Debate over the Late Quaternary megafaunal extinctions has focussed on whether human colonisation or climatic changes were more important drivers of extinction, with few extinctions being ...unambiguously attributable to either. Most analyses have been geographically or taxonomically restricted and the few quantitative global analyses have been limited by coarse temporal resolution or overly simplified climate reconstructions or proxies. We present a global analysis of the causes of these extinctions which uses high-resolution climate reconstructions and explicitly investigates the sensitivity of our results to uncertainty in the palaeological record. Our results show that human colonisation was the dominant driver of megafaunal extinction across the world but that climatic factors were also important. We identify the geographic regions where future research is likely to have the most impact, with our models reliably predicting extinctions across most of the world, with the notable exception of mainland Asia where we fail to explain the apparently low rate of extinction found in in the fossil record. Our results are highly robust to uncertainties in the palaeological record, and our main conclusions are unlikely to change qualitatively following minor improvements or changes in the dates of extinctions and human colonisation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Classically, late transition-metal organometallic compounds promote multielectron processes solely through the change in oxidation state of the metal centre. In contrast, uranium typically undergoes ...single-electron chemistry. However, using redox-active ligands can engage multielectron reactivity at this metal in analogy to transition metals. Here we show that a redox-flexible pyridine(diimine) ligand can stabilize a series of highly reduced uranium coordination complexes by storing one, two or three electrons in the ligand. These species reduce organoazides easily to form uranium-nitrogen multiple bonds with the release of dinitrogen. The extent of ligand reduction dictates the formation of uranium mono-, bis- and tris(imido) products. Spectroscopic and structural characterization of these compounds supports the idea that electrons are stored in the ligand framework and used in subsequent reactivity. Computational analyses of the uranium imido products probed their molecular and electronic structures, which facilitated a comparison between the bonding in the tris(imido) structure and its tris(oxo) analogue.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary Background Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal ...quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18–24-year-olds. Methods In this phase 3, observer-blind, randomised controlled trial, university students aged 18–24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov , registration number NCT01214850. Findings Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control 984 analysed, 979 assigned to 4CMenB 974 analysed, 988 assigned to MenACWY-CRM 983 analysed); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8–1·7) or MenACWY-CRM (0·9, 0·6–1·3) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18·2% 95% CI 3·4–30·8 carriage reduction), capsular groups BCWY (26·6% 10·5–39·9 carriage reduction), capsular groups CWY (29·6% 8·1–46·0 carriage reduction), and serogroups CWY (28·5% 2·8–47·5 carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39·0% (95% CI 17·3–55·0) carriage reduction for serogroup Y and 36·2% (15·6–51·7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified. Interpretation Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented. Funding Novartis Vaccines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Exposure to geogenic (earth-derived) particulate matter (PM) is linked to an increased prevalence of bronchiectasis and other respiratory infections in Australian Indigenous communities. Experimental ...studies have shown that the concentration of iron in geogenic PM is associated with the magnitude of respiratory health effects, however, the mechanism is unclear. We investigated the effect of geogenic PM and iron oxide on the invasiveness of non-typeable Haemophilus influenzae (NTHi). Peripheral blood mononuclear cell-derived macrophages or epithelial cell lines (A549 & BEAS-2B) were exposed to whole geogenic PM, their primary constituents (haematite, magnetite or silica) or diesel exhaust particles (DEP). The uptake of bacteria was quantified by flow cytometry and whole genome sequencing (WGS) was performed on NTHi strains. Geogenic PM increased the invasiveness of NTHi in bronchial epithelial cells. Of the primary constituents, haematite also increased NTHi invasion with magnetite and silica having significantly less impact. Furthermore, we observed varying levels of invasiveness amongst NTHi isolates. WGS analysis suggested isolates with more genes associated with heme acquisition were more virulent in BEAS-2B cells. The present study suggests that geogenic particles can increase the susceptibility of bronchial epithelial cells to select bacterial pathogens in vitro, a response primarily driven by haematite content in the dust. This demonstrates a potential mechanism linking exposure to iron-laden geogenic PM and high rates of chronic respiratory infections in remote communities in arid environments.
