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Although substantial advances in predicting the ecological impacts of global change have been made, predictions of the evolutionary impacts have lagged behind. In soil ecosystems, microbes act as the primary energetic drivers of carbon cycling; however, microbes are also capable of evolving on timescales comparable to rates of global change. Given the importance of soil ecosystems in global carbon cycling, we assess the potential impact of microbial evolution on carbon-climate feedbacks in this system. We begin by reviewing the current state of knowledge concerning microbial evolution in response to global change and its specific effect on soil carbon dynamics. Through this integration, we synthesize a roadmap detailing how to integrate microbial evolution into ecosystem biogeochemical models. Specifically, we highlight the importance of microscale mechanistic soil carbon models, including choosing an appropriate evolutionary model (e.g., adaptive dynamics, quantitative genetics), validating model predictions with ‘omics’ and experimental data, scaling microbial adaptations to ecosystem level processes, and validating with ecosystem-scale measurements. The proposed steps will require significant investment of scientific resources and might require 10–20 years to be fully implemented. However, through the application of multi-scale integrated approaches, we will advance the integration of microbial evolution into predictive understanding of ecosystems, providing clarity on its role and impact within the broader context of environmental change.

Juvenile myelomonocytic leukemia (JMML) is a hematologic malignancy of young children caused by mutations that increase Ras signaling output. Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment, but patients with relapsed or refractory (advanced) disease have dismal outcomes. This phase II trial evaluated the safety and efficacy of trametinib, an oral MEK1/2 inhibitor, in patients with advanced JMML. Ten infants and children were enrolled, and the objective response rate was 50%. Four patients with refractory disease proceeded to HSCT after receiving trametinib. Three additional patients completed all 12 cycles permitted on study and continue to receive off-protocol trametinib without HSCT. The remaining three patients had progressive disease with two demonstrating molecular evolution by the end of cycle 2. Transcriptomic and proteomic analyses provided novel insights into the mechanisms of response and resistance to trametinib in JMML. ClinicalTrials.gov Identifier: NCT03190915. Significance: Trametinib was safe and effective in young children with relapsed or refractory JMML, a lethal disease with poor survival rates. Seven of 10 patients completed the maximum 12 cycles of therapy or used trametinib as a bridge to HSCT and are alive with a median follow-up of 24 months.

The global population consumes more seafood from aquaculture today than from capture fisheries and although the aquaculture industry continues to grow, both seafood sectors will continue to be important to the global food supply into the future. As farming continues to expand into ocean systems, understanding how wild populations and fisheries will interact with farms will be increasingly important to informing sustainable ocean planning and management. Using a spatially explicit population and fishing model we simulate several impacts from ocean aquaculture (i.e., aggregation, protection from fishing, and impacts on fitness) to evaluate the mechanisms underlying interactions between aquaculture, wild populations and fisheries. We find that aggregation of species to farms can increase the benefits of protection from fishing that a farm provides and can have greater impacts on more mobile species. Splitting total farm area into smaller farms can benefit fishery catches, whereas larger farms can provide greater ecological benefits through conservation of wild populations. Our results provide clear lessons on how to design and co-manage expanding ocean aquaculture along with wild capture ecosystem management to benefit fisheries or conservation objectives.

Soil microbiomes are heterogeneous, complex microbial communities. Metagenomic analysis is generating vast amounts of data, creating immense challenges in sequence assembly and analysis. Although advances in technology have resulted in the ability to easily collect large amounts of sequence data, soil samples containing thousands of unique taxa are often poorly characterized. These challenges reduce the usefulness of genome-resolved metagenomic (GRM) analysis seen in other fields of microbiology, such as the creation of high quality metagenomic assembled genomes and the adoption of genome scale modeling approaches. The absence of these resources restricts the scale of future research, limiting hypothesis generation and the predictive modeling of microbial communities. Creating publicly available databases of soil MAGs, similar to databases produced for other microbiomes, has the potential to transform scientific insights about soil microbiomes without requiring the computational resources and domain expertise for assembly and binning.

