Recommended centrifuge method: Specific grain size separation in the <63 µm fraction of marine sediments.

The isolation of specific grain size classes of lithogenic samples and biogenic carbonate from the <63 µm fraction (i.e. clay and silt) of marine sediment is often a prerequisite to further pre-treatments and/or analytical measurements for palaeoceanographic studies. Established techniques employed have included sieving, settling and micro-filtration (and/or a combination of these). However, these methods often use significant amounts of bulk sediment (often up to ∼3 g) and/or require considerable amounts of time during sediment processing (ranging from 48 h to 3 weeks) to isolate a size specific class for further analyses. Here, we build on previous approaches to isolate three grain size classes (e.g. <2 µm, clay; 2-10 µm, fine silt; and 10-63 µm, coarse silt) from the <63 µm fraction of marine sediment with the aid of a centrifuge at varying revolutions per minute using Stokes' Law. We show the utility of our approach using two common sediment types dominated by (i) lithogenic and (ii) biogenic carbonate (specifically coccoliths) components of marine sediment cores. Our method reduces the amount of sample material required to 1-2 g to provide an isolated clay fraction (or other targeted size fraction) and decreases the sample processing time (to ∼1 hour) to enable high throughput of analysis, when compared to previous techniques for palaeoceanographic proxy measurements.•We recommend a more straightforward grain size isolation method for lithogenic sediment and biogenic carbonate sediment types•Isolating commonly targeted grain size fractions for palaeoceanographic studies using a centrifuge.

Observation of ionization trends in a laboratory photoionized plasma experiment at Z.

We report experimental and modeling results for the charge state distribution of laboratory photoionized neon plasmas in the first systematic study over nearly an order of magnitude range of ionization parameter ξ∝F/N_{e}. The range of ξ is achieved by flexibility in the experimental platform to adjust either the x-ray drive flux F at the sample or the electron number density N_{e} or both. Experimental measurements of photoionized plasma conditions over such a range of parameters enable a stringent test of atomic kinetics models used within codes that are applied to photoionized plasmas in the laboratory and astrophysics. From experimental transmission data, ion areal densities are extracted by spectroscopic analysis that is independent of atomic kinetics modeling. The measurements reveal the net result of the competition between photon-driven ionization and electron-driven recombination atomic processes as a function of ξ as it affects the charge state distribution. Results from radiation-hydrodynamics modeling calculations with detailed inline atomic kinetics modeling are compared with the experimental results. There is good agreement in the mean charge and overall qualitative similarities in the trends observed with ξ but significant quantitative differences in the fractional populations of individual ions.

Indo-Pacific Walker circulation drove Pleistocene African aridification.

Today, the eastern African hydroclimate is tightly linked to fluctuations in the zonal atmospheric Walker circulation1,2. A growing body of evidence indicates that this circulation shaped hydroclimatic conditions in the Indian Ocean region also on much longer, glacial-interglacial timescales3-5, following the development of Pacific Walker circulation around 2.2-2.0 million years ago (Ma)6,7. However, continuous long-term records to determine the timing and mechanisms of Pacific-influenced climate transitions in the Indian Ocean have been unavailable. Here we present a seven-million-year-long record of wind-driven circulation of the tropical Indian Ocean, as recorded in Mozambique Channel Throughflow (MCT) flow-speed variations. We show that the MCT flow speed was relatively weak and steady until 2.1 ± 0.1 Ma, when it began to increase, coincident with the intensification of the Pacific Walker circulation6,7. Strong increases during glacial periods, which reached maxima after the Mid-Pleistocene Transition (0.9-0.64 Ma; ref. 8), were punctuated by weak flow speeds during interglacial periods. We provide a mechanism explaining that increasing MCT flow speeds reflect synchronous development of the Indo-Pacific Walker cells that promote aridification in Africa. Our results suggest that after about 2.1 Ma, the increasing aridification is punctuated by pronounced humid interglacial periods. This record will facilitate testing of hypotheses of climate-environmental drivers for hominin evolution and dispersal.

COVID-19 testing in outbreak-free care homes: what are the public health benefits?

BACKGROUND: COVID-19 care home outbreaks represent a significant proportion of COVID-19 morbidity and mortality in the UK. National testing initially focused on symptomatic care home residents, before extending to asymptomatic cohorts. AIM: The aim was to describe the epidemiology and transmission of COVID-19 in outbreak free care homes. METHODS: A two-point prevalence survey of COVID-19, in 34 Liverpool care homes, was performed in April and May 2020. Changes in prevalence were analysed. Associations between care home characteristics, reported infection, prevention and control interventions, and COVID-19 status were described and analysed. FINDINGS: No resident developed COVID-19 symptoms during the study. There was no significant difference between: the number of care homes containing at least one test positive resident between the first (17.6%, 95% confidence interval (CI) 6.8-34.5) and second round (14.7%, 95% CI 5.0-31.1) of testing (p>0.99); and the number of residents testing positive between the first (2.1%, 95% CI 1.2-3.4) and second round (1.0%, 95% CI 0.5-2.1) of testing (P=0.11). Care homes providing nursing care (risk ratio (RR) 7.99, 95% CI 1.1-57.3) and employing agency staff (RR 8.4, 95% CI 1.2-60.8) were more likely to contain test positive residents. Closing residents shared space was not associated with residents testing positive (RR 2.63, 95% CI 0.4-18.5). CONCLUSIONS: Asymptomatic COVID-19 care homes showed no evidence of disease transmission or development of outbreaks; suggesting that current infection prevention and control measures are effective in preventing transmission. Repeat testing at two to three weeks had limited or no public health benefits over regular daily monitoring of staff and residents for symptoms. These results should inform policies calling for regular testing of asymptomatic residents.

Modelling soil erosion responses to climate change in three catchments of Great Britain.

Simulations of 21st century climate change for Great Britain predict increased seasonal precipitation that may lead to widespread soil loss by increasing surface runoff. Land use and different vegetation cover can respond differently to this scenario, mitigating or enhancing soil erosion. Here, by means of a sensitivity analysis of the PESERA soil erosion model, we test the potential for climate and vegetation to impact soil loss by surface-runoff to three differentiated British catchments. First, to understand general behaviours, we modelled soil erosion adopting regular increments for rainfall and temperature from the baseline values (1961-1990). Then, we tested future climate scenarios adopting projections from UKCP09 (UK Climate Projections) under the IPCC (Intergovernmental Panel on Climate Change) on a defined medium CO2 emissions scenario, SRES-A1B (Nakicenovic et al., 2000), at the horizons 2010-39, 2040-69 and 2070-99. Our results indicate that the model reacts to the changes of the climatic parameters and the three catchments respond differently depending on their land use arrangement. Increases in rainfall produce a rise in soil erosion while higher temperatures tend to lower the process because of the mitigating action of the vegetation. Even under a significantly wetter climate, warmer air temperatures can limit soil erosion by enhancing primary productivity and in turn improving leaf interception, infiltration-capacity, and reducing soil erodibility. Consequently, for specific land uses, the increase in air temperature associated with climate change can modify the rainfall thresholds to generate soil loss, and soil erosion rates could decline by up to about 33% from 2070 to 2099. We deduce that enhanced primary productivity due to climate change can introduce a negative-feedback mechanism limiting soil loss by surface runoff as vegetation-induced impacts on soil hydrology and erodibility offset the effects of increased precipitation. The expansion of permanent vegetation cover could provide an adaptation strategy to reduce climate-driven soil loss.

X-ray heating and electron temperature of laboratory photoionized plasmas.

We discuss the experimental and modeling results for the x-ray heating and temperature of laboratory photoionized plasmas. A method is used to extract the electron temperature based on the analysis of transmission spectroscopy data that is independent of atomic kinetics modeling. The results emphasized the critical role of x-ray heating and radiation cooling in determining the energy balance of the plasma. They also demonstrated the dramatic impact of photoexcitation on excited-state populations, line emissivity, and radiation cooling. Modeling calculations performed with astrophysical codes significantly overestimated the measured temperature.

An agent-based model about the effects of fake news on a norovirus outbreak.

BACKGROUND: Concern about health misinformation is longstanding, especially on the Internet. METHODS: Using agent-based models, we considered the effects of such misinformation on a norovirus outbreak, and some methods for countering the possible impacts of "good" and "bad" health advice. The work explicitly models spread of physical disease and information (both online and offline) as two separate but interacting processes. The models have multiple stochastic elements; repeat model runs were made to identify parameter values that most consistently produced the desired target baseline scenario. Next, parameters were found that most consistently led to a scenario when outbreak severity was clearly made worse by circulating poor quality disease prevention advice. Strategies to counter "fake" health news were tested. RESULTS: Reducing bad advice to 30% of total information or making at least 30% of people fully resistant to believing in and sharing bad health advice were effective thresholds to counteract the negative impacts of bad advice during a norovirus outbreak. CONCLUSION: How feasible it is to achieve these targets within communication networks (online and offline) should be explored.

A systematic review of infectious illness Presenteeism: prevalence, reasons and risk factors.

BACKGROUND: Workplace presenteeism is common and leads to the spread of infectious diseases. Previous reviews have focused on presenteeism in relation to general physical or mental ill health. In this systematic review we identified the prevalence of, and reasons and risk factors for, presenteeism in relation to an infectious illness. METHOD: We searched Medline, Scopus, Web of Science, PsycINFO and PsycARTICLES with terms relating to infectious illnesses and presenteeism at the work place or school; reference lists of relevant articles were also hand-searched. RESULT: Our search yielded 3580 papers after deduplication. After title, abstract and full text screening, 23 papers reporting on 24 studies were included. Twenty-three studies were cross-sectional studies and one was prospective. The quality of included studies was relatively poor due to problems such as sampling and non-response bias. Presenteeism prevalence ranged from 35 to 97%. Self-reported reasons for presenteeism fell into three main themes: 1. Organisational factors (organisational policy, presenteeism culture, disciplinary action), 2. Job characteristics (lack of cover, professionalism, job demand), and 3. Personal reasons (burden on colleagues, colleague perceptions, threshold of sickness absence and financial concerns). Statistical risk factors fell into four themes: 1. Sociodemographic, 2. Health, 3. Influenza-related behaviour, and 4. Employment characteristics. Most of the risk factors had insufficient evidence to allow us to draw any firm conclusions, and evidence regarding gender and age was inconsistent. The risk factor with the most consistent findings concerned occupation type, suggesting that those who worked in the healthcare sector, and specifically physicians, were at a higher risk of infectious illness presenteeism. CONCLUSION: Infectious illness presenteeism is common. To address the public health consequences, organisations should focus on promoting a positive working culture and developing sickness absence policies that reduce presenteeism. Further research is needed in non-health sector organisations and schools to identify risk factors related to different organisations, which can then be used to tailor interventions at the organisational and individual level.

Analysis of individual patient data to describe the incubation period distribution of Shiga-toxin producing Escherichia coli.

Shiga-toxin producing Escherichia coli (STEC) is a pathogen that can cause bloody diarrhoea and severe complications. Cases occur sporadically but outbreaks are also common. Understanding the incubation period distribution and factors influencing it will help in the investigation of exposures and consequent disease control. We extracted individual patient data for STEC cases associated with outbreaks with a known source of exposure in England and Wales. The incubation period was derived and cases were described according to patient and outbreak characteristics. We tested for heterogeneity in reported incubation period between outbreaks and described the pattern of heterogeneity. We employed a multi-level regression model to examine the relationship between patient characteristics such as age, gender and reported symptoms; and outbreak characteristics such as mode of transmission with the incubation period. A total of 205 cases from 41 outbreaks were included in the study, of which 64 cases (31%) were from a single outbreak. The median incubation period was 4 days. Cases reporting bloody diarrhoea reported shorter incubation periods compared with cases without bloody diarrhoea, and likewise, cases aged between 40 and 59 years reported shorter incubation period compared with other age groups. It is recommended that public health officials consider the characteristics of cases involved in an outbreak in order to inform the outbreak investigation and the period of exposure to be investigated.

Drumming-associated anthrax incidents: exposures to low levels of indoor environmental contamination.

Two fatal drumming-related inhalational anthrax incidents occurred in 2006 and 2008 in the UK. One individual was a drum maker and drummer from the Scottish Borders, most likely infected whilst playing a goat-skin drum contaminated with Bacillus anthracis spores; the second, a drummer and drum maker from East London, likely became infected whilst working with contaminated animal hides.We have collated epidemiological and environmental data from these incidents and reviewed them alongside three similar contemporaneous incidents in the USA. Sampling operations recovered the causative agent from drums and drum skins and from residences and communal buildings at low levels. From these data, we have considered the nature of the exposures and the number of other individuals likely to have been exposed, either to the primary infection events or to subsequent prolonged environmental contamination (or both).Despite many individual exposures to widespread low-level spore contamination in private residences and in work spaces for extended periods of time (at least 1 year in one instance), only one other individual acquired an infection (cutaneous). Whilst recognising the difficulty in making definitive inferences from these incidents to specific residual contamination levels, and by extending the risk to public health, we believe it may be useful to reflect on these findings when considering future incident management risk assessments and decisions in similar incidents that result in low-level indoor contamination.

Sea ice dynamics across the Mid-Pleistocene transition in the Bering Sea.

Sea ice and associated feedback mechanisms play an important role for both long- and short-term climate change. Our ability to predict future sea ice extent, however, hinges on a greater understanding of past sea ice dynamics. Here we investigate sea ice changes in the eastern Bering Sea prior to, across, and after the Mid-Pleistocene transition (MPT). The sea ice record, based on the Arctic sea ice biomarker IP25 and related open water proxies from the International Ocean Discovery Program Site U1343, shows a substantial increase in sea ice extent across the MPT. The occurrence of late-glacial/deglacial sea ice maxima are consistent with sea ice/land ice hysteresis and land-glacier retreat via the temperature-precipitation feedback. We also identify interactions of sea ice with phytoplankton growth and ocean circulation patterns, which have important implications for glacial North Pacific Intermediate Water formation and potentially North Pacific abyssal carbon storage.

Studies towards the synthesis of Pd(ii)-containing [2] and [3]catenanes in aqueous media.

Here is reported the investigation of a synthetic route for the preparation of Pd(ii)-containing catenanes in aqueous media. A pseudorotaxane intermediate was prepared, which can potentially be converted into a series of catenanes. From the pseudorotaxane, using a Pd(ii)-driven clipping step a dinuclear [3]catenane was obtained in the solid state.

Associations between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes.

INTRODUCTION: Existing methods to predict recipient allograft function during deceased-donor kidney procurement are imprecise. Understanding the potential renal reparative role for monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in macrophage recruitment after injury, might help predict allograft outcomes. METHODS: We conducted a sub-study of the multicenter prospective Deceased Donor Study cohort, which evaluated deceased kidney donors from five organ procurement organizations from May 2010 to December 2013. We measured urine MCP-1 (uMCP-1) concentrations from donor samples collected at nephrectomy to determine associations with donor acute kidney injury (AKI), recipient delayed graft function (DGF), 6-month estimated GFR (eGFR), and graft failure. We also assessed perfusate MCP-1 concentrations from pumped kidneys for associations with DGF and 6-month eGFR. RESULTS: AKI occurred in 111 (9%) donors. Median (interquartile range) uMCP-1 concentration was higher in donors with AKI compared to donors without AKI (1.35 [0.41-3.93] ng/ml vs. 0.32 [0.11-0.80] ng/ml, p<0.001). DGF occurred in 756 (31%) recipients, but uMCP-1 was not independently associated with DGF. Higher donor uMCP-1 concentrations were independently associated with higher 6-month eGFR in those without DGF [0.77 (0.10, 1.45) ml/min/1.73m2 per doubling of uMCP1]. However, there were no independent associations between uMCP-1 and graft failure over a median follow-up of about 2 years. Lastly, perfusate MCP-1 concentrations significantly increased during pump perfusion but were not associated with DGF or 6-month eGFR. CONCLUSION: Donor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.

A systematic review and meta-analysis on the incubation period of Campylobacteriosis.

Accurate knowledge of pathogen incubation period is essential to inform public health policies and implement interventions that contribute to the reduction of burden of disease. The incubation period distribution of campylobacteriosis is currently unknown with several sources reporting different times. Variation in the distribution could be expected due to host, transmission vehicle, and organism characteristics, however, the extent of this variation and influencing factors are unclear. The authors have undertaken a systematic review of published literature of outbreak studies with well-defined point source exposures and human experimental studies to estimate the distribution of incubation period and also identify and explain the variation in the distribution between studies. We tested for heterogeneity using I 2 and Kolmogorov-Smirnov tests, regressed incubation period against possible explanatory factors, and used hierarchical clustering analysis to define subgroups of studies without evidence of heterogeneity. The mean incubation period of subgroups ranged from 2·5 to 4·3 days. We observed variation in the distribution of incubation period between studies that was not due to chance. A significant association between the mean incubation period and age distribution was observed with outbreaks involving only children reporting an incubation of 1·29 days longer when compared with outbreaks involving other age groups.

Annually resolved North Atlantic marine climate over the last millennium.

Owing to the lack of absolutely dated oceanographic information before the modern instrumental period, there is currently significant debate as to the role played by North Atlantic Ocean dynamics in previous climate transitions (for example, Medieval Climate Anomaly-Little Ice Age, MCA-LIA). Here we present analyses of a millennial-length, annually resolved and absolutely dated marine δ18O archive. We interpret our record of oxygen isotope ratios from the shells of the long-lived marine bivalve Arctica islandica (δ18O-shell), from the North Icelandic shelf, in relation to seawater density variability and demonstrate that solar and volcanic forcing coupled with ocean circulation dynamics are key drivers of climate variability over the last millennium. During the pre-industrial period (AD 1000-1800) variability in the sub-polar North Atlantic leads changes in Northern Hemisphere surface air temperatures at multi-decadal timescales, indicating that North Atlantic Ocean dynamics played an active role in modulating the response of the atmosphere to solar and volcanic forcing.

Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development.

BACKGROUND: Recent meta-analyses of genome-wide association studies have identified single nucleotide polymorphisms (SNPs) within/near 54 genes associated with lung function measures. Current understanding of the contribution of these genes to human lung development is limited. We set out to further define i) the expression profile of these genes during human lung development using a unique set of resources to examine both mRNA and protein expression and ii) the link between key polymorphisms and genes using expression quantitative trait loci (eQTL) approaches. METHODS: The mRNA expression profile of lung function associated genes across pseudoglandular and canalicular stages of lung development were determined using expression array data of 38 human fetal lungs. eQTLs were investigated for selected genes using blood cell and lung tissue data. Immunohistochemistry of the top 5 candidates was performed in a panel of 24 fetal lung samples. RESULTS: Twenty-nine lung function associated genes were differentially expressed during lung development at the mRNA level. The greatest magnitude of effect was observed for 5 genes; TMEM163, FAM13A and HHIP which had increasing expression and CDC123 and PTCH1 with decreased expression across developmental stages. Focussed eQTL analyses investigating SNPs in these five loci identified several cis-eQTL's. Protein expression of TMEM163 increased and CDC123 decreased with fetal lung age in agreement with mRNA data. Protein expression in FAM13A, HHIP and PTCH1 remained relatively constant throughout lung development. CONCLUSIONS: We have identified that > 50 % of lung function associated genes show evidence of differential expression during lung development and we show that in particular TMEM163 and CDC123 are differentially expressed at both the mRNA and protein levels. Our data provides a systematic evaluation of lung function associated genes in this context and offers some insight into the potential role of several of these genes in contributing to human lung development.

A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences.

Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency=0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P=1.2 × 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P=4.0 × 10(-4)), chronic obstructive pulmonary disease (COPD; P=9.3 × 10(-4)), peripheral artery disease (PAD; P=0.090) and abdominal aortic aneurysms (AAAs; P=0.12), and the variant associates strongly with the early-onset forms of LC (OR=4.49, P=2.2 × 10(-4)), COPD (OR=3.22, P=2.9 × 10(-4)), PAD (OR=3.47, P=9.2 × 10(-3)) and AAA (OR=6.44, P=6.3 × 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P=6.8 × 10(-5)), particularly for early-onset cases (P=2.1 × 10(-7)). Our results are in agreement with functional studies showing that the human α4ß2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.

Translating Lung Function Genome-Wide Association Study (GWAS) Findings: New Insights for Lung Biology.

Chronic respiratory diseases are a major cause of worldwide mortality and morbidity. Although hereditary severe deficiency of α1 antitrypsin (A1AD) has been established to cause emphysema, A1AD accounts for only ∼ 1% of Chronic Obstructive Pulmonary Disease (COPD) cases. Genome-wide association studies (GWAS) have been successful at detecting multiple loci harboring variants predicting the variation in lung function measures and risk of COPD. However, GWAS are incapable of distinguishing causal from noncausal variants. Several approaches can be used for functional translation of genetic findings. These approaches have the scope to identify underlying alleles and pathways that are important in lung function and COPD. Computational methods aim at effective functional variant prediction by combining experimentally generated regulatory information with associated region of the human genome. Classically, GWAS association follow-up concentrated on manipulation of a single gene. However association data has identified genetic variants in >50 loci predicting disease risk or lung function. Therefore there is a clear precedent for experiments that interrogate multiple candidate genes in parallel, which is now possible with genome editing technology. Gene expression profiling can be used for effective discovery of biological pathways underpinning gene function. This information may be used for informed decisions about cellular assays post genetic manipulation. Investigating respiratory phenotypes in human lung tissue and specific gene knockout mice is a valuable in vivo approach that can complement in vitro work. Herein, we review state-of-the-art in silico, in vivo, and in vitro approaches that may be used to accelerate functional translation of genetic findings.