Similarity regularized sparse group lasso for cup to disc ratio computation

© 2017 Optical Society of America. Automatic cup to disc ratio (CDR) computation from color fundus images has shown to be promising for glaucoma detection. Over the past decade, many algorithms have been proposed. In this paper, we first review the recent work in the area and then present a novel similarity-regularized sparse group lasso method for automated CDR estimation. The proposed method reconstructs the testing disc image based on a set of reference disc images by integrating the similarity between testing and the reference disc images with the sparse group lasso constraints. The reconstruction coefficients are then used to estimate the CDR of the testing image. The proposed method has been validated using 650 images with manually annotated CDRs. Experimental results show an average CDR error of 0.0616 and a correlation coefficient of 0.7, outperforming other methods. The areas under curve in the diagnostic test reach 0.843 and 0.837 when manual and automatically segmented discs are used respectively, better than other methods as well

Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages.

Activation of liver X receptors (LXRs) with synthetic agonists promotes reverse cholesterol transport and protects against atherosclerosis in mouse models. Most synthetic LXR agonists also cause marked hypertriglyceridemia by inducing the expression of sterol regulatory element-binding protein (SREBP)1c and downstream genes that drive fatty acid biosynthesis. Recent studies demonstrated that desmosterol, an intermediate in the cholesterol biosynthetic pathway that suppresses SREBP processing by binding to SCAP, also binds and activates LXRs and is the most abundant LXR ligand in macrophage foam cells. Here we explore the potential of increasing endogenous desmosterol production or mimicking its activity as a means of inducing LXR activity while simultaneously suppressing SREBP1c-induced hypertriglyceridemia. Unexpectedly, while desmosterol strongly activated LXR target genes and suppressed SREBP pathways in mouse and human macrophages, it had almost no activity in mouse or human hepatocytes in vitro. We further demonstrate that sterol-based selective modulators of LXRs have biochemical and transcriptional properties predicted of desmosterol mimetics and selectively regulate LXR function in macrophages in vitro and in vivo. These studies thereby reveal cell-specific discrimination of endogenous and synthetic regulators of LXRs and SREBPs, providing a molecular basis for dissociation of LXR functions in macrophages from those in the liver that lead to hypertriglyceridemia

Multi-seeded melt growth (MSMG) of bulk Y-Ba-Cu-O using thin-film seeds

Y-Ba-Cu-O (YBCO) and Sm-Ba-Cu-O (SmBCO) thin films have been used for the first time as heterogeneous seeds to multi-seed successfully the melt growth of bulk YBCO in a multi-seeded melt growth (MSMG) process. The use of thin film seeds, which may be prepared with highly controlled orientation (i.e. with a well-defined a-b plane and precisely known a-direction), is based on their superheating properties and reduces significantly contamination of the bulk sample by the seed material. A variety of grain boundaries were obtained by varying the angle between the seeds. Microstructural studies indicate that the extent of residual melt deposited at the grain boundary decreases with increasing grain boundary contact angle. It is established that the growth front proceeds continuously at the (110)/(110) grain boundary without trapping liquid, which leads to the formation of a clean grain boundary

The clinical impact of chromosomal microarray on paediatric care in Hong Kong

Objective To evaluate the clinical impact of chromosomal microarray (CMA) on the management of paediatric patients in Hong Kong. Methods We performed NimbleGen 135k oligonucleotide array on 327 children with intellectual disability (ID)/developmental delay (DD), autism spectrum disorders (ASD), and/or multiple congenital anomalies (MCAs) in a university-affiliated paediatric unit from January 2011 to May 2013. The medical records of patients were reviewed in September 2013, focusing on the pathogenic/likely pathogenic CMA findings and their “clinical actionability” based on established criteria. Results Thirty-seven patients were reported to have pathogenic/likely pathogenic results, while 40 had findings of unknown significance. This gives a detection rate of 11% for clinically significant (pathogenic/likely pathogenic) findings. The significant findings have prompted clinical actions in 28 out of 37 patients (75.7%), while the findings with unknown significance have led to further management recommendation in only 1 patient (p<0.001). Nineteen out of the 28 management recommendations are “evidence-based” on either practice guidelines endorsed by a professional society (n = 9, Level 1) or peer-reviewed publications making medical management recommendation (n = 10, Level 2). CMA results impact medical management by precipitating referral to a specialist (n = 24); diagnostic testing (n = 25), surveillance of complications (n = 19), interventional procedure (n = 7), medication (n = 15) or lifestyle modification (n = 12). Conclusion The application of CMA in children with ID/DD, ASD, and/or MCAs in Hong Kong results in a diagnostic yield of ∼11% for pathogenic/likely pathogenic results. Importantly the yield for clinically actionable results is 8.6%. We advocate using diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility. Furthermore, it incorporates evidence-based medicine into the practice of genomic medicine. The same framework can be applied to other genomic testing strategies enabled by next-generation sequencing.published_or_final_versio

Zenker's Diverticulum: Can Protocolised Measurements with Barium SWALLOW Predict Severity and Treatment Outcomes? The "Zen-Rad" Study

Although barium swallow imaging is established in the investigation of Zenker's diverticulum (ZD), no agreed measurement protocol exists. We developed a protocol for measuring ZD dimensions and aimed to correlate measurements with symptoms and post-operative outcomes. This prospective study included patients with confirmed ZD who underwent flexible endoscopic septal division (FESD) between 2014 and 2018. ZD was confirmed on barium radiology with measurements reviewed by two consultant radiologists. Symptom severity pre- and post-FESD was measured using the Dysphagia, Regurgitation, Complications (DRC) scale. Regression analyses were conducted to identify dimensions associated with therapeutic success, defined as remission (DRC score ≤ 1) 6 months after index FESD. In total, 67 patients (mean age 74.3) were included. Interobserver reliability (intraclass correlation coefficients-ICCs) was greatest for pouch width (0.981) and pouch depth (0.934), but not oesophageal depth (0.018). Male gender (60.9%) was associated with larger pouch height (P = 0.008) and width (P = 0.004). A positive correlation was identified between baseline DRC score and pouch depth (ρ 0.326, P = 0.011), particularly the regurgitation subset score (ρ 0.330, P = 0.020). The index pouch depth was associated with FESD procedure time (rho 0.358, P = 0.041). Therapeutic success was achieved in 64.2% and was associated with shorter pouch height (median 14.5 mm vs. 19.0 mm, P = 0.030), pouch width (median 19.9 mm vs. 28.8 mm, P = 0.34) and cricopharyngeal length (median 20.2 mm vs. 26.3 mm, P = 0.036). ZD dimensions may be feasible and were evaluated using Barium radiology. Specific parameters appear to correlate with severity and post-FESD outcomes, which aid with pre-procedural planning

Tissue damage drives co-localization of NF-kappa B, Smad3, and Nrf2 to direct Rev-erb sensitive wound repair in mouse macrophages

Although macrophages can be polarized to distinct phenotypes in vitro with individual ligands, in vivo they encounter multiple signals that control their varied functions in homeostasis, immunity, and disease. Here, we identify roles of Rev-erb nuclear receptors in regulating responses of mouse macrophages to complex tissue damage signals and wound repair. Rather than reinforcing a specific program of macrophage polarization, Rev-erbs repress subsets of genes that are activated by TLR ligands, IL4, TGF beta, and damage-associated molecular patterns (DAMPS). Unexpectedly, a complex damage signal promotes co-localization of NF-kappa B, Smad3, and Nrf2 at Rev-erb-sensitive enhancers and drives expression of genes characteristic of multiple polarization states in the same cells. Rev-erb-sensitive enhancers thereby integrate multiple damage-activated signaling pathways to promote a wound repair phenotype

Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.

PURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation

Prime tight frames

We introduce a class of finite tight frames called prime tight frames and prove some of their elementary properties. In particular, we show that any finite tight frame can be written as a union of prime tight frames. We then characterize all prime harmonic tight frames and use this characterization to suggest effective analysis and synthesis computation strategies for such frames. Finally, we describe all prime frames constructed from the spectral tetris method, and, as a byproduct, we obtain a characterization of when the spectral tetris construction works for redundancies below two

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury