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2.
Nature ; 575(7782): 380-384, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31666695

RESUMO

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Potencial da Membrana Mitocondrial , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Camundongos , Camundongos Transgênicos , Compostos Organofosforados , Tomografia por Emissão de Pósitrons
3.
J Perinat Med ; 52(4): 445-451, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38436066

RESUMO

OBJECTIVES: Near infrared spectroscopy (NIRS) is a non-invasive method for monitoring regional tissue oxygen saturation (rSO2). The purpose of this study is to investigate the changes that occur in cerebral, splanchnic, and renal rSO2 and fractional tissue oxygen extraction (FTOE) in stable preterm infants in the first week of life. METHODS: Prospective observational study of infants born 30-34 weeks gestation at NYU Langone Health between November 2017 and November 2018. Cerebral, renal, and splanchnic rSO2 were monitored from 12 to 72 h of life, and at seven days. Subjects were divided into gestational age (GA) cohorts. Average rSO2, splanchnic cerebral oxygen ratio (SCOR), FTOE, and regional intra-subject variability was calculated at each location at five different time intervals: 0-12 h, 12-24 h, 24-48 h, 48-72 h, and one week of life. RESULTS: Twenty subjects were enrolled. The average cerebral rSO2 ranged from 76.8 to 92.8 %, renal rSO2 from 65.1 to 91.1 %, and splanchnic rSO2 from 36.1 to 76.3 %. The SCOR ranged from 0.45 to 0.94. The strongest correlation between the GA cohorts was in the cerebral region (R2=0.94) and weakest correlation was in the splanchnic region (R2=0.81). The FTOE increased in all three locations over time. Intra-subject variability was lowest in the cerebral region (1.3 % (±1.9)). CONCLUSIONS: The cerebral region showed the strongest correlation between GA cohorts and lowest intra-subject variability, making it the most suitable for clinical use when monitoring for tissue hypoxia. Further studies are needed to further examine rSO2 in preterm infants.


Assuntos
Recém-Nascido Prematuro , Saturação de Oxigênio , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Recém-Nascido , Saturação de Oxigênio/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Feminino , Estudos Prospectivos , Masculino , Oxigênio/metabolismo , Oxigênio/sangue , Encéfalo/metabolismo , Idade Gestacional , Rim/metabolismo
4.
EMBO J ; 38(22): e101056, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31609012

RESUMO

The mitochondrial membrane potential (ΔΨm ) is the main driver of oxidative phosphorylation (OXPHOS). The inner mitochondrial membrane (IMM), consisting of cristae and inner boundary membranes (IBM), is considered to carry a uniform ΔΨm . However, sequestration of OXPHOS components in cristae membranes necessitates a re-examination of the equipotential representation of the IMM. We developed an approach to monitor ΔΨm at the resolution of individual cristae. We found that the IMM was divided into segments with distinct ΔΨm , corresponding to cristae and IBM. ΔΨm was higher at cristae compared to IBM. Treatment with oligomycin increased, whereas FCCP decreased, ΔΨm heterogeneity along the IMM. Impairment of cristae structure through deletion of MICOS-complex components or Opa1 diminished this intramitochondrial heterogeneity of ΔΨm . Lastly, we determined that different cristae within the individual mitochondrion can have disparate membrane potentials and that interventions causing acute depolarization may affect some cristae while sparing others. Altogether, our data support a new model in which cristae within the same mitochondrion behave as independent bioenergetic units, preventing the failure of specific cristae from spreading dysfunction to the rest.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Potencial da Membrana Mitocondrial , Mitocôndrias/fisiologia , Membranas Mitocondriais/metabolismo , Mioblastos/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Células Cultivadas , Feminino , Células HeLa , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Mioblastos/citologia , Fosforilação Oxidativa
5.
Proc Natl Acad Sci U S A ; 117(13): 7374-7381, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32170007

RESUMO

Irinotecan treats a range of solid tumors, but its effectiveness is severely limited by gastrointestinal (GI) tract toxicity caused by gut bacterial ß-glucuronidase (GUS) enzymes. Targeted bacterial GUS inhibitors have been shown to partially alleviate irinotecan-induced GI tract damage and resultant diarrhea in mice. Here, we unravel the mechanistic basis for GI protection by gut microbial GUS inhibitors using in vivo models. We use in vitro, in fimo, and in vivo models to determine whether GUS inhibition alters the anticancer efficacy of irinotecan. We demonstrate that a single dose of irinotecan increases GI bacterial GUS activity in 1 d and reduces intestinal epithelial cell proliferation in 5 d, both blocked by a single dose of a GUS inhibitor. In a tumor xenograft model, GUS inhibition prevents intestinal toxicity and maintains the antitumor efficacy of irinotecan. Remarkably, GUS inhibitor also effectively blocks the striking irinotecan-induced bloom of Enterobacteriaceae in immune-deficient mice. In a genetically engineered mouse model of cancer, GUS inhibition alleviates gut damage, improves survival, and does not alter gut microbial composition; however, by allowing dose intensification, it dramatically improves irinotecan's effectiveness, reducing tumors to a fraction of that achieved by irinotecan alone, while simultaneously promoting epithelial regeneration. These results indicate that targeted gut microbial enzyme inhibitors can improve cancer chemotherapeutic outcomes by protecting the gut epithelium from microbial dysbiosis and proliferative crypt damage.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Glucuronidase/antagonistas & inibidores , Glucuronidase/efeitos dos fármacos , Animais , Antineoplásicos Fitogênicos/farmacologia , Bactérias/efeitos dos fármacos , Modelos Animais de Doenças , Disbiose/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Feminino , Glucuronidase/metabolismo , Humanos , Irinotecano/farmacologia , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico
6.
J Perinat Med ; 51(4): 586-589, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-36190160

RESUMO

OBJECTIVES: In our neonatal intensive care unit (NICU), patients are screened for colonization with Staphylococcus aureus (S. aureus) and decolonized if positive. During the COVID-19 pandemic, our NICU significantly limited its visitor policy. We assessed for a difference between S. aureus colonization rates before and after the visitor policy change, which coincided with the exponential rise of COVID-19 cases in New York City (NYC). METHODS: We calculated rates of newly S. aureus colonized NICU patients during January to June 2020 and compared rates pre- and post-implementation of the new visitor policy. Additionally, we obtained the weekly incidence of COVID-19 in NYC and assessed for a correlation between COVID-19 rates and S. aureus colonization. RESULTS: The number of newly colonized patients per thousand patient days was 4.65 pre- and 3.95 post-implementation of the new visitor policy. The difference was not statistically significant (p=0.66). Furthermore, there was no correlation between the incidence of COVID-19 in NYC and the rates of S. aureus colonization in our NICU (R2=0.02). CONCLUSIONS: Our results suggest that limiting visitation of patients is not associated with a decrease in S. aureus colonization rate. Hospital unit leaders may need to focus on other strategies in order to reduce colonization.


Assuntos
COVID-19 , Infecção Hospitalar , Infecções Estafilocócicas , Recém-Nascido , Humanos , Staphylococcus aureus , Unidades de Terapia Intensiva Neonatal , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Pandemias/prevenção & controle , Estudos Retrospectivos , COVID-19/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/prevenção & controle
7.
J Perinat Med ; 51(4): 573-579, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-36318716

RESUMO

OBJECTIVES: Antenatal corticosteroids (ACS) administered to mothers at risk for preterm delivery before 34 weeks has been standard care to improve neonatal outcomes. After introducing a new obstetric policy based on updated recommendations advising the administration of ACS to pregnant women at risk for late preterm (LPT) delivery (34-36 6/7 weeks), we set out to determine the short-term clinical impact on those LPT neonates. METHODS: Retrospective chart review of LPT neonates delivered at NYU Langone Medical Center both one year before and after the policy went into place. We excluded subjects born to mothers with pre-gestational diabetes, multiple gestations, and those with congenital/genetic abnormalities. We also excluded subjects whose mothers already received ACS previously in pregnancy. Subjects were divided into pre-policy and post-policy groups. Neonatal and maternal data were compared for both groups. RESULTS: 388 subjects; 180 in the pre-policy and 208 in the post-policy group. This policy change resulted in a significant increase in ACS administration to mothers who delivered LPT neonates (67.3 vs. 20.6%, p<0.001). In turn, there was a significant reduction in LPT neonatal intensive care unit (NICU) admissions (44.2 vs. 54.4%, p=0.04) and need for respiratory support (27.9 vs. 42.8%, p<0.01). However, we also found an increased incidence of hypoglycemia (49.5 vs. 28.3%, p<0.001). CONCLUSIONS: This LPT ACS policy appears effective in reducing the need for LPT NICU level care overall. However, clinicians must be attentive to monitor for adverse effects like hypoglycemia, and there remains a need for better understanding of potential long-term impacts.


Assuntos
Hipoglicemia , Nascimento Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Gravidez , Humanos , Feminino , Nascimento Prematuro/prevenção & controle , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Idade Gestacional , Corticosteroides/efeitos adversos , Incidência , Hipoglicemia/complicações
8.
J Am Chem Soc ; 144(42): 19508-19520, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36208192

RESUMO

The resolution, line edge roughness, and sensitivity (RLS) trade-off has fundamentally limited the lithographic performance of chemically amplified resists. Production of next-generation transistors using extreme ultraviolet (EUV) lithography depends on a solution to this problem. A resist that simultaneously increases the effective reaction radius of its photogenerated acids while limiting their diffusion radius should provide an elegant solution to the RLS barrier. Here, we describe a generalized synthetic approach to phthalaldehyde derivatives using sulfur(VI) fluoride exchange click chemistry that dramatically expands usable chemical space by enabling virtually any non-ionic photoacid generator (PAG) to be tethered to phthalaldehyde. The resulting polymers represent the first ever PAG-tethered self-immolative resists in an architecture that simultaneously displays high contrast, extraordinary sensitivity, and low roughness under EUV exposure. We believe this class of resists will ultimately enable researchers to overcome the RLS trade-off.


Assuntos
Fluoretos , Polímeros , Polímeros/química , Ácidos/química , Difusão , Enxofre
9.
Ann Surg ; 275(6): 1094-1102, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35258509

RESUMO

OBJECTIVE: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. BACKGROUND: Elective surgery is an opportunity to understand both the systemic and focal responses accompanying controlled and well-characterized injury to the human body. The overarching goal of this ongoing project is to define stereotypical responses to surgical injury, with the translational purpose of identifying targetable pathways involved in healing and resilience, and variations indicative of aberrant peri-operative outcomes. METHODS: Clinical data from the electronic medical record combined with large-scale biological data sets derived from blood, urine, fecal matter, and tissue samples are collected prospectively through the peri-operative period on patients undergoing 14 surgeries chosen to represent a range of injury locations and intensities. Specimens are subjected to genomic, transcriptomic, proteomic, and metabolomic assays to describe their genetic, metabolic, immunologic, and microbiome profiles, providing a multidimensional landscape of the human response to injury. RESULTS: The highly multiplexed data generated includes changes in over 28,000 mRNA transcripts, 100 plasma metabolites, 200 urine metabolites, and 400 proteins over the longitudinal course of surgery and recovery. In our initial pilot dataset, we demonstrate the feasibility of collecting high quality multi-omic data at pre- and postoperative time points and are already seeing evidence of physiologic perturbation between timepoints. CONCLUSIONS: This repository allows for longitudinal, state-of-the-art geno-mic, transcriptomic, proteomic, metabolomic, immunologic, and clinical data collection and provides a rich and stable infrastructure on which to fuel further biomedical discovery.


Assuntos
Biologia Computacional , Proteômica , Genômica , Humanos , Metabolômica , Estudos Prospectivos , Proteômica/métodos
10.
Appl Opt ; 61(22): 6453-6475, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36255869

RESUMO

Ocean color (OC) remote sensing requires compensation for atmospheric scattering and absorption (aerosol, Rayleigh, and trace gases), referred to as atmospheric correction (AC). AC allows inference of parameters such as spectrally resolved remote sensing reflectance (Rrs(λ);sr-1) at the ocean surface from the top-of-atmosphere reflectance. Often the uncertainty of this process is not fully explored. Bayesian inference techniques provide a simultaneous AC and uncertainty assessment via a full posterior distribution of the relevant variables, given the prior distribution of those variables and the radiative transfer (RT) likelihood function. Given uncertainties in the algorithm inputs, the Bayesian framework enables better constraints on the AC process by using the complete spectral information compared to traditional approaches that use only a subset of bands for AC. This paper investigates a Bayesian inference research method (optimal estimation [OE]) for OC AC by simultaneously retrieving atmospheric and ocean properties using all visible and near-infrared spectral bands. The OE algorithm analytically approximates the posterior distribution of parameters based on normality assumptions and provides a potentially viable operational algorithm with a reduced computational expense. We developed a neural network RT forward model look-up table-based emulator to increase algorithm efficiency further and thus speed up the likelihood computations. We then applied the OE algorithm to synthetic data and observations from the moderate resolution imaging spectroradiometer (MODIS) on NASA's Aqua spacecraft. We compared the Rrs(λ) retrieval and its uncertainty estimates from the OE method with in-situ validation data from the SeaWiFS bio-optical archive and storage system (SeaBASS) and aerosol robotic network for ocean color (AERONET-OC) datasets. The OE algorithm improved Rrs(λ) estimates relative to the NASA standard operational algorithm by improving all statistical metrics at 443, 555, and 667 nm. Unphysical negative Rrs(λ), which often appears in complex water conditions, was reduced by a factor of 3. The OE-derived pixel-level Rrs(λ) uncertainty estimates were also assessed relative to in-situ data and were shown to have skill.

11.
Am J Perinatol ; 39(13): 1441-1448, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33477175

RESUMO

OBJECTIVE: The study aimed to evaluate the effects of inhaled iloprost on oxygenation indices in neonates with persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: We conducted a retrospective chart review of 30 patients with PPHN from January 2014 to November 2018, who did not respond to inhaled nitric oxide (iNO) alone and received inhaled iloprost. Twenty-two patients met the inclusion criteria and eight patients were excluded from the study (complex cardiac disease and extreme prematurity). Patients were categorized as responders or nonresponders (patients who required extracorporeal membrane oxygenation or died). Oxygenation index, mean airway pressure (MAP), and arterial partial pressure of oxygen (PaO2) were recorded. RESULTS: Among a total of 22 patients who were included in the study, 10 were classified as nonresponders as they required either extracorporeal membrane oxygenation or died. Gestational age and gender did not differ between responders and nonresponders. The median PaO2 was lower (37 vs. 42 mm Hg; p < 0.05) and median MAP was higher (20 vs. 17 cm H2O; p < 0.02) in nonresponders compared with responders just prior to initiating iloprost. Iloprost responders had a significant increase in median PaO2 and decrease in median oxygenation index in the 24 hours after initiating treatment (p < 0.05), with no significant change in required mean airway pressure over that same period. There was no change in vasopressor use or clinically significant worsening of platelets count, liver, and kidney functions after initiating iloprost. CONCLUSION: Inhaled iloprost is well tolerated and seems to have beneficial effects in improving oxygenation indices in neonates with PPHN who do not respond to iNO. There is a need of well-designed prospective trials to further ascertain the benefits of using inhaled iloprost as an adjunct treatment in neonates with PPHN who do not respond to iNO alone. KEY POINTS: · Inhaled iloprost seems to have beneficial effects in improving oxygenation indices in PPHN.. · Inhaled iloprost is generally well tolerated in newborns with PPHN.. · There is a need for prospective randomized controlled trials to further ascertain the benefits of using inhaled iloprost..


