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Open Access Publications from the University of California

Scholarly Works (18 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2019)

Vagus nerve electrical stimulation is known to improve learning processes and augment anti-inflammatory treatment [1]. Current methods include the surgically implanted cuff electrode, or the noninvasive electric field that penetrates from the skin to the nerve. The former ensures target accuracy yet can be fraught with complications due to surgical implant, whereas the latter avoids procedural complications but may result in off target neurostimulation (i.e., other neuronal stimulation besides vagus nerve)[2]. Off target neuronal stimulation can alter cardiac function and cerebral blood flow patterns [3] [4]. Converging lines of evidence now support non-invasive high temporal and spatial resolution focused ultrasound can result in brain and peripheral nerve stimulation [4] [5] [6]. Therefore, focused ultrasound is proposed to replace electrical nerve stimulation to effectively modulate the vagus nerve as a safe and noninvasive modality. To guarantee safety and efficacious vagus nerve focused ultrasound stimulation, real-time image guidance is required to provide efficient and accurate tracking of the vagus nerve. In this work, we propose to: 1) develop real time B-mode ultrasound imaging to visualize the vagus nerve and 2) employ neural networks capable of tracking the nerve location within the view. We implement the real-time beamforming process from raw data to the reconstructed B-mode image and send it to the vagus nerve detector that is trained using convolutional neural networks. We successfully extract the location of the nerve from the beamformed data, validating the idea of real-time guidance. Future work will focus on improving the efficiency of nerve detection algorithms that are then used as feedback for an eventual autonomous closed loop focused ultrasound nerve stimulation system.

    Cover page: Real-time Detection of Vagus Nerve Using Ultrasound B-Mode Imaging and Neural Networks for Focused Ultrasound Neuromodulation Guidance
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2014)
    The intensity mapping of Ly-alpha emission during the epoch of reionization (EoR) will be contaminated by foreground emission lines from lower redshifts. We calculate the mean intensity and power spectrum of Ly-alpha emission at z~7, and estimate the uncertainties according to the relevant astrophysical processes. We find that the low-redshift emission lines from 6563 A H-alpha, 5007 A [OIII] and 3727 A [OII] will be the strong contaminants on the observed Ly-alpha power spectrum. We make use of both the star formation rate (SFR) and luminosity functions (LF) to estimate the mean intensity and power spectra of the three foreground lines at z~0.5 for H-alpha, z~0.9 for [OIII] and z~1.6 for [OII], as they will contaminate the Ly-alpha emission at z~7. The [OII] line is found to be the strongest. We analyze the masking of the bright survey pixels with a foreground line above some line intensity threshold as a way to reduce the contamination in the intensity mapping survey. We find that the foreground contamination can be neglected if we remove the pixels with fluxes above 1.4x10^-20 W/m^2.
      Cover page: FOREGROUND CONTAMINATION IN Lyα INTENSITY MAPPING DURING THE EPOCH OF REIONIZATIONCreative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2014)

      Background

      News coverage of medical research is followed closely by many Americans and affects the practice of medicine and influence of scientific research. Prior work has examined the quality of media coverage, but no investigation has characterized the choice of stories covered in a controlled manner. We examined whether the media systematically covers stories of weaker study design.

      Methods

      We compared study characteristics of 75 clinically-oriented journal articles that received coverage in the top five newspapers by circulation against 75 clinically-oriented journal articles that appeared in the top five medical journals by impact factor over a similar timespan. Subgroup analysis was performed to determine whether differences between investigations from both sources varied by study type (randomized controlled trial [RCT] or observational study).

      Results

      Investigations receiving coverage from newspapers were less likely to be RCTs (17% vs. 35%, p = 0.016) and more likely to be observational studies (75% vs. 47%, p<0.001). No difference was observed in number of people studied (median: 1034 vs. 1901, p = 0.14) or length of follow-up (median: 1.80 vs. 1.00 years, p = 0.22). In subgroup analysis, observational studies from the media used smaller sample sizes (median: 1984 vs. 21136, p = 0.029) and were more likely to be cross-sectional (71% vs. 31%, p<0.001), while no differences were observed for RCTs.

      Conclusions

      Newspapers were more likely to cover observational studies and less likely to cover RCTs than high impact journals. Additionally, when the media does cover observational studies, they select articles of inferior quality. Newspapers preferentially cover medical research with weaker methodology.
        Cover page: Media Coverage of Medical Journals: Do the Best Articles Make the News?
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2012)

        Background

        Chronic hyperglycemia in type 2 diabetes increases the risk of microvascular events. However, there is continuing uncertainty about its effect on macrovascular outcomes and death. We conducted a meta-analysis of prospective studies to estimate the association of glycosylated hemoglobin level with the risk of all-cause mortality and cardiovascular outcomes among patients with type 2 diabetes.

