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Abstract During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO2). These environments mimic the headward fluid shifts, body unloading, and elevated CO2 observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO2 (30 days with elevated ambient CO2). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO2 campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.

Laura Heathcote,1 Tushar Srivastava,1 Archita Sarmah,2 Ben Kearns,1 Anthea Sutton,1 Pascal Candolfi2 1School for Health and Related Research, the University of Sheffield, Sheffield, UK; 2Edwards Lifesciences SA, Nyon, SwitzerlandCorrespondence: Laura Heathcote, School for Health and Related Research (Scharr), the University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA., UK, Email l.heathcote@sheffield.ac.ukObjective: Transcatheter aortic valve implantation (TAVI) is a disruptive technology recommended for patients with symptomatic severe aortic stenosis (sSAS). Despite being available for over 15 years in Europe, with an extensive volume of clinical and economic evaluations across all surgical risk groups, there is little evidence on the identification of the key drivers of TAVI’s cost-effectiveness. This study sought to identify these factors and quantify their role.Methods: A systematic literature review was conducted to identify published economic evaluations of TAVI. This was supplemented by health technology assessment reports. The primary outcome was the likelihood of TAVI being found cost-effective. Secondary outcomes of TAVI being dominant, and the incremental health benefits of TAVI were also explored.Results: Forty-two studies, reporting 65 unique analyses, were identified. TAVI was found to be cost-effective and dominant in 74% and 20% of analyses, respectively. The latest generation balloon-expandable TAVI device (SAPIEN 3) was more likely to be found cost-effective, as was TAVI use in low-risk populations and when performed via transfemoral access route. There was heterogeneity in the approach taken to economic modelling, which may also influence estimates of cost-effectiveness. Analyses that found TAVI to be dominant always compared it to surgery and usually considered the latest generation balloon-expandable TAVI device. Largest health benefits were observed for the inoperable risk group.Conclusion: For patients with sSAS, TAVI is typically a cost-effective treatment option. There are important differences by device generation, risk group and access route. It is crucial to consider these differences when appraising the health economic evidence-base for TAVI.Keywords: transcatheter aortic valve implantation, cost-effectiveness, severe aortic stenosis, statistical analysis, systematic review

Nesrine Mouhoubi,1 Jessica Bamba-Funck,1,2 Angela Sutton,1,2 Lorraine Blaise,3 Olivier Seror,4 Nathalie Ganne-Carrié,3,5 Marianne Ziol,6,7 Gisèle N’Kontchou,3 Nathalie Charnaux,1,2 Pierre Nahon,3,5 Jean-Charles Nault,3,5,* Erwan Guyot1,2,* 1Université Sorbonne Paris Nord, Laboratory for VascularTranslational Science, LVTS, INSERM, UMR 1148, Bobigny, F- 93000, France; 2Service de biochimie, Hôpital Avicenne, hôpitaux universitaires Paris-Seine-Saint-Denis, Assistance publique Hôpitaux de Paris, Bobigny, F-93000, France; 3Service d’hépatologie, Hôpital Avicenne, AP-HP, hôpitaux universitaires Paris-Seine-Saint-Denis, Assistance publique Hôpitaux de Paris, Bondy, F-93143, France; 4Service de radiologie, Hôpital Avicenne, hôpitaux universitaires Paris-Seine-Saint-Denis, Assistance publique Hôpitaux de Paris, Bobigny, F-93000, France; 5Inserm, UMR 1162, Génomique fonctionnelle des tumeUrs solides, Paris, F-75010, France; 6Centre de Ressources Biologiques BB-0033-00027, Hôpital Avicenne, hôpitaux universitaires Paris-Seine-Saint-Denis, Assistance publique Hôpitaux de Paris, Bobigny, F-93000, France; 7Service d’anatomie et cytologie pathologique, Hôpital Avicenne, hôpitaux universitaires Paris-Seine-Saint-Denis, Assistance publique Hôpitaux de Paris, Bobigny, F-93000, France*These authors contributed equally to this workCorrespondence: Erwan Guyot, Hôpitaux Universitaires Paris Seine-Saint-Denis, Laboratoire Biochimie-Pharmacologie et Biologie Moléculaire, 125 Rue de Stalingrad, Bobigny, 93000, France, Tel +33 1 48 95 56 29, Fax +33 1 48 95 56 27, Email erwan.guyot@aphp.frPurpose: Sulfatase 2 (SULF2) is an enzyme related to heparan sulfate modifications. Its expression, as for some heparan sulfate proteoglycans expression, has been linked to hepatocellular carcinoma (HCC) at mRNA level and immunohistochemistry staining on biopsy samples. This study aims to evaluate the prognostic value of serum levels of SULF2 in patients with alcoholic cirrhosis with or without HCC.Patients and Methods: Two hundred and eighty-seven patients with alcoholic cirrhosis were enrolled in this study: 164 without HCC, 57 with early HCC, and 66 with advanced HCC at inclusion. We analyzed the association between SULF2 serum levels and prognosis using Kaplan–Meier method and univariate and multivariate analysis using a Cox model.Results: Child-Pugh C Patients have higher serum levels of SULF2 than Child-Pugh A patients. Serum levels of SULF2 were also higher in patients with advanced HCC compared with the other groups. In patients with advanced HCC, high serum levels of SULF2 were associated with less favorable overall survival. Combination of SULF2 with Glypican 3 (GPC3) and Syndecan 1 (SDC1) serum levels enhanced the ability to discriminate worst prognostic in advanced HCC.Conclusion: SULF2 along with GPC3 and SDC1 serum levels have been shown to be associated with a prognostic value in advanced HCC.Keywords: sulfatase 2, proteoglycans, prognosis, hepatocellular carcinoma, cirrhosis

Mariska Ackerman,1 Michael Lawless,2,3 Lewis Levitz,4 Uday Bhatt,4 Joseph A Reich,4 Gerard Sutton,2,3 Timothy V Roberts,2,3 Abi Tenen,4 Amanpreet Kaur,4 Chris Hodge2,3,5,6 1Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; 2Vision Eye Institute, Sydney, New South Wales, Australia; 3Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; 4Vision Eye Institute, Melbourne, Victoria, Australia; 5Graduate School of Health, University of Technology Sydney, Sydney, New South Wales, Australia; 6Macquarie University, Sydney, AustraliaCorrespondence: Michael Lawless, Vision Eye Institute, Level 3 270 Victoria Avenue, Chatswood, Sydney, NSW, 2067, Australia, Tel +61 2 9424 9999, Fax +61 2 9410 3000, Email michael.lawless@vei.com.auPurpose: Trifocal Intraocular Lenses (IOLs) were developed to provide patients with effective near, intermediate and distance vision, thus minimizing spectacle dependency. Residual astigmatism has previously been shown to impact unaided visual acuity across all distances; therefore, to optimise the expected outcomes, consideration of preoperative corneal astigmatism is essential. The purpose of this study was to provide a real-world, multi-site review of visual and refractive outcomes in eyes undergoing implantation with the Panoptix Trifocal toric IOL platform.Patients and Methods: This study represents a two-fold approach. Patients who had previously undergone routine cataract removal and IOL insertion with the Panoptix Toric IOL were retrospectively analysed for routine efficacy and safety endpoints (“Retrospective Cohort”). Data was retrieved from the preoperative, surgical and postoperative visits (range 2– 6 weeks). A further subset of patients undergoing lens removal and bilateral Panoptix Toric IOL insertion were identified at surgery (“Qualitative Cohort”). These patients underwent additional testing inclusive of quality of vision questionnaire and bilateral defocus curve.Results: A total of 466 eyes of 254 patients were included in the retrospective cohort. Between 91% and 98% of eyes, respectively, were within 0.50D and 1.00D of target. Mean absolute difference from Spherical Equivalent (SE) target was 0.22 ± 0.24Ds. Following surgery, 94% of eyes demonstrated a refractive astigmatism of 0.50D or less. Further, 61% eyes achieved uncorrected distance visual acuity (UDVA) of 20/20 or better, increasing to 94% achieving 20/32 or better. Seventy percent of eyes unilaterally achieved N5 unaided and 66.0% achieved N8 or better at intermediate. In the qualitative cohort, no patient described any symptom as significant or requested explant.Conclusion: In a real-world setting, the PanOptix toric trifocal IOL continues to demonstrate refractive accuracy and good visual performance at all focal distances. This IOL also exhibited good quality of vision, with minimally bothersome visual disturbances or photic phenomena.Keywords: cataract surgery, IOL, trifocal, lens extraction, visual acuity

In this randomized control study, we evaluated science teachers' pedagogical practices via classroom observations following ongoing, intensive, and structured instructional support sessions. These sessions included virtual professional development (VPD) and virtual mentoring and coaching (VMC) that accompanied a literacy-infused science curriculum. Using a low-inference observational instrument, we explored the direct impact of VPD and VMC on fifth-grade science teachers' observed time allocation in a randomized controlled trial (RCT) validation study. The observations were collected three times during science instruction from 121 teachers in 68 schools from 35 public school districts in the U.S. state of Texas, during the 2017-2018 school year. Preliminary findings revealed pedagogical differences in time allocation among teachers between treatment and control classrooms. We identified improved instructional practices within treatment classrooms, which suggests the intervention had a positive effect by enhancing the quality of pedagogy as well as the content-area instruction in science.

Abstract Research focused on microbial populations of thermoalkaline springs has been driven in a large part by the lure of discovering functional enzymes with industrial applications in high-pH and high temperature environments. While several studies have focused on understanding the fundamental ecology of these springs, the small molecule profiles of thermoalkaline springs have largely been overlooked. To better understand how geochemistry, small molecule composition, and microbial communities are connected, we conducted a three-year study of the Five Sisters (FS) springs that included high-resolution geochemical measurements, 16S rRNA sequencing of the bacterial and archaeal community, and mass spectrometry-based metabolite and extracellular small molecule characterization. Integration of the four datasets facilitated a comprehensive analysis of the interwoven thermoalkaline spring system. Over the course of the study, the microbial population responded to changing environmental conditions, with archaeal populations decreasing in both relative abundance and diversity compared to bacterial populations. Decreases in the relative abundance of Archaea were associated with environmental changes that included decreased availability of specific nitrogen- and sulfur-containing extracellular small molecules and fluctuations in metabolic pathways associated with nitrogen cycling. This multi-factorial analysis demonstrates that the microbial community composition is more closely correlated with pools of extracellular small molecules than with the geochemistry of the thermal springs. This is a novel finding and suggests that a previously overlooked component of thermal springs may have a significant impact on microbial community composition.