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PURPOSE: Ultrahigh field (≥7 T) MRI is at the cutting edge of medical imaging, enabling enhanced spatial and spectral resolution as well as enhanced susceptibility contrast. However, transmit ( B 1 + $$ {\mathrm{B}}_1^{+} $$ ) field inhomogeneity due to standing wave effects caused by the shortened RF wavelengths at 7 T is still a challenge to overcome. Novel hardware methods such as dielectric pads have been shown to improve the B 1 + $$ {\mathrm{B}}_1^{+} $$ field inhomogeneity but are currently limited in their corrective effect by the range of high-permittivity materials available and have a fixed shelf life. In this work, an optimized metasurface design is presented that demonstrates in vivo enhancement of the B 1 + $$ {\mathrm{B}}_1^{+} $$ field. METHODS: A prototype metasurface was optimized by an empirical capacitor sweep and by varying the period size. Phantom temperature experiments were performed to evaluate potential metasurface heating effects during scanning. Lastly, in vivo gradient echo images and B 1 + $$ {\mathrm{B}}_1^{+} $$ maps were acquired on five healthy subjects on a 7 T system. Dielectric pads were also used as a comparison throughout the work as a standard comparison. RESULTS: The metasurfaces presented here enhanced the average relative SNR of the gradient echo images by a factor of 2.26 compared to the dielectric pads factor of 1.61. Average B 1 + $$ {\mathrm{B}}_1^{+} $$ values reflected a similar enhancement of 27.6% with the metasurfaces present versus 8.9% with the dielectric pads. CONCLUSION: The results demonstrate that metasurfaces provide superior performance to dielectric padding as shown by B 1 + $$ {\mathrm{B}}_1^{+} $$ maps reflecting their direct effects and resulting enhancements in image SNR at 7 T.
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Diseño de Equipo , Imagen por Resonancia Magnética , Fantasmas de Imagen , Imagen por Resonancia Magnética/instrumentación , Humanos , Pierna/diagnóstico por imagen , Adulto , Aumento de la Imagen/métodos , Femenino , Masculino , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Relación Señal-RuidoRESUMEN
PURPOSE: The purpose of this study was to determine the effect of acute nicotinamide riboside (NR) supplementation on cerebral nicotinamide adenine dinucleotide (NAD+) levels in the human brain in vivo by means of downfield proton MRS (DF 1H MRS). METHODS: DF 1H MRS was performed on 10 healthy volunteers in a 7.0 T MRI scanner with spectrally selective excitation and spatially selective localization to determine cerebral NAD+ levels on two back-to-back days: once after an overnight fast (baseline) and once 4 h after oral ingestion of nicotinamide riboside (900 mg). Additionally, two more baseline scans were performed following the same paradigm to assess test-retest reliability of the NAD+ levels in the absence of NR. RESULTS: NR supplementation increased mean NAD+ concentration compared to the baseline (0.458 ± 0.053 vs. 0.392 ± 0.058 mM; p < 0.001). The additional two baseline scans demonstrated no differences in mean NAD+ concentrations (0.425 ± 0.118 vs. 0.405 ± 0.082 mM; p = 0.45), and no difference from the first baseline scan (F(2, 16) = 0.907; p = 0.424). CONCLUSION: These preliminary results confirm that acute NR supplementation increases cerebral NAD+ levels in healthy human volunteers and shows the promise of DF 1H MRS utility for robust detection of NAD+ in humans in vivo.
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We present a review outlining the basic mechanism, background, recent technical developments, and clinical applications of aqueous dielectric padding in the field of MRI. Originally meant to be a temporary solution, it has gained traction as an effective method for correcting B1 + inhomogeneities due to the unique properties of the calcium titanate and barium titanate perovskites used. Aqueous dielectric pads have used a variety of high-permittivity materials over the years to improve the quality of MRI acquisitions at 1.5 and 3 T and more recently for 7 T neuroimaging applications. The technical development and assessment of these pads have been advanced by an increased use of mathematical modeling and electromagnetic simulations. These tools have allowed for a more complete understanding of the physical interactions between dielectric pads and the RF coil, making testing and safety assessments more accurate. The ease of use and effectiveness that dielectric pads offer have allowed them to become more commonplace in tackling imaging challenges in more clinically focused environments. More recently, they have seen usage not only in anatomical imaging methods but also in specialized metabolic imaging sequences such as GluCEST and NOEMTR . New colossally high-permittivity materials have been proposed; however, practical utilization has been a continued challenge due to unfavorable frequency dependences as well as safety limitations. A new class of metasurfaces has been under development to address the shortcomings of conventional dielectric padding while also providing increased performance in enhancing MRI images.
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Imagen por Resonancia Magnética , Neuroimagen , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Agua , Ondas de Radio , Espectroscopía de Resonancia Magnética , Fantasmas de ImagenRESUMEN
PURPOSE: In vivo quantification of lactate has numerous applications in studying the pathology of both cerebral and musculoskeletal systems. Due to its low concentration (~0.5-1 mM), and overlap with lipid signals, traditional 1H MR spectra acquired in vivo using a small voxel and short echo time often result in an inadequate signal to detect and resolve the lactate peak, especially in healthy human volunteers. METHODS: In this study, using a semi-LASER acquisition with long echo time (TE = 288 ms) and large voxel size (80 × 70 × 20 mm3), we clearly visualize the combined signal of lactate and threonine. Therefore, we call the signal at 1.33 ppm Lac+ and quantify Lac+ concentration from water suppressed spectra in healthy human brains in vivo. Four participants (22-37 years old; mean age = 28 ± 5.4; three male, one female) were scanned on four separate days, and on each day four measurements were taken. Intra-day values are calculated for each participant by comparing the four measurements on a single day. Inter-day values were calculated using the mean intra-day measurements. RESULTS: The mean intra-participant Lac+ concentration, standard deviation (SD), and coefficient of variation (CV) ranged from 0.49 to 0.61 mM, 0.02 to 0.07 mM, and 4% to 13%, respectively, across four volunteers. The inter-participant Lac+ concentration, SD, and CV was 0.53 mM, ±0.06 mM, and 11%. CONCLUSION: Repeatability is shown in Lac+ measurement in healthy human brain using a long echo time semi-LASER sequence with a large voxel in about 3.5 min at 3 T.
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Encéfalo , Ácido Láctico , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Reproducibilidad de los Resultados , Ácido Láctico/metabolismo , Ácido Láctico/análisis , Espectroscopía de Resonancia Magnética/métodosRESUMEN
PURPOSE: Nuclear Overhauser effect (NOE) is based on dipolar cross-relaxation mechanism that enables the indirect detection of aliphatic protons via the water proton signal. This work focuses on determining the reproducibility of NOE magnetization transfer ratio (NOEMTR ) and isolated or relayed NOE (rNOE) contributions to the NOE MRI of the healthy human brain at 7 Tesla (T). METHODS: We optimized the B 1 + $$ {\mathrm{B}}_1^{+} $$ amplitude and length of the saturation pulse by acquiring NOE images with different B 1 + $$ {\mathrm{B}}_1^{+} $$ values with multiple saturation lengths. Repeated NOE MRI measurements were made on five healthy volunteers by using optimized saturation pulse parameters including correction of B0 and B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities. To isolate the individual contributions from z-spectra, we have fit the NOE z-spectra using multiple Lorentzians and calculated the total contribution from each pool contributing to the overall NOEMTR contrast. RESULTS: We found that a saturation amplitude of 0.72 µT and a length of 3 s provided the highest contrast. We found that the mean NOEMTR value in gray matter (GM) was 26%, and in white matter (WM) was 33.3% across the 3D slab of the brain. The mean rNOE contributions from GM and WM values were 8.9% and 9.6%, which were â¼10% of the corresponding total NOEMTR signal. The intersubject coefficient of variations (CoVs) of NOEMTR from GM and WM were 4.5% and 6.5%, respectively, whereas the CoVs of rNOE were 4.8% and 5.6%, respectively. The intrasubject CoVs of the NOEMTR range was 2.1%-4.2%, and rNOE range was 2.9%-10.5%. CONCLUSION: This work has demonstrated an excellent reproducibility of both inter- and intrasubject NOEMTR and rNOE metrics in healthy human brains at 7 T.
