The seventh inner moon of Neptune.

During its 1989 flyby, the Voyager 2 spacecraft imaged six small moons of Neptune, all with orbits well interior to that of the large, retrograde moon Triton1. Along with a set of nearby rings, these moons are probably younger than Neptune itself; they formed shortly after the capture of Triton and most of them have probably been fragmented multiple times by cometary impacts1-3. Here we report Hubble Space Telescope observations of a seventh inner moon, Hippocamp. It is smaller than the other six, with a mean radius of about 17 kilometres. We also observe Naiad, Neptune's innermost moon, which was last seen in 1989, and provide astrometry, orbit determinations and size estimates for all the inner moons, using an analysis technique that involves distorting consecutive images to compensate for each moon's orbital motion and that is potentially applicable to searches for other moons and exoplanets. Hippocamp orbits close to Proteus, the outermost and largest of these moons, and the orbital semimajor axes of the two moons differ by only ten per cent. Proteus has migrated outwards because of tidal interactions with Neptune. Our results suggest that Hippocamp is probably an ancient fragment of Proteus, providing further support for the hypothesis that the inner Neptune system has been shaped by numerous impacts.

Genetics of phenological development and implications for seed yield in lentil.

Understanding phenology, its genetics and agronomic consequences, is critical for crop adaptation. Here we aim at (1) characterising lentil response to photoperiod with a focus on five loci: the lentil ELF3 ortholog Sn, two loci linked to clusters of lentil FT orthologs and two loci without candidates in chromosomes 2 and 5 (exp. 1: 36 lines, short and long day in phytotron); (2) establishing phenology-yield relationship (exp. 2: 25 lines, 11 field environments). A vintage perspective, where we quantify time trends in phenotype over three decades of breeding, links both experiments. Yield increased linearly from older to newer varieties at 29 kg ha-1 yr-1 or 1.5% yr-1, correlated negatively with flowering time in both winter- and summer-rainfall regimes, and decoupled from biomass in favourable environments. Time to flowering shortened from older to newer varieties at -0.56 % yr-1 in the field, and -0.42 % yr-1 (short day) and -0.99 % yr-1 (long day) in the phytotron. Early-flowering lines of diverse origin carried multiple early alleles for the five loci, indicating that at least some of these loci affect phenology additively. Current germplasm primarily features the early flowering haplotype for an FTb cluster region, hence the potential to increase phenological diversity with yield implications.

The effect of fresh gas flow during induction of anaesthesia on sevoflurane usage: a quality improvement study.

Reducing fresh gas flow during inhalational anaesthesia results in cost savings and decreases environmental impact. We are interested in the influence of fresh gas flow on the early (induction) phase of overall fresh gas flow and vapour consumption. This stage is often excluded in studies of fresh gas flow. Data were collected from 3199 sevoflurane anaesthetics over an 11-month period in four operating theatres. We determined fresh gas flow at different stages of anaesthesia, and developed an explanatory model for the influence of the 'induction' period. Following a three-month collection of baseline data we emphasised the importance of the early phase to our department repeatedly over a two-week period. We explored the relationship between fresh gas flow and total vapour usage, and used a simple mathematical model to explore the effect of changes in the fresh gas flow and duration of the 'induction' phase. Mean fresh gas flow was 1.15 l.min-1 in the baseline period and 0.91 l.min-1 in the two months following our educational effort (p = 0.0005). In the following six months, mean fresh gas flow was 1.17 l.min-1 (p = 0.7726 compared with baseline). These results were driven by changes in both fresh gas flow and duration of the initial high-flow period. We found some correlation (R2  = 0.85) between overall fresh gas flow and vapour consumption; a 1 l.min-1 increase in fresh gas flow consumes an additional 18 ml.hr-1 of liquid sevoflurane. This preliminary study demonstrates that an episode of high fresh gas flow at the start of anaesthesia has a large and modifiable effect on overall fresh gas flow and vapour consumption. We also confirmed the linear relationship between fresh gas flow and vapour usage.

Intentional use of carbapenem antibiotics for valproic acid toxicity: A case report.

