Assessment of Pattern and Shape Symmetry of Bilateral Normal Corneas by Scheimpflug Technology

Purpose: The aim of this study was to assess bilateral symmetry in normal fellow eyes by using optical and geometric morphometric parameters. Methods: All participants underwent complete biocular examinations. Scheimpflug tomography data from 66 eyes of 33 patients were registered. The interocular symmetry was based on five patterns: morphogeometric symmetry, axial symmetry at the corneal vertex, angular-spatial symmetry, direct symmetry (equal octants), and enantiomorphism (mirror octants). Results: No statistically significant differences were found between right and left eyes in corneal morphogeometric (p ≥ 0.488) and aberrometric parameters (p ≥ 0.102). Likewise, no statistically significant differences were found in any of the axial symmetry parameters analyzed (p ≥ 0.229), except in the surface rotation angle beta (p = 0.102) and translation coordinates X0 and Y0 (p < 0.001) for the anterior corneal surface, and the rotation angle gamma (p < 0.001) for the posterior surface. Similarly, no statistically significant differences were identified for direct symmetry (p ≥ 0.20) and enantiomorphism (p ≥ 0.75), except for some elevation data in the posterior surface (p < 0.01). Conclusions: The level of symmetry of both corneas of a healthy individual is high, with only some level of disparity between fellow corneas in rotation and translation references. Abnormalities in this pattern of interocular asymmetry may be useful as a diagnostic tool.This publication has been carried out in the framework of the Thematic Network for Co-Operative Research in Health (RETICS), reference number RD16/0008/0012, financed by the Carlos III Health Institute–General Subdirection of Networks and Cooperative Investigation Centers (R&D&I National Plan 2013–2016) and the European Regional Development Fund (FEDER). The author David P. Piñero has been supported by the Ministry of Economy, Industry and Competitiveness of Spain within the program Ramón y Cajal, RYC-2016-20471

Reconstructing Neutrino Properties from Collider Experiments in a Higgs Triplet Neutrino Mass Model

We extend the minimal supersymmetric standard model with bilinear R-parity violation to include a pair of Higgs triplet superfields. The neutral components of the Higgs triplets develop small vacuum expectation values (VEVs) quadratic in the bilinear R-parity breaking parameters. In this scheme the atmospheric neutrino mass scale arises from bilinear R-parity breaking while for reasonable values of parameters the solar neutrino mass scale is generated from the small Higgs triplet VEVs. We calculate neutrino masses and mixing angles in this model and show how the model can be tested at future colliders. The branching ratios of the doubly charged triplet decays are related to the solar neutrino angle via a simple formula.Comment: 19 pages, 4 figures; one formula corrected, two author's names corrected; some explanatory comments adde

Neutrino masses in R-parity violating supersymmetric models

We study neutrino masses and mixing in R-parity violating supersymmetric models with generic soft supersymmetry breaking terms. Neutrinos acquire masses from various sources: Tree level neutrino--neutralino mixing and loop effects proportional to bilinear and/or trilinear R-parity violating parameters. Each of these contributions is controlled by different parameters and have different suppression or enhancement factors which we identified. Within an Abelian horizontal symmetry framework these factors are related and specific predictions can be made. We found that the main contributions to the neutrino masses are from the tree level and the bilinear loops and that the observed neutrino data can be accommodated once mild fine-tuning is allowed.Comment: 18 pages; minor typos corrected. To be published in Physical Review

Splenectomy and/or cyclophosphamide as salvage therapies in thrombotic thrombocytopenic purpura: the French TMA Reference Center experience: SALVAGE THERAPIES IN SEVERE TTP

BACKGROUND: The objective was to assess the efficacy and safety of splenectomy and cyclophosphamide as salvage therapies in severe thrombotic thrombocytopenic purpura (TTP).STUDY DESIGN AND METHODS: During a 10-year period, patients who did not improve with plasma exchanges, steroids, vincristine, and/or rituximab were considered for splenectomy or cyclophosphamide. Patients with a documented severe (&lt;10% of normal value) acquired ADAMTS13 deficiency are reported here. RESULTS: Eighteen patients with a severe acquired ADAMTS13 deficiency required a salvage therapy. Thirteen patients had a splenectomy 19 (interquartile range [IQR], 10-51) days after TTP diagnosis. One patient died the day after splenectomy. The remaining patients improved platelets (PLTs) until Day 6, along with a rapid and major lactate dehydrogenase improvement. Six patients, however, subsequently experienced a transient worsening. Durable PLT count recovery in survivors was observed within 13 (IQR, 11.5-25.5) days. Postoperative complications included thromboembolic events (two cases) and infections (five cases). Five patients received pulses of cyclophosphamide 12 (IQR, 12-15) days after TTP diagnosis. All patients recovered PLTs 10 (IQR, 9-24) days after the first pulse and two experienced a transient worsening. Three patients experienced infections. Three relapses occurred 5 months, 2.5 years, and 4.5 years after splenectomy and one relapse occurred 3.5 years after cyclophosphamide. After a 2.5 (IQR, 0.75-6.2)-year follow-up, the overall survival was 94%. CONCLUSION: Cyclophosphamide and splenectomy provide comparable high remission rates in severe TTP with acceptable side effects and should be considered in the more severe patients who do not improve with other therapies

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe

The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

The development of sensitive and non-invasive ‘‘liquid biopsies’’ presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs) is prognostic in multiple myeloma (MM), but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM) tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs

Predicting human RNA quadruplex helicases through comparative sequence approaches and helicase mRNA interactome analyses

RNA quadruplexes are non-canonical nucleic acid structures involved in several human disease states and are regulated by a specific subset of RNA helicases. Given the difficulty in identifying RNA quadruplex helicases due to the multifunctionality of these enzymes, we sought to provide a comprehensive in silico analysis of features found in validated RNA quadruplex helicases to predict novel human RNA quadruplex helicases. Using the 64 human RNA helicases, we correlated their amino acid compositions with subsets of RNA quadruplex helicases categorized by varying level of evidence of RNA quadruplex interaction. Utilizing phylogenetic and synonymous/non-synonymous substitution analyses, we identified an evolutionarily conserved pattern involving predicted intrinsic disorder and a previously identified motif. We analyzed available next generation sequencing data to determine which RNA helicases were directly interacting with predicted RNA quadruplex regions intracellularly and elucidated a relationship with miRNA binding sites adjacent to RNA quadruplexes. Finally, we employed a phylogenetic analysis of all 64 human RNA helicases to establish how RNA quadruplex detection and unwinding activity may be conserved among helicase subfamilies. This work furthers understanding of commonalities between RNA quadruplex helicases and provides support for the future validation of several human RNA helicases.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Building energy retrofit-as-a-service: a Total Value of Ownership assessment methodology to support whole life-cycle building circularity and decarbonisation: Construction Management and Economics

The regulatory drive to accelerate the clean energy and circular economy transitions in the European building stock is currently failing to overcome systemic implementation barriers. These barriers include high initial investment costs, misaligned financial incentives among stakeholders, and the relatively low cost of less sustainable energy and materials. A Product-Service Systems (PSS) approach could successfully overcome many of these barriers by (1) outsourcing capital investment, as well as financial and technical risks, (2) providing shared economic incentives to collaborating stakeholders, and (3) retaining extended producer responsibility and ownership over materials and products. However, PSS is still not seen as a viable business model when compared to both a standard “ownership” contract and a “no-retrofit” scenario. This paper proposes a Total Value of Ownership (TVO) method to evaluate the financial performance of a building energy retrofit in terms of Net Present Value, comparing a matrix of scenarios. Results show that – when accounting for capital and opportunity costs tied to alternative investments, internalising externalities, and monetising soft values such as user productivity and property value – a PSS model can deliver the highest NPV. Furthermore, results show that a PSS alternative can act as a positive future-proofing strategy to safeguard the building owner’s position in the face of uncertain future market indicators and carbon taxation. Recommendations for policymakers, investors, financiers, building owners, and end-users are presented to identify the economic value of PSS contracts, leading to better-informed decisions which can accelerate deep energy retrofit of the building stock.Building Product Innovatio

Severe Plasmodium malariae malaria in a patient with multiple susceptibility genes.

International audienceWe present a case of severe malaria due to Plasmodium malariae. Genetic testing showed that the patient was homozygous for five important gene polymorphisms previously shown to be associated with increased susceptibility to, and/or severity of, severe sepsis. Our case suggests that P. malariae may cause life-threatening disease, and that disease severity may be linked, at least in part, to multiple susceptibility genes

Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units

International audienceOBJECTIVE:The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection.METHODS:Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF.RESULTS:In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score <7 if SAT was delayed by ≥6 days (p 0.04). Healthcare-associated CP (OR 3.82, 95% CI 1.52-9.64, p 0.004), SOFA ≥8 at ICU admission (OR 2.61, 95% CI 1.08-6.34; p 0.03), and SAPS II ≥45 at SAT initiation (OR 5.08, 95% CI 1.04-12.67; p 0.001) impacted the 28-day mortality.CONCLUSIONS:In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP