Galaxy Zoo: dust and molecular gas in early-type galaxies with prominent dust lanes

We study dust and associated molecular gas in 352 nearby early-type galaxies (ETGs) with prominent dust lanes. 65% of these `dusty ETGs' (D-ETGs) are morphologically disturbed, suggesting a merger origin. This is consistent with the D-ETGs residing in lower density environments compared to the controls drawn from the general ETG population. 80% of D-ETGs inhabit the field (compared to 60% of the controls) and <2% inhabit clusters (compared to 10% of the controls). Compared to the controls, D-ETGs exhibit bluer UV-optical colours (indicating enhanced star formation) and an AGN fraction that is more than an order of magnitude greater (indicating higher incidence of nuclear activity). The clumpy dust mass residing in large-scale features is estimated, using the SDSS r-band images, to be 10^{4.5}-10^{6.5} MSun. A comparison to the total (clumpy + diffuse) dust masses- calculated using the far-IR fluxes of 15% of the D-ETGs that are detected by the IRAS- indicates that only ~20% of the dust resides in these large-scale features. The dust masses are several times larger than the maximum value expected from stellar mass loss, ruling out an internal origin. The dust content shows no correlation with the blue luminosity, indicating that it is not related to a galactic scale cooling flow. No correlation is found with the age of the recent starburst, suggesting that the dust is accreted directly in the merger rather than being produced in situ by the triggered star formation. Using molecular gas-to-dust ratios of ETGs in the literature we estimate that the median current and initial molecular gas fraction are ~1.3% and ~4%, respectively. Recent work suggests that the merger activity in nearby ETGs largely involves minor mergers (mass ratios between 1:10 and 1:4). If the IRAS-detected D-ETGs form via this channel, then the original gas fractions of the accreted satellites are 20%-44%. [Abridged]Comment: 11 pages, 18 figures, 1 table, MNRAS (Accepted for publication- 2012 March 19

The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases:an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE

Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. Methods: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. Results: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term “early metachronous metastases” applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with “late metachronous metastases” applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. Conclusions: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.</p

The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases:an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE

Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. Methods: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. Results: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term “early metachronous metastases” applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with “late metachronous metastases” applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. Conclusions: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate

A Cryogenic Silicon Interferometer for Gravitational-wave Detection

The detection of gravitational waves from compact binary mergers by LIGO has opened the era of gravitational wave astronomy, revealing a previously hidden side of the cosmos. To maximize the reach of the existing LIGO observatory facilities, we have designed a new instrument that will have 5 times the range of Advanced LIGO, or greater than 100 times the event rate. Observations with this new instrument will make possible dramatic steps toward understanding the physics of the nearby universe, as well as observing the universe out to cosmological distances by the detection of binary black hole coalescences. This article presents the instrument design and a quantitative analysis of the anticipated noise floor

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

What Electrophysiology Tells Us About Alzheimer’s Disease::A Window into the Synchronization and Connectivity of Brain Neurons

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer’s disease (AD), despite a surge in recent validated evidence. This Position Paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity reflecting thalamocortical and cortico-cortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

A verification framework for interannual-to-decadal predictions experiments

Decadal predictions have a high profile in the climate science community and beyond, yet very little is known about their skill. Nor is there any agreed protocol for estimating their skill. This paper proposes a sound and coordinated framework for verification of decadal hindcast experiments. The framework is illustrated for decadal hindcasts tailored to meet the requirements and specifications of CMIP5 (Coupled Model Intercomparison Project phase 5). The chosen metrics address key questions about the information content in initialized decadal hindcasts. These questions are: (1) Do the initial conditions in the hindcasts lead to more accurate predictions of the climate, compared to un-initialized climate change projections? and (2) Is the prediction model’s ensemble spread an appropriate representation of forecast uncertainty on average? The first question is addressed through deterministic metrics that compare the initialized and uninitialized hindcasts. The second question is addressed through a probabilistic metric applied to the initialized hindcasts and comparing different ways to ascribe forecast uncertainty. Verification is advocated at smoothed regional scales that can illuminate broad areas of predictability, as well as at the grid scale, since many users of the decadal prediction experiments who feed the climate data into applications or decision models will use the data at grid scale, or downscale it to even higher resolution. An overall statement on skill of CMIP5 decadal hindcasts is not the aim of this paper. The results presented are only illustrative of the framework, which would enable such studies. However, broad conclusions that are beginning to emerge from the CMIP5 results include (1) Most predictability at the interannual-to-decadal scale, relative to climatological averages, comes from external forcing, particularly for temperature; (2) though moderate, additional skill is added by the initial conditions over what is imparted by external forcing alone; however, the impact of initialization may result in overall worse predictions in some regions than provided by uninitialized climate change projections; (3) limited hindcast records and the dearth of climate-quality observational data impede our ability to quantify expected skill as well as model biases; and (4) as is common to seasonal-to-interannual model predictions, the spread of the ensemble members is not necessarily a good representation of forecast uncertainty. The authors recommend that this framework be adopted to serve as a starting point to compare prediction quality across prediction systems. The framework can provide a baseline against which future improvements can be quantified. The framework also provides guidance on the use of these model predictions, which differ in fundamental ways from the climate change projections that much of the community has become familiar with, including adjustment of mean and conditional biases, and consideration of how to best approach forecast uncertainty

Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms

In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC=0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4&lt;10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable