Epidemiological, social, diagnostic and economic evaluation of population screening for genital chlamydial infection

OBJECTIVES: To investigate epidemiological, social, diagnostic and economic aspects of chlamydia screening in non-genitourinary medicine settings. METHODS: Linked studies around a cross-sectional population-based survey of adult men and women invited to collect urine and (for women) vulvovaginal swab specimens at home and mail these to a laboratory for testing for Chlamydia trachomatis. Specimens were used in laboratory evaluations of an amplified enzyme immunoassay (PCE EIA) and two nucleic acid amplification tests [Cobas polymerase chain reaction (PCR), Becton Dickinson strand displacement amplification (SDA)]. Chlamydia-positive cases and two negative controls completed a risk factor questionnaire. Chlamydia-positive cases were invited into a randomised controlled trial of partner notification strategies. Samples of individuals testing negative completed psychological questionnaires before and after screening. In-depth interviews were conducted at all stages of screening. Chlamydia transmission and cost-effectiveness of screening were investigated in a transmission dynamic model. SETTING AND PARTICIPANTS: General population in the Bristol and Birmingham areas of England. In total, 19,773 women and men aged 16-39 years were randomly selected from 27 general practice lists. RESULTS: Screening invitations reached 73% (14,382/19,773). Uptake (4731 participants), weighted for sampling, was 39.5% (95% CI 37.7, 40.8%) in women and 29.5% (95% CI 28.0, 31.0%) in men aged 16-39 years. Chlamydia prevalence (219 positive results) in 16-24 year olds was 6.2% (95% CI 4.9, 7.8%) in women and 5.3% (95% CI 4.4, 6.3%) in men. The case-control study did not identify any additional factors that would help target screening. Screening did not adversely affect anxiety, depression or self-esteem. Participants welcomed the convenience and privacy of home-sampling. The relative sensitivity of PCR on male urine specimens was 100% (95% CI 89.1, 100%). The combined relative sensitivities of PCR and SDA using female urine and vulvovaginal swabs were 91.8% (86.1, 95.7, 134/146) and 97.3% (93.1, 99.2%, 142/146). A total of 140 people (74% of eligible) participated in the randomised trial. Compared with referral to a genitourinary medicine clinic, partner notification by practice nurses resulted in 12.4% (95% CI -3.7, 28.6%) more patients with at least one partner treated and 22.0% (95% CI 6.1, 37.8%) more patients with all partners treated. The health service and patients costs (2005 prices) of home-based postal chlamydia screening were 21.47 pounds (95% CI 19.91 pounds, 25.99) per screening invitation and 28.56 pounds (95% CI 22.10 pounds, 30.43) per accepted offer. Preliminary modelling found an incremental cost-effectiveness ratio (2003 prices) comparing screening men and women annually to no screening in the base case of 27,000 pounds/major outcome averted at 8 years. If estimated screening uptake and pelvic inflammatory disease incidence were increased, the cost-effectiveness ratio fell to 3700 pounds/major outcome averted. CONCLUSIONS: Proactive screening for chlamydia in women and men using home-collected specimens was feasible and acceptable. Chlamydia prevalence rates in men and women in the general population are similar. Nucleic acid amplification tests can be used on first-catch urine specimens and vulvovaginal swabs. The administrative costs of proactive screening were similar to those for opportunistic screening. Using empirical estimates of screening uptake and incidence of complications, screening was not cost-effective.

Resolving the tragedy of the commons: the feedback between intraspecific conflict and population density

Competition and conflict among individuals can favour exploitative strategies that undermine the common good. Theory suggests that this can lead to a tragedy of the commons and ultimately population extinction, a phenomenon known as evolutionary suicide. Here, I present a model of the evolutionary tragedy of the commons that explicitly considers the population dynamics where individuals invest in individually costly competitive traits. In the simplest form, this supports the notion that selection for high levels of conflict can cause evolutionary suicide. However, as competition comes with survival and fecundity costs, a feedback between the investment in competition and population density can act to reduce the level of conflict and prevent the population from going extinct. This suggests that the interaction between population ecology and the evolution of competition and conflict among individuals may be an important mechanism in resolving the level of competition and conflict among individuals.

Population pharmacokinetics of sevoflurane in conjunction with the AnaConDa: toward target-controlled infusion of volatiles into the breathing system

BACKGROUND: The Anesthetic Conserving Device (AnaConDa) uncouples delivery of a volatile anesthetic (VA) from fresh gas flow (FGF) using a continuous infusion of liquid volatile into a modified heat-moisture exchanger capable of adsorbing VA during expiration and releasing adsorbed VA during inspiration. It combines the simplicity and responsiveness of high FGF with low agent expenditures. We performed in vitro characterization of the device before developing a population pharmacokinetic model for sevoflurane administration with the AnaConDa, and retrospectively testing its performance (internal validation). MATERIALS AND METHODS: Eighteen females and 20 males, aged 31-87, BMI 20-38, were included. The end-tidal concentrations were varied and recorded together with the VA infusion rates into the device, ventilation and demographic data. The concentration-time course of sevoflurane was described using linear differential equations, and the most suitable structural model and typical parameter values were identified. The individual pharmacokinetic parameters were obtained and tested for covariate relationships. Prediction errors were calculated. RESULTS: In vitro studies assessed the contribution of the device to the pharmacokinetic model. In vivo, the sevoflurane concentration-time courses on the patient side of the AnaConDa were adequately described with a two-compartment model. The population median absolute prediction error was 27% (interquartile range 13-45%). CONCLUSION: The predictive performance of the two-compartment model was similar to that of models accepted for TCI administration of intravenous anesthetics, supporting open-loop administration of sevoflurane with the AnaConDa. Further studies will focus on prospective testing and external validation of the model implemented in a target-controlled infusion device.

Golden-winged Warbler habitat model validation for northern Wisconsin and central Minnesota

Between 1966 and 2003, the Golden-winged Warbler (Vermivora chrysoptera) experienced declines of 3.4% per year in large parts of the breeding range and has been identified by Partners in Flight as one of 28 land birds requiring expedient action to prevent its continued decline. It is currently being considered for listing under the Endangered Species Act. A major step in advancing our understanding of the status and habitat preferences of Golden-winged Warbler populations in the Upper Midwest was initiated by the publication of new predictive spatially explicit Golden-winged Warbler habitat models for the northern Midwest. Here, I use original data on observed Golden-winged Warbler abundances in Wisconsin and Minnesota to compare two population models: the hierarchical spatial count (HSC) model with the Habitat Suitability Index (HSI) model. I assessed how well the field data compared to the model predictions and found that within Wisconsin, the HSC model performed slightly better than the HSI model whereas both models performed relatively equally in Minnesota. For the HSC model, I found a 10% error of commission in Wisconsin and a 24.2% error of commission for Minnesota. Similarly, the HSI model has a 23% error of commission in Minnesota; in Wisconsin due to limited areas where the HSI model predicted absences, there was incomplete data and I was unable to determine the error of commission for the HSI model. These are sites where the model predicted presences and the Golden-winged Warbler did not occur. To compare predicted abundance from the two models, a 3x3 contingency table was used. I found that when overlapped, the models do not complement one another in identifying Golden-winged Warbler presences. To calculate discrepancy between the models, the error of commission shows that the HSI model has only a 6.8% chance of correctly classifying absences in the HSC model. The HSC model has only 3.3% chance of correctly classifying absences in the HSI model. These findings highlight the importance of grasses for nesting, shrubs used for cover and foraging, and trees for song perches and foraging as key habitat characteristics for breeding territory occupancy by singing males.

Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial-mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1 day of UUO an increasing expression of alpha-smooth muscle actin (alphaSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5'-nucleotidase (5'NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that model.

Treatment of osteoporosis in a mouse model of Duchenne muscular dystrophy using black bear parathyroid hormone

Duchenne muscular dystrophy (DMD) is a progressive disease affecting skeletal and cardiac muscle, as well as bone. Long term disuse and glucocorticoid treatments cause progressive osteoporosis in DMD patients, leading to an increase in fracture incidence. Treatments for osteoporosis in these patients have not been widely explored. Parathyroid hormone (PTH), an anabolic treatment for post-menopausal osteoporosis, could benefit DMD patients by improving skeletal properties and reducing fracture risk. Other PTH analogues are not currently FDA approved to treat osteoporosis, but may have improved osteogenic effects compared to the human analogue. Black bear PTH is especially promising as an osteoporosis treatment for the DMD population. Black bears are unique models of bone maintenance during disuse, since during six months of inactivity (hibernation), they maintain skeletal properties, unlike other hibernators. Additionally, black bear PTH has been correlated to bone formation markers during hibernation, indicating it may be, at least in part, the mechanism by which bears maintain bone during disuse. Employing black bear PTH as a treatment for osteoporosis in DMD patients could greatly improve quality of life for these individuals, and reduce the pain and expense associated with frequent fractures.

DEVELOPMENT OF AN OPTIMIZATION MODEL FOR BIOFUEL FACILITY SIZE AND LOCATION AND A SIMULATION MODEL FOR DESIGN OF A BIOFUEL SUPPLY CHAIN

A range of societal issues have been caused by fossil fuel consumption in the transportation sector in the United States (U.S.), including health related air pollution, climate change, the dependence on imported oil, and other oil related national security concerns. Biofuels production from various lignocellulosic biomass types such as wood, forest residues, and agriculture residues have the potential to replace a substantial portion of the total fossil fuel consumption. This research focuses on locating biofuel facilities and designing the biofuel supply chain to minimize the overall cost. For this purpose an integrated methodology was proposed by combining the GIS technology with simulation and optimization modeling methods. The GIS based methodology was used as a precursor for selecting biofuel facility locations by employing a series of decision factors. The resulted candidate sites for biofuel production served as inputs for simulation and optimization modeling. As a precursor to simulation or optimization modeling, the GIS-based methodology was used to preselect potential biofuel facility locations for biofuel production from forest biomass. Candidate locations were selected based on a set of evaluation criteria, including: county boundaries, a railroad transportation network, a state/federal road transportation network, water body (rivers, lakes, etc.) dispersion, city and village dispersion, a population census, biomass production, and no co-location with co-fired power plants. The simulation and optimization models were built around key supply activities including biomass harvesting/forwarding, transportation and storage. The built onsite storage served for spring breakup period where road restrictions were in place and truck transportation on certain roads was limited. Both models were evaluated using multiple performance indicators, including cost (consisting of the delivered feedstock cost, and inventory holding cost), energy consumption, and GHG emissions. The impact of energy consumption and GHG emissions were expressed in monetary terms to keep consistent with cost. Compared with the optimization model, the simulation model represents a more dynamic look at a 20-year operation by considering the impacts associated with building inventory at the biorefinery to address the limited availability of biomass feedstock during the spring breakup period. The number of trucks required per day was estimated and the inventory level all year around was tracked. Through the exchange of information across different procedures (harvesting, transportation, and biomass feedstock processing procedures), a smooth flow of biomass from harvesting areas to a biofuel facility was implemented. The optimization model was developed to address issues related to locating multiple biofuel facilities simultaneously. The size of the potential biofuel facility is set up with an upper bound of 50 MGY and a lower bound of 30 MGY. The optimization model is a static, Mathematical Programming Language (MPL)-based application which allows for sensitivity analysis by changing inputs to evaluate different scenarios. It was found that annual biofuel demand and biomass availability impacts the optimal results of biofuel facility locations and sizes.

Selection on floral traits through male fertility in a natural plant population

Most studies on selection in plants estimate female fitness components and neglect male mating success, although the latter might also be fundamental to understand adaptive evolution. Information from molecular genetic markers can be used to assess determinants of male mating success through parentage analyses. We estimated paternal selection gradients on floral traits in a large natural population of the herb Mimulus guttatus using a paternity probability model and maximum likelihood methods. This analysis revealed more significant selection gradients than a previous analysis based on regression of estimated male fertilities on floral traits. There were differences between results of univariate and multivariate analyses most likely due to the underlying covariance structure of the traits. Multivariate analysis, which corrects for the covariance structure of the traits, indicated that male mating success declined with distance from and depended on the direction to the mother plants. Moreover, there was directional selection for plants with fewer open flowers which have smaller corollas, a smaller anther-stigma separation, more red dots on the corolla and a larger fluctuating asymmetry therein. For most of these traits, however, there was also stabilizing selection indicating that there are intermediate optima for these traits. The large number of significant selection gradients in this study shows that even in relatively large natural populations where not all males can be sampled, it is possible to detect significant paternal selection gradients, and that such studies can give us valuable information required to better understand adaptive plant evolution.

Predicting the population impact of chlamydia screening programmes: comparative mathematical modelling study

BACKGROUND: Published individual-based, dynamic sexual network modelling studies reach different conclusions about the population impact of screening for Chlamydia trachomatis. The objective of this study was to conduct a direct comparison of the effect of organised chlamydia screening in different models. METHODS: Three models simulating population-level sexual behaviour, chlamydia transmission, screening and partner notification were used. Parameters describing a hypothetical annual opportunistic screening program in 16-24 year olds were standardised, whereas other parameters from the three original studies were retained. Model predictions of the change in chlamydia prevalence were compared under a range of scenarios. RESULTS: Initial overall chlamydia prevalence rates were similar in women but not men and there were age and sex-specific differences between models. The number of screening tests carried out was comparable in all models but there were large differences in the predicted impact of screening. After 10 years of screening, the predicted reduction in chlamydia prevalence in women aged 16-44 years ranged from 4% to 85%. Screening men and women had a greater impact than screening women alone in all models. There were marked differences between models in assumptions about treatment seeking and sexual behaviour before the start of the screening intervention. CONCLUSIONS: Future models of chlamydia transmission should be fitted to both incidence and prevalence data. This meta-modelling study provides essential information for explaining differences between published studies and increasing the utility of individual-based chlamydia transmission models for policy making.

A prediction model for personal radio frequency electromagnetic field exposure

Radio frequency electromagnetic fields (RF-EMF) in our daily life are caused by numerous sources such as fixed site transmitters (e.g. mobile phone base stations) or indoor devices (e.g. cordless phones). The objective of this study was to develop a prediction model which can be used to predict mean RF-EMF exposure from different sources for a large study population in epidemiological research. We collected personal RF-EMF exposure measurements of 166 volunteers from Basel, Switzerland, by means of portable exposure meters, which were carried during one week. For a validation study we repeated exposure measurements of 31 study participants 21 weeks after the measurements of the first week on average. These second measurements were not used for the model development. We used two data sources as exposure predictors: 1) a questionnaire on potentially exposure relevant characteristics and behaviors and 2) modeled RF-EMF from fixed site transmitters (mobile phone base stations, broadcast transmitters) at the participants' place of residence using a geospatial propagation model. Relevant exposure predictors, which were identified by means of multiple regression analysis, were the modeled RF-EMF at the participants' home from the propagation model, housing characteristics, ownership of communication devices (wireless LAN, mobile and cordless phones) and behavioral aspects such as amount of time spent in public transports. The proportion of variance explained (R2) by the final model was 0.52. The analysis of the agreement between calculated and measured RF-EMF showed a sensitivity of 0.56 and a specificity of 0.95 (cut-off: 90th percentile). In the validation study, the sensitivity and specificity of the model were 0.67 and 0.96, respectively. We could demonstrate that it is feasible to model personal RF-EMF exposure. Most importantly, our validation study suggests that the model can be used to assess average exposure over several months.

A model of osteoporosis impact in Switzerland 2000-2020

The aim of our study was to develop a modeling framework suitable to quantify the incidence, absolute number and economic impact of osteoporosis-attributable hip, vertebral and distal forearm fractures, with a particular focus on change over time, and with application to the situation in Switzerland from 2000 to 2020. A Markov process model was developed and analyzed by Monte Carlo simulation. A demographic scenario provided by the Swiss Federal Statistical Office and various Swiss and international data sources were used as model inputs. Demographic and epidemiologic input parameters were reproduced correctly, confirming the internal validity of the model. The proportion of the Swiss population aged 50 years or over will rise from 33.3% in 2000 to 41.3% in 2020. At the total population level, osteoporosis-attributable incidence will rise from 1.16 to 1.54 per 1,000 person-years in the case of hip fracture, from 3.28 to 4.18 per 1,000 person-years in the case of radiographic vertebral fracture, and from 0.59 to 0.70 per 1,000 person-years in the case of distal forearm fracture. Osteoporosis-attributable hip fracture numbers will rise from 8,375 to 11,353, vertebral fracture numbers will rise from 23,584 to 30,883, and distal forearm fracture numbers will rise from 4,209 to 5,186. Population-level osteoporosis-related direct medical inpatient costs per year will rise from 713.4 million Swiss francs (CHF) to CHF946.2 million. These figures correspond to 1.6% and 2.2% of Swiss health care expenditures in 2000. The modeling framework described can be applied to a wide variety of settings. It can be used to assess the impact of new prevention, diagnostic and treatment strategies. In Switzerland incidences of osteoporotic hip, vertebral and distal forearm fracture will rise by 33%, 27%, and 19%, respectively, between 2000 and 2020, if current prevention and treatment patterns are maintained. Corresponding absolute fracture numbers will rise by 36%, 31%, and 23%. Related direct medical inpatient costs are predicted to increase by 33%; however, this estimate is subject to uncertainty due to limited availability of input data.

Social Structural Effects on the Level and Development of the Individual Experience of Anomie in the German Population

Can one observe an increasing level of individual lack of orientation because of rapid social change in modern societies? This question is examined using data from a representative longitudinal survey in Germany conducted in 2002–04. The study examines the role of education, age, sex, region (east/west), and political orientation for the explanation of anomia and its development. First we present the different sources of anomie in modern societies, based on the theoretical foundations of Durkheim and Merton, and introduce the different definitions of anomia, including our own cognitive version. Then we deduce several hypotheses from the theory, which we test by means of longitudinal data for the period 2002–04 in Germany using the latent growth curve model as our statistical method. The empirical findings show that all the sociodemographic variables, including political orientation, are strong predictors of the initial level of anomia. Regarding the development of anomia over time (2002–04), only the region (west) has a significant impact. In particular, the results of a multi-group analysis show that western German people with a right-wing political orientation become more anomic over this period. The article concludes with some theoretical implications.

Flow-R, a model for susceptibility mapping of debris flows and other gravitational hazards at a regional scale

The development of susceptibility maps for debris flows is of primary importance due to population pressure in hazardous zones. However, hazard assessment by process-based modelling at a regional scale is difficult due to the complex nature of the phenomenon, the variability of local controlling factors, and the uncertainty in modelling parameters. A regional assessment must consider a simplified approach that is not highly parameter dependant and that can provide zonation with minimum data requirements. A distributed empirical model has thus been developed for regional susceptibility assessments using essentially a digital elevation model (DEM). The model is called Flow-R for Flow path assessment of gravitational hazards at a Regional scale (available free of charge under http://www.flow-r.org) and has been successfully applied to different case studies in various countries with variable data quality. It provides a substantial basis for a preliminary susceptibility assessment at a regional scale. The model was also found relevant to assess other natural hazards such as rockfall, snow avalanches and floods. The model allows for automatic source area delineation, given user criteria, and for the assessment of the propagation extent based on various spreading algorithms and simple frictional laws. We developed a new spreading algorithm, an improved version of Holmgren's direction algorithm, that is less sensitive to small variations of the DEM and that is avoiding over-channelization, and so produces more realistic extents. The choices of the datasets and the algorithms are open to the user, which makes it compliant for various applications and dataset availability. Amongst the possible datasets, the DEM is the only one that is really needed for both the source area delineation and the propagation assessment; its quality is of major importance for the results accuracy. We consider a 10 m DEM resolution as a good compromise between processing time and quality of results. However, valuable results have still been obtained on the basis of lower quality DEMs with 25 m resolution.

Complex visual hallucinations and attentional performance in eye disease and dementia: a test of the Perception and Attention Deficit model

OBJECTIVE This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

Pharmacogenetics-based population pharmacokinetic analysis of etravirine in HIV-1 infected individuals

Objectives: Etravirine (ETV) is metabolized by cytochrome P450 (CYP) 3A, 2C9, and 2C19. Metabolites are glucuronidated by uridine diphosphate glucuronosyltransferases (UGT). To identify the potential impact of genetic and non-genetic factors involved in ETV metabolism, we carried out a two-step pharmacogenetics-based population pharmacokinetic study in HIV-1 infected individuals. Materials and methods: The study population included 144 individuals contributing 289 ETV plasma concentrations and four individuals contributing 23 ETV plasma concentrations collected in a rich sampling design. Genetic variants [n=125 single-nucleotide polymorphisms (SNPs)] in 34 genes with a predicted role in ETV metabolism were selected. A first step population pharmacokinetic model included non-genetic and known genetic factors (seven SNPs in CYP2C, one SNP in CYP3A5) as covariates. Post-hoc individual ETV clearance (CL) was used in a second (discovery) step, in which the effect of the remaining 98 SNPs in CYP3A, P450 cytochrome oxidoreductase (POR), nuclear receptor genes, and UGTs was investigated. Results: A one-compartment model with zero-order absorption best characterized ETV pharmacokinetics. The average ETV CL was 41 (l/h) (CV 51.1%), the volume of distribution was 1325 l, and the mean absorption time was 1.2 h. The administration of darunavir/ritonavir or tenofovir was the only non-genetic covariate influencing ETV CL significantly, resulting in a 40% [95% confidence interval (CI): 13–69%] and a 42% (95% CI: 17–68%) increase in ETV CL, respectively. Carriers of rs4244285 (CYP2C19*2) had 23% (8–38%) lower ETV CL. Co-administered antiretroviral agents and genetic factors explained 16% of the variance in ETV concentrations. None of the SNPs in the discovery step influenced ETV CL. Conclusion: ETV concentrations are highly variable, and co-administered antiretroviral agents and genetic factors explained only a modest part of the interindividual variability in ETV elimination. Opposing effects of interacting drugs effectively abrogate genetic influences on ETV CL, and vice-versa.