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Stereolithography (SLA) 3D printing is a rapid prototyping technique and reproducible manufacturing platform, which makes it a useful tool to develop advanced microfluidic devices for bioanalytical applications. However, limited information exists regarding the physical, chemical, and biological properties of the photocured polymers printed with SLA. This study demonstrates the characterization of a commercially available SLA 3D printed polymer to evaluate the potential presence of any time-dependent changes in material properties that may affect its ability to produce functional, capillary-action microfluidic devices. The printed polymer was analyzed with Fourier transform infrared-attenuated total reflectance, contact angle measurements, tensile test, impact test, scanning electron microscopy, and fluid flow analysis. Polymer biocompatibility was assessed with propidium iodide flow cytometry and an MTT assay for cell viability. The material characterization and biocompatibility results were then implemented to design and fabricate a self-driven capillary action microfluidic device for future use as a bioanalytical assay. This study demonstrates temporally stable mechanical properties and biocompatibility of the SLA polymer. However, surface characterization through contact angle measurements shows the polymer's wettability changes over time which indicates there is a limited postprinting period when the polymer can be used for capillary-based fluid flow. Overall, this study demonstrates the feasibility of implementing SLA as a high-throughput manufacturing method for capillary action microfluidic devices.
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Tracheostomy is a lifesaving, essential procedure performed for airway obstruction in the case of head and neck cancers, prolonged ventilator use, and for long-term pulmonary care. While successful quality improvement interventions in high-income countries such as through the Global Tracheostomy Collaborative significantly reduced length of hospital stay and decreased levels of anxiety among patients, limited literature exists regarding tracheostomy care and practices in low and middle-income countries (LMIC), where most of the world resides. Given limited literature, this scoping review aims to summarize published tracheostomy studies in LMICs and highlight areas in need of quality improvement and clinical research efforts. Based on the PRISMA guidelines, a scoping review of the literature was performed through MEDLINE/PubMed and Embase using terms related to tracheostomy, educational and quality improvement interventions, and LMICs. Publications from 2000-2022 in English were included. Eighteen publications representing 10 countries were included in the final analysis. Seven studies described baseline needs assessments, 3 development of training programs for caregivers, 6 trialed home-based or hospital-based interventions, and finally 2 articles discussed development of standardized protocols. Overall, studies highlighted the unique challenges to tracheostomy care in LMICs including language, literacy barriers, resource availability (running water and electricity in patient homes), and health system access (financial costs of travel and follow-up). There is currently limited published literature on tracheostomy quality improvement and care in LMICs. Opportunities to improve quality of care include increased efforts to measure complications and outcomes, implementing evidence-based interventions tailored to LMIC settings, and using an implementation science framework to study tracheostomy care in LMICs.
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The goal of this paper was to establish a metric, which we refer to as the resilience parameter, to evaluate the ability of a material to retain tensile strength after damage recovery for shape memory polymer (SMP) systems. In this work, three SMP blends created for the additive manufacturing process of fused filament fabrication (FFF) were characterized. The three polymer systems examined in this study were 50/50 by weight binary blends of the following constituents: (1) polylactic acid (PLA) and maleated styrene-ethylene-butylene-styrene (SEBS-g-MA); (2) acrylonitrile butadiene styrene (ABS) and SEBS-g-MA); and (3) PLA and thermoplastic polyurethane (TPU). The blends were melt compounded and specimens were fabricated by way of FFF and injection molding (IM). The effect of shape memory recovery from varying amounts of initial tensile deformation on the mechanical properties of each blend, in both additively manufactured and injection molded forms, was characterized in terms of the change in tensile strength vs. the amount of deformation the specimens recovered from. The findings of this research indicated a sensitivity to manufacturing method for the PLA/TPU blend, which showed an increase in strength with increasing deformation recovery for the injection molded samples, which indicates this blend had excellent resilience. The ABS/SEBS blend showed no change in strength with the amount of deformation recovery, indicating that this blend had good resilience. The PLA/SEBS showed a decrease in strength with an increasing amount of initial deformation, indicating that this blend had poor resilience. The premise behind the development of this parameter is to promote and aid the notion that increased use of shape memory and self-healing polymers could be a strategy for mitigating plastic waste in the environment.
