The validity and validation of mathematical models: Methodological, theoretical, and practical studies with emphasis on the modelling of complex biological systems

In recent years there has been a tremendous growth in the development and application of mathematical models in all areas of science and engineering. Aided by the advances and availability of computers, models have been used in many new areas, such as biology and the social sciences, and applied to increasingly complex systems. At the same time, model validity and validation have become correspondingly more problematic yet received little attention. The aims of this thesis are to clarify the meaning of model validity, to develop a range of procedures for model validation, and to consider in depth the validity of a number of specific models. The main focus is the use of models in systems science and in biology and medicine. A review of the scientific literature of model validity and validation is made which reveals many techniques for empirical validation, but exposes the lack of a consistent conceptual approach towards model validity. In reviewing the philosophy of science with reference to validity and validation, the importance of regarding models and validation as part of an evolving research programme and of heuristic considerations in assessing model validity are emphasised. A new and innovative theory of model validity is proposed which explicates model validity as a multidimensional concept closely related to modelling objectives. The different modelling objectives and types of data are classified and the various concepts of validity are expressed as validity criteria. The general relationship between modelling objectives, data, and validity criteria is explained. The theory is then used to devise a range of validation methodologies suitable for models in research areas at different stages of development. Models of the human cardiovascular, renal, and respiratory systems are used as case studies for validation. Extensive use is made of the conceptual framework of the theory of model validity and the validation methodologies. The results are a precise delimiting of the validity of the models, the areas of uncertainty, and the potential for future development. This indicates the critical value of the theory and the appropriateness of the methodologies to complex biological models. Further support for the theory and its wide applicability is obtained in using it to consider aspects of validity and validation of models in the social sciences. Finally, the implications of the work for modelling and validation in systems science and in biology and medicine are examined. In both areas it is shown that the theory of model validity leads to an improved understanding of the nature of modelling and validity, and that the validation methodologies are suitable for the critical and effective validation of a wide range of models. In biology and medicine specific recommendations are made for the types of model appropriate to different modelling objectives and for suitable techniques and methodologies for validation. This thesis contributes to an improved understanding of the concept of model validity and offers a repertoire of validation methodologies. On another level, it is a broad methodological study of the kind urgently required in systems science. More practically, however, much of the thesis is concerned with the detailed validation of three specific biological models

Do patients with advanced breast cancer benefit from chemotherapy?

This study aimed to assess the proportion of patients with advanced breast cancer who report benefit from first-line palliative chemotherapy using a simple global measure of wellbeing and to identify factors predicting benefit. A consecutive series of women with advanced breast cancer undergoing first-line palliative chemotherapy was evaluated. The main outcome measure was patient report of overall wellbeing assessed at post-treatment interview. Physical, psychological and functional status were assessed using the Rotterdam Symptom Checklist (RSCL) on three occasions (pretreatment, at the start of the third cycle and post treatment). It was planned that treatment would be discontinued after six cycles (i.e. 18-24 weeks). One hundred and sixty patients started treatment, of whom 155 were assessable for quality of life. After treatment, 41 (26%) patients reported they felt better, 29 (19%) felt the same and 34 (22%) felt worse than they did before treatment. The other 51 (33%) patients either died or stopped attending the hospital before the post-treatment interview and were assigned as treatment 'failures'. Patients who reported feeling better after treatment had improvements in psychological distress (P < 0.0001), pain (P = 0.01), lack of energy (P = 0.02) and tiredness (P = 0.02), as well as improvement in functional status (P = 0.07). Feeling better was also correlated with disease response (P = 0.03). Feeling worse after treatment or treatment 'failure' was predicted by the pretreatment presence of a dry mouth (P = 0.003) and high levels of psychological distress (P = 0.03). Pretreatment lack of energy (P = 0.01), dry mouth (P = 0.02), presence of liver metastases (P = 0.03) and breathlessness (P = 0.03) predicted treatment 'failures'. The results of this study suggest that first-line palliative chemotherapy for advanced breast cancer confers benefit on a substantial proportion of patients, with about one-quarter feeling better after treatment and nearly a half feeling better or the same some 4-6 months after the start of treatment. Factors identified in this study may assist clinicians in deciding which patients should not be offered treatment, because of high risk of feeling worse or treatment 'failure'. This work now needs to be validated on a further cohort of women receiving chemotherapy for advanced breast cancer

Using assignment data to analyse a blended information literacy intervention: a quantitative approach

