Gurney and Fritz

Pre-print version deposited following SHERPA guidelines. This is an electronic version of an article published in Essays in Criticism Vol.59(2), 2009

The 1000 Mitoses Project: A Consensus-Based International Collaborative Study on Mitotic Figures Classification

IntroductionThe identification of mitotic figures is essential for the diagnosis, grading, and classification ofvarious different tumors. Despite its importance, there is a paucity of literature reporting theconsistency in interpreting mitotic figures among pathologists. This study leverages publiclyaccessible datasets and social media to recruit an international group of pathologists to score animage database of more than 1000 mitotic figures collectively.Materials and MethodsPathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas(TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm2 area. The first 1010submitted mitotic figures were used to create an image dataset, with each figure transformed intoan individual tile at 40x magnification. The dataset was redistributed to all pathologists to reviewand determine whether each tile constituted a mitotic figure.ResultsOverall pathologists had a median agreement rate of 80.2% (range 42.0% to 95.7%). Individualmitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement acrossall tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement ratescompared to other phases of mitosis.ConclusionThis dataset stands as the largest international consensus study for mitotic figures to date and canbe utilized as a training set for future studies. The agreement range reflects a spectrum of criteriathat pathologists use to decide what constitutes a mitotic figure, which may have potentialimplications in tumor diagnostics and clinical management.Keywords: Mitotic Figures, Mitotic Figure Mimics, Digital Pathology, InternationalCollaboration, Social Medi

Re: Recognition and management of psychosis and schizophrenia in children and young people : summary of NICE guidance.

The publication of NICE guidelines relating to the Recognition and management of Psychosis and Schizophrenia in children and young people 1 is to be welcomed given the lack of published guidance in this area, especially concerning the management of young people deemed to be at high risk of psychosis 2,3. However, we feel that the working group may have missed an opportunity to incorporate the views of current adolescent service users. The guideline development process included service-user representation at all stages. However, there was a dearth of published literature in relation to the experiences and treatment preferences of child and adolescent service users with psychosis to draw on 4 although we note the guidelines did not reference our recently published study in this area 5. Indeed, this is a patient group rarely consulted, possibly due to a perception that young people may find it difficult to articulate hallucinatory experiences or have inaccurate recall of events 6,7. However, there is a growing acceptance that eliciting and learning from service users' views is an important means of improving the quality of future health care and research within the NHS 8,9. Indeed, where the evidence base is uncertain, as in the present case, patient preferences may play a more significant role in treatment selection 10. In response to our concerns we are working with our local Early Intervention in Psychosis service to address this issue by offering information to young people describing possible therapeutic options and asking them to state their preferences

Tackling a scandal of premature mortality; time for a ‘hearts & minds’ approach

David Shiers* and Tim Kendall** suggest it is untenable in 2012 to provide healthcare which fails to address the physical needs of those with mental illness, and the mental needs of those with physical illness

The Effects of Extra-Somatic Weapons on the Evolution of Human Cooperation towards Non-Kin

Human cooperation and altruism towards non-kin is a major evolutionary puzzle, as is ‘strong reciprocity’ where no present or future rewards accrue to the co-operator/altruist. Here, we test the hypothesis that the development of extra-somatic weapons could have influenced the evolution of human cooperative behaviour, thus providing a new explanation for these two puzzles. Widespread weapons use could have made disputes within hominin groups far more lethal and also equalized power between individuals. In such a cultural niche non-cooperators might well have become involved in such lethal disputes at a higher frequency than cooperators, thereby increasing the relative fitness of genes associated with cooperative behaviour. We employ two versions of the evolutionary Iterated Prisoner's Dilemma (IPD) model – one where weapons use is simulated and one where it is not. We then measured the performance of 25 IPD strategies to evaluate the effects of weapons use on them. We found that cooperative strategies performed significantly better, and non-cooperative strategies significantly worse, under simulated weapons use. Importantly, the performance of an ‘Always Cooperate’ IPD strategy, equivalent to that of ‘strong reciprocity’, improved significantly more than that of all other cooperative strategies. We conclude that the development of extra-somatic weapons throws new light on the evolution of human altruistic and cooperative behaviour, and particularly ‘strong reciprocity’. The notion that distinctively human altruism and cooperation could have been an adaptive trait in a past environment that is no longer evident in the modern world provides a novel addition to theory that seeks to account for this major evolutionary puzzle

Changing Brains, Changing Lives: Researching the Lived Experience of Individuals Practicing Self-Directed Neuroplasticity

