Circulating Tumor DNA Profiling From Breast Cancer Screening Through to Metastatic Disease.

PURPOSE: We investigated the utility of the Oncomine Breast cfDNA Assay for detecting circulating tumor DNA (ctDNA) in women from a breast screening population, including healthy women with no abnormality detected by mammogram, and women on follow-up through to advanced breast cancer. MATERIALS AND METHODS: Blood samples were taken from 373 women (127 healthy controls recruited through breast screening, 28 ductal carcinoma in situ, 60 primary breast cancers, 47 primary breast cancer on follow-up, and 111 metastatic breast cancers [MBC]) to recover plasma and germline DNA for analysis with the Oncomine Breast cfDNA Assay on the Ion S5 platform. RESULTS: One hundred sixteen of 373 plasma samples had one or more somatic variants detected across eight of the 10 genes and were called ctDNA-positive; MBC had the highest proportion of ctDNA-positive samples (61; 55%) and healthy controls the lowest (20; 15.7%). ESR1, TP53, and PIK3CA mutations account for 93% of all variants detected and predict poor overall survival in MBC (hazard ratio = 3.461; 95% CI, 1.866 to 6.42; P = .001). Patients with MBC had higher plasma cell-free DNA levels, higher variant allele frequencies, and more polyclonal variants, notably in ESR1 than in all other groups. Only 15 individuals had evidence of potential clonal hematopoiesis of indeterminate potential mutations. CONCLUSION: We were able detect ctDNA across the breast cancer spectrum, notably in MBC where variants in ESR1, TP53, and PIK3CA predicted poor overall survival. The assay could be used to monitor emergence of resistance mutations such as in ESR1 that herald resistance to aromatase inhibitors to tailor adjuvant therapies. However, we suggest caution is needed when interpreting results from a single plasma sample as variants were also detected in a small proportion of HCs.

Zinc stable isotope analysis reveals Zn dyshomeostasis in benign tumours, breast cancer, and adjacent histologically normal tissue.

The disruption of Zn homeostasis has been linked with breast cancer development and progression. To enhance our understanding of changes in Zn homeostasis both inside and around the tumour microenvironment, Zn concentrations and isotopic compositions (δ66Zn) were determined in benign (BT) and malignant (MT) tumours, healthy tissue from reduction mammoplasty (HT), and histologically normal tissue adjacent to benign (NAT(BT)) and malignant tumours (NAT(MT)). Mean Zn concentrations in NAT(BT) are 5.5 µg g-1 greater than in NAT(MT) (p = 0.00056) and 5.1 µg g-1 greater than in HT (p = 0.0026). Zinc concentrations in MT are 12.9 µg g-1 greater than in HT (p = 0.00012) and 13.3 µg g-1 greater than in NAT(MT) (p < 0.0001), whereas δ66Zn is 0.17‰ lower in MT than HT (p = 0.017). Benign tumour Zn concentrations are also elevated compared to HT (p = 0.00013), but are not significantly elevated compared to NAT(BT) (p = 0.32). The δ66Zn of BT is 0.15‰ lower than in NAT(BT) (p = 0.045). The similar light δ66Zn of BT and MT compared to HT and NAT may be related to the isotopic compensation of increased metallothionein (64Zn-rich) expression by activated matrix metalloproteinase (66Zn-rich) in MT, and indicates a resultant 66Zn-rich reservoir may exist in patients with breast tumours. Zinc isotopic compositions thus show promise as a potential diagnostic tool for the detection of breast tumours. The revealed differences of Zn accumulation in healthy and tumour-adjacent tissues require additional investigation.

Zinc stable isotopes in urine as diagnostic for cancer of secretory organs.

Breast, prostate, and pancreatic cancers alter the zinc (Zn) metabolism. Combined analyses of urinary Zn concentrations [Zn] and Zn stable isotope compositions (δ66Zn) may provide a non-invasive approach for tracing malignancy-induced Zn dyshomeostasis. In this study, we measured [Zn] and δ66Zn in urine from prostate (n = 22), breast (n = 16), and from women with benign breast disease (n = 14) and compared those with age-matched healthy controls (22-49 years or 50+ years) and published data for pancreatic cancer (n = 17). Our results show that cancer-induced changes are reflected in higher urinary [Zn] and lower urinary δ66Zn for pancreatic and prostate cancer and benign breast disease when compared with healthy controls. For prostate cancer, the progression of low [Zn] and high δ66Zn for patients of low-risk disease toward high [Zn] and low δ66Zn for the higher risk patients demonstrates that [Zn] and δ66Zn in urine could serve as a reliable prognostic tool. Urinary excretion of isotopically light Zn by patients with prostatic and pancreatic cancer is probably the result of increased reactive oxygen species in cancerous cells, which limits the scavenging of hydroxyl radicals and thus facilitates the oxidation of metalloproteins with sulfur-rich ligands. Urine from breast cancer patients shows undistinguishable δ66Zn to healthy controls, implying that the expression of metalloproteins with sulfur-rich ligands is stronger in breast cancer tissues. In conclusion, urinary δ66Zn may provide a non-invasive diagnostic tool for pancreatic cancer and support disease prognosis for prostate cancer. These findings should translate to comprehensive transverse and longitudinal cohort studies in future.

