the gallbladder is an abnormal phenomenon that plays a role in lithogenesis and carcinogenesis. Because the pressure of the common bile duct depends on the pressures of the sphincter of Oddi, its dysfunction would be reflected in an increase in the pressure of the common bile duct in patients with cholelithiasis. Aim: The objective of this study was to measure the pressures of the common bile duct in patients with and without cholelithiasis and to relate them to the presence of pancreatobiliary reflux. Material and Method: A prospective case-control study was designed. The universe was constituted by all patients undergoing total gastrectomy for gastric cancer stages I and II during 30 months. The primary outcome measure was to establish differences between common bile duct pressures in patients with and without cholelithiasis. Results: Common bile duct pressures in patients with gallstones showed a significant elevation (16.9 mmHg) compared to patients without gallstones (3.3 mm Hg) (p < 0.0001). These pressures correlated with the levels of amylase and lipase in gallbladder bile; higher levels were found in patients with gallstones compared to patients without gallstones (p < 0.0001). Conclusions: Common bile duct pressure in patients with cholelithiasis was significantly higher compared to patients without cholelithiasis leading to pancreatobiliary reflux.
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In this era of patient-centered, outcomes-driven and adaptive radiotherapy, deep learning is now being successfully applied to tackle imaging-related workflow bottlenecks such as autosegmentation and dose planning. These applications typically require supervised learning approaches enabled by relatively large, curated radiotherapy datasets which are highly reflective of the contemporary standard of care. However, little has been previously published describing technical infrastructure, recommendations, methods or standards for radiotherapy dataset curation in a holistic fashion. Our radiation oncology department has recently embarked on a large-scale project in partnership with an external partner to develop deep-learning-based tools to assist with our radiotherapy workflow, beginning with autosegmentation of organs-at-risk. This project will require thousands of carefully curated radiotherapy datasets comprising all body sites we routinely treat with radiotherapy. Given such a large project scope, we have approached the need for dataset curation rigorously, with an aim towards building infrastructure that is compatible with efficiency, automation and scalability. Focusing on our first use-case pertaining to head and neck cancer, we describe our developed infrastructure and novel methods applied to radiotherapy dataset curation, inclusive of personnel and workflow organization, dataset selection, expert organ-at-risk segmentation, quality assurance, patient de-identification, data archival and transfer. Over the course of approximately 13 months, our expert multidisciplinary team generated 490 curated head and neck radiotherapy datasets. This task required approximately 6000 human-expert hours in total (not including planning and infrastructure development time). This infrastructure continues to evolve and will support ongoing and future project efforts.
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Deficiência de Riboflavina , Vitaminas , Recém-Nascido , Humanos , Nutrição Parenteral , RiboflavinaRESUMO
OBJECTIVES: The aim of this study was to evaluate the impact on 30-day mortality of early use of corticosteroids in COVID-19 patients with supplementary oxygen requirements and without invasive mechanical ventilation at the initiation of therapy. METHODS: All patients hospitalized with COVID-19 between April 15 and July 15, 2020, and requiring supplementary oxygen, were prospectively included in a database. Patients who died or required intubation within the first 48 hours were excluded. Patients who received corticosteroids within the first 5 days of hospitalization and at least 24 hours prior to intubation were allocated to the 'early corticosteroids' group. To compare both populations and adjust for non-random treatment assignment bias, a weight-adjusted propensity score model was used. RESULTS: In total, 571 patients met the inclusion criteria, 520 had sufficient information for the analysis. Of these, 233 received early corticosteroids and 287 did not. Analysis showed a reduction of 8.5% (p = 0.038) in 30-day mortality in the early corticosteroid group. The reduction in mortality was not significant when patients with corticosteroid initiation between day 5 and day 8 of hospitalization were included. CONCLUSION: Early corticosteroid use reduced mortality in patients with pneumonia due to COVID-19, who required supplementary oxygen but not initial invasive mechanical ventilation.
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COVID-19 , Corticosteroides/uso terapêutico , Humanos , Pontuação de Propensão , Respiração Artificial , SARS-CoV-2 , EsteroidesRESUMO
Proton therapy has a distinct dosimetric advantage over conventional photon therapy due to its Bragg peak profile. This allows greater accuracy in dose delivery and dose conformation to the target, however it requires greater precision in setup, delivery and for quality assurance (QA) procedures. The AAPM TG 224 report recommends daily range and spot position checks with tolerance on the order of a millimetre. Daily QA systems must therefore be efficient for daily use and be capable of sub-millimetre precision however few suitable commercial systems are available. In this work, a compact, real-time daily QA system is optimised and characterised for proton range verification using an ad-hoc Geant4 simulation. The system is comprised of a monolithic silicon diode array detector embedded in a perspex phantom. The detector is orientated at an angular offset to the incident proton beam to allow range in perspex to be determined for flat proton fields. The accuracy of the system for proton range in perspex measurements was experimentally evaluated over the full range of clinical proton energies. The meanR100,R90andR80ranges measured with the system were accurate within ±0.6 mm of simulated ranges in a perspex phantom for all energies assessed. This system allows real-time read-out of individual detector channels also making it appropriate for temporal beam delivery diagnostics and for spot position monitoring along one axis. The system presented provides a suitable, economical and efficient alternative for daily QA in proton therapy.
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Terapia com Prótons , Imagens de Fantasmas , Prótons , Radiometria , Dosagem Radioterapêutica , SilícioRESUMO
Cardiovascular diseases (CVDs) are the result of complex pathophysiological processes in the tissues comprising the heart and blood vessels. Inflammation is the main culprit for the development of cardiovascular dysfunction, and it may be traced to cellular stress events including apoptosis, oxidative and shear stress, and cellular and humoral immune responses, all of which impair the system's structure and function. An intracellular chaperone, heat shock protein 60 (HSP60) is an intriguing example of a protein that may both be an ally and a foe for cardiovascular homeostasis; on one hand providing protection against cellular injury, and on the other triggering damaging responses through innate and adaptive immunity. In this review we will discuss the functions of HSP60 and its effects on cells and the immune system regulation, only to later address its implications in the development and progression of CVD. Lastly, we summarize the outcome of various studies targeting HSP60 as a potential therapeutic strategy for cardiovascular and other diseases.
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Doenças Cardiovasculares , Sistema Cardiovascular , Apoptose , Chaperonina 60 , Humanos , Sistema ImunitárioRESUMO
The mitochondrial permeability transition pore (mPTP) opening is involved in the pathophysiology of multiple cardiac diseases, such as ischemia/reperfusion injury and heart failure. A growing number of evidence provided by proteomic screening techniques has demonstrated the role of post-translational modifications (PTMs) in several key components of the pore in response to changes in the extra/intracellular environment and bioenergetic demand. This could lead to a fine, complex regulatory mechanism that, under pathological conditions, can shift the state of mitochondrial functions and, thus, the cell's fate. Understanding the complex relationship between these PTMs is still under investigation and can provide new, promising therapeutic targets and treatment approaches. This review, using a systematic review of the literature, presents the current knowledge on PTMs of the mPTP and their role in health and cardiac disease.
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Insuficiência Cardíaca/metabolismo , Mitocôndrias Cardíacas/metabolismo , Poro de Transição de Permeabilidade Mitocondrial/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Processamento de Proteína Pós-Traducional , Insuficiência Cardíaca/patologia , Humanos , Mitocôndrias Cardíacas/patologia , Traumatismo por Reperfusão Miocárdica/patologia , ProteômicaRESUMO
Resumen Introducción Actualmente, la mayoría de las series que hablan sobre hernia incisional, no mencionan hernias incisionales en laparotomías de McBurney. La incidencia reportada de hernia incisional en esta laparotomía varía entre 0,7% y 2%. Aún más escasas son las publicaciones sobre sus complicaciones. El objetivo del presente reporte de casos es el de discutir el diagnóstico, tratamiento y resultados de dos pacientes operados en nuestra institución por hernia de McBurney complicada. Reporte de Casos: Se describen 2 pacientes femeninos de 68 y 65 años de edad que fueron operadas de urgencia por hernia incisional en laparotomía de McBurney complicada. La evolución postoperatoria fue diferente en ambas y una de ellas falleció. Discusión Se discuten los factores de riesgo para el desarrollo de estas hernias, el diagnóstico y tratamiento. Además, se discute la importancia de la apendicectomía laparoscópica para la prevención de estas hernias. Conclusiones Las complicaciones de la hernia en laparotomía de McBurney, las cuales son severas y potencialmente letales, se diagnostican tardíamente debido al retraso en la presentación y en el diagnóstico. La amplia utilización de la cirugía laparoscópica para la apendicectomía seguramente reducirá aún más la incidencia de este tipo de hernia durante los próximos años.
Introduction Currently, most series over incisional hernia do not mention this hernia occurring in McBurney's laparotomy. The reported incidence for this type of hernia is 0.7% to 2%. Even more scarce are publications regarding its complications. The purpose of this report is to discuss the diagnostic, treatment and outcomes of two patients operated on our institution for complicated McBurney´s hernia. Report of Cases: Two female patients 68 and 65 years-old operated on emergency grounds for complicated incisional hernia over a McBurney´s incision are described. Postoperative evolution was different in both cases and one of them died. Discussion We discuss risk factor for this specific incisional hernia development, its diagnosis and treatment. Besides, the importance of laparoscopic appendectomy was stressed. Conclusions Complicated incisional hernia over McBurney's incision is an infrequent severe clinical condition habitually diagnosed late. The widespread utilization of laparoscopic appendectomy will reduce even more the incidence of this kind of hernia within the next few years.
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Humanos , Feminino , Idoso , Complicações Pós-Operatórias , Laparoscopia/métodos , Hérnia Incisional/cirurgia , Hérnia Incisional/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To provide a proof of principle of a Pareto-based method to automatically generate optimal intensity-modulated proton therapy (IMPT) plans for various noncoplanar beam orientations. METHODS: A novel multicriteria beam orientation optimization (MCBOO) method was developed to generate Pareto database of optimal plans. The MCBOO method automatically explores the beam orientations and the scalarization parameters of the IMPT plans simultaneously. The MCBOO method is based on multicriteria bilevel optimization (i.e., hierarchical optimization with two nested levels, named the upper and lower level optimization). In MCBOO, the upper level optimization explores the noncoplanar beam orientation space, while the lower level explores the scalarization parameters for a given beam orientation. Differential evolution method was used in both levels, and the Pareto optimal plans were aggregated from the bilevel optimizations to construct the Pareto database. The MCBOO method was implemented on a multinode multi-GPU cluster, and it was tested on three brain tumor patient cases. The Pareto database of the three patients was generated for a set of DVH-based objectives. A statistical analysis was performed between a selected set of MCBOO plans and the manual plan (plan with manually selected beam orientation based on the clinical experience and optimized with the same single plan iterative optimizer used in the MCBOO). The selected set of MCBOO plans consisted of plans that matched the performance of the manual plan [i.e., MCBOO plans that have the same target coverage (within 2%) as the manual plan or better and achieved the same dose (within 2%) or lower to all of the organs at risks (OARs) but one OAR]. Additionally, a dosimetric comparison between of one of the selected MCBOO plans vs the manual plan was conducted. RESULTS: The multicriteria beam orientation optimization algorithm automatically generated Pareto plans for the three noncoplanar brain tumor cases. The MCBOO plans provided an alternative objective trade-offs to the manual plan. The selected MCBOO plans showed a reduction in dose to multiple organs at risk vs the manual plan with a maximum value which ranged between 10.8 and 12.9 Gy for the three patients. The trade-off of the OAR dose reduction resulted in higher dose to no more than one OAR for each of the selected MCBOO plans vs the manual plan. The maximum dose increase in the MCBOO plans over the manual plan ranged from 7.8 to 11.8 Gy. CONCLUSIONS: A novel multicriteria beam orientation optimization method was developed and tested on three IMPT patient cases. The method automatically generates Pareto plans database by exploring the noncoplanar beam orientations. The method was able to identify beam orientations with Pareto optimal plans that are comparable to the manually created plans with varying objective trade-offs.
