Flash visual evoked potentials and early visual development in infants born to drug misusing mothers

Background / Aims: Maternal drug misuse in pregnancy is a significant clinical and public health problem. Consequences for the newborn infant include prematurity, intrauterine growth restriction (IUGR) and neonatal abstinence syndrome (NAS). There is increasing evidence that maternal drug misuse in pregnancy may have longer term adverse effects on infant visual and neurodevelopmental outcome. Most of the evidence regarding visual outcomes in particular derives from small uncontrolled studies with a lack of adequately powered, controlled studies to date. The visual evoked potential (VEP) can be used to assess the integrity and maturity of the infant visual pathway and both visual and neurodevelopmental abnormalities can be predicted by abnormal VEPs in infancy. Drug misuse is also associated with alteration of the VEP in adults and in animal models. Many drugs used in pregnancy can cross the placenta and enter the fetal circulation, including illicit drugs and prescribed methadone, which is the currently recommended treatment for pregnant opiate-dependent women. Hitherto few studies have investigated the effects of maternal drug misuse upon the newborn infant VEP. This study investigates in detail the effects of prescribed methadone and additional illicit drug use in pregnancy upon the infant VEP recorded at birth and at six months of age, and explores any association with NAS. The range and incidence of visual and neurodevelopmental abnormalities at six months of age is described, and how these relate to a history of NAS and the pattern of in utero drug exposure is explored. Pilot work: Pilot work demonstrated the feasibility of recording neonatal flash VEPs in a small group of infants exposed to methadone in utero, and showed that drug exposed infants had abnormal VEPs compared to unmatched controls. A further pilot study described longer term visual outcomes, which included nystagmus, reduced visual acuity and strabismus, in a selected group of infants and children exposed to methadone in utero, thus informing clinical and electrophysiological assessment at six months of age. The pilot studies were followed by a major prospective cohort study. Prospective Study: One hundred and two term infants of mothers prescribed substitute methadone during pregnancy and 50 comparison infants matched for birth weight, gestation and socio-economic group were recruited in the neonatal period. Flash and flicker VEPs were recorded from the occipital scalp of infants within three days of birth. Drug exposure was determined by maternal history, maternal and infant urine and meconium toxicology. Excess alcohol exposure in utero was determined by elevated fatty acid ethyl esters in meconium. Neonatal flash VEPs were classified as mature, typical, or immature according to waveform morphology, and amplitude and latencies measured. Flicker VEPs were analysed using a fast-Fourier transformation and responses at each flicker frequency determined. The same cohort of drug-exposed and comparison infants was invited for clinical visual evaluation at six months of age in conjunction with pattern-onset VEPs and Griffiths developmental assessment. Results: Neonatal testing: Neonatal VEPs were successfully recorded from 100 drug-exposed infants and 50 matched comparison infants at a median age of 24 hours (IQR 13-44). Gestational age, birth weight and socio-economic group did not differ between groups. Flash VEPs from methadone-exposed infants had fewer P1 components (p=0.001), and were more likely to be of immature waveform (p<0.001) compared to comparisons. VEPs from methadone-exposed infants were also smaller in overall amplitude (median 27µV vs 39.5µV, p<0.001). The relative risk of an abnormal VEP in the methadone-exposed cohort was 5.6 with an attributable risk percent of 82%. The majority of infants were exposed to illicit drugs in addition to prescribed methadone, most commonly opiates (74%) and benzodiazepines (66%). VEPs did not differ between infants exposed to opiates only, those additionally exposed to benzodiazepines and those exposed to stimulants. Regression analysis confirmed that the difference in VEP parameters between drug-exposed and comparison infants was associated with methadone exposure and not other drugs of misuse. 