Substrate patterning by electron emission-induced displacement

Disclosed are methods and devices for patterning micro- and/or nano-sized pattern elements on a substrate using field emitted electrons from an element. Disclosed methods and devices can also be utilized to form nano- and micron-sized depressions in a substrate according to a more economical process than as has been utilized in the past. Methods include single-step methods by which structures can be simultaneously created and located at desired locations on a substrate. Methods include the application of a bias voltage between a probe tip and a substrate held at a relatively close gap distance. The applied voltage can promote current flow between the probe and the substrate via field emissions. During a voltage pulse, and within predetermined energy levels and tip-to-surface gap distances, three dimensional formations can be developed on the substrate surface

Sex Differences in Opioid-Induced Enhancement of Contact Hypersensitivity

Previous research has demonstrated that, in male rats, the magnitude of contact hypersensitivity (CHS) can be enhanced by morphine treatment. The present experiments test the hypothesis that the mu-opioids morphine, etorphine, and buprenorphine would produce significant sex differences in the magnitude of 2,4-dinitrofluorobenzene-induced CHS. During tests conducted over a 192-h period, morphine, etorphine, and buprenorphine administered before elicitation of CHS on the external surface of the ear (pinna) potentiated the CHS response, and the magnitude of this enhancement was significantly greater in females than males. By contrast, morphine had no effect on croton oil-induced irritant contact dermatitis, indicating that morphine's effects on CHS do not generalize to immunologically nonspecific forms of contact dermatitis. Activation of brain mu-opioid receptors is responsible for the effects of morphine on CHS, because intracerebroventricular treatment with the mu-opioid receptor antagonist beta-funaltrexamine blocked morphine potentiation of CHS in females and males. The sex differences in morphine potentiation of CHS appear to be a result of the gonadal hormonal milieu, because castration enhanced the CHS response following vehicle and morphine treatment, whereas ovariectomy significantly attenuated the enhancement of CHS by morphine. Because ovariectomy had no effect on the CHS response following vehicle treatment, the presence of female gonadal hormones may underlie the sex differences in morphine potentiation of CHS in gonadally intact animals. Overall, these results support an increased sensitivity to the modulatory effects of opioids on the CHS response in females that depends on the interaction between gonadal hormones and the central mu-opioid system

Cocaine Disrupts Pup-Induced Maternal Behavior in Juvenile and Adult Rats

Impaired onset of maternal behavior in first generation rat dams was previously correlated with rearing by cocaine-treated dams and prenatal cocaine exposure. Pup-induced maternal behavior in non-lactating rats has not been examined with regard to cocaine exposure and rearing conditions. First generation male and female juveniles and young adult males reared by cocaine-treated or control dams and prenatally exposed to either cocaine or control conditions were tested for pup-induced maternal behavior at postnatal days 28 and 60. We now report disruptions in pup-induced maternal behavior in both 28 and 60 day old first generation offspring attributable to rearing condition and prenatal cocaine exposure. Originally published Neurotoxicology and Teratology, Vol. 29, No. 6, Nov 200

Effectiveness of pneumococcal polysaccharide vaccine for preschool-age children with chronic disease.

To estimate the effectiveness of pneumococcal polysaccharide vaccine, we serotyped isolates submitted to the Pneumococcal Sentinel Surveillance System from 1984 to 1996 from 48 vaccinated and 125 unvaccinated children 2 to 5 years of age. Effectiveness against invasive disease caused by serotypes included in the vaccine was 63%. Effectiveness against serotypes in the polysaccharide vaccine but not in a proposed seven-valent protein conjugate vaccine was 94%

Early childhood epilepsies:epidemiology, classification, aetiology, and socio-economic determinants

Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years of age in Scotland presenting with epilepsies. We used two independent sources for case identification: clinical reporting and EEG record review. Capture-recapture methodology was then used to improve the accuracy of incidence estimates. Socio-demographic and clinical details were obtained at presentation, and 24 months later. Children were extensively investigated for aetiology. Whole genome sequencing was offered for all patients with drug-resistant epilepsy for whom no aetiology could yet be identified. Multivariate logistic regression modelling was used to determine associations between clinical features, aetiology, and outcome. Three hundred and ninety children were recruited over 3 years. The adjusted incidence of epilepsies presenting in the first 3 years of life was 239 per 100 000 live births [95% confidence interval (CI) 216–263]. There was a socio-economic gradient to incidence, with a significantly higher incidence in the most deprived quintile (301 per 100 000 live births, 95% CI 251–357) compared with the least deprived quintile (182 per 100 000 live births, 95% CI 139–233), χ2 odds ratio = 1.7 (95% CI 1.3–2.2). The relationship between deprivation and incidence was only observed in the group without identified aetiology, suggesting that populations living in higher deprivation areas have greater multifactorial risk for epilepsy. Aetiology was determined in 54% of children, and epilepsy syndrome was classified in 54%. Thirty-one per cent had an identified genetic cause for their epilepsy. We present novel data on the aetiological spectrum of the most commonly presenting epilepsies of early childhood. Twenty-four months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of an aetiology was the strongest determinant of both DRE and GDD. Aetiology was determined in 82% of those with DRE, and 75% of those with GDD. In young children with epilepsy, genetic testing should be prioritized as it has the highest yield of any investigation and is most likely to inform precision therapy and prognosis. Epilepsies in early childhood are 30% more common than previously reported. Epilepsies of undetermined aetiology present more frequently in deprived communities. This likely reflects increased multifactorial risk within these populations

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

The Help for People with Money, Employment or Housing Problems (HOPE) Intervention:pilot randomised trial with mixed methods feasibility research

Background:Job loss, austerity measures, financial difficulties and house repossession contribute to the risk of self-harm and suicide during recessions. Navigating the benefits system and accessing sources of welfare and debt advice is a difficult experience for vulnerable people, further contributing to their distress. Whilst there is some evidence that advice-type interventions can lead to financial gain, there is mixed evidence for their effectiveness in improving mental health in those experiencing financial difficulties. There have been no interventions targeting those who have self-harmed due to economic hardship. Methods:Our aim was to determine the feasibility and acceptability of a brief psychosocial intervention (the 'HOPE' service) for people presenting to hospital emergency departments (ED) following self-harm or in acute distress because of financial, employment or welfare (benefit) difficulties. Nineteen people consented to random allocation to the intervention or control arm on a 2:1 basis. Participants randomised to the intervention arm (n = 13) received up to six sessions of 1:1 support provided by community support staff trained in Motivational Interviewing (MI). Control participants (n = 6) received a one-off session signposting them to relevant support organisations. Fourteen participants were followed up after 3 months. Participants and mental health workers took part in qualitative interviews. The acceptability of outcome measures including the PHQ-9, GAD-7, repeat self-harm, EQ5D-5 L and questions about debt, employment and welfare benefits were explored. Results:Interviews indicated the main benefits of the service as the resolution of specific financial problems and receiving support when participants were feeling most vulnerable. Randomisation was acceptable to most participants although not always fully understood and control participants could be disappointed. Recruitment was slow (1-2 per month). The outcome measures were acceptable and appeared sensitive to change. Discussion:The HOPE intervention is feasible and acceptable. There was evidence of need and it is a relatively inexpensive intervention. Refining aspects of the intervention would be straightforward. A full-scale RCT would be feasible, if broadened eligibility criteria led to increased recruitment and improvements were made to staff training and support. Trial registration:ISRCTN58531248

Long-lived magnetism on chondrite parent bodies

publisher: Elsevier articletitle: Long-lived magnetism on chondrite parent bodies journaltitle: Earth and Planetary Science Letters articlelink: http://dx.doi.org/10.1016/j.epsl.2017.07.035 content_type: article copyright: © 2017 The Authors. Published by Elsevier B.V.© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). The attached file is the published version of the article