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Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Neoplasias Encefálicas/radioterapia , Humanos , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversosRESUMO
Resumen Introducción La lesión de la vesícula biliar secundaria a trauma abdominal cerrado constituye un evento infrecuente de perforación traumática de ella, de presentación tardía. Objetivo Revisar la literatura científica actualmente disponible y además describimos un caso. Materiales y Método Utilizando la plataforma PubMed se buscan las siguientes palabras clave: " Blunt abdominal trauma ". Se seleccionan las series con lesiones de la vesícula biliar: " Traumatic gallbladder rupture". Se seleccionan los reportes de lesiones aisladas de la vesícula biliar: " Isolated gallbladder rupture ". Se seleccionan los reportes de presentación tardía de lesiones aisladas de la vesícula biliar: " Delayed presentation of isolated gallbladder rupture ". Resultados De todas estas publicaciones se seleccionan las que a criterio de los autores son relevantes para el presente caso. Discusión La mayoría de las perforaciones de la vesícula biliar se producen en vesículas sanas de paredes delgadas distendidas por el ayuno o el consumo de alcohol. No existe una presentación clínica clásica. Los estudios imagenológicos son inespecíficos y se llega al diagnóstico definitivo durante la exploración quirúrgica. El tratamiento de esta lesión es la colecistectomía. Conclusiones El diagnóstico no es fácil, pero la resolución es relativamente simple y el pronóstico es bueno. El presente caso ilustra este tipo de lesiones en pacientes con trauma abdominal cerrado.
Introduction Gallbladder injury secondary to blunt abdominal trauma is a rare event. Aim Review the current available scientific literature and describe a case. Materials and Method Using the PubMed platform, the following keywords were searched: "Blunt abdominal trauma". Series with gallbladder lesions were selected: "Traumatic gallbladder rupture". Reports of isolated lesions of the gallbladder were selected: "Isolated gallbladder rupture". Reports of late presentation of isolated lesions of the gallbladder were selected: "Delayed presentation of isolated gallbladder rupture". Of all these publications, those that were relevant to the present case were selected according to the criteria of the authors. Case report A 20 years-old male patient suffered an abdominal trauma two weeks before presentation at our Institution. He underwent an exploratory laparotomy showing bilious content and a gallbladder perforation over the peritoneal wall as an isolated injury. Discussion Most isolated gallbladder perforations occur in healthy gallbladders with thin walls and distended because fasting or alcohol consumption. There are no classical clinical features to diagnose this specific injury and radiologic studies are nonspecific. Definitive diagnosis is often reached during surgery as it was with our patient. Recommended treatment is cholecystectomy. Conclusions This case illustrates this unique kind of gallbladder injury in patients with blunt abdominal trauma. A clear diagnosis is not easy however, the treatment is simple and prognosis is good.
