Explore the vast range of titles available.

Rabbit haemorrhagic disease virus (RHDV) is established as a landscape-scale biocontrol that assists the management of invasive European rabbits and their impacts in both Australia and New Zealand. In addition to this, it is also available to land managers to augment rabbit control efforts at a local scale. However, current methods of deploying RHDV to rabbits that rely on the consumption of virus-treated baits can be problematic as rabbits are reluctant to consume bait when there is abundant, green, protein-rich feed available. We ran a suite of interrupted time-series experiments to compare the duration of infectivity of two conventional (carrot and oat baits) and two novel (meat bait and soil burrow spray) methods of deploying RHDV to rabbits. All methods effectively killed exposed rabbits. Soil burrow spray and carrot baits resulted in infection and mortality out to 5 days post their deployment in the field, and meat baits caused infection out to 10 days post their deployment. In contrast, oat baits continued to infect and kill exposed rabbits out to 20 days post deployment. Molecular assays demonstrated high viral loads in deployed baits beyond the duration for which they were infectious or lethal to rabbits. Based on our results, we suggest that the drying of meat baits may create a barrier to effective transmission of RHDV by adult flies within 10 days. We therefore hypothesise that fly larvae production and development on infected tissues is critical to prolonged viral transmission from meat baits, and similarly from carcasses of RHDV mortalities, via mechanical fly vectors. Our study demonstrates that meat baits and soil spray could provide additional virus deployment options that remove the need for rabbits to consume baits at times when they are reluctant to do so.

Forecasting the risk of pathogen spillover from reservoir populations of wild or domestic animals is essential for the effective deployment of interventions such as wildlife vaccination or culling. Due to the sporadic nature of spillover events and limited availability of data, developing and validating robust, spatially explicit, predictions is challenging. Recent efforts have begun to make progress in this direction by capitalizing on machine learning methodologies. An important weakness of existing approaches, however, is that they generally rely on combining human and reservoir infection data during the training process and thus conflate risk attributable to the prevalence of the pathogen in the reservoir population with the risk attributed to the realized rate of spillover into the human population. Because effective planning of interventions requires that these components of risk be disentangled, we developed a multi-layer machine learning framework that separates these processes. Our approach begins by training models to predict the geographic range of the primary reservoir and the subset of this range in which the pathogen occurs. The spillover risk predicted by the product of these reservoir specific models is then fit to data on realized patterns of historical spillover into the human population. The result is a geographically specific spillover risk forecast that can be easily decomposed and used to guide effective intervention. Applying our method to Lassa virus, a zoonotic pathogen that regularly spills over into the human population across West Africa, results in a model that explains a modest but statistically significant portion of geographic variation in historical patterns of spillover. When combined with a mechanistic mathematical model of infection dynamics, our spillover risk model predicts that 897,700 humans are infected by Lassa virus each year across West Africa, with Nigeria accounting for more than half of these human infections.

Bubbles that rise to the surface of a cell suspension can damage cells when they pop. This phenomenon is particularly problematic in the biotechnology industry, as production scale bioreactors require continuous injection of oxygen bubbles to maintain cell growth. Previous studies have linked cell damage to high energy dissipation rates (EDR) and have predicted that for small bubbles the EDR could exceed values that would kill many cells used in bioreactors, including Chinese Hamster Ovary (CHO) cells. However, it’s unclear how many cells would be damaged by a particular bursting bubble, or more precisely how much volume around the bubble experiences these large energy dissipation rates. Here we quantify these volumes using numerical simulations and demonstrate that even though the volume exceeding a particular EDR increases with bubble size, on a volume-to-volume basis smaller bubbles have a more significant impact. We validate our model with high-speed experiments and present our results in a non-dimensionalized framework, enabling predictions for a variety of liquids and bubble sizes. The results are not restricted to bubbles in bioreactors and may be relevant to a variety of applications ranging from fermentation processes to characterizing the stress levels experienced by microorganisms within the sea surface microlayer.

