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"Steele, J"
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A review of sex-related differences in colorectal cancer incidence, screening uptake, routes to diagnosis, cancer stage and survival in the UK
Background
Colorectal cancer (CRC) is an illness strongly influenced by sex and gender, with mortality rates in males significantly higher than females. There is still a dearth of understanding on where sex differences exist along the pathway from presentation to survival. The aim of this review is to identify where actions are needed to improve outcomes for both sexes, and to narrow the gap for CRC.
Methods
A cross-sectional review of national data was undertaken to identify sex differences in incidence, screening uptake, route to diagnosis, cancer stage at diagnosis and survival, and their influence in the sex differences in mortality.
Results
Overall incidence is higher in men, with an earlier age distribution, however, important sex differences exist in anatomical site. There were relatively small differences in screening uptake, route to diagnosis, cancer staging at diagnosis and survival. Screening uptake is higher in women under 69 years. Women are more likely to present as emergency cases, with more men diagnosed through screening and two-week-wait. No sex differences are seen in diagnosis for more advanced disease. Overall, age-standardised 5-year survival is similar between the sexes.
Conclusions
As there are minimal sex differences in the data from routes to diagnosis to survival, the higher mortality of colorectal cancer in men appears to be a result of exogenous and/or endogenous factors pre-diagnosis that lead to higher incidence rates. There are however, sex and gender differences that suggest more targeted interventions may facilitate prevention and earlier diagnosis in both men and women.
Journal Article
Restraint in international politics
\"This book is about restraint, something I am not known to practice very frequently. But I have had to practice it in writing this book, and I've learned patience in the process because I think restraint is incredibly important for politics, and especially for international relations. I continued to slog away at this book precisely because I received so many comments, notes of encouragement, and critically important pieces of advice from friends and colleagues who also shared a sense that there needs to be a book like this one on restraint. It has taken me well over the course of five years to research, present, write, revise, and re-revise the content that went into it. In my more melodramatic moments I've referred to this book as my 'white whale'\"-- Provided by publisher.
Book
Machine learning models in electronic health records can outperform conventional survival models for predicting patient mortality in coronary artery disease
Prognostic modelling is important in clinical practice and epidemiology for patient management and research. Electronic health records (EHR) provide large quantities of data for such models, but conventional epidemiological approaches require significant researcher time to implement. Expert selection of variables, fine-tuning of variable transformations and interactions, and imputing missing values are time-consuming and could bias subsequent analysis, particularly given that missingness in EHR is both high, and may carry meaning. Using a cohort of 80,000 patients from the CALIBER programme, we compared traditional modelling and machine-learning approaches in EHR. First, we used Cox models and random survival forests with and without imputation on 27 expert-selected, preprocessed variables to predict all-cause mortality. We then used Cox models, random forests and elastic net regression on an extended dataset with 586 variables to build prognostic models and identify novel prognostic factors without prior expert input. We observed that data-driven models used on an extended dataset can outperform conventional models for prognosis, without data preprocessing or imputing missing values. An elastic net Cox regression based with 586 unimputed variables with continuous values discretised achieved a C-index of 0.801 (bootstrapped 95% CI 0.799 to 0.802), compared to 0.793 (0.791 to 0.794) for a traditional Cox model comprising 27 expert-selected variables with imputation for missing values. We also found that data-driven models allow identification of novel prognostic variables; that the absence of values for particular variables carries meaning, and can have significant implications for prognosis; and that variables often have a nonlinear association with mortality, which discretised Cox models and random forests can elucidate. This demonstrates that machine-learning approaches applied to raw EHR data can be used to build models for use in research and clinical practice, and identify novel predictive variables and their effects to inform future research.
Journal Article
A comparison of statistical methods for detecting context-modulated functional connectivity in fMRI
Many cognitive and clinical neuroscience research studies seek to determine how contextual factors modulate cognitive processes. In fMRI, hypotheses about how context modulates distributed patterns of information processing are often tested by comparing functional connectivity between neural regions A and B as a function of task conditions X and Y, which is termed context-modulated functional connectivity (FC). There exist two exploratory statistical approaches to testing context-modulated FC: the beta-series method and psychophysiological interaction (PPI) analysis methods. While these approaches are commonly used, their relative power for detecting context-modulated FC is unknown, especially with respect to real-world experimental parameters (e.g., number of stimulus repetitions, inter-trial-interval, stimulus duration). Here, we use simulations to compare power for detecting context-modulated FC between the standard PPI formulation (sPPI), generalized PPI formulation (gPPI), and beta series methods. Simulation results demonstrate that gPPI and beta series methods are generally more powerful than sPPI. Whether gPPI or beta series methods performed more powerfully depended on experiment parameters: block designs favor the gPPI, whereas the beta series method was more powerful for designs with more trial repetitions and it also retained more power under conditions of hemodynamic response function variability. On a real dataset of adolescent girls, the PPI methods appeared to have greater sensitivity in detecting task-modulated FC when using a block design and the beta series method appeared to have greater sensitivity when using an event-related design with many trial repetitions. Implications of these performance results are discussed.
•We compared statistical methods for detecting task-modulated functional connectivity•psychophyiological interaction analyses were most sensitive on block designs•beta series method was more robust to changes in the hemodynamic response function
Journal Article
C.R.A.F.T. conversations for teacher growth : how to build bridges and cultivate expertise
\"This engaging guide explains how administrators can elevate their conversations with teachers to enhance professional relationships, strengthen leadership and teaching, and improve student learning\"-- Provided by publisher.
Book
Defacing power
Defacing Power investigates how nation-states create self-images in part through aesthetics and how these images can be manipulated to challenge those states' power. Although states have long employed media, such as radio, television, and film, for their own image-making purposes, counterpower agents have also seized upon new telecommunications technologies. Most recently, the Internet has emerged as contested territory where states and other actors wage a battle of words and images. Moving beyond theory, Brent Steele illustrates his provocative argument about the vulnerability of power with examples from recent history: the My Lai Massacre and the Tet Offensive, September 11 and the al-Qaeda communiqués, the atrocities at Fallujah and Abu Ghraib, and the U.S. response to the Asian tsunami of December 2004. He demonstrates how a nation-state—even one as powerful as the United States—comes to feel threatened not only by other nation-states or terrorist organizations but also by unexpected events that challenge its self-constructed image of security. At the same time, Steele shows that as each generation uses available media to create and re-create a national identity, technological innovations allow for the shifting, upheaval, and expansion of the cultural structure of a nation.
eBook
تاريخ التعليم في إقليم طرابلس منذ الاحتلال العثماني حتى السنة الخامسة للإدارة العسكرية البريطانية للإقليم
يقدم هذا العمل تغطية لتاريخ التعليم منذ فترة الإحتلال إلى عهد الإدارة العسكرية البريطانية وتغطي الفترة الأخيرة خمس سنوات تبين التغيرات والنمو الذي تم انجازه خلال السبعين سنة الأخيرة ولقد سارت التمية تحت الإدارة العسكرية البريطانية في قسم التعليم تحت ظروف صعبة، سنة بسنة وكان ذلك في حالة المدارس الأهلية الأصعب على الإطلاق حيث أنه تمت تربية هؤلاء منذ الولادة إلى فترة المراهقة دون أن يعرفوا ماذا سيكون مستقبلهم.
Book
Opposing patterns of abnormal D1 and D2 receptor dependent cortico-striatal plasticity explain increased risk taking in patients with DYT1 dystonia
Patients with DYT1 dystonia caused by the mutated TOR1A gene exhibit risk neutral behaviour compared to controls who are risk averse in the same reinforcement learning task. It is unclear whether this behaviour can be linked to changes in cortico-striatal plasticity demonstrated in animal models which share the same TOR1A mutation. We hypothesised that we could reproduce the experimental risk taking behaviour using a model of the basal ganglia under conditions where cortico-striatal plasticity was abnormal. As dopamine exerts opposing effects on cortico-striatal plasticity via different receptors expressed on medium spiny neurons (MSN) of the direct (D1R dominant, dMSNs) and indirect (D2R dominant, iMSNs) pathways, we tested whether abnormalities in cortico-striatal plasticity in one or both of these pathways could explain the patient's behaviour. Our model could generate simulated behaviour indistinguishable from patients when cortico-striatal plasticity was abnormal in both dMSNs and iMSNs in opposite directions. The risk neutral behaviour of the patients was replicated when increased cortico-striatal long term potentiation in dMSN's was in combination with increased long term depression in iMSN's. This result is consistent with previous observations in rodent models of increased cortico-striatal plasticity at in dMSNs, but contrasts with the pattern reported in vitro of dopamine D2 receptor dependant increases in cortico-striatal LTP and loss of LTD at iMSNs. These results suggest that additional factors in patients who manifest motor symptoms may lead to divergent effects on D2 receptor dependant cortico-striatal plasticity that are not apparent in rodent models of this disease.
Journal Article