Automated assessment of disease progression in Acute Myeloid Leukemia by probabilistic analysis of flow cytometry data

Objective: Flow cytometry (FC) is a widely acknowledged technology in diagnosis of acute myeloid leukemia (AML) and has been indispensable in determining progression of the disease. Although FC plays a key role as a post-therapy prognosticator and evaluator of therapeutic efficacy, the manual analysis of cytometry data is a barrier to optimization of reproducibility and objectivity. This study investigates the utility of our recently introduced non-parametric Bayesian framework in accurately predicting the direction of change in disease progression in AML patients using FC data. Methods: The highly flexible non-parametric Bayesian model based on the infinite mixture of infinite Gaussian mixtures is used for jointly modeling data from multiple FC samples to automatically identify functionally distinct cell populations and their local realizations. Phenotype vectors are obtained by characterizing each sample by the proportions of recovered cell populations, which are in turn used to predict the direction of change in disease progression for each patient. Results: We used 200 diseased and non-diseased immunophenotypic panels for training and tested the system with 36 additional AML cases collected at multiple time points. The proposed framework identified the change in direction of disease progression with accuracies of 90% (9 out of 10) for relapsing cases and 100% (26 out of 26) for the remaining cases. Conclusions: We believe that these promising results are an important first step towards the development of automated predictive systems for disease monitoring and continuous response evaluation. Significance: Automated measurement and monitoring of therapeutic response is critical not only for objective evaluation of disease status prognosis but also for timely assessment of treatment strategies

Designing and evaluating complex interventions to improve health care

Complex interventions are “built up from a number of components, which may act both independently and interdependently.”1 2 Many health service activities should be considered as complex. Evaluating complex interventions can pose a considerable challenge and requires a substantial investment of time. Unless the trials illuminate processes and mechanisms they often fail to provide useful information. If the result is negative, we are left wondering whether the intervention is inherently ineffective (either because the intervention was inadequately developed or because all similar interventions are ineffective), whether it was inadequately applied or applied in an inappropriate context, or whether the trial used an inappropriate design, comparison groups or outcomes. If there is a positive effect, it can be hard to judge how the results of the trial might be applied to a different context (box 1)

Do medical images aid understanding and recall of medical information? An experimental study comparing the experience of viewing no image, a 2D medical image and a 3D medical image alongside a diagnosis

Objective: This study compared the experience of viewing 3D medical images, 2D medical images and no image presented alongside a diagnosis. Methods: We conducted two laboratory experiments, each with 126 healthy participants. Participants heard three diagnoses; one accompanied by 3D medical images, one accompanied by 2D medical images and one with no image. Participants completed a questionnaire after each diagnosis rating their experience. In Experiment 2, half of the participants were informed that image interpretation can be susceptible to errors. Results: Participants preferred to view 3D images alongside a diagnosis (p < .001) and reported greater understanding (p < .001), perceived accuracy (p < .001) and increased trust (p < .001) when the diagnosis was accompanied by an image compared to no image. There was no significant difference in trust between participants who were informed of errors within image interpretation and those who were not. Conclusion: When presented alongside a diagnosis, medical images may aid patient understanding, recall and trust in medical information. Practical Considerations: Medical images may be a powerful resource for patients that could be utilised by clinicians during consultations

Food for Thought: the Efficiency of Glucose Metabolism Predicts the Self-generation of Temporally Distant Cognition

The generation of thought independent of environmental input occupies almost half of mental life and is important for skills such as creativity and planning. To understand how this ubiquitous cognitive process relates to the brain's ‘energy budget’, a cross-sectional study is carried out to examine how the capacity for mental time travel relates to the efficiency with which adults metabolize glucose, the brain’s primary source of fuel. On day 1 the ability of a group of 36 younger and 36 older individuals to metabolize glucose was assessed using the gold standard two-hour glucose tolerance test. Twenty-four hours later, the same group of participants returned to the laboratory to perform a non-demanding choice reaction time task during which experience sampling was used to assess the frequency with which they generated thoughts that were unrelated to the here and now. Analysis indicated that younger individuals who were the most efficient at metabolizing glucose exhibited mental time travel that spanned longer time periods. Given the importance of self-generated thought in daily life these results suggest that the capacity to mentally simulate events not present in the immediate environment is highly dependent on efficient glucose metabolis

Are Newly Discovered HI High Velocity Clouds Minihalos in the Local Group?

A set of HI sources extracted from the north Galactic polar region by the ongoing ALFALFA survey has properties that are consistent with the interpretation that they are associated with isolated minihalos in the outskirts of the Local Group (LG). Unlike objects detected by previous surveys, such as the Compact High Velocity Clouds of Braun & Burton (1999), the HI clouds found by ALFALFA do not violate any structural requirements or halo scaling laws of the LambdaCDM structure paradigm, nor would they have been detected by extant HI surveys of nearby galaxy groups other than the LG. At a distance of d Mpc, their HI masses range between $5 x 10^4 d^2 and 10^6 d^2 solar and their HI radii between <0.4d and 1.6 d kpc. If they are parts of gravitationally bound halos, the total masses would be on order of 10^8--10^9 solar, their baryonic content would be signifcantly smaller than the cosmic fraction of 0.16 and present in a ionized gas phase of mass well exceeding that of the neutral phase. This study does not however prove that the minihalo interpretation is unique. Among possible alternatives would be that the clouds are shreds of the Leading Arm of the Magellanic Stream.Comment: 4 pages, 3 figures, 1 table; to appear Ap.J. Letter

Analysis of Fcγ receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B

The Fcγ receptors play important roles in the initiation and regulation of many immunological and inflammatory processes, and genetic variants (FCGR) have been associated with numerous autoimmune and infectious diseases. The data in rheumatoid arthritis (RA) are conflicting and we previously demonstrated an association between FCGR3A and RA. In view of the close molecular proximity with FCGR2A, FCGR2B and FCGR3B, additional polymorphisms within these genes and FCGR haplotypes were examined to refine the extent of association with RA. Biallelic polymorphisms in FCGR2A, FCGR2B and FCGR3B were examined for association with RA in two well characterized UK Caucasian and North Indian/Pakistani cohorts, in which FCGR3A genotyping had previously been undertaken. Haplotype frequencies and linkage disequilibrium were estimated across the FCGR locus and a model-free analysis was performed to determine association with RA. This was followed by regression analysis, allowing for phase uncertainty, to identify the particular haplotype(s) that influences disease risk. Our results reveal that FCGR2A, FCGR2B and FCGR3B were not associated with RA. The haplotype with the strongest association with RA susceptibility was the FCGR3A–FCGR3B 158V-NA2 haplotype (odds ratio 3.18, 95% confidence interval 1.13–8.92 [P = 0.03] for homozygotes compared with all genotypes). The association was stronger in the presence of nodules (odds ratio 5.03, 95% confidence interval 1.44–17.56; P = 0.01). This haplotype was also more common in North Indian/Pakistani RA patients than in control individuals, but not significantly so. Logistic regression analyses suggested that FCGR3A remained the most significant gene at this locus. The increased association with an FCGR3A–FCGR3B haplotype suggests that other polymorphic variants within FCGR3A or FCGR3B, or in linkage disequilibrium with this haplotype, may additionally contribute to disease pathogenesis

Digital clinical communication for families and caregivers of children or young people with short- or long-term conditions : rapid review

Background The communication relationship between parents of children or young people with health conditions and health professionals is an important part of treatment, but it is unclear how far the use of digital clinical communication tools may affect this relationship. Objective The objective of our study was to describe, assess the feasibility of, and explore the impact of digital clinical communication between families or caregivers and health professionals. Methods We searched the literature using 5 electronic databases. We considered all types of study design published in the English language from January 2009 to August 2015. The population of interest included families and caregivers of children and young people aged less than 26 years with any type of health condition. The intervention was any technology permitting 2-way communication. Results We included 31 articles. The main designs were randomized controlled trials (RCTs; n=10), cross-sectional studies (n=9), pre- and postintervention uncontrolled (pre/post) studies (n=7), and qualitative interview studies (n=2); 6 had mixed-methods designs. In the majority of cases, we considered the quality rating to be fair. Many different types of health condition were represented. A breadth of digital communication tools were included: videoconferencing or videoconsultation (n=14), and Web messaging or emails (n=12). Health care professionals were mainly therapists or cognitive behavioral therapists (n=10), physicians (n=8), and nurses (n=6). Studies were very heterogeneous in terms of outcomes. Interventions were mainly evaluated using satisfaction or acceptance, or outcomes relating to feasibility. Clinical outcomes were rarely used. The RCTs showed that digital clinical communication had no impact in comparison with standard care. Uncontrolled pre/post studies showed good rates of satisfaction or acceptance. Some economic studies suggested that digital clinical communication may save costs. Conclusions This rapid review showed an emerging body of literature on the use of digital clinical communication to improve families’ and caregivers’ involvement in the health management of children or young people. Further research with appropriate study designs and longer-term outcome measures should be encouraged. Trial Registration: PROSPERO CRD42016035467; http://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD 42016 035467(Archived by WebCite at http://www.webcitation.org/6vpgZU1FU

Volume 6, Issue 1 (2023) Criminal Justice Agents and Responsibility

This special issue of the International Journal on Responsibility (IJR) advances scholarship on the various ways responsibility infuses the roles of criminal justice agents. As the inaugural issue of my tenure as Editor-in-Chief, Volume 6 deepens our understanding of responsibility in the context of the criminal justice system, thereby fulfilling IJR’s aim and scope. Specifically, the articles highlight issues of responsibility within each component of the criminal justice system: police, courts, and corrections

Why do individuals engage in in-play sports betting? A qualitative interview study

Increasing technological advancements and changing consumer behavior has resulted in individuals having access to a wider range of online gambling markets and sporting events than ever before. Sports betting in real time has been aided by the accessibility of smartphone devices. Consequently, the popularity of live sports betting (i.e., 'in-play' betting) has spread across Europe and around the rest of world. The aim of the present exploratory study was to examine attitudes and opinions towards online sports betting. Qualitative interviews were conducted with 17 males and 2 females aged between 21 and 32 years. Participants were asked a range of semi-structured interview questions based on pre-determined topic areas. Socio-demographic data were collected and the Problem Gambling Severity Index (PGSI) was used to assess problem gambling. The data were analyzed using thematic analysis in order to identify themes. Analysis of the transcripts identified several notable areas including the ease of engaging in in-play sports betting, motivations for engaging in in-play sports betting (including increased excitement, demonstrating knowledge/skill and response to live odds), and different reasons for using the ‘cash-out’ feature. The findings will contribute to the design of future research investigating in-play sports betting behaviours