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1.
Blood ; 136(21): 2416-2427, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32603414

RESUMO

Multiple myeloma (MM) is a plasma cell neoplasm that commonly expresses CD38. Daratumumab (DARA), a human monoclonal antibody targeting CD38, has significantly improved the outcome of patients with relapsed or refractory MM, but the response is transient in most cases. Putative mechanisms of suboptimal efficacy of DARA include downregulation of CD38 expression and overexpression of complement inhibitory proteins on MM target cells as well as DARA-induced depletion of CD38high natural killer (NK) cells resulting in crippled antibody-dependent cellular cytotoxicity (ADCC). Here, we tested whether maintaining NK cell function during DARA therapy could maximize DARA-mediated ADCC against MM cells and deepen the response. We used the CRISPR/Cas9 system to delete CD38 (CD38KO) in ex vivo expanded peripheral blood NK cells. These CD38KO NK cells were completely resistant to DARA-induced fratricide, showed superior persistence in immune-deficient mice pretreated with DARA, and enhanced ADCC activity against CD38-expressing MM cell lines and primary MM cells. In addition, transcriptomic and cellular metabolic analysis demonstrated that CD38KO NK cells have unique metabolic reprogramming with higher mitochondrial respiratory capacity. Finally, we evaluated the impact of exposure to all-trans retinoic acid (ATRA) on wild-type NK and CD38KO NK cell function and highlighted potential benefits and drawbacks of combining ATRA with DARA in patients with MM. Taken together, these findings provide proof of concept that adoptive immunotherapy using ex vivo expanded CD38KO NK cells has the potential to boost DARA activity in MM.


Assuntos
ADP-Ribosil Ciclase 1/deficiência , Anticorpos Monoclonais/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Glicoproteínas de Membrana/deficiência , Mieloma Múltiplo/patologia , ADP-Ribosil Ciclase 1/genética , Transferência Adotiva , Animais , Citotoxicidade Celular Dependente de Anticorpos , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Humanos , Imunoterapia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/transplante , Masculino , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos NOD , NAD/metabolismo , Fosforilação Oxidativa , Organismos Livres de Patógenos Específicos , Tretinoína/farmacologia , Sequenciamento Completo do Genoma
2.
Crit Care ; 24(1): 702, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33357240

RESUMO

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.


Assuntos
COVID-19/diagnóstico por imagem , Consenso , Ecocardiografia/normas , Prova Pericial/normas , Internacionalidade , Sistemas Automatizados de Assistência Junto ao Leito/normas , COVID-19/terapia , Ecocardiografia/métodos , Prova Pericial/métodos , Humanos , Pulmão/diagnóstico por imagem , Tromboembolia/diagnóstico por imagem , Tromboembolia/terapia , Triagem/métodos , Triagem/normas , Ultrassonografia/normas
3.
J Ultrasound Med ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33289208

RESUMO

OBJECTIVES: B-lines are a lung ultrasound (LUS) artifact that often indicate pathology. Little is known about the optimal ultrasound machine settings to assess B-lines. We compared settings typically used to evaluate B-lines at our institution with adjusted settings based on recent studies. METHODS: In order to determine typical settings for B-line assessment, we retrospectively reviewed LUS images obtained at our institution. We then prospectively performed LUS with both typical and adjusted settings, using curvilinear and phased array probes, in 20 patients presenting to the emergency department with shortness of breath. The prospectively obtained clips were rated for quality and quantity of B-lines by 14 clinicians with experience in LUS, with 1 assigned for typical settings "much greater," 2 for typical settings "slightly greater," 3 for both settings "similar," 4 for adjusted settings "slightly greater," and 5 for adjusted settings "much greater." RESULTS: Mean ratings and 95% confidence intervals significantly exceeded the null value of 3 for both B line quality (curvilinear probe: 4.68, 4.50-4.85; phased array probe: 4.02, 3.70-4.35) and B line quantity (curvilinear probe: 4.16, 3.84-4.49; phased array probe: 3.68, 3.41-3.96). CONCLUSIONS: B-line quality and quantity were rated higher using adjusted settings based on recently published evidence than when using settings that are typically employed in our institution. Our findings suggest that B-line assessment should be performed with focal zone at the level of the pleura, harmonics off, and gain increased in the far field.

4.
J Ultrasound Med ; 38(2): 371-377, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30043460

RESUMO

OBJECTIVES: Ultrasound (US) is increasingly used in settings where commercial US gel is unavailable. This study evaluated noncommercial gel recipes compared to commercial gel. METHODS: A search for US gel formulations revealed 6 recipes. Half-strength commercial gel and a modified glucomannan recipe were also tested. Nine gels, including commercial gel, were tested in Liberia and the United States. In each session, 2 physician sonologists evaluated 9 gels on 2 models, obtaining videos from the hepatorenal space with a curvilinear transducer, the cardiac parasternal long view with a phased array transducer, and the left basilic vein with a linear transducer. The sonologists and models, who were blinded to gel identity, made independent quantitative and qualitative gel evaluations comparing the test gel to commercial gel. Two physician sonologists who were blinded to the gel identities and a US operator reviewed the images and rated their quality. An analysis of variance in repeated measures was performed to test for differences in the overall score, real-time quality, and other characteristics. Post hoc pairwise comparisons to commercial gel were performed with a Tukey-Kramer adjustment. Inter- and intra-rater reliability was calculated for the image review. RESULTS: Commercial gel earned a perfect score. Compared to commercial gel, xanthine gum gel scored highest, followed by half-strength commercial gel. Hot concentrated glucomannan and cold glucomannan gel were found to be significantly worse than commercial gel. No significant difference was found between images based on the gel used on the image review. CONCLUSIONS: No significant difference in image quality was found between commercial and noncommercial gels on US image review.


Assuntos
Géis/química , Géis/normas , Ultrassonografia/instrumentação , Braço/irrigação sanguínea , Braço/diagnóstico por imagem , Países em Desenvolvimento , Recursos em Saúde , Coração/diagnóstico por imagem , Humanos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Libéria , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Reprodutibilidade dos Testes , Transdutores , Ultrassonografia/métodos , Estados Unidos
5.
Phys Chem Chem Phys ; 20(14): 9671, 2018 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-29616253

RESUMO

Correction for 'Unravelling the impact of hydrocarbon structure on the fumarate addition mechanism - a gas-phase ab initio study' by Vivek S. Bharadwaj et al., Phys. Chem. Chem. Phys., 2015, 17, 4054-4066.

6.
J Ultrasound Med ; 37(8): 1965-1975, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29380893

RESUMO

OBJECTIVES: Emergency department (ED) transvaginal ultrasound (US) is underused in clinical practice. This study assessed pregnant women's perceptions of ED transvaginal US in terms of pain, embarrassment, anxiety, and willingness to receive the procedure. Secondary variables include physicians' perceptions of patients' experiences. METHODS: Women undergoing US examinations for complications of first-trimester pregnancy were prospectively surveyed before any US and after ED and/or radiology transvaginal US. Patients' and physicians' assessments of pain, embarrassment, and anxiety were measured with visual analog scales (0-100). RESULTS: A total of 398 women were enrolled. In the pre-US survey, the median anxiety score was 14 (interquartile range, 3-51), and 96% of patients were willing to have an ED transvaginal US if necessary. Of those who had ED transvaginal US, 96% would agree to have another examination. Patients reported minimal pain/embarrassment, and there was no difference if performed in the ED versus radiology (median pain, 11.5 versus 13; P = .433; median embarrassment, 7 versus 4; P = .345). Of the 48 who had both ED and radiology transvaginal US, 85% thought the ED transvaginal US was worthwhile. Physicians accurately assessed patient's embarrassment and pain (mean differences, 3.5 and -1.9, respectively; P > .25 for both); however, they overestimated them relative to the pelvic examination (mean difference for embarrassment, 12.8; P < .0001; pain, 8.0; P = .01). CONCLUSIONS: Pregnant ED patients report low levels of anxiety, pain, and embarrassment, and after ED transvaginal US, 96% would agree to have the examination again. There is no difference in pain/embarrassment between ED and radiology transvaginal US. Emergency department physicians accurately assessed patients' pain and embarrassment with ED transvaginal US but overestimated them compared to the pelvic examination.


