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1.
Semin Plast Surg ; 38(1): 69-73, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38495058

RESUMO

In this article, we examine the 60-year history of diversity efforts within the Section of Plastic Surgery at the University of Michigan (UofM) in the context of national trends. We describe the experiences of pioneering Underrepresented in Medicine (URiM) and female graduates of the program. James Norris, MD, and Christine Sullivan, MD, were the first URiM and female graduates from UofM in 1974 and 1989, respectively. Currently, women constitute over one-half the plastic surgery trainees at UofM, but URiM trainee representation remains limited. Dr. Adeyiza Momoh and Dr. Amy Alderman were the first URiM and female faculty members hired in 2011 and 2004, respectively. At present, there are four URiM and seven female faculty members in the Section. With a shared vision, supportive leadership, and motivation to change, faculty diversity has increased substantially. Additional strategies, including ongoing pipeline programs in medicine and science for URiM and women, are needed to further increase workforce diversity in plastic surgery.

2.
J Neurol ; 270(9): 4368-4376, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37219604

RESUMO

BACKGROUND: Enhancing brain parenchymal disease, and especially tumefactive lesions, are an uncommon manifestation of neurosarcoidosis. Little is known about the clinical features of tumefactive lesions and their impact on management and outcomes, which this study aims to characterize. METHODS: Patients with pathologically-confirmed sarcoidosis were retrospectively reviewed and included if brain lesions were: (1) intraparenchymal, (2) larger than 1 cm in diameter, and (3) associated with edema and/or mass effect. RESULTS: Nine patients (9/214, 4.2%) were included. Median onset age was 37 years. Diagnosis was confirmed by brain parenchymal biopsies in 5 (55.6%). Median modified Rankin scale (mRS) score was 2 (range 1-4) at initial presentation. Common manifestations included headache (77.8%), cognitive dysfunction (66.7%), and seizures (44.4%). Sixteen lesions were present in 9 patients. The frontal lobe (31.3%) was most affected, followed by the subinsular region (12.5%), basal ganglia (12.5%%), cerebellum (12.5%), and pons (12.5%). MRI characteristics of the dominant lesions included spherical morphology (77.8%), perilesional edema (100.0%), mass effect (55.6%), well-demarcated borders (66.7%), and contrast enhancement (100.0%; 55.6% heterogeneous). Leptomeningitis was frequently present (77.8%). All required corticosteroid-sparing treatments, and most (55.6%) needed at least a third line of treatment (infliximab used in 44.4%). All patients relapsed (median 3 relapses, range 1-9). Median last mRS was 1.0 after median follow-up of 86 months, with significant residual deficits in 55.6%. CONCLUSION: Tumefactive brain parenchymal lesions are uncommon, usually affect the supratentorial brain along with leptomeningitis, and are refractory to initial treatments with a high risk of relapse. Significant sequelae were encountered despite a favorable median last mRS.


Assuntos
Encefalopatias , Doenças do Sistema Nervoso Central , Sarcoidose , Humanos , Adulto , Estudos Retrospectivos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/patologia , Sarcoidose/diagnóstico por imagem , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia , Imageamento por Ressonância Magnética , Encefalopatias/diagnóstico por imagem , Encefalopatias/tratamento farmacológico , Encefalopatias/patologia
3.
J Phys Chem A ; 127(16): 3692-3704, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-36912654

RESUMO

The sulfones are a widespread group of organo-sulfur compounds, which contain the sulfonyl SO2 group attached to two carbons and have a formal sulfur oxidation state of +2. We have examined the sulfur K near-edge X-ray absorption spectroscopy (XAS) of a range of different sulfones and find substantial spectroscopic variability depending upon the nature of the coordination to the sulfonyl group. We have also examined the sulfur Kß X-ray emission spectroscopy (XES) of selected representative sulfones. Density functional theory simulations show satisfactory reproduction of both absorption and emission spectra while enabling assignment of the various transitions comprising the spectra. The correspondence between observed and simulated spectra shows promise for ab initio prediction of sulfur X-ray absorption and emission spectra of sulfones of any substituent. The absorption spectra and, to a lesser extent, the emission spectra are sensitive to the nature of the organic groups bound to the sulfonyl (SO2) moiety, clearly showing the potential of X-ray spectroscopy as an in situ probe of sulfone chemistry.

