700 research outputs found
Turbulent transport of impurities and their effect on energy confinement
By presenting linear and nonlinear gyrokinetic studies, based on a balanced
neutral beam injection deuterium discharge from the DIII-D tokamak, we
demonstrate that impurities alter the scaling of the transport on the charge
and mass of the main species, and even more importantly, they can dramatically
change the energy transport even in relatively small quantities. A poloidally
varying equilibrium electrostatic potential can lead to a strong reduction or
sign change of the impurity peaking factor due to the combined effect of the
in-out impurity density asymmetry and the EXB drift of impurities. We present
an approximate expression for the impurity peaking factor and demonstrate that
impurity peaking is not significantly affected by impurity self-collisions.Comment: Accepted for publication in Plasma Physics and Controlled Fusio
Direct multiscale coupling of a transport code to gyrokinetic turbulence codes
Direct coupling between a transport solver and local, nonlinear gyrokinetic
calculations using the multiscale gyrokinetic code TRINITY [M. Barnes, Ph.D.
thesis, arxiv:0901.2868] is described. The coupling of the microscopic and
macroscopic physics is done within the framework of multiscale gyrokinetic
theory, of which we present the assumptions and key results. An assumption of
scale separation in space and time allows for the simulation of turbulence in
small regions of the space-time grid, which are embedded in a coarse grid on
which the transport equations are implicitly evolved. This leads to a reduction
in computational expense of several orders of magnitude, making
first-principles simulations of the full fusion device volume over the
confinement time feasible on current computing resources. Numerical results
from TRINITY simulations are presented and compared with experimental data from
JET and ASDEX Upgrade plasmas.Comment: 12 pages, 13 figures, invited paper for 2009 APS-DPP meeting,
submitted to Phys. Plasma
Living with an Older Person Dying from Cancer, Lung Disease or Dementia: Health Outcomes from a General Practice Cohort Study
CONTEXT: Increasing numbers of people will die from chronic disease. Families contribute significantly to end-of-life care but their role may not be recognized. OBJECTIVES: To 1) establish the proportion of older cohabitees identified in primary care as "carers;" 2) describe demographic and lifestyle characteristics of cohabitees of people terminally ill with cancer, dementia, and chronic obstructive pulmonary disease (COPD); 3) describe their health a year before and after bereavement; and 5) compare health outcomes between cohabitees of people dying with cancer, COPD, or dementia. METHODS: Retrospective cohort study using a U.K. primary care database (The Health Improvement Network) of 13,693 bereaved cohabitees (a proxy marker for being a carer), aged 60 years or older of people dying from cancer, COPD, or dementia. Characteristics were described one year before and after bereavement. We compared cancer, COPD, and dementia cohabitee outcomes using incidence rate ratios one year before and after bereavement and calculated mortality risk post-bereavement. RESULTS: A total of 6.9% of cohabitees were recorded as carers. Health outcomes differed little between the three groups of cohabitees in the year prior to or after bereavement. The proportion of cohabitees with six or more consultations increased the year after bereavement (cancer cohabitees 16.0% to 18.8%, COPD cohabitees 17.8% to 20.4% and dementia cohabitees 15.5% to 17.5%). At post-bereavement (follow-up median 3 years, IQR 1.3-5.4), we found no mortality differences between the three groups. CONCLUSION: Recording of carers of terminally ill people was suboptimal. Cause of bereavement produced few differential effects on health outcomes or mortality
Homomeric Q/R edited AMPA receptors conduct when desensitized
Desensitization is a canonical property of ligand-gated ion channels, causing progressive current decline in the continued presence of agonist. AMPA-type glutamate receptors, which mediate fast excitatory signaling throughout the brain, exhibit profound desensitization. Recent cryo-EM studies of AMPAR assemblies show their ion channels to be closed in the desensitized state. Here we report the surprising finding that homomeric Q/R edited AMPARs still allow ions to flow when the receptors are desensitized. GluA2(R) expressed alone, or with auxiliary subunits (γ-2, γ-8 or GSG1L), generates large steady-state currents and anomalous current-variance relationships. Using fluctuation analysis, single-channel recording, and kinetic modeling we demonstrate that the steady-state current is mediated predominantly by ‘conducting desensitized’ receptors. When combined with crystallography this unique functional readout of a hith-erto silent state enabled us to examine cross-linked cysteine mutants to probe the conformation of the desensitized ligand binding domain of functioning AMPAR complexes within the plasma membrane
High-resolution analysis of Quaternary calcretes: a coupled stable isotope and micromorphological approach
Pedogenic calcretes are abundant in arid and semi-arid regions, and they are widely used as proxy records of palaeoclimatic change. Calcrete oxygen (δ18O) and carbon (δ13C) isotopic signatures are indicative of temperature, aridity, or vegetation at the time of calcrete formation. Their microfabrics also reflect carbonate formation mechanisms in response to the prevailing environmental conditions. Many studies have explored calcrete micromorphology or stable isotope composition, but these techniques have not yet been applied simultaneously. This co-analysis is important as it allows us to establish whether calcrete morphology directly reflects environmental change. This study tests the potential of combining these analyses to examine the relationships between calcrete microfabrics, their isotopic signals, and Quaternary climate change. Calcretes from four river terraces of the Rio Alias in southeast Spain have been analysed in detail. On the basis of morphostratigraphic correlation (Maher et al., 2007) and Uranium-series ages (Candy et al., 2005), these span the period from 304 ± 26 ka (MIS 9) to the Holocene. The oldest profiles have therefore been exposed to multiple glacial-interglacial cycles. A total of 37 micromorphological profiles have been used to extract stable oxygen and carbon isotopic indicators from 77 microfacies. The morphological and isotopic complexity of the calcrete profiles increases with progressive age. The oldest samples display multiple calcretisation phases, and their microfabrics have a larger isotopic range than the younger samples. Alpha (non-biogenic) fabrics have higher δ13C and δ18O values than beta (biogenic) fabrics. Strong positive covariance between δ13C and δ18O within all profiles suggests that both isotopes are responding to the same environmental parameter. We suggest that this is relative aridity. The study demonstrates that the detailed co-analysis of calcrete micromorphology and stable isotope signatures allows calcrete formation patterns to be placed into a wider palaeoclimatic context. Importantly, this technique provides a level of detail that is not possible through bulk isotope sampling alone. It demonstrates the potential of this technique to more reliably constrain the palaeoenvironmental significance of secondary carbonates in dryland settings where other proxy records may be poorly preserved
Molecular mechanisms contributing to TARP regulation of channel conductance and polyamine block of calcium-permeable AMPA receptors.
