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1.
Langmuir ; 39(39): 13782-13789, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37737718

RESUMO

Despite their high gravimetric and volumetric energy densities, boron (B) particles suffer from poor oxidative energy release rates as the boron oxide (B2O3) shell impedes the diffusivity of O2 to the particle interior. Recent experiemental studies have shown that the addition of metals with a lower free energy of oxidation, such as Mg, can reduce the oxide shell of B and enhance the energetic performance of B by ∼30-60%. However, the exact underlying mechanism behind the reactivity enhancement is unknown. Here, we performed DFTB-MD simulations to study the reaction of Mg vapor with a B2O3 surface. We found that the Mg becomes oxidized on the B2O3 surface, forming a MgBxOy phase, which induces a tensile strain in the B-O bond at the MgBxOy-B2O3 interface, simultaneously reducing the interfacial B and thereby developing dangling bonds. The interfacial bond straining creates an overall surface expansion, indicating the presence of a net tensile strain. The B with dangling bonds can act as active centers for gas-phase O2 adsorption, thereby increasing the adsorption rate, and the overall tensile strain on the surface will increase the diffusion flux of adsorbed O through the surface to the particle core. As the overall B particle oxidation rate is dependent on both the O adsorption and diffusion rates, the enhancement in both of these rates increases the overall reactivity of B particles.

2.
J Chem Phys ; 158(14): 144112, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37061479

RESUMO

Semi-empirical quantum models such as Density Functional Tight Binding (DFTB) are attractive methods for obtaining quantum simulation data at longer time and length scales than possible with standard approaches. However, application of these models can require lengthy effort due to the lack of a systematic approach for their development. In this work, we discuss the use of the Chebyshev Interaction Model for Efficient Simulation (ChIMES) to create rapidly parameterized DFTB models, which exhibit strong transferability due to the inclusion of many-body interactions that might otherwise be inaccurate. We apply our modeling approach to silicon polymorphs and review previous work on titanium hydride. We also review the creation of a general purpose DFTB/ChIMES model for organic molecules and compounds that approaches hybrid functional and coupled cluster accuracy with two orders of magnitude fewer parameters than similar neural network approaches. In all cases, DFTB/ChIMES yields similar accuracy to the underlying quantum method with orders of magnitude improvement in computational cost. Our developments provide a way to create computationally efficient and highly accurate simulations over varying extreme thermodynamic conditions, where physical and chemical properties can be difficult to interrogate directly, and there is historically a significant reliance on theoretical approaches for interpretation and validation of experimental results.

3.
Int J Tuberc Lung Dis ; 27(4): 322-328, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37035979

RESUMO

BACKGROUND: TB control remains a serious public health problem, compounded by poor treatment adherence, which increases the likelihood of onward transmission. We evaluated the effectiveness of medication event reminder monitoring (MERM) upon treatment adherence in a high TB burden setting.METHODS: We conducted an open-label parallel group randomised controlled trial among pulmonary TB adults. Participants were provided with a MERM device to store their medications. In the intervention arm, the devices were set to provide daily medication intake reminders. Primary outcome was the proportion of patient-months in which at least 6/30 doses were missed. Secondary outcomes included 1) the proportion of patient-months in which at least 14/30 doses were missed, and 2) the proportion of doses missed.RESULTS: Of 2,142 patients screened, 798 (37.3%) met the inclusion criteria and 250 participants were enrolled. The mean ratio (MR) for poor adherence between the intervention and control groups was 0.72 (95% CI 0.55-0.86). The intervention was also associated with a reduction in the proportion of patients missing at least 14/30 doses (MR 0.61, 95% CI 0.54-0.68) and the percentage of total doses missed (MR 0.75, 95% CI 0.68-0.80).CONCLUSION: MERM is effective in improving TB treatment adherence in a resource-limited environment.


Assuntos
Adesão à Medicação , Tuberculose Pulmonar , Adulto , Humanos , Sistemas de Alerta , Tuberculose Pulmonar/tratamento farmacológico , Monitoramento de Medicamentos
4.
CJEM ; 25(1): 48-56, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36577931

RESUMO

PURPOSE: Point-of-care ultrasonography (POCUS) is an established tool in the management of hypotensive patients in the emergency department (ED). We compared the diagnostic accuracy of a POCUS protocol versus standard assessment without POCUS in patients with undifferentiated hypotension. METHODS: This was an international, multicenter randomized controlled trial included three EDs in North America and three in South Africa from September 2012 to December 2016. Hypotensive patients were randomized to early POCUS protocol plus standard care (POCUS group) or standard care without POCUS (control group). Initial and secondary diagnoses were recorded at 0 and 60 min. The main outcome was measures of diagnostic accuracy of a POCUS protocol in differentiating between cardiogenic and non-cardiogenic shock. Secondary outcomes were diagnostic performance for shock sub-types, as well as changes in perceived category of shock and overall diagnosis. RESULTS: Follow-up was completed for 270 of 273 patients. For cardiogenic shock, the POCUS-based diagnostic approach (POCUS) performed similarly to the non-POCUS approach (control) for specificity [95.5% (89.9-98.5) vs.93.8% (87.7-97.5)]; positive likelihood ratio (17.92 vs 14.80); negative likelihood ratio (0.21 vs 0.09) and diagnostic odds ratio (85.6 vs 166.57), with a similar overall diagnostic accuracy between the two approaches [93.7% (88-97.2) vs 93.6% (87.8-97.2)]. Diagnostic performance measures were similar across sub-categories of shock. CONCLUSION: This is the first randomized controlled trial to compare diagnostic performance of a POCUS protocol to standard care without POCUS in undifferentiated hypotensive ED patients. POCUS performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test; however, performance did not differ meaningfully from standard assessment.


RéSUMé: OBJECTIF: L'échographie au point d'intervention (POCUS) est un outil bien établi dans la gestion des patients hypotendus dans le service des urgences. Nous avons comparé la précision diagnostique d'un protocole POCUS par rapport à une évaluation standard sans POCUS chez des patients présentant une hypotension indifférenciée. MéTHODES: Il s'agissait d'un essai contrôlé randomisé international multicentrique incluant 3 services d'urgence en Amérique du Nord et 3 en Afrique du Sud de septembre 2012 à décembre 2016. Les patients hypotenseurs ont été répartis par randomisation selon le protocole POCUS précoce plus les soins standard (groupe POCUS) ou les soins standard sans POCUS (groupe témoin). Les diagnostics initiaux et secondaires ont été enregistrés à 0 et 60 minutes. Le principal résultat était la mesure de la précision diagnostique d'un protocole POCUS pour différencier le choc cardiogénique du choc non cardiogénique. Les résultats secondaires étaient la performance diagnostique pour les sous-types de chocs, ainsi que les changements dans la perception de la catégorie de choc et du diagnostic global. RéSULTATS: Le suivi a été complété pour 270 des 273 patients. Pour le choc cardiogénique, l'approche diagnostique basée sur le POCUS (POCUS) a donné des résultats similaires à l'approche non-POCUS (Contrôle) pour la spécificité (95,5 % (89,9­98,5) vs 93,8 % (87,7­97,5)) ; Rapport de vraisemblance positif (17,92 vs 14,80) ; Le rapport de vraisemblance négatif (0,21 vs 0,09) et le rapport de cotes diagnostiques (85,6 vs 166,57), avec une précision diagnostique globale similaire entre les deux approches (93,7 % (88­97,2) vs 93,6 % (87,8­97,2). Les mesures de performance diagnostique étaient similaires dans toutes les sous-catégories de choc. CONCLUSION: Il s'agit du premier essai contrôlé randomisé visant à comparer la performance diagnostique d'un protocole POCUS aux soins standard sans POCUS chez des patients hypotendus indifférenciés aux urgences. La POCUS a donné de bons résultats diagnostiques chez les patients hypotendus indifférenciés, surtout en tant que test de référence ; cependant, les performances ne diffèrent pas de manière significative de l'évaluation standard.


Assuntos
Hipotensão , Choque , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia/métodos , Hipotensão/diagnóstico por imagem , Choque/diagnóstico por imagem , Serviço Hospitalar de Emergência , Choque Cardiogênico
5.
Hum Reprod ; 37(12): 2768-2776, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36223599

RESUMO

STUDY QUESTION: Is a strategy starting with transvaginal hydrolaparoscopy (THL) cost-effective compared to a strategy starting with hysterosalpingography (HSG) in the work-up for subfertility? SUMMARY ANSWER: A strategy starting with THL is cost-effective compared to a strategy starting with HSG in the work-up for subfertile women. WHAT IS KNOWN ALREADY: Tubal pathology is a common cause of subfertility and tubal patency testing is one of the cornerstones of the fertility work-up. Both THL and HSG are safe procedures and can be used as a first-line tubal patency test. STUDY DESIGN, SIZE, DURATION: This economic evaluation was performed alongside a randomized clinical trial comparing THL and HSG in 300 subfertile women, between May 2013 and October 2016. For comparisons of THL and HSG, the unit costs were split into three main categories: costs of the diagnostic procedure, costs of fertility treatments and the costs for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subfertile women scheduled for tubal patency testing were eligible. Women were randomized to a strategy starting with THL or a strategy starting with HSG. The primary outcome of the study was conception leading to a live birth within 24 months after randomization. The mean costs and outcomes for each treatment group were compared. We used a non-parametric bootstrap resampling of 1000 re-samples to investigate the effect of uncertainty and we created a cost-effectiveness plane and cost-effectiveness acceptability curves. MAIN RESULTS AND THE ROLE OF CHANCE: We allocated 149 women to THL and 151 to HSG, and we were able to achieve complete follow-up of 142 versus 148 women, respectively. After the fertility work-up women were treated according to the Dutch guidelines and based on a previously published prognostic model. In the THL group, 83 women (58.4%) conceived a live born child within 24 months after randomization compared to 82 women (55.4%) in the HSG group (difference 3.0% (95% CI: -8.3 to 14.4)). The mean total costs per woman were lower in the THL group compared to the HSG group (THL group €4991 versus €5262 in the HSG group, mean cost difference = -€271 (95% CI -€273 to -€269)). Although the costs of only the diagnostic procedure were higher in the THL group, in the HSG group more women underwent diagnostic and therapeutic laparoscopies and also had higher costs for fertility treatments. LIMITATIONS, REASONS FOR CAUTION: Our trial was conducted in women with a low risk of tubal pathology; therefore, the results of our study are not generalizable to women with high risk of tubal pathology. Furthermore, this economic analysis was based on the Dutch healthcare system, and possibly our results are not generalizable to countries with different strategies or costs for fertility treatments. WIDER IMPLICATIONS OF THE FINDINGS: After 2 years of follow-up, we found a live birth rate of 58.4% in the THL group versus 55.4% in the HSG group and a lower mean cost per woman in the THL group, with a cost difference of -€271. The findings of our trial suggest that a strategy starting with THL is cost-effective compared to a strategy starting with HSG in the workup for subfertile women. However, the cost difference between the two diagnostic strategies is limited compared to the total cost per woman in our study and before implementing THL as a first-line strategy for tubal patency testing, more research in other fields, such as patient preference and acceptance, is necessary. STUDY FUNDING/COMPETING INTEREST(S): The authors received no external financial support for the research. B.W.J.M. is supported by an NHMRC Investigator Grant (GNT1176437). B.W.J.M. reports consultancy for ObsEva, Merck KGaA, Guerbet. B.W.J.M. reports receiving travel support from Merck KGaA. C.T.P. reports consultancy for Guerbet, outside of this manuscript. All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: NTR3462.


