Estimating mixed-effects differential equation models

Ordinary differential equations (ODEs) are popular tools for modeling complicated dynamic systems in many areas. When multiple replicates of measurements are available for the dynamic process, it is of great interest to estimate mixed-effects in the ODE model for the process. We propose a semiparametric method to estimate mixed-effects ODE models. Rather than using the ODE numeric solution directly, which requires providing initial conditions, this method estimates a spline function to approximate the dynamic process using smoothing splines. A roughness penalty term is defined using the ODEs, which measures the fidelity of the spline function to the ODEs. The smoothing parameter, which controls the trade-off between fitting the data and maintaining fidelity to the ODEs, can be specified by users or selected objectively by generalized cross validation. The spline coefficients, the ODE random effects, and the ODE fixed effects are estimated in three nested levels of optimization. Two simulation studies show that the proposed method obtains good estimates for mixed-effects ODE models. The semiparametric method is demonstrated with an application of a pharmacokinetic model in a study of HIV combination therapy.     

Measuring well-being dispersion on discrete rating scales

Social Indicators Research - Average levels of well-being across countries and time periods have been reported widely over the years as one of the measures that go beyond the Gross Domestic...     

‘Ties that Bind’: A Transactional Approach to Social Capital

Abstract

The last decade has witnessed a renewed interest in the concept of social capital. However, much confusion still exists about the exact meaning of social capital. Thus, to create a foundation for future studies on social capital, this article develops a conceptual and theoretical framework to depict the stocks and flows of social capital. As such, it defines social capital formation in transactional terms so as to exploit fully the capital analogy used to characterise social capital and to place the concept of social capital on par with fixed, financial and human capital.     

The behavioral response of emerging pine snakes (<Emphasis Type="Italic">Pituophis melanoleucus</Emphasis>) to people: implications for survival and protection

Considerable attention has been devoted to the effects of people on birds and mammals, usually in wilderness areas. In contrast, human disturbance of reptiles has largely been ignored. Many reptiles, such as snakes, are hard to conserve because they are difficult to locate and protect. The young are especially vulnerable to predators when they first hatch and must emerge from nest sites. In this paper, the response of pine snake (Pituophis melanoleucus) hatchlings to the presence and handling by people was observed in the laboratory and in the field. Pine snakes lay their eggs in underground burrows in open sandy pine barrens, and the hatchlings push their way to the surface to emerge. Hatchlings that were visually-disturbed or touched as they emerged returned immediately to their tunnels and nests, and required more time to re-emerge than did their siblings that were not visually-disturbed or touched during their initial disturbance. In nature, undisturbed pine snakes showed similar re-emergence times to those from the laboratory, and disturbed snakes required longer to re-emerge. These data suggest that in nature even the presence of people in nesting areas of pine snakes would lengthen the time the young are in burrows, exposing them to additional threats from predators. This suggests that parks or nature reserves with vulnerable snake populations should restrict human disturbance during the period when young snakes are emerging from their nests. Field observations indicate that a set-back distance of more than 12 m from known nesting areas is essential to protect emerging hatchlings.     

Effects of off-road vehicles on reproductive success of pine snakes (<Emphasis Type="Italic">Pituophus melanoleucus</Emphasis>) in the New Jersey pinelands

Considerable attention has been devoted to the effects of people and their vehicles on birds and mammals, but possible effects on reptiles in populated areas have received less attention. Moreover, the effects of human activities on reptile reproductive success itself has been harder to demonstrate. This paper examines the effect of management of off-road vehicles in New Jersey’s pinelands on the reproductive success of pine snakes (Pituophus melanoleucus) from 1986 to 2005. We used the percentage of snakes in each hibernaculum that were young of the year (hatchlings) as an indicator of reproductive success, and compared this percent for five hibernacula that were in an area with varying degrees of off-road vehicle (ORV) disturbance, with 12 hibernacula in areas with no ORV disturbances (reference sites). This percent took into account differences in absolute numbers from one location to another, and over time due to hibernacula destruction (by people or predators) and natural variations (food supply). The ORV pressure in the pinelands is intense because it lies within the most densely populated urban area in the United States. Although the number of snakes in the reference hibernacula varied over the years from 46 to 63, the percent of young in these hibernacula did not vary significantly over the 20 year period (21–29%). In contrast, the percent-young in the disturbed sites differed significantly in years without ORV disturbance (28%) compared to those with ORV disturbance (15 and 16%, P < 0.01). Further, there were no differences between the percent of young in the reference sites and those in the disturbed site in years without ORV disturbance. ORV disturbance ceased only with the creation of large dirt berms coupled with fences that could not be easily broken. These data indicate the importance of having detailed population data on pine snakes in hibernacula, on ORV use (or indications of such use), and of managing ORV use to protect sensitive populations. Maintenance of healthy pine snake populations in urban areas may require continued adaptive management.     

Unpredictable endocrinology of the menopause transition: clinical, diagnostic and management implications

The approach to menopause can be divided into the early (E) and late (L) menopausal transitions (MT) on the basis of menstrual irregularity (EMT) and subsequent observation of at least one episode of 60 or more days amenorrhoea (LMT). In total, 40-60% of cycles in the LMT are anovulatory, often with low oestradiol (E2) and high follicle-stimulating hormone concentrations. The ovulatory cycles have variable endocrine characteristics, none of which is specific to EMT or LMT. Hormonal measurements of FSH and E2 are thus of little diagnostic value because of their unpredictable variability. Symptoms during the transitions may result from high or low E2 and can often be satisfactorily managed with low-dose oral contraceptives, which suppress pituitary-ovarian function.     

The use of external controls: To what extent can it currently be recommended?

With more and better clinical data being captured outside of clinical studies and greater data sharing of clinical studies, external controls may become a more attractive alternative to randomized clinical trials (RCTs). Both industry and regulators recognize that in situations where a randomized study cannot be performed, external controls can provide the needed contextualization to allow a better interpretation of studies without a randomized control. It is also agreed that external controls will not fully replace RCTs as the gold standard for formal proof of efficacy in drug development and the yardstick of clinical research. However, it remains unclear in which situations conclusions about efficacy and a positive benefit/risk can reliably be based on the use of an external control. This paper will provide an overview on types of external control, their applications and the different sources of bias their use may incur, and discuss potential mitigation steps. It will also give recommendations on how the use of external controls can be justified.     

Low socioeconomic status increases effects of negative life events on antenatal anxiety and depression

Problem

Low socioeconomic status and prior negative life events are documented risk factors for antenatal anxiety and depression, preterm birth and birth weight. We aimed to asses whether the adverse effects of prior negative life events increase with lower socioeconomic status and which aspects of socioeconomic status are most relevant.

Resident status influences perceptions about beach resource valuation and restoration

Urban Ecosystems - Sandy beaches represent typical destinations for recreation and tourism worldwide, as well as being a lifestyle for people living along the shore. In the Northeastern United...