Ice shelf basal channel shape determines channelized ice-ocean interactions.

Growing evidence has confirmed the critical role played by basal channels beneath Antarctic ice shelves in both ice shelf stability and freshwater input to the surrounding ocean. Here we show, using a 3D ice shelf-ocean boundary current model, that deeper basal channels can lead to a significant amplification in channelized basal melting, meltwater channeling, and warming and salinization of the channel flow. All of these channelized quantities are also modulated by channel width, with the level of modulation determined by channel height. The explicit quantification of channelized basal melting and the meltwater transport in terms of channel cross-sectional shape is potentially beneficial for the evaluation of ice shelf mass balance and meltwater contribution to the nearshore oceanography. Complicated topographically controlled circulations are revealed to be responsible for the unique thermohaline structure inside deep channels. Our study emphasizes the need for improvement in observations of evolving basal channels and the hydrography inside them, as well as adjacent to the ice front where channelized meltwater emerges.

FLAMINGO: calibrating large cosmological hydrodynamical simulations with machine learning.

To fully take advantage of the data provided by large-scale structure surveys, we need to quantify the potential impact of baryonic effects, such as feedback from active galactic nuclei (AGN) and star formation, on cosmological observables. In simulations, feedback processes originate on scales that remain unresolved. Therefore, they need to be sourced via subgrid models that contain free parameters. We use machine learning to calibrate the AGN and stellar feedback models for the FLAMINGO (Fullhydro Large-scale structure simulations with All-sky Mapping for the Interpretation of Next Generation Observations) cosmological hydrodynamical simulations. Using Gaussian process emulators trained on Latin hypercubes of 32 smaller volume simulations, we model how the galaxy stellar mass function (SMF) and cluster gas fractions change as a function of the subgrid parameters. The emulators are then fit to observational data, allowing for the inclusion of potential observational biases. We apply our method to the three different FLAMINGO resolutions, spanning a factor of 64 in particle mass, recovering the observed relations within the respective resolved mass ranges. We also use the emulators, which link changes in subgrid parameters to changes in observables, to find models that skirt or exceed the observationally allowed range for cluster gas fractions and the SMF. Our method enables us to define model variations in terms of the data that they are calibrated to rather than the values of specific subgrid parameters. This approach is useful, because subgrid parameters are typically not directly linked to particular observables, and predictions for a specific observable are influenced by multiple subgrid parameters.

Subglacial discharge accelerates future retreat of Denman and Scott Glaciers, East Antarctica.

Ice shelf basal melting is the primary mechanism driving mass loss from the Antarctic Ice Sheet, yet it is unknown how the localized melt enhancement from subglacial discharge will affect future Antarctic glacial retreat. We develop a parameterization of ice shelf basal melt that accounts for both ocean and subglacial discharge forcing and apply it in future projections of Denman and Scott Glaciers, East Antarctica, through 2300. In forward simulations, subglacial discharge accelerates the onset of retreat of these systems into the deepest continental trench on Earth by 25 years. During this retreat, Denman Glacier alone contributes 0.33 millimeters per year to global sea level rise, comparable to half of the contemporary sea level contribution of the entire Antarctic Ice Sheet. Our results stress the importance of resolving complex interactions between the ice, ocean, and subglacial environments in future Antarctic Ice Sheet projections.

Deep Sequencing and Molecular Characterisation of BK Virus and JC Virus WHO International Reference Materials for Clinical Diagnostic Use.

BACKGROUND: Reactivation of JC and BK polyomaviruses during immunosuppression can lead to adverse clinical outcomes. In renal transplant recipients, BKV-associated nephropathy can result in graft loss, while in patients with autoimmune disorders, prolonged immunomodulatory drug use can cause rare onset of progressive multifocal leukoencephalopathy due to JCV reactivation. In such patients, accurate BK and JC viral load determinations by molecular technologies are important for diagnosis and clinical management; however, comparability across centres requires effective standardisation of diagnostic molecular detection systems. In October 2015, the WHO Expert Committee for Biological Standardisation (ECBS) established the 1st WHO International Standards (ISs) for use as primary-order calibrants for BKV and JCV nucleic acid detection. Two multi-centre collaborative studies confirmed their utility in harmonising agreement across the wide range of BKV and JCV assays, respectively. Previous Illumina-based deep sequence analysis of these standards, however, identified deletions in different regions, including the large T-antigen coding region. Hence, further detailed characterization was warranted. METHODS: Comprehensive sequence characterisation of each preparation using short- and long-read next-generation sequencing technologies was performed with additional corroborative independent digital PCR (dPCR) determinations. Potential error rates associated with long-read sequencing were minimised by applying rolling circle amplification (RCA) protocols for viral DNA (circular dsDNA), generating a full validation of sequence identity and composition and delineating the integrity of full-length BK and JC genomes. RESULTS: The analysed genomes displayed subpopulations frequently characterised by complex gene re-arrangements, duplications and deletions. CONCLUSIONS: Despite the recognition of such polymorphisms using high-resolution sequencing methodologies, the ability of these reference materials to act to enhance assay harmonisation did not appear significantly impacted, based on data generated by the 2015 WHO collaborative studies, but highlights cautionary aspects of IS generation and commutability for clinical molecular diagnostic application.

Intrinsic host susceptibility among multiple species to intranasal SARS-CoV-2 identifies diverse virological, biodistribution and pathological outcomes.

SARS-CoV-2 exhibits a diverse host species range with variable outcomes, enabling differential host susceptibility studies to assess suitability for pre-clinical countermeasure and pathogenesis studies. Baseline virological, molecular and pathological outcomes were determined among multiple species-one Old World non-human primate (NHP) species (cynomolgus macaques), two New World NHP species (red-bellied tamarins; common marmosets) and Syrian hamsters-following single-dose, atraumatic intranasal administration of SARS-CoV-2/Victoria-01. After serial sacrifice 2, 10 and 28-days post-infection (dpi), hamsters and cynomolgus macaques displayed differential virus biodistribution across respiratory, gastrointestinal and cardiovascular systems. Uniquely, New World tamarins, unlike marmosets, exhibited high levels of acute upper airway infection, infectious virus recovery associated with mild lung pathology representing a host previously unrecognized as susceptible to SARS-CoV-2. Across all species, lung pathology was identified post-clearance of virus shedding (antigen/RNA), with an association of virus particles within replication organelles in lung sections analysed by electron microscopy. Disrupted cell ultrastructure and lung architecture, including abnormal morphology of mitochondria 10-28 dpi, represented on-going pathophysiological consequences of SARS-CoV-2 in predominantly asymptomatic hosts. Infection kinetics and host pathology comparators using standardized methodologies enables model selection to bridge differential outcomes within upper and lower respiratory tracts and elucidate longer-term consequences of asymptomatic SARS-CoV-2 infection.

High spatial and temporal variability in Antarctic ice discharge linked to ice shelf buttressing and bed geometry.

Antarctica's contribution to global mean sea level rise has been driven by an increase in ice discharge into the oceans. The rate of change and the mechanisms that drive variability in ice discharge are therefore important to consider in the context of projected future warming. Here, we report observations of both decadal trends and inter-annual variability in ice discharge across the Antarctic Ice Sheet at a variety of spatial scales that range from large drainage basins to individual outlet glacier catchments. Overall, we find a 37 ± 11 Gt year-1 increase in discharge between 1999 and 2010, but a much smaller increase of 4 ± 8 Gt year-1 between 2010 and 2018. Furthermore, comparisons reveal that neighbouring outlet glaciers can behave synchronously, but others show opposing trends, despite their close proximity. We link this spatial and temporal variability to changes in ice shelf buttressing and the modulating effect of local glacier geometry.

Seasonal variability of ocean circulation near the Dotson Ice Shelf, Antarctica.

Recent rapid thinning of West Antarctic ice shelves are believed to be caused by intrusions of warm deep water that induce basal melting and seaward meltwater export. This study uses data from three bottom-mounted mooring arrays to show seasonal variability and local forcing for the currents moving into and out of the Dotson ice shelf cavity. A southward flow of warm, salty water had maximum current velocities along the eastern channel slope, while northward outflows of freshened ice shelf meltwater spread at intermediate depth above the western slope. The inflow correlated with the local ocean surface stress curl. At the western slope, meltwater outflows followed the warm influx along the eastern slope with a ~2-3 month delay. Ocean circulation near Dotson Ice Shelf, affected by sea ice distribution and wind, appears to significantly control the inflow of warm water and subsequent ice shelf melting on seasonal time-scales.

Ice front retreat reconfigures meltwater-driven gyres modulating ocean heat delivery to an Antarctic ice shelf.

Pine Island Ice Shelf (PIIS) buttresses the Pine Island Glacier, the key contributor to sea-level rise. PIIS has thinned owing to ocean-driven melting, and its calving front has retreated, leading to buttressing loss. PIIS melting depends primarily on the thermocline variability in its front. Furthermore, local ocean circulation shifts adjust heat transport within Pine Island Bay (PIB), yet oceanic processes underlying the ice front retreat remain unclear. Here, we report a PIB double-gyre that moves with the PIIS calving front and hypothesise that it controls ocean heat input towards PIIS. Glacial melt generates cyclonic and anticyclonic gyres near and off PIIS, and meltwater outflows converge into the anticyclonic gyre with a deep-convex-downward thermocline. The double-gyre migrated eastward as the calving front retreated, placing the anticyclonic gyre over a shallow seafloor ridge, reducing the ocean heat input towards PIIS. Reconfigurations of meltwater-driven gyres associated with moving ice boundaries might be crucial in modulating ocean heat delivery to glacial ice.

Two-timescale response of a large Antarctic ice shelf to climate change.

A potentially irreversible threshold in Antarctic ice shelf melting would be crossed if the ocean cavity beneath the large Filchner-Ronne Ice Shelf were to become flooded with warm water from the deep ocean. Previous studies have identified this possibility, but there is great uncertainty as to how easily it could occur. Here, we show, using a coupled ice sheet-ocean model forced by climate change scenarios, that any increase in ice shelf melting is likely to be preceded by an extended period of reduced melting. Climate change weakens the circulation beneath the ice shelf, leading to colder water and reduced melting. Warm water begins to intrude into the cavity when global mean surface temperatures rise by approximately 7 °C above pre-industrial, which is unlikely to occur this century. However, this result should not be considered evidence that the region is unconditionally stable. Unless global temperatures plateau, increased melting will eventually prevail.

Passive immunisation of convalescent human anti-Zika plasma protects against challenge with New World Zika virus in cynomolgus macaques.

Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin administered prior to time of challenge remained present only at very low levels 42 days post-challenge. Absence of de novo antibody responses in passively immunised macaques indicate sterilising immunity compared with naïve challenge controls that exhibited active ZIKV-specific IgM and IgG responses post-challenge. Demonstration that the presence of convalescent anti-ZIKV at levels of 400 IU/mL neutralising antibody protects against virus challenge provides a scientific framework for development of anti-ZIKV vaccines and facilitates regulatory approval.

Complete Genome Sequence of Original Material Used To Derive the WHO International Standard for Human Polyomavirus BK DNA.

The complete genomic sequence was determined for the original biological material used to derive the WHO international standard for BK polyomavirus (BKV) DNA. The entire coding sequence and noncoding regions were assigned BKV subtype 1, subgroup 1b-1. This information will aid development and evaluation of human BKV DNA amplification assays.

High susceptibility, viral dynamics and persistence of South American Zika virus in New World monkey species.