        Methodology/principal findings

        We systematically searched the MEDLINE database through April 2011 by using Medical Subject Heading search terms and a standardized protocol. We included prospective cohort studies that reported data of glycosylated hemoglobin level on the risk of incident cardiovascular events and all-cause mortality. Relative risk estimates (continuous and categorical variables) were derived or abstracted from each cohort study. Twenty six studies were included in this analysis with a mean follow-up rang of 2.2-16 years. The pooled relative risk associated with a 1% increase in glycosylated hemoglobin level among patients with type 2 diabetes was 1.15 (95% CI, 1.11 to 1.20) for all-cause mortality, 1.17 (95% CI, 1.12 to 1.23) for cardiovascular disease, 1.15 (95% CI, 1.10 to 1.20) for coronary heart disease, 1.11 (95% CI, 1.05 to 1.18) for heart failure, 1.11 (95% CI, 1.06 to 1.17) for stroke, and 1.29 (95% CI, 1.18 to 1.40) for peripheral arterial disease, respectively. In addition, a positive dose-response trend existed between glycosylated hemoglobin level and cardiovascular outcomes.

        Conclusions/significance

        Chronic hyperglycemia is associated with an increased risk for cardiovascular outcomes and all-cause mortality among patients with type 2 diabetes, likely independently from other conventional risk factors.
          Cover page: Glycosylated Hemoglobin in Relationship to Cardiovascular Outcomes and Death in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
          • Article
          • Peer Reviewed
          UC Santa Cruz Previously Published Works (2015)
          The spatial fluctuations of the extragalactic background light trace the total emission from all stars and galaxies in the Universe. A multiwavelength study can be used to measure the integrated emission from first galaxies during reionization when the Universe was about 500 million years old. Here we report arcmin-scale spatial fluctuations in one of the deepest sky surveys with the Hubble Space Telescope in five wavebands between 0.6 and 1.6 μm. We model-fit the angular power spectra of intensity fluctuation measurements to find the ultraviolet luminosity density of galaxies at redshifts greater than 8 to be log ρ(UV) = 27.4(+0.2)(-1.2) ergs(-1) Hz(-1) Mpc(-3) (1σ). This level of integrated light emission allows for a significant surface density of fainter primeval galaxies that are below the point-source detection level in current surveys.
            Cover page: Ultraviolet luminosity density of the universe during the epoch of reionization.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2014)

            Background

            An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly.

            Methods

            We conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation.

            Results

            In all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged ≥ 75 years (p trend = 0.03), while no trend was seen for PDE5I (p trend = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11).

            Discussion

            In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.
              Cover page: Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2016)
              While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic data acquired from hypertensive individuals treated with atenolol, it may be possible to better understand the pathways that most impact the development of an adverse glycemic state. To identify biomarkers that can help predict susceptibility to blood glucose excursions during exposure to atenolol. Plasma samples acquired from 234 Caucasian participants treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses trial were analyzed by gas chromatography Time-Of-Flight Mass Spectroscopy. Metabolomics and genomics data were integrated by first correlating participant's metabolomic profiles to change in glucose after treatment with atenolol, and then incorporating genotype information from genes involved in metabolite pathways associated with glucose response. Our findings indicate that the baseline level of β-alanine was associated with glucose change after treatment with atenolol (Q = 0.007, β = 2.97 mg/dL). Analysis of genomic data revealed that carriers of the G allele for SNP rs2669429 in gene DPYS, which codes for dihydropyrimidinase, an enzyme involved in β-alanine formation, had significantly higher glucose levels after treatment with atenolol when compared with non-carriers (Q = 0.05, β = 2.76 mg/dL). This finding was replicated in participants who received atenolol as an add-on therapy (P = 0.04, β = 1.86 mg/dL). These results suggest that β-alanine and rs2669429 may be predictors of atenolol-induced hyperglycemia in Caucasian individuals and further investigation is warranted.
                Cover page: Novel plasma biomarker of atenolol-induced hyperglycemia identified through a metabolomics-genomics integrative approach
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2013)
                Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are poorly understood. In this study we use metabolomics, a global biochemical approach to investigate biochemical changes induced by the beta-adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma from individuals treated with atenolol was collected at baseline (untreated) and after a 9 week treatment period and analyzed using a GC-TOF metabolomics platform. The metabolomic signature of atenolol exposure included saturated (palmitic), monounsaturated (oleic, palmitoleic) and polyunsaturated (arachidonic, linoleic) free fatty acids, which decreased in Caucasians after treatment but were not different in African Americans (p<0.0005, q<0.03). Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in Caucasians by 33% (p<0.0001, q<0.0001) but was unchanged in African Americans. The contribution of genetic variation in genes that encode lipases to the racial differences in atenolol-induced changes in fatty acids was examined. SNP rs9652472 in LIPC was found to be associated with the change in oleic acid in Caucasians (p<0.0005) but not African Americans, whereas the PLA2G4C SNP rs7250148 associated with oleic acid change in African Americans (p<0.0001) but not Caucasians. Together, these data indicate that atenolol-induced changes in the metabolome are dependent on race and genotype. This study represents a first step of a pharmacometabolomic approach to phenotype patients with hypertension and gain mechanistic insights into racial variability in changes that occur with atenolol treatment, which may influence response to the drug.
                  Cover page: Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2021)
                  Qubit entanglement is a valuable resource for quantum information processing, where increasing its dimensionality provides a pathway towards higher capacity and increased error resilience in quantum communications, cluster computation and quantum phase measurements. Time-frequency entanglement, a continuous variable subspace, enables the high-dimensional encoding of multiple qubits per particle, bounded only by the spectral correlation bandwidth and readout timing jitter. Extending from a dimensionality of two in discrete polarization variables, here we demonstrate a hyperentangled, mode-locked, biphoton frequency comb with a time-frequency Hilbert space dimensionality of at least 648. Hong-Ou-Mandel revivals of the biphoton qubits are observed with 61 time-bin recurrences, biphoton joint spectral correlations over 19 frequency-bins, and an overall interference visibility of the high-dimensional qubits up to 98.4%. We describe the Schmidt mode decomposition analysis of the high-dimensional entanglement, in both time- and frequency-bin subspaces, not only verifying the entanglement dimensionality but also examining the time-frequency scaling. We observe a Bell violation of the high-dimensional qubits up to 18.5 standard deviations, with recurrent correlation-fringe Clauser-Horne-Shimony-Holt S-parameter up to 2.771. Our biphoton frequency comb serves as a platform for dense quantum information processing and high-dimensional quantum key distribution.
                    Cover page: 648 Hilbert-space dimensionality in a biphoton frequency comb: entanglement of formation and Schmidt mode decompositionCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC Davis Previously Published Works (2016)
                    Hydrochlorothiazide is among the most commonly prescribed antihypertensives; yet, <50% of hydrochlorothiazide-treated patients achieve blood pressure (BP) control. Herein, we integrated metabolomic and genomic profiles of hydrochlorothiazide-treated patients to identify novel genetic markers associated with hydrochlorothiazide BP response. The primary analysis included 228 white hypertensives treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Genome-wide analysis was conducted using Illumina Omni 1 mol/L-Quad Chip, and untargeted metabolomics was performed on baseline fasting plasma samples using a gas chromatography-time-of-flight mass spectrometry platform. We found 13 metabolites significantly associated with hydrochlorothiazide systolic BP (SBP) and diastolic BP (DBP) responses (false discovery rate, <0.05). In addition, integrating genomic and metabolomic data revealed 3 polymorphisms (rs2727563 PRKAG2, rs12604940 DCC, and rs13262930 EPHX2) along with arachidonic acid, converging in the netrin signaling pathway (P=1×10(-5)), as potential markers, significantly influencing hydrochlorothiazide BP response. We successfully replicated the 3 genetic signals in 212 white hypertensives treated with hydrochlorothiazide and created a response score by summing their BP-lowering alleles. We found patients carrying 1 response allele had a significantly lower response than carriers of 6 alleles (∆SBP/∆DBP: -1.5/1.2 versus -16.3/-10.4 mm Hg, respectively, SBP score, P=1×10(-8) and DBP score, P=3×10(-9)). This score explained 11.3% and 11.9% of the variability in hydrochlorothiazide SBP and DBP responses, respectively, and was further validated in another independent study of 196 whites treated with hydrochlorothiazide (DBP score, P=0.03; SBP score, P=0.07). This study suggests that PRKAG2, DCC, and EPHX2 might be important determinants of hydrochlorothiazide BP response.
                      Cover page: A Genetic Response Score for Hydrochlorothiazide Use
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