Abundance of Harpy and Crested Eagles from a reservoir-impact area in the Low- and Mid-Xingu River.
In the Brazilian Amazon, two monospecific genera, the Harpy Eagle and Crested Eagle have low densities and are classified by IUCN as Near Threatened due to habitat loss, deforestation, habitat degradation and hunting. In this study, we evaluate occurrence of these large raptors using the environmental surveys database from Belo Monte Hydroelectric Power Plant. Integrating the dataset from two methods, we plotted a distribution map along the Xingu River, including records over a 276-km stretch of river. Terrestrial surveys (RAPELD method) were more efficient for detecting large raptors than standardized aquatic surveys, although the latter were complementary in areas without modules. About 53% of the records were obtained during activities of wildlife rescue/flushing, vegetation suppression or in transit. Between 2012 and 2014, four Harpy Eagles were removed from the wild; two shooting victims, one injured by collision with power lines and one hit by a vehicle. Also, seven nests were mapped. The mean distance between Harpy Eagle records was 15 km along the river channel, with a mean of 20 km between nests near the channel, which allowed us to estimate 20 possible pairs using the alluvial forest, riverine forest and forest fragments. Territories of another ten pairs will probably be affected by inundation of the Volta Grande channel, which is far from the main river. The average distance between Crested Eagle records was 16 km along the river channel. The only nest found was 1.3 km away from a Harpy Eagle nest. The remnant forests are under threat of being replaced by cattle pastures, so we recommend that permanently protected riparian vegetation borders (APP) be guaranteed, and that forest fragments within 5 km of the river be conserved to maintain eagle populations.


Mitochondrial phylogeography of rock-dwelling cichlid fishes reveals evolutionary influence of historical lake level fluctuations of Lake Tanganyika, Africa.
The East African Lakes Tanganyika, Malawi and Victoria each harbour hundreds of endemic invertebrate and vertebrate species. Inferences about the ecological and evolutionary processes responsible for the origin of these species flocks will only be possible when they are made within historical and comparative frameworks. Specifically, the relative importance of intrinsic characteristics and extrinsic factors may offer information about the processes that drive diversification and speciation in these species. We investigated the sequence variation of a segment of the mitochondrial DNA control region of 32 populations representing all four nominal species in the three genera of eretmodine cichlids from Lake Tanganyika. Based on a phylogenetic analysis of these data we attempted to evaluate the importance of major lake level fluctuations on patterns of intralacustrine speciation. The geography of genetic variation reveals a high degree of within-lake endemism among genetically well-separated lineages distributed along the inferred shore lines of three historically intermittent lake basins. Seismic data indicate that extreme lowering of water levels in the Pleistocene caused the single Lake Tanganyika basin to split into three isolated ones. The strong phylogeographic structure of the Eretmodini, and the observation that some closely related populations occur on opposite shores of the lake, agree with this geological scenario. The three-clade-three-basin phylogeographic pattern was repeated twice within this tribe of cichlids. The phylogeographic pattern of eretmodine cichlids suggests that major fluctuations in the level of the lake have been important in shaping their adaptive radiation and speciation. The mitochondrially defined clades are in conflict with the current taxonomy of the group and suggest that there has been convergent evolution in trophic morphology, particularly in the shapes of oral teeth, taxonomically the most diagnostic characters of the three genera.


Modelling the implications of reducing smoking prevalence: the public health and economic benefits of achieving a 'tobacco-free' UK.
Smoking is still the most preventable cause of cancer, and a leading cause of premature mortality and health inequalities in the UK. This study modelled the health and economic impacts of achieving a 'tobacco-free' ambition (TFA) where, by 2035, less than 5% of the population smoke tobacco across all socioeconomic groups. A non-linear multivariate regression model was fitted to cross-sectional smoking data to create projections to 2035. These projections were used to predict the future incidence and costs of 17 smoking-related diseases using a microsimulation approach. The health and economic impacts of achieving a TFA were evaluated against a predicted baseline scenario, where current smoking trends continue. If trends continue, the prevalence of smoking in the UK was projected to be 10% by 2035-well above a TFA. If this ambition were achieved by 2035, it could mean 97 300 +/- 5 300 new cases of smoking-related diseases are avoided by 2035 (tobacco-related cancers: 35 900+/- 4 100; chronic obstructive pulmonary disease: 29 000 +/- 2 700; stroke: 24 900 +/- 2 700; coronary heart disease: 7600 +/- 2 700), including around 12 350 diseases avoided in 2035 alone. The consequence of this health improvement is predicted to avoid £67 +/- 8 million in direct National Health Service and social care costs, and £548 million in non-health costs, in 2035 alone. These findings strengthen the case to set bold targets on long-term declines in smoking prevalence to achieve a tobacco 'endgame'. Results demonstrate the health and economic benefits that meeting a TFA can achieve over just 20 years. Effective ambitions and policy interventions are needed to reduce the disease and economic burden of smoking.


Early sexual behaviour and Chlamydia trachomatis infection - a population based cross-sectional study on gender differences among adolescents in Norway.
Early sexual behaviour has been shown to differ significantly between genders, but few studies have addressed this topic to explain the commonly observed differences in chlamydia rates between adolescent girls and boys. Our study aimed to determine chlamydia prevalence in adolescents aged 15-20 years in a high-incidence area in Norway, and to identify gender-specific early sexual behaviours associated with infection. A population based cross-sectional study was conducted among all high school students in five towns in Finnmark county in 2009, using a web-based questionnaire and real-time Chlamydia trachomatis PCR in first-void urine samples (participation rate 85%, 800 girls/818 boys, mean age 17.2 years). Crude and multivariable logistic regression models were applied with chlamydia test result as dependent variable. Prevalence of chlamydia infection was 5.7% (95% confidence interval, CI, 4.4-7.3%). Girls were twice as likely to be infected as boys (7.3%, 5.3-9.7 vs 3.9%, 2.3-6.0). Girls reported earlier sexual debut, older partners, higher lifetime number of partners, and were poorer condom users. In girls, higher maternal education (odds ratio, OR, 2.2, 95% CI 1.1-4.4), ≥2 sexual partners past 6 months (OR 3.6, 1.8-7.3), and partner meeting venue at a private party, bar or disco (OR 5.0, 1.1-22.7) increased the odds of infection in the multivariable model. In boys, condom use at first intercourse (OR 0.06, 0.01-0.42) decreased the odds of infection, while having an older last sexual partner (OR 3.7, 1.3-11.0) increased the odds. In all participants, the risk of infection increased if residence outside the family home during school year (OR 2.0, 1.2-3.6), and decreased if condom was used at last intercourse (OR 0.2, 0.1-0.8). We detected significant gender differences in chlamydia prevalence and sexual behaviours, and accordingly differing independent risk factors for chlamydia infection. We suggest that accumulation of essentially different experiences in the early sexually active years contribute to gender disparities in chlamydia risk in individuals this age. Gender-specific approaches may be the best alternative to control chlamydia infection in age group 15-20 years.


Acquisition of Viewpoint Transformation and Action Mappings via Sequence to Sequence Imitative Learning by Deep Neural Networks.
We propose an imitative learning model that allows a robot to acquire positional relations between the demonstrator and the robot, and to transform observed actions into robotic actions. Providing robots with imitative capabilities allows us to teach novel actions to them without resorting to trial-and-error approaches. Existing methods for imitative robotic learning require mathematical formulations or conversion modules to translate positional relations between demonstrators and robots. The proposed model uses two neural networks, a convolutional autoencoder (CAE) and a multiple timescale recurrent neural network (MTRNN). The CAE is trained to extract visual features from raw images captured by a camera. The MTRNN is trained to integrate sensory-motor information and to predict next states. We implement this model on a robot and conducted sequence to sequence learning that allows the robot to transform demonstrator actions into robot actions. Through training of the proposed model, representations of actions, manipulated objects, and positional relations are formed in the hierarchical structure of the MTRNN. After training, we confirm capability for generating unlearned imitative patterns.


mGlu5 Receptor Functional Interactions and Addiction.
The idea of "receptor mosaics" is that proteins may form complex and dynamic networks with respect to time and composition. These have the potential to markedly expand the diversity and specificity of G protein-coupled receptors (GPCR) signaling, particularly in neural cells, where a few key receptors have been implicated in many neurological and psychiatric disorders, including addiction. Metabotropic glutamate type 5 receptors (mGlu5) can form complexes with other GPCRs, including adenosine A(2A) and dopamine D(2) receptors. mGlu5-containing complexes have been reported in the striatum, a brain region critical for mediating the rewarding and incentive motivational properties of drugs of abuse. mGlu5-containing complexes and/or downstream interactions between divergent receptors may play roles in addiction-relevant behaviors. Interactions between mGlu5 receptors and other GPCRs can regulate the rewarding and conditioned effects of drugs as well as drug-seeking behaviors. mGlu5 complexes may influence striatal function, including GABAergic output of striatopallidal neurons and glutamatergic input from corticostriatal afferents. Given their discrete localization, mGlu5-[non-mGlu5] receptor interactions and/or mGlu5-containing complexes may minimize off-target effects and thus provide a novel avenue for drug discovery. The therapeutic targeting of receptor-receptor functional interactions and/or receptor mosaics in a tissue specific or temporal manner (for example, a sub-population of receptors in a "pathological state") might reduce detrimental side effects that may otherwise impair vital brain functions.


Integration of phlebotomine ecological niche modelling, and mapping of cutaneous leishmaniasis surveillance data, to identify areas at risk of under-estimation.
Passive surveillance systems are thought to under-estimate the true incidence of American cutaneous leishmaniasis (ACL) by two- to five-fold. Ecological niche models based on remotely sensed data can identify environmental factors which favor phlebotomine vectors. Here we report an integrated approach to identifying areas at risk of cutaneous leishmaniasis by applying spatial analysis methods to niche model results, and local surveillance data, in two locations in Colombia with differing vector ecology. The objective was to identify townships in which later phases of the project could implement community-based surveillance to obtain direct estimates of under-reporting. The study was carried out in one municipality in each of two departments of the Andean region of Colombia: Pueblo Rico in Risaralda, and Rovira in Tolima. Niche mapping by maximum entropy, based on published and unpublished existing locations of Pintomyia (Pifanomyia) longiflocosa and Psychodopygus panamensis, and using variables on land cover, climate and elevation. Field catches were done in each municipality to test predictions of high relative probability of presence. The niche model results were included as a predictor in a conditional autoregressive spatial model, in which the outcome variable was the number of cases by township, as detected by passive surveillance. Having rarefied 173 geolocated records, 46 of Pi. longiflocosa and 57 of Ps. panamensis were used for the niche modelling. At the national level, both species had high relative probability of presence on parts of the slopes of the three Andean cordilleras. Pi. longiflocosa also has a high relative probability of presence in the higher parts of the Magdalena valley, as does Ps. panamensis in some areas close to the Caribbean coast. At the local level, field catches confirmed that Pi. longiflocosa was the most abundant species in Rovira, and likewise Ps. panamensis in Pueblo Rico. The spatial regression showed that the incidence of ACL, according to surveillance, was positively, but not statistically significantly, associated with the relative probability of presence from the risk model. These niche maps bring together published and unpublished results on phlebotomine species which are important vectors in Colombia. Maps of the fitted values of incidence were used to guide the selection of townships in which further phases of the study will attempt to quantify the extent of under-estimation of ACL incidence.


Multiteam Systems Handling Time-Sensitive Targets: Developing Situation Awareness in Distributed and Co-located Settings.
There is an increasing interest in how to organize operations carried out by multiteam systems (MTS). Large MTS typically operate with a dedicated integration team, responsible for coordinating the operation. We report a study of a military multiteam system that prosecute time-sensitive targets. We asked whether and how the integration team's efficiency depends on its communication setting. Specifically, we studied how a co-located vs. a distributed communications setting influenced the shared situation awareness and whether the shared situation awareness again influenced the outcome of the decision processes. We found that performance fell when the integration team shifted from a co-located to a distributed setting. The fall in performance seemed to be mediated by a corresponding fall in situation awareness. Moreover, while the performance improved for each run in the co-located setting, we did not see such learning in the distributed setting. Qualitative observations revealed that misunderstandings lasted longer in a distributed configuration than in a co-located setting. We found that situation awareness at level 3 was the only level of situation awareness significant for predicting all dimensions of performance. Implications for theory, research, and practice are discussed.


Integrating computationally assembled mouse transcript sequences with the Mouse Genome Informatics (MGI) database.
Databases of experimentally generated and computationally derived transcript sequences are valuable resources for genome analysis and annotation. The utility of such databases is enhanced when the sequences they contain are integrated with such biological information as genomic location, gene function, gene expression and phenotypic variation. We present the analysis and results of a semi-automated process of connecting transcript assemblies with highly curated biological information for mouse genes that is available through the Mouse Genome Informatics (MGI) database.


Can Completers, Non-Completers, and Non-Starters of Community-Based Offending Behavior Programs be Differentiated by Internal Treatment Readiness Factors?
This research aimed to determine whether completers, non-completers, and non-starters of community-based offending behavior programs could be differentiated by their levels of internal "treatment readiness." The Corrections Victoria Treatment Readiness Questionnaire (CVTRQ) measures offenders' Attitudes and Motivation, Emotional Reactions, Offending Beliefs, and Efficacy which, according to the Multifactor Offender Readiness Model (MORM), are internal dimensions of an offender's readiness to engage with treatment. Participants were offenders who had been court-mandated to attend a community-based cognitive skills offending behavior program. There were no significant differences between groups in respect of the CVTRQ total score. After controlling for risk of reconviction, however, the Self Efficacy construct differentiated program non-starters from program completers, while the Emotional Reactions construct differentiated program non-completers from program completers. In conclusion, the CVTRQ failed to differentiate program completion groups with the same success as elsewhere.


Teamwork in primary care: perspectives of general practitioners and community nurses in Lithuania.
A team approach in primary care has proven benefits in achieving better outcomes, reducing health care costs, satisfying patient needs, ensuring continuity of care, increasing job satisfaction among health providers and using human health care resources more efficiently. However, some research indicates constraints in collaboration within primary health care (PHC) teams in Lithuania. The aim of this study was to gain a better understanding of the phenomenon of teamwork in Lithuania by exploring the experiences of teamwork by general practitioners (GPs) and community nurses (CNs) involved in PHC. Six focus groups were formed with 29 GPs and 27 CNs from the Kaunas Region of Lithuania. Discussions were recorded and transcribed verbatim. A thematic analysis of these data was then performed. The analysis of focus group data identified six thematic categories related to teamwork in PHC: the structure of a PHC team, synergy among PHC team members, descriptions of roles and responsibilities of team members, competencies of PHC team members, communications between PHC team members and the organisational background for teamwork. These findings provide the basis for a discussion of a thematic model of teamwork that embraces formal, individual and organisational factors. The need for effective teamwork in PHC is an issue receiving broad consensus; however, the process of teambuilding is often taken for granted in the PHC sector in Lithuania. This study suggests that both formal and individual behavioural factors should be targeted when aiming to strengthen PHC teams. Furthermore, this study underscores the need to provide explicit formal descriptions of the roles and responsibilities of PHC team members in Lithuania, which would include establishing clear professional boundaries. The training of team members is an essential component of the teambuilding process, but not sufficient by itself.


Advancing Research and Measurement on Fathering and Child Development.
Fathers are more than social accidents. Research has demonstrated that fathers matter to children's development. Despite noted progress, challenges remain on how best to conceptualize and assess fathering and father-child relationships. The current monograph is the result of an SRCD-sponsored meeting of fatherhood scholars brought together to discuss these challenges and make recommendations for best practices for incorporating fathers in studies on parenting and children's development. The first aim of this monograph was to provide a brief update on the current state of research on fathering and to lay out a developmental ecological systems perspective as a conceptual framework for understanding the different spaces fathers inhabit in their children's lives. Because there is wide variability in fathers' roles, the ecological systems perspective situates fathers, mothers, children, and other caregivers within an evolving network of interrelated social relationships in which children and their parents change over time and space (e.g., residence). The second aim was to present examples of empirical studies conducted by members of the international working group that highlighted different methods, data collection, and statistical analyses used to capture the variability in father-child relationships. The monograph ends with a commentary that elaborates on the ecological systems framework with a discussion of the broader macrosystem and social-contextual influences that impinge on fathers and their children. The collection of articles contributes to research on father-child relationships by advancing theory and presenting varied methods and analysis strategies that assist in understanding the father-child relationship and its impact on child development.


Clinical review: humidifiers during non-invasive ventilation--key topics and practical implications.
Inadequate gas conditioning during non-invasive ventilation (NIV) can impair the anatomy and function of nasal mucosa. The resulting symptoms may have a negative effect on patients' adherence to ventilatory treatment, especially for chronic use. Several parameters, mostly technical aspects of NIV, contribute to inefficient gas conditioning. Factors affecting airway humidity during NIV include inspiratory flow, inspiratory oxygen fraction, leaks, type of ventilator, interface used to deliver NIV, temperature and pressure of inhaled gas, and type of humidifier. The correct application of a humidification system may avoid the effects of NIV-induced drying of the airway. This brief review analyses the consequences of airway dryness in patients receiving NIV and the technical tools necessary to guarantee adequate gas conditioning during ventilatory treatment. Open questions remain about the timing of gas conditioning for acute or chronic settings, the choice and type of humidification device, the interaction between the humidifier and the underlying disease, and the effects of individual humidification systems on delivered humidity.


Rural-urban differences in obstetric care, 2002-2010, and implications for the future.
Approximately 15% of the 4 million annual US births occur in rural hospitals. To (1) measure differences in obstetric care in rural and urban hospitals, and to (2) examine whether trends over time differ by rural-urban hospital location. This was a retrospective analysis of hospital discharge records for all births in the 2002-2010 Nationwide Inpatient Sample, which constitutes 20% sample of US hospitals (N = 7,188,972 births: 6,316,743 in urban hospitals, 837,772 in rural hospitals). Rates of low-risk cesarean (full-term, singleton, vertex pregnancies; no prior cesarean), vaginal birth after cesarean (VBAC), nonindicated cesarean, and nonindicated labor induction were estimated. In 2010, low-risk cesarean rates in rural and urban hospitals were 15.5% and 16.1%, respectively, and nonindicated cesarean rates were 16.9% and 17.8%, respectively. VBAC rates were 5.0% in rural and 10.0% in urban hospitals in 2010. Between 2002 and 2010, rates of low-risk cesarean and nonindicated cesarean increased, and VBAC rates decreased in both rural and urban hospitals. Nonindicated labor induction was less frequent in rural versus urban hospitals in 2002 [adjusted odds ratio = 0.79 (0.78-0.81)], but increased more rapidly in rural hospitals from 2002 to 2010 [adjusted odds ratio = 1.05 (1.05-1.06)]. In 2010, 16.5% of rural births were induced without indication (12.0% of urban births). From 2002 to 2010, cesarean rates rose and VBAC rates fell in both rural and urban hospitals. Nonindicated labor induction rates rose disproportionately faster in rural versus urban settings. Tailored clinical and policy tools are required to address differences between rural and urban hospitals.


Voxel-based morphometry versus region of interest: a comparison of two methods for analyzing gray matter differences in schizophrenia.
Many previous studies exploring cortical gray matter (GM) differences in schizophrenia have used "region of interest" (ROI) measurements to manually delineate GM volumes. Recently, some investigators have instead employed voxel-based morphometry (VBM), an automated whole-brain magnetic resonance image measurement technique. The purpose of the current study was to compare the above methods in calculating GM distributions in schizophrenia patients relative to matched controls. Using ROIs, Buchanan et al. (Buchanan, R.W., Francis, A., Arango, C., Miller, K., Lefkowitz, D.M., McMahon, R.P., Barta, P.E. and Pearlson, G.D., 2004. Morphometric assessment of the heteromodal association cortex in schizophrenia. Am J Psychiatry. 161 (2), 322-331.) found decreased dorsolateral prefrontal GM volume and altered symmetry of inferior parietal GM in schizophrenia patients. We hypothesized that VBM analyses of the same data would complement the ROI findings. As predicted, VBM analyses replicated results of less left inferior and right superior frontal cortical GM in schizophrenia. Additionally, VBM uncovered a significantly lower concentration of GM in the middle and superior temporal gyri, sought but not detected using ROIs, but did not replicate the parietal changes. The principal explanation for these differences may be the methodological differences between voxel-averaged, landmark-based ROI analyses and the single, voxel-by-voxel whole brain VBM measurements. Although VBM is rapid and fully automated, it is not a replacement for manual ROI-based analyses. Both methods provide different types of information and should thus be used in tandem.


