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1.
Mov Ecol ; 11(1): 12, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36859381

RESUMO

Acoustic telemetry has helped overcome many of the challenges faced when studying the movement ecology of aquatic species, allowing to obtain unprecedented amounts of data. This has made it into one of the most widely used methods nowadays. Many ways to analyse acoustic telemetry data have been made available and deciding on how to analyse the data requires considering the type of research objectives, relevant properties of the data (e.g., resolution, study design, equipment), habits of the study species, researcher experience, among others. To ease this decision process, here we showcase (1) some of the methods used to estimate pseudo-positions and positions from raw acoustic telemetry data, (2) methods to estimate residency and (3) methods to estimate two-dimensional home and occurrence range using geometric or hull-based methods and density-distribution methods, a network-based approach, and three-dimensional methods. We provide examples of some of these were tested using a sample of real data. With this we intend to provide the necessary background for the selection of the method(s) that better fit specific research objectives when using acoustic telemetry.

2.
Rev Sci Instrum ; 93(4): 043102, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35489906

RESUMO

We report the development of a multipurpose differential x-ray calorimeter with a broad energy bandwidth. The absorber architecture is combined with a Bayesian unfolding algorithm to unfold high energy x-ray spectra generated in high-intensity laser-matter interactions. Particularly, we show how to extract absolute energy spectra and how our unfolding algorithm can reconstruct features not included in the initial guess. The performance of the calorimeter is evaluated via Monte Carlo generated data. The method accuracy to reconstruct electron temperatures from bremsstrahlung is shown to be 5% for electron temperatures from 1 to 50 MeV. We study bremsstrahlung generated in solid target interaction showing an electron temperature of 0.56 ± 0.04 MeV for a 700 µm Ti titanium target and 0.53 ± 0.03 MeV for a 50 µm target. We investigate bremsstrahlung from a target irradiated by laser-wakefield accelerated electrons showing an endpoint energy of 551 ± 5 MeV, inverse Compton generated x rays with a peak energy of 1.1 MeV, and calibrated radioactive sources. The total energy range covered by all these sources ranges from 10 keV to 551 MeV.

3.
Sci Rep ; 11(1): 7338, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795713

RESUMO

We report on experimental investigations of proton acceleration from solid foils irradiated with PW-class laser-pulses, where highest proton cut-off energies were achieved for temporal pulse parameters that varied significantly from those of an ideally Fourier transform limited (FTL) pulse. Controlled spectral phase modulation of the driver laser by means of an acousto-optic programmable dispersive filter enabled us to manipulate the temporal shape of the last picoseconds around the main pulse and to study the effect on proton acceleration from thin foil targets. The results show that applying positive third order dispersion values to short pulses is favourable for proton acceleration and can lead to maximum energies of 70 MeV in target normal direction at 18 J laser energy for thin plastic foils, significantly enhancing the maximum energy compared to ideally compressed FTL pulses. The paper further proves the robustness and applicability of this enhancement effect for the use of different target materials and thicknesses as well as laser energy and temporal intensity contrast settings. We demonstrate that application relevant proton beam quality was reliably achieved over many months of operation with appropriate control of spectral phase and temporal contrast conditions using a state-of-the-art high-repetition rate PW laser system.

4.
Clin Genet ; 93(5): 962-971, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29293279

RESUMO

With the expansion of carrier screening to general preconception and prenatal patient populations, most patients will receive negative results, which we define as indicating <25% risk of having a child with a genetic condition. Because there is limited experience with expanded carrier screening, it is important to understand how receiving negative results affects patients, especially as providers, payers, and policymakers consider whether to offer it. In this mixed-methods study, we asked preconception patients enrolled in the NextGen study about their expectations and experiences receiving negative expanded carrier screening results. Participants completed surveys at study enrollment (n = 110 women, 51 male partners), after receiving carrier results (n = 100 women, 38 male partners), after receiving secondary findings (n = 98 women, 36 male partners), and 6 months after receiving results (n = 95 women, 28 male partners). We also interviewed a subset of participants 12 to 24 months after receiving results (n = 24 women, 12 male partners). We found minimal negative emotional impact and privacy concerns, increased confidence in reproductive plans, and few changes to health behaviors, although some patients made health decisions based on misunderstandings of their results. These findings suggest that expanded carrier screening causes minimal psychosocial harms, but systems are needed to reduce the risk of misinterpreting results.


