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1.  Focused ultrasound development and clinical adoption: 2013 update on the growth of the field 
The field of therapeutic focused ultrasound, which first emerged in the 1940s, has seen significant growth, particularly over the past decade. The eventual widespread clinical adoption of this non-invasive therapeutic modality require continued progress, in a multitude of activities including technical, pre-clinical, and clinical research, regulatory approval and reimbursement, manufacturer growth, and other commercial and public sector investments into the field, all within a multi-stakeholder environment. We present here a snapshot of the field of focused ultrasound and describe how it has progressed over the past several decades. It is assessed using metrics which include quantity and breadth of academic work (presentations, publications), funding trends, manufacturer presence in the field, number of treated patients, number of indications reaching first-in-human status, and quantity and breadth of clinical indications.
PMCID: PMC4265987  PMID: 25512866
2.  Emerging Issues in the Neuropsychology of HIV Infection 
Current HIV/AIDS reports  2008;5(4):204-211.
Neurocognitive compromise, a common sequela of HIV infection, ranges in severity from minor motor and information-processing speed decrements to severely incapacitating symptoms that affect functional independence. However, with the emergence of highly active antiretroviral therapy (HAART), neurocognitive phenotypes have become highly heterogeneous and increasingly fail to resemble pre-HAART presentations. This article provides an overview of our current knowledge of HIV-associated neuropsychological abnormalities, with an emphasis on the most recent attempts to classify cognitive impairment within Western and developing societies, the emergence of diverse cognitive presentations in the post-HAART era, factors that moderate the development or impact of HIV-related neurocognitive and functional deficits, and the neurophysiologic consequences of infection.
PMCID: PMC3616484  PMID: 18838060
3.  Medication and finance management among HIV-infected adults: The impact of age and cognition 
This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups. There were no relationships between laboratory performance and self-reported medication and finance management. The interaction of advancing age and cognitive impairment may confer significant functional limitations for HIV individuals that may be better detected by performance-based measures of functional abilities rather than patient self-report.
PMCID: PMC3616485  PMID: 20694873
Neuropsychology; HIV; Aging; Functional abilities; Medication management; Finance management
4.  Depression, Cognition, and Self-Appraisal of Functional Abilities in HIV: An Examination of Subjective Appraisal Versus Objective Performance 
The Clinical neuropsychologist  2011;25(2):224-243.
Depression frequently co-occurs with HIV infection and can result in self-reported overestimates of cognitive deficits. Conversely, genuine cognitive dysfunction can lead to an under-appreciation of cognitive deficits. The degree to which depression and cognition influence self-report of capacity for instrumental activities of daily living (IADLs) requires further investigation. This study examined the effects of depression and cognitive deficits on self-appraisal of functional competence among 107 HIV-infected adults. As hypothesized, higher levels of depression were found among those who over-reported problems in medication management, driving, and cognition when compared to those who under-reported or provided accurate self-assessments. In contrast, genuine cognitive dysfunction was predictive of under-reporting of functional deficits. Together, these results suggest that over-reliance on self-reported functional status poses risk for error when diagnoses require documentation of both cognitive impairment and associated functional disability in everyday life.
PMCID: PMC3616492  PMID: 21331979
Depression; Self-report; Functional ability; Cognition; HIV
5.  Basal ganglia structures differentially contribute to verbal fluency: Evidence from Human Immunodeficiency Virus (HIV)-infected adults 
Neuropsychologia  2011;50(3):390-395.
The basal ganglia (BG) are involved in executive language functions (i.e., verbal fluency) through their connections with cortical structures. The caudate and putamen receive separate inputs from prefrontal and premotor cortices, and may differentially contribute to verbal fluency performance. We examined BG integrity in relation to lexicosemantic verbal fluency performance among older HIV infected adults.
20 older (50+ years) HIV+ adults underwent MRI and were administered measures of semantic and phonemic fluency. BG (caudate, putamen) regions of interest were extracted.
Performance on phonemic word generation significantly predicted caudate volume, whereas performance on phonemic switching predicted putamen volume.
These findings suggest a double dissociation of BG involvement in verbal fluency tasks with the caudate subserving word generation and the putamen associated with switching. As such, verbal fluency tasks appear to be selective to BG function.
PMCID: PMC3608185  PMID: 22223078
Basal ganglia; Verbal fluency; Magnetic resonance imaging; Human Immunodeficiency Virus; Neuropsychology; Aging
6.  Antiretroviral Adherence and the Nature of HIV-Associated Verbal Memory Impairment 
The authors investigated the relationship between antiretroviral adherence and HIV-associated verbal memory impairment. HIV-positive participants demonstrated poorer verbal memory than HIV-negative participants. Both good (≥90%) and poor (<90%) adherers displayed encoding deficits as compared with controls, but only poor adherers exhibited retrieval deficits. Encoding deficits primarily accounted for reduced delayed recall in good adherers, but both encoding and retrieval deficits accounted for reduced delayed recall in poor adherers. The retrieval difference between the adherence groups might be explained by a neuroprotective effect of good antiretroviral adherence or preexisting HIV-related retrieval deficits that result in poorer adherence.
PMCID: PMC3603356  PMID: 21948894
7.  Reaction Time Variability in HIV-Positive Individuals 
Progression of HIV/AIDS is frequently associated with frontal/subcortical dysfunction and mean reaction time (RT) slowing. Beyond group means, within-subject variability of RT has been found to be particularly sensitive to frontal/subcortical dysfunction in other populations. However, the possible relevance of RT variability to HIV/AIDS patients remains unknown. This study evaluated the relationships between RT variability and indicators such as neurocognitive, behavioral, and immunological status. A total of 46 HIV-positive adults on antiretroviral medication regimens were included in this study. Overall performance of this sample was poorer than normative means on measures of RT latency, RT variability, and traditional neurocognitive domains. Results demonstrated that the measures of RT variability were associated with global cognition, medication adherence rates, and peak immunological dysfunction, above and beyond the effects of RT latency. These preliminary findings suggest that measures of RT variability may provide enhanced sensitivity to neurocognitive disease burden in HIV/AIDS relative to more traditional measures of mean RT or cognitive function.
PMCID: PMC2979347  PMID: 20798183
AIDS; Cognitive ability; Medication adherence; Immunological status; Continuous Performance Test; CPT-II
8.  Reciprocal prediction of medication adherence and neurocognition in HIV/AIDS(e–Pub ahead of print) 
Neurology  2010;74(15):1217-1222.
Antiretroviral medications have been shown to benefit neurocognition in HIV/AIDS, and neurocognitive deficits are a risk factor for poor adherence to these medications. However, little is known about the predictive pathways linking medication adherence with cognitive ability.
In the current 6-month cohort study, antiretroviral medication adherence was tracked prospectively among 91 HIV-positive adults using electronic monitoring. Comprehensive neuropsychological evaluations were performed at baseline and 6 months.
Multivariate path analyses provided evidence that antiretroviral adherence and cognitive ability are reciprocally related, although the neurocognitive pathways of this relationship appear to vary by predictive direction. Executive function and learning/memory were most strongly predictive of levels of medication adherence achieved, whereas higher levels of adherence were predictive of relative improvements in a wide range of frontostriatal brain functions including processing speed, attention, executive functions, and motor functioning.
These data provide evidence that cognition and adherence are reciprocally related in HIV/AIDS. In particular, executive dysfunction may play a key role in this relationship. Interventions aimed at improving or preserving executive functions could hold promise for interrupting progressive declines in adherence and neurocognitive ability in HIV/AIDS.
= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
= highly active antiretroviral therapy;
= Medication Event Monitoring System;
= protease inhibitor.
PMCID: PMC2865732  PMID: 20220123
9.  Functional Consequences of HIV-Associated Neuropsychological Impairment 
Neuropsychology review  2009;19(2):186-203.
This review focuses on the “real world” implications of infection with HIV/AIDS from a neuropsychological perspective. Relevant literature is reviewed which examines the relationships between HIV-associated neuropsychological impairment and employment, driving, medication adherence, mood, fatigue, and interpersonal functioning. Specifically, the relative contributions of medical, cognitive, psychosocial, and psychiatric issues on whether someone with HIV/AIDS will be able to return to work, adhere to a complicated medication regimen, or safely drive a vehicle will be discussed. Methodological issues that arise in the context of measuring medication adherence or driving capacity are also explored. Finally, the impact of HIV/AIDS on mood state, fatigue, and interpersonal relationships are addressed, with particular emphasis on how these variables interact with cognition and independent functioning. The purpose of this review is to integrate neuropsychological findings with their real world correlates of functional behavior in the HIV/AIDS population.
PMCID: PMC2871666  PMID: 19472057
HIV/AIDS; Neuropsychology; Medication adherence; Employment; Driving
The Clinical neuropsychologist  2010;24(2):265-285.
This study examined the interactive effects of cerebrovascular risks, advancing age, and HIV infection on neurocognition, and explored whether pharmacological treatment of cerebrovascular risk factors attenuated neurocognitive dysfunction. Participants included 98 HIV-seropositive adults (cerebrovascular risk: 23.5%; age >50: 27.6%). Cerebrovascular risk was associated with slower processing speed even after controlling for age effects (b = −2.071; p = .04), and the interaction of age and cerebrovascular risk was associated with poorer verbal fluency (b = 1.276, p = .002). Participants with pharmacologically untreated cerebrovascular risk demonstrated reduced processing speed, learning/memory, and executive functioning relative to those on medication. Poor cerebrovascular health confers significant risk for HIV+ individuals, and this effect may be of greater consequence than advancing age. The cognitive impact of risk appears to be more pronounced in the absence of adequate pharmacological treatment.
PMCID: PMC2863992  PMID: 20162495
Cerebrovascular; HIV/AIDS; Neurocognitive; Aging
11.  Aging, Neurocognition, and Medication Adherence in HIV Infection 
To evaluate the hypothesis that poor adherence to highly active antiretroviral treatment (HAART) would be more strongly related to cognitive impairment among older than among younger HIV-seropositive adults.
Setting and Participants
A volunteer sample of 431 HIV-infected adult patients prescribed self-administered HAART was recruited from community agencies and university-affiliated infectious disease clinics in the Los Angeles area.
Neurocognitive measures included tests of attention, information processing speed, learning/memory, verbal fluency, motor functioning, and executive functioning. Medication adherence was measured using microchip-embedded pill bottle caps (Medication Event Monitoring System) and self-report. Latent/structural analysis techniques were used to evaluate factor models of cognition and adherence.
Mean adherence rates were higher among older (≥50 years) than younger (<50 years) HIV-positive adults. However, latent/structural modeling demonstrated that neurocognitive impairment was associated with poorer medication adherence among older participants only. When cognitive subdomains were examined individually, executive functioning, motor functioning, and processing speed were most strongly related to adherence in this age group. CD4 count and drug problems were also more strongly associated with adherence among older than younger adults.
Older HIV-positive individuals with neurocognitive impairment or drug problems are at increased risk of suboptimal adherence to medication. Likewise, older adults may be especially vulnerable to immunological and neurocognitive dysfunction under conditions of suboptimal HAART adherence. These findings highlight the importance of optimizing medication adherence rates and evaluating neurocognition in the growing population of older HIV-infected patients.
PMCID: PMC2679810  PMID: 19307857
HIV; AIDS; aging; cognition; medication adherence; executive functions
12.  Resection of Abdominal Solid Organs Using High-Intensity Focused Ultrasound 
Ultrasound in medicine & biology  2007;33(8):1251-1258.
Our objective was to evaluate high-intensity focused ultrasound (HIFU) for minimizing blood loss during surgery by hemodynamically isolating large portions of solid organs before their resection. A high-power HIFU device (in-situ intensity of 9000 W/cm2, frequency of 3.3 MHz) was used to produce a wall of cautery for sealing of blood vessels along the resection line in surgically-exposed solid organs (liver lobes, spleen and kidneys) of eight adult pigs. Following HIFU application, the distal portion of the organ was excised using a scalpel. If any blood vessels were still bleeding, additional HIFU application was used to stop the bleeding. The resection was achieved in 6.0 ± 1.5 min (liver), 3.6 ± 1.1 min (spleen) and 2.8 ± 0.6 min (kidneys) of HIFU treatment time, with no occurrence of bleeding for up to 4 hours (until sacrifice). The coagulated region at the resection line had average width of 3 cm and extended through the whole thickness of the organ (up to 4 cm). Blood vessels of up to 1 cm in size were occluded. This method holds promise for future clinical applications in resection of solid tumors and hemorrhage control from high-grade organ injuries.
PMCID: PMC2701626  PMID: 17498864
High-Intensity Focused Ultrasound; Solid Organ Resection; Hemorrhage Control

Results 1-12 (12)