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Scholarly Works (34 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2016)

Clinically significant macular edema (CSME) results from the microvascular complications of diabetes in the central retina of the eye. Diabetes-induced disregulation of the intra- and extra-vascular fluid homeostasis leads to the accumulation of fluid in the retinal tissue. When left untreated, CSME can result in vision loss by disrupting normal metabolic processes, ischemia and by mechanical disruption of the intricate microstructure of the retina. CSME can be succesfully treated when detected in time. Vision loss caused by CSME is largely irreversible and, therefore, the emphasis is on early detection. Challenges in CSME detection result in a significant number of untreated patients with devastating visual consequences. Tele-medicine screening which relies on either monoscopic or stereoscopic fundus photographs is widely implemented and has good sensitivity and specificity for the detection of retinopathy levels. Contrary to that, CSME detection in fundus photographs faces substantial challenges. Stereoscopic photographs require dilation which increases the risk of vision loss due to an elevated intraocular pressure which may lead to angle closre glaucoma and is generally time consuming and incovenient for patients which further decreases compliance with screening. Non-dilated stereophotography suffers from unacceptably high number of stereophotographs of poor quality. Monoscopic images have low sensitivity for CSME detection because of the lack of stereopsis. Programs which use monoscopic images must rely on surrogate markers of CSME. There is currently no consensus on how to detect CSME in monoscopic images. Different programs use different surrogate markers primarily because there is lack of evidence in scientific literature regarding the unequivocal validity of a particular CSME detection method.

This dissertation includes three studies that share a common goal of improving the accuracy of CSME detection. The anticipated impact of this research is that we will be able to improve the efficiency with which we identify patients requiring treatment, thereby increasing their chance for reducing the risk of vision loss due to CSME.

The first study presented in Chapter 3 of this dissertation evaluates the ability of hard exudates, a surrogate marker of DME, located within one-disc diameter from the center of the macula to detect CSME. This study tests the “real world” implementation of this approach in a diabetic retinopathy screening program and attempts to resolve the discrepancies regarding the accuracy of this method that exists in the literature. The second study presented in Chapter 4 of this dissertation tests whether the proximity of hard exudates to the fovea is associated with more severe cases of CSME and thus warrants a more expedited referral and intervention. In addition, we proposed an OCT-based adaptation of CSME severity scale based on the DME severity scale derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) data. This is a step forward towards developing a more repeatable and objective structural measure of sight-threatening diabetic macular edema which correlates with functional measures of retinal health, such as visual acuity and electroretinographic recordings. Finally, the third study presented in Chapter 5 builds on the findings of the first two studies and utilizes a novel approach for the detection of CSME. This approach is based on the combined measure of the proximity of hard exudates to the fovea and the areal extent of exudation in the central macula. We have also evaluated the association of the photopic 30 Hz flicker ERG measurements with CSME. Finally, the model of CSME detection which combines relevant clinical variables was evaluated as the CSME detection tool.

The results of the studies presented in this dissertation support the use of a new approach – radially arranged sectors in the central macula - for the detection of CSME. This approach was shown to accurately classify patients with and without CSME. Moreover, the increase in the number of sectors affected by hard exudates is also associated with the increase in probability of having severe CSME, justifying a more expedited referral for treatment. Finally, while significantly associated with CSME, the latency of the 30 Hz photopic flicker ERG response does not seem to offer additional power to discriminate between patients with and without CSME.

    Cover page: Development and Validation of New Approaches for the Detection of Sight-Threatening Diabetic Macular Edema
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2022)
    OBJECTIVES: Despite documented benefits and physicians recommendations to participate in cardiac rehabilitation (CR) programs, the average dropout rate remains between 12-56%. This studys goal was to demonstrate that using personalized interventions can significantly increase patient adherence. METHOD: Ninety-five patients (ages 18-90) eligible for the CR program were randomly recruited and received personalized interventions using the Well-Beat system. Adherence levels were compared to those of a historical control group. The Well-Beat system provided Sheba CR Health Care Provider (HCP) guidelines for personalized patient-therapist dialogue. The system also generated ongoing personalized text messages for each patient sent twice a week and related each patients dynamic profile to their daily behavior, creating continuity, and reinforcing the desired behavior. RESULTS: A significant increase in patient adherence to the CR program: Three months after initiation, 76% remained active compared to the historical average of 24% in the matched control group (log-rank p-value = 0.001). CONCLUSIONS: Using an Artificial Intelligence (AI)-based engine that generated recommendations and messages made it possible to improve patient adherence without increasing HCP load, benefiting all. Presenting customized patient insights to the HCP and generating personalized communications along with action motivating text messages can also be useful for remote care.
      Cover page: Improving cardiac rehabilitation patient adherence via personalized interventions.
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2017)
      Quitting smoking and aerobic exercise each improve health. Although smokers may be concerned that quitting smoking will reduce their quality of life (QOL), recent research has shown that cessation is associated with QOL benefits. Elements of smoking cessation interventions, such as exercise, may contribute to changes in QOL. However, it is unknown whether initiating exercise in the context of smoking cessation is associated with greater or different effects on QOL than smoking cessation alone. The current study is a secondary analysis of data from a randomized trial (n = 61) of an exercise intervention for smoking cessation. We hypothesized that smoking abstinence and engagement in exercise would have positive, additive effects on QOL at end-of-treatment, 6- and, 12-month follow-ups. Sedentary adult smokers were randomized to the exercise intervention or a health education control (HEC) group. Additionally, all participants received smoking cessation counseling and nicotine patches. Data were analyzed using actual engagement in exercise, rather than group assignment as a proxy for exercise engagement, because some HEC participants also began exercising. Abstinence was positively associated with higher total and physical health QOL at follow-up. Exercise was not associated with total QOL and only marginally associated with physical health QOL, but was positively related to overall sense of well-being. Emphasizing that smoking cessation is associated with higher QOL may help motivate smokers to initiate quit attempts.
        Cover page: Quality of life after quitting smoking and initiating aerobic exercise
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2023)
        OBJECTIVE: To evaluate the effects of scleral lens size and the duration of wear on intraocular pressure (IOP) during lens wear. METHODS: Healthy adults were recruited for this prospective and randomized study. Intraocular pressure measurements were performed using a pneumotonometer. A block randomization was used to assign the order of scleral lens diameter of either 15.6 mm or 18.0 mm for 5-hr bilateral wear over a course of two visits. Scleral IOP (sIOP) was measured during the predetermined intervals, 1.25 hr apart, during the 5-hr scleral lens wear. Corneal IOP (cIOP) was measured before and after the scleral lens wear. The primary outcome measure was the mean change in sIOP from prelens insertion baseline. RESULTS: Corneal IOP unchanged after scleral lens removal compared with the baseline measurements ( P =0.878). Smaller and larger lenses introduced significantly higher sIOP at 2.5 hr after lens insertion with the mean (95% CI) increase of 1.16 (0.54, 1.78) mm Hg and 1.37 (0.76, 1.99) mm Hg, respectively. There was no difference in IOP change between the smaller and larger diameter lenses ( P =0.590). CONCLUSIONS: Well-fitted scleral lenses do not result in clinically significant changes in intraocular pressure during 5-hr lens wear in young and healthy individuals.
          Cover page: Effect of Scleral Contact Lens Size and Duration of Wear on Intraocular Pressure.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2014)
          Cellular circuits sense the environment, process signals, and compute decisions using networks of interacting proteins. To model such a system, the abundance of each activated protein species can be described as a stochastic function of the abundance of other proteins. High-dimensional single-cell technologies, such as mass cytometry, offer an opportunity to characterize signaling circuit-wide. However, the challenge of developing and applying computational approaches to interpret such complex data remains. Here, we developed computational methods, based on established statistical concepts, to characterize signaling network relationships by quantifying the strengths of network edges and deriving signaling response functions. In comparing signaling between naïve and antigen-exposed CD4(+) T lymphocytes, we find that although these two cell subtypes had similarly wired networks, naïve cells transmitted more information along a key signaling cascade than did antigen-exposed cells. We validated our characterization on mice lacking the extracellular-regulated mitogen-activated protein kinase (MAPK) ERK2, which showed stronger influence of pERK on pS6 (phosphorylated-ribosomal protein S6), in naïve cells as compared with antigen-exposed cells, as predicted. We demonstrate that by using cell-to-cell variation inherent in single-cell data, we can derive response functions underlying molecular circuits and drive the understanding of how cells process signals.
            Cover page: Conditional density-based analysis of T cell signaling in single-cell data
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2014)

            Introduction

            Previous exercise intervention studies for smoking cessation have been challenged by a number of methodological limitations that confound the potential efficacy of aerobic exercise for smoking cessation.

            Methods

            The preliminary efficacy of a behavioral exercise intervention that incorporated features designed to address prior limitations was tested in a randomized controlled trial (RCT). Sixty-one smokers (65.6% female, mean age = 47.3 years, smoked a mean of 19.7 cigarettes/day) were randomized to receive either a 12-week exercise intervention or a 12-week health education contact control. Participants in both conditions received an 8-week telephone-delivered, standard smoking cessation protocol (with the transdermal nicotine patch). Follow-ups were conducted at the end of treatment (EOT), 6- and 12-month timepoints.

            Results

            There were no differences between conditions with respect to the number of weekly exercise or health education sessions attended (9.3±2.8 vs. 9.3±3.0, respectively). While not statistically significant, participants in the exercise condition demonstrated higher verified abstinence rates (EOT: 40% vs. 22.6%, odds ratio [OR] = 2.28; 6- and 12-month follow-ups: 26.7% vs. 12.9%, OR = 2.46). Irrespective of treatment condition, higher levels of moderate-to-vigorous exercise were associated with lower levels of depressive symptoms during the intervention.

            Conclusions

            The results of this small RCT point toward the benefit of a behavioral exercise intervention designed to address previous methodological limitations for smoking cessation. Given the potential public health impact of the demonstrated efficacy of exercise for smoking cessation, the continued development and optimization of exercise interventions for smokers through larger RCTs merits pursuit.
              Cover page: A preliminary randomized controlled trial of a behavioral exercise intervention for smoking cessation.
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2021)
              Both Human Immunodeficiency Virus (HIV) and cocaine use have been associated with impairment in neuropsychological functioning. The high comorbidity between HIV and cocaine use highlights the importance of ascertaining whether there is a compounding effect of cocaine use in individuals with HIV. Among neuropsychological domains impacted by HIV, verbal memory deficits have received substantial attention partly because they have been associated with declines in functional status in HIV positive individuals. We collected California Verbal Learning Test-II data from HIV participants who met lifetime diagnostic criteria of cocaine abuse and/or dependence (HIV/CocDx+, N = 80 & HIV/CocDx-, N = 30, respectively) and those with and without recent cocaine use, which was confirmed by toxicology analysis (HIV/Coc+, N = 56 & HIV/Coc-, N = 57, respectively). The Item Specific Deficit Approach (ISDA) was employed to determine any additional cocaine-associated deficits in encoding, consolidation, and retrieval, which attempts to control for potential confounding factors of memory such as attention. Using conventional methods of evaluating memory profiles, we found that the HIV/Coc + group demonstrated worse learning, immediate and delayed free recall, and recognition in contrast to the HIV/Coc - group; although using the ISDA, we found that encoding was the only significant difference between HIV/Coc + and HIV/Coc-participant, with HIV/Coc - performing better. Our data suggest that for individuals with HIV, cocaine use is associated with a temporary decline in verbal memory, is characterized by greater encoding deficits, and these effects may reduce with abstinence. Clinically, our findings suggest that reduced encoding is the likely contributor to verbal memory decline in HIV/Coc + and these effects are partially reversible-at least to the level of their HIV/Coc - counterparts.
                Cover page: Recent cocaine use and memory impairment in HIV
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2018)