Many properties of fast synaptic transmission in the brain are influenced by transmembrane AMPAR regulatory proteins (TARPs) that modulate the pharmacology and gating of AMPA-type glutamate receptors (AMPARs). Although much is known about TARP influence on AMPAR pharmacology and kinetics through their modulation of the extracellular ligand-binding domain (LBD), less is known about their regulation of the ion channel region. TARP-induced modifications in AMPAR channel behavior include increased single-channel conductance and weakened block of calcium-permeable AMPARs (CP-AMPARs) by endogenous intracellular polyamines. To investigate how TARPs modify ion flux and channel block, we examined the action of γ-2 (stargazin) on GluA1 and GluA4 CP-AMPARs. First, we compared the permeation of organic cations of different sizes. We found that γ-2 increased the permeability of several cations but not the estimated AMPAR pore size, suggesting that TARP-induced relief of polyamine block does not reflect altered pore diameter. Second, to determine whether residues in the TARP intracellular C-tail regulate polyamine block and channel conductance, we examined various γ-2 C-tail mutants. We identified the membrane proximal region of the C terminus as crucial for full TARP-attenuation of polyamine block, whereas complete deletion of the C-tail markedly enhanced the TARP-induced increase in channel conductance; thus, the TARP C-tail influences ion permeation. Third, we identified a site in the pore-lining region of the AMPAR, close to its Q/R site, that is crucial in determining the TARP-induced changes in single-channel conductance. This conserved residue represents a site of TARP action, independent of the AMPAR LBD
Coupled micromorphological and stable isotope analysis of Quaternary
Pedogenic calcretes are widespread in arid and semi-arid regions. Using calcrete profiles from four river terraces of the Rio Alias in southeast Spain, this study explores the potential of using detailed micromorphological and stable isotopic analysis to more fully understand the impacts of Quaternary environmental change on calcrete development. The four profiles increase in carbonate complexity with progressive age, reflecting calcretisation over multiple glacial-interglacial cycles since MIS 9 (c. 300 ka). Calcrete profiles contain a mixture of Alpha (non-biogenic) and Beta (biogenic) microfabrics. Alpha fabrics have higher δ13C and δ18O values. The profiles contain a range of crystal textures, but there is little difference between the δ13C and δ18O values of spar, microspar, and micrite cements. Strong positive covariance between δ13C and δ18O suggests that both isotopes are responding to the same environmental parameter, which is inferred to be relative aridity. The study reveals that the detailed co-analysis of calcrete micromorphology and stable isotope signatures can allow patterns of calcrete formation to be placed into a wider palaeoclimatic context. This demonstrates the potential of this technique to more reliably constrain the palaeoenvironmental significance of secondary carbonates in dryland settings where other proxy records may be poorly preserved
Context, mechanisms and outcomes in end-of-life care for people with advanced dementia: family carers perspective
Background: Keeping people living with advanced dementia in their usual place of residence is becoming a key
governmental goal but to achieve this, family carers and health care professionals must negotiate how to provide
optimal care. Previously, we reported a realist analysis of the health care professional perspective. Here, we report
on family carer perspectives. We aimed to understand the similarities and differences between the two
perspectives, gain insights into how the interdependent roles of family carers and HCPs can be optimised, and
make recommendations for policy and practice.
Method: Qualitative study using a realist approach in which we used the criteria from guidance on optimal palliative
care in advanced dementia to examine key contexts, mechanisms and outcomes highlighted by family carers.
Results: The themes and views of family caregivers resonate with those of health care professionals. Their overlapping
anxieties related to business-driven care homes, uncertainty of families when making EOL decisions and the
importance of symptom management referring to contexts, mechanisms and outcomes, respectively. Contexts specific
to family carers were ad hoc information about services, dementia progression and access to funding. Not all family
carers identified dementia as terminal, but many recognised the importance of continuity of care and knowing the
wishes of the person with dementia. New mechanisms included specific resources for improving EOL care and barriers
to discussing and planning for future care. Family carers identified the importance of comfort, being present, the
meeting of basic care needs and feeling the right decisions have been made as good outcomes of care.
Conclusions: Family carers and health care professionals share similar concerns about the challenges to good EOL
dementia care. Better understanding of the effects of dementia at the advanced stages would improve confidence in
EOL care and reduce uncertainty in decision making for family carers and health care professionals
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