What can be learnt from models of incidence rates?

Models of breast cancer incidence have evolved from the observation by Armitage and Doll in the 1950s that the pattern of incidence by age differs for reproductive cancers from those of other major malignancies. Both two-stage and multistage models have been applied to breast cancer incidence. Consistent across modeling approaches, risk accumulation or the rate of increase in breast cancer incidence is most rapid from menarche to first birth. Models that account for the change in risk after menopause and the temporal sequence of reproductive events summarize risk efficiently and give added insights to potentially important mechanistic features. First pregnancy has an adverse impact on progesterone receptor negative tumors, while increasing parity reduces the risk of estrogen/progesterone receptor positive tumors but not estrogen/progesterone receptor negative tumors. Integrated prediction models that incorporate prediction of carrier status for highly penetrant genes and also account for lifestyle factors, mammographic density, and endogenous hormone levels remain to be efficiently implemented. Models that both inform and reflect the emerging understanding of the molecular and cell biology of carcinogenesis are still a long way off

Threat Assessment for Multistage Cyber Attacks in Smart Grid Communication Networks

In smart grids, managing and controlling power operations are supported by information and communication technology (ICT) and supervisory control and data acquisition (SCADA) systems. The increasing adoption of new ICT assets in smart grids is making smart grids vulnerable to cyber threats, as well as raising numerous concerns about the adequacy of current security approaches. As a single act of penetration is often not sufficient for an attacker to achieve his/her goal, multistage cyber attacks may occur. Due to the interdependence between the power grid and the communication network, a multistage cyber attack not only affects the cyber system but impacts the physical system. This thesis investigates an application-oriented stochastic game-theoretic cyber threat assessment framework, which is strongly related to the information security risk management process as standardized in ISO/IEC 27005. The proposed cyber threat assessment framework seeks to address the specific challenges (e.g., dynamic changing attack scenarios and understanding cascading effects) when performing threat assessments for multistage cyber attacks in smart grid communication networks. The thesis looks at the stochastic and dynamic nature of multistage cyber attacks in smart grid use cases and develops a stochastic game-theoretic model to capture the interactions of the attacker and the defender in multistage attack scenarios. To provide a flexible and practical payoff formulation for the designed stochastic game-theoretic model, this thesis presents a mathematical analysis of cascading failure propagation (including both interdependency cascading failure propagation and node overloading cascading failure propagation) in smart grids. In addition, the thesis quantifies the characterizations of disruptive effects of cyber attacks on physical power grids. Furthermore, this thesis discusses, in detail, the ingredients of the developed stochastic game-theoretic model and presents the implementation steps of the investigated stochastic game-theoretic cyber threat assessment framework. An application of the proposed cyber threat assessment framework for evaluating a demonstrated multistage cyber attack scenario in smart grids is shown. The cyber threat assessment framework can be integrated into an existing risk management process, such as ISO 27000, or applied as a standalone threat assessment process in smart grid use cases

Coal-exit alliance must confront freeriding sectors to propel Paris-aligned momentum

The global phase-out of coal by mid-century is considered vital to the Paris Agreement to limit warming well-below 2 \ub0C above pre-industrial levels. Since the inception of the Powering Past Coal Alliance (PPCA) at COP23, political ambitions to accelerate the decline of coal have mounted to become the foremost priority at COP26. However, mitigation research lacks the tools to assess whether this bottom-up momentum can self-propagate toward Paris alignment. Here, we introduce dynamic policy evaluation (DPE), an evidence-based approach for emulating real-world policy-making. Given empirical relationships established between energy-economic developments and policy adoption, we endogenize national political decision-making into the integrated assessment model REMIND via multistage feedback loops with a probabilistic coalition accession model. DPE finds global PPCA participation <5% likely against a current policies backdrop and, counterintuitively, foresees that intracoalition leakage risks may severely compromise sector-specific, demand-side action. DPE further enables policies to interact endogenously, demonstrated here by the PPCA’s path-dependence to COVID-19 recovery investments

Search based software engineering: Trends, techniques and applications

© ACM, 2012. This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version is available from the link below.In the past five years there has been a dramatic increase in work on Search-Based Software Engineering (SBSE), an approach to Software Engineering (SE) in which Search-Based Optimization (SBO) algorithms are used to address problems in SE. SBSE has been applied to problems throughout the SE lifecycle, from requirements and project planning to maintenance and reengineering. The approach is attractive because it offers a suite of adaptive automated and semiautomated solutions in situations typified by large complex problem spaces with multiple competing and conflicting objectives. This article provides a review and classification of literature on SBSE. The work identifies research trends and relationships between the techniques applied and the applications to which they have been applied and highlights gaps in the literature and avenues for further research.EPSRC and E

The nonmedical use of prescription ADHD medications: results from a national Internet panel

© 2007 Novak et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The effect of peer and parental smoking on adolescent smoking initiation: Exploring potential moderators