Deadwood is an important yet understudied carbon pool in tropical ecosystems. Deadwood degradation to CO2 through decomposer (microbial, termite) activities is driven by wood moisture and temperature, which are in turn strongly influenced by local climate. Thus, climate data could be used to predict CO2 fluxes from decaying wood. Given the increasing availability of gridded climate data, this link would allow for the rapid estimation of deadwood-related CO2 fluxes from tropical ecosystems worldwide. In this study, we adapted a mechanistic fuel moisture model that uses weather variables (e.g., air temperature, precipitation, solar radiation) to simulate wood moisture and temperature along a rainfall gradient in Queensland, Australia. We then developed a Bayesian statistical relationship between wood moisture and temperature and CO2 flux from pine (Pinus radiata) blocks and combined this relationship with our simulations to predict CO2 fluxes from deadwood at 1 h temporal resolution. We compared our pine-based simulations to the moisture-CO2 relationships from stems of native tree species deployed at the wettest and driest sites. Finally, we integrated fluxes over time to estimate the amount of carbon entering the atmosphere and compared these estimates to measured mass loss in pines and native stems. Our statistical model showed a positive relationship between CO2 fluxes and wood moisture and temperature. Comparing cumulative CO2 with wood mass loss, we observed that carbon from deadwood decomposition is mainly released as CO2 regardless of the precipitation regime. At the dry savanna, only about 20 % of the wood mass loss was decomposed within 48 months, compared to almost 100 % at the wet rainforest, suggesting longer residence times of deadwood compared to wetter sites. However, the amount of carbon released in situ as CO2 is lower when wood blocks are attacked by termites, especially at drier sites. These results highlight the important but understudied role of t

An important open problem in supersingular isogeny-based cryptography is to produce, without a trusted authority, concrete examples of ‘hard supersingular curves’ that is equations for supersingular curves for which computing the endomorphism ring is as difficult as it is for random supersingular curves. A related open problem is to produce a hash function to the vertices of the supersingular $ell $-isogeny graph, which does not reveal the endomorphism ring, or a path to a curve of known endomorphism ring. Such a hash function would open up interesting cryptographic applications. In this paper, we document a number of (thus far) failed attempts to solve this problem, in the hope that we may spur further research, and shed light on the challenges and obstacles to this endeavour. The mathematical approaches contained in this article include: (i) iterative root-finding for the supersingular polynomial; (ii) gcd’s of specialized modular polynomials; (iii) using division polynomials to create small systems of equations; (iv) taking random walks in the isogeny graph of abelian surfaces, and applying Kummer surfaces and (v) using quantum random walks., info:eu-repo/semantics/published

The unique conditions within the circumstellar envelopes (CSEs) of asymptotic giant branch (AGB) stars facilitate the formation of radical species and other complex molecules. While some of these molecules are destroyed within the envelope, their remnants contribute to the broader molecular lifecycle. Molecules containing the NCHOPS elements, those essential for life, are of particular interest in astrochemistry. This work presents millimeter-wave observations of CSEs and molecular clouds conducted using the Arizona Radio Observatory (ARO) 12-m and Submillimeter Telescope (SMT) to identify new interstellar molecules containing NCHOPS and other astrochemically relevant elements, as well as to examine elemental abundance gradients. Phosphorus monoxide (PO) was identified for the first time in the star-forming region Orion-KL through analysis of a 3 mm spectral line survey obtained with the ARO 12-m. By examining the line profile and LSR velocity of PO, the molecule was localized to the Plateau region of Orion-KL, providing additional evidence that shock chemistry plays a role in the formation of phosphorus molecules. Additionally, 3, 2, and 1 mm spectral line surveys were conducted towards the carbon-rich envelope of the AGB star IRC+10216 using both the 12-m and SMT telescopes. These sensitive surveys allowed for the detection of very weak rotational lines, leading to the identification of two new interstellar molecules: SiP, a phosphorus-bearing radical, and FeC, the first metal carbide (in the chemist’s sense) detected in the interstellar medium. Both molecules were found in shell distributions within the envelope of IRC+10216, with formation mechanisms likely tied to shock chemistry. To explore the molecular content of the Outer Galaxy, observations were conducted towards Galactic Edge Clouds using the ARO 12-m and IRAM 30-m telescopes. PO and PN were identified in the Edge Cloud WB89-621, located 22.6 kiloparsecs (kpc) from the Galactic Center. This discovery rep

We used morphological and molecular surveys to determine the presence or absence of Notodendrodes antarctikos and its congener, Notodendrodes hyalinosphaira, at diverse sites within McMurdo Sound, Antarctica. Morphological surveys were performed using shipboard box-core sampling, as well as handheld coring and visual inspection by divers in shallow (< 23 m) waters. Concurrent molecular analyses were performed using species- and genus-specific PCR primers on environmental DNA extracts. Both survey methods show that N. hyalinosphaira is widely distributed in the region but that N. antarctikos was not detected outside its originally reported range. The survey methods show complementary strengths and weaknesses, with morphological detection being more sensitive in areas where large and distinctive adult forms are present and with molecular detection being more effective for identification of presumed juvenile or propagule stages. Our results suggest that N. antarctikos is a highly endemic protist and may have one of the most restricted ranges ever reported for an Antarctic organism.

