Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell ...manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50-100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent increases in the frequency of Extreme Climate Events (ECEs) such as heatwaves and floods have been attributed to climate change, and could have pronounced ecosystem and evolutionary impacts ...because they provide little opportunity for organisms to acclimate or adapt. Here we synthesize information on a series of ECEs in Australia from 2011-2017 that led to well-documented, abrupt and extensive mortality of key marine habitat-forming organisms – corals, kelps, seagrasses and mangroves – along nearly more than 45% of the continental coastline of Australia. Coral bleaching occurred across much of northern Australia due to marine heatwaves affecting different regions in 2011, 2013, 2016 and 2017, while seagrass was impacted by anomalously high rainfall events in 2011 on both east and west tropical coasts. A marine heatwave off western Australia during the 2011 La Niña extended into temperate and subtropical regions, causing widespread mortality of kelp forests and seagrass communities at their northern distribution limits. Mangrove forests experienced high mortality during the 2016 El Niño across coastal areas of northern and north-western Australia due to severe water stress driven by drought and anomalously low mean sea levels. This series of ECEs reflects a variety of different events – marine heatwaves, intense rainfall from tropical storms, and drought. Their repeated occurrence and wide extent are consistent with projections of increased frequency and intensity of ECEs, and have broad implications elsewhere because similar trends are predicted globally. The unprecedented and widespread nature of these ECE impacts has likely produced substantial ecosystem-wide repercussions. Predictions from ecosystem models suggest that the widespread mortality of habitat-forming taxa will have long-term and in some cases irreversible consequences, especially if they continue to become more frequent or severe. The abrupt ecological changes that are caused by ECEs could have greater long-term impacts than slower warming that leads to gradual reorganisation and possible evolution and adaptation. ECEs are an emerging threat to marine ecosystems, and will require better seasonal prediction and mitigation strategies.
Acute limb compartment syndrome (ALCS) is a surgical emergency that can have serious consequences unless promptly diagnosed and treated, which is particularly challenging when there is an unusual ...cause. This is a comprehensive review of reported causes of ALCS. From 1068 included articles, we found 299 discrete causes of ALCS including toxins, infections, endocrine pathology, haematological emergencies, malignancy and iatrogenic ALCS. Familiarity with this wide range of ALCS causes may assist in early diagnosis of this limb‐threatening condition.
Acute limb compartment syndrome (ALCS) is a surgical emergency that can have serious consequences unless promptly diagnosed and treated, which is particularly challenging when there is an unusual cause. This is a comprehensive review of reported causes of ALCS. From 1068 included articles, we found 299 discrete causes of ALCS including toxins, infections, endocrine pathology, haematological emergencies, malignancy and iatrogenic ALCS.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Pelagic ecosystems support a significant and vital component of the ocean's productivity and biodiversity. They are also heavily exploited and, as a result, are the focus of numerous spatial planning ...initiatives. Over the past decade, there has been increasing enthusiasm for protected areas as a tool for pelagic conservation, however, few have been implemented. Here we demonstrate an approach to plan protected areas that address the physical and biological dynamics typical of the pelagic realm. Specifically, we provide an example of an approach to planning protected areas that integrates pelagic and benthic conservation in the southern Benguela and Agulhas Bank ecosystems off South Africa. Our aim was to represent species of importance to fisheries and species of conservation concern within protected areas. In addition to representation, we ensured that protected areas were designed to consider pelagic dynamics, characterized from time-series data on key oceanographic processes, together with data on the abundance of small pelagic fishes. We found that, to have the highest likelihood of reaching conservation targets, protected area selection should be based on time-specific data rather than data averaged across time. More generally, we argue that innovative methods are needed to conserve ephemeral and dynamic pelagic biodiversity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We document and evaluate the aerosol schemes as implemented in the physical and Earth system models, the Global Coupled 3.1 configuration of the Hadley Centre Global Environment Model version 3 ...(HadGEM3-GC3.1)
and the United Kingdom Earth System Model (UKESM1), which are contributing to the sixth Coupled Model Intercomparison Project (CMIP6).
The simulation of aerosols in the present-day period of the historical ensemble of these models is evaluated
against a range of observations.
Updates to the aerosol microphysics scheme are documented as well as differences in the
aerosol representation between the physical and Earth system configurations.
The additional Earth system interactions included in UKESM1 lead to differences in the emissions of
natural aerosol sources such as dimethyl sulfide, mineral dust and organic aerosol and subsequent evolution
of these species in the model.
UKESM1 also includes a stratospheric–tropospheric chemistry scheme which is fully coupled to the aerosol scheme,
while GC3.1 employs a simplified aerosol chemistry mechanism driven by prescribed monthly climatologies of
the relevant oxidants.
Overall, the simulated speciated aerosol mass concentrations compare reasonably well with observations.
Both models capture the negative trend in sulfate aerosol concentrations over Europe and the eastern United
States of America (US)
although the models tend to underestimate sulfate concentrations in both regions.
Interactive emissions of biogenic volatile organic compounds in UKESM1 lead
to an improved agreement of organic aerosol over the US.
Simulated dust burdens are similar in both models despite a 2-fold difference in dust emissions.
Aerosol optical depth is biased low in dust source and outflow regions but performs well in
other regions compared to a number of satellite and ground-based retrievals of aerosol optical depth.
Simulated aerosol number concentrations are generally within a factor of 2 of the observations, with
both models tending to overestimate number concentrations over remote ocean regions, apart from
at high latitudes, and underestimate over Northern Hemisphere continents.
Finally, a new primary marine organic aerosol source is implemented in UKESM1 for the first time.
The impact of this new aerosol source is evaluated. Over the pristine Southern Ocean, it is found to improve the seasonal
cycle of organic aerosol mass and cloud droplet number concentrations relative to GC3.1
although underestimations in cloud droplet number concentrations remain.
This paper provides a useful characterisation of the aerosol climatology in both models
and will facilitate understanding in the numerous aerosol–climate interaction studies that will
be conducted as part of CMIP6 and beyond.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science–policy body has recently ...been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientific knowledge and data compiled and critically evaluated by an overarching science–policy interface body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond data-rich regions (e.g., Europe and North America), (ii) to cover the entirety of hazardous chemicals, mixtures and wastes, (iii) to follow a one-health perspective considering the risks posed by chemicals and waste on ecosystem and human health, and (iv) to strive for solution-oriented assessments based on systems thinking. Based on multiple evidence on urgent action on a global scale, we call scientists and practitioners to mobilize their scientific networks and to intensify science–policy interaction with national governments to support the negotiations on the establishment of an intergovernmental body based on scientific knowledge explaining the anticipated benefit for human and environmental health.
In times of rapid change and rising human pressures on marine systems, information about the future state of the ocean can provide decision-makers with time to avoid adverse impacts and maximise ...opportunities. An ecological forecast predicts changes in ecosystems and its components due to environmental forcing such as climate variability and change, extreme weather conditions, pollution, or habitat change. Here, we summarise examples from several sectors and a range of locations. We describe the need, approach, forecast performance, delivery system, and end user uptake. This examination shows that near-term ecological forecasts are needed by end users, decisions are being made based on forecasts, and there is an urgent need to develop operational information systems to support sustainable ocean management. An operational information system is critical for connecting to decision makers and providing an enduring approach to forecasting and proactive decision making. These operational systems require significant investment and ongoing maintenance but are key to delivering ecological forecasts for societal benefits. Iterative forecasting practices could provide continuous improvement by incorporating evaluation and feedback to overcome the limitations of the imperfect model and incomplete observations to achieve better forecast outcomes and accuracy.
Aim The koala is a widely distributed Australian marsupial with regional populations that are in rapid decline, are stable or have increased in size. This study examined whether it is possible to use ...expert elicitation to estimate abundance and trends of populations of this species. Diverse opinions exist about estimates of abundance and, consequently, the status of populations. Location Eastern and south-eastern Australia Methods Using a structured, four-step question format, a panel of 15 experts estimated population sizes of koalas and changes in those sizes for bioregions within four states. They provided their lowest plausible estimate, highest plausible estimate, best estimate and their degree of confidence that the true values were contained within these upper and lower estimates. We derived estimates of the mean population size of koalas and associated uncertainties for each bioregion and state. Results On the basis of estimates of mean population sizes for each bioregion and state, we estimated that the total number of koalas for Australia is 329,000 (range 144,000–605,000) with an estimated average decline of 24% over the past three generations and the next three generations. Estimated percentage of loss in Queensland, New South Wales, Victoria and South Australia was 53%, 26%, 14% and 3%, respectively. Main conclusions It was not necessary to achieve high levels of certainty or consensus among experts before making informed estimates. A quantitative, scientific method for deriving estimates of koala populations and trends was possible, in the absence of empirical data on abundances.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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