Transmission of Chlamydia trachomatis through sexual partnerships: a comparison between three individual-based models and empirical data

Chlamydia trachomatis is the most common bacterial sexually transmitted infection (STI) in many developed countries. The highest prevalence rates are found among young adults who have frequent partner change rates. Three published individual-based models have incorporated a detailed description of age-specific sexual behaviour in order to quantify the transmission of C. trachomatis in the population and to assess the impact of screening interventions. Owing to varying assumptions about sexual partnership formation and dissolution and the great uncertainty about critical parameters, such models show conflicting results about the impact of preventive interventions. Here, we perform a detailed evaluation of these models by comparing the partnership formation and dissolution dynamics with data from Natsal 2000, a population-based probability sample survey of sexual attitudes and lifestyles in Britain. The data also allow us to describe the dispersion of C. trachomatis infections as a function of sexual behaviour, using the Gini coefficient. We suggest that the Gini coefficient is a useful measure for calibrating infectious disease models that include risk structure and highlight the need to estimate this measure for other STIs.

The chironomid-temperature relationship: expression in nature and palaeoenvironmental implications

Fossils of chironomid larvae (non-biting midges) preserved in lake sediments are well-established palaeotemperature indicators which, with the aid of numerical chironomid-based inference models (transfer functions), can provide quantitative estimates of past temperature change. This approach to temperature reconstruction relies on the strong relationship between air and lake surface water temperature and the distribution of individual chironomid taxa (species, species groups, genera) that has been observed in different climate regions (arctic, subarctic, temperate and tropical) in both the Northern and Southern hemisphere. A major complicating factor for the use of chironomids for palaeoclimate reconstruction which increases the uncertainty associated with chironomid-based temperature estimates is that the exact nature of the mechanism responsible for the strong relationship between temperature and chironomid assemblages in lakes remains uncertain. While a number of authors have provided state of the art overviews of fossil chironomid palaeoecology and the use of chironomids for temperature reconstruction, few have focused on examining the ecological basis for this approach. Here, we review the nature of the relationship between chironomids and temperature based on the available ecological evidence. After discussing many of the surveys describing the distribution of chironomid taxa in lake surface sediments in relation to temperature, we also examine evidence from laboratory and field studies exploring the effects of temperature on chironomid physiology, life cycles and behaviour. We show that, even though a direct influence of water temperature on chironomid development, growth and survival is well described, chironomid palaeoclimatology is presently faced with the paradoxical situation that the relationship between chironomid distribution and temperature seems strongest in relatively deep, thermally stratified lakes in temperate and subarctic regions in which the benthic chironomid fauna lives largely decoupled from the direct influence of air and surface water temperature. This finding suggests that indirect effects of temperature on physical and chemical characteristics of lakes play an important role in determining the distribution of lake-living chironomid larvae. However, we also demonstrate that no single indirect mechanism has been identified that can explain the strong relationship between chironomid distribution and temperature in all regions and datasets presently available. This observation contrasts with the previously published hypothesis that climatic effects on lake nutrient status and productivity may be largely responsible for the apparent correlation between chironomid assemblage distribution and temperature. We conclude our review by summarizing the implications of our findings for chironomid-based palaeoclimatology and by pointing towards further avenues of research necessary to improve our mechanistic understanding of the chironomid-temperature relationship.

An intercontinental comparison of chironomid palaeotemperature inference models: Europe vs North America

Chironomid-temperature inference models based on North American, European and combined surface sediment training sets were compared to assess the overall reliability of their predictions. Between 67 and 76 of the major chironomid taxa in each data set showed a unimodal response to July temperature, whereas between 5 and 22 of the common taxa showed a sigmoidal response. July temperature optima were highly correlated among the training sets, but the correlations for other taxon parameters such as tolerances and weighted averaging partial least squares (WA-PLS) and partial least squares (PLS) regression coefficients were much weaker. PLS, weighted averaging, WA-PLS, and the Modern Analogue Technique, all provided useful and reliable temperature inferences. Although jack-knifed error statistics suggested that two-component WA-PLS models had the highest predictive power, intercontinental tests suggested that other inference models performed better. The various models were able to provide good July temperature inferences, even where neither good nor close modern analogues for the fossil chironomid assemblages existed. When the models were applied to fossil Lateglacial assemblages from North America and Europe, the inferred rates and magnitude of July temperature changes varied among models. All models, however, revealed similar patterns of Lateglacial temperature change. Depending on the model used, the inferred Younger Dryas July temperature decrease ranged between 2.5 and 6°C.

Clutch-size adjustments and skew models: effects on reproductive partitioning and group stability

Reproductive skew theory seeks to integrate social and ecological factors thought to influence the division of reproduction among group-living animals. However, most reproductive skew models only examine interactions between individuals of the same sex. Here, we suggest that females can influence group stability and conflict among males by modifying their clutch size and may do so if they benefit from the presence of subordinate male helpers or from reduced conflict. We develop 3 models, based on concessions-based, restraint, and tug-of-war models, in which female clutch size is variable and ask when females will increase their clutch size above that which would be optimal in the absence of male-male conflict. In concessions-based and restraint models, females should increase clutch size above their optima if the benefits of staying for subordinate males are relatively low. Relatedness between males has no effect on clutch size. When females do increase clutch size, the division of reproduction between males is not influenced by relatedness and does not differ between restraint and concessions-based models. Both of these predictions are in sharp contrast to previous models. In tug-of-war models, clutch size is strongly influenced by relatedness between males, with the largest clutches, but the fewest surviving offspring, produced when males are unrelated. These 3 models demonstrate the importance of considering third-party interests in the decisions of group-living organisms.

Index of Complexity, Outcome and Need scored on plaster and digital models

The aim of this study was to compare standard plaster models with their digital counterparts for the applicability of the Index of Complexity, Outcome, and Need (ICON). Generated study models of 30 randomly selected patients: 30 pre- (T(0)) and 30 post- (T(1)) treatment. Two examiners, calibrated in the ICON, scored the digital and plaster models. The overall ICON scores were evaluated for reliability and reproducibility using kappa statistics and reliability coefficients. The values for reliability of the total and weighted ICON scores were generally high for the T(0) sample (range 0.83-0.95) but less high for the T(1) sample (range 0.55-0.85). Differences in total ICON score between plaster and digital models resulted in mostly statistically insignificant values (P values ranging from 0.07 to 0.19), except for observer 1 in the T(1) sample. No statistically different values were found for the total ICON score on either plaster or digital models. ICON scores performed on computer-based models appear to be as accurate and reliable as ICON scores on plaster models.

Ar diffusion in K-feldspar: present and absent

The mechanisms of Ar release from K-feldspar samples in laboratory experiments and during their geological history are assessed here. Modern petrology clearly established that the chemical and isotopic record of minerals is normally dominated by aqueous recrystallization. The laboratory critique is trickier, which explains why so many conflicting approaches have been able to survive long past their expiration date. Current models are evaluated for self-consistency; especially Arrhenian non-linearity leads to paradoxes. The models’ testable geological predictions suggest that temperature-based downslope extrapolations often overestimate observed geological Ar mobility substantially. An updated interpretation is based on the unrelatedness of geological behaviour to laboratory experiments. The isotopic record of K-feldspar in geological samples is not a unique function of temperature, as recrystallisation promoted by aqueous fluids is the predominant mechanism controlling isotope transport. K-feldspar should therefore be viewed as a hygrochronometer. Laboratory degassing proceeds from structural rearrangements and phase transitions such as are observed in situ at high temperature in Na and Pb feldspars. These effects violate the mathematics of an inert Fick’s Law matrix and preclude downslope extrapolation. The similar upward-concave, non-linear shapes of Arrhenius trajectories of many silicates, hydrous and anhydrous, are likely common manifestations of structural rearrangements in silicate structures.

MicroRNAs may mediate the down-regulation of neurokinin-1 receptor in chronic bladder pain syndrome

Bladder pain syndrome (BPS) is a clinical syndrome of pelvic pain and urinary urgency-frequency in the absence of a specific cause. Investigating the expression levels of genes involved in the regulation of epithelial permeability, bladder contractility, and inflammation, we show that neurokinin (NK)1 and NK2 tachykinin receptors were significantly down-regulated in BPS patients. Tight junction proteins zona occludens-1, junctional adherins molecule -1, and occludin were similarly down-regulated, implicating increased urothelial permeability, whereas bradykinin B(1) receptor, cannabinoid receptor CB1 and muscarinic receptors M3-M5 were up-regulated. Using cell-based models, we show that prolonged exposure of NK1R to substance P caused a decrease of NK1R mRNA levels and a concomitant increase of regulatory micro(mi)RNAs miR-449b and miR-500. In the biopsies of BPS patients, the same miRNAs were significantly increased, suggesting that BPS promotes an attenuation of NK1R synthesis via activation of specific miRNAs. We confirm this hypothesis by identifying 31 differentially expressed miRNAs in BPS patients and demonstrate a direct correlation between miR-449b, miR-500, miR-328, and miR-320 and a down-regulation of NK1R mRNA and/or protein levels. Our findings further the knowledge of the molecular mechanisms of BPS, and have relevance for other clinical conditions involving the NK1 receptor.

