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Concrete production is globally a major water consumer, and in general, drinking-quality water is mixed in the binder. In the present study, simulated sea water and reverse osmosis reject water were used as batching water for one-part (dry-mix) alkali-activated blast furnace slag mortar. Alkali-activated materials are low-CO2 alternative binders gaining world-wide acceptance in construction. However, their production requires approximately similar amount of water as regular Portland cement concrete. The results of the present study revealed that the use of saline water did not hinder strength development, increased setting time, and did not affect workability. The salts incorporated in the binder decreased the total porosity of mortar, but they did not form separate phases detectable with X-ray diffraction or scanning electron microscopy. Leaching tests for monolithic materials revealed only minimal leaching. Furthermore, results for crushed mortars (by a standard two-stage leaching test) were within the limits of non-hazardous waste. Thus, the results indicated that high-salinity waters can be used safely in one-part alkali-activated slag to prepare high-strength mortars. Moreover, alkali-activation technology could be used as a novel stabilization/solidification method for reverse osmosis reject waters, which frequently pose disposal problems. [ABSTRACT FROM AUTHOR]

Rats are an important issue in cities globally. Despite their ubiquity, perceptions and concerns about rats vary with circumstance and the context in which a person interacts with them. Municipal rat management programs are a service to communities and therefore must be responsive to the varied concerns of their residents. Understanding why communities are concerned about rats can help inform rat management programs to meet the specific needs of their residents. The objective of this study was to identify why the residents of Vancouver, Canada care about rats and what they want done to address them. To do this, we qualitatively analyzed 6,158 resident complaints about rats made to the city's municipal government between January 2014 and May 2020. Using a qualitative descriptive coding process, we found that rats were a priority in a minority of cases. In general, people were more concerned about broader community issues, such as neighborhood disorder, of which rats were one part. Complaints tended to be made when problems were highly visible, nearby, and when the complainant wanted the city to take action to alleviate this issue, particularly when they were in and around their living spaces. The rates of complaints were highest in the most economically and socially deprived neighborhoods and lowest in the most privileged neighbourhoods. We synthesize this information with a view towards understanding how to develop objectives and actions for municipal management strategies that are grounded in community concerns. [ABSTRACT FROM AUTHOR]

In longitudinal surveys, repeated measurements are collected from the same sample units over time to measure gross change (i.e., change at the level of individual sample members). Longitudinal samples are sometimes supplemented by fresh sample to measure net change (i.e., change at the aggregate level). That is, in each measurement wave, while one part of the sample is newly recruited (fresh), another part overlaps with previously interviewed sample (repeated interviews). Many aspects of survey design of longitudinal surveys have been studied extensively, such as definition of target population, sample design, survey weighting, intervals between interviews, nonresponse, and panel attrition. Although the impact of the overlap between samples on the statistical power has been studied, sample size determination lacks a formulation that takes account of these factors in longitudinal surveys that aim to measure net and gross changes simultaneously. In this study, we propose a framework for sample size calculation to measure net and gross changes in estimated means or proportions concurrently in longitudinal surveys. We present a framework to compute panel and fresh sample sizes for varying levels of net and gross change. Finally, we illustrate the framework using nchange, an R package we developed to execute the algorithm of the proposed framework. The framework and the R package will support researchers to determine sample sizes targeting specific power of analysis with respect to measuring net and gross changes in rotating- or split-panel surveys. [ABSTRACT FROM AUTHOR]

Winter mortality can strongly affect the population dynamics of blue crabs (Callinectes sapidus) near poleward range limits. We simulated winter in the lab to test the effects of temperature, salinity, and estuary of origin on blue crab winter mortality over three years using a broad range of crab sizes from both Great South Bay and Chesapeake Bay. We fit accelerated failure time models to our data and to data from prior blue crab winter mortality experiments, illustrating that, in a widely distributed, commercially valuable marine decapod, temperature, salinity, size, estuary of origin, and winter duration were important predictors of winter mortality. Furthermore, our results suggest that extrapolation of a Chesapeake Bay based survivorship model to crabs from New York estuaries yielded poor fits. As such, the severity and duration of winter can impact northern blue crab populations differently along latitudinal gradients. In the context of climate change, future warming could possibility confer a benefit to crab populations near the range edge that are currently limited by temperature-induced winter mortality by shifting their range edge poleward, but care must be taken in generalizing from models that are developed based on populations from one part of the range to populations near the edges, especially for species that occupy large geographical areas. [ABSTRACT FROM AUTHOR]

Water and land resource utilization is an important driving force of changes in ecosystem services; therefore, research on multi-parameter coupling systems that consider "ecosystem services, water resources, and land resources" together has key significance for river basins. This study aims to reveal the interaction and mutual influence of ecosystem services and water and land resources in the Daguhe River Basin, China, based on the coupling coordination degree model. The results showed that during the period from 2000 to 2010, the coupling coordination degree values for the years 2000, 2005, and 2010 were 0.6005, 0.7292, and 0.8037. The corresponding coupling coordination classifications were categorized as "primary coordinated development", "intermediate coordinated development," and "well-coordinated development", respectively. These results reflected the fact that the relationship between water and land resource utilization and the environment tends to evolve in the direction of coordinated development (an improvement in one part corresponds to an improvement in another part) with variation in water and land utilization types, and eventually pushes the whole resource, as well as ecological and environmental systems, from low to high levels of coupling coordination degrees as observed in case of the Daguhe River Basin, China. Our research provides an overview of the interaction between ecosystem services and water and land resources in the Daguhe Basin and even in the Shandong Province. With our results, we offer new perspectives on river basin management and for planning future eco-environmental policies (the policy is specifically designed for the ecological environment) by combining water and land resource utilization. [ABSTRACT FROM AUTHOR]

Scholars from different theoretical schools have posited that in recent decades, science and society have moved closer together, and the concept of academic engagement has been proposed to capture one part of this approximation empirically. This study analyzes the academic engagement of individual scholars towards politicians, industry representatives and journalists. It uses comprehensive survey data on Swiss professors from all disciplines, all the country's universities and from associated research institutes. It assesses, firstly, the degree to which these professors have professional contacts to journalists, politicians and industry representatives. Secondly, it explains the extent of these contacts, using multi-level modelling that incorporates individual factors as well as organizational and institutional contexts. Our study shows that academic engagement is quite common with strong differences between disciplines. Furthermore, professors with higher academic productivity, positive personal attitude towards communication activities as well as a leadership position have more outside contacts. The gender and nationality of the professors, however, only play a role for some of the contacts with non-scientific actors. [ABSTRACT FROM AUTHOR]

