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Insulin pump controllers seek to alleviate the chronic suffering caused by diabetes that affects over 6% of the world population. The design of control laws for insulin pump controllers has been well studied. However, the parameters involved in the control law are difficult to synthesize. Traditionally, ad hoc approaches using animal models and random sampling have been used to construct these parameters. We suggest a synthesis algorithm that uses Bayesian statistical model validation to reduce the number of simulations needed. We apply this algorithm to the problem of insulin pump controller synthesis using in silico simulation of the glucose-insulin metabolism model.

86 Background: A diagnosis of advanced cancer frequently thrusts family members into the role of caregiver. Although caregiver burdens have been well documented, less is known about the level of concern borne by the patient (pt) with cancer in placing a family member in this role, known as self-perceived burden (SPB). Methods: As part of the larger “Living with Cancer” project we prospectively surveyed 1307 pts with advanced malignancies receiving treatment with non-curative intent at 17 New Jersey cancer programs within the Regional Cancer Care Associates network between Sept 2015 and Apr 2016. Pts were asked one question about SPB on family members (5-level Likert scale). Results: Pts felt that “Living with Cancer burdens my family” all day every day 68 pts (5%), part of each day 109 pts (8%), most days 136 pts (10%), occasionally 571 pts (44%) or not at all 423 pts (32%). Twenty-four percent of responses were flagged as concerned (rated most days or greater by 313 pts). In a logistic regression model, SPB was correlated with marital status (married and divorced more concerned than single) and younger age (both p < 0.05). Patients living in lower median income neighborhoods also appeared to have a higher frequency of concern (p < 0.1) Factors not correlating with the level of SPB included gender, race, solid vs liquid tumor type, and length of cancer diagnosis. SPB was also not influenced by DNR status, having developed a Living Will, or documentation of power of attorney. Distance from the pt’s home to the cancer center was not associated with SPB on the caregiver. For comparison, on the same LWC project 38% of pts with advanced cancer were concerned about the financial toxicity of their care and 33% were concerned about pain (both p < 0.01 compared to SPB). Conclusions: Self-perceived burden on a caregiver was identified in 24% of pts with advanced cancer, less than those concerned about financial toxicity or pain, in this NJ series. Divorced/married pts and younger pts with cancer are more likely to express concern. Developing an EOLC plan (DNR/Living will/POA) does not appear to influence SPB concerns.

An effective malaria vaccine must prevent disease in a range of populations living in regions with vastly different transmission rates and protect against genetically-diverse Plasmodium falciparum (Pf) strains. The protective efficacy afforded by the currently licensed malaria vaccine, Mosquirix™, promotes strong humoral responses to Pf circumsporozoite protein (CSP) 3D7 but protection is limited in duration and by strain variation. Helper CD4 T cells are central to development of protective immune responses, playing roles in B cell activation and maturation processes, cytokine production, and stimulation of effector T cells. Therefore, we took advantage of recent in silico modeling advances to predict and analyze human leukocyte antigen (HLA)-restricted class II epitopes from PfCSP – across the entire PfCSP 3D7 sequence as well as in 539 PfCSP sequence variants – with the goal of improving PfCSP-based malaria vaccines. Specifically, we developed a systematic workflow to identify peptide sequences capable of binding HLA-DR in a context relevant to achieving broad human population coverage utilizing cognate T cell help and with limited T regulatory cell activation triggers. Through this workflow, we identified seven predicted class II epitope clusters in the N- and C-terminal regions of PfCSP 3D7 and an additional eight clusters through comparative analysis of 539 PfCSP sequence variants. A subset of these predicted class II epitope clusters was synthesized as peptides and assessed for HLA-DR binding in vitro. Further, we characterized the functional capacity of these peptides to prime and activate human peripheral blood mononuclear cells (PBMCs), by monitoring cytokine response profiles using MIMIC® technology (Modular IMmune In vitro Construct). Utilizing this decision framework, we found sufficient differential cellular activation and cytokine profiles among HLA-DR-matched PBMC donors to downselect class II epitope clusters for inclusion in a vaccine targeting PfCSP. Importantly, the downselected clusters are not highly conserved across PfCSP variants but rather, they overlap a hypervariable region (TH2R) in the C-terminus of the protein. We recommend assessing these class II epitope clusters within the context of a PfCSP vaccine, employing a test system capable of measuring immunogenicity across a broad set of HLA-DR alleles.