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 general model for MAC generation using direct injection

This paper presents a model for generating a MAC tag by injecting the input message directly into the internal state of a nonlinear filter generator. This model generalises a similar model for unkeyed hash functions proposed by Nakano et al. We develop a matrix representation for the accumulation phase of our model and use it to analyse the security of the model against man-in-the-middle forgery attacks based on collisions in the final register contents. The results of this analysis show that some conclusions of Nakano et al regarding the security of their model are incorrect. We also use our results to comment on several recent MAC proposals which can be considered as instances of our model and specify choices of options within the model which should prevent the type of forgery discussed here. In particular, suitable initialisation of the register and active use of a secure nonlinear filter will prevent an attacker from finding a collision in the final register contents which could result in a forged MAC.

General belongingness, workplace belongingness, and depressive symptoms

Research has shown that a strong relationship exists between belongingness and depressive symptoms; however, the contribution of specific types of belongingness remains unknown. Participants (N=369) completed the sense of belonging instrument, psychological sense of organizational membership, and the depression scale of the depression anxiety stress scales. Factor analysis demonstrated that workplace and general belongingness are distinct constructs. When regressed onto depressive symptoms, these belongingness types made independent contributions, together accounting for 45% of variance, with no moderation effects evident. Hence, general belongingness and specific workplace belongingness appear to have strong additive links to depressive symptoms. These results add support to the belongingness hypothesis and sociometer theory and have significant implication for depression prevention and treatment

Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia

Context: The benefits of high serum levels of 25-hydroxyvitamin D [25(OH)D] are unclear. Trials are needed to establish an appropriate evidence base. Objective: We plan to conduct a large-scale trial of vitamin D supplementation for the reduction of cancer incidence and overall mortality and report here the methods and results of a pilot trial established to inform its design. Design: Pilot D-Health was a randomized trial carried out in a general community setting with 12 months intervention and follow-up. Participants: Participants were 60- to 84-yr-old residents of one of the four eastern Australian states who did not have any vitamin D-related disorders and who were not taking more than 400 IU supplementary vitamin D per day. A total of 644 participants were randomized, and 615 completed the study (two persons withdrew because of nonserious adverse events). Interventions: The interventions were monthly doses of placebo or 30,000 or 60,000 IU vitamin D3. Main Outcomes: The main outcomes were the recruitment rate and changes in serum 25(OH)D. Results: Ten percent of those approached were recruited. At baseline, the mean 25(OH)D was 42 nmol/liter in all three study arms. The mean change in 25(OH)D in the placebo group was 0.12 nmol/liter, compared with changes of 22 and 36 nmol/liter in the 30,000- and 60,000-IU groups, respectively. Conclusions: The D-Health pilot has shown that a large trial is feasible in Australia and that a dose of 2000 IU/d will be needed to ensure that a large proportion of the population reaches the target serum 25(OH)D level. Copyright © 2012 by The Endocrine Society.

General order conditions for stochastic Runge-Kutta methods for both commuting and non-commuting stochastic ordinary differential equation systems

In many modeling situations in which parameter values can only be estimated or are subject to noise, the appropriate mathematical representation is a stochastic ordinary differential equation (SODE). However, unlike the deterministic case in which there are suites of sophisticated numerical methods, numerical methods for SODEs are much less sophisticated. Until a recent paper by K. Burrage and P.M. Burrage (1996), the highest strong order of a stochastic Runge-Kutta method was one. But K. Burrage and P.M. Burrage (1996) showed that by including additional random variable terms representing approximations to the higher order Stratonovich (or Ito) integrals, higher order methods could be constructed. However, this analysis applied only to the one Wiener process case. In this paper, it will be shown that in the multiple Wiener process case all known stochastic Runge-Kutta methods can suffer a severe order reduction if there is non-commutativity between the functions associated with the Wiener processes. Importantly, however, it is also suggested how this order can be repaired if certain commutator operators are included in the Runge-Kutta formulation. (C) 1998 Elsevier Science B.V. and IMACS. All rights reserved.

What relationships exist between general self efficacy, locus of control and the nursing practice environment and caring efficacy and job satisfaction?

Research Question: What relationships exist between general self efficacy, locus of control and the nursing practice environment and caring efficacy and job satisfaction? Background: Important characteristics of current nursing practice include nurses having the ability to develop and continue therapeutic relationships with patients, nurses having autonomy and control over the practice environment and nurses having more involvement in decision making. In addition, employee satisfaction is enhanced when organisations offer access to authority. Despite this, nurses continue to complain of feeling powerless in their ability to make decisions. Sample: The study population and criteria for selection included Registered Nurses in Australia who were at the time members of an Australian professional and industrial organisation. Methods: A cross-sectional survey was undertaken. Data analysis was conducted using descriptive and bivariate statistics, and structural equation modeling. Results: The model fit the data well (χ² = 2.3594, χ²/df = 2.3594 and CFI = 0.9987). Twenty four percent of variation in caring efficacy (CE) can be accounted for by general self-efficacy (GSE); work locus of control (WLC) and practice environment (PE) and 62% of the variation in job satisfaction (JS) can be accounted for by GSE, WLC and PE. All pathways were found to be significant except PE to CE. GSE positively explained CE (β = 0.38). WLC was negatively related to CE i.e., as CE scores increased WLC scores decreased (β = -0.23). Further testing of the model found CE was positively related to GSE (βZ = 0.38, p < 0.001) and negatively related to WLC (βZ = - 0.23, p = 0.001). PE was not significantly associated with CE (βZ = - 0.01, p = 0.85). JS was explained by PE, which was positively related (βZ = 0.69, p = < 0.001); GSE which was negatively related (βZ - 0 .09, p < 0.001) and WLC, which was also negatively related (βZ = - 0.20, p < 0.001). Implications for Practice Nursing and organisational leaders should ensure the development of strategies for professional development and orientation programmes which may enhance nurses’ ability to develop caring relationships and express caring behaviours to their patients and as a result improve organisational and patient outcomes. Nursing shortages and turnover rates are associated with job satisfaction and the nursing practice environment. Improving the nursing environment can produce benefits to the health system such as better job satisfaction, improved workforce retention and better patient outcomes.

General trajectory prior for non-rigid reconstruction

Trajectory basis Non-Rigid Structure From Motion (NRSFM) currently faces two problems: the limit of reconstructability and the need to tune the basis size for different sequences. This paper provides a novel theoretical bound on 3D reconstruction error, arguing that the existing definition of reconstructability is fundamentally flawed in that it fails to consider system condition. This insight motivates a novel strategy whereby the trajectory's response to a set of high-pass filters is minimised. The new approach eliminates the need to tune the basis size and is more efficient for long sequences. Additionally, the truncated DCT basis is shown to have a dual interpretation as a high-pass filter. The success of trajectory filter reconstruction is demonstrated quantitatively on synthetic projections of real motion capture sequences and qualitatively on real image sequences.

Menopause as a long-term risk to health : implications of general practitioner accounts of prevention for women’s choice and decision-making

Over the past two decades medical researchers and modernist feminist researchers have contested the meaning of menopause. In this article we examine various meanings of menopause in major medical and feminist literature and the construction of menopause in a semi-structured interview study of general practitioners in rural South Australia. Three discursive themes are identified in these interviews; (i) the hormonal menopause – symptoms, risk, prevention; (ii) the informed menopausal woman; and (iii) decision-making and hormone replacement therapy. By using the discourse of prevention, general practitioners construct menopause in relation to women's health care choices, empowerment and autonomy. We argue that the ways in which these concepts are deployed by general practitioners in this study produces and constrains the options available to women. The implications of these general practitioner accounts are discussed in relation to the proposition that medical and feminist descriptions of menopause posit alternative but equally-fixed truths about menopause and their relationship with the range of responses available to women at menopause. Social and cultural explanations of disease causality (c.f.Germov 1998, Hardey 1998) are absent from the new menopause despite their being an integral part of the framework of the women's health movement and health promotion drawn on by these general practitioners. Further, the shift of responsibility for health to the individual woman reinforces practice claims to empower women, but oversimplifies power relations and constructs menopause as a site of self-surveillance. The use of concepts from the women's health movement and health promotion have nevertheless created change in both the positioning of women as having ‘choices’ and the positioning of some general practitioners in terms of greater information provision to women and an attention to the woman's autonomy. In conclusion, we propose that a new menopause has evolved from a discursive shift in medicine and that there exists within this new configuration, claiming the empowerment of women as an integral part of health care for menopause, the possibility for change in medical practice which will broaden, strengthen, and maintain this position.

Nurse-led trials of medical devices: General principles and good practice

Aim To provide an overview of key governance matters relating to medical device trials and practical advice for nurses wishing to initiate or lead them. Background Medical device trials, which are formal research studies that examine the benefits and risks of therapeutic, non-drug treatment medical devices, have traditionally been the purview of physicians and scientists. The role of nurses in medical device trials historically has been as data collectors or co-ordinators rather than as principal investigators. Nurses more recently play an increasing role in initiating and leading medical device trials. Review Methods A review article of nurse-led trials of medical devices. Discussion Central to the quality and safety of all clinical trials is adherence to the International Conference on Harmonization Guidelines for Good Clinical Practice, which is the internationally-agreed standard for the ethically- and scientifically-sound design, conduct and monitoring of a medical device trial, as well as the analysis, reporting and verification of the data derived from that trial. Key considerations include the class of the medical device, type of medical device trial, regulatory status of the device, implementation of standard operating procedures, obligations of the trial sponsor, indemnity of relevant parties, scrutiny of the trial conduct, trial registration, and reporting and publication of the results. Conclusion Nurse-led trials of medical devices are demanding but rewarding research enterprises. As nursing practice and research increasingly embrace technical interventions, it is vital that nurse researchers contemplating such trials understand and implement the principles of Good Clinical Practice to protect both study participants and the research team.

Advice to consult a general medical practitioner in Western Australia : Could it be cancer?

Background: Many people will consult a medical practitioner about lower bowel symptoms, and the demand for access to general practitioners (GPs) is growing. We do not know if people recognise the symptoms of lower bowel cancer when advising others about the need to consult a doctor. A structured vignette survey was conducted in Western Australia. Method: Participants were recruited from the waiting rooms at five general practices. Respondents were invited to complete self-administered questionnaires containing nine vignettes chosen at random from a pool of 64 based on six clinical variables. Twenty-seven vignettes described high-risk bowel cancer scenarios. Respondents were asked if they would recommend a medical consultation for the case described and whether they believed the scenario was a cancer presentation. Logistic regression was used to estimate the independent effects of each variable on the respondent's judgement. Two-hundred and sixty-eight completed responses were collected over eight weeks. Results: The majority (61%) of respondents were female, aged 40 years and older. A history of rectal bleeding, six weeks of symptoms, and weight loss independently increased the odds of recommending a consultation with a medical practitioner by a factor of 7.64, 4.11 and 1.86, respectively. Most cases that were identified as cancer (75.2%) would not be classified as such on current research evidence. Factors that predict recognition of cancer presentations include rectal bleeding, weight loss and diarrhoea.

General practice patients in the emergency department

One of the mysteries of public policy is that at times the public discourse settles on a perspective that is based on flimsy or even contradictory evidence. One such discussion relates to the factors that contribute to the congestion of hospital emergency departments (EDs) in Australia.