•Geogenic particles are linked to severe respiratory infections in Indigenous Australian communities, but the mechanism is unknown.•Particles containing haematite increased susceptibility of the airway epithelium to invasion by non-typeable Haemophilus influenzae.•Whole genome sequencing identified genes related to heme acquisition that were associated with this response.•This has implications for communities exposed to high levels of iron-laden particles.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite persistent calls to measure the effectiveness of educational interventions on patient outcomes, few studies have been conducted. Within musculoskeletal physiotherapy, the effects of clinical ...mentoring on postgraduate physiotherapists have been explored, but its impact on patient outcomes is unknown. The objective of this trial was to assess the effectiveness of a work-based mentoring programme to facilitate physiotherapist clinical reasoning on patient outcomes.
In a stepped-wedge cluster RCT in the musculoskeletal physiotherapy outpatient departments of a large NHS organisation, 16 physiotherapists were randomised by cluster to receive the intervention-150 hours of mentored clinical practice-at one of 3 time periods; control was usual training. 441 patients submitted outcome measures: Patient-Specific Functional Scale (PSFS) (primary outcome measure), EQ-5D-5L, patient activation and patient satisfaction (secondary outcome measures). A further secondary outcome measure of physiotherapist performance was collected by an independent assessor observing the physiotherapists practice.
80.0% of intervention patients achieved clinically significant PSFS scores compared with 63.8% of control patients. Binary logistic regression analysis modelling for time, cluster and patient characteristics showed strong statistical evidence for this difference (p = 0.023; odds ratio 4.24, 95%CI 1.22, 14.79). Physiotherapist performance scores improved from a mean of 47.8% (SD 3.60) pre-intervention to a mean of 56.0% (SD 4.24) (p<0.001). There was no statistical evidence for differences between groups on other secondary outcomes.
This is the first study that we aware of that provides patient outcomes measurement of an established educational intervention in physiotherapy, providing evidence that this type of intervention positively impacts patient outcomes and physiotherapist performance. This provides a basis for further research in education across other healthcare disciplines and outcome measures.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aromatic organic salts such as benzoates or phthalates may be widespread degradation products of organic molecules at the surface of Mars. The low volatility of these aromatic carboxylic salts could ...have compromised their detection through thermal extraction in situ analyses such as those performed by the Viking landers. However, over the years, analytical chemistry laboratories on board current and future Martian surface missions, such as the Sample Analysis at Mars (SAM) instrument suite on board the Curiosity rover and the Mars Organic Molecule Analyzer (MOMA) instrument of the Rosalind Franklin ExoMars rover, respectively, have evolved. These instruments have improved in efficiency to detect refractory and polar organic compounds, which could influence the detection of aromatic organic salts. To evaluate the capability of detecting aromatic organic salts on Mars with in situ instruments, we performed laboratory experiments under Viking, SAM, and MOMA-like Gas Chromatography-Mass Spectrometry (GC–MS) conditions with two carboxylic acid/salt couples: phthalic acid/calcium phthalate and benzoic acid/calcium benzoate. We studied the behavior and signatures of both molecular forms when using pyrolysis and derivatization experiments and the implications of these results in the search for organic molecules on Mars. This study showed that the Viking experiments could not have detected the presence of aromatic carboxylic salts in Martian samples because its maximum pyrolysis temperature was too low (500 °C). However, we showed that calcium benzoate and calcium phthalate, despite their refractory nature, could be identified indirectly through the detection of thermal and derivatized degradation products, both with SAM and MOMA. No conclusive proof of the presence of these aromatic organic salt species have been found in the SAM in situ data but given the right instrumental set-up they could be detected if present. The conclusions of this work raise essential questions on the detectability of refractory molecules, the analytical efficiency of flight instruments, and the interpretation of in situ data.
