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1.
Ann Dermatol Venereol ; 148(4): 238-240, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34176640

RESUMO

OBJECTIVES: To determine the prevalence of Chlamydia trachomatis (CT) in the population screened at sexually transmitted infection (STI) clinics on Reunion Island and to identify risk factors for CT infection. PATIENTS AND METHODS: This cross-sectional multicenter study was conducted in 2017-2018. Data were obtained from self-administered questionnaires and multiplex PCR tests. RESULTS: The overall prevalence of CT in the screened population was 8.6% (95% CI 7.7-9.5%). The prevalence of urogenital CT was highest in women under 18 (13.2%, 95% CI 9.3-18.1%) and in men who have sex with men under 18 (13.3%, 95% CI 1.6-48.2%). Risk factors associated with CT infection in multivariate analysis were: female gender, being born in Reunion Island, having had a large number of sexual partners in the past year, and being co-infected with another STI. CONCLUSIONS: The prevalence of CT in the screened population is higher in Reunion Island than in mainland France, especially in minors. Prevention campaigns targeting minors should be strengthened.


Assuntos
Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Chlamydia trachomatis , Estudos Transversais , Feminino , Homossexualidade Masculina , Humanos , Masculino , Menores de Idade , Reunião/epidemiologia
2.
Nervenarzt ; 89(5): 524-529, 2018 May.
Artigo em Alemão | MEDLINE | ID: mdl-29327100

RESUMO

As a result of a literature-based expert process, this review provides an overview about the principles of palliative care for people with advanced dementia that are relevant for clinical practice. In particular, the indications, impact and aims of palliative care for advanced dementia are described. Life-prolonging measures and management of symptoms at the end of life are discussed. Furthermore, the overview focuses on the legal basis of decision making.


Assuntos
Demência , Cuidados Paliativos , Tomada de Decisões , Humanos , Cuidados Paliativos/legislação & jurisprudência
3.
Phys Chem Chem Phys ; 17(39): 25998-6007, 2015 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-26292724

RESUMO

The final products obtained by the oxidation of small model peptides containing the thioether function, either methionine or S-methyl cysteine, have been characterized by tandem mass spectrometry and IR Multiple Photon Dissociation (IRMPD) spectroscopy. The modified positions have been clearly identified by the CID-MS(2) fragmentation mass spectra with or without loss of sulfenic acid, as well as by the vibrational signature of the sulfoxide bond at around 1000 cm(-1). The oxidation of the thioether function did not lead to the same products in these model peptides. The sulfoxide and sulfone (to a lesser extent) have been clearly identified as final products of the oxidation of S-methyl-glutathione (GS-Me). Decarboxylation or hydrogen loss are the major oxidation pathways in GS-Me, while they have not been observed in tryptophan-methionine and methionine-tryptophan (Trp-Met and Met-Trp). Interestingly, tryptophan is oxidized in the dipeptide Met-Trp, while that is not the case in the reverse sequence (Trp-Met).


Assuntos
Dipeptídeos/química , Glutationa/análogos & derivados , Glutationa/química , Oxirredução , Espectrofotometria Infravermelho/métodos , Sulfonas/análise , Sulfóxidos/análise , Espectrometria de Massas em Tandem/métodos
4.
Int J Med Inform ; 191: 105566, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39079316

RESUMO

BACKGROUND: Mental health issues among healthcare workers remain a serious problem globally. Recent surveys continue to report high levels of depression, anxiety, burnout and other conditions amongst various occupational groups. Novel approaches are needed to support clinician well-being. OBJECTIVE: This integrative literature review aims to explore the current state of research examining the use of generative artificial intelligence (GenAI) and machine learning (ML) systems to predict mental health issues and identify associated risk factors amongst healthcare professionals. METHODS: A literature search of databases was conducted in Medline then adapted as necessary to Scopus, Web of Science, Google Scholar, PubMed and CINAHL with Full Text. Eleven studies met the inclusion criteria for the review. RESULTS: Nine studies employed various machine learning techniques to predict different mental health outcomes among healthcare workers. Models showed good predictive performance, with AUCs ranging from 0.82 to 0.904 for outcomes such as depression, anxiety and safety perceptions. Key risk factors identified included fatigue, stress, burnout, workload, sleep issues and lack of support. Two studies explored the potential of sensor-based technologies and GenAI analysis of physiological data. None of the included studies focused on the use of GenAI systems specifically for providing mental health support to healthcare workers. CONCLUSION: Preliminary research demonstrates that AI/ML models can effectively predict mental health issues. However, more work is needed to evaluate the real-world integration and impact of these tools, including GenAI systems, in identifying clinician distress and supporting well-being over time. Further research should aim to explore how GenAI may be developed and applied to provide mental health support for healthcare workers.


Assuntos
Inteligência Artificial , Pessoal de Saúde , Saúde Mental , Humanos , Pessoal de Saúde/psicologia , Esgotamento Profissional/psicologia , Aprendizado de Máquina , Depressão , Transtornos Mentais , Fatores de Risco , Ansiedade
5.
Biochim Biophys Acta ; 1818(9): 2314-24, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22580228

RESUMO

NADPH-oxidase is an enzyme that represents, when activated, the major source of non-mitochondrial reactive oxygen species. In phagocytes, this production is an indispensable event for the destruction of engulfed pathogens. The functional NADPH-oxidase complex consists of a catalytic membrane flavocytochrome b (Cytb(558)) and four cytosolic proteins p47(phox), p67(phox), Rac and p40(phox). The NADPH-oxidase activity is finely regulated spatially and temporally by cellular signaling events that trigger the translocation of the cytosolic subunits to its membrane partner involving post-translational modifications and activation by second messengers such as arachidonic acid (AA). Arachidonic acid in its natural cis-poly unsaturated form (C20:4) has been described to be an efficient activator of the enzyme in vivo and in vitro. In this work, we examined in a cell-free system whether a change of the natural cis geometry to the trans configuration, which could occur either by diet or be produced by the action of free radicals, may have consequences on the functioning of NADPH-oxidase. We showed the inability of mono-trans AA isomers to activate the NADPH-oxidase complex and demonstrated the inhibitory effect on the cis-AA-induced NADPH oxidase activation. The inhibition is mediated by a direct effect of the mono-trans AA which targets both the membrane fraction containing the cytb(558) and the cytosolic p67(phox). Our results suggest that the loss of the natural geometric feature (cis-AA) induces substantial structural modifications of p67(phox) that prevent its translocation to the complex.


Assuntos
Ácido Araquidônico/química , NADPH Oxidases/antagonistas & inibidores , Fosfoproteínas/fisiologia , Animais , Bovinos , Membrana Celular/metabolismo , Grupo dos Citocromos b/química , Citosol/enzimologia , Citosol/metabolismo , Relação Dose-Resposta a Droga , Ácidos Graxos/química , Modelos Biológicos , NADPH Oxidases/química , Neutrófilos/metabolismo , Fagócitos/enzimologia , Fosfoproteínas/química , Pichia/metabolismo , Ligação Proteica , Conformação Proteica , Proteínas Recombinantes/química , Fatores de Tempo , Triptofano/química
6.
Infection ; 40(1): 35-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21866338

RESUMO

PURPOSE: Patients with hemoglobinopathies who undergo splenectomy are at risk for invasive infections. The aim of this investigation was to present the clinical spectrum of infections in splenectomized patients. METHODS: The study cohort comprised 54 splenectomized patients with beta-thalassemia (ß-thalassemic) and sickle cell disease. The incidence of serious invasive bacterial infections was recorded. All patients received pneumococcal vaccine and all received oral prophylactic penicillin. RESULTS: A total of 22 episodes of serious bacterial infections were identified in 19 patients among the study cohort of 54 splenectomized patients (35%). The clinical spectrum included sepsis (10 patients), bacteremia (8), liver abscess (1), forearm abscess (1), and urinary tract infection (2). The most frequent pathogens were Escherichia coli (8 cases), Steptococcus pneumoniae (5), and Campylobacter (2). 22 patients with ß thalassemia died during the study period: 6 due to bacterial infection and 18 due to cardiomyopathy. The time elapsed between splenectomy and S. pneumoniae infection was significantly shorter than that between splenectomy and infections caused by other pathogens (18 ± 14 vs. 115 ± 93 months, respectively; p = 0.035). CONCLUSIONS: Splenectomized patients with ß thalassemia and sickle cell disease are predisposed to severe infections, with the majority of these infections being caused by Gram-negative microorganisms. The attending physician(s) should take these findings into consideration when deciding upon an empiric antibiotic treatment for splenectomized patients who present with fever or sepsis.


Assuntos
Anemia Falciforme/complicações , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Esplenectomia/efeitos adversos , Talassemia beta/complicações , Adolescente , Adulto , Antibacterianos/uso terapêutico , Bactérias/classificação , Bactérias/isolamento & purificação , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Seguimentos , Humanos , Incidência , Israel/epidemiologia , Penicilinas/uso terapêutico , Vacinas Pneumocócicas/uso terapêutico , Fatores de Risco
7.
Med Phys ; 37(11): 5838-49, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21158296

RESUMO

PURPOSE: This study aims to address design considerations of a high resolution, high sensitivity positron emission tomography scanner dedicated to breast imaging. METHODS: The methodology uses a detailed Monte Carlo model of the system structures to obtain a quantitative evaluation of several performance parameters. Special focus was given to the effect of dense mechanical structures designed to provide mechanical robustness and thermal regulation to the minuscule and temperature sensitive detectors. RESULTS: For the energies of interest around the photopeak (450-700 keV energy window), the simulation results predict a 6.5% reduction in the single photon detection efficiency and a 12.5% reduction in the coincidence photon detection efficiency in the case that the mechanical structures are interspersed between the detectors. However for lower energies, a substantial increase in the number of detected events (approximately 14% and 7% for singles at a 100-200 keV energy window and coincidences at a lower energy threshold of 100 keV, respectively) was observed with the presence of these structures due to backscatter. The number of photon events that involve multiple interactions in various crystal elements is also affected by the presence of the structures. For photon events involving multiple interactions among various crystal elements, the coincidence photon sensitivity is reduced by as much as 20% for a point source at the center of the field of view. There is no observable effect on the intrinsic and the reconstructed spatial resolution and spatial resolution uniformity. CONCLUSIONS: Mechanical structures can have a considerable effect on system sensitivity, especially for systems processing multi-interaction photon events. This effect, however, does not impact the spatial resolution. Various mechanical structure designs are currently under evaluation in order to achieve optimum trade-off between temperature stability, accurate detector positioning, and minimum influence on system performance.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Tomografia por Emissão de Pósitrons/métodos , Diagnóstico por Imagem/métodos , Desenho de Equipamento , Humanos , Método de Monte Carlo , Fótons , Reprodutibilidade dos Testes , Espalhamento de Radiação , Temperatura , Fatores de Tempo
8.
Int J Tuberc Lung Dis ; 24(8): 802-810, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32912385

RESUMO

BACKGROUND: Despite a scarcity of tuberculosis (TB) cost data, a substantial body of evidence has been accumulating for drug-susceptible TB (DS-TB) treatment. In this study, we review unit costs for DS-TB treatment from a provider´s perspective. We also examine factors driving cost variations and extrapolate unit costs across low- and middle-income countries (LMICs).METHODS: We searched published and grey literature for any empirically collected TB cost estimates. We selected a subgroup of estimates looking at DS-TB treatment. We extracted information on activities and inputs included. We standardised costs into an average per person-month, fitted a multi-level regression model and cross-validated country-level predictions. We then extrapolated estimates for facility-based, directly observed DS-TB treatment across countries.RESULTS: We included 95 cost estimates from 28 studies across 17 countries. Costs predictions were sensitive to characteristics such as delivery mode, whether hospitalisation was included, and inputs accounted for, as well as gross domestic product per capita. Extrapolation results are presented with uncertainty intervals (UIs) for LMICs. Predicted median costs per 6 months of treatment were US$315.30 (95% CI US$222.60-US$417.20) for low-income, US$527.10 (95% CI US$395.70-US$743.70) for lower middle-income and US$896.40 (95% CI US$654.00-US$1214.40) for upper middle-income countries.CONCLUSIONS: Our study provides country-level DS-TB treatment cost estimates suitable for priority setting. These estimates, while not standing as a substitute for local high-quality primary data, can inform global, regional and national exercises.


Assuntos
Países em Desenvolvimento , Tuberculose , Análise Custo-Benefício , Produto Interno Bruto , Custos de Cuidados de Saúde , Humanos , Pobreza , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia
9.
BJOG ; 116(6): 768-79, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19432565

RESUMO

OBJECTIVE: To assess the comparative health and economic outcomes associated with three alternative first-trimester abortion techniques in Mexico City and to examine the policy implications of increasing access to safe abortion modalities within a restrictive setting. DESIGN: Cost-effectiveness analysis. SETTING: Mexico City. POPULATION: Reproductive-aged women with unintended pregnancy seeking first-trimester abortion. METHODS: Synthesising the best available data, a computer-based model simulates induced abortion and its potential complications and is used to assess the cost-effectiveness of alternative safe modalities for first-trimester pregnancy termination: (1) hospital-based dilatation and curettage (D&C), (2) hospital-based manual vacuum aspiration (MVA), (3) clinic-based MVA and (4) medical abortion using vaginal misoprostol. MAIN OUTCOME MEASURES: Number of complications, lifetime costs, life expectancy, quality-adjusted life expectancy. RESULTS: In comparison to the magnitude of health gains associated with all safe abortion modalities, the relative differences between strategies were more pronounced in terms of their economic costs. Assuming all options were equally available, clinic-based MVA was the least costly and most effective. Medical abortion with misoprostol provided comparable benefits to D&C, but cost substantially less. Enhanced access to safe abortion was always more influential than shifting between safe abortion modalities. CONCLUSIONS: This study demonstrates that the provision of safe abortion is cost-effective and will result in reduced complications, decreased mortality and substantial cost savings compared with unsafe abortion. In Mexico City, shifting from a practice of hospital-based D&C to clinic-based MVA and enhancing access to medical abortion will have the best chance to minimise abortion-related morbidity and mortality.


Assuntos
Aborto Induzido/economia , Abortivos não Esteroides/efeitos adversos , Abortivos não Esteroides/economia , Aborto Induzido/efeitos adversos , Aborto Induzido/métodos , Adulto , Análise Custo-Benefício , Dilatação e Curetagem/efeitos adversos , Dilatação e Curetagem/economia , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Humanos , México , Misoprostol/efeitos adversos , Misoprostol/economia , Modelos Econométricos , Gravidez , Primeiro Trimestre da Gravidez , Anos de Vida Ajustados por Qualidade de Vida , Curetagem a Vácuo/efeitos adversos , Curetagem a Vácuo/economia
10.
Med Mal Infect ; 49(4): 241-249, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30266431

RESUMO

OBJECTIVES: To assess the perceptions, attitudes, and practices of French junior physicians regarding antibiotic use and resistance, and then to identify the characteristics of junior physicians associated with appropriate practices of antibiotic use. METHOD: European junior physicians received an email invitation to complete a 49 item web questionnaire between September 2015 and January 2016. We present the French data. Multivariate regression models were used to identify the characteristics of junior physicians associated with appropriate prescription practices and with consideration of the antibiotic prescription consequences. RESULTS: The questionnaire was completed by 641 junior physicians: family medicine (37%), other medical specialties (e.g., pediatrics, internal medicine, neurology: 45%), surgical specialties (11%), and anesthesiology-intensive care specialty (7%). Most respondents (93%) declared being aware of the risk of bacterial resistance and 41% acknowledged prescribing antibiotics more often than necessary. Two factors were independently associated with appropriate prescription practices: a high perceived level of education on antibiotic use (OR=1.51; 95% CI [1.01-2.30]) and a medical specialty (OR=1.69; 95% CI [1.16-2.46]). Factors independently associated with taking into account adverse events of antibiotics were a good perceived knowledge of antibiotics (OR=3.71; 95% CI [2.09-6.61]), and a high perceived education level on antibiotics (OR=1.70; 95% CI [1.11-2.58]). CONCLUSION: Our data can help better define interventions targeting junior physicians in antibiotic stewardship programs.


Assuntos
Antibacterianos/uso terapêutico , Atitude do Pessoal de Saúde , Resistência Microbiana a Medicamentos , Corpo Clínico Hospitalar , Percepção , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Gestão de Antimicrobianos/métodos , Gestão de Antimicrobianos/normas , Gestão de Antimicrobianos/estatística & dados numéricos , Feminino , França/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Corpo Clínico Hospitalar/psicologia , Corpo Clínico Hospitalar/estatística & dados numéricos , Médicos/psicologia , Médicos/estatística & dados numéricos , Inquéritos e Questionários
11.
Soc Sci Med ; 220: 141-149, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30428401

RESUMO

Health interventions often depend on a complex system of human and capital infrastructure that is shared with other interventions, in the form of service delivery platforms, such as healthcare facilities, hospitals, or community services. Most forms of health system strengthening seek to improve the efficiency or effectiveness of such delivery platforms. This paper presents a typology of ways in which health system strengthening can improve the economic efficiency of health services. Three types of health system strengthening are identified and modelled: (1) investment in the efficiency of an existing shared platform that generates positive benefits across a range of existing interventions; (2) relaxing a capacity constraint of an existing shared platform that inhibits the optimization of existing interventions; (3) providing an entirely new shared platform that supports a number of existing or new interventions. Theoretical models are illustrated with examples, and illustrate the importance of considering the portfolio of interventions using a platform, and not just piecemeal individual analysis of those interventions. They show how it is possible to extend principles of conventional cost-effectiveness analysis to identify an optimal balance between investing in health system strengthening and expenditure on specific interventions. The models developed in this paper provide a conceptual framework for evaluating the cost-effectiveness of investments in strengthening healthcare systems and, more broadly, shed light on the role that platforms play in promoting the cost-effectiveness of different interventions.


Assuntos
Análise Custo-Benefício , Atenção à Saúde , Programas Governamentais , Humanos , Modelos Teóricos
12.
IEEE Trans Med Imaging ; 27(1): 58-63, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18270062

RESUMO

We present a phantom study to evaluate the performance of the eXplore Optix (Advanced Research Technologies-GE Healthcare), the first commercially available time-domain tomography system for small animal fluorescence imaging, and compare its capabilities with the widely used IVIS 200 (Xenogen Corporation-Caliper) continuous wave planar imaging system. The eXplore Optix, based on point-wise illumination and collection scheme, is found to be a log order more sensitive with significantly higher detection depth and spatial resolution as compared with the wide-area illumination IVIS 200 under the conditions tested. A time-resolved detection system allows the eXplore Optix to measure the arrival time distribution of fluorescence photons. This enables fluorescence lifetime measurement, absorption mapping, and estimation of fluorescent inclusion depth, which in turn is used by a reconstruction algorithm to calculate the volumetric distribution of the fluorophore concentration. An increased acquisition time and lack of ability to image multiple animals simultaneously are the main drawbacks of the eXplore Optix as compared with the IVIS 200.


Assuntos
Aumento da Imagem/instrumentação , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Microscopia de Fluorescência/instrumentação , Microscopia de Fluorescência/veterinária , Tomografia Óptica/instrumentação , Tomografia Óptica/veterinária , Animais , Desenho de Equipamento , Análise de Falha de Equipamento , Aumento da Imagem/métodos , Microscopia de Fluorescência/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Óptica/métodos
13.
Phys Med Biol ; 52(13): 3753-72, 2007 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-17664575

RESUMO

We are studying two new detector technologies that directly measure the three-dimensional coordinates of 511 keV photon interactions for high-resolution positron emission tomography (PET) systems designed for small animal and breast imaging. These detectors are based on (1) lutetium oxyorthosilicate (LSO) scintillation crystal arrays coupled to position-sensitive avalanche photodiodes (PSAPD) and (2) cadmium zinc telluride (CZT). The detectors have excellent measured 511 keV photon energy resolutions (8% photon sensitivity for the LSO-PSAPD box configuration and >15% for CZT box geometry, using a 350-650 keV energy window setting. These simulation results compare well with analytical estimations. The trend is different for a clinical whole-body PET system that uses conventional LSO-PMT block detectors with larger crystal elements. Simulations predict roughly the same sensitivity for both box and cylindrical detector configurations. This results from the fact that a large system diameter (>80 cm) results in relatively small inter-module gaps in clinical whole-body PET. In addition, the relatively large block detectors (typically >5 x 5 cm(2) cross-sectional area) and large crystals (>4 x 4 x 20 mm(3)) enable a higher fraction of detector scatter photons to be absorbed compared to a small animal system. However, if the four detector sides (panels) of a box-shaped system geometry are configured to move with respect to each other, to better fit the transaxial FOV to the actual size of the object to be imaged, a significant increase in photon sensitivity is possible. Simulation results predict a 60-100% relative increase of photon sensitivity for the proposed small animal PET box configurations and >60% increase for a clinical whole-body system geometry. Thus, simulation results indicate that for a PET system built from rectangular-shaped detector modules, arranging them into a box-shaped system geometry may help us to significantly boost photon sensitivity for both small animal and clinical PET systems.


Assuntos
Fótons , Tomografia por Emissão de Pósitrons/instrumentação , Tomografia por Emissão de Pósitrons/métodos , Animais , Compostos de Cádmio/química , Simulação por Computador , Cristalização , Desenho de Equipamento , Processamento de Imagem Assistida por Computador , Lutécio/química , Método de Monte Carlo , Sensibilidade e Especificidade , Silicatos/química , Telúrio/química , Transdutores , Zinco/química
14.
Phys Med Biol ; 61(21): 7639-7651, 2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27740946

RESUMO

Time of flight (TOF) and depth of interaction (DOI) capabilities can significantly enhance the quality and uniformity of positron emission tomography (PET) images. Many proposed TOF/DOI PET detectors require complex readout systems using additional photosensors, active cooling, or waveform sampling. This work describes a high performance, low complexity, room temperature TOF/DOI PET module. The module uses multiplexed timing channels to significantly reduce the electronic readout complexity of the PET detector while maintaining excellent timing, energy, and position resolution. DOI was determined using a two layer light sharing scintillation crystal array with a novel binary position sensitive network. A 20 mm effective thickness LYSO crystal array with four 3 mm × 3 mm silicon photomultipliers (SiPM) read out by a single timing channel, one energy channel and two position channels achieved a full width half maximum (FWHM) coincidence time resolution of 180 ± 2 ps with 10 mm of DOI resolution and 11% energy resolution. With sixteen 3 mm × 3 mm SiPMs read out by a single timing channel, one energy channel and four position channels a coincidence time resolution 204 ± 1 ps was achieved with 10 mm of DOI resolution and 15% energy resolution. The methods presented here could significantly simplify the construction of high performance TOF/DOI PET detectors.


Assuntos
Tomografia por Emissão de Pósitrons/instrumentação , Tomografia por Emissão de Pósitrons/métodos , Radiometria/instrumentação , Silício/química , Algoritmos , Eletrônica , Humanos , Interpretação de Imagem Assistida por Computador
15.
Phys Med Biol ; 61(7): 2879-92, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-26987898

RESUMO

Using time of flight (ToF) measurements for positron emission tomography (PET) is an attractive avenue for increasing the signal to noise (SNR) ratio of PET images. However, achieving excellent time resolution required for high SNR gain using silicon photomultipliers (SiPM) requires many resource heavy high bandwidth readout channels. A method of multiplexing many SiPM signals into a single electronic channel would greatly simplify ToF PET systems. However, multiplexing SiPMs degrades time resolution because of added dark counts and signal shaping. In this work the relative contribution of dark counts and signal shaping to timing degradation is simulated and a baseline correction technique to mitigate the effect of multiplexing on the time resolution of analog SiPMs is simulated and experimentally verified. A charge sharing network for multiplexing is proposed and tested. Results show a full width at half maximum (FWHM) coincidence time resolution of [Formula: see text] ps for a single 3 mm × 3 mm × 20 mm LYSO scintillation crystals coupled to an array of sixteen 3 mm × 3 mm SiPMs that are multiplexed to a single timing channel (in addition to 4 position channels). A [Formula: see text] array of 3 mm × 3 mm × 20 mm LFS crystals showed an average FWHM coincidence time resolution of [Formula: see text] ps using the same timing scheme. All experiments were performed at room temperature with no thermal regulation. These results show that excellent time resolution for ToF can be achieved with a highly multiplexed analog SiPM readout.


Assuntos
Contagem de Cintilação/instrumentação , Eletrônica , Tomografia por Emissão de Pósitrons/métodos , Contagem de Cintilação/métodos , Silício/química , Tomografia Computadorizada por Raios X/métodos
16.
Phys Med Biol ; 61(16): N427-40, 2016 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-27484131

RESUMO

Multiplexing many SiPMs to a single readout channel is an attractive option to reduce the readout complexity of high performance time of flight (TOF) PET systems. However, the additional dark counts and shaping from each SiPM cause significant baseline fluctuations in the output waveform, degrading timing measurements using a leading edge threshold. This work proposes the use of a simple analog filtering network to reduce the baseline fluctuations in highly multiplexed SiPM readouts. With 16 SiPMs multiplexed, the FWHM coincident timing resolution for single [Formula: see text] mm LYSO crystals was improved from 401 ± 4 ps without filtering to 248 ± 5 ps with filtering. With 4 SiPMs multiplexed, using an array of [Formula: see text] mm LFS crystals the mean time resolution was improved from 436 ± 6 ps to 249 ± 2 ps. Position information was acquired with a novel binary positioning network. All experiments were performed at room temperature with no active temperature regulation. These results show a promising technique for the construction of high performance multiplexed TOF PET readout systems using analog leading edge timing pickoff.


Assuntos
Amplificadores Eletrônicos , Filtração/instrumentação , Tomografia por Emissão de Pósitrons/instrumentação , Contagem de Cintilação/instrumentação , Silício/química , Tomografia Computadorizada por Raios X/instrumentação , Humanos , Tomografia por Emissão de Pósitrons/métodos , Contagem de Cintilação/métodos , Tomografia Computadorizada por Raios X/métodos
17.
Int J Pharm ; 292(1-2): 187-94, 2005 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-15725565

RESUMO

Keratolytic efficacy of topical preparations containing salicylic acid was studied in humans utilizing adhesive tape stripping and quantifying SC removal by protein analysis. In combination with tape stripping, squamometry was used to evaluate the influence of salicylic acid on skin surface scaliness and desquamation. Furthermore, skin barrier perturbation and skin irritancy was recorded and related to the dermatopharmacological effect of the preparations. In contrast to squamometry, tape stripping combined with protein analysis was sensitive in detecting keratolytic effect of salicylic acid within hours of application. Importantly, whereas the pH of the preparations only minimally influenced efficacy, local dermatotoxicity was significantly increased at acidic pH. This indicates that the quest to increase the amount of free, non-dissociated SA is, in fact, counterproductive as the more acidic preparations resulted in skin irritation and barrier disruption.


Assuntos
Administração Cutânea , Avaliação de Medicamentos/métodos , Ceratolíticos/uso terapêutico , Ácido Salicílico/efeitos adversos , Adulto , Dermatologia/métodos , Dermatologia/tendências , Eritema/induzido quimicamente , Feminino , Humanos , Concentração de Íons de Hidrogênio , Ceratolíticos/administração & dosagem , Ceratolíticos/química , Masculino , Mentol/administração & dosagem , Mentol/efeitos adversos , Ácido Salicílico/administração & dosagem , Testes de Irritação da Pele/métodos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Soluções/administração & dosagem , Soluções/efeitos adversos , Soluções/química , Fatores de Tempo , Perda Insensível de Água/efeitos dos fármacos , Perda Insensível de Água/fisiologia
18.
Phys Med Biol ; 60(9): 3795-806, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25905626

RESUMO

The design of combined positron emission tomography/magnetic resonance (PET/MR) systems presents a number of challenges to engineers, as it forces the PET system to acquire data in a space constrained environment that is sensitive to electro-magnetic interference and contains high static, radio frequency and gradient fields. In this work we validate fast timing performance of a PET scintillation detector using a potentially very compact, very low power, and MR compatible readout method in which analog silicon photomultipliers (SiPM) signals are transmitted optically away from the MR bore with little or even no additional readout electronics. This analog 'electro-optial' method could reduce the entire PET readout in the MR bore to two compact, low power components (SiPMs and lasers). Our experiments show fast timing performance from analog electro-optical readout with and without pre-amplification. With 3 mm × 3 mm × 20 mm lutetium-yttrium oxyorthosilicate (LYSO) crystals and Excelitas SiPMs the best two-sided fwhm coincident timing resolution achieved was 220 +/- 3 ps in electrical mode, 230 +/- 2 ps in electro-optical with preamp mode, and 253 +/- 2 ps in electro-optical without preamp mode. Timing measurements were also performed with Hamamatsu SiPMs and 3 mm × 3 mm × 5 mm crystals. In the future the timing degradation seen can be further reduced with lower laser noise or improvements SiPM rise time or gain.


Assuntos
Amplificadores Eletrônicos , Imageamento por Ressonância Magnética/instrumentação , Imagem Multimodal/instrumentação , Tomografia por Emissão de Pósitrons/instrumentação , Lutécio/química , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons/métodos , Sensibilidade e Especificidade , Silicatos/química , Silício/química , Fatores de Tempo
19.
J Thromb Haemost ; 13(7): 1285-92, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25876182

RESUMO

BACKGROUND: The FYB gene encodes adhesion and degranulation-promoting adaptor protein (ADAP), a hematopoietic-specific protein involved in platelet activation, cell motility and proliferation, and integrin-mediated cell adhesion. No ADAP-related diseases have been described in humans, but ADAP-deficient mice have mild thrombocytopenia and increased rebleeding from tail wounds. PATIENTS AND METHODS: We studied a previously reported family of five children from two consanguineous sibships of Arab Christian descent affected with a novel autosomal recessive bleeding disorder with small-platelet thrombocytopenia. Homozygosity mapping and exome sequencing were used to identify the genetic lesion causing the disease phenotype on chromosome 5. Bone-marrow morphology and platelet function were analyzed. Platelets were characterized by scanning electron microscopy. RESULTS: We identified a homozygous deleterious nonsense mutation, c.393G>A, in FYB. A reduced percentage of mature megakaryocytes was found in the bone marrow. Patients' platelets showed increased basal expression of P-selectin and PAC-1, and reduced increments of activation markers after stimulation with ADP, as detected by flow cytometry; they also showed reduced pseudopodium formation and the presence of trapped platelets between the fibrin fibers after thrombin addition, as observed on scanning electron microscopy. CONCLUSIONS: This is the first report of a disease caused by an FYB defect in humans, manifested by remarkable small-platelet thrombocytopenia and a significant bleeding tendency. The described phenotype shows ADAP to be important for normal platelet production, morphologic changes, and function. It is suggested that mutation analysis of this gene be included in the diagnosis of inherited thrombocytopenia.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Plaquetas/ultraestrutura , Códon sem Sentido , Hemorragia/genética , Hemostasia/genética , Trombocitopenia/genética , Árabes/genética , Plaquetas/metabolismo , Tamanho Celular , Análise Mutacional de DNA , Fosfatase 2 de Especificidade Dupla/sangue , Exoma , Marcadores Genéticos , Predisposição Genética para Doença , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/etnologia , Heterozigoto , Homozigoto , Humanos , Israel/epidemiologia , Microscopia Eletrônica de Varredura , Selectina-P/sangue , Linhagem , Fenótipo , Testes de Função Plaquetária , Valor Preditivo dos Testes , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Trombocitopenia/etnologia
20.
Free Radic Res ; 49(4): 347-73, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25812585

RESUMO

Protein oxidation is increasingly recognised as an important modulator of biochemical pathways controlling both physiological and pathological processes. While much attention has focused on cysteine modifications in reversible redox signalling, there is increasing evidence that other protein residues are oxidised in vivo with impact on cellular homeostasis and redox signalling pathways. A notable example is tyrosine, which can undergo a number of oxidative post-translational modifications to form 3-hydroxy-tyrosine, tyrosine crosslinks, 3-nitrotyrosine and halogenated tyrosine, with different effects on cellular functions. Tyrosine oxidation has been studied extensively in vitro, and this has generated detailed information about the molecular mechanisms that may occur in vivo. An important aspect of studying tyrosine oxidation both in vitro and in biological systems is the ability to monitor the formation of oxidised derivatives, which depends on a variety of analytical techniques. While antibody-dependent techniques such as ELISAs are commonly used, these have limitations, and more specific assays based on spectroscopic or spectrometric techniques are required to provide information on the exact residues modified and the nature of the modification. These approaches have helped understanding of the consequences of tyrosine oxidation in biological systems, especially its effects on cell signalling and cell dysfunction, linking to roles in disease. There is mounting evidence that tyrosine oxidation processes are important in vivo and can contribute to cellular pathology.


Assuntos
Tirosina/metabolismo , Oxirredução , Estresse Oxidativo , Tirosina/química , Tirosina/fisiologia
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