Population Based Patient Navigation : 24-Hour Personalized Cancer Care for the Entire Cancer Continuum

Cancer One word that bears immense significance for so many individuals For some, it is the word that took them by surprise, imposing new routines and adjustments to daily life as quickly and succinctly as it rolls off the tongue For others, the word evokes complex and multifaceted emotions fear, strength, apathy, gratitude, anger, hope, grief, determination the list is endless and ever changing The impact of this diagnosis extends far beyond the patient to their family, their care team, their community and more In 2017 there will be an estimated 1 688 780 new cancer cases diagnosed in the United States 1 Of those diagnosed, every cancer journey will be unique Standard differences in cancer site, stage, treatment modalities and outcomes, coupled with variances in patient age, receptivity to treatments, and patient preference of therapies compels oncologists and cancer care teams to design treatment plans patient by patient, providing a vastly individualized and intricate approach to the treatment of cancer With the complexities involved across the cancer care continuum, the need emerged for trained individuals uniquely qualified to assist patients, providers, and families navigate this expounded realm of cancer care From this need arose the field of patient navigatio

Provision of Survivorship Care Plans in Hard to Reach Patient Populations

Table of ContentsAcknowledgments [page] 1The Case for Survivorship Care Plans [page] 3Accreditation Standards for Survivorship Programs [page] 4Hard to Reach Patient Populations [page] 5Methods [page] 6Models of Collaboration to Reach Survivors of Urological Cancers [page] 8Model #1 [page] 9Model #2 [page] 13Summary of Collaborations [page] 16References [page] 1

Moral motivation and the affective appeal

Proponents of “the affective appeal” (e.g. Dancy in Ethics 124(4):787–812, 2014; Zagzebski in Philos Phenomenol Res 66(1):104–124, 2003) argue that we can make progress in the longstanding debate about the nature of moral motivation by appealing to the affective dimension of affective episodes such as emotions, which allegedly play either a causal or constitutive role in moral judgements. Specifically, they claim that appealing to affect vindicates a version of Motivational Internalism—roughly, the view that there is a necessary connection between moral judgment and motivation—that is both more empirically respectable and less theoretically controversial than non-affective versions. We here argue that the affective appeal fails: versions of Internalism which appeal to affect are neither more empirically supported, nor clearly less controversial, than versions of Internalism which make no such appeal. Although affect doubtless has an important role to play in explaining moral motivation, we are sceptical that establishing any such role advances the debate

Evaluation of an FDA approved library against laboratory models of human intestinal nematode infections

Treatment options for infections with soil-transmitted helminths (STH) - Ascaris lumbricoides, Trichuris trichiura and the two hookworm species, Ancylostoma duodenale and Necator americanus - are limited despite their considerable global health burden. The aim of the present study was to test the activity of an openly available FDA library against laboratory models of human intestinal nematode infections.; All 1,600 drugs were first screened against Ancylostoma ceylanicum third-stage larvae (L3). Active compounds were scrutinized and toxic compounds, drugs indicated solely for topical use, and already well-studied anthelmintics were excluded. The remaining hit compounds were tested in parallel against Trichuris muris first-stage larvae (L1), Heligmosomoides polygyrus third-stage larvae (L3), and adult stages of the three species in vitro. In vivo studies were performed in the H. polygyrus and T. muris mice models.; Fifty-four of the 1,600 compounds tested revealed an activity of > 60 % against A. ceylanicum L3 (hit rate of 3.4 %), following incubation at 200 μM for 72 h. Twelve compounds progressed into further screens. Adult A. ceylanicum were the least affected (1/12 compounds active at 50 μM), while eight of the 12 test compounds revealed activity against T. muris L1 (100 μM) and adults (50 μM), and H. polygyrus L3 (200 μM). Trichlorfon was the only compound active against all stages of A. ceylanicum, H. polygyrus and T. muris. In addition, trichlorfon achieved high worm burden reductions of 80.1 and 98.9 %, following a single oral dose of 200 mg/kg in the T. muris and H. polygyrus mouse model, respectively.; Drug screening on the larval stages of intestinal parasitic nematodes is feasible using small libraries and important given the empty drug discovery and development pipeline for STH infections. Differences and commonalities in drug activities across the different STH species and stages were confirmed. Hits identified might serve as a starting point for drug discovery for STH

The role of the thymic medulla in T cell development and tolerance induction

The thymus is organised into functionally distinct microenvironments that facilitates development of a diverse and self-tolerant T cell repertoire. Following positive selection, thymocytes undergo chemotactic migration from the cortex to the medulla, a site that mediates negative selection of potentially autoreactive CD4+ and CD8+ single positive (SP) thymocytes. Importantly, current models suggest that the medulla also fosters the continued maturation of SP thymocytes, post-selection. However, the mechanisms of thymic medulla function remain unclear. Using a novel approach based on chemokine receptor expression, we have mapped stages in the positive selection process, and developed a model to study αβT cell development in the absence of medullary thymic epithelial cells (mTEC), but in the presence of an otherwise intact immune system. We show that mTEC are dispensible for the continued development of newly selected CD4+CD69+ SP thymocytes, yet are essential for the generation of FoxP3+ regulatory T cells and their FoxP3-CD25+ progenitors. In addition, although CCR4 represents a marker of early stage CD4+ SP positive selection, it is dispensable for SP medullary accumulation and intrathymic development. Collectively these findings highlight differences in the developmental requirements of conventional and regulatory CD4+ T cells, and rule out a role for CCR4 in cortex to medulla migration