Background: There has been a rapid increase in the number of cases of COVID-19 in Latin America, Africa, Asia and many countries that have an insufficient number of physicians and other health care personnel, and the need for the inclusion of medical students on health teams is a very important issue. It has been recommended that medical students work as volunteers, undergo appropriate training, not undertake any activity beyond their level of competence, and receive continuous supervision and adequate personal protective equipment. However, the motivation of medical students must be evaluated to make volunteering a more evidence-based initiative. The aim of our study was to evaluate the motivation of medical students to be part of health teams to aid in the COVID-19 pandemic. Methods and findings: We developed a questionnaire specifically to evaluate medical students' perceptions about participating in the care of patients with suspected infection with coronavirus during the COVID-19 pandemic. The questionnaire had two parts: a) one part with questions on individual characteristics, year in medical school and geographic location of the medical school and b) a second part with twenty-eight statements assessed on a 5-point Likert scale (totally agree, agree, neither agree nor disagree, disagree and totally disagree). To develop the questionnaire, we performed consensus meetings with a group of faculty and medical students. The questionnaire was sent to student organizations of 257 medical schools in Brazil and answered by 10,433 students. We used multinomial logistic regression models to analyze the data. Statements associated with greater odds ratios for participation of medical students in the COVID-19 pandemic were related to a sense of purpose or duty ("It is the duty of the medical student to put himself or herself at the service of the population in the pandemic"), altruism ("I am willing to take risks by participating in practice in the context of the pandemic"), and perception of good performance and professional identity ("I will be a better health professional for having experienced the pandemic"). Males were more prone than females to believe that only interns should participate in the care of patients with COVID-19 (odds ratio 1.36 [coefficient interval 95%:1.24–1.49]) and that all students should participate (OR 1.68 [CI:1.4–1.91]). Conclusions: Medical students are more motivated by a sense of purpose or duty, altruism, perception of good performance and values of professionalism than by their interest in learning. These results have implications for the development of volunteering programs and the design of health force policies in the present pandemic and in future health emergencies. [ABSTRACT FROM AUTHOR]

Just like everything in nature, scientific topics flourish and perish. While existing literature well captures article's life-cycle via citation patterns, little is known about how scientific popularity and impact evolves for a specific topic. It would be most intuitive if we could 'feel' topic's activity just as we perceive the weather by temperature. Here, we conceive knowledge temperature to quantify topic overall popularity and impact through citation network dynamics. Knowledge temperature includes 2 parts. One part depicts lasting impact by assessing knowledge accumulation with an analogy between topic evolution and isobaric expansion. The other part gauges temporal changes in knowledge structure, an embodiment of short-term popularity, through the rate of entropy change with internal energy, 2 thermodynamic variables approximated via node degree and edge number. Our analysis of representative topics with size ranging from 1000 to over 30000 articles reveals that the key to flourishing is topics' ability in accumulating useful information for future knowledge generation. Topics particularly experience temperature surges when their knowledge structure is altered by influential articles. The spike is especially obvious when there appears a single non-trivial novel research focus or merging in topic structure. Overall, knowledge temperature manifests topics' distinct evolutionary cycles. [ABSTRACT FROM AUTHOR]

Introduction: The management of patients who need chronic and complex care is a focus of attention internationally, brought about by an increase in chronic conditions, requiring significantly more care over longer periods of time. The increase in chronic conditions has placed pressure on health services, financially and physically, bringing about changes in the way care is delivered, with hospital avoidance and home-based care encouraged. In this environment, nurses play an important role in co-ordinating care across services. This review formed one part of a funded project that explored the nurse navigator role within a proposed 24-hour telephone-call service in one regional area that has a diverse population in terms of cultural identity and geographical location in relation to service access. Aim: The review reports on the extant literature on the nurse's role in the provision of afterhours telephone services for patients with chronic and complex conditions. The specific aim was to explore the effectiveness of services for patients in geographically isolated locations. Methods: The methodological approach to the review followed the Preferred Reporting System for Meta-Analyses (PRISMA) guidelines. A thematic analysis was used to identify themes with chronic care models underpinning analysis. Results: Three themes were identified; nurse-led decision making; consumer profile; and program outcomes. Each theme was divided into two sub-themes. The two sub-themes for decision making were: the experience of the staff who provided the service and the tool or protocol used. The two sub-themes for consumers profile were; the geographic/demographic identity of the consumers, and consumer satisfaction. The final theme of outcomes describes how the effectiveness of the service is measured, broken into two sub-themes: the economic/workforce outcomes and the consumer outcomes. Discussion: The provision of an after-hours telephone service, in whatever model used should align with a Chronic Care Model. In this way, after-hours telephone services provided by experienced nurses, supported by ongoing professional development and relevant protocols, form part of the ongoing improvement for chronic and complex care management as a health priority. [ABSTRACT FROM AUTHOR]

The existence of excess zeros in the distribution of antenatal care (ANC) visits in Bangladesh raises the research question of whether there are two separate generating processes in taking ANC and the frequency of ANC. Thus the main objective of this study is to identify a proper count regression model for the number of ANC visits by pregnant women in Bangladesh covering the issues of overdispersion, zero-inflation, and intra-cluster correlation with an additional objective of determining risk factors for ANC use and its frequency. The data have been extracted from the nationally representative 2014 Bangladesh Demographic and Health Survey, where 22% of the total 4493 women did not take any ANC during pregnancy. Since these zero ANC visits can be either structural or sampling zeros, two-part zero-inflated and hurdle regression models are investigated along with the standard one-part count regression models. Correlation among response values has been accounted for by incorporating cluster-specific random effects in the models. The hurdle negative binomial regression model with cluster-specific random intercepts in both the zero and the count part is found to be the best model according to various diagnostic tools including likelihood ratio and uniformity tests. The results show that women who have poor education, live in poor households, have less access to mass media, or belong to the Sylhet and Chittagong regions are less likely to use ANC and also have fewer ANC visits. Additionally, women who live in rural areas, depend on family members' decisions to take health care, and have unintended pregnancies had fewer ANC visits. The findings recommend taking both cluster-specific random effects and overdispersion and zero-inflation into account in modelling the ANC data of Bangladesh. Moreover, safe motherhood programmes still need to pay particular attention to disadvantaged and vulnerable subgroups of women. [ABSTRACT FROM AUTHOR]

Whether or not depth perception influences brightness and/or lightness perception has been repeatedly discussed, and some studies have emphasized its importance. In addition, a small number of studies have empirically tested and shown the effect of depth inversion, such as seen in the Mach card illusion, on perceived lightness, and they interpreted such results in terms of lightness constancy. However, how perceived brightness changes contingent on depth inversion remains unexplained. Therefore, this study used the matching method to examine changes in brightness perception when depth inversion is observed. We created and used a three-dimensional (3D) concave object, composed of three sides made of card stock, which could be perceived as having two different shapes in 3D; it could be perceived as a horizontal concave object, corresponding to its actual physical structure, and as a convex standing object, similar in shape to a building. Participants observed this object as both a concave object and as a convex object, and judged the brightness of its surfaces during each observation. Our results show that the perception of the brightness of the object's surfaces clearly changed depending on the perception of depth. When the object was seen as convex, one part of the surface was perceived as darker than when the object was seen as concave, but the other part of the surface remained unchanged. Here we discuss the relationship between depth perception and brightness perception in terms of perceptual organization. [ABSTRACT FROM AUTHOR]

A new method is introduced allowing seamless assembly of independent, functionally tested, blunt-end double strand nucleic acid (DNA fragments not supplied in vectors such as plasmids) into more complex biological (e.g. protein expression vectors) and higher order multi-device (e.g. biochemical pathways). Individual parts include bacterial selection markers and origins of replication, promoters useful in a variety of species, transcription terminators, shuttle sequences and a variety of “N” and “C” terminal solubility/affinity protein tags. Parts are not subjected to pre-assembly manipulation with nucleic acid modifying enzymes. Instead, they are simply mixed in appropriate pre-defined combinations and concentrations and then seamlessly linked into devices employing a specialized thermostable enzyme blend. Combinatorial assembly of parts is an inherent time-saving feature of the new method, in contrast to hierarchical binary assembly (“one part at a time”) methods. This feature substantially simplifies and speeds optimization of device and system development. The versatility and functionality of the new method was shown by combinatorial assembly of parts into vector devices, one of which optimally expressed protein from a model gene. Also, a four-enzyme biosynthetic pathway system was re-created by combinatorial construction from parts and devices. Concepts discussed in this paper provide synthetic biologists, chemists and bio-engineers with improved and expanded capability to create novel biological molecules and systems. [ABSTRACT FROM AUTHOR]

Once in the ocean, plastics are rapidly colonized by complex microbial communities. Factors affecting the development and composition of these communities are still poorly understood. Additionally, whether there are plastic-type specific communities developing on different plastics remains enigmatic. We determined the development and succession of bacterial communities on different plastics under ambient and dim light conditions in the coastal Northern Adriatic over the course of two months using scanning electron microscopy and 16S rRNA gene analyses. Plastics used were low- and high-density polyethylene (LDPE and HDPE, respectively), polypropylene (PP) and polyvinyl chloride with two typical additives (PVC DEHP and PVC DINP). The bacterial communities developing on the plastics clustered in two groups; one group was found on PVC and the other group on all the other plastics and on glass, which was used as an inert control. Specific bacterial taxa were found on specific surfaces in essentially all stages of biofilm development and in both ambient and dim light conditions. Differences in bacterial community composition between the different plastics and light exposures were stronger after an incubation period of one week than at the later stages of the incubation. Under both ambient and dim light conditions, one part of the bacterial community was common on all plastic types, especially in later stages of the biofilm development, with families such as Flavobacteriaceae, Rhodobacteraceae, Planctomycetaceae and Phyllobacteriaceae presenting relatively high relative abundances on all surfaces. Another part of the bacterial community was plastic-type specific. The plastic-type specific fraction was variable among the different plastic types and was more abundant after one week of incubation than at later stages of the succession. [ABSTRACT FROM AUTHOR]

Background and aim: Self-medication (SM) is one part of self-care which is known to contribute to primary health care. If practiced appropriately, it has major benefits for the consumers such as self-reliance and decreased expense. However, inappropriate practice can have potential dangers such as incorrect self-diagnosis, dangerous drug-drug interactions, incorrect manner of administration, incorrect dosage, incorrect choice of therapy, masking of a severe disease, and/or risk of dependence and abuse. The main objective of this study was to assess the prevalence and determinants of the self-medication practice (SMP) in Addis Ababa. Methodology: A community based cross-sectional study was conducted among selected households in Addis Ababa from April 2016 to May 2016, with a recall period of two months before its conduction. Trained data collectors were employed to collect the data from the 604 sampled participants using pre-tested and validated questionnaires. Result: Among the 604 participants involved in this study, 422 (69.9%) were female and 182 (30.1%) were male and there was a mean age of 41.04 (± 13.45) years. The prevalence of SM in this study was 75.5%. The three most frequently reported ailments were headache 117 (25.7%), abdominal pain 59 (12.9%) and cough 54 (11.8%). The two main reasons for SM were mildness of illness 216 (47.4%) and previous knowledge about the drug 106 (23.2%). The two most frequently consumed medications were paracetamol 92 (20.2%) and traditional remedies 73 (16.0%), while drug retail outlets 319 (83.3%) were the main source of drugs. The two most frequently reported source of drug information were health professionals 174 (45.4%) and experience from previous treatment 82 (21.4%). Moreover, there were statistically significant differences among respondents who reported practicing SM based on income and knowledge about appropriate SMP. Conclusion and recommendation: Self-medication was practiced with a range of drugs from the conventional paracetamol and NSAIDs to antimicrobials. Being that the practice of SM is inevitable, health authorities and professionals are highly demanded to educate the public not only on the advantages and disadvantages of SM but on its proper use. [ABSTRACT FROM AUTHOR]

Even among isogenic cells, the time to progress through the cell cycle, or the intermitotic time (IMT), is highly variable. This variability has been a topic of research for several decades and numerous mathematical models have been proposed to explain it. Previously, we developed a top-down, stochastic drift-diffusion+threshold (DDT) model of a cell cycle checkpoint and showed that it can accurately describe experimentally-derived IMT distributions [Leander R, Allen EJ, Garbett SP, Tyson DR, Quaranta V. Derivation and experimental comparison of cell-division probability densities. J. Theor. Biol. 2014;358:129–135]. Here, we use the DDT modeling approach for both descriptive and predictive data analysis. We develop a custom numerical method for the reliable maximum likelihood estimation of model parameters in the absence of a priori knowledge about the number of detectable checkpoints. We employ this method to fit different variants of the DDT model (with one, two, and three checkpoints) to IMT data from multiple cell lines under different growth conditions and drug treatments. We find that a two-checkpoint model best describes the data, consistent with the notion that the cell cycle can be broadly separated into two steps: the commitment to divide and the process of cell division. The model predicts one part of the cell cycle to be highly variable and growth factor sensitive while the other is less variable and relatively refractory to growth factor signaling. Using experimental data that separates IMT into G1 vs. S, G2, and M phases, we show that the model-predicted growth-factor-sensitive part of the cell cycle corresponds to a portion of G1, consistent with previous studies suggesting that the commitment step is the primary source of IMT variability. These results demonstrate that a simple stochastic model, with just a handful of parameters, can provide fundamental insights into the biological underpinnings of cell cycle progression. [ABSTRACT FROM AUTHOR]

Young children not only need to learn how to perform isolated actions, but also temporally and spatially coordinated actions such as using a knife and fork. Routes to learning such coordinated actions include imitation and participation in joint action. However, little is known about the mechanisms guiding transmission of coordinated actions through observation and joint action performance. This paper reports an experiment comparing children’s tendency to imitate multiple, coordinated actions following demonstration by a single model acting bimanually (Bimanual Observation condition), two models performing the same actions jointly with one performing each hand action (Joint Observation condition) and a condition in which the child actively takes part in the joint action demonstration by performing one part in coordination with a partner (Joint Action condition). When children were subsequently left alone to perform the task independently, they were more likely to imitate both coordinated actions in the two observation conditions than in the Joint Action condition, with no difference between performance in Bimanual and Joint Observation conditions. It is argued that this is due to children being more able to form a global representation of both actions and the relations between the two when observing from a distance than when actively involved in the task. [ABSTRACT FROM AUTHOR]

We investigated soluble carbohydrate transport in trees that differed in their phloem loading strategies in order to better understand the transport of photosynthetic products into the roots and the rhizosphere as this knowledge is needed to better understand the respiratory processes in the rhizosphere. We compared beech, which is suggested to use mainly passive loading of transport sugars along a concentration gradient into the phloem, with ash that uses active loading and polymer trapping of raffinose family oligosaccharides (RFOs). We pulse-labeled 20 four-year old European beech and 20 four-year old ash trees with 13CO2 and tracked the fate of the label within different plant compartments. We extracted soluble carbohydrates from leaves, bark of stems and branches, and fine roots, measured their amount and isotopic content and calculated their turnover times. In beech one part of the sucrose was rapidly transported into sink tissues without major exchange with storage pools whereas another part of sucrose was strongly exchanged with unlabeled possibly stored sucrose. In contrast the storage and allocation patterns in ash depended on the identity of the transported sugars. RFO were the most important transport sugars that had highest turnover in all shoot compartments. However, the turnover of RFOs in the roots was uncoupled from the shoot. The only significant relation between sugars in the stem base and in the roots of ash was found for the amount (r2 = 0.50; p = 0.001) and isotopic content (r2 = 0.47; p = 0.01) of sucrose. The negative relation of the amounts suggested an active transport of sucrose into the roots of ash. Sucrose concentration in the root also best explained the concentration of RFOs in the roots suggesting that RFO in the roots of ash may be resynthesized from sucrose. Our results interestingly suggest that in both tree species only sucrose directly entered the fine root system and that in ash RFOs are transported indirectly into the fine roots only. The direct transport of sucrose might be passive in beech but active in ash (sustained active up- and unloading to co-cells), which would correspond to the phloem loading strategies. Our results give first hints that the transport of carbohydrates between shoot and root is not necessarily continuous and involves passive (beech) and active (ash) transport processes, which may be controlled by the phloem unloading. [ABSTRACT FROM AUTHOR]

Usually, the origin of a within-cohort bimodal size distribution is assumed to be caused by initial size differences or by one discrete period of accelerated growth for one part of the population. The aim of this study was to determine if more continuous pathways exist allowing shifts from the small to the large fraction within a bimodal age-cohort. Therefore, a Eurasian perch population, which had already developed a bimodal size-distribution and had differential resource use of the two size-cohorts, was examined. Results revealed that formation of a bimodal size-distribution can be a continuous process. Perch from the small size-cohort were able to grow into the large size-cohort by feeding on macroinvertebrates not used by their conspecifics. The diet shifts were accompanied by morphological shape changes. Intra-specific competition seemed to trigger the development towards an increasing number of large individuals. A stage-structured matrix model confirmed these assumptions. The fact that bimodality can be a continuous process is important to consider for the understanding of ecological processes and links within ecosystems. [ABSTRACT FROM AUTHOR]

Many challenging engineering problems are regular, meaning solutions to one part of a problem can be reused to solve other parts. Evolutionary algorithms with indirect encoding perform better on regular problems because they reuse genomic information to create regular phenotypes. However, on problems that are mostly regular, but contain some irregularities, which describes most real-world problems, indirect encodings struggle to handle the irregularities, hurting performance. Direct encodings are better at producing irregular phenotypes, but cannot exploit regularity. An algorithm called HybrID combines the best of both: it first evolves with indirect encoding to exploit problem regularity, then switches to direct encoding to handle problem irregularity. While HybrID has been shown to outperform both indirect and direct encoding, its initial implementation required the manual specification of when to switch from indirect to direct encoding. In this paper, we test two new methods to improve HybrID by eliminating the need to manually specify this parameter. Auto-Switch-HybrID automatically switches from indirect to direct encoding when fitness stagnates. Offset-HybrID simultaneously evolves an indirect encoding with directly encoded offsets, eliminating the need to switch. We compare the original HybrID to these alternatives on three different problems with adjustable regularity. The results show that both Auto-Switch-HybrID and Offset-HybrID outperform the original HybrID on different types of problems, and thus offer more tools for researchers to solve challenging problems. The Offset-HybrID algorithm is particularly interesting because it suggests a path forward for automatically and simultaneously combining the best traits of indirect and direct encoding. [ABSTRACT FROM AUTHOR]

Colony Collapse Disorder (CCD) has become a global problem for beekeepers and for the crops that depend on bee pollination. While many factors are known to increase the risk of colony collapse, the ectoparasitic mite Varroa destructor is considered to be the most serious one. Although this mite is unlikely to cause the collapse of hives itself, it is the vector for many viral diseases which are among the likely causes for Colony Collapse Disorder. The effects of V. destructor infestation differ from one part of the world to another, with greater morbidity and higher colony losses in European honey bees (EHB) in Europe, Asia and North America. Although this mite has been present in Brazil for many years, there have been no reports of colony losses amongst Africanized Honey Bees (AHB). Studies carried out in Mexico have highlighted different behavioral responses by the AHB to the presence of the mite, notably as far as grooming and hygienic behavior are concerned. Could these explain why the AHB are less susceptible to Colony Collapse Disorder? In order to answer this question, we have developed a mathematical model of the infestation dynamics to analyze the role of resistance behavior by bees in the overall health of the colony, and as a consequence, its ability to face epidemiological challenges. [ABSTRACT FROM AUTHOR]

Reliable and real-time information on soil and crop properties is important for the development of management practices in accordance with the requirements of a specific soil and crop within individual field units. This is particularly the case in salt-affected agricultural landscape where managing the spatial variability of soil salinity is essential to minimize salinization and maximize crop output. The primary objectives were to use linear mixed-effects model for soil salinity and crop yield calibration with horizontal and vertical electromagnetic induction (EMI) measurements as ancillary data, to characterize the spatial distribution of soil salinity and crop yield and to verify the accuracy of spatial estimation. Horizontal and vertical EMI (type EM38) measurements at 252 locations were made during each survey, and root zone soil samples and crop samples at 64 sampling sites were collected. This work was periodically conducted on eight dates from June 2012 to May 2013 in a coastal salt-affected mud farmland. Multiple linear regression (MLR) and restricted maximum likelihood (REML) were applied to calibrate root zone soil salinity (ECe) and crop annual output (CAO) using ancillary data, and spatial distribution of soil ECe and CAO was generated using digital soil mapping (DSM) and the precision of spatial estimation was examined using the collected meteorological and groundwater data. Results indicated that a reduced model with EMh as a predictor was satisfactory for root zone ECe calibration, whereas a full model with both EMh and EMv as predictors met the requirement of CAO calibration. The obtained distribution maps of ECe showed consistency with those of EMI measurements at the corresponding time, and the spatial distribution of CAO generated from ancillary data showed agreement with that derived from raw crop data. Statistics of jackknifing procedure confirmed that the spatial estimation of ECe and CAO exhibited reliability and high accuracy. A general increasing trend of ECe was observed and moderately saline and very saline soils were predominant during the survey period. The temporal dynamics of root zone ECe coincided with those of daily rainfall, water table and groundwater data. Long-range EMI surveys and data collection are needed to capture the spatial and temporal variability of soil and crop parameters. Such results allowed us to conclude that, cost-effective and efficient EMI surveys, as one part of multi-source data for DSM, could be successfully used to characterize the spatial variability of soil salinity, to monitor the spatial and temporal dynamics of soil salinity, and to spatially estimate potential crop yield. [ABSTRACT FROM AUTHOR]

Human social interaction is often intermittent. Two acquainted persons can have extended periods without social interaction punctuated by periods of repeated interaction. In this case, the repeated interaction can be characterized by a seed initiative by either of the persons and a number of follow-up interactions. The tendency to initiate social interaction plays an important role in the formation of social networks and is in general not symmetric between persons. In this paper, we study the dynamics of initiative by analysing and modeling a detailed call and text message network sampled from a group of 700 individuals. We show that in an average relationship between two individuals, one part is almost twice as likely to initiate communication compared to the other part. The asymmetry has social consequences and ultimately might lead to the discontinuation of a relationship. We explain the observed asymmetry by a positive feedback mechanism where individuals already taking initiative are more likely to take initiative in the future. In general, people with many initiatives receive attention from a broader spectrum of friends than people with few initiatives. Lastly, we compare the likelihood of taking initiative with the basic personality traits of the five factor model. [ABSTRACT FROM AUTHOR]

Studies of marine viromes (viral metagenomes) have revealed that DNA viruses are highly diverse and exhibit biogeographic patterns. However, little is known about the diversity of RNA viruses, which are mostly composed of eukaryotic viruses, and their biogeographic patterns in the oceans. A growth in global commerce and maritime traffic may accelerate spread of diverse and non-cosmopolitan DNA viruses and potentially RNA viruses from one part of the world to another. Here, we demonstrated through metagenomic analyses that failure to comply with mid-ocean ballast water exchange regulation could result in movement of viromes including both DNA viruses and RNA viruses (including potential viral pathogens) unique to geographic and environmental niches. Furthermore, our results showed that virus richness (known and unknown viruses) in ballast water is associated with distance between ballast water exchange location and its nearest shoreline as well as length of water storage time in ballast tanks (voyage duration). However, richness of only known viruses is governed by local environmental conditions and different viral groups have different responses to environmental variation. Overall, these results identified ballast water as a factor contributing to ocean virome transport and potentially increased exposure of the aquatic bioshpere to viral invasion. [ABSTRACT FROM AUTHOR]

Purpose: To examine the associations between overweight/obesity and occupation among Hispanics/Latinos, the largest minority population in the U.S. Methods: This study included 7,409 employed individuals in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a prospective study of Hispanic/Latino individuals aged 18–74 in four communities in the U.S. We independently examined the relationships between BMI, Occupational Activity (OA), and Total Hours Worked, quantified via self-reported hours worked per week and occupation-assigned Metabolic Equivalents (METs). Results: More than three quarters of the participants were either overweight (39.3%) or obese (37.8%). Individuals with a primary occupation and those employed in a secondary occupation worked an average of 36.8 and 14.6 hrs/wk, respectively. The overall adjusted odds for being obese compared to normal weight were 3.2% (AOR = 1.03, 95% CI 1.01, 1.05) and 14.4% (AOR = 1.14 95% Cl 1.07, 1.23) greater for each 10 MET•hrs/wk unit of increased OA, and each 10-hrs/wk unit of Total Hours Worked, respectively. Conclusion: This study presents the first findings on the association between OA with overweight/obesity among Hispanic/Latino individuals in the U.S. Increasing OA and Total Hours Worked per week were independently associated with increasing odds of overweight/obesity suggesting that the workplace is only one part of the overall energy expenditure dynamic. Our findings point to the need to emphasize engaging employed individuals in greater levels of PA outside of the work environment to impact overweight/obesity. [ABSTRACT FROM AUTHOR]

Human observers are remarkably proficient at recognizing expressions of emotions and at readily grouping them into distinct categories. When morphing one facial expression into another, the linear changes in low-level features are insufficient to describe the changes in perception, which instead follow an s-shaped function. Important questions are, whether there are single diagnostic regions in the face that drive categorical perception for certain parings of emotion expressions, and how information in those regions interacts when presented together. We report results from two experiments with morphed fear-anger expressions, where (a) half of the face was masked or (b) composite faces made up of different expressions were presented. When isolated upper and lower halves of faces were shown, the eyes were found to be almost as diagnostic as the whole face, with the response function showing a steep category boundary. In contrast, the mouth allowed for a substantially lesser amount of accuracy and responses followed a much flatter psychometric function. When a composite face consisting of mismatched upper and lower halves was used and observers were instructed to exclusively judge either the expression of mouth or eyes, the to-be-ignored part always influenced perception of the target region. In line with experiment 1, the eye region exerted a much stronger influence on mouth judgements than vice versa. Again, categorical perception was significantly more pronounced for upper halves of faces. The present study shows that identification of fear and anger in morphed faces relies heavily on information from the upper half of the face, most likely the eye region. Categorical perception is possible when only the upper face half is present, but compromised when only the lower part is shown. Moreover, observers tend to integrate all available features of a face, even when trying to focus on only one part. [ABSTRACT FROM AUTHOR]

Existing estimates of fish and consumer biomass in the world’s oceans are disparate. This creates uncertainty about the roles of fish and other consumers in biogeochemical cycles and ecosystem processes, the extent of human and environmental impacts and fishery potential. We develop and use a size-based macroecological model to assess the effects of parameter uncertainty on predicted consumer biomass, production and distribution. Resulting uncertainty is large (e.g. median global biomass 4.9 billion tonnes for consumers weighing 1 g to 1000 kg; 50% uncertainty intervals of 2 to 10.4 billion tonnes; 90% uncertainty intervals of 0.3 to 26.1 billion tonnes) and driven primarily by uncertainty in trophic transfer efficiency and its relationship with predator-prey body mass ratios. Even the upper uncertainty intervals for global predictions of consumer biomass demonstrate the remarkable scarcity of marine consumers, with less than one part in 30 million by volume of the global oceans comprising tissue of macroscopic animals. Thus the apparently high densities of marine life seen in surface and coastal waters and frequently visited abundance hotspots will likely give many in society a false impression of the abundance of marine animals. Unexploited baseline biomass predictions from the simple macroecological model were used to calibrate a more complex size- and trait-based model to estimate fisheries yield and impacts. Yields are highly dependent on baseline biomass and fisheries selectivity. Predicted global sustainable fisheries yield increases ≈4 fold when smaller individuals (< 20 cm from species of maximum mass < 1kg) are targeted in all oceans, but the predicted yields would rarely be accessible in practice and this fishing strategy leads to the collapse of larger species if fishing mortality rates on different size classes cannot be decoupled. Our analyses show that models with minimal parameter demands that are based on a few established ecological principles can support equitable analysis and comparison of diverse ecosystems. The analyses provide insights into the effects of parameter uncertainty on global biomass and production estimates, which have yet to be achieved with complex models, and will therefore help to highlight priorities for future research and data collection. However, the focus on simple model structures and global processes means that non-phytoplankton primary production and several groups, structures and processes of ecological and conservation interest are not represented. Consequently, our simple models become increasingly less useful than more complex alternatives when addressing questions about food web structure and function, biodiversity, resilience and human impacts at smaller scales and for areas closer to coasts. [ABSTRACT FROM AUTHOR]

Developing generalisations of invasive species is an important part of invasion biology. However, trends and generalisations from one part of the world may not necessarily hold elsewhere. We present the first inventory and analysis of all Hymenoptera alien to New Zealand, and compare patterns from New Zealand with those previously published from Europe (DAISIE). Between the two regions there was broad correlation between families with the highest number of alien species (Braconidae, Encyrtidae, Pteromalidae, Eulophidae, Formicidae, Aphelinidae). However, major differences also existed. The number of species alien to New Zealand is higher than for Europe (334 vs 286), and major differences include: i) the much lower proportion of intentionally released species in New Zealand (21% vs 63% in Europe); and ii) the greater proportion of unintentionally introduced parasitoids in New Zealand (71.2% vs 22.6%). The disharmonic ‘island’ nature of New Zealand is shown, as a high proportion of families (36%) have no native representatives, and alien species also represent >10% of the native fauna for many other families. A much larger proportion of alien species are found in urban areas in New Zealand (60%) compared to Europe (~30%), and higher numbers of alien species were present earlier in New Zealand (especially <1950). Differences in the origins of alien species were also apparent. Unlike Europe, the New Zealand data reveals a change in the origins of alien species over time, with an increasing dominance of alien species from Australasia (a regional neighbour) during the past 25 years. We recommend that further effort be made towards the formation, and analysis, of regional inventories of alien species. This will allow a wider range of taxa and regions to be examined for generalisations, and help assess and prioritise the risk posed by certain taxa towards the economy or environment. [ABSTRACT FROM AUTHOR]

Phenotypic mosaic trees offer an ideal system for studying differential gene expression. We have investigated two mosaic eucalypt trees from two closely related species (Eucalyptus melliodora and E. sideroxylon), which each support two types of leaves: one part of the canopy is resistant to insect herbivory and the remaining leaves are susceptible. Driving this ecological distinction are differences in plant secondary metabolites. We used these phenotypic mosaics to investigate genome wide patterns of foliar gene expression with the aim of identifying patterns of differential gene expression and the somatic mutation(s) that lead to this phenotypic mosaicism. We sequenced the mRNA pool from leaves of the resistant and susceptible ecotypes from both mosaic eucalypts using the Illumina HiSeq 2000 platform. We found large differences in pathway regulation and gene expression between the ecotypes of each mosaic. The expression of the genes in the MVA and MEP pathways is reflected by variation in leaf chemistry, however this is not the case for the terpene synthases. Apart from the terpene biosynthetic pathway, there are several other metabolic pathways that are differentially regulated between the two ecotypes, suggesting there is much more phenotypic diversity than has been described. Despite the close relationship between the two species, they show large differences in the global patterns of gene and pathway regulation. [ABSTRACT FROM AUTHOR]

The need for interfacing structural biology and biophysics to molecular evolution is being increasingly recognized. One part of the big problem is to understand how physics and chemistry shape the sequence space available to functional proteins, while satisfying the needs of biology. Here we present a quantitative, structure-based analysis of a high-resolution map describing the tolerance to all substitutions in all positions of a functional enzyme, namely a TEM lactamase previously studied through deep sequencing of mutants growing in competition experiments with selection against ampicillin. Substitutions are rarely observed within 7 Å of the active site, a stringency that is relaxed slowly and extends up to 15–20 Å, with buried residues being especially sensitive. Substitution patterns in over one third of the residues can be quantitatively modeled by monotonic dependencies on amino acid descriptors and predictions of changes in folding stability. Amino acid volume and steric hindrance shape constraints on the protein core; hydrophobicity and solubility shape constraints on hydrophobic clusters underneath the surface, and on salt bridges and polar networks at the protein surface together with charge and hydrogen bonding capacity. Amino acid solubility, flexibility and conformational descriptors also provide additional constraints at many locations. These findings provide fundamental insights into the chemistry underlying protein evolution and design, by quantitating links between sequence and different protein traits, illuminating subtle and unexpected sequence-trait relationships and pinpointing what traits are sacrificed upon gain-of-function mutation. [ABSTRACT FROM AUTHOR]

Aphids exhibit a form of phenotypic plasticity, called polyphenism, in which genetically identical females reproduce sexually during one part of the life cycle and asexually (via parthenogenesis) during the remainder of the life cycle. The molecular basis for aphid parthenogenesis is unknown. Cytological observations of aphid parthenogenesis suggest that asexual oogenesis evolved either through a modification of meiosis or from a mitotic process. As a test of these alternatives, we assessed the expression levels and expression patterns of canonical meiotic recombination and germline genes in the sexual and asexual ovaries of the pea aphid, Acyrthosiphon pisum. We observed expression of all meiosis genes in similar patterns in asexual and sexual ovaries, with the exception that some genes encoding Argonaute-family members were not expressed in sexual ovaries. In addition, we observed that asexual aphid tissues accumulated unspliced transcripts of Spo11, whereas sexual aphid tissues accumulated primarily spliced transcripts. In situ hybridization revealed Spo11 transcript in sexual germ cells and undetectable levels of Spo11 transcript in asexual germ cells. We also found that an obligately asexual strain of pea aphid produced little spliced Spo11 transcript. Together, these results suggest that parthenogenetic oogenesis evolved from a meiosis-like, and not a mitosis-like, process and that the aphid reproductive polyphenism may involve a modification of Spo11 gene activity. [ABSTRACT FROM AUTHOR]

In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model. [ABSTRACT FROM AUTHOR]

Implantation failure and early pregnancy loss have been reported to be closely related to the quality of mammalian oocytes; however, the pregnant outcome of embryos from in-vitro matured (IVM) oocytes remains unknown. In this study we examined spindle assembly and chromosome segregation during differentiation, and the duration of IVM of mouse oocytes. The resulting implantation and pregnancy outcomes were analyzed to clarify the relationship between the spindle and chromosomes of IVM oocytes and implantation and early pregnancy. Cumulus-enclosed germinal vesicle oocytes were collected and randomly cultured in IVM medium with different IVM durations. One part of IVM oocytes were analyzed the spindle and chromosome morphology by immunofluorescence method, and the other part of them were fertilized by intracytoplasmic sperm injection. The resulting embryos were transferred into pseudo-pregnant female mice, and the post-implantation and full term development was observed. The chromosome aberrations and incorrect spindle assembly seems not affect the early development and blastocyst cell number derived from IVM oocytes, however the development potential of the resulting embryos after implantation were significant decreased with the ratio increasing of chromosome aberrations and incorrect spindle assembly. Accordingly, the full-term development was also decreased. In conclusion, the present study showed the spindle assembly of in vitro-matured oocytes was one of the most important factors that affected the implantation and ongoing pregnancy rates of IVM oocytes, and the improvement by an appropriate duration of maturation in vitro will enhance the post-implantation development potential of the resulting embryos, and decrease implantation failure and early pregnancy loss. [ABSTRACT FROM AUTHOR]

Introduction: To combat the AIDS epidemic and increase HIV treatment access, the South African government implemented a nurse-based, doctor-supported model of care that decentralizes administration of antiretroviral treatment (ART) for HIV positive patients through nurse initiated and managed ART. Médecins Sans Frontières (MSF) implemented a mentorship programme to ensure successful task-shifting, subsequently assessing the quality of clinical care provided by nurses. Methods: A before-after cross-sectional study was conducted on nurses completing the mentorship programme in Khayelitsha, South Africa, from February 2011-September 2012. Routine clinical data from 229 patient folders and 21 self-assessment questionnaires was collected to determine the number of patients initiated on ART by nurses; quality of ART management before-after mentorship; patient characteristics for doctor and nurse ART initiations; and nurse self-assessments after mentorship. Results: Twenty one nurses were authorized by one nurse mentor with one part-time medical officer's support, resulting in nurses initiating 77% of ART eligible patients. Improvements in ART management were found for drawing required bloods (91% vs 99%, p = 0.03), assessing adherence (50% vs 78%, p<0.001) and WHO staging (63% vs 91%, p<0.001). Nurse ART initiation indicators were successfully completed at 95–100% for 11 of 16 indicators: clinical presentation; patient weight; baseline blood work (CD4, creatinine, haemoglobin); STI screening; WHO stage, correlating medical history; medications prescribed appropriately; ART start date; and documented return date. Doctors initiated more patients with TB/HIV co-infection and WHO Stage 3 and 4 disease than nurses. Nurse confidence improved for managing HIV-infected children and pregnant women, blood result interpretation and long-term side effects. Conclusions: Implementation of a clinical mentorship programme in Khayelitsha led to nurse initiation of a majority of eligible patients, enabling medical officers to manage complex cases. As mentorship can increase clinical confidence and enhance professional development, it should be considered essential for universal ART access in resource limited settings. [ABSTRACT FROM AUTHOR]

