894 research outputs found
Quantum phase transition in a single-molecule quantum dot
Quantum criticality is the intriguing possibility offered by the laws of
quantum mechanics when the wave function of a many-particle physical system is
forced to evolve continuously between two distinct, competing ground states.
This phenomenon, often related to a zero-temperature magnetic phase transition,
can be observed in several strongly correlated materials such as heavy fermion
compounds or possibly high-temperature superconductors, and is believed to
govern many of their fascinating, yet still unexplained properties. In contrast
to these bulk materials with very complex electronic structure, artificial
nanoscale devices could offer a new and simpler vista to the comprehension of
quantum phase transitions. This long-sought possibility is demonstrated by our
work in a fullerene molecular junction, where gate voltage induces a crossing
of singlet and triplet spin states at zero magnetic field. Electronic tunneling
from metallic contacts into the quantum dot provides here the
necessary many-body correlations to observe a true quantum critical behavior.Comment: 8 pages, 5 figure
Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Assessment of Substrate for Ventricular Tachycardia With Hemodynamic Compromise.
Background: The majority of data regarding tissue substrate for post myocardial infarction (MI) VT has been collected during hemodynamically tolerated VT, which may be distinct from the substrate responsible for VT with hemodynamic compromise (VT-HC). This study aimed to characterize tissue at diastolic locations of VT-HC in a porcine model. Methods: Late Gadolinium Enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging was performed in eight pigs with healed antero-septal infarcts. Seven pigs underwent electrophysiology study with venous arterial-extra corporeal membrane oxygenation (VA-ECMO) support. Tissue thickness, scar and heterogeneous tissue (HT) transmurality were calculated at the location of the diastolic electrograms of mapped VT-HC. Results: Diastolic locations had median scar transmurality of 33.1% and a median HT transmurality 7.6%. Diastolic activation was found within areas of non-transmural scar in 80.1% of cases. Tissue activated during the diastolic component of VT circuits was thinner than healthy tissue (median thickness: 5.5 mm vs. 8.2 mm healthy tissue, p < 0.0001) and closer to HT (median distance diastolic tissue: 2.8 mm vs. 11.4 mm healthy tissue, p < 0.0001). Non-scarred regions with diastolic activation were closer to steep gradients in thickness than non-scarred locations with normal EGMs (diastolic locations distance = 1.19 mm vs. 9.67 mm for non-diastolic locations, p < 0.0001). Sites activated late in diastole were closest to steep gradients in tissue thickness. Conclusions: Non-transmural scar, mildly decreased tissue thickness, and steep gradients in tissue thickness represent the structural characteristics of the diastolic component of reentrant circuits in VT-HC in this porcine model and could form the basis for imaging criteria to define ablation targets in future trials
Arginine deprivation alters microglia polarity and synergises with radiation to eradicate non arginine auxotrophic glioblastoma tumors
New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine depleting agent ADI-PEG20 in a non-arginine auxotrophic cellular background (Arginine Succinate Synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response with extended disease-free survival in an orthotopic immune competent model of GBM with no significant toxicity. ADI-PEG20 not only enhances the cellular sensitivity of Arginine succinate synthetase 1 positive GBM to ionising radiation by elevated production of nitric oxide (NO) and hence generation of cytotoxic peroxynitrites, but also promotes glioma-associated macrophages/microglia infiltration into tumors and turns their classical anti-inflammatory (pro-tumor) phenotype into a pro-inflammatory (anti-tumor) phenotype. Our results provide an effective, well-tolerated and simple strategy to improve GBM treatment which merits consideration for early evaluation in clinical trials
Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice
Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals,
there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death
receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival
and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic
proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To
investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1
transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional
Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the
macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was
striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells
(TCRβ+
CD4–
CD8–
B220+
) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr
mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating
autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene
by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell
population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the
development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other
haemopoietic cell types
From evidence to best practice in the management of fractures of the distal radius in adults: working towards a research agenda
BACKGROUND: Fracture of the distal radius is a common clinical problem, particularly in older white women with osteoporosis. We report our work towards evidence-based and patient-centred care for adults with these injuries. METHODS: We developed a systematic programme of research that built on our systematic review of the evidence of effectiveness of treatment interventions for these fractures. We devised schemata showing 'typical' care pathways and identified over 100 patient management questions. These depicted the more important decisions taken when progressing along each care pathway. We compiled a comprehensive document summarising the evidence available for each decision point from our reviews of randomised trials of treatment interventions. Using these documents, we undertook a formal and structured consultation process involving key players, including a patient representative, to obtain their views on the available evidence and to establish a research agenda. The resulting feedback was then processed and interpreted, using systematic methods. RESULTS: Some evidence from 114 randomised trials was available for 31 of the 117 patient management questions. However, there was sufficient evidence to base some conclusions of effectiveness for particular interventions in only five of these. Though only 60% of those approached responded, the responses received from the consultation group were often comprehensive and provided important insights into treatment practice and policy. There was a clear acceptance of the aims of the project and, aside from some suggestions for the more explicit inclusion of secondary prevention and management of complications, of the care pathways scheme. Though some respondents stressed that randomised trials were not always appropriate, there was no direct overall criticism of the evidence document and underlying processes. We were able to identify important core themes that underpin management decisions and research from the feedback of the consultation exercise. CONCLUSIONS: Overall, this project is an important advance towards evidence-based and patient-centred management of adults with distal radial fractures. It exposes the serious deficiency in the available evidence but also provides a template for further action. As well as being a valuable basis for viewing and informing current practice, the insights gained from this project should inform a future research agenda
Ambient biomass smoke and cardio-respiratory hospital admissions in Darwin, Australia
<p>Abstract</p> <p>Background</p> <p>Increasing severe vegetation fires worldwide has been attributed to both global environmental change and land management practices. However there is little evidence concerning the population health effects of outdoor air pollution derived from biomass fires. Frequent seasonal bushfires near Darwin, Australia provide an opportunity to examine this issue. We examined the relationship between atmospheric particle loadings <10 microns in diameter (PM<sub>10</sub>), and emergency hospital admissions for cardio-respiratory conditions over the three fire seasons of 2000, 2004 and 2005. In addition we examined the differential impacts on Indigenous Australians, a high risk population subgroup.</p> <p>Methods</p> <p>We conducted a case-crossover analysis of emergency hospital admissions with principal ICD10 diagnosis codes J00–J99 and I00–I99. Conditional logistic regression models were used to calculate odds ratios for admission with 10 μg/m<sup>3 </sup>rises in PM<sub>10</sub>. These were adjusted for weekly influenza rates, same day mean temperature and humidity, the mean temperature and humidity of the previous three days, days with rainfall > 5 mm, public holidays and holiday periods.</p> <p>Results</p> <p>PM<sub>10 </sub>ranged from 6.4 – 70.0 μg/m<sup>3 </sup>(mean 19.1). 2466 admissions were examined of which 23% were for Indigenous people. There was a positive relationship between PM<sub>10 </sub>and admissions for all respiratory conditions (OR 1.08 95%CI 0.98–1.18) with a larger magnitude in the Indigenous subpopulation (OR1.17 95% CI 0.98–1.40). While there was no relationship between PM<sub>10 </sub>and cardiovascular admissions overall, there was a positive association with ischaemic heart disease in Indigenous people, greatest at a lag of 3 days (OR 1.71 95%CI 1.14–2.55).</p> <p>Conclusion</p> <p>PM10 derived from vegetation fires was predominantly associated with respiratory rather than cardiovascular admissions. This outcome is consistent with the few available studies of ambient biomass smoke pollution. Indigenous people appear to be at higher risk of cardio-respiratory hospital admissions associated with exposure to PM10.</p
Observation of the Charmed Baryon at CLEO
The CLEO experiment at the CESR collider has used 13.7 fb of data to
search for the production of the (css-ground state) in
collisions at {\rm GeV}. The modes used to
study the are ,
, , , and
. We observe a signal of 40.49.0(stat) events
at a mass of 2694.62.6(stat)1.9(syst) {\rm MeV/}, for all modes
combined.Comment: 10 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
Evidence of New States Decaying into
Using 13.7 of data recorded by the CLEO detector at CESR, we report
evidence for two new charmed baryons: one decaying into
with the subsequent decay , and its
isospin partner decaying into followed by
. We measure the following mass differences
for the two states: =318.2+-1.3+-2.9 MeV,
and =324.0+-1.3+-3.0 MeV. We interpret
these new states as the particles, the charmed-strange
analogs of the .Comment: 10 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
Observation of and
We have studied two-body charmless hadronic decays of mesons into the
final states phi K and phi K^*. Using 9.7 million pairs collected
with the CLEO II detector, we observe the decays B- -> phi K- and B0 -> phi K*0
with the following branching fractions: BR(B- -> phi K-)=(5.5 +2.1-1.8 +- 0.6)
x 10^{-6} and BR(B0 -> phi K*0)=(11.5 +4.5-3.7 +1.8-1.7) x 10^{-6}. We also see
evidence for the decays B0 -> phi K0 and B- -> phi K*-. However, since the
statistical significance is not overwhelming for these modes we determine upper
limits of <12.3 x 10^{-6} and <22.5 x 10^{-6} (90% C.L.) respectively.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
Measurement of the Relative Branching Fraction of to Charged and Neutral B-Meson Pairs
We analyze 9.7 x 10^6 B\bar{B}$ pairs recorded with the CLEO detector to
determine the production ratio of charged to neutral B-meson pairs produced at
the Y(4S) resonance. We measure the rates for B^0 -> J/psi K^{(*)0} and B^+ ->
J/psi K^{(*)+} decays and use the world-average B-meson lifetime ratio to
extract the relative widths f+-/f00 = Gamma(Y(4S) -> B+B-)/Gamma(Y(4S) ->
B0\bar{B0}) = = 1.04 +/- 0.07(stat) +/- 0.04(syst). With the assumption that
f+- + f00 = 1, we obtain f00 = 0.49 +/- 0.02(stat) +/- 0.01(syst) and f+- =
0.51 +/- 0.02(stat) +/- 0.01(syst). This production ratio and its uncertainty
apply to all exclusive B-meson branching fractions measured at the Y(4S)
resonance.Comment: 11 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
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