Northeastern Atlantic benthic foraminifera during the last 45,000 years: Changes in productivity seen from the bottom up

We studied benthic foraminifera from the last 45 kyr in the >63 mu m size fraction in Biogeochemical Ocean Flux Studies (BOFS) cores 5K (50 degrees 41.3'N, 21 degrees 51.9'W, depth 3547 m) and 14K (58 degrees 37.2'N, 19 degrees 26.2'W, depth 1756 m), at a time resolution of several hundreds to a thousand years. The deepest site showed the largest fluctuations in faunal composition, species richness, and benthic foraminiferal accumulation rates; the fluctuations resulted from changes in abundance of Epistominella exigua and Alabaminella weddellensis. In the present oceans, these species bloom opportunistically when a spring plankton bloom results in seasonal deposition of phytodetritus on the seafloor. The ''phytodetritus species'' had very low relative abundances and accumulation rates during the last glacial maximum. A strong increase in absolute and relative abundance of E. exigua and A weddellensis during deglaciation paralleled the decrease in abundance of the polar planktonic foraminifer Neogloboquadrina pachyderma (s), and the increase in abundance of warmer water planktonic species such as Globigerina bulloides. This strong increase in relative abundance of the ''phytodetritus species'' and the coeval increase in benthic foraminiferal accumulation rate were thus probably caused by an increase in the deposition of phytodetritus to the seafloor (and thus probably of surface productivity) when the polar front retreated to higher latitudes. The abundance of ''phytodetritus species'' decreased during the Younger Dryas, but not to the low levels of fully glacial conditions. During Heinrich events (periods of excessive melt-water formation and ice rafting) benthic accumulation rates were very low, as were the absolute and relative abundances of the ''phytodetritus species'', supporting suggestions that surface productivity was very low during these events. In both cores Pullenia and Cassidulina species were common during isotope stages 2, 3 and 4, as were bolivinid, buliminid and uvigerinid species. High relative abundances of these species have been interpreted as indicative either of sluggish deep water circulation or of high organic carbon fluxes to the seafloor. In our cores, relative abundances of these species are negatively correlated with benthic foraminiferal accumulation rates, and we can thus not interpret them as indicative of increased productivity during glacials. The percentage of these ''low oxygen'' species calculated on a ''phytodetritus species'' - free basis decreased slightly at deglaciation at 5K, but not at 14K. This suggests that decreased production of North Atlantic Deep Water during the last glacial might have slightly affected benthic foraminiferal faunas in the eastern North Atlantic at 3547 m depth, but not at 1756 m. In conclusion, major changes in deep-sea benthic foraminiferal faunas over the last 45,000 years in our cores from the northeastern Atlantic were the result of changes in surface water productivity, not of changes in deep water circulation; productivity was lower during the glacial, probably because of extensive ice cover

Cell-Cell Spread of Human Immunodeficiency Virus Type 1 Overcomes Tetherin/BST-2-Mediated Restriction in T cells

Direct cell-to-cell spread of human immunodeficiency virus type 1 (HIV-1) between T cells at the virological synapse (VS) is an efficient mechanism of viral dissemination. Tetherin (BST-2/CD317) is an interferon-induced, antiretroviral restriction factor that inhibits nascent cell-free particle release. The HIV-1 Vpu protein antagonizes tetherin activity; however, whether tetherin also restricts cell-cell spread is unclear. We performed quantitative cell-to-cell transfer analysis of wild-type (WT) or Vpu-defective HIV-1 in Jurkat and primary CD4+ T cells, both of which express endogenous levels of tetherin. We found that Vpu-defective HIV-1 appeared to disseminate more efficiently by cell-to-cell contact between Jurkat cells under conditions where tetherin restricted cell-free virion release. In T cells infected with Vpu-defective HIV-1, tetherin was enriched at the VS, and VS formation was increased compared to the WT, correlating with an accumulation of virus envelope proteins on the cell surface. Increasing tetherin expression with type I interferon had only minor effects on cell-to-cell transmission. Furthermore, small interfering RNA (siRNA)-mediated depletion of tetherin decreased VS formation and cell-to-cell transmission of both Vpu-defective and WT HIV-1. Taken together, these data demonstrate that tetherin does not restrict VS-mediated T cell-to-T cell transfer of Vpu-defective HIV-1 and suggest that under some circumstances tetherin might promote cell-to-cell transfer, either by mediating the accumulation of virions on the cell surface or by regulating integrity of the VS. If so, inhibition of tetherin activity by Vpu may balance requirements for efficient cell-free virion production and cell-to-cell transfer of HIV-1 in the face of antiviral immune responses

Machine Learning Approaches to Determine Feature Importance for Predicting Infant Autopsy Outcome

Introduction: Sudden unexpected death in infancy (SUDI) represents the commonest presentation of postneonatal death. We explored whether machine learning could be used to derive data driven insights for prediction of infant autopsy outcome. Methods: A paediatric autopsy database containing >7,000 cases, with >300 variables, was analysed by examination stage and autopsy outcome classified as ‘explained (medical cause of death identified)’ or ‘unexplained’. Decision tree, random forest, and gradient boosting models were iteratively trained and evaluated. Results: Data from 3,100 infant and young child (<2 years) autopsies were included. Naïve decision tree using external examination data had performance of 68% for predicting an explained death. Core data items were identified using model feature importance. The most effective model was XG Boost, with overall predictive performance of 80%, demonstrating age at death, and cardiovascular and respiratory histological findings as the most important variables associated with determining medical cause of death. Conclusion: This study demonstrates feasibility of using machine-learning to evaluate component importance of complex medical procedures (paediatric autopsy) and highlights value of collecting routine clinical data according to defined standards. This approach can be applied to a range of clinical and operational healthcare scenario

Impact of the COVID-19 pandemic on radiology appointments in a tertiary children's hospital: a retrospective study

In this retrospective observational study, we evaluated the impact of the COVID-19 pandemic in London on paediatric radiology activity, as a surrogate of overall hospital activity. We showed a large reduction in overall outpatient imaging activity: 49 250 records occurred in the 371 days post COVID-19 period compared with an expected 67 806 records pre COVID-19 period, representing 18 556 ‘missed’ records. Governmental restrictions were associated with reductions in activity, with the largest reduction in activity during tiers 3 and 4 restrictions. Rescheduling such missed outpatients’ appointments represents considerable resource planning and the associated clinical impact on paediatric healthcare remains to be determined

Intraoperative anti-A/B immunoadsorption is associated with significantly reduced blood product utilization with similar outcomes in pediatric ABO-incompatible heart transplantation

BACKGROUND: Intraoperative anti-A/B immunoadsorption (ABO-IA) was recently introduced for ABO-incompatible heart transplantation. Here we report the first case series of patients transplanted with ABO-IA, and compare outcomes with those undergoing plasma exchange facilitated ABO-incompatible heart transplantation (ABO-PE). METHODS: Data were retrospectively analysed on all ABO-incompatible heart transplants undertaken at a single centre between January 1, 2000 and June 1, 2020. Data included all routine laboratory tests, demographics and pre-operative characteristics, intraoperative details and post-operative outcomes. Primary outcome measures were volume of blood product transfusions, maximum post-transplant isohaemagglutinin titres, occurrence of rejection and graft survival. Secondary outcome measures were length of intensive care and hospital stay. Demographic and survival data were also obtained for ABO-compatible transplants during the same time period for comparison. RESULTS: Thirty-seven patients underwent ABO-incompatible heart transplantation, with 27 (73%) using ABO-PE and 10 (27%) using ABO-IA. ABO-IA patients were significantly older than ABO-PE patients (p < 0.001) and the total volume of blood products transfused during the hospital admission was significantly lower (164 [126-212] ml/kg vs 323 [268-379] ml/kg, p < 0.001). No significant differences were noted between methods in either pre or post-transplant maximum isohaemagglutinin titres, incidence of rejection, length of intensive care or total hospital stay. Survival comparison showed no significant difference between antibody reduction methods, or indeed ABO-compatible transplants (p = 0.6). CONCLUSIONS: This novel technique appears to allow a significantly older population than typical to undergo ABO-incompatible heart transplantation, as well as significantly reducing blood product utilization. Furthermore, intraoperative anti-A/B immunoadsorption does not demonstrate increased early post-transplant isohaemagglutinin accumulation or rates of rejection compared to ABO-PE. Early survival is equivalent between ABO-IA, ABO-PE and ABO-compatible heart transplantation

Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying ‘high-risk’ comorbidities in a paediatric population

Background: There is evolving evidence of significant differences in severity and outcomes of coronavirus disease 2019 (COVID-19) in children compared to adults. Underlying medical conditions associated with increased risk of severe disease are based on adult data, but have been applied across all ages resulting in large numbers of families undertaking social ‘shielding’ (vulnerable group). We conducted a retrospective analysis of children with suspected COVID-19 at a Specialist Children’s Hospital to determine outcomes based on COVID-19 testing status and underlying health vulnerabilities. Methods: Routine clinical data were extracted retrospectively from the Institution’s Electronic Health Record system and Digital Research Environment for patients with suspected and confirmed COVID-19 diagnoses. Data were compared between Sars-CoV-2 positive and negative patients (CoVPos / CoVNeg respectively), and in relation to presence of underlying health vulnerabilities based on Public Health England guidance. Findings Between 1st March and 15th May 2020, 166 children (<18 years of age) presented to a specialist children’s hospital with clinical features of possible COVID-19 infection. 65 patients (39.2%) tested positive for SARS-CoV-2 virus. CoVPos patients were older (median 9 [0.9 - 14] years vs median 1 [0.1 - 5.7.5] years respectively, p<0.001). There was a significantly reduced proportion of vulnerable cases (47.7% vs 72.3%, p=0.002), but no difference in proportion of vulnerable patients requiring ventilation (61% vs 64.3%, p = 0.84) between CoVPos and CoVNeg groups. However, a significantly lower proportion of CoVPos patients required mechanical ventilation support compared to CoVNeg patients (27.7 vs 57.4%, p<0.001). Mortality was not significantly different between CoVPos and CoVNeg groups (1.5 vs 4% respectively, p=0.67) although there were no direct COVID-19 related deaths in this highly preselected paediatric population. Interpretation COVID-19 infection may be associated with severe disease in childhood presenting to a specialist hospital, but does not appear significantly different in severity to other causes of similar clinical presentations. In children presenting with pre-existing ‘COVID-19 vulnerable’ medical conditions at a specialist centre, there does not appear to be significantly increased risk of either contracting COVID-19 or severe complications, apart from those undergoing chemotherapy, who are over-represented. Competing Interest Statement The authors have declared no competing interest. Funding Statement: Funding RI is funded by a British Heart Foundation Research Fellowship Grant. HH is funded by NIHR UCLH BRC and HDRUK, NJS is funded by GOSHCC and HDRUK. Role of the funding source The study sponsor / funders had no role or influence in study design, in the collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the paper for publicatio

Thermal quenches in N=2* plasmas

We exploit gauge/gravity duality to study `thermal quenches' in a plasma of the strongly coupled N=2* gauge theory. Specifically, we consider the response of an initial thermal equilibrium state of the theory under variations of the bosonic or fermionic mass, to leading order in m/T<<1. When the masses are made to vary in time, novel new counterterms must be introduced to renormalize the boundary theory. We consider transitions the conformal super-Yang-Mills theory to the mass deformed gauge theory and also the reverse transitions. By construction, these transitions are controlled by a characteristic time scale \calt and we show how the response of the system depends on the ratio of this time scale to the thermal time scale 1/T. The response shows interesting scaling behaviour both in the limit of fast quenches with T\calt<<1 and slow quenches with T\calt>>1. In the limit that T\calt\to\infty, we observe the expected adiabatic response. For fast quenches, the relaxation to the final equilibrium is controlled by the lowest quasinormal mode of the bulk scalar dual to the quenched operator. For slow quenches, the system relaxes with a (nearly) adiabatic response that is governed entirely by the late time profile of the mass. We describe new renormalization scheme ambiguities in defining gauge invariant observables for the theory with time dependant couplings.Comment: 78 pages, 17 figure

Groups without cultured representatives dominate eukaryotic picophytoplankton in the oligotrophic South East Pacific Ocean

Background: Photosynthetic picoeukaryotes (PPE) with a cell size less than 3 µm play a critical role in oceanic primary production. In recent years, the composition of marine picoeukaryote communities has been intensively investigated by molecular approaches, but their photosynthetic fraction remains poorly characterized. This is largely because the classical approach that relies on constructing 18S rRNA gene clone libraries from filtered seawater samples using universal eukaryotic primers is heavily biased toward heterotrophs, especially alveolates and stramenopiles, despite the fact that autotrophic cells in general outnumber heterotrophic ones in the euphotic zone. Methodology/Principal Findings: In order to better assess the composition of the eukaryotic picophytoplankton in the South East Pacific Ocean, encompassing the most oligotrophic oceanic regions on earth, we used a novel approach based on flow cytometry sorting followed by construction of 18S rRNA gene clone libraries. This strategy dramatically increased the recovery of sequences from putative autotrophic groups. The composition of the PPE community appeared highly variable both vertically down the water column and horizontally across the South East Pacific Ocean. In the central gyre, uncultivated lineages dominated: a recently discovered clade of Prasinophyceae (IX), clades of marine Chrysophyceae and Haptophyta, the latter division containing a potentially new class besides Prymnesiophyceae and Pavlophyceae. In contrast, on the edge of the gyre and in the coastal Chilean upwelling, groups with cultivated representatives (Prasinophyceae clade VII and Mamiellales) dominated. Conclusions/Significance: Our data demonstrate that a very large fraction of the eukaryotic picophytoplankton still escapes cultivation. The use of flow cytometry sorting should prove very useful to better characterize specific plankton populations by molecular approaches such as gene cloning or metagenomics, and also to obtain into culture strains representative of these novel groups

Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease

Tissue fibrosis is a core pathologic process that contributes to mortality in ∼45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis