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1.
Cell ; 186(12): 2506-2509, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-37295395

RESUMO

The number of diversity, equity, and inclusion (DEI) initiatives in science, technology, engineering, mathematics, and medicine (STEMM) have grown over the last few years. We asked several Black scientists what impact they have and why STEMM still needs them. They answer these questions and describe how DEI initiatives should evolve.


Assuntos
População Negra , Engenharia , Humanos , Tecnologia
2.
Cell ; 186(15): 3138-3142, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37478817

RESUMO

Despite tremendous diversity, Asian Americans in STEM are grouped and viewed as a homogeneous monolith, facing stereotypes and disparities. We propose solutions that include disaggregating the Asian American grouping and recognizing the diverse individual ethnic subgroups that comprise Americans of Asian ancestry to implement change within the STEM field.


Assuntos
Asiático , Humanos , Estados Unidos
3.
N Engl J Med ; 387(3): 237-247, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35857660

RESUMO

BACKGROUND: FLT180a (verbrinacogene setparvovec) is a liver-directed adeno-associated virus (AAV) gene therapy that uses a synthetic capsid and a gain-of-function protein to normalize factor IX levels in patients with hemophilia B. METHODS: In this multicenter, open-label, phase 1-2 trial, we assessed the safety and efficacy of varying doses of FLT180a in patients with severe or moderately severe hemophilia B (factor IX level, ≤2% of normal value). All the patients received glucocorticoids with or without tacrolimus for immunosuppression to decrease the risk of vector-related immune responses. After 26 weeks, patients were enrolled in a long-term follow-up study. The primary end points were safety and efficacy, as assessed by factor IX levels at week 26. RESULTS: Ten patients received one of four FLT180a doses of vector genomes (vg) per kilogram of body weight: 3.84×1011 vg, 6.40×1011 vg, 8.32×1011 vg, or 1.28×1012 vg. After receiving the infusion, all the patients had dose-dependent increases in factor IX levels. At a median follow-up of 27.2 months (range, 19.1 to 42.4), sustained factor IX activity was observed in all the patients except one, who resumed factor IX prophylaxis. As of the data-cutoff date (September 20, 2021), five patients had normal factor IX levels (range, 51 to 78%), three patients had levels from 23 to 43%, and one had a level of 260%. Of the reported adverse events, approximately 10% were related to FLT180a and 24% to immunosuppression. Increases in liver aminotransferase levels were the most common FLT180a-related adverse events. Late increases in aminotransferase levels occurred in patients who had received prolonged tacrolimus beyond the glucocorticoid taper. A serious adverse event of arteriovenous fistula thrombosis occurred in the patient with high factor IX levels. CONCLUSIONS: Sustained factor IX levels in the normal range were observed with low doses of FLT180a but necessitated immunosuppression with glucocorticoids with or without tacrolimus. (Funded by Freeline Therapeutics; ClinicalTrials.gov numbers, NCT03369444 and NCT03641703; EudraCT numbers, 2017-000852-24 and 2017-005080-40.).


Assuntos
Dependovirus , Terapia Genética , Glucocorticoides , Hemofilia B , Dependovirus/genética , Fator IX/análise , Fator IX/genética , Seguimentos , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Vetores Genéticos/uso terapêutico , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Hemofilia B/genética , Hemofilia B/metabolismo , Hemofilia B/terapia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Transaminases/análise
4.
Curr Opin Ophthalmol ; 35(3): 260-264, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38484226

RESUMO

PURPOSE OF REVIEW: Over the past decade, the number of studies published using network meta-analyses (NMAs) has rapidly increased, and there have been continued advancements to further advance this analysis approach. Due to the fast moving and changing landscape in the infancy of NMA methodology, there is a lack of consistency and standardization for this approach. This article aims to summarize the crucial components of an NMA for both future readers, and for potential NMA authors. RECENT FINDINGS: Key components of NMAs include, but are not limited to, reporting the proposed analysis methods, assessment of risk of bias within the included studies, reporting the overall quality of the available evidence, and defining the parameters in which the results will be presented. Although NMA allows for a comprehensive evaluation of all available treatment options for a given condition, we believe that there is importance in ensuring clear understanding and appropriate interpretation of results to inform clinical practice. SUMMARY: While many components of NMA mirror those of traditional pairwise meta-analysis, there are many novel methodologies that are specific to this approach. It is imperative that future NMAs follow guidance from key methodology groups, as these provide valuable tools for conducting and reporting NMAs.


Assuntos
Oftalmologistas , Humanos , Previsões , Metanálise em Rede
5.
Am J Physiol Heart Circ Physiol ; 325(5): H965-H982, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37624101

RESUMO

With sparse treatment options, cardiac disease remains a significant cause of death among humans. As a person ages, mitochondria breakdown and the heart becomes less efficient. Heart failure is linked to many mitochondria-associated processes, including endoplasmic reticulum stress, mitochondrial bioenergetics, insulin signaling, autophagy, and oxidative stress. The roles of key mitochondrial complexes that dictate the ultrastructure, such as the mitochondrial contact site and cristae organizing system (MICOS), in aging cardiac muscle are poorly understood. To better understand the cause of age-related alteration in mitochondrial structure in cardiac muscle, we used transmission electron microscopy (TEM) and serial block facing-scanning electron microscopy (SBF-SEM) to quantitatively analyze the three-dimensional (3-D) networks in cardiac muscle samples of male mice at aging intervals of 3 mo, 1 yr, and 2 yr. Here, we present the loss of cristae morphology, the inner folds of the mitochondria, across age. In conjunction with this, the three-dimensional (3-D) volume of mitochondria decreased. These findings mimicked observed phenotypes in murine cardiac fibroblasts with CRISPR/Cas9 knockout of Mitofilin, Chchd3, Chchd6 (some members of the MICOS complex), and Opa1, which showed poorer oxidative consumption rate and mitochondria with decreased mitochondrial length and volume. In combination, these data show the need to explore if loss of the MICOS complex in the heart may be involved in age-associated mitochondrial and cristae structural changes.NEW & NOTEWORTHY This article shows how mitochondria in murine cardiac changes, importantly elucidating age-related changes. It also is the first to show that the MICOS complex may play a role in outer membrane mitochondrial structure.


Assuntos
Mitocôndrias , Miocárdio , Humanos , Masculino , Camundongos , Animais , Mitocôndrias/metabolismo , Miocárdio/metabolismo , Coração , Envelhecimento , Transdução de Sinais , Proteínas Mitocondriais/metabolismo
6.
Ophthalmology ; 130(11): 1201-1211, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37429499

RESUMO

TOPIC: We reviewed the use of patient-reported outcome measures (PROMs) in the treatment of ophthalmologic conditions as recommended by the Clinical Practice Guidelines (CPGs) published by the American Academy of Ophthalmology (AAO). CLINICAL RELEVANCE: Patient-reported outcome measures are standardized instruments that provide information regarding a patient's health status or health-related quality of life. Patient-reported outcome measures are increasingly used to inform study end points in ophthalmology studies. However, the extent to which PROMs are ultimately informing patient management recommendations in ophthalmology as part of CPGs remains an area of evidence gap. METHODS: We included all CPGs published by the AAO from inception to June 2022. We also included all primary studies and systematic reviews cited in the treatment sections of the CPGs evaluating treatment of an ophthalmic condition. The primary outcome was the frequency of PROMs discussed in CPGs and in cited studies evaluating treatment. Secondary outcomes included frequency of minimal important difference (MID) use to contextualize PROM results and percentage of strong and discretionary recommendations supported by PROMs. We published a study protocol a priori on PROSPERO (CRD42022307427). Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We assessed risk of bias using the Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. RESULTS: We identified 24 eligible CPGs, providing 2458 cited studies (2191 primary, 267 secondary) evaluating treatment of eye conditions. Ten CPGs (41.7%) reported consideration of PROMs. Of these, 31 of 94 (33%) recommendations were informed by studies evaluating a PROM as an outcome. Across all studies cited in the development of CPGs, 221 (9.0%) used PROMs as a primary or secondary outcome, of which 4 PROM results (1.8%) were interpreted using an empirically determined MID. Overall, the risk of bias was low for all CPGs. CONCLUSIONS: Overall, outcomes of PROMs are seldom used in ophthalmology CPGs published by the AAO and in cited primary and secondary research on treatments. When PROMs were considered, their interpretation was seldom based on an MID. To improve patient care, guideline developers may consider incorporating PROMs and applicable MIDs to inform key outcomes when formulating treatment recommendations. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

7.
Opt Lett ; 48(7): 1942-1945, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37221805

RESUMO

High-resolution tunable laser absorption spectroscopy is used to measure time-resolved absorption spectra for six neutral uranium transitions in a laser-produced plasma. Analysis of the spectra shows that kinetic temperatures are similar for all six transitions, but excitation temperatures are higher than kinetic temperatures from 10-100 µs, indicating departures from local thermodynamic equilibrium.

8.
J Chem Phys ; 159(17)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37916590

RESUMO

The role of ambient oxygen gas (O2) on molecular and nanoparticle formation and agglomeration was studied in laser ablation plumes. As a lab-scale surrogate to a high explosion detonation event, nanosecond laser ablation of an aluminum alloy (AA6061) target was performed in atmospheric pressure conditions. Optical emission spectroscopy and two mass spectrometry techniques were used to monitor the early to late stages of plasma generation to track the evolution of atoms, molecules, clusters, nanoparticles, and agglomerates. The experiments were performed under atmospheric pressure air, atmospheric pressure nitrogen, and 20% and 5% O2 (balance N2), the latter specifically with in situ mass spectrometry. Electron microscopy was performed ex situ to identify crystal structure and elemental distributions in individual nanoparticles. We find that the presence of ≈20% O2 leads to strong AlO emission, whereas in a flowing N2 environment (with trace O2), AlN and strong, unreacted Al emissions are present. In situ mass spectrometry reveals that as O2 availability increases, Al oxide cluster size increases. Nanoparticle agglomerates formed in air are found to be larger than those formed under N2 gas. High-resolution transmission electron microscopy demonstrates that Al2O3 and AlN nanoparticle agglomerates are formed in both environments; indicating that the presence of trace O2 can lead to Al2O3 nanoparticle formation. The present results highlight that the availability of O2 in the ambient gas significantly impacts spectral signatures, cluster size, and nanoparticle agglomeration behavior. These results are relevant to understanding debris formation in an explosion event, and interpreting data from forensic investigations.

9.
Appl Opt ; 62(29): 7643-7657, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37855472

RESUMO

We present experimental results using a swept-wavelength external cavity quantum cascade laser (swept-ECQCL) diagnostic to measure broadband absorption spectra over a range of 920-1180c m -1 (8.47-10.87 µm) with 2 ms temporal resolution in premixed hydrogen/oxygen flames propagating inside an enclosed chamber. Broadband spectral fits are used to determine time-resolved temperatures and column densities of H 2 O produced during combustion. Modeling of the flowfield within the test chamber under both equilibrium conditions and using a 1D freely propagating flame model is compared with the experiment in terms of temporal dynamics, temperatures, and H 2 O column density. Outputs from the numerical models were used to simulate radiative transport through an inhomogeneous combustion region and evaluate the performance of the spectral fitting model. Simulations show that probing hot-band H 2 O transitions in the high-temperature combustion regions minimizes errors due to spatial inhomogeneity. Good agreement is found between the experimental and modeling results considering experimental uncertainties and model assumptions.

10.
Ophthalmology ; 129(5): 498-508, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34871637

RESUMO

TOPIC: To investigate the effect of anti-vascular endothelial growth factor (VEGF) therapy on intraocular pressure (IOP) 12 and 24 months after initiation. CLINICAL RELEVANCE: It is unclear whether serial anti-VEGF injections result in sustained IOP increases. METHODS: Randomized controlled trials (RCTs) comparing anti-VEGF agents with each other or with controls for the treatment of neovascular age-related macular degeneration, retinal vein occlusions, or diabetic macular edema were included. Pairwise meta-analysis and Bayesian network meta-analysis examined the proportion of patients whose IOP (1) increased 5 mmHg or more from baseline on consecutive visits, (2) increased 10 mmHg or more from baseline at any visit, (3) was 21 mmHg or more on consecutive visits, (4) was 25 mmHg or more at any visit, (5) was 30 mmHg or more at any visit, (6) prompted initiation of IOP-lowering medications, or (7) increased as per the clinicians' discretion. Grading of Recommendations Assessments, Development, and Evaluations methodology informed the certainty of evidence. RESULTS: Twenty-six RCTs of 12 522 eyes were included. Aflibercept, bevacizumab, ranibizumab (0.3 mg and 0.5 mg), and noninjection controls were analyzed. Eighty-three of 84 network estimates for comparisons between anti-VEGF agents demonstrated no statistically significant difference (low to moderate certainty of evidence). Ranibizumab 0.5 mg showed higher rates than bevacizumab of IOP measurements of 30 mmHg or more at 12 months (low certainty of evidence). Fifty-three of 56 network estimates for comparisons between anti-VEGF agents and controls demonstrated no statistically significant difference (low to moderate certainty of evidence). Ranibizumab 0.5 mg showed higher rates of consecutive IOP increases of 5 mmHg or more at 24 months (low certainty of evidence) and higher rates of IOP increases as per the clinicians' discretion at 12 and 24 months (low and very low certainty of evidence, respectively). The 95% credible intervals in comparisons without statistically significant effects did not rule out important clinical effects. The certainty of evidence in these comparisons is limited by imprecision. CONCLUSION: This network meta-analysis does not show any clear difference in IOP increases 12 and 24 months after treatment initiation between anti-VEGF agents and controls. Imprecision precludes definitive conclusions.


Assuntos
Pressão Intraocular , Ranibizumab , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Humanos , Injeções Intravítreas , Metanálise em Rede , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
11.
Opt Lett ; 47(10): 2502-2505, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35561385

RESUMO

Broadband and high-resolution absorption spectra of molecular cerium oxide (CeO) are obtained in a laser-produced plasma using dual-comb spectroscopy. Simultaneous measurements of Ce and CeO are used to probe time-resolved dynamics of the system. A spectral resolution of 1.24 GHz (2.4 pm) over a bandwidth of 378.7-383.7 THz (781.1-791.5 nm) allows simultaneous detection of hundreds of closely spaced rotational transitions in complex CeO bands.

12.
Catheter Cardiovasc Interv ; 100(5): 759-762, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36098336

RESUMO

INTRODUCTION: One strategy to improve the effectiveness of intravascular brachytherapy (IVBT) is to study its failures. Previous investigations described mostly discrete, focal recurrences, typically at the proximal or distal edges of the irradiated segment after plain angioplasty or bare metal stents. We reviewed failure patterns of 30 unselected drug-eluting stent (DES) patients who had follow-up angiograms for recurrence within their IVBT-treated vessel. METHODS: Records of 53 unselected IVBT patients treated between 2016 and 2021 were reviewed. Thirty of the 53 patients had at least one subsequent percutaneous intervention (PCI) for in-stent restenosis (ISR) after IVBT. Angiographic findings of those 30 patients with ISR within their previously irradiated vessel are reported here. RESULTS: Of the 30 patients, 21 (70%) developed recurrent ISR within the irradiated segment. Six of the 21 patients who failed within the irradiated segment also experienced ISR proximal or distal to the irradiated segment. Only 15 patients (50%) failed exclusively within the irradiated segment. In nine patients (30%), restenosis occurred proximally and/or distally to the irradiated segment, but not inside of the irradiated segment itself. CONCLUSIONS: We have shown here that 50% of failures after coronary IVBT for DES ISR occur exclusively within the irradiated segment. An additional 20% of patients had failure within and outside of the irradiated segment. These percentages suggest that a higher radiation dose might improve the long-term patency rates, a conclusion that should be tempered by the lack of universal follow-up.