Assuntos
Histerossalpingografia , Infertilidade , Feminino , Humanos , Gravidez , Coeficiente de Natalidade , Análise Custo-Benefício , Nascido Vivo
6.
Dermatologie (Heidelb) ; 73(11): 829-837, 2022 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-36167913

RESUMO

BACKGROUND: Due to the corona pandemic and also to the new competence-oriented catalogue of learning objectives in medicine and the master plan for medical studies 2020, the development of digital and practical teaching concepts has experienced a great increase in importance. AIM OF THE WORK: As a result of this development, it was an important task to establish this combination and incorporate it into the curricular teaching process. MATERIAL AND METHODS: The "Toolkit dermatology" was established, which was sent to a total of more than 650 students at German university dermatology clinics. Using educational films, the students were able to practice their skills. In a further development, the toolkit was combined with classroom lectures and the students were asked to evaluate the toolkit online. RESULTS: The vast majority of students (95-100%) clearly stated that the toolkit helped them to develop their practical skills. Some of them were in fact motivated to complete a clinical traineeship/practical tertial year in dermatology (21-88%). The combination of toolkit and subsequent classroom teaching was also rated very positively (82.2%), as this hybrid mode of teaching provided a better understanding. DISCUSSION: Digital teaching formats as part of the concept of blended learning, i.e. the combination of virtual and analogue teaching formats, are becoming increasingly more important. Solutions for the disadvantages, such as the lack of real interaction and suitable examination formats, still remain to be found; however, the toolkit project demonstrates that hands-on and digital teaching can lead to high student motivation as well as a high educational standard.


Assuntos
Dermatologia , Estudantes de Medicina , Humanos , Dermatologia/educação , Aprendizagem , Motivação
7.
Front Cardiovasc Med ; 9: 956538, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990966

RESUMO

Background: The phosphoinositide 3-kinase (PI3K) signaling pathway is an interesting target in cancer treatment. The awareness of the proarrhythmic risk of PI3K inhibitors was raised because PI3K is also involved in regulating signaling toward cardiac ion channels. Canine cardiomyocytes treated with PI3K inhibitors show an increased action potential duration and reduced cardiac repolarizing currents. Now, the potential proarrhythmic effect of chronic treatment of PI3K/mTOR inhibitor GSK2126458 (omipalisib) was investigated in the atrioventricular (AV) block dog model. Methods: Purpose-bred Mongrel dogs received complete AV block by ablation of the bundle of His and their hearts were paced in the right ventricular apex at VDD-mode (RVA-VDD). In this way, sinus rhythm was maintained for 15 ± 1 days and thereby bradycardia-induced cardiac remodeling was prevented. Dogs received 1 mg/kg omipalisib once (n = 3) or twice (n = 10) a day via oral administration for 7 days. Under standardized conditions (anesthesia, bradycardia at 60 beats/min, and a dofetilide challenge), potential proarrhythmic effects of omipalisib were investigated. Results: Twice daily dosing of omipalisib increased accumulative plasma levels compared to once daily dosing accompanied with adverse events. Omipalisib prolonged the QT interval at baseline and more strongly after the dofetilide challenge (490 ± 37 to 607 ± 48 ms). The arrhythmic outcome after omipalisib resulted in single ectopic beats in 30% of dogs perpetuating in multiple ectopic beats and TdP arrhythmia in 20% of dogs. Isolated ventricular cardiomyocytes from omipalisib-treated dogs showed a diminished IKs current density. Conclusion: Chronic treatment of PI3K/mTOR inhibitor omipalisib prolonged the QT interval in a preclinical model under standardized proarrhythmic conditions. Furthermore, this study showed that electrical remodeling induced by omipalisib had a mild proarrhythmic outcome.

8.
HPB (Oxford) ; 24(1): 17-29, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34172378

RESUMO

BACKGROUND: Indeterminate strictures pose a therapeutic dilemma. In recent years, cholangioscopy has evolved and the availability of cholangioscopy has increased. However, the position of cholangioscopy in the diagnostic algorithm to diagnose malignancy have not been well established. We aim to develop a consensus statement regarding the clinical role of cholangioscopy in the diagnosis of indeterminate biliary strictures. METHODS: The international experts reviewed the evidence and modified the statements using a three-step modified Delphi method. Each statement achieves consensus when it has at least 80% agreement. RESULTS: Nine final statements were formulated. An indeterminate biliary stricture is defined as that of uncertain etiology under imaging or tissue diagnosis. When available, cholangioscopic assessment and guided biopsy during the first round of ERCP may reduce the need to perform multiple procedures. Cholangioscopy are helpful in diagnosing malignant biliary strictures by both direct visualization and targeted biopsy. The absence of disease progression for at least 6 months is supportive of non-malignant etiology. Direct per-oral cholangioscopy provides the largest accessory channel, better image definition, with image enhancement but is technically demanding. Image enhancement during cholangioscopy may increase the diagnostic sensitivity of visual impression of malignant biliary strictures. Cholangioscopic imaging characteristics including tumor vessels, papillary projection, nodular or polypoid mass, and infiltrative lesions are highly suggestive for neoplastic/malignant biliary disease. The risk of cholangioscopy related cholangitis is higher than in standard ERCP, necessitating prophylactic antibiotics and ensuring adequate biliary drainage. Per-oral cholangioscopy may not be the modality of choice in the evaluation of distal biliary strictures due to inherent technical difficulties. CONCLUSION: Evidence supports that cholangioscopy has an adjunct role to abdominal imaging and ERCP tissue acquisition in order to evaluate and diagnose indeterminate biliary strictures.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar , Colestase , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Biópsia/efeitos adversos , Biópsia/métodos , Colestase/diagnóstico por imagem , Colestase/etiologia , Consenso , Constrição Patológica/diagnóstico , Constrição Patológica/etiologia , Humanos
9.
J Chem Theory Comput ; 17(7): 4435-4448, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34128678

RESUMO

Density functional tight binding (DFTB) is an attractive method for accelerated quantum simulations of condensed matter due to its enhanced computational efficiency over standard density functional theory (DFT) approaches. However, DFTB models can be challenging to determine for individual systems of interest, especially for metallic and interfacial systems where different bonding arrangements can lead to significant changes in electronic states. In this regard, we have created a rapid-screening approach for determining systematically improvable DFTB interaction potentials that can yield transferable models for a variety of conditions. Our method leverages a recent reactive molecular dynamics force field where many-body interactions are represented by linear combinations of Chebyshev polynomials. This allows for the efficient creation of multi-center representations with relative ease, requiring only a small investment in initial DFT calculations. We have focused our workflow on TiH2 as a model system and show that a relatively small training set based on unit-cell-sized calculations yields a model accurate for both bulk and surface properties. Our approach is easy to implement and can yield reliable DFTB models over a broad range of thermodynamic conditions, where physical and chemical properties can be difficult to interrogate directly and there is historically a significant reliance on theoretical approaches for interpretation and validation of experimental results.

10.
Orbit ; 40(3): 243-246, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32449417

RESUMO

Purpose: To describe and evaluate a novel technique for eyelid margin repair without the use of marginal sutures.Methods: A retrospective chart review of patients who underwent primary repair of full-thickness lid margin defects using the described technique between March 2013 and May 2019 was performed. Clinical data such as indication for repair as well as size of defect was analyzed. The primary outcome measures included presence or absence of lid notching and post-operative complications such as wound dehiscence, infection, eyelid malposition, and keratopathy. Descriptive statistics were used.Results: A total of 31 cases were identified. Five were excluded in post-operative analysis for follow-up of less than 2 weeks. The average age was 59.6 years (range 22-88) and 54.8% of patients were female. Average follow up in post-operative analysis group was 17.0 weeks (range 2 weeks to 42 months). Average defect size was 5.77 mm (range 2-12 mm). Reasons for repair were resection of eyelid lesion in 25/31 (80.6%), floppy eyelid in 4/31 (12.9%), trauma in 1/31 (3.2%), and trichiasis in 1/31 (3.2%). Post-operative eyelid notching was noted in 2/26 patients (7.7%), and there were no instances of wound dehiscence, infection, eyelid malposition, or keratopathy noted.Conclusions: Our technique for full-thickness eyelid margin repair without the use of marginal sutures successfully repairs defects up to 12 mm for various indications. We observed comparable cosmetic outcomes to previously described techniques as well as a low rate of complications using our technique.