Neuroplasticity refers to the brain’s ability to change and adapt both structure and function in response to sensory experiences. Self-directed neuroplasticity (SDN) specifically addresses the capacity to proactively modify cerebral function through volitional control and the intentional practice of focusing attention in desired ways. In other words, the mind can consciously change the brain. Self-directed neuroplasticity (SDN) approaches are successfully used to treat a range of challenges such as obsessive-compulsive disorder (OCD), depression, and emotional response regulation. However, no research describes the lived experiences of individuals practicing SDN across multiple modalities. Using semi-structured, in-depth interviews, this phenomenological inquiry describes the lived experiences of 13 participants practicing SDN. In addition to identifying SDN uses and multifaceted aspects to SDN practices outside of current academic literature, this study utilized thematic analysis to uncover four themes: Seeking, Empowerment, Growth in Relationships, and Transformation. Results offer insights into expanding SDN uses, broadening practice context, and life-changing transformation. Implications include the need to increase awareness, education, and integration of SDN within holistic health and other communities, as well as expand research regarding SDN uses, application among various populations, and longitudinal efficacy

The Cost Effectiveness of Pharmacological Treatments for Generalized Anxiety Disorder

Background: Generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders, with important implications for patients and healthcare resources. However, few economic evaluations of pharmacological treatments for GAD have been published to date, and those available have assessed only a limited number of drugs. / Objective: To assess the cost effectiveness of pharmacological interventions for patients with GAD in the UK. / Methods: A decision-analytic model in the form of a decision tree was constructed to compare the costs and QALYs of six drugs used as first-line pharmacological treatments in people with GAD (duloxetine, escitalopram, paroxetine, pregabalin, sertraline and venlafaxine extended release [XL]) and ‘no pharmacological treatment’. The analysis adopted the perspective of the NHS and Personal Social Services (PSS) in the UK. Efficacy data were derived from a systematic literature review of double-blind, randomized controlled trials and were synthesized using network meta-analytic techniques. Two network meta-analyses were undertaken to assess the comparative efficacy (expressed by response rates) and tolerability (expressed by rates of discontinuation due to intolerable side effects) of the six drugs and no treatment in the study population. Cost data were derived from published literature and national sources, supplemented by expert opinion. The price year was 2011. Probabilistic sensitivity analysis was conducted to evaluate the underlying uncertainty of the model input parameters. / Results: Sertraline was the best drug in limiting discontinuation due to side effects and the second best drug in achieving response in patients not discontinuing treatment due to side effects. It also resulted in the lowest costs and highest number of QALYs among all treatment options assessed. Its probability of being the most cost-effective drug reached 75 % at a willingness-to-pay threshold of £20,000 per extra QALY gained. / Conclusion: Sertraline appears to be the most cost-effective drug in the treatment of patients with GAD. However, this finding is based on limited evidence for sertraline (two published trials). Sertraline is not licensed for the treatment of GAD in the UK, but is commonly used by primary care practitioners for the treatment of depression and mixed depression and anxiety

Employers' and Educators' Perceptions of Job-Related Competencies Needed by Entry-Level International Development Agents

The purpose of this study was to determine employees (NGOs) and educators (AIAEE members) perceptions of job-related competencies for entry-level international development agents. Nine constructs were garnered from research, conflict management and resolution, cultural diversity, , management responsibility, personal and professional development, personal skills, program planning and evaluation, public relations, staff relations, and work habits. The populations included 90 NGO employees, and 178 members of AIAEE. Both populations were surveyed using an online questionnaire. This descriptive study generated a 36% response rate for NGO employees, and 49% for AIAEE members.Findings and Conclusions: Both populations rated all nine constructs as somewhat important or important. However, when asked to rank the constructs in order of importance, the NGO population ranked work habits as most important, followed by personal skills, and management responsibility. Whereas, the AIAEE population ranked program planning and evaluation as most important followed by cultural diversity, and work habits. However, only a weak correlational relationship was evident for age and international work experience to the nine constructs. Pertaining to the demographics of the populations, the NGO contained a larger percentage of females than did the AIAEE population. Both populations indicated they culturally indentify with the western culture, however both populations indicated they have worked throughout the world. The largest number of respondents indicated they had worked in Asia, Africa, North America, or the Middle East. However, AIAEE members had more years of experience in their current positions, but NGO employees had more years of experience residing in a foreign country. When AIAEE members were asked how many undergraduate or graduate courses they taught that prepare students for employment in international development, almost half taught no courses. However, qualitative data gathered from a telephone interview of an international recruiter indicated that students today are better prepared than those five years ago.Department of Agricultural Education, Communications, and Leadershi