Mammalian pregnancy requires gradual yet extreme remodeling of the reproductive organs to support the growth of the embryos and their birth. After delivery, the reproductive organs return to their non-pregnant state. As pregnancy has traditionally been understudied, there are many unknowns pertaining to the mechanisms behind this remarkable remodeling and repair process which, when not successful, can lead to pregnancy-related complications such as maternal trauma, pre-term birth, and pelvic floor disorders. This study presents the first longitudinal imaging data that focuses on revealing anatomical alterations of the vagina, cervix, and uterine horns during pregnancy and postpartum using the mouse model. By utilizing advanced magnetic resonance imaging (MRI) technology, T1-weighted and T2-weighted images of the reproductive organs of three mice in their in vivo environment were collected at five time points: non-pregnant, mid-pregnant (gestation day: 9–10), late pregnant (gestation day: 16–17), postpartum (24–72 h after delivery) and three weeks postpartum. Measurements of the vagina, cervix, and uterine horns were taken by analyzing MRI segmentations of these organs. The cross-sectional diameter, length, and volume of the vagina increased in late pregnancy and then returned to non-pregnant values three weeks after delivery. The cross-sectional diameter of the cervix decreased at mid-pregnancy before increasing in late pregnancy. The volume of the cervix peaked at late pregnancy before shortening by 24–72 h postpartum. As expected, the uterus increased in cross-sectional diameter, length, and volume during pregnancy. The uterine horns decreased in size postpartum, ultimately returning to their average non-pregnant size three weeks postpartum. The newly developed methods for acquiring longitudinal in vivo MRI scans of the murine reproductive system can be extended to future studies that evaluate functional and morphological alterations of this system due to patholog

Public value and city governance are fundamental notions in contemporary settings, but, currently conceived, they are not fit for the challenges presented by the proposed new epoch of geological time – the Anthropocene. Walking through the locked-down streets or calle of Venice, we face the sudden emptiness that starkly reveals the impact of human activity on the city and its waterways. Reflecting on the walk, our starting point is to problematize how a city organizes and manages public value and what actually constitutes public value. In this, we develop a new definition, ‘New Public Value for the Anthropocene Epoch’ (NPVA), which expands the notion of public value through the questions: ‘who’ is it valuable to do things for, beyond humans and economic actors, building on a relational epistemology to incorporate the planet and its biosphere; and ‘what’ is valuable to do, in order to ensure the inclusion of social, environmental, and cultural values alongside economic values. We conclude by arguing that NPVA is organized across scales in a manner that embeds global attentiveness towards local ecosystems solutions to drive the global response to the environmental crisis we all face.

Background:There is no standard definition of respiratory-related hospitalisation, a common end-point in idiopathic pulmonary fibrosis (IPF) clinical trials. As diverse aetiologies and complicating comorbidities can present similarly, external adjudication is sometimes employed to achieve standardisation of these events. Methods:An algorithm for respiratory-related hospitalisation was developed through a literature review of IPF clinical trials with respiratory-related hospitalisation as an end-point. Experts reviewed the algorithm until a consensus was reached. The algorithm was validated using data from the phase 3 ISABELA trials (clinicaltrials.gov identifiers NCT03711162 and NCT03733444), by assessing concordance between nonadjudicated, investigator-defined, respiratory-related hospitalisations and those defined by the adjudication committee using the algorithm. Results:The algorithm classifies respiratory-related hospitalisation according to cause: extraparenchymal (worsening respiratory symptoms due to left heart failure, volume overload, pulmonary embolism, pneumothorax or trauma); other (respiratory tract infection, right heart failure or exacerbation of COPD); “definite” acute exacerbation of IPF (AEIPF) (worsening respiratory symptoms within 1 month, with radiological or histological evidence of diffuse alveolar damage); or “suspected” AEIPF (as for “definite” AEIPF, but with no radiological or histological evidence of diffuse alveolar damage). Exacerbations (“definite” or “suspected”) with identified triggers (infective, post-procedural or traumatic, drug toxicity-or aspiration-related) are classed as “known AEIPF”; “idiopathic AEIPF” refers to exacerbations with no identified trigger. In the ISABELA programme, there was 94% concordance between investigator-and adjudication committee-determined causes of respiratory-related hospitalisation. Conclusion:The algorithm could help

Microbes are essential for the functioning of all ecosystems, and as global warming and anthropogenic pollution threaten ecosystems, it is critical to understand how microbes respond to these changes. We investigated the climate response of Sphingomonas, a widespread gram-negative bacterial genus, during an 18-month microbial community reciprocal transplant experiment across a Southern California climate gradient. We hypothesized that after 18 months, the transplanted Sphingomonas clade and functional composition would correspond with site conditions and reflect the Sphingomonas composition of native communities. We extracted Sphingomonas sequences from metagenomic data across the gradient and assessed their clade and functional composition. Representatives of at least 12 major Sphingomonas clades were found at varying relative abundances along the climate gradient, and transplanted Sphingomonas clade composition shifted after 18 months. Site had a significant effect (PERMANOVA; P < 0.001) on the distribution of both Sphingomonas functional (R2 = 0.465) and clade composition (R2 = 0.400), suggesting that Sphingomonas composition depends on climate parameters. Additionally, for both Sphingomonas clade and functional composition, ordinations revealed that the transplanted communities shifted closer to the native Sphingomonas composition of the grassland site compared with the site they were transplanted into. Overall, our results indicate that climate and substrate collectively determine Sphingomonas clade and functional composition.IMPORTANCESphingomonas is the most abundant gram-negative bacterial genus in litter-degrading microbial communities of desert, grassland, shrubland, and forest ecosystems in Southern California. We aimed to determine whether Sphingomonas responds to climate change in the same way as gram-positive bacteria and whole bacterial communities in these ecosystems. Within Sphingomonas, both clade composition and functional genes shifted in resp

