Emotional orienting during interoceptive threat in orthostatic intolerance: dysautonomic contributions to psychological symptomatology in the postural tachycardia syndrome and vasovagal syncope

Cognitive and emotional processes are influenced by interoception (homeostatic somatic feedback), particularly when physiological arousal is unexpected and discrepancies between predicted and experienced interoceptive signals may engender anxiety. Due to the vulnerability for comorbid psychological symptoms in forms of orthostatic intolerance (OI), this study investigated psychophysiological contributions to emotional symptomatology in 20 healthy control participants (13 females, mean age 36 ± 8 years), 20 postural tachycardia syndrome (PoTS) patients (18 females, mean age 38 ± 13 years) and 20 vasovagal syncope (VVS) patients (15 females, mean age 39 ± 12 years). We investigated indices of emotional orienting responses (OR) to randomly presented neutral, pleasant and unpleasant images in the supine position and during the induced interoceptive threat of symptom provocation of head-up tilt (HUT). PoTS and VVS patients produced greater indices of emotional responsivity to unpleasant images and, to a lesser degree, pleasant images, during interoceptive threat. Our findings are consistent with biased deployment of response-focused emotion regulation (ER) while patients are symptomatic, providing a mechanistic underpinning of how pathological autonomic overexcitation predisposes to anxiogenic traits in PoTS and VVS patients. This hypothesis may improve our understanding of why orthostasis exacerbates cognitive symptoms despite apparently normal cerebral autoregulation, and offer novel therapeutic targets for behavioural interventions aimed at reducing comorbid cognitive-affective symptoms in PoTS and VVS

Aberrant Development of Thymocytes in Mice Lacking Laminin-2

In previous in vitro studies, we proposed a role for the extracellular matrix component, laminin- 2, and its integrin receptor, VLA-6, in thymocyte development. The characterization of two dystrophic mouse strains with different defects in laminin-2 allowed us to examine this proposal in vivo. Mice deficient in laminin-2, dy/dy, show a significant reduction in thymus size and number of thymocytes compared to normal littermates. These mice also exhibited apparent alterations of thymic architecture. Examination of the CD4/CD8 populations in dy/dy thymi showed large relative increases in the DN (CD4-CD8-) and SP (CD4+CD8-, CD4-CD8+) populations and a significant decrease in the DP (CD4+CD8+) population. Further examination of the DN population for CD44 and CD25 expression showed a remarkable decrease in the more mature pre-T cell populations. Analysis of apoptosis in situ, and by flow cytometry, in dy/dy thymi revealed a significant increase in apoptotic DN thymocytes in the capsule and subcapsular regions. Interestingly, thymocyte development appeared to proceed normally in dystrophic mice expressing a mutant form of laminin-2, dy2J, as well as, in fetal and neonatal dy/dy mice. We propose that laminin-2 plays an active role in thymocyte development by delivering cell survival and differentiation signals at specific stages of development in young adult mice

Drug therapy for alcohol dependence in primary care in the UK:A Clinical Practice Research Datalink study

AIM:To evaluate drug therapy for alcohol dependence in the 12 months after first diagnosis in UK primary care. DESIGN:Open cohort study. SETTING:General practices contributing data to the UK Clinical Practice Research Database. PARTICIPANTS:39,980 people with an incident diagnosis of alcohol dependence aged 16 years or older between 1 January 1990 and 31 December 2013. MAIN OUTCOME MEASURE:Use of pharmacotherapy (acamprosate, disulfiram, naltrexone, baclofen and topiramate) to promote abstinence from alcohol or reduce drinking to safe levels in the first 12 months after a recorded diagnosis of alcohol dependence. FINDINGS:Only 4,677 (11.7%) of the cohort received relevant pharmacotherapy in the 12 months following diagnosis. Of the 35,303 that did not receive pharmacotherapy, 3,255 (9.2%) received psychosocial support. The remaining 32,048 (80.2%) did not receive either mode of treatment in the first 12 months. Factors that independently reduced the likelihood of receiving pharmacotherapy included: being male (Odds Ratio [OR] 0.74; 95% CI 0.69 to 0.78); older (65-74 years: OR 0.61; 95% CI 0.49 to 0.77); being from a practice based in the most deprived quintile (OR 0.58; 95% CI 0.53 to 0.64); and being located in Northern Ireland (OR 0.78; 95% CI 0.67 to 0.91). The median duration to initiation of pharmacotherapy was 0.80 months (95% CI 0.70 to 1.00) for acamprosate and 0.60 months (95% CI 0.43 to 0.73) for disulfiram. Persistence analysis for those receiving acamprosate and disulfiram revealed that many patients never received a repeat prescription; persistence at 6 months was 27.7% for acomprosate and 33.2% for disulfiram. The median duration of therapy was 2.10 months (95% CI 1.87 to 2.53) for acamprosate and 3.13 months (95% CI 2.77 to 3.36) for disulfiram. CONCLUSION:Drug therapy to promote abstinence in alcohol dependent patients was low, with the majority of patients receiving no therapy, either psychological or pharmacological. When drug therapy was prescribed, persistence was low with most patients receiving only one prescription. Our data show that treatment for alcohol dependence is haphazard, and there is an urgent need to explore strategies for improving clinical management of this patient group

Broadened assessments, health education and cognitive aids in the remote memory clinic

The prevalence of dementia is increasing and poses a health challenge for individuals and society. Despite the desire to know their risks and the importance of initiating early therapeutic options, large parts of the population do not get access to memory clinic-based assessments. Remote memory clinics facilitate low-level access to cognitive assessments by eschewing the need for face-to-face meetings. At the same time, patients with detected impairment or increased risk can receive non-pharmacological treatment remotely. Sensor technology can evaluate the efficiency of this remote treatment and identify cognitive decline. With remote and (partly) automatized technology the process of cognitive decline can be monitored but more importantly also modified by guiding early interventions and a dementia preventative lifestyle. We highlight how sensor technology aids the expansion of assessments beyond cognition and to other domains, e.g., depression. We also illustrate applications for aiding remote treatment and describe how remote tools can facilitate health education which is the cornerstone for long-lasting lifestyle changes. Tools such as transcranial electric stimulation or sleep-based interventions have currently mostly been used in a face-to-face context but have the potential of remote deployment—a step already taken with memory training apps. Many of the presented methods are readily scalable and of low costs and there is a range of target populations, from the worried well to late-stage dementia

Novel low energy hydrogen–deuterium isotope breakthrough separation using a trapdoor zeolite

AbstractCs-chabazite, a type of zeolite with caesium counter-cations, possesses interesting gas separation properties due to a highly selective molecular “trapdoor” effect. Herein the use of this material for H2/D2 isotope separation is demonstrated. Isotope separation was achieved using breakthrough separation with a single pass through a packed bed at moderate temperatures (293K) and pressures (0.17MPa) when one species was in a sufficiently low concentration. The breakthrough separation curves were successfully modelled using the Thomas kinetic breakthrough model and the Yoon and Nelson kinetic breakthrough model, where working transferable kinetic rate constants were developed. Use of this material for hydrogen isotope separation would significantly lower the total energy demand compared with current hydrogen isotope separation techniques such as cryogenic distillation and is applicable to separating out low concentrations of D2 (0.0156%) present in standard grade H2

Propagation of cosmic-ray nucleons in the Galaxy

We describe a method for the numerical computation of the propagation of primary and secondary nucleons, primary electrons, and secondary positrons and electrons. Fragmentation and energy losses are computed using realistic distributions for the interstellar gas and radiation fields, and diffusive reacceleration is also incorporated. The models are adjusted to agree with the observed cosmic-ray B/C and 10Be/9Be ratios. Models with diffusion and convection do not account well for the observed energy dependence of B/C, while models with reacceleration reproduce this easily. The height of the halo propagation region is determined, using recent 10Be/9Be measurements, as >4 kpc for diffusion/convection models and 4-12 kpc for reacceleration models. For convection models we set an upper limit on the velocity gradient of dV/dz < 7 km/s/kpc. The radial distribution of cosmic-ray sources required is broader than current estimates of the SNR distribution for all halo sizes. Full details of the numerical method used to solve the cosmic-ray propagation equation are given.Comment: 15 pages including 23 ps-figures and 3 tables, latex2e, uses emulateapj.sty (ver. of 11 May 1998, enclosed), apjfonts.sty, timesfonts.sty. To be published in ApJ 1998, v.509 (December 10 issue). More details can be found at http://www.gamma.mpe-garching.mpg.de/~aws/aws.html Some references are correcte

Particles at oil–air surfaces : powdered oil, liquid oil marbles, and oil foam

The type of material stabilized by four kinds of fluorinated particles (sericite and bentonite platelet clays and spherical zinc oxide) in air–oil mixtures has been investigated. It depends on the particle wettability and the degree of shear. Upon vigorous agitation, oil dispersions are formed in all the oils containing relatively large bentonite particles and in oils of relatively low surface tension (γla &lt; 26 mN m⁻¹) like dodecane, 20 cS silicone, and cyclomethicone containing the other fluorinated particles. Particle-stabilized oil foams were obtained in oils having γla > 26 mN m⁻¹ where the advancing air–oil–solid contact angle θ lies between ca. 90° and 120°. Gentle shaking, however, gives oil-in-air liquid marbles with all the oil–particle systems except for cases where θ is &lt;60°. For oils of tension >24 mN m⁻¹ with omniphobic zinc oxide and sericite particles for which advancing θ ≥ 90°, dry oil powders consisting of oil drops in air which do not leak oil could be made upon gentle agitation up to a critical oil:particle ratio (COPR). Above the COPR, catastrophic phase inversion of the dry oil powders to air-in-oil foams was observed. When sheared on a substrate, the dry oil powders containing at least 60 wt % of oil release the encapsulated oil, making these materials attractive formulations in the cosmetic and food industries

Characterisation of cognitive load using machine learning classifiers of electroencephalogram data

A high cognitive load can overload a person, potentially resulting in catastrophic accidents. It is therefore important to ensure the level of cognitive load associated with safety-critical tasks (such as driving a vehicle) remains manageable for drivers, enabling them to respond appropriately to changes in the driving environment. Although electroencephalography (EEG) has attracted significant interest in cognitive load research, few studies have used EEG to investigate cognitive load in the context of driving. This paper presents a feasibility study on the simulation of various levels of cognitive load through designing and implementing four driving tasks. We employ machine learning-based classification techniques using EEG recordings to differentiate driving conditions. An EEG dataset containing these four driving tasks from a group of 20 participants was collected to investigate whether EEG can be used as an indicator of changes in cognitive load. The collected dataset was used to train four Deep Neural Networks and four Support Vector Machine classification models. The results showed that the best model achieved a classification accuracy of 90.37%, utilising statistical features from multiple frequency bands in 24 EEG channels. Furthermore, the Gamma and Beta bands achieved higher classification accuracy than the Alpha and Theta bands during the analysis. The outcomes of this study have the potential to enhance the Human–Machine Interface of vehicles, contributing to improved safety

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo