Rayleigh-B\'{e}nard convection in a homeotropically aligned nematic liquid crystal

We report experimental results for convection near onset in a thin layer of a homeotropically aligned nematic liquid crystal heated from below as a function of the temperature difference $\Delta T$ and the applied vertical magnetic field $H$ and compare them with theoretical calculations. The experiments cover the field range 8 \alt h \equiv H/ H_{F} \alt 80 ($H_F =$ is the Fr\'eedericksz field). For $h$ less than a codimension-two field $h_{ct} \simeq 46$ the bifurcation is subcritical and oscillatory, with travelling- and standing-wave transients. Beyond $h_{ct}$ the bifurcation is stationary and subcritical until a tricritical field $h_t= 57.2$ is reached, beyond which it is supercritical. The bifurcation sequence as a function of $h$ found in the experiment confirms the qualitative aspects of the theoretical predictions. However, the value of $h_{ct}$ is about 10% higher than the predicted value and the results for $k_c$ are systematically below the theory by about 2% at small $h$ and by as much as 7% near $h_{ct}$. At $h_{ct}$, $k_c$ is continuous within the experimental resolution whereas the theory indicates a 7% discontinuity. The theoretical tricritical field $h_t^{th} = 51$ is somewhat below the experimental one. The fully developed flow above $R_c$ for $h < h_{ct}$ is chaotic. For $h_{ct} < h < h_t$ the subcritical stationary bifurcation also leads to a chaotic state. The chaotic states persist upon reducing the Rayleigh number below $R_c$, i.e. the bifurcation is hysteretic. Above the tricritical field $h_t$, we find a bifurcation to a time independent pattern which within our resolution is non-hysteretic.Comment: 15 pages incl. 23 eps figure

Dynamics and Selection of Giant Spirals in Rayleigh-Benard Convection

For Rayleigh-Benard convection of a fluid with Prandtl number \sigma \approx 1, we report experimental and theoretical results on a pattern selection mechanism for cell-filling, giant, rotating spirals. We show that the pattern selection in a certain limit can be explained quantitatively by a phase-diffusion mechanism. This mechanism for pattern selection is very different from that for spirals in excitable media

Whirling Hexagons and Defect Chaos in Hexagonal Non-Boussinesq Convection

We study hexagon patterns in non-Boussinesq convection of a thin rotating layer of water. For realistic parameters and boundary conditions we identify various linear instabilities of the pattern. We focus on the dynamics arising from an oscillatory side-band instability that leads to a spatially disordered chaotic state characterized by oscillating (whirling) hexagons. Using triangulation we obtain the distribution functions for the number of pentagonal and heptagonal convection cells. In contrast to the results found for defect chaos in the complex Ginzburg-Landau equation and in inclined-layer convection, the distribution functions can show deviations from a squared Poisson distribution that suggest non-trivial correlations between the defects.Comment: 4 mpg-movies are available at http://www.esam.northwestern.edu/~riecke/lit/lit.html submitted to New J. Physic

Inhibition of insulin-like growth factor-1 receptor signaling enhances growth-inhibitory and proapoptotic effects of gefitinib (Iressa) in human breast cancer cells

INTRODUCTION: Gefitinib (Iressa, ZD 1839, AstraZeneca) blocks the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and inhibits proliferation of several human cancer cell types including breast cancer. Phase II clinical trials with gefitinib monotherapy showed an objective response of 9 to 19% in non-small-cell lung cancer patients and less than 10% for breast cancer, and phase III results have indicated no benefit of gefitinib in combination with chemotherapy over chemotherapy alone. In order to improve the antineoplastic activity of gefitinib, we investigated the effects of blocking the signalling of the insulin-like growth factor 1 receptor (IGF-1R), a tyrosine kinase with a crucial role in malignancy that is coexpressed with EGFR in most human primary breast carcinomas. METHODS: AG1024 (an inhibitor of IGF-1R) was used with gefitinib for treatment of MDA468, MDA231, SK-BR-3, and MCF-7 breast cancer lines, which express similar levels of IGF-1R but varying levels of EGFR. Proliferation assays, apoptosis induction studies, and Western blot analyses were conducted with cells treated with AG1024 and gefitinib as single agents and in combination. RESULTS: Gefitinib and AG1024 reduced proliferation in all lines when used as single agents, and when used in combination revealed an additive-to-synergistic effect on cell growth inhibition. Flow cytometry measurements of cells stained with annexin V-propidium iodide and cells stained for caspase-3 activation indicated that adding an IGF-1R-targeting strategy to gefitinib results in higher levels of apoptosis than are achieved with gefitinib alone. Gefitinib either reduced or completely inhibited p42/p44 Erk kinase phosphorylation, depending on the cell line, while Akt phosphorylation was reduced by a combination of the two agents. Overexpression of IGF-1R in SK-BR-3 cells was sufficient to cause a marked enhancement in gefitinib resistance. CONCLUSION: These results indicate that IGF-1R signaling reduces the antiproliferative effects of gefitinib in several breast cancer cell lines, and that the addition of an anti-IGF-1R strategy to gefitinib treatment may be more effective than a single-agent approach

