First-in-Human PET Imaging of [F]SDM-4MP3: A Cautionary Tale.

[F]SynVesT-1 is a PET radiopharmaceutical that binds to the synaptic vesicle protein 2A (SV2A) and serves as a biomarker of synaptic density with widespread clinical research applications in psychiatry and neurodegeneration. The initial goal of this study was to concurrently conduct PET imaging studies with [F]SynVesT-1 at our laboratories. However, the data in the first two human PET studies had anomalous biodistribution despite the injected product meeting all specifications during the prerelease quality control protocols.

Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [F]SynVesT-1 PET in Parkinson's Disease.

Synaptic density in the central nervous system can be measured using PET with [F]SynVesT-1. While [F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson's disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification.

Multisensory learning binds neurons into a cross-modal memory engram.

Associating multiple sensory cues with objects and experience is a fundamental brain process that improves object recognition and memory performance. However, neural mechanisms that bind sensory features during learning and augment memory expression are unknown. Here we demonstrate multisensory appetitive and aversive memory in Drosophila.

Characterization of the minimal residual disease state reveals distinct evolutionary trajectories of human glioblastoma.

Recurrence of solid tumors renders patients vulnerable to advanced, treatment-refractory disease state with mutational and oncogenic landscape distinctive from initial diagnosis. Improving outcomes for recurrent cancers requires a better understanding of cell populations that expand from the post-therapy, minimal residual disease (MRD) state. We profile barcoded tumor stem cell populations through therapy at tumor initiation, MRD, and recurrence in our therapy-adapted, patient-derived xenograft models of glioblastoma (GBM).

Clogging and avalanches in quasi-two-dimensional emulsion hopper flow.

We experimentally and computationally study the flow of a quasi-two-dimensional emulsion through a constricting hopper shape. Our area fractions are above jamming such that the droplets are always in contact with one another and are in many cases highly deformed. At the lowest flow rates, the droplets often clog and thus exit the hopper via intermittent avalanches.

Development, validation, qualification, and dissemination of quantitative MR methods: Overview and recommendations by the ISMRM quantitative MR study group.

On behalf of the International Society for Magnetic Resonance in Medicine (ISMRM) Quantitative MR Study Group, this article provides an overview of considerations for the development, validation, qualification, and dissemination of quantitative MR (qMR) methods. This process is framed in terms of two central technical performance properties, i.e.

A practical method for post-acquisition reduction of bias in fast, whole-brain B1-maps.

Large consistent differences have been observed between maps of the flip angle correction factor (commonly called "B-maps") produced with different fast methods in the human brain. We present an empirical procedure for first-order multiplicative bias correction that can be applied when more than one B-mapping method is available. We use a B-map measurement in a calibration phantom as a reference and the voxel-wise histogram mode between ratios of B-maps produced from different methods to calculate determine the bias as a multiplicative correcting scale factor.

The Impact of Mental Health Conditions on Public Insurance Costs of Treating HIV/AIDS.

Medicare and Medicaid insurance claims data for Californians living with HIV are analyzed in order to determine: (1)The prevalence of treatment for particular mental health diagnoses among people living with HIV (PLWH) with Medicare or Medicaid insurance in 2010; (2)The relationship between individual mental health conditions and total medical care expenditures; (3)The impact of individual mental health diagnoses on the cost of treating non-mental health conditions; and (4)The implications of the cost of mental health diagnoses for setting managed care capitation payments. We find that the prevalence of mental health conditions among PLWH is high (23% among Medicare and 28% among Medicaid enrollees). PLWH with mental health conditions have significantly higher treatment costs for both mental health and non-mental health conditions.

Sensitivity of coda wave interferometry to fluid migration through rock.

The sound speed of a porous medium changes with fluid substitution when the fluids have different acoustic properties. The authors demonstrate that coda wave interferometry is capable of sensing subtle local sound speed changes associated with minute fluid displacements, Δh. In fact the resolution on fluid motion is given by a simple scaling relationship, Δh/λ∼te, where t is the waveform time, λ is the wavelength, γ is a constant that varies based on the nature of the acoustic propagation, and α is a system specific acoustic attenuation coefficient.

Association between Federally Qualified Health Center usage and emergency department utilization among California's HIV-infected Medicaid beneficiaries, 2009.

Federally Qualified Health Centers (FQHCs) have long been important sources of care for publicly insured people living with HIV. FQHC users have historically used emergency departments (EDs) at a higher-than-average rate. This paper examines whether this greater use relates to access difficulties in FQHCs or to characteristics of FQHC users.

Risk Factors for Substance Use Among Youth Experiencing Homelessness.

Background: Youth experiencing homelessness are at high risk for frequent substance use. This study examines individual, interpersonal, and contextual factors associated with substance use among such youth, age 13-24.

Methods: Data were collected through computer-assisted structured interviews with participants (N=474) recruited at service agencies in Los Angeles.

Do Medicare Beneficiaries Living With HIV/AIDS Choose Prescription Drug Plans That Minimize Their Total Spending?

This article examines whether California Medicare beneficiaries with HIV/AIDS choose Part D prescription drug plans that minimize their expenses. Among beneficiaries without low-income supplementation, we estimate the excess cost, and the insurance policy and beneficiary characteristics responsible, when the lowest cost plan is not chosen. We use a cost calculator developed for this study, and 2010 drug use data on 1453 California Medicare beneficiaries with HIV who were taking antiretroviral medications.

Trauma, Family Factors and the Mental Health of Homeless Adolescents.

Family factors, such as poor family functioning and trauma, have been associated with negative outcomes for homeless adolescents. Further study is needed to better understand how family factors and trauma jointly relate to mental health problems and externalizing behaviors among homeless adolescents. Structural equation modeling was used to examine the influence of trauma (encompassing traumatic events experienced prior to, and after, becoming homeless) and family factors (poor family functioning and family conflict) on mental health problems and externalizing behaviors (substance use, delinquent behaviors, and sexual risk) among 201 homeless adolescents, ages 12 to 17 years.

Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions.

Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods.

Water Exchange Rate Constant as a Biomarker of Treatment Efficacy in Patients With Brain Metastases Undergoing Stereotactic Radiosurgery.

Purpose: This study was designed to evaluate whether changes in metastatic brain tumors after stereotactic radiosurgery (SRS) can be seen with quantitative MRI early after treatment.

Methods And Materials: Using contrast-enhanced MRI, a 3-water-compartment tissue model consisting of intracellular (I), extracellular-extravascular (E), and vascular (V) compartments was used to assess the intra-extracellular water exchange rate constant (k), efflux rate constant (k), and water compartment volume fractions (M, M, M). In this prospective study, 19 patients were MRI-scanned before treatment and 1 week and 1 month after SRS.

Antiretroviral Therapy: Racial Disparities among Publicly Insured Californians with HIV.

Only 43% of Americans with HIV are virally suppressed; the rate is lower for African Americans, even among insured populations. This study uses 2010 Medicare and Medicaid data for HIV-positive Californians to examine how antiretroviral treatment (ART) relates to patient and provider characteristics. Logistic regressions isolated the effect of race/ethnicity on receipt of ART.

Transitioning From Medicaid Disability Coverage to Long-Term Medicare Coverage: The Case of People Living With HIV/AIDS in California.

Medicaid can serve as a bridge to Medicare coverage for the long-term disabled with sufficient covered work experience. We perform multinomial logistic regression on 2007-2010 Medicare and Medicaid claims data to examine transitions to Medicare for people living with HIV/AIDS (PLWHA) in California who had Medicaid coverage in 2007. We find only 16% had obtained Medicare coverage by 2010.

Differentiation between Radiation Necrosis and Tumor Progression Using Chemical Exchange Saturation Transfer.

Stereotactic radiosurgery (SRS) is a common treatment used in patients with brain metastases and is associated with high rates of local control, however, at the risk of radiation necrosis. It is difficult to differentiate radiation necrosis from tumor progression using conventional MRI, making it a major diagnostic dilemma for practitioners. This prospective study investigated whether chemical exchange saturation transfer (CEST) was able to differentiate these two conditions.

Chemical exchange saturation transfer for predicting response to stereotactic radiosurgery in human brain metastasis.

Purpose: The purpose of this work was to determine the predictive value of chemical exchange saturation transfer (CEST) metrics in brain metastases treated with stereotactic radiosurgery (SRS).

Methods: CEST spectra at a radiofrequency power of 0.52 µT were collected on a 3 Tesla (T) magnetic resonance imaging from 25 patients at three time points: pretreatment, 1 week, and 1 month post-treatment.

Quality of Care for HIV/AIDS and for Primary Prevention by HIV Specialists and Nonspecialists.

The role of HIV specialists in providing primary care to persons living with HIV/AIDS is evolving, given their increased incidence of comorbidities. Multivariate logit analysis compared compliance with sentinel preventive screening tests and interventions among publicly insured Californians with and without access to HIV specialists in 2010. Quality-of-care indicators [visit frequency, CD4 and viral load (VL) assessments, influenza vaccine, tuberculosis (TB) testing, lipid profile, glucose blood test, and Pap smears for women] were related to patient characteristics and provider HIV caseload.

Differences in iron and manganese concentration may confound the measurement of myelin from R1 and R2 relaxation rates in studies of dysmyelination.

A model of dysmyelination, the Long Evans Shaker (les) rat, was used to study the contribution of myelin to MR tissue properties in white matter. A large region of white matter was identified in the deep cerebellum and was used for measurements of the MR relaxation rate constants, R1  = 1/T1 and R2  = 1/T2 , at 7 T. In this study, R1 of the les deep cerebellar white matter was found to be 0.

Measurement of Stress Redistribution in Flowing Emulsions.

We study how local rearrangements alter droplet stresses within flowing dense quasi-two-dimensional emulsions at area fractions ϕ≥0.88. Using microscopy, we measure droplet positions while simultaneously using their deformed shape to measure droplet stresses.