Rapid scale-up and production of active-loaded PEGylated liposomes

Manufacturing of liposomal nanomedicines (e.g. Doxil®/Caelyx®) is a challenging and slow process based on multiple-vessel and batch processing techniques. As a result, the translation of these nanomedicines from bench to bedside has been limited. Microfluidic-based manufacturing offers the opportunity to address this issue, and de-risk the wider adoption of nanomedicines. Here we demonstrate the applicability of microfluidics for continuous manufacturing of PEGylated liposomes encapsulating ammonium sulfate (250 mM). Doxorubicin was subsequently active-loaded into these pre-formed liposomes. Critical process parameters and material considerations demonstrated to influence the liposomal product attributes included solvent selection and lipid concentration, flow rate ratio, and temperature and duration used for drug loading. However, the total flow rate did not affect the liposome product characteristics, allowing high production speeds to be adopted. The final liposomal product comprised of 80–100 nm vesicles (PDI < 0.2) encapsulating ≥ 90% doxorubicin, with matching release profiles to the innovator product and is stable for at least 6 months. Additionally, vincristine and acridine orange were active-loaded into these PEGylated liposomes (≥ 90% and ~100 nm in size) using the same process. These results demonstrate the ability to produce active-loaded PEGylated liposomes with high encapsulation efficiencies and particle sizes which support tumour targeting

Measurement of the t(t)over-bar production cross section in pp collisions at root s=7 TeV in dilepton final states containing a tau

The top quark pair production cross section is measured in dilepton events with one electron or muon, and one hadronically decaying tau lepton from the decay t (t) over bar -> (l nu(l))((sic)(h)nu((sic)))b (b) over bar, (l = e, mu). The data sample corresponds to an integrated luminosity of 2.0 fb(-1) for the electron channel and 2.2 fb(-1) for the muon channel, collected by the CMS detector at the LHC. This is the first measurement of the t (t) over bar cross section explicitly including tau leptons in proton- proton collisions at root s = 7 TeV. The measured value sigma(t (t) over bar) = 143 +/- 14(stat) +/- 22(syst) +/- 3(lumi) pb is consistent with the standard model predictions

Study of Z boson production in pPb collisions at √sNN=5.02 TeV

The production of Z bosons in pPb collisions at root S-NN = 5.02 TeV is studied by the CMS experiment via the electron and muon decay channels. The inclusive cross section is compared to pp collision predictions, and found to scale with the number of elementary nucleon-nucleon collisions. The differential cross sections as a function of the Z boson rapidity and transverse momentum are measured. Though they are found to be consistent within uncertainty with theoretical predictions both with and without nuclear effects, the forward-backward asymmetry suggests the presence of nuclear effects at large rapidities. These results provide new data for constraining nuclear parton distribution functions

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals

Measurement of quark- and gluon-like jet fractions using jet charge in PbPb and pp collisions at 5.02 TeV

The momentum-weighted sum of the electric charges of particles inside a jet, known as jet charge, is sensitive to the electric charge of the particle initiating the parton shower. This paper presents jet charge distributions in root sNN = 5.02 TeV lead-lead (PbPb) and proton-proton (pp) collisions recorded with the CMS detector at the LHC. These data correspond to integrated luminosities of 404 mu b(-1)and 27.4 pb(-1)for PbPb and pp collisions, respectively. Leveraging the sensitivity of the jet charge to fundamental differences in the electric charges of quarks and gluons, the jet charge distributions from simulated events are used as templates to extract the quark- and gluon-like jet fractions from data. The modification of these jet fractions is examined by comparing pp and PbPb data as a function of the overlap of the colliding Pb nuclei (centrality). This measurement tests the color charge dependence of jet energy loss due to interactions with the quark-gluon plasma. No significant modification between different centrality classes and with respect to pp results is observed in the extracted quark- and gluon-like jet fractions.Peer reviewe

Survival outcomes of patients with cervical cancer and accompanying hydronephrosis: A systematic review of the literature

Hydronephrosis is a sign of advanced stage disease in patients with cervical cancer. Its presence is believed to negatively affect the survival of patients. To date, however, consensus in this field is still lacking. The purpose of the present systematic review is to gather the available data and to provide directions for future research in the field. We systematically searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRA and Google Scholar databases from inception till June 2018. Overall, 22 studies were included in the present systematic review that evaluated outcomes from 8521 patients with cervical cancer. The findings of our systematic review support that hydronephrosis negatively affects the overall survival of cervical cancer patients. Specifically, the reported 5-year OS hazards ratio for hydronephrosis ranged between 1.34 and 3.74. Outcomes concerning the disease-free survival of these patients were, however, less discrete. None of the included studies reported whether the decreased survival of patients with hydronephrosis was attributed to complications of obstructive uropathy such as uremia and sepsis. Thus, it remains, to date, unclear whether placement of ureteral stents or percutaneous nephrostomy may actually benefit these patients. More studies are needed to evaluate the actual impact of hydronephrosis on survival rates at the various stages of cervical cancer and to help establish consensus regarding the optimal mode of management of these patients

Grocery Waste Compost as an Alternative Hydroponic Growing Medium

Modern hydroponic substrates have contributed significantly to the popularity and progress of hydroponic cultivations worldwide, nevertheless, their development, transportation, and disposal often come at a significant environmental cost. Here we investigate the feasibility of partial to total replacement of conventional organic growing media constituents, such as cocodust (C), in a 20% perlite (P) and 80% cocodust substrate (hereafter control 8C), with compost from locally sourced grocery waste (W). For this purpose, four treatment mixtures were developed (6C:2W, 4C:4W, 2C:6W, 8W), with the grocery waste-compost fraction ranging from 20 to 80%, respectively (perlite constant at 20%). The new substrates were tested on hydroponic lettuce (Lactuca sativa var. Tanius) cultivation. During the 35-day experiment, lettuce physiology was evaluated using chlorophyll concentration [SPAD], chlorophyll fluorescence [Fv/Fm], number of leaves, and plant growth index. At harvest, the plant yield was evaluated using leaf area [cm2], leaf fresh and dry weight [g], as well as leaf firmness [g]. Results show that substrates with compost led to superior physiology and yield characteristics, with 8W inducing a significant increase in leaf area, chlorophyll concentration, dry weight, and firmness, by 11.6%, 5.4%, 19.8% and 12.8%, respectively, compared to the control treatment 8C. Results indicate that grocery waste-based compost is an excellent sustainable alternative for the soilless cultivation of lettuce. After its use in hydroponic cultivation, substrate material is safe to dispose of or be used as a soil amendment, thus contributing to a circular agro-food economy model

Random urine uric acid to creatinine and prediction of perinatal asphyxia: a meta-analysis

<p><b>Objective:</b> The purpose of the present review is to evaluate whether urine uric acid to creatinine ratio is increased in perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE), as well as to assess its predictive accuracy in the disease.</p> <p><b>Methods:</b> We used the Medline (1966–2017), Scopus (2004–2017), Clinicaltrials.gov (2008–2017), Embase (1980–2017), Cochrane Central Register of Controlled Trials CENTRAL (1999–2017), and Google Scholar (2004–2017) databases in our primary search along with the reference lists of electronically retrieved full-text papers. The hierarchical summary receiver operating characteristic (HSROC) model was used for the meta-analysis of diagnostic accuracy.</p> <p><b>Results:</b> Fourteen studies were finally included in the present review, that investigated 1226 neonates. Urinary uric acid to creatinine ratio was significantly higher in neonates with perinatal asphyxia than in healthy controls (mean differences (MD): 1.43 95%CI [1.17, 1.69]). Specifically, the mean difference for Sarnat stage 1 was 0.70 (95%CI [0.28, 1.13]), for stage 2 1.41 (95%CI [0.99, 1.84]), and for stage 3 2.71 (95%CI [2.08, 3.35]). The estimated sensitivity for the summary point was 0.90 (95%CI (0.82–0.95)), the specificity was 0.88 (95%CI (0.73–0.95)) and the diagnostic odds ratio was calculated at 63.62 (95%CI (17.08–236.96)).</p> <p><b>Conclusions:</b> Urinary uric acid to creatinine ratio is a rapid and an easily detected biomarker that may help physicians identify neonates at risk of developing perinatal asphyxia and HIE. However, large-scale prospective studies are still needed to determine its value in predicting mortality, as well as short- and long-term adverse neurological outcomes.</p

Complejidad, caos y educación

Se informa de una investigación etnográfica sobre la educación informal en escolar chileno, rural y urbano marginal, de Educación General Básica.  Se caracterizan y comparan las modalidades educativas formal, no formal e informal.  Se señala que es erróneo caracterizar a la educación informal como asistemática, refleja y espontánea, pues esconde sus potencialidades, marginándola del estudio académico y de la práctica profesional.  Se llama la atención sobre la capacidad de esos niños para aprender en ambientes informales, que contrastan con el bajo rendimiento escolar, panificado e intencionado, que los convierte en futuros desertores y marginados sociales.  Se dan algunas razones que lo explican: la complejidad, el caos, la improvisación, la imitación, el juego, la paradoja, etc., que nos son considerados apropiados por la escuela.  Se aboga por la necesidad de investigar sus características a fin de ayudar a desescolarizar la escuela.Finalmente, se caracteriza a la educación informal como un proceso de creación de relaciones posibles, a diferencia de la educación formal y no formal que son un proceso de repetición de relaciones pre-establecidas

On Solving the Initial Problem of LR Arrays

Heme-copper oxidases (HCOs) are key enzymes in prokaryotes and eukaryotes for energy production during aerobic respiration. They catalyze the reduction of the terminal electron acceptor, oxygen, and utilize the Gibbs free energy to transport protons across a membrane to generate a proton (ΔpH) and electrochemical gradient termed proton motive force (PMF), which provides the driving force for the adenosine triphosphate (ATP) synthesis. Excessive PMF is known to limit the turnover of HCOs, but the molecular mechanism of this regulatory feedback remains relatively unexplored. Here we present a single-enzyme study that reveals that cytochrome <i>bo</i>₃ from <i>Escherichia coli</i>, an HCO closely homologous to Complex IV in human mitochondria, can enter a rare, long-lifetime leak state during which proton flow is reversed. The probability of entering the leak state is increased at higher ΔpH. By rapidly dissipating the PMF, we propose that this leak state may enable cytochrome <i>bo</i>₃, and possibly other HCOs, to maintain a suitable ΔpH under extreme redox conditions