A Cocurricular Program That Encourages Specific Study Skills and Habits Improves Academic Performance and Retention of First-Year Undergraduates in Introductory Biology.

Students must master content for success in science, technology, engineering, and mathematics (STEM), but "how to" is rarely taught in college. Faculty are reluctant to sacrifice class time, believe such instruction is remedial, or assume students possess or will attain these skills independently. To determine whether explicit instruction would improve skills and performance by first-year undergraduates likely to major in STEM, we invited all students in an introductory biology course to participate in an 8-week Co-Curricular (CoC) program. Students who participated improved time management, used more methods to plan and organize their study, and used a variety of active-learning strategies. A validated model was used to predict students' probability of achieving a "C+" or better in the course. The model, based on 5 years of data, used students' demographic characteristics and previous academic performance to provide a measure of their preparedness. Students with low and medium preparedness who participated in CoC performed better than those who did not participate. All students who participated were retained in the course compared with 88.7% of students who did not participate. Specific behavioral changes at the start of STEM gateway courses can dramatically improve student metacognition, retention, and academic performance, particularly for students underrepresented in the discipline.

Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer.

BACKGROUND: Breast cancer (BC) is the most common cancer in women, and despite the introduction of new screening programmes, therapies and monitoring technologies, there is still a need to develop more useful tests for monitoring treatment response and to inform clinical decision making. The purpose of this study was to compare circulating cell-free DNA (cfDNA) and circulating tumour cells (CTCs) with conventional breast cancer blood biomarkers (CA15-3 and alkaline phosphatase (AP)) as predictors of response to treatment and prognosis in patients with metastatic breast cancer (MBC). METHODS: One hundred ninety-four female patients with radiologically confirmed MBC were recruited to the study. Total cfDNA levels were determined by qPCR and compared with CELLSEARCH® CTC counts and CA15-3 and alkaline phosphatase (AP) values. Blood biomarker data were compared with conventional tumour markers, treatment(s) and response as assessed by RECIST and survival. Non-parametric statistical hypothesis tests were used to examine differences, correlation analysis and linear regression to determine correlation and to describe its effects, logistic regression and receiver operating characteristic curve (ROC curve) to estimate the strength of the relationship between biomarkers and clinical outcomes and value normalization against standard deviation to make biomarker values comparable. Kaplan-Meier estimator and Cox regression models were used to assess survival. Univariate and multivariate models were performed where appropriate. RESULTS: Multivariate analysis showed that both the amount of total cfDNA (p value = 0.024, HR = 1.199, CI = 1.024-1.405) and the number of CTCs (p value = 0.001, HR = 1.243, CI = 1.088-1.421) are predictors of overall survival (OS), whereas total cfDNA levels is the sole predictor for progression-free survival (PFS) (p value = 0.042, HR = 1.193, CI = 1.007-1.415) and disease response when comparing response to non-response to treatment (HR = 15.917, HR = 12.481 for univariate and multivariate analysis, respectively). Lastly, combined analysis of CTCs and cfDNA is more informative than the combination of two conventional biomarkers (CA15-3 and AP) for prediction of OS. CONCLUSION: Measurement of total cfDNA levels, which is a simpler and less expensive biomarker than CTC counts, is associated with PFS, OS and response in MBC, suggesting potential clinical application of a cheap and simple blood-based test.

The Clinical and Cost-Effectiveness of 4 Enzyme-Linked Immunosorbent Assay Kits for Monitoring Infliximab in Crohn Disease Patients: Protocol for a Validation Study.

BACKGROUND: Currently, treatment decisions for people with Crohn disease are based on clinical judgment and trial and error. Consequently, people may continue to receive high drug dosages and experience unnecessary toxicity when it is possible to reduce or discontinue without a detrimental effect on clinical outcomes. Therapeutic drug monitoring (TDM) involves regularly testing blood samples for drug and antibody levels that could help clinicians identify the optimal treatment strategy and pre-empt treatment failure. However, heterogeneity in the assays can lead to a discrepancy in results and difficulties in decision-making. Standardization of the kits, and therefore results, would allow clinicians to optimize the use of biologics. Currently, there is also a lack of evidence for the cost-effectiveness of TDM using commercial test kits. OBJECTIVE: This study aims to analyze the clinical and cost-effectiveness of 4 commercial enzyme-linked immunosorbent assay (ELISA) kits (LISA TRACKER, IDKmonitor, Promonitor, and RIDASCREEN) to generate evidence which could support a recommendation for wider adoption in the National Health Service. METHODS: We propose to carry out a prospective-retrospective predictive biomarker validation study using the blood samples and clinical/utilization data collected during the ongoing SPARE trial (NCT02177071). A total of 200 stored samples from people with Crohn's disease who respond to treatment with infliximab will be used along with clinical and cost data from the trial. We will investigate the relationship between the drug and antidrug antibody levels with the main clinical outcomes (relapse rate at 2 years and time spent in remission), as well as resource utilization and quality of life. RESULTS: Funding is being sought to conduct this research. CONCLUSIONS: This is the first study to compare the 4 ELISA kits for monitoring infliximab in patients with Crohn disease. It aims to address the uncertainties in the potential benefits of using the technologies for TDM. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/11218.

SecurAcath for Securing Peripherally Inserted Central Catheters: A NICE Medical Technology Guidance.

Central venous catheters are commonly used to deliver therapies and to monitor patients, and require securing at the point of percutaneous entry to avoid dislodgement. SecurAcath is a catheter securement device designed for central venous catheters. The National Institute for Health and Care Excellence, as a part of its Medical Technologies Evaluation Programme, selected this device for evaluation and invited the manufacturer, Interrad Medical, to submit clinical and economic evidence. The King's Technology Evaluation Centre, an External Assessment Centre commissioned by the National Institute for Health and Care Excellence, independently critiqued the manufacturer's submissions. The External Assessment Centre found a lack of evidence comparing SecurAcath with alternative approaches to securement (StatLock, suturing, tape securement), with one unpublished randomised controlled trial providing the strongest evidence. The External Assessment Centre conducted a new systematic review and meta-analysis and concluded that there is some evidence indicating the non-inferiority of SecurAcath compared to StatLock. The External Assessment Centre considered the manufacturer's economic model to be appropriate but made revisions to some parameters and noted significant heterogeneity in the included studies. The revised model indicated that StatLock was more cost effective than SecurAcath for catheter indwell times of up to 5 days; however, for medium- and long-term indwell times, SecurAcath was the most cost-effective option. The National Institute for Health and Care Excellence Medical Technologies Guidance MTG 34, issued in June 2017, recommended the adoption of SecurAcath for securing peripherally inserted central catheters within the National Health Service in England.

Enhancer mapping uncovers phenotypic heterogeneity and evolution in patients with luminal breast cancer.

The degree of intrinsic and interpatient phenotypic heterogeneity and its role in tumor evolution is poorly understood. Phenotypic drifts can be transmitted via inheritable transcriptional programs. Cell-type specific transcription is maintained through the activation of epigenetically defined regulatory regions including promoters and enhancers. Here we have annotated the epigenome of 47 primary and metastatic estrogen-receptor (ERα)-positive breast cancer clinical specimens and inferred phenotypic heterogeneity from the regulatory landscape, identifying key regulatory elements commonly shared across patients. Shared regions contain a unique set of regulatory information including the motif for transcription factor YY1. We identify YY1 as a critical determinant of ERα transcriptional activity promoting tumor growth in most luminal patients. YY1 also contributes to the expression of genes mediating resistance to endocrine treatment. Finally, we used H3K27ac levels at active enhancer elements as a surrogate of intra-tumor phenotypic heterogeneity to track the expansion and contraction of phenotypic subpopulations throughout breast cancer progression. By tracking the clonality of SLC9A3R1-positive cells, a bona fide YY1-ERα-regulated gene, we show that endocrine therapies select for phenotypic clones under-represented at diagnosis. Collectively, our data show that epigenetic mechanisms significantly contribute to phenotypic heterogeneity and evolution in systemically treated breast cancer patients.

Comparing the Diagnostic Accuracy of Simple Tests to Screen for Diabetic Peripheral Neuropathy: Protocol for a Cross-Sectional Study.

BACKGROUND: Various tests are used to detect diabetic peripheral neuropathy by assessing sense perception in the feet. Tests vary in terms of time and resources required. Simple tests are those that can be conducted quickly and easily in primary care without laboratory equipment. There are some limitations to these simple tests, an example being the variable amplitude of the 128 Hz tuning fork. A new test, VibraTip (McCallan Medical, UK), might be a valuable alternative as it emits a consistent amplitude and may offer improved diagnostic accuracy. OBJECTIVE: The aims of this study are to estimate the diagnostic accuracy of the VibraTip device for diabetic peripheral neuropathy against the reference standard of sural nerve conduction velocity measurement, and to assess whether the VibraTip offers superior diagnostic accuracy to other routine tests based on vibration or touch. METHODS: The study will prospectively recruit adults with type 2 diabetes who are due to attend a routine follow-up clinic. A cross-sectional study design will be employed to assess the diagnostic accuracy of 5 standard index tests for peripheral neuropathy, including VibraTip. The reference test will be sural nerve conduction velocity measurement. RESULTS: Funding is being sought to conduct this research. The outcomes assessed will be the diagnostic accuracy of the 5 index tests against sural nerve conduction velocity measurement, including sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. Receiver operating characteristic curves will be constructed and compared for each test. CONCLUSIONS: This study will be the first within-study comparison of 5 simple tests for screening diabetic peripheral neuropathy and will address uncertainties in the potential benefits of using VibraTip in comparison with the other tests.

Mutation Analysis of Cell-Free DNA and Single Circulating Tumor Cells in Metastatic Breast Cancer Patients with High Circulating Tumor Cell Counts.

PURPOSE: The purpose of this study was to directly compare mutation profiles in multiple single circulating tumor cells (CTC) and cell-free DNA (cfDNA) isolated from the same blood samples taken from patients with metastatic breast cancer (MBC). We aimed to determine whether cfDNA would reflect the heterogeneity observed in 40 single CTCs. EXPERIMENTAL DESIGN: CTCs were enumerated by CELLSEARCH. CTC count was compared with the quantity of matched cfDNA and serum CA15-3 and alkaline phosphatase (ALP) in 112 patients with MBC. In 5 patients with ≥100 CTCs, multiple individual EpCAM-positive CTCs were isolated by DEPArray and compared with matched cfDNA and primary tumor tissue by targeted next-generation sequencing (NGS) of about 2,200 mutations in 50 cancer genes. RESULTS: In the whole cohort, total cfDNA levels and cell counts (≥5 CTCs) were both significantly associated with overall survival, unlike CA15-3 and ALP. NGS analysis of 40 individual EpCAM-positive CTCs from 5 patients with MBC revealed mutational heterogeneity in PIK3CA, TP53, ESR1, and KRAS genes between individual CTCs. In all 5 patients, cfDNA profiles provided an accurate reflection of mutations seen in individual CTCs. ESR1 and KRAS gene mutations were absent from primary tumor tissue and therefore likely either reflect a minor subclonal mutation or were acquired with disease progression. CONCLUSIONS: Our results demonstrate that cfDNA reflects persisting EpCAM-positive CTCs in patients with high CTC counts and therefore may enable monitoring of the metastatic burden for clinical decision-making. Clin Cancer Res; 23(1); 88-96. ©2016 AACR.

Next Generation Sequencing of Circulating Cell-Free DNA for Evaluating Mutations and Gene Amplification in Metastatic Breast Cancer.

BACKGROUND: Breast cancer tissues are heterogeneous and show diverse somatic mutations and somatic copy number alterations (CNAs). We used a novel targeted next generation sequencing (NGS) panel to examine cell-free DNA (cfDNA) to detect somatic mutations and gene amplification in women with metastatic breast cancer (MBC). METHODS: cfDNA from pretreated patients (n = 42) and 9 healthy controls were compared with matched lymphocyte DNA by NGS, using a custom 158 amplicon panel covering hot-spot mutations and CNAs in 16 genes, with further validation of results by droplet digital PCR. RESULTS: No mutations were identified in cfDNA of healthy controls, whereas exactly half the patients with metastatic breast cancer had at least one mutation or amplification in cfDNA (mean 2, range 1-6) across a total of 13 genes. Longitudinal follow up showed dynamic changes to mutations and gene amplification in cfDNA indicating clonal and subclonal response to treatment that was more dynamic than cancer antigen 15-3 (CA15-3). Interestingly, at the time of blood sampling disease progression was occurring in 7 patients with erb-b2 receptor tyrosine kinase 2 (ERBB2) gene amplification in their cfDNA and 3 of these patients were human epidermal growth factor receptor 2 (HER2) negative at diagnosis, suggesting clonal evolution to a more aggressive phenotype. Lastly, 6 patients harbored estrogen receptor 1 (ESR1) mutations in cfDNA, suggesting resistance to endocrine therapy. Overall 9 of 42 patients (21%) had alterations in cfDNA that could herald a change in treatment. CONCLUSIONS: Targeted NGS of cfDNA has potential for monitoring response to targeted therapies through both mutations and gene amplification, for analysis of dynamic tumor heterogeneity and stratification to targeted therapy.

Time to decide? Simplicity and congruity in comparative judgment.

What is the relationship between magnitude judgments relying on directly available characteristics versus probabilistic cues? Question frame was manipulated in a comparative judgment task previously assumed to involve inference across a probabilistic mental model (e.g., "Which city is largest"--the "larger" question-vs. "Which city is smallest"--the "smaller" question). Participants identified either the largest or smallest city (Experiments 1a and 2) or the richest or poorest person (Experiment 1b) in a 3-alternative forced-choice (3-AFC) task (Experiment 1) or a 2-AFC task (Experiment 2). Response times revealed an interaction between question frame and the number of options recognized. When participants were asked the smaller question, response times were shorter when none of the options were recognized. The opposite pattern was found when participants were asked the larger question: response time was shorter when all options were recognized. These task-stimuli congruity results in judgment under uncertainty are consistent with, and predicted by, theories of magnitude comparison, which make use of deductive inferences from declarative knowledge.

Automation bias: empirical results assessing influencing factors.

OBJECTIVE: To investigate the rate of automation bias - the propensity of people to over rely on automated advice and the factors associated with it. Tested factors were attitudinal - trust and confidence, non-attitudinal - decision support experience and clinical experience, and environmental - task difficulty. The paradigm of simulated decision support advice within a prescribing context was used. DESIGN: The study employed within participant before-after design, whereby 26 UK NHS General Practitioners were shown 20 hypothetical prescribing scenarios with prevalidated correct and incorrect answers - advice was incorrect in 6 scenarios. They were asked to prescribe for each case, followed by being shown simulated advice. Participants were then asked whether they wished to change their prescription, and the post-advice prescription was recorded. MEASUREMENTS: Rate of overall decision switching was captured. Automation bias was measured by negative consultations - correct to incorrect prescription switching. RESULTS: Participants changed prescriptions in 22.5% of scenarios. The pre-advice accuracy rate of the clinicians was 50.38%, which improved to 58.27% post-advice. The CDSS improved the decision accuracy in 13.1% of prescribing cases. The rate of automation bias, as measured by decision switches from correct pre-advice, to incorrect post-advice was 5.2% of all cases - a net improvement of 8%. More immediate factors such as trust in the specific CDSS, decision confidence, and task difficulty influenced rate of decision switching. Lower clinical experience was associated with more decision switching. Age, DSS experience and trust in CDSS generally were not significantly associated with decision switching. CONCLUSIONS: This study adds to the literature surrounding automation bias in terms of its potential frequency and influencing factors.

Automation bias: a systematic review of frequency, effect mediators, and mitigators.

Automation bias (AB)--the tendency to over-rely on automation--has been studied in various academic fields. Clinical decision support systems (CDSS) aim to benefit the clinical decision-making process. Although most research shows overall improved performance with use, there is often a failure to recognize the new errors that CDSS can introduce. With a focus on healthcare, a systematic review of the literature from a variety of research fields has been carried out, assessing the frequency and severity of AB, the effect mediators, and interventions potentially mitigating this effect. This is discussed alongside automation-induced complacency, or insufficient monitoring of automation output. A mix of subject specific and freetext terms around the themes of automation, human-automation interaction, and task performance and error were used to search article databases. Of 13 821 retrieved papers, 74 met the inclusion criteria. User factors such as cognitive style, decision support systems (DSS), and task specific experience mediated AB, as did attitudinal driving factors such as trust and confidence. Environmental mediators included workload, task complexity, and time constraint, which pressurized cognitive resources. Mitigators of AB included implementation factors such as training and emphasizing user accountability, and DSS design factors such as the position of advice on the screen, updated confidence levels attached to DSS output, and the provision of information versus recommendation. By uncovering the mechanisms by which AB operates, this review aims to help optimize the clinical decision-making process for CDSS developers and healthcare practitioners.

Tracking speakers' false beliefs: is theory of mind available earlier for word learning?

Happé and Loth (2002) describe word learning as a 'privileged domain' in the development of a theory of mind. We test this claim in a series of experiments based on the Sally-Anne paradigm. Three- and 4-year-old children's ability to represent others' false beliefs was investigated in tasks that required the child either to predict the actions of a protagonist in a story or to learn the meaning of a new word used by the protagonist. Experiment 1 replicated previous findings of better performance in a false belief word-learning task compared to a false belief action-prediction task. However, systematic manipulation of the task parameters in Experiments 2 and 3 revealed that this performance discrepancy disappeared when tasks were equated in their 'referential pull' (Perner, Rendl & Garnham, 2007). We conclude that the notion of a precocious theory of mind for word learning is not required to explain dissociations in performance on false belief tasks.

Decision support and automation bias: methodology and preliminary results of a systematic review.

Automation bias - or a tendency to over-rely on automation - is a subject which has been studied in a variety of academic fields. Clinical Decision Support Systems (CDSS) aim to benefit the clinical decision making process. Although most research shows overall improved performance with use, there is often a failure to recognize the new errors that CDSS can introduce, and as such the healthcare field has a gap in this research. This paper summarizes the methodology and preliminary results of a systematic review over a broad range of fields into the effects of over-reliance on automation. Results indicate that though automation bias is a significant phenomenon, it is not well defined, and there is a gap in the research which must be addressed to optimize the use of decision support.

Automation bias - a hidden issue for clinical decision support system use.

Automation bias - the tendency to over-rely on automation - has been studied in a variety of academic fields. Clinical Decision Support Systems aim to benefit the clinical decision making process. Although most research shows overall improved performance with use, there is often a failure to recognize the new errors that CDSS can introduce, and the healthcare field has a gap in this research. This paper outlines some of the most compelling theoretical factors in the literature involved in automation bias, and builds a simple model to be tested empirically. Ultimately, this will uncover the mechanisms by which this bias operates and help CDSS producers and healthcare practitioners optimize the medical decision making process.

Evaluation of alert-based monitoring in a computerised blood transfusion management system.

Blood transfusion is a critical and multi-step process that can be lifesaving. At the same time, any mistakes can be life threatening. An electronic blood transfusion system has been designed to ensure the correctness and safety of the blood transfusion process. The standards for the system include notification mechanisms to inform system managers of any errors in the process. Analysis of system alerts has been used to evaluate the performance of the system. The majority of alerts were classified as 'moderate' in terms of risk (i.e. operational rather than affecting clinical safety) and tended to result from user error. The process of alert acknowledgement and resolution by the system administrator acted as a bottleneck whenever the alerts increased above 100 items per month. Although there was no statistically significant correlation between the number of alerts and the number of transfusions or number of the new users of the system, relatively similar patterns were observable in their charts. A major benefit is that the alerts automatically provided information that would not be captured in a manual transfusion process.

Formatively evaluating the importance of different aspects of an electronic blood transfusion system from the end users' point of view: a questionnaire study.

Blood transfusion is a process in which potential errors may result in serious adverse events to patients. To help improve the safety and efficiency of the blood transfusion process an electronic clinical transfusion management system is being piloted by NHS Connecting for Health. Evaluation of the implementation is being carried out in parallel. One component of the evaluation project aims to assess the importance placed in the various potential benefits of this new system by patients and healthcare workers. A questionnaire was generated and completed by healthcare workers and patients. Results indicate respondents viewing all factors as at least "important". "System" factors were deemed most important. Overall, clinical workers expressed the lowest importance to new process factors. Ultimately these results will be measured against final satisfaction with the system to assess 'fit' between perceived importance and satisfaction to guide areas for attention and resource allocation.

Fast and frugal framing effects?

Using 3 experiments, we examine whether simple pairwise comparison judgments, involving the recognition heuristic (Goldstein & Gigerenzer, 2002), are sensitive to implicit cues to the nature of the comparison required. In Experiments 1 and 2, we show that participants frequently choose the recognized option of a pair if asked to make "larger" judgments but are significantly less likely to choose the unrecognized option when asked to make "smaller" judgments. In Experiment 3, we demonstrate that, overall, participants consider recognition to be a more reliable guide to judgments of a magnitude criterion than lack of recognition and that this intuition drives the framing effect. These results support the idea that when making pairwise comparison judgments, inferring that the recognized item is large is simpler than inferring that the unrecognized item is small.