Glioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing aggressiveness through blood vessel obstruction events

Background: Glioblastoma (GBM) is one of the most lethal tumor types. Hypercellular regions, named pseudo- palisades, are characteristic in these tumors and have been hypothesized to be waves of migrating glioblastoma cells.These “waves” of cells are thought to be induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. Although the universal presence of these structures in GBM tumors suggests that they may play an instrumental role in GBM’s spread and invasion, the recreation of these structures in vitro has remained challenging. Methods: Here we present a new microfluidic model of GBM that mimics the dynamics of pseudopalisade forma- tion.To do this, we embedded U-251 MG cells within a collagen hydrogel in a custom-designed microfluidic device. By controlling the medium flow through lateral microchannels, we can mimic and control blood-vessel obstruction events associated with this disease. Results: Through the use of this new system, we show that nutrient and oxygen starvation triggers a strong migratory process leading to pseudopalisade generation in vitro.These results validate the hypothesis of pseudo- palisade formation and show an excellent agreement with a systems-biology model based on a hypoxia-driven phenomenon. Conclusions: This paper shows the potential of microfluidic devices as advanced artificial systems capable of mod- eling in vivo nutrient and oxygen gradients during tumor evolution

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

An Overview of the 2014 ALMA Long Baseline Campaign

A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ~15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from September to late November 2014, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at ~350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in the Astrophysical Journal Letters; this version with small changes to affiliation

Medical record linkage in health information systems by approximate string matching and clustering

BACKGROUND: Multiplication of data sources within heterogeneous healthcare information systems always results in redundant information, split among multiple databases. Our objective is to detect exact and approximate duplicates within identity records, in order to attain a better quality of information and to permit cross-linkage among stand-alone and clustered databases. Furthermore, we need to assist human decision making, by computing a value reflecting identity proximity. METHODS: The proposed method is in three steps. The first step is to standardise and to index elementary identity fields, using blocking variables, in order to speed up information analysis. The second is to match similar pair records, relying on a global similarity value taken from the Porter-Jaro-Winkler algorithm. And the third is to create clusters of coherent related records, using graph drawing, agglomerative clustering methods and partitioning methods. RESULTS: The batch analysis of 300,000 "supposedly" distinct identities isolates 240,000 true unique records, 24,000 duplicates (clusters composed of 2 records) and 3,000 clusters whose size is greater than or equal to 3 records. CONCLUSION: Duplicate-free databases, used in conjunction with relevant indexes and similarity values, allow immediate (i.e.: real-time) proximity detection when inserting a new identity

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Intraoperative and external radiotherapy in resected gastric cancer: updated report of a phase II trial

From September 1984 to August 1991, 48 evaluable patients with resected gastric cancer and apparent disease confined to locoregional area were treated with intraoperative electron beam boost to the celiac axis and peripancreatic nodal areas (15 Gy) and external irradiation (40 to 46 Gy in 4 to 5 weeks) including the gastric bed and upper abdominal nodal draining regions. At the time of evaluation for IORT, the disease was primary in 38 cases, recurrent but resectable in four (anastomosis), and unresectable in four (nodal). Post operative complications were reversible. Acute tolerance to the complete treatment program was acceptable. Late complications included life-threatening events: Six episodes of gastro intestinal bleeding (three of them had an arteriographic documentation of arterioenteric fistula) and nine with severe enteritis (five required reoperation). Other long-term treatment related complications were six cases of vertebral collapse. The median follow-up time for the entire group is 22 months. Locoregional recurrence/persistence of disease has been identified in five patients (three with residual and/or recurrent postsurgical tumor). Systemic tumor progression has been detected in 15 patients (11 in intra-abdominal sites). Overall actuarial survival for patients with positive or negative serosal involvement was 33% versus 56%. It is concluded that the treatment program described is able to induce a high locoregional tumor control rate (100%) when used strictly in an adjuvant setting and might control long term, a small portion of patients not amenable for curative surgery (2 out of 8 patients with confirmed residual post-surgical disease). Gastrointestinal bleeding and enteritis are findings that indicate treatment intensity at the upper limits of tissue tolerance. Assessment of long term tolerance of pancreatic parenchyma and large blood vessels (tissues included in the IRORT field) are pending for longer follow-up and the appropriate selective studies

Search for charginos in e+e- interactions at sqrt(s) = 189 GeV

An update of the searches for charginos and gravitinos is presented, based on a data sample corresponding to the 158 pb^{-1} recorded by the DELPHI detector in 1998, at a centre-of-mass energy of 189 GeV. No evidence for a signal was found. The lower mass limits are 4-5 GeV/c^2 higher than those obtained at a centre-of-mass energy of 183 GeV. The (\mu,M_2) MSSM domain excluded by combining the chargino searches with neutralino searches at the Z resonance implies a limit on the mass of the lightest neutralino which, for a heavy sneutrino, is constrained to be above 31.0 GeV/c^2 for tan(beta) \geq 1.Comment: 22 pages, 8 figure

Hadronization properties of b quarks compared to light quarks in e+e- -> q qbar from 183 to 200 GeV

The DELPHI detector at LEP has collected 54 pb^{-1} of data at a centre-of-mass energy around 183 GeV during 1997, 158 pb^{-1} around 189 GeV during 1998, and 187 pb^{-1} between 192 and 200 GeV during 1999. These data were used to measure the average charged particle multiplicity in e+e- -> b bbar events, _{bb}, and the difference delta_{bl} between _{bb} and the multiplicity, _{ll}, in generic light quark (u,d,s) events: delta_{bl}(183 GeV) = 4.55 +/- 1.31 (stat) +/- 0.73 (syst) delta_{bl}(189 GeV) = 4.43 +/- 0.85 (stat) +/- 0.61 (syst) delta_{bl}(200 GeV) = 3.39 +/- 0.89 (stat) +/- 1.01 (syst). This result is consistent with QCD predictions, while it is inconsistent with calculations assuming that the multiplicity accompanying the decay of a heavy quark is independent of the mass of the quark itself.Comment: 13 pages, 2 figure

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio

Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP

Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure