Consistency of fish-shoal social network structure under laboratory conditions.

We investigated the consistency of association network structure for groups of sticklebacks Gasterosteus aculeatus. Each group was observed twice and we varied the duration between observations and the size of the experimental arena that they were observed in. At the dyad level, we found positive correlations between dyad interaction frequencies across observations. At the group level we found variation in four network metrics between observations, but only in treatments where the duration between observations was short. Specifically, fish formed more and smaller groups in the second observation in this treatment. Fish were also organized into more subunits in the larger arenas. Finally, we saw positive correlations between some group network metrics across observations suggesting relative consistency at the group level. There are several processes that might drive these interaction patterns. Our findings have implications for experimental design and the comparison and integration of findings of experiments from different studies carried out under different conditions.

Characterizing selection in black-throated blue warblers using a sexual network approach.

Our understanding of trait evolution is built upon studies that examine the correlation between traits and fitness, most of which implicitly assume all individuals experience similar selective environments. However, accounting for differences in selective pressures, such as variation in the social environment, can advance our understanding of how selection shapes individual traits and subsequent fitness. In this study, we test whether variation in the social environment affects selection on individual phenotype. We apply a new sexual network framework to quantify each male's social environment as the mean body size of his primary competitors. We test for direct and social selection on male body size using a 10-year data set on black-throated blue warblers (Setophaga caerulescens), a territorial species for which body size is hypothesized to mediate competition for mates. We found that direct selection on body size was weak and nonsignificant, as was social selection via the body size of the males' competitors. Analysing both types of selection simultaneously allows us to firmly reject a role for body size in competitive interactions between males and subsequent male fitness in this population. We evaluate the application of the sexual network approach to empirical data and suggest that other phenotypic traits such as song characteristics and plumage may be more relevant than body size for male-male competition in this small passerine bird.

Differential activation of immune/inflammatory response-related co-expression modules in the hippocampus across the major psychiatric disorders.

The Stanley Neuropathology Consortium Integrative Database (SNCID, http://sncid.stanleyresearch.org) is a data-mining tool that includes 379 neuropathology data sets from hippocampus, as well as RNA-Seq data measured in 15 well-matched cases in each of four groups: schizophrenia, bipolar disorder (BPD), major depression (MD) and unaffected controls. We analyzed the neuropathology data from the hippocampus to identify those abnormalities that are shared between psychiatric disorders and those that are specific to each disorder. Of the 379 data sets, 20 of them showed a significant abnormality in at least one disorder as compared with unaffected controls. GABAergic markers and synaptic proteins were mainly abnormal in schizophrenia and the two mood disorders, respectively. Two immune/inflammation-related co-expression modules built from RNA-seq data from both schizophrenia and controls combined were associated with disease status, as well as negatively correlated with the GABAergic markers. The correlation between immune-related modules and schizophrenia was replicated using microarray data from an independent tissue collection. Immune/inflammation-related co-expression modules were also built from RNA-seq data from BPD cases or from MD cases but were not preserved when using data from control cases. Moreover, there was no overlap in the genes that comprise the immune/inflammation response-related modules across the different disorders. Thus, there appears to be differential activation of the immune/inflammatory response, as determined by co-expression of genes, which is associated with the major psychiatric disorders and which is also associated with the abnormal neuropathology in the disorders.

Effect of yeast supplementation on performance, rumination time, and rumen pH of dairy cows in commercial farm environments.

The aims of the present study were to evaluate the effects of live yeast supplementation (Vistacell MUCL 39855, AB Vista, Marlborough, UK) on performance, rumination time, and rumen pH on dairy cows in commercial farm environments. Three trials were carried out, the trials lasted 12 (trial 1), 15 (trial 2), and 19 wk (trial 3). In each trial, 14 multiparous Holstein dairy cows were allocated to 2 groups that received (trial 1) a standard diet plus yeast, (trial 2) an acidogenic diet plus yeast, and (trial 3) grazing pasture plus yeast. Milk production, milk chemical characteristics, body weight and body condition score, rumination time, and rumen pH were monitored for each group throughout the 3 trials. No statistically significant differences were observed in any of the 3 trials for any of the recorded variables. In contrast, an effect of time (period or days in milk) on rumen pH was observed in all 3 of the trials, as time spent under the acidotic thresholds increased across the experimental periods; however the differences were not associated with live yeast supplementation. No effect of live yeast supplementation was observed in any of the 3 trials reported. Further research should include studies on animals at different stages of lactation (with emphasis on transition period and early lactation), consuming more challenging diets (higher level of inclusion of concentrates or starch), or under different environments such as grazing of succulent forages. Such studies might be required to elucidate any possible effect of live yeast supplementation of dairy cows when the rumen environment is under challenge.

Quantifying BTEX in aqueous solutions with potentially interfering hydrocarbons using a partially selective sensor array.

Partially selective gold nanoparticle sensors have the sensitivity and selectivity to discriminate and quantify benzene, toluene, ethylbenzene, p-xylene and naphthalene (BTEXN) at concentrations relevant to the US Environmental Protection Agency. In this paper we demonstrate that gold nanoparticle chemiresistors can do so in the presence of 16 other hydrocarbons and that they did not reduce the discriminating power of the array. A two-level full factorial designed experiment was performed on unary, binary, ternary, quaternary, quinary combinations of BTEXN analytes with and without the possibly interfering hydrocarbons. The nominal component concentration of the mixtures was 100 µg L(-1), equivalent to approximately 100 parts per billion (ppb). Concentrations predicted with the random forests method had an average root mean square error of 10-20% of the component concentrations. This level of accuracy was achieved regardless of whether or not the 16 possibly interfering hydrocarbons were present. This work shows that the sensitivity and selectivity of gold nanoparticles chemiresistor sensors towards BTEXN analytes are not unduly affected by the other hydrocarbons that are expected to be present at a petroleum remediation site.

The utility of a 'non-significant' coronary angiogram.

BACKGROUND: Coronary angiography is the gold standard for assessing coronary artery disease (CAD). In many patients with chest pain, no or mild CAD (< 50% stenosis) is found. It is uncertain whether this 'non-significant' result influences management and outcomes. We reviewed characteristics and outcomes in a contemporary cohort of chest pain referrals who had mild or absent CAD on coronary angiography. METHOD: All patients undergoing coronary angiography at Auckland City Hospital during July 2010-October 2011 were reviewed (n = 2983). Of these, 12.3% (n = 366) underwent coronary angiography for evaluation of chest pain and were found to have absent or mild CAD. These patients were followed up for 2.3 ± 0.6 years. RESULTS: Mean age was 60.0 ± 12.3 years, 56.1% were female. The ECG was abnormal in 55.0% of patients. Stress testing for inducible ischaemia was undertaken in 40.7% of patients and was abnormal in 57.7%. Following angiography, 43.2% had no changes to cardiac medications. Additional drug therapy (aspirin, statin, beta-blockers, ACE-inhibitor) was commenced in around 14.2-22.1% of cases. These drugs were discontinued in 4.1-8.2% of patients. Rates of major adverse cardiovascular events and readmissions with chest pain were 0.3% (1) and 1.9% (7) respectively at 30 days, and 1.9% (7) and 6.0% (22) at 1 year. CONCLUSION: Although even non-obstructive atheroma may justify medical therapy to limit disease progression, our findings may suggest that in these cases, invasive coronary angiography, may not lead to the patient/physician reassurance justified by historical data.

Characterization of microsatellite markers for the Restinga Antwren, Formicivora littoralis (Thamnophilidae), an endangered bird endemic to Brazil.

Molecular markers are important tools in determining parentage, gene flow, and the genetic structure of species. In the case of rare, endemic, and/or threatened species, these markers can be used to understand key ecological questions and support conservation actions. We developed seven microsatellite markers for the only bird endemic to the Restinga ecosystem. Microsatellite loci were isolated from a library that was based on 10 individuals (six males and four females). Primers were tested in 107 individuals of the same population. The number of alleles per locus ranged from 4 to 19, and the observed and expected heterozygosity varied from 0.15 to 0.84 and from 0.60 to 0.89, respectively. We expect that the polymorphic microsatellite loci we describe will be useful for other studies, particularly in the Tropics.

Familiarity affects social network structure and discovery of prey patch locations in foraging stickleback shoals.

Numerous factors affect the fine-scale social structure of animal groups, but it is unclear how important such factors are in determining how individuals encounter resources. Familiarity affects shoal choice and structure in many social fishes. Here, we show that familiarity between shoal members of sticklebacks (Gasterosteus aculeatus) affects both fine-scale social organization and the discovery of resources. Social network analysis revealed that sticklebacks remained closer to familiar than to unfamiliar individuals within the same shoal. Network-based diffusion analysis revealed that there was a strong untransmitted social effect on patch discovery, with individuals tending to discover a task sooner if a familiar individual from their group had previously done so than if an unfamiliar fish had done so. However, in contrast to the effect of familiarity, the frequency with which individuals had previously associated with one another had no effect upon the likelihood of prey patch discovery. This may have been due to the influence of fish on one another's movements; the effect of familiarity on discovery of an empty 'control' patch was as strong as for discovery of an actual prey patch. Our results demonstrate that factors affecting fine-scale social interactions can also influence how individuals encounter and exploit resources.

Health care delivery for head-and-neck cancer patients in Alberta: a practice guideline.

BACKGROUND: The treatment of head-and-neck cancer is complex and requires the involvement of various health care professionals with a wide range of expertise. We describe the process of developing a practice guideline with recommendations about the organization and delivery of health care services for head-and-neck cancer patients in Alberta. METHODS: Outcomes of interest included composition of the health care team, qualification requirements for team members, cancer centre and team member volumes, infrastructure needs, and wait times. A search for existing practice guidelines and a systematic review of the literature addressing the organization and delivery of health care services for head-and-neck cancer patients were conducted. The search included the Standards and Guidelines Evidence (sage) directory of cancer guidelines and PubMed. RESULTS: One practice guideline was identified for adaptation. Three additional practice guidelines provided supplementary evidence to inform guideline recommendations. Members of the Alberta Provincial Head and Neck Tumour Team (consisting of various health professionals from across the province) provided expert feedback on the adapted recommendations through an online and in-person review process. Selected experts in head-and-neck cancer from outside the province participated in an external online review. SUMMARY: The recommendations outlined in this practice guideline are based on existing guidelines that have been modified to fit the Alberta context. Although specific to Alberta, the recommendations lend credence to similar published guidelines and could be considered for use by groups lacking the resources of appointed guideline panels. The recommendations are meant to be a guide rather than a fixed protocol. The implementation of this practice guideline will depend on many factors, including but not limited to availability of trained personnel, adequate funding of infrastructure, and collaboration with other associations of health care professionals in the province.

Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement.

Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

Annotated computed tomography coronary angiogram images and associated data of normal and diseased arteries.

Computed Tomography Coronary Angiography (CTCA) is a non-invasive method to evaluate coronary artery anatomy and disease. CTCA is ideal for geometry reconstruction to create virtual models of coronary arteries. To our knowledge there is no public dataset that includes centrelines and segmentation of the full coronary tree. We provide anonymized CTCA images, voxel-wise annotations and associated data in the form of centrelines, calcification scores and meshes of the coronary lumen in 20 normal and 20 diseased cases. Images were obtained along with patient information with informed, written consent as part of the Coronary Atlas. Cases were classified as normal (zero calcium score with no signs of stenosis) or diseased (confirmed coronary artery disease). Manual voxel-wise segmentations by three experts were combined using majority voting to generate the final annotations. Provided data can be used for a variety of research purposes, such as 3D printing patient-specific models, development and validation of segmentation algorithms, education and training of medical personnel and in-silico analyses such as testing of medical devices.

Information flow through threespine stickleback networks without social transmission.

Social networks can result in directed social transmission of learned information, thus influencing how innovations spread through populations. Here we presented shoals of threespine sticklebacks (Gasterosteous aculeatus) with two identical foraging tasks and applied network-based diffusion analysis (NBDA) to determine whether the order in which individuals in a social group contacted and solved the tasks was affected by the group's network structure. We found strong evidence for a social effect on discovery of the foraging tasks with individuals tending to discover a task sooner when others in their group had previously done so, and with the spread of discovery of the foraging tasks influenced by groups' social networks. However, the same patterns of association did not reliably predict spread of solution to the tasks, suggesting that social interactions affected the time at which the tasks were discovered, but not the latency to its solution following discovery. The present analysis, one of the first applications of NBDA to a natural animal system, illustrates how NBDA can lead to insight into the mechanisms supporting behaviour acquisition that more conventional statistical approaches might miss. Importantly, we provide the first compelling evidence that the spread of novel behaviours can result from social learning in the absence of social transmission, a phenomenon that we refer to as an untransmitted social effect on learning.

Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders.

Cytoarchitectural abnormalities have been described in the prefrontal cortex (PFC) of subjects with psychiatric disorders. We explored the possible genetic causalities that may underlie the cytoarchitectural abnormalities of calbindin-containing γ-aminobutyric acid (GABA)ergic neurons and perineuronal oligodendrocytes in the PFC of subjects with psychiatric disorders by converging results from genome-wide single-nucleotide polymorphism (SNP) scans for the traits and expression SNP (eSNP) associations. In the initial genome-wide scans, we identified several development- and apoptosis-related genes associated with the cytoarchitectural traits. Moreover, the susceptibility gene for bipolar disorder, PPP2R2C, was found to be associated with the number of perineuronal oligodendrocytes. Further eSNP analyses indicated that two novel candidate genes, RAB2A and SLC38A1, were associated with the density of calbindin-positive neurons and the number of perineuronal oligodendrocytes, respectively. Our findings may provide novel insights into the genetic causalities associated with cytoarchitectural abnormalities in the PFC of subjects with major psychiatric disorders as well as into the etiology of such disorders.

Dynamic molecular and anatomical changes in the glucocorticoid receptor in human cortical development.

The glucocorticoid receptor (GR) has a critical role in determining the brain's capacity to respond to stress, and has been implicated in the pathogenesis of psychiatric illness. We hypothesized that key changes in cortical GR occur during adolescence and young adulthood, at a time when individuals are at increased risk of developing schizophrenia, bipolar disorder and major depression. We investigated the mRNA and protein expression of GR in the dorsolateral prefrontal cortex across seven developmental time points from infancy to adulthood. GR mRNA expression, determined by microarray and quantitative real-time PCR, was lowest in neonates and peaked around young adulthood. Western blotting revealed two dynamic patterns of GRα protein expression across the lifespan, with N-terminal variants displaying differing unique patterns of abundance. GRα-A and a 67-kDa GRα isoform mirrored mRNA trends and peaked in toddlers and late in adolescence, whereas a 40-kDa isoform, very likely a GRα-D variant, peaked in neonates and decreased across the lifespan. GRα protein was localized to pyramidal neurons throughout life and most strikingly in young adulthood, but to white matter astrocytes only in neonates and infants (<130 days). These results suggest that the neonatal and late adolescent periods represent critical windows of stress pathway development, and highlight the importance of white matter astrocytes and pyramidal neurons, respectively, at these stages of cortical development. Evidence of dynamic patterns of GR isoform expression and cellular localization across development strengthens the hypothesis that windows of vulnerability to stress exist across human cortical development.

Reproductive state affects reliance on public information in sticklebacks.

The degree to which animals use public and private sources of information has important implications for research in both evolutionary ecology and cultural evolution. While researchers are increasingly interested in the factors that lead individuals to vary in the manner in which they use different sources of information, to date little is known about how an animal's reproductive state might affect its reliance on social learning. Here, we provide experimental evidence that in foraging ninespine sticklebacks (Pungitius pungitius), gravid females increase their reliance on public information generated by feeding demonstrators in choosing the richer of two prey patches than non-reproductive fish, while, in contrast, reproductive males stop using public information. Subsequent experiments revealed reproductive males to be more efficient asocial foragers, less risk-averse and generally less social than both reproductive females and non-reproductives. These findings are suggestive of adaptive switches in reliance on social and asocial sources of information with reproductive condition, and we discuss the differing costs of reproduction and the proximate mechanisms that may underlie these differences in information use. Our findings have important implications for our understanding of adaptive foraging strategies in animals and for understanding the way information diffuses through populations.

The opportunity for sexual selection: not mismeasured, just misunderstood.

Evolutionary biologists have developed several indices, such as selection gradients (ß) and the opportunity for sexual selection (I(s) ), to quantify the actual and/or potential strength of sexual selection acting in natural or experimental populations. In a recent paper, Klug et al. (J. Evol. Biol.23, 2010, 447) contend that selection gradients are the only legitimate metric for quantifying sexual selection. They argue that I(s) and similar mating-system-based metrics provide unpredictable results, which may be uncorrelated with selection acting on a trait, and should therefore be abandoned. We find this view short-sighted and argue that the choice of metric should be governed by the research question at hand. We describe insights that measures such as the opportunity for selection can provide and also argue that Klug et al. have overstated the problems with this approach while glossing over similar issues with the interpretation of selection gradients. While no metric perfectly characterizes sexual selection in all circumstances, thoughtful application of existing measures has been and continues to be informative in evolutionary studies.

Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders.

Cytoarchitectural abnormalities have been described in the prefrontal cortex of subjects with schizophrenia, bipolar disorder and depression. However, little is known about the gene expression profiles associated with these abnormalities. Genome-wide expression profiling technology provides an unbiased approach to identifying candidate genes and biological processes that may be associated with complex biological traits such as cytoarchitecture. In this study, we explored expression profiles associated with the abnormalities by using publicly available microarray metadata and cytoarchitectural data from post-mortem samples of the frontal cortex from 54 subjects (schizophrenia, n=14; bipolar disorder, n=13; depression, n=12 and controls n=15). Correlation analysis between genome-wide expression levels and cytoarchitectural traits revealed that 818 genes were significantly correlated with a decrease in the number of perineuronal oligodendrocytes across all subjects. A total of 600 genes were significantly correlated with a decrease in density of calbindin-positive interneurons across all subjects. Multiple biological processes including cellular metabolism, central nervous system development, cell motility and programmed cell death were significantly overrepresented in both correlated gene lists. These findings may provide novel insights into the molecular mechanisms that underlie the cytoarchitectural abnormalities of perineuronal oligodendrocytes and calbindin-containing GABAergic interneurons in the prefrontal cortex of the major psychiatric disorders.

Snow on Arctic Sea Ice in a Warming Climate as Simulated in CESM.

Earth system models are valuable tools for understanding how the Arctic snow-ice system and the feedbacks therein may respond to a warming climate. In this analysis, we investigate snow on Arctic sea ice to better understand how snow conditions may change under different forcing scenarios. First, we use in situ, airborne, and satellite observations to assess the realism of the Community Earth System Model (CESM) in simulating snow on Arctic sea ice. CESM versions one and two are evaluated, with V1 being the Large Ensemble experiment (CESM1-LE) and V2 being configured with low- and high-top atmospheric components. The assessment shows CESM2 underestimates snow depth and produces overly uniform snow distributions, whereas CESM1-LE produces a highly variable, excessively-thick snow cover. Observations indicate that snow in CESM2 accumulates too slowly in autumn, too quickly in winter-spring, and melts too soon and rapidly in late spring. The 1950-2050 trends in annual mean snow depths are markedly smaller in CESM2 (-0.8 cm decade-1) than in CESM1-LE (-3.6 cm decade-1) due to CESM2 having less snow overall. A perennial, thick sea-ice cover, cool summers, and excessive summer snowfall facilitate a thicker, longer-lasting snow cover in CESM1-LE. Under the SSP5-8.5 forcing scenario, CESM2 shows that, compared to present-day, snow on Arctic sea ice will: (1) undergo enhanced, earlier spring melt, (2) accumulate less in summer-autumn, (3) sublimate more, and (4) facilitate marginally more snow-ice formation. CESM2 also reveals that summers with snow-free ice can occur ∼30-60 years before an ice-free central Arctic, which may promote faster sea-ice melt.

Behavioural thermoregulation in two freshwater fish species.

In the presence of a vertical thermal gradient, juvenile three-spined sticklebacks Gasterosteus aculeatus and minnows Phoxinus phoxinus positioned themselves higher in the water column compared with adult conspecifics. This result was consistent regardless of whether age cohorts were tested separately or together. Furthermore, juveniles but not adult fishes positioned themselves higher in water column in the presence of a thermal gradient compared with those in the absence of a thermal gradient. Juvenile G. aculeatus and adult fish of both species did opt to position themselves higher in the water column in the hours immediately following a feeding event relative to their positions in the same gradient when they had not fed.

Transmembrane domain sequence requirements for activation of the p185c-neu receptor tyrosine kinase.

The receptor tyrosine kinase p185c-neu can be constitutively activated by the transmembrane domain mutation Val664-->Glu, found in the oncogenic mutant p185neu. This mutation is predicted to allow intermolecular hydrogen bonding and receptor dimerization. Understanding the activation of p185c-neu has assumed greater relevance with the recent observation that achondroplasia, the most common genetic form of human dwarfism, is caused by a similar transmembrane domain mutation that activates fibroblast growth factor receptor (FGFR) 3. We have isolated novel transforming derivatives of p185c-neu using a large pool of degenerate oligonucleotides encoding variants of the transmembrane domain. Several of the transforming isolates identified were unusual in that they lacked a Glu at residue 664, and others were unique in that they contained multiple Glu residues within the transmembrane domain. The Glu residues in the transforming isolates often exhibited a spacing of seven residues or occurred in positions likely to represent the helical interface. However, the distinction between the sequences of the transforming clones and the nontransforming clones did not suggest clear rules for predicting which specific sequences would result in receptor activation and transformation. To investigate these requirements further, entirely novel transmembrane sequences were constructed based on tandem repeats of simple heptad sequences. Activation was achieved by transmembrane sequences such as [VVVEVVA]n or [VVVEVVV]n, whereas activation was not achieved by a transmembrane domain consisting only of Val residues. In the context of these transmembrane domains, Glu or Gln were equally activating, while Lys, Ser, and Asp were not. Using transmembrane domains with two Glu residues, the spacing between these was systematically varied from two to eight residues, with only the heptad spacing resulting in receptor activation. These results are discussed in the context of activating mutations in the transmembrane domain of FGFR3 that are responsible for the human developmental syndromes achondroplasia and acanthosis nigricans with Crouzon Syndrome.