Background: The most distinguishing genetic feature of hepatitis C virus (HCV) is its remarkable diversity and variation. To understand this feature, we previously performed genetic analysis of HCV in the long-term culture of human hepatoma HuH-7-derived HCV RNA-replicating cell lines. On the other hand, we newly established HCV RNA-replicating cell lines using human hepatoma Li23 cells, which were distinct from HuH-7 cells. Methodology/Principal Findings: Li23-derived HCV RNA-replicating cells were cultured for 4 years. We performed genetic analysis of HCVs recovered from these cells at 0, 2, and 4 years in culture. Most analysis was performed in two separate parts: one part covered from the 5′-terminus to NS2, which is mostly nonessential for RNA replication, and the other part covered from NS3 to NS5B, which is essential for RNA replication. Genetic mutations in both regions accumulated in a time-dependent manner, and the mutation rates in the 5′-terminus-NS2 and NS3-NS5B regions were 4.0–9.0×10−3 and 2.7–4.0×10−3 base substitutions/site/year, respectively. These results suggest that the variation in the NS3-NS5B regions is affected by the pressure of RNA replication. Several in-frame deletions (3–105 nucleotides) were detected in the structural regions of HCV RNAs obtained from 2-year or 4-year cultured cells. Phylogenetic tree analyses clearly showed that the genetic diversity of HCV was expanded in a time-dependent manner. The GC content of HCV RNA was significantly increased in a time-dependent manner, as previously observed in HuH-7-derived cell systems. This phenomenon was partially due to the alterations in codon usages for codon optimization in human cells. Furthermore, we demonstrated that these long-term cultured cells were useful as a source for the selection of HCV clones showing resistance to anti-HCV agents. Conclusions/Significance: Long-term cultured HCV RNA-replicating cells are useful for the analysis of evolutionary dynamics and variations of HCV and for drug-resistance analysis. [ABSTRACT FROM AUTHOR]

Recent years have seen a growing consensus that events during one part of an animal's annual cycle can detrimentally affect its future fitness. Notably, migratory species have been shown to commonly display such carry-over effects, facing severe time constraints and physiological stresses that can influence events across seasons. However, to date, no study has examined a full annual cycle to determine when these carry-over effects arise and how long they persist within and across years. Understanding when carry-over effects are created and how they persist is critical to identifying those periods and geographic locations that constrain the annual cycle of a population and determining how selection is acting upon individuals throughout the entire year. Using three consecutive years of migration tracks and four consecutive years of breeding success data, we tested whether carry-over effects in the form of timing deviations during one migratory segment of the annual cycle represent fitness costs that persist or accumulate across the annual cycle for a long-distance migratory bird, the Hudsonian godwit, Limosa haemastica. We found that individual godwits could migrate progressively later than population mean over the course of an entire migration period, especially southbound migration, but that these deviations did not accumulate across the entire year and were not consistently detected among individuals across years. Furthermore, neither the accumulation of lateness during previous portions of the annual cycle nor arrival date at the breeding grounds resulted in individuals suffering reductions in their breeding success or survival. Given their extreme life history, such a lack of carry-over effects suggests that strong selection exists on godwits at each stage of the annual cycle and that carry-over effects may not be able to persist in such a system, but also emphasizes that high-quality stopover and wintering sites are critical to the maintenance of long-distance migratory populations. [ABSTRACT FROM AUTHOR]

Background: Multiple biomarker testing is necessary to facilitate individualized treatment of lung cancer patients. More than 80% of lung cancers are diagnosed based on very small tumor samples. Often there is not enough tissue for molecular analysis. We compared three minimal invasive sampling methods with respect to RNA quantity for molecular testing. Methods: 106 small biopsies were prospectively collected by three different methods forceps biopsy, endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA), and CT-guided core biopsy. Samples were split into two halves. One part was formalin fixed and paraffin embedded for standard pathological evaluation. The other part was put in RNAlater for immediate RNA/DNA extraction. If the pathologist confirmed the diagnosis of non-small cell lung cancer(NSCLC), the following molecular markers were tested: EGFR mutation, ERCC1, RRM1 and BRCA1. Results: Overall, RNA-extraction was possible in 101 out of 106 patients (95.3%). We found 49% adenocarcinomas, 38% squamouscarcinomas, and 14% non-otherwise-specified(NOS). The highest RNA yield came from endobronchial ultrasound guided needle aspiration, which was significantly higher than bronchoscopy (37.74±41.09 vs. 13.74±15.53 ng respectively, P = 0.005) and numerically higher than CT-core biopsy (37.74±41.09 vs. 28.72±44.27 ng respectively, P = 0.244). EGFR mutation testing was feasible in 100% of evaluable patients and its incidence was 40.8%, 7.9% and 14.3% in adenocarcinomas, squamouscarcinomas and NSCLC NOS subgroup respectively. There was no difference in the feasibility of molecular testing between the three sampling methods with feasibility rates for ERCC1, RRM1 and BRCA1 of 91%, 87% and 81% respectively. Conclusion: All three methods can provide sufficient tumor material for multiple biomarkers testing from routinely obtained small biopsies in lung cancer patients. In our study EBUS guided needle aspiration provided the highest amount of tumor RNA compared to bronchoscopy or CT guided core biopsy. Thus EBUS should be considered as an acceptable option for tissue acquisition for molecular testing. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrosis, as a hallmark of atrial structure remodeling, plays an important role in maintenance of chronic atrial fibrillation, but interrelationship of atrial fibrosis and atrial fibrillation is uncertain. Label-free proteomics can implement high throughput screening for finding and analyzing pivotal proteins related to the disease.. Therefore, we used label-free proteomics to explore and analyze differentially proteins in chronic atrial fibrillation patients with mitral valve disease. Methods: Left and right atrial appendages obtained from patients with mitral valve disease were both in chronic atrial fibrillation (CAF, AF≥6 months, n = 6) and in sinus rhythm (SR, n = 6). One part of the sample was used for histological analysis and fibrosis quantification; other part were analyzed by label-free proteomic combining liquid chromatography with mass spectrometry (LC-MS), we utilized bioinformatics analysis to identify differential proteins. Results: Degree of atrial fibrosis was higher in CAF patients than that of SR patients. 223 differential proteins were detected between two groups. These proteins mainly had vital functions such as cell proliferation, stress response, focal adhesion apoptosis. We evaluated that serine/threonine protein kinase N2 (PKN2), dermatopontin(DP), S100 calcium binding protein B(S100B), protein tyrosine kinase 2(PTK2) and discoidin domain receptor tyrosine kinase 2(DDR2) played important roles in fibrotic process related to atrial fibrillation. Conclusion: The study presented differential proteins responsible for atrial fibrosis in chronic atrial fibrillation patients through label-free proteomic analysis. We assessed some vital proteins including their characters and roles. These findings may open up new realm for mechanism research of atrial fibrillation. [ABSTRACT FROM AUTHOR]

Open-bore MRI scanners allow joint soft tissue to be imaged over a large, uninterrupted range of flexion. Using an openbore scanner, 3D para-sagittal images of the posterior cruciate ligament (PCL) were collected from seven healthy subjects in unloaded, recumbent knee extension and flexion. PCL length was measured from one 2D MRI slice partition per flexion angle, per subject. The anterior surface of the PCL lengthened significantly between extension and flexion (p<0.001). Conversely, the posterior surface did not. Changes were not due to the PCL moving relative to the 2D slice partition; measurements made from 3D reconstructions, which compensated for PCL movement, did not differ significantly from measurements made from 2D slice partitions. In a second experiment, videos of knee flexion were made by imaging two subjects at several flexion angles. Videos allowed soft tissue tracking; examples are included. In a third experiment, unloaded knees of seven healthy, recumbent subjects were imaged at extension and at 40°, 70°, 90°, 100°, 110° and 120° flexion.The distance between PCL attachments increased between extension and 100°, and then decreased (p<0.001). The anterior surface of the PCL lengthened over the flexion angles measured (p<0.01). The posterior surface of the PCL lengthened between extension and 40° and then shortened (p<0.001). Both attachment separation and anterior surface length increased dramatically between extension and 40°, but varied less afterwards. Results indicate that PCL dynamics differ between terminal extension and active function sub-arcs. Also, attachment separation cannot predict the lengthening of all parts of the PCL, nor can lengthening of one part of the PCL predict the lengthening of another part. A potential connection between lengthening and loading is discussed. We conclude that low-field MRI can assess ligament lengthening during flexion, and that the dynamics of the PCL for any given region and sub-arc should be measured directly. [ABSTRACT FROM AUTHOR]

Generally, chemical tissue clearing is performed by a solution consisting of two parts benzyl benzoate and one part benzyl alcohol. However, prolonged exposure to this mixture markedly reduces the fluorescence of GFP expressing specimens, so that one has to compromise between clearing quality and fluorescence preservation. This can be a severe drawback when working with specimens exhibiting low GFP expression rates. Thus, we screened for a substitute and found that dibenzyl ether (phenylmethoxymethylbenzene, CAS 103-50-4) can be applied as a more GFP-friendly clearing medium. Clearing with dibenzyl ether provides improved tissue transparency and strikingly improved fluorescence intensity in GFP expressing mouse brains and other samples as mouse spinal cords, or embryos. Chemical clearing, staining, and embedding of biological samples mostly requires careful foregoing tissue dehydration. The commonly applied tissue dehydration medium is ethanol, which also can markedly impair GFP fluorescence. Screening for a substitute also for ethanol we found that tetrahydrofuran (CAS 109-99-9) is a more GFP-friendly dehydration medium than ethanol, providing better tissue transparency obtained by successive clearing. Combined, tetrahydrofuran and dibenzyl ether allow dehydration and chemical clearing of even delicate samples for UM, confocal microscopy, and other microscopy techniques. [ABSTRACT FROM AUTHOR]

Background: Complex networks can often be decomposed into less complex sub-networks whose structures can give hints about the functional organization of the network as a whole. However, these structural motifs can only tell one part of the functional story because in this analysis each node and edge is treated on an equal footing. In real networks, two motifs that are topologically identical but whose nodes perform very different functions will play very different roles in the network. Methodology/Principal Findings: Here, we combine structural information derived from the topology of the neuronal network of the nematode C. elegans with information about the biological function of these nodes, thus coloring nodes by function. We discover that particular colorations of motifs are significantly more abundant in the worm brain than expected by chance, and have particular computational functions that emphasize the feed-forward structure of information processing in the network, while evading feedback loops. Interneurons are strongly over-represented among the common motifs, supporting the notion that these motifs process and transduce the information from the sensor neurons towards the muscles. Some of the most common motifs identified in the search for significant colored motifs play a crucial role in the system of neurons controlling the worm's locomotion. Conclusions/Significance: The analysis of complex networks in terms of colored motifs combines two independent data sets to generate insight about these networks that cannot be obtained with either data set alone. The method is general and should allow a decomposition of any complex networks into its functional (rather than topological) motifs as long as both wiring and functional information is available. [ABSTRACT FROM AUTHOR]

Background: Tumor DNA has been shown to be present both in circulating tumor cells in blood and as fragments in the plasma of metastatic cancer patients. The identification of ultra-rare tumor-specific mutations in blood would be the ultimate marker to measure efficacy of cancer therapy and/ or early recurrence. Herein we present a method for detecting microinsertions/deletions/indels (MIDIs) at ultra-high analytical selectivity. MIDIs comprise about 15% of mutations. Methods and Findings: We describe MIDI-Activated Pyrophosphorolysis (MAP), a method of ultra-high analytical selectivity for detecting MIDIs. The high analytical selectivity of MAP is putatively due to serial coupling of two rare events: heteroduplex slippage and mis-pyrophosphorolysis. MAP generally has an analytical selectivity of one mutant molecule per .1 billion wild type molecules and an analytical sensitivity of one mutant molecule per reaction. The analytical selectivity of MAP is about 100,000-fold better than that of our previously described method of Pyrophosphorolysis Activated Polymerization-Allele specific amplification (PAP-A) for detecting MIDIs. The utility of this method is illustrated in two ways. 1) We demonstrate that two EGFR deletions commonly found in lung cancers are not present in tissue from four normal human lungs (107 copies of gDNA each) or in blood samples from 10 healthy individuals (107 copies of gDNA each). This is inconsistent, at least at an analytical sensitivity of 10-7, with the hypotheses of (a) hypermutation or (b) strong selection of these growth factor-mutated cells during normal lung development leads to accumulation of pre-neoplastic cells with these EGFR mutations, which sometimes can lead to lung cancer in late adulthood. Moreover, MAP was used for large scale, high throughput ''gene pool'' analysis. No germline or early embryonic somatic mosaic mutation was detected (at a frequency of >0.3%) for the 15/18 bp EGFR deletion mutations in 6,400 individuals, suggesting that early embryonic EGFR somatic mutation is very rare, inconsistent with hypermutation or strong selection of these deletions in the embryo. 2) The second illustration of MAP utility is in personalized monitoring of therapy and early recurrence in cancer. Tumor-specific p53 mutations identified at diagnosis in the plasma of six patients with stage II and III breast cancer were undetectable after therapy in four women, consistent with clinical remission, and continued to be detected after treatment in two others, reflecting tumor progression. Conclusions: MAP has an analytical selectivity of one part per billion for detection of MIDIs and an analytical sensitivity of one molecule. MAP provides a general tool for monitoring ultra-rare mutations in tissues and blood. As an example, we show that the personalized cancer signature in six out of six patients with non-metastatic breast cancer can be detected and that levels over time are correlated with the clinical course of disease. [ABSTRACT FROM AUTHOR]

The main purpose of this study is to compare two different feedback controllers for the stabilization of quiet standing in humans, taking into account that the intrinsic ankle stiffness is insufficient and that there is a large delay inducing instability in the feedback loop: 1) a standard linear, continuous-time PD controller and 2) an intermittent PD controller characterized by a switching function defined in the phase plane, with or without a dead zone around the nominal equilibrium state. The stability analysis of the first controller is carried out by using the standard tools of linear control systems, whereas the analysis of the intermittent controllers is based on the use of Poincaré maps defined in the phase plane. When the PDcontrol is off, the dynamics of the system is characterized by a saddle-like equilibrium, with a stable and an unstable manifold. The switching function of the intermittent controller is implemented in such a way that PD-control is 'off' when the state vector is near the stable manifold of the saddle and is 'on' otherwise. A theoretical analysis and a related simulation study show that the intermittent control model is much more robust than the standard model because the size of the region in the parameter space of the feedback control gains (P vs. D) that characterizes stable behavior is much larger in the latter case than in the former one. Moreover, the intermittent controller can use feedback parameters that are much smaller than the standard model. Typical sway patterns generated by the intermittent controller are the result of an alternation between slow motion along the stable manifold of the saddle, when the PD-control is off, and spiral motion away from the upright equilibrium determined by the activation of the PD-control with low feedback gains. Remarkably, overall dynamic stability can be achieved by combining in a smart way two unstable regimes: a saddle and an unstable spiral. The intermittent controller exploits the stabilizing effect of one part of the saddle, letting the system evolve by alone when it slides on or near the stable manifold; when the state vector enters the strongly unstable part of the saddle it switches on a mild feedback which is not supposed to impose a strict stable regime but rather to mitigate the impending fall. The presence of a dead zone in the intermittent controller does not alter the stability properties but improves the similarity with biological sway patterns. The two types of controllers are also compared in the frequency domain by considering the power spectral density (PSD) of the sway sequences generated by the models with additive noise. Different from the standard continuous model, whose PSD function is similar to an over-damped second order system without a resonance, the intermittent control model is capable to exhibit the two power law scaling regimes that are typical of physiological sway movements in humans. [ABSTRACT FROM AUTHOR]