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Algorithms for synchronization of parallel discrete event simulation have historically been divided between conservative methods that require lookahead but not rollback, and optimistic methods that require rollback but not lookahead. In this paper we present a new approach in the form of a framework called Unified Virtual Time (UVT) that unifies the two approaches, combining the advantages of both within a single synchronization theory. Whenever timely lookahead information is available, a logical process (LP) executes conservatively using an irreversible event handler. When lookahead information is not available the LP does not block, as it would in a classical conservative execution, but instead executes optimistically using a reversible event handler. The switch from conservative to optimistic synchronization and back is decided on an event-by-event basis by the simulator, transparently to the model code. UVT treats conservative synchronization algorithms as optional accelerators for an underlying optimistic synchronization algorithm, enabling the speed of conservative execution whenever it is applicable, but otherwise falling back on the generality of optimistic execution. We describe UVT in a novel way, based on fundamental invariants, monotonicity requirements, and synchronization rules. UVT permits zero-delay messages and pays careful attention to tie-handling using superposition. We prove that under fairly general conditions a UVT simulation always makes progress in virtual time. This is Part 1 of a trio of papers describing the UVT framework for PDES, mixing conservative and optimistic synchronization and integrating throttling control.

This is Part 2 of a trio of works intended to provide a unifying framework in which conservative and optimistic synchronization for parallel discrete event simulations can be freely and transparently combined in the same logical process on an event-by-event basis. In this article, we continue the outline of an approach called Unified Virtual Time (UVT) that was introduced in Part 1 , showing in detail via two extended examples how conservative synchronization can be refactored and combined with optimistic synchronization in the UVT framework. We describe UVT versions of both a basic time windowing algorithm called Unified Simple Time Windows and a refactored version of the Chandy-Misra-Bryant Null Message algorithm called Unified CMB .

Viral infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induce a dynamic immune environment. Using nasal mucosal samples in 139 participants from the STOIC study (community-based randomised clinical trial for the use of budesonide in early onset SARS-CoV-2, NCT04416399), we applied predefined immune mediator nodes in relation to clinical outcomes and viral burden. Interferon- and chemokine-dominant nodes increased expression as compared to health, validating our modular approach. Next, we demonstrated that an increase in mucosal immunity-like node consisting of CCL13, CCL17, IL-33, among others was associated with a mean 3.7-day quicker recovery with no primary outcome events, irrespective of treatment arm. By day 14 the mucosal node divided into two daughter nodes linked to interferon molecules and was transcriptionally detectable in nasal cavity basal, hillock and ciliated cells (as per public single cell dataset EGAD00001007718). Our data suggest mucosal-associated mediators are key for early symptom resolution of SARS-CoV-2.

Digital breast tomosynthesis (DBT) is a main imaging modality for breast imaging. However, shielding calculations for DBT are commonly based on previous technology with softer beam spectra. In addition, shielding calculations often assume some patient attenuation is provided in locations to the posterior of the patient but without quantification of this attenuation. In this work, recent research in DBT shielding is validated by measuring scatter radiation in the vertical plane. It is also extended upon by measuring the scatter radiation in the horizontal plane and the effect of patient attenuation. These measurements are weighted by our local patient compressed breast thickness distribution to provide a simple scattering factor. Air kerma distributions are provided demonstrating the distribution of scatter radiation around the DBT system in the presence of patient body attenuation. The highest air kerma measured in any direction from a 4-view per patient screening tomosynthesis exam based on the local patient workload is 55 μGy at 1 m. This value can be used to conservatively treat the scatter radiation as an isotropic distribution for shielding assessments. This work is consistent with many recent publications, with the notable exception of the forward scattered peak which is smaller than previous studies. Under our locally encountered breast thickness distribution, the increased scatter radiation and consequent increased minimum shielding requirements is small in most cases. With 400 patients per week, the air kerma at 1 m is 22 mGy and, for a fully occupied public area 2 m away, this requires a gypsum plasterboard thickness of 18.0 mm which is 3.6 mm more than previous data suggests. Although the increase is minimal, standard manufacturing thicknesses of shielding material may not be automatically assumed to be sufficient and careful consideration of the scatter radiation is warranted.

Current land use systems in the Amazon largely consist of extensive conventional livestock operations that drive deforestation, degrade soil ecosystems, and tend to be socioeconomically unsustainable. Silvopastoral systems (SPS) have been promoted for decades as an alternative but widespread uptake has yet to be seen. We explore the main drivers and barriers to uptake through a bespoke survey of 172 farms in the Caquetá region of the Colombian Amazon split equally between adoption and non-adoption. Pearson’s chi-square tests and logistic regression models are used to analyse the effects of categorical and continuous predictor variables on a binary adoption variable. Results show that knowledge gaps, years of experience in farming, as well as infrastructure issues around poor road access were negatively related to adoption, while perception of SPS benefits, proximity to other SPS farms, training in SPS, and understanding of SPS were positively related to adoption with statistical significance. The most promising intervention strategies involve addr­essing knowledge gaps via training and specialised extension and improving market access by removing regulatory barriers and strengthening demand for agroforestry products.

By Robert Bruce, edited by David Searle (Fearn: Christian Heritage, 2019), 624pp., hbk, £29.99. ISBN 9781527103634

A recent study shows that chemokine receptor 1 (CCR1) plays a role in eosinophilic inflammation and that its ligand CCL15 is increased in asthmatic eosinophils (Du et al.). A companion study reports that N-truncated forms of CCL15 generated by tissue proteases induce biased CCR1 signaling (Shao et al.). These insights may provide the basis for the generation of more effective CCR antagonists as an oral therapy for asthma.

The common bean (Phaseolus vulgaris L.) provides numerous benefits for the rural poor. Heat tolerant varieties require rapid adoption of new seeds to replace traditional varieties. However, a numbe...

Chromobacterium violaceum is a rare bacterium found in water and soil in tropical regions and typically presents with a localized skin infection or lymphadenitis which can progress to fulminant septicemia and even death. We describe a case of a 2-year-old boy with C. violaceum septicemia from a suspected skin source which was confirmed by wound, tissue and blood cultures. The discovery of this rare organism, subsequently led to the evaluation and identification of underlying chronic granulomatous disease.

Ocean warming is increasing the incidence, scale, and severity of global-scale coral bleaching and mortality, culminating in the third global coral bleaching event that occurred during record marine heatwaves of 2014-2017. While local effects of these events have been widely reported, the global implications remain unknown. Analysis of 15,066 reef surveys during 2014-2017 revealed that 80% of surveyed reefs experienced significant coral bleaching and 35% experienced significant coral mortality. The global extent of significant coral bleaching and mortality was assessed by extrapolating results from reef surveys using comprehensive remote-sensing data of regional heat stress. This model predicted that 51% of the world’s coral reefs suffered significant bleaching and 15% significant mortality, surpassing damage from any prior global bleaching event. These observations demonstrate that global warming’s widespread damage to coral reefs is accelerating and underscores the threat anthropogenic climate change poses for the irreversible transformation of these essential ecosystems.

The purpose of this project was to update competencies for spiritual care professionals specializing in palliative and bereavement care in Canada. Phase one feedback was obtained from 11 clients: six inpatients with greater than two weeks of life expectancy using interviews and five bereaved family members in a focus group. Results were analyzed for congruence or discordance with draft competencies. In phase two, 22 spiritual care experts reached a consensus on nine competencies using a modified Delphi survey. Two limitations were the small sample size and cultural and religious homogeneity of participants.

Voluntary uptake of climate-adapted beans is driven by farmers’ climate change perceptions. Identifying these perceptions and understanding their determinants help public agencies and seed supplier...

Candidates for liver transplantation (LT) with hepatocellular carcinoma (HCC) undergo a large number of diagnostic and interventional radiology procedures. A significant proportion of such procedures involve ionizing radiation with increased lifetime risk of cancer. The objective of our study was to review LT candidates with HCC to quantify ionizing radiation doses from different radiology procedures performed at a single transplant center.We retrospectively reviewed 179 adult patients with HCC (median age 58.6 years [IQR, 55-62]; 155 [86.6%] males) who were accepted for LT between April 2010 and Dec 2018. Radiology procedures and radiation doses were retrieved and the total and median radiation effective dose in millisieverts (mSv) were calculated for different procedures. Exposure to ionizing radiation was categorized based on previously reported thresholds.We assessed 9,986 radiology procedures for our cohort. Patients had a median effective dose prior to transplantation of 254 mSv (IQR, 130-421) with an annualized rate of 152 mSv (IQR, 92-266). Patient median dose increased to 316 mSv (IQR, 159-478) when including exposures post-LT within the study period. 85% of overall exposure was in the extremely high exposure category (100 mSv). Interventional procedures represented 13% of procedures with substantial radiation and contributed to 45% of radiation exposure while abdominal CTs represented 39% of total procedures and contributed to 45% of radiation exposure.Patients with HCC considered for LT undergo radiology procedures with significant cumulative radiation exposure. Attempts to reduce radiation exposure are suggested by minimizing unnecessary procedures and utilizing ones without ionizing radiation. Improving interventional techniques to reduce radiation doses is needed without compromising treatment delivery.

In-water shark-based tourism is growing worldwide and whale sharks (Rhincodon typus) are one of the most popular targets of this industry. It is important to monitor tourism industries to minimize any potential impacts on target species. At Ningaloo, Western Australia, Electronic Monitoring Systems (EMS) have been installed on licensed tour vessels to collect information on encounters between snorkelers and whale sharks. This study combined data from the EMS with whale shark identification photographs, to assess the impact of in-water tourism on the encounter duration for individual sharks. During 2011 and 2012, 948 encounters with 229 individual sharks were recorded using EMS. Encounter durations between whale sharks and tourism vessels ranged between 1 and 59 min (mean = 11 min 42 s, SD = ±11 min 19 s). We found no evidence for a decline in encounter duration after repeated tourist encounters with individual sharks. Encounter duration varied among tourism operator vessels and were shorter when the sex of the whale shark could not be identified. Given that individual sharks were swum with on average 2.4 times per day (±SD 2.08), and up to 16 times over the course of the study, our results suggest that there is no evidence of long-term impacts of tourism on the whale sharks at Ningaloo. However, the inclusion of well-defined categories of whale shark behaviors and information regarding how interactions between tourists and whale sharks end will complement the data already collected by the EMS. This preliminary investigation demonstrates the potential for the EMS as a data resource to better understand and monitor the impacts of tourism interactions on whale sharks.

Western Australia’s coral reefs have largely escaped the chronic pressures affecting other reefs around the world, but are regularly affected by seasonal storms and cyclones, and increasingly by heat stress and coral bleaching. Reef systems north of 18°S have been impacted by heat stress and coral bleaching during strong El Nino phases and those further south during strong La Nina phases. Cumulative heat stress and the extent of bleaching throughout the northern reefs in 2016 were higher than at any other time on record. To assess the changing regime of disturbance to reef systems across Western Australia (WA), we linked their site-specific exposure to damaging waves and heat stress since 1990 with mean changes in coral cover. Since 2010, there has been a noticeable increase in heat stress and coral bleaching across WA. Over half the reef systems have been severely impacted by coral bleaching since 2010, which was further compounded by cyclones at some reefs. For most (75%) reef systems with long-term data (5–26 yrs), mean coral cover is currently at (or near) the lowest on record and a full recovery is unlikely if disturbances continue to intensify with climate change. However, some reefs have not yet experienced severe bleaching and their coral cover has remained relatively stable or increased in recent years. Additionally, within all reef systems the condition of communities and their exposure to disturbances varied spatially. Identifying the communities least susceptible to future disturbances and linking them through networks of protected areas, based on patterns of larval connectivity, are important research and management priorities in coming years while the causes of climate change are addressed.

Legumes form part of an ecological based solution to intensification in areas with limited access to external inputs or to support increased efficiency of available fertiliser nutrients. Despite a number of decades of intervention, uptake of legumes has been slow within smallholder farming systems in Sub-Saharan Africa. This paper explores the drivers behind adoption of legumes by developing an indicator of household legume cultivation (HLC) from a bespoke survey of 274 small-scale farm households in Kenya and the Democratic Republic of the Congo.We decompose this indicator using a beta regression framework and find a range of intensities across sites and farms, indicating limited influence of agro-ecological zones and formal institutions on uptake. There was some commonality in drivers across sites, though age, income and gender have positive but very marginal effects. Farm households with more intense legume cultivation were less driven by commercial growth objectives and have limited access to markets. There was little interest in expanding farm area which reflects the lack of assets available to these farmers and, as a consequence, promotes the use of legumes in providing home nutrition, or supporting farm fertility and provision of livestock feed. Further development of this HLC metric would be enabled by consistent data gathering across regions, or at least equally detailed studies of legume uptake. Overcoming constraints to increasing use of legumes should be a significant component of local and international agricultural intervention as countries experience increasing environmental and social pressures and the need to commercialise as farming develops.

Strategies for achieving environmental sustainability of protein production vary regionally. In this study, a framework was applied that would quantify a region-specific contribution to global protein supply with a special focus on protein quality i.e. essential amino acid composition. The framework was applied in Scotland and showed that high-quality human-edible protein from that region currently emerges mainly from animal production. Considering future protein scenarios, the land requirement for pulses for producing a certain amount of essential amino acids in Scotland would be similar to the land requirement for potentially human-edible feeds needed in cattle production. Reducing the current use of agricultural by-products in livestock feeding would considerably increase the land use demand for other, potentially human edible feed crops.

There is a marked increase in oxidative stress in the lungs of patients with COPD, as measured by increased exhaled 8-isoprostane, ethane, and hydrogen peroxide in the breath. The lung may be exposed to exogenous oxidative stress from cigarette smoking and indoor or outdoor air pollution and to endogenous oxidative stress from reactive oxygen species released from activated inflammatory cells, particularly neutrophils and macrophages, in the lungs. Oxidative stress in COPD may be amplified by a reduction in endogenous antioxidants and poor intake of dietary antioxidants. Oxidative stress is a major driving mechanism of COPD through the induction of chronic inflammation, induction of cellular senescence and impaired autophagy, reduced DNA repair, increased autoimmunity, increased mucus secretion, and impaired anti-inflammatory response to corticosteroids. Oxidative stress, therefore, drives the pathology of COPD and may increase disease progression, amplify exacerbations, and increase comorbidities through systemic oxidative stress. This suggests that antioxidants may be effective as disease-modifying treatments. Unfortunately, thiol-based antioxidants, such as N-acetylcysteine, have been poorly effective, as they are inactivated by oxidative stress in the lungs, so there is a search for more effective and safer antioxidants. New antioxidants in development include mitochondria-targeted antioxidants, NOX inhibitors, and activators of the transcription factor Nrf2, which regulates several antioxidant genes.

The Ningaloo coast of north-western Australia (eastern Indian Ocean) hosts one of the world's longest and most extensive fringing coral reef systems, along with globally significant abundances of large marine fauna such as whale sharks. These characteristics – which have contributed to its inscription on the World Heritage list – exist because of the unique climatic, geomorphologic and oceanographic conditions. The region is hot and arid, so runoff of water from land is low, facilitating clear water that allows corals to grow close to the shore. The poleward-flowing Leeuwin Current is an important influence, bringing warm water and generally suppressing coastal upwelling. During the austral summer, strong southerly winds generate the equatorward-flowing Ningaloo Current on the inner shelf – this current facilitates sporadic upwelling events that enhance concentrations of nutrients, which in turn enhance pelagic primary productivity that supports the reef's biota. The coast has experienced several marine heatwaves since 2011 that have caused mortality of corals and probably seagrass, albeit relatively less than elsewhere along the coast. Wind-generated surface waves break over the fringing reef crest, causing cooling currents that tend to dampen warming – although this mechanism seems not to have prevented some areas from experiencing damaging heat, and corals in places that do not receive the wave-generated currents have experienced substantial mortality. Herbivores, from fish to green turtles, are abundant, and in the lagoon, extensive stands of large brown algae provide an important habitat for newly recruited fish. There has been a decline in abundance of some fish. Predictions of future pressures include a weaker but more variable Leeuwin Current and increased human use. The ability of Ningaloo's 144ecosystems to withstand growing pressures will depend partly on the rate and magnitude of global warming but also on actions that manage local pressures from increasing human use. These actions will rely on continued science to provide the evidence needed to identify the pressures, the changes they create and the ways that we can mitigate them.