Bubbles are ubiquitous in biological environments, emerging during the complex dynamics of waves breaking in the open oceans or being intentionally formed in bioreactors. From formation, through motion, until death, bubbles play a critical role in the oxygenation and mixing of natural and artificial ecosystems. However, their life is also greatly influenced by the environments in which they emerge. This interaction between bubbles and microorganisms is a subtle affair in which surface tension plays a critical role. Indeed, it shapes the role of bubbles in mixing or oxygenating microorganisms, but also determines how microorganisms affect every stage of the bubble’s life. In this review, we guide the reader through the life of a bubble from birth to death, with particular attention to the microorganism–bubble interaction as viewed through the lens of fluid dynamics.

Background COVID-19 lockdowns have reduced opportunities for physical activity (PA) and encouraged more sedentary lifestyles. A concomitant of sedentariness is compromised mental health. We investigated the effects of COVID-19 lockdown on PA, sedentary behavior, and mental health across four Western nations (USA, UK, France, and Australia). Methods An online survey was administered in the second quarter of 2020 ( N  = 2541). We measured planned and unplanned dimensions of PA using the Brunel Lifestyle Physical Activity Questionnaire and mental health using the 12-item General Health Questionnaire. Steps per day were recorded only from participants who used an electronic device for this purpose, and sedentary behavior was reported in hours per day (sitting and screen time). Results In the USA and Australia samples, there was a significant decline in planned PA from pre- to during lockdown. Among young adults, Australians exhibited the lowest planned PA scores, while in middle-aged groups, the UK recorded the highest. Young adults exhibited the largest reduction in unplanned PA. Across nations, there was a reduction of ~ 2000 steps per day. Large increases in sedentary behavior emerged during lockdown, which were most acute in young adults. Lockdown was associated with a decline in mental health that was more pronounced in women. Conclusions The findings illustrate the deleterious effects of lockdown on PA, sedentary behavior, and mental health across four Western nations. Australian young and lower middle-aged adults appeared to fare particularly badly in terms of planned PA. The reduction in steps per day is equivalent to the non-expenditure of ~ 100 kcal. Declines in mental health show how harmful lockdowns can be for women in particular.

Background: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs. Methods: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined. Results: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup ( P =0.006). Conclusions: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies.

The precise mass, bulk density, porosity and internal structure of the nucleus of comet 67P/Churyumov–Gerasimenko are calculated, on the basis of its gravity field, showing it to be dusty, homogeneous, low-density and highly porous. An 'icy dirtball' cometary nucleus We are familiar with the bright coma and characteristic dust and plasma tails of comets when observed from ground, but the nucleus itself is hidden inside the coma. Comet nuclei consist of dust and mostly water ice, but their internal structure is essentially unknown. This paper reports results from the Radio Science Investigation (RSI) experiment on the Rosetta spacecraft that provide the precise mass, bulk density, porosity and internal structure of the nucleus of comet 67P/Churyumov–Gerasimenko based on its gravity field. Results point to a low-density, highly porous nucleus containing four times more dust than ice by mass and two times more dust than ice by volume. The authors conclude that the interior of the nucleus is homogeneous and constant in density on a global scale, with no large voids. Cometary nuclei consist mostly of dust and water ice 1 . Previous observations have found nuclei to be low-density and highly porous bodies 2 , 3 , 4 , but have only moderately constrained the range of allowed densities because of the measurement uncertainties. Here we report the precise mass, bulk density, porosity and internal structure of the nucleus of comet 67P/Churyumov–Gerasimenko on the basis of its gravity field. The mass and gravity field are derived from measured spacecraft velocity perturbations at fly-by distances between 10 and 100 kilometres. The gravitational point mass is GM  = 666.2 ± 0.2 cubic metres per second squared, giving a mass M  = (9,982 ± 3) × 10 9 kilograms. Together with the current estimate of the volume of the nucleus 5 , the average bulk density of the nucleus is 533 ± 6 kilograms per cubic metre. The nucleus appears to be a low-density, highly porous (72–74 per cent) dusty body, similar to that of comet 9P/Tempel 1 2 , 3 . The most likely composition mix has approximately four times more dust than ice by mass and two times more dust than ice by volume. We conclude that the interior of the nucleus is homogeneous and constant in density on a global scale without large voids. The high porosity seems to be an inherent property of the nucleus material.

Background Verbal autopsy is an increasingly important methodology for assigning causes to otherwise uncertified deaths, which amount to around 50% of global mortality and cause much uncertainty for health planning. The World Health Organization sets international standards for the structure of verbal autopsy interviews and for cause categories that can reasonably be derived from verbal autopsy data. In addition, computer models are needed to efficiently process large quantities of verbal autopsy interviews to assign causes of death in a standardised manner. Here, we present the InterVA-5 model, developed to align with the WHO-2016 verbal autopsy standard. This is a harmonising model that can process input data from WHO-2016, as well as earlier WHO-2012 and Tariff-2 formats, to generate standardised cause-specific mortality profiles for diverse contexts. The software development involved building on the earlier InterVA-4 model, and the expanded knowledge base required for InterVA-5 was informed by analyses from a training dataset drawn from the Population Health Metrics Research Collaboration verbal autopsy reference dataset, as well as expert input. Results The new model was evaluated against a test dataset of 6130 cases from the Population Health Metrics Research Collaboration and 4009 cases from the Afghanistan National Mortality Survey dataset. Both of these sources contained around three quarters of the input items from the WHO-2016, WHO-2012 and Tariff-2 formats. Cause-specific mortality fractions across all applicable WHO cause categories were compared between causes assigned in participating tertiary hospitals and InterVA-5 in the test dataset, with concordance correlation coefficients of 0.92 for children and 0.86 for adults. The InterVA-5 model’s capacity to handle different input formats was evaluated in the Afghanistan dataset, with concordance correlation coefficients of 0.97 and 0.96 between the WHO-2016 and the WHO-2012 format for children and adults respectively, and 0.92 and 0.87 between the WHO-2016 and the Tariff-2 format respectively. Conclusions Despite the inherent difficulties of determining “truth” in assigning cause of death, these findings suggest that the InterVA-5 model performs well and succeeds in harmonising across a range of input formats. As more primary data collected under WHO-2016 become available, it is likely that InterVA-5 will undergo minor re-versioning in the light of practical experience. The model is an important resource for measuring and evaluating cause-specific mortality globally.

Objective Colonic fermentation in patients with UC in remission was compared with that in matched healthy subjects on habitual diets and when dietary fibre was increased. Design Fibre intake, faecal output of fibre (measured as non-starch polysaccharide (NSP)), starch, microbiota and fermentation products, and whole gut transit time (WGTT) were assessed in association with habitual diet and when dietary intake of wheat bran (WB)-associated fibre and high amylose-associated resistant starch (RS) was increased in an 8-week, randomised, single-blind, cross-over study. Results Despite a tendency to lower habitual fibre intake in UC patients, faecal NSP and starch concentrations were threefold higher than in controls, whereas concentrations of phenols and short-chain fatty acids, pH and WGTT were similar. Increasing RS/WB intake was well tolerated. In controls (n=10), it more than doubled faecal NSP and starch excretion (p=0.002 for both), had no effect on NSP usage and reduced WGTT (p=0.024). In UC patients (n=19), high intake of RS/WB tended to normalise gut transit, but did not increase the proportion of NSP fermented. Increasing intake of RS/WB had little effect on faecal fermentation patterns or the structure of the microbiota. However, faeces from the UC cohort had lower proportions of Akkermansia muciniphila and increased diversity within Clostridium cluster XIVa compared to controls. Conclusions Gut fermentation of NSP and starch is diminished in patients with UC. This cannot be explained by abnormal gut transit and was not corrected by increasing RS/WB intake, and may be due to abnormal functioning of the gut microbiota. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12614000271606.

Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure. Why the latter occurs is poorly understood. Here we demonstrate senescence development in extrahepatic organs and associated organ dysfunction in response to liver senescence using liver injury models and genetic models of hepatocyte-specific senescence. In patients with severe acute liver failure, we show that the extent of hepatocellular senescence predicts disease outcome, the need for liver transplantation and the occurrence of extrahepatic organ failure. We identify the TGFβ pathway as a critical mediator of systemic spread of senescence and demonstrate that TGFβ inhibition in vivo blocks senescence transmission to other organs, preventing liver senescence induced renal dysfunction. Our results highlight the systemic consequences of organ-specific senescence, which, independent of ageing, contributes to multi-organ dysfunction. Kiourtis et al. show that liver senescence triggers senescence and dysfunction in other organs through TGFβ secretion from the liver.