Adaptive statistical iterative reconstruction improves image quality without affecting perfusion CT quantitation in primary colorectal cancer

Objectives: To determine the effect of Adaptive Statistical Iterative Reconstruction (ASIR) on perfusion CT (pCT) parameter quantitation and image quality in primary colorectal cancer. Methods: Prospective observational study. Following institutional review board approval and informed consent, 32 patients with colorectal adenocarcinoma underwent pCT (100 kV, 150 mA, 120 s acquisition, axial mode). Tumour regional blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were determined using identical regions-of-interests for ASIR percentages of 0%, 20%, 40%, 60%, 80% and 100%. Image noise, contrast-to-noise ratio (CNR) and pCT parameters were assessed across ASIR percentages. Coefficients of variation (CV), repeated measures analysis of variance (rANOVA) and Spearmanâ rank order correlation were performed with statistical significance at 5%. Results: With increasing ASIR percentages, image noise decreased by 33% while CNR increased by 61%; peak tumour CNR was greater than 1.5 with 60% ASIR and above. Mean BF, BV, MTT and PS differed by less than 1.8%, 2.9%, 2.5% and 2.6% across ASIR percentages. CV were 4.9%, 4.2%, 3.3% and 7.9%; rANOVA P values: 0.85, 0.62, 0.02 and 0.81 respectively. Conclusions: ASIR improves image noise and CNR without altering pCT parameters substantially. Keywords: Perfusion imaging, Multidetector computed tomography, Colorectal neoplasms, Computer-assisted image processing, Radiation dosag

Progenitors for the corneal endothelium and trabecular meshwork: a potential source for personalized stem cell therapy in corneal endothelial diseases and glaucoma

Several adult stem cell types have been found in different parts of the eye, including the corneal epithelium, conjunctiva, and retina. In addition to these, there have been accumulating evidence that some stem-like cells reside in the transition area between the peripheral corneal endothelium (CE) and the anterior nonfiltering portion of the trabecular meshwork (TM), which is known as the Schwalbe's Ring region. These stem/progenitor cells may supply new cells for the CE and TM. In fact, the CE and TM share certain similarities in terms of their embryonic origin and proliferative capacity in vivo. In this paper, we discuss the putative stem cell source which has the potential for replacement of lost and nonfunctional cells in CE diseases and glaucoma. The future development of personalized stem cell therapies for the CE and TM may reduce the requirement of corneal grafts and surgical treatments in glaucoma.published_or_final_versio

Spastin recovery in hereditary spastic paraplegia by preventing neddylation-dependent degradation

Hereditary Spastic Paraplegia (HSP) is a neurodegenerative disease most commonly caused by autosomal dominant mutations in the SPG4 gene encoding the microtubule-severing protein spastin. We hypothesise that SPG4-HSP is attributable to reduced spastin function because of haploinsufficiency; thus, therapeutic approaches which elevate levels of the wild-type spastin allele may be an effective therapy. However, until now, how spastin levels are regulated is largely unknown. Here, we show that the kinase HIPK2 regulates spastin protein levels in proliferating cells, in differentiated neurons and in vivo. Our work reveals that HIPK2-mediated phosphorylation of spastin at S268 inhibits spastin K48-poly-ubiquitination at K554 and prevents its neddylation-dependent proteasomal degradation. In a spastin RNAi neuronal cell model, overexpression of HIPK2, or inhibition of neddylation, restores spastin levels and rescues neurite defects. Notably, we demonstrate that spastin levels can be restored pharmacologically by inhibiting its neddylation-mediated degradation in neurons derived from a spastin mouse model of HSP and in patient-derived cells, thus revealing novel therapeutic targets for the treatment of SPG4-HSP

Serum Concentrations of Myostatin and Myostatin-Interacting Proteins do not differ between young and Scarcopenic elderly men

Peer reviewedPostprin

Interlayer Registry Determines the Sliding Potential of Layered Metal Dichalcogenides: The case of 2H-MoS2

We provide a simple and intuitive explanation for the interlayer sliding energy landscape of metal dichalcogenides. Based on the recently introduced registry index (RI) concept, we define a purely geometrical parameter which quantifies the degree of interlayer commensurability in the layered phase of molybdenum disulphide (2HMoS2). A direct relation between the sliding energy landscape and the corresponding interlayer registry surface of 2H-MoS2 is discovered thus marking the registry index as a computationally efficient means for studying the tribology of complex nanoscale material interfaces in the wearless friction regime.Comment: 13 pages, 7 figure

Discovery of a polyomavirus in European badgers (Meles meles) and the evolution of host range in the family Polyomaviridae.

