1,010 research outputs found
Prediction of the First Variceal Haemorrhage
We followed 87 cirrhotic patients with esophageal varices and without previous hemorrhage for a mean period of 24 mo to prospectively evaluate the occurance of variceal bleeding within (early) or after (late) 6 mo from entry and the contribution of portal Doppler ultrasound parameters to the prediction of early and late hemorrhage. Clinical, biochemical, endoscopic and portal Doppler ultrasound parameters were recorded at entry. Variceal bleeding occurred in 22 patients (25.3%). Nine (40.9%) bled within the first 6 mo. Cox regression analysis identified variceal size, cherry-red spots, serum bilirubin and congestion index of the portal vein (the ratio of portal vein [cross-sectional area] and portal blood flow velocity) as the only independent predictors of first variceal hemorrhage. Discriminant analysis was used to find the prognostic index cut off points to identify patients who bled within 6 mo (prognostic group 1) or after 6 mo (prognostic group 2) or remained free of bleeding (prognostic group 3). The cumulative proportion of patients correctly classified was 73% in prognostic group 1, 47% in prognostic group 2 and more than 80% in prognostic group 3. The addition of Doppler ultrasound flowmetry to clinical, biochemical and endoscopic parameter only improved the classification of patients with early bleeding
Long Term Variceal Sclerotherapy: Is Endoscopic Sclerosis a Unique Therapeutic Approach and a True Alternative to Surgery?
Endoscopic sclerotherapy has been used to control acute variceal haemorrhage which persists despite
conservative therapy, prevent recurrent variceal haemorrhage in patients with a history of oesophageal
haemorrhage, and to prevent a haemorrhage in patients with oesophageal varices who never bled
Stochastic semi-continuous simulation for extreme flood estimation in catchments with combined rainfall–snowmelt flood regimes
Simulation methods for extreme flood estimation represent an important
complement to statistical flood frequency analysis because a spectrum of
catchment conditions potentially leading to extreme flows can be assessed. In
this paper, stochastic, semi-continuous simulation is used to estimate
extreme floods in three catchments located in Norway, all of which are
characterised by flood regimes in which snowmelt often has a significant
role. The simulations are based on SCHADEX, which couples a precipitation
probabilistic model with a hydrological simulation such that an exhaustive
set of catchment conditions and responses is simulated. The precipitation
probabilistic model is conditioned by regional weather patterns, and a
bottom–up classification procedure was used to define a set of weather
patterns producing extreme precipitation in Norway. SCHADEX estimates for the
1000-year (Q1000) discharge are compared with those of several standard
methods, including event-based and long-term simulations which use a single
extreme precipitation sequence as input to a hydrological model, statistical
flood frequency analysis based on the annual maximum series, and the GRADEX
method. The comparison suggests that the combination of a precipitation
probabilistic model with a long-term simulation of catchment conditions,
including snowmelt, produces estimates for given return periods which are
more in line with those based on statistical flood frequency analysis, as
compared with the standard simulation methods, in two of the catchments. In
the third case, the SCHADEX method gives higher estimates than statistical
flood frequency analysis and further suggests that the seasonality of the
most likely Q1000 events differs from that of the annual maximum flows. The
semi-continuous stochastic simulation method highlights the importance of
considering the joint probability of extreme precipitation, snowmelt rates
and catchment saturation states when assigning return periods to floods
estimated by precipitation-runoff methods. The SCHADEX methodology, as
applied here, is dependent on observed discharge data for calibration of a
hydrological model, and further study to extend its application to ungauged
catchments would significantly enhance its versatility
Retinitis pigmentosa: rapid neurodegeneration is governed by slow cell death mechanisms
For most neurodegenerative diseases the precise duration of an individual cell's death is unknown, which is an obstacle when counteractive measures are being considered. To address this, we used the rd1 mouse model for retinal neurodegeneration, characterized by phosphodiesterase-6 (PDE6) dysfunction and photoreceptor death triggered by high cyclic guanosinemono-phosphate (cGMP) levels. Using cellular data on cGMP accumulation, cell death, and survival, we created mathematical models to simulate the temporal development of the degeneration. We validated model predictions using organotypic retinal explant cultures derived from wild-type animals and exposed to the selective PDE6 inhibitor zaprinast. Together, photoreceptor data and modeling for the first time delineated three major cell death phases in a complex neuronal tissue: (1) initiation, taking up to 36 h, (2) execution, lasting another 40 h, and finally (3) clearance, lasting about 7 h. Surprisingly, photoreceptor neurodegeneration was noticeably slower than necrosis or apoptosis, suggesting a different mechanism of death for these neurons. Cell Death and Disease (2013) 4, e488; doi: 10.1038/cddis.2013.12; published online 7 February 201
Dissection of synaptic pathways through the CSF biomarkers for predicting Alzheimer's disease
OBJECTIVE: To assess the ability of a combination of synaptic CSF biomarkers to separate AD and non-AD disorders and to help in the differential diagnosis between neurocognitive diseases. METHODS: Retrospective cross-sectional monocentric study. All participants explored with CSF assessments for neurocognitive decline were invited to participate. After complete clinical and imaging evaluations, 243 patients were included. CSF synaptic (GAP-43, neurogranin, SNAP-25 total, SNAP-25 aa40, synaptotagmin-1) and AD biomarkers were blindly quantified using ELISA or mass spectrometry. Statistical analysis compared CSF levels between various groups AD dementias n=81, MCI-AD n=30, other MCI n=49, other dementias (OD) n=49, neurological controls n=35) as well as their discriminatory powers. RESULTS: All synaptic biomarkers were significantly increased in MCI-AD and AD -dementias patients compared to other groups. All synaptic biomarkers could efficiently discriminate AD dementias from OD (AUC ≥0.80). All but synaptotagmin were also able to discriminate MCI-AD from controls (AUC ≥0.85) and AD dementias from controls (AUC ≥0.80). Overall, CSF SNAP 25aa40 had the highest discriminative power (AUC=0.93) between AD dementias and controls or OD, and AUC=0.90 between MCI-AD and controls. Higher levels were associated with two alleles of apolipoprotein E (APOE) ε4. CONCLUSION: All synaptic biomarkers tested had a good discriminatory power to distinguish patients with AD abnormal CSF from non-AD disorders. SNAP25aa40 demonstrated the highest power to discriminate AD CSF positive patients from non-AD patients and neurological controls in this cohort. CLASSIFICATION OF EVIDENCE: This retrospective study provides Class II evidence that CSF synaptic biomarkers discriminate patients with AD from non-AD patients
Microscopic Functional Integral Theory of Quantum Fluctuations in Double-Layer Quantum Hall Ferromagnets
We present a microscopic theory of zero-temperature order parameter and
pseudospin stiffness reduction due to quantum fluctuations in the ground state
of double-layer quantum Hall ferromagnets. Collective excitations in this
systems are properly described only when interactions in both direct and
exchange particle-hole channels are included. We employ a functional integral
approach which is able to account for both, and comment on its relation to
diagrammatic perturbation theory. We also discuss its relation to Gaussian
fluctuation approximations based on Hubbard-Stratonovich-transformation
representations of interactions in ferromagnets and superconductors. We derive
remarkably simple analytical expressions for the correlation energy,
renormalized order parameter and renormalized pseudospin stiffness.Comment: 15 pages, 5 figure
Full-length and C-terminal neurogranin in Alzheimer's disease cerebrospinal fluid analyzed by novel ultrasensitive immunoassays
Background: Neurogranin (Ng) is a neuron-specific and postsynaptic protein that is abundantly expressed in the
brain, particularly in the dendritic spine of the hippocampus and cerebral cortex. The enzymatic cleavage of Ng
produces fragments that are released into cerebrospinal (CSF), which have been shown to be elevated in
Alzheimer’s disease (AD) patients and predict cognitive decline. Thus, quantification of distinctive cleavage products
of Ng could elucidate different features of the disease.
Methods: In this study, we developed novel ultrasensitive single molecule array (Simoa) assays for measurement of
full-length neurogranin (FL-Ng) and C-terminal neurogranin (CT-Ng) fragments in CSF. The Ng Simoa assays were
evaluated in CSF samples from AD patients (N = 23), mild cognitive impairment due to AD (MCI-AD) (N = 18), and
from neurological controls (N = 26).
Results: The intra-assay repeatability and inter-assay precision of the novel methods had coefficients of variation
below 7% and 14%, respectively. CSF FL-Ng and CSF CT-Ng median concentrations were increased in AD patients
(6.02 ng/L, P < 0.00001 and 452 ng/L, P = 0.00001, respectively) and in patients with MCI-AD (5.69 ng/L, P < 0.00001
and 566 ng/L, P < 0.00001) compared to neurological controls (0.644 ng/L and 145 ng/L). The median CSF ratio of
CT-Ng/FL-Ng were decreased in AD patients (ratio = 101, P = 0.008) and in patients with MCI-AD (ratio = 115, P =
0.016) compared to neurological controls (ratio = 180). CSF of FL-Ng, CT-Ng, and ratio of CT-Ng/FL-Ng could each
significantly differentiate AD patients from controls (FL-Ng, AUC = 0.907; CT-Ng, AUC = 0.913; CT-Ng/FL-Ng, AUC =
0.775) and patients with MCI-AD from controls (FL-Ng, AUC = 0.937; CT-Ng, AUC = 0.963; CT-Ng/FL-Ng, AUC = 0.785).
Conclusions: Assessments of the FL-Ng and CT-Ng levels in CSF with the novel sensitive immunoassays provide a
high separation of AD from controls, even in early phase of the disease. The novel Ng assays are robust and highly
sensitive and may be valuable tools to study synaptic alteration in AD, as well as to monitor the effect on synaptic
integrity of novel drug candidates in clinical trials
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