WHAT IS KNOWN AND OBJECTIVE: The interaction between valproic acid (VPA) and carbapenem antibiotics is well described with previous reports suggesting a reduction in VPA half-life between 47% and 90%. As described in this case, this interaction might be beneficial in the setting of toxic VPA ingestion. CASE DESCRIPTION: An intubated, unresponsive patient arrived via emergency medical services after toxic VPA ingestion. Meropenem was prescribed for a suspected pneumonia and to take advantage of the VPA interaction. We observed a 56% decline in half-life with short-term meropenem dosing and an improvement in mental status shortly after administration. WHAT IS NEW AND CONCLUSION: Our findings suggest a potential role for short-term carbapenem therapy for VPA overdose.

Civilian and military doctors' knowledge of tranexamic acid (TXA) use in major trauma: a comparison study.

INTRODUCTION: Tranexamic acid (TXA) administration within the recommended time of 3 hours has been demonstrated to improve outcomes following trauma. The aim of this study was to identify potential knowledge gaps in the administration of TXA in order to target further educational training in those doctors responsible for the management of acute trauma. METHODS: 104 military and 852 civilian doctors were invited to complete a four-item web-based questionnaire pertaining to the indications, dose, side effects and evidence base for TXA administration in trauma. Doctors of all grades and surgical specialties including emergency trainees and anaesthetics were surveyed. RESULTS: 65 military and 460 civilian doctors responded with a response rate of 62% and 54%, respectively. Responses were required for every question to allow progression and submission. 93% of military doctors knew the initial dose of TXA compared with 34% of civilian doctors. The Clinical randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH) 2 trial was known to 91% of military doctors compared with 24% of civilian doctors. The optimal time for delivery of TXA in under 3 hours was correctly identified by 91% of military doctors compared with 10% by civilian doctors. DISCUSSION: Military doctors are more familiar with TXA and its side effect profile. Given the potential impact of TXA on patient outcome and the findings of this study, further education of all doctors is recommended including dose, timing and potential side effects.

Trends in the use of emergency contraception in Britain: evidence from the second and third National Surveys of Sexual Attitudes and Lifestyles.

OBJECTIVE: To examine the changes in the prevalence of, and the factors associated with, the use of emergency contraception (EC) in Britain between 2000 and 2010, spanning the period of deregulation and increase in pharmacy supply. DESIGN: Cross-sectional probability sample surveys. SETTING AND POPULATION: British general population. METHODS: Data were analysed from the second and third British National Surveys of Sexual Attitudes and Lifestyles (Natsal), undertaken in 1999-2001 and 2010-12. Univariate and logistic regression analyses were used to measure change in EC use amongst sexually active women aged 16-44 years not intending pregnancy. MAIN OUTCOME MEASURES: Prevalence of EC use and factors associated with use. RESULTS: Of the 5430 women surveyed in 1999-2001 and the 4825 women surveyed in 2010-12, 2.3 and 3.6%, respectively, reported using EC in the year prior to interview (P = 0.0019 for change over time). The prevalence of EC use increased amongst single women and those with higher educational attainment (adjusted odds ratio, aOR 1.51; 95% confidence interval, 95% CI 1.04-2.20; P = 0.0308). Increases in EC use were generally greater among women without behavioural risk factors, such as those with no history of abortion within 5 years (aOR 1.57; 95% CI 1.17-2.12; P = 0.0029), or those whose first heterosexual intercourse occurred after the age of 16 years (aOR 1.68; 95% CI 1.21-2.35; P = 0.0021). The increase in EC use was also more marked among women usually accessing contraception from retail sources than among those doing so from healthcare sources, which may reflect a use of condoms amongst EC users. CONCLUSION: The increase in EC use among women in Britain in the first decade of the 21st century was associated with some, but not all, risk factors for unplanned pregnancy. Advice and provision may need to be targeted at those at highest risk of unplanned pregnancy. TWEETABLE ABSTRACT: Despite pharmacy access, only a small rise in emergency contraception use has been seen in Britain over 10 years.

Quantification of Yield Loss Caused by Triticum mosaic virus and Wheat streak mosaic virus in Winter Wheat Under Field Conditions.

Triticum mosaic virus (TriMV) and Wheat streak mosaic virus (WSMV) infect winter wheat (Triticum aestivum) in the Great Plains region of the United States. The two viruses are transmitted by wheat curl mites (Aceria tosichella), which also transmit High Plains virus. In a field study conducted in 2011 and 2012, winter wheat cultivars Millennium (WSMV-susceptible) and Mace (WSMV-resistant) were mechanically inoculated with TriMV, WSMV, TriMV+WSMV, or sterile water at the two-leaf growth stage. Chlorophyll meter (soil plant analysis development [SPAD]) readings, area under the SPAD progress curve (AUSPC), grain yield (=yield), yield components (spikes/m2, kernels/spike, 1,000-kernel weight), and aerial dry matter were determined. In Millennium, all measured variables were significantly reduced by single or double virus inoculation, with the greatest reductions occurring in the double-inoculated treatment. Among the yield components, the greatest reductions occurred in spikes/m2. In Mace, only AUSPC was significantly reduced by the TriMV+WSMV treatment in 2012. There was a significant (P ≤ 0.05), negative linear relationship between SPAD readings and day of year in all inoculation treatments in Millennium and in the TriMV+WSMV treatment in Mace. There were significant (P ≤ 0.05), positive linear relationships between yield and SPAD readings and between yield and aerial dry matter in Millennium but not in Mace. The results from this study indicate that under field conditions, (i) Mace, a WSMV-resistant cultivar, is also resistant to TriMV, and (ii) double inoculation of winter wheat by TriMV and WSMV exacerbates symptom expression and yield loss in a susceptible cultivar.

Functional connectivity during facial and vocal emotion recognition: Preliminary evidence for dissociations in developmental change by nonverbal modality.

The developmental trajectory of emotion recognition (ER) skills is thought to vary by nonverbal modality, with vocal ER becoming mature later than facial ER. To investigate potential neural mechanisms contributing to this dissociation at a behavioural level, the current study examined whether youth's neural functional connectivity during vocal and facial ER tasks showed differential developmental change across time. Youth ages 8-19 (n = 41) completed facial and vocal ER tasks while undergoing functional magnetic resonance imaging, at two timepoints (1 year apart; n = 36 for behavioural data, n = 28 for neural data). Partial least squares analyses revealed that functional connectivity during ER is both distinguishable by modality (with different patterns of connectivity for facial vs. vocal ER) and across time-with changes in connectivity being particularly pronounced for vocal ER. ER accuracy was greater for faces than voices, and positively associated with age; although task performance did not change appreciably across a 1-year period, changes in latent functional connectivity patterns across time predicted participants' ER accuracy at Time 2. Taken together, these results suggest that vocal and facial ER are supported by distinguishable neural correlates that may undergo different developmental trajectories. Our findings are also preliminary evidence that changes in network integration may support the development of ER skills in childhood and adolescence.

Spontaneous X chromosome MI and MII nondisjunction events in Drosophila melanogaster oocytes have different recombinational histories.

Recent studies of human oocytes have demonstrated an enrichment for distal exchanges among meiosis I (MI) nondisjunction events and for proximal exchanges among meiosis II (MII) events. Our characterization of 103 cases of spontaneous X chromosome nondisjunction in Drosophila oocytes strongly parallels these observations. The recombinational histories of MI (97/103) and MII (6/103) nondisjunctional ova were strikingly different. MI nondisjunction occurred primarily in oocytes with non-exchange X chromosomes; of the new nondisjoining exchange bivalents, most carried distal crossovers. Thus, spontaneous MI nondisjunction reflects the failure of the achiasmate segregation systems. MII nondisjunction occurred only in oocytes with proximal exchanges. We propose several models to explain how very proximal exchanges might impair proper segregation.

Effective size of a wild salmonid population is greatly reduced by hatchery supplementation.

Many declining and commercially important populations are supplemented with captive-born individuals that are intentionally released into the wild. These supplementation programs often create large numbers of offspring from relatively few breeding adults, which can have substantial population-level effects. We examined the genetic effects of supplementation on a wild population of steelhead (Oncorhynchus mykiss) from the Hood River, Oregon, by matching 12 run-years of hatchery steelhead back to their broodstock parents. We show that the effective number of breeders producing the hatchery fish (broodstock parents; N(b)) was quite small (harmonic mean N(b)=25 fish per brood-year vs 373 for wild fish), and was exacerbated by a high variance in broodstock reproductive success among individuals within years. The low N(b) caused hatchery fish to have decreased allelic richness, increased average relatedness, more loci in linkage disequilibrium and substantial levels of genetic drift in comparison with their wild-born counterparts. We also documented a substantial Ryman-Laikre effect whereby the additional hatchery fish doubled the total number of adult fish on the spawning grounds each year, but cut the effective population size of the total population (wild and hatchery fish combined) by nearly two-thirds. We further demonstrate that the Ryman-Laikre effect is most severe in this population when (1) >10% of fish allowed onto spawning grounds are from hatcheries and (2) the hatchery fish have high reproductive success in the wild. These results emphasize the trade-offs that arise when supplementation programs attempt to balance disparate goals (increasing production while maintaining genetic diversity and fitness).

Effects of Single and Double Infections of Winter Wheat by Triticum mosaic virus and Wheat streak mosaic virus on Yield Determinants.

Triticum mosaic virus (TriMV) is a recently discovered virus infecting wheat (Triticum aestivum) in the Great Plains region of the United States. It is transmitted by wheat curl mites (Aceria tosichella) which also transmit Wheat streak mosaic virus (WSMV) and Wheat mosaic virus. In a greenhouse study, winter wheat 'Millennium' (WSMV susceptible) and 'Mace' (WSMV resistant) were mechanically inoculated with TriMV, WSMV, TriMV+WSMV, or sterile water at the two-leaf growth stage. At 28 days after inoculation, final chlorophyll meter (soil plant analysis development [SPAD]) readings, area under the SPAD progress curve (AUSPC), the number of tillers per plant, shoot and root weight, and total nitrogen and carbon content were determined. In Millennium, all measured variables were significantly reduced by single or double virus infections, with the greatest reductions occurring in the double-infection treatment. In Mace, only final SPAD readings, AUSPC, and total nitrogen were significantly reduced by single or double virus infections. There was a significant (P ≤ 0.05), positive linear relationship between SPAD readings and shoot weight in Millennium but not in Mace. The relationship between total nitrogen and shoot weight was positive, linear, and significant in both cultivars. The results from this study indicate that Mace, a WSMV-resistant cultivar, is also resistant to TriMV, and double infection of winter wheat by TriMV and WSMV exacerbates symptom expression and loss of biomass in susceptible cultivars.

Aspects of the biology of Galaxias maculatus.

The biology of three landlocked and a riverine population of Galaxias maculatus were examined in western Victoria, Australia. All systems supported reproducing populations of these fish, including Lake Corangamite which had salinities that on occasion reached 82. Spawning sites in Lake Corangamite were located in adjacent tributaries and not in the main lake as was the case for other populations. The smallest fish were found in the fresh water Lake Purrumbete and the largest in the hypersaline Lake Corangamite. The size at which 50% of the population attained sexual maturity varied across sites, with fish maturing at a smaller size in Lake Purrumbete, followed by the Merri River, Lake Bullen Merri and Lake Corangamite. Condition was higher in the freshwater Lake Purrumbete and there was no relationship between condition and temperature, conductivity, turbidity and pH; but there was a positive relationship between condition and dissolved oxygen. Length frequency analysis suggested that the majority of fishes live for a year.

Interactions of key charged residues contributing to selective block of neuronal sodium channels by µ-conotoxin KIIIA.

Voltage-gated sodium channels are important in initiating and propagating nerve impulses in various tissues, including cardiac muscle, skeletal muscle, the brain, and the peripheral nerves. Hyperexcitability of these channels leads to such disorders as cardiac arrhythmias (Na(v)1.5), myotonias (Na(v)1.4), epilepsies (Na(v)1.2), and pain (Na(v)1.7). Thus, there is strong motivation to identify isoform-specific blockers and the molecular determinants underlying their selectivity among these channels. µ-Conotoxin KIIIA blocks rNa(v)1.2 (IC(50), 5 nM), rNa(v)1.4 (37 nM), and hNa(v)1.7 (97 nM), expressed in mammalian cells, with high affinity and a maximal block at saturating concentrations of 90 to 95%. Mutations of charged residues on both the toxin and channel modulate the maximal block and/or affinity of KIIIA. Two toxin substitutions, K7A and R10A, modulate the maximal block (52-70%). KIIIA-H12A and R14A were the only derivatives tested that altered Na(v) isoform specificity. KIIIA-R14A showed the highest affinity for Na(v)1.7, a channel involved in pain signaling. Wild-type KIIIA has a 2-fold higher affinity for Na(v)1.4 than for Na(v)1.7, which can be attributed to a missing outer vestibule charge in domain III of Na(v)1.7. Reciprocal mutations Na(v)1.4 D1241I and Na(v)1.7 I1410D remove the affinity differences between these two channels for wild-type KIIIA without affecting their affinities for KIIIA-R14A. KIIIA is the first µ-conotoxin to show enhanced activity as pH is lowered, apparently resulting from titration of the free N terminus. Removal of this free amino group reduced the pH sensitivity by 10-fold. Recognition of these molecular determinants of KIIIA block may facilitate further development of subtype-specific, sodium channel blockers to treat hyperexcitability disorders.

Orientation of µ-conotoxin PIIIA in a sodium channel vestibule, based on voltage dependence of its binding.

Mutant cycle analysis has been used in previous studies to constrain possible docking orientations for various toxins. As an independent test of the bound orientation of µ-conotoxin PIIIA, a selectively targeted sodium channel pore blocker, we determined the contributions to binding voltage dependence of specific residues on the surface of the toxin. A change in the "apparent valence" (zδ) of the block, which is associated with a change of a specific toxin charge, reflects a change in the charge movement within the transmembrane electric field as the toxin binds. Toxin derivatives with charge-conserving mutations (R12K, R14K, and K17R) showed zδ values similar to those of wild type (0.61 ± 0.01, mean ± S.E.M.). Charge-changing mutations produced a range of responses. Neutralizing substitutions for Arg14 and Lys17 showed the largest reductions in zδ values, to 0.18 ± 0.06 and 0.20 ± 0.06, respectively, whereas unit charge-changing substitutions for Arg12, Ser13, and Arg20 gave intermediate values (0.24 ± 0.07, 0.33 ± 0.04, and 0.32 ± 0.05), which suggests that each of these residues contributes to the dependence of binding on the transmembrane voltage. Two mutations, R2A and G6K, yielded no significant change in zδ. These observations suggest that the toxin binds with Arg2 and Gly6 facing the extracellular solution, and Arg14 and Lys17 positioned most deeply in the pore. In this study, we used molecular dynamics to simulate toxin docking and performed Poisson-Boltzmann calculations to estimate the changes in local electrostatic potential when individual charges were substituted on the toxin's surface. Consideration of two limiting possibilities suggests that most of the charge movement associated with toxin binding reflects sodium redistribution within the narrow part of the pore.

CD40 antibody evokes a cytotoxic T-cell response that eradicates lymphoma and bypasses T-cell help.

CD40 is essential in enabling antigen-presenting cells to process and present antigen effectively to T cells. We demonstrate here that when antibody against CD40 is used to treat mice with syngeneic lymphoma, a rapid cytotoxic T-cell response independent of T-helper cells occurs, with tenfold expansion of CD8+ T cells over a period of 5 days. This response eradicates the lymphoma and provides protection against tumor rechallenge without further antibody treatment. Thus, it seems that by treating mice with monoclonal antibody against CD40, we are immunizing against syngeneic tumors. The phenomenon proved reproducible with two antibodies against CD40 (3/23 and FGK-45) in three CD40+ lymphomas (A20, A31 and BCL1) and gave partial protection in one of two CD40- lymphomas (EL4 and Ten1). Although the nature of the target antigens on these lymphomas is unknown, CD8+ T cells recovered from responding mice showed powerful cytotoxic activity against the target B-cell lymphoma in vitro.

Neoplasia and granulomas surrounding microchip transponders in Damaraland mole rats (Cryptomys damarensis).

Damaraland mole rats (Cryptomys damarensis) are among the longest-living rodents, with a maximum longevity of approximately 16 years. As one of the few mammals termed eusocial, these animals have been used in behavioral, genetic, metabolic, and physiologic research at the University of Connecticut since 1997. For individual identification at 3 to 4 months of age, mole rats were subcutaneously implanted with microchip transponders (11 mm in length) in the dorsal cervical region. In 2007, 2 of the 90 implanted adults, 10-year-old and 9-year-old females, developed subcutaneous masses at the site of the implant. Histopathological and immunohistochemical examinations revealed amelanotic melanoma and fibrosarcoma, respectively, with metastasis of the amelanotic melanoma. In 2008, a total of 3 adult males were castrated as part of a sex behavior study; 3 months later, all 3 castrated males developed subcutaneous masses around their implants, whereas none of the noncastrated males had masses. After an additional 9 months, these masses were found to be granulomas. To the authors' knowledge, this is the first report of neoplasia in this species. Both the tumors and the granulomas surrounded the microchip transponder.

Mortality of one-week-old chickens during naturally occurring Marek's disease virus infection.

Marek's disease (MD) is a disease of chickens that occurs worldwide and has serious economic consequences. MD can present as one of several forms, with the most commonly occurring forms being the lymphoproliferative diseases. Under experimental conditions, an early mortality syndrome has been recognized following infection by some but not all strains of MD virus (MDV). This is the first report of a confirmed case of mortality due to naturally occurring MDV infection in 1-week-old, nonvaccinated, chickens. Necrotizing lesions were observed in the bursa of Fabricius, lung, duodenum, jejunum, and proventriculus, and large intranuclear inclusion bodies were a striking feature in tissues with lesions in all birds. Immunohistochemical staining for the pp38 protein of MDV revealed abundant pp38 antigen in the affected tissues, confirming the presence of MDV within the lesions. PCR yielded an amplicon with 97% homology to the meq gene of MDV. No evidence of co-infection by either of the immunosuppressive agents chicken anemia virus and infectious bursal disease virus was detected.

Social brain networks: Resting-state and task-based connectivity in youth with and without epilepsy.

Individuals with epilepsy often experience social difficulties and deficits in social cognition. It remains unknown how disruptions to neural networks underlying such skills may contribute to this clinical phenotype. The current study compared the organization of relevant brain circuits-the "mentalizing network" and a salience-related network centered on the amygdala-in youth with and without epilepsy. Functional connectivity between the nodes of these networks was assessed, both at rest and during engagement in a social cognitive task (facial emotion recognition), using functional magnetic resonance imaging. There were no group differences in resting-state connectivity within either neural network. In contrast, youth with epilepsy showed comparatively lower connectivity between the left posterior superior temporal sulcus and the medial prefrontal cortex-but greater connectivity within the left temporal lobe-when viewing faces in the task. These findings suggest that the organization of a mentalizing network underpinning social cognition may be disrupted in youth with epilepsy, though differences in connectivity within this circuit may shift depending on task demands. Our results highlight the importance of considering functional task-based engagement of neural systems in characterizations of network dysfunction in epilepsy.

The effect of predictive display on the control of step changes in effect site sevoflurane levels.

Graphical displays of past and future levels of drugs may be a useful adjunct to manual dosing. We have previously found that a display of predicted future values speeds step changes in end-tidal sevoflurane. In this study anaesthetists made step changes of 0.3% in effect site sevoflurane, with and without the display and as increases and decreases. We analysed 91 changes. When the predictive display was present, users made larger vaporiser dial changes of 3.9% vs 3.1% (95% CI for the difference -1.3% to -0.01%, p = 0.046) reflected in larger end-tidal changes (95% CI for the difference -0.009 vol% to -0.34 vol%, p = 0.06). There was no difference in the speed of change (220 vs 227 s (95% CI for the difference -51 to 32 s)), or in the accuracy of the change. In this study the predictive display influenced the magnitude of the step changes made by anaesthetists but did not affect the speed or overall accuracy of the change.