Compressed intramolecular dispersion interactions.

The feasibility of the compression of localized virtual orbitals is explored in the context of intramolecular long-range dispersion interactions. Singular value decomposition (SVD) of coupled cluster doubles amplitudes associated with the dispersion interactions is analyzed for a number of long-chain systems, including saturated and unsaturated hydrocarbons and a silane chain. Further decomposition of the most important amplitudes obtained from these SVDs allows for the analysis of the dispersion-specific virtual orbitals that are naturally localized. Consistent with previous work on intermolecular dispersion interactions in dimers, it is found that three important geminals arise and account for the majority of dispersion interactions at the long range, even in the many body intramolecular case. Furthermore, it is shown that as few as three localized virtual orbitals per occupied orbital can be enough to capture all pairwise long-range dispersion interactions within a molecule

Fully anharmonic infrared cascade spectra of polycyclic aromatic hydrocarbons

The infrared (IR) emission of polycyclic aromatic hydrocarbons (PAHs) permeates our universe; astronomers have detected the IR signatures of PAHs around many interstellar objects. The IR emission of interstellar PAHs differs from their emission as seen under conditions on Earth, as they emit through a collisionless cascade down through their excited vibrational states from high internal energies. The difficulty in reproducing interstellar conditions in the laboratory results in a reliance on theoretical techniques. However, the size and complexity of PAHs requires careful consideration when producing the theoretical spectra. In this work we outline the theoretical methods necessary to lead to a fully theoretical IR cascade spectra of PAHs including: an anharmonic second order vibrational perturbation theory (VPT2) treatment; the inclusion of Fermi resonances through polyads; and the calculation of anharmonic temperature band shifts and broadenings (including resonances) through a Wang--Landau approach. We also suggest a simplified scheme to calculate vibrational emission spectra that retains the essential characteristics of the full IR cascade treatment and can directly transform low temperature absorption spectra in IR cascade spectra. Additionally we show that past astronomical models were in error in assuming a 15 cm$^{-1}$ correction was needed to account for anharmonic emission effects

Adjuvant interferon alpha 2b in high risk melanoma – the Scottish study

In 1989, the Scottish melanoma group initiated a randomized trial, comparing observation alone with 6 months' therapy with low dose interferon α (given subcutaneously 3 MU day–1, thrice weekly), for patients with primary melanomas of at least 3 mm Breslow thickness, or with evidence of regional node involvement. The trial was closed in 1993 with only 95 eligible patients randomized. There were no toxic deaths, and no patient failed to complete the treatment for reasons of toxicity. 6 months' treatment with low-dose interferon-α resulted in a statistically significant improved disease-free survival for up to 24 months after randomization (P< 0.05). However, at a median follow-up of over 6 years, although there was an apparent improvement in disease-free survival (from 9 to 22 months), and overall survival (from 27 to 39 months), consistent with larger studies powered to detect such differences, these differences were not statistically significant. The data therefore suggest that 6 months of low-dose interferon is active, and confirm the importance of the large randomized studies, such as the UKCCCR AIM-High and EORTC trials, that seek to confirm a possible survival advantage for low or intermediate dose interferon. © 2001 Cancer Research Campaign http://www.bjcancer.co

The RoboCOS Study : Development of an international core outcome set for the comprehensive evaluation of patient, surgeon, organisational and population level impacts of robotic assisted surgery

ACKNOWLEDGEMENTS We would like to thank sincerely all those who contributed to the interviews, the focus group, the Delphi survey and the consensus meeting, and Paul Manson (Health Services Research Unit, University of Aberdeen) for helping to retrieve full text copies of reports identified by the literature search. We also thank HSRU (Health Services Research Unit) at University of Aberdeen for providing support for this work. Funding: The study was funded from NHS Grampian Endowment Fund and the University of Aberdeen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2023 Robertson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Peer reviewedPublisher PD

Transcriptional Profiling of Chondrodysplasia Growth Plate Cartilage Reveals Adaptive ER-Stress Networks That Allow Survival but Disrupt Hypertrophy

Metaphyseal chondrodysplasia, Schmid type (MCDS) is characterized by mild short stature and growth plate hypertrophic zone expansion, and caused by collagen X mutations. We recently demonstrated the central importance of ER stress in the pathology of MCDS by recapitulating the disease phenotype by expressing misfolding forms of collagen X (Schmid) or thyroglobulin (Cog) in the hypertrophic zone. Here we characterize the Schmid and Cog ER stress signaling networks by transcriptional profiling of microdissected mutant and wildtype hypertrophic zones. Both models displayed similar unfolded protein responses (UPRs), involving activation of canonical ER stress sensors and upregulation of their downstream targets, including molecular chaperones, foldases, and ER-associated degradation machinery. Also upregulated were the emerging UPR regulators Wfs1 and Syvn1, recently identified UPR components including Armet and Creld2, and genes not previously implicated in ER stress such as Steap1 and Fgf21. Despite upregulation of the Chop/Cebpb pathway, apoptosis was not increased in mutant hypertrophic zones. Ultrastructural analysis of mutant growth plates revealed ER stress and disrupted chondrocyte maturation throughout mutant hypertrophic zones. This disruption was defined by profiling the expression of wildtype growth plate zone gene signatures in the mutant hypertrophic zones. Hypertrophic zone gene upregulation and proliferative zone gene downregulation were both inhibited in Schmid hypertrophic zones, resulting in the persistence of a proliferative chondrocyte-like expression profile in ER-stressed Schmid chondrocytes. Our findings provide a transcriptional map of two chondrocyte UPR gene networks in vivo, and define the consequences of UPR activation for the adaptation, differentiation, and survival of chondrocytes experiencing ER stress during hypertrophy. Thus they provide important insights into ER stress signaling and its impact on cartilage pathophysiology

Suitability of UK biobank retinal images for automatic analysis of morphometric properties of the vasculature

To assess the suitability of retinal images held in the UK Biobank--the largest retinal data repository in a prospective population-based cohort--for computer assisted vascular morphometry, generating measures that are commonly investigated as candidate biomarkers of systemic disease.Non-mydriatic fundus images from both eyes of 2,690 participants--people with a self-reported history of myocardial infarction (n=1,345) and a matched control group (n=1,345)--were analysed using VAMPIRE software. These images were drawn from those of 68,554 UK Biobank participants who underwent retinal imaging at recruitment. Four operators were trained in the use of the software to measure retinal vascular tortuosity and bifurcation geometry.Total operator time was approximately 360 hours (4 minutes per image). 2,252 (84%) of participants had at least one image of sufficient quality for the software to process, i.e. there was sufficient detection of retinal vessels in the image by the software to attempt the measurement of the target parameters. 1,604 (60%) of participants had an image of at least one eye that was adequately analysed by the software, i.e. the measurement protocol was successfully completed. Increasing age was associated with a reduced proportion of images that could be processed (p=0.0004) and analysed (p<0.0001). Cases exhibited more acute arteriolar branching angles (p=0.02) as well as lower arteriolar and venular tortuosity (p<0.0001).A proportion of the retinal images in UK Biobank are of insufficient quality for automated analysis. However, the large size of the UK Biobank means that tens of thousands of images are available and suitable for computational analysis. Parametric information measured from the retinas of participants with suspected cardiovascular disease was significantly different to that measured from a matched control group