Drug Polymer Thermodynamic Phase Diagrams in the Selection of Optimal API-Polymer Compositions for Amorphous Solid Dispersions

Purpose The aim of this work was to examine, for amorphous solid dispersions, how the thermal analysis method selected impacts on the construction of thermodynamic phase diagrams, and to assess the predictive value of such phase diagrams in the selection of optimal, physically stable API-polymer compositions. Methods Thermodynamic phase diagrams for two API/polymer systems (naproxen/HPMC AS LF and naproxen/Kollidon 17 PF) were constructed from data collected using two different thermal analysis methods. The “dynamic” method involved heating the physical mixture at a rate of 1 &[deg]C/minute. In the "static" approach, samples were held at a temperature above the polymer Tg for prolonged periods, prior to scanning at 10 &[deg]C/minute. Subsequent to construction of phase diagrams, solid dispersions consisting of API-polymer compositions representative of different zones in the phase diagrams were spray dried and characterised using DSC, pXRD, TGA, FTIR, DVS and SEM. The stability of these systems was investigated under the following conditions: 25 &[deg]C, desiccated; 25 &[deg]C, 60 % RH; 40 &[deg]C, desiccated; 40 &[deg]C, 60 % RH. Results Endset depression occurred with increasing polymer volume fraction (Figure 1a). In conjunction with this data, Flory-Huggins and Gordon-Taylor theory were applied to construct thermodynamic phase diagrams (Figure 1b). The Flory-Huggins interaction parameter (&[chi]) for naproxen and HPMC AS LF was + 0.80 and + 0.72, for the dynamic and static methods respectively. For naproxen and Kollidon 17 PF, the dynamic data resulted in an interaction parameter of - 1.1 and the isothermal data produced a value of - 2.2. For both systems, the API appeared to be less soluble in the polymer when the dynamic approach was used. Stability studies of spray dried solid dispersions could be used as a means of validating the thermodynamic phase diagrams. Conclusion The thermal analysis method used to collate data has a deterministic effect on the phase diagram produced. This effect should be considered when constructing thermodynamic phase diagrams, as they can be a useful tool in predicting the stability of amorphous solid dispersions.

Academic selection and Northern Ireland

An overview of research and public policy debate on academic selection in Northern Ireland. The chapter examines the outcomes of the major investigation of the effects of the selective system of secondary education published in 2000, including a consideration of comparative evidence collected in Scotland. The paper outlines the debate which followed the publication of the Burns Report and presents the current state of play in policy and practice.

Using interviewer random effects to remove selection bias from HIV prevalence estimates

Background: Selection bias in HIV prevalence estimates occurs if non-participation in testing is correlated with HIV status. Longitudinal data suggests that individuals who know or suspect they are HIV positive are less likely to participate in testing in HIV surveys, in which case methods to correct for missing data which are based on imputation and observed characteristics will produce biased results. Methods: The identity of the HIV survey interviewer is typically associated with HIV testing participation, but is unlikely to be correlated with HIV status. Interviewer identity can thus be used as a selection variable allowing estimation of Heckman-type selection models. These models produce asymptotically unbiased HIV prevalence estimates, even when non-participation is correlated with unobserved characteristics, such as knowledge of HIV status. We introduce a new random effects method to these selection models which overcomes non-convergence caused by collinearity, small sample bias, and incorrect inference in existing approaches. Our method is easy to implement in standard statistical software, and allows the construction of bootstrapped standard errors which adjust for the fact that the relationship between testing and HIV status is uncertain and needs to be estimated. Results: Using nationally representative data from the Demographic and Health Surveys, we illustrate our approach with new point estimates and confidence intervals (CI) for HIV prevalence among men in Ghana (2003) and Zambia (2007). In Ghana, we find little evidence of selection bias as our selection model gives an HIV prevalence estimate of 1.4% (95% CI 1.2% – 1.6%), compared to 1.6% among those with a valid HIV test. In Zambia, our selection model gives an HIV prevalence estimate of 16.3% (95% CI 11.0% - 18.4%), compared to 12.1% among those with a valid HIV test. Therefore, those who decline to test in Zambia are found to be more likely to be HIV positive. Conclusions: Our approach corrects for selection bias in HIV prevalence estimates, is possible to implement even when HIV prevalence or non-participation is very high or very low, and provides a practical solution to account for both sampling and parameter uncertainty in the estimation of confidence intervals. The wide confidence intervals estimated in an example with high HIV prevalence indicate that it is difficult to correct statistically for the bias that may occur when a large proportion of people refuse to test.

On the Assumption of Bivariate Normality in Selection Models: A Copula Approach Applied to Estimating HIV Prevalence

Background: Heckman-type selection models have been used to control HIV prevalence estimates for selection bias when participation in HIV testing and HIV status are associated after controlling for observed variables. These models typically rely on the strong assumption that the error terms in the participation and the outcome equations that comprise the model are distributed as bivariate normal.
Methods: We introduce a novel approach for relaxing the bivariate normality assumption in selection models using copula functions. We apply this method to estimating HIV prevalence and new confidence intervals (CI) in the 2007 Zambia Demographic and Health Survey (DHS) by using interviewer identity as the selection variable that predicts participation (consent to test) but not the outcome (HIV status).
Results: We show in a simulation study that selection models can generate biased results when the bivariate normality assumption is violated. In the 2007 Zambia DHS, HIV prevalence estimates are similar irrespective of the structure of the association assumed between participation and outcome. For men, we estimate a population HIV prevalence of 21% (95% CI = 16%–25%) compared with 12% (11%–13%) among those who consented to be tested; for women, the corresponding figures are 19% (13%–24%) and 16% (15%–17%).
Conclusions: Copula approaches to Heckman-type selection models are a useful addition to the methodological toolkit of HIV epidemiology and of epidemiology in general. We develop the use of this approach to systematically evaluate the robustness of HIV prevalence estimates based on selection models, both empirically and in a simulation study.

On Variable Selection of a Nonlinear Non-parametric System with a Limited Data Set: A Stepwise Algorithm

his paper considers a problem of identification for a high dimensional nonlinear non-parametric system when only a limited data set is available. The algorithms are proposed for this purpose which exploit the relationship between the input variables and the output and further the inter-dependence of input variables so that the importance of the input variables can be established. A key to these algorithms is the non-parametric two stage input selection algorithm.

Spatio-temporal feeding selection of red deer in a mountainous landscape

Understanding the dietary consumption and selection of wild populations of generalist herbivores is hampered by the complex array of factors. Here, we determine the influence of habitat, season, and animal density, sex, and age on the diet consumption and selection of 426 red deer (Cervus elaphus scoticus) culled in Fiordland National Park, New Zealand. Our site differs from studies elsewhere both in habitat (evergreen angiosperm-dominated forests) and the intensity of hunting pressures. We predicted that deer would not consume forage in proportion to its relative availability, and that dietary consumption would change among and within years in response to hunting pressures that would also limit opportunities for age and sex segregation. Using canonical correspondence analysis, we evaluated the relative importance of different drivers of variation in diet consumption assessed from gut content and related these to available forage in the environment. We found that altitude explained the largest proportion of variation in diet consumption, reflecting the ability of deer to alter their consumption and selection in relation to their foraging grounds. Grasses formed a high proportion of the diet consumption, even for deer culled several kilometres from the alpine grasslands. In the winter months, when the alpine grasslands were largely inaccessible, less grass was eaten and deer resorted to woody plants that were avoided in the summer months. Surprisingly, there were no significant dietary differences between adults and juveniles and only subtle differences between the sexes. Sex-based differences in diet consumption are commonly observed in ungulate species and we suggest that they may have been reduced in our study area owing to decreased heterogeneity in available forage as the diversity of palatable species decreased under high deer browsing pressures, or by intense hunting pressure. © 2009 The Authors. Journal compilation © 2009 Ecological Society of Australia.