Maternal milk consumption, fetal growth, and the risks of neonatal complications: the Generation R Study.
Maternal cow-milk consumption may increase birth weight. Previous studies did not assess the association of maternal milk consumption with trimester-specific fetal growth. The objective was to assess associations of first-trimester maternal milk consumption with fetal growth characteristics in different trimesters and the risk of neonatal complications. In total, 3405 mothers participating in a prospective cohort study completed a 293-item semiquantitative food-frequency questionnaire to obtain information about dairy consumption during the first trimester of pregnancy. Fetal head circumference, femur length, and weight were estimated in the second and third trimesters by ultrasonography. Maternal milk consumption of >3 glasses/d was associated with greater fetal weight gain in the third trimester of pregnancy, which led to an 88-g (95% CI: 39, 135 g) higher birth weight than that with milk consumption of 0 to 1 glass/d. In addition, head circumference tended to be 2.3 cm (95% CI: -0.0, 4.6 cm) larger when mothers consumed >3 glasses/d. Maternal milk consumption was not associated with length growth. Maternal protein intake (P for trend = 0.01), but not fat or carbohydrate intake, from dairy products was associated with higher birth weight. This association appeared to be limited to milk (P for trend < 0.01), whereas protein intake from nondairy food or cheese was not associated with birth weight. Maternal milk consumption is associated with greater fetal weight gain. The association seems to be due to milk protein, or milk components closely associated with protein, rather than to the fat or carbohydrate fraction of milk.


Effect of oxygen minimum zone formation on communities of marine protists.
Changes in ocean temperature and circulation patterns compounded by human activities are leading to oxygen minimum zone (OMZ) expansion with concomitant alteration in nutrient and climate active trace gas cycling. Here, we report the response of microbial eukaryote populations to seasonal changes in water column oxygen-deficiency using Saanich Inlet, a seasonally anoxic fjord on the coast of Vancouver Island British Columbia, as a model ecosystem. We combine small subunit ribosomal RNA gene sequencing approaches with multivariate statistical methods to reveal shifts in operational taxonomic units during successive stages of seasonal stratification and renewal. A meta-analysis is used to identify common and unique patterns of community composition between Saanich Inlet and the anoxic/sulfidic Cariaco Basin (Venezuela) and Framvaren Fjord (Norway) to show shared and unique responses of microbial eukaryotes to oxygen and sulfide in these three environments. Our analyses also reveal temporal fluctuations in rare populations of microbial eukaryotes, particularly anaerobic ciliates, that may be of significant importance to the biogeochemical cycling of methane in OMZs. Eukaryotic 18S rRNA gene sequences recovered from the Saanich Inlet water column on were deposited in Genbank under accession numbers HQ864863–HQ871151.


Mechanisms of G protein-coupled receptors regulation.
Within the last two decades of studies in the ever-expanding field of GPCR signaling, challenging insights were adopted. Growing evidence now asists the shift from classical linear model of signaling towards a considerably complex network of signaling pathways with many shared proteins and cross-talks. Considering the extensive and intriguing network of pathways activated by these receptors, it is apparent that multi-level system of regulation must exist to rigorously modulate the amplitude, duration and spatial aspects of the GPCR signaling. This review summarizes the principal mechanisms of GPCR regulation and gives the overview of recent advances in this field of research.


Guillain-Barré syndrome subtypes related to Campylobacter infection.
In Guillain-Barré syndrome (GBS), the diversity in electrophysiological subtypes is unexplained but may be determined by geographical factors and preceding infections. Acute motor axonal neuropathy (AMAN) is a frequent GBS variant in Japan and one study proposed that in Japan, Campylobacter jejuni infections exclusively elicit AMAN. In The Netherlands C jejuni is the predominant type of preceding infection yet AMAN is rare. This may indicate that not all Dutch GBS patients with C jejuni infections have AMAN. To determine if GBS patients with a preceding C jejuni infection in The Netherlands exclusively have AMAN. Retrospective analysis of preceding infections in relation to serial electrophysiology and clinical data from 123 GBS patients. C jejuni related cases were defined as having preceding diarrhoea and positive C jejuni serology. Electrophysiological characteristics in C jejuni related cases were compared with those in viral related GBS patients. In addition, eight GBS patients from another cohort with positive stool cultures for C jejuni were analysed. 17 (14%) of 123 patients had C jejuni related GBS. C jejuni patients had lower motor and higher sensory action potentials compared with viral related cases. Nine (53%) C jejuni patients had either AMAN or inexcitable nerves. However, three (18%) patients fulfilled the criteria for acute inflammatory demyelinating polyneuropathy (AIDP). Also, two (25%) of eight additional patients with a C jejuni positive stool sample had AIDP. In The Netherlands, C jejuni infections are strongly, but not exclusively, associated with axonal GBS. Some patients with these infections fulfil current criteria for demyelination.


Preparation of reactive three-dimensional microstructures via direct laser writing and thiol-ene chemistry.
Three-dimensional microstructures are fabricated employing the direct laser writing process and radical thiol-ene polymerization. The resin system consists of a two-photon photoinitiator and multifunctional thiols and olefins. Woodpile photonic crystals with 22 layers and a rod distance of 2 μm are fabricated. The structures are characterized via scanning electron microscopy and focused ion beam milling. The thiol-ene polymerization during fabrication is verified via infrared spectroscopy. The structures are grafted in a subsequent thiol-Michael addition reaction with different functional maleimides. The success of the grafting reaction is evaluated via laser scanning microscopy and X-ray photoelectron spectroscopy. The grafting density is calculated to be close to 200 molecules μm(-2) .


A clinicopathologic study of in vitro sensitivity testing and Acanthamoeba keratitis.
To examine the extent of any correlation between the in vitro sensitivity and the clinical outcomes of Acanthamoeba keratitis. The clinical outcomes were correlated with the in vitro sensitivity of 23 isolates of 23 patients with culture-positive Acanthamoeba keratitis. The laboratory assay assessed the amoebicidal and cysticidal efficacy of 13 drugs. Most agents were effective against the trophozoites in vivo. Polyhexamethylene biguanide (PHMB) and chlorhexidine were the most successful cysticidal agents, followed by sepazonium and propamidine. Clotrimazole, paramomycin, and ketoconazole were cysticidal in a few specimens, but usually in high concentrations. Neomycin was ineffective against cysts in vivo. Nineteen patients were treated with topical propamidine and neomycin, and a medical cure was obtained in nine (47%). There was poor correlation between the clinical outcomes of individual cases and the in vitro sensitivity testing. The medical failures were treated with topical PHMB and propamidine and eight of ten (80%) of these were medically cured. Two patients, however, were still culture positive after 28 and 41 weeks of treatment. PHMB has an excellent in vitro sensitivity profile, but the two cases of failure were sensitive to the drug and resistance had not developed. In vitro sensitivity testing has been important in the screening of new agents, although disappointing in the management of individual cases in this set of studies.


A facile method to prepare molecularly imprinted layer-by-layer nanostructured multilayers using postinfiltration and a subsequent photo-cross-linking strategy.
In this paper, we have demonstrated a facile strategy to prepare molecularly imprinted layer-by-layer nanostructured films. This strategy has circumvented the requirement of using photocross-linkable polymers, which suffered from tedious synthetic processes in the construction of surface molecular imprinting in layer-by-layer (SMI-LbL) devices. The described SMI-LbL device was constructed by employing the traditional construction procedures of LbL systems, followed by the postinfiltration of bifunctional photosensitive cross-linking agent 4,4'-diazostilbene-2,2'-disulfonic acid disodium salt into the prepared multilayers, and subsequent photocross-linking. A robust SMI-LbL device with high fatigue-resistance was achieved. The preparation conditions have been optimized to achieve repeated unloading and rebinding of the targeting molecule with high fidelity. The combination of templating and cross-linking is the core factor to achieve high fidelity and high efficiency of the SMI-LbL device.


Error rates of human reviewers during abstract screening in systematic reviews.
Automated approaches to improve the efficiency of systematic reviews are greatly needed. When testing any of these approaches, the criterion standard of comparison (gold standard) is usually human reviewers. Yet, human reviewers make errors in inclusion and exclusion of references. To determine citation false inclusion and false exclusion rates during abstract screening by pairs of independent reviewers. These rates can help in designing, testing and implementing automated approaches. We identified all systematic reviews conducted between 2010 and 2017 by an evidence-based practice center in the United States. Eligible reviews had to follow standard systematic review procedures with dual independent screening of abstracts and full texts, in which citation inclusion by one reviewer prompted automatic inclusion through the next level of screening. Disagreements between reviewers during full text screening were reconciled via consensus or arbitration by a third reviewer. A false inclusion or exclusion was defined as a decision made by a single reviewer that was inconsistent with the final included list of studies. We analyzed a total of 139,467 citations that underwent 329,332 inclusion and exclusion decisions from 86 unique reviewers. The final systematic reviews included 5.48% of the potential references identified through bibliographic database search (95% confidence interval (CI): 2.38% to 8.58%). After abstract screening, the total error rate (false inclusion and false exclusion) was 10.76% (95% CI: 7.43% to 14.09%). This study suggests important false inclusion and exclusion rates by human reviewers. When deciding the validity of a future automated study selection algorithm, it is important to keep in mind that the gold standard is not perfect and that achieving error rates similar to humans may be adequate and can save resources and time.