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Introduction: In the era of big data, gene-set pathway analyses derived from multi-omics are exceptionally powerful. When preparing and analyzing high-dimensional multi-omics data, the installation process and programing skills required to use existing tools can be challenging. This is especially the case for those who are not familiar with coding. In addition, implementation with high performance computing solutions is required to run these tools efficiently. Methods: We introduce an automatic multi-omics pathway workflow, a point and click graphical user interface to Multivariate Single Sample Gene Set Analysis (MOGSA), hosted on the Cancer Genomics Cloud by Seven Bridges Genomics. This workflow leverages the combination of different tools to perform data preparation for each given data types, dimensionality reduction, and MOGSA pathway analysis. The Omics data includes copy number alteration, transcriptomics data, proteomics and phosphoproteomics data. We have also provided an additional workflow to help with downloading data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium and preprocessing these data to be used for this multi-omics pathway workflow. Results: The main outputs of this workflow are the distinct pathways for subgroups of interest provided by users, which are displayed in heatmaps if identified. In addition to this, graphs and tables are provided to users for reviewing. Conclusion: Multi-omics Pathway Workflow requires no coding experience. Users can bring their own data or download and preprocess public datasets from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium using our additional workflow based on the samples of interest. Distinct overactivated or deactivated pathways for groups of interest can be found. This useful information is important in effective therapeutic targeting.
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Despite recent advances, hypoplastic left heart syndrome (HLHS) patients subsequent to the Fontan still have significant morbidity and mortality. Some require heart transplant due to systemic ventricular dysfunction. Limited data exist on timing for transplant referral. This study aims to correlate systemic ventricular strain by echocardiography to transplant-free survival. HLHS patients who had Fontan palliation at our institution were included. Patients were divided into: 1) Required transplant or experienced mortality (composite end point); 2) Did not require transplant or survived. For those who experienced the composite endpoint, the last echocardiogram prior to the composite outcome was used, while for those who did not experience the composite endpoint the last echocardiogram obtained was used. Several qualitative and quantitative parameters were analyzed with focus on strain parameters. Ninety-five patients with HLHS Fontan palliation were identified. Sixty-six had adequate images and eight (12%) experienced transplant or mortality. These patients had greater myocardial performance index by flow Doppler (0.72 versus 0.53, p = 0.01), higher systolic/diastolic duration ratio (1.51 versus 1.13, p = 0.02), lower fractional area change (17.65 versus 33.99, p < 0.01), lower global longitudinal strain (GLS) (-8.63 versus - 17.99, p < 0.01), lower global longitudinal strain rate (GLSR) (- 0.51 versus - 0.93, p < 0.01), lower global circumferential strain (GCS) (-6.68 versus -18.25, p < 0.01), and lower (GCSR) global circumferential strain rate (-0.45 versus -1.01, p < 0.01). ROC analysis demonstrated predictive value for GLS - 7.6 (71% sensitive, 97% specific, AUC 81%), GLSR -0.58 (71% sensitive, 88% specific, AUC 82%), GCS - 10.0 (86% sensitive, 91% specific, AUC 82%), and GCSR -0.85 (100% sensitive, 71% specific, AUC 90%). GLS and GCS can help predict transplant-free survival in patients with hypoplastic left heart syndrome having undergone Fontan palliation. Higher strain values (closer to zero) may be a helpful tool in determining when transplant evaluation is warranted in these patients.
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ABSTRACT: The lack of sensitive and robust behavioral assessments of pain in preclinical models has been a major limitation for both pain research and the development of novel analgesics. Here, we demonstrate a novel data acquisition and analysis platform that provides automated, quantitative, and objective measures of naturalistic rodent behavior in an observer-independent and unbiased fashion. The technology records freely behaving mice, in the dark, over extended periods for continuous acquisition of 2 parallel video data streams: (1) near-infrared frustrated total internal reflection for detecting the degree, force, and timing of surface contact and (2) simultaneous ongoing video graphing of whole-body pose. Using machine vision and machine learning, we automatically extract and quantify behavioral features from these data to reveal moment-by-moment changes that capture the internal pain state of rodents in multiple pain models. We show that these voluntary pain-related behaviors are reversible by analgesics and that analgesia can be automatically and objectively differentiated from sedation. Finally, we used this approach to generate a paw luminance ratio measure that is sensitive in capturing dynamic mechanical hypersensitivity over a period and scalable for high-throughput preclinical analgesic efficacy assessment.
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Analgesia , Dolor , Ratones , Animales , Dolor/diagnóstico , Dolor/tratamiento farmacológico , Manejo del Dolor , Analgésicos/farmacología , Analgésicos/uso terapéutico , Dimensión del DolorRESUMEN
In this study, three types of electrospun scaffolds, including furfuryl-gelatin (f-gelatin) alone, f-gelatin with polycaprolactone (PCL) in a 1:1 ratio, and coaxial scaffolds with PCL (core) and f-gelatin (sheath), were developed for tissue engineering applications. Scaffolds were developed through single nozzle electrospinning and coaxial electrospinning, respectively, to serve as scaffolds for cardiac tissue engineering. Uniform fibrous structures were revealed in the scaffolds with significantly varying average fiber diameters of 760 ± 80 nm (f-gelatin), 420 ± 110 nm [f-gelatin and PCL (1:1)], and 810 ± 60 nm (coaxial f-gelatin > PCL) via scanning electron microscopy. The distinction between the core and the sheath of the fibers of the coaxial f-gelatin > PCL electrospun fibrous scaffolds was revealed by transmission electron microscopy. Thermal analysis and Fourier transformed infrared (FTIR) spectroscopy revealed no interactions between the polymers in the blended electrospun scaffolds. The varied blending methods led to significant differences in the elastic moduli of the electrospun scaffolds with the coaxial f-gelatin > PCL revealing the highest elastic modulus of all scaffolds (164 ± 3.85 kPa). All scaffolds exhibited excellent biocompatibility by supporting the adhesion and proliferation of human AC16 cardiomyocytes cells. The biocompatibility of the coaxial f-gelatin > PCL scaffolds with superior elastic modulus was assessed further through adhesion and functionality of human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes, thereby demonstrating the potential of the coaxially spun scaffolds as an ideal platform for developing cardiac tissue-on-a-chip models. Our results demonstrate a facile approach to produce visible light cross-linkable, hybrid, biodegradable nanofibrous scaffold biomaterials, which can serve as platforms for cardiac tissue engineered models.
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The work presented here describes a paradigm for the design of materials for additive manufacturing platforms based on taking advantage of unique physical properties imparted upon the material by the fabrication process. We sought to further investigate past work with binary shape memory polymer blends, which indicated that phase texturization caused by the fused filament fabrication (FFF) process enhanced shape memory properties. In this work, two multi-constituent shape memory polymer systems were developed where the miscibility parameter was the guide in material selection. A comparison with injection molded specimens was also carried out to further investigate the ability of the FFF process to enable enhanced shape memory characteristics as compared to other manufacturing methods. It was found that blend combinations with more closely matching miscibility parameters were more apt at yielding reliable shape memory polymer systems. However, when miscibility parameters differed, a pathway towards the creation of shape memory polymer systems capable of maintaining more than one temporary shape at a time was potentially realized. Additional aspects related to impact modifying of rigid thermoplastics as well as thermomechanical processing on induced crystallinity are also explored. Overall, this work serves as another example in the advancement of additive manufacturing via materials development.
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BACKGROUND AND PURPOSE: Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or TRPA1 activators can silence nociceptors. In this study, we describe BW-031, a novel more potent cationic sodium channel inhibitor, and test whether its application alone can inhibit pain associated with tissue inflammation and whether this strategy can also inhibit cough. EXPERIMENTAL APPROACH: We tested the ability of BW-031 to inhibit pain in three models of tissue inflammation:- inflammation in rat paws produced by complete Freund's adjuvant or by surgical incision and a mouse ultraviolet (UV) burn model. We tested the ability of BW-031 to inhibit cough induced by inhalation of dilute citric acid in guinea pigs. KEY RESULTS: BW-031 inhibited Nav 1.7 and Nav 1.1 channels with approximately sixfold greater potency than QX-314 when introduced inside cells. BW-031 inhibited inflammatory pain in all three models tested, producing more effective and longer-lasting inhibition of pain than QX-314 in the mouse UV burn model. BW-031 was effective in reducing cough counts by 78%-90% when applied intratracheally under isoflurane anaesthesia or by aerosol inhalation in guinea pigs with airway inflammation produced by ovalbumin sensitization. CONCLUSION AND IMPLICATIONS: BW-031 is a novel cationic sodium channel inhibitor that can be applied locally as a single agent to inhibit inflammatory pain. BW-031 can also effectively inhibit cough in a guinea pig model of citric acid-induced cough, suggesting a new clinical approach to treating cough.
