Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
8
result(s) for
"Fields, Bryan W"
Sort by:
Lunchbox and the aliens
Lunchbox is an ordinary basset hound until he is abducted by aliens, zapped by a mental enhancer, and sent back to convert Earth's garbage into food--a task that would be easier if he had opposable thumbs, or at least tentacles.
Book
Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels
T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.
Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared \"public\" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.
Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 85.1% [95% CI = 79.9-89.7]; Day 8-14 = 94.8% [90.7-98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1-98.3]).
The approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring.
Journal Article
Outcome for Arthroscopic Treatment of Anterior Inferior Iliac Spine/Subspine Related Hip Impingement
Objectives:
Extra-articular disorders of the hip are under-recognized and under-reported. Extra-articular forms of hip impingement can include anterior inferior iliac spine (AIIS) related subspine impingement. The purpose of this study was to investigate the outcome after arthroscopic treatment of anterior inferior iliac spine (AIIS)/Subspine related hip impingement.
Methods:
A prospective institutional hip preservation registry was reviewed to identify patients that underwent isolated arthroscopic AIIS decompression. Primary outcome tools captured in the registry included: the modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS) and the international Hip Outcome Tool (iHOT-33). Patients with minimum one-year follow-up were included. Meaningful outcome improvement was determined based on minimal clinically important difference (MCID). Statistical analyses were primarily descriptive.
Results:
Thirty-three patients with mean follow-up 19.1 months (range: 12-44 months) were identified. All patients were female with a mean age of 26.1 (+ 10.3) years. All patients were found to have an associated labral tear and the mean acetabular version was increased at 2 and 3 o’clock (14.5 and 19.8 respectively). Mean pre-operative outcome scores on the mHHS, HOS activities of daily living (ADL), HOS Sport and iHOT-33 were 57.2 (SD+15.3), 66.9 (SD+18.8), 43.9 (SD+23.6) and 33.5 (SD+18.3) respectively. At final available follow-up, mean scores on these outcome measures were 79.5 (SD+19.0), 86.8 (SD+15.8), 70.4 (SD+32.8) and 65.0 (SD+31.0) respectively. By the one-year follow-up interval MCID had been achieved in the majority of patients across all four tools.
Conclusion:
There is a paucity of outcome evidence on AIIS/Subspine related hip impingement. This study demonstrates that isolated subspine impingement can be a cause of hip disability even in the absence of FAI. Patients with isolated subspine impingement are more likely to be women and they present with low patient reported outcome scores. Meaningful outcome improvement can be achieved however with arthroscopic AIIS decompression.
Journal Article
Quantitative MRI Evaluation of Articular Cartilage Using T2 Mapping Following Hip Arthroscopy for Femoroacetabular Impingement
Objectives:
Cam-type femoroacetabular impingement (FAI) causes a shearing and delamination injury to the acetabular articular cartilage due to a mismatch between the size of the femoral head and the acetabulum. This mechanism is thought to lead to early osteoarthritis in this population. Cam decompression has been advocated to eliminate impingement, with the ultimate goal of halting the progression of articular cartilage delamination. Although outcomes following this procedure in the young adult population have been favorable at short and medium term follow up, it is not known whether the articular cartilage itself is protected from further injury by changing the biomechanics of the joint with decompression of the cam morphology. The purpose of this study is to compare the pre- and post-operative integrity of the acetabular articular cartilage using T2 mapping to determine if hip arthroscopy is protective of the articular cartilage at short- to medium term follow up.
Methods:
Males between 18 and 35 years of age who had pre-operative T2 mapping MRIs, underwent hip arthroscopy for cam or mixed-type FAI with an alpha angle greater than 50°, and had at least 2 year follow-up were identified. Post-operative MRIs were performed and T2 relaxation times in the transition zone and weight bearing articular cartilage in the anterosuperior acetabulum at deep and superficial chondral layers were recorded at nine points on three sagittal sequences on pre and post-operative MRIs. A paired t-test was used to compare T2 relaxation values between pre-operative and post-operative scans.
Results:
Eleven hips were evaluated. Mean age was 26.3 years (range 21 - 35). Mean follow up time to post-operative T2 mapping MRI was 2.6 years (range 2.4 - 2.7). The change in T2 relaxation time was not significantly different between pre- and post-operative MRI scans for any of the nine regions in the deep zone of the acetabular cartilage (p=0.065 - 0.969) or the superficial zone of the acetabular cartilage (p= 0.133 - 0.966).
Conclusion:
There was no significant progression of acetabular cartilage degeneration as measured by structural collagen organization and integrity on T2 mapping from pre-operative imaging to the time of two year follow up. Based on this data, it appears that hip arthroscopy for decompression of cam- type FAI slows or halts the process of cartilage degeneration caused by the mechanical wear known to occur in cam-type FAI which is associated with progression to osteoarthritis.
Journal Article
Complete Response to Neoadjuvant Chemoradiation for Rectal Cancer Does Not Influence Survival
Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation.
From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses.
No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases.
Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.
Journal Article
Human Papillomavirus DNA versus Papanicolaou Screening Tests for Cervical Cancer
To the Editor:
The outcome measures appear to have been chosen post hoc by Mayrand et al. (Oct. 18 issue)
1
in their screening trial comparing human papillomavirus (HPV) testing with Papanicolaou (Pap) testing.
1
,
2
The “conservative” outcome definition excludes biopsy-confirmed lesions identified at colposcopy but not verified on final excision or on biopsy immediately before ablation. Such lesions are included in the “liberal” definition, along with lesions identified by random biopsy and endocervical curettage. With the conservative definition, HPV testing is clearly superior, whereas with the liberal definition, neither strategy is clearly superior. Lesions included in the liberal definition may . . .
Journal Article
A pan-cancer PDX histology image repository with genomic and pathological annotations for deep learning analysis
Patient-derived xenografts (PDXs) model human intra-tumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histological imaging via hematoxylin and eosin (H&E) staining is performed on PDX samples for routine assessment and, in principle, captures the complex interplay between tumor and stromal cells. Deep learning (DL)-based analysis of large human H&E image repositories has extracted inter-cellular and morphological signals correlated with disease phenotype and therapeutic response. Here, we present an extensive, pan-cancer repository of nearly 1,000 PDX and paired human progenitor H&E images. These images, curated from the PDXNet consortium, are associated with genomic and transcriptomic data, clinical metadata, pathological assessment of cell composition, and, in several cases, detailed pathological annotation of tumor, stroma, and necrotic regions. We demonstrate that DL can be applied to these images to classify tumor regions and to predict xenograft-transplant lymphoproliferative disorder, the unintended outgrowth of human lymphocytes at the transplantation site. This repository enables PDX-specific, investigations of cancer biology through histopathological analysis and contributes important model system data that expand on existing human histology repositories. We expect the PDXNet Image Repository to be valuable for controlled digital pathology analysis, both for the evaluation of technical issues such as stain normalization and for development of novel computational methods based on spatial behaviors within cancer tissues. Competing Interest Statement The University of Utah may choose to license PDX models developed in the Welm labs, which may result in tangible property royalties to Dr Welm and members of their lab who developed the models. Michael T. Lewis is a founder and limited partner in StemMed Ltd. and a manager in StemMed Holdings, it's general partner. He is a founder and equity stake holder in Tvardi Therapeutics Inc. Some PDX are exclusively licensed to StemMed Ltd. resulting in royalty income to MTL. Lacey Dobrolecki is a compensated employee of StemMed Ltd. The other authors declare no competing interest.
Paper
Regional to Global Assessments of Phytoplankton Dynamics From The SeaWiFS Mission
Photosynthetic production of organic matter by microscopic oceanic phytoplankton fuels ocean ecosystems and contributes roughly half of the Earth's net primary production. For 13 years, the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) mission provided the first consistent, synoptic observations of global ocean ecosystems. Changes in the surface chlorophyll concentration, the primary biological property retrieved from SeaWiFS, have traditionally been used as a metric for phytoplankton abundance and its distribution largely reflects patterns in vertical nutrient transport. On regional to global scales, chlorophyll concentrations covary with sea surface temperature (SST) because SST changes reflect light and nutrient conditions. However, the oceanmay be too complex to be well characterized using a single index such as the chlorophyll concentration. A semi-analytical bio-optical algorithm is used to help interpret regional to global SeaWiFS chlorophyll observations from using three independent, well-validated ocean color data products; the chlorophyll a concentration, absorption by CDM and particulate backscattering. First, we show that observed long-term, global-scale trends in standard chlorophyll retrievals are likely compromised by coincident changes in CDM. Second, we partition the chlorophyll signal into a component due to phytoplankton biomass changes and a component caused by physiological adjustments in intracellular chlorophyll concentrations to changes in mixed layer light levels. We show that biomass changes dominate chlorophyll signals for the high latitude seas and where persistent vertical upwelling is known to occur, while physiological processes dominate chlorophyll variability over much of the tropical and subtropical oceans. The SeaWiFS data set demonstrates complexity in the interpretation of changes in regional to global phytoplankton distributions and illustrates limitations for the assessment of phytoplankton dynamics using chlorophyll retrievals alone.
Journal Article