Biomarker-indicated extent of oxidation of plant-derived organic carbon (OC) in relation to geomorphology in an arsenic contaminated Holocene aquifer, Cambodia

The poisoning of rural populations in South and Southeast Asia due to high groundwater arsenic concentrations is one of the world’s largest ongoing natural disasters. It is important to consider environmental processes related to the release of geogenic arsenic, including geomorphological and organic geochemical processes. Arsenic is released from sediments when iron-oxide minerals, onto which arsenic is adsorbed or incorporated, react with organic carbon (OC) and the OC is oxidised. In this study we build a new geomorphological framework for Kandal Province, a highly studied arsenic affected region of Cambodia, and tie this into wider regional environmental change throughout the Holocene. Analyses shows that the concentration of OC in the sediments is strongly inversely correlated to grainsize. Furthermore, the type of OC is also related to grain size with the clay containing mostly (immature) plant derived OC and sand containing mostly thermally mature derived OC. Finally, analyses indicate that within the plant derived OC relative oxidation is strongly grouped by stratigraphy with the older bound OC more oxidised than younger OC

Low potency toxins reveal dense interaction networks in metabolism

Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. Results Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. Conclusions The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved

Lateral distribution of muons in IceCube cosmic ray events

In cosmic ray air showers, the muon lateral separation from the center of the shower is a measure of the transverse momentum that the muon parent acquired in the cosmic ray interaction. IceCube has observed cosmic ray interactions that produce muons laterally separated by up to 400 m from the shower core, a factor of 6 larger distance than previous measurements. These muons originate in high p(T) (>2 GeV/c) interactions from the incident cosmic ray, or high-energy secondary interactions. The separation distribution shows a transition to a power law at large values, indicating the presence of a hard p(T) component that can be described by perturbative quantum chromodynamics. However, the rates and the zenith angle distributions of these events are not well reproduced with the cosmic ray models tested here, even those that include charm interactions. This discrepancy may be explained by a larger fraction of kaons and charmed particles than is currently incorporated in the simulations.R. Abbasi ... G. C. Hill ... et al. (IceCube Collaboration

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Search for time-independent neutrino emission from astrophysical sources with 3 yr of IceCube data

We present the results of a search for neutrino point sources using the IceCube data collected between 2008 April and 2011 May with three partially completed configurations of the detector: the 40-, 59-, and 79-string configurations. The live-time of this data set is 1040 days. An unbinned maximum likelihood ratio test was used to search for an excess of neutrinos above the atmospheric background at any given direction in the sky. By adding two more years of data with improved event selection and reconstruction techniques, the sensitivity was improved by a factor of 3.5 or more with respect to the previously published results obtained with the 40-string configuration of IceCube. We performed an all-sky survey and a dedicated search using a catalog of a priori selected objects observed by other telescopes. In both searches, the data are compatible with the background-only hypothesis. In the absence of evidence for a signal, we set upper limits on the flux of muon neutrinos. For an E-2 neutrino spectrum, the observed limits are (0.9-5) x 10(-12) TeV-1 cm(-2) s(-1) for energies between 1 TeV and 1 PeV in the northern sky and (0.9-23.2) x 10(-12) TeV-1 cm(-2) s(-1) for energies between 10(2) TeV and 10(2) PeV in the southern sky. We also report upper limits for neutrino emission from groups of sources that were selected according to theoretical models or observational parameters and analyzed with a stacking approach. Some of the limits presented already reach the level necessary to quantitatively test current models of neutrino emission

Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the 21st century

During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed with regional decision makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include: warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land-use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia's role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large scale water withdrawals, land use and governance change) and potentially restrict or provide new opportunities for future human activities. Therefore, we propose that Integrated Assessment Models are needed as the final stage of global change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts

Multipotent Capacity of Immortalized Human Bronchial Epithelial Cells

While the adult murine lung utilizes multiple compartmentally restricted progenitor cells during homeostasis and repair, much less is known about the progenitor cells from the human lung. Translating the murine stem cell model to humans is hindered by anatomical differences between species. Here we show that human bronchial epithelial cells (HBECs) display characteristics of multipotent stem cells of the lung. These HBECs express markers indicative of several epithelial types of the adult lung when experimentally tested in cell culture. When cultured in three different three-dimensional (3D) systems, subtle changes in the microenvironment result in unique responses including the ability of HBECs to differentiate into multiple central and peripheral lung cell types. These new findings indicate that the adult human lung contains a multipotent progenitor cell whose differentiation potential is primarily dictated by the microenvironment. The HBEC system is not only important in understanding mechanisms for specific cell lineage differentiation, but also for examining changes that correlate with human lung diseases including lung cancer

An Amish founder variant consolidates disruption of CEP55 as a cause of hydranencephaly and renal dysplasia

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.The centrosomal protein 55 kDa (CEP55 (OMIM 610000)) plays a fundamental role in cell cycle regulation and cytokinesis. However, the precise role of CEP55 in human embryonic growth and development is yet to be fully defined. Here we identified a novel homozygous founder frameshift variant in CEP55, present at low frequency in the Amish community, in two siblings presenting with a lethal foetal disorder. The features of the condition are reminiscent of a Meckel-like syndrome comprising of Potter sequence, hydranencephaly, and cystic dysplastic kidneys. These findings, considered alongside two recent studies of single families reporting loss of function candidate variants in CEP55, confirm disruption of CEP55 function as a cause of this clinical spectrum and enable us to delineate the cardinal clinical features of this disorder, providing important new insights into early human development.Medical Research CouncilNewlife Foundation for disabled childre

Relationship between B-type natriuretic peptide levels and echocardiographic indices of left ventricular filling pressures in post-cardiac surgery patients

<p>Abstract</p> <p>Background</p> <p>B-type natriuretic peptide (BNP) is increased in post-cardiac surgery patients, however the mechanisms underlying BNP release are still unclear. In the current study, we aimed to assess the relationship between postoperative BNP levels and left ventricular filling pressures in post-cardiac surgery patients.</p> <p>Methods</p> <p>We prospectively enrolled 134 consecutive patients referred to our Center 8 ± 5 days after cardiac surgery. BNP was sampled at hospital admission and related to the following echocardiographic parameters: left ventricular (LV) diastolic volume (DV), LV systolic volume (SV), LV ejection fraction (EF), LV mass, relative wall thickness (RWT), indexed left atrial volume (_iLAV), mitral inflow E/A ratio, mitral E wave deceleration time (DT), ratio of the transmitral E wave to the Doppler tissue early mitral annulus velocity (E/E').</p> <p>Results</p> <p>A total of 124 patients had both BNP and echocardiographic data. The BNP values were significantly elevated (mean 353 ± 356 pg/ml), with normal value in only 17 patients (13.7%). Mean LVEF was 59 ± 10% (LVEF ≥50% in 108 pts). There was no relationship between BNP and LVEF (p = 0.11), LVDV (p = 0.88), LVSV (p = 0.50), E/A (p = 0.77), DT (p = 0.33) or RWT (p = 0.50). In contrast, BNP was directly related to E/E' (p < 0.001), LV mass (p = 0.006) and _iLAV (p = 0.026). At multivariable regression analysis, age and E/E' were the only independent predictors of BNP levels.</p> <p>Conclusion</p> <p>In post-cardiac surgery patients with overall preserved LV systolic function, the significant increase in BNP levels is related to E/E', an echocardiographic parameter of elevated LV filling pressures which indicates left atrial pressure as a major determinant in BNP release in this clinical setting.</p

Cost-effectiveness analysis of cetuximab/irinotecan vs active/best supportive care for the treatment of metastatic colorectal cancer patients who have failed previous chemotherapy treatment

The treatment of colorectal cancer is rapidly becoming a significant financial burden to health-care systems within economically developed nations. A current challenge for oncologists and health-care payers is to integrate new, often high-cost, biologic therapies into clinical practice. Inherent to this process is the consideration of cost-effectiveness. The aim of this study was to compare the cost-effectiveness of cetuximab plus irinotecan with an appropriate comparator from a National Health Service (NHS) perspective. This economic evaluation is a trial-based study of cetuximab vs active/best supportive care. Effectiveness estimates for the treatment groups were modelled from key clinical trials. Cunningham et al (2004) compared cetuximab/irinotecan with cetuximab monotherapy; Cunningham et al (1998) compared irinotecan monotherapy in a second-line setting with supportive care. Modelling was necessary owing to an absence of head-to-head clinical trial data of cetuximab/irinotecan vs current standard care. Costs were calculated for the study drugs received, associated administration, palliative chemotherapy for patients in the standard care arm and other nonchemotherapy resources. The discounted life-expectancy of patients treated with cetuximab/irinotecan was 0.91 life-years, and 0.47 discounted life-years for patients receiving active/best supportive care. Patients treated with cetuximab/irinotecan accumulated mean additional costs of £18 901 per patient relative to the comparator arm, with £11 802 attributable to cetuximab. The incremental cost per life-year gained with cetuximab/irinotecan therapy compared with active/best supportive care was £42 975. The incremental cost per quality adjusted life-year gained was £57 608. The incremental cost per life-year gained for cetuximab/irinotecan is relatively high compared with other health-care interventions. However, this result should be considered in the context of a number of factors specific to the treated patient population