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OBJECTIVE: Wear of articular cartilage is not well understood. We hypothesize that cartilage wears due to fatigue failure in repetitive compression instead of reciprocating friction. DESIGN: This study compares reciprocating sliding of immature bovine articular cartilage against glass in two testing configurations: (1) a stationary contact area configuration (SCA), which results in static compression, interstitial fluid depressurization, and increasing friction coefficient during reciprocating sliding, and (2) a migrating contact area configuration (MCA), which maintains pressurization and low friction while producing repetitive compressive loading in addition to reciprocating sliding. Contact pressure, sliding duration, and sliding distance were controlled to be similar between test groups. RESULTS: SCA tests exhibited an average friction coefficient of µ=0.084±0.032, while MCA tests exhibited a lower average friction coefficient of µ=0.020±0.008 (p<10-4). Despite the lower friction, MCA cartilage samples exhibited clear surface damage with a significantly greater average surface deviation from a fitted plane after wear testing (Rq=0.125±0.095 mm) than cartilage samples slid in a SCA configuration (Rq=0.044±0.017 mm, p=0.002), which showed minimal signs of wear. Polarized light microscopy confirmed that delamination damage occurred between the superficial and middle zones of the articular cartilage in MCA samples. CONCLUSIONS: The greatest wear was observed in the group with lowest friction coefficient, subjected to cyclical instead of static compression, implying that friction is not the primary driver of cartilage wear. Delamination between superficial and middle zones implies the main mode of wear is fatigue failure under cyclical compression, not fatigue or abrasion due to reciprocating frictional sliding.
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Cartílago Articular , Animales , Bovinos , Fricción , Líquido Extracelular , Presión , Estrés MecánicoRESUMEN
BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.
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COVID-19 , Neoplasias , COVID-19/epidemiología , Humanos , Oncología Médica , Neoplasias/epidemiología , Neoplasias/terapia , Pandemias , Estudios ProspectivosRESUMEN
In 2016, comparisons of activity measurements of 18F and 64Cu using the Transfer Instrument of the International Reference System (SIRTI) took place at the National Institute of Standards and Technology (NIST, USA). This is the first SIRTI comparison for 64Cu. Ampoules containing about 27 kBq of 18F and 100 kBq of 64Cu solutions were measured in the SIRTI for about 5 and 1.5 half-lives, respectively. The NIST standardized the activity in the ampoules by ionization chamber measurements traceable to 4π(LS)ß-γ anticoincidence measurements. The comparisons, identifiers BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Cu-64, are linked to the corresponding BIPM.RI(II)-K1.F-18 and BIPM.RI(II)-K1.Cu-64 comparisons and degrees of equivalence with the respective key comparison reference values have been evaluated. The NIST replaces its earlier degree of equivalence for 18F obtained in the frame of the CCRI(II)-K3.F-18 comparison in 2001.
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Fourier transform infrared (FTIR) spectroscopy is a powerful tool for the identification and characterization of pollen and spores. However, interpretation and multivariate analysis of infrared microscopy spectra of single pollen grains are hampered by Mie-type scattering. In this paper, we introduce a novel sampling setup for infrared microspectroscopy of pollens preventing strong Mie-type scattering. Pollen samples were embedded in a soft paraffin layer between two sheets of polyethylene foils without any further sample pretreatment. Single-grain infrared spectra of 13 different pollen samples, belonging to 11 species, were obtained and analyzed by the new approach and classified by sparse partial least-squares regression (PLSR). For the classification, chemical and physical information were separated by extended multiplicative signal correction and used together to build a classification model. A training set of 260 spectra and an independent test set of 130 spectra were used. Robust sparse classification models allowing the biochemical interpretation of the classification were obtained by the sparse PLSR, because only a subset of variables was retained for the analysis. With accuracy values of 95% and 98%, for the independent test set and full cross-validation respectively, the method is outperforming the previously published studies on development of an automated pollen analysis. Since the method is compatible with standard air-samplers, it can be employed with minimal modification in regular aerobiology studies. When compared with optical microscopy, which is the benchmark method in pollen analysis, the infrared microspectroscopy method offers better taxonomic resolution, as well as faster, more economical, and bias-free measurement.
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Alérgenos/análisis , Alérgenos/química , Polen/química , Análisis de los Mínimos Cuadrados , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
In this paper, we first provide an overview of the Mie type scattering at absorbing materials and existing correction methods, followed by a new method to obtain the pure absorbance spectra of biological systems with spherical symmetry. This method is a further development of the recently described iterative algorithm of van Dijk et al. The method is tested on FTIR synchrotron spectra of polymethyl methacrylate (PMMA) microspheres and pollen grains with approximately spherical shape. The imaginary part of the refractive index was successfully recovered for both systems. Good agreement was obtained between the pure absorbance spectra obtained by this method and the measured spectra.
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Cupressaceae/química , Polen/química , Polimetil Metacrilato/química , Algoritmos , Luz , Tamaño de la Partícula , Refractometría , Dispersión de Radiación , Espectroscopía Infrarroja por Transformada de Fourier , SincrotronesRESUMEN
AIMS: Development of efficacious grey water (GW) treatment systems would benefit from detailed knowledge of the bacterial composition of GW. Thus, the aim of this study was to characterize the bacterial composition from (i) various points throughout a GW recycling system that collects shower and sink handwash (SH) water into an equalization tank (ET) prior to treatment and (ii) laundry (LA) water effluent of a commercial-scale washer. METHODS AND RESULTS: Bacterial composition was analysed by high-throughput pyrosequencing of the 16S rRNA gene. LA was dominated by skin-associated bacteria, with Corynebacterium, Staphylococcus, Micrococcus, Propionibacterium and Lactobacillus collectively accounting for nearly 50% of the total sequences. SH contained a more evenly distributed community than LA, with some overlap (e.g. Propionibacterium), but also contained distinct genera common to wastewater infrastructure (e.g. Zoogloea). The ET contained many of these same wastewater infrastructure-associated bacteria, but was dominated by genera adapted for anaerobic conditions. CONCLUSIONS: The data indicate that a relatively consistent set of skin-associated genera are the dominant human-associated bacteria in GW, but infrastructure-associated bacteria from the GW collection system and ET used for transient storage will be the most common bacteria entering GW treatment and reuse systems. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to use high-throughput sequencing to identify the bacterial composition of various GW sources.
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Bacterias/aislamiento & purificación , Aguas Residuales/microbiología , Bacterias/clasificación , Bacterias/genética , Humanos , Datos de Secuencia Molecular , Filogenia , Piel/microbiología , Purificación del Agua/instrumentación , Abastecimiento de AguaRESUMEN
After discovering a discrepancy in the transfer standard currently being disseminated by the National Institute of Standards and Technology (NIST), we have performed a new primary standardization of the alpha-emitter (223)Ra using Live-timed Anticoincidence Counting (LTAC) and the Triple-to-Double Coincidence Ratio Method (TDCR). Additional confirmatory measurements were made with the CIEMAT-NIST efficiency tracing method (CNET) of liquid scintillation counting, integral γ-ray counting using a NaI(Tl) well counter, and several High Purity Germanium (HPGe) detectors in an attempt to understand the origin of the discrepancy and to provide a correction. The results indicate that a -9.5 % difference exists between activity values obtained using the former transfer standard relative to the new primary standardization. During one of the experiments, a 2 % difference in activity was observed between dilutions of the (223)Ra master solution prepared using the composition used in the original standardization and those prepared using 1 mol·L(-1) HCl. This effect appeared to be dependent on the number of dilutions or the total dilution factor to the master solution, but the magnitude was not reproducible. A new calibration factor ("K-value") has been determined for the NIST Secondary Standard Ionization Chamber (IC "A"), thereby correcting the discrepancy between the primary and secondary standards.
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This paper describes a new method, based on Hertzian biphasic theory (HBT), to characterize properties of biphasic materials with reduced time demands, increased surface sensitivity, and reduced computational demands compared to the current gold standards. Indentation experiments were conducted at a single location on a representative osteochondral plug to demonstrate and validate the HBT method against two gold standards, linear biphasic theory (LBT) and tension-compression nonlinear biphasic theory (TCN). The 1) aggregate moduli, 2) permeability and 3) tensile moduli from HBT, LBT, and TCN were 1) HA =0.47, 0.47, and 0.40 MPa, 2) k=0.0026, 0.0014 and 0.0016mm4/Ns, and 3) Et =8.7, 0.46, and 10.3MPa, respectively. The results support the HBT method and encourage its use, especially in light of its practical advantages.
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The ß--emitter 166Ho is of interest as a potential radiolabel for therapeutic medical applications. A new decay data evaluation for 166Ho has been performed using the Decay Data Evaluation Project (DDEP) methodology. New recommended values for the half-life, γ-ray emission probabilities, ß-- branching ratios, and other relevant nuclear and atomic data are provided. This paper provides a summary of the evaluation; the complete set of recommended data tables and detailed evaluator comments are available at the DDEP website.
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Absolute gamma-ray emission intensities for 36 characteristic gamma rays from the decay of 224Ra, 212Pb, and their progeny were determined by measuring sources calibrated for activity by means of primary methods based on well-defined high-purity germanium (HPGe) detectors at both NIST and NPL. Results from the two laboratories agree with recent data evaluations, except for gamma rays with low emission intensities. The decay schemes have been re-balanced based on the new results. In addition, the half-life for 212Pb was measured using several HPGe detectors, ionization chambers, and a well-type NaI(Tl) detector.
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The International Atomic Energy Agency (IAEA) has organized an international comparison to assess Single Photon Emission Computed Tomography (SPECT) image quantification capabilities in 12 countries. Iodine-131 was chosen as the radionuclide for the comparison because of its wide use around the world, but for logistical reasons solid (133)Ba sources were used as a long-lived surrogate for (131)I. For this study, we designed a set of solid cylindrical sources so that each site could have a set of phantoms (having nominal volumes of 2 mL, 4 mL, 6 mL, and 23 mL) with traceable activity calibrations so that the results could be properly compared. We also developed a technique using two different detection methods for individually calibrating the sources for (133)Ba activity based on a National standard. This methodology allows for the activity calibration of each (133)Ba source with a standard uncertainty on the activity of 1.4 % for the high-level 2-, 4-, and 6-mL sources and 1.7 % for the lower-level 23 mL cylinders. This level of uncertainty allows for these sources to be used for the intended comparison exercise, as well as in other SPECT image quantification studies.
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The National Institute of Standards and Technology (NIST) performed new standardization measurements for 124I. As part of this work the absolute photon emission intensity for the main gamma-rays of 124I were determined using several high-purity germanium (HPGe) detectors. In addition, the half-life for 124I was also determined using an HPGe detector. Ionization chamber measurements were performed for additional sources, but it was not possible to obtain a precise half-life value.
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Human T-lymphotropic virus type-1 (HTLV-1), the first human retrovirus discovered, is the causative agent of adult T-cell leukemia/lymphoma (ATL) and a number of lymphocyte-mediated inflammatory conditions including HTLV-1-associated myelopathy/tropical spastic paraparesis. Development of animal models to study the pathogenesis of HTLV-1-associated diseases has been problematic. Mechanisms of early infection and cell-to-cell transmission can be studied in rabbits and nonhuman primates, but lesion development and reagents are limited in these species. The mouse provides a cost-effective, highly reproducible model in which to study factors related to lymphoma development and the preclinical efficacy of potential therapies against ATL. The ability to manipulate transgenic mice has provided important insight into viral genes responsible for lymphocyte transformation. Expansion of various strains of immunodeficient mice has accelerated the testing of drugs and targeted therapy against ATL. This review compares various mouse models to illustrate recent advances in the understanding of HTLV-1-associated ATL development and how improvements in these models are critical to the future development of targeted therapies against this aggressive T-cell lymphoma.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Inmunidad Innata/inmunología , Leucemia-Linfoma de Células T del Adulto/inmunología , Paraparesia Espástica Tropical/inmunología , Animales , Modelos Animales de Enfermedad , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia-Linfoma de Células T del Adulto/genética , Ratones , Ratones Endogámicos NOD , Ratones SCID , Ratones Transgénicos , Paraparesia Espástica Tropical/genéticaRESUMEN
The National Institute of Standards and Technology (NIST) measured the internal pair production branching ratio of 90Y using two sources and four high purity germanium (HPGe) detectors to detect the resulting annihilation radiation. The internal pair production branching ratio determined from these measurements, (32.0⯱â¯1.5)â¯×â¯10-6 (kâ¯=â¯1), agrees within 1 standard uncertainty with the recommended value of (32.6⯱â¯0.7)â¯×â¯10-6 (kâ¯=â¯1) from the DDEP database.
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The pineal body and the retina of the neonatal Sprague-Dawley rat were studied by light and electron microscopy, and the morphologic differentiation of the parenchymal cells of the pineal body was compared with that of the developing photoreceptor cells of the retina. Between the ages of 4 and 12 days after birth, some of the developing pinealocytes were observed to become elongated and polarized, with their nuclei located at one pole. "Synaptic" ribbons were observed within the cell body. At the opposite pole the cells developed elongated cell processes that initially contained microtubules and ribosomes. These cell processes projected into luminal spaces and were attached by structures resembling zonulae adherentes to the adjacent cells. Extending from the tips of the cell processes, cilia with a 9 + 0 arrangement were observed. Lamellated and vesicular membranes were noted at the tips of the cilia. Such morphologic differentiation, however, could be observed only in rats younger than 17 days. Comparison of the morphologic features of the neonatal pinealocytes with those of the developing retinal photoreceptor cells showed much similarity. It is suggested that the pinealocytes of the neonatal rat undergo "photoreceptor-like" differentiation during a transient neonatal period. Such morphologic differentiation may provide an explanation for light-induced biochemical changes described in neonatal rats whose eyes had been enucleated.
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Células Fotorreceptoras/citología , Glándula Pineal/citología , Animales , Animales Recién Nacidos , Diferenciación Celular , Núcleo Celular/ultraestructura , Cilios/ultraestructura , Microscopía Electrónica , Organoides/ultraestructura , Células Fotorreceptoras/ultraestructura , Glándula Pineal/crecimiento & desarrollo , Glándula Pineal/ultraestructura , Ratas , Retina/citología , Retina/crecimiento & desarrollo , Retina/ultraestructura , Sinapsis/ultraestructuraRESUMEN
Infection with human T-cell leukemia virus type 1 (HTLV-1) leads sometimes to the development of adult T-cell lymphoma/leukemia (ATL), which is invariably fatal and often associated with humoral hypercalcemia of malignancy. The transformation of infected CD4 T cells and the pathogenesis of leukemia have been studied with great limitation in tissue culture and patients. To better understand the pathogenesis and perform preclinical drug studies, animal models of ATL are urgently needed. In mice, inoculation of HTLV-1 cell lines mostly leads to development of localized lymphomas. To develop an ATL animal model with leukemic spread of ATL cells, mouse strains with different well-defined immune deficiencies were inoculated intraperitoneally with different HTLV-1-infected cell lines (ACH.2, C8166, MT-2, MET-1). Inoculation of MET-1 cells into NOD/SCID mice provided the best model system for slowly developing T-cell leukemia with multiple organ involvement. In leukemic mice, an increase in serum calcium levels correlated with expression of receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand on leukemic cells and secretion of parathyroid hormone-related protein and interleukin-6. In contrast to the other cell lines that did not spread systemically, MET-1 expressed both the adhesion molecules CD11a (LFA-1alpha) and CD49d (VLA-4alpha) and produced or induced expression of matrix metalloproteinases 1, 2, 3, and 9, thus underlining the importance of these molecules in the spread of adult T-cell leukemia cells. The MET-1/NOD/SCID model will be useful for developing interventions against invasion and spread of leukemic cells and subsequent humoral hypercalcemia of malignancy.
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Modelos Animales de Enfermedad , Hipercalcemia/etiología , Leucemia-Linfoma de Células T del Adulto/inmunología , Ratones Endogámicos NOD/inmunología , Ratones SCID/inmunología , Animales , Basigina/inmunología , Western Blotting/veterinaria , Antígeno CD11a/inmunología , Línea Celular , Femenino , Humanos , Hipercalcemia/inmunología , Inmunohistoquímica/veterinaria , Integrina alfa4/inmunología , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/inmunología , Ratones , Ratones Noqueados , Proteína Relacionada con la Hormona Paratiroidea/genética , Proteína Relacionada con la Hormona Paratiroidea/inmunología , Ligando RANK/inmunología , ARN/química , ARN/genética , Receptores de Quimiocina/genética , Receptores de Quimiocina/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinariaRESUMEN
A solution of 124I was standardized for activity by 4πß(LS)-γ(NaI) live-timed anticoincidence (LTAC) counting, with confirmatory measurements by triple-to-double coincidence ratio (TDCR) and CIEMAT-NIST efficiency tracing (CNET) liquid scintillation counting. The LTAC-based standard was shown to be in agreement (within kâ¯=â¯1 uncertainties) with previous measurements at NIST and elsewhere. Calibration settings for radionuclide calibrators were determined and a discrepancy with literature values, partially due to a calibration methodology dependent upon an erroneous setting for 18F, was identified and explained.
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A solution containing (68)Ge in equilibrium with its daughter, (68)Ga, has been standardized for the first time at the National Institute of Standards and Technology (NIST) using 3 liquid scintillation-based techniques: live-timed 4πß -γ anticoincidence (LTAC) counting, the Triple-to-Double Coincidence Ratio (TDCR) method, and (3)H-standard efficiency tracing with the CIEMAT(1)/NIST (CNET) method. The LTAC technique is much less dependent on level scheme data and model-dependent parameters and was thus able to provide a reference activity concentration value for the master solution with a combined standard uncertainty of about 0.3 %. The other two methods gave activity concentration values with respective differences from the reference value of +1.2 % and -1.5 %, which were still within the experimental uncertainties. Measurements made on the NIST "4π"γ secondary standard ionization chamber allowed for the determination of calibration factors for that instrument, allowing future calibrations to be made for (68)Ge/(68)Ga without the need for a primary measurement. The ability to produce standardized solutions of (68)Ge presents opportunities for the development of a number of NIST-traceable calibration sources with very low (<1 %) relative standard uncertainties that can be used in diagnostic medical imaging.
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A radioactivity measurement comparison for solutions of (131)I was conducted by the International Atomic Energy Agency for participants in one of its Cooperative Research Projects aimed at enhancing quality assurance practices in nuclear medicine. The comparison solutions were prepared from a single master stock solution and distributed to the participating laboratories, who measured the activity concentration of the solution using either the laboratory's radionuclide activity calibrator or primary standardization methods. From the 7 results received, a Comparison Reference Value was calculated to be 37.35(78)MBqg(-1) at the reference time. Degrees of equivalence, as defined by the Mutual Recognition Agreement (MRA) of the Comité International des Poids et Mesures (CIPM), were calculated for each laboratory, demonstrating that equivalence to within +/-4% could be achieved. The comparison has been registered as a supplementary comparison with the CIPM, Consultative Committee for Ionizing Radiation, Section II-measurement of radionuclides (CCRI(II)) for the purposes of allowing the participants to establish traceability to international standards for this radionuclide.
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Recent liquid scintillation (LS) measurements at the National Institute of Standards and Technology (NIST) and at the Laboratoire National Henri Becquerel (LNHB) on a standardized (63)Ni solution that has been tracked for nearly 40 years have resulted in several important findings: (i) a (63)Ni half-life value of 101.2 +/- 1.5 a has been determined with the present decay data. This value is consistent with a previous specific activity determination and with an earlier value from decay measurements; and it appears to be more satisfactory than a recent data evaluator's recommended value of 98.7 a. (ii) All solution standards of (63)Ni as disseminated by NIST for the past 38(+) years are internally consistent with past and recent standardizations. (iii) Primary LS standardizations of (63)Ni by the triple-to-double coincidence ratio (TDCR) method and by CIEMAT/NIST (3)H-standard efficiency tracing (CNET) appear to be comparable, although the latter methodology is believed to be inherently inferior. (iv) There is excellent measurement agreement between NIST and LNHB for (63)Ni primary standardizations.