Conjunctival Flap Covering Combined with Antiviral and Steroid Therapy for Severe Herpes Simplex Virus Necrotizing Stromal Keratitis

Herpes simplex virus (HSV) necrotizing stromal keratitis is a common type of herpetic stromal keratitis (HSK). Antiviral medication alone cannot control the disease, and corticosteroid eye drops may aggravate the ulcer and result in corneal perforation. Amniotic membrane transplantation effectively treats superficial corneal ulcer resulting from necrotizing stromal HSK. However, the efficacy of this approach seems to be limited for more serious cases. This study presented the clinical treatment of severe HSV necrotizing stromal keratitis (ulcer depth greater than half of the corneal stroma) by conjunctival flap covering surgery in 25 patients (25 eyes) combined with antivirus and corticosteroid treatment at Shandong Eye Hospital from January 2007 to December 2013. Clinical results showed that the mean best spectacle-corrected visual acuity improved from preoperative 20/333 to postoperative 20/40 (P<0.05). All patients recovered ocular surface stabilization. There was recurrence in two eyes, which was cured with antiviral medication. Conjunctival flap covering combined with antivirus and corticosteroid treatment is effective in treating severe HSV necrotizing stromal keratitis

Decoding the spermatogonial stem cell niche under physiological and recovery conditions in adult mice and humans

The intricate interaction between spermatogonial stem cell (SSC) and testicular niche is essential for maintaining SSC homeostasis; however, this interaction remains largely uncharacterized. In this study, to characterize the underlying signaling pathways and related paracrine factors, we delineated the intercellular interactions between SSC and niche cell in both adult mice and humans under physiological conditions and dissected the niche-derived regulation of SSC maintenance under recovery conditions, thus uncovering the essential role of C-C motif chemokine ligand 24 and insulin-like growth factor binding protein 7 in SSC maintenance. We also established the clinical relevance of specific paracrine factors in human fertility. Collectively, our work on decoding the adult SSC niche serves as a valuable reference for future studies on the aetiology, diagnosis, and treatment of male infertility.</p

A combination of climatic conditions determines major within-season dengue outbreaks in Guangdong Province, China

Background: China’s Guangdong Province experienced a major dengue outbreak in 2014. Here we investigate if the weather conditions contributing to the outbreak can be elucidated by multi-scale models. Methods: A multi-scale modelling framework, parameterized by available weather, vector and human case data, was used to examine the integrative effect of temperature and precipitation variation on the effective reproduction number (ERN) of dengue fever. Results: With temperature in the range of 25–30 °C, increasing precipitation leads to an increase in the ERN with an average lag of 10 days. With monthly precipitation fixed, the more regular the pattern of rainfall (i.e. higher numbers of rainy days), the larger is the total number of adult mosquitoes. A rainfall distribution peaking in June and July produces a large ERN, beneficial to transmission. Climate conditions conducive to major outbreaks within a season are a combination of relatively high temperature, high precipitation peaking in June and July, and uninterrupted drizzle or regular rainfall. Conclusions: Evaluating a set of weather conditions favourable to a future major dengue outbreak requires near-future prediction of temperature variation, total rainfall and its peaking times. Such information permits seasonal rapid response management decisions due to the lags between the precipitation events and the realisation of the ERN

Relationship between the morphology of the foveal avascular zone, retinal structure, and macular circulation in patients with diabetes mellitus

Diabetic Retinopathy (DR) is an extremely severe and common degenerative disease. The purpose of this study was to quantify the relationship between various parameters including the Foveal Avascular Zone (FAZ) morphology, retinal layer thickness, and retinal hemodynamic properties in healthy controls and patients with diabetes mellitus (DM) with and with no mild DR (MDR) using Spectral-Domain Optical Coherence Tomography (Spectralis SDOCT, Heidelberg Engineering GmbH, Germany) and the Retinal Function Imager (Optical Imaging, Ltd., Rehovot, Israel). Our results showed a higher FAZ area and diameter in MDR patients. Blood flow analysis also showed that there is a significantly smaller venous blood flow velocity in MDR patients. Also, a significant difference in roundness was observed between DM and MDR groups supporting the development of asymmetrical FAZ expansion with worsening DR. Our results suggest a potential anisotropy in the mechanical properties of the diabetic retina with no retinopathy that may trigger the FAZ elongation in a preferred direction resulting in either thinning or thickening of intraretinal layers in the inner and outer segments of the retina as a result of autoregulation. A detailed understanding of these relationships may facilitate earlier detection of DR, allowing for preservation of vision and better clinical outcomes

A haplotype map of allohexaploid wheat reveals distinct patterns of selection on homoeologous genomes

BACKGROUND: Bread wheat is an allopolyploid species with a large, highly repetitive genome. To investigate the impact of selection on variants distributed among homoeologous wheat genomes and to build a foundation for understanding genotype-phenotype relationships, we performed population-scale re-sequencing of a diverse panel of wheat lines. RESULTS: A sample of 62 diverse lines was re-sequenced using the whole exome capture and genotyping-by-sequencing approaches. We describe the allele frequency, functional significance, and chromosomal distribution of 1.57 million single nucleotide polymorphisms and 161,719 small indels. Our results suggest that duplicated homoeologous genes are under purifying selection. We find contrasting patterns of variation and inter-variant associations among wheat genomes; this, in addition to demographic factors, could be explained by differences in the effect of directional selection on duplicated homoeologs. Only a small fraction of the homoeologous regions harboring selected variants overlapped among the wheat genomes in any given wheat line. These selected regions are enriched for loci associated with agronomic traits detected in genome-wide association studies. CONCLUSIONS: Evidence suggests that directional selection in allopolyploids rarely acted on multiple parallel advantageous mutations across homoeologous regions, likely indicating that a fitness benefit could be obtained by a mutation at any one of the homoeologs. Additional advantageous variants in other homoelogs probably either contributed little benefit, or were unavailable in populations subjected to directional selection. We hypothesize that allopolyploidy may have increased the likelihood of beneficial allele recovery by broadening the set of possible selection targets

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Variational Inverting Network for Statistical Inverse Problems of Partial Differential Equations

To quantify uncertainties of the inverse problems governed by partial differential equations (PDEs), the inverse problems are transformed into statistical inference problems based on Bayes' formula. Recently, infinite-dimensional Bayesian analysis methods are introduced to give a rigorous characterization and construct dimension-independent algorithms. However, there are three major challenges for infinite-dimensional Bayesian methods: prior measures usually only behaves like regularizers (can hardly incorporate prior information efficiently); complex noises (e.g., more practical non-identically distributed noises) are rarely considered; many computationally expensive forward PDEs need to be solved in order to estimate posterior statistical quantities. To address these issues, we propose a general infinite-dimensional inference framework based on a detailed analysis on the infinite-dimensional variational inference method and the ideas of deep generative models that are popular in the machine learning community. Specifically, by introducing some measure equivalence assumptions, we derive the evidence lower bound in the infinite-dimensional setting and provide possible parametric strategies that yield a general inference framework named variational inverting network (VINet). This inference framework has the ability to encode prior and noise information from learning examples. In addition, relying on the power of deep neural networks, the posterior mean and variance can be efficiently generated in the inference stage in an explicit manner. In numerical experiments, we design specific network structures that yield a computable VINet from the general inference framework.Numerical examples of linear inverse problems governed by an elliptic equation and the Helmholtz equation are given to illustrate the effectiveness of the proposed inference framework.Comment: 46 page