Polyomaviruses infect a diverse range of mammalian and avian hosts, and are associated with a variety of symptoms. However, it is unknown whether the viruses are found in all mammalian families and the evolutionary history of the polyomaviruses is still unclear. Here, we report the discovery of a novel polyomavirus in the European badger (Meles meles), which to our knowledge represents the first polyomavirus to be characterized in the family Mustelidae, and within a European carnivoran. Although the virus was discovered serendipitously in the supernatant of a cell culture inoculated with badger material, we subsequently confirmed its presence in wild badgers. The European badger polyomavirus was tentatively named Meles meles polyomavirus 1 (MmelPyV1). The genome is 5187 bp long and encodes proteins typical of polyomaviruses. Phylogenetic analyses including all known polyomavirus genomes consistently group MmelPyV1 with California sea lion polyomavirus 1 across all regions of the genome. Further evolutionary analyses revealed phylogenetic discordance amongst polyomavirus genome regions, possibly arising from evolutionary rate heterogeneity, and a complex association between polyomavirus phylogeny and host taxonomic groups

Synthesis and characterization of smooth ultrananocrystalline diamond films via low pressure bias-enhanced nucleation and growth

This letter describes the fundamental process underlying the synthesis of ultrananocrystalline diamond (UNCD) films, using a new low-pressure, heat-assisted bias-enhanced nucleation (BEN)/bias enhanced growth (BEG) technique, involving H2/CH4 gas chemistry. This growth process yields UNCD films similar to those produced by the Ar-rich/CH4 chemistries, with pure diamond nanograins (3–5 nm), but smoother surfaces (~6 nm rms) and higher growth rate (~1 µm/h). Synchrotron-based x-Ray absorption spectroscopy, atomic force microscopy, and transmission electron microscopy studies on the BEN-BEG UNCD films provided information critical to understanding the nucleation and growth mechanisms, and growth condition-nanostructure-property relationships

NeuroSAFE frozen section during robot-assisted radical prostatectomy (RARP): Peri-operative and Histopathological Outcomes from the NeuroSAFE PROOF Feasibility Randomised Controlled Trial

Objectives: To report on the methods, peri‐operative outcomes and histopathological concordance between frozen and final section from the NeuroSAFE PROOF Feasibility study (NCT03317990). Patients and Methods: Between May 2018 and March 2019 49 men at 2 UK centres underwent robot‐assisted robotic prostatectomy (RARP). 25 men were randomised to NeuroSAFE RARP (intervention arm) vs. 24 men to standard RARP (control arm). Frozen section was compared to final paraffin section margin assessment in the 25 men in the NeuroSAFE arm. Operation timings and complications were collected prospectively in both arms. Results: 50 NVB from 25 patients in the NeuroSAFE arm were analysed. When analysed by each pathological section (n=250, average 5 per side) we note sensitivity 100%, specificity 99.2%, AUC was 0.994 (95% CI 0.985 to 1, P= <.001). On an NVB basis (n=50) we note sensitivity of 100%, specificity 92.7%, and AUC of 0.963 (95% CI 0.914 to 1, p = <0.001. NeuroSAFE RARP lasted a mean 3 hours 16 minutes (knife to skin to off table, 95% CI 3 hrs 2 mins ‐ 3 hrs 30 mins) compared to 2 hours 14 minutes (2 hrs 2 mins ‐ 2 hours 25 mins, P=<0.001) for standard RARP. There was no morbidity associated with the additional length of operation in the NeuroSAFE arm. Conclusion: This feasibility study demonstrates the safety, the reproducibility and the excellent histopathological concordance of the NeuroSAFE technique in the NeuroSAFE PROOF trial. Though the technique increases the duration of RARP, this does not cause short‐term harm. Confirmation of feasibility has led to the opening of the fully powered NeuroSAFE PROOF RCT, which is currently underway at 4 sites in the UK