Assuntos
Triagem de Portadores Genéticos , Aconselhamento Genético/psicologia , Participação do Paciente/psicologia , Diagnóstico Pré-Natal/psicologia , Adulto , Feminino , Humanos , Masculino , Resultados Negativos , Gravidez , Inquéritos e Questionários
5.
Eye (Lond) ; 32(2): 384-390, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28912520

RESUMO

PurposeWe present a novel variation of the traction test of the inferior oblique (IO) muscle. We demonstrate the correlation between the traction test and clinically graded IO overaction and describe the utility of this test to confirm IO weakening.MethodsWe performed a retrospective chart review on all patients who underwent IO surgery and intraoperative intorsion traction tests by a single surgeon over a 10-year period. We compared the traction test results, in 'clock hours' of freedom, before and after IO surgery. We correlated the torsion test at start of surgery with clinical observed IO overaction (scale 0 to +4) in 67 IO operations (56 myectomies, 6 anterior transpositions, 4 myotomies, and 1 recession) and compared to a control group of 23 eyes with minimal or no IO overaction.ResultsThe mean intorsion freedom in the eyes undergoing IO surgery was less than in control eyes (1.63 vs 1.89 clock hour; P<0.00005). There was a significant inverse relationship between grading of clinical IO action and the intorsion test result (Pearson rank coefficient, (r=-0.45; P<0.00001)). Myectomy produced the greatest change in torsion freedom (mean 1.32 clock hour), with all myectomies showing at least 1 clock hour extra freedom after the surgery.ConclusionsThe intorsion traction test confirmed that the IO stiffness correlated with pre-operative IO overaction grade. While it can be helpful in confirming that the entire IO muscle was weakened, it does not substitute for the careful inspection at the end of surgery to ensure there are no remaining IO fibers.


Assuntos
Monitorização Intraoperatória/métodos , Transtornos da Motilidade Ocular/cirurgia , Músculos Oculomotores , Procedimentos Cirúrgicos Oftalmológicos , Tração , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Músculos Oculomotores/fisiologia , Músculos Oculomotores/cirurgia , Estudos Retrospectivos
6.
Rev Sci Instrum ; 87(8): 083310, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27587116

RESUMO

In this paper, a scintillator-based online beam profile detector for the characterization of laser-driven proton beams is presented. Using a pixelated matrix with varying absorber thicknesses, the proton beam is spatially resolved in two dimensions and simultaneously energy-resolved. A thin plastic scintillator placed behind the absorber and read out by a CCD camera is used as the active detector material. The spatial detector resolution reaches down to ∼4 mm and the detector can resolve proton beam profiles for up to 9 proton threshold energies. With these detector design parameters, the spatial characteristics of the proton distribution and its cut-off energy can be analyzed online and on-shot under vacuum conditions. The paper discusses the detector design, its characterization and calibration at a conventional proton source, as well as the first detector application at a laser-driven proton source.

7.
Ethics Med Public Health ; 2(3): 334-342, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28180146

RESUMO

BACKGROUND: The recent introduction of cell-free DNA-based non-invasive prenatal screening (cfDNA screening) into clinical practice was expected to revolutionize prenatal testing. cfDNA screening for fetal aneuploidy has demonstrated higher test sensitivity and specificity for some conditions than conventional serum screening and can be conducted early in the pregnancy. However, it is not clear whether and how clinical practices are assimilating this new type of testing into their informed consent and counselling processes. Since the introduction of cfDNA screening into practice in 2011, the uptake and scope have increased dramatically. Prenatal care providers are under pressure to stay up to date with rapidly changing cfDNA screening panels, manage increasing patient demands, and keep up with changing test costs, all while attempting to use the technology responsibly and ethically. While clinical literature on cfDNA screening has shown benefits for specific patient populations, it has also identified significant misunderstandings among providers and patients alike about the power of the technology. The unique features of cfDNA screening, in comparison to established prenatal testing technologies, have implications for informed decision-making and genetic counselling that must be addressed to ensure ethical practice. OBJECTIVES: This study explored the experiences of prenatal care providers at the forefront of non-invasive genetic screening in the United States to understand how this testing changes the practice of prenatal medicine. We aimed to learn how the experience of providing and offering this testing differs from established prenatal testing methodologies. These differences may necessitate changes to patient education and consent procedures to maintain ethical practice. METHODS: We used the online American Congress of Obstetricians and Gynecologists Physician Directory to identify a systematic sample of five prenatal care providers in each U.S. state and the District of Columbia. Beginning with the lowest zip code in each state, we took every fifth name from the directory, excluding providers who were retired, did not currently practice in the state in which they were listed, or were not involved in a prenatal specialty. After repeating this step twice and sending a total of 461 invitations, 37 providers expressed interest in participating, and we completed telephone interviews with 21 providers (4.6%). We developed a semi-structured interview guide including questions about providers' use of and attitudes toward cfDNA screening. A single interviewer conducted and audio-recorded all interviews by telephone, and the interviews lasted approximately 30 minutes each. We collaboratively developed a codebook through an iterative process of transcript review and code application, and a primary coder coded all transcripts. RESULTS: Prenatal care providers have varying perspectives on the advantages of cfDNA screening and express a range of concerns regarding the implementation of cfDNA screening in practice. While providers agreed on several advantages of cfDNA, including increased accuracy, earlier return of results, and decreased risk of complications, many expressed concern that there is not enough time to adequately counsel and educate patients on their prenatal screening and testing options. Providers also agreed that demand for cfDNA screening has increased and expressed a desire for more information from professional societies, labs, and publications. Providers disagreed about the healthcare implications and future of cfDNA screening. Some providers anticipated that cfDNA screening would decrease healthcare costs when implemented widely and expressed optimism for expanded cfDNA screening panels. Others were concerned that cfDNA screening would increase costs over time and questioned whether the expansion to include microdeletions could be done ethically. CONCLUSIONS: The perspectives and experiences of the providers in this study allow insight into the clinical benefit, burden on prenatal practice, and potential future of cfDNA screening in clinical practice. Given the likelihood that the scope and uptake of cfDNA screening will continue to increase, it is essential to consider how these changes will affect frontline prenatal care providers and, in turn, patients. Providers' requests for additional guidance and data as well as their concerns with the lack of time available to explain screening and testing options indicate significant potential issues with patient care. It is important to ensure that the clinical integration of cfDNA screening is managed responsibly and ethically before it expands further, exacerbating pre-existing issues. As prenatal screening evolves, so should informed consent and the resources available to women making decisions. The field must take steps to maximize the advantages of cfDNA screening and responsibly manage its ethical issues.


CONTEXTE: L'introduction récente du dépistage prénatal non invasif (dépistage cfDNA) exempt de cellules à base d'ADN dans la pratique clinique devait révolutionner le dépistage prénatal. Le dépistage cfDNA de l'aneuploïdie fœtale a démontré une meilleure sensibilité et spécificité que le dépistage sérique classique et peut être effectué au début de la grossesse. Cependant, on ne sait pas si et comment les pratiques cliniques assimilent ce nouveau type de test dans leurs processus de consentement et de conseil éclairés. Depuis l'introduction du dépistage cfDNA dans la pratique en 2011, l'absorption et la portée ont augmenté de façon spectaculaire. Les professionnels sont sous pression pour rester à jour avec l'évolution rapide des échantillons cfDNA, gérer la demande croissante des patients, et suivre l'évolution des coûts de test, tout en essayant d'utiliser la technologie de manière responsable et éthique. Bien que la littérature clinique sur le dépistage cfDNA a montré des avantages pour les populations de patients spécifiques, elle a également identifié des malentendus importants entre les professionnels et les patients sur le pouvoir de la technologie. Les caractéristiques uniques du dépistage cfDNA, par rapport aux technologies de dépistage prénatal établies, ont des implications pour la prise de décisions éclairées et le conseil génétique qui rentrent en compte pour assurer une pratique éthique. OBJECTIFS: Cette étude a exploré les expériences des professionnels à la pointe du dépistage génétique non invasif aux États-Unis pour comprendre comment ce test modifie la pratique de la médecine prénatale. Nous avons cherché à savoir comment l'expérience de fournir et d'offrir ce test diffère des méthodes plus anciennes de dépistage prénatal. Ces différences peuvent nécessiter des changements dans l'éducation du patient et les procédures de consentement pour maintenir une pratique éthique. MÉTHODES: Nous avons utilisé l'annuaire en ligne du Congrès américain des médecins obstétriciens et gynécologues pour identifier un échantillon systématique de cinq fournisseurs de soins prénatals dans chaque État américain et le District de Columbia. En commençant par le code postal le plus bas dans chaque état, nous avons pris tous les cinquièmes noms de l'annuaire, à l'exclusion des prestataires qui étaient à la retraite, ne pratiquait pas actuellement dans l'état dans lequel ils ont été énumérés, ou ne sont pas impliqués dans une spécialité prénatale. Après avoir répété cette étape deux fois et l'envoi d'un total de 461 invitations, 37 professionnels ont exprimé leur intérêt à participer, et nous avons réalisé des entrevues téléphoniques avec 21 fournisseurs (4,6 %). Nous avons développé un entretien semi-dirigé comprenant des questions sur l'utilisation de fournisseurs de dépistage et les attitudes envers le cfDNA. Un seul intervieweur a mené et enregistré toutes les interviews par téléphone, les entretiens ont duré environ 30 minutes chacun. Nous avons développé en collaboration un dictionnaire par un processus itératif d'examen de la transcription et de l'application du code, et un codeur primaire a codé toutes les transcriptions. RÉSULTATS: Les professionnels de soins prénataux ont des points de vue variés sur les avantages du dépistage cfDNA et expriment une gamme de préoccupations concernant la mise en œuvre du dépistage cfDNA dans la pratique. S'ils ont convenu de plusieurs avantages de cfDNA, y compris une précision accrue, un retour plus rapide des résultats et une diminution de risque de complications, une préoccupation exprimée est qu'il n'y a pas suffisamment pour conseiller et éduquer les patients sur les options de dépistage et de dépistage prénatal. Les professionnels ont également convenu que la demande pour le dépistage cfDNA a augmenté et ont souhaité plus d'informations émanant des sociétés professionnelles, des laboratoires et des publications. Les fournisseurs étaient en désaccord au sujet des implications sur la santé et sur l'avenir du dépistage cfDNA. Certains fournisseurs prévoyaient que le dépistage cfDNA diminuerait les coûts des soins de santé lorsqu'ils seront appliqués largement et a exprimé son optimisme pour l'élargissement des échantillons de dépistage cfDNA. D'autres craignaient que le dépistage cfDNA augmenterait les coûts au fil du temps et se sont demandé si la possibilité d'y inclure les microdélétions pourrait être fait sur le plan éthique. CONCLUSIONS: Les perspectives et les expériences des fournisseurs dans cette étude permettent d'avoir un aperçu de l'avantage clinique, de la charge sur la pratique prénatale, et du futur potentiel du dépistage cfDNA dans la pratique clinique. Compte tenu de la probabilité que la portée et l'acceptation du dépistage cfDNA vont continuer à augmenter, il est essentiel d'examiner comment ces changements auront une incidence sur les fournisseurs de soins prénataux de première ligne et sur les patients. Les demandes de professionnels pour obtenir des conseils et des données supplémentaires ainsi que leurs préoccupations sur le manque de temps disponible pour expliquer aux patients les options de dépistage et de tests indiquent des problèmes potentiellement lourds. Il est important de veiller à ce que l'intégration clinique du dépistage cfDNA soit gérée de façon responsable et éthique avant qu'il ne se développe davantage, aggravant les problèmes préexistants. Comme le dépistage prénatal évolue, de même devrait évoluer le consentement éclairé et les ressources disponibles pour que les femmes puissent prendre leur décision. La discipline doit prendre des mesures pour maximiser les avantages du dépistage cfDNA et gérer de façon responsable les questions éthiques qui s'y rapportent.

8.
Vet Comp Oncol ; 14(1): 28-38, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23782408

RESUMO

18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG-PET/CT) has been shown to be effective for staging human oral squamous cell carcinoma (SCC) but its application for cats with oral SCC is unknown. Twelve cats with biopsy-proven oral SCC were imaged with whole body 18FDG-PET/CT to determine its value as a diagnostic imaging and staging tool and fine needle aspirates were obtained of accessible regional lymph nodes. All tumors were FDG avid and conspicuous on 18FDG-PET/CT images, with an average of the maximum standardized uptake value 9.88 ± 5.33 SD (range 2.9-24.9). Soft tissue infiltrative tumors that were subtle and ill defined on CT were highly visible and more extensive on FDG-PET/CT. Tumors invading the osseous structures were more similar in extent on 18FDG-PET/CT and CT although they were more conspicuous on PET images. Three cytologically confirmed metastases were hypermetabolic on PET, while two of those metastases were equivocal on CT.


Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças do Gato/diagnóstico , Fluordesoxiglucose F18/farmacologia , Neoplasias Bucais/veterinária , Tomografia por Emissão de Pósitrons/veterinária , Tomografia Computadorizada por Raios X/veterinária , Animais , Carcinoma de Células Escamosas/diagnóstico , Doenças do Gato/patologia , Gatos , Feminino , Linfonodos/patologia , Masculino , Neoplasias Bucais/diagnóstico
10.
Glob Chang Biol ; 21(12): 4673-84, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26146813

RESUMO

Variations in photosynthesis still cause substantial uncertainties in predicting photosynthetic CO2 uptake rates and monitoring plant stress. Changes in actual photosynthesis that are not related to greenness of vegetation are difficult to measure by reflectance based optical remote sensing techniques. Several activities are underway to evaluate the sun-induced fluorescence signal on the ground and on a coarse spatial scale using space-borne imaging spectrometers. Intermediate-scale observations using airborne-based imaging spectroscopy, which are critical to bridge the existing gap between small-scale field studies and global observations, are still insufficient. Here we present the first validated maps of sun-induced fluorescence in that critical, intermediate spatial resolution, employing the novel airborne imaging spectrometer HyPlant. HyPlant has an unprecedented spectral resolution, which allows for the first time quantifying sun-induced fluorescence fluxes in physical units according to the Fraunhofer Line Depth Principle that exploits solar and atmospheric absorption bands. Maps of sun-induced fluorescence show a large spatial variability between different vegetation types, which complement classical remote sensing approaches. Different crop types largely differ in emitting fluorescence that additionally changes within the seasonal cycle and thus may be related to the seasonal activation and deactivation of the photosynthetic machinery. We argue that sun-induced fluorescence emission is related to two processes: (i) the total absorbed radiation by photosynthetically active chlorophyll; and (ii) the functional status of actual photosynthesis and vegetation stress.


Assuntos
Clorofila/fisiologia , Fotossíntese , Tecnologia de Sensoriamento Remoto/métodos , Espectrometria de Fluorescência , Luz Solar , Fluorescência
11.
J Vet Intern Med ; 29(1): 97-103, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25273956

RESUMO

BACKGROUND: Computed tomography (CT) is highly accurate for diagnosing pancreatitis in humans. The diagnosis of pancreatitis in dogs is based on clinical signs, laboratory findings, and ultrasonographic (US) changes. There are, however, inherent limitations in relying on laboratory and ultrasound findings for the clinical diagnosis of pancreatitis in dogs. HYPOTHESIS/OBJECTIVES: We hypothesized that CT angiography would be a rapid and reliable method to confirm pancreatitis in dogs compared to ultrasonography. The aim was to describe the CT characteristics and compare them to ultrasound findings and correlate the CT appearance to the severity of the patients' clinical course. ANIMALS: A prospective pilot case series; 10 dogs with pancreatitis were enrolled if the history, clinical signs, laboratory, and ultrasonographic findings were indicative of pancreatitis. METHODS: A 3-phase angiographic CT was performed under sedation. Afterward, each dog had US-guided aspirates of the pancreas collected and blood drawn for cPLi assay. Images were evaluated for portion of visible pancreas, pancreatic size and margin, pancreatic parenchyma, presence of peripancreatic changes and contrast enhancement pattern. The results were compared with outcome. RESULTS: An enlarged, homogeneously to heterogeneously attenuating and contrast-enhancing pancreas with ill-defined borders was identified in all dogs. CT identified more features characterizing pancreatic abnormalities compared to US. Thrombi were found in 3/10 dogs. Three dogs with heterogeneous contrast enhancement had an overall poorer outcome than those with homogenous enhancement. CONCLUSIONS AND CLINICAL IMPORTANCE: CT angiography under sedation was used in dogs to confirm clinically suspected pancreatitis and identified clinically relevant and potentially prognostic features of pancreatitis in dogs.


Assuntos
Angiografia/veterinária , Sedação Consciente/veterinária , Doenças do Cão/diagnóstico , Pancreatite/veterinária , Tomografia Computadorizada por Raios X/veterinária , Angiografia/métodos , Animais , Cães , Feminino , Masculino , Pancreatite/diagnóstico , Projetos Piloto , Tomografia Computadorizada por Raios X/métodos
12.
Spinal Cord ; 52(4): 316-21, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24418957

RESUMO

STUDY DESIGN: Cross-sectional cohort study. OBJECTIVES: To investigate a mediational model where pain (intensity and interference) and fatigue mediate the relationship between the use of mobility aids and moderate-to-severe depressive symptomatology among ambulatory participants with spinal cord injury (SCI). SETTING: A medical university in the southeastern United States. METHODS: Ambulatory adults (N=652) with chronic SCI responded to a mail-in survey. The Patient Health Questionnaire-9 was used to assess moderate-to-severe depressive symptomatology. The Brief Pain Inventory was used to assess pain intensity and interference, and the Modified Fatigue Impact Scale-5-item version was used to assess fatigue. Participants self-reported use of mobility aids. RESULTS: On examining mobility aids used for ambulation, 65% were found to have used at least one aid. Severe pain intensity was reported by 11%, and 14% reported severe pain interference. Disabling fatigue was reported by 10% of the participants. Twenty-one percent (n=138) reported moderate-to-severe levels of depressive symptoms. On examining the relationships between mobility aids and depressive symptomatology, using people as a mobility aid was associated with increased odds of depressive symptomatology (2.6) and always using a wheelchair was associated with lower odds (0.3). However, these relationships were no longer significant after controlling for the mediating variables pain intensity, pain interference and fatigue. CONCLUSIONS: Pain and fatigue mediate the relationship between usage of certain mobility aids and depressive symptomatology. The use of people to assist in ambulation is associated with greater odds of moderate-to-severe depressive symptomatology, while always using a wheelchair is associated with lower odds.


Assuntos
Depressão/fisiopatologia , Fadiga/fisiopatologia , Equipamentos Ortopédicos , Dor/fisiopatologia , Tecnologia Assistiva , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Escalas de Graduação Psiquiátrica , Autorrelato , Índice de Gravidade de Doença , Traumatismos da Medula Espinal/psicologia , Inquéritos e Questionários , Cadeiras de Rodas
13.
Ann Oncol ; 24(2): 530-537, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23035153

RESUMO

BACKGROUND: The cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors are not well understood. Squamous cell carcinoma (SCC), keratoacanthoma, and photosensitivity have been described in patients taking BRAF inhibitors. PATIENTS AND METHODS: To characterize the timing and frequency of skin lesions in patients receiving BRAF inhibitor therapy, we utilized a retrospective case review of 53 patients undergoing treatment with BRAF inhibitors for 4-92 weeks of therapy. Patients were evaluated at baseline, and then followed at 4- to 12-week intervals. Charts were retrospectively reviewed, and the morphology and timing of cutaneous events were recorded. RESULTS: Thirty-three of the 53 charts met exclusion/inclusion criteria, 15 were treated with vemurafenib, and 18 were treated with GSK 2118436/GSK 1120212. Of 33 patients treated with BRAF inhibitor, 13 developed photosensitivity (39.4%), 10 developed actinic keratoses (30.3%), 10 developed warts (30.3%), and 6 developed SCC (18.2%). CONCLUSIONS: Multiple cutaneous findings were observed in the 33 patients taking BRAF inhibitors. The previously described association with SCC and photosensitivity was observed in these patients as well. Over half of the observed SCCs were invasive in nature. Photosensitivity continues to be frequent with BRAF inhibitors. Patients taking BRAF inhibitors should have regular full body skin exams. Further studies are necessary to better elucidate the rates of these adverse cutaneous effects.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Dermatopatias/induzido quimicamente , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/induzido quimicamente , Feminino , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Indóis/efeitos adversos , Indóis/uso terapêutico , Ceratoacantoma/induzido quimicamente , Ceratose Actínica/induzido quimicamente , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Oximas/efeitos adversos , Oximas/uso terapêutico , Transtornos de Fotossensibilidade/induzido quimicamente , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Pirimidinonas/efeitos adversos , Pirimidinonas/uso terapêutico , Estudos Retrospectivos , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Vemurafenib , Verrugas/induzido quimicamente
15.
Nat Commun ; 3: 874, 2012 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-22673901

RESUMO

High-intensity laser plasma-based ion accelerators provide unsurpassed field gradients in the megavolt-per-micrometer range. They represent promising candidates for next-generation applications such as ion beam cancer therapy in compact facilities. The weak scaling of maximum ion energies with the square-root of the laser intensity, established for large sub-picosecond class laser systems, motivates the search for more efficient acceleration processes. Here we demonstrate that for ultrashort (pulse duration ~30 fs) highly relativistic (intensity ~10(21) W cm(-2)) laser pulses, the intra-pulse phase of the proton acceleration process becomes relevant, yielding maximum energies of around 20 MeV. Prominent non-target-normal emission of energetic protons, reflecting an engineered asymmetry in the field distribution of promptly accelerated electrons, is used to identify this pre-thermal phase of the acceleration. The relevant timescale reveals the underlying physics leading to the near-linear intensity scaling observed for 100 TW class table-top laser systems.

16.
Med Phys ; 39(5): 2447-55, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22559615

RESUMO

PURPOSE: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 10(11) Gy∕s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors. METHODS: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL, and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer, and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were tested. RESULTS: The dosimeters are dose rate independent up to 4●10(9) Gy∕s within 2% (OSL and TLD) and up to 15●10(9) Gy∕s within 5% (EBT films). The diamond detectors show strong dose rate dependence. CONCLUSIONS: TLD, OSL dosimeters, and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.


Assuntos
Diamante , Dosimetria Fotográfica/métodos , Dosimetria Termoluminescente/métodos
17.
Rev Sci Instrum ; 83(12): 123301, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23277976

RESUMO

In recent years, a new generation of high repetition rate (~10 Hz), high power (~100 TW) laser systems has stimulated intense research on laser-driven sources for fast protons. Considering experimental instrumentation, this development requires online diagnostics for protons to be added to the established offline detection tools such as solid state track detectors or radiochromic films. In this article, we present the design and characterization of a scintillator-based online detector that gives access to the angularly resolved proton distribution along one spatial dimension and resolves 10 different proton energy ranges. Conceived as an online detector for key parameters in laser-proton acceleration, such as the maximum proton energy and the angular distribution, the detector features a spatial resolution of ~1.3 mm and a spectral resolution better than 1.5 MeV for a maximum proton energy above 12 MeV in the current design. Regarding its areas of application, we consider the detector a useful complement to radiochromic films and Thomson parabola spectrometers, capable to give immediate feedback on the experimental performance. The detector was characterized at an electrostatic Van de Graaff tandetron accelerator and tested in a laser-proton acceleration experiment, proving its suitability as a diagnostic device for laser-accelerated protons.

18.
Klin Monbl Augenheilkd ; 228(4): 322-5, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21484638

RESUMO

BACKGROUND: The aim of this study is to report the geometric range of angle kappa formation in patients with and without strabismus. PATIENTS AND METHODS: This is a retrospective study of three patients with angle kappa in different planes. Routine eye examinations, including visual acuity, slit-lamp examination, and ophthalmoscopy, were performed. A thorough orthoptic examination revealed a notable difference between the prism and alternate-cover test and the Hirschberg measurements. RESULTS: The first patient exhibited a bilateral vertical angle kappa into opposite directions due to retinochoroidal scars. Two other patients presented with horizontal angle kappa deviations. In one patient a true accommodative esotropia was exaggerated by a right negative angle kappa. The other patient had a pseudoexotropia due to bilateral positive angle kappa. Macular ectopia was noted in all cases. CONCLUSIONS: The patients herein reported demonstrate a marked variability of angle kappa occurrence in the horizontal and vertical plane. The angle kappa can exaggerate or conceal the size of the true heterotropia.


Assuntos
Técnicas de Diagnóstico Oftalmológico , Estrabismo/diagnóstico , Estrabismo/fisiopatologia , Adulto , Criança , Feminino , Humanos , Masculino
19.
Phys Med Biol ; 56(6): 1529-43, 2011 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-21325708

RESUMO

An integrated dosimetry and cell irradiation system (IDOCIS) with laser-accelerated proton beams was developed, characterized, calibrated and successfully used for systematic in vitro experiments. Due to the broad exponentially shaped energy spectrum, the low-energy range of the protons (<20 MeV) and the high pulse dose, the absolute dosimetry for this beam quality is challenging. Therefore, a dedicated Faraday cup is used as an energy and dose rate independent absolute dosimeter that has been calibrated consistently with three independent methods. A transmission ionization chamber providing online relative dose information is cross-calibrated against the Faraday cup. Providing both online and absolute dose information, the IDOCIS allows for quantitative dosimetric and radiobiological studies at current low-energy laser-accelerated proton beams. Finally, first dosimetric characterizations of a laser-accelerated proton beam with the IDOCIS are presented.


Assuntos
Células/efeitos da radiação , Lasers , Radiometria/instrumentação , Radioterapia de Alta Energia/instrumentação , Calibragem , Humanos , Prótons , Radiometria/métodos , Dosagem Radioterapêutica , Radioterapia de Alta Energia/métodos
20.
Allergy ; 66(5): 605-11, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21241315

RESUMO

BACKGROUND: Most functions of tetraspanins are not related to cell-surface receptor ligand binding, but are mediated by direct interactions with their partner proteins. Functions of trimeric FcɛRI, expressed by antigen-presenting cells (APCs), range from amplification of allergic inflammatory reactions to their active suppression. Cell-type-specific protein-protein interactions might play a role in the regulation of these bidirectional tasks. Therefore, we intended to study the interactions of trimeric FcɛRI with tetraspanins. METHODS: The expression levels of tetraspanins CD9, CD37, CD53, CD63, CD81, CD82, and CD151 on skin dendritic cells of atopic dermatitis (AD) patients or healthy individuals were detected by flow cytometry. Tetraspanin expression on FcɛRI(pos) and FcɛRI(neg) monocyte subpopulations was evaluated. Flow cytometry, confocal microscopy, immunoprecipitation, and immunoblotting experiments were performed to observe the relationship between tetraspanins CD9 and CD81 and FcɛRI. Furthermore, plate stimulation experiments were performed, and cytokines in the supernatants were detected. RESULTS: We found that human FcɛRI(pos) APCs expressed high amounts of tetraspanins and that the tetraspanins CD9 and CD81 were associated with FcɛRI. Concomitant activation of FcɛRI and CD9 on human monocytes increased FcɛRI-mediated cytokine release. CONCLUSION: Taken together, we show for the first time that CD9 and CD81 act as molecular partners of trimeric FcɛRI on human APC, which might be of importance in allergic diseases such as AD.


Assuntos
Células Apresentadoras de Antígenos/química , Antígenos CD/metabolismo , Células Dendríticas/química , Dermatite Atópica/imunologia , Glicoproteínas de Membrana/metabolismo , Receptores de IgE/metabolismo , Células Apresentadoras de Antígenos/imunologia , Antígenos CD/análise , Estudos de Casos e Controles , Humanos , Glicoproteínas de Membrana/análise , Ligação Proteica , Receptores de IgE/análise , Pele/patologia , Tetraspanina 28 , Tetraspanina 29
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