Maternal Attachment Style and Responses to Adolescents’ Negative Emotions: The Mediating Role of Maternal Emotion Regulation

This is an Accepted Manuscript of an article published by Taylor & Francis in Parenting: Science and Practice on November 11, 2014, available online: https://doi.org/10.1080/15295192.2014.972760 .Objective. Previous research has examined the developmental consequences, particularly in early childhood, of parents’ supportive and unsupportive responses to children’s negative emotions. Much less is known about factors that explain why parents respond in ways that may support or undermine their children’s emotions, and even less is known about how these parenting processes unfold with adolescents. In the present study, researchers examined the associations between mothers’ attachment styles and their distress, harsh, and supportive responses to their adolescents’ negative emotions two years later and whether these links were mediated by maternal emotion regulation difficulties. Design. Mothers in a longitudinal study (n = 230) reported on their attachment style, difficulties regulating their emotions, and their hypothetical responses to their adolescents’ negative emotions, respectively, at consecutive laboratory visits one year apart. Results. Mothers who reported greater attachment-related avoidance and anxiety reported having greater difficulties with emotion regulation one year later. Emotion dysregulation, in turn, predicted more distressed, harsher, and less supportive maternal responses to adolescents’ negative emotions the following year. In addition, greater avoidance directly predicted harsher maternal responses two years later. Conclusions. These findings extend previous research by identifying maternal attachment style as a predictor of responses to adolescent distress and by documenting the underlying role of emotion dysregulation in the link between adult attachment style and parenting.https://doi.org/10.1080/15295192.2014.97276

Global Expression Profiling in Atopic Eczema Reveals Reciprocal Expression of Inflammatory and Lipid Genes

Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood.We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE.Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. The full data set is available at http://microarray-pubs.stanford.edu/eczema

The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial

Background: Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. Methods: This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). Findings: 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95–1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83–1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08–1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319–1·458) compared with 1·222 (1·110–1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. Interpretation: These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. Funding: National Institute for Health Research Health Technology Assessment programme

The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial

Background: Valproate is a first-line treatment for patients with newly diagnosed idiopathic generalised or difficult to classify epilepsy, but not for women of child-bearing potential because of teratogenicity. Levetiracetam is increasingly prescribed for these patient populations despite scarcity of evidence of clinical effectiveness or cost-effectiveness. We aimed to compare the long-term clinical effectiveness and cost-effectiveness of levetiracetam compared with valproate in participants with newly diagnosed generalised or unclassifiable epilepsy. Methods: We did an open-label, randomised controlled trial to compare levetiracetam with valproate as first-line treatment for patients with generalised or unclassified epilepsy. Adult and paediatric neurology services (69 centres overall) across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked generalised or unclassifiable seizures. Participants were randomly allocated (1:1) to receive either levetiracetam or valproate, using a minimisation programme with a random element utilising factors. Participants and investigators were aware of treatment allocation. For participants aged 12 years or older, the initial advised maintenance doses were 500 mg twice per day for levetiracetam and valproate, and for children aged 5–12 years, the initial daily maintenance doses advised were 25 mg/kg for valproate and 40 mg/kg for levetiracetam. All drugs were administered orally. SANAD II was designed to assess the non-inferiority of levetiracetam compared with valproate for the primary outcome time to 12-month remission. The non-inferiority limit was a hazard ratio (HR) of 1·314, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on valproate. All participants were included in the intention-to-treat (ITT) analysis. Per-protocol (PP) analyses excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analyses included all participants who received one dose of any study drug. This trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). Findings: 520 participants were recruited between April 30, 2013, and Aug 2, 2016, and followed up for a further 2 years. 260 participants were randomly allocated to receive levetiracetam and 260 participants to receive valproate. The ITT analysis included all participants and the PP analysis included 255 participants randomly allocated to valproate and 254 randomly allocated to levetiracetam. Median age of participants was 13·9 years (range 5·0–94·4), 65% were male and 35% were female, 397 participants had generalised epilepsy, and 123 unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission (HR 1·19 [95% CI 0·96–1·47]); non-inferiority margin 1·314. The PP analysis showed that the 12-month remission was superior with valproate than with levetiracetam. There were two deaths, one in each group, that were unrelated to trial treatments. Adverse reactions were reported by 96 (37%) participants randomly assigned to valproate and 107 (42%) participants randomly assigned to levetiracetam. Levetiracetam was dominated by valproate in the cost-utility analysis, with a negative incremental net health benefit of −0·040 (95% central range −0·175 to 0·037) and a probability of 0·17 of being cost-effectiveness at a threshold of £20 000 per quality-adjusted life-year. Cost-effectiveness was based on differences between treatment groups in costs and quality-adjusted life-years. Interpretation: Compared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate. Funding: National Institute for Health Research Health Technology Assessment Programme

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

The Origin and Fate of O₂ in Europa’s Ice: An Atmospheric Perspective

International audienceThe early prediction and subsequent detection of an O2 atmosphere on Europa, coupled with the discovery that Europa has an ocean under its ice mantle, has made this moon a prime astrobiologic target, soon to be visited by the JUICE and Europa Clipper spacecraft. In spite of the considerable number of observational, modeling, and laboratory efforts, understanding the physics leading to the observed morphology of Europa’s near-surface O2 atmosphere has been problematic. This is the case as the observed emissions depend on the local incident plasma ion flux, the local temperature and composition of the regolith, as well as on the near-surface electron temperature and density. Here we rely heavily on earlier reviews briefly summarizing the observational, laboratory and simulation efforts. Although it is agreed that radiolysis of the surface ice by the incident Jovian plasma is the ultimate source of observed O2, a recent, simple model of thermal desorption from a regolith permeated with O2 has changed the usual paradigm. In that model, the observed orbital dependence of the local source of the near-surface O2 atmosphere is suggested to be due to the release of O2 likely trapped on the ice grains at dangling bonds by the solar flux with a smaller contribution due to direct sputtering. This assumes that Europa’s icy regolith is permeated with trapped O2, which could also affect our understanding of the suggestion that the radiolytic products in Europa’s regolith might be a source of oxidants for its underground ocean

Dusk over dawn O₂ asymmetry in Europa's near-surface atmosphere

International audienceThe evolution of Europa's water-product exosphere over its 85-h day, based on current models, has not been shown to exhibit any diurnal asymmetries. Here we simulate Europa's exosphere using a 3-D Monte Carlo routine including, for the first time, the role of Europa's rotation on the evolution of exospheric molecules tracked throughout the orbit. In this work we focus on understanding the behavior of a single atmospheric constituent, O2, sputtered by a trailing hemisphere source with a temperature-dependence under isotropic plasma conditions as also modeled by previous works. Under rotation, the O2 is also subject to the centrifugal and Coriolis forces in addition to the standard gravitational forces by Jupiter and Europa in our model. We find that the O2 component, while global, is not homogeneous in Europa local time. Rather, the O2 consistently accumulates along the direction of Europa's rotation at the dusk hemisphere. When rotation is explicitly excluded in our simulations, no diurnal asymmetries exist, and any accumulation is due to the prescribed geometry of the sputtering source. We find that the assumed thermal-dependence on the O2 source is critical for a diurnal asymmetry: the diurnal surface temperature profile is imprinted on to the near-surface O2 atmosphere, due to small hop times for the non-adsorbing O2, which then effectively rotates with Europa. Simulation tests demonstrate that the diurnal asymmetry is not driven by the thermal inertia of the ice, found to have only a weak dependence (<7%) Altogether, the various test cases presented in this work conclude that the dusk-over-dawn asymmetry is driven by Europa's day-night O2 cycle synchronized with Europa's orbital period based on our model assumptions on O2 production and loss. This conclusion is in agreement with the recent understanding that a non-adsorbing, rotating O2 source peaking at noon will naturally accumulate from dawn-to-dusk, should the O2 lifetime be sufficiently long compared to the orbital period. Lastly we compare hemispherically-averaged dusk-over-dawn ratios to the recently observed oxygen emission data by the Hubble Space Telescope. We find that while the simulations are globally consistent with brighter oxygen emission at dusk than at dawn, the orbital evolution of the asymmetries in our simulations can be improved by ameliorating the O2 source & loss rates, and possibly adsorption onto the regolith

Effects of cardiac rehabilitation and exercise programs on exercise capacity, coronary risk factors, behavior, and quality of life in patients with coronary artery disease

Previous studies have indicated the benefits of cardiac rehabilitation programs after major coronary artery disease (CAD) events. We studied 591 consecutive patients from two academic institutions before and after completion of a cardiac rehabilitation and exercise training program to determine the effects of this therapy on exercise capacity, indices of obesity, plasma lipid values, behavioral characteristics, and quality of life parameters. After cardiac rehabilitation, statistically significant improvements occurred in exercise capacity (+33%), percent body fat (4%), body mass index (-1%), HDL-C (+5%), triglycerides (-9%), LDL-C/HDL-C (-6%), anxiety score (-39%), depression score (-35%), somatization score (-37%), and in all parameters of quality of life studied (total +14%). These data further support the ability of cardiac rehabilitation and exercise training programs to improve exercise capacity, plasma lipid values, obesity indices, behavioral characteristics, and quality of life parameters in a large cohort of patients who have had major CAD events