Clinics are very important as they offer treatment and are equipped with medical equipment, which helps in the diagnosis and treatment of many types of diseases. A good and organized filing system is also crucial for clinics, as it ensures the proper filing of patient's medical records and facilitates easy retrieval, contributing to the decreased waiting time for patients. School Health Services are developed on the school grounds to promote the health of students and employees through disease prevention. The clinic services offered by ABC School include Telemedicine and Teleconsult Services, Dental Services, and Medical Services for students and employees. In this Feasibility Study, our team aims to improve the proper filing and procedures of services in the clinic of ABC School. As the school is considering face-to-face classes with limited restrictions, it is essential to be prepared and ensure the safety of every student and employee. Since schools bring together a large number of students and staff, a system must be in place to handle their documents and records[1]. The ABC School Clinic is effective in managing the health of its staff and students. However, they struggle with organizing their records, which are currently only available in hard copy, such as book records, folders, and forms. The pandemic has made their work more challenging, as they need to quickly respond to the health needs of those attending the school, ensuring that no one has symptoms of Covid-19 and conducting contact tracing, which requires proper record-keeping. To gather data for this feasibility study, we interviewed the head nurse to learn about their filing system and service procedures, particularly during the pandemic. We also conducted a survey with a few ABC School clinic personnel to understand their issues and address their needs. Keeping these documents for future reference is crucial, as they help in organizing, systematizing, and ensuring efficiency and transparency. In thi

Since the insights by Charles Darwin, heterostyly, a floral polymorphism with morphs bearing stigmas and anthers at reciprocal heights, has become a model system for the study of natural selection. Based on his archetypal heterostylous flower, including regular symmetry, few stamens and a tube, Darwin hypothesised that heterostyly evolved to promote outcrossing through efficient pollen transfer between morphs involving different areas of a pollinator’s body, thus proposing his seminal pollination-precision hypothesis. Here we update the number of heterostylous and other style-length polymorphic taxa to 247 genera belonging to 34 families, notably expanding known cases by 20%. Using phylogenetic and comparative analyses across the angiosperms, we show numerous independent origins of style-length polymorphism associated with actinomorphic, tubular flowers with a low number of sex organs, stamens fused to the corolla, and pollination by long-tongued insects. These associations provide support for the Darwinian pollination-precision hypothesis as a basis for convergent evolution of heterostyly across angiosperms.

Significant advances have been achieved through the latest improvements in the photometric observations accomplished by the recent space missions, substantially boosting the study of pulsating stars via asteroseismology. The TESS mission has already proven to be of relevance for pulsating white dwarf and pre-white dwarf stars. We report a detailed asteroseismic analysis of the pulsating PG 1159 star NGC 246 (TIC3905338), the central star of the planetary nebula NGC 246, based on high-precision photometric data gathered by the TESS space mission. We reduced TESS observations of NGC 246 and performed a detailed asteroseismic analysis using fully evolutionary PG 1159 models computed accounting for the complete prior evolution of their progenitors. We constrained the mass of this star by comparing the measured mean period spacing with the average of the computed period spacings of the models and also employed the observed individual periods to search for a seismic stellar model. We extracted 17 periodicities from the TESS light curves from the two sectors where NGC246 was observed. All the oscillation frequencies are associated with g-mode pulsations, with periods spanning from ~1460 to ~1823s. We found a constant period spacing of $\Delta\Pi= 12.9$s, allowing us to deduce that the stellar mass is larger than ~0.87 Mo if the period spacing is assumed to be associated with l= 1 modes, and ~ 0.568 Mo if it is associated with l= 2 modes. The less massive models are more consistent with the distance constraint from Gaia parallax. Although we were not able to find a unique asteroseismic model for this star, the period-to-period fit analyses suggest a high-stellar mass ($\gtrsim$0.74 Mo) when the observed periods are associated with modes with l= 1 only, and both a high ($\gtrsim$ 0.74 Mo) and intermediate (~0.57 Mo) stellar mass when the observed periods are associated with modes with l= 1 and 2., Comment: 14 pages, 11 figures. Accepted for publication in Astronomy & Astrophysics

Motivated by the stability of the electroweak Higgs vacuum we consider the possibility that the Standard Model might work up to large scales between about $10^{10}$ GeV and close to the Planck scale. A plausible scenario is an emergent Standard Model with gauge symmetries originating in some topological like phase transition deep in the ultraviolet. In this case the cosmological constant scale and neutrino masses should be of similar size, suppressed by factor of the large scale of emergence. The key physics involves a subtle interplay of Poincar\'e invariance, mass generation and renormalisation group invariance. The Higgs mass would be environmentally selected in connection with vacuum stability. Consequences for dark matter scenarios are discussed., Comment: 21 pages, Contribution to "The Particle-Gravity Frontier" theme issue in Philosophical Transactions of the Royal Society A, based on the 2022 Humboldt Kolleg in Kitzb\"uhel

Agrifood systems are facing significant challenges, science and innovation are key to shift the trajectory towards ensuring sustainability and resilience. Thus, scaling assumes a critical role in agricultural research for development (AR4D). Scaling consists of a continuous process in which innovations are tailored, used, and embedded into societal dynamics adapted to various contexts, aiming to create widespread positive impacts. This systematic literature review explores scaling within the context of AR4D, with a particular focus on the role of social capital. Using bibliometric and factor analysis methods, we identified the intellectual structure in the field of scaling, revealing the knowledge domains and disciplines that have determined their emergence and growth as a scientific discipline. Then, we analyzed the role of social capital in the scaling literature. Our results showed that the field of scaling is composed by four distinct literature clusters: the innovation and adoption of agricultural technology, the economics of technology adoption, sustainability in agricultural innovations, and the emergence of scaling as a research field. Disciplines such as sustainable agriculture, systemic thinking, technological transitions, and technology adoption have contributed to the development of the field. The results indicate that the explicit consideration of social capital in the scaling literature within AR4D is limited despite the importance of relationships, trust, and reciprocity values in the process of scaling. This study highlights the continuous growth and multidisciplinary nature of scaling as a research field in AR4D, reflecting its complexity. International agricultural research centers and universities from developed countries have significantly advanced this field, also underlying the importance of locally rooted, and participatory research. Future research on the creation, development, and strengthening of social capital in scaling processes can c

A validation methodology is proposed and implemented for natural language software specifications of standard graphics functions. Checks are made for consistency, completeness, and lack of ambiguity in data element and function descriptions. Functions and data elements are maintained in a relational database representation. The appropriate checks are performed by sequences of database operations. The relational database manager INGRES was used to support a prototype implementation of the proposed technique. The methodology supports the development of a scenario-based prototype from the information available in the specification. This permits various function sequences to be checked without implementation of the environment specified. The application of a prototype implementation of the proposed methodology to the specification of the Graphics Kernel System (GKS) software package demonstrates the practicability of the method. Several inconsistencies in GKS related to the definition of data elements have been identified.

Rationale: A phase II trial reported clinical benefit over 28 weeks in patients with idiopathic pulmonary fibrosis who received zinpentraxin alfa. Objectives: To investigate the efficacy and safety of zinpentraxin alfa in patients with idiopathic pulmonary fibrosis in a phase III trial. Methods: This 52-week phase III, double-blind, placebo-controlled, pivotal trial was conducted at 275 sites in 29 countries. Patients with idiopathic pulmonary fibrosis were randomized 1:1 to intravenous placebo or zinpentraxin alfa 10 mg/kg every four weeks. The primary endpoint was absolute change from baseline to Week 52 in forced vital capacity. Secondary endpoints included absolute change from baseline to Week 52 in percent predicted forced vital capacity and six-minute walking distance. Safety was monitored via adverse events. Post-hoc analysis of the phase II and phase III data explored changes in forced vital capacity and their impact on the efficacy results. Measurements and main results: Of 664 randomized patients, 333 were assigned to placebo and 331 to zinpentraxin alfa. Four of the 664 randomized patients were never administered study drug. The trial was terminated early following a pre-specified futility analysis that demonstrated no treatment benefit of zinpentraxin alfa over placebo. In the final analysis, absolute change from baseline to Week 52 in forced vital capacity was similar between placebo and zinpentraxin alfa (‒214.89 mL and ‒235.72 mL; P = 0.5420); there were no apparent treatment effects on secondary endpoints. Overall, 72.3% and 74.6% of patients receiving placebo and zinpentraxin alfa, respectively, experienced ≥1 adverse event. Post-hoc analysis revealed that extreme forced vital capacity decline in two placebo-treated patients resulted in the clinical benefit of zinpentraxin alfa reported by phase II. Conclusions: Zinpentraxin alfa treatment did not benefit patients with idiopathic pulmonary fibrosis over placebo. Learnings from this program may help

This publication contains data on revenues and expenditures per pupil made by school districts for school year 2007-08. Median per pupil revenue and expenditure data are reported by state, as well as values at the 5th and 95th percentiles. Data for charter schools are reported separately. There are also discussions on the different types of school districts, and other resources that may be helpful in analyzing school district level data. Revenues and expenditures for the 100 largest school districts are included, as well as federal revenues by program. Appended are methodology and technical notes and a Common Core of Data glossary. For total revenues and expenditures for public education made by states and the nation, readers should refer to the state-level "Revenues and Expenditures for Public Elementary and Secondary Education: School Year 2007-08" NCES 2010-326 (ED506358). (Contains 8 tables and 1 related data file.)

