Simulating organic aerosol in Delhi with WRF-Chem using the volatility-basis-set approach: exploring model uncertainty with a Gaussian process emulator

The nature and origin of organic aerosol in the atmosphere remain unclear. The gas–particle partitioning of semi-volatile organic compounds (SVOCs) that constitute primary organic aerosols (POAs) and the multigenerational chemical aging of SVOCs are particularly poorly understood. The volatility basis set (VBS) approach, implemented in air quality models such as WRF-Chem (Weather Research and Forecasting model with Chemistry), can be a useful tool to describe emissions of POA and its chemical evolution. However, the evaluation of model uncertainty and the optimal model parameterization may be expensive to probe using only WRF-Chem simulations. Gaussian process emulators, trained on simulations from relatively few WRF-Chem simulations, are capable of reproducing model results and estimating the sources of model uncertainty within a defined range of model parameters. In this study, a WRF-Chem VBS parameterization is proposed; we then generate a perturbed parameter ensemble of 111 model runs, perturbing 10 parameters of the WRF-Chem model relating to organic aerosol emissions and the VBS oxidation reactions. This allowed us to cover the model's uncertainty space and to compare outputs from each run to aerosol mass spectrometer observations of organic aerosol concentrations and O:C ratios measured in New Delhi, India. The simulations spanned the organic aerosol concentrations measured with the aerosol mass spectrometer (AMS). However, they also highlighted potential structural errors in the model that may be related to unsuitable diurnal cycles in the emissions and/or failure to adequately represent the dynamics of the planetary boundary layer. While the structural errors prevented us from clearly identifying an optimized VBS approach in WRF-Chem, we were able to apply the emulator in the following two periods: the full period (1–29 May) and a subperiod period of 14:00–16:00 h LT (local time) on 1–29 May. The combination of emulator analysis and model evaluation metrics allowed us to identify plausible parameter combinations for the analyzed periods. We demonstrate that the methodology presented in this study can be used to determine the model uncertainty and to identify the appropriate parameter combination for the VBS approach and hence to provide valuable information to improve our understanding of OA production

Spinal infection: state of the art and management algorithm

Spinal infection is a rare pathology although a concerning rising incidence has been observed in recent years. This increase might reflect a progressively more susceptible population but also the availability of increased diagnostic accuracy. Yet, even with improved diagnosis tools and procedures, the delay in diagnosis remains an important issue. This review aims to highlight the importance of a methodological attitude towards accurate and prompt diagnosis using an algorithm to aid on spinal infection management. METHODS: Appropriate literature on spinal infection was selected using databases from the US National Library of Medicine and the National Institutes of Health. RESULTS: Literature reveals that histopathological analysis of infected tissues is a paramount for diagnosis and must be performed routinely. Antibiotic therapy is transversal to both conservative and surgical approaches and must be initiated after etiological diagnosis. Indications for surgical treatment include neurological deficits or sepsis, spine instability and/or deformity, presence of epidural abscess and upon failure of conservative treatment. CONCLUSIONS: A methodological assessment could lead to diagnosis effectiveness of spinal infection. Towards this, we present a management algorithm based on literature findings

Evolutionary Sequence Modeling for Discovery of Peptide Hormones

There are currently a large number of “orphan” G-protein-coupled receptors (GPCRs) whose endogenous ligands (peptide hormones) are unknown. Identification of these peptide hormones is a difficult and important problem. We describe a computational framework that models spatial structure along the genomic sequence simultaneously with the temporal evolutionary path structure across species and show how such models can be used to discover new functional molecules, in particular peptide hormones, via cross-genomic sequence comparisons. The computational framework incorporates a priori high-level knowledge of structural and evolutionary constraints into a hierarchical grammar of evolutionary probabilistic models. This computational method was used for identifying novel prohormones and the processed peptide sites by producing sequence alignments across many species at the functional-element level. Experimental results with an initial implementation of the algorithm were used to identify potential prohormones by comparing the human and non-human proteins in the Swiss-Prot database of known annotated proteins. In this proof of concept, we identified 45 out of 54 prohormones with only 44 false positives. The comparison of known and hypothetical human and mouse proteins resulted in the identification of a novel putative prohormone with at least four potential neuropeptides. Finally, in order to validate the computational methodology, we present the basic molecular biological characterization of the novel putative peptide hormone, including its identification and regional localization in the brain. This species comparison, HMM-based computational approach succeeded in identifying a previously undiscovered neuropeptide from whole genome protein sequences. This novel putative peptide hormone is found in discreet brain regions as well as other organs. The success of this approach will have a great impact on our understanding of GPCRs and associated pathways and help to identify new targets for drug development

Small-molecule agonists and antagonists of the opioid receptor-like receptor (ORL1, NOP): Ligand-based analysis of structural factors influencing intrinsic activity at NOP

The recently discovered fourth member of the opioid receptor family, the nociceptin receptor (NOP) and its endogenous ligand, the heptadecaptide nociceptin, are involved in several central nervous system pathways, such as nociception, reward, tolerance, and feeding. The discovery of small-molecule ligands for NOP is being actively pursued for several therapeutic applications. This review presents a brief overview of the several recently reported NOP ligands, classified as NOP agonists and antagonists, with an emphasis on the analysis of the structural features that may be important for modulating the agonist/antagonist profile (intrinsic activity) of these ligands. Structure-activity relationships in our own series of dihydroindolinone-based NOP ligands and those of the various reported ligands indicate that the lipophilic substituent on the common basic nitrogen present in all NOP ligands plays a role in determining the agonist/antagonist profile of the NOP ligand. This analysis provides a basis for the rational drug design of NOP ligands of desired intrinsic activity and provides a framework for developing pharmacophore models for high affinity binding and intrinsic activity at the NOP receptor. Since NOP agonists and antagonists both have therapeutic value, rational approaches for obtaining both within a high-affinity binding class of compounds are very useful for designing potent and selective NOP ligands with the desired profile of intrinsic efficacy

Clinical outcomes of 4-point scleral fixated 1-piece hydrophobic acrylic equiconvex intraocular lens using polytetrafluoroethylene suture

Nimesh A Patel, Parth Shah, Nicolas A Yannuzzi, Zubair Ansari, Jill S Zaveri, Nidhi Relhan, Basil K Williams Jr, Ajay E Kuriyan, Christopher R Henry, Jayanth Sridhar, Luis Haddock, Jorge A Fortun, Thomas A Albini, Janet L Davis, Harry W Flynn JrDepartment of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL 33136, USA Purpose: To report the visual outcomes and complications of scleral fixated intraocular lenses (IOLs) using Gore-Tex suture.Methods: The current study is a retrospective noncomparative case series including patients who underwent scleral fixation of IOL (Akreos AO60) using Gore-Tex suture from August 2015 to March 2017 at a university teaching center. Primary outcome measures were visual acuity and complications at last follow-up.Results: The current study included 49 eyes of 48 patients. Mean follow-up duration postsurgery was 6.9 months (range: 0.9–29.4 months). The indications for secondary IOL surgery were dislocated IOL in 16/49 (33%), subluxed IOL in 9/49 (18%), dislocated or subluxed crystalline lens in 9/49 (18%), traumatic cataract in 8/49 (16%), and complicated cataract surgery in 7/49 (14%). Mean best-corrected logMAR visual acuity improved from 1±0.7 (20/200 Snellen equivalent) preoperatively to 0.5±0.5 (20/63 Snellen equivalent) at last follow-up. There were no intraoperative complications noted. Early postoperative complications included significant persistent corneal edema (longer than 1 week) in 4/49 (8.2%), ocular hypertension (intraocular pressure ≥25 mmHg) in 8/49 (16.3%), hypotony (intraocular pressure ≤5 mmHg) in 6/49 (12.2%), cystoid macular edema 3/21 (6.1%), IOL tilt 2/49 (4.1%), hyphema in 2/49 (4.1%), and vitreous hemorrhage in 5/49 (4.8%). There was one case of recurrent retinal detachment. One patient presented with an erosion of the Gore-Tex suture through the conjunctiva resulting in a purulent scleritis 6 months after the initial surgery, and was managed with removal of the IOL, debridement, and cryotherapy. Forty-one of 49 patients completed 3-month follow-up, among which visual acuity improved, deteriorated, or remained same compared to baseline in 27/49 (55.1%), 8/49 (16.3%), and 6/49 (12.2%) eyes, respectively.Conclusion: In the current study, visual acuity outcomes were generally favorable. The complications were largely transient. Significant complications included a suture-related infection, which required removal of the IOL, and a recurrence of a retinal detachment. Keywords: Gore-Tex, secondary intraocular lens, scleral fixation, clinical outcome

Towards Open Data Quality Improvements Based on Root Cause Analysis of Quality Issues

Part 2: Open Data, Linked Data, and Semantic WebInternational audienceCommercial reuse of open government data in value added services has gained a lot of interest both as practice and as a research topic over the last few years. However, utilizing open data without proper understanding of potential quality issues carries the risk of undermining the value of the service that relies on public sector information. Instead of establishing a data quality assessment framework this research considers a review of typical open data quality issues and intends to connect them to the causes leading to these various data problems. Open data specific problems are concluded from a case study and then theoretical and empirical arguments are used to connect them to root causes emerging from the peculiarities of the public sector data management process. This way both practitioners could be more conscious about appropriate cleansing methods and participants shaping the data management process could aim at eliminating root causes of data quality issues