Open Access Publications from the University of California

(2019)

## The Natural History of Meniscus Tears.

(2019)

In order to determine whether treatments are effective in the treatment of meniscus tears, it is first necessary to understand the natural history of meniscus tears. The purpose of this paper is to review the literature to ascertain the natural history of meniscus tears in children and adolescents. A search of the Pubmed and Embase databases was performed using the search terms "meniscus tears," "natural history of meniscus tears," "knee meniscus," "discoid meniscus," and "natural history of discoid meniscus tears." A total of 2567 articles on meniscus tears, 28 articles on natural history of meniscus tears, 8065 articles on "menisci," 396 articles on "discoid meniscus," and only 2 on the "natural history of discoid meniscus" were found. After reviewing the titles of these articles and reviewing the abstracts of 237 articles, it was clear that there was little true long-term natural history data of untreated meniscus tears nor whether treating meniscus tears altered the natural history. Twenty-five articles were chosen as there was some mention of natural history in their studies. There are few long-term data on untreated meniscal tears or discoid meniscus, or tears in children and adolescents. The literature suggests that there is a higher incidence of chondral injury and subsequent osteoarthritis, but there are many confounding variables which are not controlled for in these relatively short-term papers.

## Context shapes early diversity in abstract thought.

(2019)

Early abstract reasoning has typically been characterized by a "relational shift," in which children initially focus on object features but increasingly come to interpret similarity in terms of structured relations. An alternative possibility is that this shift reflects a learned bias, rather than a typical waypoint along a universal developmental trajectory. If so, consistent differences in the focus on objects or relations in a child's learning environment could create distinct patterns of relational reasoning, influencing the type of hypotheses that are privileged and applied. Specifically, children in the United States may be subject to culture-specific influences that bias their reasoning toward objects, to the detriment of relations. In experiment 1, we examine relational reasoning in a population with less object-centric experience-3-y-olds in China-and find no evidence of the failures observed in the United States at the same age. A second experiment with younger and older toddlers in China (18 to 30 mo and 30 to 36 mo) establishes distinct developmental trajectories of relational reasoning across the two cultures, showing a linear trajectory in China, in contrast to the U-shaped trajectory that has been previously reported in the United States. In a third experiment, Chinese 3-y-olds exhibit a bias toward relational solutions in an ambiguous context, while those in the United States prefer object-based solutions. Together, these findings establish population-level differences in relational bias that predict the developmental trajectory of relational reasoning, challenging the generality of an initial object focus and suggesting a critical role for experience.

## Utilization of Hospital Room Hospitality Features on Patient-Controlled Tablet Computers: Cohort Study.

(2019)

BACKGROUND:Patient portals tethered to electronic health records can improve patient experience, activation, and outcomes. However, adoption of inpatient portals has been challenging. One way to potentially increase inpatient portal usage is to integrate it with a room control (RC) app on a common tablet computer. OBJECTIVE:The aim of this study was to perform a retrospective analysis of patient usage of an RC app provided on tablet computers in patient rooms of our new inpatient tower. METHODS:We identified all patients who were admitted for >24 hours to our new inpatient tower over a 90-day period from September 1 to November 30, 2017. After excluding newborn patients from our analysis, we then identified patients who used the RC app at least one time during their admission. We linked these data to patient demographics (including age, sex, and race) and admitting service. We then performed univariable and multivariable logistic regression to assess patterns of RC app usage. RESULTS:A total of 3411 patients were admitted over the course of the study period; 2242/3411 (65.73%) used the RC app during their hospitalization. Compared with white patients, other/mixed/unknown race and Asian, Hawaiian, Pacific Islander, American Indian race were significantly associated with increased use of the RC app in a multivariable analysis. Increasing age was significantly associated with increased usage of the RC app. Usage of the RC app also varied by admitting services. Compared with general medicine, bone marrow transplant and general surgery patients had increased usage of the RC app. Conversely, critical care, medical specialties, neurology, surgical subspecialties, and obstetrics/gynecology were all associated with decreased usage of the RC app. CONCLUSIONS:Our study shows that one-third of patients are not using the RC app for critical room functions. Future initiatives to increase RC usage should take these populations into consideration. Contrary to common belief, older patients may use tablet-enabled RCs just as often, if not more often, than younger patients. Certain admitting services, such as neurology and surgical subspecialties, may have had lower usage rates owing to accessibility issues. Our study allows hospitals to tailor support for specific patient populations to increase RC app usage.

## Temporal and spatial effects and survival outcomes associated with concordance between tissue and blood KRAS alterations in the pan-cancer setting.

(2019)

We investigated the impact of time interval, primary vs. metastatic biopsy site, variant allele fraction (VAF) and histology on concordance of KRAS alterations in tissue vs. circulating tumor DNA (ctDNA), and association of concordance with survival. Blood and tissue were evaluated by next-generation sequencing in 433 patients with diverse cancers. Altogether, 101 patients (23.3%) had KRAS alterations: 56, ctDNA (12.9%); 81, tissue (18.7%); and 36, both (8.3%). The overall blood and tissue concordance rate for KRAS alterations was 85%, but was mainly driven by the large negative/negative subset. Therefore, specificity of one test for the other was high (88.1-94.3%), while sensitivity was not high (44.4-64.3%) and was lower still in patients with >6 vs. ≤2 months between blood and tissue sampling (31.0-40.9% vs. 51.2-84.0%; p = 0.14 time interval-dependent sensitivity of blood for tissue; p = 0.003, tissue for blood). Positive concordance rate for KRAS alterations was 57.1% vs. 27.4% (colorectal vs. noncolorectal cancer; p = 0.01), but site of biopsy (primary vs. metastatic) and VAF (%ctDNA) was not impactful. The presence of KRAS alterations in both tests was independently associated with shorter survival from diagnosis (hazard ratio, 1.72; 95% confidence interval, 1.04-2.86) and from recurrent/metastatic disease (1.70; 1.03-2.81). Positive concordance of KRAS alterations between ctDNA and tissue was negatively affected by a longer time period between blood and tissue sampling and was higher in colorectal cancer than in other malignancies. The presence of KRAS alterations in both tests was an independent prognostic factor for poor survival.

## The MOSDEF survey: a census of AGN-driven ionized outflows at $z = 1.4-3.8$

(2019)

Using data from the MOSFIRE Deep Evolution Field (MOSDEF) survey, we present a census of AGN-driven ionized outflows in a sample of 159 AGNs at $1.4 \le z \le 3.8$. The sample spans AGN bolometric luminosities of $10^{44-47} \mathrm{~erg~s}^{-1}$ and includes both quiescent and star-forming galaxies extending across three orders of magnitude in stellar mass. We identify and characterize outflows from the \hbeta, [OIII], \halpha ~and [NII] emission line spectra. We detect outflows in $17\%$ of the AGNs, seven times more often than in a mass-matched sample of inactive galaxies in MOSDEF. The outflows are fast and galaxy-wide, with velocities of $\sim 400-3500 ~\mathrm{km~s}^{-1}$ and spatial extents of $0.3-11.0$ kpc. The incidence of outflows among AGNs is independent of the stellar mass of the host galaxy, with outflows detected in both star-forming and quiescent galaxies. This suggests that outflows exist across different phases in galaxy evolution. We investigate relations between outflow kinematic, spatial, and energetic properties and both AGN and host galaxy properties. Our results show that AGN-driven outflows are widespread in galaxies along the star-forming main sequence. The mass-loading factors of the outflows are typically $0.1-1$ and increase with AGN luminosity, capable of exceeding unity at $L_\mathrm{AGN} \gtrsim 10^{46.3} \mathrm{~erg~s}^{-1}$. In these more luminous sources the ionized outflow alone is likely sufficient to regulate star formation, and when combined with outflowing neutral and molecular gas may be able to quench star formation in their host galaxies.

## Conditional Effects of Lifetime Alcohol Consumption on Methamphetamine-Associated Neurocognitive Performance.

(2019)

OBJECTIVES:Methamphetamine (MA) dependence contributes to neurotoxicity and neurocognitive deficits. Although combined alcohol and MA misuse is common, how alcohol consumption relates to neurocognitive performance among MA users remains unclear. We hypothesized that alcohol and MA use would synergistically diminish neurocognitive functioning, such that greater reported alcohol consumption would exert larger negative effects on neurocognition among MA-dependent individuals compared to MA-nonusing persons. METHODS:Eighty-seven MA-dependent (MA+) and 114 MA-nonusing (MA-) adults underwent neuropsychological and substance use assessments. Linear and logistic regressions examined the interaction between MA status and lifetime average drinks per drinking day on demographically corrected global neurocognitive T scores and impairment rates, controlling for recent alcohol use, lifetime cannabis use, WRAT reading performance, and lifetime depression. RESULTS:MA+ displayed moderately higher rates of impairment and lower T scores compared to MA-. Lifetime alcohol use significantly interacted with MA status to predict global impairment (ORR = 0.70, p = .003) such that greater lifetime alcohol use increased likelihood of impairment in MA-, but decreased likelihood of impairment in MA+. Greater lifetime alcohol use predicted poorer global T scores among MA- (b = -0.44, p = .030) but not MA+ (b = 0.08, p = .586). CONCLUSIONS:Contrary to expectations, greater lifetime alcohol use related to reduced risk of neurocognitive impairment among MA users. Findings are supported by prior research identifying neurobiological mechanisms by which alcohol may attenuate stimulant-driven vasoconstriction and brain thermotoxicity. Replication and examination of neurophysiologic mechanisms underlying alcohol use in the context of MA dependence are warranted to elucidate whether alcohol confers a degree of neuroprotection.

(2019)

(2019)

## Effects of comorbidity burden and age on brain integrity in HIV.

(2019)

OBJECTIVE:The influence of confounding neurocognitive comorbidities in people living with HIV (PLWH) on neuroimaging has not been systematically evaluated. We determined associations between comorbidity burden and brain integrity and examined the moderating effect of age on these relationships. DESIGN:Observational, cross-sectional substudy of the CNS HIV Antiretroviral Therapy Effects Research cohort. METHODS:A total of 288 PLWH (mean age = 44.2) underwent structural MRI and magnetic resonance spectroscopy as well as neurocognitive and neuromedical assessments. Consistent with Frascati criteria for HIV-associated neurocognitive disorders (HAND), neuromedical and neuropsychiatric comorbidity burden was classified as incidental (mild), contributing (moderate), or confounding (severe-exclusionary) to a diagnosis of HAND. Multiple regression modeling predicted neuroimaging outcomes as a function of comorbidity classification, age, and their interaction. RESULTS:Comorbidity classifications were 176 incidental, 77 contributing, and 35 confounded; groups did not differ in HIV disease characteristics. Relative to incidental and contributing participants, confounded participants had less cortical gray matter and more abnormal white matter and ventricular cerebrospinal fluid, alongside more neuroinflammation (choline, myo-inositol) and less neuronal integrity (N-acetylaspartate). Older age exacerbated the impact of comorbidity burden: to a greater extent in the confounded group, older age was associated with more abnormal white matter (P = 0.017), less total white matter (P = 0.015), and less subcortical gray matter (P = 0.014). CONCLUSION:Neuroimaging in PLWH reveals signatures associated with confounding neurocognitive conditions, emphasizing the importance of evaluating these among individuals with suspected HAND. Older age amplifies subcortical and white matter tissue injury, especially in PLWH with severe comorbidity burden, warranting increased attention to this population as it ages.