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Rydberg excited states of the OCS molecule in the energy range 70500–86000 cm-1 have been investigated via the two and three photon resonance enhancements they provide in the mass resolved multiphoton ionization (MPI) spectrum of a jet-cooled sample of the parent molecule. Spectral interpretation has been assisted by companion measurements of the kinetic energies of the photoelectrons that accompany the various MPI resonances. The present study supports the earlier conclusions of Weinkauf and Boesl [J. Chem. Phys. 98, 4459 (1993)] regarding five Rydberg origins in the 70500–73000 cm-1 energy range, attributable to, respectively, states of 3Π, 1Π, 3Δ, 1Δ and 1Σ+ symmetry arising from the 4pλ←3π orbital promotion. We also identify a further 21 Rydberg origins at higher energies. These partition into clumps with quantum defects ca. 3.5 and 4.5, which we associate with the orbital promotions npλ←3π (n=5,6), and others with near integer quantum defect which are interpretable in terms of excitation to s,d and (possibly) f Rydberg orbitals. We also identify MPI resonances attributable to CO(X 1Σ+) fragments and to S atoms in both their ground (3P) and excited (1D) electronic states. Analysis of the former resonances confirms that the CO(X) fragments resulting from one photon dissociation of OCS at excitation wavelengths ca. 230 nm are formed with a highly inverted, bimodal rotational state population distribution, whilst the latter are consistent with previous reports of the wavelength dependence for forming ground and excited state S atoms in the near uv photolysis of OCS. © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Rydberg excited states of the CS2 molecule in the energy range 56 000–81 000 cm-1 have been further investigated via the two and three photon resonance enhancements they provide in the mass resolved multiphoton ionization (MPI) spectrum of a jet-cooled sample of the parent molecule. Spectral interpretation has been aided by parallel measurements of the kinetic energies of the photoelectrons that accompany the various MPI resonances. Thus we have been able to extend, and clarify, previous analyses of the tangled spin–orbit split vibronic structure associated with the 3Πu and 1Πu states derived from the configuration [2Πg]4pσu and the 3Δu, 1Δu, and 1Σ+u states resulting from the configuration [2Πg]4pπu, and to deduce an approximate wave number for the origin of the hitherto unidentified 3Σ+u state derived from this same configuration. Moving to higher energies we are able to locate, unambiguously, the origins of the next (n=5) members of four of these [2Πg]np Rydberg series, and to identify extensive series based on the presumed Rydberg configurations [2Πg]nsσg and [2Πg]nfλu with, in both cases, n≤10. We also identify MPI resonances attributable to CS(a 3Π) fragments, to ground state C atoms, and to S atoms in both their ground (3P) and excited (1S) electronic states. Analysis of the former resonances indicates that the CS(a 3Π) fragments resulting from two photon dissociation of CS2 at excitation wavelengths around 300 nm are formed with substantial rovibrational excitation. © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Knowledge of atrial wall thickness (AWT) has the potential to provide important information for patient stratification and the planning of interventions in atrial arrhythmias. To date, information about AWT has only been acquired in post-mortem or poor-contrast computed tomography (CT) studies, providing limited coverage and highly variable estimates of AWT. We present a novel contrast agent-free MRI sequence for imaging AWT and use it to create personalized AWT maps and a biatrial atlas. A novel black-blood phase-sensitive inversion recovery protocol was used to image ten volunteers and, as proof of concept, two atrial fibrillation patients. Both atria were manually segmented to create subject-specific AWT maps using an average of nearest neighbors approach. These were then registered non-linearly to generate an AWT atlas. AWT was 2.4 ± 0.7 and 2.7 ± 0.7 mm in the left and right atria, respectively, in good agreement with post-mortem and CT data, where available. AWT was 2.6 ± 0.7 mm in the left atrium of a patient without structural heart disease, similar to that of volunteers. In a patient with structural heart disease, the AWT was increased to 3.1 ± 1.3 mm. We successfully designed an MRI protocol to non-invasively measure AWT and create the first whole-atria AWT atlas. The atlas can be used as a reference to study alterations in thickness caused by atrial pathology. The protocol can be used to acquire personalized AWT maps in a clinical setting and assist in the treatment of atrial arrhythmias. [ABSTRACT FROM PUBLISHER]

Background: Electromagnetic navigation has been approved for use as an adjunct to standard bronchoscopy. The diagnostic yield varies depending on the size of the lesion and successful navigation to the lesion. Objectives: The performance of two different biopsy tools, i.e. catheter aspiration and forceps biopsy, in the diagnosis of small pulmonary nodules (SPN) guided by electromagnetic navigational bronchoscopy (ENB) was examined. Methods: 54 patients referred for suspected lung cancer underwent ENB and 55 SPN (<3 cm) were sampled using both techniques. Endobronchial ultrasound (EBUS) was used to verify the accuracy of target lesion localization by ENB. Primary end points of the study were successful navigation to the lesion and a positive diagnosis. Patients were followed until a definitive diagnosis was obtained. Results: All 55 lesions were accessed. Two lesions were excluded from data analysis as the patients were lost to follow-up and their diagnoses could not be confirmed. Of the remaining 53 lesions, 40 samples (75.5%) were diagnostic. Compared to forceps biopsy, catheter aspiration was positively correlated with the success rate (36/40 vs. 22/40; p = 0.035). The diagnostic yield was 93% when EBUS verified the lesion location after navigation and only 48% when lesion location was not confirmed. There were no significant complications. Conclusions: ENB is a useful tool in the evaluation of SPN <3 cm in diameter. For malignant lesions, sampling by catheter aspiration is associated with a higher diagnostic yield than sampling by forceps biopsy alone, in particular when EBUS could not confirm lesion location prior to sampling. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Eosinophils interact with nerve cells, leading to changes in neurotransmitter release, altered nerve growth, and protection from cytokine-induced apoptosis. In part, these interactions occur as a result of activation of neural nuclear factor (NF)-κB, which is activated by adhesion of eosinophils to neural intercellular adhesion molecule-1 (ICAM-1). The mechanism and consequence of signaling after eosinophil adhesion to nerve cells were investigated. Eosinophil membranes, which contain eosinophil adhesion molecules but not other eosinophil products, were coincubated with IMR-32 cholinergic nerve cells. The studies showed that there were two mechanisms of activation of NF-κB, one of which was dependent on reactive oxygen species, since it was inhibited with diphenyleneiodonimn. This occurred at least 30 min after coculture of eosinophils and nerves. An earlier phase of NF-κB activation occurred within 2 min of eosinophil adhesion and was mediated by tyrosine kinase-dependent phosphorylation of interleukin-1 receptor-associated kinase 1 (IRAK-1). Co-immunoprecipitation experiments showed that both extracellular signal regulated kinase ½ and IRAK-1 were recruited to ICAM-1 rapidly after coculture with eosinophil membranes. This was accompanied by an induction of ICAM-1, which was mediated by an IRAK-l-dependent pathway. These data indicate that adhesion of eosinophils to IMR-32 nerves via ICAM-1 leads to important signaling events, mediated via IRAK-1, and these in turn lead to expression of adhesion molecules. [ABSTRACT FROM AUTHOR]

Studies whether depressive illness is related to low plasma cholesterol concentrations in men 50 years of age or older. Use of Beck depression inventories; Finding that low plasma cholesterol is associated with depressive symptoms in elderly men; Observations that very low total cholesterol may be related to suicide and violent death; Study details.

PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates the mitogen-activated protein kinase (MAPK) pathway upstream of KRAS and MEK. PTPN11/Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, the role of mutated PTPN11 in lung cancer tumourigenesis and its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from the tumour and matched the normal tissue of 356 NSCLC patients (98 adenocarcinomas (LUAD) and 258 squamous cell carcinomas (LUSC)). Further, PTPN11 mutation cases were identified in additional cohorts, including TCGA, Broad, and MD Anderson datasets and the COSMIC database. PTPN11 constructs harbouring PTPN11 E76A, A72D and C459S mutations were stably expressed in IL-3 dependent BaF3 cells and NSCLC cell lines (NCI-H1703, NCI-H157, NCI-H1299). The MAPK and PI3K pathway activation was evaluated using Western blotting. PTPN11/Shp2 phosphatase activity was measured in whole-cell protein lysates using an Shp2 assay kit. The Shp2 inhibitor (SHPi) was assessed both in vitro and in vivo in a PTPN11-mutated cell line for improved responses to MAPK and PI3K targeting therapies. Somatic PTPN11 hotspot mutations occurred in 4/98 (4.1%) adenocarcinomas and 7/258 (2.7%) squamous cells of 356 NSCLC patients. Additional 26 PTPN11 hotspot mutations occurred in 23 and 3 adenocarcinomas and squamous cell carcinoma, respectively, across the additional cohorts. Mutant PTPN11 significantly increased the IL-3 independent survival of Ba/F3 cells compared to wildtype PTPN11 (p < 0.0001). Ba/F3, NCI-H1703, and NCI-H157 cells expressing mutant PTPN11 exhibited increased PTPN11/Shp2 phosphatase activity and phospho-ERK1/2 levels compared to cells expressing wildtype PTPN11. The transduction of the PTPN11 inactivating mutation C459S into NSCLC cell lines led to decreased phospho-ERK, as well as decreased phospho-AKT in the PTPN11-mutated NCI-H661 cell line. NCI-H661 cells (PTPN11-mutated, KRAS-wild type) were significantly more sensitive to growth inhibition by the PI3K inhibitor copanlisib (IC50: 13.9 ± 4.7 nM) compared to NCI-H1703 (PTPN11/KRAS-wild type) cells (IC50: >10,000 nM). The SHP2 inhibitor, in combination with the PI3K targeting therapy copanlisib, showed no significant difference in tumour development in vivo; however, this significantly prevented MAPK pathway induction in vitro (p < 0.0001). PTPN11/Shp2 demonstrated the in vitro features of a driver oncogene and could potentially sensitize NSCLC cells to PI3K inhibition and inhibit MAPK pathway activation following PI3K pathway targeting. [ABSTRACT FROM AUTHOR]

This article presents a letter to the editor in response to "Anchors away," by C. Calfee, S. Shah and others in the February 1, 2007 issue.

Introduction: There are few existing severity scoring systems in the literature, and no formally widely accepted chest X‐ray template for reporting COVID‐19 infection. We aimed to modify the chest X‐ray COVID‐19 severity scoring system from the Brixia scoring system with placement of more emphasis on consolidation and to assess if the scoring tool could help predict intubation. Methods: A severity chest X‐ray scoring system was modified from the Brixia scoring system. PCR positive COVID‐19 positive patient's chest X‐rays admitted to our hospital over 3 months were reviewed and correlated with; non‐invasive ventilation, intubation and death. An analysis was performed using a receiver operating curve to predict intubation from all admission chest X‐rays. Results: The median score of all 325 admission chest X‐rays was 3 (Interquartile range (IQR) 0–6.5). The median score of admission chest X‐rays of those who did not require ICU admission and survived was 1.5 (IQR 0–5); and 9 (IQR 4.75–12) was median admission score of those requiring intubation. The median scores of the pre‐intubation ICU chest X‐rays was 11.5 (IQR 9–14.125), this increased from a median admission chest X‐ray score for this group of 9 (P‐value < 0.01). A cut‐off score of 6 had a sensitivity of 77% and specificity of 73% in predicting the need for intubation. Conclusion: Higher chest X‐ray severity scores are associated with intubation, need for non‐invasive ventilation and death. This tool may also be helpful in predicting intubation. [ABSTRACT FROM AUTHOR]

• Exhaled Breath (EBC) and plasma were analysed for 5 genetic alterations using ultrasensitive PCR in lung cancer patients. • Results were compared to corresponding diagnostic tissue samples analysed using targeted NextGeneration Sequencing (NGS). • Higher failure rates owing to unamplifiable DNA were noted in tissue NGS compared to EBC and Plasma. • Significantly higher numbers of mutations in EGFR, KRAS and PIK3CA were identified in EBC and plasma than tissue NGS. • Overlap and divergence was noted in the mutation profiles between EBC and plasma. Small diagnostic tissue samples can be inadequate in testing an expanding list of validated oncogenic driver alterations and fail to reflect intratumour heterogeneity (ITGH) in lung cancer. Liquid biopsies are non-invasive and may better reflect ITGH. Most liquid biopsies are performed in the context of circulating tumour DNA (ctDNA) in plasma but Exhaled Breath Condensate (EBC) shows promise as a lung-specific liquid biopsy. In this prospective, proof-of-concept study we carried out targeted Next Generation Sequencing (NGS) on diagnostic tissue samples from 125 patients with lung cancer and compared results to plasma and EBC for 5 oncogenic driver mutations (EGFR, KRAS, PIK3CA, ERBB2, BRAF) using an ultrasensitive PCR technique (UltraSEEK™ Lung Panel on the MassARRAY® System, Agena Bioscience, San Diego, CA, USA). There was a significantly higher failure rate due to unamplifiable DNA in tissue NGS (57/125, 45.6%) compared to plasma (27/125, 21.6%, p < 0.001 and EBC (26/125,20.8%, p ≤ 0.001. Consequently, both plasma and EBC identified higher number of mutations compared to tissue NGS. Specifically, there were significantly higher numbers of mutations detected in EGFR, KRAS and PIK3CA in plasma (p = 9.82 × 10−3, p = 3.14 × 10−5, p = 1.95 × 10−3) and EBC (p = 2.18 × 10−3, p = 2.28 × 10−4,p = 0.016) compared to tissue NGS. There was considerable divergence in mutation profiles between plasma and EBC with 34/76 (44%) mutations detected in plasma and 37/74 (41.89%) in EBC unique to their respective liquid biopsy. The results suggest that EBC is effective in identifying clinically relevant alterations in patients with lung cancer using UltraSEEK™ and has a potential role as an adjunct to plasma testing. [ABSTRACT FROM AUTHOR]

