Selection of modalities, prescription, and technical issues in children on peritoneal dialysis

Peritoneal dialysis (PD) is widely employed as a dialytic therapy for uraemic children, especially in its automated form (APD), that is associated with less burden of care on patient and family than continuous ambulatory PD. Since APD offers a wide range of treatment options, based on intermittent and continuous regimens, prescription can be individualized according to patient’s age, body size, residual renal function, nutritional intake, and growth-related metabolic needs. Transport capacity of the peritoneal membrane of each individual patient should be assessed, and regularly monitored, by means of standardized peritoneal function tests validated in pediatric patients. To ensure maximum recruitment of peritoneal exchange area, fill volume should be scaled to body surface area and adapted to each patient, according to clinical tolerance and intraperitoneal pressure. PD solutions should be employed according to their biocompatibility and potential ultrafiltration capacity; new pH-neutral, glucose-free solutions can be used in an integrated way in separate dwells, or by appropriately mixing during the same dialytic session. Kinetic modelling software programs may help in the tailoring of PD prescription to individual patients’ characteristics and needs. Owing to advances in the technology of new APD machines, greater programming flexibility, memorized delivery control, and tele-dialysis are currently possible

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

E2F1-Mediated Upregulation of p19INK4d Determines Its Periodic Expression during Cell Cycle and Regulates Cellular Proliferation

BACKGROUND: A central aspect of development and disease is the control of cell proliferation through regulation of the mitotic cycle. Cell cycle progression and directionality requires an appropriate balance of positive and negative regulators whose expression must fluctuate in a coordinated manner. p19INK4d, a member of the INK4 family of CDK inhibitors, has a unique feature that distinguishes it from the remaining INK4 and makes it a likely candidate for contributing to the directionality of the cell cycle. p19INK4d mRNA and protein levels accumulate periodically during the cell cycle under normal conditions, a feature reminiscent of cyclins. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we demonstrate that p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter. Ablation of this regulation reduced p19 levels and restricted its expression during the cell cycle, reflecting the contribution of a transcriptional effect of E2F1 on p19 periodicity. The induction of p19INK4d is delayed during the cell cycle compared to that of cyclin E, temporally separating the induction of these proliferative and antiproliferative target genes. Specific inhibition of the E2F1-p19INK4d pathway using triplex-forming oligonucleotides that block E2F1 binding on p19 promoter, stimulated cell proliferation and increased the fraction of cells in S phase. CONCLUSIONS/SIGNIFICANCE: The results described here support a model of normal cell cycle progression in which, following phosphorylation of pRb, free E2F induces cyclin E, among other target genes. Once cyclinE/CDK2 takes over as the cell cycle driving kinase activity, the induction of p19 mediated by E2F1 leads to inhibition of the CDK4,6-containing complexes, bringing the G1 phase to an end. This regulatory mechanism constitutes a new negative feedback loop that terminates the G1 phase proliferative signal, contributing to the proper coordination of the cell cycle and provides an additional mechanism to limit E2F activity

CDK2 and PKA Mediated-Sequential Phosphorylation Is Critical for p19INK4d Function in the DNA Damage Response

DNA damage triggers a phosphorylation-based signaling cascade known as the DNA damage response. p19INK4d, a member of the INK4 family of CDK4/6 inhibitors, has been reported to participate in the DNA damage response promoting DNA repair and cell survival. Here, we provide mechanistic insight into the activation mechanism of p19INK4d linked to the response to DNA damage. Results showed that p19INK4d becomes phosphorylated following UV radiation, β-amyloid peptide and cisplatin treatments. ATM-Chk2/ATR-Chk1 signaling pathways were found to be differentially involved in p19INK4d phosphorylation depending on the type of DNA damage. Two sequential phosphorylation events at serine 76 and threonine 141 were identified using p19INK4d single-point mutants in metabolic labeling assays with 32P-orthophosphate. CDK2 and PKA were found to participate in p19INK4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19INK4d induced by DNA damage was shown to be dependent on serine 76 phosphorylation. Most importantly, both phosphorylation sites were found to be crucial for p19INK4d function in DNA repair and cell survival. In contrast, serine 76 and threonine 141 were dispensable for CDK4/6 inhibition highlighting the independence of p19INK4d functions, in agreement with our previous findings. These results constitute the first description of the activation mechanism of p19INK4d in response to genotoxic stress and demonstrate the functional relevance of this activation following DNA damage

Measurement of the W±Z boson pair-production cross section in pp collisions at √s=13TeV with the ATLAS detector

published_or_final_versio

Search for anomalous couplings in the W tb vertex from the measurement of double differential angular decay rates of single top quarks produced in the t-channel with the ATLAS detector

The electroweak production and subsequent decay of single top quarks is determined by the properties of the Wtb vertex. This vertex can be described by the complex parameters of an effective Lagrangian. An analysis of angular distributions of the decay products of single top quarks produced in the t -channel constrains these parameters simultaneously. The analysis described in this paper uses 4.6 fb−1 of proton-proton collision data at √s =7 TeV collected with the ATLAS detector at the LHC. Two parameters are measured simultaneously in this analysis. The fraction f 1 of decays containing transversely polarised W bosons is measured to be 0.37 ± 0.07 (stat.⊕syst.). The phase δ − between amplitudes for transversely and longitudinally polarised W bosons recoiling against left-handed b-quarks is measured to be −0.014π ± 0.036π (stat.⊕syst.). The correlation in the measurement of these parameters is 0.15. These values result in two-dimensional limits at the 95% confidence level on the ratio of the complex coupling parameters g R and V L, yielding Re[g R /V L] ∈ [−0.36, 0.10] and Im[g R /V L] ∈ [−0.17, 0.23] with a correlation of 0.11. The results are in good agreement with the predictions of the Standard Model

Measurement of the transverse polarization of Λ and Λ¯ hyperons produced in proton-proton collisions at √s=7 TeV using the ATLAS detector

The transverse polarization of Λ and Λ¯ hyperons produced in proton-proton collisions at a center-of-mass energy of 7 TeV is measured. The analysis uses 760  μb−1 of minimum bias data collected by the ATLAS detector at the LHC in the year 2010. The measured transverse polarization averaged over Feynman xF from 5×10−5 to 0.01 and transverse momentum pT from 0.8 to 15 GeV is −0.010±0.005(stat)±0.004(syst) for Λ and 0.002±0.006(stat)±0.004(syst) for Λ¯. It is also measured as a function of xF and pT, but no significant dependence on these variables is observed. Prior to this measurement, the polarization was measured at fixed-target experiments with center-of-mass energies up to about 40 GeV. The ATLAS results are compatible with the extrapolation of a fit from previous measurements to the xF range covered by this measurement

Measurement of Higgs boson production in the diphoton decay channel in pp collisions at center-of-mass energies of 7 and 8 TeV with the ATLAS detector

A measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5  fb[superscript −1] of proton-proton collisions data at √s=7  TeV and 20.3  fb[superscript −1] at √s=8  TeV collected by the ATLAS detector at the Large Hadron Collider. The number of observed Higgs boson decays to diphotons divided by the corresponding Standard Model prediction, called the signal strength, is found to be μ=1.17±0.27 at the value of the Higgs boson mass measured by ATLAS, m[subscript H]=125.4  GeV. The analysis is optimized to measure the signal strengths for individual Higgs boson production processes at this value of m[subscript H]. They are found to be μ[subscript ggF]=1.32±0.38, μ[subscript VBF]=0.8±0.7, μ[subscript WH]=1.0±1.6, μ[subscript ZH]=0.1[superscript +3.7 subscript −0.1], and μ[subscript t [bar over t] H] =1.6[superscript +2.7 subscript −1.8], for Higgs boson production through gluon fusion, vector-boson fusion, and in association with a W or Z boson or a top-quark pair, respectively. Compared with the previously published ATLAS analysis, the results reported here also benefit from a new energy calibration procedure for photons and the subsequent reduction of the systematic uncertainty on the diphoton mass resolution. No significant deviations from the predictions of the Standard Model are found.European Organization for Nuclear ResearchUnited States. Dept. of EnergyNational Science Foundation (U.S.)Brookhaven National Laborator

Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC

Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators

Measurement of the inelastic proton-proton cross section at √s=13 TeV with the ATLAS detector at the LHC

This Letter presents a measurement of the inelastic proton-proton cross section using 60  μb −1 of pp collisions at a center-of-mass energy √s of 13 TeV with the ATLAS detector at the LHC. Inelastic interactions are selected using rings of plastic scintillators in the forward region (2.0710 −6 , where M X is the larger invariant mass of the two hadronic systems separated by the largest rapidity gap in the event. In this ξ range the scintillators are highly efficient. For diffractive events this corresponds to cases where at least one proton dissociates to a system with M X >13  GeV . The measured cross section is compared with a range of theoretical predictions. When extrapolated to the full phase space, a cross section of 78.1±2.9  mb is measured, consistent with the inelastic cross section increasing with center-of-mass energy