An oxygen-rich atmosphere or systemic fluoxetine extend the time to respiratory arrest in a rat model of obstructive apnea.

Audiogenic seizure-prone mice can be protected from seizure-associated death by exposure to an oxygen atmosphere or treatment with selective serotonergic reuptake inhibitors (SSRIs). We have shown previously in a rat model that epileptic seizure activity can spread through brainstem areas to cause sufficient laryngospasm for obstructive apnea and that the period of seizure-associated obstructive apnea can last long enough for respiratory arrest to occur. We hypothesized that both the oxygen-rich atmosphere and SSRIs function by prolonging the time to respiratory arrest, thus ensuring that seizure activity stops before the point of respiratory arrest to allow recovery of respiratory function. To test this hypothesis, we evaluated each preventative treatment in a rat model of controlled airway occlusion where the times to respiratory arrest can be measured. Adult male Sprague Dawley rats (median age = 66 days) were studied in the absence of any seizure activity. By directly studying responses to controlled airway occlusion, rather than airway occlusion secondary to seizure activity, we could isolate the effects of manipulations that might prolong respiratory arrest from the effects of those manipulations on seizure intensity. All group sizes were ≥ 8 animals per group. We found that both oxygen exposure and fluoxetine significantly increased the time to respiratory arrest by up to 65% (p < .0001 for 5 min oxygen exposure; p = .031 for 25 mg/kg fluoxetine tested 60 min after injection) and, given that neither treatment has been shown to significantly alter seizure duration, these increases can account for the protection of either manipulation against death in sudden death models. Importantly, we found that 30 s of exposure to oxygen produced nearly the same protection as 5 min exposure suggesting that oxygen exposure could start after a seizure starts (p = .0012 for 30 s oxygen exposure). Experiments with 50% oxygen/50% air mixtures indicate that the oxygen concentration needs to be above about 60% to ensure that times to respiratory arrest will always be longer than a period of seizure-induced airway occlusion. Selective serotonin reuptake inhibitors, while instructive with regard to mechanism, require impractical dosing and may carry additional risk in the form of greater challenges for resuscitation. We conclude that oxygen exposure or SSRI treatment prevent seizure associated death by sufficiently prolonging the time to respiratory arrest so that respiratory function can recover after the seizure abates and eliminates the stimulus for seizure-induced apnea.

A Wolf-Rayet-like progenitor of SN 2013cu from spectral observations of a stellar wind.

The explosive fate of massive Wolf-Rayet stars (WRSs) is a key open question in stellar physics. An appealing option is that hydrogen-deficient WRSs are the progenitors of some hydrogen-poor supernova explosions of types IIb, Ib and Ic (ref. 2). A blue object, having luminosity and colours consistent with those of some WRSs, has recently been identified in pre-explosion images at the location of a supernova of type Ib (ref. 3), but has not yet been conclusively determined to have been the progenitor. Similar work has so far only resulted in non-detections. Comparison of early photometric observations of type Ic supernovae with theoretical models suggests that the progenitor stars had radii of less than 10(12) centimetres, as expected for some WRSs. The signature of WRSs, their emission line spectra, cannot be probed by such studies. Here we report the detection of strong emission lines in a spectrum of type IIb supernova 2013cu (iPTF13ast) obtained approximately 15.5 hours after explosion (by 'flash spectroscopy', which captures the effects of the supernova explosion shock breakout flash on material surrounding the progenitor star). We identify Wolf-Rayet-like wind signatures, suggesting a progenitor of the WN(h) subclass (those WRSs with winds dominated by helium and nitrogen, with traces of hydrogen). The extent of this dense wind may indicate increased mass loss from the progenitor shortly before its explosion, consistent with recent theoretical predictions.

Diving responses elicited by nasopharyngeal irrigation mimic seizure-associated central apneic episodes in a rat model.

The spread of epileptic seizure activity to brainstem respiratory and autonomic regions can elicit episodes of obstructive apnea and of central apnea with significant oxygen desaturation and bradycardia. Previously, we argued that central apneic events were not consequences of respiratory or autonomic activity failure, but rather an active brainstem behavior equivalent to the diving response resulting from seizure spread. To test the similarities of spontaneous seizure-associated central apneic episodes to evoked diving responses, we used nasopharyngeal irrigation with either cold water or mist for 10 or 60 s to elicit the diving response in urethane-anesthetized animals with or without kainic acid-induced seizure activity. Diving responses included larger cardiovascular changes during mist stimuli than during water stimuli. Apneic responses lasted longer than 10 s in response to 10 s stimuli or about 40 s in response to 60 s stimuli, and outlasted bradycardia. Repeated 10 s mist applications led to an uncoupling of the apneic episodes (which always occurred) from the bradycardia (which became less pronounced with repetition). These uncoupled events matched the features of observed spontaneous seizure-associated central apneic episodes. The duration of spontaneous central apneic episodes correlated with their frequency, i.e. longer events occurred when there were more events. Based on our ability to replicate the properties of seizure-associated central apneic events with evoked diving responses during seizure activity, we conclude that seizure-associated central apnea and the diving response share a common neural basis and may reflect an attempt by brainstem networks to protect core physiology during seizure activity.

An outburst from a massive star 40 days before a supernova explosion.

Some observations suggest that very massive stars experience extreme mass-loss episodes shortly before they explode as supernovae, as do several models. Establishing a causal connection between these mass-loss episodes and the final explosion would provide a novel way to study pre-supernova massive-star evolution. Here we report observations of a mass-loss event detected 40 days before the explosion of the type IIn supernova SN 2010mc (also known as PTF 10tel). Our photometric and spectroscopic data suggest that this event is a result of an energetic outburst, radiating at least 6 × 10(47) erg of energy and releasing about 10(-2) solar masses of material at typical velocities of 2,000 km s(-1). The temporal proximity of the mass-loss outburst and the supernova explosion implies a causal connection between them. Moreover, we find that the outburst luminosity and velocity are consistent with the predictions of the wave-driven pulsation model, and disfavour alternative suggestions.

Seizure-associated central apnea in a rat model: Evidence for resetting the respiratory rhythm and activation of the diving reflex.

Respiratory derangements, including irregular, tachypnic breathing and central or obstructive apnea can be consequences of seizure activity in epilepsy patients and animal models. Periods of seizure-associated central apnea, defined as periods >1s with rapid onset and offset of no airflow during plethysmography, suggest that seizures spread to brainstem respiratory regions to disrupt breathing. We sought to characterize seizure-associated central apneic episodes as an indicator of seizure impact on the respiratory rhythm in rats anesthetized with urethane and given parenteral kainic acid to induce recurring seizures. We measured central apneic period onsets and offsets to determine if onset-offset relations were a consequence of 1) a reset of the respiratory rhythm, 2) a transient pausing of the respiratory rhythm, resuming from the pause point at the end of the apneic period, 3) a transient suppression of respiratory behavior with apnea offset predicted by a continuation of the breathing pattern preceding apnea, or 4) a random re-entry into the respiratory cycle. Animals were monitored with continuous ECG, EEG, and plethysmography. One hundred ninety central apnea episodes (1.04 to 36.18s, mean: 3.2±3.7s) were recorded during seizure activity from 7 rats with multiple apneic episodes. The majority of apneic period onsets occurred during expiration (125/161 apneic episodes, 78%). In either expiration or inspiration, apneic onsets tended to occur late in the cycle, i.e. between the time of the peak and end of expiration (82/125, 66%) or inspiration (34/36, 94%). Apneic period offsets were more uniformly distributed between early and late expiration (27%, 34%) and inspiration (16%, 23%). Differences between the respiratory phase at the onset of apnea and the corresponding offset phase varied widely, even within individual animals. Each central apneic episode was associated with a high frequency event in EEG or ECG records at onset. High frequency events that were not associated with flatline plethysmographs revealed a constant plethysmograph pattern within each animal, suggesting a clear reset of the respiratory rhythm. The respiratory rhythm became highly variable after about 1s, however, accounting for the unpredictability of the offset phase. The dissociation of respiratory rhythm reset from the cessation of airflow also suggested that central apneic periods involved activation of brainstem regions serving the diving reflex to eliminate the expression of respiratory movements. This conclusion was supported by the decreased heart rate as a function of apnea duration. We conclude that seizure-associated central apnea episodes are associated with 1) a reset of the respiratory rhythm, and 2) activation of brainstem regions serving the diving reflex to suppress respiratory behavior. The significance of these conclusions is that these details of seizure impact on brainstem circuitry represent metrics for assessing seizure spread and potentially subclassifying seizure patterns.

Cognitive abilities on transitive inference using a novel touchscreen technology for mice.

Cognitive abilities are impaired in neurodevelopmental disorders, including autism spectrum disorder (ASD) and schizophrenia. Preclinical models with strong endophenotypes relevant to cognitive dysfunctions offer a valuable resource for therapeutic development. However, improved assays to test higher order cognition are needed. We employed touchscreen technology to design a complex transitive inference (TI) assay that requires cognitive flexibility and relational learning. C57BL/6J (B6) mice with good cognitive skills and BTBR T+tf/J (BTBR), a model of ASD with cognitive deficits, were evaluated in simple and complex touchscreen assays. Both B6 and BTBR acquired visual discrimination and reversal. BTBR displayed deficits on components of TI, when 4 stimuli pairs were interspersed, which required flexible integrated knowledge. BTBR displayed impairment on the A > E inference, analogous to the A > E deficit in ASD. B6 and BTBR mice both reached criterion on the B > D comparison, unlike the B > D impairment in schizophrenia. These results demonstrate that mice are capable of complex discriminations and higher order tasks using methods and equipment paralleling those used in humans. Our discovery that a mouse model of ASD displays a TI deficit similar to humans with ASD supports the use of the touchscreen technology for complex cognitive tasks in mouse models of neurodevelopmental disorders.

Adaptive contraction of diet breadth affects sexual maturation and specific nutrient consumption in an extreme generalist omnivore.

Animals balance their intake of specific nutrients, but little is known about how they do so when foraging in an environment with toxic resources and whether toxic foods promote adaptations that affect life history traits. In German cockroach (Blattella germanica) populations, glucose aversion has evolved in response to glucose-containing insecticidal baits. We restricted newly eclosed glucose-averse (GA) and wild-type (WT) female cockroaches to nutritionally defined diets varying in protein-to-carbohydrate (P : C) ratio (3 : 1, 1 : 1, or 1 : 3) or gave them free choice of the 3 : 1 and 1 : 3 diets, with either glucose or fructose as the sole carbohydrate source. We measured consumption of each diet over 6 days and then dissected the females to measure the length of basal oocytes in their ovaries. Our results showed significantly lower consumption by GA compared to WT cockroaches when restricted to glucose-containing diets, but also lower fructose intake by GA compared to WT cockroaches when restricted to high fructose diets or given choice of fructose-containing diets. Protein intake was regulated tightly regardless of carbohydrate intake, except by GA cockroaches restricted to glucose-containing diets. Oocyte growth was completely suppressed in GA females restricted to glucose-containing diets, but also significantly slower in GA than in WT females restricted to fructose-containing diets. Our findings suggest that GA cockroaches have adapted to reduced diet breadth through endocrine adjustments which reduce requirements for energetic fuels. Our study illustrates how an evolutionary change in the chemosensory system may affect the evolution of other traits that govern animal life histories.

Supernova 2007bi as a pair-instability explosion.

Stars with initial masses such that 10M[symbol: see text] or= 140M[symbol: see text] (if such exist) develop oxygen cores with masses, M(core), that exceed 50M[symbol: see text], where high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs before oxygen ignition and leads to a violent contraction which triggers a nuclear explosion that unbinds the star in a pair-instability supernova. Transitional objects with 100M[symbol: see text] < M(initial) < 140M[symbol: see text] may end up as iron-core-collapse supernovae following violent mass ejections, perhaps as a result of brief episodes of pair instability, and may already have been identified. Here we report observations of supernova SN 2007bi, a luminous, slowly evolving object located within a dwarf galaxy. We estimate the exploding core mass to be M(core) approximately 100M[symbol: see text], in which case theory unambiguously predicts a pair-instability supernova. We show that >3M[symbol: see text] of radioactive (56)Ni was synthesized during the explosion and that our observations are well fitted by models of pair-instability supernovae. This indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic stellar mass limit, which perhaps result from processes similar to those that created the first stars in the Universe.

Diet specialization in an extreme omnivore: nutritional regulation in glucose-averse German cockroaches.

Organisms have diverse adaptations for balancing dietary nutrients, but often face trade-offs between ingesting nutrients and toxins in food. While extremely omnivorous cockroaches would seem excluded from such dietary trade-offs, German cockroaches (Blattella germanica) in multiple populations have rapidly evolved a unique dietary specialization - an aversion to glucose, the phagostimulant in toxic baits used for pest control. We used factorial feeding experiments within the geometric framework to test whether glucose-averse (GA) cockroaches with limited access to this critical metabolic fuel have compensatory behavioural and physiological strategies for meeting nutritional requirements. GA cockroaches had severely constrained intake, fat and N mass, and performance on glucose-based diets relative to wild-type (WT) cockroaches and did not appear to exhibit digestive strategies for retaining undereaten nutrients. However, a GA × WT 'hybrid' had lower glucose aversion than GA and greater access to macronutrients within glucose-based diets - while still having lower intake and survival than WT. Given these intermediate foraging constraints, hybrids may be a reservoir for this maladaptive trait in the absence of positive selection and may account for the rapid evolution of this trait following bait application.

Tar pollution event (2021) at the Southeastern Levantine oligotrophic basin, short-term impacts and operational oceanography perspectives.

The Levantine basin (LB) in the Southeastern Mediterranean Sea is a high-risk oil pollution hot spot owing to its dense maritime traffic and intense oil and gas exploration and exploitation activities. In February 2021 the Israeli LB shorelines were impacted by an exceptional tar pollution event (~550 tons; average distribution: ~3 kg tar m-1 front beach) of an unknown oil spill source. Here we report on the immediate numerical modelling assessment of the oil spill propagation and tar distribution; operational use of underwater gliders for tracking water column anomalies of dissolved polycyclic aromatic hydrocarbons (PAHs) and turbidity signals; the beached tar composition and amounts and the short-term response of the microbial population along the ~180 km shoreline. This pollution event emphasizes the need for improving the early warning systems for oil spills and implementing continuous operational monitoring at high-risk, ecologically sensitive and valuable resource areas like the Israeli LB waters.

Motherhood and HIV risk among female sex workers in Andhra Pradesh, India: the need to consider women's life contexts.

This study examines whether the challenges of motherhood among female sex workers (FSW) are linked with vulnerability to sexual risk factors for HIV. FSW at least 18 years of age (n = 850) were recruited through respondent driven sampling for a survey on HIV risk in the Rajahmundry area of Andhra Pradesh, India. Logistic regression models adjusted for demographic characteristics were used to assess the relation between reported caretaking challenges and sexual risk indicators for HIV. In adjusted logistic regression models, FSW who reported three or more children in their household or current child health concerns were significantly less likely to report consistent condom use (adjusted odds ratios (AORs) range: 0.5-0.6) and more likely to take more money for sex without a condom (both AORs: 2.5). Women who reported current child health concerns were also more likely to report an STI symptom in the past 6 months (AOR = 1.6; 95 % confidence interval: 1.1-2.3). Findings suggest that challenging responsibilities related to caretaking of children are associated with heightened vulnerability to HIV risk among FSW. Such findings add to the cumulating evidence urging for the implementation of HIV prevention interventions that consider the multiple challenges across various domains of women's lives.

Mediating effects of inequitable gender norms on intimate partner violence and contraceptive use in a cluster randomized control trial in Niger: A causal inference mediation analysis.

Background: Gender inequity, a deeply-rooted driver of poor health globally, is expressed in society through gender norms, the unspoken rules that govern gender-related roles and behavior. The development of public health interventions focused on promoting equitable gender norms are gaining momentum internationally, but there remain critical gaps in the evidence about how these interventions are working to change behavioral outcomes. Methods: A four-arm cluster randomized control trial (cRCT) was conducted to evaluate the effects of the Reaching Married Adolescents in Niger (RMA) intervention on modern contraceptive use and intimate partner violence (IPV) among married adolescent girls and their husbands in Dosso, Niger (T1: 1042 dyads; 24 mos. follow-up: 737 dyads, 2016-2019). This study seeks to understand if changes in perceived inequitable gender norms among husbands are the mechanism behind effects on modern contraceptive use and IPV. We estimated natural direct and indirect effects via these gender norms using inverse odds ratio weighting. An intention-to-treat approach and a difference-in-differences estimator in a hierarchical linear probability model was used to estimate prevalence differences, along with bootstrapping to estimate confidence intervals. Results: The total effects of the RMA small group intervention (Arm 2) is estimated to be an 8% reduction in prevalence of IPV [95% CI: -0.18, 0.01]. For this arm, the natural indirect effect through gender inequitable social norms is associated with a 2% decrease (95% CI: -0.07, 0.12), accounting for 22.3% of this total effect, and the natural direct effect with a 6% decrease (95% CI: -0.20, -0.02) in IPV. Of the total effect of the RMA household visit intervention (Arm 1) on contraceptive use (20% increase), indirect effects via inequitable gender norms were associated with an 11% decrease (95% CI: -0.18, -0.01) and direct effects with a 32% increase (95% CI: 0.13, 0.44) in contraceptive use. For the combination arm, of the total effects on contraceptive use (19% increase), indirect effects were associated with a 9% decrease (95% CI: -0.20, 0.02) and direct effects with a 28% increase (95% CI: 0.12, 0.46). Conclusion: The present study contributes experimental evidence that the small group RMA intervention reduced IPV partially via reductions in perceived inequitable gender norms among husbands. Evidence also suggests that increases in perceived inequitable gender norms resulted in decreased contraceptive use among those receiving the household visit intervention component. Not only do these results open the "black box" around how the RMA small group intervention may create behavior change to help inform its future use, they provide evidence supporting behavior change theories and frameworks that postulate the importance of changing underlying social norms in order to reduce IPV and increase modern contraceptive use.

Generalization of the prion hypothesis to other neurodegenerative diseases: an imperfect fit.

Protein misfolding diseases have been classically understood as diffuse errors in protein folding, with misfolded protein arising autonomously throughout a tissue due to a pathologic stressor. The field of prion science has provided an alternative mechanism whereby a seed of pathologically misfolded protein, arising exogenously or through a rare endogenous structural fluctuation, yields a template to catalyze misfolding of the native protein. The misfolded protein may then spread intercellularly to communicate the misfold to adjacent areas and ultimately infect a whole tissue. Mounting evidence implicates a prion-like process in the propagation of several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and the tauopathies. However, the parallels between the events observed in these conditions and those in prion disease are often incomplete. The aim of this review was to examine the current state of knowledge concerning the mechanisms of protein misfolding and aggregation for neurodegeneration-associated proteins. In addition, possible methods of intercellular spread are described that focus on the hypothesis that released microvesicles function as misfolded protein delivery vehicles, and the therapeutic options enabled by viewing these diseases from the prion perspective.

Abnormal electrophysiological phenotypes and sleep deficits in a mouse model of Angelman Syndrome.

