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Over the past two decades, with recognition that the ocean's sea-ice cover is neither insensitive to climate change nor a barrier to light and matter, research in sea-ice biogeochemistry has accelerated significantly, bringing together a multi-disciplinary community from a variety of fields. This disciplinary diversity has contributed a wide range of methodological techniques and approaches to sea-ice studies, complicating comparisons of the results and the development of conceptual and numerical models to describe the important biogeochemical processes occurring in sea ice. Almost all chemical elements, compounds, and biogeochemical processes relevant to Earth system science are measured in sea ice, with published methods available for determiningbiomass, pigments, net community production, primary production, bacterial activity, macronutrients, numerous natural and anthropogenic organic compounds, trace elements, reactive and inert gases, sulfur species, the carbon dioxide system parameters, stable isotopes, and water-ice-Atmosphere fluxes of gases, liquids, and solids. For most of these measurements, multiple sampling and processing techniques are available, but to date there has been little intercomparison or intercalibration between methods. In addition, researchers collect different types of ancillary data and document their samples differently, further confounding comparisons between studies. These problems are compounded by the heterogeneity of sea ice, in which even adjacent cores can have dramatically different biogeochemical compositions. We recommend that, in future investigations, researchers design their programs based on nested sampling patterns, collect a core suite of ancillary measurements, and employ a standard approach for sample identification and documentation. In addition, intercalibration exercises are most critically needed for measurements of biomass, primary production, nutrients, dissolved and particulate organic matter (including exopolymers), the CO2 system, air-ice gas fluxes, and aerosol production. We also encourage the development of in situ probes robust enough for long-Term deployment in sea ice, particularly for biological parameters, the CO2 system, and other gases.

The in vitro Bacterial Reverse Mutation (Ames) Test is crucial for evaluating the mutagenicity of pharmaceutical impurities. For N-nitrosamines (NAs) historical data indicated that for certain members of this chemical class the outcomes of the Ames Test did not correlate with their associated rodent carcinogenicity outcomes. This has resulted in negative outcomes in an OECD aligned Ames Test alone (standard or enhanced) no longer being considered sufficient by regulatory authorities to assess potential carcinogenic risk of NAs if present as impurities in drug products. Consequently, extensive follow-up in vivo testing can be required to characterise the potential mutagenicity and genotoxic carcinogenicity of NA impurities (i.e., beyond that defined in the ICH M7 guideline for non-NA impurities). We previously demonstrated that the mutagenicity of alkyl-nitrosamines can be detected by the appropriately designed, OECD aligned Ames Test and identified those conditions that contributed most to assay sensitivity. This OECD aligned Ames Test design was used to assess seven NAs, i.e. (methyl(neopentyl)nitrosamine, N-methyl-N-nitroso-2-propanamine, N-nitrosodiisopropylamine, bis(2-methoxyethyl)nitrosoamine, N-nitroso-N-methyl-4-fluoroaniline, dinitrosoethambutol, (R,R)- and mononitrosocaffeidine) that were reported to be negative in historical Ames Tests but positive in rodent carcinogenicity studies. All seven of the NAs were demonstrated to be mutagenic in the OECD aligned Ames test and therefore these compounds should no longer be considered as discordant (false negatives) with respect to the correlation of the Ames Test and rodent carcinogenicity. These results confirm the sensitivity of the OECD aligned Ames Test for the detection of NA mutagenicity and provides further support of its pivotal placement within the ICH M7 framework for the assessment of mutagenic impurities in pharmaceuticals to limit potential carcinogenic risk. In addition, we present data for 1-cyclopentyl-4-nitrosopiperazine, that indicates it could serve as a suitable positive control to provide further confidence in the sensitivity of the Ames Test for the NA chemical class., (© The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.)

Emerging evidence indicates that micro- and macro-plastics present in water can support a diverse microbial community, including potential human pathogens (e.g., bacteria, viruses). This interaction raises important concerns surrounding the role and suitability of current bathing water regulations and associated pathogen exposure risk within beach environments. In response to this, we critically evaluated the available evidence on plastic-pathogen interactions and identified major gaps in knowledge. This review highlighted the need for a conceptual shift in risk management at public beaches recognising: (i) interconnected environmental risks, e.g., associations between microbial compliance parameters, potential pathogens and both contemporary and legacy plastic pollution; and (ii) an appreciation of risk of exposure to plastic co-pollutants for both water and waterside users. We present a decision-making framework to identify options to manage plastic-associated pathogen risks alongside short- and longer-term research priorities. This advance will help deliver improvements in managing plastic-associated pathogen risk, acknowledging that human exposure potential is not limited to only those who engage in water-based activity. We argue that adopting these recommendations will help create an integrated approach to managing and reducing human exposure to pathogens at bathing, recreational water and beach environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although many studies predict extensive future biodiversity loss and redistribution in the terrestrial realm, future changes in marine biodiversity remain relatively unexplored. In this work, we model global shifts in one of the most important marine functional groups-ecosystem-structuring macrophytes-and predict substantial end-of-century change. By modelling the future distribution of 207 brown macroalgae and seagrass species at high temporal and spatial resolution under different climate-change projections, we estimate that by 2100, local macrophyte diversity will decline by 3-4% on average, with 17 to 22% of localities losing at least 10% of their macrophyte species. The current range of macrophytes will be eroded by 5-6%, and highly suitable macrophyte habitat will be substantially reduced globally (78-96%). Global macrophyte habitat will shift among marine regions, with a high potential for expansion in polar regions., (© 2024. The Author(s).)

