Convection Enhanced Drug Delivery for the Treatment of Brain Gliomas

Malignant brain gliomas are almost always fatal, with a five year survival rate of only 3%. This is due in part to the difficulty of treating tumors chemically or surgically. They are often deep within the brain, where drugs cannot easily diffusive due to the blood-brain barrier and where surgery could be deadly. Emerging techniques for improved treatment include direct infusion of treatment drugs, like Paclitaxel, into the tumor in a procedure known as convection-enhanced drug delivery. These procedures require days of carefully monitored infusion to ensure tumor destruction while preserving surrounding tissue. To better understand the drug distribution and dosing options for different tumor sizes without dangerous medical tests, we have modeled the drug distribution within the tumor and surrounding tissue computationally. The model shows drug distributions consistent with current clinical results after a five day procedure. This model could now be used to better define dosing levels and procedure parameters to maximize tumor removal while preserving healthy tissue in individually unique cases

Employed Parents of Children With Mental Health Disorders: Achieving Work–Family Fit, Flexibility, and Role Quality

Extensive interviews with 60 employed parents of school-age children treated for mental health problems explored work–family fit, flexibility, family support, and work–life strategies in relation to role quality. Role quality was measured as employment and parenting rewards and concerns. Work–family fit was positively related to family flexibility but not work flexibility. Higher flexibility in work and family predicted lower job concerns, and work flexibility and work–family fit were predictors of job rewards. Parental concerns were dependent on flexibility and work–family strategies. Single parents had significantly fewer sources of family support and used fewer work–family strategies than caregivers with partners. Human services providers should collaborate with families by jointly exploring new flexibility and support strategies in work and family domains

Orthogonal realizations of random sign patterns and other applications of the SIPP

A sign pattern is an array with entries in $\{+,-,0\}$. A matrix $Q$ is row orthogonal if $QQ^T = I$. The Strong Inner Product Property (SIPP), introduced in [B.A.~Curtis and B.L.~Shader, Sign patterns of orthogonal matrices and the strong inner product property, Linear Algebra Appl. 592: 228--259, 2020], is an important tool when determining whether a sign pattern allows row orthogonality because it guarantees there is a nearby matrix with the same property, allowing zero entries to be perturbed to nonzero entries, while preserving the sign of every nonzero entry. This paper uses the SIPP to initiate the study of conditions under which random sign patterns allow row orthogonality with high probability. Building on prior work, $5\times n$ nowhere zero sign patterns that minimally allow orthogonality are determined. Conditions on zero entries in a sign pattern are established that guarantee any row orthogonal matrix with such a sign pattern has the SIPP

The Impact of Comprehensive Case Management on HIV Client Outcomes

In 1990, New York State instituted Comprehensive Medicaid Case Management, also known as Target Case Management (TCM), for people dealing with multiple comorbid conditions, including HIV. The goal of TCM is to assist clients in navigating the health care system to increase care engagement and treatment adherence for individuals with complex needs. HIV-positive individuals engaged in care are more likely to be virally suppressed, improving clinical outcomes and decreasing chances of HIV transmission. The purpose of this study was to understand the impact of TCM management on outcomes for people with HIV. Data were obtained from Amida Care, which operates not-for-profit managed care Medicaid and Medicare Special Needs Plans (SNPs) for HIV clients. Changes in clinical, cost, as well as medical and pharmacy utilization data among TCM clients were examined between January 2011 through September 2012 from the start of case management enrollment through the end of the study period (i.e., up to 6 months after disenrollment). Additionally, CD4 counts were compared between Amida Care TCM clients and non-TCM clients. Notable findings include increased CD4 counts for TCM clients over the one-year study period, achieving parity with non-TCM clients (i.e., Mean CD4 count > 500). When looking exclusively at TCM clients, there were increases in medication costs over time, which were concomitant with increased care engagement. Current findings demonstrate that TCM is able to achieve its goals of improving care engagement and treatment adherence. Subsequent policy changes resulting from the Affordable Care Act and the New York State Medicaid Redesign have made the Health Home the administrator of TCM services. Government entities charged with securing and managing TCM and care coordination for people with HIV should provide thoughtful and reasonable guidance and oversight in order to maintain optimal clinical outcomes for TCM clients and reduce the transmission of HIV

Habitual physical activity and the risk for depressive and anxiety disorders among older men and women

Background: Regular physical activity is generally associated with psychological well-being, although there are relatively few prospective studies in older adults. We investigated habitual physical activity as a risk factor for de novo depressive and anxiety disorders in older men and women from the general population.Methods: In this nested case-control study, subjects aged 60 years or more were identified from randomly selected cohorts being followed prospectively in the Geelong Osteoporosis Study. Cases were individuals with incident depressive or anxiety disorders, diagnosed using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no history of these disorders.Habitual physical activity,measured using a validated questionnaire, and other exposures were documented at baseline, approximately four years prior to psychiatric interviews. Those with depressive or anxiety disorders that pre-dated baseline were excluded.Results: Of 547 eligible subjects, 14 developed de novo depressive or anxiety disorders and were classified as cases; 533 controls remained free of disease. Physical activity was protective against the likelihood of depressive and anxiety disorders; OR = 0.55 (95% CI 0.32&ndash;0.94), p = 0.03; each standard deviation increase in the transformed physical activity score was associated with an approximate halving in the likelihood of developing depressive or anxiety disorders. Leisure-time physical activity contributed substantially to the overall physical activity score. Age, gender, smoking, alcohol consumption, weight and socioeconomic status did not substantially confound the association.Conclusion: This study provides evidence consistent with the notion that higher levels of habitual physical activity are protective against the subsequent risk of development of de novo depressive and anxiety disorders.<br /

Three dimensional in vitro models of cancer: Bioprinting multilineage glioblastoma models

International audienceThree dimensional (3D) bioprinting of multiple cell types within optimised extracellular matrices has the potential to more closely model the 3D environment of human physiology and disease than current alternatives. In this study, we used a multi-nozzle extrusion bioprinter to establish models of glioblastoma made up of cancer and stromal cells printed within matrices comprised of alginate modified with RGDS cell adhesion peptides, hyaluronic acid and collagen-1. Methods were developed using U87MG glioblastoma cells and MM6 monocyte/macrophages, whilst more disease relevant constructs contained glioblastoma stem cells (GSCs), co-printed with glioma associated stromal cells (GASCs) and microglia. Printing parameters were optimised to promote cell-cell interaction, avoiding the 'caging in' of cells due to overly dense cross-linking. Such printing had a negligible effect on cell viability, and cells retained robust metabolic activity and proliferation. Alginate gels allowed the rapid recovery of printed cell protein and RNA, and fluorescent reporters provided analysis of protein kinase activation at the single cell level within printed constructs. GSCs showed more resistance to chemotherapeutic drugs in 3D printed tumour constructs compared to 2D monolayer cultures, reflecting the clinical situation. In summary, a novel 3D bioprinting strategy is developed which allows control over the spatial organisation of tumour constructs for pre-clinical drug sensitivity testing and studies of the tumour microenvironment