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Addressing Label Variability in Deep Learning-Based Segmentation for Radiation Therapy
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.Accurate segmentation of tumor and surrounding organs-at-risk (OARs) is important for radiotherapy treatment(RT) planning. Manual segmentation by physicians currently used in clinical practice is time consuming and highly depends on the physicians' skill and experience, leading to large inter-and intra-observer variation. Deep learning(DL) algorithms, such as those used for image recognition, has been promising in the development of automated segmentation tools for medical imaging. Contouring in RT has some specific challenges as opposed to semantic segmentation in other spaces. DL segmentation models are trained with large, annotated datasets. The annotations play such an important role since these labels are the supervisory signals teaching the model how to segment. Majority of the times, a very high-quality dataset is unavailable. The datasets available are usually biased, noisy, and sometimes scarcely annotated. One of the primary sources of noise in RT datasets is annotation variations. This dissertation addresses the challenge of label variability and investigates different methods to deal with various kinds of label variability. The thesis studies the impact that label variability has on automation performance as well as patient outcome and devices ways to reduce or to respect this variability. Computed Tomography based segmentation model for intact and post-operative prostate cancer RT planning are proposed and developed for clinical use. Uncertainty in the automated label prediction for CTV and OARs are evaluated in detail. Impact of inter-physician variability on patient outcome for post-operative prostate cancer is investigated and instead of segmenting a general CTV , PSA-Net is proposed that respects style variations across physicians as well as across institutions. For dealing with systematic label variability in some structures, a prior-guided deep difference meta-learner is proposed that can segment a structure in a new labelling style from just a handful of prior segmented patients. A multi-modality IPA segmentation model is proposed to reduce label variability due to expertise differences among physicians in clinical trials. This model can effectively help inexperienced physicians in producing expert segmentations. The contributions of this thesis are expected to facilitate better understanding of label variability in RT and help in avoiding/respecting label variability when developing deep learning models for RT
Developing an Intervention to Promote Lethal Means Safety in Suicidal Adolescents
No full textSuicide in adolescents has become an epidemic with limited understanding of the most effective interventions to reduce suicidal ideation, attempts, and deaths. Despite this uncertainty, research points to lethal means counseling with the parent of the suicidal teen as crucial and potentially the single-most powerful intervention a clinician can conduct. However, there is limited literature on how to conduct lethal means counseling and few interventions to support in lethal means safety adherence. As such, this study focused on 1) establishing an understanding of current lethal means counseling and practices through conducting semi-structured qualitative interviews with parents (N = 6) and clinicians (N = 12) and 2) developing a text-based intervention to promote adherence to means safety (named the Safe Home intervention) and 3) examining the acceptability, feasibility, and perceived effect of this intervention. The Safe Home intervention utilizes nudges, a behavioral economics approach, to prompt parents to adhere to lethal means safety practices through twice-a-week texts consisting of brief reminders as well as a questionnaire we developed to aid parents in assessing their teen's access to lethal means. Results from this mixed-methods study indicate that our text-based intervention meets a significant need identified by parents and clinicians: it provides consistency, structure, and support specific to lethal means adherence. On the Client Satisfaction Questionnaire-8, parents (N = 9) reported overwhelming satisfaction with the intervention (M = 28, SD = 3.46) and stated the texts aided them in maintaining a safe home for their teen. In addition, parents overwhelmingly reported (88.9%) that they would continue utilizing the intervention past the study window. All parents reported that the intervention prompted them to adhere to lethal means safety practices, including buying a lockbox, searching their child's room, and securing medications. The Safe Home intervention was found to be both acceptable and feasible in a pilot setting. This study increases the literature on lethal means safety and the experiences of both clinicians and parents regarding lethal means counseling. Finally, this research indicates that this intervention is a promising tool to support parents and clinicians in keeping dangerous items out of the hands of suicidal teens
Prison
Get PDFThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2024 On My Own Time (OMOT) Art Show.Prison was written during a recent, institutionally mandated isolation for COVID - it felt more like a vacation, since I was barely symptomatic. James Berry is a professor and Vice-Chair in the Department of Anesthesiology and Pain Management at UT Southwestern. He serves as the Section Editor of "Mind to Mind", a creative writing section of the journal "Anesthesiology". His work has been published in the journals "Anesthesiology" and "Chest", as well as in online poetry venues
Standardizing Treatment for Acute Exacerbations of COPD (AECOPD) at a Large Academic Hospital
No full textThe 62nd Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 30, 2024, 3-6 p.m., D1.700 Lecture Hall)BACKGROUND: Acute exacerbations of COPD (AECOPD) are a common problem faced by patients with chronic obstructive pulmonary disease (COPD). There are discrepancies in AECOPD treatment that impact patient outcomes. Despite evidence of improved or non-inferiority outcomes and reduced cost with short oral regimens, steroid prescribing patterns remain variable. Furthermore, there is confusion regarding antibiotic choice that contributes to the problem.
LOCAL PROBLEM: The local problem is the lack of standardization of care for AECOPD at Clements University Hospital (CUH). Data from 6/1/2021-5/31/2023 shows that AECOPD treatment at CUH has been variable despite the availability of evidence-based medications.
AIM: The aim of this project is to improve the adherence to evidence-based selection of steroids and antibiotics for AECOPD at CUH by 75% at 1 year after the intervention along with a 10% decrease in length of stay and readmissions.
