A new approach to optimal designs for correlated observations

This paper presents a new and efficient method for the construction of optimal designs for regression models with dependent error processes. In contrast to most of the work in this field, which starts with a model for a finite number of observations and considers the asymptotic properties of estimators and designs as the sample size converges to infinity, our approach is based on a continuous time model. We use results from stochastic anal- ysis to identify the best linear unbiased estimator (BLUE) in this model. Based on the BLUE, we construct an efficient linear estimator and corresponding optimal designs in the model for finite sample size by minimizing the mean squared error between the opti- mal solution in the continuous time model and its discrete approximation with respect to the weights (of the linear estimator) and the optimal design points, in particular in the multi-parameter case. In contrast to previous work on the subject the resulting estimators and corresponding optimal designs are very efficient and easy to implement. This means that they are practi- cally not distinguishable from the weighted least squares estimator and the corresponding optimal designs, which have to be found numerically by non-convex discrete optimization. The advantages of the new approach are illustrated in several numerical examples.Comment: Keywords and Phrases: linear regression, correlated observations, optimal design, Gaussian white mouse model, Doob representation, quadrature formulas AMS Subject classification: Primary 62K05; Secondary: 62M0

Bayesian optimal designs for dose-response curves with common parameters

The issue of determining not only an adequate dose but also a dosing frequency of a drug arises frequently in Phase II clinical trials. This results in the comparison of models which have some parameters in common. Planning such studies based on Bayesian optimal designs offers robustness to our conclusions since these designs, unlike locally optimal designs, are efficient even if the parameters are misspecified. In this paper we develop approximate design theory for Bayesian D-optimality for nonlinear regression models with common parameters and investigate the cases of common location or common location and scale parameters separately. Analytical characterisations of saturated Bayesian D-optimal designs are derived for frequently used dose-response models and the advantages of our results are illustrated via a numerical investigation

Refugee camp health services utilisation by non-camp residents as an indicator of unaddressed health needs of surrounding populations: a perspective from Mae La refugee camp in Thailand during 2006 and 2007

Introduction: this study explored the differences on the level of medical care required by camp and non-camp resident patients during utilisation of the health services in Mae La refugee camp, Tak province, Thailand during the years 2006 and 2007. Methods: data were extracted from camp registers and the Health Information System used during the years 2006 and 2007 and statistical analysis was performed. Results: the analysis showed that during 2006 and 2007 non-camp resident patients, coming from Thailand as well as Myanmar, who sought care in the outpatient depart-ment (OPD) of the camp required at a significantly higher proportion admission to the inpatient department (IPD) or referral to the district hospital compared to camp resident patients. Although there was a statistically significant increased mortality of the non-camp resident patients admitted in the IPD compared to camp resident patients, there was no significant difference in mortality among these two groups when the re-ferrals to the district hospital were analysed. Conclusion: non-camp resident patients tended to need a more advanced level of medical care compared to camp resident patients. Provided that this it is further vali-dated, the above observed pattern might be potentially useful as an indirect indicator of unaddressed health needs of populations surrounding a refugee camp

Optimal designs for full and partial likelihood information — With application to survival models

Time-to-event data are often modelled through Cox’s proportional hazards model for which inference is based on the partial likelihood function. We derive a general expression for the asymptotic covariance matrix of Cox’s partial likelihood estimator for the covariate coefficients. Our approach is illustrated through an application to the special case of only one covariate, for which we construct minimum variance designs for different censoring mechanisms and both binary and interval design spaces. We compare these designs with the corresponding ones found using the full likelihood approach and demonstrate that the latter designs are highly efficient also for partial likelihood estimation

STRENGTHENING THE ACTIVE CITIZENSHIP OF ROMA WOMEN THROUGH THEIR PARTICIPATION IN THE ROMA POLITICAL SCHOOL IN GREECE

This article explores the participation of Roma women in public life and how this is strengthened through their participation in the Roma Political School in Greece. The study focused on the reasons for participation and the expectations of women from their participation in the Roma Political School, but also on the barriers they encounter and the opportunities they are given to participate in social and political events. It has highlighted the emergence of proposals for the empowerment and strengthening of the position of Roma women in politics. A qualitative methodology was followed, and data was collected through semi-structured interviews with 4 Roma women and two officials of the Council of Europe who participated in the Roma Political School in Greece. The findings of the study showed that progress has been made towards the active citizenship of Greek Roma women and, through their participation in the RPS, women expect to acquire the necessary knowledge and skills in order to actively participate in the community and contribute to resolving the problems and addressing the needs of their community. However, there are also several inhibiting factors that affect the active citizenship of women: stereotypical perceptions of the position of women prevailing in the Gypsy community, women's low level of education, and their lack of self-confidence. The main proposals that emerged in relation to strengthening women's participation in the public sphere are related to information and the dissemination of information, the strengthening of women's participation in associations, the participation of women in education and adult education and in specialized political programs, and the breaking down of stereotypes concerning the position of women.  Article visualizations

Heterogeneous Monetary Policy Transmission in the US Housing Market

We assess the effects of monetary policy on real house prices and housing investment across the US states during the period 1983-2008. We find that an expansionary monetary shock generates higher housing investment and house prices at the national level. At the state level, however the responses of housing investment and house prices differ from the nation-wide responses. We relate this heterogeneity to various observable factors such as property tax rates, howeownership, income inequality, poverty and demographic factors. All these factors are crucial in explaining the heterogeneity of the state-level responses

Optimal designs for regression with spherical data

In this paper optimal designs for regression problems with spherical predictors of arbitrary dimension are considered. Our work is motivated by applications in material sciences, where crystallographic textures such as the missorientation distribution or the grain boundary distribution (depending on a four dimensional spherical predictor) are represented by series of hyperspherical harmonics, which are estimated from experimental or simulated data. For this type of estimation problems we explicitly determine optimal designs with respect to Kiefers op-criteria and a class of orthogonally invariant information criteria recently introduced in the literature. In particular, we show that the uniform distribution on the m-dimensional sphere is optimal and construct discrete and implementable designs with the same information matrices as the continuous optimal designs. Finally, we illustrate the advantages of the new designs for series estimation by hyperspherical harmonics, which are symmetric with respect to the first and second crystallographic point group

Characterising In-111-anti-γH2AX-TAT in targeting the DNA damage signal associated with Wnt activated colorectal cancer

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the UK and has a poor 60% 5-year survival rate. The Wnt signalling pathway is fundamental for homeostasis of the intestinal epithelium and its deregulation drives development of CRC and induces DNA damage. Histone-2AX (H2AX) is a component of the nucleosome whose phosphorylated form, γH2AX, is a marker of DNA damage. Objectives: Using a well-characterised inducible CRC mouse model of early Wnt deregulation, and established Apc-deficient driven tumour and ex vivo organoid models, we have assessed whether the spontaneous DNA damage generated in these models can be targeted using 111In-anti-γH2AX-TAT (RH2AX), a radio-labelled antibody targeting γH2AX. Methods: Deletion of the Apc gene was effected in the intestine of VilCreERApcfl/fl and Lgr5CreERApcfl/fl models by intraperitoneal or oral induction with tamoxifen. γH2AX immunohistochemical (IHC) characterisation of intestines were performed as well as γH2AX whole mount immunofluorescent analysis on organoids derived from them. RH2AX, an anti-γH2AX antibody conjugated to the cell-penetrating peptide TAT to allow cellular internalisation and nuclear localisation, was used in these models as an imaging agent SPECT/CT imaging and biodistribution studies were conducted after oral induction of VilCreERApcfl/fl and intravenous injection of RH2AX. γH2AX and Lgr5 FACS analysis were carried out on intestinal crypt cells of VilCreERApcfl/fl mice expressing Lgr5-EGFP reporter. Results: Intestinal Apc deficiency increased DNA damage levels in the small intestine of both dysplastic (VilCreERApcfl/fl) and tumour CRC mouse (Lgr5CreERApcfl/fl) models. Apc-deficiency-associated DNA damage is most likely generated through WNT signalling pathway activation and, more specifically, by c-Myc transcription. For the first time, we demonstrated that intestinal dysplasia can be identified through in vivo SPECT imaging, using low SA RH2AX treatment. Low SA RIC treatment in intestinal dysplasia increased the DNA damage levels in healthy and Apc-deficient small and large intestines, increased proliferation in the Apc-deficient tissue and resulted in variable levels of apoptosis depending on the tissue. Conclusion: These findings together indicate that DNA damage is induced by Apc-deficiency, and that there is the possibility to exploit the endogenously-increased DNA damage signal, γH2AX, to attract the RH2AX for in vivo imaging of intestinal dysplasia. This could help diagnose early stages of CRC to provide patients with the appropriate treatment sooner and increase their survival