Estimating EQ-5D utilities based on the Short-Form Long Term Conditions Questionnaire (LTCQ-8)

Purpose: The aim of this work was to develop a mapping algorithm for estimating EuroQoL 5 Dimension (EQ-5D) utilities from responses to the Long-Term Conditions Questionnaire (LTCQ), thus increasing LTCQ’s potential as a comprehensive outcome measure for evaluating integrated care initiatives. Methods: We combined data from three studies to give a total sample of 1334 responses. In each of the three datasets, we randomly selected 75% of the sample and combined the selected random samples to generate the estimation dataset, which consisted of 1001 patients. The unselected 25% observations from each dataset were combined to generate an internal validation dataset of 333 patients. We used direct mapping models by regressing responses to the LTCQ-8 directly onto EQ-5D-5L and EQ-5D-3L utilities as well as response (or indirect) mapping to predict the response level that patients selected for each of the five EQ-5D-5L domains. Several models were proposed and compared on mean squared error and mean absolute error. Results: A two-part model with OLS was the best performing based on the mean squared error (0.038) and mean absolute error (0.147) when estimating the EQ-5D-5L utilities. A multinomial response mapping model using LTCQ-8 responses was used to predict EQ-5D-5L responses levels. Conclusions: This study provides a mapping algorithm for estimating EQ-5D utilities from LTCQ responses. The results from this study can help broaden the applicability of the LTCQ by producing utility values for use in economic analyses

Altered expression of anti-apoptotic proteins in non-involved tissue from cancer-containing breasts.

In a previous investigation reduced apoptosis was identified in normal breast tissue from cancer-containing breasts away from the cancer in comparison to age-matched normal breast from women without cancer. The hypothesis for this study was that defects in expression of apoptotic regulatory and DNA repair proteins would facilitate persistence of genetic alterations and predispose to breast cancer development. Using immunohistochemistry normal breast from 120 age-matched women (58 with breast cancer, 62 without) was analysed for proliferation, apoptosis, bcl2, BAX, caspase 3, Hsp27, Hsp70, BRCA1, ATM and BARD1. All assessments were performed without knowledge as to whether it was a cancer case or control. A significant difference was found for apoptotic index which was higher in controls (P < 0.02). There was no change in apoptotic and proliferation index with age for cancer cases unlike controls. Higher expression of bcl2 (P = 0.001) and Hsp27 (P = 0.001) was found in normal breast from cancer-containing breast in comparison to controls. There were no differences in the other proteins. Apoptosis has been found to be reduced in normal breast in a separate cohort of women with breast cancer, along with increased expression of the anti-apoptotic proteins bcl2 and Hsp27. These alterations in apoptotic regulation would enhance tumour development. Further studies are needed to examine the value of these proteins as risk markers

Investigating high-energy proton-induced reactions on spherical nuclei: Implications for the preequilibrium exciton model

Background: A number of accelerator-based isotope production facilities utilize 100- to 200-MeV proton beams due to the high production rates enabled by high-intensity beam capabilities and the greater diversity of isotope production brought on by the long range of high-energy protons. However, nuclear reaction modeling at these energies can be challenging because of the interplay between different reaction modes and a lack of existing guiding cross-section data. Purpose: A Tri-lab collaboration has been formed among the Lawrence Berkeley, Los Alamos, and Brookhaven National Laboratories to address these complexities by characterizing charged-particle nuclear reactions relevant to the production of established and novel radioisotopes. Method: In the inaugural collaboration experiments, stacked-targets of niobium foils were irradiated at the Brookhaven Linac Isotope Producer (Ep=200MeV) and the Los Alamos Isotope Production Facility (Ep=100MeV) to measure Nb93(p,x) cross sections between 50 and 200 MeV. First measurements of the Nb93(p,4n)Mo90 beam monitor reaction beyond 100 MeV are reported in this work, as part of the broadest energy-spanning dataset for the reaction to date. Nb93(p,x) production cross sections are additionally reported for 22 other measured residual products. The measured cross-section results were compared with literature data as well as the default calculations of the nuclear model codes TALYS, CoH, EMPIRE, and ALICE. Results: The default code predictions largely failed to reproduce the measurements, with consistent underestimation of the preequilibrium emission. Therefore, we developed a standardized procedure that determines the reaction model parameters that best reproduce the most prominent reaction channels in a physically justifiable manner. The primary focus of the procedure was to determine the best parametrization for the preequilibrium two-component exciton model via a comparison to the energy-dependent Nb93(p,x) data, as well as previously published La139(p,x) cross sections. Conclusions: This modeling study revealed a trend toward a relative decrease for internal transition rates at intermediate proton energies (Ep=20-60 MeV) in the current exciton model as compared to the default values. The results of this work are instrumental for the planning, execution, and analysis essential to isotope production