BACKGROUND: Angelman Syndrome (AS) is a rare genetic disorder characterized by impaired communication, motor and balance deficits, intellectual disabilities, recurring seizures and abnormal sleep patterns. The genetic cause of AS is neuronal-specific loss of expression of UBE3A (ubiquitin-protein ligase E6-AP), an imprinted gene. Seizure and sleep disorders are highly prevalent (> 80%) in the AS population. The present experiments were designed to identify translational, neurophysiological outcome measures in a model of AS. METHODS: We used the exon-2 deletion mouse (Ube3a-del) on a C57BL/6J background to assess seizure, sleep and electrophysiological phenotypes. Seizure susceptibility has been reported in Ube3a-del mice with a variety of seizure induction methods. Here, we provoked seizures by a single high-dose injection of 80 mg/kg pentylenetetrazole. Novel experiments included the utilization of wireless telemetry devices to acquire global electroencephalogram (EEG) and neurophysiological data on electrographic seizures, power spectra, light-dark cycles, sleep stages and sleep spindles in Ube3a-del and WT mice. RESULTS: Ube3a-del mice exhibited reduced seizure threshold compared to WT. EEG illustrated that Ube3a-del mice had increased epileptiform spiking activity and delta power, which corroborates findings from other laboratories and recapitulates clinical reports in AS. This is the first report to use a cortical surface-based recording by a wireless telemetry device over tethered/fixed head-mount depth recordings. Less time in both paradoxical and slow-wave sleep, longer latencies to paradoxical sleep stages and total less sleep time in Ube3a-del mice were observed compared to WT. For the first time, we detected fewer sleep spindles in the AS mouse model. LIMITATIONS: This study was limited to the exon 2 deletion mouse model, and future work will investigate the rat model of AS, containing a complete Ube3a deletion and pair EEG with behavior. CONCLUSIONS: Our data enhance rigor and translatability as our study provides important corroboration of previous reports on epileptiform and elevated delta power. For the first time we report neurophysiological phenotypes collected via translational methodology. Furthermore, this is the first report of reduced sleep spindles, a critical marker of memory consolidation during sleep, in an AS model. Our results are useful outcomes for therapeutic testing.

Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development.

BACKGROUND: One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification and the genes that regulate chromatin. AT-rich interactive domain 1B (ARID1B), a chromatin modifier, has been linked to autism spectrum disorder and to affect rare and inherited genetic variation in a broad set of NDDs. METHODS: A novel preclinical mouse model of Arid1b deficiency was created and validated to characterize and define neuroanatomical, behavioral and transcriptional phenotypes. Neuroanatomy was assessed ex vivo in adult animals and in vivo longitudinally from birth to adulthood. Behavioral testing was also performed throughout development and tested all aspects of motor, learning, sociability, repetitive behaviors, seizure susceptibility, and general milestones delays. RESULTS: We validated decreased Arid1b mRNA and protein in Arid1b+/- mice, with signatures of increased axonal and synaptic gene expression, decreased transcriptional regulator and RNA processing expression in adult Arid1b+/- cerebellum. During neonatal development, Arid1b+/- mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. In addition, a striking sex effect was observed neuroanatomically throughout development. Behaviorally, as adults, Arid1b+/- mice showed low motor skills in open field exploration and normal three-chambered approach. Arid1b+/- mice had learning and memory deficits in novel object recognition but not in visual discrimination and reversal touchscreen tasks. Social interactions in the male-female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviors were observed. Brains of adult Arid1b+/- mice had a smaller cerebellum and a larger hippocampus and corpus callosum. The corpus callosum increase seen here contrasts previous reports which highlight losses in corpus callosum volume in mice and humans. LIMITATIONS: The behavior and neuroimaging analyses were done on separate cohorts of mice, which did not allow a direct correlation between the imaging and behavioral findings, and the transcriptomic analysis was exploratory, with no validation of altered expression beyond Arid1b. CONCLUSIONS: This study represents a full validation and investigation of a novel model of Arid1b+/- haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs.

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms.

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage (European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region.

Republished paper: assessment of doctors' consultation skills in the paediatric setting: the Paediatric Consultation Assessment Tool.

OBJECTIVE: To determine the utility of a novel Paediatric Consultation Assessment Tool (PCAT). DESIGN: Developed to measure clinicians' communication behaviour with children and their parents/guardian, PCAT was designed according to consensus guidelines and refined at a number of stages. Volunteer clinicians provided videotaped real consultations. Assessors were trained to score communication skills using PCAT, a novel rating scale. SETTING: Eight UK paediatric units. PARTICIPANTS: 19 paediatricians collected video-recorded material; a second cohort of 17 clinicians rated the videos. MAIN OUTCOME MEASURES: Itemised and aggregated scores were analysed (means and 95% confidence intervals) to determine measurement characteristics and relationship to patient, consultation, clinician and assessor attributes; generalisability coefficient of aggregate score; factor analysis of items; comparison of scores between groups of patients, consultations, clinicians and assessors. RESULTS: 188 complete consultations were analysed (median per doctor = 10). 3 videos marked by any trained assessor are needed to reliably (r > 0.8) assess a doctor's triadic consultation skills using PCAT, 4 to assess communication with just children or parents. Performance maps to two factors - "clinical skills" and "communication behaviour"; clinicians score more highly on the former (mean (SD) 95% CI 0.52 (0.075)). There were significant differences in scores for the same skills applied to parent and child, especially between the ages of 2 and 10 years, and for information-sharing rather than relationship building skills (2-tailed significance < 0.001). Conclusions The PCAT appears to be reliable, valid and feasible for the assessment of triadic consultation skills by direct observation.

Combined effect of hemipteran control and liquid bait on Argentine ant populations.

The invasive Argentine ant, Linepithema humile (Mayr), has become a worldwide problem capable of inflicting significant ecological and economic injury on urban, agricultural, and natural environments. The mobility of this pest ant has long been noted, rapidly moving nests to new food resources and then away as resources are depleted. This ant, like many pest ant species, has a special affinity for honeydew excreted by phloem-feeding Hemiptera. We investigated the effect of various hemipteran control strategies on terrapin scale densities and measured their indirect effect on local Argentine ant densities and foraging effort. We then determined whether this indirect treatment strategy improved the performance of an ant bait. We predicted that Argentine ants would move nests away from trees treated for Hemiptera and then move nests back when a liquid bait was offered, followed by a decline in ant numbers due to intake of the toxicant. A horticultural oil spray and soil application of the systemic insecticide, imidacloprid, had no effect on terrapin scale numbers. However, trunk-injected dicrotophos caused a reduction in scale and a decline in local Argentine ant nest density and canopy foraging effort. We also recorded a reduction in local Argentine ant ground foraging when large amounts of liquid bait were applied, and we found no evidence that combining dicrotophos with liquid ant bait performed better than each treatment alone. We suggest that a strategy of combined hemipteran control plus application of liquid ant bait can reduce local Argentine ant densities, when both components of this system are highly efficacious.

Legacy groundwater pollution as a source of mercury enrichment in marine food web, Haifa Bay, Israel.

Haifa Bay (HB), located along the northern Mediterranean shore of Israel was polluted with Hg from a chlor-alkali plant (ECI) and from the Qishon River industries, for decades. From the mid-1980s industrial Hg loads into HB decreased dramatically until their complete cessation in 2000. Consequently, concentrations in marine biota and sediments decreased almost to reference levels. However, during 2006-2014, an unexpected increase of total Hg (THg) concentrations was observed in three commercial fish species collected at northern HB (N.HB). To determine the cause of this increase, THg and methyl Hg (MeHg) were measured in seawater, coastal groundwater, suspended particulate matter, plankton, macroalgae, benthic fauna, and in marine and beach sediments. THg in groundwater and sediments from the vicinity of ECI were extremely high (up to 251 µg L-1 and 2200 ng g-1, respectively). MeHg concentrations in groundwater were low and constituted <0.1% of THg, except in the surf zone opposite the ECI, where MeHg constituted 0.2% of the THg. THg and MeHg concentrations were consistently higher in benthic biota and plankton from N.HB and northwards, compared to corresponding samples from southern HB (S.HB) and the reference site (RS). MeHg in bivalves and sponges from N.HB and SZ was higher than from S.HB and RS, despite having similar THg concentrations, which suggests a stronger source of MeHg in N.HB. Our findings suggest that the discharge into N.HB of Hg polluted groundwater under the ECI increased during the period 2006-2014. The Hg was assimilated by plankton or adsorbed onto inorganic particles, which were further ingested by benthic and pelagic consumers, as well as transported northward with the alongshore current. These findings demonstrate for the first time the potential of relic pollution in groundwater to increase heavy metal burdens in local marine food webs.