                We previously developed a distress tolerance (DT)-based treatment that showed promising results for smokers with a history of early lapse. In the current study, we conducted a randomized controlled trial of this DT treatment for a general population of smokers not limited to those with a history of early lapse. We randomized 116 participants (41% female) to DT or standard treatment (ST). Both treatments included 1 individual session during Week 1 followed by 7 group sessions during Weeks 2-9 (quit date at Session 4), two 20-min phone sessions, and 8 weeks of transdermal nicotine patch. Results indicated no significant differences between conditions in the primary outcome of biochemically verified 7-day point prevalence smoking abstinence or in time to 1st lapse. Verified abstinence rates in DT were 38.7%, 38.7%, 46.77%, 40.32%, 20.9%, and 17.7% versus 40.7%, 37.0%, 53.7%, 44.4%, 33.3%, and 22.2% in ST at 1, 2, 4, 8, 13, and 26 weeks postquit, respectively. Additionally, we found no significant moderators of treatment efficacy and few differences in treatment process variables. These findings stand somewhat in contrast to those in our previous study and other recent studies of similar acceptance-based treatments. However, differences in methodology, inclusion of nicotine replacement therapy in both treatment conditions, and strict inclusion-exclusion criteria that excluded many smokers with affective vulnerabilities may underlie this discrepancy. Future research should evaluate the utility of DT and other acceptance-based treatments in populations with affective vulnerabilities who might specifically benefit from a DT-based approach. (PsycINFO Database Record
                  Cover page: A Randomized Controlled Trial of Distress Tolerance Treatment for Smoking Cessation
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2021)
                  Assessing decapod sensitivity to regional-scale ocean acidification (OA) conditions is limited because of a fragmented understanding of the thresholds at which they exhibit biological response. To address this need, we undertook a three-step data synthesis: first, we compiled a dataset composed of 27,000 datapoints from 55 studies of decapod responses to OA. Second, we used statistical threshold analyses to identify OA thresholds using pH as a proxy for 13 response pathways from physiology to behavior, growth, development and survival. Third, we worked with the panel of experts to review these thresholds, considering the contributing datasets based on quality of the study, and assign a final thresholds and associated confidence scores based on quality and consistency of findings among studies. The duration-dependent thresholds were within a pH range from 7.40 to 7.80, ranging from behavioral and physiological responses to mortality, with many of the thresholds being assigned medium-to-high confidence. Organism sensitivity increased with the duration of exposure but was not linked to a specific life-stage. The thresholds that emerge from our analyses provide the foundation for consistent interpretation of OA monitoring data or numerical ocean model simulations to support climate change marine vulnerability assessments and evaluation of ocean management strategies.
                    Creative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2013)

                    Introduction

                    An inability to tolerate distress is a significant predictor of early smoking lapse following a cessation attempt. We conducted a preliminary randomized controlled trial to compare a distress tolerance (DT) treatment that incorporated elements of exposure-based therapies and Acceptance and Commitment Therapy to standard smoking cessation treatment (ST).

                    Methods

                    Smokers with a history of early lapse in prior quit attempts received either DT (N = 27; 9 2-hr group and 6 50-min individual sessions) or ST (N = 22; 6 90-min group and 1 20-min individual session), plus 8 weeks of transdermal nicotine patch.

                    Results

                    At the end of behavioral treatment, odds of abstinence among participants receiving DT were 6.46 times greater than among participants receiving ST (66.7% vs. 31.8%), equivalent to a medium- to large-effect size. Odds of abstinence for DT were still 1.73 times greater at 8 weeks, corresponding to a small- to medium-effect size, although neither this difference nor those at 13 and 26 weeks were statistically significant. Furthermore, of those who lapsed to smoking during the first week postquit, DT participants had more than 4 times greater odds of abstinence than ST participants at the end of treatment. Relative to ST, DT participants also reported a larger decrease in experiential avoidance, a hypothesized DT treatment mediator, prior to quit day. The trajectory of negative mood and withdrawal symptoms in DT differed from ST and was largely consistent with hypotheses.

                    Conclusions

                    Reasons for the decrease in abstinence in DT after treatment discontinuation and suggestions for future research are discussed.
                      Cover page: Development and preliminary randomized controlled trial of a distress tolerance treatment for smokers with a history of early lapse.
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