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Algoritmos , Neoplasias Encefálicas , Humanos , Reproducibilidad de los Resultados , Interpretación de Imagen Asistida por Computador/métodos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , ProtonesRESUMEN
PURPOSE: To monitor the metabolic turnover of ß-hydroxybutyrate (BHB) oxidation using 2 H-MRS in conjunction with intravenous administration of 2 H labeled BHB. METHODS: Nine-month-old mice were infused with [3,4,4,4]-2 H4 -BHB (d4 -BHB; 3.11 g/kg) through the tail vein using a bolus variable infusion rate for a period of 90 min. The labeling of downstream cerebral metabolites from the oxidative metabolism of d4 -BHB was monitored using 2 H-MRS spectra acquired with a home-built 2 H surface coil on a 9.4T preclinical MR scanner with a temporal resolution of 6.25 min. An exponential model was fit to the BHB and glutamate/glutamine (Glx) turnover curves to determine rate constants of metabolite turnover and to aid in the visualization of metabolite time courses. RESULTS: Deuterium label was incorporated into Glx from BHB metabolism through the tricarboxylic acid (TCA) cycle, with an increase in the level of [4,4]-2 H2 -Glx (d2 -Glx) over time and reaching a quasi-steady state concentration of â¼0.6 ± 0.1 mM following 30 min of infusion. Complete oxidative metabolic breakdown of d4 -BHB also resulted in the formation of semi-heavy water (HDO), with a four-fold (10.1 to â¼42.1 ± 7.3 mM) linear (R2 = 0.998) increase in its concentration by the end of infusion. The rate constant of Glx turnover from d4 -BHB metabolism was determined to be 0.034 ± 0.004 min-1 . CONCLUSION: 2 H-MRS can be used to monitor the cerebral metabolism of BHB with its deuterated form by measuring the downstream labeling of Glx. The integration of 2 H-MRS with deuterated BHB substrate provides an alternative and clinically promising MRS tool to detect neurometabolic fluxes in healthy and disease conditions.
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Encéfalo , Ratones , Animales , Ácido 3-Hidroxibutírico , Deuterio , Oxidación-Reducción , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismoRESUMEN
PURPOSE: Nuclear Overhauser effect magnetization transfer ratio (NOEMTR ) is a technique used to investigate brain lipids and macromolecules in greater detail than other techniques and benefits from increased contrast at 7 T. However, this contrast can become degraded because of B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities present at ultra-high field strengths. High-permittivity dielectric pads (DP) have been used to correct for these inhomogeneities via displacement currents generating secondary magnetic fields. The purpose of this work is to demonstrate that dielectric pads can be used to mitigate B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities and improve NOEMTR contrast in the temporal lobes at 7 T. METHODS: Partial 3D NOEMTR contrast images and whole brain B 1 + $$ {\mathrm{B}}_1^{+} $$ field maps were acquired on a 7 T MRI across six healthy subjects. Calcium titanate DP, having a relative permittivity of 110, was placed next to the subject's head near the temporal lobes. Pad corrected NOEMTR images had a separate postprocessing linear correction applied. RESULTS: DP provided supplemental B 1 + $$ {\mathrm{B}}_1^{+} $$ to the temporal lobes while also reducing the B 1 + $$ {\mathrm{B}}_1^{+} $$ magnitude across the posterior and superior regions of the brain. This resulted in a statistically significant increase in NOEMTR contrast in substructures of the temporal lobes both with and without linear correction. The padding also produced a convergence in NOEMTR contrast toward approximately equal mean values. CONCLUSION: NOEMTR images showed significant improvement in temporal lobe contrast when DP were used, which resulted from an increase in B 1 + $$ {\mathrm{B}}_1^{+} $$ homogeneity across the entire brain slab. DP-derived improvements in NOEMTR are expected to increase the robustness of the brain substructural measures both in healthy and pathological conditions.
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Encéfalo , Cabeza , Humanos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico , Campos Magnéticos , 5-Metiltetrahidrofolato-Homocisteína S-MetiltransferasaRESUMEN
Innovation - the ability to solve problems in a novel way - is not only associated with cognitive abilities and relative brain size, but also by noncognitive traits, such as personality and motivation. We used a novel foraging task with three access options to determine how neophobia, exploration, and persistence influence innovation in 12 habituated bat-eared foxes (Otocyon megalotis) in the Kalahari Desert. Bat-eared foxes offer a unique system to understand cognition as they have the smallest relative brain size of measured canids and a specialized, termite-based diet, yet have displayed foraging innovations. Interestingly, most of our individuals solved the task at least once and six individuals solved the task in every trial. Neophobia did not influence success on the first trial, but both exploration and persistence influenced success across all trials. Those individuals that solved the puzzle over multiple trials became faster over time, suggesting that they learned how to open the box more efficiently. We found some variation in the method to open the puzzle box with six individuals solving the puzzle using two methods and one individual using all three methods. This is the first study to show innovation in a novel foraging task in wild bat-eared foxes.