The factors that contribute to smoking initiation among adolescents are poorly understood. The current approaches to smoking prevention may have achieved their maximum potential as evidenced by a stalling in the decline in smoking rates. To date, approaches to smoking prevention based on social and individual factors have previously met with limited success. A promising new approach will be to examine the interaction between social and individual factors and the effects of their interaction on smoking initiation. Parental and peer smoking behaviors are well-known risk factors for smoking initiation. Several theoretical models suggest that perceptual or interpretative processes may moderate the influence of factors such as these on the smoking initiation process. This study looks at age (as a proxy for adolescent development), depression and school performance as potential moderators of the impact of parental or peer smoking. This study uses a large longitudinal sample (The Teenage Attitudes and Practices Surveys -- 1989 and 1993) to explore for these relationships. Results show very limited support for the impact of potential moderated relationships, with only one of the six hypothesized interactions being supported (peer smoking and school performance). This would suggest that theoretical models which include concepts of perceptual or interpretative processes as moderating influences need to continue to evaluate their validity. Another finding of the study is a significant main effect of school performance on smoking initiation --a relationship which has not been previously reported in a national longitudinal sample. This study also found support for depression as an antecedent to smoking initiation -- a relationship whose causal direction continues to be controversial. Continued exploration of the complex relationships between these social and individual factors may allow for the development of more effective evidence-based smoking prevention programs

Novel methods based on regression techniques to analyze multistate models and high-dimensional omics data.

The dissertation is based on four distinct research projects that are loosely interconnected by the common link of a regression framework. Chapter 1 provides an introductory outline of the problems addressed in the projects along with a detailed review of the previous works that have been done on them and a brief discussion on our newly developed methodologies. Chapter 2 describes the first project that is concerned with the identification of hidden subject-specific sources of heterogeneity in gene expression profiling analyses and adjusting for them by a technique based on Partial Least Squares (PLS) regression, in order to ensure a more accurate inference on the expression pattern of the genes over two different varieties of samples. Chapter 3 focuses on the development of an R package based on Project 1 and its performance evaluation with respect to other popular software dealing with differential gene expression analyses. Chapter 4 covers the third project that proposes a non-parametric regression method for the estimation of stage occupation probabilities at different time points in a right-censored multistate model data, using an Inverse Probability of Censoring (IPCW) (Datta and Satten, 2001) based version of the backfitting principle (Hastie and Tibshirani, 1992). Chapter 5 describes the fourth project which deals with the testing for the equality of the residual distributions after adjusting for available covariate information from the right censored waiting times of two groups of subjects, by using an Inverse Probability of Censoring weighted (IPCW) version of the Mann-Whitney U test

Towards an understanding of the burdens of medication management affecting older people: the MEMORABLE realist synthesis

Background More older people are living in the community with multiple diagnoses and medications. Managing multiple medications produces issues of unrivalled complexity for those involved. Despite increasing literature on the subject, gaps remain in understanding how, why and for whom complex medication management works, and therefore how best to improve practice and outcomes. MEMORABLE, MEdication Management in Older people: Realist Approaches Based on Literature and Evaluation, aimed to address these gaps. Methods MEMORABLE used realism to understand causal paths within medication management. Informed by RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines, MEMORABLE involved three overlapping work packages: 1) Realist Review of the literature (24 articles on medication management exploring causality); 2) Realist Evaluation (50 realist-informed interviews with older people, family carers and health and care practitioners, explaining their experiences); and 3) data synthesis and theorising from 1) and 2). Results Medication management was viewed from the perspective of ‘implementation’ and structured into five stages: identifying a problem (Stage 1), getting a diagnosis and/or medications (Stage 2), starting, changing or stopping medications (Stage 3), continuing to take medications (Stage 4), and reviewing/reconciling medications (Stage 5). Three individual stages (1, 3 and 4) are conducted by the older person sometimes with family carer support when they balance routines, coping and risk. Stages 2 and 5 are interpersonal where the older person works with a practitioner-prescriber-reviewer, perhaps with carer involvement. Applying Normalisation Process Theory, four steps were identified within each stage: 1) sense making: information, clarification; 2) action: shared-decision-making; 3) reflection/monitoring; and 4) enduring relationships, based on collaboration and mutual trust. In a detailed analysis of Stage 5: Reviewing/reconciling medications, adopting the lens of ‘burden’, MEMORABLE identified five burdens amenable to mitigation: ambiguity, concealment, unfamiliarity, fragmentation and exclusion. Two initial improvement propositions were identified for further research: a risk screening tool and individualised information. Conclusions Older people and family carers often find medication management challenging and burdensome particularly for complex regimens. Practitioners need to be aware of this potential challenge, and work with older people and their carers to minimise the burden associated with medication management. Trial registration PROSPERO 2016:CRD42016043506