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Open Access Publications from the University of California

Scholarly Works (4 results)

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

Understanding how individual neurons within a circuit process sensory information and influence broader network dynamics to drive behavior is a longstanding goal of neuroscience. The larval zebrafish, Danio rerio, is an excellent model organism for behavioral circuit investigation, providing genetic and optical access and a variety of visually evoked behaviors. Psychophysics can investigate features of visual stimuli crucial for behavior. Together with two-photon calcium imaging this approach can locate brain regions involved in processing these stimuli, for example retinorecipient areas such as the optic tectum. These sensory processing regions send information downstream towards motor related areas, including the nucleus of the medial longitudinal fasciculus (nMLF). The nMLF is a midbrain nucleus, shown to be active during visually evoked behavior. Optogenetics is a powerful technique for exploring circuit function, especially in motor areas. Light from an optic fiber can be used to activate a population of neurons in the nMLF, inducing behavior, and together with ablations shows a crucial role for this area in postural control. These approaches can find the role of a population of neurons, however understanding the functional impact of individual neurons within a circuit is a greater challenge. To increase the resolution of circuit investigation, we have designed a holographic light-shaping system that enables activation with single neuron precision. A protocol was developed that combines this approach with simultaneous imaging and behavior, to relate behavioral output to functional properties of the circuit. This system creates a combined approach that can extract functional information from individual neurons in behavioral circuits.

    Cover page: Exploring behavioral circuits with holographic optogenetics and network imaging
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2020)
    The delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to "rule out" TBM.
      Cover page: Xpert MTB/RIF Ultra for the Diagnosis of Tuberculous Meningitis: A Small Step Forward
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2019)
      Meningitis is a relatively rare form of tuberculosis, but it carries a high mortality rate, reaching 50% in some settings, with higher rates among patients with HIV co-infection and those with drug-resistant disease. Most studies of tuberculosis meningitis (TBM) tend to focus on better diagnosis, drug treatment and supportive care for patients in hospital. However, there is significant variability in mortality between settings, which may be due to specific variation in the availability and quality of health care services, both prior to, during, and after hospitalization. Such variations have not been studied thoroughly, and we therefore present a theoretical framework that may help to identify where efforts should be focused in providing optimal services for TBM patients. As a first step, we propose an adjusted cascade of care for TBM and patient pathway studies that might help identify factors that account for losses and delays across the cascade. Many of the possible gaps in the TBM cascade are related to health systems factors; we have selected nine domains and provide relevant examples of systems factors for TBM for each of these domains that could be the basis for a health needs assessment to address such gaps. Finally, we suggest some immediate action that could be taken to help make improvements in services. Our theoretical framework will hopefully lead to more health system research and improved care for patients suffering from this most dangerous form of tuberculosis.
        Cover page: Establishing the cascade of care for patients with tuberculous meningitis
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2019)
        In those who survive tuberculous meningitis (TBM), the long-term outcome is uncertain; individuals may suffer neurocognitive, functional and psychiatric impairment, which may significantly affect their ability to lead their lives as they did prior to their diagnosis of TBM. In children who survive, severe illness has occurred at a crucial timepoint in their development, which can lead to behavioural and cognitive delay. The extent and nature of this impairment is poorly understood, particularly in adults. This is in part due to a lack of observational studies in this area but also inconsistent inclusion of outcome measures which can quantify these deficits in clinical studies. This leads to a paucity of appropriate rehabilitative therapies available for these individuals and their caregivers, as well as burden at a socioeconomic level. In this review, we discuss what is known about neurocognitive impairment in TBM, draw on lessons learnt from other neurological infections and discuss currently available and emerging tools to evaluate function and cognition and their value in TBM. We make recommendations on which measures should be used at what timepoints to assess for impairment, with a view to optimising and standardising assessment of neurocognitive and functional impairment in TBM research.
          Cover page: Neurocognitive and functional impairment in adult and paediatric tuberculous meningitis
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