Search

This project examines multi-hazard risks and the performance of emergency evacuation routes in California using spatial synthesis, mapping, modeling, and performance analysis techniques. It enhances evacuation planning by analyzing road networks under natural hazard scenarios. Key tasks included: 1. Collecting and organizing evacuation route data for 190 cities, revealing that only 23 had comprehensive GIS maps, highlighting gaps in current planning. 2. Assessing road network performance under various hazards for 450 cities, identifying high-risk areas, and classifying cities based on risk levels and concentration. 3. Analyzing evacuation routes during the 2018 Camp and Thomas fires, using mathematical modeling and Omniscape to assess bottlenecks and evacuation efficiency. 4. Evaluating evacuation route performance for different population segments and proposing improvements, including using public transit for future wildfire evacuations. The findings provide actionable insights for improving emergency evacuation strategies in the state. View the NCST Project Webpage

Sky High Insights: Campus Facility Management with Drones:This lightning talk will explore the integration of drone technology in university campus facility management. We will discuss how drone flights capture high-resolution images, enabling the creation of detailed 3D models of campus infrastructure. Leveraging advanced image processing and machine learning algorithms, these models facilitate enhanced data analysis for maintenance and planning.Key benefits include enhanced accuracy in monitoring facility conditions, proactive maintenance strategies, and optimized resource allocation. Through case studies, we will demonstrate how to prepare for drone flights and illustrate how the integration of drones with AI and machine learning can transform facility management, fostering smarter and more sustainable campus environments.Building accurate range maps for California’s 104 tree species:Biogeography is the study of the distribution of biota across space. In this way, it can inform every kind of ecological study. So, if we’re going to study biota across space, including predicting where those biota might be in the future or how they could respond to external pressures, we need a good estimate of where those biota are now. In essence, we need a good species range map. The last major effort to systematically map tree species ranges in California was done by Griffin and Critchfield (1972) of the U.S. Forest Service, over 50 years ago. Since then, thousands of studies have been completed with coordinates for trees, and many thousands more civilians have collected GPS points in public repositories for citizen science, advocacy, or enjoyment. After vetting for accuracy, this data can significantly enhance existing range maps. Also, recent high-quality vegetation mapping efforts by public agencies can provide both additional “presence” data to expand range maps beyond existing known boundaries and “absence” data in the sense that they can be used to subtract out unlikely range area within existing known boundaries.In this presentation, we’ll discuss the partially-automated GIS workflow we’ve developed for building the most accurate and comprehensive range maps for California’s 104 tree species, from creating the highest-quality-ever digitization of the Griffin and Critchfield (1972) range maps to collecting, processing, and incorporating hundreds of additional datasets to subtracting out non-range areas. We’ll also discuss how we’re using these state-of-the-art maps to assess the climate exposure, fire risk, and operational priority (seed demand) of each tree species to inform seed collection efforts for reforestation, as well as examples of how the actual map-building process can be used to address some fundamental questions in biogeographical theory.Hand-drawn historic maps: Utilization and conversion of unique features into Geographic Information Systems (GIS):The GIS Center at the University of California, Merced provides research services to faculty and is responsible for managing and maintaining a geospatial collection for our students and researchers. We support Geographic Information Systems (GIS) software for over 500 users yearly and provide workshops and consultations. GIS Center technical research staff have provided consulting services to researchers and direct project support. Through four case studies, we will detail our processes for converting historic maps into GIS products that contribute to research publications and data sets. Specifically, we will discuss the technical demands and research benefits of georeferencing and vectorizing digitized historic maps utilizing various methods including machine learning and heads up digitizing and sharing that data via ArcGIS Online and other cloud-based applications. We conclude with recommendations for others embarking upon this type of work.

OBJECTIVE: Quality of care (QoC) delivery in rheumatoid arthritis (RA) continues to suffer from various challenges (eg, delay in diagnosis and referral) that can lead to poor patient outcomes. This study aimed to identify good practice interventions that address these challenges in RA care in North America. METHODS: The study was conducted in three steps: (1) literature review of existing publications and guidelines (April 2005 to April 2021) on QoC in RA; (2) in-person visits to >50 individual specialists and health care professionals across nine rheumatology centers in the United States and Canada to identify challenges in RA care and any corresponding good practice interventions; and (3) collation and organization of findings of the two previous methods by commonalities to identify key good practice interventions, followed by further review by RA experts to ensure key challenges and gaps in RA care were captured. RESULTS: Several challenges and eight good practice interventions were identified in RA care. The interventions were prioritized based on the perceived positive impact on the challenges in care and ease of implementation. High-priority interventions included the use of technology to improve care, streamlining specialist treatment, and facilitating comorbidity assessment and care. Other interventions included enabling patient access to optimal medication regimens and improving patient self-management strategies. CONCLUSION: Learnings from the study can be implemented in other rheumatology centers throughout North America to improve RA care. Although the study was completed before the COVID-19 pandemic, the findings remain relevant.

Climate change is an existential threat to the environmental and socioeconomic sustainability of the coastal zone and impacts will be complex and widespread. Evidence from California and across the United States shows that climate change is impacting coastal communities and challenging managers with a plethora of stressors already present. Widespread action could be taken that would sustain California's coastal ecosystems and communities. In this perspective, we highlight the main threat to coastal sustainability: the compound effects of episodic events amplified with ongoing climate change, which will present unprecedented challenges to the state. We present two key challenges for California's sustainability in the coastal zone: 1) accelerating sea-level rise combined with storm impacts, and 2) continued warming of the oceans and marine heatwaves. Cascading effects from these types of compounding events will occur within the context of an already stressed system that has experienced extensive alterations due to intensive development, resource extraction and harvesting, spatial containment, and other human use pressures. There are critical components that could be used to address these immediate concerns, including comanagement strategies that include diverse groups and organizations, strategic planning integrated across large areas, rapid implementation of solutions, and a cohesive and policy relevant research agenda for the California coast. Much of this has been started in the state, but the scale could be increased, and timelines accelerated. The ideas and information presented here are intended to help expand discussions to sharpen the focus on how to encourage sustainability of California's iconic coastal region.

In this review and synthesis, we argue that California is an important test case for the nation and world because terrestrial biodiversity is very high, present and anticipated threats to biodiversity from climate change and other interacting stressors are severe, and innovative approaches to protecting biodiversity in the context of climate change are being developed and tested. We first review salient dimensions of Californias terrestrial physical, biological, and human diversity. Next, we examine four facets of the threat to their sustainability of these dimensions posed by climate change: direct impacts, illustrated by a new analysis of shifting diversity hotspots for plants; interactive effects involving invasive species, land-use change, and other stressors; the impacts of changing fire regimes; and the impacts of land-based renewable energy development. We examine recent policy responses in each of these areas, representing attempts to better protect biodiversity while advancing climate adaptation and mitigation. We conclude that Californias ambitious 30 × 30 Initiative and its efforts to harmonize biodiversity conservation with renewable energy development are important areas of progress. Adapting traditional suppression-oriented fire policies to the reality of new fire regimes is an area in which much progress remains to be made.

Rhamnogalacturonan II (RG-II) is a structurally complex and conserved domain of the pectin present in the primary cell walls of vascular plants. Borate cross-linking of RG-II is required for plants to grow and develop normally. Mutations that alter RG-II structure also affect cross-linking and are lethal or severely impair growth. Thus, few genes involved in RG-II synthesis have been identified. Here, we developed a method to generate viable loss-of-function Arabidopsis (Arabidopsis thaliana) mutants in callus tissue via CRISPR/Cas9-mediated gene editing. We combined this with a candidate gene approach to characterize the male gametophyte defective 2 (MGP2) gene that encodes a putative family GT29 glycosyltransferase. Plants homozygous for this mutation do not survive. We showed that in the callus mutant cell walls, RG-II does not cross-link normally because it lacks 3-deoxy-D-manno-octulosonic acid (Kdo) and thus cannot form the α-L-Rhap-(1→5)-α-D-kdop-(1→sidechain). We suggest that MGP2 encodes an inverting RG-II CMP-β-Kdo transferase (RCKT1). Our discovery provides further insight into the role of sidechains in RG-II dimerization. Our method also provides a viable strategy for further identifying proteins involved in the biosynthesis of RG-II.

BackgroundThe accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues.ResultsA total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5' untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue-tissue interconnection involved in different traits and construct the first bovine trait similarity network.ConclusionsThese validated results show significant improvement over current bovine genome annotations.

Effective waterfowl management relies on the collection of relevant demographic data to inform land-management decisions; however, some types of data are difficult to obtain. For waterfowl, brood surveys are difficult to conduct because wetland habitats often obscure ducklings from being visually assessed. Here, we used Unoccupied Aerial Systems (UAS) to assess what wetland habitat characteristics influenced brood abundance in Suisun Marsh, California, USA. Using a thermal-imaging camera, we surveyed 17 wetland units that encompassed 332ha of flooded area on the premises of seven waterfowl hunting clubs during the waterfowl breeding season. Additionally, using a combination of multi-spectral imagery collected from the UAS flights and LiDAR data from the previous year, we mapped habitat composition within each unit to relate to brood observation counts. From June 3–7, 2019, we identified 113 individual broods comprising 827 ducklings. We found a positive relationship between the number of broods observed and the proportion of the unit that was flooded. We also found a positive relationship between the number of broods observed and the area of effective habitat—a metric of flooded habitat within two times the 95th-percentile Euclidean distance that all broods were observed from any vegetated cover. Brood surveys using UAS could complement the traditional Breeding Population Survey and provide local managers with fine-scale and timely information about shifts in brood abundance in the region.

Youth screen media activity is a growing concern, though few studies include objective usage data. Through the longitudinal, U.S.-based Adolescent Brain Cognitive Development (ABCD) Study, youth (mage = 14; n = 1415) self-reported their typical smartphone use and passively recorded three weeks of smartphone use via the ABCD-specific Effortless Assessment Research System (EARS) application. Here we describe and validate passively-sensed smartphone keyboard and app use measures, provide code to harmonize measures across operating systems, and describe trends in adolescent smartphone use. Keyboard and app-use measures were reliable and positively correlated with one another (r = 0.33) and with self-reported use (rs = 0.21-0.35). Participants recorded a mean of 5 h of daily smartphone use, which is two more hours than they self-reported. Further, females logged more smartphone use than males. Smartphone use was recorded at all hours, peaking on average from 8 to 10 PM and lowest from 3 to 5 AM. Social media and texting apps comprised nearly half of all use. Data are openly available to approved investigators ( https://nda.nih.gov/abcd/ ). Information herein can inform use of the ABCD dataset to longitudinally study health and neurodevelopmental correlates of adolescent smartphone use.

BackgroundEstimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030.Methods and findingsUsing the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts.ConclusionsThe PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.

BackgroundHospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005-2018 among adult PWH in NA-ACCORD.MethodsLinear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (

As the title of The American Indian and the Problem of History suggest, this work has a historiographic emphasis. In the wake of revisionist trends of the 1970s, Indian historians face a number of knotty problems as they endeavor to avoid ethnocentric biases and to incorporate Native American sources and perspectives. Collectively, the papers in this volume assess the achievements and pitfalls of revisionist history and consider methods and goals for future scholarship. For Martin and many of the contributors, a principal concern is the need to integrate an understanding of the interplay between religion and the environment in writing Indian history. ‘What was their metaphysics? Everything we write about [native Americans],” says Martin, “should follow from this seminal question” (p.216). Having circulated copies of his article, ‘the metaphysics of Writing Indian history” (reprinted here as Chapter 1), martin asked for the “large contours” of Indian and white history and “what it all means” (p.5). he evoked a variety of searching responses from his eighteen distinguished contributors, including veteran historians Robert Berthofer, Jr., Wilcolm Washburn, Cornelius Jaenen, Mary Young, henry Dobyns, vine Deloria, Jr. , and a number of equally impressive, younger scholars. The essys range in style and content from Berkhofer’s excellent essay, ‘Cultural Pluralism Versus Ethnocentrism in the New Indian History,” to Neil Salisbury’s useful overview of Indian prehistory, to Gerald Vizenor’s mythic satire, “Socioacupunture: Mythic Reversals and Striptease in four Scenes,” making provocative reading.

Aim: To describe barriers to implementation of diabetic retinopathy (DR) teleretinal screening programs and artificial intelligence (AI) integration at the University of California (UC). Methods: Institutional representatives from UC Los Angeles, San Diego, San Francisco, Irvine, and Davis were surveyed for the year of their program's initiation, active status at the time of survey (December 2021), number of primary care clinics involved, screening image quality, types of eye providers, image interpretation turnaround time, and billing codes used. Representatives were asked to rate perceptions toward barriers to teleretinal DR screening and AI implementation using a 5-point Likert scale. Results: Four UC campuses had active DR teleretinal screening programs at the time of survey and screened between 246 and 2,123 patients at 1-6 clinics per campus. Sites reported variation between poor-quality photos (

Divergence time estimation is crucial to provide temporal signals for dating biologically important events from species divergence to viral transmissions in space and time. With the advent of high-throughput sequencing, recent Bayesian phylogenetic studies have analyzed hundreds to thousands of sequences. Such large-scale analyses challenge divergence time reconstruction by requiring inference on highly correlated internal node heights that often become computationally infeasible. To overcome this limitation, we explore a ratio transformation that maps the original $N-1$ internal node heights into a space of one height parameter and $N-2$ ratio parameters. To make the analyses scalable, we develop a collection of linear-time algorithms to compute the gradient and Jacobian-associated terms of the log-likelihood with respect to these ratios. We then apply Hamiltonian Monte Carlo sampling with the ratio transform in a Bayesian framework to learn the divergence times in 4 pathogenic viruses (West Nile virus, rabies virus, Lassa virus, and Ebola virus) and the coralline red algae. Our method both resolves a mixing issue in the West Nile virus example and improves inference efficiency by at least 5-fold for the Lassa and rabies virus examples as well as for the algae example. Our method now also makes it computationally feasible to incorporate mixed-effects molecular clock models for the Ebola virus example, confirms the findings from the original study, and reveals clearer multimodal distributions of the divergence times of some clades of interest.

Sea-level rise is particularly concerning for tidal wetlands that reside within an area with steep topography or are constrained by human development and alteration of sedimentation. Sediment augmentation to increase wetland elevations has been considered as a potential strategy for such areas to prevent wetland loss over the coming decades. However, there is little information on the best approaches and whether adaptive management actions can mimic natural processes to build sea-level rise resilience. In addition, the lack of information on long-term marsh characteristics, processes, and variability can hamper development of effective augmentation strategies. Here, we assess a case study in a southern California marsh to determine the nature of the pre-existing sediments and variability of the site in relation to sediments applied during an augmentation experiment. Although sediment cores revealed natural variations in the grain size and organic content of sediments deposited at the site over the past 1500 years, the applied sediments were markedly coarser in grain size than prehistoric sediments at the site (100% maximum sand versus 76% maximum sand). The rate of the experimental sediment application (25.1 ± 1.09 cm in ~2 months) was also much more rapid than natural accretion rates measured for the site historically. In contrast, post-augmentation sediment accretion rates on the augmentation site have been markedly slower than pre-augmentation rates or current rates on a nearby control site. The mismatch between the characteristics of the applied sediment and thickness of application and the historic conditions are likely strong contributors to the slow initial recovery of vegetation. Sediment augmentation has been shown to be a useful strategy in some marshes, but this case study illustrates that vegetation recovery may be slow if applied sediments are not similar or at a thickness similar to historic conditions. However, testing adaptation strategies to build wetland elevations is important given the long-term risk of habitat loss with sea-level rise. Lessons learned in the case study could be applied elsewhere.

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.

Abstract: Variations in fault zone maturity have intermittently been invoked to explain variations in some seismological observations for large earthquakes. However, the lack of a unified geological definition of fault maturity makes quantitative assessment of its importance difficult. We evaluate the degree of empirical correlation between geological and geometric measurements commonly invoked as indicative of fault zone maturity and remotely measured seismological source parameters of 34MW ≥ 6.0 shallow strike‐slip events. Metrics based on surface rupture segmentation, such as number of segments and surface rupture azimuth changes, correlate best with seismic source attributes while the correlations with cumulative fault slip are weaker. Average rupture velocity shows the strongest correlation with metrics of maturity, followed by relative aftershock productivity. Mature faults have relatively lower aftershock productivity and higher rupture velocity. A more complex relation is found with moment‐scaled radiated energy. There appears to be distinct behavior of very immature events which radiate modest seismic energy, while intermediate mature faults have events with higher moment‐scaled radiated energy and very mature faults with increasing cumulative slip tend to have events with reduced moment‐scaled radiated energy. These empirical comparisons establish that there are relationships between remote seismological observations and fault system maturity that can help to understand variations in seismic hazard among different fault environments and to assess the relative maturity of inaccessible or blind fault systems for which direct observations of maturity are very limited.

Two major earthquakes (MW 7.8 and MW 7.7) ruptured left-lateral strike-slip faults of the East Anatolian Fault Zone (EAFZ) on February 6, 2023, causing >59,000 fatalities and ~$119B in damage in southeastern Türkiye and northwestern Syria. Here we derived kinematic rupture models for the two events by inverting extensive seismic and geodetic observations using complex 5-6 segment fault models constrained by satellite observations and relocated aftershocks. The larger event nucleated on a splay fault, and then propagated bilaterally ~350 km along the main EAFZ strand. The rupture speed varied from 2.5-4.5 km/s, and peak slip was ~8.1 m. 9-h later, the second event ruptured ~160 km along the curved northern EAFZ strand, with early bilateral supershear rupture velocity (>4 km/s) followed by a slower rupture speed (~3 km/s). Coulomb Failure stress increase imparted by the first event indicates plausible triggering of the doublet aftershock, along with loading of neighboring faults.

Marine heatwaves cause widespread environmental, biological, and socio-economic impacts, placing them at the forefront of 21st-century management challenges. However, heatwaves vary in intensity and evolution, and a paucity of information on how this variability impacts marine species limits our ability to proactively manage for these extreme events. Here, we model the effects of four recent heatwaves (2014, 2015, 2019, 2020) in the Northeastern Pacific on the distributions of 14 top predator species of ecological, cultural, and commercial importance. Predicted responses were highly variable across species and heatwaves, ranging from near total loss of habitat to a two-fold increase. Heatwaves rapidly altered political bio-geographies, with up to 10% of predicted habitat across all species shifting jurisdictions during individual heatwaves. The variability in predicted responses across species and heatwaves portends the need for novel management solutions that can rapidly respond to extreme climate events. As proof-of-concept, we developed an operational dynamic ocean management tool that predicts predator distributions and responses to extreme conditions in near real-time.

We present a sample-variance-limited measurement of the temperature power spectrum (TT) of the cosmic microwave background using observations of a ∼1500 deg2 field made by the SPT-3G in 2018. We report multifrequency power spectrum measurements at 95, 150, and 220 GHz covering the angular multipole range 750≤ℓ

Severe maternal morbidity (SMM) refers to any unexpected outcome directly related to pregnancy and childbirth that results in both short-term delivery complications and long-term consequences to a womens health. This affects about 60,000 women annually in the United States. Cardiovascular contributions to SMM including cardiac arrest, arrhythmia, and acute myocardial infarction are on the rise, probably driven by changing demographics of the pregnant population including more women of extreme maternal age and an increased prevalence of cardiometabolic and structural heart disease. The utilization of SMM prediction tools and risk scores specific to cardiovascular disease in pregnancy has helped with risk stratification. Furthermore, health system data monitoring and reporting to identify and assess etiologies of cardiovascular complications has led to improvement in outcomes and greater standardization of care for mothers with cardiovascular disease. Improving cardiovascular disease-related SMM relies on a multipronged approach comprised of patient-level identification of risk factors, individualized review of SMM cases, and validation of risk stratification tools and system-wide improvements in quality of care. In this article, we review the epidemiology and cardiac causes of SMM, we provide a framework of risk prediction clinical tools, and we highlight need for organization of care to improve outcomes.

Rapid venting of volcanic material during the 15 January 2022 Tonga eruption generated impulsive downward reaction forces on the Earth of ~2.0 × 1013 N that radiated seismic waves observed throughout the planet, with ~25 s source bursts persisting for ~4.5 hours. The force time history is determined by analysis of teleseismic P waves and Rayleigh waves with periods approximately

IntroductionPlant functional traits (FTs) are important for understanding plant ecological strategies (e.g., drought avoidance), especially in the nutrient-poor soils of serpentine ecosystems. In the Mediterranean areas, such ecosystems are characterized by climatic factors (e.g., summer drought) that exert a filtering effect.Material and methodsIn our study, we analyzed 24 species with varying serpentine affinity, from strictly serpentine plants to generalist plants, from two ultramafic shrublands in southern Spain, considering four FTs: plant height (H), leaf area (LA), specific leaf area (SLA), and stem specific density (SSD). Additionally, we also identified the species' dominant strategies to avoid drought and those strategies' relationship to serpentine affinity. We used principal component analysis to identify combinations of FTs, and cluster analysis to define Functional Groups (FGs).Results and discussionWe defined eight FGs, which suggests that such Mediterranean serpentine shrublands are composed of species with wide-ranging of FTs. Indicator traits explained 67-72% of the variability based on four strategies: (1) lower H than in other Mediterranean ecosystems; (2) middling SSD; (3) low LA; and (4) low SLA due to thick and/or dense leaves, which contribute to long leaf survival, nutrient retention, and protection from desiccation and herbivory. Generalist plants had higher SLA than obligate serpentine plants, whereas the obligate serpentine plants showed more drought avoidance mechanisms than the generalists. Although most plant species inhabiting Mediterranean serpentine ecosystems have shown similar ecological adaptations in response to the Mediterranean environment, our results suggest that serpentine obligate plant species could present greater resilience to climate change. Given greater number and more pronounced drought avoidance mechanisms in these species compared with generalists, and the high number of FGs identified, the serpentine plants have shown adaptation to severe drought.

Strong tsunami excitation from slow rupture of shallow subduction zone faults is recognized as a key concern for tsunami hazard assessment. Three months after the 22 July 2020 magnitude 7.8 thrust earthquake struck the plate boundary below the Shumagin Islands, Alaska, a magnitude 7.6 aftershock ruptured with complex intraplate faulting. Despite the smaller size and predominantly strike-slip faulting mechanism inferred from seismic waves for the aftershock, it generated much larger tsunami waves than the mainshock. Here we show through detailed analysis of seismic, geodetic, and tsunami observations of the aftershock that the event implicated unprecedented source complexity, involving weakly tsunamigenic fast rupture of two intraplate faults located below and most likely above the plate boundary, along with induced strongly tsunamigenic slow thrust slip on a third fault near the shelf break likely striking nearly perpendicular to the trench. The thrust slip took over 5 min, giving no clear expression in seismic or geodetic observations while producing the sizeable far-field tsunami.

So far in this century, six very large-magnitude earthquakes (MW ≥ 7.8) have ruptured separate portions of the subduction zone plate boundary of western South America along Ecuador, Peru, and Chile. Each source region had last experienced a very large earthquake from 74 to 261 y earlier. This history led to their designation in advance as seismic gaps with potential to host future large earthquakes. Deployments of geodetic and seismic monitoring instruments in several of the seismic gaps enhanced resolution of the subsequent faulting processes, revealing preevent patterns of geodetic slip deficit accumulation and heterogeneous coseismic slip on the megathrust fault. Localized regions of large slip, or asperities, appear to have influenced variability in how each source region ruptured relative to prior events, as repeated ruptures have had similar, but not identical slip distributions. We consider updated perspectives of seismic gaps, asperities, and geodetic locking to assess current very large earthquake hazard along the South American subduction zone, noting regions of particular concern in northern Ecuador and Colombia (1958/1906 rupture zone), southeastern Peru (southeasternmost 1868 rupture zone), north Chile (1877 rupture zone), and north-central Chile (1922 rupture zone) that have large geodetic slip deficit measurements and long intervals (from 64 to 154 y) since prior large events have struck those regions. Expanded geophysical measurements onshore and offshore in these seismic gaps may provide critical information about the strain cycle and fault stress buildup late in the seismic cycle in advance of the future great earthquakes that will eventually strike each region.

PurposeAdvanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental designDiscovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).ResultsInfiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).ConclusionsAn infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

BackgroundGenetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain.MethodsWe engineered a novel App knock-in mouse model (AppSAA) using homologous recombination to introduce three disease-causing coding mutations (Swedish, Arctic and Austrian) to the mouse App gene. Amyloid-β pathology, neurodegeneration, glial responses, brain metabolism and behavioral phenotypes were characterized in heterozygous and homozygous AppSAA mice at different ages in brain and/ or biofluids. Wild type littermate mice were used as experimental controls. We used in situ imaging technologies to define the whole-brain distribution of amyloid plaques and compare it to other AD mouse models and human brain pathology. To further explore the microglial response to AD relevant pathology, we isolated microglia with fibrillar Aβ content from the brain and performed transcriptomics and metabolomics analyses and in vivo brain imaging to measure energy metabolism and microglial response. Finally, we also characterized the mice in various behavioral assays.ResultsLeveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The AppSAA knock-in mouse model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered astroglial and microglial responses and elevation of CSF markers of neurodegeneration. Those observations were associated with increased TSPO and FDG-PET brain signals and a hyperactivity phenotype as the animals aged.DiscussionOur findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology.

Objective/hypothesisTo investigate the clinical features, management strategies and outcomes for patients with metastatic primary skull base chordomas.Study designSystematic review.MethodsA systematic search through Pubmed/Medline, Web of Science, and EBSCOhost (CINAHL) was conducted without restriction on dates. After study screening and full-text assessment, two authors independently extracted all data using a pre-established abstraction form.ResultsForty cases were included from 38 studies. The average age (standard deviation [SD]) of the sample at presentation was 28.5 (23.3) and was equally distributed across genders. The average time (SD) between initial diagnosis to local recurrence was 40.1 (60.3) months. The average time (SD) from primary tumor detection to the diagnosis of metastatic disease was 55.2 (49.0) months. The most common subsite for metastatic spread were the lungs (32.5%). Of the 33 patients with data on outcomes, 48.5% were found to have expired by the time of publication. The median overall survival was estimated to be 84 months (95% confidence interval [CI] 62.3-105.7).ConclusionsThe most common subsites for metastatic spread of skull base chordoma were the lungs and bone. Overall survival for patients in the current cohort was a median of 84 months, with no significant differences noted when stratifying by the extent of surgery or the site of metastases.Level of evidence3a.

BackgroundThe updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)-specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality.MethodsBecause complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age 500 copies/mL, CD4 count

BackgroundIndependent of CD4 cell count, a low CD4/CD8 ratio in people with HIV (PWH) is associated with deleterious immune senescence, activation, and inflammation, which may contribute to carcinogenesis and excess cancer risk. We examined whether low CD4/CD8 ratios predicted cancer among PWH in the United States and Canada.MethodsWe examined all cancer-free PWH with 1 or more CD4/CD8 values from North American AIDS Cohort Collaboration on Research and Design observational cohorts with validated cancer diagnoses between 1998 and 2016. We evaluated the association between time-lagged CD4/CD8 ratio and risk of specific cancers in multivariable, time-updated Cox proportional hazard models using restricted cubic spines. Models were adjusted for age, sex, race and ethnicity, hepatitis C virus, and time-updated CD4 cell count, HIV RNA, and history of AIDS-defining illness.ResultsAmong 83 893 PWH, there were 5628 incident cancers, including lung cancer (n = 755), Kaposi sarcoma (n = 501), non-Hodgkin lymphoma (n = 497), and anal cancer (n = 439). The median age at cohort entry was 43 years. The overall median 6-month lagged CD4/CD8 ratio was 0.52 (interquartile range = 0.30-0.82). Compared with a 6-month lagged CD4/CD8 of 0.80, a CD4/CD8 of 0.30 was associated with increased risk of any incident cancer (adjusted hazard ratio = 1.24 [95% confidence interval = 1.14 to 1.35]). The CD4/CD8 ratio was also inversely associated with non-Hodgkin lymphoma, Kaposi sarcoma, lung cancer, anal cancer, and colorectal cancer in adjusted analyses (all 2-sided P

Antenatal multiple micronutrient supplements (MMS) are more effective than iron and folic acid (IFA) supplements in reducing adverse pregnancy outcomes. Questions remain, however, about the ability of MMS to prevent anemia as effectively as IFA, especially at a lower dose of daily iron and in areas of high anemia prevalence. Analyzing data from 11 trials from a recent Cochrane review, we compared MMS to IFA, delivering either 30 or 60 mg of iron, in sustaining hemoglobin and preventing third trimester anemia and iron deficiency anemia (IDA), accounting for daily iron dose, total supplemental iron intake, and baseline prevalence of anemia. There were no differences between MMS and IFA in third trimester hemoglobin concentration or risks of anemia or IDA by iron dose or total supplemental iron consumed. MMS providing 30 mg of iron was comparable to IFA with 60 mg of iron: mean hemoglobin difference of -0.26 g/L (95% CI: -1.41 to 0.89), risk ratios of 0.99 (95% CI: 0.92-1.07) for anemia, and 1.31 (95% CI: 0.66-2.60) for IDA. Baseline prevalence of anemia did not explain heterogeneity in findings. Compared to IFA, MMS results in comparable hemoglobin concentration and protection against anemia during pregnancy, independently of iron dose.

PROBLEM: In the 2021 residency application cycle, the average otolaryngology applicant applied to more than half of programs. Increasing application numbers make it difficult for applicants to stand out to programs of interest and for programs to identify applicants with sincere interest. APPROACH: As part of the 2021 Match, otolaryngology applicants could participate in a preference signaling process, signaling up to 5 programs of particular interest at the time of application submission. Programs received a list of applicants who submitted signals to consider during interview offer deliberations. Applicants and program directors completed surveys to evaluate the signaling process and assess the impact of signals on interview offers. OUTCOMES: All otolaryngology residency programs participated in the signaling process. In total, 611 students submitted applications for otolaryngology residency programs, 559 applicants submitted a Match list including an otolaryngology program, and 558 applicants participated in the signaling process. The survey response rate was 42% for applicants (n = 233) and 52% for program directors (n = 62). The rate of receiving an interview offer was significantly higher from signaled programs (58%) than from both nonsignaled programs (14%; P < .001) and the comparative nonsignal program (23%; P < .001) (i.e., the program an applicant would have signaled given a sixth signal). This impact was consistent across the spectrum of applicant competitiveness. Applicants (178, 77%) and program directors (53, 91%) strongly favored continuing the program. NEXT STEPS: Many specialties face high residency application numbers. Programs have difficulty identifying applicants with sincere interest, and applicants face limited opportunities to identify programs of particular interest. Applicants to these specialties may benefit from a preference signaling process like that in otolaryngology. Additional evaluation is needed to determine the impact of signals across racial and demographic lines and to validate these early outcomes.

OBJECTIVE: Surgical education is changing in an era of new regulations and evolving training cultures. We sought to understand the factors that affect operative experiences during otolaryngology residency. METHODS: From December 2019 to December 2020, five otolaryngology training programs used the SIMPL OR smartphone application to evaluate residents after each operation. Residents and attendings rated the trainees autonomy on a 4-level Zwisch scale, performance on a 5-level scale, and case complexity on a 3-level scale. We examined associations between ratings of autonomy and performance with variables including postgraduate year (PGY), case complexity, gender, week of the academic year (AY), and whether multiple procedures were logged. RESULTS: 78 attendings and 92 residents logged 2984 evaluations. PGY level and week of the AY were positively associated with attending ratings of autonomy and performance (PGY3 vs. PGY2: B = 0.63, p

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with HIV (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCLs) in the modern antiretroviral therapy era. North American AIDS Cohort Collaboration on Research and Design and Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study, 52, 64, 101, 500, and 246 PWH with histologic confirmation of TCL, primary central nervous system lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphoma (DLBCL), and Hodgkin's lymphoma (HL), respectively, and 450 TCLs without HIV were eligible for analysis. At the time of TCL diagnosis, anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. Although PWH with TCL diagnosed between 1996 and 2009 experienced a low 5-year survival probability at 0.23 (95% confidence interval [CI]: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010 and 2016 (0.69; 95% CI: 0.48, 1; P = .04) in contrast to TCLs among PWoH (0.45; 95% CI: 0.41, 0.51; P = .53). Similarly, PWH with ALCLs diagnosed between 1996 and 2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt's (0.43; 95% CI:0.33, 0.57; P = .09) and DLBCL (0.17; 95% CI: 0.06, 0.46; P = .11) and behind HL (0.57; 95% CI: 0.50, 0.65; P < .0001). Despite a small number, those diagnosed between 2010 and 2016 experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison with PWoH (0.76; 95% CI: 0.66, 0.87; P = .58). Thus, our analysis confirms improved overall survival for aggressive B- and T-cell malignancies among PWH in the last decade.

A key function of a highway network is to maintain access during normal and emergency operations. During wildfire evacuations, first-responders and firefighters depend on highways and local roads for transporting heavy equipment to communities in need. The California Department of Transportation (Caltrans) is expanding vegetation management to begin establishing defensible space zones along California’s nearly 16,000 miles of state highways and in about 230,000 acres of highway right-ofway. However, extended drought, a longer fire season, and higher temperatures brought on by climate change, along with the spread of invasive weeds and dense, dry vegetation, have created new challenges.The California Department of Forestry and Fire Protection produced a Community Wildfire Prevention and Mitigation Report in 2019 with a methodology to assess wildfire risk. Caltrans and researchers at the University of California, Davis applied these methods to develop a highway-segment-specific prioritization model for vegetation management within highway rights-of-way. The researchers also interviewed Caltrans staff about opportunities for and obstacles to increasing the pace and scale of vegetation treatments. This policy brief summarizes the findings from that research and provides policy implications.View the NCST Project Webpage

The reduced emissions in deforestation and degradation (REDD+) initiative uses payments for ecosystem services as incentives for developing countries to manage and protect their forests. REDD+ initiatives also prioritize social (and environmental) co-benefits aimed at improving the livelihoods of communities that are dependent on forests. Despite the incorporation of co-benefits into REDD+ goals, carbon sequestration remains the primary metric for which countries can receive payments from REDD+, but after more than 10 years of REDD+, many site-specific programs have failed to complete the carbon verification process. Here, we examine whether the REDD+ social co-benefits alone are sufficient to have slowed deforestation in the absence of carbon payments on Pemba, Tanzania. Using satellite imagery (Landsat archive), we quantified forest cover change for the period before (2001-2010) and after (2010-2018) the launch in 2010-2011 of Pemba island's REDD+ readiness project. We then compared rates of forest cover change between shehia (administrative units) that were part of REDD+ readiness intervention and those that were not, adjusting for confounding variables and the non-random selection of REDD+ shehia with a statistical matching procedure. Despite considerable variation in forest outcomes among shehia, the associated co-benefits with the Pemba REDD+ project had no discernible effect on forest cover change. Likewise, we did not detect an effect of socioecological covariates on forest cover change across all shehia, though island-wide human population growth since 2012 may have played a role. These findings are unsurprising given the failure to secure carbon payments on Pemba and indicate that co-benefits alone are insufficient to reduce deforestation. We conclude that better oversight of all-involved parties is needed to ensure that REDD+ interventions satisfactorily conclude the process of securing a mechanism for carbon payments, if slowing deforestation is to be achieved.

The emergence of SARS-CoV-2 variants of concern suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on the characterization of changes in the spike protein in variants of concern, mutations outside of spike are likely to contribute to adaptation. Here, using unbiased abundance proteomics, phosphoproteomics, RNA sequencing and viral replication assays, we show that isolates of the Alpha (B.1.1.7) variant3 suppress innate immune responses in airway epithelial cells more effectively than first-wave isolates. We found that the Alpha variant has markedly increased subgenomic RNA and protein levels of the nucleocapsid protein (N), Orf9b and Orf6-all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein that is required for activation of the RNA-sensing adaptor MAVS. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful transmission of the Alpha variant, and may increase in vivo replication and duration of infection4. The importance of mutations outside the spike coding region in the adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the N and Orf9b regulatory regions of the Delta and Omicron variants.

High-resolution historical climate grids are readily available and frequently used as inputs for a wide range of regional management and risk assessments, including water supply, ecological processes, and as baseline for climate change impact studies that compare them to future projected conditions. Because historical gridded climates are produced using various methods, their portrayal of landscape conditions differ, which becomes a source of uncertainty when they are applied to subsequent analyses. Here we tested the range of values from five gridded climate datasets. We compared their values to observations from 1231 weather stations, first using each dataset’s native scale, and then after each was rescaled to 270-m resolution. We inputted the downscaled grids to a mechanistic hydrology model and assessed the spatial results of six hydrological variables across California, in 10 ecoregions and 11 large watersheds in the Sierra Nevada. PRISM was most accurate for precipitation, ClimateNA for maximum temperature, and TopoWx for minimum temperature. The single most accurate dataset overall was PRISM due to the best performance for precipitation and low air temperature errors. Hydrological differences ranged up to 70% of the average monthly streamflow with an average of 35% disagreement for all months derived from different historical climate maps. Large differences in minimum air temperature data produced differences in modeled actual evapotranspiration, snowpack, and streamflow. Areas with the highest variability in climate data, including the Sierra Nevada and Klamath Mountains ecoregions, also had the largest spread for snow water equivalent, recharge, and runoff.

The statistical models used to derive the results of experimental analyses are of incredible scientific value and are essential information for analysis preservation and reuse. In this paper, we make the scientific case for systematically publishing the full statistical models and discuss the technical developments that make this practical. By means of a variety of physics cases - including parton distribution functions, Higgs boson measurements, effective field theory interpretations, direct searches for new physics, heavy flavor physics, direct dark matter detection, world averages, and beyond the Standard Model global fits - we illustrate how detailed information on the statistical modelling can enhance the short- and long-term impact of experimental results.

Understanding species’ elevational distributions in mountain ecosystems is needed under climate change, but remote biodiverse mountain areas may be poorly documented. National Forest Inventories (NFIs) offer a potential source of data. We used NFI records from Bhutan to ask three questions about elevational richness patterns of Himalayan woody plant species. First, does the mean elevation for all species differ from those species whose entire elevational distribution is recorded in the survey? Second, how does the elevation of maximum richness differ when combining species originating from temperate and tropical regions vs. analyzing them separately? And third, do the highest species turnover rates adjoin elevation zones of maximum species richness? We used 32,198 species records from 1685 forest plots along a 7570 m gradient to map species elevation ranges. Species whose entire range was documented were those whose lowest records are located above 400 m, while bare rock defined all species’ upper limits. We calculated species richness and turnover using 400 m elevation bands. Of 569 species, 79% of temperate and 61% of tropical species’ elevation ranges were fully sampled within the NFI data. Mean elevation of tree and shrub species differed significantly for temperate and tropical species. Maximum combined species richness is from 1300 to 1700 m (277 species), differing significantly from maximum tropical (900–1300 m, 169) and temperate species richness (2500–2900 m, 92). Temperate tree turnover rate was highest in the bands adjoining its maximum species richness (2500–2900 m). But turnover for tropical trees was highest several bands above their maximum species richness, where turnover and decrease in richness interact. Shrub species turnover patterns are similar, but rates were generally higher than for trees. Bhutan’s NFI records show that woody plant species are arrayed on the Himalaya in part according to floristic origins, and that combining temperate- and tropical-originating floras for gradient-based studies such as species richness and turnover obscures actual elevational patterns. In addition, species whose ranges extend below the Himalayan elevation gradient should be accounted for in future studies that correlate climate and environment factors with elevational species richness patterns.

We perform the first simultaneous Bayesian parameter inference and optimal reconstruction of the gravitational lensing of the cosmic microwave background (CMB), using 100 deg2 of polarization observations from the SPTpol receiver on the South Pole Telescope. These data reach noise levels as low as 5.8 µK arcmin in polarization, which are low enough that the typically used quadratic estimator (QE) technique for analyzing CMB lensing is significantly suboptimal. Conversely, the Bayesian procedure extracts all lensing information from the data and is optimal at any noise level. We infer the amplitude of the gravitational lensing potential to be A f =0.949\,\pm \,0.122 using the Bayesian pipeline, consistent with our QE pipeline result, but with 17% smaller error bars. The Bayesian analysis also provides a simple way to account for systematic uncertainties, performing a similar job as frequentist "bias hardening"or linear bias correction, and reducing the systematic uncertainty on A f due to polarization calibration from almost half of the statistical error to effectively zero. Finally, we jointly constrain A f along with A L, the amplitude of lensing-like effects on the CMB power spectra, demonstrating that the Bayesian method can be used to easily infer parameters both from an optimal lensing reconstruction and from the delensed CMB, while exactly accounting for the correlation between the two. These results demonstrate the feasibility of the Bayesian approach on real data, and pave the way for future analysis of deep CMB polarization measurements with SPT-3G, Simons Observatory, and CMB-S4, where improvements relative to the QE can reach 1.5 times tighter constraints on A f and seven times lower effective lensing reconstruction noise.

From 2005 to 2018, among 32013 adults with human immunodeficiency virus entering care, median time to antiretroviral therapy (ART) prescription declined from 69 to 6 days, CD4 count at entry into care increased from 300 to 362 cells/μL, and CD4 count at ART prescription increased from 160 to 364 cells/μL.

Landscape connectivity improves species’ capacity to adapt to climate change. These models are increasingly needed and available for climate-change conservation planning. However, their relative strengths and weaknesses are unclear. We asked how well do the spatial outputs from four connectivity models intended to support climate change conservation agree? To understand the implications of selecting one or several approaches, we compared various combinations of four connectivity models for ecoregions in California, U.S.A. Two models are based on landscape structure, Land Facet Corridors and Omniscape, while two other models, Meta-Corridor Approach and Network Flow Analysis (NFA), use focal species’ range dynamics to determine connectivity. We also describe how each approach integrates climate-adaptive connectivity concepts. Variation in modeling methods, objectives, inputs, and landscape representations strongly affects the modeled connectivity patterns. For the region where all four models were run, almost three quarters of the landscape was selected by one or more models, but three or more agree for only 9.5% of the area, all of which is riparian. This emphasizes the importance of riparian areas for climate adaptation. We found NFA prioritized connections close to protected areas, while Meta-Corridor avoided higher cost agricultural and developed areas. The structural models agreed in areas with low human impact but Omniscape avoided areas of low topographic diversity and Land Facet Corridors avoided connections in areas with no protected areas. Connectivity models should be selected based on the conservation objectives, such as spatial scale to be implemented, and a combination of models may be best.

BackgroundUnderstanding advances in the care and treatment of adults with HIV as well as remaining gaps requires comparing differences in mortality between persons entering care for HIV and the general population.ObjectiveTo assess the extent to which mortality among persons entering HIV care in the United States is elevated over mortality among matched persons in the general U.S. population and trends in this difference over time.DesignObservational cohort study.SettingThirteen sites from the U.S. North American AIDS Cohort Collaboration on Research and Design.Participants82 766 adults entering HIV clinical care between 1999 and 2017 and a subset of the U.S. population matched on calendar time, age, sex, race/ethnicity, and county using U.S. mortality and population data compiled by the National Center for Health Statistics.MeasurementsFive-year all-cause mortality, estimated using the Kaplan-Meier estimator of the survival function.ResultsOverall 5-year mortality among persons entering HIV care was 10.6%, and mortality among the matched U.S. population was 2.9%, for a difference of 7.7 (95% CI, 7.4 to 7.9) percentage points. This difference decreased over time, from 11.1 percentage points among those entering care between 1999 and 2004 to 2.7 percentage points among those entering care between 2011 and 2017.LimitationMatching on available covariates may have failed to account for differences in mortality that were due to sociodemographic factors rather than consequences of HIV infection and other modifiable factors.ConclusionMortality among persons entering HIV care decreased dramatically between 1999 and 2017, although those entering care remained at modestly higher risk for death in the years after starting care than comparable persons in the general U.S. population.Primary funding sourceNational Institutes of Health.

Time-resolved crystallography of biomolecules in action has advanced rapidly as methods for serial crystallography have improved, but the large number of crystals and the complex experimental infrastructure that are required remain serious obstacles to its widespread application. Here, millisecond mix-and-quench crystallography (MMQX) has been developed, which yields millisecond time-resolved data using far fewer crystals and routine remote synchrotron data collection. To demonstrate the capabilities of MMQX, the conversion of oxaloacetic acid to phosphoenolpyruvate by phosphoenolpyruvate carboxy-kinase (PEPCK) is observed with a time resolution of 40 ms. By lowering the entry barrier to time-resolved crystallography, MMQX should enable a broad expansion in structural studies of protein dynamics.

The many Gondwanic vegetation types found across the extensive latitudes and elevation gradients of South America's southern cone contribute to Chile's global biodiversity hotspot ranking. Species loss in global biodiversity hotspots is an ongoing climate change concern and land managers need spatially explicit climate risk maps to adapt conservation strategies to climate change in these areas. We modeled future climate risk for Chile's terrestrial vegetation using a high-resolution vegetation map and tested the relationship to climate risk for each type's latitudinal and elevation range. We found that 43.6% of all vegetation has high climate risk in Global Circulation Models (GCMs) under a high emissions scenario (RCP8.5). All forest types in the country, including Southern Beech (Nothofagus sp.), Alerce (Fitzroya cupressoides), Araucaria (Araucaria araucana), and Sclerophyllous, as well as the Valdivian rainforest, Altiplanic Steppes, and Salares, face high levels of climate risk. Tests for trends in risk across elevation and latitude showed that exposure for all types increased with elevation based on the MIROC5 GCM, and decreased with latitude based on the Had2GEM-ES GCM. Our results suggest that vegetation types with smaller latitudinal ranges typically have higher levels of climate risk, but a type's elevation range is not significantly correlated with risk of exposure. We identified climatically stable areas which could act as vegetation refugia in Patagonia, the central Andes mountains between latitudes 27.5°S and 32.5°S, and some coastal areas. Conservation strategies in Chile should include the protection of climatically stable areas to safeguard current Gondwanic biodiversity and active habitat restoration in climatically exposed areas to facilitate vegetation shifts.

We study an analog of Serre's modularity conjecture for projective representations [Formula: see text], where K is a totally real number field. We prove cases of this conjecture when [Formula: see text].

BackgroundPersons with HIV (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk.MethodsIn six US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (Years 2-5) and long-term (Years 6-11) suppression and lowest pre-suppression CD4 count 500 cells/μL had an aIRR of 1.44 during early suppression (95% CI 1.01-2.06), and 1.67 (1.03-2.72) during long-term suppression. Among patients with lowest pre-suppression CD4 ≥200 (56%), patients with current CD4 351-500 versus >500 cells/μL had an aIRR of 1.22 (0.93-1.60) during early suppression and 2.09 (1.18-3.70) during long-term suppression.ConclusionsVirologically suppressed patients with lower CD4 counts experienced higher hospitalization rates, and could potentially benefit from targeted clinical management strategies.

Mapping the elderly population exposure to heat hazard in urban areas is important to inform adaptation strategies for increasingly-deadly urban heat under climate change. However, fine-scale mapping is lacking, because global climate change projections have not previously been integrated with urban heat island effects especially with urban three-dimensional characteristics for within-city heat risk analyses. This study compared the spatial patterns of deadly heat exposure for elderly populations in two East Asian megacities, Seoul and Tokyo, using current climate (2006–2015) and two future periods (2040s and 2090s). We integrated global warming projections (the Shared Socioeconomic Pathway 5 based on Representative Concentration Pathway 8.5) with local urban characteristics and demographics. We found that, for the historical period, the overall hotspots of elderly population exposure to urban heat was larger in Tokyo because of relatively higher maximum air temperatures and lack of green spaces, whereas in the future periods, Seoul will have larger hotspots because the elderly population density will have increased. About 20% of the area in Seoul and 0.3–1% of Tokyo will be hotpots in the 2040s, and the size of these hotspots increases to 25–26% and 2–3%, respectively, in the 2090s. The spatial patterns of hotspots identify different types of priority areas and suggest that alternative adaptation strategies for two cities are appropriate. The approach introduced here will be useful for identifying sustainable thermal environments in other cities with high density elderly population and severe heat hazard.