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1.
Front Microbiol ; 15: 1348171, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389541

RESUMO

Introduction: Intensive beef cattle production systems are frequently implicated as a source of bacteria that can be transferred to nearby humans and animals via effluent water, manure used as fertilizer, or airborne particulate matter. It is crucial to understand microbial population dynamics due to manure pack desiccation, antibiotic usage, and antibiotic alternatives within beef cattle and their associated feedyard environment. Understanding how bacterial communities change in the presence of antibiotics can also improve management practices for reducing the spread of foodborne bacteria. Methods: In this study, we aimed to compare the microbiomes within cattle feces, the feedyard environment and artificially produced airborne particulate matter as a function of pen change and treatment with tylosin or probiotics. We utilized 16S rRNA sequencing to compare bacterial communities among sample types, study days, and treatment groups. Results: Bacterial community diversity varied as a function of sampling day and pen change (old or new) within fecal and manure pack samples. Manure pack samples from old pens and new pens contained diverse communities of bacteria on days 0 and 84; however, by day 119 of the study these taxonomic differences were less evident. Particulate matter samples exhibited significant differences in community diversity and predominant bacterial taxa compared to the manure pack they originated from. Treatment with tylosin did not meaningfully impact bacterial communities among fecal, environmental, or particulate matter samples; however, minor differences in bacterial community structure were observed in feces from cattle treated with probiotics. Discussion: This study was the first to characterize and compare microbial communities within feces, manure pack, and airborne particulate matter from the same location and as a function of tylosin and probiotic treatment, and pen change. Although fecal and environmental samples are commonly used in research studies and other monitoring programs to infer public health risk of bacteria and antimicrobial resistance determinants from feedyard environments, our study suggests that these samples may not be appropriate to infer public health risk associated with airborne particulate matter.

2.
Animals (Basel) ; 13(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37893894

RESUMO

Post-harvest Salmonella mitigation techniques are insufficient at addressing Salmonella harbored in cattle lymph nodes, necessitating the exploration of pre-harvest alternatives that reduce Salmonella prior to dissemination to the lymph nodes. A 2 × 2, unbalanced experiment was conducted to determine the effectiveness of pre-harvest treatments applied to the pen surface for Salmonella mitigation in cattle. Treatments included manure slurry intended to mimic pen run-off water (n = 4 pens), a bacteriophage cocktail (n = 4), a combination of both treatments (n = 5), and a control group (n = 5) that received no treatment. Environment samples from 18 feedlot pens and fecal grabs, hide swabs, and subiliac lymph nodes from 178 cattle were collected and selectively enriched for Salmonella, and Salmonella isolates were sequenced. The combination treatment was most effective at reducing Salmonella, and the prevalence was significantly lower compared with the control group for rump swabs on Days 14 and 21. The treatment impact on Salmonella in the lymph nodes could not be determined due to low prevalence. The reduction on cattle hides suggests that bacteriophage or water treatments applied to the feedlot pen surface may reduce Salmonella populations in cattle during the pre-harvest period, resulting in reduced contamination during slaughter and processing.

3.
BMJ Open Ophthalmol ; 8(Suppl 3): A1, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37797997

RESUMO

INTRODUCTION: Prompt detection of childhood uveitis is key to minimising negative impact. From an internationally unique inception cohort, we report pathways to disease detection.UNICORNS is a national childhood non-infectious uveitis study with longitudinal collection of a standardised clinical dataset and patient reported outcomes. Descriptive analysis of baseline characteristics are reported.Amongst 150 recruited children (51% female, 31% non-white ethnicity) age at detection ranged from 2-18yrs (median 10). In 69%, uveitis was diagnosed following onset of symptoms: time from first symptoms to uveitis detection ranged from 0-739days (median 7days), with longer time to detection for those presenting initially to their general practitioner. Non symptomatic children were detected through JIA/other disease surveillance (16%), routine optometry review (5%) or child visual health screening (1%). Commonest underlying diagnoses at uveitis detection were JIA (17%), TINU (9%, higher than pre-pandemic reported UK disease frequency) and sarcoid (1%). 60% had no known systemic disease at uveitis detection. At disease detection, in at least one eye: 34% had structural complications (associated with greater time to detection - 17 days versus 4 days for uncomplicated presentation).The larger relative proportions of children with non-JIA uveitis reported here increase the importance of improving awareness of childhood uveitis amongst the wider clinical communities. There is scope for improvement of pathways to detection. Forthcoming analysis on the full cohort (251 recruited to date across 33 hospitals and 4 nations) will provide nationally representative data on management and the determinants of visual and broader developmental/well-being outcomes.


Assuntos
Artrite Juvenil , Uveíte , Criança , Humanos , Feminino , Pré-Escolar , Adolescente , Masculino , Estudos de Coortes , Artrite Juvenil/complicações , Uveíte/diagnóstico , Reino Unido/epidemiologia
4.
Strabismus ; 31(1): 26-30, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36529745

RESUMO

BACKGROUND: Acute acquired concomitant esotropia (AACE) is usually a benign form of strabismus that infrequently is associated with intracranial pathology. Clinicians have noted an increase in its incidence and theorize that it may be related to public health "lockdown" measures taken in response to the COVID-19 pandemic. With an increased incidence of AACE clinicians must firstly differentiate AACE from common accommodative esotropia and secondly recognize AACE as a possible sign of serious neuropathology.Diffuse Intrinsic Pontine Glioma (DIPG) is a devastating diagnosis for affected families. Children typically present at age 6-7 years with cranial nerve palsies, long tract signs, and/or cerebellar signs. Diagnosis is made from characteristic findings on magnetic resonance brain imaging (MRI brain) and treatment includes radiotherapy and palliative care. Two years from diagnosis, 90% of affected children will have died from their disease. CASE SERIES: We present four cases that attended our pediatric ophthalmology clinic with AACE either as a presenting sign of DIPG or as a clinical finding following a DIPG diagnosis. Patient A (age 5 years) presented to the emergency eye clinic with sudden onset diplopia and intermittent esotropia. Suppression later developed, they had 0.00 logMAR visual acuity either eye, and bilateral physiological hypermetropia. MRI brain imaging requested as a result of the unusual presentation led to the DIPG diagnosis. The other 3 cases (ages 11, 5 & 5 years) were assessed post DIPG diagnosis and found to have an esotropia measuring bigger on 1/3-meter fixation than 6-meter fixation, full ocular motility, physiological hypermetropia or emmetropia, and visual acuity normal for age. Other than patient B (age 11 years), who had papilledema and gaze evoked nystagmus when they were assessed 2 weeks prior to death, no patient had any other clinical eye findings. CONCLUSIONS: This small series of 4 patients attending our clinic within a 12-month period supports the notion that children presenting with AACE should routinely be offered brain MRI. Not all children with DIPG-associated AACE have significant ophthalmic findings indicative of intracranial pathology. With the potential for increased incidence of AACE related to lockdowns, clinicians should be reminded of the infrequent possibility their patient has a more serious condition.


Assuntos
COVID-19 , Glioma Pontino Intrínseco Difuso , Esotropia , Hiperopia , Estrabismo , Criança , Humanos , Pré-Escolar , Esotropia/diagnóstico , Esotropia/etiologia , Esotropia/cirurgia , Glioma Pontino Intrínseco Difuso/complicações , Pandemias , COVID-19/complicações , Controle de Doenças Transmissíveis , Estrabismo/complicações , Doença Aguda , Estudos Retrospectivos
5.
BMJ Mil Health ; 169(e1): e24-e28, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-33785588

RESUMO

INTRODUCTION: Atrial fibrillation (AF) is an arrhythmia impacting military occupational performances. Despite being a recognised disqualifying condition, there is no literature describing US military service members with AF. This study aims to describe members with AF diagnoses, the distribution of treatment strategies and associated deployment and retention rates. METHODS: Active duty service members identified with AF from 2004 to 2019 were investigated. Cardiovascular profiles, AF management strategies and military dispositions were assessed by electronic medical record review. RESULTS: 386 service members (mean age 35.0±9.4 years; 94% paroxysmal AF) with AF diagnoses were identified. 91 (24%) had hypertension followed by 75 (19%) with sleep apnoea. Mean CHA2DS2-VASc scores were low (0.39±0.65). Rhythm treatments were used in 173 (45%) followed by rate control strategies in 155 (40%). 161 (42%) underwent pulmonary vein isolation (PVI). In subgroup analysis of 365 personnel, 147 (40%) deployed and 248 (68%) remained active duty after AF diagnosis. Deployment and retention rates did not differ between those who received no medical therapy, rate control or rhythm strategies (p=0.9039 and p=0.6192, respectively). PVI did not significantly impact deployment or retention rates (p=0.3903 and p=0.0929, respectively). CONCLUSION: Service members with AF are young with few AF risk factors. Rate and rhythm medical therapies were used evenly. Over two-thirds met retention standards and 40% deployed after diagnosis. There were no differences in deployment or retention between groups who receive rate therapy, rhythm medical therapy or PVI. Prospective evaluation of the efficacy of specific AF therapies on AF burden and symptomatology in service members is needed.


Assuntos
Fibrilação Atrial , Militares , Veias Pulmonares , Humanos , Adulto , Fibrilação Atrial/diagnóstico , Resultado do Tratamento , Fatores de Risco
7.
Epidemiol Infect ; 144(10): 2184-90, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26947456

RESUMO

Patients with methicillin-resistant Staphylococcus aureus (MRSA) clones, which were traditionally seen in the community setting (USA400/CMRSA7 and USA300/CMRSA10), are often identified as hospital-acquired (HA) infections using Infection Prevention and Control (IPC) surveillance definitions. This study examined the demographics and healthcare risk factors of patients with HA-MRSA to help understand if community MRSA clones are from a source internal or external to the hospital setting. Despite USA300/CMRSA10 being the predominant clone in Alberta, hospital clones (USA100/CMRSA2) still dominated in the acute care setting. In the Alberta hospitalized population, patients with USA400/CMRSA7 and USA300/CMRSA10 clones were significantly younger, had fewer comorbidities, and a greater proportion had none or ambulatory care-only healthcare exposure. These findings suggest that there are two distinct populations of HA-MRSA patients, and the patients with USA400/CMRSA7 and USA300/CMRSA10 clones identified in hospital more greatly resemble patients affected by those clones in the community. It is possible that epidemiological assessment overidentifies HA acquisition of MRSA in patients unscreened for MRSA on admission to acute care.


Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Alberta/epidemiologia , Infecção Hospitalar/microbiologia , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/genética , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos , Infecções Estafilocócicas/microbiologia
8.
Mol Psychiatry ; 20(3): 298-310, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25560757

RESUMO

A single injection of N-methyl-D-aspartate receptor (NMDAR) antagonists produces a rapid antidepressant response. Lasting changes in the synapse structure and composition underlie the effectiveness of these drugs. We recently discovered that rapid antidepressants cause a shift in the γ-aminobutyric acid receptor (GABABR) signaling pathway, such that GABABR activation shifts from opening inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting dendritic calcium signal and mammalian Target of Rapamycin activity. However, little is known about the molecular and biochemical mechanisms that initiate this shift. Herein, we show that GABABR signaling to Kir3 (GIRK) channels decreases with NMDAR blockade. Blocking NMDAR signaling stabilizes the adaptor protein 14-3-3η, which decouples GABABR signaling from Kir3 and is required for the rapid antidepressant efficacy. Consistent with these results, we find that key proteins involved in GABABR signaling bidirectionally change in a depression model and with rapid antidepressants. In socially defeated rodents, a model for depression, GABABR and 14-3-3η levels decrease in the hippocampus. The NMDAR antagonists AP5 and Ro-25-6981, acting as rapid antidepressants, increase GABABR and 14-3-3η expression and decrease Kir3.2. Taken together, these data suggest that the shift in GABABR function requires a loss of GABABR-Kir3 channel activity mediated by 14-3-3η. Our findings support a central role for 14-3-3η in the efficacy of rapid antidepressants and define a critical molecular mechanism for activity-dependent alterations in GABABR signaling.


Assuntos
Proteínas 14-3-3/metabolismo , Antidepressivos/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/metabolismo , Neurônios/efeitos dos fármacos , Receptores de GABA-B/metabolismo , Proteínas 14-3-3/genética , Animais , Animais Recém-Nascidos , Células Cultivadas , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Imunoprecipitação , Masculino , Camundongos , Fenóis/farmacologia , Fenóis/uso terapêutico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Córtex Pré-Frontal/citologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de GABA-B/genética , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/patologia , Estresse Psicológico/fisiopatologia , Natação/psicologia , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Transdução Genética , Valina/análogos & derivados , Valina/farmacologia , Valina/uso terapêutico
9.
J Hosp Infect ; 89(2): 132-5, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25578685

RESUMO

Most studies of meticillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) reflect a convenience sample from a single hospital or a small group of hospitals. From April 2011 to March 2013, cases of MRSA BSI diagnosed in all hospitals in Alberta, Canada were captured prospectively. Isolates were spa typed. In total, there were 299 cases of MRSA BSI, equating to 3.95 cases per 100,000 population. Community-acquired BSI accounted for 66.9% of cases, and 33.1% of cases were hospital acquired. Cases were predominantly seen in tertiary care (36.4%) and large urban hospitals (34.3%), but were also common in regional and rural hospitals. Paediatric hospitals had very few cases (3.0%). Two clones, CMRSA 10 (USA 300; 40.2%) and CMRSA 2 (USA 100/800; 38.0%), predominated.


Assuntos
Bacteriemia/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/epidemiologia , Idoso , Alberta/epidemiologia , Bacteriemia/microbiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Feminino , Hospitais Urbanos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Estafilocócicas/microbiologia , Centros de Atenção Terciária
10.
Rev Sci Tech ; 31(1): 43-56, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22849267

RESUMO

Antimicrobial agents that target the bacterial cell wall or cell membrane have been used effectively for the past 70 years. Among the agents that inhibit bacterial cell wall synthesis, the beta-lactam antibiotics have emerged into broad-spectrum agents that inhibit most pathogenic bacteria, but are now being threatened by the rapid spread of drug-inactivating beta-lactamases. Glycopeptides still retain high activity against staphylococci, but resistance among the enterococci has become a major problem. Recently, fosfomycin has been used in the treatment of multidrug-resistant Gram-negative bacteria. Daptomycin, which targets both membrane function and peptidoglycan synthesis, is especially effective in treating staphylococcal infections. The polymyxin antibiotics that target cell membranes are being used more frequently to treat multidrug-resistant Gram-negative infections. The ionophore antibiotics, used in veterinary medicine, target membranes in many microbial and animal species. Although increasing resistance is a continuing concern, these classes of bactericidal agents can provide highly effective antibiotics.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias/ultraestrutura , Glicopeptídeos/química , Glicopeptídeos/farmacologia , Humanos , Ionóforos/química , Ionóforos/farmacologia , Lipopeptídeos/química , Lipopeptídeos/farmacologia , Ácidos Fosforosos/química , Ácidos Fosforosos/farmacologia , beta-Lactamas/química , beta-Lactamas/farmacologia
11.
Med Phys ; 39(6Part17): 3816-3817, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28517440

RESUMO

PURPOSE: The Acuros XB (AXB) Advanced Dose algorithm (Varian Medical Systems) represents a dramatic shift in clinical photon dose calculation methodology from pencil-beam superposition/convolution methods. Early studies evaluating the accuracy of the algorithm in lung have found good agreement with both measurement and Monte Carlo based dose calculations. In this study, a dosimetric validation of Acuros is performed for clinical SBRT lung planning cases using Monte Carlo (MC) calculations as a benchmark. METHODS: MC simulations using BEAMnrc/DOSXYZnrc were carried out for 8 AXB calculated 6/10 MV arc plans delivered on a TrueBeamTM STx linac in high-dose-rate flattening filter free mode. Clinical planning constraints were applied in each case with plans normalized to achieve 95% PTV coverage. Metrics used in the evaluation include: maximum and minimum GTV/PTV dose, PTV isodose coverage, conformity and dose profile comparisons. To understand the impact of moving toward to AXB calculations in SBRT lung planning, calculations using the Analytical Anisotropic Algorithm (AAA) are presented for each plan. RESULTS: For both 6 and 10MV energies, consistent mean GTV dose and PTV isodose coverage was observed for AXB and MC calculations. GTV mean dose was observed to deviate by <2% for all cases. Isodose coverage for MC simulations ranged from 92%-98%. AAA was also in agreement with MC simulations within the GTV to within 2%. AXB and MC maximum and minimum PTV dose differences were larger (up to 9%) but not of clinical concern. In several cases, AXB exhibited a significant improvement in dose calculation accuracy in the lung region surrounding the GTV over AAA, particularly with lung densities < 0.1 g/cc. CONCLUSION: AcurosXB provides increased accuracy in modelling dose deposition for SBRT lung over AAA and is found to be in good agreement with MC calculations.

12.
Med Phys ; 39(6Part18): 3827, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28518495

RESUMO

PURPOSE: The AcurosXB Advanced Dose algorithm (Varian Medical Systems) was reported to give more accurate dose calculation in heterogeneous medium compared with the AAA algorithm. In this work, a validation of AcurosXB dose calculation accuracy is performed for use in lung SBRT. METHODS: A CIRS (Computerized Imaging Reference Systems, Inc.) lung phantom was used with a tissue equivalent 2cm circular target inserted into the lung. The phantom was customized to hold a Gafchromic EBT2 film through the center of the target. The phantom was CT scanned, and single field (3cm by 3cm anterior/lateral) plans, as well as VMAT plans were created for 6 and 10 MV energies with different delivery modalities (with/without a flattening filter). All plans delivered 500 cGy to the PTV which was the target plus 0.5 cm uniform margin. Plans were delivered on a Varian TrueBeamTM STx using image guidance to locate the isocenter. The film dose was compared with Eclipse v10.0 dose calculated with AAA and Acuros algorithms using FilmQA software (3cognition). Monte Carlo simulations (BEAMnrc/DOSXYZnrc) were performed to further validate AcurosXB calculations. RESULTS: Within the GTV, AAA and Acuros algorithms were in good agreement with the film measurements to within 2% mean dose difference. AAA calculation consistently overestimated the dose to the lung surrounding the GTV by 5-9% for the 10MV beam and 2-4% for the 6MV beam. Acuros and MC calculations were found to be in good agreement with EBT2 film measurement within 2% at 6MV including the build up and build down regions. CONCLUSIONS: The CIRS customized lung phantom with EBT2 films was found to be an excellent tool in validating the dose calculation algorithm for lung SBRT application. AcurosXB was found to be more accurate than AAA algorithm in lung and near lung/tissue interfaces.

13.
Med Phys ; 39(6Part24): 3909, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28518679

RESUMO

PURPOSE: The increasing use of unflattened high dose rate and/or small sized fields in stereotactic body radiosurgery (SBRT) presents a significant challenge and calls for new tools for dosimetric measurements and quality assurance (QA). The purpose of this work is to investigate a high spatial resolution (0.2mm) and high frame rate (50Hz) amorphous silicon flat-panel electronic portal imaging device (EPID) from Perkin Elmer for SBRT. METHODS: A Monte Carlo N-Particle eXtended (MCNPX) simulation and convolution based calibration procedure has been developed to derive a voxel-based response function specific to the EPID construct and beam characteristics. Both standard photon beams and flattening filter free (FFF) beams of all energies from Varian TrueBeam STX were studied and the linearity and dose rate dependence were tested. EPID with detailed materials composition was simulated using the MCNPX to generate a scatter kernel composed of dose deposition in the EPID phosphor, and optical photon spreading and to deconvolve the EPID images to high spatial resolution photon fluence map. The fluence map was convolved with MCNPX generated kernels to the 3D dose distribution in the phantom and compared with pinpoint ion chamber and film measurements. RESULTS: EPID response showed excellent linearity (R2>0.9998) and dose rate dependence less than 1.8% for up to 2400MU/min. Output factors for field sizes ranging from 1×1 to 20×20cm2 were measured and used to fit the optical photon glare kernel. Fluence profiles deconvolved using MCNPX scattering kernel agrees with the measurements to within 2%. Results of typical pre-treatment QA test exhibit excellent spatial resolution required for SBRT. CONCLUSIONS: The high spatial resolution and high frame rate EPID proved to be an accurate and efficient tool for SBRT QA. Through convolution with MCNPX scattering core and comprehensive EPID calibration, accurate 3D dose maps can be generated for independent dosimetric verification of SBRT treatments.

14.
Med Phys ; 38(4): 2208-21, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21626955

RESUMO

PURPOSE: The dosimetric accuracy of the recently released Acuros XB advanced dose calculation algorithm (Varian Medical Systems, Palo Alto, CA) is investigated for single radiation fields incident on homogeneous and heterogeneous geometries, and a comparison is made to the analytical anisotropic algorithm (AAA). METHODS: Ion chamber measurements for the 6 and 18 MV beams within a range of field sizes (from 4.0 x 4.0 to 30.0 x 30.0 cm2) are used to validate Acuros XB dose calculations within a unit density phantom. The dosimetric accuracy of Acuros XB in the presence of lung, low-density lung, air, and bone is determined using BEAMnrc/DOSXYZnrc calculations as a benchmark. Calculations using the AAA are included for reference to a current superposition/convolution standard. RESULTS: Basic open field tests in a homogeneous phantom reveal an Acuros XB agreement with measurement to within +/- 1.9% in the inner field region for all field sizes and energies. Calculations on a heterogeneous interface phantom were found to agree with Monte Carlo calculations to within +/- 2.0% (sigmaMC = 0.8%) in lung (p = 0.24 g cm(-3)) and within +/- 2.9% (sigmaMC = 0.8%) in low-density lung (p = 0.1 g cm(-3)). In comparison, differences of up to 10.2% and 17.5% in lung and low-density lung were observed in the equivalent AAA calculations. Acuros XB dose calculations performed on a phantom containing an air cavity (p = 0.001 g cm(-3)) were found to be within the range of +/- 1.5% to +/- 4.5% of the BEAMnrc/DOSXYZnrc calculated benchmark (sigmaMC = 0.8%) in the tissue above and below the air cavity. A comparison of Acuros XB dose calculations performed on a lung CT dataset with a BEAMnrc/DOSXYZnrc benchmark shows agreement within +/- 2%/2mm and indicates that the remaining differences are primarily a result of differences in physical material assignments within a CT dataset. CONCLUSIONS: By considering the fundamental particle interactions in matter based on theoretical interaction cross sections, the Acuros XB algorithm is capable of modeling radiotherapy dose deposition with accuracy only previously achievable with Monte Carlo techniques.


Assuntos
Método de Monte Carlo , Fótons , Doses de Radiação , Algoritmos , Osso e Ossos/diagnóstico por imagem , Humanos , Pulmão/diagnóstico por imagem , Imagens de Fantasmas , Radiometria , Tomografia Computadorizada por Raios X
15.
Phys Med Biol ; 55(16): 4465-79, 2010 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-20668338

RESUMO

The aim of the study was to perform the Monte Carlo (MC) evaluation of RapidArc (Varian Medical Systems, Palo Alto, CA) dose calculations for four oropharynx midline sparing planning strategies. Six patients with squamous cell cancer of the oropharynx were each planned with four RapidArc head and neck treatment strategies consisting of single and double photon arcs. In each case, RTOG0522 protocol objectives were used during planning optimization. Dose calculations performed with the analytical anisotropic algorithm (AAA) are compared against BEAMnrc/DOSXYZnrc dose calculations for the 24-plan dataset. Mean dose and dose-to-98%-of-structure-volume (D(98%)) were used as metrics in the evaluation of dose to planning target volumes (PTVs). Mean dose and dose-to-2%-of-structure-volume (D(2%)) were used to evaluate dose differences within organs at risk (OAR). Differences in the conformity index (CI) and the homogeneity index (HI) as well as 3D dose distributions were also observed. AAA calculated PTV mean dose, D(98%), and HIs showed very good agreement with MC dose calculations within the 0.8% MC (statistical) calculation uncertainty. Regional node volume (PTV-80%) mean dose and D(98%) were found to be overestimated (1.3%, sigma = 0.8% and 2.3%, sigma = 0.8%, respectively) by the AAA with respect to MC calculations. Mean dose and D(2%) to OAR were also observed to be consistently overestimated by the AAA. Increasing dose calculation differences were found in planning strategies exhibiting a higher overall fluence modulation. From the plan dataset, the largest local dose differences were observed in heavily shielded regions and within the esophageal and sinus cavities. AAA dose calculations as implemented in RapidArc demonstrate excellent agreement with MC calculations in unshielded regions containing moderate inhomogeneities. Acceptable agreement is achieved in regions of increased MLC shielding. Differences in dose are attributed to inaccuracies in the AAA-modulated fluence modeling, modeling of material inhomogeneities and dose deposition within low-density materials. The use of MC dose calculations leads to the same general conclusion as using AAA that a two arc delivery with limited collimator opening can provide the greatest amount of midline sparing compared to the other techniques investigated.


Assuntos
Neoplasias Orofaríngeas/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Radioterapia/métodos , Algoritmos , Anisotropia , Humanos , Método de Monte Carlo , Imagens de Fantasmas , Fótons , Dosagem Radioterapêutica , Reprodutibilidade dos Testes
16.
J Clin Microbiol ; 48(9): 3353-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20592149

RESUMO

The susceptibility of 513 clinical isolates to doripenem was determined by broth microdilution, agar dilution, and Etest. Overall agreements for Etest and agar dilution MIC values compared to reference broth microdilution at +/-1 log(2) dilution were 88% and 94%, respectively. Etest MIC values demonstrated 98% agreement within +/-2 log(2) dilutions compared to the reference broth microdilution method.


Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Doripenem , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Testes de Sensibilidade Microbiana/métodos
18.
J Biomed Mater Res A ; 90(4): 999-1009, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-18655147

RESUMO

Precisely engineering the surface chemistry of biomaterials to modulate the adsorption and functionality of biochemical signaling molecules that direct cellular functions is critical in the development of tissue engineered scaffolds. Specifically, this study describes the use of functionalized self-assembled monolayers (SAMs) as a model system to assess the effects of biomaterial surface properties on controlling fibronectin (FN) conformation and concentration as well as keratinocyte function. By systematically analyzing FN adsorption at low and saturated surface densities, we distinguished between SAM-dependent effects of FN concentration and conformation on presenting cellular binding domains that direct cellular functions. Quantitative image analyses of immunostained samples showed that modulating the availability of the FN synergy site directly correlated with changes in keratinocyte attachment, spreading, and differentiation, through integrin-mediated signaling mechanisms. The results of this study will be used to elucidate design features that can be incorporated into dermal equivalents and percutaneous implants to enhance the rate of re-epithelialization and tissue regeneration. Furthermore, these findings indicate that SAM-based model systems are a valuable tool for designing and investigating the development of scaffolds that regulate the conformation of extracellular matrix cues and cellular functions that accelerate the rate of tissue regeneration.


