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Building on previous research, this qualitative exploratory study investigates the impact of ChatGPT on English language classes among Korean university students. The researcher uses pre- and post-training surveys, in-class observations, and interviews to explore 120 students' perceptions of their experiences over a 15-week semester. Results indicate largely positive attitudes, with students expressing optimism about ChatGPT's potential to enhance language skills. Classroom engagement was high, fostering collaboration and active participation. Post-training interviews revealed improved confidence, collaborative learning experiences, and a shift toward metacognitive awareness in learners and autonomous learning. Some technical and language challenges surfaced, as well as skepticism from a small number of learners. Long-term post-training surveys highlight sustained engagement and real-world applications. The findings provide insights for educators and policymakers considering the integration of AI tools in language education, emphasizing the importance of ongoing support and flexibility in implementation strategies.

The design and optimization of laser-Compton x-ray systems based on compact distributed charge accelerator structures can enable micron-scale imaging of disease and the concomitant production of beams of Very High Energy Electrons (VHEEs) capable of producing FLASH-relevant dose rates. The physics of laser-Compton x-ray scattering ensures that the scattered x-rays follow exactly the trajectory of the incident electrons, thus providing a route to image-guided, VHEE FLASH radiotherapy. The keys to a compact architecture capable of producing both laser-Compton x-rays and VHEEs are the use of X-band RF accelerator structures which have been demonstrated to operate with over 100 MeV/m acceleration gradients. The operation of these structures in a distributed charge mode in which each radiofrequency (RF) cycle of the drive RF pulse is filled with a low-charge, high-brightness electron bunch is enabled by the illumination of a high-brightness photogun with a train of UV laser pulses synchronized to the frequency of the underlying accelerator system. The UV pulse trains are created by a patented pulse synthesis approach which utilizes the RF clock of the accelerator to phase and amplitude modulate a narrow band continuous wave (CW) seed laser. In this way it is possible to produce up to 10 μA of average beam current from the accelerator. Such high current from a compact accelerator enables production of sufficient x-rays via laser-Compton scattering for clinical imaging and does so from a machine of "clinical" footprint. At the same time, the production of 1000 or greater individual micro-bunches per RF pulse enables > 10 nC of charge to be produced in a macrobunch of < 100 ns. The design, construction, and test of the 100-MeV class prototype system in Irvine, CA is also presented.

Abstract: —J. Blunden and T. Boyer In 2023, La Niña conditions that generally prevailed in the eastern Pacific Ocean from mid-2020 into early 2023 gave way to a strong El Niño by October. Atmospheric concentrations of Earth’s major greenhouse gases—carbon dioxide, methane, and nitrous oxide—all increased to record-high levels. The annual global average carbon dioxide concentration in the atmosphere rose to 419.3±0.1 ppm, which is 50% greater than the pre-industrial level. The growth from 2022 to 2023 was 2.8 ppm, the fourth highest in the record since the 1960s. The combined short-term effects of El Niño and the long-term effects of increasing levels of heat-trapping gases in the atmosphere contributed to new records for many essential climate variables reported here. The annual global temperature across land and oceans was the highest in records dating as far back as 1850, with the last seven months (June–December) having each been record warm. Over land, the globally averaged temperature was also record high. Dozens of countries reported record or near-record warmth for the year, including China and continental Europe as a whole (warmest on record), India and Russia (second warmest), and Canada (third warmest). Intense and widespread heatwaves were reported around the world. In Vietnam, an all-time national maximum temperature record of 44.2°C was observed at Tuong Duong on 7 May, surpassing the previous record of 43.4°C at Huong Khe on 20 April 2019. In Brazil, the air temperature reached 44.8°C in Araçuaí in Minas Gerais on 20 November, potentially a new national record and 12.8°C above normal. The effect of rising temperatures was apparent in the cryosphere, where snow cover extent by June 2023 was the smallest in the 56-year record for North America and seventh smallest for the Northern Hemisphere overall. Heatwaves contributed to the greatest average mass balance loss for Alpine glaciers around the world since the start of the record in 1970. Due to rapid volume loss beginning in 2021, St. Anna Glacier in Switzerland and Ice Worm Glacier in the United States disappeared completely. In August, as a direct result of glacial thinning over the past 20 years, a glacial lake on a tributary of the Mendenhall Glacier in Alaska burst through its ice dam and caused unprecedented flooding on Mendenhall River near Juneau. Across the Arctic, the annual surface air temperature was the fourth highest in the 124-year record, and summer (July–September) was record warm. Smaller-than-normal snow cover extent in May and June contributed to the third-highest average peak tundra greenness in the 24-year record. In September, Arctic minimum sea ice extent was the fifth smallest in the 45-year satellite record. The 17 lowest September extents have all occurred in the last 17 years. In Antarctica, temperatures for much of the year were up to 6°C above average over the Weddell Sea and along coastal Dronning Maud Land. The Antarctic Peninsula also experienced well-above-average temperatures during the 2022/23 melt season, which contributed to its fourth consecutive summer of above-average surface melt. On 21 February, Antarctic sea ice extent and sea ice area both reached all-time lows, surpassing records set just a year earlier. Over the course of the year, new daily record-low sea ice extents were set on 278 days. In some instances, these daily records were set by a large margin, for example, the extent on 6 July was 1.8 million km2 lower than the previous record low for that day. Across the global oceans, the annual sea surface temperature was the highest in the 170-year record, far surpassing the previous record of 2016 by 0.13°C. Daily and monthly records were set from March onward, including an historic-high daily global mean sea surface temperature of 18.99°C recorded on 22 August. Approximately 94% of the ocean surface experienced at least one marine heatwave in 2023, while 27% experienced at least one cold spell. Globally averaged ocean heat content from the surface to 2000-m depth was record high in 2023, increasing at a rate equivalent to ∼0.7 Watts per square meter of energy applied over Earth’s surface. Global mean sea level was also record high for the 12th consecutive year, reaching 101.4 mm above the 1993 average when satellite measurements began, an increase of 8.1±1.5 mm over 2022 and the third highest year-over-year increase in the record. A total of 82 named tropical storms were observed during the Northern and Southern Hemispheres’ storm seasons, below the 1991–2020 average of 87. Hurricane Otis became the strongest landfalling hurricane on record for the west coast of Mexico at 140 kt (72 m s−1), causing at least 52 fatalities and $12–16 billion U.S. dollars in damage. Freddy became the world’s longest-lived tropical cyclones on record, developing into a tropical cyclone on 6 February and finally dissipating on 12 March. Freddy crossed the full width of the Indian Ocean and made one landfall in Madagascar and two in Mozambique. In the Mediterranean Sea—outside of traditional tropical cyclone basins—heavy rains and flooding from Storm Daniel killed more than 4300 people and left more than 8000 missing in Libya. The record-warm temperatures in 2023 created conditions that helped intensify the hydrological cycle. Measurements of total-column water vapor in the atmosphere were the highest on record, while the fraction of cloud area in the sky was the lowest since records began in 1980. The annual global mean precipitation total over land surfaces for 2023 was among the lowest since 1979, but global one-day maximum totals were close to average, indicating an increase in rainfall intensity. In July, record-high areas of land across the globe (7.9%) experienced extreme drought, breaking the previous record of 6.2% in July 2022. Overall, 29.7% of land experienced moderate or worse categories of drought during the year, also a record. Mexico reported its driest (and hottest) year since the start of its record in 1950. In alignment with hot and prolonged dry conditions, Canada experienced its worst national wildfire season on record. Approximately 15 million hectares burned across the country, which was more than double the previous record from 1989. Smoke from the fires were transported far into the United States and even to western European countries. August to October 2023 was the driest three-month period in Australia in the 104-year record. Millions of hectares of bushfires burned for weeks in the Northern Territory. In South America, extreme drought developed in the latter half of the year through the Amazon basin. By the end of October, the Rio Negro at Manaus, a major tributary of the Amazon River, fell to its lowest water level since records began in 1902. The transition from La Niña to El Niño helped bring relief to the prolonged drought conditions in equatorial eastern Africa. However, El Niño along with positive Indian Ocean dipole conditions also contributed to excessive rainfall that resulted in devastating floods over southeastern Ethiopia, Somalia, and Kenya during October to December that displaced around 1.5 million people. On 5 September, the town of Zagora, Greece, broke a national record for highest daily rainfall (754 mm in 21 hours, after which the station ceased reporting) due to Storm Daniel; this one-day accumulation was close to Zagora’s normal annual total.

Abstract Background Lipoproteins and their component apolipoproteins play an important role in sepsis. However, little is known with regard to the association and causal contribution of these proteins to mortality in patients of different ancestries following septic shock. The objective of this study was to determine whether lipoprotein and apolipoprotein levels, and related genetic variants, are associated with clinical outcomes in septic shock. Methods We investigated the association between lipoprotein and apolipoprotein levels at the point of admission to the intensive care unit and in-hospital mortality in 687 Japan patients diagnosed with septic shock. For each clinically significant candidate protein, we extracted haplotype tag single nucleotide polymorphisms (SNPs) of the corresponding gene and examined the association of the candidate gene variants with 28-day mortality and organ dysfunction. We tested for replication in a Caucasian septic shock cohort (Vasopressin and Septic Shock Trial, VASST, n = 474). To determine whether the candidate lipoprotein causally contributed to septic shock outcome, we used a Mendelian randomization analysis based on polygenic scores generated from a genome-wide association study (GWAS) in the Japan cohort. Results In the Japan cohort, low apolipoprotein A-II levels were associated with increased septic shock mortality (adjusted odds ratio, 1.05; 95%CI, 1.02–1.09; P

Abstract Since the late 1990s, summer surface melt across ice shelves in the Ross-Amundsen Sea sector of West Antarctica increased significantly, as demonstrated by satellite measurements and MetUM simulations. This contrasts with the period from 1979 to the late 1990s, which witnessed a decreasing summer melt trend driven by the positive trend in Southern Annular Mode. The increase in summer melt since the late 1990s is linked to an increase in geopotential height and intensified anticyclonic blocking along coastal West Antarctica, which strengthened northerly winds over the Ross-Amundsen Sea sector, leading to enhanced advection of warm, marine air. Our analysis reveals a strong connection between summer melt indices and sea surface temperatures in the South Pacific Convergence Zone during this period. Moreover, increased summer precipitation in South Pacific Convergence Zone since the late 1990s strengthened the Rossby wave teleconnection toward West Antarctica, contributing to enhanced blocking along the coastal region. This is consistent with the transition of the Interdecadal Pacific Oscillation to its negative phase.

IntroductionThe number of American Indian and Alaska Native (AI/AN) elders is expected to double by 2060. Thus it is imperative to retain AI/AN participants in longitudinal research studies to identify novel risk factors and potential targets for intervention for Alzheimer's disease and related dementias in these communities.MethodsThe National Alzheimer's Coordinating Center houses uniformly collected longitudinal data from the network of National Institute on Aging (NIA)-funded Alzheimer's Disease Research Centers (ADRCs). We used logistic regression to quantify participant retention at 43 ADRCs, comparing self-identified AI/AN participants to non-Hispanic White (NHW) participants, adjusting for potential confounding factors including baseline diagnosis, age, sex, education, and smoking.ResultsThe odds of AI/AN participant retention at the first follow-up visit were significantly lower than those for NHW participants (adjusted odds ratio [aOR]: 0.599; 95%: 0.46-0.78; p

Abstract: We study how firms target and influence expert intermediaries. In our context, pharmaceutical manufacturers provide payments to physicians during promotional interactions. We develop an identification strategy based on plausibly exogenous variation in payments driven by differential exposure to spillovers from AMC CoI policies. Using a case study of an important class of cardiovascular drugs, we estimate heterogeneous effects of payments on prescribing, with firms targeting highly responsive physicians. We also develop a model of supply and demand, which allows us to quantify how oligopoly prices reduce drug prescribing, and how payments move prescribing closer to the optimal level, but at great financial cost. In our estimated model, whether consumers are harmed by payments depends on whether there is substantial under-prescribing due to behavioural or other frictions. In a final exercise, we calibrate such frictions using clinical data and estimate that payments benefit consumers in this case study.

Locus coeruleus (LC) projections to the hippocampus play a critical role in learning and memory. However, the precise timing of LC-hippocampus communication during learning and which LC-derived neurotransmitters are important for memory formation in the hippocampus are currently unknown. Although the LC is typically thought to modulate neural activity via the release of norepinephrine, several recent studies have suggested that it may also release dopamine into the hippocampus and other cortical regions. In some cases, it appears that dopamine release from LC into the hippocampus may be more important for memory than norepinephrine. Here, we extend these data by characterizing the phasic responses of the LC and its projections to the dorsal hippocampus during trace fear conditioning in mice. We find that the LC and its projections to the hippocampus respond to task-relevant stimuli and that amplifying these responses with optogenetic stimulation can enhance long-term memory formation. We also demonstrate that LC activity increases both norepinephrine and dopamine content in the dorsal hippocampus and that the timing of hippocampal dopamine release during trace fear conditioning is similar to the timing of LC activity. Finally, we show that hippocampal dopamine is important for trace fear memory formation, while norepinephrine is not.

Abstract Understanding which viral variants evade neutralization is crucial for improving antibody-based treatments, especially with rapidly evolving viruses like SARS-CoV-2. Yet, conventional assays are labor intensive and cannot capture the full spectrum of variants. We present a deep learning approach to predict changes in neutralizing antibody activity of COVID-19 therapeutics and vaccine-elicited sera/plasma against emerging viral variants. Our approach leverages data of 67,885 unique SARS-CoV-2 Spike sequences and 7,069 in vitro assays. The resulting model accurately predicted fold changes in neutralizing activity (R2 = 0.77) for a test set (N = 980) of data collected up to eight months after the training data. Next, the model was used to predict changes in activity of current therapeutic and vaccine-induced antibodies against emerging SARS-CoV-2 lineages. Consistent with other work, we found significantly reduced activity against newer XBB descendants, notably EG.5, FL.1.5.1, and XBB.1.16; primarily attributed to the F456L spike mutation.

Abstract Distinguishing periods of intermittent unrest from the run-up to eruption is a major challenge at volcanoes around the globe. Comparing multidisciplinary monitoring data with mineral chemistry that records the physical and spatio-temporal evolution of magmas fundamentally advances our ability to forecast eruptions. The recent eruption of Mauna Loa, Earth’s largest active volcano, provides a unique opportunity to differentiate unrest from run-up and improve forecasting of future eruptions. After decades of intermittent seismic and geodetic activity over 38 years of repose, Mauna Loa began erupting on 27 November 2022. Here we present a multidisciplinary synthesis that tracks the spatio-temporal evolution of precursory activity by integrating mineral and melt chemistry, fluid inclusion barometry, numerical modeling of mineral zoning, syn-eruptive gas plume measurements, the distribution and frequency of earthquake hypocenters, seismic velocity changes, and ground deformation. These diverse data indicate that the eruption occurred following a 2-month period of sustained magma intrusion from depths of 3–5 km up to 1–2 km beneath the summit caldera, providing a new model of the plumbing system at this very high threat volcano. Careful correlation of both the geochemistry and instrumental monitoring data improves our ability to distinguish unrest from the run-up to eruption by providing deeper understanding of the both the monitoring data and the magmatic system—an approach that could be applied at other volcanic systems worldwide.

Abstract Background Chronic pain from peripheral neuromas is difficult to manage and often requires surgical excision, though intraoperative identification of neuromas can be challenging due to anatomical ambiguity. Mechanical manipulation of the neuroma during surgery can elicit a characteristic “startle sign”, which can help guide surgical management. However, it is unknown how anesthetic management affects detection of the startle sign. Methods We performed a retrospective cohort study of 73 neuroma excision surgeries performed recently at Massachusetts General Hospital. Physiological changes in the anesthetic record were analyzed to identify associations with a startle sign event. Anesthesia type and doses of pharmacological agents were analyzed between startle sign and no-startle sign groups. Results Of the 64 neuroma resection surgeries included, 13 had a startle sign. Combined intravenous and inhalation anesthesia (CIVIA) was more frequently used in the startle sign group vs. no-startle sign group (54% vs. 8%), while regional blockade with monitored anesthetic care was not associated with the startle sign group (12% vs. 0%), p = 0.001 for anesthesia type. Other factors, such as neuromuscular blocking agents, ketamine infusion, remifentanil infusion, and intravenous morphine equivalents showed no differences between groups. Conclusions Here, we identified hypothesis-generating descriptive differences in anesthetic management associated with the detection of the neuroma startle sign during neuroma excision surgery, suggesting ways to deliver anesthesia facilitating detection of this phenomenon. Prospective trials are needed to further validate the hypotheses generated.

Abstract Metabolite exchange mediates crucial interactions in microbial communities, significantly impacting global carbon and nitrogen cycling. Understanding these chemically-mediated interactions is essential for elucidating natural community functions and developing engineered synthetic communities. This study investigated membrane-separated bioreactors (mBRs) as a novel tool to identify transient metabolites and their producers/consumers in mixed microbial communities. We compared three co-culture methods (direct mixed, 2-chamber mBR, and 3-chamber mBR) to grow a synthetic binary community of the cyanobacterium Synechococcus elongatus PCC 7942 and the fungus Rhodotorula toruloides NBRC 0880, as well as axenic S. elongatus. Despite not being natural lichen constituents, these organisms exhibited interactions resembling those in cyanolichens. S. elongatus fixed CO2 into sugars as the primary shared metabolite, while R. toruloides secreted various biochemicals, predominantly sugar alcohols, mirroring the metabolite exchange observed in natural lichens. The mBR systems successfully captured metabolite gradients and revealed rapidly consumed compounds, including TCA cycle intermediates and amino acids. Our approach demonstrated that the 2-chamber mBR optimally balanced metabolite exchange and growth dynamics. This study provides insights into cross-species metabolic interactions and presents a valuable tool for investigating and engineering synthetic microbial communities with potential applications in biotechnology and environmental science.

Background: Hip arthroscopy has become an effective method for treating several symptomatic disorders of the hip, which includes femoroacetabular impingement (FAI). Capsulotomy is often necessary for visualization of hip pathology; however, this presents multiple challenges in both capsular management intraoperatively and final capsule closure. Current techniques include use of capsular suspension sutures to provide adequate views of the central and peripheral compartments. We present an atraumatic technique that may be used in conjunction with suspension sutures to decrease the need for excessive capsular debridement, additional personnel, and risk of injury for adequate visualization. Indications: Indications for using the “chopsticks” method for capsular retraction include patients with FAI who require osteochondroplasty or debridement of pathology within the peripheral compartment during hip arthroscopy. Technique Description: The patient is positioned supine with post-free traction applied. An anterolateral portal is established, followed by a modified mid-anterior portal under direct visualization. An interportal cut is performed for better visualization and access. A diagnostic arthroscopy of the central compartment is performed, and pathology is addressed as needed, including labral repair, subspine decompression or pincer resection, and chondroplasty. Traction is subsequently released, and if needed for visualization, a T-capsulotomy is performed to separate the medial and lateral limbs of the iliofemoral ligament with the knee and hip under slight flexion. Two switching sticks are inserted in the anterolateral portal. With the camera in the modified mid-anterior portal, 1 switching stick is placed intracapsular laterally (between the femoral neck and capsule) while the other is placed intracapsular medially (between the femoral neck and capsule) to retract the capsule and allow for osteochondroplasty. Complete capsular closure is performed following adequate cam decompression and removal of debris. Results: Careful retraction of the capsule intraoperatively decreases the need for excessive capsular debridement and retains adequate tissue for repair of the capsule at the end of the procedure. Numerous cadaveric and clinical studies have shown the importance of capsular closure in optimizing post-operative outcomes and, similarly, the importance of decreasing iatrogenic injury to the capsule intraoperatively. This also decreases the need of additional personnel in the operating room as capsular suspension sutures can require an assistant to hold traction to improve visualization or, in other cases, an assitant must flex/extend/internally and externally rotate the leg in order to achieve adequate visualization of the femoral head-neck junction. Discussion: The “chopsticks” method of capsular retraction presents a technically straightforward, economic approach to capsular retraction and allows for better visualization of cam deformities for resection. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Mosquito-transmitted viruses such as dengue are a global and growing public health challenge. Without widely available vaccines, mosquito control is the primary tool for fighting the spread of these viruses. New mosquito control technologies are needed to complement existing methods, given current challenges with scalability, acceptability, and effectiveness. A field trial was conducted in collaboration with the Communities Organized to Prevent Arboviruses project in Ponce, Puerto Rico, to measure entomological and epidemiological effects of reducing Aedes aegypti populations using Wolbachia incompatible insect technique. We packed and shipped Wolbachia-males from California and released them into 19 treatment clusters from September 2020 to December 2020. Preliminary evaluation revealed sub-optimal Wolbachia-male densities and impact on the wild-type population. In 2021, we shifted to a phased release strategy starting in four clusters, reducing the mosquito population by 49% (CI 29-63%). We describe the investigation into male quality and other factors that may have limited the impact of Wolbachia-male releases. Laboratory assays showed a small but significant impact of packing and shipping on male fitness. However, mark-release-recapture assessments suggest that male daily survival rates in the field may have been significantly impacted. We compared induced-sterility levels and suppression of the wild population and found patterns consistent with mosquito population compensation in response to our intervention. Analysis of epidemiological impact was not possible due to very low viral transmission rates during the intervention period. Our entomological impact data provide evidence that Wolbachia incompatible-male releases reduced Ae. aegypti populations, although efficacy will be maximized when releases are part of an integrated control program. With improvement of shipping vessels and shipped male fitness, packing and shipping male mosquitoes could provide a key solution for expanding access to this technology. Our project underscores the challenges involved in large and complex field effectiveness assessments of novel vector control methods.

ABSTRACT Willows (genus Salix) are increasingly used in operational‐scale ecosystem reclamation; however, different opinions exist regarding the optimal cutting size for planting under field conditions. We compared the survival of field‐planted willow cuttings sourced from upland and lowland areas with varying diameters and lengths across two growing seasons. Cuttings were grouped into 15 size classes with different diameters (0.5, 1.0, 2.0, and 3.0 cm) and lengths (15, 30, 50, and 100 cm) and planted in groups according to their source (upland or lowland, each area potentially reflecting a different assemblage of species) within three reclaimed industrial borrow pits east of Peace River, Alberta. We considered cuttings that displayed leaf flushing as surviving individuals. Survival probability tended to be greater for larger diameter and length cuttings sourced from lowland habitats. Cutting survival was greatly reduced in year two, especially for upland‐sourced cuttings. The greater survival in larger sizes we observed may be due to greater total carbohydrates available for leaf flushing and rooting. As we did not control for species composition, the higher survival of cuttings from low‐lying areas may result from species‐specific differences among cutting sources, reflected by compositional differences we detected among surviving individuals in year two. Our findings suggest that under field settings, cuttings with > 2.0 cm diameter by 50–100 cm length sourced from low‐lying flood‐prone areas may be optimal for willow establishment. Further studies should examine the role of species and population‐level genetics in driving the upland versus lowland differences in observed willow‐cutting survival.

Plant traits play a pivotal role in steering ecosystem dynamics. As plant canopies have evolved to interact with light, spectral data convey information on a variety of plant traits. Machine learning techniques have been used successfully to retrieve diverse traits from hyperspectral data. Nonetheless, the efficacy of machine learning is restricted by limited access to high-quality reference data for training. Previous studies showed that aggregating data across domains, sensors, or growth forms provided by collaborative efforts of the scientific community enables the creation of transferable models. However, even such curated databases are still sparse for several traits. To address these challenges, we investigated the potential of filling such data gaps with simulated hyperspectral data generated through the most widely-used radiative transfer model (RTM) PROSAIL. We coupled trait information from the TRY plant trait database with information on plant communities from the sPlot database, to build a realistic input trait dataset for the RTM-based simulation of canopy spectra. Our findings indicate that simulated data can alleviate the effects of data scarcity for highly underrepresented traits. In most other cases, however, the effects of including simulated data from RTMs are negligible or even negative. While more complex RTM models promise further improvements, their parameterization remains challenging. This highlights two key observations: firstly, RTM models, such as PROSAIL, exhibit limitations in producing realistic spectra across diverse ecosystems; secondly, real-world data repurposed from various sources exhibit superior retrieval success compared to simulated data. As a result, we advocate to emphasize the importance of active data sharing over secrecy and overreliance on modeling to address data limitations.

Microbial production of valuable bioproducts is a promising route towards green and sustainable manufacturing. The oleaginous yeast, Rhodosporidium toruloides, has emerged as an attractive host for the production of biofuels and bioproducts from lignocellulosic hydrolysates. 3-hydroxypropionic acid (3HP) is an attractive platform molecule that can be used to produce a wide range of commodity chemicals. This study focuses on establishing and optimizing the production of 3HP in R. toruloides. As R. toruloides naturally has a high metabolic flux towards malonyl-CoA, we exploited this pathway to produce 3HP. Upon finding the yeast capable of catabolizing 3HP, we then implemented functional genomics and metabolomic analysis to identify the catabolic pathways. Deletion of a putative malonate semialdehyde dehydrogenase gene encoding an oxidative 3HP pathway was found to significantly reduce 3HP degradation. We further explored monocarboxylate transporters to promote 3HP transport and identified a novel 3HP transporter in Aspergillus pseudoterreus by RNA-seq and proteomics. Combining these engineering efforts with media optimization in a fed-batch fermentation resulted in 45.4 g/L 3HP production. This represents one of the highest 3HP titers reported in yeast from lignocellulosic feedstocks. This work establishes R. toruloides as a host for 3HP production from lignocellulosic hydrolysate at high titers, and paves the way for further strain and process optimization towards enabling industrial production of 3HP in the future.

Objective:. To assess the relationship between postoperative opioid consumption and frailty status. Background:. Physiologic reserve can be assessed through both chronologic age as well as measures of frailty. Although prior studies suggest that older individuals may require less opioid following surgery, chronologic age, and frailty do not always align, and little is known regarding postoperative opioid consumption patterns by frailty. Methods:. We conducted a retrospective analysis of opioid-naïve adult patients undergoing common general, vascular, and gynecologic procedures across a statewide quality improvement program from November 6, 2017 to February 28, 2021. Our primary outcome was postoperative patient-reported opioid consumption within 30 days of surgery in oral morphine equivalents (OME). Our primary exposure was frailty status defined by the modified frailty index (mFi-5) criteria. Other covariates included patient demographic and clinical attributes, procedural factors, discharge opioid prescription size, and postoperative complications. Linear regression was performed to assess the association of frailty status and opioid consumption, stratified by age. Results:. In this cohort of 34,854 patients, 10,596 had an mFi-5 score of ≤1 and 3,635 had a score of >1. A score of >1 was associated with increased patient-reported opioid consumption (OMEs 3.3 greater; 95% CI = 1.5–5.1). This held true for individuals over 65 (OMEs 2.7 greater; 95% CI = 0.2–5.1). Frailty status, regardless of score, was negatively associated with an opioid prescription at discharge. Conclusions:. Frailty status is associated with increased opioid consumption after common operations. Future prescribing guidelines and outcomes analyses should consider this marker when reviewing opioid consumption data and related adverse outcomes.

Background Understanding the processes that influence distribution of organisms is a major goal in evolutionary biology. Speciation in freshwater fishes is mainly associated with the “island-like” model of evolution, in which the formation of land barriers between different hydrographic basins interrupts gene flow and promotes isolation. Freshwater fish therefore provide an excellent model system for macro- and micro-evolutionary studies. The Mesa Silverside, Chirostoma jordani, is one of the most widespread freshwater fish species in the Mexican Plateau, a geologically complex physiographic region with a long history of genesis, destruction and compartmentalization of hydrographic basins that has promoted the dispersal and isolation of freshwater fishes. Methods We used mitochondrial (Cytb and D-loop) and nuclear (first intron of the ribosomal protein S7) data and used phylogeographic and coalescent based methods to elucidate the evolutionary history of C. jordani throughout its distributional range on the Mexican Plateau. Results The results obtained in the present study revealed that C. jordani consists of two main genetic groups with geographical correspondence. Clade I occur exclusively in north-western basin and shows population structure. Clade II is widely distributed across the west, central and eastern basins without population structure. The split between these two main clades was estimated at 1.4 Mya. This cladogenetic event may be associated with the allopatric process promoted by the fragmentation and compartmentalization of hydrographic basins induced by the geological and climatic history of the Mexican Plateau.