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Abstract The Observing Air–Sea Interactions Strategy (OASIS) is a new United Nations Decade of Ocean Science for Sustainable Development programme working to develop a practical, integrated approach for observing air–sea interactions globally for improved Earth system (including ecosystem) forecasts, CO2 uptake assessments called for by the Paris Agreement, and invaluable surface ocean information for decision makers. Our “Theory of Change” relies upon leveraged multi-disciplinary activities, partnerships, and capacity strengthening. Recommendations from >40 OceanObs’19 community papers and a series of workshops have been consolidated into three interlinked Grand Ideas for creating #1: a globally distributed network of mobile air–sea observing platforms built around an expanded array of long-term time-series stations; #2: a satellite network, with high spatial and temporal resolution, optimized for measuring air–sea fluxes; and #3: improved representation of air–sea coupling in a hierarchy of Earth system models. OASIS activities are organized across five Theme Teams: (1) Observing Network Design & Model Improvement; (2) Partnership & Capacity Strengthening; (3) UN Decade OASIS Actions; (4) Best Practices & Interoperability Experiments; and (5) Findable–Accessible–Interoperable–Reusable (FAIR) models, data, and OASIS products. Stakeholders, including researchers, are actively recruited to participate in Theme Teams to help promote a predicted, safe, clean, healthy, resilient, and productive ocean.

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

Nicole Unger-Manhart,1,* Martina Morokutti-Kurz,1,* Petra U Zieglmayer,2,3 Patrick Lemell,2 Markus Savli,4 René Zieglmayer,2 Eva Prieschl-Grassauer1 1Marinomed Biotech AG, Korneuburg, Austria; 2Vienna Challenge Chamber, Vienna, Austria; 3Competence Center for Allergology and Immunology, Karl Landsteiner University, Krems, Austria; 4Biostatistik & Consulting GmbH, Zurich, Switzerland*These authors contributed equally to this workCorrespondence: Eva Prieschl-Grassauer, Marinomed Biotech AG, Hovengasse 25, Korneuburg, 2100, Austria, Tel +43 226292300, Email office@marinomed.comPurpose: Nonpharmacological, barrier-forming nasal sprays are used to manage symptoms of allergic rhinitis. We aim to evaluate the safety and effectiveness of Callergin (investigational product, IP), a nasal spray containing barrier-forming iota-carrageenan, in the treatment of allergic rhinitis (AR).Methods: In this randomized, controlled, crossover trial, adults with grass pollen allergy underwent a treatment sequence with IP, VisAlpin (comparator product, CP), and no treatment in random order. Treatment blocks consisted in prophylactic administration of the assigned treatment or no treatment, followed by a 3-hr allergen exposure, and were separated by a washout period of 7 days. Primary endpoint was a mean change from baseline in “Total Nasal Symptom Score” (TNSS, sum of rhinorrhea, itching, sneezing, and congestion scores) over 3 hr, recorded every 15 min during the challenge period.Results: A total of 42 participants underwent randomization. Exposure to grass pollen for 3 hr induced a notable TNSS increase from baseline in all participants at all times. Mean TNSS change from baseline over 3 hr was lower when participants received IP compared to no treatment, although the difference did not reach statistical significance (untreated 6.96 ± 2.30; IP 6.59 ± 1.93; difference 0.37 points [95% CI (confidence interval) − 0.17 to 0.91]; p=0.170). In a post-hoc analysis, mean TNSS at 3 hr was significantly reduced after IP treatment compared to no treatment (untreated 8.29 ± 2.64; IP 7.70 ± 2.56; difference 0.60 points [95% CI − 0.10 to 1.29] p=0.028). While all individual nasal symptoms contributed to this effect, rhinorrhea (p=0.013) and congestion (p=0.076) contributed most. Consistently, nasal secretion weight was slightly reduced with IP treatment (p=0.119). IP was safe and well-tolerated, with similar incidence of adverse events across treatment groups.Conclusion: Prophylactic treatment with the iota-carrageenan nasal spray IP is safe, well-tolerated, and alleviates nasal allergy symptoms in adults with grass pollen-induced AR.Trial Registration: NCT04531358.Keywords: allergic rhinitis, nonpharmacological, drug-free, barrier, iota-carrageenan

Martina Morokutti-Kurz, 1 Nicole Unger-Manhart, 1 Philipp Graf, 1 Pia Rauch, 2 Julia Kodnar, 1 Maximilian Große, 2 Christian Setz, 2 Markus Savli, 3 Friedrich Ehrenreich, 4 Andreas Grassauer, 1 Eva Prieschl-Grassauer, 1 Ulrich Schubert 2 1Marinomed Biotech AG, Korneuburg, 2100, Austria; 2Institute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany; 3Biostatistik & Consulting Savli, Hartberg, 8230, Austria; 4Practice Dr. Friedrich Ehrenreich, Vienna, 1170, AustriaCorrespondence: Martina Morokutti-KurzMarinomed Biotech AG, Korneuburg, 2100, AustriaEmail martina.morokutti-kurz@marinomed.comUlrich SchubertInstitute of Virology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, GermanyEmail ulrich.schubert@fau.dePurpose: The aim of this study was to investigate whether sucking of an iota-carrageenan containing lozenge releases sufficient iota-carrageenan into the saliva of healthy subjects to neutralize representatives of the most common respiratory virus families causing common cold and SARS-CoV-2.Patients and Methods: In this monocentric, open label, prospective clinical trial, 31 healthy subjects were included to suck a commercially available iota-carrageenan containing lozenge. Saliva samples from 27 subjects were used for ex vivo efficacy analysis. The study’s primary objective was to assess if the mean iota-carrageenan concentration of the saliva samples exceeded 5 μg/mL, which is the concentration known to reduce replication of human rhinovirus (hRV) 1a and 8 by 90%. The iota-carrageenan concentration of the saliva samples was analyzed by UV-Vis spectroscopy. The antiviral effectiveness of the individual saliva samples was determined in vitro against a panel of respiratory viruses including hRV1a, hRV8, human coronavirus OC43, influenza virus A H1N1pdm09, coxsackievirus A10, parainfluenza virus 3 and SARS-CoV-2 using standard virological assays.Results: The mean iota-carrageenan concentration detected in the saliva exceeds the concentration needed to inhibit 90% of hRV1a and hRV8 replication by 134-fold (95% CI 116.3– 160.8-fold; p < 0.001). Thus, the study met the primary endpoint. Furthermore, the iota-carrageenan saliva concentration was 60 to 30,351-fold higher than needed to reduce viral replication/binding of all tested viruses by at least 90% (p < 0.001). The effect was most pronounced in hCoV OC43; in case of SARS-CoV-2, the IC 90 was exceeded by 121-fold (p < 0.001).Conclusion: Sucking an iota-carrageenan containing lozenge releases sufficient iota-carrageenan to neutralize and inactivate the most abundant respiratory viruses as well as pandemic SARS-CoV-2. The lozenges are therefore an appropriate measure to reduce the viral load at the site of infection, hereby presumably limiting transmission within a population as well as translocation to the lower respiratory tract.Trial Registration: NCT04533906.Keywords: iota-carrageenan, respiratory viruses, corona virus, lozenges, antiviral, clinical study, SARS-CoV-2

Christine Graf,1 Andreas Bernkop-Schnürch,2 Alena Egyed,1 Christiane Koller,1 Eva Prieschl-Grassauer,1 Martina Morokutti-Kurz1 1Marinomed Biotech AG, Vienna, Austria; 2ThioMatriX, Innsbruck, Austria Introduction: Xylometazoline hydrochloride (HCl) is a nasal decongestant that causes vasoconstriction in the nasal submucosa. It has been used for more than 50 years for the treatment of nasal congestion caused by rhinitis/sinusitis. Iota-carrageenan is effective against a broad variety of respiratory viruses, which are the most common cause of infections of the upper respiratory tract. Therefore, it is used as the active component in the antiviral nasal spray ­Coldamaris prophylactic (1.2 mg/mL iota-carrageenan in 0.5% NaCl) and other medical device nasal sprays that are approved and marketed in the EU. Recently, we developed a nasal spray formulation containing both xylometazoline HCl (0.05%) and iota-carrageenan (0.12%) that provides decongestion and antiviral protection of the nasal mucosa at the same time. Results: A set of in vitro experiments revealed that the vasoconstrictive properties of xylometazoline HCl and the antiviral effectiveness of iota-carrageenan against human rhinovirus (hRV) 1a, hRV8 and human coronavirus OC43 were maintained in the formulation containing these two compounds. Permeation experiments using bovine nasal mucosa showed that iota-carrageenan had no significant influence on the permeation of xylometazoline HCl. Finally, in the local tolerance and toxicity study, it was shown that the formulation was well tolerated at the application site with no occurrence of erythema or edema in the nostrils of all rabbits or any signs of toxicity in any of the organs and tissues inspected. Conclusion: Investigations on compatibility of xylometazoline HCl and iota-carrageenan demonstrated that the substances do not influence each other, allowing both to fulfill their known specific clinical efficacy (xylometazoline HCl) and effectiveness (iota-carrageenan). Keywords: antiviral, permeation, toxicity, vasoconstriction

Martina Morokutti-Kurz, Christine Graf, Eva Prieschl-Grassauer Marinomed Biotechnologie GmbH, Vienna, Austria Abstract: Up to 80% of sore throats are caused by viruses. Several over the counter products are available which provide symptomatic, not causal relief. For such lozenges, containing the antiseptics and local anesthetics amylmetacresol (AMC) and 2,4-dichlorobenzyl alcohol (DCBA) or hexylresorcinol (HR), recently an additional virucidal effect was published. Therefore, we tested a set of Strepsils® lozenges, containing either HR (Max [#2]) or AMC/DCBA (Original [#3], Extra Strong [#4], Warm [#5], Orange and Vitamin C [#6], Sugar free Lemon [#7], Children/Strawberry [#8] and Soothing Honey and Lemon [#9]) for their antiviral efficiency against representatives of respiratory viruses known to cause sore throat: human rhinovirus (HRV) 1a, HRV8, influenza virus A H1N1n, Coxsackievirus A10, and human coronavirus (hCoV) OC43. The lozenges were tested head to head with Coldamaris® lozenges (#1), which contain the patented antiviral iota-carrageenan. None of the tested AMC/DCBA or HR containing lozenges shows any antiviral effectiveness against HRV8 at the tested concentrations, whereas all are moderately active against HRV1a. Only lozenge #5 shows any activity against hCoV OC43 and Coxsackievirus A10 at the tested concentrations. Similarly, only lozenge #3 is moderately active against influenza A H1N1n virus. The data indicates that neither the isolated effect of the active ingredients nor the pH but rather one or more of the excipients of the specific formulations are responsible for the antiviral effect of some of the AMC/DCBA or HR containing lozenges. In contrast, carrageenan-containing lozenges are highly active against all viruses tested. In another experiment, we showed that binding and inactivation of virus particles by iota-carrageenan are fast and highly effective. During the residence time of the lozenge in the mouth, the viral titer is reduced by 85% and 91% for influenza A virus and hCoV OC43, respectively. Carrageenan-containing lozenges are, therefore, suitable as causative therapy against viral infections of the throat. Keywords: local anesthetics, polymer, antiviral, respiratory viruses

Linear programming (LP) is taught in different departments across college campuses with engineering and management curricula. Modeling an LP problem is taught in every linear programming class. As faculty teaching in Engineering and Management departments, the depth to which teachers should expect students to master this particular type of modeling is often discussed. Does a student's understanding of this critical concept differ across the curriculum? The authors look at students' abilities to model LP problems in two different departments: Industrial Engineering and Management. The authors compare the results and look for differences and reasons for those differences.

The observation that many lavas associated with mantle plumes have higher 3He/4He ratios than the upper convecting mantle underpins geophysical, geodynamic and geochemical models of Earth’s deep interior. High 3He/4He ratios are thought to derive from the solar nebula or from solar-wind-irradiated material that became incorporated into Earth during early planetary accretion. Traditionally, this high-3He/4He component has been considered intrinsic to the mantle, having avoided outgassing caused by giant impacts and billions of years of mantle convection1–4. Here we report the highest magmatic 3He/4He ratio(67.2 ± 1.8 times the atmospheric ratio) yet measured in terrestrial igneous rocks, in olivines from Baffin Island lavas. We argue that the extremely high-3He/4He helium in these lavas might derive from Earth’s core5–9. The viability of the core hypothesis relaxes the long-standing constraint—based on noble gases in lavas associated with mantle plumes globally—that volatile elements from the solar nebula have survived in the mantle since the early stages of accretion.Olivines from Baffin Island lavas have the highest magmatic 3He/4He ratio measured so far in terrestrial igneous rocks, indicating that the helium in these lavas might derive from Earth’s core. [ABSTRACT FROM AUTHOR]