Towards Energy Consumption Measurement in a Cloud Computing Wireless Testbed

The evolution of the Next Generation Networks, especially the wireless broadband access technologies such as Long Term Evolution (LTE) and Worldwide Interoperability for Microwave Access (WiMAX), have increased the number of "all-IP" networks across the world. The enhanced capabilities of these access networks has spearheaded the cloud computing paradigm, where the end-users aim at having the services accessible anytime and anywhere. The services availability is also related with the end-user device, where one of the major constraints is the battery lifetime. Therefore, it is necessary to assess and minimize the energy consumed by the end-user devices, given its significance for the user perceived quality of the cloud computing services. In this paper, an empirical methodology to measure network interfaces energy consumption is proposed. By employing this methodology, an experimental evaluation of energy consumption in three different cloud computing access scenarios (including WiMAX) were performed. The empirical results obtained show the impact of accurate network interface states management and application network level design in the energy consumption. Additionally, the achieved outcomes can be used in further software-based models to optimized energy consumption, and increase the Quality of Experience (QoE) perceived by the end-users.

A Calculus of Evolving Objects

The demands of developing modern, highly dynamic applications have led to an increasing interest in dynamic programming languages and mechanisms. Not only applications must evolve over time, but the object models themselves may need to be adapted to the requirements of different run-time contexts. Class-based models and prototype-based models, for example, may need to co-exist to meet the demands of dynamically evolving applications. Multi-dimensional dispatch, fine-grained and dynamic software composition, and run-time evolution of behaviour are further examples of diverse mechanisms which may need to co-exist in a dynamically evolving run-time environment How can we model the semantics of these highly dynamic features, yet still offer some reasonable safety guarantees? To this end we present an original calculus in which objects can adapt their behaviour at run-time to changing contexts. Both objects and environments are represented by first-class mappings between variables and values. Message sends are dynamically resolved to method calls. Variables may be dynamically bound, making it possible to model a variety of dynamic mechanisms within the same calculus. Despite the highly dynamic nature of the calculus, safety properties are assured by a type assignment system.

A Calculus of Evolving Objects

The demands of developing modern, highly dynamic applications have led to an increasing interest in dynamic programming languages and mechanisms. Not only must applications evolve over time, but the object models themselves may need to be adapted to the requirements of different run-time contexts. Class-based models and prototype-based models, for example, may need to co-exist to meet the demands of dynamically evolving applications. Multi-dimensional dispatch, fine-grained and dynamic software composition, and run-time evolution of behaviour are further examples of diverse mechanisms which may need to co-exist in a dynamically evolving run-time environment. How can we model the semantics of these highly dynamic features, yet still offer some reasonable safety guarantees? To this end we present an original calculus in which objects can adapt their behaviour at run-time. Both objects and environments are represented by first-class mappings between variables and values. Message sends are dynamically resolved to method calls. Variables may be dynamically bound, making it possible to model a variety of dynamic mechanisms within the same calculus. Despite the highly dynamic nature of the calculus, safety properties are assured by a type assignment system.

Retention in care under universal antiretroviral therapy for HIV-infected pregnant and breastfeeding women ('Option B+') in Malawi

OBJECTIVE To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') in Malawi. DESIGN, SETTING, AND PARTICIPANTS We examined retention in care, from the date of ART initiation up to 6 months, for women in the Option B+ program. We analysed nationwide facility-level data on women who started ART at 540 facilities (n = 21 939), as well as individual-level data on patients who started ART at 19 large facilities (n = 11 534). RESULTS Of the women who started ART under Option B+ (n = 21 939), 17% appeared to be lost to follow-up 6 months after ART initiation. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count 350 cells/μl or less, to never return after their initial clinic visit [odds ratio (OR) 5.0, 95% confidence interval (CI) 4.2-6.1]. Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (OR 2.2, 95% CI 1.8-2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0 to 58%. CONCLUSION Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community or family-based models of care could improve its effectiveness.

Modeled Interaction of Comet 67P/Churyumov-Gerasimenko with the Solar Wind Inside 2 AU

Periodic comets move around the Sun on elliptical orbits. As such comet 67P/Churyumov-Gerasimenko (hereafter 67P) spends a portion of time in the inner solar system where it is exposed to increased solar insolation. Therefore given the change in heliocentric distance, in case of 67P from aphelion at 5.68 AU to perihelion at ~1.24 AU, the comet’s activity—the production of neutral gas and dust—undergoes significant variations. As a consequence, during the inbound portion, the mass loading of the solar wind increases and extends to larger spatial scales. This paper investigates how this interaction changes the character of the plasma environment of the comet by means of multifluid MHD simulations. The multifluid MHD model is capable of separating the dynamics of the solar wind ions and the pick-up ions created through photoionization and electron impact ionization in the coma of the comet. We show how two of the major boundaries, the bow shock and the diamagnetic cavity, form and develop as the comet moves through the inner solar system. Likewise for 67P, although most likely shifted back in time with respect to perihelion passage, this process is reversed on the outbound portion of the orbit. The presented model herein is able to reproduce some of the key features previously only accessible to particle-based models that take full account of the ions’ gyration. The results shown herein are in decent agreement to these hybrid-type kinetic simulations.