Background: Plastics pollution and antimicrobial resistance (AMR) are two major environmental threats, but potential connections between plastic associated biofilms, the 'plastisphere', and dissemination of AMR genes are not well explored., Results: We conducted mesocosm experiments tracking microbial community changes on plastic surfaces transitioning from wastewater effluent to marine environments over 16 weeks. Commonly used plastics, polypropylene (PP), high density polyethylene (HDPE), low density polyethylene (LDPE) and polyethylene terephthalate (PET) incubated in wastewater effluent, river water, estuarine water, and in the seawater for 16 weeks, were analysed via 16S rRNA gene amplicon and shotgun metagenome sequencing. Within one week, plastic-colonizing communities shifted from wastewater effluent-associated microorganisms to marine taxa, some members of which (e.g. Oleibacter-Thalassolituus and Sphingomonas spp., on PET, Alcanivoracaceae on PET and PP, or Oleiphilaceae, on all polymers), were selectively enriched from levels undetectable in the starting communities. Remarkably, microbial biofilms were also susceptible to parasitism, with Saprospiraceae feeding on biofilms at late colonisation stages (from week 6 onwards), while Bdellovibrionaceae were prominently present on HDPE from week 2 and LDPE from day 1. Relative AMR gene abundance declined over time, and plastics did not become enriched for key AMR genes after wastewater exposure., Conclusion: Although some resistance genes occurred during the mesocosm transition on plastic substrata, those originated from the seawater organisms. Overall, plastic surfaces incubated in wastewater did not act as hotspots for AMR proliferation in simulated marine environments., (© 2024. The Author(s).)

The robust control of genotoxic N-nitrosamine (NA) impurities is an important safety consideration for the pharmaceutical industry, especially considering recent drug product withdrawals. NAs belong to the 'cohort of concern' list of genotoxic impurities (ICH M7) because of the mutagenic and carcinogenic potency of this chemical class. In addition, regulatory concerns exist regarding the capacity of the Ames test to predict the carcinogenic potential of NAs because of historically discordant results. The reasons postulated to explain these discordant data generally point to aspects of Ames test study design. These include vehicle solvent choice, liver S9 species, bacterial strain, compound concentration, and use of pre-incubation versus plate incorporation methods. Many of these concerns have their roots in historical data generated prior to the harmonization of Ames test guidelines. Therefore, we investigated various Ames test assay parameters and used qualitative analysis and quantitative benchmark dose modelling to identify which combinations provided the most sensitive conditions in terms of mutagenic potency. Two alkyl-nitrosamines, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) were studied. NDMA and NDEA mutagenicity was readily detected in the Ames test and key assay parameters were identified that contributed to assay sensitivity rankings. The pre-incubation method (30-min incubation), appropriate vehicle (water or methanol), and hamster-induced liver S9, alongside Salmonella typhimurium strains TA100 and TA1535 and Escherichia coli strain WP2uvrA(pKM101) provide the most sensitive combination of assay parameters in terms of NDMA and NDEA mutagenic potency in the Ames test. Using these parameters and further quantitative benchmark dose modelling, we show that N-nitrosomethylethylamine (NMEA) is positive in Ames test and therefore should no longer be considered a historically discordant NA. The results presented herein define a sensitive Ames test design that can be deployed for the assessment of NAs to support robust impurity qualifications., (© The Author(s) 2023. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.)

There is an urgent need to understand and address the risks associated with a warming climate for ecosystems and societies in the Arctic and sub-Arctic regions. There are major gaps in our understanding of the complex effects of climate change-including extreme events, cascading impacts across ecosystems, and the underlying socioecological dynamics and feedbacks-all of which need collaborative efforts to be resolved. Here, we present results where climate scientists, ecologists, social scientists, and practitioners were asked to identify the most urgent research needs for understanding climate change impacts and to identify the actions for reducing future risks in catchment areas in the Norwegian High North, a region that encompasses both Arctic and sub-Arctic climates in northern Norway. From a list of 77 questions, our panel of 19 scientists and practitioners identified 15 research needs that should be urgently addressed. We particularly urge researchers to investigate cross-ecosystem impacts and the socioecological feedbacks that could amplify or reduce risks for society., (© 2023. The Author(s).)

Aim: To evaluate the safety and efficacy of transarterial chemoembolisation (TACE) in patients with very early and early stage hepatocellular carcinoma (VES-HCC)., Materials and Methods: A retrospective analysis was performed for all TACE procedures done at King's College Hospital, a tertiary liver centre, for VES-HCC during a 5-year period (January 2014-December 2018). Patients with solitary tumours ≤5 cm and patients with 2-3 tumours (each ≤3 cm) were included., Results: Two hundred and thirty-seven eligible patients were included. Technical success was achieved in 233 (98.3%) procedures. TACE using drug-eluting beads (DEB-TACE) was performed in 192 (82.4%) procedures. A complete response was achieved in 109 (45.9%) patients. The recurrence rate was 44% (48 cases), during a median imaging follow-up of 31.9 months (IQR 15.9-44.7). Median overall survival was 71.1 months (95% confidence interval [CI]: 62.9-79.3). Median recurrence-free survival was 58.9 months (95% CI: 47.1-70.7). Sixty-six (27.8%) patients eventually underwent transplantation, and six (2.5%) patients underwent surgical resection. Mild, moderate, and severe adverse events were encountered in 2.9%, 5.4%, and 0.8% of cases, respectively. No 30-day mortality was encountered., Conclusion: DEB-TACE is safe and effective for treating VES-HCC patients, who are unsuitable for thermal ablation or surgery, and may offer comparable survival benefit. It can also be used as a bridge to transplantation for these patients., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Four lytic mycobacteriophages, namely, SynergyX, Abinghost, Bananafish, and Delton, were isolated from soil in Washington, DC, using the bacterial host Mycobacterium smegmatis mc 2 155. Analysis of the genomes revealed that they belong to two subclusters of actinobacteriophage cluster B (subclusters B2 and B3) and subcluster D1 of cluster D.

Network theory offers innovative tools to explore the complex ecological mechanisms regulating species associations and interactions. Although interest in ecological networks has grown steadily during the last two decades, the application of network approaches has been unequally distributed across different study systems: while some kinds of interactions (e.g. plant-pollinator and host-parasite) have been extensively investigated, others remain relatively unexplored. Among the latter, aquatic macrophyte-animal associations in coastal environments have been largely neglected, despite their major role in littoral ecosystems. The ubiquity of macrophyte systems, their accessibility and multi-faceted ecological, economical and societal importance make macrophyte-animal systems an ideal subject for ecological network science. In fact, macrophyte-animal networks offer an aquatic counterpart to terrestrial plant-animal networks. In this review, we show how the application of network analysis to aquatic macrophyte-animal associations has the potential to broaden our understanding of how coastal ecosystems function. Network analysis can also provide a key to understanding how such ecosystems will respond to on-going and future threats from anthropogenic disturbance and environmental change. For this, we: (i) identify key issues that have limited the application of network theory and modelling to aquatic animal-macrophyte associations; (ii) illustrate through examples based on empirical data how network analysis can offer new insights on the complexity and functioning of coastal ecosystems; and (iii) provide suggestions for how to design future studies and establish this new research line into network ecology., (© 2022 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

The Arctic Ocean is undergoing rapid change: sea ice is being lost, waters are warming, coastlines are eroding, species are moving into new areas, and more. This paper explores the many ways that a changing Arctic Ocean affects societies in the Arctic and around the world. In the Arctic, Indigenous Peoples are again seeing their food security threatened and cultural continuity in danger of disruption. Resource development is increasing as is interest in tourism and possibilities for trans-Arctic maritime trade, creating new opportunities and also new stresses. Beyond the Arctic, changes in sea ice affect mid-latitude weather, and Arctic economic opportunities may re-shape commodities and transportation markets. Rising interest in the Arctic is also raising geopolitical tensions about the region. What happens next depends in large part on the choices made within and beyond the Arctic concerning global climate change and industrial policies and Arctic ecosystems and cultures., (© 2021. The Author(s).)

Background: Recurrent reports of suboptimal influenza vaccine effectiveness have renewed calls to develop improved, broadly cross-protective influenza vaccines. Here, we evaluated the safety and immunogenicity of a novel, saponin (Matrix-M)-adjuvanted, recombinant hemagglutinin (HA) quadrivalent nanoparticle influenza vaccine (qNIV)., Methods: We conducted a randomized, observer-blind, comparator-controlled (trivalent high-dose inactivated influenza vaccine [IIV3-HD] or quadrivalent recombinant influenza vaccine [RIV4]), safety and immunogenicity trial of qNIV (5 doses/formulations) in healthy adults ≥65 years. Vaccine immunogenicity was measured by hemagglutination-inhibition assays using reagents that express wild-type hemagglutination inhibition (wt-HAI) sequences and cell-mediated immune responses., Results: A total of 1375 participants were randomized, immunized, and followed for safety and immunogenicity. Matrix-M-adjuvanted qNIV induced superior wt-HAI antibody responses against 5 of 6 homologous or drifted strains compared with unadjuvanted qNIV. Adjuvanted qNIV induced post-vaccination wt-HAI antibody responses at day 28 that were statistically higher than IIV3-HD against a panel of homologous or drifted A/H3N2 strains, similar to IIV3-HD against homologous A/H1N1 and B (Victoria) strains and similar to RIV4 against all homologous and drifted strains evaluated. The qNIV formulation with 75 µg Matrix-M adjuvant induced substantially higher post-vaccination geometric mean fold increases of influenza HA-specific polyfunctional CD4+ T cells compared with IIV3-HD or RIV4. Overall, similar frequencies of solicited and unsolicited adverse events were reported in all treatment groups., Conclusions: qNIV with 75 µg Matrix-M adjuvant was well tolerated and induced robust antibody and cellular responses, notably against both homologous and drifted A/H3N2 viruses. Further investigation in a pivotal phase 3 trial is underway., Clinical Trials Registration: NCT03658629., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Poly-3-hydroxyalkanoic acids (PHAs) are bacterial storage polymers commonly used in bioplastic production. Halophilic bacteria are industrially interesting organisms, as their salinity tolerance and psychrophilic nature lowers sterility requirements and subsequent production costs. We investigated PHA synthesis in two bacterial strains, Halomonas sp. 363 and Paracoccus sp. 392, isolated from Southern Ocean sea ice and elucidated the related PHA biopolymer accumulation and composition with various approaches, such as transcriptomics, microscopy, and chromatography. We show that both bacterial strains produce PHAs at 4°C when the availability of nitrogen and/or oxygen limited growth. The genome of Halomonas sp. 363 carries three phaC synthase genes and transcribes genes along three PHA pathways (I to III), whereas Paracoccus sp. 392 carries only one phaC gene and transcribes genes along one pathway (I). Thus, Halomonas sp. 363 has a versatile repertoire of phaC genes and pathways enabling production of both short- and medium-chain-length PHA products. IMPORTANCE Plastic pollution is one of the most topical threats to the health of the oceans and seas. One recognized way to alleviate the problem is to use degradable bioplastic materials in high-risk applications. PHA is a promising bioplastic material as it is nontoxic and fully produced and degraded by bacteria. Sea ice is an interesting environment for prospecting novel PHA-producing organisms, since traits advantageous to lower production costs, such as tolerance for high salinities and low temperatures, are common. We show that two sea-ice bacteria, Halomonas sp. 363 and Paracoccus sp. 392, are able to produce various types of PHA from inexpensive carbon sources. Halomonas sp. 363 is an especially interesting PHA-producing organism, since it has three different synthesis pathways to produce both short- and medium-chain-length PHAs.

Purpose: Glofitamab is a T-cell-engaging bispecific antibody possessing a novel 2:1 structure with bivalency for CD20 on B cells and monovalency for CD3 on T cells. This phase I study evaluated glofitamab in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Data for single-agent glofitamab, with obinutuzumab pretreatment ( Gpt ) to reduce toxicity, are presented., Methods: Seven days before the first dose of glofitamab (0.005-30 mg), all patients received 1,000 mg Gpt . Dose-escalation steps were determined using a Bayesian continuous reassessment method with overdose control. Primary end points were safety, pharmacokinetics, and the maximum tolerated dose of glofitamab., Results: Following initial single-patient cohorts, 171 patients were treated within conventional multipatient cohorts and received at least one dose of glofitamab. This trial included heavily pretreated patients with R/R B-NHL; most were refractory to prior therapy (155; 90.6%) and had received a median of three prior therapies. One hundred and twenty-seven patients (74.3%) had diffuse large B-cell lymphoma, transformed follicular lymphoma, or other aggressive histology, and the remainder had indolent lymphoma subtypes. Five (2.9%) patients withdrew from treatment because of adverse events. Cytokine release syndrome occurred in 86 of 171 (50.3%) patients (grade 3 or 4: 3.5%); two (1.2%) patients experienced grade 3, transient immune effector cell-associated neurotoxicity syndrome-like symptoms. The overall response rate was 53.8% (complete response [CR], 36.8%) among all doses and 65.7% (CR, 57.1%) in those dosed at the recommended phase II dose. Of 63 patients with CR, 53 (84.1%) have ongoing CR with a maximum of 27.4 months observation., Conclusion: In patients with predominantly refractory, aggressive B-NHL, glofitamab showed favorable activity with frequent and durable CRs and a predictable and manageable safety profile., Competing Interests: Martin HutchingsConsulting or Advisory Role: Takeda, Roche, GenmabResearch Funding: Celgene, Genmab, Roche, Takeda, Novartis Franck MorschhauserConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Celgene, Bristol Myers Squibb, AbbVie, Epizyme, ServierSpeakers' Bureau: RocheExpert Testimony: Roche/Genentech Gloria IacoboniHonoraria: Gilead Sciences, Novartis, Roche/Genentech, Celgene/Bristol Myers Squibb, JanssenConsulting or Advisory Role: Novartis, Celgene/Bristol Myers Squibb, Gilead SciencesTravel, Accommodations, Expenses: Gilead Sciences, Novartis, Celgene/Bristol Myers Squibb Carmelo Carlo-StellaHonoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca, Celgene, Takeda, Incyte, Gilead SciencesConsulting or Advisory Role: Sanofi, ADC Therapeutics, Roche, Karyopharm Therapeutics, Celgene/Bristol Myers Squibb, IncyteResearch Funding: ADC Therapeutics, Sanofi, RocheTravel, Accommodations, Expenses: Roche, Janssen, Takeda, ADC Therapeutics Anna SuredaHonoraria: Takeda, Bristol Myers Squibb, Merck Sharp & Dohme, Celgene, Janssen, Sanofi, Roche, Novartis, Gilead Sciences, Janssen-CilagConsulting or Advisory Role: Takeda, Bristol Myers Squibb, Gilead Sciences, Celgene, Janssen, NovartisSpeakers' Bureau: TakedaOther Relationship: Sanofi, Takeda, Roche, Celgene, Gilead Sciences Gilles SallesHonoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, AbbVie, MorphoSysConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Sciences, Genmab, Debiopharm Group, Velosbio, Bristol Myers Squibb, BeiGene, Incyte, Miltenyi Biotec Joaquín Martínez-LopezSpeakers' Bureau: Roche, Janssen-Cilag, BMSiResearch Funding: Astellas Pharma, Bristol Myers Squibb Michael CrumpHonoraria: Gilead Sciences, Servier/PfizerConsulting or Advisory Role: Servier, Gilead Sciences, Novartis Canada Pharmaceuticals IncResearch Funding: Roche Canada Denise N. ThomasEmployment: Roche TCRC, Genmab, Cellectis Peter N. MorcosEmployment: Roche/Genentech, BayerStock and Other Ownership Interests: Roche/Genentech, Bayer Cristiano FerliniEmployment: Roche/Genentech, AstraZenecaStock and Other Ownership Interests: AstraZeneca, Roche Ann-Marie E. BröskeEmployment: RocheStock and Other Ownership Interests: Roche, BioNTech AG Anton BelousovEmployment: Roche Marina BacacEmployment: RocheStock and Other Ownership Interests: RocheResearch Funding: RochePatents, Royalties, Other Intellectual Property: Coinventor in Roche patentsTravel, Accommodations, Expenses: Roche Natalie DimierEmployment: RocheStock and Other Ownership Interests: RocheTravel, Accommodations, Expenses: Roche David J. CarlileEmployment: Roche, AstraZenecaStock and Other Ownership Interests: AstraZeneca, Roche Linda LundbergEmployment: F. Hoffmann LaRocheStock and Other Ownership Interests: F. Hoffmann LaRoche David Perez-CallejoEmployment: RocheStock and Other Ownership Interests: Roche Pablo UmañaEmployment: RocheLeadership: RocheStock and Other Ownership Interests: RochePatents, Royalties, Other Intellectual Property: Co-inventor in Roche-owned patents on glofitamab and obinutuzumabTravel, Accommodations, Expenses: Roche Tom MooreEmployment: RocheStock and Other Ownership Interests: RocheTravel, Accommodations, Expenses: Roche Martin WeisserEmployment: RocheStock and Other Ownership Interests: RochePatents, Royalties, Other Intellectual Property: I hold patents for biomarkers and drug combinations. These are not related to the present study. I do not receive royalties Michael J. DickinsonHonoraria: Roche, Amgen, MSD, Janssen, Bristol Myers Squibb, NovartisConsulting or Advisory Role: Novartis, Bristol Myers Squibb, Gilead Sciences, Roche, JanssenSpeakers' Bureau: NovartisResearch Funding: Novartis, Roche, Takeda, Celgene, MSDTravel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.

The relative flow of carbon through the viral shunt and the microbial loop is a pivotal factor controlling the contribution of secondary production to the food web and to rates of nutrient remineralization and respiration. The current study examines the significance of these processes in the coastal waters of the Antarctic during the productive austral summer months. Throughout the study a general trend towards lower bacterioplankton and heterotrophic nanoflagellate (HNF) abundances was observed, whereas virioplankton concentration increased. A corresponding decline of HNF grazing rates and shift towards viral production, indicative of viral infection, was measured. Carbon flow mediated by HNF grazing decreased by more than half from 5.7 µg C L -1 day -1 on average in December and January to 2.4 µg C L -1 day -1 in February. Conversely, carbon flow through the viral shunt increased substantially over the study from on average 0.9 µg C L -1 day -1 in December to 7.6 µg C L -1 day -1 in February. This study shows that functioning of the coastal Antarctic microbial community varied considerably over the productive summer months. In early summer, the system favors transfer of matter and energy to higher trophic levels via the microbial loop, however towards the end of summer carbon flow is redirected towards the viral shunt, causing a switch towards more recycling and therefore increased respiration and regeneration.

Introduction: This pilot/feasibility study evaluated a new diagnostic and treatment paradigm for patients with lower urinary tract symptoms using a software platform comprised of a mobile app, validated patient reported outcome questionnaires, bladder diaries and remote patient monitoring., Methods: New urology referrals for lower urinary tract symptoms completed validated lower urinary tract symptoms questionnaires and 24-hour bladder diaries on a mobile app. Patients were triaged based on symptom severity into an urgent or routine office visit or a remote visit. Outcome metrics assessed include acceptability, practicality, implementation and integration., Results: Of 500 urology consults there were 226 (45%) patients with new lower urinary tract symptoms referrals of whom 201 (89%) had email addresses. In all there were 182 men and 19 women, aged 18 to 87 years (mean 59, SD 17), of whom 71/201 (35%) registered, 57/71 (80%) completed the app and 41/57 (72%) elected remote visits. Mean time from urology referral to initiation of a remote or in-office diagnostic and treatment plan was 7.4 days (SD 5.9) and 7.7 days (SD 7.6), respectively., Conclusions: Of patients who completed the app 72% were triaged to a remote visit. Time from urology referral to initiation of remote or in-office diagnostic and treatment plan averaged 1 week. This paradigm for management of lower urinary tract symptoms has potential to optimize the clinical workflow, improve health care outcomes and reduce costs.

GlaxoSmithKline and Astex Pharmaceuticals recently disclosed the discovery of the potent H-PGDS inhibitor GSK2894631A 1a (IC 50  = 9.9 nM) as part of a fragment-based drug discovery collaboration with Astex Pharmaceuticals. This molecule exhibited good murine pharmacokinetics, allowing it to be utilized to explore H-PGDS pharmacology in vivo. Yet, with prolonged dosing at higher concentrations, 1a induced CNS toxicity. Looking to attenuate brain penetration in this series, aza-quinolines, were prepared with the intent of increasing polar surface area. Nitrogen substitutions at the 6- and 8-positions of the quinoline were discovered to be tolerated by the enzyme. Subsequent structure activity studies in these aza-quinoline scaffolds led to the identification of 1,8-naphthyridine 1y (IC 50  = 9.4 nM) as a potent peripherally restricted H-PGDS inhibitor. Compound 1y is efficacious in four in vivo inflammatory models and exhibits no CNS toxicity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Marine hydrocarbon-degrading bacteria play an important role in natural petroleum biodegradation processes and were initially associated with man-made oil spills or natural seeps. There is no full clarity though on what, in the absence of petroleum, their natural niches are. Few studies pointed at some marine microalgae that produce oleophilic compounds (alkanes, long-chain fatty acids, and alcohols) as potential natural hosts of these bacteria. We established Dansk crude oil-based enrichment cultures with photobioreactor-grown marine microalgae cultures Pavlova lutheri and Nannochloropsis oculata and analyzed the microbial succession using cultivation and SSU (16S) rRNA amplicon sequencing. We found that petroleum enforced a strong selection for members of Alpha- and Gamma-proteobacteria in both enrichment cultures with the prevalence of Alcanivorax and Marinobacter spp., well-known hydrocarbonoclastic bacteria. In total, 48 non-redundant bacterial strains were isolated and identified to represent genera Alcanivorax , Marinobacter , Thalassospira , Hyphomonas , Halomonas , Marinovum , Roseovarius , and Oleibacter , which were abundant in sequencing reads in both crude oil enrichments. Our assessment of public databases demonstrated some overlaps of geographical sites of isolation of Nannochloropsis and Pavlova with places of molecular detection and isolation of Alcanivorax and Marinobacter spp. Our study suggests that these globally important hydrocarbon-degrading bacteria are associated with P. lutheri and N. oculata ., (Copyright © 2020 Chernikova, Bargiela, Toshchakov, Shivaraman, Lunev, Yakimov, Thomas and Golyshin.)

Mini-percutaneous nephrolithotomy (mini-PCNL) has been described as a safe and effective technique to eliminate stones in patients in whom a less-invasive approach is desired. It was originally developed to treat stones in the pediatric population, but has since been adapted to serve a role in the adult urologic community. This approach has been reported to result in less blood loss and postoperative pain when compared with traditional PCNL. Herein, we present a case in which a recurrent caliceal diverticulum containing stones was managed using a mini-PCNL technique in a patient who previously failed multiple other retrograde endoscopic approaches., Competing Interests: No competing financial interests exist., (Copyright 2020, Mary Ann Liebert, Inc., publishers.)

Background: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants., Methods: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%)., Results: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups., Conclusions: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.)., (Copyright © 2020 Massachusetts Medical Society.)

Current concerns about climate change have led to intensive research attempting to understand how climate-driven stressors affect the performance of organisms, in particular the offspring of many invertebrates and fishes. Although stressors are likely to act on several stages of the life cycle, little is known about their action across life phases, for instance how multiple stressors experienced simultaneously in the maternal environment can modulate the responses to the same stressors operating in the offspring environment. Here, we study how performance of offspring of a marine invertebrate (shore crab Carcinus maenas ) changes in response to two stressors (temperature and salinity) experienced during embryogenesis in brooding mothers from different seasons. On average, offspring responses were antagonistic: high temperature mitigated the negative effects of low salinity on survival. However, the magnitude of the response was modulated by the temperature and salinity conditions experienced by egg-carrying mothers. Performance also varied among cohorts, perhaps reflecting genetic variation, and/or maternal conditions prior to embryogenesis. This study contributes towards the understanding of how anthropogenic modification of the maternal environment drives offspring performance in brooders.

Diatoms are significant primary producers in sea ice, an ephemeral habitat with steep vertical gradients of temperature and salinity characterizing the ice matrix environment. To cope with the variable and challenging conditions, sea ice diatoms produce polysaccharide-rich extracellular polymeric substances (EPS) that play important roles in adhesion, cell protection, ligand binding and as organic carbon sources. Significant differences in EPS concentrations and chemical composition corresponding to temperature and salinity gradients were present in sea ice from the Weddell Sea and Eastern Antarctic regions of the Southern Ocean. To reconstruct the first metabolic pathway for EPS production in diatoms, we exposed Fragilariopsis cylindrus, a key bi-polar diatom species, to simulated sea ice formation. Transcriptome profiling under varying conditions of EPS production identified a significant number of genes and divergent alleles. Their complex differential expression patterns under simulated sea ice formation was aligned with physiological and biochemical properties of the cells, and with field measurements of sea ice EPS characteristics. Thus, the molecular complexity of the EPS pathway suggests metabolic plasticity in F. cylindrus is required to cope with the challenging conditions of the highly variable and extreme sea ice habitat.

Objective: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules., Methods: Placebo, or vaccine with 60μg or 120μg RSV F protein and 0.2, 0.4, or 0.8mg aluminum, were administered intramuscularly on Days 0 and 28 to healthy women 18-35years old. Immunogenicity was assessed from Days 0 through 91 based on anti-F IgG and palivizumab-competitive antibody (PCA) by ELISA, and RSV A and B neutralizing antibodies by microneutralization (MN) assay. Solicited adverse events were collected through Day 7 and unsolicited adverse events through Day 91., Results: All formulations were well-tolerated, with no treatment-related serious adverse events. Anti-F IgG and PCA responses were correlated and increased after both doses, while MN increased significantly only after the first dose, then plateaued. The timeliest and most robust antibody responses followed one dose of 120μg RSV F protein and 0.4mg aluminum, but persistence through 91days was modestly (∼25%) superior following two doses of 60μg RSV F protein and 0.8mg aluminum. Western blot analysis showed RSV infections in active vaccinees were reduced by 52% overall (p=0.009 overall) over the Day 0 through 90 period., Conclusions: RSV F nanoparticle vaccine formulations were well tolerated and immunogenic. The optimal combination of convenience and rapid response for immunization in the third trimester occurred with 120μg RSV F and 0.4mg aluminum, which achieved peak immune responses in 14days and sufficient persistence through 91days to allow for passive transfer of IgG antibodies to the fetus. NCT01960686., (Copyright © 2017 Novavax. Published by Elsevier Ltd.. All rights reserved.)

Background: A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 μg RSV F protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study., Results: A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine., Conclusions: RSV F protein nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.

Background: Respiratory syncytial virus (RSV) is a leading cause of infant morbidity and mortality. A recombinant RSV fusion protein nanoparticle vaccine (RSV F vaccine) candidate for maternal immunization was tested for safety and immunogenicity in women of childbearing age., Methods: Three hundred thirty women (18-35 years) were randomized to receive 1 or 2 doses of RSV F vaccine (60 or 90 µg) with or without aluminum phosphate adjuvant, or placebo at days 0 and 28. Safety was evaluated over 180 days; immunogenicity and RSV infection rates were evaluated over 112 days., Results: All vaccine formulations were well tolerated, without vaccine-related serious adverse events. Anti-F immunoglobulin G antibodies rose 6.5-15.6-fold, with significantly higher levels in 2-dose, adjuvanted regimens at day 56. Palivizumab-competitive antibody levels were undetectable at day 0 but increased up to 325 µg/mL at day 56. A 2.7- and 3.5-fold rise in RSV/A and RSV/B microneutralization antibodies were noted at day 56. Between days 56 and 112, 21% (12/56) of placebo recipients and 11% of vaccinees (26/244) showed evidence of a recent RSV infection (P = .04)., Conclusions: The vaccine appeared safe, immunogenic, and reduced RSV infections. Further development as a vaccine for use in maternal immunization is warranted., Clinical Trials Registration: NCT01704365., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Climate change scenarios for northern boreal regions indicate that there will be increasing temperature and precipitation, and the changes are expected to be larger in winter than in summer. These precipitation and discharge patterns, coupled with shorter ice cover/soil frost periods in the future would be expected to contribute significantly to changing flow paths of organic matter over a range of land use patterns. In order to study the impact of climate change on the seasonality of organic matter export we compared total organic carbon (TOC) and total organic nitrogen (TON) concentrations and export, during different seasons and climatically different years, over 12 years for 30 Finnish rivers separated into forest, agriculture and peat dominated catchments. The mean monthly TOC concentrations were highest during autumn and there was also a peak in May during the highest flow period. The mean monthly concentrations of TON were lowest during winter, increased in spring and remaining high throughout summer and autumn. The TOC/TON ratios were lowest during summer and highest during winter, and in all seasons the ratios were lowest in catchments with a high proportion of agricultural land and highest in peat-dominated catchments. The seasonality of TOC and TON exports reflected geographical location, hydrology and land use patterns. Most of the TOC and TON were transported during the high flow following the spring snowmelt and during rainfall in autumn. In all catchments the relative importance of the spring snowmelt decreased in wet and warm years. However, in peat-dominated catchments the proportion of spring period was over 30% of the annual export even in these wet and warm years, while in other catchments the proportion was about 20%. This might be linked to the northern location of the peat-dominated catchments and the permanent snow cover and spring snowmelt, even in warm years., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The increasing need for environmentally sound aquaculture development can, in part, be addressed by using halophytic plants in integrated multitrophic aquaculture systems (IMTA) to remove waste dissolved nitrogen (N). However, knowledge of plant ability to take up nitrogen is of foremost importance to predict plants performance in such systems. Two species, Salicornia europaea and Aster tripolium, have been identified as potential candidates for IMTA due to their salt tolerance, potential N removal capabilities and their high commercial value as an additional crop. This study investigated the growth and N uptake rates of these two species under different N supply (NH4(+), NO3(-), NH4NO3). S. europaea plants produced a lower biomass when grown in NH4(+) compared to NO3(-) or NH4NO3, while A. tripolium biomass was not affected by the form in which N was supplied. N uptake in plants incubated at different concentrations of (15)N enriched solution (up to 2 mmol l(-1)) fitted the Michaelis-Menten model. While S. europaea NH4-N maximum uptake did not differ between starved and non-starved plants, A. tripolium NH4-N uptake was higher in starved plants when supplied alone. When NO3(-) was supplied alone, NO3-N maximum uptake was lower, for both species, when the plants were not starved. Comparison of starved and non-starved plants N uptake demonstrates the need for cautious interpretation of N uptake rates across different conditions. According to the observed results, both S. europaea and A. tripolium are capable of significantly high biomass production and N removal making them potential species for inclusion in efficient IMTA., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study measured the effects of land use on organic matter released to surface waters in a boreal peat catchment using radiocarbon dating of particulate and dissolved organic carbon (POC and DOC), DOC concentration, stable carbon and nitrogen isotope composition, and optical measurements. Undisturbed sites invariably released modern DOC and POC (<20 years old), and seasonal forcing had little impact on the age distribution. Release of pre-1950 carbon was detected at peat extraction, agricultural and drained sites, and was consistently observed at agricultural and peat extraction areas throughout the seasons. Conventional mean DOC ages reached 3,100 (±122) years before collection. On average, DOC concentrations were up to 38% higher at impacted sites compared to natural areas, but there was no significant effect of land use on surface water DOC concentrations. The study indicates that the true extent of land use impacts is not necessarily detectible through changes in DOC concentration alone: Radiocarbon dating was essential to show that leaching of old soil organic matter at modified sites had replaced, rather than supplemented, the modern DOM that is usually released from pristine peatlands. Relationships between the specific fluorescence intensity of DOM and its radiocarbon age were identified, indicating that optical techniques may provide a method for the detection of changes in DOM age.

The structure of sea-ice bacterial communities is frequently different from that in seawater. Bacterial entrainment in sea ice has been studied with traditional microbiological, bacterial abundance, and bacterial production methods. However, the dynamics of the changes in bacterial communities during the transition from open water to frozen sea ice is largely unknown. Given previous evidence that the nutritional status of the parent water may affect bacterial communities during ice formation, bacterial succession was studied in under ice water and sea ice in two series of mesocosms: the first containing seawater from the North Sea and the second containing seawater enriched with algal-derived dissolved organic matter (DOM). The composition and dynamics of bacterial communities were investigated with terminal restriction fragment length polymorphism (T-RFLP), and cloning alongside bacterial production (thymidine and leucine uptake) and abundance measurements (measured by flow cytometry). Enriched and active sea-ice bacterial communities developed in ice formed in both unenriched and DOM-enriched seawater (0-6 days). γ-Proteobacteria dominated in the DOM-enriched samples, indicative of their capability for opportunistic growth in sea ice. The bacterial communities in the unenriched waters and ice consisted of the classes Flavobacteria, α- and γ-Proteobacteria, which are frequently found in natural sea ice in polar regions. Furthermore, the results indicate that seawater bacterial communities are able to adapt rapidly to sudden environmental changes when facing considerable physicochemical stress such as the changes in temperature, salinity, nutrient status, and organic matter supply during ice formation., (© 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Sea ice can contain high concentrations of dissolved organic carbon (DOC), much of which is carbohydrate-rich extracellular polymeric substances (EPS) produced by microalgae and bacteria inhabiting the ice. Here we report the concentrations of dissolved carbohydrates (dCHO) and dissolved EPS (dEPS) in relation to algal standing stock [estimated by chlorophyll (Chl) a concentrations] in sea ice from six locations in the Southern and Arctic Oceans. Concentrations varied substantially within and between sampling sites, reflecting local ice conditions and biological content. However, combining all data revealed robust statistical relationships between dCHO concentrations and the concentrations of different dEPS fractions, Chl a, and DOC. These relationships were true for whole ice cores, bottom ice (biomass rich) sections, and colder surface ice. The distribution of dEPS was strongly correlated to algal biomass, with the highest concentrations of both dEPS and non-EPS carbohydrates in the bottom horizons of the ice. Complex EPS was more prevalent in colder surface sea ice horizons. Predictive models (validated against independent data) were derived to enable the estimation of dCHO concentrations from data on ice thickness, salinity, and vertical position in core. When Chl a data were included a higher level of prediction was obtained. The consistent patterns reflected in these relationships provide a strong basis for including estimates of regional and seasonal carbohydrate and dEPS carbon budgets in coupled physical-biogeochemical models, across different types of sea ice from both polar regions.

Genetic-modification strategies are currently being developed to reduce the transmission of vector-borne diseases, including African trypanosomiasis. For tsetse, the vector of African trypanosomiasis, a paratransgenic strategy is being considered: this approach involves modification of the commensal symbiotic bacteria Sodalis to express trypanosome-resistance-conferring products. Modified Sodalis can then be driven into the tsetse population by cytoplasmic incompatibility (CI) from Wolbachia bacteria. To evaluate the effectiveness of this paratransgenic strategy in controlling African trypanosomiasis, we developed a three-species mathematical model of trypanosomiasis transmission among tsetse, humans, and animal reservoir hosts. Using empirical estimates of CI parameters, we found that paratransgenic tsetse have the potential to eliminate trypanosomiasis, provided that any extra mortality caused by Wolbachia colonization is low, that the paratransgene is effective at protecting against trypanosome transmission, and that the target tsetse species comprises a large majority of the tsetse population in the release location.