A system in balance? ? Implications of deep vertical mixing for the nitrogen budget in the northern Red Sea, including the Gulf of Aqaba (Eilat)

International audienceWe investigated the implications of deep winter mixing for the nitrogen budget in two adjacent systems, the northern Red Sea proper, and the Gulf of Aqaba. Both are subtropical oligotrophic water bodies. The main difference is that in the gulf deep winter mixing takes place regularly, whereas the northern Red Sea proper is permanently stratified. In the Gulf of Aqaba, we observed significantly lower nitrate deficits, i.e. deviations from the Redfield ratio, than in the northern Red Sea proper. Assuming that other external inputs and losses in N or P are very similar in both systems, the higher nitrate deficit can be explained by either lower nitrogen fixation in the (stratified) northern Red Sea, which seems unlikely. An alternative explanation would be higher rates of benthic denitrification than in the gulf. By comparing the two systems we have indirect evidence that benthic denitrification was much lower in the Gulf of Aqaba due to higher oxygen concentrations. This we attributed to the occurrence of deep winter mixing, and as a consequence, the nitrate deficit was close to zero (i.e. N:P ratio close to "Redfield"). If both nitrogen fixation and benthic denitrification take place, as in the northern Red Sea proper, the result was a positive nitrate deficit (i.e. a deficit in nitrate) in the ambient water. The nitrate deficit in the northern Red Sea was observed in spite of high iron deposition from the surrounding desert. Our results strongly support the concept of nitrogen as the proximate, and phosphate as the ultimate limiting nutrient for primary production in the sea. This must not be neglected in efforts for protecting the adjacent reefs against eutrophication

Nitrogen and phosphorus limitation of oceanic microbial growth during spring in the Gulf of Aqaba

Bioassay experiments were performed to identify how growth of key groups within the microbial community was simultaneously limited by nutrient (nitrogen and phosphorus) availability during spring in the Gulf of Aqaba's oceanic waters. Measurements of chlorophyll a (chl a) concentration and fast repetition rate (FRR) fluorescence generally demonstrated that growth of obligate phototrophic phytoplankton was co-limited by N and P and growth of facultative aerobic anoxygenic photoheterotropic (AAP) bacteria was limited by N. Phytoplankton exhibited an increase in chl a biomass over 24 to 48 h upon relief of nutrient limitation. This response coincided with an increase in photosystem II (PSII) photochemical efficiency (F v /F m), but was preceded (within 24 h) by a decrease in effective absorption crosssection (σPSII) and electron turnover time (τ). A similar response for τ and bacterio-chl a was observed for the AAPs. Consistent with the up-regulation of PSII activity with FRR fluorescence were observations of newly synthesized PSII reaction centers via low temperature (77K) fluorescence spectroscopy for addition of N (and N + P). Flow cytometry revealed that the chl a and thus FRR fluorescence responses were partly driven by the picophytoplankton (æ10 μm) community, and in particular Synechococcus. Productivity of obligate heterotrophic bacteria exhibited the greatest increase in response to a natural (deep water) treatment, but only a small increase in response to N and P addition, demonstrating the importance of additional substrates (most likely dissolved organic carbon) in moderating the heterotrophs. These data support previous observations that the microbial community response (autotrophy relative to heterotrophy) is critically dependent upon the nature of transient nutrient enrichment. © Inter-Research 2009

Edoxaban: an update on the new oral direct factor Xa inhibitor.

Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options

Rationale and design of the NODE-303 study: evaluating the safety of symptom-prompted, self-administered etripamil for paroxysmal supraventricular tachycardia episodes in real-world settings.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting. METHODS: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. RESULTS: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. CONCLUSIONS: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Multicenter, Phase 2, Randomized Controlled Study of the Efficacy and Safety of Etripamil Nasal Spray for the Acute Reduction of Rapid Ventricular Rate in Patients With Symptomatic Atrial Fibrillation (ReVeRA-201).

BACKGROUND: Despite chronic therapies, atrial fibrillation (AF) leads to rapid ventricular rates (RVR) often requiring intravenous treatments. Etripamil is a fast-acting, calcium-channel blocker administered intranasally affecting the atrioventricular node within minutes. METHODS: Reduction of Ventricular Rate in Patients with Atrial Fibrillation evaluated the efficacy and safety of etripamil for the reduction of ventricular rate (VR) in patients presenting urgently with AF-RVR (VR ≥110 beats per minute [bpm]), was randomized, double-blind, placebo-controlled, and conducted in Canada and the Netherlands. Patients presenting urgently with AF-RVR were randomized (1:1, etripamil nasal spray 70 mg: placebo nasal spray). The primary objective was to demonstrate the effectiveness of etripamil in reducing VR in AF-RVR within 60 minutes of treatment. Secondary objectives assessed achievement of VR <100 bpm, reduction by ≥10% and ≥20%, relief of symptoms and treatment effectiveness; adverse events; and additional measures to 360 minutes. RESULTS: Sixty-nine patients were randomized, 56 dosed with etripamil (n=27) or placebo (n=29). The median age was 65 years; 39% were female patients; proportions of AF types were similar between groups. The difference of mean maximum reductions in VR over 60 minutes, etripamil versus placebo, adjusting for baseline VR, was -29.91 bpm (95% CI, -40.31 to -19.52; P<0.0001). VR reductions persisted up to 150 minutes. Significantly greater proportions of patients receiving etripamil achieved VR reductions <100 bpm (with longer median duration <100 bpm), or VR reduction by ≥10% or ≥20%, versus placebo. VR reduction ≥20% occurred in 66.7% of patients in the etripamil arm and no patients in placebo. Using the Treatment Satisfaction Questionnaire for Medication-9, there was significant improvement in satisfaction on symptom relief and treatment effectiveness with etripamil versus placebo. Serious adverse events were rare; 1 patient in the etripamil arm experienced transient severe bradycardia and syncope, assessed as due to hypervagotonia. CONCLUSIONS: Intranasal etripamil 70 mg reduced VR and improved symptom relief and treatment satisfaction. These data support further development of self-administered etripamil for the treatment of AF-RVR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04467905

The Biology and Economics of Coral Growth

To protect natural coral reefs, it is of utmost importance to understand how the growth of the main reef-building organisms—the zooxanthellate scleractinian corals—is controlled. Understanding coral growth is also relevant for coral aquaculture, which is a rapidly developing business. This review paper provides a comprehensive overview of factors that can influence the growth of zooxanthellate scleractinian corals, with particular emphasis on interactions between these factors. Furthermore, the kinetic principles underlying coral growth are discussed. The reviewed information is put into an economic perspective by making an estimation of the costs of coral aquaculture

Adaptations to Endosymbiosis in a Cnidarian-Dinoflagellate Association: Differential Gene Expression and Specific Gene Duplications

Trophic endosymbiosis between anthozoans and photosynthetic dinoflagellates forms the key foundation of reef ecosystems. Dysfunction and collapse of symbiosis lead to bleaching (symbiont expulsion), which is responsible for the severe worldwide decline of coral reefs. Molecular signals are central to the stability of this partnership and are therefore closely related to coral health. To decipher inter-partner signaling, we developed genomic resources (cDNA library and microarrays) from the symbiotic sea anemone Anemonia viridis. Here we describe differential expression between symbiotic (also called zooxanthellate anemones) or aposymbiotic (also called bleached) A. viridis specimens, using microarray hybridizations and qPCR experiments. We mapped, for the first time, transcript abundance separately in the epidermal cell layer and the gastrodermal cells that host photosynthetic symbionts. Transcriptomic profiles showed large inter-individual variability, indicating that aposymbiosis could be induced by different pathways. We defined a restricted subset of 39 common genes that are characteristic of the symbiotic or aposymbiotic states. We demonstrated that transcription of many genes belonging to this set is specifically enhanced in the symbiotic cells (gastroderm). A model is proposed where the aposymbiotic and therefore heterotrophic state triggers vesicular trafficking, whereas the symbiotic and therefore autotrophic state favors metabolic exchanges between host and symbiont. Several genetic pathways were investigated in more detail: i) a key vitamin K–dependant process involved in the dinoflagellate-cnidarian recognition; ii) two cnidarian tissue-specific carbonic anhydrases involved in the carbon transfer from the environment to the intracellular symbionts; iii) host collagen synthesis, mostly supported by the symbiotic tissue. Further, we identified specific gene duplications and showed that the cnidarian-specific isoform was also up-regulated both in the symbiotic state and in the gastroderm. Our results thus offer new insight into the inter-partner signaling required for the physiological mechanisms of the symbiosis that is crucial for coral health

Impacts of Sediments on Coral Energetics: Partitioning the Effects of Turbidity and Settling Particles

Sediment loads have long been known to be deleterious to corals, but the effects of turbidity and settling particles have not previously been partitioned. This study provides a novel approach using inert silicon carbide powder to partition and quantify the mechanical effects of sediment settling versus reduced light under a chronically high sedimentary regime on two turbid water corals commonly found in Singapore (Galaxea fascicularis and Goniopora somaliensis). Coral fragmentswere evenly distributed among three treatments: an open control (30% ambient PAR), a shaded control (15% ambient PAR) and sediment treatment (15% ambient PAR; 26.4 mg cm22 day21). The rate of photosynthesis and respiration, and the dark-adapted quantum yield were measured once a week for four weeks. By week four, the photosynthesis to respiration ratio (P/R ratio) and the photosynthetic yield (Fv/Fm) had fallen by 14% and 3–17% respectively in the shaded control,contrasting with corals exposed to sediments whose P/R ratio and yield had declined by 21% and 18–34% respectively. The differences in rates between the shaded control and the sediment treatment were attributed to the mechanical effects of sediment deposition. The physiological response to sediment stress differed between species with G. fascicularis experiencing a greater decline in the net photosynthetic yield (13%) than G. somaliensis (9.5%), but a smaller increase in the respiration rates (G. fascicularis = 9.9%, G. somaliensis = 14.2%). These different physiological responses were attributed, in part, to coral morphology and highlighted key physiological processes that drive species distribution along high to low turbidity and depositional gradients