Animal-Assisted Interventions in Health Care Settings: A Best Practices Manual for Establishing New Programs: Volunteer Manual Template

This document accompanies Animal-Assisted Interventions in Health Care Settings: A Best Practices Manual for Establishing New Programs (Purdue Press, 2019) and serves as a template for readers to personalize for their facility. The generic terms “ABC Health Care Facility” and “AAI Program” are intended to be replaced by the names of the reader\u27s facility and AAI program. The book can be purchased from Purdue University Press

Densities of internally mixed organic-inorganic particles from mobility diameter measurements of aerodynamically classified aerosols

Accurate knowledge of particle density is essential for many aspects of aerosol science. Yet, density is often characterized poorly and incompletely for internally mixed particles, particularly for dry particles, with previous studies focused primarily on deliquescent (aqueous) droplets. Instead, densities for dry internally mixed particles are often inferred from mass composition measurements in combination with predictive models assuming ideal mixing, with the accuracy of such models not estimated. We determined particle densities from mobility diameter measurements (using a Scanning Mobility Particle Sizer, SMPS) for dried particles classified by their aerodynamic size (using an Aerosol Aerodynamic Classifier, AAC) for a range of two-component organic-inorganic particles containing known proportions of organic and inorganic species. We examined all permutations of mixing between four different organic (water soluble nigrosin dye, citric acid, polyethylene glycol-400, and ascorbic acid) and three different inorganic (sodium chloride, ammonium sulfate, and sodium nitrate) species. The accuracy and precision in our measured particle densities were ∼5% and ∼1%, respectively, for nonvolatile particles. Substantial deviations in particle density from ideal mixing (up to 20%) were observed. We tested descriptions of the non-ideal mixing for our systems by representing the volume change of mixing using Redlich-Kister (RK) polynomials in terms of mass fraction or in terms of mole fraction, with both approaches performing similarly.</p

DNA repair biomarkers XPF and phospho-MAPKAP kinase 2 correlate with clinical outcome in advanced head and neck cancer.

BackgroundInduction chemotherapy is a common therapeutic option for patients with locoregionally-advanced head and neck cancer (HNC), but it remains unclear which patients will benefit. In this study, we searched for biomarkers predicting the response of patients with locoregionally-advanced HNC to induction chemotherapy by evaluating the expression pattern of DNA repair proteins.MethodsExpression of a panel of DNA-repair proteins in formalin-fixed paraffin embedded specimens from a cohort of 37 HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation were analyzed using quantitative immunohistochemistry.ResultsWe found that XPF (an ERCC1 binding partner) and phospho-MAPKAP Kinase 2 (pMK2) are novel biomarkers for HNSCC patients undergoing platinum-based induction chemotherapy. Low XPF expression in HNSCC patients is associated with better response to induction chemoradiotherapy, while high XPF expression correlates with a worse response (p = 0.02). Furthermore, low pMK2 expression was found to correlate significantly with overall survival after induction plus chemoradiation therapy (p = 0.01), suggesting that pMK2 may relate to chemoradiation therapy.ConclusionsWe identified XPF and pMK2 as novel DNA-repair biomarkers for locoregionally-advanced HNC patients undergoing platinum-based induction chemotherapy prior to definitive chemoradiation. Our study provides insights for the use of DNA repair biomarkers in personalized diagnostics strategies. Further validation in a larger cohort is indicated

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects

Using clinical risk factors and bone mineral density to determine who among patients undergoing bone densitometry should have vertebral fracture assessment

Vertebral fracture assessment (VFA) is a new method for imaging thoracolumbar spine on bone densitometer. Among patients referred for bone densitometry, the selection of patients for VFA testing can be optimized using an index derived from clinical risk factors and bone density measurement. VFA, a method for imaging thoracolumbar spine on bone densitometer, was developed because vertebral fractures, although common and predictive of future fractures, are often not clinically diagnosed. The study objective was to develop a strategy for selecting patients for VFA. A convenience sample from a university hospital bone densitometry center included 892 subjects (795 women) referred for bone mineral density (BMD) testing. We used questionnaires to capture clinical risk factors and dual-energy X-ray absorptiometry to obtain BMD and VFA. Prevalence of vertebral fractures was 18% in women and 31% in men (p = 0.003 for gender difference). In women, age, height loss, glucocorticoid use, history of vertebral and other fractures, and BMD T-score were significantly and independently associated with vertebral fractures. A multivariate model which included above predictors had an area under the receiver operating curve of 0.85 with 95% confidence interval (CI) of 0.81 to 0.89. A risk factor index was derived from the above multivariate model. Using a level of 2 as a cut-off yielded 93% sensitivity (95% CI 87, 96) and 48% specificity (95% CI 69, 83). Assuming a 15% prevalence of vertebral fractures, this cut-off value had a 24% positive and 97% negative predictive value and required VFA scanning of three women at a cost of $60 (assuming a$20 cost/VFA scan) to detect one with vertebral fracture(s). Selecting patients for VFA can be optimized using an index derived from BMD measurement and easily obtained clinical risk factors

Uncertainty-Informed Deep Learning Models Enable High-Confidence Predictions for Digital Histopathology

A model's ability to express its own predictive uncertainty is an essential attribute for maintaining clinical user confidence as computational biomarkers are deployed into real-world medical settings. In the domain of cancer digital histopathology, we describe a novel, clinically-oriented approach to uncertainty quantification (UQ) for whole-slide images, estimating uncertainty using dropout and calculating thresholds on training data to establish cutoffs for low- and high-confidence predictions. We train models to identify lung adenocarcinoma vs. squamous cell carcinoma and show that high-confidence predictions outperform predictions without UQ, in both cross-validation and testing on two large external datasets spanning multiple institutions. Our testing strategy closely approximates real-world application, with predictions generated on unsupervised, unannotated slides using predetermined thresholds. Furthermore, we show that UQ thresholding remains reliable in the setting of domain shift, with accurate high-confidence predictions of adenocarcinoma vs. squamous cell carcinoma for out-of-distribution, non-lung cancer cohorts

Therapeutic exploitation of IPSE, a urogenital parasite-derived host modulatory protein, for chemotherapy-induced hemorrhagic cystitis

Chemotherapy-induced hemorrhagic cystitis (CHC) can be difficult to manage. Prior work suggests IL-4 alleviates ifosfamide-induced hemorrhagic cystitis (IHC), but systemically administered IL-4 causes significant side effects. We hypothesized that the Schistosoma haematobium homolog of Interleukin-4-inducing principle from Schistosoma mansoni Eggs (H-IPSE), would reduce IHC and associated bladder pathology. IPSE binds IgE on basophils and mast cells, triggering IL-4 secretion by these cells. IPSE is also an “infiltrin”, translocating into the host nucleus to modulate gene transcription. Mice were administered IL-4, H-IPSE protein or its nuclear localization sequence (NLS) mutant with or without neutralizing anti-IL-4 antibody, or MESNA, followed by ifosfamide. Bladder tissue damage and hemoglobin content were measured. Spontaneous and evoked pain, urinary frequency and gene expression were assessed. Pain behaviors were interpreted in a blinded fashion. One dose of H-IPSE was superior to MESNA and IL-4 in suppressing bladder hemorrhage in an IL-4-and NLS-dependent fashion, and comparable to MESNA in dampening ifosfamide-triggered pain behaviors in an NLS-dependent manner. H-IPSE also accelerated urothelial repair following IHC. Our work represents the first therapeutic exploitation of a uropathogen-derived host modulatory molecule in a clinically relevant bladder disease model, and indicates that IPSE may be an alternative to MESNA for mitigating CHC

Major combined electrolyte deficiency during therapy with low-dose Cisplatin, 5-Fluorouracil and Interferon alpha: report on several cases and review of the literature [ISRCTN62866759]

BACKGROUND: Low-dose Cisplatin and Interferon alpha treatment of solid tumors rarely has been associated with severe hypocalcaemia. To the authors knowledge the phenomenon has not been reported previously in patients with pancreatic carcinoma. CASE PRESENTATION: A patient with resected adenocarcinoma of the pancreas was treated with adjuvant radio-chemo-immunotherapy using a combination of low-dose Cisplatin, 5-Fluorouracil and Interferon alpha together with external beam radiation. Severe hypocalcaemia without signs of acute renal failure or electrolyte disturbance occurred within 2 days at the 4th week of treatment and required intensive care treatment. CONCLUSION: Combination of biological and cytotoxic therapies may increase the incidence of severe hypocalcaemia in pancreatic cancer. Oncologists should remain attentive of this problem as more highly active regimes become available