Erythropoietin Modulates Cerebral and Serum Degradation Products from Excess Calpain Activation following Prenatal Hypoxia-Ischemia.
Preterm infants suffer central nervous system (CNS) injury from hypoxia-ischemia and inflammation - termed encephalopathy of prematurity. Mature CNS injury activates caspase and calpain proteases. Erythropoietin (EPO) limits apoptosis mediated by activated caspases, but its role in modulating calpain activation has not yet been investigated extensively following injury to the developing CNS. We hypothesized that excess calpain activation degrades developmentally regulated molecules essential for CNS circuit formation, myelination and axon integrity, including neuronal potassium-chloride co-transporter (KCC2), myelin basic protein (MBP) and phosphorylated neurofilament (pNF), respectively. Further, we predicted that post-injury EPO treatment could mitigate CNS calpain-mediated degradation. Using prenatal transient systemic hypoxia-ischemia (TSHI) in rats to mimic CNS injury from extreme preterm birth, and postnatal EPO treatment with a clinically relevant dosing regimen, we found sustained postnatal excess cortical calpain activation following prenatal TSHI, as shown by the cleavage of alpha II-spectrin (αII-spectrin) into 145-kDa αII-spectrin degradation products (αII-SDPs) and p35 into p25. Postnatal expression of the endogenous calpain inhibitor calpastatin was also reduced following prenatal TSHI. Calpain substrate expression following TSHI, including cortical KCC2, MBP and NF, was modulated by postnatal EPO treatment. Calpain activation was reflected in serum levels of αII-SDPs and KCC2 fragments, and notably, EPO treatment also modulated KCC2 fragment levels. Together, these data indicate that excess calpain activity contributes to the pathogenesis of encephalopathy of prematurity. Serum biomarkers of calpain activation may detect ongoing cerebral injury and responsiveness to EPO or similar neuroprotective strategies.


Importance of Resolving Fungal Nomenclature: the Case of Multiple Pathogenic Species in the Cryptococcus Genus.
Cryptococcosis is a major fungal disease caused by members of the Cryptococcus gattii and Cryptococcus neoformans species complexes. After more than 15 years of molecular genetic and phenotypic studies and much debate, a proposal for a taxonomic revision was made. The two varieties within C. neoformans were raised to species level, and the same was done for five genotypes within C. gattii. In a recent perspective (K. J. Kwon-Chung et al., mSphere 2:e00357-16, 2017, https://doi.org/10.1128/mSphere.00357-16), it was argued that this taxonomic proposal was premature and without consensus in the community. Although the authors of the perspective recognized the existence of genetic diversity, they preferred the use of the informal nomenclature "C. neoformans species complex" and "C. gattii species complex." Here we highlight the advantage of recognizing these seven species, as ignoring these species will impede deciphering further biologically and clinically relevant differences between them, which may in turn delay future clinical advances.


A case-control study on the association between rheumatoid arthritis and bladder pain syndrome/interstitial cystitis.
While bladder pain syndrome/interstitial cystitis (BPS/IC) has been suggested by a number of studies to have autoimmune character, no population-based study to date has been conducted investigating its association with rheumatoid arthritis (RA). This study aimed to examine the association between IC/BPS and having previously been diagnosed with RA. We conducted this study by using administrative claims data sourced from the Taiwan National Health Insurance Database. Our study included 9,269 cases with BPS/IC and 46,345 randomly selected controls. Conditional logistic regression was performed to calculate the odds ratio (OR) for the association between previously diagnosed RA and IC/BPS. RA was found among 202 (2.2%) cases and 504 (1.12%) controls. Conditional logistic regression analysis suggested that when compared with controls, the OR for prior RA among cases was 1.66 (95% CI = 1.47-1.87, P < 0.001) after adjusting for diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, asthma, overactive bladder, tobacco use disorder, and alcohol abuse. Additionally, BPS/IC was consistently and significantly associated with a previous diagnosis of RA regardless of prescription drug use; the OR for prior RA among groups prescribed ≤1 type of disease-modifying antirheumatic drug (DMARD), two types of DMARDs, and ≥3 types of DMARDs or TNF-alpha inhibitor when compared to controls were 1.49 (95% CI = 1.28-1.72), 1.91 (95% CI = 1.38-2.68), and 2.36 (95% CI = 1.77-3.17), respectively. There is an association between RA and BPS/IC after adjusting for socio-demographic characteristics and medical co-morbidities.


Cytokine-mediated communication between dendritic epidermal T cells and Langerhans cells. In vitro studies using cell lines.
Murine epidermis contains two leukocyte populations: Langerhans cells (LC), which are APC of dendritic cell (DC) lineage, and dendritic epidermal T cells (DETC), which are members of the tissue-type gamma delta T cell family. Despite close physical approximation in vivo, the extent to which LC and DETC affect each other's function has remained unknown. We addressed this question using the long term DC line XS52 and the gamma delta T cell line 7-17, both of which were established from mouse epidermis, and both of which retain important features of the resident populations from which they were derived. XS52 DC proliferated maximally when cocultured with gamma-irradiated 7-17 DETC. They also proliferated in response to culture supernatants collected from anti-CD3- or Con A-activated 7-17 DETC, but not from nonstimulated DETC. In both systems, DETC-induced XS52 DC growth was inhibited partially (up to 70%) by Abs against granulocyte/macrophage CSF (GM-CSF) or CD115 (CSF-1 receptor) and nearly completely (up to 90%) by both together. Among 28 tested cytokines, only GM-CSF, CSF-1, IL-4, and IL-13 promoted XS52 DC growth significantly. Anti-IL-4 failed to inhibit DETC-induced XS52 cell growth, and IL-4 was not detectable in DETC supernatants. Thus, we conclude that GM-CSF and CSF-1 (and perhaps IL-13) account for the DC growth-promoting activity secreted by DETC. These results suggest that during coculture, XS52 DC activate 7-17 DETC to secrete both GM-CSF and CSF-1. In fact, when cultured with XS52 DC, 7-17 DETC also elevated their expression of the gamma c receptor and acquired proliferative responsiveness to their own growth factor IL-15. We propose that LC and DETC in situ may interact with each other in a similar manner, thereby regulating their residence and function.


Recent progress and perspectives of gas sensors based on vertically oriented ZnO nanomaterials.
Vertically oriented zinc oxide (ZnO) nanomaterials, such as nanorods (NRs), nanowires (NWs), nanotubes (NTs), nanoneedles (NNs), and nanosheets (NSs), are highly ordered architectures that provide remarkable properties for sensors. Furthermore, these nanostructures have fascinating features, including high surface-area-to-volume ratios, high charge carrier concentrations, and many surface-active sites. These features make vertically oriented ZnO nanomaterials exciting candidates for gas sensor fabrication. The development of efficient methods for the production of vertically oriented nanomaterial electrode surfaces has resulted in improved stability, high reproducibility, and gas sensing performance. Moving beyond conventional fabrication processes that include binders and nanomaterial deposition steps has been crucial, as the materials from these processes suffer from poor stability, low reproducibility, and marginal sensing performance. In this feature article, we comprehensively describe vertically oriented ZnO nanomaterials for gas sensing applications. The uses of such nanomaterials for gas sensor fabrication are discussed in the context of ease of growth, stability on an electrode surface, growth reproducibility, and enhancements in device efficiency as a result of their unique and advantageous features. In addition, we summarize applications of gas sensors for a variety of toxic and volatile organic compound (VOC) gases, and we discuss future directions of the vertically oriented ZnO nanomaterials.


Magneto-Structural Correlations in Pseudotetrahedral Forms of the [Co(SPh)4]2- Complex Probed by Magnetometry, MCD Spectroscopy, Advanced EPR Techniques, and ab Initio Electronic Structure Calculations.
The magnetic properties of pseudotetrahedral Co(II) complexes spawned intense interest after (PPh4)2[Co(SPh)4] was shown to be the first mononuclear transition-metal complex displaying slow relaxation of the magnetization in the absence of a direct current magnetic field. However, there are differing reports on its fundamental magnetic spin Hamiltonian (SH) parameters, which arise from inherent experimental challenges in detecting large zero-field splittings. There are also remarkable changes in the SH parameters of [Co(SPh)4]2- upon structural variations, depending on the counterion and crystallization conditions. In this work, four complementary experimental techniques are utilized to unambiguously determine the SH parameters for two different salts of [Co(SPh)4]2-: (PPh4)2[Co(SPh)4] (1) and (NEt4)2[Co(SPh)4] (2). The characterization methods employed include multifield SQUID magnetometry, high-field/high-frequency electron paramagnetic resonance (HF-EPR), variable-field variable-temperature magnetic circular dichroism (VTVH-MCD), and frequency domain Fourier transform THz-EPR (FD-FT THz-EPR). Notably, the paramagnetic Co(II) complex [Co(SPh)4]2- shows strong axial magnetic anisotropy in 1, with D = -55(1) cm-1 and E/D = 0.00(3), but rhombic anisotropy is seen for 2, with D = +11(1) cm-1 and E/D = 0.18(3). Multireference ab initio CASSCF/NEVPT2 calculations enable interpretation of the remarkable variation of D and its dependence on the electronic structure and geometry.


Increasing lean muscle mass in mice via nanoparticle-mediated hepatic delivery of follistatin mRNA.
Muscle atrophy occurs during chronic diseases, resulting in diminished quality of life and compromised treatment outcomes. There is a high demand for therapeutics that increase muscle mass while abrogating the need for special dietary and exercise requirements. Therefore, we developed an efficient nanomedicine approach capable of increasing muscle mass. Methods: The therapy is based on nanoparticle-mediated delivery of follistatin messenger RNA (mRNA) to the liver after subcutaneous administration. The delivered mRNA directs hepatic cellular machinery to produce follistatin, a glycoprotein that increases lean mass through inhibition of negative regulators of muscle mass (myostatin and activin A). These factors are elevated in numerous disease states, thereby providing a target for therapeutic intervention. Results: Animal studies validated that mRNA-loaded nanoparticles enter systemic circulation following subcutaneous injection, accumulate and internalize in the liver, where the mRNA is translated into follistatin. Follistatin serum levels were elevated for 72 h post injection and efficiently reduced activin A and myostatin serum concentrations. After eight weeks of repeated injections, the lean mass of mice in the treatment group was ~10% higher when compared to that of the controls. Conclusion: Based on the obtained results demonstrating an increased muscle mass as well as restricted fat accumulation, this nanoplatform might be a milestone in the development of mRNA technologies and the treatment of muscle wasting disorders.