4.
Front Immunol ; 14: 1105103, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969261

RESUMO

Introduction: MISTRG mice have been genetically modified to allow development of a human myeloid compartment from engrafted human CD34+ haemopoietic stem cells, making them particularly suited to study the human innate immune system in vivo. Here, we characterized the human neutrophil population in these mice to establish a model that can be used to study the biology and contribution in immune processes of these cells in vivo. Methods and results: We could isolate human bone marrow neutrophils from humanized MISTRG mice and confirmed that all neutrophil maturation stages from promyelocytes (CD11b-CD16-) to end-stage segmented cells (CD11b+CD16+) were present. We documented that these cells possessed normal functional properties, including degranulation, reactive oxygen species production, adhesion, and antibody-dependent cellular cytotoxicity towards antibody-opsonized tumor cells ex vivo. The acquisition of functional capacities positively correlated with the maturation state of the cell. We found that human neutrophils were retained in the bone marrow of humanized MISTRG mice during steady state. However, the mature segmented CD11b+CD16+ human neutrophils were released from the bone marrow in response to two well-established neutrophil-mobilizing agents (i.e., G-CSF and/or CXCR4 antagonist Plerixafor). Moreover, the neutrophil population in the humanized MISTRG mice actively reacted to thioglycolate-induced peritonitis and could infiltrate implanted human tumors, as shown by flow cytometry and fluorescent microscopy. Discussion: These results show that functional human neutrophils are generated and can be studied in vivo using the humanized MISTRG mice, providing a model to study the various functions of neutrophils in inflammation and in tumors.


Assuntos
Compostos Heterocíclicos , Neutrófilos , Humanos , Camundongos , Animais , Mobilização de Células-Tronco Hematopoéticas , Medula Óssea , Imunidade
5.
J Environ Manage ; 336: 117689, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36924710

RESUMO

Multi-objective design approaches can help identify future infrastructure system designs that appropriately balance different engineering, environmental, and other societal goals. Planners benefit from assessing the trade-offs implied by the best-performing infrastructure system solutions. However, a large number of possible efficient system designs, obtained when using multi-objective optimization, can be overwhelming to interpret. This study attempts to aid decision-making in multi-criteria infrastructure system design by reducing the complexity of the identified set of efficient infrastructure designs, i.e., the Pareto-front. A soft clustering algorithm is applied, which identifies similarities between solutions, partitions the front accordingly, and selects a set of representative solutions while preserving the multi-dimensional structure of the solutions on the efficiency frontier. Three post-optimization decision-making metrics are introduced to help quantify the overall performance of the Pareto-optimal designs to further summarize design process outputs for decision-makers. We apply the method to an illustrious urban drainage network case study. Results show how the approach can simplify Pareto-fronts with thousands of solutions into sets of highlighted designs that aid interpreting the trade-offs implied by the best-performing simulated systems.


Assuntos
Algoritmos , Engenharia , Tomada de Decisões
6.
Inorg Chem ; 62(6): 2637-2651, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36716427

RESUMO

Desferrioxamine (DFO) has long been considered the gold standard chelator for incorporating [89Zr]Zr4+ in radiopharmaceuticals for positron emission tomography (PET) imaging. To improve the stability of DFO with zirconium-89 and to expand its coordination sphere to enable binding of large therapeutic radiometals, we have synthesized the highest denticity DFO derivatives to date: dodecadentate DFO2 and DFO2p. In this study, we describe the synthesis and characterization of a novel DFO-based chelator, DFO2p, which is comprised of two DFO strands connected by an p-NO2-phenyl linker and therefore contains double the chelating moieties of DFO (potential coordination number up to 12 vs 6). The chelator DFO2p offers an optimized synthesis comprised of only a single reaction step and improves water solubility relative to DFO2, but the shorter linker reduces molecular flexibility. Both DFO2 and DFO2p, each with 6 potential hydroxamate ligands, are able to reach a more energetically favorable 8-coordinate environment for Zr(IV) than DFO. The zirconium(IV) coordination environment of these complexes were evaluated by a combination of density functional theory (DFT) calculations and synchrotron spectroscopy (extended X-ray absorption fine structure), which suggest the inner-coordination sphere of zirconium(IV) to be comprised of the outermost four hydroxamate ligands. These results also confirm a single Zr(IV) in each chelator, and the hydroxide ligands which complete the coordination sphere of Zr(IV)-DFO are absent from Zr(IV)-DFO2 and Zr(IV)-DFO2p. Radiochemical stability studies with zirconium-89 revealed the order of real-world stability to be DFO2 > DFO2p ≫ DFO. The zirconium-89 complexes of these new high-denticity chelators were found to be far more stable than DFO, and the decreased molecular flexibility of DFO2p, relative to DFO2, could explain its decreased stability, relative to DFO2.

7.
Cancer Biother Radiopharm ; 38(8): 528-535, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33481653

RESUMO

Background: Targeted α particle therapy using long-lived in vivo α particle generators is cytotoxic to target tissues. However, the redistribution of released radioactive daughters through the circulation should be considered. A mathematical model was developed to describe the physicochemical kinetics of 212Pb-labeled pharmaceuticals and its radioactive daughters. Materials and Methods: A bolus of 212Pb-labeled pharmaceuticals injected in a developed compartmental model was simulated. The contributions of chelated and free radionuclides to the total released energy were investigated for different dissociation fractions of 212Bi for different chelators, for example, 36% for DOTA. The compartmental model was applied to describe a 212Bi retention study and to assess the stability of the 212Bi-1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (212Bi-DOTAM) complex after ß- decay of 212Pb. Results: The simulation of the injection showed that α emissions contribute 75% to the total released energy, mostly from 212Po (72%). The simulation of the 212Bi retention study showed that (16 ± 5)% of 212Bi atoms dissociate from the 212Bi-DOTAM complexes. The fractions of energies released by free radionuclides were 21% and 38% for DOTAM and DOTA chelators, respectively. Conclusion: The developed α particle generator model allows for simulating the radioactive kinetics of labeled and unlabeled pharmaceuticals being released from the chelating system due to a preceding disintegration.


Assuntos
Partículas alfa , Quelantes , Humanos , Quelantes/química , Chumbo , Radioisótopos/química , Modelos Teóricos , Preparações Farmacêuticas , Compostos Radiofarmacêuticos
8.
Nature ; 610(7932): 485-490, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36261554

RESUMO

Attitude control is an essential flight capability. Whereas flying robots commonly rely on accelerometers1 for estimating attitude, flying insects lack an unambiguous sense of gravity2,3. Despite the established role of several sense organs in attitude stabilization3-5, the dependence of flying insects on an internal gravity direction estimate remains unclear. Here we show how attitude can be extracted from optic flow when combined with a motion model that relates attitude to acceleration direction. Although there are conditions such as hover in which the attitude is unobservable, we prove that the ensuing control system is still stable, continuously moving into and out of these conditions. Flying robot experiments confirm that accommodating unobservability in this manner leads to stable, but slightly oscillatory, attitude control. Moreover, experiments with a bio-inspired flapping-wing robot show that residual, high-frequency attitude oscillations from flapping motion improve observability. The presented approach holds a promise for robotics, with accelerometer-less autopilots paving the road for insect-scale autonomous flying robots6. Finally, it forms a hypothesis on insect attitude estimation and control, with the potential to provide further insight into known biological phenomena5,7,8 and to generate new predictions such as reduced head and body attitude variance at higher flight speeds9.


Assuntos
Fenômenos Biomecânicos , Fluxo Óptico , Robótica , Animais , Voo Animal , Insetos , Modelos Biológicos , Robótica/métodos , Asas de Animais , Acelerometria , Biomimética , Materiais Biomiméticos , Movimento (Física)
9.
Nat Commun ; 13(1): 5041, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-36028486

RESUMO

The 2030 Sustainable Development Goals (SDGs) aim at jointly improving economic, social, and environmental outcomes for human prosperity and planetary health. However, designing national economic policies that support advancement across multiple Sustainable Development Goals is hindered by the complexities of multi-sector economies and often conflicting policies. To address this, we introduce a national-scale design framework that can enable policymakers to sift through complex, non-linear, multi-sector policy spaces to identify efficient policy portfolios that balance economic, social, and environmental goals. The framework combines economy-wide sustainability simulation and artificial intelligence-driven multiobjective, multi-SDG policy search and machine learning. The framework can support multi-sector, multi-actor policy deliberation to screen efficient policy portfolios. We demonstrate the utility of the framework for a case study of Egypt by identifying policy portfolios that achieve efficient mixes of poverty and inequality reduction, economic growth, and climate change mitigation. The results show that integrated policy strategies can help achieve sustainable development while balancing adverse economic, social, and political impacts of reforms.


Assuntos
Inteligência Artificial , Desenvolvimento Sustentável , Mudança Climática , Egito , Humanos , Pobreza
10.
Fetal Diagn Ther ; 49(9-10): 377-384, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36044834

RESUMO

BACKGROUND: Given the maternal morbidity of open fetal surgery, the development of prenatal fetoscopic repair for spina bifida aperta (SBA) is encouraged. OBJECTIVE: We hereby report the early results from our center, using a laparotomy-assisted CO2-fetoscopic approach. METHODS: This study was conducted in patients with an SBA < T1 and >S1, <26 weeks of gestation, with Chiari II. Fetoscopic repair was performed using 2 operating trocars in the uterus exteriorized through a transverse laparotomy. Endoscopy was performed under humidified and heated CO2 insufflation. Following dissection of the lesion, a 1-layer approach was performed with a muscle/skin flap sutured over a patch of Duragen. Main outcomes were watertight repair at birth and the need for postnatal neurosurgical surgery including shunting within 6 months. RESULTS: Of 87 women assessed for prenatal therapy, 7 were included. Surgery was performed at 24 (23-26) weeks' gestation. There was no fetal demise. Conversion to hysterotomy was not performed, although surgery could not be performed in 1 case because of fetal position. Severe preeclampsia developed postoperatively in 1 case. In the other 6 cases, follow-up was uneventful except for premature rupture membranes which occurred in 3/6 cases at 30, 34, and 36+5 weeks' gestation. Gestational age at delivery was 32 + 5 (31-36 + 5) weeks' gestation. Repair was watertight at birth except in 2 cases which required complementary postnatal surgical repair. Reverse hindbrain herniation during pregnancy was observed in 4/6 cases. In 3/6 cases, shunting was necessary within 6 months after birth. At 12 months, a functional gain of ≥2 metameric levels was observed in 3 cases of the 6 survivors. CONCLUSION: Laparotomy-assisted fetoscopic repair is a reasonable option for women who choose and are eligible for antenatal surgery, both in terms of maternal and perinatal morbidity.


Assuntos
Meningomielocele , Espinha Bífida Cística , Recém-Nascido , Gravidez , Feminino , Humanos , Lactente , Espinha Bífida Cística/diagnóstico por imagem , Espinha Bífida Cística/cirurgia , Paris , Laparotomia , Dióxido de Carbono , Fetoscopia/métodos , Idade Gestacional , França , Meningomielocele/cirurgia
11.
Energy Econ ; 111: None, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35781933

RESUMO

Large energy infrastructure can imply special financing arrangements between governments in developing economies and investors or lenders. These arrangements can lead to economy-wide and sector-specific impacts which need to be considered in the project economic evaluation. By considering the case of the Bui Dam in Ghana, we use a macroeconomic approach to determine how the economic performance of critical energy infrastructure manifests during the construction, financing and operation phases. The analysis uses an integrated modelling framework that combines a Computable General Equilibrium (CGE) model of Ghana with a water balance model of the Lower Volta River Basin. The results highlight the importance of including indirect and induced effects, in addition to the direct effects from project operation, as they influence the scale and temporal evolution of the economic impacts. The collateral from the infrastructure loan agreement consisting in cocoa exports to China nearly doubles the project's positive GDP impact and has a significant multiplier effect over urban and rural household income compared to a standard commercial loan. We finish with a discussion of how the proposed investment-oriented modelling framework can contribute to ex-ante strategic assessments of proposed energy infrastructure in developing countries.