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Humanos , Masculino , Adulto Jovem , Ferimentos não Penetrantes/cirurgia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico , Colecistectomia/métodos , Vesícula Biliar/lesões , Tomografia Computadorizada por Raios X , Vesícula Biliar/cirurgia , Traumatismos Abdominais/cirurgia , Traumatismos Abdominais/complicações , Traumatismos Abdominais/diagnósticoRESUMO
In this research, fault detection and diagnosis (FDD) scheme for isolating the damaged injector of an internal combustion engine is formulated and experimentally applied. The FDD scheme is based on a temporal analysis (statistical methods), as well as in a frequency analysis (fast Fourier transform) of the fuel rail pressure. The arrangement of the scheme consists of three coupled artificial neural networks (ANNs) to classify the faulty injector correctly. The ANNs were trained considering five different scenarios, one scenario without fault in the injection system, and the other four scenarios represent a fault per injector (1 to 4). The Levenberg-Marquardt (LM), BFGS quasi-Newton, gradient descent (GD), and extreme learning machine (ELM) algorithms were tested to select the best training algorithm to classify the faults. Experimental results obtained from the implementation in a VW four-cylinder CBU 2.5L vehicle in idle operating conditions (800 rpm) show the effectiveness of the proposed FDD scheme.
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BACKGROUND/AIMS: Cyclophilin D (CypD) mediates the mitochondrial permeability transition pore (mPTP) opening that contributes to mitochondrial dysfunction. CypD is regulated by its acetylation/deacetylation state that depends on Sirtuin-3 (SIRT3) mitochondrial deacetylase. Since obesity and metabolic syndrome decrease SIRT3 activity and expression, we tested the hypothesis that CypD hyperacetylation promotes mitochondrial dysfunction under this pathophysiological state, which is associated with ventricular dysfunction and heart failure. METHODS: Myocardial tissue samples from patients with left ventricular heart failure, with either obesity or normal weight, were processed for the expression of SIRT3 and acetylation profile by Western Blot (WB). In addition, a rat model of obesity and metabolic syndrome induced by 30% (w/v) of sucrose was conducted. The WB analysis was used to determine the levels of mitochondrial expression of SIRT3, Adenine Nucleotide Translocator (ANT), CypD and the acetylation profile, as well as immunoprecipitation to establish the acetylation levels of CypD. Mitochondrial function was assessed by oxygen consumption analysis and maximum Ca2+ retention capacity. Oxidative stress was assessed by aconitase activity, protein carbonyl and thiol groups content. RESULTS: SIRT3 expression in the biopsies of the failing human hearts showed a 46% decrease in the expression levels of obese patients in comparison to the non-obese patients (p=0.0219). Remarkably, body mass index was associated with protein acetylation (0.627; p = 0.035), suggesting that the acetylation profiles of the failing hearts of obese patients are partly mediated by a reduction in SIRT3, which is also associated with higher BNP levels, indicating a more severe ventricular dysfunction (-0.636; p = 0.043). Accordingly, obese rats demonstrated a SIRT3 mitochondrial expression decrease of 22% concomitantly with a hyperacetylated mitochondrial profile, including CypD. Cardiac mitochondria from obese animals were 2.5-fold more prone to mPTP opening than the controls. CONCLUSION: Our results indicate that obesity reduces SIRT3 expression and that CypD hyperacetylation increases mPTP opening, suggesting that the activation of SIRT3 might be a potential target to decrease ventricular dysfunction and slow the progression of heart failure.
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Mitocôndrias Cardíacas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Obesidade/metabolismo , Sirtuína 3/metabolismo , Acetilação , Adulto , Idoso , Animais , Índice de Massa Corporal , Cálcio/metabolismo , Peptidil-Prolil Isomerase F , Ciclofilinas/metabolismo , Feminino , Insuficiência Cardíaca/metabolismo , Humanos , Imunoprecipitação , Técnicas In Vitro , Masculino , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Translocases Mitocondriais de ADP e ATP/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Consumo de Oxigênio/fisiologia , Ratos , Ratos WistarRESUMO
INTRODUCTION: Chronic granulomatous disease (CGD) is a disorder of phagocyte function, characterized by pyogenic infections and granuloma formation caused by defects in NADPH oxidase complex activity. Although the effect of CGD mainly reflects the phagocytic compartment, B cell responses are also impaired in patients with CGD. MATERIALS AND METHODS: Flow cytometric analysis was performed on peripheral blood samples from 35 CGD patients age-matched with healthy controls (HC). The target cells of our study were the naive (IgD+/CD27-), memory (IgD-/CD27+), and B1a (CD5+) cells. Immunoglobulins (Igs) were also measured. This study was performed in a Latin American cohort. RESULTS: We found significantly higher levels of naive B cells and B1a cells, but lower levels of memory B cells were found in CGD patients compared to HC. There was no significant difference of cell percentages per inheritance type. DISCUSSION: Our findings suggest that the deficiency of NADPH oxidase components can affect the differentiation of naive B cells to memory B cells. Consequently, memory cells will be low, which also influenced the expression of CD27 in memory B cells and as a result, the percentage of naive cells increases. An altered phenotype of B lymphocytes in CGD patients may contribute to the opportunistic infections and autoimmune disorders that are seen in this disease.
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Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , Doença Granulomatosa Crônica/imunologia , NADPH Oxidase 2/genética , Adolescente , Adulto , Separação Celular , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Citometria de Fluxo , Doença Granulomatosa Crônica/genética , Humanos , Memória Imunológica , Imunofenotipagem , Lactente , Masculino , México , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Adulto JovemRESUMO
The purpose of this work was to develop an end-to-end patient-specific quality assurance (QA) technique for spot-scanned proton therapy that is more sensitive and efficient than traditional approaches. The patient-specific methodology relies on independently verifying the accuracy of the delivered proton fluence and the dose calculation in the heterogeneous patient volume. A Monte Carlo dose calculation engine, which was developed in-house, recalculates a planned dose distribution on the patient CT data set to verify the dose distribution represented by the treatment planning system. The plan is then delivered in a pre-treatment setting and logs of spot position and dose monitors, which are integrated into the treatment nozzle, are recorded. A computational routine compares the delivery log to the DICOM spot map used by the Monte Carlo calculation to ensure that the delivered parameters at the machine match the calculated plan. Measurements of dose planes using independent detector arrays, which historically are the standard approach to patient-specific QA, are not performed for every patient. The nozzle-integrated detectors are rigorously validated using independent detectors in regular QA intervals. The measured data are compared to the expected delivery patterns. The dose monitor reading deviations are reported in a histogram, while the spot position discrepancies are plotted vs. spot number to facilitate independent analysis of both random and systematic deviations. Action thresholds are linked to accuracy of the commissioned delivery system. Even when plan delivery is acceptable, the Monte Carlo second check system has identified dose calculation issues which would not have been illuminated using traditional, phantom-based measurement techniques. The efficiency and sensitivity of our patient-specific QA program has been improved by implementing a procedure which independently verifies patient dose calculation accuracy and plan delivery fidelity. Such an approach to QA requires holistic integration and maintenance of patient-specific and patient-independent QA.
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Modelagem Computacional Específica para o Paciente , Terapia com Prótons/métodos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Algoritmos , Humanos , Método de Monte Carlo , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Terapia com Prótons/normas , Terapia com Prótons/estatística & dados numéricos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Estudos RetrospectivosRESUMO
BACKGROUND: The sequence of prenatal growth restraint and postnatal catch-up growth leads to a thicker intima-media and more pre-peritoneal fat by age 3-6 years. OBJECTIVES: To study whether carotid intima-media thickness (cIMT) and pre-peritoneal fat differ already between catch-up small-for-gestational-age (SGA) infants and appropriate-for-gestational-age (AGA) controls in late infancy (ages 1 and 2 years) and whether such differences - if any - are accompanied by differences in cardiac morphology and function. METHODS: Longitudinal assessments included body height and weight; fasting glucose, insulin, Insulin-like growth factor (IGF-I), high-molecular-weight adiponectin; body composition (by absorptiometry); cIMT, aortic IMT, pre-peritoneal fat partitioning (by ultrasound); cardiac morphometry and function (by echocardiography) in AGA and SGA infants at birth, at age 1 year (N = 87), and again at age 2 years (N = 68). RESULTS: Catch-up SGA infants had already a thicker cIMT than AGA controls at ages 1 and 2 years, and more pre-peritoneal fat by age 2 years (all p values between <0.01 and <0.0001); all cardiac and endocrine-metabolic results were similar in AGA and SGA infants at ages 1 and 2 years. CONCLUSIONS: From late infancy onwards, catch-up SGA infants have a thicker cIMT and more pre-peritoneal fat than AGA controls, but their cardiac morphology and function remain reassuringly similar.
Assuntos
Gordura Abdominal/fisiologia , Espessura Intima-Media Carotídea/estatística & dados numéricos , Desenvolvimento Infantil/fisiologia , Coração/fisiologia , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Adiponectina/sangue , Glicemia/fisiologia , Composição Corporal/fisiologia , Estatura , Peso Corporal , Pré-Escolar , Ecocardiografia/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Estudos Longitudinais , Masculino , Gravidez , Estudos ProspectivosRESUMO
PURPOSE: Provide an adaptive multicriteria optimization (MCO) method for intensity-modulated proton therapy (IMPT) utilizing GPU technology. Previously described limitations of MCO such as Pareto approximation and limitation on the number of objectives were addressed. METHODS: The treatment planning process for IMPT must account for multiple objectives, which requires extensive treatment planning resources. Often a large number of objectives (>10) are required. Hence the need for an MCO algorithm that can handle large number of objectives. The novelty of the MCO method presented here lies on the introduction of the adaptive weighting scheme that can generate a well-distributed and dense representation of the Pareto surface for a large number of objectives in an efficient manner. In our approach the generated Pareto surface is constructed for a set of DVH objectives. The MCO algorithm is based on the augmented weighted Chebychev metric (AWCM) method with an adaptive weighting scheme. This scheme uses the differential evolution (DE) method to generate a set of well-distributed Pareto points. The quality of the Pareto points' distribution in the objective space was assessed quantitatively using the Pareto sampling metric. The MCO algorithm was developed to perform multiple parallel searches to achieve a rapid mapping of the Pareto surface, produce clinically deliverable plans, and was implemented on a GPU cluster. The MCO algorithm was tested on two clinical cases with 10 and 18 objectives. For each case one of the MCO-generated plans was selected for comparison with the clinically generated plan. The MCO plan was randomly selected out of the set of MCO plans that had target coverage similar to the clinically generated plan and the same or better sparing of the organs at risk (OAR). Additionally, a validation study of the AWCM method vs the weighted sum method was performed. RESULTS: The adaptive MCO algorithm generated Pareto points on the Pareto hypersurface in a fast (2-3 hr) and efficient manner for 2 cases with 10 and 18 objectives. The MCO algorithm generated a dense and well-distributed set of Pareto points on the objective space, and was able to achieve minimization of the Pareto sampling metric. The selected MCO plan showed an improvement of the DVH objectives in comparison to the clinically optimized plan in both cases. For case one, the MCO plan showed a 48% reduction of the 50% dose to OARs and a 16% reduction of the 1% dose to OARs. For case 2, the MCO plan showed a 72% reduction of the 50% dose to OARs and a 42% reduction of the 1% dose to OARs. The comparison of AWCM to WS showed that the AWCM method has a dosimetric advantage over WS for both patient cases. CONCLUSION: We introduced an adaptive MCO algorithm for IMPT accelerated using GPUs. The algorithm is based on an adaptive method for generating Pareto plans in the objective space. We have shown that the algorithm can provide rapid and efficient mapping of the multicriteria Pareto surface with clinically deliverable plans.