A general method to determine sampling windows for nonlinear mixed effects models with an application to population pharmacokinetic studies

Optimal design methods have been proposed to determine the best sampling times when sparse blood sampling is required in clinical pharmacokinetic studies. However, the optimal blood sampling time points may not be feasible in clinical practice. Sampling windows, a time interval for blood sample collection, have been proposed to provide flexibility in blood sampling times while preserving efficient parameter estimation. Because of the complexity of the population pharmacokinetic models, which are generally nonlinear mixed effects models, there is no analytical solution available to determine sampling windows. We propose a method for determination of sampling windows based on MCMC sampling techniques. The proposed method attains a stationary distribution rapidly and provides time-sensitive windows around the optimal design points. The proposed method is applicable to determine sampling windows for any nonlinear mixed effects model although our work focuses on an application to population pharmacokinetic models.

A controlled, longitudinal study of home visits compared to telephone contacts to prevent early childhood caries

Background Home visits (HV) provide excellent opportunities for health promotion. Aim This longitudinal study compared the effects of HV and telephone contacts (TC) in preventing early childhood caries (ECC) and colonisation of mutans streptococci (MS) and lactobacilli (LB) from 0 to 24 months. Design A total of 325 children were recruited from community health centres at mean age of 42 days, and randomly assigned to receive either HV or TC. A total of 188 children completed three, 6 monthly HV, and another 58 had three, 6 monthly TC. An additional 40 age-matched children from childcare facilities served as reference controls (RC). At 24 months, all groups were examined at a community dental clinic. Results At 24 months, three HV children of 188 (1.5%) had caries, compared to four TC of 58 (6.8%) and nine RC of 40 (22.5%) (P < 0.001 for HV versus RC; P = 0.05 for HV versus TC and P = 0.03 for TC versus RC). There were also more children with MS in the TC (47%) and RC (35%) compared to HV (28%) group (P = 0.01 and P = 0.02). Conclusions Home visits and telephone contacts conducted 6 monthly from birth are effective in reducing ECC prevalence by 24 months.

Inhibition of maize streak virus (MSV) replication by transient and transgenic expression of MSV replication-associated protein mutants

Maize streak disease is a severe agricultural problem in Africa and the development of maize genotypes resistant to the causal agent, Maize streak virus (MSV), is a priority. A transgenic approach to engineering MSV-resistant maize was developed and tested in this study. A pathogen-derived resistance strategy was adopted by using targeted deletions and nucleotide-substitution mutants of the multifunctional MSV replication-associated protein gene (rep). Various rep gene constructs were tested for their efficacy in limiting replication of wild-type MSV by co-bombardment of maize suspension cells together with an infectious genomic clone of MSV and assaying replicative forms of DNA by quantitative PCR. Digitaria sanguinalis, an MSV-sensitive grass species used as a model monocot, was then transformed with constructs that had inhibited virus replication in the transient-expression system. Challenge experiments using leafhopper-transmitted MSV indicated significant MSV resistance - from highly resistant to immune - in regenerated transgenic D. sanguinalis lines. Whereas regenerated lines containing a mutated full-length rep gene displayed developmental and growth defects, those containing a truncated rep gene both were fertile and displayed no growth defects, making the truncated gene a suitable candidate for the development of transgenic MSV-resistant maize. © 2007 SGM.

Enriching students’ intellectual diet through inquiry based learning

Traditionally, Science education has stressed the importance of teaching students to conduct ‘scientific inquiry’, with the main focus being the experimental model of inquiry used by real world scientists. Current educational approaches using constructivist pedagogy recognise the value of inquiry as a method for promoting the development of deep understanding of discipline content. A recent Information Learning Activity undertaken by a Grade Eight Science class was observed to discover how inquiry based learning is implemented in contemporary Science education. By analysing student responses to questionnaires and assessment task outcomes, the author was able to determine the level of inquiry inherent in the activity and how well the model supported student learning and the development of students’ information literacy skills. Although students achieved well overall, some recommendations are offered that may enable teachers to better exploit the learning opportunities provided by inquiry based learning. Planning interventions at key stages of the inquiry process can assist students to learn more effective strategies for dealing with cognitive and affective challenges. Allowing students greater input into the selection of topic or focus of the activity may encourage students to engage more deeply with the learning task. Students are likely to experience greater learning benefit from access to developmentally appropriate resources, increased time to explore topics and multiple opportunities to undertake information searches throughout the learning activity. Finally, increasing the cognitive challenge can enhance both the depth of students’ learning and their information literacy skills.

In vitro physical stimulation of tissue-engineered and native cartilage

Because of the limited availability of donor cartilage for resurfacing defects in articular surfaces, there is tremendous interest in the in vitro bioengineering of cartilage replacements for clinical applications. However, attaining mechanical properties in engineered cartilaginous constructs that approach those of native cartilage has not been previously achieved when constructs are cultured under free-swelling conditions. One approach toward stimulating the development of constructs that are mechanically more robust is to expose them to physical environments that are similar, in certain ways, to those encountered by native cartilage. This is a strategy motivated by observations in numerous short-term experiments that certain mechanical signals are potent stimulators of cartilage metabolism. On the other hand, excess mechanical loading can have a deleterious effect on cartilage. Culture conditions that include a physical stimulation component are made possible by the use of specialized bioreactors. This chapter addresses some of the issues involved in using bioreactors as integral components of cartilage tissue engineering and in studying the physical regulation of cartilage. We first consider the generation of cartilaginous constructs in vitro. Next we describe the rationale and design of bioreactors that can impart either mechanical deformation or fluid-induced mechanical signals.

A Reliability test system for educational purposes-basic results

A set of basic reliability indices at the generation and composite generation and transmission levels for a small reliability test system are presented. The test system and the results presented have evolved from reliability research and teaching programs. The indices presented are for fundamental reliability applications which should be covered in a power system reliability teaching program. The RBTS test system and the basic indices provide a valuable reference for faculty and students engaged in reliability teaching and research

Glider path-planning for optimal sampling of mesocale eddies

Ocean gliders constitute an important advance in the highly demanding ocean monitoring scenario. Their effciency, endurance and increasing robustness make these vehicles an ideal observing platform for many long term oceanographic applications. However, they have proved to be also useful in the opportunis-tic short term characterization of dynamic structures. Among these, mesoscale eddies are of particular interest due to the relevance they have in many oceano-graphic processes.

A vibrational spectroscopic study of philipsbornite PbAl3(AsO4)2(OH)5⋅H2O-molecular structural implications and relationship to the crandallite subgroup arsenates

The presence of arsenic in the environment is a hazard. The accumulation of arsenate by a range of cations in the formation of minerals provides a mechanism for the remediation of arsenate contamination. The formation of the crandallite group of minerals provides a mechanism for arsenate accumulation. Among the crandallite minerals are philipsbornite, arsenocrandallite and arsenogoyazite. Raman spectroscopy complimented with infrared spectroscopy has enabled aspects of the structure of philipsbornite to be studied. The Raman spectrum of philipsbornite displays an intense band at around 840 cm−1 attributed to the overlap of the symmetric and antisymmetric stretching modes. Raman bands observed at 325, 336, 347, 357, 376 and 399 cm−1 are assigned to the ν2 (AsO4)3− symmetric bending vibration (E) and to the ν4 bending vibration (F2). The observation of multiple bending modes supports the concept of a reduction in symmetry of the arsenate anion in philipsbornite. Evidence for phosphate in the mineral is provided. By using an empirical formula, hydrogen bond distances for the OH units in philipsbornite of 2.8648 Å, 2.7864 Å, 2.6896 Å cm−1 and 2.6220 were calculated.

Reverse biased Schottky contact hydrogen sensors based on Pt∕nanostructured ZnO∕SiC

Pt/nanostructured ZnO/SiC Schottky contact devices were fabricated and characterized for hydrogen gas sensing. These devices were investigated in reverse bias due to greater sensitivity, which attributes to the application of nanostructured ZnO. The current-voltage (I-V) characteristics of these devices were measured in different hydrogen concentrations. Effective change in the barrier height for 1% hydrogen was calculated as 27.06 meV at 620°C. The dynamic response of the sensors was also investigated and a voltage shift of 325 mV was recorded at 620°C during exposure to 1% hydrogen in synthetic air.

The 'Stakeholder Approach' to corporate governance and regulation : an assessment

The framework by which organizations are governed has been changed. A reason for this change is related with the force of stakeholders that compel the political power and the business society to review the ways in which companies are governed. Stakeholder thinking has gradually put this change at the center of research into business and society relations. Based on the stakeholder thinking, the corporate regulation framework has extended a new dimension in the business and society interface. This article assesses these issues.

Exact and approximate Bayesian inference for low count time series models with intractable likelihoods

In this paper we present a new simulation methodology in order to obtain exact or approximate Bayesian inference for models for low-valued count time series data that have computationally demanding likelihood functions. The algorithm fits within the framework of particle Markov chain Monte Carlo (PMCMC) methods. The particle filter requires only model simulations and, in this regard, our approach has connections with approximate Bayesian computation (ABC). However, an advantage of using the PMCMC approach in this setting is that simulated data can be matched with data observed one-at-a-time, rather than attempting to match on the full dataset simultaneously or on a low-dimensional non-sufficient summary statistic, which is common practice in ABC. For low-valued count time series data we find that it is often computationally feasible to match simulated data with observed data exactly. Our particle filter maintains $N$ particles by repeating the simulation until $N+1$ exact matches are obtained. Our algorithm creates an unbiased estimate of the likelihood, resulting in exact posterior inferences when included in an MCMC algorithm. In cases where exact matching is computationally prohibitive, a tolerance is introduced as per ABC. A novel aspect of our approach is that we introduce auxiliary variables into our particle filter so that partially observed and/or non-Markovian models can be accommodated. We demonstrate that Bayesian model choice problems can be easily handled in this framework.

Refined plastic hinge analysis of steel frame structures comprising non-compact sections : II : verification

Application of "advanced analysis" methods suitable for non-linear analysis and design of steel frame structures permits direct and accurate determination of ultimate system strengths, without resort to simplified elastic methods of analysis and semi-empirical specification equations. However, the application of advanced analysis methods has previously been restricted to steel frames comprising only compact sections that are not influenced by the effects of local buckling. A refined plastic hinge method suitable for practical advanced analysis of steel frame structures comprising non-compact sections is presented in a companion paper. The method implicitly accounts for the effects of gradual cross-sectional yielding, longitudinal spread of plasticity, initial geometric imperfections, residual stresses, and local buckling. The accuracy and precision of the method for the analysis of steel frames comprising non-compact sections is established in this paper by comparison with a comprehensive range of analytical benchmark frame solutions. The refined plastic hinge method is shown to be more accurate and precise than the conventional individual member design methods based on elastic analysis and specification equations.

Predicate encryption for multi-inner-products

Predicate encryption is a new primitive that supports flexible control over access to encrypted data. We study predicate encryption systems, evaluating a wide class of predicates. Our systems are more expressive than the existing attribute-hiding systems in the sense that the proposed constructions support not only all existing predicate evaluations but also arbitrary conjunctions and disjunctions of comparison and subset queries. Toward our goal, we propose encryption schemes supporting multi-inner-product predicate and provide formal security analysis. We show how to apply the proposed schemes to achieve all those predicate evaluations.

Association of estrogen receptor and glucocorticoid receptor gene polymorphisms with sporadic breast cancer

We have utilized a cross-sectional association approach to investigate sporadic breast cancer. Polymorphisms in 2 candidate genes, ESRalpha and GRL, were examined in an unrelated breast cancer-affected and age-matched control population. Several polymorphic regions within the ESRalpha gene have been identified, and some alleles of these polymorphisms have been found to occur at increased levels in breast-cancer patients. Additionally, variations in GRL have the potential to disrupt cell transcription and may be associated with cancer formation. We analyzed 3 polymorphisms, from codons 10 (TCT to TCC), 325 (CCC to CCG) and 594 (ACA to ACG) of ESRalpha, and a highly polymorphic dinucleotide repeat, D5S207, located within 200 kb of the GRL. When allelic frequencies of the codon 594 (exon 8) ESR polymorphism were compared between affected and unaffected populations, a significant difference was observed (p = 0.005). Results from the D5S207 dinucleotide repeat located near GRL also indicated a significant difference between the tested case and control populations (p = 0.001). Allelic frequencies of the codon 10 and codon 325 ESR polymorphisms were not significantly different between populations (p = 0.152 and 0.181, respectively). Our results indicate that specific alleles of the ESR gene (alpha subtype) and a marker for the GRL gene locus are associated with sporadic breast-cancer development in the tested Caucasian population and justify further investigation of the role of these and other nuclear steroid receptors in the etiology of breast cancer.