Effects of Endotracheal Administration of Epinephrine in Cardiac Arrest of Adult and Pediatric Swine

BACKGROUND: Few studies have investigated the effects of hypovolemia on area under the curve (AUC) and the return of spontaneous circulation (ROSC) comparing adults and children in cardiac arrest.AIMS: To compare the epinephrine endotracheal (ET) administration relative to AUC, rate, time to, and odds of achieving ROSC between hypovolemic adult and pediatric cardiac arrest models.METHODS: This was an experimental study using male Adult ET and Pediatric ET swine. Pediatric ET pigs (N=7) weighed 20-30 kg representing the average weight for a child between 5 and 6 years of age. Adult ET pigs (N=7) weighed 60 to 80 kg. All were exsanguinated 35% of their blood volume. Swine were put into arrest for 2 minutes. Cardiopulmonary resuscitation (CPR) was initiated for 2 minutes; epinephrine was then administered. Blood samples were collected over 5 minutes. RESULTS: No significant difference occurred in AUC between the groups (p > 0.05). The Pediatric ET group had higher rates of ROSC and a shorter time to ROSC (p < 0.05). Pediatric ET group had a 15 times greater odds of achieving ROSC compared to the Adult ET group. CONCLUSION: Based on the results of this study, we recommend epinephrine administration via ET within the pediatric arrest model, but not for the adult

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

Nine hundred million people are infected with the soil-transmitted helminths Ascaris lumbricoides (roundworm), hookworm, and Trichuris trichiura (whipworm). However, low single-dose cure rates of the benzimidazole drugs, the mainstay of preventative chemotherapy for whipworm, together with parasite drug resistance, mean that current approaches may not be able to eliminate morbidity from trichuriasis. We are seeking to develop new anthelmintic drugs specifically with activity against whipworm as a priority and previously identified a hit series of dihydrobenzoxazepinone (DHB) compounds that block motility of ex vivo Trichuris muris. Here, we report a systematic investigation of the structure–activity relationship of the anthelmintic activity of DHB compounds. We synthesized 47 analogues, which allowed us to define features of the molecules essential for anthelmintic action as well as broadening the chemotype by identification of dihydrobenzoquinolinones (DBQs) with anthelmintic activity. We investigated the activity of these compounds against other parasitic nematodes, identifying DHB compounds with activity against Brugia malayi and Heligmosomoides polygyrus. We also demonstrated activity of DHB compounds against the trematode Schistosoma mansoni, a parasite that causes schistosomiasis. These results demonstrate the potential of DHB and DBQ compounds for further development as broad-spectrum anthelmintics

Overturning established chemoselectivities : selective reduction of arenes over malonates and cyanoacetates by photoactivated organic electron donors

The prevalence of metal-based reducing reagents, including metals, metal complexes, and metal salts, has produced an empirical order of reactivity that governs our approach to chemical synthesis. However, this reactivity may be influenced by stabilization of transition states, intermediates, and products through substrate-metal bonding. This article reports that in the absence of such stabilizing interactions, established chemoselectivities can be overthrown. Thus, photoactivation of the recently developed neutral organic superelectron donor 5 selectively reduces alkyl-substituted benzene rings in the presence of activated esters and nitriles, in direct contrast to metal-based reductions, opening a new perspective on reactivity. The altered outcomes arising from the organic electron donors are attributed to selective interactions between the neutral organic donors and the arene rings of the substrates

EAU-EANM Consensus Statements on the Role of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Patients with Prostate Cancer and with Respect to [177Lu]Lu-PSMA Radioligand Therapy

Funding support and role of sponsor: The EAU/EANM PSMA-based imaging and therapy consensus meeting was supported by an unrestricted educational grant from Novartis; Novartis had no influence over the content of the meeting or the publication. Medical writing support was funded by the European Association of Urology Research Foundation. Acknowledgements: The authors acknowledge Emily Spieker (Management Assistant, European Association of Urology) for project management. Medical writing support was provided by Angela Corstorphine of Kstorfin Medical Communications (KMC) limited.Peer reviewedPublisher PD

Very Large Array Radio Study of a Sample of Nearby X-Ray and Optically Bright Early-type Galaxies

Abstract Many massive early-type galaxies host central radio sources and hot X-ray atmospheres indicating the presence of radio-mechanical active galactic nucleus (AGN) feedback. The duty cycle and detailed physics of the radio-mode AGN feedback is still a matter of debate. To address these questions, we present 1–2 GHz Karl G. Jansky Very Large Array radio observations of a sample of the 42 nearest optically and X-ray brightest early-type galaxies. We detect radio emission in 41/42 galaxies. However, the galaxy without a radio source, NGC 499, has recently been detected at lower frequencies by the Low-Frequency Array. Furthermore, 27/42 galaxies in our sample host extended radio structures and 34/42 sources show environmental interactions in the form of X-ray cavities. We find a significant correlation between the radio flux density and the largest linear size of the radio emission and between the radio power and the luminosity of the central X-ray point source. The central radio spectral indices of the galaxies span a wide range of values, with the majority of the systems having steep spectra and the rest flat spectra. These results are consistent with AGN activity, where the central radio sources are mostly switched on, thus the duty cycle is very high. Seven out of 14 galaxies with pointlike radio emission (Fanaroff–Riley Class 0; FR 0) also show X-ray cavities indicating that, despite the lack of extended radio structures at 1–2 GHz, these AGNs do launch jets capable of inflating lobes and cavities.</jats:p

Alterations in anatomic and functional imaging parameters with repeated FDG PET-CT and MRI during radiotherapy for head and neck cancer: a pilot study

Background: The use of imaging to implement on-treatment adaptation of radiotherapy is a promising paradigm but current data on imaging changes during radiotherapy is limited. This is a hypothesis-generating pilot study to examine the changes on multi-modality anatomic and functional imaging during (chemo)radiotherapy treatment for head and neck squamous cell carcinoma (HNSCC). Methods: Eight patients with locally advanced HNSCC underwent imaging including computed tomography (CT), Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT and magnetic resonance imaging (MRI) (including diffusion weighted (DW) and dynamic contrast enhanced (DCE)) at baseline and during (chemo)radiotherapy treatment (after fractions 11 and 21). Regions of interest (ROI) were drawn around the primary tumour at baseline and during treatment. Imaging parameters included gross tumour volume (GTV) assessment, SUVmax, mean ADC value and DCE-MRI parameters including Plasma Flow (PF). On treatment changes and correlations between these parameters were analysed using a Wilcoxon rank sum test and Pearson’s linear correlation coefficient respectively. A p-value <0.05 was considered statistically significant. Results: Statistically significant reductions in GTV-CT, GTV-MRI and GTV-DW were observed between all imaging timepoints during radiotherapy. Changes in GTV-PET during radiotherapy were heterogeneous and non-significant. Significant changes in SUVmax, mean ADC value, Plasma Flow and Plasma Volume were observed between the baseline and the fraction 11 timepoint, whilst only changes in SUVmax between baseline and the fraction 21 timepoint were statistically significant. Significant correlations were observed between multiple imaging parameters, both anatomical and functional; 20 correlations between baseline to the fraction 11 timepoint; 12 correlations between baseline and the fraction 21 timepoints; and 4 correlations between the fraction 11 and fraction 21 timepoints. Conclusions: Multi-modality imaging during radiotherapy treatment demonstrates early changes (by fraction 11) in both anatomic and functional imaging parameters. All functional imaging modalities are potentially complementary and should be considered in combination to provide multi-parametric tumour assessment, to guide potential treatment adaptation strategies. Trial Registration: ISRCTN Registry: ISRCTN34165059. Registered 2nd February 2015

The influence of fines content and size-ratio on the micro-scale properties of dense bimodal materials

This paper considers factors influencing the fabric of bimodal or gap-graded soils. Discrete element method simulations were carried out in which the volumetric fines content and the size ratio between coarse and fine particles were systematically varied. Frictionless particles were used during isotropic compression to create dense samples; the coefficient of friction was then set to match that of spherical glass beads. The particle-scale data generated in the simulations revealed key size ratios and fines contents at which transitions in soil fabric occur. These transitions are identified from changes in the contact distributions and stress-transfer characteristics of the soils and by changes in the size of the void space between the coarse particles. The results are broadly in agreement with available experimental data on minimum void ratio and contact distributions. The results have implications for engineering applications including assessment of the internal stability of gap-graded soils in embankment dams and flood embankments

The Mid-infrared Instrument for JWST and Its In-flight Performance

The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI