Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients.

BackgroundKetoconazole is a well-known CYP17-targeted systemic treatment for castration-resistant prostate cancer (CRPC). However, most of the published data has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy setting has not been as widely described. Chemotherapy-naïve patients treated with attenuated doses of ketoconazole (200-300 mg three times daily) had PSA response rate (>50% decline) of 21-62%. We hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerability in the CRPC post-chemotherapy state.MethodsMen with CRPC and performance status 0-3, adequate organ function and who had received prior docetaxel were treated with low-dose ketoconazole (200 mg orally three times daily) and hydrocortisone (20 mg PO qAM and 10 mg PO qPM) until disease progression. Primary endpoint was PSA response rate (>50% reduction from baseline) where a rate of 25% was to be considered promising for further study (versus a null rate of <5%); 25 patients were required. Secondary endpoints included PSA response >30% from baseline, progression-free survival (PFS), duration of stable disease and evaluation of adverse events (AEs).ResultsThirty patients were accrued with median age of 72 years (range 55-86) and median pre-treatment PSA of 73 ng ml(-1) (range 7-11,420). Twenty-nine patients were evaluable for response and toxicity. PSA response (>50% reduction) was seen in 48% of patients; PSA response (>30% reduction) was seen in 59%. Median PFS was 138 days; median duration of stable disease was 123 days. Twelve patients experienced grade 3 or 4 AEs. Of the 17 grade 3 AEs, only 3 were attributed to treatment. None of the two grade 4 AEs were considered related to treatment.ConclusionsIn docetaxel pre-treated CRPC patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. A prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy

Age differences in the use of serving size information on food labels: numeracy or attention?

ObjectiveThe ability to use serving size information on food labels is important for managing age-related chronic conditions such as diabetes, obesity and cancer. Past research suggests that older adults are at risk for failing to accurately use this portion of the food label due to numeracy skills. However, the extent to which older adults pay attention to serving size information on packages is unclear. We compared the effects of numeracy and attention on age differences in accurate use of serving size information while individuals evaluated product healthfulness.DesignAccuracy and attention were assessed across two tasks in which participants compared nutrition labels of two products to determine which was more healthful if they were to consume the entire package. Participants' eye movements were monitored as a measure of attention while they compared two products presented side-by-side on a computer screen. Numeracy as well as food label habits and nutrition knowledge were assessed using questionnaires.SettingSacramento area, California, USA, 2013-2014.SubjectsStratified sample of 358 adults, aged 20-78 years.ResultsAccuracy declined with age among those older adults who paid less attention to serving size information. Although numeracy, nutrition knowledge and self-reported food label use supported accuracy, these factors did not influence age differences in accuracy.ConclusionsThe data suggest that older adults are less accurate than younger adults in their use of serving size information. Age differences appear to be more related to lack of attention to serving size information than to numeracy skills

Child sexual exploitation : definition & guide for professionals: extended text

This work was commissioned by the Department for Education (DfE) and is the extended text from which the DfE document ‘Child Sexual Exploitation: Definition and a guide for practitioners, local leaders and decision makers working to protect children from child sexual exploitation’ has been drawn. This can be viewed at www.gov.uk. The document outlines the new civil definition of child sexual exploitation, developed by the Home Office and DfE, together with an overview of our current understanding of the issue and an evidence-informed set of principles for responding. This extended version of the ‘guide’ provides professionals1 with further background information about child sexual exploitation and offers additional commentary around some of the complexities of practically responding to the issue. The document should be read in conjunction with Working together to safeguard children: A guide to inter-agency working to safeguard and promote the welfare of children (hereafter referred to as Working Together), that provides the statutory framework for responding to child sexual exploitation and all other forms of abuse. The content of this document does not in any way supersede the statutory provisions of Working Together, but rather considers some of the nuances and challenges of applying its requirements and principles to this particular form of abuse. This extended version of the ‘guide’ draws on the existing evidence base to identify issues that have proved challenging to address in practice and to draw out lessons learnt in relation to this. It does not seek to provide readers with a ‘step-by-step’ approach to addressing child sexual exploitation, but instead provides a high-level framework for building a locally informed enhanced response that concurrently addresses prevention, and responses to victimhood and perpetration, and supports the exercise of ‘professional curiosity’ within this. Although the document focuses on child sexual exploitation, many of the principles outlined herein hold relevance for responding to other forms of exploitation, abuse and vulnerability in adolescence and readers are encouraged to consider the interconnectedness of these issues and the transferability of learning between them

Misunderstanding of Front-Of-Package Nutrition Information on US Food Products.

Front-of-package nutrition symbols (FOPs) are presumably readily noticeable and require minimal prior nutrition knowledge to use. Although there is evidence to support this notion, few studies have focused on Facts Up Front type symbols which are used in the US. Participants with varying levels of prior knowledge were asked to view two products and decide which was more healthful. FOPs on packages were manipulated so that one product was more healthful, allowing us to assess accuracy. Attention to nutrition information was assessed via eye tracking to determine what if any FOP information was used to make their decisions. Results showed that accuracy was below chance on half of the comparisons despite consulting FOPs. Negative correlations between attention to calories, fat, and sodium and accuracy indicated that consumers over-relied on these nutrients. Although relatively little attention was allocated to fiber and sugar, associations between attention and accuracy were positive. Attention to vitamin D showed no association to accuracy, indicating confusion surrounding what constitutes a meaningful change across products. Greater nutrition knowledge was associated with greater accuracy, even when less attention was paid. Individuals, particularly those with less knowledge, are misled by calorie, sodium, and fat information on FOPs

Relationships among food label use, motivation, and dietary quality.

Nutrition information on packaged foods supplies information that aids consumers in meeting the recommendations put forth in the US Dietary Guidelines for Americans such as reducing intake of solid fats and added sugars. It is important to understand how food label use is related to dietary intake. However, prior work is based only on self-reported use of food labels, making it unclear if subjective assessments are biased toward motivational influences. We assessed food label use using both self-reported and objective measures, the stage of change, and dietary quality in a sample of 392 stratified by income. Self-reported food label use was assessed using a questionnaire. Objective use was assessed using a mock shopping task in which participants viewed food labels and decided which foods to purchase. Eye movements were monitored to assess attention to nutrition information on the food labels. Individuals paid attention to nutrition information when selecting foods to buy. Self-reported and objective measures of label use showed some overlap with each other (r=0.29, p<0.001), and both predicted dietary quality (p<0.001 for both). The stage of change diminished the predictive power of subjective (p<0.09), but not objective (p<0.01), food label use. These data show both self-reported and objective measures of food label use are positively associated with dietary quality. However, self-reported measures appear to capture a greater motivational component of food label use than do more objective measures

Zoning patterns of Fe and V in spinel from a type B Ca-Al-rich inclusion: Constraints on subsolidus thermal history

We obtained two-dimensional concentration maps for the minor elements Fe and V in 21 spinel crystals in the Allende type B1 inclusion TS-34 with a 4–5 μm resolution. Locally high concentrations of Fe occur along at least one edge of the spinels and decrease toward the center of the grains. Enrichment in V can also occur along edges or at corners. In general, there is no overall correlation of the Fe and V distributions, but in local regions of two grains, the V and Fe distributions are correlated, strongly suggesting a local source for both elements. In these two grains, opaque assemblages are present that appear to locally control the V distributions. This, coupled with previous work, suggests that prior to alteration, TS-34 contained V-rich metal. Oxidation of this metal during alteration can account for the edge/corner V enrichments, but provide only minor FeO contributions, explaining the overall lack of correlation between Fe and V. Most of the FeO appears to have been externally introduced along spinel boundaries during alteration. These alteration phases served as sources for diffusion of FeO into spinel. FeO distributions in spinel lead to a mean attenuation length of ~8 μm and, using literature diffusion coefficients in isothermal and exponential cooling approximations for peak temperatures in the range 600–700°C, this leads to a time scale for calcium-aluminum-rich inclusion (CAI) alteration in the range of decades to centuries

Confidentiality and public protection: ethical dilemmas in qualitative research with adult male sex offenders

This paper considers the ethical tensions present when engaging in in-depth interviews with convicted sex offenders. Many of the issues described below are similar to those found in other sensitive areas of research. However, confidentiality and public protection are matters that require detailed consideration when the desire to know more about men who have committed serious and harmful offences is set against the possibility of a researcher not disclosing previously unknown sensitive information that relates to the risk of someone being harmed.</p