Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As ...a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017.
We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates.
In 2017, an estimated 48·9 million (95% uncertainty interval UI 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia.
Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa.
The Bill & Melinda Gates Foundation, the National Institutes of Health, the University of Pittsburgh, the British Columbia Children's Hospital Foundation, the Wellcome Trust, and the Fleming Fund.
Applying machine learning to continuous acoustic emissions, signals previously deemed noise, from laboratory faults and slowly slipping subduction‐zone faults, demonstrates hidden signatures are ...emitted that describe physical details, including fault displacement and friction. However, no evidence currently exists to demonstrate that similar hidden signals occur during seismogenic stick‐slip on earthquake faults—the damaging earthquakes of most societal interest. We show that continuous seismic emissions emitted during the 2018 multi‐month caldera collapse sequence at the Kı̄lauea volcano in Hawai'i contain hidden signatures characterizing the earthquake cycle. Multi‐spectral data features extracted from 30 s intervals of the continuous seismic emission are used to train a gradient boosted tree regression model to predict the GNSS‐derived contemporaneous surface displacement and time‐to‐failure of the upcoming collapse event. This striking result suggests that at least some faults emit such signals and provide a potential path to characterizing the instantaneous and future behavior of earthquake faults.
Plain Language Summary
Applications of machine learning have revealed that continuous acoustic emissions from laboratory earthquake experiments contain continuous, hidden signatures that describe the fault slip. In these laboratory studies, the acoustic emissions signals that were previously deemed to be dominantly noise, are found to be rich with details that can describe physical properties such as the fault displacement, friction, and fault thickness. By applying similar machine learning approaches, it was discovered that signatures of surface displacement exist in the seismic emissions from slowly slipping subduction zone faults. However, there has yet to be similar evidence observed during seismogenic stick‐slip on earthquake faults–the damaging earthquakes of most societal interest. Here we study a repeating caldera collapse sequence with short enough repeat times to mimic the experiments performed in the laboratory. We find that seismic emissions from seismogenic fault slip associated with the 2018 caldera collapse at the Kı̄lauea volcano in Hawai'i, also contain hidden signatures informing of instantaneous surface displacement associated with fault slip at depth, as well as time‐to‐failure of the upcoming slip event. These observations suggest that at least some seismogenic faults emit such signals, and provide a potential path to characterizing the instantaneous and future behavior of earthquake faults.
Key Points
Features extracted from 30 s of continuous seismic waveforms contain information about contemporaneous GNSS ground displacements
A gradient boosted tree model predicts GNSS ground displacements and timing of the next caldera collapse event
The observations suggest some seismogenic faults emit precursory signals, providing a potential path to characterize behavior of faults
Establishing what controls the timing of earthquakes is fundamental to understanding the nature of the earthquake cycle and critical to determining time-dependent earthquake hazard. Seasonal loading ...provides a natural laboratory to explore the crustal response to a quantifiable transient force. In California, water storage deforms the crust as snow and water accumulates during the wet wintermonths. We used 9 years of global positioning system (GPS) vertical deformation time series to constrain models of monthly hydrospheric loading and the resulting stress changes on fault planes of small earthquakes. The seasonal loading analysis reveals earthquakes occurring more frequently during stress conditions that favor earthquake rupture. We infer that California seismicity rates are modestly modulated by natural hydrological loading cycles.
Molecular sieving metal-organic framework (MOF) membranes have great
potential for energy-efficient chemical separations, but a major hurdle
is the lack of a scalable and inexpensive membrane ...fabrication
mechanism. We describe a route for processing MOF membranes in polymeric
hollow fibers, combining a two-solvent interfacial approach for
positional control over membrane formation (at inner and outer surfaces,
or in the bulk, of the fibers), a microfluidic approach to replenishment
or recycling of reactants, and an in situ module for membrane
fabrication and permeation. We fabricated continuous molecular sieving
ZIF-8 membranes in single and multiple poly(amide-imide) hollow fibers,
with H2/C3H8 and
C3H6/C3H8 separation
factors as high as 370 and 12, respectively. We also demonstrate
positional control of the ZIF-8 films and characterize the contributions
of membrane defects and lumen bypass.
Poly(ethylene terephthalate) (PET) is one of the most abundantly produced synthetic polymers and is accumulating in the environment at a staggering rate as discarded packaging and textiles. The ...properties that make PET so useful also endow it with an alarming resistance to biodegradation, likely lasting centuries in the environment. Our collective reliance on PET and other plastics means that this buildup will continue unless solutions are found. Recently, a newly discovered bacterium, Ideonella sakaiensis 201-F6, was shown to exhibit the rare ability to grow on PET as a major carbon and energy source. Central to its PET biodegradation capability is a secreted PETase (PET-digesting enzyme). Here, we present a 0.92 Å resolution X-ray crystal structure of PETase, which reveals features common to both cutinases and lipases. PETase retains the ancestral α/β-hydrolase fold but exhibits a more open active-site cleft than homologous cutinases. By narrowing the binding cleft via mutation of two active-site residues to conserved amino acids in cutinases, we surprisingly observe improved PET degradation, suggesting that PETase is not fully optimized for crystalline PET degradation, despite presumably evolving in a PET-rich environment. Additionally, we show that PETase degrades another semiaromatic polyester, polyethylene-2,5-furandicarboxylate (PEF), which is an emerging, bioderived PET replacement with improved barrier properties. In contrast, PETase does not degrade aliphatic polyesters, suggesting that it is generally an aromatic polyesterase. These findings suggest that additional protein engineering to increase PETase performance is realistic and highlight the need for further developments of structure/activity relationships for biodegradation of synthetic polyesters.
Data-driven machine-learning for predicting instantaneous and future fault-slip in laboratory experiments has recently progressed markedly, primarily due to large training data sets. In Earth ...however, earthquake interevent times range from 10's-100's of years and geophysical data typically exist for only a portion of an earthquake cycle. Sparse data presents a serious challenge to training machine learning models for predicting fault slip in Earth. Here we describe a transfer learning approach using numerical simulations to train a convolutional encoder-decoder that predicts fault-slip behavior in laboratory experiments. The model learns a mapping between acoustic emission and fault friction histories from numerical simulations, and generalizes to produce accurate predictions of laboratory fault friction. Notably, the predictions improve by further training the model latent space using only a portion of data from a single laboratory earthquake-cycle. The transfer learning results elucidate the potential of using models trained on numerical simulations and fine-tuned with small geophysical data sets for potential applications to faults in Earth.
Highlights • Lignin valorization is a primary challenge in the integrated lignocellulosic biorefinery. • Lignin heterogeneity is a key hurdle for its effective upgrading to value-added products. • ...Microbes are able to ‘biologically funnel’ heterogeneous aromatic compounds to single compounds. • This biological funneling concept may enable selective lignin valorization to target chemicals and fuels. • To enable biological funneling will require a co-design problem with the substrate, microbe, pathways, and processing.