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Quirópteros , Zorros , Animales , Solución de Problemas , Cognición , AprendizajeRESUMEN
In the field of liquid chromatography-mass spectrometry (LC-MS)-based proteomics, increases in the sampling depth and proteome coverage have mainly been accomplished by rapid advances in mass spectrometer technology. The comprehensiveness and quality of the data that can be generated do, however, also depend on the performance provided by nano-liquid chromatography (nanoLC) separations. Proper selection of reversed-phase separation columns can be important to provide the MS instrument with peptides at the highest possible concentration and separated at the highest possible resolution. In the current contribution, we evaluate the use of the prototype generation 2 µPAC nanoLC columns, which use C18-functionalized superficially porous micropillars as a stationary phase. When compared to traditionally used fully porous silica stationary phases, more precursors could be characterized when performing single shot data-dependent LC-MS/MS analyses of a human cell line tryptic digest. Up to 30% more protein groups and 60% more unique peptides were identified for short gradients (10 min) and limited sample amounts (10-100 ng of cell lysate digest). With LC-MS gradient times of 10, 60, 120, and 180 min, respectively, we identified 2252, 6513, 7382, and 8174 protein groups with 25, 500, 1000, and 2000 ng of the sample loaded on the column. Reduction of sample carryover to the next run (up to 2 to 3%) and decreased levels of methionine oxidation (up to 3-fold) were identified as additional figures of merit. When analyzing a disuccinimidyl dibutyric urea-crosslinked synthetic library, 29 to 59 more unique crosslinked peptides could be identified at an experimentally validated false discovery rate of 1-2%.
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Proteoma , Espectrometría de Masas en Tándem , Humanos , Cromatografía Liquida/métodos , Proteoma/análisis , Porosidad , Péptidos/análisisRESUMEN
PURPOSE: Ultra-high field MR imaging lacks B1 + inhomogeneity due to shorter RF wavelengths used at higher field strengths compared to human anatomy. CEST techniques tend to be highly susceptible to B1 + inhomogeneities due to a high and uniform B1 + field being necessary to create the endogenous contrast. High-permittivity dielectric pads have seen increasing usage in MR imaging due to their ability to tailor the spatial distribution of the B1 + field produced. The purpose of this work is to demonstrate that dielectric materials can be used to improve glutamate weighted CEST (gluCEST) at 7T. THEORY AND METHODS: GluCEST images were acquired on a 7T system on six healthy volunteers. Aqueous calcium titanate pads, with a permittivity of approximately 110, were placed on either side in the subject's head near the temporal lobes. A post-processing correction algorithm was implemented in combination with dielectric padding to compare contrast improvement. Tissue segmentation was performed to assess the effect of dielectric pads on gray and white matter separately. RESULTS: GluCEST images demonstrated contrast enhancement in the lateral temporal lobe regions with dielectric pad placement. Tissue segmentation analysis showed an increase in correction effectiveness within the gray matter tissue compared to white matter tissue. Statistical testing suggested a significant difference in gluCEST contrast when pads were used and showed a difference in the gray matter tissue segment. CONCLUSION: The use of dielectric pads improved the B1 + field homogeneity and enhanced gluCEST contrast for all subjects when compared to data that did not incorporate padding.
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Ácido Glutámico , Sustancia Blanca , Algoritmos , Sustancia Gris , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
Use of recommended preventive care services in the United States is not universal and varies considerably by socio-economic status. We examine whether widespread eligibility for Medicare at age 65 narrows disparate preventive service use by race and ethnicity. Using data across 12 cycles of the Household Component of the Medical Expenditure Panel Survey (2005-2016), we employ a regression discontinuity design to assess changes in the use of preventive services. Our sample included: 8847 Hispanic respondents, 9908 non-Hispanic Black respondents, and 29,527 non-Hispanic White respondents. We examined six preventive services: routine check-ups, blood cholesterol screenings, receipt of the influenza vaccine, blood pressure screenings, mammograms, and colorectal cancer screenings. For non-Hispanic Black adults, we found that preventive service use increased after age 65 across a range of measures including a 4.8 percentage-point (95% confidence interval (CI)1.4, 8.2) increase in blood cholesterol screening, and a 9.1 percentage-point (95% CI 2.1, 15.9) increase in mammograms for Black women. For all four preventive health measures that were lower for Hispanic adults compared with non-Hispanic White adults prior to age 65, service use was indistinguishable (p > 0.10) between these groups after reaching the Medicare eligibility age. Medicare eligibility appeared to reduce most racial and ethnic disparities in preventive service use.
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Etnicidad , Medicare , Adulto , Anciano , Población Negra , Femenino , Disparidades en Atención de Salud , Hispánicos o Latinos , Humanos , Servicios Preventivos de Salud , Estados UnidosRESUMEN
In the light of the ongoing single-cell revolution, scientific disciplines are combining forces to retrieve as much relevant data as possible from trace amounts of biological material. For single-cell proteomics, this implies optimizing the entire workflow from initial cell isolation down to sample preparation, liquid chromatography (LC) separation, mass spectrometer (MS) data acquisition, and data analysis. To demonstrate the potential for single-cell and limited sample proteomics, we report on a series of benchmarking experiments where we combine LC separation on a new generation of micropillar array columns with state-of-the-art Orbitrap MS/MS detection and high-field asymmetric waveform ion mobility spectrometry (FAIMS). This dedicated limited sample column has a reduced cross section and micropillar dimensions that have been further downscaled (interpillar distance and pillar diameter by a factor of 2), resulting in improved chromatography at reduced void times. A dilution series of a HeLa tryptic digest (5-0.05 ng/µL) was used to explore the sensitivity that can be achieved. Comparative processing of the MS/MS data with Sequest HT, MS Amanda, Mascot, and SpectroMine pointed out the benefits of using Sequest HT together with INFERYS when analyzing sample amounts below 1 ng. Here, 2855 protein groups were identified from just 1 ng of HeLa tryptic digest hereby increasing detection sensitivity as compared to a previous contribution by a factor well above 10. By successfully identifying 1486 protein groups from as little as 250 pg of HeLa tryptic digest, we demonstrate outstanding sensitivity with great promise for use in limited sample proteomics workflows.
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Espectrometría de Movilidad Iónica , Espectrometría de Masas en Tándem , Cromatografía Liquida , Proteínas , TecnologíaRESUMEN
One of the most prominent life-history trade-offs involves the cost of reproduction. Oxidative stress has been proposed to be involved in this trade-off and has been associated with reduced life span. There is currently an unclear relationship between oxidative cost and the reproduction-longevity trade-off. The current study, using a non-lethal and minimally invasive (only a single blood sample and no euthanasia) method, investigated whether an oxidative cost (oxidative stress) to reproduction would be apparent in two long-lived eusocial mole-rats, the naked mole-rat (NMR), Heterocephalus glaber, and the Damaraland mole-rat (DMR), Fukomys damarensis, where breeding colony members live longer than non-breeder conspecifics. We measured the direct redox balance in plasma by measuring the oxidative stress index (OSI) based on the ratio of total oxidant status and total antioxidant activity in breeders and non-breeders of both sexes, in the two species. NMR had significantly higher OSI between breeders and non-breeders of each sex, whereas DMR showed no significant differences except for total antioxidant capacity (TAC). The mode of reproductive suppression and the degree of reproductive investment in NMR may explain to some degree the redox balance difference between breeders and non-breeders. DMR show minimal physiological changes between breeders and non-breeders except for the mode of reproduction, which may explain some variations in TAC and TOS values, but similar OSI between breeders and non-breeders.
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Modelling of anthropogenic induced climate suggests more frequent and severe heatwaves in the future, which are likely to result in the mass die-off of several species of organisms. Oxidative stress induced by severe heat stress has previously been associated with a reduction in animal cognitive performance, depressed reproduction and lower life expectancy. Little is known about the non-lethal consequences of species should they survive extreme heat exposure. We investigated the oxidative stress experienced by the Namaqua rock mouse, a nocturnal rodent, using two experimental heat stress protocols, a 6 hour acute heat stress protocol without access to water and a 3-day heatwave simulation with ad libitum water. Oxidative stress was determined in the liver, kidney and brain using malondialdehyde (MDA) and protein carbonyl (PC) as markers of oxidative damage, and superoxide dismutase (SOD) and total antioxidant capacity (TAC) as markers of antioxidant defence. Incubator heat stress (heat and dehydration stress) was brought about by increasing the body temperatures of animals to 39-40.8 °C for 6 hours. Following incubator heat stress, significantly higher levels of MDA were observed in the liver. Dehydration did not explain the variation in oxidative markers and is likely a combined effect of thermal and dehydration stress. Individual body mass was significantly negatively correlated to kidney SOD and lipid peroxidation. A heatwave was simulated using a temperature cycle that would naturally occur during a heatwave in the species' local habitat, with a maximal ambient temperature of 38 °C. Following the simulated heatwave, SOD activity of the kidney demonstrated significantly lowered activity suggesting oxidative stress. Current heat waves in this species have the potential of causing oxidative stress. Heat and dehydration stress following exacerbated temperatures are likely to incur significant oxidative stress in multiple tissues demonstrating the importance of water availability to allow for rehydration to prevent oxidative stress.
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Respuesta al Choque Térmico , Estrés Oxidativo , Animales , Encéfalo/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Carbonilación Proteica , Superóxido Dismutasa/metabolismoRESUMEN
Activity of animals is influenced by ambient temperature and increasing temperatures brought about by climate change may impose a heat stress risk. Previous studies investigating the effect of heat waves on activity usually measure animals at different, but constant temperatures, however, rarely are they studied under a natural temperature cycle. General activity, behavioural flexibility and frequency of water drinking counts during a normal day, hot day and a simulated heat wave temperature cycle were studied in the crepuscular four-striped field mouse, Rhabdomys dilectus, and the nocturnal Namaqua rock mouse, Micaelamys namaquensis. Both R. dilectus and M. namaquensis showed typical daily locomotor activity under control conditions. During the heat wave, peak activity times changed for R. dilectus, but both species exhibited higher bouts of activity for the heat wave during the day compared to the control, which was accompanied by an increased amount of time spent drinking water. The increased activity during the heat wave is likely due to enhanced water requirements and potentially a form of behavioural thermoregulation as animals may be uncomfortable and try to move to cooler areas. Thus, in the absence of a typical microclimate, access to water may allow rodents to overcome heat stress from extreme temperatures without having to shift their temporal active times.
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Respuesta al Choque Térmico , Locomoción , Muridae/fisiología , Animales , Temperatura Corporal , Ingestión de Líquidos , Conducta AlimentariaRESUMEN
Capitalizing on the massive increase in sample concentrations which are produced by extremely low elution volumes, nanoliquid chromatography-electrospray ionization-tandem mass spectrometry (nano-LC-ESI-MS/MS) is currently one of the most sensitive analytical technologies for the comprehensive characterization of complex protein samples. However, despite tremendous technological improvements made in the production and the packing of monodisperse spherical particles for nanoflow high-pressure liquid chromatography (HPLC), current state-of-the-art systems still suffer from limits in operation at the maximum potential of the technology. With the recent introduction of the µPAC system, which provides perfectly ordered micropillar array based chromatographic support materials, completely new chromatographic concepts for optimization toward the needs of ultrasensitive proteomics become available. Here we report on a series of benchmarking experiments comparing the performance of a commercially available 50 cm micropillar array column to a widely used nanoflow HPLC column for the proteomics analysis of 10 ng of tryptic HeLa cell digest. Comparative analysis of LC-MS/MS-data corroborated that micropillar array cartridges provide outstanding chromatographic performance, excellent retention time stability, and increased sensitivity in the analysis of low-input proteomics samples and thus repeatedly yielded almost twice as many unique peptide and unique protein group identifications when compared to conventional nanoflow HPLC columns.
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Proteínas/análisis , Proteómica/métodos , Cromatografía Líquida de Alta Presión/métodos , Células HeLa , Humanos , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
There is widespread agreement that taxpayers pay more when Medicare beneficiaries are enrolled in Medicare Advantage (MA) plans than if those beneficiaries were enrolled in traditional Medicare. MA plans are paid on the basis of submitted diagnoses and thus have a clear incentive to encourage providers to find and report as many diagnoses for their enrollees as possible. Two mechanisms that MA plans use to identify diagnoses that are not available for beneficiaries in traditional Medicare are in-home health risk assessments and chart reviews. Using MA encounter data for 2015-20, I isolated the impact of these two types of encounters on the risk scores used for payments to MA plans during 2016-21. I found that encounter-based risk scores for MA enrollees were higher by 0.091 points, or 7.4 percent, in 2021 when in-home health risk assessments and chart reviews were included than they would have been without the use of these tools.
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Medicare Part C , Humanos , Estados Unidos , Medición de Riesgo , Anciano , Masculino , Femenino , Anciano de 80 o más Años , Codificación Clínica , Servicios de Atención de Salud a Domicilio/economíaRESUMEN
The United States offers two markedly different subsidy structures for private health insurance. When covered through employer-based plans, employees and their dependents benefit from the exclusion from taxable income of the premiums. Individuals without access to employer coverage may obtain subsidies for Marketplace coverage. This paper seeks to understand how the public subsidies embedded in the privately financed portion of the U.S. healthcare system impact the payments families are required to make under both ESI and Marketplace coverage, and the implications for finance equity. Using the Household Component of the Medical Expenditure Panel Survey (MEPS-HC) and Marketplace premium data, we assess horizontal and vertical equity by calculating public subsidies for and expected family spending under each coverage source and using Lorenz curves and Gini and concentration coefficients. Our study pooled the 2018 and 2019 MEPS-HC to achieve a sample size of 10,593 observations. Our simulations showed a marked horizontal inequity for lower-income families with access to employer coverage who cannot obtain Marketplace subsidies. Relative to both the financing of employer coverage and earlier Marketplace tax credits, the more generous Marketplace premium subsidies, first made available in 2021 under the American Rescue Plan Act, substantially increased the vertical equity of Marketplace financing. While Marketplace subsidies have clearly improved equity within the United States, we conclude with a comparison to other OECD countries highlighting the persistence of inequities in the U.S. stemming from its noteworthy reliance on employer-based private health insurance.
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Seguro de Salud , Humanos , Estados Unidos , Seguro de Salud/economía , Seguro de Salud/estadística & datos numéricos , Financiación Gubernamental/estadística & datos numéricos , Financiación Gubernamental/economía , Cobertura del Seguro/estadística & datos numéricos , Cobertura del Seguro/economía , Intercambios de Seguro Médico/economía , Intercambios de Seguro Médico/estadística & datos numéricos , Sector Privado/economía , Sector Privado/estadística & datos numéricos , Planes de Asistencia Médica para Empleados/economía , Planes de Asistencia Médica para Empleados/estadística & datos numéricosRESUMEN
BACKGROUND: The imaging of patients with implanted electrically-conductive devices via magnetic resonance imaging at ultra-high fields is hampered by uncertainties relating to the potential for inducing tissue heating adjacent to the implant due to coupling of energy from the incident electromagnetic field into the implant. Existing data in the peer-reviewed literature of comparisons across field strengths of tissue heating and its surrogate, the specific absorption rate (SAR), is scarce and contradictory, leading to further doubts pertaining to the safety of imaging patients with such devices. PURPOSE: The radiofrequency-induced SAR adjacent to orthopedic screws of varying length and at frequencies of 64 to 498 MHz was investigated via full-wave electromagnetic simulations, to provide an accurate comparison of SAR across MRI field strengths. METHODS: Dipole antennas were used for RF transmission to achieve a uniform electric field tangential to the screws located 120 mm above the antenna midpoints, embedded in a bone-mimicking material. The input power to the antennas was constrained to achieve the following targets without the screw present: (i) E = 100 V/m, (ii) B1 + = 2 µT, and (iii) global-average-SAR = 3.2 W/kg. Simulations were performed with a spatial resolution of 0.2 mm in the volume surrounding the screws, resulting in 76-137 MCells, noting the maximum 1 g-averaged SAR value in each case. Simulations were repeated at 128 and 297 MHz for screws embedded in muscle tissue. RESULTS: The peak SAR, occurring at the resonant screw length, substantially increased as the frequency decreased when the input power to the dipole antenna was constrained to achieve constant electric field in background tissue at the screws' locations. A similar pattern was observed when constraining input power to achieve constant B1 + and global-average-SAR. The dielectric properties of the tissue in which the screws were embedded dominated the SAR comparisons between 297 and 128 MHz. CONCLUSIONS: The study design allowed for a direct comparison to be performed of SAR across frequencies and implant lengths without the confounding effect of variable incident electric field. Lower frequencies produced substantially larger SAR values for implants approaching the resonant length for the worst-case uniform incident electric field along the screws' length. The data may inform risk-benefit assessments for imaging patients with orthopedic implants at the new clinical field strength of 7 Tesla.