Comparative Study of Multicellular Tumor Spheroid Formation Methods and Implications for Drug Screening

Improved in vitro models are needed to better understand cancer progression and bridge the gap between in vitro proof-of-concept studies, in vivo validation, and clinical application. Multicellular tumor spheroids (MCTS) are a popular method for three-dimensional (3D) cell culture, because they capture some aspects of the dimensionality, cell–cell contact, and cell–matrix interactions seen in vivo. Many approaches exist to create MCTS from cell lines, and they have been used to study tumor cell invasion, growth, and how cells respond to drugs in physiologically relevant 3D microenvironments. However, there are several discrepancies in the observations made of cell behaviors when comparing between MCTS formation methods. To resolve these inconsistencies, we created and compared the behavior of breast, prostate, and ovarian cancer cells across three MCTS formation methods: in polyNIPAAM gels, in microwells, or in suspension culture. These methods formed MCTS via proliferation from single cells or passive aggregation, and therefore showed differential reliance on genes important for cell–cell or cell–matrix interactions. We also found that the MCTS formation method dictated drug sensitivity, where MCTS formed over longer periods of time via clonal growth were more resistant to treatment. Toward clinical application, we compared an ovarian cancer cell line MCTS formed in polyNIPAAM with cells from patient-derived malignant ascites. The method that relied on clonal growth (PolyNIPAAM gel) was more time and cost intensive, but yielded MCTS that were uniformly spherical, and exhibited the most reproducible drug responses. Conversely, MCTS methods that relied on aggregation were faster, but yielded MCTS with grape-like, lobular structures. These three MCTS formation methods differed in culture time requirements and complexity, and had distinct drug response profiles, suggesting the choice of MCTS formation method should be carefully chosen based on the application required

Race, Socioeconomic Status, and Age: Exploring Intersections in Preterm Birth Disparities among Teen Mothers

Few studies have examined disparities in adverse birth outcomes and compared contributingsocioeconomic factors specifically between African-American and White teen mothers. Thisstudy examined intersections between neighborhood socioeconomic status (as defined by censustractmedian household income), maternal age, and racial disparities in preterm birth (PTB)outcomes between African-American and White teen mothers in North Carolina. Using a linkeddataset with state birth record data and socioeconomic information from the 2010 US Census,disparities in preterm birth outcomes for 16,472 teen mothers were examined through bivariateand multilevel analyses. African-American teens had significantly greater odds of PTB outcomesthan White teens (OR = 1.38, 95% CI 1.21, 1.56). Racial disparities in PTB rates significantlyvaried by neighborhood income; PTB rates were 2.1 times higher for African-American teens inhigher income neighborhoods compared to White teens in similar neighborhoods. Disparities inPTB did not vary significantly between teens younger than age 17 and teens ages 17–19,although the magnitude of racial disparities was larger between younger African-American andWhite teens. These results justify further investigations using intersectional frameworks to testthe effects of racial status, neighborhood socioeconomic factors, and maternal age on birthoutcome disparities among infants born to teen mothers

Aqueous Complexation Reactions Governing the Rate and Extent of Biogeochemical U(VI) Reduction

The proposed research will elucidate the principal biogeochemical reactions that govern the concentration, chemical speciation, and reactivity of the redox-sensitive contaminant uranium. The results will provide an improved understanding and predictive capability of the mechanisms that govern the biogeochemical reduction of uranium in subsurface environments. In addition, the work plan is designed to: (1) Generate fundamental scientific understanding on the relationship between U(VI) chemical speciation and its susceptibility to biogeochemical reduction reactions. (2) Elucidate the controls on the rate and extent of contaminant reactivity. (3) Provide new insights into the aqueous and solid speciation of U(VI)/U(IV) under representative groundwater conditions

Coupling Between Flow and Precipitation in Heterogeneous Subsurface Environments and Effects On Contaminant Fate and Transport

Reactive mixing fronts can occur at large scales, e.g. when chemical amendments are injected in wells, or at small scales (pore-scales) when reactive intermediates are being generated in situ at grain boundaries, cell surfaces and adjacent to biofilms. The product of the reactions such as mineral precipitates, biofilms or filtered colloids modifies permeability leading to the complex coupling between flow and reactions and precipitation. The objectives are to determine how precipitates are distributed within large and small scale mixing fronts, how permeability and flow is modified by precipitation, how the mobility of a representative contaminant, strontium, is affected by the precipitation of carbonates, and how subsequent dissolution of the carbonates result in mobilization of Sr and increased flow. The desired outcomes of the project are to help develop methods leading to sequestration of metal contaminants, and to determine how macroscopic field-scale modeling can be applied to predict the outcome of remediation activities

Relations of Mindfulness and Illness Acceptance With Psychosocial Functioning in Patients With Metastatic Breast Cancer and Caregivers

Objectives: To examine relationships in mindfulness and illness acceptance and psychosocial functioning in patients with metastatic breast cancer and their family caregivers. Sample & setting: 33 dyads from an academic cancer center in the United States. Methods & variables: Participants completed questionnaires on mindfulness, illness acceptance, relationship quality, anxiety, and depressive symptoms. Dyadic, cross-sectional data were analyzed using actor-partner interdependence models. Results: Greater nonjudging, acting with awareness, and illness acceptance among caregivers were associated with patients' and caregivers' perceptions of better relationship quality. Higher levels of these processes were associated with reduced anxiety and depressive symptoms in patients and caregivers. Implications for nursing: Aspects of mindfulness and illness acceptance in dyads confer benefits that are primarily intrapersonal in nature. Nurses may consider introducing mindfulness and acceptance-based interventions to patients and caregivers with adjustment difficulties

Spectroscopic and computational insights on catalytic synergy in bimetallic aluminophosphate catalysts

A combined electronic structure computational and X-ray absorption spectroscopy study was used to investigate the nature of the active sites responsible for catalytic synergy in Co-Ti bimetallic nanoporous frameworks. Probing the nature of the molecular species at the atomic level has led to the identification of a unique Co-O-Ti bond, which serves as the loci for the superior performance of the bimetallic catalyst, when compared with its analogous monometallic counterpart. The structural and spectroscopic features associated with this active site have been characterized and contrasted, with a view to affording structure property relationships, in the wider context of designing sustainable catalytic oxidations with porous solids

Searches After Gravitational-waves Using ARizona Observatories (SAGUARO): System Overview and First Results from Advanced LIGO/Virgo's Third Observing Run

We present Searches After Gravitational-waves Using ARizona Observatories (SAGUARO), a comprehensive effort dedicated to the discovery and characterization of optical counterparts to gravitational wave (GW) events. SAGUARO utilizes ground-based facilities ranging from 1.5m to 10m in diameter, located primarily in the Northern Hemisphere. We provide an overview of SAGUARO's telescopic resources, pipeline for transient detection, and database for candidate visualization. We describe SAGUARO's discovery component, which utilizes the $5$~deg$^2$ field-of-view optical imager on the Mt. Lemmon 1.5m telescope, reaching limits of $\approx 21.3$~AB mag while rapidly tiling large areas. We also describe the follow-up component of SAGUARO, used for rapid vetting and monitoring of optical candidates. With the onset of Advanced LIGO/Virgo's third observing run, we present results from the first three SAGUARO searches following the GW events S190408an, S190425z and S190426c, which serve as a valuable proof-of-concept of SAGUARO. We triggered and searched 15, 60 and 60 deg$^{2}$ respectively, 17.6, 1.4 and 41.8 hrs after the initial GW alerts. We covered 7.8, 3.0 and 5.1\% of the total probability within the GW event localizations, reaching 3$\sigma$ limits of 19.8, 21.3 and 20.8 AB mag, respectively. Although no viable counterparts associated with these events were found, we recovered 6 known transients and ruled out 5 potential candidates. We also present Large Binocular Telescope spectroscopy of PS19eq/SN2019ebq, a promising kilonova candidate that was later determined to be a supernova. With the ability to tile large areas and conduct detailed follow-up, SAGUARO represents a significant addition to GW counterpart searches.Comment: 16 pages, 7 figures, 1 table. Accepted to ApJ

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening