Cold gas accretion in galaxies

Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53–442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC50 >8000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL

In the eye of the beholder: Eye-tracking assessment of social information processing in aggressive behavior

# The Author(s) 2009. This article is published with open access at Springerlink.com Abstract Acording to social information processing theories, aggressive children are hypersensitive to cues of hostility and threat in other people’s behavior. However, even though there is ample evidence that aggressive children over-interpret others ’ behaviors as hostile, it is unclear whether this hostile attribution tendency does actually result from overattending to hostile and threatening cues. Since encoding is posited to consist of rapid automatic processes, it is hard to assess with the selfreport measures that have been used so far. Therefore, we used a novel approach to investigate visual encoding of social information. The eye movements of thirty 10–13 year old children with lower levels and thirty children with higher levels of aggressive behavior were monitored in real time with an eyetracker, as the children viewed ten different cartoon series of ambiguous provocation situations. In addition, participants answered questions concerning encoding and interpretation. Aggressive children did not attend more to hostile cues, nor attend less to non-hostile cues than non-aggressive children. Contrary, aggressive children looked longer at non-hostile cues, but nonetheless attributed more hostile intent than their non-aggressive peers. These findings contradict the traditional bottom-up processing hypotheses that aggressive behavior would be related with failure to attend to non-hostile cues. The findings seem best explained by topdown information processing, where aggressive children’s pre-existing hostile intent schemata (1) direct attention towards schema inconsistent nonhostile cues, (2) prevent further processing and recall of such schema-inconsistent information, and (3) lead to hostil

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Accuracy and reproducibility of quantitation of left ventricular function by real-time three-dimensional echocardiography versus cardiac magnetic resonance

The aim of this study was to investigate the accuracy and reproducibility of the quantification of left ventricular (LV) function by real-time 3-dimensional echocardiography (RT3DE) using current state-of-the-art hardware and software. Compared with cardiac magnetic resonance (CMR), previous generations of hardware and software for RT3DE significantly underestimated LV volumes partly because of inherent factors such as limited spatial and temporal resolution. Also, RT3DE volumes were compared with short-axis CMR data, whereas a combined short-axis and long-axis analysis is known to be superior. Twenty-four subjects (mean age 51 +/- 12 years, 17 men) in sinus rhythm and with good to excellent 2-dimensional image quality underwent RUDE and CMR within 1 day. The acquisition of RUDE data was done with current state-of-the-art hardware and software. Two blinded experts performed off-line LV volume analysis. Global LV volumes were determined from semiautomated border detection on the basis of endocardial speckle tracking with biplane projections using QLAB version 6.0. Volumes derived by magnetic resonance imaging were quantified from combined short-axis and long-axis series. The volume-rate on RT3DE was 33 +/- 8 Hz (range 19 to 42). Excellent correlations were found (R-2 >= 0.97) between CMR and RT3DE for global LV end-diastolic volume, LV end-systolic volume, the LV ejection fraction, and LV phase volumes (24 phases/cardiac cycle). Bland-Altman analyses showed mean differences of -7.1 ml, -4.2 ml, 0.2%, and -5.8 ml and 95% limits of agreement of +/- 19.7 ml, +/- 8.3 ml, +/- 6.2%, and +/- 15.4 ml for global LV end-diastolic volume, LV end-systolic volume, the LV ejection fraction, and LV phase volumes, respectively. Interobserver variability was 5.2% for global LV end-diastolic volume, 6.4% for LV end-systolic volume, and 7.6% for the LV ejection fraction. In conclusion, in patients with good acoustic windows, RUDE using state-of-the-art technology provides accurate and reproducible measurements of global LV volumes, LV volume changes over time, and the LV ejection fraction. (C) 2008 Elsevier Inc. All rights reserved