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Tos , Bloqueadores de los Canales de Sodio , Animales , Tos/inducido químicamente , Tos/tratamiento farmacológico , Cobayas , Ratones , Nociceptores , Dolor/tratamiento farmacológico , Ratas , Bloqueadores de los Canales de Sodio/farmacología , Bloqueadores de los Canales de Sodio/uso terapéutico , Canales Catiónicos TRPVRESUMEN
BACKGROUND: Failure of the pulmonary valve autograft (PVA) after the Ross procedure (RP) has discouraged its widespread use and has led to modifications or alternatives to the procedure. We sought to analyze whether certain technical modifications could improve results of the RP in children. METHODS: Sixty-nine patients (median age, 12 years; range, 0.25-17.9) underwent the RP between January 1996 and December 2018. A concomitant Konno procedure was performed on 20 of 69 patients (29%). Prior interventions included balloon valvuloplasty in 30 (44%) and/or surgical valvuloplasty in 39 (57%). Technical modifications included using the native aortic root for external annuloplasty, implanting the autograft using uniplanar horizontal sutures through the aortic wall, normalizing the sinotubular junction, and wrapping the native root remnant around the PVA. RESULTS: Operative mortality was 1 of 69 patients (1.5%), with no late deaths. No patient had neoaortic valvar stenosis and 7 of 68 (10%) had mild regurgitation on discharge echocardiogram. At latest follow-up (median, 9.4 years; range, 0.4-21.3) there was no significant change in Z scores of annulus, sinus, or sinotubular junction diameters when compared with those at discharge. Three patients (4.4%) required late autograft replacement, 2 PVA repair, and 2 resection of a pseudoaneurysm. Actuarial freedom from PVA replacement was 87% at 20 years. Freedom from right ventricular outflow tract catheter reintervention or reoperation was 83% and 80%, respectively. CONCLUSIONS: Technical modifications of the RP used in this cohort might successfully prolong the life of the PVA without compromising its growth, an important advantage in pediatric patients.
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Enfermedad de la Válvula Aórtica/cirugía , Valvuloplastia con Balón/métodos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Válvula Pulmonar/trasplante , Adolescente , Enfermedad de la Válvula Aórtica/diagnóstico , Enfermedad de la Válvula Aórtica/mortalidad , Autoinjertos , Valvuloplastia con Balón/mortalidad , Niño , Preescolar , Ecocardiografía Transesofágica , Femenino , Estudios de Seguimiento , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Humanos , Illinois/epidemiología , Lactante , Masculino , Reoperación , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
BACKGROUND: Tetralogy of Fallot is a congenital heart defect diagnosed in infancy. Assessment of right ventricular size and function is important for evaluation of patients with tetralogy of Fallot, but these quantitative measures are challenging by echocardiography. This study evaluates a semi-automated software (EchoInsight®, Epsilon Imaging) by comparing its measures to manual measures in children with tetralogy of Fallot. METHODS: Echocardiographic measurements were performed using manual techniques and semi-automated software. Right ventricular measurements included end-diastolic and end-systolic area, fractional area change, chamber dimensions, and tricuspid annular plane systolic excursion. Reliability, correlation, and agreement between manual and semi-automated measures were assessed. RESULTS: Echocardiograms for 46 patients were analysed. Intra- and inter-observer reliabilities for semi-automated measures were good with intraclass correlation coefficients all over 0.95 and 0.85, respectively. There was high correlation between manual and semi-automated methods for areas and dimensions (r = 0.91-0.98). Tricuspid annular plane systolic excursion measures and fractional area change also correlated, albeit less strongly. The semi-automated measurements of end-systolic and end-diastolic area were a 20 and 47% higher than manual methods, respectively.The semi-automated method yielded a relative 52% lower fractional area change compared to the manual method. CONCLUSIONS: The semi-automated software generates quantitative right ventricular measures in children with tetralogy of Fallot with good reliability and good correlation with manual methods for all measures, but with significant difference between manual and semi-automated techniques for area and functional measures. The specific right ventricular geometry in tetralogy of Fallot children may be why, compared to normal anatomy, greater differences were observed between the two techniques.
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Tetralogía de Fallot , Disfunción Ventricular Derecha , Niño , Diástole , Ecocardiografía , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Reproducibilidad de los Resultados , Tetralogía de Fallot/diagnóstico por imagen , Disfunción Ventricular Derecha/diagnóstico por imagen , Función Ventricular DerechaRESUMEN
It is impossible to secure the airway of a patient with "neck-only" breathing transorally or transnasally. Surgical removal of the larynx (laryngectomy) or tracheal rerouting (tracheoesophageal diversion or laryngotracheal separation) creates anatomic discontinuity. Misguided attempts at oral intubation of neck breathers may cause hypoxic brain injury or death. We present national data from the American Academy of Otolaryngology-Head and Neck Surgery, the American Head and Neck Society, and the United Kingdom's National Reporting and Learning Service. Over half of US otolaryngologist respondents reported instances of attempted oral intubations among patients with laryngectomy, with a mortality rate of 26%. UK audits similarly revealed numerous resuscitation efforts where misunderstanding of neck breather status led to harm or death. Such data underscore the critical importance of staff education, patient engagement, effective signage, and systems-based best practices to reliably clarify neck breather status and provide necessary resources for safe patient airway management.
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Manejo de la Vía Aérea/normas , Intubación Intratraqueal/métodos , Intubación Intratraqueal/normas , Laringectomía , Otolaringología , Encuestas de Atención de la Salud , Humanos , Intubación Intratraqueal/efectos adversos , Boca , Seguridad del PacienteRESUMEN
OBJECTIVE: To evaluate risk factors for pediatric posttonsillectomy hemorrhage (PTH) and the need for transfusion using a national database. STUDY DESIGN: Retrospective cohort study. SETTING: The study was conducted using the Pediatric Health Information System (PHIS) database. METHODS: Children ≤18 years who underwent tonsillectomy with or without adenoidectomy (T±A) between 2004 and 2015 were included. We evaluated the risk of PTH requiring cauterization according to patient demographics, comorbidities, indication for surgery, medications, year of surgery, and geographic region. RESULTS: Of the 551,137 PHIS patients who underwent T±A, 8735 patients (1.58%) experienced a PTH. The risk of PTH increased from 1.33% (95% confidence interval [CI]: 1.15%, 1.53%) in 2010 to 1.91% (95% CI: 1.64%, 2.24%) in 2015 (P < .001). Older age (≥12 vs <5 years old: adjusted odds ratio [aOR] 3.17; 95% CI: 2.86, 3.52), male sex (aOR 1.11; 95% CI: 1.05, 1.17), medical comorbidities (aOR 1.18; 95% CI: 1.08, 1.29), recurrent tonsillitis (aOR 1.15; 95% CI: 1.07, 1.24), and intensive care unit admission (aOR 1.74; 95% CI: 1.55, 1.95) were significantly associated with an increased risk of PTH. Use of ibuprofen (aOR 1.36; 95% CI: 1.22, 1.52), ketorolac (aOR 1.39; 95% CI: 1.14, 1.69), anticonvulsant (aOR 1.23; 95% CI: 1.03, 1.76), and antidepressants (aOR 1.35; 95% CI: 1.03, 1.76) were also associated with an increased risk of PTH. The need for blood transfusion was 2.1% (181/8735). CONCLUSION: The incidence of PTH increased significantly between 2011 and 2015, and ibuprofen appears to be one contributing factor. Given the benefits of ibuprofen, it is unclear whether this increased risk warrants a change in practice.
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Analgésicos no Narcóticos/uso terapéutico , Ibuprofeno/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Hemorragia Posoperatoria/epidemiología , Tonsilectomía/efectos adversos , Adenoidectomía/efectos adversos , Adolescente , Transfusión Sanguínea , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Pautas de la Práctica en Medicina , Estudios Retrospectivos , Factores de Riesgo , Tonsilitis/cirugíaRESUMEN
PURPOSE: Complications in facial plastic surgery can lead to pain, suffering, and permanent harm. Yet, the etiology and outcomes of adverse events are understudied. This study aims to determine the etiology and outcomes of adverse events reported in aesthetic facial plastic surgery and identify quality improvement opportunities. MATERIAL AND METHODS: A cross-sectional survey analysis was conducted using an anonymous 22-item questionnaire distributed to members of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS). Participants were queried on demographics, practice type, and adverse events related to aesthetic facial surgeries. RESULTS: Two hundred fifty-three individuals participated; nearly half of respondents (49.0%) held membership in both AAO-HNS and AAFPRS. Of these, 40.8% of respondents reported at least one adverse event within the past 12 months of practice. A total of 194 adverse events were reported, most commonly related to facelift (n = 59/194, 30.4%), rhinoplasty (n = 55/194, 28.4%), and injection procedures (n = 38/194, 19.6%), with hematoma or seroma being the most commonly described. Most adverse events were self-limited, but approximately 68% resulted in further procedures. Surgeon error or poor judgement (n = 42) and patient non-adherence (n = 18) were the most commonly ascribed reasons for adverse events; 37.1% of participants reported a change in clinical practice after the incident. CONCLUSIONS: Adverse events were not infrequent in facial plastic surgery. Understanding these adverse events can provide impetus for tracking outcomes, standardization, and engagement with lifelong learning, self-assessment, and evaluation of practice performance.
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Cara/cirugía , Mejoramiento de la Calidad , Calidad de la Atención de Salud , Autoevaluación (Psicología) , Cirujanos/psicología , Cirugía Plástica/efectos adversos , Estudios Transversales , Femenino , Humanos , Aprendizaje , Masculino , Seguridad del Paciente , Complicaciones Posoperatorias , Pautas de la Práctica en Medicina , Encuestas y Cuestionarios , Estados UnidosRESUMEN
The BioCompute Object (BCO) standard is an IEEE standard (IEEE 2791-2020) designed to facilitate the communication of next-generation sequencing data analysis with applications across academia, government agencies, and industry. For example, the Food and Drug Administration (FDA) supports the standard for regulatory submissions and includes the standard in their Data Standards Catalog for the submission of HTS data. We created the BCO App to facilitate BCO generation in a range of computational environments and, in part, to participate in the Advanced Track of the precisionFDA BioCompute Object App-a-thon. The application facilitates the generation of BCOs from both workflow metadata provided as plaintext and from workflow contents written in the Common Workflow Language. The application can also access and ingest task execution results from the Cancer Genomics Cloud (CGC), an NCI funded computational platform. Creating a BCO from a CGC task significantly reduces the time required to generate a BCO on the CGC by auto-populating workflow information fields from CGC workflow and task execution results. The BCO App supports exporting BCOs as JSON or PDF files and publishing BCOs to both the CGC platform and to GitHub repositories.
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Biología Computacional , Aplicaciones Móviles , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Flujo de TrabajoRESUMEN
Human papillomavirus (HPV) 16 displays substantial sequence variation; four HPV16 lineages (A, B, C, and D) have been described as well as multiple sublineages. To identify molecular events associated with HPV16 carcinogenesis, we evaluated viral variation, the integration of HPV16, and somatic mutation in 96 cervical cancer samples from Guatemala. A total of 65% (62/96) of the samples had integrated HPV16 sequences and integration was associated with an earlier age of diagnosis and premenopausal disease. HPV16 integration sites were broadly distributed in the genome, but in one tumor, HPV16 integrated into the promoter of the IFN regulatory factor 4 (IRF4) gene, which plays an important role in the regulation of the IFN response to viral infection. The HPV16 D2 and D3 sublineages were found in 23% and 30% of the tumors, respectively, and were significantly associated with adenocarcinoma. D2-positive tumors had a higher rate of integration, earlier age of diagnosis, and a lower rate of somatic mutation, whereas D3-positive tumors were less likely to integrate, had later age of diagnosis, and exhibited a higher rate of somatic mutation. In conclusion, Guatemalan cervical tumors have a high frequency of very high-risk HPV16 D2 and D3 sublineages harboring distinct histology, which may help guide future therapeutic strategies to target the tumor and reduce recurrence. SIGNIFICANCE: This study details the biological and molecular properties of the most pathogenic forms of HPV16, the cause of the majority of cervical cancers.
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Adenocarcinoma/genética , Papillomavirus Humano 16/genética , Factores Reguladores del Interferón/genética , Infecciones por Papillomavirus/genética , Neoplasias del Cuello Uterino/genética , Integración Viral/genética , Adenocarcinoma/virología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Fosfatidilinositol 3-Quinasa Clase I/genética , ADN Viral/análisis , ADN Viral/genética , Femenino , Genoma Viral , Guatemala , Papillomavirus Humano 16/clasificación , Humanos , Persona de Mediana Edad , Mutación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Lesiones Precancerosas/complicaciones , Lesiones Precancerosas/genética , Lesiones Precancerosas/virología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
3D transesophageal echocardiography (3D-TEE) has proven useful and accurate during some operating room (OR), interventional cardiac catheterization (Cath), and electrophysiologic (EP) procedures. The use of 3D-TEE during similar procedures in patients who have undergone Fontan surgery and its additional value have not been previously reported. To determine if live 3D-TEE during procedures post Fontan has added value, 3D-TEEs in 58 post-Fontan patients over a 5-year study period were reviewed. Additional information provided by 3D-TEE (over 2D-TEE) was classified into the following: A: new information which changed/refined the plan and 0: no new important information. Pre- and post-bypass OR 3D-TEEs were counted as one study. A total of 67 3D-TEEs (41 Cath, 13 OR, and 13 EP procedures) were performed. Median age was 14 years (6-39 years). Median weight was 47 kg (21-109 kg). In Cath procedures, only 2/41 (5%) were graded A (R to L atrial level shunt [Fontan leak], n = 1; thrombus in pulmonary artery stump, n = 1). In the OR, 6/13 (46%) were graded A (atrioventricular valvuloplasty, n = 1; neo-aortic valvuloplasty, n = 1; relief of systemic and pulmonary venous outflow obstruction, n = 2 and n = 2; respectively). In EP procedures, 4/13 (31%) were graded A (thrombus, n = 3; mapping for lead placement to assist in multisite pacing for dyssynchrony, n = 1). 3D-TEE of Fontan improved visualization and frequently added value in the OR/EP lab and may be helpful in select catheterization cases. Future studies with a larger sample could build on this data to identify when 3D-TEE will be most useful.
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Ecocardiografía Tridimensional/estadística & datos numéricos , Ecocardiografía Transesofágica/estadística & datos numéricos , Procedimiento de Fontan/métodos , Cardiopatías Congénitas/cirugía , Adolescente , Adulto , Cateterismo Cardíaco/métodos , Niño , Ecocardiografía Tridimensional/métodos , Ecocardiografía Transesofágica/métodos , Femenino , Atrios Cardíacos/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Humanos , Masculino , Trombosis/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Inconsistent and poorly coordinated systems of tracheostomy care commonly result in frustrations, delays, and harm. Quality improvement strategies described by exemplar hospitals of the Global Tracheostomy Collaborative have potential to mitigate such problems. This 3 yr guided implementation programme investigated interventions designed to improve the quality and safety of tracheostomy care. METHODS: The programme management team guided the implementation of 18 interventions over three phases (baseline/implementation/evaluation). Mixed-methods interviews, focus groups, and Hospital Anxiety and Depression Scale questionnaires defined outcome measures, with patient-level databases tracking and benchmarking process metrics. Appreciative inquiry, interviews, and Normalisation Measure Development questionnaires explored change barriers and enablers. RESULTS: All sites implemented at least 16/18 interventions, with the magnitude of some improvements linked to staff engagement (1536 questionnaires from 1019 staff), and 2405 admissions (1868 ICU/high-dependency unit; 7.3% children) were prospectively captured. Median stay was 50 hospital days, 23 ICU days, and 28 tracheostomy days. Incident severity score reduced significantly (n=606; P<0.01). There were significant reductions in ICU (-;0.25 days month-1), ventilator (-;0.11 days month-1), tracheostomy (-;0.35 days month-1), and hospital (-;0.78 days month-1) days (all P<0.01). Time to first vocalisation and first oral intake both decreased by 7 days (n=733; P<0.01). Anxiety decreased by 44% (from 35.9% to 20.0%), and depression decreased by 55% (from 38.7% to 18.3%) (n=385; both P<0.01). Independent economic analysis demonstrated £33 251 savings per patient, with projected annual UK National Health Service savings of £275 million. CONCLUSIONS: This guided improvement programme for tracheostomy patients significantly improved the quality and safety of care, contributing rich qualitative improvement data. Patient-centred outcomes were improved along with significant efficiency and cost savings across diverse UK hospitals. CLINICAL TRIAL REGISTRATION: IRAS-ID-206955; REC-Ref-16/LO/1196; NIHR Portfolio CPMS ID 31544.
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Evaluación de Programas y Proyectos de Salud/métodos , Mejoramiento de la Calidad/estadística & datos numéricos , Traqueostomía/métodos , Traqueostomía/normas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Hospitales , Humanos , Lactante , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Reino Unido , Adulto JovenRESUMEN
There is growing recognition of the need for a coordinated, systematic approach to caring for patients with a tracheostomy. Tracheostomy-related adverse events remain a pervasive global problem, accounting for half of all airway-related deaths and hypoxic brain damage in critical care units. The Global Tracheostomy Collaborative (GTC) was formed in 2012 to improve patient safety and quality of care, emphasising knowledge, skills, teamwork, and patient-centred approaches. Inspired by quality improvement leads in Australia, the UK, and the USA, the GTC implements and disseminates best practices across hospitals and healthcare trusts. Its database collects patient-level information on quality, safety, and organisational efficiencies. The GTC provides an organising structure for quality improvement efforts, promoting safety of paediatric and adult patients. Successful implementation requires instituting key drivers for change that include effective training for health professionals; multidisciplinary team collaboration; engagement and involvement of patients, their families, and carers; and data collection that allows tracking of outcomes. We report the history of the collaborative, its database infrastructure and analytics, and patient outcomes from more than 6500 patients globally. We characterise this patient population for the first time at such scale, reporting predictors of adverse events, mortality, and length of stay indexed to patient characteristics, co-morbidities, risk factors, and context. In one example, the database allowed identification of a previously unrecognised association between bleeding and mortality, reflecting ability to uncover latent risks and promote safety. The GTC provides the foundation for future risk-adjusted benchmarking and a learning community that drives ongoing quality improvement efforts worldwide.
Asunto(s)
Cooperación Internacional , Participación del Paciente/métodos , Seguridad del Paciente , Guías de Práctica Clínica como Asunto , Mejoramiento de la Calidad , Traqueostomía/educación , Traqueostomía/métodos , Humanos , Comunicación Interdisciplinaria , Traqueostomía/normasRESUMEN
BACKGROUND: The authors investigated the durability of vaccine efficacy (VE) against human papillomavirus (HPV)16 or 18 infections and antibody response among nonrandomly assigned women who received a single dose of the bivalent HPV vaccine compared with women who received multiple doses and unvaccinated women. METHODS: HPV infections were compared between HPV16 or 18-vaccinated women aged 18 to 25 years who received one (N = 112), two (N = 62), or three (N = 1365) doses, and age- and geography-matched unvaccinated women (N = 1783) in the long-term follow-up of the Costa Rica HPV Vaccine Trial. Cervical HPV infections were measured at two study visits, approximately 9 and 11 years after initial HPV vaccination, using National Cancer Institute next-generation sequencing TypeSeq1 assay. VE and 95% confidence intervals (CIs) were estimated. HPV16 or 18 antibody levels were measured in all one- and two-dose women, and a subset of three-dose women, using a virus-like particle-based enzyme-linked immunosorbent assay (n = 448). RESULTS: Median follow-up for the HPV-vaccinated group was 11.3 years (interquartile range = 10.9-11.7 years) and did not vary by dose group. VE against prevalent HPV16 or 18 infection was 80.2% (95% CI = 70.7% to 87.0%) among three-dose, 83.8% (95% CI = 19.5% to 99.2%) among two-dose, and 82.1% (95% CI = 40.2% to 97.0%) among single-dose women. HPV16 or 18 antibody levels did not qualitatively decline between years four and 11 regardless of the number of doses given, although one-dose titers continue to be statistically significantly lower compared with two- and three-dose titers. CONCLUSION: More than a decade after HPV vaccination, single-dose VE against HPV16 or 18 infection remained high and HPV16 or 18 antibodies remained stable. A single dose of bivalent HPV vaccine may induce sufficiently durable protection that obviates the need for more doses.