The advancement of microbioreactor technology in recent years has transformed early- and mid-stage process development. The monitoring and control capabilities of microbioreactors not only promote the quick accumulation of process knowledge but has also led to an increased scalability when compared to traditionally used systems such as shake flasks and microtitre plates. This study seeks to establish a framework for the micro-Matrix microbioreactor (Applikon-Biotechnology BV) as process development tool.
View Article and Find Full Text PDFIntroduction: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection.
Methods: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded.
Traumatic brain injury (TBI), particularly of greater severity (i.e., moderate to severe), has been identified as a risk factor for all-cause dementia and Parkinson's disease, with risk for specific dementia subtypes being more variable.
View Article and Find Full Text PDFThe study of protein O-glycosylation is important in biological research as O-glycans have been reported to regulate a multitude of molecular and cell biology processes occurring in cancer. It is known that alterations in O-glycosylation are involved in the development and progression of cancer. Their easy accessibility makes in vitro established cell lines suitable and useful models for studying biological mechanisms in disease.
View Article and Find Full Text PDFImportance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood.
View Article and Find Full Text PDFLocoregional delivery of chimeric antigen receptor (CAR) T cells has resulted in objective responses in adults with glioblastoma, but the feasibility and tolerability of this approach is yet to be evaluated for pediatric central nervous system (CNS) tumors. Here we show that engineering of a medium-length CAR spacer enhances the therapeutic efficacy of human erb-b2 receptor tyrosine kinase 2 (HER2)-specific CAR T cells in an orthotopic xenograft medulloblastoma model. We translated these findings into BrainChild-01 ( NCT03500991 ), an ongoing phase 1 clinical trial at Seattle Children's evaluating repetitive locoregional dosing of these HER2-specific CAR T cells to children and young adults with recurrent/refractory CNS tumors, including diffuse midline glioma.
View Article and Find Full Text PDFCardiovascular disease (CVD), diabetes and cancer pose increasing global healthcare burdens. New biomarkers could enable earlier diagnosis of these diseases, leading to more effective treatment and lower associated healthcare burden. Elevated sialic acid concentration in plasma and serum has been positively correlated with the presence of CVDs, diabetes and the development of malignant tumors.
View Article and Find Full Text PDFObjective: To compare malpractice claim rates before and after participation in simulation training, which focused on team training during a high-acuity clinical case.
Methods: We performed a retrospective analysis comparing the claim rates before and after simulation training among 292 obstetrician-gynecologists, all of whom were insured by the same malpractice insurer, who attended one or more simulation training sessions from 2002 to 2019. The insurer provided malpractice claims data involving study physicians, along with durations of coverage, which we used to calculate claim rates, expressed as claims per 100 physician coverage years.
While individuals diagnosed with autism spectrum disorders (ASD) have higher levels of antibodies directed towards gliadin, a component of wheat gluten, no study has examined anti-gliadin antibodies (AGA) in etiologically relevant periods before diagnosis. The objective of this study was to investigate if maternal levels of AGA, during pregnancy and at the time of birth, are associated with ASD in offspring. We analyzed AGA in archived neonatal dried blood spots (NDBS) for 921 ASD cases and 1090 controls, and in paired maternal sera collected earlier in pregnancy for a subset of 547 cases and 428 controls.
View Article and Find Full Text PDFPurpose: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model.
Experimental Design: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses.
Aims: Implantable device-based sensor measurements including heart sounds, markers of ventilation, and thoracic impedance have been shown to predict heart failure (HF) hospitalizations. We sought to assess how these parameters changed prior to COVID-19 (Cov-19) and how these compared with those presenting with decompensated HF or pneumonia.
Methods And Results: This retrospective analysis explores patterns of changes in daily measurements by implantable sensors in 10 patients with Cov-19 and compares these findings with those observed prior to HF (n = 88) and pneumonia (n = 12) hospitalizations from the MultiSENSE, PREEMPT-HF, and MANAGE-HF trials.
CA1 and subiculum (SUB) connect the hippocampus to numerous output regions. Cells in both areas have place-specific firing fields, although they are more dispersed in SUB. Weak responses to head direction and running speed have been reported in both regions.
View Article and Find Full Text PDFUnlabelled: Recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B-cell malignancies are immunocompromised and at risk for serious infections. Vaccine immunogenicity is unknown in this population. We conducted a prospective observational study of the humoral immunogenicity of 2019-2020 inactivated influenza vaccines (IIV) in children and adults immediately prior to (n=7) or 13-57 months after (n=15) CD19-, CD20-, or BCMA-targeted CAR-T-cell therapy, as well as controls (n=8).
View Article and Find Full Text PDFTo this day, there are limited data about the effects and management of coronavirus disease infection in pediatric patients with sickle cell disease. We present the management and successful clinical course of an 8-year-old female with homozygous sickle cell disease (SS) and severe acute chest syndrome secondary to coronavirus disease 2019 infection, complicated by cortical vein thrombosis.
View Article and Find Full Text PDFBACKGROUNDLittle is known about pathogen-specific humoral immunity after chimeric antigen receptor-modified T (CAR-T) cell therapy for B cell malignancies.METHODSWe conducted a prospective cross-sectional study of CD19-targeted or B cell maturation antigen-targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected ("epitope hits") using a serological profiling assay.
View Article and Find Full Text PDFMeasuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms.
View Article and Find Full Text PDFSeveral extensions of the Standard Model predict the production of dark matter particles at the LHC. An uncharted signature of dark matter particles produced in association with VV=W^{±}W^{∓} or ZZ pairs from a decay of a dark Higgs boson s is searched for using 139 fb^{-1} of pp collisions recorded by the ATLAS detector at a center-of-mass energy of 13 TeV. The s→V(qq[over ¯])V(qq[over ¯]) decays are reconstructed with a novel technique aimed at resolving the dense topology from boosted VV pairs using jets in the calorimeter and tracking information.
View Article and Find Full Text PDFThe first measurement of longitudinal decorrelations of harmonic flow amplitudes v_{n} for n=2-4 in Xe+Xe collisions at sqrt[s_{NN}]=5.44 TeV is obtained using 3 μb^{-1} of data with the ATLAS detector at the LHC. The decorrelation signal for v_{3} and v_{4} is found to be nearly independent of collision centrality and transverse momentum (p_{T}) requirements on final-state particles, but for v_{2} a strong centrality and p_{T} dependence is seen.
View Article and Find Full Text PDFObjective: To establish the acceptability and feasibility of delivering the Active Communication Education (ACE) programme to increase quality of life through improving communication and hearing aid use in the UK National Health Service.
Design: Randomised controlled, open feasibility trial with embedded economic and process evaluations.
Setting: Audiology departments in two hospitals in two UK cities.
Importance: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients.
Objective: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI.
Design, Setting, And Participants: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018.