Assuntos
Blefaroplastia , Doenças Palpebrais , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Palpebrais/cirurgia , Pálpebras/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Suturas , Resultado do Tratamento , Adulto Jovem
11.
HIV Med ; 22(1): 28-36, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32964664

RESUMO

OBJECTIVES: We aimed to compare the effectiveness of antiretroviral therapy (ART) classes for achieving HIV RNA suppression to < 50 HIV-1 RNA copies/mL within 6 months of initiation with high viral loads (VLs). Secondary objectives were to compare viral suppression (VS) at 12 weeks and 12 months, partial HIV RNA suppression to < 200 copies/mL, time to VS, time to rebound, and change in CD4 cell count. METHODS: This was a multicentre, retrospective, observational study. Adult patients were included if they initiated ART between January 2005 and December 2016 with a VL ≥ 100 000 copies/mL. RESULTS: There were 220 patients included in the study. The median VL was 252 919 [interquartile range (IQR) 149 472-500 000] copies/mL. Nonnucleoside reverse transcriptase inhibitor (NNRTI) recipients were more likely to achieve VS by 6 months compared to those initiating ART containing protease inhibitors (PIs) [75.4% vs. 44.1%, respectively; odds ratio (OR) 3.34; 95% confidence interval (CI) 1.62-6.90] or integrase strand transfer inhibitors (INSTIs) (75.4% vs. 55.8%, respectively; OR 2.40; 95% CI 1.03-5.58). VS at 12 weeks was more frequent with INSTI-containing regimens than with PIs (28.9% vs. 9.0%, respectively; OR 4.10; 95% CI 1.69-9.92). VS at 12 months did not significantly differ between treatment regimens. Median time to complete VS for INSTI, PI and NNRTI recipients was 22.3 (95% CI 13.4-33), 30.1 (95% CI 25-36) and 19.9 (95% CI 16-22.3) weeks, respectively. There were no significant differences in time to viral rebound or change in CD4 cell counts. CONCLUSIONS: Patients with high VLs initiated on NNRTIs were more likely to achieve VS by 6 months on ART compared to INSTI and PI recipients.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral/efeitos dos fármacos , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral/estatística & dados numéricos
12.
Mar Pollut Bull ; 153: 110999, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32275548

RESUMO

Marine microplastic pollution is an issue of great concern nowadays since high concentrations have been detected in the ocean, mainly in the subtropical gyres that accumulate this type of debris. The long-term effects of this pollution on ecosystems and marine biota are still unknown. The aim of this study is to quantify and characterise microplastics and neustonic zooplankton in sub-surface waters of the Macaronesian region, an area that has been little studied to date. Our results show a great variability in the concentration of microplastics with values between 15,283 items/km2 in Los Gigantes (Tenerife, Canary Islands) and 1,007,872 items/km2 in Las Canteras (Gran Canaria, Canary Islands). The main types of debris found were plastic fragments and fibres. The abundances of neustonic zooplankton were also very variable between the different sampling areas, being the main components copepods and eggs. Regarding the microplastics-zooplankton ratio, values were obtained between 0.002 and 0.22. In Las Canteras, the highest accumulation zone, was found twice as much microplastics as zooplankton for the 1-5 mm fraction in dry weight. These values highlight the potential hazard of microplastics - and its associated chemical contaminants - for marine biota, especially for large filter feeders.


Assuntos
Monitoramento Ambiental , Microplásticos , Poluentes Químicos da Água , Animais , Ecossistema , Plásticos , Espanha
13.
Sci Rep ; 10(1): 4879, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32165655

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

14.
Sci Adv ; 5(11): eaav9879, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31807694

RESUMO

In both human and murine systems, we have developed an adoptive cellular therapy platform against medulloblastoma and glioblastoma that uses dendritic cells pulsed with a tumor RNA transcriptome to expand polyclonal tumor-reactive T cells against a plurality of antigens within heterogeneous brain tumors. We demonstrate that peripheral TCR Vß repertoire analysis after adoptive cellular therapy reveals that effective response to adoptive cellular therapy is concordant with massive in vivo expansion and persistence of tumor-specific T cell clones within the peripheral blood. In preclinical models of medulloblastoma and glioblastoma, and in a patient with relapsed medulloblastoma receiving adoptive cellular therapy, an early and massive expansion of tumor-reactive lymphocytes, coupled with prolonged persistence in the peripheral blood, is observed during effective therapeutic response to immunotherapy treatment.


Assuntos
Transferência Adotiva , Neoplasias Cerebelares , Imunoterapia Adotiva , Meduloblastoma , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Linfócitos T , Animais , Linhagem Celular Tumoral , Neoplasias Cerebelares/imunologia , Neoplasias Cerebelares/terapia , Humanos , Meduloblastoma/imunologia , Meduloblastoma/patologia , Meduloblastoma/terapia , Camundongos , Camundongos Transgênicos , Linfócitos T/imunologia , Linfócitos T/patologia
15.
Sci Rep ; 9(1): 15843, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676767

RESUMO

Deep-sea sponge grounds are vulnerable marine ecosystems, which through their benthic-pelagic coupling of nutrients, are of functional relevance to the deep-sea realm. The impact of fishing bycatch is here evaluated for the first time at a bathyal, sponge-dominated ecosystem in the high seas managed by the Northwest Atlantic Fisheries Organization. Sponge biomass surfaces created from research survey data using both random forest modeling and a gridded surface revealed 231,140 t of sponges in the area. About 65% of that biomass was protected by current fisheries closures. However, projections of trawling tracks estimated that the sponge biomass within them would be wiped out in just 1 year by the current level of fishing activity if directed on the sponges. Because these sponges filter 56,143 ± 15,047 million litres of seawater daily, consume 63.11 ± 11.83 t of organic carbon through respiration, and affect the turnover of several nitrogen nutrients, their removal would likely affect the delicate ecological equilibrium of the deep-sea benthic ecosystem. We estimated that, on Flemish Cap, the economic value associated with seawater filtration by the sponges is nearly double the market value of the fish catch. Hence, fishery closures are essential to reach sponge conservation goals as economic drivers cannot be relied upon.


Assuntos
Conservação dos Recursos Naturais/economia , Ecossistema , Pesqueiros/economia , Oceanos e Mares , Poríferos , Animais
16.
Burns ; 45(3): 509-525, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29914737

RESUMO

PURPOSE: Measuring gastric residual volumes (GRV) is common in intensive care units (ICU) in patients receiving enteral nutrition (EN) and are a common source of feeding interruptions. Interruptions in EN yield adverse outcomes and are an area of improvement in burn care. The objectives of this study are to summarize the literature's ICU GRV practices and offer practical suggestions to GRV management in the burn patient. METHODS: PubMed, SCOPUS, and OvidSP Medline were systematically reviewed using the keywords: burns; thermal injury; gastric residual volume; enteral feeding; tube feeding; enteral nutrition; gastric intolerance; ICU; critical illness. Reviews, case reports, and consensus and opinion papers were excluded. RESULTS: 26 articles were identified. Six burn-specific studies were identified. GRV practices vary widely and are a common cause of EN interruption. Elevated GRVs do not equate to gastrointestinal intolerance and do not always reflect aspiration risk. CONCLUSIONS: We advocate a GRV threshold of 500mL should be used to optimize the benefits of EN in burn ICUs. A single incident of elevated GRVs should not mandate immediate EN rate reduction or cessation but should prompt a thoughtful examination of secondary causes of gastrointestinal intolerance. Randomized controlled trials are needed to define the ideal GRV threshold and re-evaluate its role in burn care.


