Seismic evidence for complex sedimentary control of Greenland Ice Sheet flow

The land-terminating margin of the Greenland Ice Sheet has slowed down in recent decades, although the causes and implications for future ice flow are unclear. Explained originally by a self-regulating mechanism where basal slip reduces as drainage evolves from low to high efficiency, recent numerical modeling invokes a sedimentary control of ice sheet flow as an alternative hypothesis. Although both hypotheses can explain the recent slowdown, their respective forecasts of a long-term deceleration versus an acceleration of ice flow are contradictory. We present amplitude-versus-angle seismic data as the first observational test of the alternative hypothesis. We document transient modifications of basal sediment strengths by rapid subglacial drainages of supraglacial lakes, the primary current control on summer ice sheet flow according to our numerical model. Our observations agree with simulations of initial postdrainage sediment weakening and ice flow accelerations, and subsequent sediment restrengthening and ice flow decelerations, and thus confirm the alternative hypothesis. Although simulated melt season acceleration of ice flow due to weakening of subglacial sediments does not currently outweigh winter slowdown forced by self-regulation, they could dominate over the longer term. Subglacial sediments beneath the Greenland Ice Sheet must therefore be mapped and characterized, and a sedimentary control of ice flow must be evaluated against competing self-regulation mechanismspublishersversionPeer reviewe

Sources of non-methane hydrocarbons in surface air in Delhi, India

Rapid economic growth and development have exacerbated air quality problems across India, driven by many poorly understood pollution sources and understanding their relative importance remains critical to characterising the key drivers of air pollution. A comprehensive suite of measurements of 90 non-methane hydrocarbons (NMHCs) (C2–C14), including 12 speciated monoterpenes and higher molecular weight monoaromatics, were made at an urban site in Old Delhi during the pre-monsoon (28-May to 05-Jun 2018) and post-monsoon (11 to 27-Oct 2018) seasons using dual-channel gas chromatography (DC-GC-FID) and two-dimensional gas chromatography (GC×GC-FID). Significantly higher mixing ratios of NMHCs were measured during the post-monsoon campaign, with a mean night-time enhancement of around 6. Like with NOx and CO, strong diurnal profiles were observed for all NMHCs, except isoprene, with very high NMHC mixing ratios between 35–1485 ppbv. The sum of mixing ratios of benzene, toluene, ethylbenzene and xylenes (BTEX) routinely exceeded 100 ppbv at night during the post-monsoon period, with a maximum measured mixing ratio of monoaromatic species of 370 ppbv. The mixing ratio of highly reactive monoterpenes peaked at around 6 ppbv in the post-monsoon campaign and correlated strongly with anthropogenic NMHCs, suggesting a strong non-biogenic source in Delhi. A detailed source apportionment study was conducted which included regression analysis to CO, acetylene and other NMHCs, hierarchical cluster analysis, EPA UNMIX 6.0, principal component analysis/absolute principal component scores (PCA/APCS) and comparison with NMHC ratios (benzene/toluene and i-/n-pentane) in ambient samples to liquid and solid fuels. These analyses suggested the primary source of anthropogenic NMHCs in Delhi was from traffic emissions (petrol and diesel), with average mixing ratio contributions from Unmix and PCA/APCS models of 38% from petrol, 14% from diesel and 32% from liquified petroleum gas (LPG) with a smaller contribution (16%) from solid fuel combustion. Detailed consideration of the underlying meteorology during the campaigns showed that the extreme night-time mixing ratios of NMHCs during the post-monsoon campaign were the result of emissions into a very shallow and stagnant boundary layer. The results of this study suggest that despite widespread open burning in India, traffic-related petrol and diesel emissions remain the key drivers of gas-phase urban air pollution in Delhi

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Developments and applications of the OPTIMADE API for materials discovery, design, and data exchange

The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the upcoming v1.2 release, and has underpinned multiple scientific studies. In this work, we highlight the latest features of the API format, accompanying software tools, and provide an update on the implementation of OPTIMADE in contributing materials databases. We end by providing several use cases that demonstrate the utility of the OPTIMADE API in materials research that continue to drive its ongoing development

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Fitness Consequences of Advanced Ancestral Age over Three Generations in Humans

A rapid rise in age at parenthood in contemporary societies has increased interest in reports of higher prevalence of de novo mutations and health problems in individuals with older fathers, but the fitness consequences of such age effects over several generations remain untested. Here, we use extensive pedigree data on seven pre-industrial Finnish populations to show how the ages of ancestors for up to three generations are associated with fitness traits. Individuals whose fathers, grandfathers and great-grandfathers fathered their lineage on average under age 30 were ~13% more likely to survive to adulthood than those whose ancestors fathered their lineage at over 40 years. In addition, females had a lower probability of marriage if their male ancestors were older. These findings are consistent with an increase of the number of accumulated de novo mutations with male age, suggesting that deleterious mutations acquired from recent ancestors may be a substantial burden to fitness in humans. However, possible non-mutational explanations for the observed associations are also discussed

Emissions of non-methane volatile organic compounds from combustion of domestic fuels in Delhi, India

Twenty-nine different fuel types used in residential dwellings in northern India were collected from across Delhi (76 samples in total). Emission factors of a wide range of non-methane volatile organic compounds (NMVOCs) (192 compounds in total) were measured during controlled burning experiments using dualchannel gas chromatography with flame ionisation detection (DC-GC-FID), two-dimensional gas chromatography (GC×GC-FID), proton-transfer-reaction time-of-flight mass spectrometry (PTR-ToF-MS) and solid-phase extraction two-dimensional gas chromatography with time-offlight mass spectrometry (SPE-GC×GC-ToF-MS). On average, 94% speciation of total measured NMVOC emissions was achieved across all fuel types. The largest contributors to emissions from most fuel types were small non-aromatic oxygenated species, phenolics and furanics. The emission factors (in g kg-1) for total gas-phase NMVOCs were fuelwood (18.7, 4.3-96.7), cow dung cake (62.0, 35.3-83.0), crop residue (37.9, 8.9-73.8), charcoal (5.4, 2.4-7.9), sawdust (72.4, 28.6-115.5), municipal solid waste (87.3, 56.6- 119.1) and liquefied petroleum gas (5.7, 1.9-9.8). The emission factors measured in this study allow for better characterisation, evaluation and understanding of the air quality impacts of residential solid-fuel combustion in India

Emissions of intermediate-volatility and semi-volatile organic compounds from domestic fuels used in Delhi, India

Biomass burning emits significant quantities of intermediate-volatility and semi-volatile organic compounds (I/SVOCs) in a complex mixture, probably containing many thousands of chemical species. These components are significantly more toxic and have poorly understood chemistry compared to volatile organic compounds routinely quantified in ambient air; however, analysis of I/SVOCs presents a difficult analytical challenge. The gases and particles emitted during the test combustion of a range of domestic solid fuels collected from across Delhi were sampled and analysed. Organic aerosol was collected onto Teflon (PTFE) filters, and residual low-volatility gases were adsorbed to the surface of solid-phase extraction (SPE) discs. A new method relying on accelerated solvent extraction (ASE) coupled to comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-ToF-MS) was developed. This highly sensitive and powerful analytical technique enabled over 3000 peaks from I/SVOC species with unique mass spectra to be detected. A total of 15 %-100% of gas-phase emissions and 7 %-100% of particle-phase emissions were characterised. The method was analysed for suitability to make quantitative measurements of I/SVOCs using SPE discs. Analysis of SPE discs indicated phenolic and furanic compounds were important for gas-phase I/SVOC emissions and levoglucosan to the aerosol phase. Gas- and particle-phase emission factors for 21 polycyclic aromatic hydrocarbons (PAHs) were derived, including 16 compounds listed by the US EPA as priority pollutants. Gas-phase emissions were dominated by smaller PAHs. The new emission factors were measured (mg kg-1) for PAHs from combustion of cow dung cake (615), municipal solid waste (1022), crop residue (747), sawdust (1236), fuelwood (247), charcoal (151) and liquefied petroleum gas (56). The results of this study indicate that cow dung cake and municipal solid waste burning are likely to be significant PAH sources, and further study is required to quantify their impact alongside emissions from fuelwood burning