Assuntos
Braquiterapia , Reestenose Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/radioterapia , Braquiterapia/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Stents , Constrição Patológica/etiologia , Angiografia Coronária
13.
Phys Chem Chem Phys ; 24(43): 26583-26590, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36285772

RESUMO

The evolution from gas-phase oxidation to nanoparticle and agglomerate formation was studied in nanosecond laser-produced plasmas of a multi-principal element alloy target in air. Gas-phase oxidation of plasma species was monitored in situ via optical emission spectroscopy, while a custom-built single particle mass spectrometer was used to measure size and compositions of agglomerated nanoparticles formed in laser ablation plumes. Ex situ analysis employing transmission electron microscopy was used to study nanoparticle morphology, crystal structure, and element distribution at the nanoscale. Emission spectra indicate that gas-phase oxidation of elements in the alloy target are formed at varying times during plume evolution, and mass spectrometry results indicate fractal agglomerates contain all principal alloying elements and their oxides. Finally, electron microscopy characterization illustrates that these agglomerates consist of multiple material types: sub-10 nm diameter amorphous, multi-element nanoparticles, ≈10-30 nm diameter Ti-rich crystalline oxide nanoparticles, and ejected base material. Results highlight that the multi-component target composition impacts molecular formation in the gas phase and the morphology, composition, and structure of nanoparticles and agglomerates formed.

14.
Ophthalmologica ; 245(2): 101-110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34731858

RESUMO

OBJECTIVES: The present review aimed to synthesize evidence from randomized controlled trials (RCTs) that compared outcomes of pars plana vitrectomy (PPV) with and without a supplementary scleral buckle (SB) for management of rhegmatogenous retinal detachment (RRD). METHODS: The authors searched MEDLINE, Embase, and CENTRAL to identify RCTs in English that compared PPV with and without supplemental SB. Risk of bias was assessed according to the Cochrane Risk of Bias 2 tool. We present risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs) estimated using random-effects meta-analyses. RESULTS: We identified 6 RCTs involving 705 eyes. Primary reattachment (6 studies, 345 eyes PPV, 324 eyes PPV + SB; RR 0.99, 95% CI 0.93-1.06, I2 = 0%, p = 0.78) and final anatomic success rates (4 studies, 272 eyes PPV, 267 eyes PPV + SB; RR 1.00, 95% CI 0.98-1.02, I2 = 0%, p = 0.89) were similar between the 2 groups. Postoperative visual acuity improvement (5 studies, 244 eyes PPV, 222 eyes PPV + SB; MD 6.09 letters, 95% CI -0.47-12.64, I2 = 69%, p = 0.07) and frequency of adverse events (6 studies, 1,294 observations PPV, 1,221 observations PPV + SB; RR 0.76, 95% CI 0.57-1.01, I2 = 25%, p = 0.06) likewise did not differ significantly between the treatment groups. CONCLUSION: Low-certainty evidence from RCTs did not demonstrate a benefit in placement of a supplemental SB during vitrectomy for management of RRD in the current analysis. Additional high-quality trials are needed to provide more precise estimates of the effect.


Assuntos
Descolamento Retiniano , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Recurvamento da Esclera/efeitos adversos , Resultado do Tratamento , Vitrectomia
15.
J Appl Clin Med Phys ; 23(4): e13513, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34985180

RESUMO

PURPOSE: Total body irradiation (TBI) is an integral part of stem cell transplant. However, patients are at risk of treatment-related toxicities, including radiation pneumonitis. While lung dose is one of the most crucial aspects of TBI dosimetry, currently available data are based on point doses. As volumetric dose distribution could be substantially altered by lung block parameters, we used 3D dosimetry in our treatment planning system to estimate volumetric lung dose and measure the impact of various lung block designs. MATERIALS AND METHODS: We commissioned a TBI beam model in RayStation that matches the measured tissue-phantom ratio under our clinical TBI setup. Cerrobend blocks were automatically generated in RayStation on thoracic Computed Tomography (CT) scans from three anonymized patients using the lung, clavicle, spine, and diaphragmatic contours. The margin for block edge was varied to 0, 1, or 2 cm from the superior, lateral, and inferior thoracic borders, with a uniform margin 2.5 cm lateral to the vertebral bodies. The lung dose was calculated and compared with a prescription dose of 1200 cGy in six fractions (three with blocks and three without). RESULT: The point dose at midplane under the block and the average lung dose are at the range of 73%-76% and 80%-88% of prescription dose respectively regardless of the block margins. In contrast, the percent lung volume receiving 10 Gy increased by nearly two-fold, from 31% to 60% over the margins from 0 to 2 cm. CONCLUSIONS: The TPS-derived 3D lung dose is substantially different from the nominal dose assumed with HVL lung blocks. Point doses under the block are insufficient to accurately gauge the relationship between dose and pneumonitis, and TBI dosimetry could be highly variable between patients and institutions as more descriptive parameters are not included in protocols. Much progress remains to be made to optimize and standardize technical aspects of TBI, and better dosimetry could provide more precise dosimetric predictors for pneumonitis risk.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Irradiação Corporal Total , Humanos , Pulmão/efeitos da radiação , Radiometria/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Irradiação Corporal Total/métodos
16.
Knee Surg Sports Traumatol Arthrosc ; 30(7): 2364-2376, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35112181

RESUMO

PURPOSE: The primary aim of this network meta-analysis (NMA) is to compare the incidence of venous thromboembolisms (VTE) and bleeding risk following the use of pharmacological and non-pharmacological thromboprophylaxis for arthroscopic knee surgery (AKS). This study assumed the null hypothesis which was that there will be no difference in the incidence of VTE and bleeding risk when comparing no treatment, pharmacological treatment, and non-pharmacological treatment for preventing VTE events following AKS. METHODS: A systematic electronic search of CENTRAL, Medline, Embase, and ClinicalTrials.gov was carried out. All English language prospective randomized clinical trials published from date of database inception to November 21, 2021 were eligible for inclusion. All papers addressing arthroscopic knee surgery were eligible for inclusion regardless of timing of surgery, operation, surgical technique, or rehabilitation. Multiple random effects NMAs were conducted to compare all treatments for each outcome. The primary outcome was the incidence of pulmonary embolism (PE) and secondary outcomes consisted of overall deep vein thrombosis (DVT), symptomatic DVT, asymptomatic DVT, and all-cause mortality. Adverse outcomes consisted of major and minor bleeding, as well as adverse events. RESULTS: A total of nine studies with 4526 patients were included for analysis. There were 1054 patients in the no treatment/placebo group (NT/Placebo), 1646 patients in the graduated compression stockings, 810 patients in the extended-duration (> 10 days) low molecular weight heparin (Ext-LMWH) group, 650 patients in the short-duration (< 10 days) LMWH group (Short-LMWH), and 356 patients in the rivaroxaban group. GCS, Ext-LMWH, Short-LMWH and rivaroxaban all demonstrated low risks of PE, symptomatic DVT, asymptomatic DVT, combined DVT and all-cause mortality. Similarly, all interventions demonstrated a low risk of major bleeding. CONCLUSION: There is no significant difference in the risk reduction of PEs, symptomatic DVTs, major/minor bleeding, and/or all-cause mortality when using LWMH (including short or extended regimens), rivaroxaban, graduated compression stockings or no treatment following arthroscopic knee surgery. Future primary research on the efficacy of thromboprophylaxis following arthroscopic knee surgery should stratify outcomes based on key patient (i.e., age, sex, comorbidities) and surgical (i.e., major vs. minor surgery) characteristics and should include acetylsalicylic acid as an intervention. LEVEL OF EVIDENCE: I, network meta-analysis of Level I studies.


Assuntos
Anticoagulantes , Artroscopia , Trombose Venosa , Anticoagulantes/uso terapêutico , Artroscopia/efeitos adversos , Hemorragia/epidemiologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Metanálise em Rede , Estudos Prospectivos , Medição de Risco , Rivaroxabana/uso terapêutico , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controle
17.
Int J Mol Sci ; 23(3)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35162994

RESUMO

Experimental evolution with Drosophila melanogaster has been used extensively for decades to study aging and longevity. In recent years, the addition of DNA and RNA sequencing to this framework has allowed researchers to leverage the statistical power inherent to experimental evolution to study the genetic basis of longevity itself. Here, we incorporated metabolomic data into to this framework to generate even deeper insights into the physiological and genetic mechanisms underlying longevity differences in three groups of experimentally evolved D. melanogaster populations with different aging and longevity patterns. Our metabolomic analysis found that aging alters mitochondrial metabolism through increased consumption of NAD+ and increased usage of the TCA cycle. Combining our genomic and metabolomic data produced a list of biologically relevant candidate genes. Among these candidates, we found significant enrichment for genes and pathways associated with neurological development and function, and carbohydrate metabolism. While we do not explicitly find enrichment for aging canonical genes, neurological dysregulation and carbohydrate metabolism are both known to be associated with accelerated aging and reduced longevity. Taken together, our results provide plausible genetic mechanisms for what might be driving longevity differences in this experimental system. More broadly, our findings demonstrate the value of combining multiple types of omic data with experimental evolution when attempting to dissect mechanisms underlying complex and highly polygenic traits such as aging.


Assuntos
Envelhecimento/genética , Drosophila melanogaster/fisiologia , Genômica/métodos , Metabolômica/métodos , Envelhecimento/metabolismo , Animais , Metabolismo dos Carboidratos , Ciclo do Ácido Cítrico , Evolução Molecular Direcionada , Drosophila melanogaster/genética , Longevidade , Mitocôndrias/metabolismo , Herança Multifatorial , NAD/metabolismo , Polimorfismo de Nucleotídeo Único
18.
Mol Ecol ; 30(4): 877-879, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33410164

RESUMO

The ability to predict how natural populations will evolve and adapt to major changes in environmental conditions has long been of interest to evolutionary biologists and ecologists alike. The reality of global climate change has also created a pressing need for advancement in this particular area of research, as species are increasingly faced with rapid shifts in abiotic and biotic conditions. Evolutionary genomics has the potential to be incredibly useful as we move forward in addressing this need and in particular, evolve and resequence (E&R) studies-where researchers combine experimental evolution with whole-genome sequencing-have an important role to play. However, while E&R studies have shown a great deal of promise in tackling fundamental questions regarding the genetics of adaptation (Long et al., 2015; Schlötterer et al., 2014), it is unclear whether results from laboratory experiments can be directly translated to natural populations. In a From the Cover article in this issue of Molecular Ecology, Hsu et al. (Mol Ecol, 29, 2020) explicitly contend with this issue by examining the overlap between genes implicated in thermal adaptation in a Drosophila melanogaster E&R study and genes identified by comparing natural populations from different latitudinal clines. They report significant correlations between the two sets of temperature-adaptive genes and ultimately conclude that E&R studies can indeed generate insights applicable to populations inhabiting complex natural environments. While more work is needed to assess the generality of these conclusions, Hsu and Belmouaden (Mol Ecol, 29, 2020) contribute an important precedent.


Assuntos
Drosophila melanogaster , Seleção Genética , Animais , Drosophila melanogaster/genética , Expressão Gênica , Genética Populacional , Laboratórios
19.
Opt Lett ; 46(4): 860-863, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33577532

RESUMO

We introduce a new, to the best of our knowledge, modality of dual-comb spectroscopy (DCS) that enables a simplified and powerful new approach for time-resolved measurements with increased acquisition rates. This "burst mode" form of DCS relies on the multiplexing of each probe pulse into a short train of pulses. With this approach we demonstrate a time-resolved series of absorption-based spectroscopic measurements of a laser-induced plasma using only a single laser ablation shot and identify 22 Nd lines not previously reported in the literature. The transmission spectra spanned 3.1 THz and were acquired at an effective acquisition rate of 25 kHz with 40 µs time resolution. This simple modification to ∼100MHz level dual-comb systems provides a flexible approach for studying transient and low-duty-cycle events such as laser-induced plasmas, combustion, and explosive reactions.

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