Droughts are becoming more frequent and intense with climate change. As plants and microbes respond to drought, there may be consequences for the vast stocks of organic carbon stored in soils. If microbes sustain their activity under drought, soils could lose carbon, especially if inputs from plants decline. Empirical and theoretical studies reveal multiple mechanisms of microbial drought resistance, including tolerance and avoidance. Physiological responses allow microbes to acclimate to drought within minutes to days. Along with dispersal, shifts in community composition could allow microbiomes to maintain functioning despite drought. Microbes might also adapt to drier conditions through evolutionary processes. Together, these mechanisms could result in soil carbon losses larger than currently anticipated under climate change.

This handbook has been designed as the national standard for state and local education agencies to use in tracking and reporting financial data for school districts to use in preparing their comprehensive annual financial reports (CAFRs). The purpose of the handbook is to ensure that education fiscal data can be reported in a comprehensive manner. The 2009 Edition contains guidance conforming to Governmental Accounting Standards Board Statements, up to Statement 47. There are chapters on budgeting, governmental accounting and financial reporting. Account codes have been updated to reflect changes in the new reporting requirements and developments in technology and security. There are also special chapters on accounting student activity funds and a model for school level program cost accounting. Eight chapters comprise this guide: (1) Introduction; (2) Financial Reporting Within a System of Education Information; (3) Budgeting; (4) Government Accounting; (5) Financial Reporting; (6) Account Classification Descriptions; (7) Cost Accounting and Reporting for Educational Programs; and (8) Activity Fund Guidelines. Appendices include: (1) Summary of Account Code Changes Since 2003; (2) Other Resources; (3) Glossary of Acronyms; (4) Illustrative Financial Statements for an Independent School District; and (5) Criteria for Distinguishing Equipment from Supply Items. (Contains 27 exhibits.)

The science of child development and the core capabilities of adults point to a set of "design principles" that policymakers and practitioners in many different sectors can use to improve outcomes for children and families. That is, to be maximally effective, policies and services should: (1) support responsive relationships for children and adults; (2) strengthen core life skills; and (3) reduce sources of stress in the lives of children and families. These three principles can guide decision-makers as they choose among policy alternatives, design new approaches, and shift existing practice in ways that will best support building healthy brains and bodies. They point to a set of key questions: (1) What are current policies, systems, or practices doing to address each principle?; (2) What could be done to address them better?; and (3) What barriers prevent addressing them more effectively? This science-based framework offers a promising guide for generating new ideas about how to meet the objectives of each policy or practice system more effectively--and, in the end, achieve significant improvements in outcomes for the children and families who are the foundation of our communities and our shared future. The science in this report draws principally from the work of the National Scientific Council on the Developing Child. A list of additional resources is provided. [Additional funding was provided by the Chan Zuckerberg Initiative DAF, an advised fund of the Silicon Valley Community Foundation; Genentech; Hemera Foundation; Palix Foundation; and Tikun Olam Foundation.]

To develop chemical kinetics models for the combustion of ionic liquid-based monopropellants, identification of the elementary steps in the thermal and catalytic decomposition of components such as 2-hydroxyethylhydrazinium nitrate (HEHN) is needed but is currently not well understood. The first decomposition step in protic ionic liquids such as HEHN is typically the proton transfer from the cation to the anion, resulting in the formation of 2-hydroxyethylhydrazine (HEH) and HNO3. In the first part of this investigation, the high-temperature thermal decomposition of HEH is probed with flash pyrolysis (<1400 K) and vacuum ultraviolet (10.45 eV) photoionization time-of-flight mass spectrometry (VUV-PI-TOFMS). Next, the investigation into the thermal and catalytic decomposition of HEHN includes two mass spectrometric techniques: (1) tunable VUV-PI-TOFMS (7.4-15 eV) and (2) ambient ionization mass spectrometry utilizing both plasma and laser ionization techniques whereby HEHN is introduced onto a heated inert or iridium catalytic surface and the products are probed. The products can be identified by their masses, their ionization energies, and their collision-induced fragmentation patterns. Formation of product species indicates that catalytic surface recombination is an important reaction process in the decomposition mechanism of HEHN. The products and their possible elementary reaction mechanisms are discussed.

The "gunsight approach" was initially described as the use of overlapping snares and through- and-through puncture of the portal vein and inferior vena cava for the creation of a transcaval portosystemic shunt. This technique can be adapted for the creation of an extra-anatomic chan- nel between any 2 locations where snares can be deployed. We explain the technique, discuss finer technical points, and describe 2 cases where refractory vascular occlusions are crossed using this technique. The first case involves an extensively calcified femoral arterial chronic total occlusion where subintimal tracking past the occlusion is achieved, but luminal re-entry is ham- pered by dense calcific plaque refractory to multiple re-entry devices. The second case involves a chronic venous occlusion along the femoral vein with loss of in-line flow due to prior stenting. In both cases, the gunsight technique was successfully used as a bailout option after standard recanalization techniques were unsuccessful.

Renal cell carcinomas present with locally advanced or metastatic disease in 25% of patients. Thermal ablation may be considered in selected patients with single-site or oligometastatic disease in selected patients. We describe single-session transarterial particle embolization with the assistance of a balloon-occlusion catheter and microwave ablation of a large hypervascular adrenal metastasis using cone beam CT and fluoroscopic XperGuide needle guidance.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Background: Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of infants and toddlers. Upfront therapies typically include high-dose cytarabine or azacitidine, but the only definitive treatment is hematopoietic stem cell transplantation (HSCT). While HSCT cures ~50% of patients, the prognosis is dismal for those who relapse. In the absence of a second HSCT, patients who relapse have a 2-year overall survival of ~10%. JMML is initiated by germline and somatic driver mutations in NF1, KRAS, NRAS, PTPN11, and CBL. These mutations converge on Ras signaling, leading to elevated levels of active Ras-GTP in specific cell lineages. Genetically engineered mouse (GEM) models accurately model key molecular, biologic, and biochemical features of JMML. Preclinical trials of the allosteric MEK inhibitors in Kras and Nf1 mutant mice demonstrated dramatic phenotypic responses with reduction in white blood cell counts, resolution of splenomegaly, and reversion to normal erythropoiesis. Based on the promising efficacy signal in GEM models, we evaluated trametinib, an orally bioavailable allosteric inhibitor of MEK1/2, in a prospective clinical trial in children with relapsed or refractory JMML to determine the overall response rate to trametinib. Results: Ten infants and children with JMML (median age 23.6 months) were enrolled and all were evaluable for safety and efficacy. Patients received age-adjusted dosing of trametinib for 28-day cycles and could remain on study for up to 12 cycles in the absence of disease progression or toxicity. A clonal Ras pathway mutation was confirmed in the blood and/or bone marrow of all patients. The objective response rate was 50% (two complete and three partial clinical responses). Four patients proceeded to HSCT after receiving protocol therapy and remain alive in complete remission with undetectable levels of the Ras pathway mutation identified at enrollment. Three additional patients completed 12 cycles of tram

Growth is an important toxicity end-point in ecotoxicology but is rarely used in soil ecotoxicological studies. Here, we assessed the growth change of Oppia nitens when exposed to reference and heavy metal toxicants. To assess mite growth, we developed an image analysis methodology to measure colour spectrum changes of the mite integument at the final developmental stage, as a proxy for growth change. We linked the values of red, green, blue, key-black, and light colour of mites to different growth stages. Based on this concept, we assessed the growth change of mites exposed to cadmium, copper, zinc, lead, boric acid, or phenanthrene at sublethal concentrations in LUFA 2.2 soil for 14 days. Sublethal effects were detected after 7 days of exposure. The growth of O. nitens was more sensitive than survival and reproduction when exposed to copper (EC50growth = 1360 mg/kg compared to EC50reproduction = 2896 mg/kg). Mite growth sensitivity was within the same order of magnitude to mite reproduction when exposed to zinc (EC50growth = 1785; EC50reproduction = 1562 mg/kg). At least 25% of sublethal effects of boric acid and phenanthrene were detected in the mites but growth was not impacted when O. nitens were exposed to lead. Consistent with previous studies, cadmium was the most toxic metal to O. nitens. The mite growth pattern was comparable to mite survival and reproduction from previous studies. Mite growth is a sensitive toxicity endpoint, ecologically relevant, fast, easy to detect, and can be assessed in a non-invasive fashion, thereby complimenting existing O. nitens testing protocols.

Atmospheric nitrogen (N) deposition is enriching soils with N across biomes. Soil N enrichment can increase plant productivity and affect microbial activity, thereby increasing soil organic carbon (SOC), but such responses vary across biomes. Drylands cover ~45% of Earth's land area and store ~33% of global SOC contained in the top 1 m of soil. Nitrogen fertilization could, therefore, disproportionately impact carbon (C) cycling, yet whether dryland SOC storage increases with N remains unclear. To understand how N enrichment may change SOC storage, we separated SOC into plant-derived, particulate organic C (POC), and largely microbially derived, mineral-associated organic C (MAOC) at four N deposition experimental sites in Southern California. Theory suggests that N enrichment increases the efficiency by which microbes build MAOC (C stabilization efficiency) if soil pH stays constant. But if soils acidify, a common response to N enrichment, then microbial biomass and enzymatic organic matter decay may decrease, increasing POC but not MAOC. We found that N enrichment had no effect on C fractions except for a decrease in MAOC at one site. Specifically, despite reported increases in plant biomass in three sites and decreases in microbial biomass and extracellular enzyme activities in two sites that acidified, POC did not increase. Furthermore, microbial C use and stabilization efficiency increased in a non-acidified site, but without increasing MAOC. Instead, MAOC decreased by 16% at one of the sites that acidified, likely because it lost 47% of the exchangeable calcium (Ca) relative to controls. Indeed, MAOC was strongly and positively affected by Ca, which directly and, through its positive effect on microbial biomass, explained 58% of variation in MAOC. Long-term effects of N fertilization on dryland SOC storage appear abiotic in nature, such that drylands where Ca-stabilization of SOC is prevalent and soils acidify, are most at risk for significant C loss.

Item does not contain fulltext, AIMS: The aim of this TeleCheck-AF sub-analysis was to evaluate motivation and adherence to on-demand heart rate/rhythm monitoring app in patients with atrial fibrillation (AF). METHODS AND RESULTS: Patients were instructed to perform 60 s app-based heart rate/rhythm recordings 3 times daily and in case of symptoms for 7 consecutive days prior to teleconsultation. Motivation was defined as number of days in which the expected number of measurements (≥3/day) were performed per number of days over the entire prescription period. Adherence was defined as number of performed measurements per number of expected measurements over the entire prescription period.Data from 990 consecutive patients with diagnosed AF [median age 64 (57-71) years, 39% female] from 10 centres were analyzed. Patients with both optimal motivation (100%) and adherence (≥100%) constituted 28% of the study population and had a lower percentage of recordings in sinus rhythm [90 (53-100%) vs. 100 (64-100%), P < 0.001] compared with others. Older age and absence of diabetes were predictors of both optimal motivation and adherence [odds ratio (OR) 1.02, 95% coincidence interval (95% CI): 1.01-1.04, P < 0.001 and OR: 0.49, 95% CI: 0.28-0.86, P = 0.013, respectively]. Patients with 100% motivation also had ≥100% adherence. Independent predictors for optimal adherence alone were older age (OR: 1.02, 95% CI: 1.00-1.04, P = 0.014), female sex (OR: 1.70, 95% CI: 1.29-2.23, P < 0.001), previous AF ablation (OR: 1.35, 95% CI: 1.03-1.07, P = 0.028). CONCLUSION: In the TeleCheck-AF project, more than one-fourth of patients had optimal motivation and adherence to app-based heart rate/rhythm monitoring. Older age and absence of diabetes were predictors of optimal motivation/adherence.

DISCLOSURES: Funding for this summary was contributed by Blue Cross Blue Shield of MA, California Healthcare Foundation, The Patrick and Catherine Weldon Donaghue Medical Research Foundation, Arnold Ventures, and Kaiser Foundation Health Plan Inc., to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, AbbVie, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy Solutions, Express Scripts, Genentech/ Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health First, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer. Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, Sun Life Financial, uniQure, and United Healthcare. Mr Nikitin, Ms McKenna, Ms Richardson, and Drs Rind and Pearson are employed by ICER. Through their affiliated institutions, Drs Makam, Carlson, and Suh received funding from ICER for the work described in this summary.

Despite much progress, image processing remains a significant bottleneck for high-throughput analysis of microscopy data. One popular platform for single-cell time-lapse imaging is the mother machine, which enables long-term tracking of microbial cells under precisely controlled growth conditions. While several mother machine image analysis pipelines have been developed in the past several years, adoption by a non-expert audience remains a challenge. To fill this gap, we implemented our own software, MM3, as a plugin for the multidimensional image viewer napari. napari-MM3 is a complete and modular image analysis pipeline for mother machine data, which takes advantage of the high-level interactivity of napari. Here, we give an overview of napari-MM3 and test it against several well-designed and widely-used image analysis pipelines, including BACMMAN and DeLTA. In addition, the rapid adoption and widespread popularity of deep-learning methods by the scientific community raises an important question: to what extent can users trust the results generated by such "black box" methods? We explicitly demonstrate "What You Put Is What You Get" (WYPIWYG); i.e., the image analysis results can reflect the user bias encoded in the training dataset. Finally, while the primary purpose of this work is to introduce the image analysis software that we have developed over a decade in our lab, we also provide useful information for those who want to implement mother-machine-based high-throughput imaging and image analysis methods in their research. This includes our guiding principles and best practices to ensure transparency and reproducible results.