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Extension professionals face challenges in quantifying the impact of their efforts in advancing the decision-making process inherent in setting natural resources policy. We developed a flexible tool that measures the impact of improving decision makers' planning efforts. The tool consists of two sets of survey questions that can be modified to fit an Extension program's goals. We illustrated how to use the tool by surveying leaders working with private forest owners to advance natural resources management. However, the tool can be of use to Extension professionals across various program areas.

Abstract Overstory trees serve multiple functions in grassy savannas. Past research has shown that understory species can vary along gradients of canopy cover and basal area in savannas. This variation is frequently associated with light availability but could also be related to other mechanisms, such as heterogeneity in soil and litter depth and fire intensity. Several savanna studies have found differences in understory plant functional groups within the local environment near trees versus away from them in canopy openings. Although small‐scale variation is known to be high in southeastern U.S. pine savannas, patterns in understory species diversity have not been examined at the scale of individual overstory pine trees in this system. We conducted an observational study of the relationship between understory plant communities and proximity to individual pine trees in xeric and mesic pine savannas in frequently burned sites (1–3 year intervals). We recorded the plant community composition in plots adjacent to tree boles (basal) or outside crown driplines (open). Within each environment, raw species richness was significantly greater in open locations, where light transmittance was greater. In contrast, rarified species richness did not differ. Multivariate analyses showed that community composition differed significantly between basal and open plots. One native, woody species in each environment, Serenoa repens (W. Bartram) Small in mesic and Diospyros virginiana L. in xeric, was more abundant in basal plots. In mesic environments, eight species had greater occurrence in open plots. In xeric environments, four understory forbs were more abundant in open plots. Our results support previous research indicating that individual pine trees are associated with significant variation in understory vegetation in pine savannas.

Climate change and inter-annual variability cause variation in rainfall commencement and cessation which has consequences for the maize growing season length and thus impact yields. This study therefore sought to determine the spatially explicit optimum maize sowing dates to enable site specific recommendations in Nigeria. Gridded weather and soil data, crop management and cultivar were used to simulate maize yield from 1981-2019 at a scale of 0.5°. A total of 37 potential sowing dates between 1 March and 7 November at an interval of 7 days for each year were evaluated. The optimum sowing date was the date which maximizes yield at harvest, keeping all other management factors constant. The results show that optimum sowing dates significantly vary across the country with northern Nigeria having notably delayed sowing dates compared to southern Nigeria which has earlier planting dates. The long-term optimal sowing dates significantly (p

IntroductionParenteral nutrition (PN) is widely used in palliative care (PC), but there is limited evidence to support its use at the end of life (EOL). This aim of this was to investigate the relationship between routine laboratory parameters and survival in patients receiving PN, and to develop a decision tree model to support clinicians decide whether to start or forgo PN.MethodsThe laboratory parameters of 113 patients with advanced diseases who were admitted to a specialized palliative care unit (PCU) were analyzed at two points in time: T0 = before PN, T1 = two weeks after initiation of PN. Univariate Mann-Whitney U-tests and multivariate linear regression models, as well as a decision tree analysis were computed; all in relation to survival time.ResultsThe final regression model was significant with p = 0.001 (adjusted R2 = 0.15) and included two predictors for survival time after PN initiation: the CRP/albumin ratio and urea at T1 (ps = 0.019). Decision tree analysis revealed three important predictors for classification of survival time after PN initiation: CRP, urea, and LDH (all at T0).DiscussionThe decision tree model may help to identify patients likely to benefit from PN, thus supporting the clinical decision whether or not to start PN.

Anti-neuronal autoantibodies can be transplacentally transferred during pregnancy and may cause detrimental effects on fetal development. It is unclear whether autoantibodies against synapsin-I, one of the most abundant synaptic proteins, are associated with developmental abnormalities in humans. We recruited a cohort of 263 pregnant women and detected serum synapsin-I IgG autoantibodies in 13.3% using cell-based assays. Seropositivity was strongly associated with abnormalities of fetal development including structural defects, intrauterine growth retardation, amniotic fluid disorders and neuropsychiatric developmental diseases in previous children (odds ratios of 3–6.5). Autoantibodies reached the fetal circulation and were mainly of IgG1/IgG3 subclasses. They bound to conformational and linear synapsin-I epitopes, five distinct epitopes were identified using peptide microarrays. The findings indicate that synapsin-I autoantibodies may be clinically useful biomarkers or even directly participate in the disease process of neurodevelopmental disorders, thus being potentially amenable to antibody-targeting interventional strategies in the future.

Summary: Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cause cognitive dysfunction. After passive transfer of patients’ cerebrospinal fluid or human monoclonal anti-GluN1-autoantibodies in mice, we find a disrupted excitatory-inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA receptor (AMPAR) signaling, and faster synaptic inhibition in acute hippocampal slices. Functional alterations are also reflected in widespread remodeling of the hippocampal proteome, including changes in glutamatergic and GABAergic neurotransmission. NMDAR-Abs amplify network γ oscillations and disrupt θ-γ coupling. A data-informed network model reveals that lower AMPAR strength and faster GABAA receptor current kinetics chiefly account for these abnormal oscillations. As predicted in silico and evidenced ex vivo, positive allosteric modulation of AMPARs alleviates aberrant γ activity, reinforcing the causative effects of the excitatory-inhibitory imbalance. Collectively, NMDAR-Ab-induced aberrant synaptic, cellular, and network dynamics provide conceptual insights into NMDAR-Ab-mediated pathomechanisms and reveal promising therapeutic targets that merit future in vivo validation.

The German site selection procedure for a high-level nuclear waste repository is entering a stage in which preliminary safety assessments have to be conducted and the release of radionuclides has to be estimated for a large number of potential sites. Here, we present TransPyREnd, a 1D finite-differences code for modeling the transport of radionuclides in the subsurface at geological timescales. The code simulates the processes advection, diffusion, equilibrium sorption, decay of radionuclides, and the build-up of daughter nuclides. We summarize the modeled physical processes, their mathematical description and our numerical approach to solve the governing equations. Finally, two simple tests are shown, one considering diffusion, sorption, and radioactive decay, the other involving diffusion and a radioactive decay chain. In both tests, the code shows good agreement with the reference solutions. Caveats of the model and future additions are discussed.

Summary: The recurrent emerging of novel viral variants of concern (VOCs) with evasion of preexisting antibody immunity upholds severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case numbers and maintains a persistent demand for updated therapies. We selected the patient-derived antibody CV38-142 based on its potency and breadth against the VOCs Alpha, Beta, Gamma, and Delta for preclinical development into a therapeutic. CV38-142 showed in vivo efficacy in a Syrian hamster VOC infection model after post-exposure and therapeutic application and revealed a favorable safety profile in a human protein library screen and tissue cross-reactivity study. Although CV38-142 targets the same viral surface as sotrovimab, which maintains activity against Omicron, CV38-142 did not neutralize the Omicron lineages BA.1 and BA.2. These results highlight the contingencies of developing antibody therapeutics in the context of antigenic drift and reinforce the need to develop broadly neutralizing variant-proof antibodies against SARS-CoV-2.

Introduction: The antibody repertoire from CSF-derived antibody-secreting cells and memory B-cells in patients with encephalitis contains a considerable number of antibodies that do not target the disease-defining autoantigen such as the GABA or NMDA receptors. This study focuses on the functional relevance of autoantibodies to brain blood vessels in patients with GABAA and NMDA receptor encephalitis.Methods: We tested 149 human monoclonal IgG antibodies from the cerebrospinal fluid of six patients with different forms of autoimmune encephalitis on murine brain sections for reactivity to blood vessels using immunohistochemistry. Positive candidates were tested for reactivity with purified brain blood vessels, effects on transendothelial electrical resistance (TEER), and expression of tight junction proteins as well as gene regulation using human brain microvascular endothelial hCMEC/D3 cells as in vitro blood-brain barrier model. One blood-vessel reactive antibody was infused intrathecally by pump injection in mice to study in vivo binding and effects on tight junction proteins such as Occludin. Target protein identification was addressed using transfected HEK293 cells.Results: Six antibodies reacted with brain blood vessels, three were from the same patient with GABAAR encephalitis, and the other three were from different patients with NMDAR encephalitis. One antibody from an NMDAR encephalitis patient, mAb 011-138, also reacted with cerebellar Purkinje cells. In this case, treatment of hCMEC/D3 cells resulted in decreased TEER, reduced Occludin expression, and mRNA levels. Functional relevance in vivo was confirmed as Occludin downregulation was observed in mAb 011-138-infused animals. Unconventional Myosin-X was identified as a novel autoimmune target for this antibody.Discussion: We conclude that autoantibodies to blood vessels occur in autoimmune encephalitis patients and might contribute to a disruption of the blood-brain barrier thereby suggesting a potential pathophysiological relevance of these antibodies.

Maternal autoantibodies can be transmitted diaplacentally, with potentially deleterious effects on neurodevelopment. Synapsin 1 (SYN1) is a neuronal protein that is important for synaptic communication and neuronal plasticity. While monoallelic loss of function (LoF) variants in the SYN1 gene result in X-linked intellectual disability (ID), learning disabilities, epilepsy, behavioral problems, and macrocephaly, the effect of SYN1 autoantibodies on neurodevelopment remains unclear. We recruited a clinical cohort of 208 mothers and their children with neurologic abnormalities and analyzed the role of maternal SYN1 autoantibodies. We identified seropositivity in 9.6% of mothers, and seropositivity was associated with an increased risk for ID and behavioral problems. Furthermore, children more frequently had epilepsy, macrocephaly, and developmental delay, in line with the SYN1 LoF phenotype. Whether SYN1 autoantibodies have a direct pathogenic effect on neurodevelopment or serve as biomarkers requires functional experiments.

The Federal Company for Radioactive Waste Disposal (BGE) is responsible for the search for a site with the best possible safety for the disposal of high-level radioactive waste in Germany. The site selection procedure is regulated in a law that was adopted by the German Federal Parliament (Repository Site Selection Act – StandAG, 2017, last updated 2020) and aims to be a participatory, transparent, learning, and self-questioning process based on scientific expertise. The first step of the first phase of the site selection procedure was completed in September 2020 and resulted in the identification of sub-areas that give reason to expect favorable geological conditions for the long-term storage of nuclear waste in the subsurface. These sub-areas cover approximately 54 % of Germany and are located in three different host rocks: rock salt – halite, claystone, and crystalline rock. The challenge for the next step is to find suitable siting regions within the previously determined sub-areas that are then considered further in the next phase of the site selection procedure. In the following, the methodology of the so-called representative preliminary safety analyses is described, which constitute one of the tools to identify siting regions, and some first insight on how they are planned to be implemented in practice is given.

Sukhvir Wright et al. present a NMDAR antibody-induced model of encephalitis in rats and use in vitro, in vivo, and in silico electrophysiology to examine alterations in neural circuit behavior. Their results suggest that reduction of NMDARs leads to increased excitability and seizure activity, and highlights the potential use of receptor-specific treatments in antibody-mediated seizures and epilepsy.

This paper describes a collaboration between Mathematics Education and English as a Second Language (ESL) Education programs that presented opportunities for preservice teachers from both programs to work together to address curricular and linguistic gaps that occur for English language learners (ELL) in content area classrooms. By modeling collaboration, facilitating group interactions, and creating authentic field experiences, two faculty members created a space for preservice teachers to practice collaboration and to develop the necessary knowledge, skills, and dispositions to address the educational needs of diverse students. The goals for the students were for them to develop: (1) understanding of their own perspectives and those of the students they teach; (2) observing ELL in mathematics and ESL classes; (3) comparing standards for both programs; (4) identifying gaps in content standards and World-Class Instructional Design and Assessment (WIDA) Can-Do Descriptors (the language ELLs are able to understand and produce in the classroom); (5) planning instruction with support for ELL; (6) working collaboratively to design, implement, and assess the impact of their mathematics lessons for ELL; (7) presenting their projects; and (8) reflecting on their collaborative process in working with a group to complete the project.

Abstract Background Repertoire analysis of patient-derived recombinant monoclonal antibodies is an important tool to study the role of B cells in autoimmune diseases of the human brain and beyond. Current protocols for generation of patient-derived recombinant monoclonal antibody libraries are time-consuming and contain repetitive steps, some of which can be assisted with the help of software automation. Results We developed BASE, an easy-to-use software for complete data analysis in single cell immunoglobulin cloning. BASE consists of two modules: aBASE for immunological annotations and cloning primer lookup, and cBASE for plasmid sequence identity confirmation before expression. Comparing automated BASE analysis with manual analysis we confirmed the validity of BASE output: identity between manual and automated aBASE analysis was 100% for all outputs, except for immunoglobulin isotype determination. In this case, aBASE yielded correct results in 96% of cases, whereas 4% of cases required manual confirmation. cBASE automatically concluded expression recommendations in 89.8% of cases, 91.8% of which were identical to manually derived results and none of them were false-positive. Conclusions BASE offers an easy-to-use software solution suitable for complete Ig sequence data analysis and tracking during recombinant mAb cloning from single cells. Plasmid sequence identity confirmation by cBASE offers functionality not provided by existing software solutions in the field and will help to reduce time-consuming steps of the monoclonal antibody generation workflow. BASE can be installed locally or accessed online at Code Ocean.

Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression. Further, we studied the L-1236, L-428, L-540, SUP-HD1, KM-H2, and HDLM-2 classical Hodgkin lymphoma cell lines by FACS and Western blot for mGluR5-expression, and by transcriptome analysis. mGluR5 surface expression differed significantly in terms of receptor density, distribution pattern, and percentage of positive cells. The highest expression levels were found in the L-1236 line. RNA-sequencing revealed more than 800 genes that were higher expressed in the L-1236 line in comparison to the other classical Hodgkin lymphoma cell lines. High mGluR5-expression was associated with upregulation of PI3K/AKT and MAPK pathways and of downstream targets (e.g., EGR1) known to be involved in classical Hodgkin lymphoma progression. Finally, mGluR5 expression was increased in the classical Hodgkin lymphoma-tissue of our Ophelia syndrome patient in contrast to five classical Hodgkin lymphoma-patients without autoimmune encephalitis. Given the association of encephalitis and classical Hodgkin lymphoma in Ophelia syndrome, it is possible that mGluR5-expression in classical Hodgkin lymphoma cells not only drives tumor progression but also triggers anti-mGluR5 encephalitis even before classical Hodgkin lymphoma becomes manifest.

Widespread fire exclusion and land-use activities across many southeastern United States forested ecosystems have resulted in altered species composition and structure. These changes in composition and structure have been implicated in positive fire-vegetation feedbacks termed “mesophication” where fire spread and intensity are diminished. In forests and woodlands, inherent flammability of different species is the mechanistic driver of mesophication. To date, there has been limited work on documenting the high diversity of flammability among species in the region, limiting the ability to differentiate among species to restore fuels that sustain fire regimes. Here, we coalesce disparate flammability data and add missing species across the spectrum from species that facilitate fire (so called “pyrophytes”) to those that dampen fire (so called “mesophytes”). We present data on 50 important tree species from across the southeast, all burned using identical laboratory methods. We divide our results for four dominant ecosystems: Coastal Plain uplands, oak-hickory woodlands, Appalachian forests, and bottomland forests. Across ecosystems, the most flammable species were American chestnut (Castanea dentata), a suite of pines (Pinus palustris, P. elliottii, P. serotina, and P. rigida), several oaks (Q. laevis, Q. falcata, Q. margaretta, and Q. alba), and sourwood (Oxydendrum arboreum). At the mesophytic end, the least flammable species were Tsuga canadensis, Acer rubrum, and several other hardwoods previously implicated in mesophication. Each of the four ecosystems we studied contained species that spanned the pyrophytic to mesophytic gradient. These data fill in some key holes in our understanding of southeastern fire adaptations, but also provide context for restoration decisions and fire management prioritization efforts to restore and sustain fire-prone ecosystems of the region.

Background Patients with metastatic breast cancer (MBC) have a considerable symptom burden and may require extensive care for a long period of time. Palliative care (PC) has the potential to improve their quality of care and reduce their use of medical services. However, the role of specialised PC (SPC) in patients with MBC remains unclear.Patients and methods We performed a retrospective analysis of the medical records of patients diagnosed with breast cancer (BC) from 2008 to 2018 at an university-based referral centre to examine the extent of early and late integration of SPC services for patients with MBC. A descriptive analysis of the patients was also established.Results In all, 932 patients were diagnosed with BC from 2008 to 2018; 225 of these patients had or developed metastases related to their BC. In addition, 132 patients received SPC (58.7%) and 93 patients did not receive SPC (41.3%). The median probability of overall survival (OS) for patients who did not receive SPC services was 3.6 years (95% CI 2.0 to 5.1) and 1.8 years (95% CI 1.3 to 2.3) (p

Low and declining soil fertility has been recognized for a long time as a major impediment to intensifying agriculture in sub-Saharan Africa (SSA). Consequently, from the inception of international agricultural research, centres operating in SSA have had a research programme focusing on soil and soil fertility management, including the International Institute of Tropical Agriculture (IITA). The scope, content, and approaches of soil and soil fertility management research have changed over the past decades in response to lessons learnt and internal and external drivers and this paper uses IITA as a case study to document and analyse the consequences of strategic decisions taken on technology development, validation, and ultimately uptake by smallholder farmers in SSA. After an initial section describing the external environment within which soil and soil fertility management research is operating, various dimensions of this research area are covered: (i) ‘strategic research’, ‘Research for Development’, partnerships, and balancing acts, (ii) changing role of characterization due to the expansion in geographical scope and shift from soils to farms and livelihoods, (iii) technology development: changes in vision, content, and scale of intervention, (iv) technology validation and delivery to farming communities, and (v) impact and feedback to the technology development and validation process. Each of the above sections follows a chronological approach, covering the last five decades (from the late 1960s till today). The paper ends with a number of lessons learnt which could be considered for future initiatives aiming at developing and delivering improved soil and soil fertility management practices to smallholder farming communities in SSA.

Abstract Fire‐stimulated or pyrogenic flowering is one of many traits that enable plants in fire‐prone ecosystems to persist or dominate following frequent fires. Obligate pyrogenic flowering has long been observed in wiregrass (Aristida beyrichiana), a foundation bunchgrass in frequently burned longleaf pine ecosystems in the southeastern United States. Widespread fire exclusion in this ecosystem has contributed to well‐documented declines in plant and animal biodiversity prompting the need for restoration efforts. We studied the effect of fire reintroduction on the flowering of wiregrass in northern Florida, USA. Prescribed fires were ignited in a 50‐yr unburned site and an adjacent frequently burned site in the summer of 2017. Wiregrass was measured eight months after the burns in both stands. As expected, the frequently burned stand had higher density, basal area, and percent flowering of wiregrass tussocks. Logistic regression revealed that wiregrass initiated flowering at significantly larger sizes in the long‐unburned stand. Despite these differences, wiregrass size distributions were similar in both stands, with the long‐unburned stand lacking tussocks in the largest (100+ cm2) size class. We did not find differences in the number of flower culms per unit of mass between the two stands. Even though diminished in nearly every measure, the ability of wiregrass to flower after five decades of fire exclusion, and presumably no sexual reproduction, provides evidence of resilience of the dominant herb of these ecosystems.

State-of-the-art hydrological applications require a process-based, spatially distributed hydrological model. Runoff characteristics are demanded to be well reproduced by the model. Despite that, the model should be able to describe the processes at a subcatchment scale in a physically credible way. The objective of this study is to present a robust procedure to generate various sets of parameterisations of soil hydraulic functions for the description of soil heterogeneity on a subgrid scale. Relations between Rosetta-generated values of saturated hydraulic conductivity (Ks) and van Genuchten's parameters of soil hydraulic functions were statistically analysed. An universal function that is valid for the complete bandwidth of Ks values could not be found. After concentrating on natural texture classes, strong correlations were identified for all parameters. The obtained regression results were used to parameterise sets of hydraulic functions for each soil class. The methodology presented in this study is applicable on a wide range of spatial scales and does not need input data from field studies. The developments were implemented into a hydrological modelling system.

Abstract Fire exclusion in eastern North American Quercus–Carya woodlands has resulted in overstory compositional changes, linked to altered fuel composition, structure, and ultimately, altered fire regimes. These compositional changes have been implicated in a dampening effect on fire behavior in formerly fire‐prone ecosystems, the positive feedback termed “mesophication.” Several proposed mechanisms are likely involved in this process; however, few have been examined. We evaluated the potential mechanism of dampened forest floor flammability through changes in litter composition in a southeastern U.S. oak–hickory forest undergoing mesophication. Laboratory drying and burning experiments revealed that increasing the relative contribution of litter from fire‐sensitive mesophytic tree species (Liquidambar styraciflua, Ulmus alata, and Cornus florida) increased moisture retention and diminished litter flammability. Litterbeds composed of ≥66% mesophyte litter gained the most moisture following fuelbed saturation and were consistently wetter than pyrophyte litter following 12 and 24 h of drying. Flammability metrics decreased with increasing contribution of mesophyte litter with reductions most pronounced under more moist conditions. Under dry conditions, where litter moisture did not differ across compositional treatments, mesophyte litter was less flammable than fuelbeds that contained any pyrophyte litter. The combined effects of moisture retention and less flammable litter reveal an important synergistic impact that may result with increased dominance of fire‐sensitive mesophytic species. Restoration efforts in long‐unburned eastern hardwood forests may require altering stand composition to limit mesophytic litter input or developing burn prescriptions that intensify surface fire behavior in less flammable fuels.

This paper proposes the Uncertainty Driven Action (UDA) model, which unifies the fragmented literature on design activity. The UDA model conceptualises design activity as a process consisting of three core actions: information action, knowledge-sharing action, and representation action, which are linked via uncertainty perception. The foundations of the UDA model in the design literature are elaborated in terms of the three core actions and their links to designer cognition and behaviour, utilising definitions and concepts from Activity Theory. The practical relevance and theoretical contributions of the UDA model are discussed. This paper contributes to the design literature by offering a comprehensive formalisation of design activity of individual designers, which connects cognition and action, to provide a foundation for understanding previously disparate descriptions of design activity.