Culture of human cell lines by a pathogen-inactivated human platelet lysate

Alternatives to the use of fetal bovine serum (FBS) have been investigated to ensure xeno-free growth condition. In this study we evaluated the efficacy of human platelet lysate (PL) as a substitute of FBS for the in vitro culture of some human cell lines. PL was obtained by pools of pathogen inactivated human donor platelet (PLT) concentrates. Human leukemia cell lines (KG-1, K562, JURKAT, HL-60) and epithelial tumor cell lines (HeLa and MCF-7) were cultured with either FBS or PL. Changes in cell proliferation, viability, morphology, surface markers and cell cycle were evaluated for each cell line. Functional characteristics were analysed by drug sensitivity test and cytotoxicity assay. Our results demonstrated that PL can support growth and expansion of all cell lines, although the cells cultured in presence of PL experienced a less massive proliferation compared to those grown with FBS. We found a comparable percentage of viable specific marker-expressing cells in both conditions, confirming lineage fidelity in all cultures. Functionality assays showed that cells in both FBS- and PL-supported cultures maintained their normal responsiveness to adriamycin and NK cell-mediated lysis. Our findings indicate that PL is a feasible serum substitute for supporting growth and propagation of haematopoietic and epithelial cell lines with many advantages from a perspective of process standardization, ethicality and product safety

Two-year observations of the Jupiter polar regions by JIRAM on board Juno

We observed the evolution of Jupiter's polar cyclonic structures over two years between February 2017 and February 2019, using polar observations by the Jovian InfraRed Auroral Mapper, JIRAM, on the Juno mission. Images and spectra were collected by the instrument in the 5‐μm wavelength range. The images were used to monitor the development of the cyclonic and anticyclonic structures at latitudes higher than 80° both in the northern and the southern hemispheres. Spectroscopic measurements were then used to monitor the abundances of the minor atmospheric constituents water vapor, ammonia, phosphine and germane in the polar regions, where the atmospheric optical depth is less than 1. Finally, we performed a comparative analysis with oceanic cyclones on Earth in an attempt to explain the spectral characteristics of the cyclonic structures we observe in Jupiter's polar atmosphere

Health technology assessment of pathogen reduction technologies applied to plasma for clinical use

Although existing clinical evidence shows that the transfusion of blood components is becoming increasingly safe, the risk of transmission of known and unknown pathogens, new pathogens or re-emerging pathogens still persists. Pathogen reduction technologies may offer a new approach to increase blood safety. The study is the output of collaboration between the Italian National Blood Centre and the Post-Graduate School of Health Economics and Management, Catholic University of the Sacred Heart, Rome, Italy. A large, multidisciplinary team was created and divided into six groups, each of which addressed one or more HTA domains.Plasma treated with amotosalen + UV light, riboflavin + UV light, methylene blue or a solvent/detergent process was compared to fresh-frozen plasma with regards to current use, technical features, effectiveness, safety, economic and organisational impact, and ethical, social and legal implications. The available evidence is not sufficient to state which of the techniques compared is superior in terms of efficacy, safety and cost-effectiveness. Evidence on efficacy is only available for the solvent/detergent method, which proved to be non-inferior to untreated fresh-frozen plasma in the treatment of a wide range of congenital and acquired bleeding disorders. With regards to safety, the solvent/detergent technique apparently has the most favourable risk-benefit profile. Further research is needed to provide a comprehensive overview of the cost-effectiveness profile of the different pathogen-reduction techniques. The wide heterogeneity of results and the lack of comparative evidence are reasons why more comparative studies need to be performed

GMF: A Model Migration Case for the Transformation Tool Contest

Using a real-life evolution taken from the Graphical Modeling Framework, we invite submissions to explore ways in which model transformation and migration tools can be used to migrate models in response to metamodel adaptation.Comment: In Proceedings TTC 2011, arXiv:1111.440

Prioritization of high-cost new drugs for HCV: making sustainability ethical

Hepatitis C virus (HCV) infection is a major health problem worldwide. Chronic HCV infection may in the long run cause cirrhosis, hepatic decompensation and hepatocellular carcinoma, with an ultimate disease burden of at least 350,000 deaths per year worldwide. The new generation of highly effective direct acting antivirals (DAA) to treat HCV infection brings major promises to infected patients in terms of exceedingly high rates of sustained virological response (SVR) but also of tolerability, allowing even the sickest patients to be treated. Even in the face of the excellent safety and efficacy and wide theoretical applicability of these regimens, their introduction is currently facing cost and access issues denying their use to many patients in need. Health systems in all countries are facing a huge problem of distributive justice, since while they should guarantee individual rights, among which the right to health in its broader sense, therefore not limited to healing, but extended to quality of life, they must also grant equal access to the healthcare resources and keep the distribution system sustainable. In the face of a disease with a relatively unpredictable course, where many but not of all chronically infected will eventually die of liver disease, selective allocation of this costly resource is debatable. In most countries the favorite solution has been a stratification of patients for prioritization of treatment, which means allowing Interferon-free DAA treatment only in patients with advanced fibrosis or cirrhosis, while keeping on hold persons with lesser stages of liver disease. In this report, we will perform an ethical assessment addressing the issues linked to access to new therapies, prioritization and eligibility criteria, analyzing the meaning of the term “distributive justice” and the different approaches that can guide us (individualistic libertarianism, social utilitarianism and egalitarianism) on this specific matter. Even if over time the price of new DAA will be reduced through competition and eventual patent expiration, the phenomenon of high drug costs will go on in the next decades and we need adequate tools to face the problems of distributive justice that come with it

A Comparison of Model Migration Tools

International audienceModelling languages and thus their metamodels are subject to change. When a metamodel evolves, existing models may no longer conform to the evolved metamodel. To avoid rebuilding them from scratch, existing models must be migrated to conform to the evolved metamodel. Manually migrating existing models is tedious and errorprone. To alleviate this, several tools have been proposed to build a migration strategy that automates the migration of existing models. Little is known about the advantages and disadvantages of the tools in different situations. In this paper, we thus compare a representative sample of migration tools - AML, COPE, Ecore2Ecore and Epsilon Flock - using common migration examples. The criteria used in the comparison aim to support users in selecting the most appropriate tool for their situation

Characterization of Mesoscale Waves in the Jupiter NEB by Jupiter InfraRed Auroral Mapper on board Juno

In 2017, the Jupiter InfraRed Auroral Mapper (JIRAM), on board the NASA-ASI Juno mission, observed a wide longitude region (50° W–80° E in System III) that was perturbed by a wave pattern centered at 15° N in the Jupiter's North Equatorial Belt (NEB). We analyzed JIRAM data acquired on 2017 July 10 using the M-channel and on 2017 February 2 with the spectrometer. The two observations occurred at different times and at slightly different latitudes. The waves appear as clouds blocking the deeper thermal emission. The wave crests are oriented north–south, and the typical wave packet contains 10 crests and 10 troughs. We used Fourier analysis to rigorously determine the wavenumbers associated with the observed patterns at a confidence level of 90%. Wavelet analysis was also used to constrain the spatial localization of the largest energies involved in the process and determine the wavelengths carrying the major contribution. We found wavelengths ranging from 1400 to 1900 km, and generally decreasing toward the west. Where possible, we also computed a vertical location of the cloud pressure levels from the inversion of the spectral radiances measured by the JIRAM spectrometer. The waves were detected at pressure levels consistent with the NH3 as well as NH4SH clouds. Phase velocities could not be determined with sufficient confidence to discriminate whether the alternating crests and troughs are a propagating wave or a manifestation of a fluid dynamical instability

The Health Status of Dentists Exposed to Mercury from Silver Amalgam Tooth Restorations

The authors employed pharmacy utilization data to evaluate the health status of a representative sample of 600 dentists, matched to control subjects, for gender, age, geographical area, and insurance plan structure. Dentists demonstrated significantly more prescription utilization of specific illness medications than did Controls, for the following disease categories: Neuropsychological, Neurological, Respiratory, and Cardiovascular. The greater majority of pediatric and general practice dentists still use mercury amalgam restorations. This places them at greater risk than the general population for those disorders, as well as threatening the future health of America's children and adults who continue to receive silver amalgam restorations.

The role of tau in the pathological process and clinical expression of Huntington's disease.

Huntington's disease is a neurodegenerative disorder caused by an abnormal CAG repeat expansion within exon 1 of the huntingtin gene HTT. While several genetic modifiers, distinct from the Huntington's disease locus itself, have been identified as being linked to the clinical expression and progression of Huntington's disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated in Huntington's disease. We explored this association in more detail at the neuropathological, genetic and clinical level. We first investigated tau pathology by looking for the presence of hyperphosphorylated tau aggregates, co-localization of tau with mutant HTT and its oligomeric intermediates in post-mortem brain samples from patients with Huntington's disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype-phenotype analysis of a large cohort of patients with Huntington's disease (n = 960) with a particular focus on cognitive decline. We report not only on the tau pathology in the Huntington's disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some instances with mutant HTT. We confirmed this related to the disease process rather than age, by showing it is also present in two patients with young-onset Huntington's disease (26 and 40 years old at death). In addition we demonstrate that tau oligomers (suggested to be the most likely neurotoxic tau entity) are present in the Huntington's disease brains. Finally we highlight the clinical significance of this pathology by demonstrating that the MAPT haplotypes affect the rate of cognitive decline in a large cohort of patients with Huntington's disease. Our findings therefore highlight a novel important role of tau in the pathogenic process and clinical expression of Huntington's disease, which in turn opens up new therapeutic avenues for this incurable condition.The authors thank the EHDN REGISTRY Study Group investigators (listed in the Supplementary material) for collecting the data and all participating REGISTRY patients for their time and efforts, the Cambridge Brain Bank for the post-mortem tissue which is supported by a grant to the NIHR Cambridge Biomedical Research Centre and in particular to J. Wilson and Dr D. O’ Donovan. We are grateful to S. Sawcer and M. Ban in the Neurology Unit at the University of Cambridge, for their help with the genotyping, C.H. Williams-Gray at the John van Geest Centre for Brain Repair, University of Cambridge, for her help with the statistical analyses, J. Hardy, J.L. Holton, and T. Revesz at the UCL Institute of Neurology for their helpful discussions as well as K. Strand, F. Javad and A. Posada Bórbon, at the UCL Institute of Neurology, for their support with the experimental work, R. Kayed at the University of Texas Medical Branch, Galveston, for providing the TOMA and T22 antibodies. Finally, P. Tyers, R. Raha-Chowdhury, A. Tolkovsky, B. Ossola and J. Simpson for their support and encouragement throughout this work.This is the final version of the article. It was first available from Oxford University Press viahttp://dx.doi.org/10.1093/brain/awv10