Assuntos
Hipertensão Pulmonar , Síndrome da Persistência do Padrão de Circulação Fetal , Administração por Inalação , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Iloprosta/uso terapêutico , Recém-Nascido , Óxido Nítrico , Oxigênio , Síndrome da Persistência do Padrão de Circulação Fetal/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Vasodilatadores/uso terapêutico
12.
Remote Sens Environ ; 266: 1-14, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36424983

RESUMO

Lakes and other surface fresh waterbodies provide drinking water, recreational and economic opportunities, food, and other critical support for humans, aquatic life, and ecosystem health. Lakes are also productive ecosystems that provide habitats and influence global cycles. Chlorophyll concentration provides a common metric of water quality, and is frequently used as a proxy for lake trophic state. Here, we document the generation and distribution of the complete MEdium Resolution Imaging Spectrometer (MERIS; Appendix A provides a complete list of abbreviations) radiometric time series for over 2300 satellite resolvable inland bodies of water across the contiguous United States (CONUS) and more than 5,000 in Alaska. This contribution greatly increases the ease of use of satellite remote sensing data for inland water quality monitoring, as well as highlights new horizons in inland water remote sensing algorithm development. We evaluate the performance of satellite remote sensing Cyanobacteria Index (CI)-based chlorophyll algorithms, the retrievals for which provide surrogate estimates of phytoplankton concentrations in cyanobacteria dominated lakes. Our analysis quantifies the algorithms' abilities to assess lake trophic state across the CONUS. As a case study, we apply a bootstrapping approach to derive a new CI-to-chlorophyll relationship, ChlBS, which performs relatively well with a multiplicative bias of 1.11 (11%) and mean absolute error of 1.60 (60%). While the primary contribution of this work is the distribution of the MERIS radiometric timeseries, we provide this case study as a roadmap for future stakeholders' algorithm development activities, as well as a tool to assess the strengths and weaknesses of applying a single algorithm across CONUS.

13.
Genet Med ; 21(3): 631-640, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30093709

RESUMO

PURPOSE: We conducted a consented pilot newborn screening (NBS) for Pompe, Gaucher, Niemann-Pick A/B, Fabry, and MPS 1 to assess the suitability of these lysosomal storage disorders (LSDs) for public health mandated screening. METHODS: At five participating high-birth rate, ethnically diverse New York City hospitals, recruiters discussed the study with postpartum parents and documented verbal consent. Screening on consented samples was performed using multiplexed tandem mass spectrometry. Screen-positive infants underwent confirmatory enzymology, DNA testing, and biomarker quantitation when available. Affected infants are being followed for clinical management and long-term outcome. RESULTS: Over 4 years, 65,605 infants participated, representing an overall consent rate of 73%. Sixty-nine infants were screen-positive. Twenty-three were confirmed true positives, all of whom were predicted to have late-onset phenotypes. Six of the 69 currently have undetermined disease status. CONCLUSION: Our results suggest that NBS for LSDs is much more likely to detect individuals at risk for late-onset disease, similar to results from other NBS programs. This work has demonstrated the feasibility of using a novel consented pilot NBS study design that can be modified to include other disorders under consideration for public health implementation as a means to gather critical evidence for evidence-based NBS practices.


Assuntos
Doenças por Armazenamento dos Lisossomos/diagnóstico , Doenças por Armazenamento dos Lisossomos/genética , Triagem Neonatal/métodos , Teste em Amostras de Sangue Seco/métodos , Feminino , Testes Genéticos/métodos , Genômica , Humanos , Recém-Nascido , Masculino , Cidade de Nova Iorque , Pais , Projetos Piloto , Análise de Sequência de DNA , Espectrometria de Massas em Tandem
14.
Am J Perinatol ; 36(9): 918-923, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30414601

RESUMO

OBJECTIVE: To determine longitudinal measurements of resting energy expenditure (REE) by indirect calorimetry (IC) in healthy term infants during the first 2 months of life. STUDY DESIGN: An outpatient prospective pilot study was performed in healthy term infants to estimate REE by measuring expired gas fractions of oxygen (O2) and carbon dioxide (CO2) with IC in a respiratory and metabolic steady state. RESULTS: A total of 30 measurements were performed. Fourteen subjects completed measurements at both 1 and 2 months of life, and two subjects had only measurements made at 1 month of life. Mean REE values were 64.1 ± 12.7 and 58.4 ± 14.3 kcal/kg/d at 1 and 2 months of age, respectively. Mean O2 consumption and CO2 production measurements were 9.3 ± 2.0 and 7.7 ± 1.2 mL/kg/min and 8.1 ± 2.2 and 6.4 ± 1.1 mL/kg/min at 1 and 2 months of age, respectively. CONCLUSION: This pilot study demonstrates longitudinal measurements of REE by IC in healthy term infants during the first 2 months of life. We also demonstrate that, overall, there is consistency in REE values in this population, with a likely decrease in individual longitudinal measurements over the first 2 months of life.


Assuntos
Metabolismo Basal/fisiologia , Calorimetria Indireta , Recém-Nascido/metabolismo , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Estudos Prospectivos
15.
Sensors (Basel) ; 19(9)2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083477

RESUMO

Small unmanned aircraft systems (sUAS) are rapidly transforming atmospheric research. With the advancement of the development and application of these systems, improving knowledge of best practices for accurate measurement is critical for achieving scientific goals. We present results from an intercomparison of atmospheric measurement data from the Lower Atmospheric Process Studies at Elevation-a Remotely piloted Aircraft Team Experiment (LAPSE-RATE) field campaign. We evaluate a total of 38 individual sUAS with 23 unique sensor and platform configurations using a meteorological tower for reference measurements. We assess precision, bias, and time response of sUAS measurements of temperature, humidity, pressure, wind speed, and wind direction. Most sUAS measurements show broad agreement with the reference, particularly temperature and wind speed, with mean value differences of 1.6 ± 2 . 6 ∘ C and 0.22 ± 0 . 59 m/s for all sUAS, respectively. sUAS platform and sensor configurations were found to contribute significantly to measurement accuracy. Sensor configurations, which included proper aspiration and radiation shielding of sensors, were found to provide the most accurate thermodynamic measurements (temperature and relative humidity), whereas sonic anemometers on multirotor platforms provided the most accurate wind measurements (horizontal speed and direction). We contribute both a characterization and assessment of sUAS for measuring atmospheric parameters, and identify important challenges and opportunities for improving scientific measurements with sUAS.

16.
J Pediatr ; 197: 109-115.e1, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29571927

RESUMO

OBJECTIVE: To assess whether neonatologists show implicit racial and/or socioeconomic biases and whether these are predictive of recommendations at extreme periviability. STUDY DESIGN: A nationwide survey using a clinical vignette of a woman in labor at 232/7 weeks of gestation asked physicians how likely they were to recommend intensive vs comfort care. Participants were randomized to 1 of 4 versions of the vignette in which racial and socioeconomic stimuli were varied, followed by 2 implicit association tests (IATs). RESULTS: IATs revealed implicit preferences favoring white (mean IAT score = 0.48, P < .001) and greater socioeconomic status (mean IAT score = 0.73, P < .001). Multivariable linear regression analysis showed that physicians with implicit bias toward greater socioeconomic status were more likely than those without bias to recommend comfort care when presented with a patient of high socioeconomic status (P = .037). No significant effect was seen for implicit racial bias. CONCLUSIONS: Building on previous demonstrations of unconscious racial and socioeconomic biases among physicians and their predictive validity, our results suggest that unconscious socioeconomic bias influences recommendations when counseling at the limits of viability. Physicians who display a negative socioeconomic bias are less likely to recommend resuscitation when counseling women of high socioeconomic status. The influence of implicit socioeconomic bias on recommendations at periviability may influence neonatal healthcare disparities and should be explored in future studies.


Assuntos
Atitude do Pessoal de Saúde , Aconselhamento/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Neonatologistas/estatística & dados numéricos , Preconceito/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Classe Social , Inquéritos e Questionários , Estados Unidos
17.
Pediatr Crit Care Med ; 19(1): 48-55, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29189671

RESUMO

OBJECTIVE: To compare neurally adjusted ventilatory assist and conventional ventilation on patient-ventilator interaction and neural breathing patterns, with a focus on central apnea in preterm infants. DESIGN: Prospective, observational cross-over study of intubated and ventilated newborns. Data were collected while infants were successively ventilated with three different ventilator conditions (30 min each period): 1) synchronized intermittent mandatory ventilation (SIMV) combined with pressure support at the clinically prescribed, SIMV with baseline settings (SIMVBL), 2) neurally adjusted ventilatory assist, 3) same as SIMVBL, but with an adjustment of the inspiratory time of the mandatory breaths (SIMV with adjusted settings [SIMVADJ]) using feedback from the electrical activity of the diaphragm). SETTING: Regional perinatal center neonatal ICU. PATIENTS: Neonates admitted in the neonatal ICU requiring invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Twenty-three infants were studied, with median (range) gestational age at birth 27 weeks (24-41 wk), birth weight 780 g (490-3,610 g), and 7 days old (1-87 d old). Patient ventilator asynchrony, as quantified by the NeuroSync index, was lower during neurally adjusted ventilatory assist (18.3% ± 6.3%) compared with SIMVBL (46.5% ±11.7%; p < 0.05) and SIMVADJ (45.8% ± 9.4%; p < 0.05). There were no significant differences in neural breathing parameters, or vital signs, except for the end-expiratory electrical activity of the diaphragm, which was lower during neurally adjusted ventilatory assist. Central apnea, defined as a flat electrical activity of the diaphragm more than 5 seconds, was significantly reduced during neurally adjusted ventilatory assist compared with both SIMV periods. These results were comparable for term and preterm infants. CONCLUSIONS: Patient-ventilator interaction appears to be improved with neurally adjusted ventilatory assist. Analysis of the neural breathing pattern revealed a reduction in central apnea during neurally adjusted ventilatory assist use.


Assuntos
Respiração Artificial/métodos , Apneia do Sono Tipo Central/etiologia , Ventiladores Mecânicos/estatística & dados numéricos , Estudos Cross-Over , Humanos , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Unidades de Terapia Intensiva Neonatal , Estudos Prospectivos , Respiração Artificial/efeitos adversos , Apneia do Sono Tipo Central/terapia , Ventiladores Mecânicos/efeitos adversos
18.
J Perinat Med ; 46(1): 81-86, 2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-28803228

RESUMO

BACKGROUND: Due to the extremely low incidence of TORCH (toxoplasmosis, rubella, CMV, herpes simplex virus) infections, diagnostic testing of all small for gestational age (SGA) infants aimed at TORCH etiologies may incur unnecessary tests and cost. OBJECTIVE: To determine the frequency of urine CMV PCR and total IgM testing among infants with birth weight <10% and the rate of test positivity. To evaluate the frequency of alternative etiologies of SGA in tested infants. METHODS: Retrospective chart review of SGA infants admitted to the neonatal intensive care unit (NICU) at NYU Langone Medical Center between 2007 and 2012. Subjects were classified as being SGA with or without intrauterine growth restriction (IUGR). The IUGR subjects were then further categorized as having either symmetric or asymmetric IUGR utilizing the Fenton growth chart at birth. Initial testing for TORCH infections, which included serum total IgM, CMV PCR and head ultrasound, were reviewed and analyzed. RESULTS: Three hundred and eighty-six (13%) infants from a total of 2953 NICU admissions had a birth weight ≤10th percentile. Of these, 44% were IUGR; 34% being symmetric IUGR and 10% asymmetric. A total of 32% of SGA infants had urine CMV PCR and total IgM tested with no positive results. As expected, significantly higher percentage of symmetric IUGR infants were tested compared to asymmetric IUGR and non-IUGR SGA infants, (64% vs. 47% vs. 19%) P≤0.01. However, 63% of infants with a known cause for IUGR had same testing done aimed at TORCH infections. We calculated additional charges of $64,065 that were incurred by such testing. CONCLUSIONS: The majority of infants in our study who received testing for urine CMV PCR and total IgM aimed at TORCH infections had one or more other known non-infectious etiologies for IUGR. Because the overall yield of such testing is extremely low, we suggest tests for possible TORCH infections may be limited to symmetric IUGR infants without other known etiologies. Improved guidelines testing for TORCH infections can result in reducing hospital charges and unnecessary studies.


Assuntos
Citomegalovirus/isolamento & purificação , Retardo do Crescimento Fetal/etiologia , Imunoglobulina M/sangue , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Triagem Neonatal/estatística & dados numéricos , Adulto , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/urina , Reação em Cadeia da Polimerase/estatística & dados numéricos , Gravidez , Estudos Retrospectivos , Procedimentos Desnecessários
19.
J Perinat Med ; 46(8): 934-941, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-29451862

RESUMO

Background Following neonatal resuscitation program (NRP) training, decay in clinical skills can occur. Simulation-based deliberate practice (SBDP) has been shown to maintain NRP skills to a variable extent. Our study objectives were (a) to determine whether a single 30 min simulation-based intervention that incorporates SBDP and mastery learning (ML) can effectively restore skills and prevent skill decay and (b) to compare different timing options. Methods Following NRP certification, pediatric residents were randomly assigned to receive a video-recorded baseline assessment plus SBDP-ML refresher education at between 6 and 9 months (early) or between 9 and 12 months (late). One year following initial certification, participants had repeat skill retention videotaped evaluations. Participants were scored by blinded NRP instructors using validated criteria scoring tools and assigned a global performance rating score (GRS). Results Twenty-seven participants were included. Residents in both early and late groups showed significant skill decay 7 and 10 months after initial NRP. SBDP-ML booster sessions significantly improved participants' immediate NRP performance scores (p<0.001), which persisted for 2 months, but were again lower 4 months later. Conclusions NRP skills may be boosted to mastery levels after a short SBDP-ML intervention and do not appear to significantly decline after 2 months. Brief booster training could potentially serve as a useful supplement to traditional NRP training for pediatric residents.


Assuntos
Competência Clínica/estatística & dados numéricos , Pediatria/educação , Ressuscitação/educação , Treinamento por Simulação/métodos , Feminino , Humanos , Internato e Residência , Masculino
20.
Sensors (Basel) ; 18(12)2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30558335

RESUMO

Concentrations of airborne chemical and biological agents from a hazardous release are not spread uniformly. Instead, there are regions of higher concentration, in part due to local atmospheric flow conditions which can attract agents. We equipped a ground station and two rotary-wing unmanned aircraft systems (UASs) with ultrasonic anemometers. Flights reported here were conducted 10 to 15 m above ground level (AGL) at the Leach Airfield in the San Luis Valley, Colorado as part of the Lower Atmospheric Process Studies at Elevation-a Remotely-Piloted Aircraft Team Experiment (LAPSE-RATE) campaign in 2018. The ultrasonic anemometers were used to collect simultaneous measurements of wind speed, wind direction, and temperature in a fixed triangle pattern; each sensor was located at one apex of a triangle with ∼100 to 200 m on each side, depending on the experiment. A WRF-LES model was used to determine the wind field across the sampling domain. Data from the ground-based sensors and the two UASs were used to detect attracting regions (also known as Lagrangian Coherent Structures, or LCSs), which have the potential to transport high concentrations of agents. This unique framework for detection of high concentration regions is based on estimates of the horizontal wind gradient tensor. To our knowledge, our work represents the first direct measurement of an LCS indicator in the atmosphere using a team of sensors. Our ultimate goal is to use environmental data from swarms of sensors to drive transport models of hazardous agents that can lead to real-time proper decisions regarding rapid emergency responses. The integration of real-time data from unmanned assets, advanced mathematical techniques for transport analysis, and predictive models can help assist in emergency response decisions in the future.

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