94 research outputs found
The receptor guanylyl cyclase Npr2 is essential for sensory axon bifurcation within the spinal cord
Sensory axonal projections into the spinal cord display a highly stereotyped pattern of T- or Y-shaped axon bifurcation at the dorsal root entry zone (DREZ). Here, we provide evidence that embryonic mice with an inactive receptor guanylyl cyclase Npr2 or deficient for cyclic guanosine monophosphate-dependent protein kinase I (cGKI) lack the bifurcation of sensory axons at the DREZ, i.e., the ingrowing axon either turns rostrally or caudally. This bifurcation error is maintained to mature stages. In contrast, interstitial branching of collaterals from primary stem axons remains unaffected, indicating that bifurcation and interstitial branching are processes regulated by a distinct molecular mechanism. At a functional level, the distorted axonal branching at the DREZ is accompanied by reduced synaptic input, as revealed by patch clamp recordings of neurons in the superficial layers of the spinal cord. Hence, our data demonstrate that Npr2 and cGKI are essential constituents of the signaling pathway underlying axonal bifurcation at the DREZ and neuronal connectivity in the dorsal spinal cord
Domain wall QCD with physical quark masses
We present results for several light hadronic quantities (, ,
, , , , ) obtained from simulations of 2+1
flavor domain wall lattice QCD with large physical volumes and nearly-physical
pion masses at two lattice spacings. We perform a short, O(3)%, extrapolation
in pion mass to the physical values by combining our new data in a simultaneous
chiral/continuum `global fit' with a number of other ensembles with heavier
pion masses. We use the physical values of , and to
determine the two quark masses and the scale - all other quantities are outputs
from our simulations. We obtain results with sub-percent statistical errors and
negligible chiral and finite-volume systematics for these light hadronic
quantities, including: = 130.2(9) MeV; = 155.5(8) MeV; the
average up/down quark mass and strange quark mass in the scheme
at 3 GeV, 2.997(49) and 81.64(1.17) MeV respectively; and the neutral kaon
mixing parameter, , in the RGI scheme, 0.750(15) and the
scheme at 3 GeV, 0.530(11).Comment: 131 pages, 30 figures. Updated to match published versio
Fermionic R-Operator and Algebraic Structure of 1D Hubbard Model: Its application to quantum transfer matrix
The algebraic structure of the 1D Hubbard model is studied by means of the
fermionic R-operator approach. This approach treats the fermion models directly
in the framework of the quantum inverse scattering method. Compared with the
graded approach, this approach has several advantages. First, the global
properties of the Hamiltonian are naturally reflected in the algebraic
properties of the fermionic R-operator. We want to note that this operator is a
local operator acting on fermion Fock spaces. In particular, SO(4) symmetry and
the invariance under the partial particle hole transformation are discussed.
Second, we can construct a genuinely fermionic quantum transfer transfer matrix
(QTM) in terms of the fermionic R-operator. Using the algebraic Bethe Ansatz
for the Hubbard model, we diagonalize the fermionic QTM and discuss its
properties.Comment: 22 pages, no figure
Refractory and relapsed paediatric ACC in the MET studies – a challenging situation necessitating novel diagnostic and therapeutic concepts
Background
Paediatric adrenocortical carcinomas (ACC) are highly aggressive malignancies with a dismal prognosis in advanced and metastatic disease. Little is known about outcome of patients with refractory and relapsed (r/r) disease.
Procedure
National retrospective multicentre study including r/r ACC diagnosed in patients aged <18 years registered in the MET studies between January 1997 and December 2021
Results
A total of 16 patients (5 male; median age 12.9 years) with refractory disease were included. Median time to progression was 0.6 years [0.0-1.3]. Site of progression was locoregional (n=1), distant (n=3), and combined (n=12). 3-year overall (OS) and progression-free (PFS) survival were both 0%.
Thirty patients with relapse (11 male; median age 7.3 years) were identified. Median time to relapse was 0.7 years [0.1-3.2]. Site of relapse was locoregional (n=8), distant (n=15), and combined (n=7). At last follow-up, 20 patients had died of disease or complications or were alive with disease, 10 patients were in second complete remission (median follow-up: 6.8 years [0-10.5]). 3-year OS and PFS following relapse were 39.1% and 31.9%. Survival was superior in patients with distant relapse (59.6%) compared to locoregional (28.6%) and combined (14.3%) (p=0.028) and in patients with complete surgical resection of all sites of recurrence (70.0%) compared to incomplete (21.4%) and no surgery (0%) (p=0.003).
Conclusions
For patients nonresponsive to first-line therapy or who experience relapse, prognosis is dismal and options are scarce. Site of relapse and resectability define prognosis. Novel therapeutic concepts are needed to improve the outcome of paediatric patients with r/r ACC
Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta‑analysis
Background
Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave’s syndrome (BS).
Methods
We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission.
Results
Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8–5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2–7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2–6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p < 0.001), compared with late TOD. In BS, no associations between TOD and outcomes were found. When combining IEP and BS, early TOD was associated with a 6% decrease in overall mortality (10% vs. 16%, OR 2.1, 95% CI 1.1–3.9), a 19% decrease in re-interventions (26% vs. 45%, OR 1.9, 95% CI 1.1–3.2) and a 35% decrease in mean length of hospital stay (16 vs. 22 days, p = 0.001), compared with late TOD.
Conclusions
This individual patient data meta-analysis confirms the general opinion that an early (≤ 24 h) compared to a late diagnosis (> 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome.publishedVersio
Tenacidad a la fractura de compuestos cermets 3Al2O3*2SiO2/Ag manufacturados por molienda de alta energĂa
La fabricaciĂłn de materiales compuestos de matriz cerámica reforzados con partĂculas metálicas han propiciado la formaciĂłn de nuevos materiales conocidos como compuestos CERMETS, materiales que debido a sus elementos precursores poseen propiedades distintas a las de los materiales convencionales. En este trabajo se establece la ruta de fabricaciĂłn de materiales compuestos cermets base 3Al2O3*2SiO2 reforzados con partĂculas metálicas de Ag a partir de la formaciĂłn de la composiciĂłn quĂmica en peso de polvos de 3Al2O3*2SiO2 / 1% Ag en busca de un aumento en la tenacidad a la fractura con respecto al cerámico base. La composiciĂłn quĂmica de polvos es sometida a un proceso de mezcla molienda de alta energĂa en seco en un molino tipo planetario por 2 horas a 200 rpm. Los polvos posteriormente son conformados en muestras cilĂndricas de 20 mm de diámetro y 3 mm de espesor mediante la aplicaciĂłn de carga uniaxial en frĂo de 200 MPa. Las muestras son sinterizadas a 1500°C y 1600°C por una y dos horas en un horno de resistencia elĂ©ctrica en atmĂłsfera controlada de gas nitrĂłgeno. Los compuestos fabricados son analizados microestructuralmente por microscopia Ăłptica y electrĂłnica de barrido. Se determina la densidad y las propiedades mecánicas de dureza y tenacidad a la fractura, las dos Ăşltimas por el mĂ©todo de indentaciĂłn. Los resultados muestran la viabilidad de fabricaciĂłn de materiales compuestos cermets asĂ como los cambios en la densidad, la dureza y la tenacidad a la fractura, con respecto al cerámico 3Al2O3*2SiO2 sin refuerzo metálico
Early diagnosis is associated with improved clinical outcomes in benign esophageal perforation: an individual patient data meta-anal
Background: Time of diagnosis (TOD) of benign esophageal perforation is regarded as an important risk factor for clinical outcome, although convincing evidence is lacking. The aim of this study is to assess whether time between onset of perforation and diagnosis is associated with clinical outcome in patients with iatrogenic esophageal perforation (IEP) and Boerhaave’s syndrome (BS). Methods: We searched MEDLINE, Embase and Cochrane library through June 2018 to identify studies. Authors were invited to share individual patient data and a meta-analysis was performed (PROSPERO: CRD42018093473). Patients were subdivided in early (≤ 24 h) and late (> 24 h) TOD and compared with mixed effects multivariable analysis while adjusting age, gender, location of perforation, initial treatment and center. Primary outcome was overall mortality. Secondary outcomes were length of hospital stay, re-interventions and ICU admission. Results: Our meta-analysis included IPD of 25 studies including 576 patients with IEP and 384 with BS. In IEP, early TOD was not associated with overall mortality (8% vs. 13%, OR 2.1, 95% CI 0.8–5.1), but was associated with a 23% decrease in ICU admissions (46% vs. 69%, OR 3.0, 95% CI 1.2–7.2), a 22% decrease in re-interventions (23% vs. 45%, OR 2.8, 95% CI 1.2–6.7) and a 36% decrease in length of hospital stay (14 vs. 22 days, p 24 h) in benign esophageal perforations, particularly in IEP, is associated with improved clinical outcome
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