Decision Tree Analysis as a Supplementary Tool to Enhance Histomorphological Differentiation when Distinguishing Human from Non-human Cranial Bone in both Burnt and Unburnt States: A feasibility study

This feasibility study was undertaken to describe and record the histological characteristics of burnt and unburnt cranial bone fragments from human and non-human bones. Reference series of fully mineralised, transverse sections of cranial bone, from all variables and specimen states were prepared by manual cutting and semi-automated grinding and polishing methods. A photomicrograph catalogue reflecting differences in burnt and unburnt bone from human and non-humans was recorded and qualitative analysis was performed using an established classification system based on primary bone characteristics. The histomorphology associated with human and non-human samples was, for the main part, preserved following burning at high temperature. Clearly, fibro-lamellar complex tissue subtypes, such as plexiform or laminar primary bone, were only present in non-human bones. A decision tree analysis based on histological features provided a definitive identification key for distinguishing human from non-human bone, with an accuracy of 100%. The decision tree for samples where burning was unknown was 96% accurate, and multi-step classification to taxon was possible with 100% accuracy. The results of this feasibility study, strongly suggest that histology remains a viable alternative technique if fragments of cranial bone require forensic examination in both burnt and unburnt states. The decision tree analysis may provide an additional, but vital tool to enhance data interpretation. Further studies are needed to assess variation in histomorphology taking into account other cranial bones, ontogeny, species and burning conditions

Comparing the measurement equivalence of EQ-5D-5L across different modes of administration

Background: Interest in collecting Patient Reported Outcomes using electronic methods such as mobile phones has increased in recent years. However there is debate about the level of measurement equivalence between the traditional paper and newer electronic modes. Information about the acceptability of the electronic versions to respondents is also required. The aim of this study is to compare the equivalence of delivering a widely used generic measure of health status (EQ-5D-5L) across two administration modes (paper and mobile phone). Methods: Respondents from a research cohort of people in South Yorkshire were identified, and randomly allocated to one of two administration modes (paper vs. mobile phone) based on stratifications for age and gender (and across a range of self-reported health conditions). A parallel group design was used where each respondent only completed EQ-5D-5L using one of the modes. In total, 70 respondents completed the measure in the mobile phone arm, and 66 completed the standard paper version. Follow up usability questions were also included to assess the acceptability of the mobile version of EQ-5D-5L. Measurement equivalence was compared at the dimension, utility score and visual analogue scale level using chi square analysis and ANOVA, and by comparing mean differences to an estimated minimally important difference value. Results: Response rates were higher in the mobile arm. The mean EQ-5D-5L utility and VAS scores, and the frequency of respondents endorsing individual EQ-5D-5L dimension response levels did not significantly differ across the administration modes. The majority of the mobile arm agreed that the mobile version of EQ-5D-5L was easy to complete, and that the phone was easy to use, and that they would complete mobile health measures again. Conclusions: Completing health status measures such as EQ-5D using mobile phones produces equivalent results to more traditional methods, but with added benefits (for example lessening the burden of data entry). Respondents are positive towards completing questionnaires using these methods. The results provide evidence that electronic measures are valid for use to collect data in a range of settings including clinical trials, routine care, and in health diary settings

Are preferences over health states informed?

BACKGROUND: The use of preference-elicitation tasks for valuing health states is well established, but little is known about whether these preferences are informed. Preferences may not be informed because individuals with little experience of ill health are asked to value health states. The use of uninformed preferences in cost-effectiveness can result in sub-optimal resource allocation. The aim of this study was to pilot a novel method to assess whether members of the public are informed about health states they value in preference-elicitation tasks. METHODS: The general public was said to be informed if the expectations of the public about the effect of ill health on people's lives were in agreement with the experience of patients. Sixty-two members of the public provided their expectations of the consequences of ill health on five life domains (activities, enjoyment, independence, relationships, and avoiding being a burden). A secondary dataset was used to measure patient experience on those five consequences. RESULTS: There were differences between the expectations of the public and the experience of patients. For example, for all five life consequences the public underestimated the effects of problems in usual activities compared to problems in mobility. They also underestimated the effect of 'anxiety or depression' compared to physical problems on enjoyment of life and on the quality of personal relationships. CONCLUSIONS: This proof-of-concept study showed that it is possible to test whether preferences are informed. This study should be replicated using a larger sample. The findings suggest that preferences over health states in this sample are not fully informed because the participants do not have accurate expectations about the consequences of ill health. These uninformed preferences may not be adequate for allocation of public resources, and research is needed into methods to make them better informed

Lifestyle behaviours of young adult survivors of childhood cancer

This cross-sectional study collected baseline data on the health behaviours of a large population of survivors of childhood cancer in the UK, aged 18–30 years, compared with those of sex- and age-matched controls. Data from 178 young adult survivors of childhood cancer, diagnosed and treated at Bristol Children's Hospital, 184 peers from the survivors' GP practices and 67 siblings were collected by postal questionnaire. Conditional logistic regression analysis showed that, for matched sets of survivors and controls, survivors of a variety of childhood cancers reported lower levels of alcohol consumption (P=0.005), lower levels of cigarette smoking (P=0.027) and lower levels of recreational drug use (P=0.001) than controls. Analysis of matched sets of survivors and siblings showed similar trends but no significant differences. A health behaviour index for each participant was constructed from the data collected on five key health behaviours which influence future health status. Comparison of the means for each case group showed that survivors of childhood cancer were leading healthier lives than controls or siblings. This finding was expressed most clearly as the difference in the means of the health behaviour index for each case group, derived from five health behaviours (one-way ANOVA, P<0.001)

Sex-related variation in compact bone microstructure of the femoral diaphysis in juvenile rabbits

<p>Abstract</p> <p>Background</p> <p>While gross morphological changes in the skeleton between males and females are well know, differences between sexes in the histomorphology are less known. It is important to have knowledge on the bone structure of rabbits, as this is a widely used species in biomedical research. A study was performed to evaluate the association between sex and the compact bone morphology of the femoral diaphysis in juvenile rabbits.</p> <p>Methods</p> <p>Seventeen clinically healthy 2–3 month-old rabbits (9 females, 8 males) were included in the study. The rabbits were euthanized and the right femur was sampled for analysis. 70–80 microns thick bone sections of the femoral diaphysis were prepared using standard histological equipment. The qualitative histological characteristics were determined according to internationally accepted classification systems while the quantitative parameters were assessed using the software Scion Image. Areas, perimeters, minimum and maximum diameters of primary osteons' vascular canals, Haversian canals and secondary osteons were measured. Additionally, blood plasma concentrations of progesterone, corticosterone, IGF-I, testosterone and estradiol were analyzed.</p> <p>Results</p> <p>Qualitative histological characteristics were similar for both sexes. However, variations of certain quantitative histological characteristics were identified. Measured parameters of the primary osteons' vascular canals were higher in males than for females. On the other hand, females had significant higher values of secondary osteons parameters. Differences in Haversian canals parameters were only significant for minimum diameter.</p> <p>Conclusion</p> <p>The study demonstrated that quantitative histological characteristics of compact bone tissue of the femoral diaphysis in juvenile rabbits were sex dependent. The variations may be associated with different growth and modeling of the femur through influence by sex-specific steroids, mechanical loads, genetic factors and a multitude of other sources. The results can be applied in experimental studies focusing on comparison of the skeletal biology of the sexes.</p

Using lithium as a neuroprotective agent in patients with cancer

Neurocognitive impairment is being increasingly recognized as an important issue in patients with cancer who develop cognitive difficulties either as part of direct or indirect involvement of the nervous system or as a consequence of either chemotherapy-related or radiotherapy-related complications. Brain radiotherapy in particular can lead to significant cognitive defects. Neurocognitive decline adversely affects quality of life, meaningful employment, and even simple daily activities. Neuroprotection may be a viable and realistic goal in preventing neurocognitive sequelae in these patients, especially in the setting of cranial irradiation. Lithium is an agent that has been in use for psychiatric disorders for decades, but recently there has been emerging evidence that it can have a neuroprotective effect.This review discusses neurocognitive impairment in patients with cancer and the potential for investigating the use of lithium as a neuroprotectant in such patients.<br /

Using lithium as a neuroprotective agent in patients with cancer

Neurocognitive impairment is being increasingly recognized as an important issue in patients with cancer who develop cognitive difficulties either as part of direct or indirect involvement of the nervous system or as a consequence of either chemotherapy-related or radiotherapy-related complications. Brain radiotherapy in particular can lead to significant cognitive defects. Neurocognitive decline adversely affects quality of life, meaningful employment, and even simple daily activities. Neuroprotection may be a viable and realistic goal in preventing neurocognitive sequelae in these patients, especially in the setting of cranial irradiation. Lithium is an agent that has been in use for psychiatric disorders for decades, but recently there has been emerging evidence that it can have a neuroprotective effect.This review discusses neurocognitive impairment in patients with cancer and the potential for investigating the use of lithium as a neuroprotectant in such patients.<br /

ReAsH/FlAsH Labeling and Image Analysis of Tetracysteine Sensor Proteins in Cells

Fluorescent proteins and dyes are essential tools for the study of protein trafficking, localization and function in cells. While fluorescent proteins such as green fluorescence protein (GFP) have been extensively used as fusion partners to proteins to track the properties of a protein of interest, recent developments with smaller tags enable new functionalities of proteins to be examined in cells such as conformational change and protein-association. One small tag system involves a tetracysteine motif (CCXXCC) genetically inserted into a target protein, which binds to biarsenical dyes, ReAsH (red fluorescent) and FlAsH (green fluorescent), with high specificity even in live cells. The TC/biarsenical dye system offers far less steric constraints to the host protein than fluorescent proteins which has enabled several new approaches to measure conformational change and protein-protein interactions. We recently developed a novel application of TC tags as sensors of oligomerization in cells expressing mutant huntingtin, which when mutated aggregates in neurons in Huntington disease. Huntingtin was tagged with two fluorescent dyes, one a fluorescent protein to track protein location, and the second a TC tag which only binds biarsenical dyes in monomers. Hence, changes in colocalization between protein and biarsenical dye reactivity enabled submicroscopic oligomer content to be spatially mapped within cells. Here, we describe how to label TC-tagged proteins fused to a fluorescent protein (Cherry, GFP or CFP) with FlAsH or ReAsH in live mammalian cells and how to quantify the two color fluorescence (Cherry/FlAsH, CFP/FlAsH or GFP/ReAsH combinations)