48% of the methadone-exposed cohort developed NAS requiring pharmacological treatment; there was no association between neonatal VEPs and subsequent onset or severity of NAS. Flicker VEP analysis demonstrated an optimal flicker frequency of 4.6 Hz in both groups, but there were few differences in the proportion of responses between groups. Six month follow-up: Retention rate to six month follow-up was 79% for the methadone-exposed cohort and 52% for comparison infants. Age at assessment (median 27 weeks, range 26-30 wk), weight and OFC did not differ between groups. The demographic characteristics of comparison infants who were followed up were compared to those of comparison infants who were not followed up. There were no significant differences in birth weight (2 sample t-test p=0.445), OFC (2 sample t-test p=0.712), gestation (Mann-Whitney test p=0.984), 5-minute Apgar score (Mann-Whitney test p=0.263) or DEPCAT score (Mann-Whitney test p=0.258) between groups. Methadone-exposed infants were more likely to have visual abnormalities than comparison infants, even after correcting for excess in utero alcohol exposure (40% vs 8%; adjusted p=0.007). Abnormalities in the methadone-exposed cohort included nystagmus (11%), strabismus (25%) and reduced visual acuity (22%). The relative risk of an abnormal visual outcome in the methadone-exposed cohort was 5.1 with an attributable risk percent of 80%. Electrophysiological abnormalities persisted at six months of age: methadone- exposed infants had smaller amplitude pattern VEPs (25 μV vs 34 μV; p=0.005) with delayed peak latencies (115ms vs 99ms; p=0.019) and fewer responses at the small check size (p=0.003), compared to controls. Methadone-exposed infants had significantly lower neurodevelopmental scores compared to comparison infants (GQ 97 for cases vs 105 for controls; p<0.001), even after correcting for maternal smoking, antidepressant treatment and excess alcohol consumption during pregnancy. Infants exposed to poly-drug misuse and treated for NAS in the newborn period performed particularly poorly on their neurodevelopmental scores. Visual impairment was an independent predictor of poor neurodevelopmental outcome and most infants scoring <85 on neurodevelopmental assessment had co-existing visual problems. Conclusions: In utero exposure to prescribed methadone and other substances of misuse is associated with an alteration in visual electrophysiology in the newborn period suggestive of immature visual maturation. These changes are independent of additional benzodiazepine or stimulant exposure, and appear to be associated with prescribed substitute methadone. At six months of age, there is a high incidence of clinical visual abnormalities in infants exposed to methadone and other drugs of misuse in utero. Persistence of electrophysiological abnormalities beyond the neonatal period suggests that opiates may have a longer term effect on the developing visual system. Drug-exposed infants also have poorer neurodevelopmental scores than matched comparison infants after correcting for maternal smoking and excess alcohol intake. The bias of loss to follow-up was minimised by the high retention rate of drug-exposed infants. Although there was a higher loss of comparison infants, there were no differences in demographic characteristics between comparison infants followed up and those not followed up, suggesting the groups were similar. In addition, published data suggest the incidence of visual abnormalities described in the comparison population to be representative of the larger population. Infants born to drug-misusing mothers are highly vulnerable and warrant early comprehensive visual assessment

