2015 Update on Acute Adverse Reactions to Gadolinium based Contrast Agents in Cardiovascular MR. Large Multi-National and Multi-Ethnical Population Experience With 37788 Patients From the EuroCMR Registry

Objectives: Specifically we aim to demonstrate that the results of our earlier safety data hold true in this much larger multi-national and multi-ethnical population. Background: We sought to re-evaluate the frequency, manifestations, and severity of acute adverse reactions associated with administration of several gadolinium- based contrast agents during routine CMR on a European level. Methods: Multi-centre, multi-national, and multi-ethnical registry with consecutive enrolment of patients in 57 European centres. Results: During the current observation 37788 doses of Gadolinium based contrast agent were administered to 37788 patients. The mean dose was 24.7 ml (range 5–80 ml), which is equivalent to 0.123 mmol/kg (range 0.01 - 0.3 mmol/kg). Forty-five acute adverse reactions due to contrast administration occurred (0.12 %). Most reactions were classified as mild (43 of 45) according to the American College of Radiology definition. The most frequent complaints following contrast administration were rashes and hives (15 of 45), followed by nausea (10 of 45) and flushes (10 of 45). The event rate ranged from 0.05 % (linear non-ionic agent gadodiamide) to 0.42 % (linear ionic agent gadobenate dimeglumine). Interestingly, we also found different event rates between the three main indications for CMR ranging from 0.05 % (risk stratification in suspected CAD) to 0.22 % (viability in known CAD). Conclusions: The current data indicate that the results of the earlier safety data hold true in this much larger multi-national and multi-ethnical population. Thus, the “off-label” use of Gadolinium based contrast in cardiovascular MR should be regarded as safe concerning the frequency, manifestation and severity of acute events

The determinants of election to the United Nations Security Council

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11127-013-0096-4.The United Nations Security Council (UNSC) is the foremost international body responsible for the maintenance of international peace and security. Members vote on issues of global importance and consequently receive perks—election to the UNSC predicts, for instance, World Bank and IMF loans. But who gets elected to the UNSC? Addressing this question empirically is not straightforward as it requires a model that allows for discrete choices at the regional and international levels; the former nominates candidates while the latter ratifies them. Using an original multiple discrete choice model to analyze a dataset of 180 elections from 1970 to 2005, we find that UNSC election appears to derive from a compromise between the demands of populous countries to win election more frequently and a norm of giving each country its turn. We also find evidence that richer countries from the developing world win election more often, while involvement in warfare lowers election probability. By contrast, development aid does not predict election

The total mass of the Large Magellanic Cloud from its perturbation on the Orphan stream

In a companion paper by Koposov et al., RR Lyrae from \textit{Gaia} Data Release 2 are used to demonstrate that stars in the Orphan stream have velocity vectors significantly misaligned with the stream track, suggesting that it has received a large gravitational perturbation from a satellite of the Milky Way. We argue that such a mismatch cannot arise due to any realistic static Milky Way potential and then explore the perturbative effects of the Large Magellanic Cloud (LMC). We find that the LMC can produce precisely the observed motion-track mismatch and we therefore use the Orphan stream to measure the mass of the Cloud. We simultaneously fit the Milky Way and LMC potentials and infer that a total LMC mass of $1.38^{+0.27}_{-0.24} \times10^{11}\,\rm{M_\odot}$ is required to bend the Orphan Stream, showing for the first time that the LMC has a large and measurable effect on structures orbiting the Milky Way. This has far-reaching consequences for any technique which assumes that tracers are orbiting a static Milky Way. Furthermore, we measure the Milky Way mass within 50 kpc to be $3.80^{+0.14}_{-0.11}\times10^{11} M_\odot$. Finally, we use these results to predict that, due to the reflex motion of the Milky Way in response to the LMC, the outskirts of the Milky Way's stellar halo should exhibit a bulk, upwards motion.Comment: 17 pages, 11 figures. Updated to version accepted to MNRAS after minor revisio

Stepwise-edited, human melanoma models reveal mutations' effect on tumor and microenvironment.

Establishing causal relationships between genetic alterations of human cancers and specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly disrupted melanoma pathways, forming nine genetically distinct cellular models of melanoma. We connected mutant melanocyte genotypes to malignant cell expression programs in vitro and in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis, and histopathology. Mutations in malignant cells also affected tumor microenvironment composition and cell states. Our melanoma models shared genotype-associated expression programs with patient melanomas, and a deep learning model showed that these models partially recapitulated genotype-associated histopathological features as well. Thus, a progressive series of genome-edited human cancer models can causally connect genotypes carrying multiple mutations to phenotype

The creation of new rotation arc to the rat latissimus dorsi musculo-cutaneous flap with delay procedures

BACKGROUND: Latissimus dorsi musculocutaneous flap is one of the most frequently performed reconstructive techniques in surgery. Latissimus dorsi muscle has two arcs of rotation. It is classified as type V muscle. This muscle can be elevated on the thoracodorsal artery to cover large defects in the anterior chest and also, the muscle can be elevated on the segmental vessels to cover midline defects posteriorly. The aim of this study was to create a new arc of rotation on a vertical axis for the muscle and investigate effectiveness of vascular and chemical delays on the latissimus dorsi muscle flap with an inferior pedicle in an experimental rat model. We hypothesized that the latissimus dorsi muscle would be based on inferior pedicle by delay procedures. METHODS: We tested two different types of delay: vascular and combination of vascular and chemical. We also tried to determine how many days of "delay" can elicit beneficial effects of vascular and combination delays in an inferior pedicled latissimus dorsi musculocutaneous flap. To accomplish this, 48 male Sprague-Dawley rats were randomly subjected to vascular or combination delay (vascular and chemical). In addition, one ear of each rat was assigned into a delay procedure and the other ear was used as a control. Results were evaluated macroscopically, and micro-angiography and histological examinations were also performed. As a result, there was a significant difference in viable flap areas between vascular delay alone and control groups (p < 0.05). RESULTS: The higher rate of flap viability was obtained in seven-day vascular delay alone. However, there was no significant difference in the viability between seven-day vascular delay and five-day vascular delay (p < 0.05), so the earliest time when the flap viability could be obtained was at five days. The rate of flap viability was significantly higher in the vascular delay combined with chemical delay than the control group (p < 0.05). CONCLUSION: The combination of vascular and chemical delays increased the rate of viability. Nevertheless, there was no significant difference between vascular delay alone and combination of vascular and chemical delays. Chemical delay did not significantly decrease the delay period. Better histological and microangiographical results were achieved in delay groups compared to control groups. We concluded that the arch of the latissimus dorsi musculocutaneous flap can be changed and the flap can be used for various purposes with the delay procedures