Assuntos
Serviço Hospitalar de Emergência , Satisfação do Paciente/estatística & dados numéricos , Complicações na Gravidez/diagnóstico por imagem , Primeiro Trimestre da Gravidez , Ultrassonografia Pré-Natal/métodos , Adolescente , Adulto , Feminino , Humanos , Gravidez , Estudos Prospectivos , Vagina/diagnóstico por imagem , Adulto Jovem
7.
Pediatr Emerg Care ; 34(6): 376-380, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28221281

RESUMO

OBJECTIVE: The aim of this study was to examine the success rates, longevity, and complications of ultrasound-guided peripheral intravenous lines (USgPIVs) placed in a pediatric emergency department. METHODS: The study analyzed 300 USgPIV attempts in an urban tertiary-care pediatric emergency department. Data regarding USgPIV placement were collected from a 1-page form completed by the clinician placing the USgPIV. The time and reason for USgPIV removal were extracted from the medical record for patients with USgPIVs admitted to the hospital. A Kaplan-Meier survival analysis was performed. RESULTS: This study demonstrated a success rate of 68% and 87% for the first and second attempts with USgPIV. Fifty-five percent of patients had 1 or more prior traditional intravenous access attempt. Most USgPIVs placed on patients admitted to the hospital were removed because they were no longer needed (101/160). We calculated a Kaplan-Meier median survival of 143 hours (6 days; interquartile range, 68-246 hours). The failure rate at 48 hours was 25%. CONCLUSION: Ultrasound-guided intravenous access is a feasible alternative to traditional peripheral intravenous access in the pediatric emergency setting. We observed a high first-stick success rate even in patients who had failed traditional peripheral intravenous access attempts, few complications, and a long intravenous survival time.


Assuntos
Cateterismo Periférico/métodos , Ultrassonografia de Intervenção/métodos , Adolescente , Cateterismo Periférico/efeitos adversos , Criança , Pré-Escolar , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Estimativa de Kaplan-Meier , Longevidade , Masculino , Ultrassonografia de Intervenção/efeitos adversos
8.
Clin Immunol ; 177: 3-11, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26883680

RESUMO

Cell therapy is a promising alternative to harsh chemotherapy and radiation therapy for cancer. Natural killer (NK) cells in particular have great potential for direct use in adoptive immunotherapy (AI) for cancer and to improve the graft-vs-leukemia (GVL) effect of hematopoietic stem cell transplants (HSCTs). NK cell number and function are associated with a strong GVL effect without inducing graft-versus-host disease in most settings. Clinical trials demonstrating the therapeutic role of NK cells in HSCT recipients or testing the safety and efficacy of AI with NK cells have been primarily directed at treating acute myeloid leukemia, although investigators have used NK cells for treatment of other hematological diseases, sarcomas, carcinomas, and brain tumors. Major challenges must be overcome in making NK cell-based therapy cost-effective, the most important being the need to collect or generate an adequate number of effector cells. In this review, we discuss protocols for isolation, expansion, and in vitro propagation of large quantities of functional NK cells that meet the criteria for clinical applications. Among the methods described are the use of bioreactors for scaling up production and expansion of NK cells in the presence of interleukins and feeder cells. We also discuss novel methodologies that optimize the generation of clinical grade NK-cell products for AI.


Assuntos
Imunoterapia Adotiva , Células Matadoras Naturais/transplante , Animais , Transplante de Células , Humanos , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos
9.
N Engl J Med ; 371(12): 1100-10, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-25229916

RESUMO

BACKGROUND: There is a lack of consensus about whether the initial imaging method for patients with suspected nephrolithiasis should be computed tomography (CT) or ultrasonography. METHODS: In this multicenter, pragmatic, comparative effectiveness trial, we randomly assigned patients 18 to 76 years of age who presented to the emergency department with suspected nephrolithiasis to undergo initial diagnostic ultrasonography performed by an emergency physician (point-of-care ultrasonography), ultrasonography performed by a radiologist (radiology ultrasonography), or abdominal CT. Subsequent management, including additional imaging, was at the discretion of the physician. We compared the three groups with respect to the 30-day incidence of high-risk diagnoses with complications that could be related to missed or delayed diagnosis and the 6-month cumulative radiation exposure. Secondary outcomes were serious adverse events, related serious adverse events (deemed attributable to study participation), pain (assessed on an 11-point visual-analogue scale, with higher scores indicating more severe pain), return emergency department visits, hospitalizations, and diagnostic accuracy. RESULTS: A total of 2759 patients underwent randomization: 908 to point-of-care ultrasonography, 893 to radiology ultrasonography, and 958 to CT. The incidence of high-risk diagnoses with complications in the first 30 days was low (0.4%) and did not vary according to imaging method. The mean 6-month cumulative radiation exposure was significantly lower in the ultrasonography groups than in the CT group (P<0.001). Serious adverse events occurred in 12.4% of the patients assigned to point-of-care ultrasonography, 10.8% of those assigned to radiology ultrasonography, and 11.2% of those assigned to CT (P=0.50). Related adverse events were infrequent (incidence, 0.4%) and similar across groups. By 7 days, the average pain score was 2.0 in each group (P=0.84). Return emergency department visits, hospitalizations, and diagnostic accuracy did not differ significantly among the groups. CONCLUSIONS: Initial ultrasonography was associated with lower cumulative radiation exposure than initial CT, without significant differences in high-risk diagnoses with complications, serious adverse events, pain scores, return emergency department visits, or hospitalizations. (Funded by the Agency for Healthcare Research and Quality.).


Assuntos
Nefrolitíase/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Distribuição por Idade , Idoso , Pesquisa Comparativa da Efetividade , Serviço Hospitalar de Emergência , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Ultrassonografia , Adulto Jovem
10.
J Ultrasound Med ; 36(6): 1189-1194, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28258591

RESUMO

OBJECTIVES: Few studies of point-of-care ultrasound training and use in low resource settings have reported the impact of examinations on clinical management or the longer-term quality of trainee-performed studies. We characterized the long-term effect of a point-of-care ultrasound program on clinical decision making, and evaluated the quality of clinician-performed ultrasound studies. METHODS: We conducted point-of-care ultrasound training for physicians from Rwandan hospitals. Physicians then used point-of-care ultrasound and recorded their findings, interpretation, and effects on patient management. Data were collected for 6 months. Trainee studies were reviewed for image quality and accuracy. RESULTS: Fifteen participants documented 1158 ultrasounds; 590 studies (50.9%) had matched images and interpretations for review. Abdominal ultrasound for free fluid was the most frequently performed application. The mean image quality score was 2.36 (95% confidence interval, 2.28-2.44). Overall sensitivity and specificity for trainee-performed examinations was 94 and 98%. Point-of-care ultrasound use most commonly changed medications administered (42.4%) and disposition (30%). CONCLUSIONS: A point-of-care ultrasound training intervention in a low-resource setting resulted in high numbers of diagnostic-quality studies over long-term follow-up. Ultrasound use routinely changed clinical decision making.


Assuntos
Competência Clínica/estatística & dados numéricos , Tomada de Decisão Clínica/métodos , Avaliação Educacional/estatística & dados numéricos , Sistemas Automatizados de Assistência Junto ao Leito/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Revisão da Utilização de Recursos de Saúde , Adulto , Estudos de Coortes , Feminino , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Ruanda/epidemiologia , Sensibilidade e Especificidade
11.
Trop Med Int Health ; 21(12): 1531-1538, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27758005

RESUMO

OBJECTIVE: We delivered a point-of-care ultrasound training programme in a resource-limited setting in Rwanda, and sought to determine participants' knowledge and skill retention. We also measured trainees' assessment of the usefulness of ultrasound in clinical practice. METHODS: This was a prospective cohort study of 17 Rwandan physicians participating in a point-of-care ultrasound training programme. The follow-up period was 1 year. Participants completed a 10-day ultrasound course, with follow-up training delivered over the subsequent 12 months. Trainee knowledge acquisition and skill retention were assessed via observed structured clinical examinations (OSCEs) administered at six points during the study, and an image-based assessment completed at three points. RESULTS: Trainees reported minimal structured ultrasound education and little confidence using point-of-care ultrasound before the training. Mean scores on the image-based assessment increased from 36.9% (95% CI 32-41.8%) before the initial 10-day training to 74.3% afterwards (95% CI 69.4-79.2; P < 0.001). The mean score on the initial OSCE after the introductory course was 81.7% (95% CI 78-85.4%). The mean OSCE performance at each subsequent evaluation was at least 75%, and the mean OSCE score at the 58-week follow up was 84.9% (95% CI 80.9-88.9%). CONCLUSIONS: Physicians providing acute care in a resource-limited setting demonstrated sustained improvement in their ultrasound knowledge and skill 1 year after completing a clinical ultrasound training programme. They also reported improvements in their ability to provide patient care and in job satisfaction.


Assuntos
Competência Clínica , Educação , Exame Físico , Médicos , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia , Atitude do Pessoal de Saúde , Avaliação Educacional , Humanos , Satisfação no Emprego , Estudos Prospectivos , Ruanda
12.
Phys Chem Chem Phys ; 18(12): 8437-52, 2016 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-26931444

RESUMO

The intramolecular ring closure reactions of unsaturated hydrocarbon radicals potentially play an important role for the formation of molecular weight growth species, especially during the pyrolysis and oxidation of alkenes under low to intermediate temperatures. In this work we investigated a series of intramolecular cycloaddition reactions of both allylic- and alkyl-type dienyl radicals. In the first set of reactions, a resonant linear radical is converted into a non-resonant cyclic radical. In the second set, a non-resonant linear alkenyl radical isomerizes to either a resonant cyclic radical or a cyclic carbinyl radical. In both cases, three different reaction schemes are examined based on the location of the partially-formed resonance structure in the cyclic transition state. For each reaction scheme, both the endo- and exo-pathways were investigated. High pressure rate parameters are obtained from the results of CBS-QB3 electronic structure calculations combined with canonical transition state theory calculations. The results are discussed in the context of a Benson-type model to examine the impact of the partially-formed resonance stabilization on both the activation energies and pre-exponential factors. The results are compared to previously reported rate parameters for cycloaddition reactions of alkenyl radicals. The differences in the activation energies are primarily due to the bimolecular component of the activation energy. However, in some cases, the presence of the partial resonance structure significantly increases the strain energy for the ring that is formed in the transition state. The pre-exponential factors are also impacted by the formation of a partial resonance structure in the transition state. Lastly, the C6H9 potential energy surface is examined to show how the trends that are outlined here can be used to estimate rate parameters, which are needed to analyze pressure-dependent reaction systems.

13.
Chemphyschem ; 16(12): 2635-45, 2015 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-26212671

RESUMO

A series of intramolecular H-atom shift reactions of both alkenyl and allylic radicals were investigated by using CBS-QB3 electronic structure calculations. In the first set of reactions, an alkyl radical site was converted into an allylic radical site. In the second set, an allylic radical was converted into another allylic radical. The results are discussed in the context of a Benson-type model to examine the impact of the transition-state partial resonance stabilization on both the activation energies and the pre-exponential factors. In most cases, the differences in the activation energies relative to those for the analogous alkyl radicals are primarily due to the barriers of the bimolecular reaction component of the activation energy. For the first set of reactions, there is additional entropy loss relative to the alkyl radical analogues. This additional loss of entropy may be smaller than some previous estimates. The pre-exponential factors for the second set of reactions are generally similar to those of the analogous alkyl radical reactions (once the double bond in the transition state is accounted for).

14.
Phys Chem Chem Phys ; 17(9): 6255-73, 2015 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-25648200

RESUMO

The reactions of allylic radicals have the potential to play a critical role in molecular weight growth (MWG) kinetics during hydrocarbon oxidation and/or pyrolysis. Due to their stability (when compared to alkyl radicals), they can accumulate to relatively high concentrations. Thus, even though the rate coefficients for their various reactions are small, the rates of these reactions may be significant. In this work, we use electronic structure calculations to examine the recombination, addition, and abstraction reactions of allylic radicals. For the recombination reaction of allyl radicals, we assign a high pressure rate rule that is based on experimental data. Once formed, the recombination product can potentially undergo an H-atom abstraction reaction followed by unimolecular cyclization and ß-scission reactions. Depending upon the conditions (e.g., higher pressures) these pathways can lead to the formation of stable MWG species. The addition of allylic radicals to olefins can also lead to MWG species formation. Once again, cyclization of the adduct followed by ß-scission is an important energy accessible route. Since the recombination and addition reactions produce chemically-activated adducts, we have explored the pressure- and temperature-dependence of the overall rate constants as well as that for the multiple product channels. We describe a strategy for estimating these pressure-dependencies for systems where detailed electronic structure information is not available. We also derive generic rate rules for hydrogen abstraction reactions from olefins and diolefins by methyl and allyl radicals.

15.
Phys Chem Chem Phys ; 17(6): 4054-66, 2015 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-25566585

RESUMO

The fumarate addition reaction mechanism is central to the anaerobic biodegradation pathway of various hydrocarbons, both aromatic (e.g., toluene, ethyl benzene) and aliphatic (e.g., n-hexane, dodecane). Succinate synthase enzymes, which belong to the glycyl radical enzyme family, are the main facilitators of these biochemical reactions. The overall catalytic mechanism that converts hydrocarbons to a succinate molecule involves three steps: (1) initial H-abstraction from the hydrocarbon by the radical enzyme, (2) addition of the resulting hydrocarbon radical to fumarate, and (3) hydrogen abstraction by the addition product to regenerate the radical enzyme. Since the biodegradation of hydrocarbon fuels via the fumarate addition mechanism is linked to bio-corrosion, an improved understanding of this reaction is imperative to our efforts of predicting the susceptibility of proposed alternative fuels to biodegradation. An improved understanding of the fuel biodegradation process also has the potential to benefit bioremediation. In this study, we consider model aromatic (toluene) and aliphatic (butane) compounds to evaluate the impact of hydrocarbon structure on the energetics and kinetics of the fumarate addition mechanism by means of high level ab initio gas-phase calculations. We predict that the rate of toluene degradation is ∼100 times faster than butane at 298 K, and that the first abstraction step is kinetically significant for both hydrocarbons, which is consistent with deuterium isotope effect studies on toluene degradation. The detailed computations also show that the predicted stereo-chemical preference of the succinate products for both toluene and butane are due to the differences in the radical addition rate constants for the various isomers. The computational and kinetic modeling work presented here demonstrates the importance of considering pre-reaction and product complexes in order to accurately treat gas phase systems that involve intra and inter-molecular non-covalent interactions.


Assuntos
Butanos/química , Fumaratos/química , Tolueno/química , Biocatálise , Enzimas/química , Radicais Livres/química , Cinética , Teoria Quântica , Estereoisomerismo , Succinatos/química , Temperatura , Termodinâmica
16.
J Phys Chem A ; 119(28): 7205-21, 2015 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-25563061

RESUMO

Intramolecular H atom shift reactions of alkyl radicals and cycloaddition reactions of alkenyl radicals are two important reaction classes in hydrocarbon combustion and pyrolysis. In this work, we derive high-pressure rate estimation rules that are based on the results of electronic structure calculations at the CBS-QB3 level of theory combined with transition state theory calculations. The rules for the H atom shift reactions of alkyl radicals cover the 1,2- up to the 1,7-H shifts. The rules for the cycloaddition reactions of alkenyl radicals are for both the endo- and exo-cycloaddition and include the formation of three- to seven-member ring products. The results are in good agreement with available experiment measurements and other theoretical studies. Both types of reactions proceed via cyclic transition state structures. The impact of ring size and substituent groups on pre-exponential factors and activation energies are discussed in the context of a Benson-type structure-reactivity relationship. Similar relationships between the pre-exponential factors and the number of internal rotors lost in formation of the transition state are derived for both H-shift and cycloaddition reactions. The activation energies are found to be more complicated. The ring strain contribution to the barrier is much lower for the exo-cycloaddition reactions than it is for the other two investigated reaction systems. The ring strains for the H-shift and endo-cycloaddition are similar to one another and are comparable to that of cycloalkanes for three- to six-member rings, but are significantly lower for the larger rings. The results suggest that the 1,6-H shift and 1,7-endo-cycloaddition reactions might be faster than previous estimates.

17.
Pediatr Crit Care Med ; 16(3): 219-26, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25607741

RESUMO

OBJECTIVES: To determine the feasibility and describe the process of implementing a pediatric critical care bedside ultrasound program in a large academic PICU and to evaluate the impact of bedside ultrasound on clinical management. DESIGN: Retrospective case series, description of program implementation. SETTING: Single-center quaternary noncardiac PICU in a children's hospital. PATIENTS: Consecutive patients from January 22, 2012, to July 22, 2012, with bedside ultrasounds performed and interpreted by pediatric critical care practitioners. INTERVENTIONS: A pediatric critical care bedside ultrasound program consisting of a 2-day immersive course followed by clinical performance with internal quality assurance review was implemented. Studies performed in the PICU following training were documented and reviewed against reference standards including subspecialist-performed ultrasound or clinical response. MEASUREMENTS AND MAIN RESULTS: Seventeen critical care faculties and eight fellows recorded 201 bedside ultrasound studies over 6 months in defined core applications: 57 procedural (28%), 76 hemodynamic (38%), 35 thoracic (17%), and 33 abdominal (16%). A quality assurance review identified 23 studies (16% of all nonprocedural studies) as critical (affected clinical management or gave valuable information). Forty-eight percent of those studies (11/23) were within the hemodynamic core. The proportion of critical studies were not significantly different across the applications (hemodynamic, 11/76 [15%] vs thoracic and abdominal, 12/68 [18%]; p = 0.65). Examples of critical studies include evidence of tamponade secondary to pleural effusions, identification of pulmonary hypertension, hemodynamic assessment before tracheal intubation, recognition of hypovolemia and systemic vascular resistance abnormalities, determination of pneumothorax, location of chest tube and urinary catheter, and differentiation of pleural fluid from pulmonary consolidation. CONCLUSIONS: Implementation of a critical care bedside ultrasound program for critical care providers in a large academic PICU is feasible. Bedside ultrasound evaluation and interpretation by intensivists affected the management of critically ill children.


Assuntos
Cuidados Críticos/métodos , Hospitais Pediátricos , Unidades de Terapia Intensiva Pediátrica/normas , Sistemas Automatizados de Assistência Junto ao Leito/normas , Avaliação de Programas e Projetos de Saúde/métodos , Ultrassonografia , Adolescente , Criança , Pré-Escolar , Feminino , Hemodinâmica , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Lactente , Masculino , Derrame Pleural/diagnóstico por imagem , Pneumotórax/diagnóstico por imagem , Estudos Retrospectivos , Adulto Jovem
18.
Am J Emerg Med ; 33(10): 1402-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26279392

RESUMO

STUDY OBJECTIVE: We sought to identify findings on bedside renal ultrasound that predicted need for hospitalization in patients with suspected nephrolithiasis. METHODS: A convenience sample of patients with suspected nephrolithiasis was prospectively enrolled and underwent bedside ultrasound of the kidneys and bladder to determine the presence and degree of hydronephrosis and ureteral jets. Sonologists were blinded to any other laboratory and imaging data. Patients were followed up at 30 days by phone call and review of medical records. RESULTS: Seventy-seven patients with suspected renal colic were included in the analysis. Thirteen patients were admitted. Reasons for admission included intractable pain, infection, or emergent urologic intervention. All 13 patients requiring admission had hydronephrosis present on initial bedside ultrasound. Patients with moderate hydronephrosis had a higher admission rate (36%) than those with mild hydronephrosis (24%), P<.01. Of patients without hydronephrosis, none required admission within 30 days. The sensitivity and specificity of hydronephrosis for predicting subsequent hospitalization were 100% and 44%, respectively. Loss of the ipsilateral ureteral jet was not significantly associated with subsequent hospital admission and did not improve the predictive value when used in combination with the degree of hydronephrosis. CONCLUSIONS: No patients with suspected renal colic and absence of hydronephrosis on bedside ultrasound required admission within 30 days. Ureteral jet evaluation did not help in prediction of 30-day outcomes and may not be useful in the emergency department management of renal colic.


Assuntos
Hidronefrose/diagnóstico por imagem , Rim/diagnóstico por imagem , Nefrolitíase/diagnóstico por imagem , Cólica Renal/diagnóstico por imagem , Ureter/diagnóstico por imagem , Bexiga Urinária/diagnóstico por imagem , Adulto , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Seguimentos , Hospitais de Ensino , Hospitais Urbanos , Humanos , Hidronefrose/complicações , Masculino , Pessoa de Meia-Idade , Nefrolitíase/complicações , Nefrolitíase/etiologia , Admissão do Paciente , Sistemas Automatizados de Assistência Junto ao Leito , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Cólica Renal/complicações , Cólica Renal/etiologia , Índice de Gravidade de Doença , Ultrassonografia , Ureter/patologia , Ureter/fisiopatologia
19.
Am J Emerg Med ; 33(6): 743-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25817202

RESUMO

BACKGROUND: For patients with early intrauterine pregnancy (IUP), the sonographic signs of the gestation may be below the resolution of transabdominal ultrasound (TAU); however, it may be identified by transvaginal ultrasound (TVU). We sought to determine how often TVU performed in the emergency department (ED) reveals a viable IUP after a nondiagnostic ED TAU and the impact of ED TVU on patient length of stay (LOS). METHODS: This was a retrospective cohort study of women presenting to our ED with complications of early pregnancy from January 1, 2007 to February 28, 2009 in a single urban adult ED. Abstractors recorded clinical and imaging data in a database. Patient imaging modality and results were recorded and compared with respect to ultrasound (US) findings and LOS. RESULTS: Of 2429 subjects identified, 795 required TVU as part of their care. Emergency department TVU was performed in 528 patients, and 267 went to radiology (RAD). Emergency department TVU identified a viable IUP in 261 patients (49.6%). Patients having initial ED US had shorter LOS than patients with initial RAD US (median 4.0 vs 6.0 hours; P < .001). Emergency department LOS was shorter for women who had ED TVU performed compared with those sent for RAD TVU regardless of the findings of the US (median 4.9 vs 6.7 hours; P < .001). There was no increased LOS for patients who needed further RAD US after an indeterminate ED TVU (7.0 vs 7.1 hours; P = .43). There was no difference in LOS for those who had a viable IUP confirmed on ED TAU vs ED (median 3.1 vs 3.2 hours, respectively; P < .32). CONCLUSION: When an ED TVU was performed, a viable IUP was detected 49.6% of the time. Emergency department LOS was significantly shorter for women who received ED TVU after indeterminate ED TAU compared with those sent to RAD for TVU, with more marked time savings among those with live IUP diagnosed on ED TVU. For patients who do not receive a definitive diagnosis of IUP on ED TVU, this approach does not result in increased LOS.


Assuntos
Complicações na Gravidez/diagnóstico por imagem , Primeiro Trimestre da Gravidez , Ultrassonografia Pré-Natal , Adolescente , Adulto , Serviço Hospitalar de Emergência , Feminino , Hospitais Urbanos , Humanos , Pessoa de Meia-Idade , Pennsylvania , Gravidez , Gravidez Ectópica/diagnóstico por imagem , Estudos Retrospectivos
20.
Ann Emerg Med ; 64(3): 277-285.e2, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24875894

RESUMO

The value of point-of-care ultrasound education in resource-limited settings is increasingly recognized, though little guidance exists on how to best construct a sustainable training program. Herein we offer a practical overview of core factors to consider when developing and implementing a point-of-care ultrasound education program in a resource-limited setting. Considerations include analysis of needs assessment findings, development of locally relevant curriculum, access to ultrasound machines and related technological and financial resources, quality assurance and follow-up plans, strategic partnerships, and outcomes measures. Well-planned education programs in these settings increase the potential for long-term influence on clinician skills and patient care.


Assuntos
Educação Médica Continuada/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia , Efeitos Psicossociais da Doença , Currículo , Países em Desenvolvimento , Recursos em Saúde , Humanos , Garantia da Qualidade dos Cuidados de Saúde/métodos , Ultrassonografia/instrumentação
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