Lignin represents an untapped feedstock for the production of fuels and chemicals, but its intrinsic heterogeneity makes lignin valorization a significant challenge. In nature, many aerobic organisms ...degrade lignin-derived aromatic molecules through conserved central intermediates including catechol and protocatechuate. Harnessing this microbial approach offers potential for lignin upgrading in modern biorefineries, but significant technical development is needed to achieve this end. Catechol and protocatechuate are subjected to aromatic ring cleavage by dioxygenase enzymes that, depending on the position, ortho or meta relative to adjacent hydroxyl groups, result in different products that are metabolized through parallel pathways for entry into the TCA cycle. These degradation pathways differ in the combination of succinate, acetyl-CoA, and pyruvate produced, the reducing equivalents regenerated, and the amount of carbon emitted as CO2—factors that will ultimately impact the yield of the targeted product. As shown here, the ring-cleavage pathways can be interchanged with one another, and such substitutions have a predictable and substantial impact on product yield. We demonstrate that replacement of the catechol ortho degradation pathway endogenous to Pseudomonas putida KT2440 with an exogenous meta-cleavage pathway from P. putida mt-2 increases yields of pyruvate produced from aromatic molecules in engineered strains. Even more dramatically, replacing the endogenous protocatechuate ortho pathway with a meta-cleavage pathway from Sphingobium sp. SYK-6 results in a nearly five-fold increase in pyruvate production. We further demonstrate the aerobic conversion of pyruvate to l-lactate with a yield of 41.1±2.6% (wt/wt). Overall, this study illustrates how aromatic degradation pathways can be tuned to optimize the yield of a desired product in biological lignin upgrading.
•We engineered Pseudomonas putida strains to degrade lignin monomers using different pathways.•We compared yields of pyruvate and lactate produced from benzoate or p-coumarate.•Catechol and PCA meta-cleavage pathways outperformed the ortho-cleavage pathways.•Conversion of pyruvate to lactate resulted in greater overall product yields.•Yields from the PCA 4,5 meta-cleavage were 75.1% of the theoretical maximum.
Lignin is an energy-dense, heterogeneous polymer comprised of phenylpropanoid monomers used by plants for structure, water transport, and defense, and it is the second most abundant biopolymer on ...Earth after cellulose. In production of fuels and chemicals from biomass, lignin is typically underused as a feedstock and burned for process heat because its inherent heterogeneity and recalcitrance make it difficult to selectively valorize. In nature, however, some organisms have evolved metabolic pathways that enable the utilization of lignin-derived aromatic molecules as carbon sources. Aromatic catabolism typically occurs via upper pathways that act as a “biological funnel” to convert heterogeneous substrates to central intermediates, such as protocatechuate or catechol. These intermediates undergo ring cleavage and are further converted via the β-ketoadipate pathway to central carbon metabolism. Here, we use a natural aromatic-catabolizing organism, Pseudomonas putida KT2440, to demonstrate that these aromatic metabolic pathways can be used to convert both aromatic model compounds and heterogeneous, lignin-enriched streams derived from pilot-scale biomass pretreatment into medium chain-length polyhydroxyalkanoates (mcl -PHAs). mcl -PHAs were then isolated from the cells and demonstrated to be similar in physicochemical properties to conventional carbohydrate-derived mcl -PHAs, which have applications as bioplastics. In a further demonstration of their utility, mcl -PHAs were catalytically converted to both chemical precursors and fuel-range hydrocarbons. Overall, this work demonstrates that the use of aromatic catabolic pathways enables an approach to valorize lignin by overcoming its inherent heterogeneity to produce fuels, chemicals, and materials.
Abstract
Muconic acid is a bioprivileged molecule that can be converted into direct replacement chemicals for incumbent petrochemicals and performance-advantaged bioproducts. In this study,
...Pseudomonas putida
KT2440 is engineered to convert glucose and xylose, the primary carbohydrates in lignocellulosic hydrolysates, to muconic acid using a model-guided strategy to maximize the theoretical yield. Using adaptive laboratory evolution (ALE) and metabolic engineering in a strain engineered to express the D-xylose isomerase pathway, we demonstrate that mutations in the heterologous D-xylose:H
+
symporter (XylE), increased expression of a major facilitator superfamily transporter (PP_2569), and overexpression of
aroB
encoding the native 3-dehydroquinate synthase, enable efficient muconic acid production from glucose and xylose simultaneously. Using the rationally engineered strain, we produce 33.7 g L
−1
muconate at 0.18 g L
−1
h
−1
and a 46% molar yield (92% of the maximum theoretical yield). This engineering strategy is promising for the production of other shikimate pathway-derived compounds from lignocellulosic sugars.