Europium, Samarium, and Neodymium Isotopic Fractions in Metal-Poor Stars

We have derived isotopic fractions of europium, samarium, and neodymium in two metal-poor giants with differing neutron-capture nucleosynthetic histories. These isotopic fractions were measured from new high resolution (R ~ 120,000), high signal-to-noise (S/N ~ 160-1000) spectra obtained with the 2dCoude spectrograph of McDonald Observatory's 2.7m Smith telescope. Synthetic spectra were generated using recent high-precision laboratory measurements of hyperfine and isotopic subcomponents of several transitions of these elements and matched quantitatively to the observed spectra. We interpret our isotopic fractions by the nucleosynthesis predictions of the stellar model, which reproduces s-process nucleosynthesis from the physical conditions expected in low-mass, thermally-pulsing stars on the AGB, and the classical method, which approximates s-process nucleosynthesis by a steady neutron flux impinging upon Fe-peak seed nuclei. Our Eu isotopic fraction in HD 175305 is consistent with an r-process origin by the classical method and is consistent with either an r- or an s-process origin by the stellar model. Our Sm isotopic fraction in HD 175305 suggests a predominantly r-process origin, and our Sm isotopic fraction in HD 196944 is consistent with an s-process origin. The Nd isotopic fractions, while consistent with either r-process or s-process origins, have very little ability to distinguish between any physical values for the isotopic fraction in either star. This study for the first time extends the n-capture origin of multiple rare earths in metal-poor stars from elemental abundances to the isotopic level, strengthening the r-process interpretation for HD 175305 and the s-process interpretation for HD196944.Comment: 40 pages, 16 figures. Accepted for publication in ApJ. Full versions of tables 4 and 5 are available from the first author upon reques

Exposure of Heligmosomoides polygyrus and Trichuris muris to albendazole, albendazole sulfoxide, mebendazole and oxantel pamoate in vitro and in vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes

Millions of people are treated with anthelmintics to control soil-transmitted helminth infections; yet, drug distribution in the plasma and gastrointestinal tract compartments and the pathway of drug uptake into gastrointestinal nematodes responsible for the pharmacological effect are unknown. We assessed the distribution and uptake of albendazole, albendazole sulfoxide, albendazole sulfone in the hookworm Heligmosomoides polygyrus in vitro and in vivo as well as the distribution and uptake of albendazole, mebendazole, and oxantel pamoate in the whipworm Trichuris muris in vitro and invivo. Oral and intraperitoneal treatments (100 mg/kg) were studied. Drug quantities in helminths and host compartments (stomach, the contents and mucosa of the small and large intestine, and the plasma) were determined using HPLC-UV/vis and anthelmintic activities were recorded using phenotypic readout. The influence of 1-aminobenzotriazole (ABT), an irreversible and unspecific cytochrome P450 inhibitor, on albendazole disposition in mice harboring H. polygyrus was evaluated. In vivo, albendazole was found in quantities up to 10 nmol per ten H. polygyrus and up to 31 nmol per ten T. muris. ABT did not change the levels of albendazole or its metabolites in the plasma of mice harboring H. polygyrus or in H. polygyrus, whereas drug levels in the gastrointestinal tract of host mice doubled. Mebendazole and oxantel pamoate quantities per ten T. muris were as high as 21 nmol and 34 nmol, respectively. Albendazole revealed a very dynamic distribution and high rate of metabolism, hence, H. polygyrus and T. muris are exposed to albendazole and both metabolites via multiple pathways. Diffusion through the cuticle seems to be the crucial pathway of oxantel pamoate uptake into T. muris, and likely also for mebendazole. No relationship between concentrations measured in helminths and concentrations in plasma, intestinal content and mucosa of mice, or drug efficacy was noted for any of the drugs studied

Development and deployment of an at-home strength and conditioning program to support a phase I trial in persons with chronic spinal cord injury

Study design Nonrandomized clinical trial (NCT02354625).Objectives As a part of a Phase I clinical trial to assess the safety of autologous human Schwann cells (ahSC) in personswith chronic spinal cord injury (SCI), participants engaged in a multimodal conditioning program pre- and post-ahSCtransplantation. The program included a home-based strength and endurance training program to prevent lack of fitness andposttransplantation detraining from confounding potential ahSC therapeutic effects. This paper describes development,deployment, outcomes, and challenges of the home-based training program.Setting University-based laboratory.Methods Development phase: two men with paraplegia completed an 8-week laboratory-based ‘test’ of the home-basedprogram. Deployment phase: the first four (two males, two females) participant cohort of the ahSC trial completed theprogram at home for 12 weeks pre and 20 weeks post ahSC transplant.Results Development phase: both participants improved their peak aerobic capacity (VO2peak) (≥17%), peak power output(POpeak) (≥8%), and time to exhaustion (TTE) (≥7%). Deployment phase: pretransplant training minimally increased fitness inthe two male participants (≥6% POpeak and ≥9% TTE). The two women had no POpeak changes and slight TTE changes (+2.6and −1.2%, respectively.) All four participants detrained during the posttransplant recovery period. After posttransplantretraining, all four participants increased TTE (4–24%), three increased VO2peak (≥11%), and two increased POpeak (≥7%).Conclusions Home-based strength and condition programs can be effective and successfully included in therapeutic SCItrials. However, development of these programs requires substantial content knowledge and experience