Impaired cardiac autonomic nervous control after cardiac bypass surgery for congenital heart disease

We undertook a study to describe changes in heart rate variability (HRV) postoperatively in children undergoing cardiac bypass surgery for congenital heart disease (CHD). HRV was recorded for a 1-h period preoperatively and a 24-h period postoperatively in 20 children with CHD. We found a highly significant reduction in HRV in both time and frequency domain indices compared to preoperative values, which was sustained throughout the 24-h study period. There was a negative correlation between both time and frequency domain HRV measurements and length of cardiac bypass. HRV is reduced postoperatively and correlates with cardiac bypass time. Length of cardiac bypass time may be one mechanism whereby HRV is reduced following surgery

Tropical forcing of increased Southern Ocean climate variability revealed by a 140-year subantarctic temperate reconstruction

Occupying 14% of the world’s surface, the Southern Ocean plays a fundamental role in global climate, ocean circulation, carbon cycling and Antarctic ice-sheet stability. Unfortunately, high interannual variability and a dearth of instrumental observations before the 1950s limits our understanding of how marine-atmosphere-ice domains interact on multi-decadal timescales and the impact of anthropogenic forcing. Here we integrate climate-sensitive tree growth with ocean and atmospheric observations on southwest Pacific subantarctic islands that lie at the boundary of polar and subtropical climates (52–54˚S). Our annually-resolved temperature reconstruction captures regional change since the 1870s and demonstrates a significant increase in variability from the mid-twentieth century, a phenomenon predating the observational record. Climate reanalysis and modelling shows a parallel change in tropical Pacific sea surface temperatures that generate an atmospheric Rossby wave train which propagates across a large part of the Southern Hemisphere during the austral spring and summer

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction

Hunt for new phenomena using large jet multiplicities and missing transverse momentum with ATLAS in 4.7 fb−1 of √s=7 TeV proton-proton collisions

Results are presented of a search for new particles decaying to large numbers of jets in association with missing transverse momentum, using 4.7 fb−1 of pp collision data at s√=7TeV collected by the ATLAS experiment at the Large Hadron Collider in 2011. The event selection requires missing transverse momentum, no isolated electrons or muons, and from ≥6 to ≥9 jets. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of a MSUGRA/CMSSM supersymmetric model, where, for large universal scalar mass m 0, gluino masses smaller than 840 GeV are excluded at the 95% confidence level, extending previously published limits. Within a simplified model containing only a gluino octet and a neutralino, gluino masses smaller than 870 GeV are similarly excluded for neutralino masses below 100 GeV

Developmental perspectives on interpersonal affective touch

In the last decade, philosophy, neuroscience and psychology alike have paid increasing attention to the study of interpersonal affective touch, which refers to the emotional and motivational facets of tactile sensation. Some aspects of affective touch have been linked to a neurophysiologically specialised system, namely the C tactile (CT) system. While the role of this sys-tem for affiliation, social bonding and communication of emotions have been widely investigated, only recently researchers have started to focus on the potential role of interpersonal affective touch in acquiring awareness of the body as our own, i.e. as belonging to our psychological ‘self’. We review and discuss recent developmental and adult findings, pointing to the central role of interpersonal affective touch in body awareness and social cognition in health and disorders. We propose that interpersonal affective touch, as an interoceptive modality invested of a social nature, can uniquely contribute to the ongoing debate in philosophy about the primacy of the relational nature of the minimal self

Pig farmers’ willingness to pay for management strategies to reduce aggression between pigs

When deciding whether to invest in an improvement to animal welfare, farmers must trade-off the relative costs and benefits. Despite the existence of effective solutions to many animal welfare issues, farmers’ willingness to pay for them is largely unknown. This study modelled pig farmers’ decisions to improve animal welfare using a discrete choice experiment focused on alleviating aggression between growing/finishing pigs at regrouping. Eighty-two UK and Irish pig farm owners and managers were asked to choose between hypothetical aggression control strategies described in terms of four attributes; installation cost, on-going cost, impact on skin lesions from aggression and impact on growth rate. If they did not like any of the strategies they could opt to keep their current farm practice. Systematic variations in product attributes allowed farmers’ preferences and willingness to pay to be estimated and latent class modelling accounted for heterogeneity in responses. The overall willingness to pay to reduce lesions was low at £0.06 per pig place (installation cost) and £0.01 per pig produced (running cost) for each 1% reduction in lesions. Results revealed three independent classes of farmers. Farmers in Class 1 were unlikely to regroup unfamiliar growing/finishing pigs, and thus were unwilling to adopt measures to reduce aggression at regrouping. Farmers in Classes 2 and 3 were willing to adopt measures providing certain pre-conditions were met. Farmers in Class 2 were motivated mainly by business goals, whilst farmers in Class 3 were motivated by both business and animal welfare goals, and were willing to pay the most to reduce aggression; £0.11 per pig place and £0.03 per pig produced for each 1% reduction in lesions. Farmers should not be considered a homogeneous group regarding the adoption of animal welfare innovations. Instead, campaigns should be targeted at subgroups according to their independent preferences and willingness to pay