•Calcium phthalate and benzoate could be indirectly detected on Mars with SAM and MOMA.•Calcium carboxylic salts produce characteristic pyrolysis byproducts.•Calcium salts can be derivatized with MTBSTFA, DMFDMA and TMAH.•Tandem analyses are necessary to identify the presence of aromatic carboxylic salts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Evolved gas analysis (EGA) data from the Sample Analysis at Mars (SAM) instrument suite indicated Fe-rich smectite, carbonate, oxidized organics, Fe/Mg sulfate, and chloride in sedimentary rocks from ...the Glen Torridon (GT) region of Gale crater that displayed phyllosilicate spectral signatures from orbit. SAM evolved H2O data indicated that the primary phyllosilicate in all GT samples was an Fe-rich dioctahedral smectite (e.g., nontronite) with lesser amounts of a phyllosilicate such as mixed layer talc-serpentine or greenalite-minnesotaite. CO(2) data supported the identification of siderite in several samples, and CO(2) and CO data was also consistent with trace oxidized organic compounds such as oxalate salts. SO(2) data indicated trace and/or amorphous Fe sulfates in all samples and one sample may contain Fe sulfides. SO(2) data points to significant Mg sulfates in two samples, and lesser amounts in several other samples. A lack of evolved O(2) indicated the absence of oxychlorine salts and Mn3+/Mn4+ oxides. The lack of, or very minor, evolved NO revealed absent or very trace nitrate/nitrite salts. HCl data suggested chloride salts in GT samples. Constraints from EGA data on mineralogy and chemistry indicated that the environmental history of GT involved alteration with fluids of variable redox potential, chemistry and pH under a range of fluid-to-rock ratio conditions. Several of the fluid episodes could have provided habitable environmental conditions and carbon would have been available to any past microbes though the lack of significant N could have been a limiting factor for microbial habitability in the GT region.
Abstract
We present a family of self-consistent axisymmetric rotating globular cluster models which are fitted to spectroscopic data for NGC 362, NGC 1851, NGC 2808, NGC 4372, NGC 5927 and NGC 6752 ...to provide constraints on their physical and kinematic properties, including their rotation signals. They are constructed by flattening Modified Plummer profiles, which have the same asymptotic behaviour as classical Plummer models, but can provide better fits to young clusters due to a slower turnover in the density profile. The models are in dynamical equilibrium as they depend solely on the action variables. We employ a fully Bayesian scheme to investigate the uncertainty in our model parameters (including mass-to-light ratios and inclination angles) and evaluate the Bayesian evidence ratio for rotating to non-rotating models. We find convincing levels of rotation only in NGC 2808. In the other clusters, there is just a hint of rotation (in particular, NGC 4372 and NGC 5927), as the data quality does not allow us to draw strong conclusions. Where rotation is present, we find that it is confined to the central regions, within radii of R ≤ 2r
h
. As part of this work, we have developed a novel q-Gaussian basis expansion of the line-of-sight velocity distributions, from which general models can be constructed via interpolation on the basis coefficients.
A considerable bottleneck in serial crystallography at XFEL and synchrotron sources is the efficient production of large quantities of homogenous, well diffracting microcrystals. Efficient ...high‐throughput screening of batch‐grown microcrystals and the determination of ground‐state structures from different conditions is thus of considerable value in the early stages of a project. Here, a highly sample‐efficient methodology to measure serial crystallography data from microcrystals by raster scanning within standard in situ 96‐well crystallization plates is described. Structures were determined from very small quantities of microcrystal suspension and the results were compared with those from other sample‐delivery methods. The analysis of a two‐dimensional batch crystallization screen using this method is also described as a useful guide for further optimization and the selection of appropriate conditions for scaling up microcrystallization.
A sample‐ and time‐efficient method to obtain serial crystallography data from batch‐grown microcrystals dispensed as drops on a 96‐well crystallization plate is described. This offers a versatile method to obtain low‐dose room‐temperature structures and guide the optimization of microcrystallization for synchrotron and XFEL serial crystallography experiments.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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