Assuntos
Materiais Biocompatíveis/farmacologia , Queratinócitos/citologia , Alicerces Teciduais/química , Adsorção , Materiais Biocompatíveis/química , Adesão Celular , Diferenciação Celular , Forma Celular , Matriz Extracelular , Fibronectinas/química , Humanos , Recém-Nascido , Queratinócitos/efeitos dos fármacos , Engenharia Tecidual/métodos
19.
Phys Med Biol ; 53(19): N359-70, 2008 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-18758001

RESUMO

RapidArc radiotherapy technology from Varian Medical Systems is one of the most complex delivery systems currently available, and achieves an entire intensity-modulated radiation therapy (IMRT) treatment in a single gantry rotation about the patient. Three dynamic parameters can be continuously varied to create IMRT dose distributions-the speed of rotation, beam shaping aperture and delivery dose rate. Modeling of RapidArc technology was incorporated within the existing Vancouver Island Monte Carlo (VIMC) system (Zavgorodni et al 2007 Radiother. Oncol. 84 S49, 2008 Proc. 16th Int. Conf. on Medical Physics). This process was named VIMC-Arc and has become an efficient framework for the verification of RapidArc treatment plans. VIMC-Arc is a fully automated system that constructs the Monte Carlo (MC) beam and patient models from a standard RapidArc DICOM dataset, simulates radiation transport, collects the resulting dose and converts the dose into DICOM format for import back into the treatment planning system (TPS). VIMC-Arc accommodates multiple arc IMRT deliveries and models gantry rotation as a series of segments with dynamic MLC motion within each segment. Several verification RapidArc plans were generated by the Eclipse TPS on a water-equivalent cylindrical phantom and re-calculated using VIMC-Arc. This includes one 'typical' RapidArc plan, one plan for dual arc treatment and one plan with 'avoidance' sectors. One RapidArc plan was also calculated on a DICOM patient CT dataset. Statistical uncertainty of MC simulations was kept within 1%. VIMC-Arc produced dose distributions that matched very closely to those calculated by the anisotropic analytical algorithm (AAA) that is used in Eclipse. All plans also demonstrated better than 1% agreement of the dose at the isocenter. This demonstrates the capabilities of our new MC system to model all dosimetric features required for RapidArc dose calculations.


Assuntos
Método de Monte Carlo , Radioterapia de Intensidade Modulada/métodos , Algoritmos , Anisotropia , Humanos , Imagens de Fantasmas , Radiometria , Dosagem Radioterapêutica
20.
Phys Med Biol ; 53(18): N337-47, 2008 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-18711246

RESUMO

As radiotherapy treatment planning moves toward Monte Carlo (MC) based dose calculation methods, the MC beamlet is becoming an increasingly common optimization entity. At present, methods used to produce MC beamlets have utilized a particle source model (PSM) approach. In this work we outline the implementation of a phase-space-based approach to MC beamlet generation that is expected to provide greater accuracy in beamlet dose distributions. In this approach a standard BEAMnrc phase space is sorted and divided into beamlets with particles labeled using the inheritable particle history variable. This is achieved with the use of an efficient sorting algorithm, capable of sorting a phase space of any size into the required number of beamlets in only two passes. Sorting a phase space of five million particles can be achieved in less than 8 s on a single-core 2.2 GHz CPU. The beamlets can then be transported separately into a patient CT dataset, producing separate dose distributions (doselets). Methods for doselet normalization and conversion of dose to absolute units of Gy for use in intensity modulated radiation therapy (IMRT) plan optimization are also described.


Assuntos
Algoritmos , Modelos Estatísticos , Radiometria/métodos , Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Simulação por Computador , Método de Monte Carlo , Dosagem Radioterapêutica , Espalhamento de Radiação
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