METHODS: The intervention is an order set containing guidelines and treatments for AECOPD that can be implemented into Epic electronic health records. Emergency department physicians, hospitalists, and pulmonologists were consulted for insight about treatment recommendations. This advice along with the GOLD guidelines and additional research were used to create the order set.
RESULTS: The order set is now ready for implementation into Epic after being presented to physicians and respiratory therapists for feedback. After implementation, data will be collected on the usage and effectiveness of the order set and analyzed for up to one-year post-intervention.
CONCLUSION: AECOPD is a complex disease that is treated with various medications that can lead to the different outcomes. Insight from various physician specialties was helpful to understand methods at CUH at different stages of the AECOPD journey. Due to the complexity, the order set can be a helpful resource for physicians when choosing treatments to improve adherence to evidence-based medications and patient outcomes.Southwestern Medical Foundatio
We Lie on the Floor
Get PDFThe author submitted this entry in the Open Verse Poetry category (Amateur division) for the 2024 On My Own Time (OMOT) Art Show.I wrote this poem after comforting a mother whose adult child died of cancer. Her anguish touched me, and I felt compelled to articulate the powerful ways that her family and friends were supporting her in this devastating moment. Experiencing something like this can feel so isolating, even when you are surrounded by people who grieve alongside you
No Regrets
Get PDFThe author submitted this entry in the 10-Word Story category (Amateur division) for the 2024 On My Own Time (OMOT) Art Show.We've all fantasized about the past and the things we wish we could change, and if we just had a time machine, we could make things better, rectify mistakes, revisit lost loved ones. But then for some, you get to a point in your life where things are at their best. You meet someone who changes everything for you, and you realize you are exactly where you should be. Changing the past would change the future and that is no longer a desire, because you're happy. This is exactly how I feel now. No regrets, because through it all, I found her
UBE2J1 Is the E2 Ubiquitin Conjugating Enzyme Regulating AR Degradation and Resistance to Antiandrogen
No full textProstate cancer (PCa) is primarily driven by aberrant Androgen Receptor (AR) signaling. Although there has been substantial advancement in antiandrogen therapies, resistance to these treatments remains a significant obstacle, often marked by continuous or enhanced AR signaling in resistant tumors. While the dysregulation of the ubiquitination-based protein degradation process is instrumental in the accumulation of oncogenic proteins, including AR, the molecular mechanism of ubiquitination-driven AR degradation remains largely undefined. We identified UBE2J1 as the critical E2 ubiquitin conjugating enzyme responsible for guiding AR ubiquitination and eventual degradation. The absence of UBE2J1, found in 5-15% of PCa patients, results in disrupted AR ubiquitination and degradation. This disruption leads to an accumulation of AR proteins, promoting resistance to antiandrogen treatments. By employing a ubiquitination-centric AR degrader to adeptly restore AR ubiquitination, we reestablished AR degradation and curtailed the proliferation of antiandrogen-resistant PCa tumors. These findings underscore the fundamental role of UBE2J1 in AR degradation and illuminate an uncharted mechanism through which PCa maintains heightened AR protein levels, fostering resistance to antiandrogen therapies
Investigating Atypical Signaling of N-Methyl-D-Aspartate Receptors
No full textThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.N-methyl-D-aspartate (NMDA) receptors are ionotropic ligand-gated channels that require ligand binding jointly with membrane depolarization to become active. This unique characteristic of the NMDA receptor coupled with previously published data suggests they may signal in a metabotropic fashion i.e., ligand binding triggers downstream conformational changes and signaling events independent of ion influx. It has been shown that long-term depression (LTD) can still be maintained in hippocampal slices treated with the open channel blocker MK-801 while the ligand binding site antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) blocks LTD. However, conflicting data was published suggesting MK-801 does not block LTD warranting further study. My work aimed to answer the following question: can NMDA receptors signal in a metabotropic fashion? First, live cell imaging in primary hippocampal cultures infected with GCaMP6s or GCaMP6s fused to postsynaptic density protein 95 (PSD95-GCaMP6s) were used to measure NMDA receptor dependent calcium signaling events. Next, phosphorylation levels of proteins that had been implicated in a proposed metabotropic signaling cascade were measured to determine the plausibility of this model and subsequent metabotropic NMDA receptor signaling. Lastly, extracellular field recordings were conducted to replicate and advance previously published data that originally suggested NMDA receptors signal in a metabotropic fashion. D-AP5 and MK-801 reduced NMDA receptor dependent calcium signaling events similarly in both GCaMP6s and PSD95-GCaMP6s infected cultures indicating ionotropic NMDA receptor signaling. The biochemical screen was unable to substantiate the previously published model of metabotropic signaling but did further support my calcium imaging data whereby MK-801 can decrease postsynaptic calcium influx within 20 minutes. In our system, metabotropic NMDA receptor signaling is merely an artifact from the confounding effects of picrotoxin and a higher concertation of MK-801. By using a more physiologically relevant experimental design I showed MK-801 is a less effective blocker of LTD and requires pretreatment while D-AP5 can block this form of plasticity in as little as 15-minutes. The data from my project helps advance our understanding of downstream postsynaptic excitatory signaling and could assist with the development of therapeutics that target the NMDA receptor
ACHD in the 21st century: changing demographics of the adult congenital heart disease population and evolution of the field
Get PDFDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin
From mystery to mastery: game-changing tools for low-risk MDS
Get PDFDetailed formal protocol with illustrations and extensive bibliography.A recording of the protocol presentation is available on UT Southwestern's Mediasite. Note: Access to the video is restricted to authorized UT Southwestern users only.UT Southwestern--Internal Medicin