Should adrenaline be used in patients with hemodynamically stable anaphylaxis? Incident case control study nested within a retrospective cohort study

Although adrenaline (epinephrine) is a cornerstone of initial anaphylaxis treatment, it is not often used. We sought to assess whether use of adrenaline in hemodynamically stable patients with anaphylaxis could prevent the development of hypotension. We conducted a retrospective cohort study of 761 adult patients with anaphylaxis presenting to the emergency department (ED) of a tertiary care hospital over a 10-year period. We divided the patients into two groups according to the occurrence of hypotension and compared demographic characteristics, clinical features, treatments and outcomes. Of the 340 patients with anaphylaxis who were normotensive at first presentation, 40 patients experienced hypotension during their ED stay. The ED stay of the hypotension group was significantly longer than that of patients who did not experience hypotension (496 min vs 253 min, P = 0.000). Adrenaline use in hemodynamically stable anaphylaxis patient was independently associated with a lower risk of developing in-hospital occurrence of hypotension: OR, 0.254 [95% CI, 0.091-0.706]. Adrenaline use in hemodynamically stable anaphylaxis patients was associated with a reduced risk of developing in-hospital occurrence of hypotension. Adverse events induced by adrenaline were rare when the intramuscular route was used

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2021 revision and update

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients

The international WAO/EAACI guideline for the management of hereditary angioedema - The 2021 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients

Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly) innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km) for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR) of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP) pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways

Multimessenger NuEM Alerts with AMON

The Astrophysical Multimessenger Observatory Network (AMON), has developed a real-time multi-messenger alert system. The system performs coincidence analyses of datasets from gamma-ray and neutrino detectors, making the Neutrino-Electromagnetic (NuEM) alert channel. For these analyses, AMON takes advantage of sub-threshold events, i.e., events that by themselves are not significant in the individual detectors. The main purpose of this channel is to search for gamma-ray counterparts of neutrino events. We will describe the different analyses that make-up this channel and present a selection of recent results

Searching for VHE gamma-ray emission associated with IceCube neutrino alerts using FACT, H.E.S.S., MAGIC, and VERITAS

The realtime follow-up of neutrino events is a promising approach to searchfor astrophysical neutrino sources. It has so far provided compelling evidencefor a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 observedin coincidence with the high-energy neutrino IceCube-170922A detected byIceCube. The detection of very-high-energy gamma rays (VHE, $\mathrm{E} >100\,\mathrm{GeV}$) from this source helped establish the coincidence andconstrained the modeling of the blazar emission at the time of the IceCubeevent. The four major imaging atmospheric Cherenkov telescope arrays (IACTs) -FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program oftarget-of-opportunity observations of neutrino alerts sent by IceCube. Thisprogram has two main components. One are the observations of known gamma-raysources around which a cluster of candidate neutrino events has been identifiedby IceCube (Gamma-ray Follow-Up, GFU). Second one is the follow-up of singlehigh-energy neutrino candidate events of potential astrophysical origin such asIceCube-170922A. GFU has been recently upgraded by IceCube in collaborationwith the IACT groups. We present here recent results from the IACT follow-upprograms of IceCube neutrino alerts and a description of the upgraded IceCubeGFU system.<br