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1.
Strahlenther Onkol ; 200(3): 202-207, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37640867

RESUMO

PURPOSE: Node-positive prostate cancer is a potentially curable disease. Definitive radiotherapy to the prostate and lymphatic drainage is an effective treatment option but prospective long-term outcome data are scarce. Thus, the current study aimed to evaluate the toxicity and efficacy of definitive radiation therapy for men with prostate cancer and nodal metastases using modern irradiation techniques. METHODS: A total of 40 treatment-naïve men with node-positive prostate cancer were allocated to the trial. All patients received definitive radiation therapy at two German university hospitals between 2009 and 2018. Radiation was delivered as intensity-modulated radiation therapy (IMRT) with 51 Gy to the lymphatic drainage with simultaneous integrated boost (SIB) up to 61.2 Gy to involved nodes and 76.5 Gy to the prostate in 34 fractions. Feasibility and safety, overall and progression-free survival, toxicity, and quality of life measurements were analyzed. RESULTS: During a median follow-up of 79 months, median overall survival was 107 months and progression-free survival was 78 months. Based on imaging follow-up, no infield relapse was reported during the first 24 months of follow-up. There were 3 (8%) potentially treatment-related grade 3 toxicities. Common iliac node involvement was associated with a higher risk of progression (HR 15.8; 95% CI 2.1-119.8; p = 0.007). CONCLUSION: Definitive radiation to the lymphatic drainage with SIB to the involved nodes and prostate is a safe and effective treatment approach for patients with treatment-naïve, node-positive prostate cancer with excellent infield tumor control rates and tolerable toxicity. Location rather than number of involved nodes is a major risk factor for progression.


Assuntos
Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Masculino , Humanos , Próstata/patologia , Estudos Prospectivos , Qualidade de Vida , Recidiva Local de Neoplasia/etiologia , Neoplasias da Próstata/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos
2.
Phys Rev Lett ; 131(9): 091801, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37721818

RESUMO

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

3.
Phys Rev Lett ; 127(6): 061801, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34420312

RESUMO

We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σ_{E}=3.86±0.04(stat)_{-0.00}^{+0.19}(syst) eV. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV/c^{2}, with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.

4.
Phys Rev Lett ; 127(8): 081802, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34477436

RESUMO

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) achieved efficient detection of very small recoil energies in its germanium target, resulting in sensitivity to lightly ionizing particles (LIPs) in a previously unexplored region of charge, mass, and velocity parameter space. We report first direct-detection limits calculated using the optimum interval method on the vertical intensity of cosmogenically produced LIPs with an electric charge smaller than e/(3×10^{5}), as well as the strongest limits for charge ≤e/160, with a minimum vertical intensity of 1.36×10^{-7} cm^{-2} s^{-1} sr^{-1} at charge e/160. These results apply over a wide range of LIP masses (5 MeV/c^{2} to 100 TeV/c^{2}) and cover a wide range of ßγ values (0.1-10^{6}), thus excluding nonrelativistic LIPs with ßγ as small as 0.1 for the first time.

5.
Ann Oncol ; 31(1): 137-143, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31912788

RESUMO

BACKGROUND: Convolutional neural networks (CNNs) efficiently differentiate skin lesions by image analysis. Studies comparing a market-approved CNN in a broad range of diagnoses to dermatologists working under less artificial conditions are lacking. MATERIALS AND METHODS: One hundred cases of pigmented/non-pigmented skin cancers and benign lesions were used for a two-level reader study in 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Additionally, dermoscopic images were classified by a CNN approved for the European market as a medical device (Moleanalyzer Pro, FotoFinder Systems, Bad Birnbach, Germany). Primary endpoints were the sensitivity and specificity of the CNN's dichotomous classification in comparison with the dermatologists' management decisions. Secondary endpoints included the dermatologists' diagnostic decisions, their performance according to their level of experience, and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC). RESULTS: The CNN revealed a sensitivity, specificity, and ROC AUC with corresponding 95% confidence intervals (CI) of 95.0% (95% CI 83.5% to 98.6%), 76.7% (95% CI 64.6% to 85.6%), and 0.918 (95% CI 0.866-0.970), respectively. In level I, the dermatologists' management decisions showed a mean sensitivity and specificity of 89.0% (95% CI 87.4% to 90.6%) and 80.7% (95% CI 78.8% to 82.6%). With level II information, the sensitivity significantly improved to 94.1% (95% CI 93.1% to 95.1%; P < 0.001), while the specificity remained unchanged at 80.4% (95% CI 78.4% to 82.4%; P = 0.97). When fixing the CNN's specificity at the mean specificity of the dermatologists' management decision in level II (80.4%), the CNN's sensitivity was almost equal to that of human raters, at 95% (95% CI 83.5% to 98.6%) versus 94.1% (95% CI 93.1% to 95.1%); P = 0.1. In contrast, dermatologists were outperformed by the CNN in their level I management decisions and level I and II diagnostic decisions. More experienced dermatologists frequently surpassed the CNN's performance. CONCLUSIONS: Under less artificial conditions and in a broader spectrum of diagnoses, the CNN and most dermatologists performed on the same level. Dermatologists are trained to integrate information from a range of sources rendering comparative studies that are solely based on one single case image inadequate.


Assuntos
Melanoma , Neoplasias Cutâneas , Dermatologistas , Dermoscopia , Alemanha , Humanos , Masculino , Melanoma/diagnóstico por imagem , Redes Neurais de Computação
6.
J Eur Acad Dermatol Venereol ; 34(6): 1355-1361, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31856342

RESUMO

BACKGROUND: Deep learning convolutional neural networks (CNN) may assist physicians in the diagnosis of melanoma. The capacity of a CNN to differentiate melanomas from combined naevi, the latter representing well-known melanoma simulators, has not been investigated. OBJECTIVE: To assess the diagnostic performance of a CNN when used to differentiate melanomas from combined naevi in comparison with dermatologists. METHODS: In this study, a CNN with regulatory approval for the European market (Moleanalyzer-Pro, FotoFinder Systems GmbH, Bad Birnbach, Germany) was used. We attained a dichotomous classification (benign, malignant) in dermoscopic images of 36 combined naevi and 36 melanomas with a mean Breslow thickness of 1.3 mm. Primary outcome measures were the CNN's sensitivity, specificity and the diagnostic odds ratio (DOR) in comparison with 11 dermatologists with different levels of experience. RESULTS: The CNN revealed a sensitivity, specificity and DOR of 97.1% (95% CI [82.7-99.6]), 78.8% (95% CI [62.8-89.1.3]) and 34 (95% CI [4.8-239]), respectively. Dermatologists showed a lower mean sensitivity, specificity and DOR of 90.6% (95% CI [84.1-94.7]; P = 0.092), 71.0% (95% CI [62.6-78.1]; P = 0.256) and 24 (95% CI [11.6-48.4]; P = 0.1114). Under the assumption that dermatologists use the CNN to verify their (initial) melanoma diagnosis, dermatologists achieve an increased specificity of 90.3% (95% CI [79.8-95.6]) at an almost unchanged sensitivity. The largest benefit was observed in 'beginners', who performed worst without CNN verification (DOR = 12) but best with CNN verification (DOR = 98). CONCLUSION: The tested CNN more accurately classified combined naevi and melanomas in comparison with trained dermatologists. Their diagnostic performance could be improved if the CNN was used to confirm/overrule an initial melanoma diagnosis. Application of a CNN may therefore be of benefit to clinicians.


Assuntos
Aprendizado Profundo , Dermatologistas , Diagnóstico por Computador/métodos , Melanoma/diagnóstico por imagem , Nevo Pigmentado/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Idoso , Competência Clínica , Dermoscopia , Feminino , Humanos , Masculino , Melanócitos/patologia , Melanoma/patologia , Pessoa de Meia-Idade , Nevo Pigmentado/patologia , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , Adulto Jovem
7.
Hautarzt ; 71(9): 691-698, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32720165

RESUMO

ADVANTAGES OF ARTIFICIAL INTELLIGENCE (AI): With responsible, safe and successful use of artificial intelligence (AI), possible advantages in the field of dermato-oncology include the following: (1) medical work can focus on skin cancer patients, (2) patients can be more quickly and effectively treated despite the increasing incidence of skin cancer and the decreasing number of actively working dermatologists and (3) users can learn from the AI results. POTENTIAL DISADVANTAGES AND RISKS OF AI USE: (1) Lack of mutual trust can develop due to the decreased patient-physician contact, (2) additional time effort will be necessary to promptly evaluate the AI-classified benign lesions, (3) lack of adequate medical experience to recognize misclassified AI decisions and (4) recontacting a patient in due time in the case of incorrect AI classifications. Still problematic in the use of AI are the medicolegal situation and remuneration. Apps using AI currently cannot provide sufficient assistance based on clinical images of skin cancer. REQUIREMENTS AND POSSIBLE USE OF SMARTPHONE PROGRAM APPLICATIONS: Smartphone program applications (apps) can be implemented responsibly when the image quality is good, the patient's history can be entered easily, transmission of the image and results are assured and medicolegal aspects as well as remuneration are clarified. Apps can be used for disease-specific information material and can optimize patient care by using teledermatology.


Assuntos
Inteligência Artificial , Dermatologia/métodos , Melanoma/diagnóstico por imagem , Aplicativos Móveis , Neoplasias Cutâneas/diagnóstico por imagem , Smartphone , Telemedicina/instrumentação , Humanos , Interpretação de Imagem Assistida por Computador , Oncologia , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico
9.
Br J Dermatol ; 180(2): 390-396, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30218575

RESUMO

BACKGROUND: The Psoriasis Area and Severity Index (PASI) represents the gold standard for psoriasis severity assessments but is limited by its subjectivity and low intra- and inter-rater consistency. OBJECTIVES: To investigate the precision and reproducibility of automated, computer-guided PASI measurements (ACPMs) in comparison with three trained physicians. METHODS: This was a comparative observational study assessing ACPMs attained by automated total-body imaging and computerized digital image analysis in a cohort of 120 patients affected by plaque psoriasis of various severities. The level of agreement between ACPMs and physicians' PASI measurements was calculated by the intraclass correlation coefficient (ICC). The reproducibility of ACPMs in comparison with physicians' PASI measurements was investigated by performing two successive 'repeat PASI calculations' in the same patients. RESULTS: The agreement between ACPMs and physicians' PASI calculations in 120 fully evaluable patients was high (ICC 0·86, 95% confidence interval 0·80-0·90, mean absolute difference 2·5 PASI points). Repeat ACPMs to measure the reproducibility showed an excellent ICC of 0·99 (95% confidence interval 0·98-0·99) with a mean absolute difference of 0·5 PASI points. The ACPMs thus outperformed the three physicians for intrarater reliability (mean ICC 0·86). CONCLUSIONS: The results of this first clinical study investigating ACPMs in 120 patients with psoriasis indicate a similar precision and higher reproducibility in comparison with trained physicians. Limitations arise from poorly observable body sites and from patients unable to attain predefined postures during automated image acquisition.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Psoríase/diagnóstico , Índice de Gravidade de Doença , Adulto , Dermatologistas/estatística & dados numéricos , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/instrumentação , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Fotografação , Reprodutibilidade dos Testes , Pele/diagnóstico por imagem
10.
Hautarzt ; 70(4): 295-311, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30895329

RESUMO

The use of dermoscopy by dermatologists across Europe has become a standard examination for benign and malignant skin lesions and increasingly also for inflammatory skin diseases. However, based on the experience of the authors from numerous dermoscopy courses, knowledge about important dermoscopic features in special locations such as mucosa or nails is often limited. This may be explained by (1) a different anatomy of the skin and its adnexa in special locations in comparison to the remaining integument, (2) difficult technical access to special locations with a dermatoscope, and (3) a rather low incidence of malignant skin neoplasms in areas of special locations (with the exception of facial skin/scalp). This article aims at explaining dermoscopic characteristics and features of important benign and malignant lesions of nails, acral skin, face, and mucosa.


Assuntos
Dermoscopia/métodos , Melanoma , Unhas , Neoplasias Cutâneas , Europa (Continente) , Humanos , Mucosa
11.
Ann Oncol ; 29(8): 1836-1842, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29846502

RESUMO

Background: Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, but data comparing a CNN's diagnostic performance to larger groups of dermatologists are lacking. Methods: Google's Inception v4 CNN architecture was trained and validated using dermoscopic images and corresponding diagnoses. In a comparative cross-sectional reader study a 100-image test-set was used (level-I: dermoscopy only; level-II: dermoscopy plus clinical information and images). Main outcome measures were sensitivity, specificity and area under the curve (AUC) of receiver operating characteristics (ROC) for diagnostic classification (dichotomous) of lesions by the CNN versus an international group of 58 dermatologists during level-I or -II of the reader study. Secondary end points included the dermatologists' diagnostic performance in their management decisions and differences in the diagnostic performance of dermatologists during level-I and -II of the reader study. Additionally, the CNN's performance was compared with the top-five algorithms of the 2016 International Symposium on Biomedical Imaging (ISBI) challenge. Results: In level-I dermatologists achieved a mean (±standard deviation) sensitivity and specificity for lesion classification of 86.6% (±9.3%) and 71.3% (±11.2%), respectively. More clinical information (level-II) improved the sensitivity to 88.9% (±9.6%, P = 0.19) and specificity to 75.7% (±11.7%, P < 0.05). The CNN ROC curve revealed a higher specificity of 82.5% when compared with dermatologists in level-I (71.3%, P < 0.01) and level-II (75.7%, P < 0.01) at their sensitivities of 86.6% and 88.9%, respectively. The CNN ROC AUC was greater than the mean ROC area of dermatologists (0.86 versus 0.79, P < 0.01). The CNN scored results close to the top three algorithms of the ISBI 2016 challenge. Conclusions: For the first time we compared a CNN's diagnostic performance with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN. Irrespective of any physicians' experience, they may benefit from assistance by a CNN's image classification. Clinical trial number: This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).


Assuntos
Aprendizado Profundo , Dermatologistas/estatística & dados numéricos , Processamento de Imagem Assistida por Computador/métodos , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Competência Clínica , Estudos Transversais , Dermoscopia , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Cooperação Internacional , Curva ROC , Estudos Retrospectivos , Pele/diagnóstico por imagem
12.
Phys Rev Lett ; 121(5): 051301, 2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-30118251

RESUMO

We present the first limits on inelastic electron-scattering dark matter and dark photon absorption using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs (CDMS HVeV, a 0.93 g CDMS high-voltage device). These electron-recoil limits significantly improve experimental constraints on dark matter particles with masses as low as 1 MeV/c^{2}. We demonstrate a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure (0.49 g d). These results demonstrate the scientific potential of phonon-mediated semiconductor detectors that are sensitive to single electronic excitations.

13.
Br J Dermatol ; 179(2): 478-485, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29569229

RESUMO

BACKGROUND: Early detection is a key factor in improving survival from melanoma. Today, the clinical diagnosis of cutaneous melanoma is based mostly on visual inspection and dermoscopy. Preclinical studies in freshly excised or paraffin-embedded tissue have shown that the melanin fluorescence spectra after stepwise two-photon excitation, a process termed dermatofluoroscopy, differ between cutaneous melanoma and melanocytic naevi. However, confirmation from a larger prospective clinical study is lacking. OBJECTIVES: The primary end point of this study was to determine the diagnostic accuracy of dermatofluoroscopy in melanoma detection. Secondary end points included the collection of data for improving the computer algorithm that classifies skin lesions based on melanin fluorescence and the assessment of safety aspects. METHODS: This was a prospective, blinded, multicentre clinical study in patients with pigmented skin lesions (PSLs) indicated for excision either to rule out or to confirm cutaneous melanoma. All included lesions underwent dermoscopy and dermatofluoroscopy in vivo before lesions were excised and subjected to histopathological examination. RESULTS: In total, 369 patients and 476 PSLs were included in the final analysis. In 101 of 476 lesions (21·2%) histopathology revealed melanoma. The observed sensitivity of dermatofluoroscopy was 89·1% (90 of 101 melanomas identified), with an observed specificity of 44·8%. The positive and negative predictive values were 30·3% and 93·9%, respectively. No adverse events occurred. CONCLUSIONS: Dermatofluoroscopy is a safe and accurate diagnostic method to aid physicians in diagnosing cutaneous melanoma. Limitations arise from largely amelanotic or regressing lesions lacking sufficient melanin fluorescence.


Assuntos
Dermoscopia/métodos , Detecção Precoce de Câncer/métodos , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Idoso , Biópsia , Dermoscopia/efeitos adversos , Dermoscopia/instrumentação , Detecção Precoce de Câncer/efeitos adversos , Detecção Precoce de Câncer/instrumentação , Estudos de Viabilidade , Feminino , Fluoroscopia/efeitos adversos , Fluoroscopia/instrumentação , Fluoroscopia/métodos , Humanos , Melanoma/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Pele/diagnóstico por imagem , Pele/patologia , Neoplasias Cutâneas/patologia
14.
J Eur Acad Dermatol Venereol ; 32(8): 1314-1319, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29569769

RESUMO

BACKGROUND: The Psoriasis Area and Severity Index (PASI) is the standard for psoriasis severity assessment. However, PASI measurement is complex and subjective, frequently leading to a high intra- and interobserver variability. To date, the precise extent of variability in PASI measurements and its underlying causes remain unknown. OBJECTIVE: To determine the inter- and intrarater variability of image-based PASI measurements by calculating Intra-Class-Correlation-Coefficients (ICCs) and to investigate the impact of the different PASI components and specific anatomic regions on the extent of variability. METHODS: First, the methodology of 'image-based' vs. commonly used 'live' PASI measurements was validated in a pilot study. Next, in an observational cohort study, PASI scores of 120 patients affected by plaque psoriasis were prospectively evaluated by three formally trained physicians by means of total body images (TBI). Each observer independently performed two rounds of image-based PASI calculations in all patients at two different time points. RESULTS: Overall, 720 image-based PASI scores were calculated with a mean PASI of 8.8 (range 0.7-34.8). An interrater variability with an ICC of 0.895 and mean absolute difference (MAD) of 3.3 PASI points were observed. Intrarater variability showed a mean ICC of 0.877 and a MAD of 2.2 points. When considering specific PASI components, the highest agreement was found for the assessment of the involved body surface area (BSA), while the lowest ICCs were calculated for severity scoring of 'scaling' and 'induration'. As BSA scores serve as a multiplier in the calculation of PASI, minor inaccuracies were capable of inducing a large share of variability. CONCLUSION: The overall inter- and intrarater reliability of image-based PASI measurements in this study was good. However, physicians were formally trained and experienced, which frequently is not the case in a real-life clinical setting. Therefore, new strategies for higher standardization and objectivity of PASI calculations are needed.


Assuntos
Fotografação , Psoríase/diagnóstico por imagem , Índice de Gravidade de Doença , Superfície Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Projetos Piloto , Estudos Prospectivos , Reprodutibilidade dos Testes
15.
J Intellect Disabil Res ; 62(5): 359-370, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29266505

RESUMO

BACKGROUND: The phenotypical consequence of the heterozygous chromosome 7q11.23 interstitial microdeletion is the Williams-Beuren syndrome, a very well-known genetic multi-systemic disorder. Much less is known about the reverse condition, the heterozygous interstitial microduplication of 7q11.23 region. The first molecular cytogenetic description was published in 2005, and only after several years were the reported patients numerous enough to attempt a description of a common phenotype. METHOD: By using a broad multidisciplinary approach, we investigated 12 patients with this rare genetic anomaly. Ten of them harboured the duplication of the classical Williams-Beuren syndrome region and two a slightly larger duplication. Upon a detailed description of the clinical and psychological features, we used electroencephalography and magnetic resonance imaging to explore neurophysiological function and brain structures. RESULTS: We analysed the clinical, psychological, neuroradiological and neurophysiological features of 12 yet-unpublished individuals affected by this rare genetic anomaly, focusing specifically on the last two aspects. Several structural abnormalities of the central nervous system were detected, like ventriculomegaly, hypotrophic cerebellum, hypotrophic corpus callosum and hypoplastic temporal lobes. Although only one of 12 individuals suffered from seizures during childhood, three others had abnormal electroencephalography findings prominent in the anterior brain regions, without any visible seizures to date. CONCLUSION: Taken together, we enlarged the yet-underrepresented cohort in the literature of patients affected by 7q11.23 microduplication syndrome and shed further light on neuroradiological and neurophysiological aspects of this rare genetic syndrome.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Imageamento por Ressonância Magnética/métodos , Síndrome de Williams/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
16.
Phys Biol ; 14(1): 016001, 2017 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-28004641

RESUMO

Astrocytes form interconnected networks in the brain and communicate via calcium signaling. We investigate how modes of coupling between astrocytes influence the spatio-temporal patterns of calcium signaling within astrocyte networks and specifically how these network interactions promote coordination within this group of cells. To investigate these complex phenomena, we study reduced cultured networks of astrocytes and neurons. We image the spatial temporal patterns of astrocyte calcium activity and quantify how perturbing the coupling between astrocytes influences astrocyte activity patterns. To gain insight into the pattern formation observed in these cultured networks, we compare the experimentally observed calcium activity patterns to the patterns produced by a reduced computational model, where we represent astrocytes as simple units that integrate input through two mechanisms: gap junction coupling (network transport) and chemical release (extracellular diffusion). We examine the activity patterns in the simulated astrocyte network and their dependence upon these two coupling mechanisms. We find that gap junctions and extracellular chemical release interact in astrocyte networks to modulate the spatiotemporal patterns of their calcium dynamics. We show agreement between the computational and experimental findings, which suggests that the complex global patterns can be understood as a result of simple local coupling mechanisms.


Assuntos
Astrócitos/citologia , Astrócitos/metabolismo , Sinalização do Cálcio , Cálcio/metabolismo , Junções Comunicantes/metabolismo , Animais , Transporte Biológico , Comunicação Celular , Células Cultivadas , Simulação por Computador , Difusão , Modelos Neurológicos , Ratos Wistar
17.
Skin Res Technol ; 23(3): 261-271, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27878858

RESUMO

BACKGROUND: While the excisional biopsy and histological examination of suspicious lesions remains the current gold standard for diagnosing cutaneous melanoma (CM), there is a demand for more objective and non-invasive examination methods that may support clinicians in their decision when to biopsy or not. METHODS: This review is based on publications and guidelines retrieved by a selective search in PubMed and MEDLINE and focused on non-invasive diagnostic strategies for detecting melanoma. RESULTS: Ten different non-invasive techniques were compared with regard to applicability, status of development, and resources necessary for introduction into clinical routine (dermoscopy, sequential digital dermoscopy, total body photography, computer-aided multispectral digital analysis, electrical impedance spectroscopy, Raman spectroscopy, reflectance confocal microscopy, multiphoton tomography, stepwise two-photon-laser spectroscopy, quantitative dynamic infrared imaging). In an effort to create a classification based on our analyses, we suggest to differentiate i) tools for screening of patients in daily clinical routine, ii) tools for examination of a restricted number of preselected lesions that produce an automated diagnostic score, iii) tools for examination of a restricted number of preselected lesions at specialized centers requiring extensive training, iv) devices at an experimental stage of development. CONCLUSION: None of the discussed examination techniques is able to provide a definite and final diagnosis or to completely replace the histopathological examination. Up to date, the need for fully automated devices offering a complete skin cancer screening has not been satisfied.


Assuntos
Dermoscopia/métodos , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Idoso , Biópsia/métodos , Diagnóstico por Computador/métodos , Diagnóstico Diferencial , Espectroscopia Dielétrica/instrumentação , Espectroscopia Dielétrica/métodos , Detecção Precoce de Câncer/instrumentação , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Microscopia Confocal/métodos , Fotografação/métodos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Análise Espectral Raman/instrumentação , Análise Espectral Raman/métodos , Melanoma Maligno Cutâneo
18.
J Eur Acad Dermatol Venereol ; 31(1): 70-74, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27393707

RESUMO

BACKGROUND: Photodynamic therapy is an effective treatment for actinic keratoses. Nevertheless, severe pain during the procedure is a serious adverse effect, which leads to interruption or even termination. Complete pain relief remains a difficult challenge. OBJECTIVE: To evaluate the effect of a nitrous oxide/oxygen mixture on pain intensity during photodynamic therapy. METHODS: This clinical trial has been designed as a prospective, single-centre, explorative, controlled, observational study. RESULTS: We were able to detect a significant overall pain reduction of 55.2% after application of a nitrous oxide/oxygen mixture by means of an intra-individual comparison. Furthermore, the total number of therapy interruption significantly decreased by 82% after the inhalation analgesia. Additionally, treatment satisfaction ranged from 'extremely to very satisfied'. CONCLUSIONS: This study shows that analgesia by means of a nitrous oxide/oxygen mixture is a very effective and well-tolerated method for achieving significant pain reduction during photodynamic therapy.


Assuntos
Óxido Nitroso/administração & dosagem , Oxigênio/administração & dosagem , Manejo da Dor/métodos , Fotoquimioterapia , Humanos , Estudos Prospectivos
19.
J Eur Acad Dermatol Venereol ; 31(6): 972-977, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27896853

RESUMO

BACKGROUND: What lesions to select for a most efficient dermatoscopic monitoring of patients with multiple nevi remains an unresolved issue. OBJECTIVE: To compare the grade of atypia of melanomas and nevi of the same patient at baseline. METHODS: Prospective observational study using 236 dermatoscopic baseline images (59 quartets from 59 patients, each including one melanoma detected during follow-up and three nevi). Dermatologists (n = 26) were asked to assess the 'grade of dermatoscopic atypia' on a numerical scale and to identify the melanomas. RESULTS: On average, each dermatologist identified 24 of 59 melanomas (40%, range: 11-37). The number of correct picks was greater for dermatologists with moderate (mean: 28) or high (mean: 28) experience compared to beginners (mean 17; P < 0.001). In three of the 59 sets, none of the 26 dermatologists identified the melanoma. The mean grade of dermatoscopic atypia was 2.5 for nevi (95% CI: 2.4-2.6) and 3.0 for melanomas (95% CI: 2.9-3.1, P < 0.001). LIMITATIONS: Rating dermatologists were informed that each quartet of images included one melanoma creating substantial deviation from a real-life situation. CONCLUSION: A significant proportion of melanomas detected during follow-up cannot be differentiated from nevi at baseline. This necessitates the additional inclusion of less atypical lesions for monitoring.


Assuntos
Dermoscopia/métodos , Melanoma/patologia , Monitorização Fisiológica/métodos , Nevo/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Knee Surg Sports Traumatol Arthrosc ; 25(5): 1561-1567, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-26272060

RESUMO

PURPOSE: The structural properties of hamstring tendon grafts were evaluated in a porcine model, after processing it to a flat shape, to better replace or augment anatomic flat structures (e.g. ACL, MPFL or MCL). METHODS: In this biomechanical study, porcine flexor tendons were used which have a comparable shape to semitendinosus and gracilis tendons. One part of the tendon was prepared to a flat tendon construct by splitting the tendon longitudinally with a knife to half of the diameter of the tendon. The semi-split tendon was scratched out to a flat shape. The other matched part was tested in its original round shape. The tendons (n = 40) have been fixed in a uniaxial testing machine (Zwick/Roell) by cryo-clamps after preparing the fixed ends by 2-0 polyester sutures (2-0 Ethibond® EXCEL, Ethicon, Somerville, NJ). In every specimen, there was a free 60-mm tendon part between both clamps. The tendons have been loaded to failure to evaluate typical biomechanical parameters such as stiffness, yield load and maximum load. RESULTS: No statistically significant differences (n.s.) regarding stiffness, yield load and maximum load between natively round and processed flat tendons could be detected. CONCLUSION: A prepared flat-shaped tendon does not show any different structural properties compared with an original round tendon. Therefore, a flat tendon seems to be a biomechanical stable graft option for anatomic reconstruction or augmentation of injured natively flat-shaped structures such as MCL, MPFL or ACL.


Assuntos
Artroplastia/métodos , Tendões/transplante , Animais , Ligamento Cruzado Anterior/cirurgia , Fenômenos Biomecânicos , Cadáver , Humanos , Poliésteres , Suturas , Suínos , Tendões/fisiologia , Suporte de Carga
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