The impact of childhood cancer on parents' socio-economic situation-A systematic review.

OBJECTIVE: Taking care of children diagnosed with cancer may have considerable consequences on parents' socio-economic situation. Our systematic review aimed to evaluate and synthesise the evidence on the impact of childhood cancer on parents' socio-economic situation. METHODS: Systematic literature searches for articles published between January 2000 and January 2019 were performed in PubMed, Scopus, and PsycINFO. Findings of eligible articles were narratively synthesised and quality appraised. RESULTS: Our systematic review included 35 eligible articles. Childhood cancer had a substantial impact on parents' socio-economic situation across all studies. This impact varied largely by geographical region. We observed a high prevalence of disruptions in parental employment such as job quitting or job loss, particularly among mothers. The associated income losses further contributed to families' perceived financial burden in addition to increased cancer-related expenses. Adverse socio-economic consequences were most pronounced shortly after diagnosis, however, persisted into early survivorship for certain groups of parents. We identified families of children diagnosed with haematological cancers, younger age at diagnosis, and lower parental socio-economic position to be at particular risk for adverse socio-economic consequences. CONCLUSIONS: Following the child's cancer diagnosis, parents experience a broad range of adverse socio-economic consequences. Further effort is needed to systematically implement an assessment of financial hardship in paediatric oncology together with appropriate support services along the cancer trajectory

Pharmacokinetic Properties of Liraglutide as Adjunct to Insulin in Subjects with Type 1 Diabetes Mellitus.

BACKGROUND: The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D. METHODS: Subjects (18-64 years; body mass index 20.0-28.0 kg/m(2); glycated hemoglobin ≤9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration-time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D. RESULTS: The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration-time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose-normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D. CONCLUSIONS: Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665

Diffuse idiopathic skeletal hyperostosis (DISH): relation to vertebral fractures and bone density

UnlabelledRadiographs and spinal bone mineral density (BMD) were evaluated from 342 elderly men regarding possible effects of diffuse idiopathic skeletal hyperostosis (DISH) on vertebral fractures and densitometry measurements. Prevalent vertebral fractures were more frequent among men with DISH compared to men with no DISH even after fracture prevalence was adjusted for BMD. Paravertebral calcifications should be considered in patients with DISH when interpreting BMD measurements because both dual X-ray absorptiometry (DXA) and quantitative CT (QCT) densitometry may not be reliable.IntroductionThe purpose of this study is to evaluate the prevalence of DISH in older men and its association with vertebral fractures and with BMD determined by DXA and QCT.MethodsLateral radiographs of the spine were analyzed in a sample of 342 men aged ≥ 65 years participating in the MrOS Study concerning the presence and grade of DISH and vertebral fractures. Lumbar BMD was measured by both DXA (areal, grams per square centimeter) and QCT (volumetric, grams per cubic centimeter). The association between DISH, BMD, and presence of fractures was studied using χ ( 2 ) and t tests.ResultsDISH was present in 52% (178/342) of the men. Men with DISH were older (mean, 75.1 vs 73.3, p < 0.05) and more likely to have prevalent fractures (28% vs 20%, p < p = 0.09). BMD assessed with DXA (1.08 vs 1.00 g/cm(2), p ≤ 0.0001), but not with QCT (0.11 vs 0.11 g/cm3, p = 0.65), was significantly higher in men with DISH compared to men without DISH. Significantly lower BMD of men with both DISH and fractures compared to men with DISH but without fractures was only detected by QCT (-25%, 0.09 vs 0.12, p < 0.05). Both DXA BMD and QCT BMD were significantly higher in severe lumbar DISH (+22% and +31%, p < 0.0001), respectively.ConclusionDISH was associated with a higher prevalence of vertebral fractures in elderly men. Lumbar ossifications related to DISH should be considered when interpreting BMD measurements to predict their fracture risk

The anticancer activity of lytic peptides is inhibited by heparan sulfate on the surface of the tumor cells

<p>Abstract</p> <p>Background</p> <p>Cationic antimicrobial peptides (CAPs) with antitumor activity constitute a promising group of novel anticancer agents. These peptides induce lysis of cancer cells through interactions with the plasma membrane. It is not known which cancer cell membrane components influence their susceptibility to CAPs. We have previously shown that CAPs interact with the two glycosaminoglycans (GAGs), heparan sulfate (HS) and chondroitin sulfate (CS), which are present on the surface of most cells. The purpose of this study was to investigate the role of the two GAGs in the cytotoxic activity of CAPs.</p> <p>Methods</p> <p>Various cell lines, expressing different levels of cell surface GAGs, were exposed to bovine lactoferricin (LfcinB) and the designer peptide, KW5. The cytotoxic effect of the peptides was investigated by use of the colorimetric MTT viability assay. The cytotoxic effect on wild type CHO cells, expressing normal amounts of GAGs on the cell surface, and the mutant pgsA-745, that has no expression of GAGs on the cell surface, was also investigated.</p> <p>Results</p> <p>We show that cells not expressing HS were more susceptible to CAPs than cells expressing HS at the cell surface. Further, exogenously added heparin inhibited the cytotoxic effect of the peptides. Chondroitin sulfate had no effect on the cytotoxic activity of KW5 and only minor effects on LfcinB cytotoxicity.</p> <p>Conclusion</p> <p>Our results show for the first time that negatively charged molecules at the surface of cancer cells inhibit the cytotoxic activity of CAPs. Our results indicate that HS at the surface of cancer cells sequesters CAPs away from the phospholipid bilayer and thereby impede their ability to induce cytolysis.</p

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models

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