12.
ACS Chem Neurosci ; 13(12): 1756-1768, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35543423

RESUMO

Mercury is ubiquitous in the environment, with rising levels due to pollution and climate change being a current global concern. Many mercury compounds are notorious for their toxicity, with the potential of organometallic mercury compounds for devastating effects on the structures and functions of the central nervous system being of particular concern. Chronic exposure of human populations to low levels of methylmercury compounds occurs through consumption of fish and other seafood, although the health consequences, if any, from this exposure remain controversial. We have used high energy resolution fluorescence detected X-ray absorption spectroscopy to determine the speciation of mercury and selenium in human brain tissue. We show that the molecular fate of mercury differs dramatically between individuals who suffered acute organometallic mercury exposure (poisoning) and individuals with chronic low-level exposure from a diet rich in marine fish. For long-term low-level methylmercury exposure from fish consumption, mercury speciation in brain tissue shows methylmercury coordinated to an aliphatic thiolate, resembling the coordination environment observed in marine fish. In marked contrast, for short-term high-level exposure, we observe the presence of biologically less available mercuric selenide deposits, confirmed by X-ray fluorescence imaging, as well as mercury(II)-bis-thiolate complexes, which may be signatures of severe poisoning in humans. These differences between low-level and high-level exposures challenge the relevance of studies involving acute exposure as a proxy for low-level chronic exposure.


Assuntos
Compostos de Mercúrio , Mercúrio , Compostos de Metilmercúrio , Animais , Encéfalo , Peixes , Contaminação de Alimentos/análise , Humanos , Mercúrio/análise , Mercúrio/toxicidade , Compostos de Metilmercúrio/análise , Compostos de Metilmercúrio/toxicidade
14.
Inorg Chem ; 61(13): 5201-5214, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35073478

RESUMO

Mercury is in some sense an enigmatic element. The element and some of its compounds are a natural part of the biogeochemical cycle; while many of these can be deadly poisons at higher levels, environmental levels in the absence of anthropogenic contributions would generally be below the threshold for concern. However, mercury pollution, particularly from burning fossil fuels such as coal, is providing dramatic and increasing emissions into the environment. Because of this, the environmental chemistry and toxicology of mercury are of growing importance, with the fate of mercury being vitally dependent upon its speciation. X-ray absorption spectroscopy (XAS) provides a powerful tool for in situ chemical speciation, but is severely limited by poor spectroscopic energy resolution. Here, we provide a systematic examination of mercury Lα1 high energy resolution fluorescence detected XAS (HERFD-XAS) as an approach for chemical speciation of mercury, in quantitative comparison with conventional Hg LIII-edge XAS. We show that, unlike some lighter elements, chemical shifts in the Lα1 X-ray fluorescence energy can be safely neglected, so that mercury Lα1 HERFD-XAS can be treated simply as a high-resolution version of conventional XAS. We present spectra of a range of mercury compounds that may be relevant to the environmental and life science research and show that density functional theory can produce adequate simulations of the spectra. We discuss strengths and limitations of the method and quantitatively demonstrate improvements both in speciation for complex mixtures and in background rejection for low concentrations.


Assuntos
Mercúrio , Espectroscopia por Absorção de Raios X
15.
J Environ Manage ; 302(Pt A): 114035, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34741946

RESUMO

Climate change is a challenge to drinking water providers worldwide and to regulatory frameworks that consider long-term investment decisions. Coping with an unstable climate warrants adjustments in regulations and new investments. The investment required to maintain a selected service level needs to balance the potential for high regret stranded assets with the political and socioeconomic consequences of not meeting water demands. In recent years, the City of Santiago in Chile has seen drought events associated with climate change, which could worsen in the future. Chile's drinking water regulatory framework does not account for uncertainty in infrastructure design to cope with the potential impacts of such events. This work presents an adaptation option design process that considers multiple plausible climate change-impacted future scenarios, accommodating both structural and nonstructural measures. In our Santiago case study adaptation measures include extensions to the existing Chilean water market and traditional structural alternatives (e.g., storage infrastructure); all are represented in a simulation model of the water utility. We evaluate and optimize packages of efficient adaptation measures for various climate scenarios. This allows comparing different portfolios of combined institutional and infrastructure interventions via a range of stakeholder measures and comparing their tradeoffs under different plausible climate-impacted hydrological scenarios. Results showed that water supply performance without climate change adaptation is worse under climate scenarios with lower water availability, which are likely to be associated with higher GHG emission scenarios such as RCP 8.5. The optimized portfolios implement various combinations of adaptation strategies to reduce the impacts of this poor performance. Considering the uncertainty on future climate scenarios, the use of nonstructural adaptation measures such as option contracts exhibits the advantage of providing water in critical periods while avoiding large investments such as building reservoirs or the purchase of permanent water rights, which could end up underused if favorable climate scenarios manifest.


Assuntos
Mudança Climática , Água Potável , Chile , Secas , Abastecimento de Água
16.
J Neurol ; 269(4): 2064-2072, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34487233

RESUMO

BACKGROUND: Tumor necrosis factor (TNF) alpha is critical in the development of granulomas and multiple recent reports have highlighted the role of infliximab, an infused TNF alpha inhibitor, in the treatment of neurosarcoidosis. As a self-injected TNF alpha inhibitor, adalimumab has certain advantages over infused medications, including greater patient freedom and autonomy. Experience with adalimumab is not well reported in the literature. OBJECTIVE: To report clinical experience with adalimumab in the treatment of central nervous system (CNS) sarcoidosis by combining observations in our center with those that have been reported in the literature. METHODS: Patients were identified from the Mass General Brigham Research Patient Data Registry and in the literature by searching PubMed. Patients with CNS manifestations of sarcoidosis treated with adalimumab were included for retrospective review and analyzed for baseline characteristics, treatment indications, outcomes, and adverse effects. RESULTS: Adalimumab was commonly started after failure of or intolerance to infliximab and methotrexate. Of those with adequate follow-up, 5/10 ultimately improved, remission was maintained in 3/10, and 2/10 with active disease remained stable without further worsening. One patient suffered a relapse, likely multifactorial in etiology, but has remained relapse free on adalimumab for 10 months subsequently. Three patients ultimately discontinued adalimumab. CONCLUSIONS: Preliminary evidence suggests that adalimumab may be a reasonable therapeutic option for patients with neurosarcoidosis affecting the CNS, including those with medically refractory disease.


Assuntos
Doenças do Sistema Nervoso Central , Sarcoidose , Adalimumab/uso terapêutico , Sistema Nervoso Central , Doenças do Sistema Nervoso Central/tratamento farmacológico , Humanos , Infliximab/uso terapêutico , Sarcoidose/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico
17.
J Synchrotron Radiat ; 28(Pt 6): 1845-1849, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34738938

RESUMO

Oxygen K-edge X-ray absorption spectroscopy is used routinely to study a range of solid materials. However, liquid samples are studied less frequently at the oxygen K-edge due to the combined challenges of high-vacuum conditions and oxygen contamination of window materials. A modular sample holder design with a twist-seal sample containment system that provides a simple method to encapsulate liquid samples under high-vacuum conditions is presented. This work shows that pure silicon nitride windows have lower oxygen contamination than both diamond- and silicon-rich nitride windows, that the levels of oxygen contamination are related to the age of the windows, and provides a protocol for minimizing the background oxygen contamination. Acid-washed 100 nm-thick silicon nitride windows were found to give good quality oxygen K-edge data on dilute liquid samples.


Assuntos
Oxigênio , Radiografia , Espectroscopia por Absorção de Raios X , Raios X
18.
Presse Med ; 50(2): 104092, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34715293

RESUMO

BACKGROUND AND OBJECTIVES: Despite immense progress of imaging and updates in the MacDonald criteria, the diagnosis of multiple sclerosis remains difficult as it must integrate history, clinical presentation, biological markers, and imaging. There is a multitude of syndromes resembling multiple sclerosis both clinically or on imaging. The goal of this review is to help clinicians orient themselves in these various diagnoses. We organized our review in two categories: inflammatory and autoimmune diseases that are close or can be confused with multiple sclerosis, and non-inflammatory syndromes that can present with symptoms or imaging mimicking those of multiple sclerosis. METHOD: Review of literature CONCLUSION: Progress of imaging and biological sciences have drastically changed the approach and management of multiple sclerosis. But these developments have also shined a light on a variety of diseases previously unknown or poorly known, therefore greatly expanding the differential diagnosis of multiple sclerosis. While autoimmune, many of these diseases have underlying biological mechanisms that are very different from those of multiple sclerosis, rendering MS therapies usually inefficient. It is crucial to approach these diseases with utmost thoroughness, integrating history, clinical exam, and evolving ancillary tests.


Assuntos
Esclerose Múltipla/diagnóstico por imagem , Doença Aguda , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Doença Crônica , Diagnóstico Diferencial , Encefalite/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Transtornos de Enxaqueca/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/tratamento farmacológico , Doenças do Nervo Óptico/diagnóstico por imagem , Doenças do Nervo Óptico/tratamento farmacológico , Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Parestesia/diagnóstico , Sarcoidose/diagnóstico por imagem , Prevenção Secundária/métodos , Transtornos Somatoformes/diagnóstico
19.
Front Immunol ; 12: 725989, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566984

RESUMO

Approximately 1 in 4 pregnant women in the United States undergo labor induction. The onset and establishment of labor, particularly induced labor, is a complex and dynamic process influenced by multiple endocrine, inflammatory, and mechanical factors as well as obstetric and pharmacological interventions. The duration from labor induction to the onset of active labor remains unpredictable. Moreover, prolonged labor is associated with severe complications for the mother and her offspring, most importantly chorioamnionitis, uterine atony, and postpartum hemorrhage. While maternal immune system adaptations that are critical for the maintenance of a healthy pregnancy have been previously characterized, the role of the immune system during the establishment of labor is poorly understood. Understanding maternal immune adaptations during labor initiation can have important ramifications for predicting successful labor induction and labor complications in both induced and spontaneous types of labor. The aim of this study was to characterize labor-associated maternal immune system dynamics from labor induction to the start of active labor. Serial blood samples from fifteen participants were collected immediately prior to labor induction (baseline) and during the latent phase until the start of active labor. Using high-dimensional mass cytometry, a total of 1,059 single-cell immune features were extracted from each sample. A multivariate machine-learning method was employed to characterize the dynamic changes of the maternal immune system after labor induction until the establishment of active labor. A cross-validated linear sparse regression model (least absolute shrinkage and selection operator, LASSO) predicted the minutes since induction of labor with high accuracy (R = 0.86, p = 6.7e-15, RMSE = 277 min). Immune features most informative for the model included STAT5 signaling in central memory CD8+ T cells and pro-inflammatory STAT3 signaling responses across multiple adaptive and innate immune cell subsets. Our study reports a peripheral immune signature of labor induction, and provides important insights into biological mechanisms that may ultimately predict labor induction success as well as complications, thereby facilitating clinical decision-making to improve maternal and fetal well-being.


Assuntos
Adaptação Fisiológica/imunologia , Trabalho de Parto Induzido , Trabalho de Parto/imunologia , Adulto , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Imunoensaio , Modelos Lineares , Aprendizado de Máquina , Gravidez , Fatores de Transcrição STAT/imunologia , Transdução de Sinais/imunologia , Estados Unidos
20.
Nat Commun ; 12(1): 5622, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556643

RESUMO

The landscape of water infrastructure in the Nile Basin is changing with the construction of the Grand Ethiopian Renaissance Dam. Although this dam could improve electricity supply in Ethiopia and its neighbors, there is a lack of consensus between Ethiopia, Sudan, and Egypt on the dam operation. We introduce a new modeling framework that simulates the Nile River System and Egypt's macroeconomy, with dynamic feedbacks between the river system and the macroeconomy. Because the two systems "coevolve" throughout multi-year simulations, we term this a "coevolutionary" modeling framework. The framework is used to demonstrate that a coordinated operating strategy could allow the Grand Ethiopian Renaissance Dam to help meet water demands in Egypt during periods of water scarcity and increase hydropower generation and storage in Ethiopia during high flows. Here we show the hydrological and macroeconomic performance of this coordinated strategy compared to a strategy that resembles a recent draft proposal for the operation of the dam discussed in Washington DC.

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