A recurrent RNA-splicing mutation in the SEDL gene causes X-linked spondyloepiphyseal dysplasia tarda.
Spondyloepiphyseal dysplasia tarda (SEDL) is a genetically heterogeneous disorder characterized by mild-to-moderate short stature and early-onset osteoarthritis. Both autosomal and X-linked forms have been described. Elsewhere, we have reported the identification of the gene for the X-linked recessive form, which maps to Xp22.2. We now report characterization of an exon-skipping mutation (IVS3+5G-->A at the intron 3 splice-donor site) in two unrelated families with SEDL. Using reverse transcriptase (RT)-PCR, we demonstrated that the mutation resulted in elimination of the first 31 codons of the open reading frame. The mutation was not detected in 120 control X chromosomes. Articular cartilage from an adult who had SEDL and carried this mutation contained chondrocytes with abundant Golgi complexes and dilated rough endoplasmic reticulum (ER). RT-PCR experiments using mouse/human cell hybrids revealed that the SEDL gene escapes X inactivation. Homologues of the SEDL gene include a transcribed retropseudogene on chromosome 19, as well as expressed genes in mouse, rat, Drosophila melanogaster Caenorhabditis elegans, and Saccharomyces cerevisiae. The latter homologue, p20, has a putative role in vesicular transport from ER to Golgi complex. These data suggest that SEDL mutations may perturb an intracellular pathway that is important for cartilage homeostasis.


Analgesia from electrical stimulation in the brainstem of the rat.
Stimulation at several mesencephalic and diencephalic sites abolished responsiveness to intense pain in rats while leaving responsiveness to other sensory modes relatively unaffected. The peripheral field of analgesia was usually restricted to one-half or to one quadrant of the body, and painful stimuli applied outside this field elicited a normal reaction. Analgesia outlasted stimulation by up to 5 minutes. Most electrode placements that produced analgesia also supported self-stimulation. One placement supported self-stimulation only in the presence of pain.


Thermal effects in kilowatt all-fiber MOPA.
Thermal effects and output power characteristics of kilowatt all-fiber master-oscillator power amplifier (MOPA) are investigated. Proper designs for cooling apparatus are proposed and demonstrated experimentally, for the purpose of minimizing splice heating which is critical for the reliability of high power operation. By using these optimized methods, a thermal damage-free, highly efficient ytterbium-doped double-clad fiber MOPA operating at 1080 nm with 1.17 kW output was obtained. The maximum surface temperature at the pump light launching end splice of the booster amplifier was 345 K, and the temperature rise for this key splice was 0.052 K/W.


Specific induction of endogenous viral restriction factors using CRISPR/Cas-derived transcriptional activators.
Whereas several mammalian proteins can restrict the replication of HIV-1 and other viruses, these are often not expressed in relevant target cells. A potential method to inhibit viral replication might therefore be to use synthetic transcription factors to induce restriction factor expression. In particular, mutants of the RNA-guided DNA binding protein Cas9 that have lost their DNA cleavage activity could be used to recruit transcription activation domains to specific promoters. However, initial experiments revealed only weak activation unless multiple promoter-specific single guide RNAs (sgRNAs) were used. Recently, the recruitment of multiple transcription activation domains by a single sgRNA, modified to contain MS2-derived stem loops that recruit fusion proteins consisting of the MS2 coat protein linked to transcription activation domains, was reported to induce otherwise silent cellular genes. Here, we demonstrate that such "synergistic activation mediators" can induce the expression of two restriction factors, APOBEC3G (A3G) and APOBEC3B (A3B), in human cells that normally lack these proteins. We observed modest activation of endogenous A3G or A3B expression using single sgRNAs but high expression when two sgRNAs were used. Whereas the induced A3G and A3B proteins both blocked infection by an HIV-1 variant lacking a functional vif gene by inducing extensive dC-to-dU editing, only the induced A3B protein inhibited wild-type HIV-1. These data demonstrate that Cas9-derived transcriptional activators have the potential to be used for screens for endogenous genes that affect virus replication and raise the possibility that synthetic transcription factors might prove clinically useful if efficient delivery mechanisms could be developed.


Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development.
Bone Morphogenetic Proteins (BMPs) play crucial roles in a variety of developmental processes, but their functions during early vertebrate brain development are largely unknown. To investigate this problem, we have compared by in situ hybridization the expression of five Bmp genes belonging to the Drosophila Decapentaplegic (Bmp2 and Bmp4) and 60A subgroups (Bmp5, Bmp6 and Bmp7). Striking co-expression of these Bmps is observed within the dorsomedial telencephalon, coincident with a future site of choroid plexus development. Bmp co-expression overlaps that of Msx1 and Hfh4, and is complementary to that of Bf1. The domain of Bmp co-expression is also associated with limited growth of the neuroectoderm, as revealed by morphological observation, reduced cell proliferation, and increased local programmed cell death. In vitro experiments using explants from the embryonic lateral telencephalic neuroectoderm reveal that exogenous BMP proteins (BMP4 and BMP2) induce expression of Msx1 and inhibit Bf1 expression, a finding consistent with their specific expression patterns in vivo. Moreover, BMP proteins locally inhibit cell proliferation and increase apoptosis in the explants. These results provide evidence that BMPs function during regional morphogenesis of the dorsal telencephalon by regulating specific gene expression, cell proliferation and local cell death.


When do octopuses play? Effects of repeated testing, object type, age, and food deprivation on object play in Octopus vulgaris.
Studying play behavior in octopuses is an important step toward understanding the phylogenetic origins and function of play as well as the cognitive abilities of invertebrates. Fourteen Octopus vulgaris (7 subadults and 7 adults) were presented 2 Lego objects and 2 different food items on 7 consecutive days under 2 different levels of food deprivation. Nine subjects showed play-like behavior with the Lego objects. There was no significant difference in play-like behavior corresponding to food deprivation, age, and sex of the octopuses. The sequence of behaviors, from exploration to play-like behavior, had a significant influence on the establishment of play-like behavior, as it occurred mostly on Days 3-6 of the 7-day experiment. The pattern of development of play-like activities after a period of exploration and habituation in this study agrees with the hypothesis that object play follows object exploration. A homologous origin of this behavioral trait in vertebrates and invertebrates is highly unlikely, as the last common ancestor might not have had the cognitive capacity to possess this trait.


Structural analysis of the O-acetylated O-polysaccharide isolated from Salmonella paratyphi A and used for vaccine preparation.
Salmonella paratyphi A is increasingly recognized as a common cause of enteric fever cases and there are no licensed vaccines against this infection. Antibodies directed against the O-polysaccharide of the lipopolysaccharide of Salmonella are protective and conjugation of the O-polysaccharide to a carrier protein represents a promising strategy for vaccine development. O-Acetylation of S. paratyphi A O-polysaccharide is considered important for the immunogenicity of S. paratyphi A conjugate vaccines. Here, as part of a programme to produce a bivalent conjugate vaccine against both S. typhi and S. paratyphi A diseases, we have fully elucidated the O-polysaccharide structure of S. paratyphi A by use of HPLC-SEC, HPAEC-PAD/CD, GLC, GLC-MS, 1D and 2D-NMR spectroscopy. In particular, chemical and NMR studies identified the presence of O-acetyl groups on C-2 and C-3 of rhamnose in the lipopolysaccharide repeating unit, at variance with previous reports of O-acetylation at a single position. Moreover HR-MAS NMR analysis performed directly on bacterial pellets from several strains of S. paratyphi A also showed O-acetylation on C-2 and C-3 of rhamnose, thus this pattern is common and not an artefact from O-polysaccharide purification. Conjugation of the O-polysaccharide to the carrier protein had little impact on O-acetylation and therefore should not adversely affect the immunogenicity of the vaccine.


KRAB-Induced Heterochromatin Effectively Silences PLOD2 Gene Expression in Somatic Cells and is Resilient to TGFβ1 Activation.
Epigenetic editing, an emerging technique used for the modulation of gene expression in mammalian cells, is a promising strategy to correct disease-related gene expression. Although epigenetic reprogramming results in sustained transcriptional modulation in several in vivo models, further studies are needed to develop this approach into a straightforward technology for effective and specific interventions. Important goals of current research efforts are understanding the context-dependency of successful epigenetic editing and finding the most effective epigenetic effector(s) for specific tasks. Here we tested whether the fibrosis- and cancer-associated PLOD2 gene can be repressed by the DNA methyltransferase M.SssI, or by the non-catalytic Krüppel associated box (KRAB) repressor directed to the PLOD2 promoter via zinc finger- or CRISPR-dCas9-mediated targeting. M.SssI fusions induced de novo DNA methylation, changed histone modifications in a context-dependent manner, and led to 50%-70% reduction in PLOD2 expression in fibrotic fibroblasts and in MDA-MB-231 cancer cells. Targeting KRAB to PLOD2 resulted in the deposition of repressive histone modifications without DNA methylation and in almost complete PLOD2 silencing. Interestingly, both long-term TGFβ1-induced, as well as unstimulated PLOD2 expression, was completely repressed by KRAB, while M.SssI only prevented the TGFβ1-induced PLOD2 expression. Targeting transiently expressed dCas9-KRAB resulted in sustained PLOD2 repression in HEK293T and MCF-7 cells. Together, these findings point to KRAB outperforming DNA methylation as a small potent targeting epigenetic effector for silencing TGFβ1-induced and uninduced PLOD2 expression.


Colonoscopy, tumors, and inflammatory bowel disease - new diagnostic methods.
Accurate detection of premalignant lesions and early cancers in the colon is essential for curative endoscopic or surgical therapy, since the prognosis for the affected patients is closely related to the size and stage of the neoplastic lesion. Total colonoscopy is the accepted gold standard for screening and surveillance of colorectal cancer. This review summarizes recently published diagnostic developments and key findings in the areas of colonoscopy, colonic tumors, and inflammatory bowel diseases. Relevant findings have been reported for chromo-endoscopy in the diagnosis of colitis-associated neoplasia, as well as flat and depressed adenomas. Real-time Doppler capabilities have now been added to endoscopic optical coherence tomography; the results of large-scale testing of narrow-band imaging endoscopy in the colon are being awaited; and fluorescence imaging has recently been added to the facilities available in video endoscopy. Most importantly, endomicroscopy now for the first time allows single-cell subsurface imaging during ongoing colonoscopy procedures, opening the way to in-vivo molecular and functional imaging.


Inhibitory actions of delta 1-, delta 2-, and mu-opioid receptor agonists on excitatory transmission in lamina II neurons of adult rat spinal cord.
This study examined the electrophysiological consequences of selective activation of delta 1-, delta 2-, or mu-opioid receptors using whole-cell recordings made from visually identified lamina II neurons in thin transverse slices of young adult rat lumbar spinal cord. Excitatory postsynaptic currents (EPSCs) or potentials (EPSPs) were evoked electrically at the ipsilateral dorsal root entry zone after blocking inhibitory inputs with bicuculline and strychnine, and NMDA receptors with D-2-amino-5-phosphonopentanoic acid. Bath application of the mu receptor agonist [D-Ala2, N-MePhe4, Gly5-ol]enkephalin (DAMGO) or the delta 1 receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) produced a long-linear, concentration-dependent reduction in the amplitude of the evoked EPSP/EPSC. By comparison, the delta 2 receptor agonist [D-Ala2,Glu4]deltorphin (DELT) was unable to reduce the evoked EPSP/EPSC by more than 50% at 100 microM, the highest concentration tested. At concentrations that reduced evoked EPSP/EPSCs by 40-60%, neither DAMGO, DPDPE, nor DELT decreased the amplitude of the postsynaptic current produced by brief pressure ejection of (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, suggesting a presynaptic site of action of these opioid receptor agonists. Bath application of 200 nM naltriben (NTB), a delta 2 receptor antagonist, competitively increased the EC75 of DELT by 15.3-fold, but did not antagonize either DPDPE or DAMGO. The EC75 of DELT was further increased by 169.7-fold in the presence of 1 microM NTB. However, this high concentration of NTB also increased the EC50 of DPDPE by about threefold in a noncompetitive manner and antagonized DAMGO in a noncompetitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)


Latent manganese deficiency increases transpiration in barley (Hordeum vulgare).
To investigate if latent manganese (Mn) deficiency leads to increased transpiration, barley plants were grown for 10 weeks in hydroponics with daily additions of Mn in the low nM range. The Mn-starved plants did not exhibit visual leaf symptoms of Mn deficiency, but Chl a fluorescence measurements revealed that the quantum yield efficiency of PSII (F(v)/F(m)) was reduced from 0.83 in Mn-sufficient control plants to below 0.5 in Mn-starved plants. Leaf Mn concentrations declined from 30 to 7 microg Mn g(-1) dry weight in control and Mn-starved plants, respectively. Mn-starved plants had up to four-fold higher transpiration than control plants. Stomatal closure and opening upon light/dark transitions took place at the same rate in both Mn treatments, but the nocturnal leaf conductance for water vapour was still twice as high in Mn-starved plants compared with the control. The observed increase in transpiration was substantiated by (13)C-isotope discrimination analysis and gravimetric measurement of the water consumption, showing significantly lower water use efficiency in Mn-starved plants. The extractable wax content of leaves of Mn-starved plants was approximately 40% lower than that in control plants, and it is concluded that the increased leaf conductance and higher transpirational water loss are correlated with a reduction in the epicuticular wax layer under Mn deficiency.


Heterogeneity in development of adolescent anxiety disorder symptoms in an 8-year longitudinal community study.
In this study, we prospectively examined developmental trajectories of five anxiety disorder symptom dimensions (generalized anxiety disorder, panic disorder, school anxiety, separation anxiety disorder, and social anxiety disorder) from early to late adolescence in a community sample of 239 adolescents, assessed annually over 8 years. Latent growth modeling indicated different developmental trajectories from early into late adolescence for the different anxiety disorder symptoms, with some symptoms decreasing and other symptoms increasing over time. Sex differences in developmental trajectories were found for some symptoms, but not all. Furthermore, latent class growth analysis identified a normal developmental profile (including a majority of adolescents reporting persistent low anxiety disorder symptoms over 8 years) and an at-risk developmental profile (including a minority of adolescents reporting persistent high anxiety disorder symptoms over 8 years) for all of the anxiety disorder symptom dimensions except panic disorder. Additional analyses longitudinally supported the validity of these normal and at-risk developmental profiles and suggested differential associations between different anxiety disorder symptom dimensions and developmental trajectories of substance use, parenting, and identity development. Taken together, our results emphasize the importance of examining separate dimensions of anxiety disorder symptoms in contrast to a using a global, one-dimensional approach to anxiety.


The mifepristone-misoprostol regimen for early medical abortion.
The combination of mifepristone, an antiprogesterone known in the United States as Mifeprex (Danco Laboratories, New York, NY), and misoprostol, a prostaglandin analogue marketed in the United States under the brand name Cytotec (Pharmacia [formerly Searle], Peapack, NJ), provides a nonsurgical abortion in the early stages of a pregnancy. Mifepristone blocks the action of progesterone, a hormone necessary to sustain a pregnancy, whereas misoprostol causes contractions that expel the embryo and other pregnancy tissue. Since September 2000, mifepristone has been approved by the United States Food and Drug Administration for induced abortions of gestations of 49 days or less since the last menstrual period, but is not yet approved for any other uses. Misoprostol has long been approved to prevent and treat stomach ulcers.


Simulation studies of the electrocardiogram. II. Ischemia and infarction.
Experimental studies of the myocardial action potentials following coronary artery occlusion have shown that the resulting regional ischemia is reflected by characteristics changes in the shapes of the action potentials in the ischemic region. The principal changes are decreases in the magnitude of the resting potential and in the action potential duration. Action potentials with prolonged durations have been observed in the infarcted regions of experimental animals after the development of inverted T waves in the surface electrocardiogram (ECG). We use such abnormal action potentials in our digital computer model to study the effects of acute myocardial ischemia and infarction on the surface ECG. The heart is represented in sufficient detail to allow variations in the location and size of the ischemic injury and in the distribution of the severity of injury within the injured region. The evolution of acute infarctions is simulated by progressively modifying the abnormal action potentials assigned to the injured region. Calculated standard 12 lead ECGs and torso isopotential surface maps for simulated acute ischemia and infarction are in good agreement with patient data reported in the literature. Typical simulations include anterior and inferior transmural ischemia and infarction and anterior subendocardial ischemia. The model is used to examine relationships between torso surface potentials during ventricular activation and recovery and the site and size of the ischemic injury.


Capacity-building efforts by the AFHSC-GEIS program.
Capacity-building initiatives related to public health are defined as developing laboratory infrastructure, strengthening host-country disease surveillance initiatives, transferring technical expertise and training personnel. These initiatives represented a major piece of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) contributions to worldwide emerging infectious disease (EID) surveillance and response. Capacity-building initiatives were undertaken with over 80 local and regional Ministries of Health, Agriculture and Defense, as well as other government entities and institutions worldwide. The efforts supported at least 52 national influenza centers and other country-specific influenza, regional and U.S.-based EID reference laboratories (44 civilian, eight military) in 46 countries worldwide. Equally important, reference testing, laboratory infrastructure and equipment support was provided to over 500 field sites in 74 countries worldwide from October 2008 to September 2009. These activities allowed countries to better meet the milestones of implementation of the 2005 International Health Regulations and complemented many initiatives undertaken by other U.S. government agencies, such as the U.S. Department of Health and Human Services, the U.S. Agency for International Development and the U.S. Department of State.


Effect of Carotid Revascularization Endarterectomy Versus Stenting Trial Results on the Performance of Carotid Artery Stent Placement and Carotid Endarterectomy in the United States.
CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) results, published in 2010, showed no difference in the rates of composite outcome (stroke, myocardial infarction, or death) between carotid artery stent placement (CAS) and carotid endarterectomy (CEA). To identify any changes in use and outcomes of CAS and CEA subsequent to the CREST results. We estimated the frequency of CAS and CEA procedures in the years 2009 (pre-CREST period) and 2011 (post-CREST period), using data from the National Inpatient Sample (NIS). Demographic and clinical characteristics and in-hospital outcomes of pre- and post-CREST CAS-treated and post-CREST CEA-treated patients were compared with pre-CREST CEA-treated patients. A total of 225,191 patients underwent CEA or CAS in the pre- and post-CREST periods. The frequency of CAS among carotid revascularization procedures did not change after publication of the CREST results (12.3% vs. 12.7%, P = .9). In the pre-CREST period, the CAS group (compared with the CEA group) had higher rates of congestive heart failure (P < .001), coronary artery disease (P < .001), and renal failure (P < .001). The post-CREST CAS group had a higher frequency of atrial fibrillation (P = .003), congestive heart failure (P < .0001), coronary artery disease (P < .0001), and renal failure (P = .0001). Discharge with moderate to severe disability (P < .0001) and postprocedure neurological complications (P = .005) were more frequently reported in the post-CREST CAS group. After adjusting for age, sex, and risk factors, the odds ratio (OR) for moderate to severe disability was 1.0 (95% confidence interval [CI]: 0.8-1.2) in the pre-CREST CAS group and 1.4 (95% CI: 1.1-1.7) in the post-CREST CAS group compared with the reference group. The adjusted OR for neurological complications in the pre-CREST CAS group was 1.6 (95% CI: 1.2-2.1, P = .002), and 1.5 (95% CI: 1.1-2.0, P = .01) in the post-CREST CAS group. The frequency of CAS and CEA for carotid artery stenosis has not changed after publication of the CREST. The demographics, pretreatment comorbidity profile, and in-hospital complication rates remained unchanged during the 2 time periods.


Simultaneous measurement of cyclopentyladenosine-induced contraction and intracellular calcium in bronchial rings from allergic rabbits and it's antagonism.
We reported previously that adenosine is a specific contractile agonist in the asthmatic airways of allergic rabbits; cyclopentyladenosine (CPA) was the most potent bronchoconstrictor in this model. The aim of the present investigation was to examine the contracting effect of CPA, an A1 adenosine receptor agonist, in relation to the role of intracellular calcium ([Ca++]i) in airway smooth muscle of allergic rabbits in the presence and absence of extracellular calcium (Ca++). The effects of adenosine receptor antagonists theophylline (xanthine) and CGS-15943 (nonxanthine) were also evaluated on these responses. CPA (10(-9)-10(-4) M) produced a dose-dependent contraction of tertiary airway smooth muscle of allergic rabbits. An increase in tension of airway smooth muscle was accompanied by a quantitative increase in [Ca++]i in the presence of extracellular Ca++. CGS-21680, an A2 agonist, produced only marginal changes in force and [Ca++]i compared with CPA. The CPA-induced contraction as well as changes in [Ca++]i were significantly inhibited by both antagonists at a concentration of 10(-7) M. CGS-15943 and theophylline changed the EC50 values for the force from 1.1 x 10(-7) M to 2.3 x 10(-6) M and 1.0 x 10(-6) M, respectively. In Ca(++)-free medium, CPA (10(-4) M) induced only a 15 to 20% contraction compared with Ca(++)-containing medium. The changes in [Ca++]i were also reduced accordingly. CGS-15943 significantly inhibited the CPA-induced tension and changes in [Ca++]i whereas theophylline failed to inhibit these responses. 8-Cyclopentyl-1,3-dipropylxanthine, an A1-specific and potent antagonist, also did not inhibit the CPA-induced force and [Ca++]i in a separate set of experiments. The tertiary airway smooth muscle rings from age-matched normal rabbits did not respond to CPA and there was no detectable change in [Ca++]i. These data suggest that the asthmatic airway smooth muscle contraction has both extracellular Ca(++)-dependent and -independent components and the Ca(++)-independent component is xanthine insensitive.


Inhibition of adenovirus infection and adenain by green tea catechins.
Green tea catechins have been reported to inhibit proteases involved in cancer metastasis and infection by influenza virus and HIV. To date there are no effective anti-adenoviral therapies. Consequently, we studied the effect of green tea catechins, and particularly the predominant component, epigallocatechin-3-gallate (EGCG), on adenovirus infection and the viral protease adenain, in cell culture. Adding EGCG (100 microM) to the medium of infected cells reduced virus yield by two orders of magnitude, giving and IC(50) of 25 microM and a therapeutic index of 22 in Hep2 cells. The agent was the most effective when added to the cells during the transition from the early to the late phase of viral infection suggesting that EGCG inhibits one or more late steps in virus infection. One of these steps appears to be virus assembly because the titer of infectious virus and the production of physical particles was much more affected than the synthesis of virus proteins. Another step might be the maturation cleavages carried out by adenain. Of the four catechins tested on adenain, EGCG was the most inhibitory with an IC(50) of 109 microM, compared with an IC(50) of 714 microM for PCMB, a standard cysteine protease inhibitor. EGCG and different green teas inactivated purified adenovirions with IC(50) of 250 and 245-3095, respectively. We conclude that the anti-adenoviral activity of EGCG manifests itself through several mechanisms, both outside and inside the cell, but at effective drug concentrations well above that reported in the serum of green tea drinkers.


Meta Analysis of Gene Expression Data within and Across Species.
Since the second half of the 1990s, a large number of genome-wide analyses have been described that study gene expression at the transcript level. To this end, two major strategies have been adopted, a first one relying on hybridization techniques such as microarrays, and a second one based on sequencing techniques such as serial analysis of gene expression (SAGE), cDNA-AFLP, and analysis based on expressed sequence tags (ESTs). Despite both types of profiling experiments becoming routine techniques in many research groups, their application remains costly and laborious. As a result, the number of conditions profiled in individual studies is still relatively small and usually varies from only two to few hundreds of samples for the largest experiments. More and more, scientific journals require the deposit of these high throughput experiments in public databases upon publication. Mining the information present in these databases offers molecular biologists the possibility to view their own small-scale analysis in the light of what is already available. However, so far, the richness of the public information remains largely unexploited. Several obstacles such as the correct association between ESTs and microarray probes with the corresponding gene transcript, the incompleteness and inconsistency in the annotation of experimental conditions, and the lack of standardized experimental protocols to generate gene expression data, all impede the successful mining of these data. Here, we review the potential and difficulties of combining publicly available expression data from respectively EST analyses and microarray experiments. With examples from literature, we show how meta-analysis of expression profiling experiments can be used to study expression behavior in a single organism or between organisms, across a wide range of experimental conditions. We also provide an overview of the methods and tools that can aid molecular biologists in exploiting these public data.


Optimal management of substrates in anaerobic co-digestion: An ant colony algorithm approach.
Sewage sludge (SWS) is inevitably produced in urban wastewater treatment plants (WWTPs). The treatment of SWS on site at small WWTPs is not economical; therefore, the SWS is typically transported to an alternative SWS treatment center. There is increased interest in the use of anaerobic digestion (AnD) with co-digestion as an SWS treatment alternative. Although the availability of different co-substrates has been ignored in most of the previous studies, it is an essential issue for the optimization of AnD co-digestion. In a pioneering approach, this paper applies an Ant-Colony-Optimization (ACO) algorithm that maximizes the generation of biogas through AnD co-digestion in order to optimize the discharge of organic waste from different waste sources in real-time. An empirical application is developed based on a virtual case study that involves organic waste from urban WWTPs and agrifood activities. The results illustrate the dominate role of toxicity levels in selecting contributions to the AnD input. The methodology and case study proposed in this paper demonstrate the usefulness of the ACO approach in supporting a decision process that contributes to improving the sustainability of organic waste and SWS management.


[Antipsychotic-induced weight gain--pharmacogenetic studies].
Drug-naive patients with schizophrenia often present metabolic abnormalities and obesity. Weight gain may be the side effect of treatment with many antipsychotic drugs. Genetic effects, besides many other factors, are known to influence obesity in patients with schizophrenia treated with antipsychotics. Numerous studies of several genes' polymorphisms have been performed. -759C/T polymorphism of 5HT2C gene attracted most attention. In 5 independent studies of this polymorphism the association between T allele with the lower AP-induced weight gain was detected. No associations could be detected between weight gain and other polymorphisms of serotonergic system genes as well as histaminergic system genes. Studies of adrenergic and dopaminergic system have neither produced any unambiguous results. Analysis of the newest candidate genes (SAP-25, leptin gene) confirmed the role of genetic factors in AP-induced weight gain. It is worth emphasising, that the studies have been conducted in relatively small and heterogenic groups and that various treatment strategies were used.


Promiscuous DNA in the nuclear genomes of hemiascomycetous yeasts.
Abstract Transfer of fragments of mtDNA to the nuclear genome is a general phenomenon that gives rise to NUMTs (NUclear sequences of MiTochondrial origin). We present here the first comparative analysis of the NUMT content of entirely sequenced species belonging to a monophyletic group, the hemiascomycetous yeasts (Candida glabrata, Kluyveromyces lactis, Kluyveromyces thermotolerans, Debaryomyces hansenii and Yarrowia lipolytica, along with the updated NUMT content of Saccharomyces cerevisiae). This study revealed a huge diversity in NUMT number and organization across the six species. Debaryomyces hansenii harbors the highest number of NUMTs (145), half of which are distributed in numerous large mosaics of up to eight NUMTs arising from multiple noncontiguous mtDNA fragments inserted at the same chromosomal locus. Most NUMTs, in all species, are found within intergenic regions including seven NUMTs in pseudogenes. However, five NUMTs overlap a gene, suggesting a positive impact of NUMTs on protein evolution. Contrary to the other species, K. lactis and K. thermotolerans harbor only a few diverged NUMTs, suggesting that mitochondrial transfer to the nuclear genome has decreased or ceased in these phylogenetic branches. The dynamics of NUMT acquisition and loss are illustrated here by their species-specific distribution.


Performance parameters for screening and diagnostic mammography in a community practice: are there differences between specialists and general radiologists?
The purpose of this study was to compare the performance of general radiologists in interpretation of mammograms with that of breast imaging specialists in a high-volume community hospital-based private practice. A retrospective observational study was conducted with data prospectively collected over a 5-year period in a community hospital-based practice in which 106,405 screening and 52,149 diagnostic mammograms were performed. The performance of three radiologists specializing in breast imaging was compared with that of six general radiologists. The following data were extracted and analyzed: recall rate, biopsy recommendation rate, and cancer detection rate. Statistical analysis was performed with a chi-square test and two-tailed calculation of p values. The recall rates of the specialists and generalists were nearly the same at 6.5% and 6.7%, respectively. The biopsy recommendation rate at recall from screening examinations was nearly the same for generalists and specialists (1.2% and 1.1%, respectively; p = 0.4504). This rate also was similar for diagnostic examinations (8.5% for generalists; 8.4% for specialists; p = 0.4086). The cancer detection rate in the screening setting was slightly higher for specialists than for generalists: 2.5 and 2.0 cancers per 1,000 cases, respectively (p = 0.0614). The cancer detection rate in the diagnostic setting was 24.2% higher among specialists (20.0 cancers per 1,000 cases) compared with generalists (16.1 cancers per 1,000 cases) (p = 0.0177). The only statistically significant difference between generalists and specialists was in cancer detection rate among patients undergoing diagnostic mammography. No statistically significant difference was identified between the two groups in terms of recall rate, biopsy recommendation rate, or percentage of favorable-prognosis cases of cancer detected. There was a trend toward greater cancer detection by specialists in the screening setting.


Molecular basis of RNA polymerase III transcription repression by Maf1.
RNA polymerase III (Pol III) transcribes short RNAs required for cell growth. Under stress conditions, the conserved protein Maf1 rapidly represses Pol III transcription. We report the crystal structure of Maf1 and cryo-electron microscopic structures of Pol III, an active Pol III-DNA-RNA complex, and a repressive Pol III-Maf1 complex. Binding of DNA and RNA causes ordering of the Pol III-specific subcomplex C82/34/31 that is required for transcription initiation. Maf1 binds the Pol III clamp and rearranges C82/34/31 at the rim of the active center cleft. This impairs recruitment of Pol III to a complex of promoter DNA with the initiation factors Brf1 and TBP and thus prevents closed complex formation. Maf1 does however not impair binding of a DNA-RNA scaffold and RNA synthesis. These results explain how Maf1 specifically represses transcription initiation from Pol III promoters and indicate that Maf1 also prevents reinitiation by binding Pol III during transcription elongation.


Standardizing psycho-medical torture during the War on Terror: Why it happened, how it happened, and why it didn't work.
After 9/11/2001 the United States launched a global War on Terror. As part of this War, terrorism suspects were detained by the U.S. military and by the C.I.A. It is now widely recognized that the United States tortured a number of these detainees in the context of its 'enhanced interrogation' programme. This article examines how and why U.S. organizations developed standards that allowed healthcare professionals to become involved in torture; why the standards developed by U.S. security institutions failed to control the actions of enhanced interrogation personnel on the ground; and what the role of standards were in stopping the enhanced interrogation initiative. The article concludes by discussing the general lessons that the enhanced interrogation programme has for social science research on standards, namely that individuals can experience ambivalence when caught between competing organizational and professional standards and that it might be inherently difficult to successfully enact certain protocols when these relate to deviant or destructive acts.


Deep tissue volumetric optoacoustic tracking of individual circulating tumor cells in an intracardially perfused mouse model.
Widespread metastasis is the major cause of death from melanoma and other types of cancer. At present, the dynamic aspects of the metastatic cascade remain enigmatic. The feasibility to track circulating melanoma cells deep within living intact organisms can greatly impact our knowledge on tumor metastasis, but existing imaging approaches lack the sensitivity, spatio-temporal resolution or penetration depth to capture flowing tumor cells over large fields of view within optically-opaque biological tissues. Vast progress with the development of optoacoustic tomography technologies has recently enabled two- and three-dimensional imaging at unprecedented frame rates in the order of hundreds of Hertz, effectively mapping up to a million image voxels within a single volumetric snapshot. Herein, we employ volumetric optoacoustic tomography for real-time visualization of passage and trapping of individual B16 melanoma cells in the whole mouse brain. Detection of individual circulating melanoma cells was facilitated by substituting blood with an artificial cerebrospinal fluid that removes the strong absorption background in the optoacoustic images. The approach can provide new opportunities for studying trafficking and accumulation of metastatic melanoma cells in different organs.


Non-resonant and non-enhanced Raman correlation spectroscopy.
We present the first non-resonant and non-enhanced Raman correlation spectroscopy experiments. They are conducted on a confocal microscope combined with a Raman spectrometer. The thermal fluctuations of the Raman intensities scattered by dispersions of polystyrene particles of sub-micrometric diameters are measured and analysed by deriving the autocorrelation functions (ACFs) of the intensities. We show that for particles of diameter down to 200 nm, RCS measurements are successfully obtained in spite of the absence of any source of amplification of the Raman signal. For particles of diameter ranging from 200 to 750 nm, the ACFs present a time-decay behaviour in accordance with the model of free Brownian particles. For particles of 1000 nm in diameter, the AFCs present a different behaviour with a much smaller characteristic time. This results from the dynamics of a single-Brownian particle trapped in the confocal volume by the optical forces of the focus spot.


A longitudinal study of gastrointestinal parasites in Canadian dairy farms. The value of an indirect Ostertagia ostertagi ELISA as a monitoring tool.
The general objective of this study was to evaluate a crude Ostertagia ostertagi antigen enzyme-linked immunosorbent assay (ELISA) for monitoring gastrointestinal parasites in lactating dairy cattle. A longitudinal study of gastrointestinal parasites in lactating dairy cows was carried out in 38 herds in four provinces of Canada (Prince Edward Island, Quebec, Ontario and Saskatchewan) from September 1999 to October 2000. Bulk tank milk, cow milk, serum and fecal samples were collected monthly or quarterly from all these farms. Information on herd management factors was collected by a standard questionnaire and individual cow production data were obtained from an electronic database. The overall mean optical density ratio (ODR) was 0.30 and ranged from -0.05 to 1.55. Although a clear seasonal pattern was not observed, the ODR values tended to decrease during the housing period and start increasing in the spring before the cows went out to pasture. The second and third or greater lactation cows had significantly higher ODR values compared with first lactation animals. The individual cow ODR had a very low correlation with individual squared root fecal egg counts but showed a reasonably high correlation when herd averages values were computed (r=0.73). A moderate correlation (r approximately 0.50) between the bulk tank and herd average ODR was observed. Milk yield was negatively associated with individual cow milk ODR and a quadratic effect on ODR was observed for days in milk. Twenty-eight of the herds participated in a clinical trial of eprinomectin (Ivomec Eprinex) treatment at calving. The cow level ODR values determined late in the previous lactation had a marginally significant effect (P=0.07) on treatment response, suggesting that high OD cows responded better to the anthelmintic treatment. However, because of the small sample size available in this model, more research is needed to better understand this relationship. In conclusion, the indirect ELISA using an O. ostertagi crude antigen appears useful as a technique for monitoring gastrointestinal parasite burdens in adult dairy cows and holds promise as a potential predictor of response to anthelmintic treatment.


Structural factors influencing patterns of drug selling and use and HIV risk in the San Salvador metropolitan area.
This article explores differences in the social context in which crack sales and use and HIV risk take place in seven low-income communities in San Salvador, and structural factors that may influence these differences. The organization of drug selling varied among the communities on a number of dimensions including: whether drug sales were open or closed systems; the type of drug-selling site; and the participation of drug users in drug-distribution roles. Drug-use sites also varied according to whether crack was used in private, semiprivate, or public spaces, and whether individuals used drugs alone or with other drug users. Three patterns of drug use and selling were identified based on the dimensions outlined above. Structural factors that influenced these patterns included the geographic location of the communities, their physical layout, gang involvement in drug sales, and police surveillance. Implications for HIV risk and prevention are explored for each pattern.


Beneficial effects of antecedent exercise training on limb motor function and calpain expression in a rat model of stroke.
[Purpose] In the present study, we investigated the effects of antecedent exercise on functional recovery and calpain protein expression following focal cerebral ischemia injury. [Subjects and Methods] The rat middle cerebral artery occlusion model was employed. Adult male Sprague-Dawley rats were randomly divided into 4 groups. Group I comprised untreated normal rats (n=10); Group II comprised untreated rats with focal cerebral ischemia (n=10); Group III comprised rats that performed treadmill exercise (20 m/min) training after focal cerebral ischemia (n=10); and Group IV comprised rats that performed antecedent treadmill exercise (20 m/min) training before focal cerebral ischemia (n=10). At different time points (1, 7, 14, and 21 days), limb placement test score and the levels of calpain protein in the hippocampus were examined. [Results] In the antecedent exercise group, improvements in the motor behavior index (limb placement test) were observed and hippocampal calpain protein levels were decreased. [Conclusion] These results indicated that antecedent treadmill exercise prior to focal cerebral ischemia exerted neuroprotective effects against ischemic brain injury by improving motor performance and decreasing the levels of calpain expression. Furthermore, these results suggest that antecedent treadmill exercise of an appropriate intensity is critical for post-stroke rehabilitation.


Creating non-believed memories for recent autobiographical events.
A recent study showed that many people spontaneously report vivid memories of events that they do not believe to have occurred [1]. In the present experiment we tested for the first time whether, after powerful false memories have been created, debriefing might leave behind nonbelieved memories for the fake events. In Session 1 participants imitated simple actions, and in Session 2 they saw doctored video-recordings containing clips that falsely suggested they had performed additional (fake) actions. As in earlier studies, this procedure created powerful false memories. In Session 3, participants were debriefed and told that specific actions in the video were not truly performed. Beliefs and memories for all critical actions were tested before and after the debriefing. Results showed that debriefing undermined participants' beliefs in fake actions, but left behind residual memory-like content. These results indicate that debriefing can leave behind vivid false memories which are no longer believed, and thus we demonstrate for the first time that the memory of an event can be experimentally dissociated from the belief in the event's occurrence. These results also confirm that belief in and memory for an event can be independently-occurring constructs.


Active adenoviral vascular penetration by targeted formation of heterocellular endothelial-epithelial syncytia.
The endothelium imposes a structural barrier to the extravasation of systemically delivered oncolytic adenovirus (Ad). Here, we introduced a transendothelial route of delivery in order to increase tumor accumulation of virus particles (vp) beyond that resulting from convection-dependent extravasation alone. This was achieved by engineering an Ad encoding a syncytium-forming protein, gibbon ape leukemia virus (GALV) fusogenic membrane glycoprotein (FMG). The expression of GALV was regulated by a hybrid viral enhancer-human promoter construct comprising the human cytomegalovirus (CMV) immediate-early enhancer and the minimal human endothelial receptor tyrosine kinase promoter ("eTie1"). Endothelial cell-selectivity of the resulting Ad-eTie1-GALV vector was demonstrated by measuring GALV mRNA transcript levels. Furthermore, Ad-eTie1-GALV selectively induced fusion between infected endothelial cells and uninfected epithelial cells in vitro and in vivo, allowing transendothelial virus penetration. Heterofusion of infected endothelium to human embryonic kidney 293 (HEK 293) cells, in mixed in vitro cultures or in murine xenograft models, permitted fusion-dependent transactivation of the replication-deficient Ad-eTie1-GALV, due to enabled access to viral E1 proteins derived from the HEK 293 cytoplasm. These data provide evidence to support our proposed use of GALV to promote Ad penetration through tumor-associated vasculature, an approach that may substantially improve the efficiency of systemic delivery of oncolytic viruses to disseminated tumors.


Acute malnutrition in Latin America: the challenge of ending avoidable deaths.
In Latin America and the Caribbean, malnutrition still represents a health concern expressed mainly as stunting and micronutrient deficiencies, lessening the attention given to acute malnutrition (moderate and severe); however, the latter has a high fatality rate. Ending these avoidable deaths represents a major health and ethical challenge in the region. Acute malnutrition plus infections (mainly diarrhea and pneumonia) determine an important fraction of the fatality rate due to malnutrition in most regions, especially those with higher poverty and social instability. Application of the World Health Organization guidelines for the treatment of children with acute severe malnutrition reduces the fatality rate significantly. Among the many possibilities for treatment, systems based on day care centers and at home should be promoted. Training in the application of the World Health Organization guidelines should be incorporated into the curricula of health-related professions in countries where malnutrition is prevalent.