Background: The current COVID-19 pandemic has placed enormous strain on healthcare systems worldwide. Understanding of COVID-19 is rapidly evolving. Pneumonia associated with COVID-19 may lead to respiratory failure requiring mechanical ventilation. The rise in patients requiring mechanical ventilation may lead to an increase in tracheostomies being performed in patients with COVID-19. Performing tracheostomy in patients with active SARS-CoV-2 infection poses a number of challenges.Methods: These guidelines were written following multidisciplinary agreement between Otolaryngology, Head and Neck Surgery, Respiratory Medicine and the Department of Anaesthetics and Critical Care Medicine in the Royal College of Surgeons in Ireland. A literature review was performed and a guideline for elective tracheostomy insertion in patients with COVID-19 proposed.Conclusion: The decision to perform tracheostomy in patients with COVID-19 should be undertaken by senior members of the multidisciplinary team. Steps should be taken to minimise risks to healthcare workers. [ABSTRACT FROM AUTHOR]

Left atrial appendage (LAA) closure is being developed as an alternative for stroke prevention in patients with atrial fibrillation that cannot tolerate long-term oral anticoagulation. To assess the feasibility, safety, and performance of a novel modified Occlutech LAA closure device in a preclinical porcine model, the modified Occlutech modified Occlutech Plus LAA closure device was implanted in 12 female pigs (25–39 kg body weight) under fluoroscopic and transesophageal echocardiography (TEE) guidance. Procedural and technical success, as well as safety of LAA closure, were evaluated peri-procedurally and after 4, 8, and 12 weeks. Moreover, after 4, 8 and, 12 weeks animals were sacrificed for pathological analysis (e.g., thrombus formation, device ingrowth, endothelialization, and inflammation). All LAA closure devices were successfully implanted. On follow-up, no serious adverse events such as device-associated thrombus or translocalization/embolization were observed. A clinically non-significant pericarditis was observed in 4 animals at the time of autopsy. Endothelialization of the device was visible after 4 weeks, advanced after 8 weeks and completed after 12 weeks. Immunohistochemistry showed low amounts of inflammatory infiltration on the edges of the device. The results of this study indicate that implantation of a modified Occlutech LAA closure device is feasible with rapid endothelialization and low inflammatory infiltration in a porcine model. Human data are needed to further characterize safety and efficacy. [ABSTRACT FROM AUTHOR]

Keywords: blood group; coagulopathy; COVID-19; haemorrhage; transfusion EN blood group coagulopathy COVID-19 haemorrhage transfusion 132 134 3 12/17/20 20210101 NES 210101 Since the emergence of COVID-19 in late 2019, our knowledge of the clinical implications of infection with SARS-CoV-2 has steadily grown. In the 35 patients who required critical care, clinical and transfusion records were reviewed to determine the rates of clinically relevant non-major bleeding (CRNMB), major bleeding (MB), thrombosis and clotting of lines/circuits. Blood group, coagulopathy, COVID-19, haemorrhage, transfusion. [Extracted from the article]

Thedisposal of associated gas can be a significant impedimentto remote oilfield development. Although several associated gas managementoptions exist, most either are too costly or cannot be moved to theoilfield. The production of syngas can be achieved by a variety oftechniques, but again some of these require a dedicated air separationunit, which adds complexity and safety risks to the facility. Fischer–Tropschsynthesis has been shown to produce high-quality fuels from syngassince the late 1930s. CompactGTL has been able to develop a proprietarySMR technology for the production of syngas, which is then used inthe Fischer–Tropsch process to produce a blendable syncrude.The proprietary reactor designs and catalysts resulted in a significantreduction in the footprint of a gas-to-liquid plant, such that thesecould be installed on a floating production, storage, and offloadingvessel for access to associated gas at offshore fields. To date, CompactGTL’sfully integrated gas-to-liquid plant is the first one of its kindbeing operated at a demonstration scale. This technology allows monetizationof associated gas and/or avoids taxation by flaring of methane. [ABSTRACT FROM AUTHOR]

Enteric neural dysfunction leads to increased mucous production and dysmotility in inflammatory bowel disease (IBD). Prior studies have shown that tissue eosinophilia is related to disease activity. We hypothesized that interactions between eosinophils and nerves contribute to neural dysfunction in IBD. Tissue from patients with intractable IBD, endoscopic biopsies from patients with steroid responsive IBD, both when active and quiescent, and control tissue were studied. Immunohistochemical studies showed that eosinophils localize to nerves in the mucosal layer of patients with Crohn’s disease (CD) (p<0.001) and ulcerative colitis (UC), (p<0.01). Eosinophils localized to substance P and choline acetyltransferase (ChAT) immunostained nerves. Real time PCR of laser capture micro-dissected enteric ganglia demonstrated Intercellular Adhesion Molecule 1 (ICAM-1) mRNA was increased 7-fold in UC (n = 4), (p = 0.03), and 10-fold in CD (n = 3), (p = 0.05). Compared with controls, eotaxin-3 (CCL-26) mRNA was increased 9-fold in UC (p = 0.04) and 15-fold in CD (p = 0.06). Eosinophil numbers correlated with disease activity, while deposition of major basic protein (MBP) and eosinophil Transforming Growth Factor β -1 (TGFβ-1) expression were seen in therapeutically responsive disease. These data indicate a significant localization of eosinophils to nerves in IBD, mediated through neurally expressed ICAM-1 and eotaxin-3. This cell/neural interaction may influence the function of nerves and contribute to symptoms in IBD. [ABSTRACT FROM AUTHOR]

Abstract: In allergen challenged animal models, eosinophils localize to airway nerves leading to vagally-mediated hyperreactivity. We hypothesized that in allergic rhinitis eosinophils recruited to nasal nerves resulted in neural hyperreactivity. Patients with persistent allergic rhinitis (n=12), seasonal allergic rhinitis (n=7) and controls (n=10) were studied. Inferior nasal turbinate biopsies were obtained before, 8 and 48h after allergen challenge. Eighthours after allergen challenge eosinophils localized to nerves in both rhinitis groups; this was sustained through 48h. Bradykinin challenge, with secretion collection on the contralateral side, was performed to demonstrate nasal nerve reflexes. Twenty fourhours after allergen challenge, bradykinin induced a significant increase in secretions, indicating nasal hyperreactivity. Histological studies showed that nasal nerves expressed both vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-C motif) ligand 26 (CCL-26). Hence, after allergen challenge eosinophils are recruited and retained at nerves and so may be a mechanism for neural hyperreactivity. [Copyright &y& Elsevier]

Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of lung adenocarcinoma first described in the early 1990s in a lung tumour with overlapping lung and small intestine features. It is a rare tumour with fewer than 300 cases described in the published literature and was only formally classified in 2011. Given these characteristics the diagnosis is challenging, but even more so in a patient with prior gastrointestinal malignancy. A 68-year-old Caucasian female presented with a cough and was found to have a right upper lobe mass. Her history was significant for a pT3N1 colon adenocarcinoma. The resected lung tumour showed invasive lung adenocarcinoma but also features of colorectal origin. Immuno-stains were strongly and diffusely positive for lung and enteric markers. Multi-region, whole-exome sequencing of the mass and archival tissue from the prior colorectal cancer showed distinct genomic signatures with higher mutational burden in the PEAC and very minimal overlap in mutations between the two tumours. This case highlights the challenge of diagnosing rare lung tumours, but more specifically PEAC in a patient with prior gastro-intestinal cancer. Our use of multi-region, next-generation sequencing revealed distinct genomic signatures between the two tumours further supporting our diagnosis, and evidence of PEAC intra-tumour heterogeneity. [ABSTRACT FROM AUTHOR]