Atlantic overturning in decline?

Global ocean circulation is an important factor in climate variability and change. In particular, changes in the strength of the Atlantic meridional overturning circulation (AMOC) have been implicated in ancient climate events, as well as in recent climate anomalies such as the rapid warming of the North Atlantic Ocean in the mid-1990s. A series of moored current meters and temperature sensors deployed in the Atlantic at 26° N known as the RAPID-MOCHA array has been used to monitor the strength of meridional overturning since 2004. The data indicate a decline in this strength over the period 2004–20123. Here, using additional observations and climate model simulations we suggest that this measured decline is not merely a short-term fluctuation, but is part of a substantial reduction in meridional overturning occurring on a decadal timescale

Historical simulations with HadGEM3-GC3.1 for CMIP6

We describe and evaluate historical simulations which use the third Hadley Centre Global Environment Model in the Global Coupled configuration 3.1 (HadGEM3-GC3.1) model and which form part of the UK's contribution to the sixth Coupled Model Intercomparison Project, CMIP6. These simulations, run at two resolutions, respond to historically evolving forcings such as greenhouse gases, aerosols, solar irradiance, volcanic aerosols, land use, and ozone concentrations. We assess the response of the simulations to these historical forcings and compare against the observational record. This includes the evolution of global mean surface temperature, ocean heat content, sea ice extent, ice sheet mass balance, permafrost extent, snow cover, North Atlantic sea surface temperature and circulation, and decadal precipitation. We find that the simulated time evolution of global mean surface temperature broadly follows the observed record but with important quantitative differences which we find are most likely attributable to strong effective radiative forcing from anthropogenic aerosols and a weak pattern of sea surface temperature response in the low to middle latitudes to volcanic eruptions. We also find evidence that anthropogenic aerosol forcings play a role in driving the Atlantic Multidecadal Variability and the Atlantic Meridional Overturning Circulation, which are key features of the North Atlantic ocean. Overall, the model historical simulations show many features in common with the observed record over the period 1850–2014 and so provide a basis for future in-depth study of recent climate change

Decadal prediction of the North Atlantic subpolar gyre in the HiGEM high-resolution climate model

This paper presents an analysis of initialised decadal hindcasts of the North Atlantic subpolar gyre (SPG) using the HiGEM model, which has a nominal grid-spacing of 90 km in the atmosphere, and 1/3 ∘∘ in the ocean. HiGEM decadal predictions (HiGEM-DP) exhibit significant skill at capturing 0–500 m ocean heat content in the SPG, and outperform historically forced transient integrations and persistence for up to a decade ahead. An analysis of case-studies of North Atlantic decadal change, including the 1960s cooling, the mid-1990s warming, and the post-2005 cooling, show that changes in ocean circulation and heat transport dominate the predictions of the SPG. However, different processes are found to dominate heat content changes in different regions of the SPG. Specifically, ocean advection dominates in the east, but surface fluxes dominate in the west. Furthermore, compared to previous studies, we find a smaller role for ocean heat transport changes due to ocean circulation anomalies at the latitudes of the SPG, and, for the 1960s cooling, a greater role for surface fluxes. Finally, HiGEM-DP predicts the observed positive state of the North Atlantic Oscillation in the early 1990s. These results support an important role for the ocean in driving past changes in the North Atlantic region, and suggest that these changes were predictable

Aerosol-forced AMOC changes in CMIP6 historical simulations

The Atlantic Meridional Overturning Circulation (AMOC) has been, and will continue to be, a key factor in the modulation of climate change both locally and globally. However, there remains considerable uncertainty in recent AMOC evolution. Here, we show that the multi-model mean AMOC strengthened by approximately 10% from 1850-1985 in new simulations from the 6th Coupled Model Inter-comparison Project (CMIP6), a larger change than was seen in CMIP5. Across the models, the strength of the AMOC trend up to 1985 is related to a proxy for the strength of the aerosol forcing. Therefore, the multi-model difference is a result of stronger anthropogenic aerosol forcing on average in CMIP6 than CMIP5, which is primarily due to more models including aerosol-cloud interactions. However, observational constraints - including a historical sea surface temperature fingerprint and shortwave radiative forcing in recent decades - suggest that anthropogenic forcing and/or the AMOC response may be overestimated

Specificity and disease in the ubiquitin system

Post-translational modification (PTM) of proteins by ubiquitination is an essential cellular regulatory process. Such regulation drives the cell cycle and cell division, signalling and secretory pathways, DNA replication and repair processes and protein quality control and degradation pathways. A huge range of ubiquitin signals can be generated depending on the specificity and catalytic activity of the enzymes required for attachment of ubiquitin to a given target. As a consequence of its importance to eukaryotic life, dysfunction in the ubiquitin system leads to many disease states, including cancers and neurodegeneration. This review takes a retrospective look at our progress in understanding the molecular mechanisms that govern the specificity of ubiquitin conjugation

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. METHODS: We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. RESULTS: We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. CONCLUSIONS: We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).This research was supported by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute and by a National Cancer Institute Strategic Partnering to Evaluate Cancer Signatures (SPECS II) grant (5U01CA157581-05). R.S. was supported by the Dr Mildred Scheel Stiftung für Krebsforschung (Deutsche Krebshilfe). D.J.H. was a Kay Kendall Leukaemia Fund Intermediate research fellow. M.K. was supported by the National Institutes of Health Oxford-Cambridge Scholars Program and the Washington University in St. Louis Medical Scientist Training Progra

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