Plasma REST: A novel candidate biomarker of Alzheimer\u27s disease is modified by psychological intervention in an at-risk population

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain’s stress response. It is reduced in conditions of stress and Alzheimer’s disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention—mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit

Time to publication for NIHR HTA programme-funded research: a cohort study

ObjectiveTo assess the time to publication of primary research and evidence syntheses funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme published as a monograph in Health Technology Assessment and as a journal article in the wider biomedical literature.Study designRetrospective cohort study.SettingPrimary research and evidence synthesis projects funded by the HTA Programme were included in the cohort if they were registered in the NIHR research programmes database and was planned to submit the draft final report for publication in Health Technology Assessment on or before 9 December 2011.Main outcome measuresThe median time to publication and publication at 30?months in Health Technology Assessment and in an external journal were determined by searching the NIHR research programmes database and HTA Programme website.ResultsOf 458 included projects, 184 (40.2%) were primary research projects and 274 (59.8%) were evidence syntheses. A total of 155 primary research projects had a completion date; the median time to publication was 23?months (26.5 and 35.5?months to publish a monograph and to publish in an external journal, respectively) and 69% were published within 30?months. The median time to publication of HTA-funded trials (n=126) was 24?months and 67.5% were published within 30?months. Among the evidence syntheses with a protocol online date (n=223), the median time to publication was 25.5?months (28?months to publication as a monograph), but only 44.4% of evidence synthesis projects were published in an external journal. 65% of evidence synthesis studies had been published within 30.0?months.ConclusionsResearch funded by the HTA Programme publishes promptly. The importance of Health Technology Assessment was highlighted as the median time to publication was 9?months shorter for a monograph than an external journal article

Vortex Velocity in Turbulent He II Counterflow

We have used the ion-vortex interaction to measure the drift velocity of the vorticity present in turbulent counterflow, and find that it moves in the direction of normal-fluid flow. The result is in direct conflict with a central assumption of the presently accepted model of the turbulent state

Identifying Heating Technologies suitable for Historic Churches, Taking into Account Heating Strategy and Conservation through Pairwise Analysis

As a result of difficulty meeting energy efficiency through fabric alteration, historic churches must focus on heating systems and operational strategy as key to reducing carbon emissions. Strategies can be defined as local or central heating. Local heating strives to heat occupants, while central heating aims to heat the building fabric and therefore the occupants. Each strategy requires a different approach to control and technology in response to priorities such as conservation, comfort and cost. This paper reviews current and emerging technologies in the context of church heating. The fuel source, heat generation technology and heat emitter are arranged in a matrix, with pairwise analysis undertaken to create weightings for each assessment criteria. The process of constructing the matrix and undertaking pairwise analysis using personas is discussed. The result is a ranking of fuels and technologies appropriate to the main priorities and individual preferences. Some desirable technologies are inherently more damaging to historic church environments due to invasive installation. These technologies score poorly when the aim is fabric preservation. Greener fuels, like biomass, may rank lower than fossil fuels, due in part to operational differences

Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit

Multistability of free spontaneously-curved anisotropic strips

Multistable structures are objects with more than one stable conformation, exemplified by the simple switch. Continuum versions are often elastic composite plates or shells, such as the common measuring tape or the slap bracelet, both of which exhibit two stable configurations: rolled and unrolled. Here we consider the energy landscape of a general class of multistable anisotropic strips with spontaneous Gaussian curvature. We show that while strips with non-zero Gaussian curvature can be bistable, strips with positive spontaneous curvature are always bistable, independent of the elastic moduli, strips of spontaneous negative curvature are bistable only in the presence of spontaneous twist and when certain conditions on the relative stiffness of the strip in tension and shear are satisfied. Furthermore, anisotropic strips can become tristable when their bending rigidity is small. Our study complements and extends the theory of multistability in anisotropic shells and suggests new design criteria for these structures.Comment: 20 pages, 10 figure

Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: A longitudinal household study

Background. Natural immunity to Streptococcus pneumoniae is thought to be induced by exposure to S. pneumoniae or cross-reactive antigens. No longitudinal studies of carriage of and immune responses to S. pneumoniae have been conducted using sophisticated immunological laboratory techniques.Methods. We enrolled 121 families with young children into this study. Nasopharyngeal (NP) swabs were collected monthly for 10 months from all family members and were cultured in a standard fashion. Cultured S. pneumoniae isolates were serotyped. At the beginning (month 0) and end (month 10) of the study, venous blood was collected from family members 118 years old. Serotype-specific antipolysaccharide immunoglobulin G (IgG) and functional antibody and antibodies to pneumolysin, pneumococcal surface protein A (PspA), and pneumococcal surface antigen A (PsaA) were measured in paired serum samples.Results. Levels of anticapsular IgG increased significantly after carriage of serotypes 9V, 14, 18C, 19F, and 23F by an individual or family member. For serotype 14, a higher level of anticapsular IgG at the beginning of the study was associated with reduced odds of carriage (P = .0006). There was a small (similar to 20%) but significant increase in titers of antibodies to PsaA and pneumolysin but no change in titers of antibody to PspA.Conclusions. Adults respond to NP carriage by mounting anticapsular and weak antiprotein antibody responses, and naturally induced anticapsular IgG can prevent carriage

Diffractive Contribution to the Elasticity and the Nucleonic Flux in the Atmosphere

We calculate the average elasticity considering non-diffractive and single diffractive interactions and perform an analysis of the cosmic-ray flux by means of an analytical solution for the nucleonic diffusion equation. We show that the diffractive contribution is important for the adequate description of the nucleonic and hadronic fluxes in the atmosphere.Comment: 10 pages, latex, 2 figures (uuencoded PostScript

Fast Simulation of Facilitated Spin Models

We show how to apply the absorbing Markov chain Monte Carlo algorithm of Novotny to simulate kinetically constrained models of glasses. We consider in detail one-spin facilitated models, such as the East model and its generalizations to arbitrary dimensions. We investigate how to maximise the efficiency of the algorithms, and show that simulation times can be improved on standard continuous time Monte Carlo by several orders of magnitude. We illustrate the method with equilibrium and aging results. These include a study of relaxation times in the East model for dimensions d=1 to d=13, which provides further evidence that the hierarchical relaxation in this model is present in all dimensions. We discuss how the method can be applied to other kinetically constrained models.Comment: 8 pages, 4 figure