Assuntos
Queimaduras/terapia , Nutrição Enteral/métodos , Esvaziamento Gástrico , Aspiração Respiratória/epidemiologia , Estômago , Cuidados Críticos , Estado Terminal , Humanos , Unidades de Terapia Intensiva
17.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 6553-6556, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31947343

RESUMO

Magnetic Resonance Imaging (MRI) can provide 3D morphological information on brain structures. Such information is particularly relevant for carrying out morphometric brain analysis, especially in the newborn and in the case of prematurity. However, 3D neonatal MRI acquired in clinical environments are low-resolution, anisotropic images, making segmentation a challenging task. In this context, preprocessing techniques aim to increase the image resolution. Interpolation techniques were classically used; super-resolution (SR) techniques have recently appeared as an emerging alternative. In this paper, we evaluate the performance of different SR methods against the classical interpolation in the application of neonatal cortex segmentation. Additionally, we assess the robustness of different segmentation methods for each estimation of high resolution MRI input. Results are evaluated both qualitatively and quantitatively with neonatal clinical MRI.


Assuntos
Algoritmos , Imageamento por Ressonância Magnética , Anisotropia , Encéfalo , Humanos , Recém-Nascido , Manejo de Espécimes
19.
Burns ; 44(8): 2006-2010, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30115532

RESUMO

OBJECTIVE: "NPO at midnight" is a standard preoperative practice intended to reduce aspiration risk but can result in prolonged feeding interruptions in critically ill burn patients. Postoperative hyperalimentation in the form of a "catch-up" tube feeding protocol is routine. A retrospective review of our perioperative fasting practices and "catch-up" enteral feeding protocols was performed. METHODS: Patients admitted to the Burn ICU from July 1st, 2015 to August 31st, 2016 were reviewed. Patients who had a protected airway in place, prescribed enteral nutrition, and underwent surgery were included. The time from NPO to surgical start (NPO-SS), NPO to feeding restart (NPO-FR), and calories received/prescribed were quantified. The efficacy of a postoperative catch-up feeding protocol was analyzed. RESULTS: There were 41 patients that fit inclusion criteria with some undergoing multiple surgeries, yielding 109 surgeries/discrete perioperative events. The average total body surface area burn (38.1±23.6%), age (38.8±20.1years), ICU days (45.0±37.3 days), and ventilator days (35.1±33.8 days) were calculated. Average fasting durations of NPO-SS and NPO-FR were 9.3±3.1 and 14.2±4.1h, respectively. The average caloric deficit to prescribed calories ratio during the NPO-SS and NPO-FR periods were 1154±629/3534±851kcal and 1765±928/3534±851kcal, respectively. A post-operative catch-up protocol completely compensated for perioperative caloric deficits 68.8% (22/32) of the time. CONCLUSIONS: In critically ill burn patients, a preoperative fast resulted in an average loss of greater than 50% of prescribed calories on the day of surgery. Clinicians should re-evaluate the standard practice of making preoperative patients "NPO at midnight". An effective catch-up protocol can adequately reduce caloric deficits.


Assuntos
Queimaduras/cirurgia , Nutrição Enteral/métodos , Jejum , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios/métodos , Adolescente , Adulto , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
20.
Inorg Chem ; 57(16): 9839-9843, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30067340

RESUMO

Computer simulations are carried out to characterize the variation of spin-crossover (SCO) behavior of the prototypical {Fe(pz)[Pt(CN)4]} metal-organic framework (MOF) upon adsorption of chemically and structurally different guest molecules. A detailed analysis of both strength and anisotropy of guest molecule-framework interactions reveals direct correlations between the mobility of the guest molecules inside the MOF pores, the rotational mobility of the pyrazine rings of the framework, and the stabilization of the low-spin state of the material. On the basis of these correlations, precise molecular criteria are established for predicting the spin state of {Fe(pz)[Pt(CN)4]} upon guest adsorption. Finally, predictions of the SCO temperature upon adsorption of various toxic gases demonstrate that in silico modeling can provide fundamental insights and design principles for the development of spin-crossover MOFs for applications in gas detection and chemical sensing.

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