Intracranial stimulation for children with epilepsy

OBJECTIVES: To evaluate the efficacy of intracranial stimulation to treat refractory epilepsy in children. METHODS: This is a retrospective analysis of a pilot study on all 8 children who had intracranial electrical stimulation for the investigation and treatment of refractory epilepsy at King's College Hospital between 2014 and 2015. Five children (one with temporal lobe epilepsy and four with frontal lobe epilepsy) had subacute cortical stimulation (SCS) for a period of 20-161 h during intracranial video-telemetry. Efficacy of stimulation was evaluated by counting interictal discharges and seizures. Two children had thalamic deep brain stimulation (DBS) of the centromedian nucleus (one with idiopathic generalized epilepsy, one with presumed symptomatic generalized epilepsy), and one child on the anterior nucleus (right fronto-temporal epilepsy). The incidence of interictal discharges was evaluated visually and quantified automatically. RESULTS: Among the three children with DBS, two had >60% improvement in seizure frequency and severity and one had no improvement. Among the five children with SCS, four showed improvement in seizure frequency (>50%) and one chid did not show improvement. Procedures were well tolerated by children. CONCLUSION: Cortical and thalamic stimulation appear to be effective and well tolerated in children with refractory epilepsy. SCS can be used to identify the focus and predict the effects of resective surgery or chronic cortical stimulation. Further larger studies are necessary

Acquisition of a Unique Onshore/Offshore Geophysical and Geochemical Dataset in the Northern Malawi (Nyasa) Rift

The Study of Extension and maGmatism in Malawi aNd Tanzania (SEGMeNT) project acquired a comprehensive suite of geophysical and geochemical datasets across the northern Malawi (Nyasa) rift in the East Africa rift system. Onshore/offshore active and passive seismic data, long‐period and wideband magnetotelluric data, continuous Global Positioning System data, and geochemical samples were acquired between 2012 and 2016. This combination of data is intended to elucidate the sedimentary, crustal, and upper‐mantle architecture of the rift, patterns of active deformation, and the origin and age of rift‐related magmatism. A unique component of our program was the acquisition of seismic data in Lake Malawi, including seismic reflection, onshore/offshore wide‐angle seismic reflection/refraction, and broadband seismic data from lake‐bottom seismometers, a towed streamer, and a large towed air‐gun source

Immunological resilience and biodiversity for prevention of allergic diseases and asthma

Increase of allergic conditions has occurred at the same pace with the Great Acceleration, which stands for the rapid growth rate of human activities upon earth from 1950s. Changes of environment and lifestyle along with escalating urbanization are acknowledged as the main underlying causes. Secondary (tertiary) prevention for better disease control has advanced considerably with innovations for oral immunotherapy and effective treatment of inflammation with corticosteroids, calcineurin inhibitors, and biological medications. Patients are less disabled than before. However, primary prevention has remained a dilemma. Factors predicting allergy and asthma risk have proven complex: Risk factors increase the risk, while protective factors counteract them. Interaction of human body with environmental biodiversity with micro-organisms and biogenic compounds as well as the central role of epigenetic adaptation in immune homeostasis have given new insight. Allergic diseases are good indicators of the twisted relation to environment. In various non-communicable diseases, the protective mode of the immune system indicates low-grade inflammation without apparent cause. Giving microbes, pro- and prebiotics, has shown some promise in prevention and treatment. The real-world public health programme in Finland (2008-2018) emphasized nature relatedness and protective factors for immunological resilience, instead of avoidance. The nationwide action mitigated the allergy burden, but in the lack of controls, primary preventive effect remains to be proven. The first results of controlled biodiversity interventions are promising. In the fast urbanizing world, new approaches are called for allergy prevention, which also has a major cost saving potential.Peer reviewe

Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

BACKGROUND: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. METHODS: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. FINDINGS: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. INTERPRETATION: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications

Need for recovery amongst emergency physicians in the UK and Ireland: A cross-sectional survey

OBJECTIVES: To determine the need for recovery (NFR) among emergency physicians and to identify demographic and occupational characteristics associated with higher NFR scores. DESIGN: Cross-sectional electronic survey. SETTING: Emergency departments (EDs) (n=112) in the UK and Ireland. PARTICIPANTS: Emergency physicians, defined as any registered physician working principally within the ED, responding between June and July 2019. MAIN OUTCOME MEASURE: NFR Scale, an 11-item self-administered questionnaire that assesses how work demands affect intershift recovery. RESULTS: The median NFR Score for all 4247 eligible, consented participants with a valid NFR Score was 70.0 (95% CI: 65.5 to 74.5), with an IQR of 45.5-90.0. A linear regression model indicated statistically significant associations between gender, health conditions, type of ED, clinical grade, access to annual and study leave, and time spent working out-of-hours. Groups including male physicians, consultants, general practitioners (GPs) within the ED, those working in paediatric EDs and those with no long-term health condition or disability had a lower NFR Score. After adjusting for these characteristics, the NFR Score increased by 3.7 (95% CI: 0.3 to 7.1) and 6.43 (95% CI: 2.0 to 10.8) for those with difficulty accessing annual and study leave, respectively. Increased percentage of out-of-hours work increased NFR Score almost linearly: 26%-50% out-of-hours work=5.7 (95% CI: 3.1 to 8.4); 51%-75% out-of-hours work=10.3 (95% CI: 7.6 to 13.0); 76%-100% out-of-hours work=14.5 (95% CI: 11.0 to 17.9). CONCLUSION: Higher NFR scores were observed among emergency physicians than reported in any other profession or population to date. While out-of-hours working is unavoidable, the linear relationship observed suggests that any reduction may result in NFR improvement. Evidence-based strategies to improve well-being such as proportional out-of-hours working and improved access to annual and study leave should be carefully considered and implemented where feasible

Evidence that Ca within the microdomain of the l-type voltage gated Ca channel activates ERK in MIN6 cells in response to glucagon-like peptide-1

Evidence that Ca within the microdomain of the l-type voltage gated Ca channel activates ERK in MIN6 cells in response to glucagon-like peptide-