Cooperative Beamforming and User Selection for Improving the Security of Relay-aided Systems

A relay network in which a source wishes to convey a confidential message to a legitimate destination with the assistance of trusted relays is considered. In particular, cooperative beamforming and user selection techniques are applied to protect the confidential message. The secrecy rate (SR) and secrecy outage probability (SOP) of the network are investigated first, and a tight upper bound for the SR and an exact formula for the SOP are derived. Next, asymptotic approximations for the SR and SOP in the high signal-to-noise ratio (SNR) regime are derived for two different schemes: i) cooperative beamforming and ii) multiuser selection. Further, a new concept of cooperative diversity gain, namely, adapted cooperative diversity gain (ACDG), which can be used to evaluate security level of a cooperative relaying network, is investigated. It is shown that the ACDG of cooperative beamforming is equal to the conventional cooperative diversity gain of traditional multiple-input single-output networks, while the ACDG of the multiuser scenario is equal to that of traditional single-input multiple-output networks.

Tenure-track contract helps self-selection

Tenure-track contract is criticized for curbing the incentives to expend effort after obtaining tenured status. Yet the most productive faculties seem to work on a tenure contract, and schools which aim to employ the best faculty seem to prefer to offer tenure-track contracts to their new recruits. I argue that tenure-track contracts are by construction more attractive to more able freshly minted PhDs, and therefore the observed sorting is rationalizable.

Environmental selection on transcriptome-derived SNPs in a high gene flow marine fish, the Atlantic herring (Clupea harengus)

High gene flow is considered the norm for most marine organisms and is expected to limit their ability to adapt to local environments. Few studies have directly compared the patterns of differentiation at neutral and selected gene loci in marine organisms. We analysed a transcriptome-derived panel of 281 SNPs in Atlantic herring (Clupea harengus), a highly migratory small pelagic fish, for elucidating neutral and selected genetic variation among populations and to identify candidate genes for environmental adaptation. We analysed 607 individuals from 18 spawning locations in the northeast Atlantic, including two temperature clines (5-12 °C) and two salinity clines (5-35‰). By combining genome scan and landscape genetic analyses, four genetically distinct groups of herring were identified: Baltic Sea, Baltic-North Sea transition area, North Sea/British Isles and North Atlantic; notably, samples exhibited divergent clustering patterns for neutral and selected loci. We found statistically strong evidence for divergent selection at 16 outlier loci on a global scale, and significant correlations with temperature and salinity at nine loci. On regional scales, we identified two outlier loci with parallel patterns across temperature clines and five loci associated with temperature in the North Sea/North Atlantic. Likewise, we found seven replicated outliers, of which five were significantly associated with low salinity across both salinity clines. Our results reveal a complex pattern of varying spatial genetic variation among outlier loci, likely reflecting adaptations to local environments. In addition to disclosing the fine scale of local adaptation in a highly vagile species, our data emphasize the need to preserve functionally important biodiversity.

Star-planet interactions and selection effects from planet detection methods

Planets may have effects on their host stars by tidal or magnetic interaction. Such star-planet interactions are thought to enhance the activity level of the host star. However, stellar activity also affects the sensitivity of planet detection methods. Samples of planet-hosting stars which are investigated for such star-planet interactions are therefore subject to strong selection effects which need to be taken into account.

Signal Reliability Improvement Using Selection Combining Based Macro-Diversity for Off-Body Communications At 868 MHz

This paper investigates the potential improvement in signal reliability for outdoor short-range off-body communications channels at 868 MHz using the macro-diversity offered by multiple co-located base stations. In this study, ten identical hypothetical base stations were positioned equidistantly around the perimeter of a rectangle of length 6.67 m and width 3.3 m. A body worn node was placed on the central chest region of an adult male. Five scenarios, each considering different user trajectories, were then analyzed to test the efficacy of using macro-diversity when the desired link is subject to shadowing caused by the human body. A number of selection combining based macro-diversity configurations consisting of four and then ten base stations were considered. It was found that using a macro-diversity system consisting of four base stations (or equivalently signal branches), a maximum diversity gain of 22.5 dB could be obtained while implementing a 10-base station setup this figure could be improved to 25.2 dB.