Convective infux/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways

Tracers injected into CSF pass into the brain alongside arteries and out again. This has been recently termed the "glymphatic system" that proposes tracers enter the brain along periarterial "spaces" and leave the brain along the walls of veins. The object of the present study is to test the hypothesis that: (1) tracers from the CSF enter the cerebral cortex along pial-glial basement membranes as there are no perivascular "spaces" around cortical arteries, (2) tracers leave the brain along smooth muscle cell basement membranes that form the Intramural Peri-Arterial Drainage (IPAD) pathways for the elimination of interstitial fluid and solutes from the brain. 2 μL of 100 μM soluble, fluorescent fixable amyloid β (Aβ) were injected into the CSF of the cisterna magna of 6-10 and 24-30 month-old male mice and their brains were examined 5 and 30 min later. At 5 min, immunocytochemistry and confocal microscopy revealed Aβ on the outer aspects of cortical arteries colocalized with α-2 laminin in the pial-glial basement membranes. At 30 min, Aβ was colocalised with collagen IV in smooth muscle cell basement membranes in the walls of cortical arteries corresponding to the IPAD pathways. No evidence for drainage along the walls of veins was found. Measurements of the depth of penetration of tracer were taken from 11 regions of the brain. Maximum depths of penetration of tracer into the brain were achieved in the pons and caudoputamen. Conclusions drawn from the present study are that tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways. The exit route is along IPAD pathways in which Aβ accumulates in cerebral amyloid angiopathy (CAA) in Alzheimer's disease. Results from this study suggest that CSF may be a suitable route for delivery of therapies for neurological diseases, including CAA

Trajectory of social isolation following hip fracture: an analysis of the English Longitudinal Study of Ageing (ELSA) cohort

Background: social isolation is defined as a lack of meaningful and sustained communication or interactions with social networks. There is limited understanding on the prevalence of social isolation and loneliness in people following hip fracture and no previous understanding of how this changes over time. Objective: to determine the prevalence and trajectory of social isolation and loneliness before a hip fracture, during the recovery phase and a minimum of 2 years post-hip fracture in an English population. Methods: data were from the English Longitudinal Study of Ageing (ELSA) cohort (2004/5–2014/15). The sample comprised of 215 participants who had sustained a hip fracture. Measures of social isolation and loneliness were analysed through multilevel modelling to determine their trajectories during three-time intervals (pre-fracture; interval at hip fracture and recovery; minimum 2 years post-fracture). The prevalence of social isolation and loneliness were determined pre- and post-fracture. Results: prevalence of social isolation was 19% post-hip fracture and loneliness 13% post-hip fracture. There was no statistically significant change in social isolation pre-fracture compared to a minimum of 2 years post-fracture (P = 0.78). Similarly, there was no statistically significant change in loneliness pre-fracture compared to a minimum of 2 years post-fracture (P = 0.12). Conclusion: this analysis has determined that whilst social isolation and loneliness do not change over time following hip fracture, these remain a significant problem for this population. Interventions are required to address these physical and psychological health needs. This is important as they may have short and longer term health benefits for people post-hip fracture

Changes in social isolation and loneliness following total hip and knee arthroplasty: longitudinal analysis of the English Longitudinal Study of Ageing (ELSA) cohort

Objective: To determine the prevalence and change in social isolation and loneliness in people before and after THA and TKA in England. Design: The English Longitudinal Study of Ageing dataset, a prospective study of community-dwelling older adults, was used to identify people who had undergone primary THA or TKA because of osteoarthritis. Social isolation was assessed using the ELSA Social Isolation Index. Loneliness was evaluated using the Revised University of California, Los Angeles (UCLA) Loneliness Scale. The prevalence of social isolation and loneliness were calculated and multilevel modelling was performed to assess the potential change of these measures before arthroplasty, within a two-year operative-recovery phase and a following two-year follow-up. Results: The sample consisted of 393 people following THA and TKA. The prevalence of social isolation and loneliness changed from 16.9% and 18.8% pre-operative to 21.8% and 18.9% at the final post-operative follow-up respectively. This was not a statistically significant change for either measure (p=0.15; p=0.74). There was a significant difference in social isolation at the recovery phase compared to the pre-operative phase (p=0.01), where people following arthroplasty reported an increase in social isolation (16.9% to 21.4%). There was no significant difference between the assessment phases in respect to UCLA Loneliness Scale score (p≥0.74). Conclusions: Given the negative physical and psychological consequences which social isolation and loneliness can have on individuals following THA or TKA, clinicians should be mindful of this health challenge for this population. The reported prevalence of social isolation and loneliness suggests this is an important issue

Trajectory of physical activity following total hip and knee arthroplasty: data from the English Longitudinal Study of Ageing (ELSA) cohort

Purpose: To determine the prevalence and trajectory of physical activity levels in people before and after total hip (THA) and total knee arthroplasty (TKA).  Materials and Methods: An analysis of the English Longitudinal Study of Ageing (ELSA) (2004/5 to 2014/15) cohort study, a prospective study of community-dwelling older adults. 201 people who received a THA or TKA for the management of osteoarthritis were identified. Physical activity was assessed through the frequency of engagement in sedentary, mild, moderate and high physical activity levels pre-operatively, during the recovery phase and a minimum of two years’ post-operatively.  Results: There was a statistically significant decrease in physical activity from the pre-arthroplasty phase to the operative-recovery phase (p<0.01), and a significant increase in physical activity from the operative-recovery phase to final follow-up (p=0.05). However, overall there was no significant change in physical activity from pre-operatively to final follow-up where prevalence altered from 8% (95% Confidence Intervals (CI): 5% to 12%) to 13% (95% CI: 9% to 18%)(p=0.15). Increasing age, male gender and greater depressive symptoms were explanatory variables associated with physical inactivity (p<0.02).  Conclusion: Physical activity does not increase following THA or TKA. A proportion of the arthroplasty population remain physically inactive

Excitations in the Halo Nucleus He-6 Following The Li-7(gamma,p)He-6 Reaction

A broad excited state was observed in 6-He with energy E_x = 5 +/- 1 MeV and width Gamma = 3 +/- 1 MeV, following the reaction Li-7(gamma,p)He-6. The state is consistent with a number of broad resonances predicted by recent cluster model calculations. The well-established reaction mechanism, combined with a simple and transparent analysis procedure confers considerable validity to this observation.Comment: 3 pages of LaTeX, 3 figures in PostScript, approved for publication in Phys. Rev. C, August, 200

First measurements of the ^16O(e,e'pn)^14N reaction

This paper reports on the first measurement of the ^16O(e,e'pn)^14N reaction. Data were measured in kinematics centred on a super-parallel geometry at energy and momentum transfers of 215 MeV and 316 MeV/c. The experimental resolution was sufficient to distinguish groups of states in the residual nucleus but not good enough to separate individual states. The data show a strong dependence on missing momentum and this dependence appears to be different for two groups of states in the residual nucleus. Theoretical calculations of the reaction using the Pavia code do not reproduce the shape or the magnitude of the data.Comment: 10 pages, 11 figures, 2 tables, Accepted for publication in EPJ

Upgrade of the Glasgow photon tagging spectrometer for Mainz MAMI-C

The Glasgow photon tagging spectrometer at Mainz has been upgraded so that it can be used with the 1500 MeV electron beam now available from the Mainz microtron MAMI-C. The changes made and the resulting properties of the spectrometer are discussed.Comment: 20 pages, 12 figure

In-medium modifications of the ππ\pi\pi interaction in photon-induced reactions

Differential cross sections of the reactions $(\gamma,\pi^\circ\pi^\circ)$ and $(\gamma,\pi^\circ\pi^++\pi^\circ\pi^-)$ have been measured for several nuclei ($^1$H,$^{12}$C, and $^{\rm nat}$Pb) at an incident-photon energy of $E_{\gamma}$=400-460 MeV at the tagged-photon facility at MAMI-B using the TAPS spectrometer. A significant nuclear-mass dependence of the $\pi\pi$ invariant-mass distribution is found in the $\pi^\circ\pi^\circ$ channel. This dependence is not observed in the $\pi^\circ\pi^{+/-}$ channel and is consistent with an in-medium modification of the $\pi\pi$ interaction in the $I$=$J$=0 channel. The data are compared to $\pi$-induced measurements and to calculations within a chiral-unitary approach

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Properties of 42 Solar-type Kepler Targets from the Asteroseismic Modeling Portal

Recently the number of main-sequence and subgiant stars exhibiting solar-like oscillations that are resolved into individual mode frequencies has increased dramatically. While only a few such data sets were available for detailed modeling just a decade ago, the Kepler mission has produced suitable observations for hundreds of new targets. This rapid expansion in observational capacity has been accompanied by a shift in analysis and modeling strategies to yield uniform sets of derived stellar properties more quickly and easily. We use previously published asteroseismic and spectroscopic data sets to provide a uniform analysis of 42 solar-type Kepler targets from the Asteroseismic Modeling Portal (AMP). We find that fitting the individual frequencies typically doubles the precision of the asteroseismic radius, mass and age compared to grid-based modeling of the global oscillation properties, and improves the precision of the radius and mass by about a factor of three over empirical scaling relations. We demonstrate the utility of the derived properties with several applications.Comment: 12 emulateapj pages, 9 figures, 1 online-only extended figure, 1 table, ApJS accepted (typo corrected in Eq.8