2,836 research outputs found
Exposure to secondhand smoke and cognitive impairment in non-smokers: national cross sectional study with cotinine measurement.
addresses: Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 2SR. [email protected]: PMCID: PMC2643443types: Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov'tCopyright © 2009 by the BMJ Publishing Group Ltd. This articles was first published in: BMJ, 2009, Vol. 338, pp. b462 -To examine the association between a biomarker of exposure to secondhand smoke (salivary cotinine concentration) and cognitive impairment
Late Cenozoic deepening of Yosemite Valley, USA
Although Yosemite Valley, USA, catalyzed the modern environmental movement and fueled foundational debates in geomorphology, a century of investigation has failed to definitively determine when it formed. The non-depositional nature of the landscape and homogeneous bedrock have prevented direct geological assessments. Indirect assumptions about the age of downcutting have ranged from pre-Eocene to Pleistocene. Clarity on this issue would not only satisfy public interest but also provide a new constraint for contentious debates about the Cenozoic tectonic and geomorphologic history of the Sierra Nevada in California. Here we use thermochronometric analysis of radiogenic helium in apatite crystals, coupled with numerical models of crustal temperatures beneath evolving topography, to demonstrate significant late Cenozoic deepening of Tenaya Canyon, Yosemite’s northeastern branch. Approximately 40%–90% of the current relief has developed since 10 Ma and most likely since 5 Ma. This coincides with renewed regional tectonism, which is a long-hypothesized but much debated driver of Sierran canyon development. Pleistocene glaciation caused spatially variable incision and valley widening in Yosemite Valley, whereas little contemporaneous erosion occurred in the adjacent upper Tuolumne watershed. Such variations probably arise from glacial erosion’s dependence on topographic focusing of ice discharge into zones of rapid flow, and on the abundance of pre-existing fractures in the substrate. All available data, including those from our study, are consistent with a moderately high and slowly eroding mid-Cenozoic Sierra Nevada followed by significant late Cenozoic incision of some, but not all, west-side canyon
Serum leptin and risk of cognitive decline in elderly italians.
Background: US studies suggest that leptin, a fat-derived hormone, may be protective against the development of dementia. Objective: To investigate the complex relationship between leptin levels and cognitive decline in elderly Italians. Methods: We studied circulating fasting leptin levels in 809 elderly adults free from dementia who participated in the prospective Italian population-based InCHIANTI study between 1998 and 2009 (mean follow-up of 8.0 years). Global cognitive decline was defined as a reduction of ≥5 points on the Mini-Mental State Examination (MMSE). Trail-Making Tests A and B were also incorporated, with cognitive decline defined as discontinued testing or the worst 10% of change from baseline. We also investigated whether any association could be explained by midlife weight and whether cognitive decline was associated with changing leptin levels. Results: The multivariate adjusted relative risk ([RR]; 95% confidence interval [CI]) of cognitive decline on the MMSE was 0.84 (95% CI 0.73–0.97) in relation to baseline sex-standardized log-leptin levels. High leptin levels showed a non-significant trend toward a reduced risk of decline on the Trail-Making Tests A (RR = 0.85, 95% CI 0.71–1.02) and B (RR = 0.90, 0.79–1.02). Adjusting for midlife weight or change in weight did not alter the pattern of results, and cognitive decline was not associated with changing leptin levels. Conclusions: High leptin levels were independently associated with a reduced risk of cognitive decline in elderly Italians.Italian Ministry of HealthU.S. National Institute on AgingAlzheimer’s AssociationNational Institute for Health Research (NIHR)National Institute of Health (Baltimore)National Institute of Health (Maryland)Mary Kinross Charitable TrustJames Tudor FoundationHalpin TrustSir Halley Stewart TrustAge Related Diseases and Health TrustNorman Family Charitable Trus
The actions of methotrexate on endothelial cells are dependent on the shear stress-induced regulation of one carbon metabolism
Objectives: The disease-modifying anti-rheumatic drug methotrexate (MTX) is recognized to reduce cardiovascular risk in patients with systemic inflammatory diseases. However, the molecular basis for these cardioprotective effects remains incompletely understood. This study evaluated the actions of low-dose MTX on the vascular endothelium. Methods: Human endothelial cells (EC) were studied under in vitro conditions relevant to inflammatory arthritis. These included culture in a pro-inflammatory microenvironment and exposure to fluid shear stress (FSS) using a parallel plate model. Respectively treated cells were analyzed by RNA sequencing and quantitative real-time PCR for gene expression, by immunoblotting for protein expression, by phosphokinase activity arrays, by flow cytometry for cell cycle analyses and by mass spectrometry to assess folate metabolite levels. Results: In static conditions, MTX was efficiently taken up by EC and caused cell cycle arrest concurrent with modulation of cell signaling pathways. These responses were reversed by folinic acid (FA), suggesting that OCM is a predominant target of MTX. Under FSS, MTX did not affect cell proliferation or pro-inflammatory gene expression. Exposure to FSS downregulated endothelial one carbon metabolism (OCM) as evidenced by decreased expression of key OCM genes and metabolites. Conclusion: We found that FSS significantly downregulated OCM and thereby rendered EC less susceptible to the effects of MTX treatment. The impact of shear stress on OCM suggested that MTX does not directly modulate endothelial function. The cardioprotective actions of MTX likely reflect direct actions on inflammatory cells and indirect benefit on the vascular endothelium
Vitamin D and Risk of Neuroimaging Abnormalities.
Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25-50 nmol/L) were 0.76 (0.35-1.66) and 1.09 (0.76-1.55) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20-1.19) and 1.12 (0.79-1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84-4.54) and 0.73 (0.47-1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with the development of cerebrovascular or neurodegenerative neuroimaging abnormalities in Cardiovascular Health Study participants.The Cardiovascular Health Study was supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG023629, AG20098, AG15928 and HL084443 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at chs-nhlbi.org. Additional support was also provided by NIRG-11-200737 from the Alzheimer’s Association, the Mary Kinross Charitable Trust, the James Tudor Foundation, the Halpin Trust, the Age Related Diseases and Health Trust, and the Norman Family Charitable Trust (to D.J.L.). This research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The National Institutes of Health was involved in the original design and conduct of the Cardiovascular Health Study and in the data collection methods
A momentum-dependent perspective on quasiparticle interference in Bi_{2}Sr_{2}CaCu_{2}O_{8+\delta}
Angle Resolved Photoemission Spectroscopy (ARPES) probes the momentum-space
electronic structure of materials, and provides invaluable information about
the high-temperature superconducting cuprates. Likewise, the cuprate
real-space, inhomogeneous electronic structure is elucidated by Scanning
Tunneling Spectroscopy (STS). Recently, STS has exploited quasiparticle
interference (QPI) - wave-like electrons scattering off impurities to produce
periodic interference patterns - to infer properties of the QP in
momentum-space. Surprisingly, some interference peaks in
Bi_{2}Sr_{2}CaCu_{2}O_{8+\delta} (Bi-2212) are absent beyond the
antiferromagnetic (AF) zone boundary, implying the dominance of particular
scattering process. Here, we show that ARPES sees no evidence of quasiparticle
(QP) extinction: QP-like peaks are measured everywhere on the Fermi surface,
evolving smoothly across the AF zone boundary. This apparent contradiction
stems from different natures of single-particle (ARPES) and two-particle (STS)
processes underlying these probes. Using a simple model, we demonstrate
extinction of QPI without implying the loss of QP beyond the AF zone boundary
Quasi-particle interference and superconducting gap in a high-temperature superconductor Ca2-xNaxCuO2Cl2
High-transition-temperature (high-Tc) superconductivity is ubiquitous in the
cuprates containing CuO2 planes but each cuprate has its own character. The
study of the material dependence of the d-wave superconducting gap (SG) should
provide important insights into the mechanism of high-Tc. However, because of
the 'pseudogap' phenomenon, it is often unclear whether the energy gaps
observed by spectroscopic techniques really represent the SG. Here, we report
spectroscopic imaging scanning tunneling microscopy (SI-STM) studies of
nearly-optimally-doped Ca2-xNaxCuO2Cl2 (Na-CCOC) with Tc = 25 ~ 28 K. They
enable us to observe the quasi-particle interference (QPI) effect in this
material, through which unambiguous new information on the SG is obtained. The
analysis of QPI in Na-CCOC reveals that the SG dispersion near the gap node is
almost identical to that of Bi2Sr2CaCu2Oy (Bi2212) at the same doping level,
while Tc of Bi2212 is 3 times higher than that of Na-CCOC. We also find that SG
in Na-CCOC is confined in narrower energy and momentum ranges than Bi2212. This
explains at least in part the remarkable material dependence of TcComment: 13pages, 4fig
Colossal magnetocapacitance and scale-invariant dielectric response in phase-separated manganites
Thin films of strongly-correlated electron materials (SCEM) are often grown
epitaxially on planar substrates and typically have anisotropic properties that
are usually not captured by edge-mounted four-terminal electrical measurements,
which are primarily sensitive to in-plane conduction paths. Accordingly, the
correlated interactions in the out-of-plane (perpendicular) direction cannot be
measured but only inferred. We address this shortcoming and show here an
experimental technique in which the SCEM under study, in our case a 600
Angstrom-thick (La1-yPry)0.67Ca0.33MnO3 (LPCMO) film, serves as the base
electrode in a metal-insulator-metal (MIM) trilayer capacitor structure. This
unconventional arrangement allows for simultaneous determination of colossal
magnetoresistance (CMR) associated with dc transport parallel to the film
substrate and colossal magnetocapacitance (CMC) associated with ac transport in
the perpendicular direction. We distinguish two distinct strain-related
direction-dependent insulator-metal (IM) transitions and use Cole-Cole plots to
establish a heretofore unobserved collapse of the dielectric response onto a
universal scale-invariant power-law dependence over a large range of frequency,
temperature and magnetic field.Comment: 32 pages, 4 figures, Supplementary section included, Submitted to
Nature Physic
Sensory Electrical Stimulation Improves Foot Placement during Targeted Stepping Post-Stroke
Proper foot placement is vital for maintaining balance during walking, requiring the integration of multiple sensory signals with motor commands. Disruption of brain structures post-stroke likely alters the processing of sensory information by motor centers, interfering with precision control of foot placement and walking function for stroke survivors. In this study, we examined whether somatosensory stimulation, which improves functional movements of the paretic hand, could be used to improve foot placement of the paretic limb. Foot placement was evaluated before, during, and after application of somatosensory electrical stimulation to the paretic foot during a targeted stepping task. Starting from standing, twelve chronic stroke participants initiated movement with the non-paretic limb and stepped to one of five target locations projected onto the floor with distances normalized to the paretic stride length. Targeting error and lower extremity kinematics were used to assess changes in foot placement and limb control due to somatosensory stimulation. Significant reductions in placement error in the medial–lateral direction (p = 0.008) were observed during the stimulation and post-stimulation blocks. Seven participants, presenting with a hip circumduction walking pattern, had reductions (p = 0.008) in the magnitude and duration of hip abduction during swing with somatosensory stimulation. Reductions in circumduction correlated with both functional and clinical measures, with larger improvements observed in participants with greater impairment. The results of this study suggest that somatosensory stimulation of the paretic foot applied during movement can improve the precision control of foot placement
Single and two-particle energy gaps across the disorder-driven superconductor-insulator transition
The competition between superconductivity and localization raises profound
questions in condensed matter physics. In spite of decades of research, the
mechanism of the superconductor-insulator transition (SIT) and the nature of
the insulator are not understood. We use quantum Monte Carlo simulations that
treat, on an equal footing, inhomogeneous amplitude variations and phase
fluctuations, a major advance over previous theories. We gain new microscopic
insights and make testable predictions for local spectroscopic probes. The
energy gap in the density of states survives across the transition, but
coherence peaks exist only in the superconductor. A characteristic pseudogap
persists above the critical disorder and critical temperature, in contrast to
conventional theories. Surprisingly, the insulator has a two-particle gap scale
that vanishes at the SIT, despite a robust single-particle gap.Comment: 7 pages, 5 figures (plus supplement with 4 pages, 5 figures
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