South American Zika virus (ZIKV) recently emerged as a novel human pathogen, linked with neurological disorders. However, comparative ZIKV infectivity studies in New World primates are lacking. Two members of the Callitrichidae family, common marmosets (Callithrix jacchus) and red-bellied tamarins (Saguinus labiatus), were highly susceptible to sub-cutaneous challenge with the Puerto Rico-origin ZIKVPRVABC59 strain. Both exhibited rapid, high, acute viraemia with early neuroinvasion (3 days) in peripheral and central nervous tissue. ZIKV RNA levels in blood and tissues were significantly higher in New World hosts compared to Old World species (Macaca mulatta, Macaca fascicularis). Tamarins and rhesus macaques exhibited loss of zonal occludens-1 (ZO-1) staining, indicative of a compromised blood-brain barrier 3 days post-ZIKV exposure. Early, widespread dissemination across multiple anatomical sites distant to the inoculation site preceded extensive ZIKV persistence after 100 days in New and Old World lineages, especially lymphoid, neurological and reproductive sites. Prolonged persistence in brain tissue has implications for otherwise resolved human ZIKV infection. High susceptibility of distinct New World species underscores possible establishment of ZIKV sylvatic cycles in primates indigenous to ZIKV endemic regions. Tamarins and marmosets represent viable New World models for ZIKV pathogenesis and therapeutic intervention studies, including vaccines, with contemporary strains.

Genomic Sequence of the WHO International Standard for Hepatitis A Virus RNA.

The World Health Organization (WHO) international standard for hepatitis A virus (HAV) RNA nucleic acid assays was characterized by complete genome sequencing. The entire coding sequence and noncoding regions were assigned HAV genotype IB. This information will aid the design, development, and evaluation of HAV RNA amplification assays.

Complete Genome Sequence of the WHO International Standard for Hepatitis B Virus DNA.

The World Health Organization (WHO) international standard (IS) for hepatitis B virus (HBV) DNA for use in nucleic acid amplification assays was characterized by determining the complete genome sequence, which was assigned genotype A. This information will aid the design, development, and evaluation of HBV DNA amplification assays.

Mechanisms driving variability in the ocean forcing of Pine Island Glacier.

Pine Island Glacier (PIG) terminates in a rapidly melting ice shelf, and ocean circulation and temperature are implicated in the retreat and growing contribution to sea level rise of PIG and nearby glaciers. However, the variability of the ocean forcing of PIG has been poorly constrained due to a lack of multi-year observations. Here we show, using a unique record close to the Pine Island Ice Shelf (PIIS), that there is considerable oceanic variability at seasonal and interannual timescales, including a pronounced cold period from October 2011 to May 2013. This variability can be largely explained by two processes: cumulative ocean surface heat fluxes and sea ice formation close to PIIS; and interannual reversals in ocean currents and associated heat transport within Pine Island Bay, driven by a combination of local and remote forcing. Local atmospheric forcing therefore plays an important role in driving oceanic variability close to PIIS.

Vigorous lateral export of the meltwater outflow from beneath an Antarctic ice shelf.

The instability and accelerated melting of the Antarctic Ice Sheet are among the foremost elements of contemporary global climate change. The increased freshwater output from Antarctica is important in determining sea level rise, the fate of Antarctic sea ice and its effect on the Earth's albedo, ongoing changes in global deep-ocean ventilation, and the evolution of Southern Ocean ecosystems and carbon cycling. A key uncertainty in assessing and predicting the impacts of Antarctic Ice Sheet melting concerns the vertical distribution of the exported meltwater. This is usually represented by climate-scale models as a near-surface freshwater input to the ocean, yet measurements around Antarctica reveal the meltwater to be concentrated at deeper levels. Here we use observations of the turbulent properties of the meltwater outflows from beneath a rapidly melting Antarctic ice shelf to identify the mechanism responsible for the depth of the meltwater. We show that the initial ascent of the meltwater outflow from the ice shelf cavity triggers a centrifugal overturning instability that grows by extracting kinetic energy from the lateral shear of the background oceanic flow. The instability promotes vigorous lateral export, rapid dilution by turbulent mixing, and finally settling of meltwater at depth. We use an idealized ocean circulation model to show that this mechanism is relevant to a broad spectrum of Antarctic ice shelves. Our findings demonstrate that the mechanism producing meltwater at depth is a dynamically robust feature of Antarctic melting that should be incorporated into climate-scale models.

Complete Genome Sequence of a Reference Stock of Simian Immunodeficiency Virus RNA (SIVmac251/32H/L28) Determined by Deep Sequencing.

A reference preparation for simian immunodeficiency virus (SIV) RNA nucleic acid assays was characterized by complete genome deep sequencing. The entire coding sequence and flanking long terminal repeats, including minority species, were determined. This information will inform SIV research investigations and aid evaluation and development of amplification assays for SIV RNA quantification.

Strong sensitivity of Pine Island ice-shelf melting to climatic variability.

Pine Island Glacier has thinned and accelerated over recent decades, significantly contributing to global sea-level rise. Increased oceanic melting of its ice shelf is thought to have triggered those changes. Observations and numerical modeling reveal large fluctuations in the ocean heat available in the adjacent bay and enhanced sensitivity of ice-shelf melting to water temperatures at intermediate depth, as a seabed ridge blocks the deepest and warmest waters from reaching the thickest ice. Oceanic melting decreased by 50% between January 2010 and 2012, with ocean conditions in 2012 partly attributable to atmospheric forcing associated with a strong La Niña event. Both atmospheric variability and local ice shelf and seabed geometry play fundamental roles in determining the response of the Antarctic Ice Sheet to climate.

Vaccine-related mumps infections in Thailand and the identification of a novel mutation in the mumps fusion protein.

An outbreak of nine cases of mumps was reported from a total of 97 vaccinated nursing students at two medical colleges in Thailand in 2010, 16-26 days after administration of MMR vaccine containing the L-Zagreb mumps strain. Symptoms ranged in severity from fever and parotid swelling to orchitis. Clinical samples were obtained from seven patients and three were suitable for further study. Sequencing confirmed that the SH gene of the mumps virus in the unpassaged clinical specimens was identical to the L-Zagreb SH gene in the vaccine. Further analysis of the viral genome identified nucleotide position 5170 as a novel mutation which corresponds to an amino acid change in the fusion protein. This study provides another virologically confirmed example of mumps resulting from the L-Zagreb vaccine strain.

Investigation of porcine circovirus contamination in human vaccines.

DNA from porcine circovirus type 1 (PCV1) and 2 (PCV2) has recently been detected in two vaccines against rotaviral gastroenteritis from manufacturers A and B. We investigated if PCV1 sequences are present in other viral vaccines. We screened seeds, bulks and final vaccine preparations from ten manufacturers using qRT-PCR. We detected 3.8 × 10³ to 1.9 × 107 PCV1 DNA copies/milliliter in live poliovirus seeds for inactivated polio vaccine (IPV) from manufacturer A, however, following inactivation and purification, the finished IPV was PCV1-negative. PCV1 DNA was not detectable in live polio preparations from other vaccine producers. There was no detectable PCV1 DNA in the measles, mumps, rubella and influenza vaccines analysed including material supplied by manufacturer A. We confirmed that the PCV1 genome in the rotavirus vaccine from manufacturer A is near full-length. It contains two mutations in the PCV cap gene, which may result from viral adaptation to Vero cells. Bulks of this vaccine contained 9.8 × 10¹° to 1.8 × 10¹¹ PCV1 DNA copies/millilitre and between 4.1 × 107 and 5.5 × 108 DNA copies were in the final doses. We found traces of PCV1 and PCV2 DNA in the rotavirus vaccine from manufacturer B. This highlights the issue of vaccine contamination and may impact on vaccine quality control.