This research sought to determine whether a blended information literacy learning and teaching intervention could statistically significantly enhance undergraduates’ information discernment compared to standard face-to-face delivery. A mixture of face-to-face and online activities, including online social media learning, was used. Three interventions were designed to develop the information literacies of first-year undergraduates studying Sport and Exercise at Staffordshire University and focused on one aspect of information literacy: the ability to evaluate source material effectively. An analysis was devised where written evaluations of found information for an assessment were converted into numerical scores and then measured statistically. This helped to evaluate the efficacy of the interventions and provided data for further analysis. An insight into how the information literacy pedagogical intervention and the cognitive processes involved in enabling participants to interact critically with information is provided. The intervention which incorporated social media learning proved to be the most successful learning and teaching approach. The data indicated that undergraduate students’ information literacy can be developed. However, additional long-term data is required to establish whether this intervention would have a lasting impact

Medical Evidence of Human Rights Violations against Non-Arabic-Speaking Civilians in Darfur: A Cross-Sectional Study

Alexander Tsai and colleagues review medical records from the Amel Centre, Sudan, to assess consistency between recorded medical evidence and patient reports of human rights violations by the Government of Sudan and Janjaweed forces

Description and consequences of sexual violence in Ituri province, Democratic Republic of Congo

ABSTRACT: BACKGROUND: The war in eastern Democratic Republic of Congo has been the subject of numerous studies related to the problem of sexual violence. Historically, such violence is known to be part of strategic war plans to conquer and destroy communities, but it is now unfortunately prevalent in times of relative calm. METHODS: We describe the characteristics and consequences of sexual violence in Ituri province of Democratic Republic of Congo through the retrospective analysis of 2,565 patients who received medical care in the Medecins Sans Frontieres sexual violence clinic in the capital of Ituri province, Bunia, between September 2005 and December 2006. Using a standardised questionnaire, we report patients' demographics, number and status of aggressor(s), forced detention and violent threats among other variables for all patients presenting for medical consultation after a sexually violent event during this period. RESULTS: Ninety-six percent of our cohort were female and 29.3% minors, 18-29 years was the most represented age group. Acts of sexual violence (n= 2,565) were reported to be mainly perpetrated by men with military affiliations (73%), although civilians were implicated in 21% of crimes. The attack was perpetrated by two or more persons in over 74% of cases and most commonly perpetrators were unknown armed males, (87.2%). Male victims accounted for 4% (n=103) of our cohort. Forty-eight percent of our patients reported being attacked whilst performing daily domestic duties outside the home and 18% of victims being detained by their perpetrators, the majority of whom were held for less than 2 weeks (61.6%). CONCLUSIONS: The characteristics of sexually violent acts in Ituri province during this period cannot be simply explained as a 'weapon of war' as described in the literature, meaning the use of sexual violence within a military strategy where it is employed under the orders of a commander to harm a particular community. Whilst the majority of aggressions were by armed men there was an important proportion in which civilian perpetrators were implicated. This type of violence has become part of the general characteristics of violence in this war-torn population. Sometimes, as a means for some military factions to acquire remuneration with impunity and for some civilians, a means to counteract confronting, changing social norms occurring during chronic conflict

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Dividend Stickiness in Japan

markdownabstract__Abstract__ The paper describes the introduction of an emphasis on ‘personal security’ in human security thinking and practice, as part of the ultimately unsuccessful attempt to compartmentalize the pursuit of security. It reviews the past twenty years of attention to ‘personal security’: both in compartments that consider organized physical violence or threats to personal safety and property (‘citizen security’), and as parts of more wide-ranging examination of threats to fulfilment of basic needs and rights, for example in comprehensive mapping exercises undertaken in various UNDP Regional and National Human Development Reports or in studies of women’s security. The paper reflects on the complex process of opening-up conventional security thinking and practice, seeking value-added and depth without shrinking into preconceived compartments

A narrative review of health research capacity strengthening in low and middle-income countries: lessons for conflict-affected areas

Abstract Conducting health research in conflict-affected areas and other complex environments is difficult, yet vital. However, the capacity to undertake such research is often limited and with little translation into practice, particularly in poorer countries. There is therefore a need to strengthen health research capacity in conflict-affected countries and regions. In this narrative review, we draw together evidence from low and middle-income countries to highlight challenges to research capacity strengthening in conflict, as well as examples of good practice. We find that authorship trends in health research indicate global imbalances in research capacity, with implications for the type and priorities of research produced, equity within epistemic communities and the development of sustainable research capacity in low and middle-income countries. Yet, there is little evidence on what constitutes effective health research capacity strengthening in conflict-affected areas. There is more evidence on health research capacity strengthening in general, from which several key enablers emerge: adequate and sustained financing; effective stewardship and equitable research partnerships; mentorship of researchers of all levels; and effective linkages of research to policy and practice. Strengthening health research capacity in conflict-affected areas needs to occur at multiple levels to ensure sustainability and equity. Capacity strengthening interventions need to take into consideration the dynamics of conflict, power dynamics within research collaborations, the potential impact of technology, and the wider political environment in which they take place