Hydrothermal discharge during submarine eruptions : the importance of detection, response, and new technology

Author Posting. © The Oceanography Society, 2012. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 25, no. 1 (2012): 128–141, doi:10.5670/oceanog.2012.11.Submarine volcanic eruptions and intrusions construct new oceanic crust and build long chains of volcanic islands and vast submarine plateaus. Magmatic events are a primary agent for the transfer of heat, chemicals, and even microbes from the crust to the ocean, but the processes that control these transfers are poorly understood. The 1980s discovery that mid-ocean ridge eruptions are often associated with brief releases of immense volumes of hot fluids ("event plumes") spurred interest in methods for detecting the onset of eruptions or intrusions and for rapidly organizing seagoing response efforts. Since then, some 35 magmatic events have been recognized and responded to on mid-ocean ridges and at seamounts in both volcanic arc and intraplate settings. Field responses at mid-ocean ridges have found that event plumes occur over a wide range of eruption styles and sizes, and thus may be a common consequence of ridge eruptions. The source(s) of event plume fluids are still debated. Eruptions detected at ridges generally have high effusion rates and short durations (hours to days), whereas field responses at arc volcanic cones have found eruptions with very low effusion rates and durations on the scale of years. New approaches to the study of submarine magmatic events include the development of autonomous vehicles for detection and response, and the establishment of permanent seafloor observatories at likely future eruption sites.Support for these efforts came from the NOAA Vents Program and the National Science Foundation, primarily through its long-term funding of the RIDGE and Ridge 2000 Programs, including grants OCE-9812294 and OCE-0222069. SOSUS detection efforts were supported from 2006 to 2009 by the National Science Foundation, grant OCE-0623649

From Your Nose to Your Toes: A Review of Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic‒Associated Pernio

Despite thousands of reported patients with pandemic-associated pernio, low rates of seroconversion and PCR positivity have defied causative linkage to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pernio in uninfected children is associated with monogenic disorders of excessive IFN-1 immunity, whereas severe COVID-19 pneumonia can result from insufficient IFN-1. Moreover, SARS-CoV-2 spike protein and robust IFN-1 response are seen in the skin of patients with pandemic-associated pernio, suggesting an excessive innate immune skin response to SARS-CoV-2. Understanding the pathophysiology of this phenomenon may elucidate the host mechanisms that drive a resilient immune response to SARS-CoV-2 and could produce relevant therapeutic targets

Hydrothermal Discharge During Submarine Eruptions

Submarine volcanic eruptions and intrusions construct new oceanic crust and build long chains of volcanic islands and vast submarine plateaus. Magmatic events are a primary agent for the transfer of heat, chemicals, and even microbes from the crust to the ocean, but the processes that control these transfers are poorly understood. The 1980s discovery that mid-ocean ridge eruptions are often associated with brief releases of immense volumes of hot fluids ("event plumes") spurred interest in methods for detecting the onset of eruptions or intrusions and for rapidly organizing seagoing response efforts. Since then, some 35 magmatic events have been recognized and responded to on mid-ocean ridges and at seamounts in both volcanic arc and intraplate settings. Field responses at mid-ocean ridges have found that event plumes occur over a wide range of eruption styles and sizes, and thus may be a common consequence of ridge eruptions. The source(s) of event plume fluids are still debated. Eruptions detected at ridges generally have high effusion rates and short durations (hours to days), whereas field responses at arc volcanic cones have found eruptions with very low effusion rates and durations on the scale of years. New approaches to the study of submarine magmatic events include the development of autonomous vehicles for detection and response, and the establishment of permanent seafloor observatories at likely future eruption sites.Keywords: de Fuca Ridge, East Pacific rise, Event plumes, Subsurface biosphere, sea floor, Mid-Atlantic Ridge, Military hydrophone arrays, Volcanic eruption, Spreading Gakkel Ridge, Midocean ridg

JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies

BACKGROUND. Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease. METHODS. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. RESULTS. Eighteen patients were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93-1.78) to 0.25 (IQR, 0.1-0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31-1.09) to 0.11 mg/kg/day (IQR, 0.02-0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients' quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. CONCLUSION. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment

A Multicenter Pilot Evaluation of the National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Therapeutic Response Measures: Feasibility, Interrater Reliability, and Minimum Detectable Change

The lack of standardized criteria for measuring therapeutic response is a major obstacle to the development of new therapeutic agents for chronic graft-versus-host disease (cGVHD). National Institutes of Health (NIH) consensus criteria for evaluating therapeutic response were published in 2006. We report the results of four consecutive pilot trials evaluating the feasibility and estimating the inter-rater reliability and minimum detectable change of these response criteria

Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2

We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Assumption without representation: the unacknowledged abstraction from communities and social goods

We have not clearly acknowledged the abstraction from unpriceable “social goods” (derived from communities) which, different from private and public goods, simply disappear if it is attempted to market them. Separability from markets and economics has not been argued, much less established. Acknowledging communities would reinforce rather than undermine them, and thus facilitate the production of social goods. But it would also help economics by facilitating our understanding of – and response to – financial crises as well as environmental destruction and many social problems, and by reducing the alienation from economics often felt by students and the public

Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations

Background Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals. Conclusions Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families