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Termination of an existing failed corn stand before replanting is essential. Two studies were conducted in Stoneville and Verona, MS, from 2020 to 2021 to evaluate timing of corn or soybean replanting following different herbicide treatments applied to simulated failed stands of corn. Treatments included paraquat alone at 841 g ai ha−1, paraquat at 841 g ha−1 + metribuzin at 211 g ai ha−1, and clethodim at 51 g ai ha−1 + glyphosate at 1,121 g ae ha−1 applied at the V2 growth stage. Replant timings were 1 and 7 d after herbicide treatment (DAT). Pooled across replant timings, paraquat + metribuzin provided the greatest control 3 DAT compared with other treatments in both studies. At 14 and 21 DAT, clethodim + glyphosate controlled more corn than did paraquat + metribuzin and paraquat alone. Control of a simulated failed corn stand with paraquat alone never exceeded 50% at 3 to 21 DAT. Soybean yield in all plots receiving herbicide treatment targeting simulated failed corn stands were similar and ≥2,150 kg ha−1. When applied at the V2 corn growth stage, both clethodim + glyphosate and paraquat + metribuzin controlled a simulated failed stand of corn. This study demonstrated the importance of terminating failed stands of corn before replanting because of dramatic reductions in yield in the plots not treated with herbicide.
Background: The complement component C5 inhibitor, ravulizumab, is approved in Canada for the treatment of adults with AQP4-Ab+ NMOSD. Updated efficacy and safety results from the ongoing CHAMPION-NMOSD (NCT04201262) trial are reported. Methods: Participants received IV-administered, weight-based dosing of ravulizumab, with loading on day 1 and maintenance doses on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Outcome measures included safety, time to first adjudicated on-trial relapse (OTR), risk reduction, and disability scores. Results: 56/41 patients entered/completed the LTE as of June 14, 2024. Median follow-up was 170.3 weeks (186.6 patient-years). No patients experienced an OTR. 94.8% (55/58 patients) had stable or improved Hauser Ambulation Index scores. 89.7% (52/58 patients) had no clinically important worsening in Expanded Disability Status Scale scores. Treatment-emergent adverse events (98.4%) were predominantly mild and unrelated to ravulizumab. Serious adverse events occurred in 25.9% of patients. Two cases of meningococcal infection occurred during the PTP, and none in the LTE. One unrelated death (cardiovascular) occurred during the LTE. Conclusions: Ravulizumab demonstrated long-term clinical benefit in AQP4-Ab+ NMOSD relapse prevention while maintaining or improving disability measures, with no new safety concerns.
Background: Inuit children have been observed to have high rates of macrocephaly, which leads to burdensome travel for medical evaluation, often with no pathology identified. Given reports that WHO growth charts may not reflect all populations, we compared head circumference (HC) measurements in a cohort of Inuit children with the WHO charts. Methods: We extracted HC data from a retrospective cohort study where, with Inuit partnership, we reviewed medical records of Inuit children, born between 2010-2013, and residing in Nunavut. We excluded children with preterm birth, documented neurologic/genetic disease, and most congenital anomalies. We compared HC values with the 2007 WHO charts. Results: We analyzed records of 1960 Inuit children (8866 data points). Most data were from ages 0-36 months. At all age points, the cohort had statistically significantly larger HC than WHO medians. At age 12 months, median HC were 1.3 cm and 1.5 cm larger for male and female Inuit children. Using WHO growth curves, macrocephaly was overdiagnosed and microcephaly underdiagnosed. Conclusions: Our results support the observation that Inuit children from Nunavut have larger HCs, and use of the WHO charts may lead to overdiagnosis of macrocephaly and underdiagnosis of microcephaly. Population specific growth curves for Inuit children should be considered.
Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.
Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP), a rare, progressive, immune-mediated disease that can lead to irreversible disability. The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) trial assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to weekly efgartigimod or placebo for ≤48 weeks (stage-B). This posthoc analysis evaluated changes from run-in baseline (study enrollment) to stage-B last assessment and items of the Inflammatory Rasch-built Overall Disability Scale (I-RODS). Results: Of 322 participants who entered stage-A, 221 were randomized and treated in stage-B, and 191/221 had data for run-in baseline and post–stage-B timepoints. Mean (SE) I-RODS change at stage-B last assessment vs run-in baseline was 5.7 (1.88) and -4.9 (1.82) in participants randomized to efgartigimod and placebo, respectively. 37/97 (38.1%) and 24/92 (26.1%) participants randomized to efgartigimod and placebo, respectively, experienced ≥4-point improvements in I-RODS score. Efgartigimod-treated participants improved ≥1 point in I-RODS items of clinical interest. Conclusions: Participants who received efgartigimod in stage-B experienced improvements in I-RODS score from study enrollment to stage-B last assessment.
Incorporating paleontological data into phylogenetic inference can greatly enrich our understanding of evolutionary relationships by providing insights into the diversity and morphological evolution of a clade over geological timescales. Phylogenetic analysis of fossil data has been significantly aided by the introduction of the fossilized birth–death (FBD) process, a model that accounts for fossil sampling through time. A decade on from the first implementation of the FBD model, we explore its use in more than 170 empirical studies, summarizing insights gained through its application. We identify a number of challenges in applying the model in practice: it requires a working knowledge of paleontological data and their complex properties, Bayesian phylogenetics, and the mechanics of evolutionary models. To address some of these difficulties, we provide an introduction to the Bayesian phylogenetic framework, discuss important aspects of paleontological data, and finally describe the assumptions of the models used in paleobiology. We also present a number of exemplar empirical studies that have used the FBD model in different ways. Through this review, we aim to provide clarity on how paleontological data can best be used in phylogenetic inference. We hope to encourage communication between model developers and empirical researchers, with the ultimate goal of developing models that better reflect the data we have and the processes that generated them.
Florpyrauxifen-benzyl is a postemergence rice herbicide that has reduced rice yield in some situations, and producers are concerned that the impact could be even greater with low rice seeding densities. Therefore, research was conducted in Stoneville, MS, from 2019 to 2021, to evaluate the effect of florpyrauxifen-benzyl on rice yield when a hybrid was seeded at reduced densities. Rice cultivar FullPage RT 7521 FP was seeded at 10, 17, 24, 30, and 37 kg ha−1. At the 4-leaf to 1-tiller growth stage, florpyrauxifen-benzyl was applied at 0 or 58 g ai ha−1. Rice injury following application of florpyrauxifen-benzyl was ≤8% across all seeding rates and evaluation intervals. Application of florpyrauxifen-benzyl reduced plant heights by 14% to all seeding rates but did not result in delayed rice maturity. When florpyrauxifen-benzyl was not applied to rice that was seeded at 10 and 17 kg ha−1 seeding rates, rice matured slower than when it was seeded at 24, 30, and 37 kg ha−1. When florpyrauxifen-benzyl was applied, rough rice grain yields were reduced by at the 17 and 37 kg ha−1 seeding rates, but not at any other seeding rate. In conclusion, application of florpyrauxifen-benzyl at a 2× rate can cause a loss of yield resulting from variation in rice densities.
Objectives/Goals: Cerebral amyloid angiopathy (CAA) characterized by the accumulation of amyloid-beta in the cerebrovasculature, affects blood vessel integrity leading to brain hemorrhages and an accelerated cognitive decline in Alzheimer’s disease patients. In this study, we are conducting a genome-wide association study to identify genetic risk factors for CAA. Methods/Study Population: We genotyped 1253 additional AD cases using and curated existing genome-wide genotype data from 110 AD and 502 non-AD donors from the Mayo Clinic Brain Bank. We performed QC and imputation of all datasets. We conducted GWAS in AD only (N = 1,363), non-AD only, as well as the combined cohort (N = 1,865) by testing imputed variant dosages for association with square root transformed CAA using linear regression, adjusting for relevant covariates. To assess associations in the context of major CAA risk factors, we performed interaction analysis with APOEe4 presence and sex; and pursued stratified analyses. We collected peripheral gene expression measures using RNA isolated from 188 PAXgene tube samples of 95 donors collected across multiple time points. More than 1/3 of these participants have MRI measures collected. Results/Anticipated Results: Variants at the APOE locus were identified as the most significant in our study. In addition, several other variants with suggestive association were found under the main model adjusting for AD neuropathology (Braak and Thal). LINC-PINT splice variant remained associated with lower CAA scores in AD cases without the APOEe4 risk allele. To enhance the robustness of our findings, we are pursuing further expansion of our study cohort. In the periphery, we expect to identify expression changes associated with neuroimaging indicators of CAA and determine if variants and genes discovered via GWAS are implicated in these changes. Discussion/Significance of Impact: We expect this study will provide further insight into the genetic architecture underlying risk for CAA both in the context of significant AD pathology and without. Characterization of genetic variants and functional outcomes in the context of neuropathology may lead to new avenues of research aimed at identifying biomarkers and therapies to treat CAA
Age estimates from bomb 14C dating conflict with a well-recognized age reading protocol (grinding, polishing and staining in the sagittal plane) for otoliths of European eel (Anguilla anguilla). Proper alignment of calculated hatch years for 14C measurements taken from the earliest otolith growth—among the smallest otolith extractions to date for successful 14C analysis due to the advent of gas-AMS—was not achieved using age estimates from an accepted method. The realignment of otolith 14C values to a tropical bomb 14C reference chronology, which is most applicable to the Sargasso Sea as the natal origin of European eel, led to an increase of the original age estimates by 8 to 32 years. A maximum age of approximately 46 years was determined for the European eel specimen with the most massive otolith, of which mass is a reasonable proxy for age and was instrumental in identifying age estimate discrepancies. By extending the otolith mass-to-age relationships from this study to the most massive otoliths available from archived otoliths of Norway, an increase of up to several decades from the original otolith age estimates was discovered, leading to support for a potential lifespan of 70–100 years in the natural environment.
Early gut microbiome development may impact brain and behavioral development. Using a nonhuman primate model (Macaca mulatta), we investigated the association between social environments and the gut microbiome on infant neurodevelopment and cognitive function. Infant rhesus monkeys (n = 33) were either mother-peer-reared (MPR) or nursery-reared (NR). Neurodevelopmental outcomes, namely emotional responsivity, visual orientation, and motor maturity, were assessed with the Primate Neonatal Neurobehavioral Assessment (PNNA) at 14–30 days. Cognitive development was assessed through tasks evaluating infant reward association, cognitive flexibility, and impulsivity at 6–8 months. The fecal microbiome was quantified from rectal swabs via 16S rRNA sequencing. Factor analysis was used to identify “co-abundance factors” describing patterns of microbial composition. We used multiple linear regressions with AIC Model Selection and differential abundance analysis (MaAsLin2) to evaluate relationships between co-abundance factors, microbiome diversity, and neuro-/cognitive development outcomes. At 30 days of age, a gut microbiome co-abundance factor, or pattern, with high Prevotella and Lactobacillus (β = −0.88, p = 0.04, AIC Weight = 68%) and gut microbiome alpha diversity as measured by Shannon diversity (β = −1.33, p = 0.02, AIC Weight = 80%) were both negatively associated with infant emotional responsivity. At 30 days of age, being NR was also associated with lower emotional responsivity (Factor 1 model: β = −3.13, p < 0.01; Shannon diversity model: β = −3.77, p < 0.01). The infant gut microbiome, along with early-rearing environments, may shape domains of neuro-/cognitive development related to temperament.
Objectives: As life expectancy continues to rise globally, the prevalence of dementia is also increasing. However, there is a lack of studies in Latin American countries that describe the sociodemographic and clinical characteristics of dementia patients and their caregivers, potentially overlooking important differences that could impact diagnosis in a diverse population. This study aims to elucidate the sociodemographic characteristics of patients with Behavioral Variant Frontotemporal Dementia (bvFTD) and Early-Onset Alzheimer’s Disease (AD), as well as their primary caregivers in Colombia, while also examining the clinical presentation ofdementia.
Methods: A total of 83 Colombian participants were included in the study, consisting of 40 healthy controls and 43 individuals previously diagnosed with bvFTD (n = 20) and early-onset AD (n = 23). Diagnoses were established based on the current diagnostic criteria for both conditions. Participants underwent sociodemographic assessments, and a clinical evaluation was conducted. Additionally, caregivers were characterized sociodemographically.
Results: Most participants were female (67%) with a mean age of 63 years. Educational levels were comparable between the dementia group (12.4 years) and the control group (12.9 years). A higher proportion of dementia cases were observed in lower socioeconomic status categories (1 to 3). Past medical history of hypertension, type 2 diabetes, and traumatic brain injury was more prevalent in the bvFTD group, whereas coronary disease was more common in the AD group. Initial psychiatric misdiagnosis occurred more frequently in bvFTD (50%) compared to AD (26%), with depression being the most common misdiagnosis in both groups (37.5%), followed by bipolar disorder (25%) and anxiety (25%). Most caregivers were female (70%) with a mean age of 50 years. The most common caregiver-patient relationships were daughter (25.6%) and husband (25.6%), followed by wife (23.3%). The mean educational level of bvFTD caregivers (13.95) was higher than that of AD caregivers (12.87).
Conclusions: These findings provide valuable insights into the sociodemographic characteristics of dementia patients and their caregivers in Latin America, a population that is often underrepresented in research. Further exploration of diagnostic variations may be warranted, given the high prevalence of misdiagnosis in this region.
The stakeholder analysis approach has historically been top-down rather than collaborative with key partners. However, this approach poses challenges for key partner engagement and community-engaged research, which aims to incorporate key partners throughout the project. This study, conducted by the Community Engagement Network at a Midwest Academic Medical Center, seeks to examine the value of community-engaged research for diverse key partners to increase collaboration, strengthen partnerships, and enhance impact, ultimately driving key partner engagement.
Methods:
The study involved semi-structured interviews with 38 key partners from diverse groups, including community members, community organizations, Practice-Based Research Network members, researchers, research administration, university administration, and potential funders. The interview guide, informed by an extensive literature review, assessed perceived value, barriers, and improvement strategies for community-engaged research, supplemented by value proposition statements.
Results:
The analysis revealed three main themes: 1) Fostering Community Buy-In: Authentic representation and inclusive partnerships were essential for trust and commitment; 2) Enhancing Communication and Dissemination: Effective communication strategies were vital for maintaining engagement and sharing research outcomes; and 3) Building Capacity and Ensuring Sustainability: Continuous learning and long-term investments were crucial for sustaining community-engaged research efforts.
Discussion:
This study underscores the value of incorporating key partners into stakeholder analyses to enhance collaboration, strengthen partnerships, and improve the impact of community-engaged research. The findings offer valuable insight for institutional transformation and implementation of effective stakeholder analyses and engagement tools, ultimately enhancing the effectiveness of research strategies and initiatives.
Edited by
David M. Greer, Boston University School of Medicine and Boston Medical Center,Neha S. Dangayach, Icahn School of Medicine at Mount Sinai and Mount Sinai Health System
Stroke represents one of the most prominent causes of disability and mortality worldwide and poses significant costs to healthcare services. As many as 24.9 million people living worldwide have suffered an ischemic stroke, and projections suggest that by 2030, an additional 3.4 million adults older than 18 years in the United States will have had a stroke.[1] Stroke can be deadly, with mortality rates at 1 year post-stroke (both ischemic and hemorrhagic) running from 8 to 36%, with the higher mortality rates occurring in the elderly. [1] But more than this, stroke leads to disability in a large number of patients. Approximately half of stroke survivors remain disabled, with 20% requiring care at a facility.[2] These sobering data highlight the economic and medical importance of understanding stroke mechanisms, stroke management, and stroke prognosis.
Despite the potential catastrophic outcomes of stroke, not all patients suffer significant morbidity, and some patients even show considerable improvement over time.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Legislation is a powerful tool for facilitating mental healthcare. Gender is an important social determinant of physical and mental health. Many jurisdictions are in the process of revising their mental health law, to align with human rights commitments. Consideration of gender in these revisions could enhance the mental healthcare received by women, transgender and non-binary individuals.
Aim:
This paper examines gender-based provisions in mental health law published in English.
Methods:
Countries that use English as an official language were identified. Jurisdictions in these countries with stand-alone mental health laws were included. Legislation was reviewed for gender-specific provisions.
Results:
Seventy-five countries were evaluated; 71 jurisdictions were included. Thirty-eight jurisdictions had 88 gender-specific provisions. These addressed ten key areas, including: general gender-based protections, female representation on boards and review panels, protections during searching and restraint, gender separated facilities, protections in relation to parenting, fertility, sterilisation and termination. Fiji, Ghana, India, and the Australian jurisdictions had the highest number of gender-specific laws. However, gender-specific provisions are highly heterogeneous and are drafted from a cisnormative perspective and fail to adequately address the specific needs of individuals outside of that framework.
Conclusion:
Gender-specific provisions can enhance the protections afforded by mental health law. However, as legislation can be a blunt instrument, careful consideration must be given to potential unintended consequences. During revisions of mental health law consideration should be given to gender-specific provisions and legislation must be inclusive of individuals identifying as transgender, non-binary and other genders.
According to International Union for the Conservation of Nature (IUCN) guidelines, all species must be assessed against all criteria during the Red Listing process. For organismal groups that are diverse and understudied, assessors face considerable challenges in assembling evidence due to difficulty in applying definitions of key terms used in the guidelines. Challenges also arise because of uncertainty in population sizes (Criteria A, C, D) and distributions (Criteria A2/3/4c, B). Lichens, which are often small, difficult to identify, or overlooked during biodiversity inventories, are one such group for which specific difficulties arise in applying Red List criteria. Here, we offer approaches and examples that address challenges in completing Red List assessments for lichens in a rapidly changing arena of data availability and analysis strategies. While assessors still contend with far from perfect information about individual species, we propose practical solutions for completing robust assessments given the currently available knowledge of individual lichen life-histories.
Researchers generally do an excellent job tracking the scientific impacts of their scholarship in ways that are relevant for academia (e.g., publications, grants) but too often neglect to focus on broader impacts on population health and equity. The National Cancer Institute’s Implementation Science Centers in Cancer Control (ISC3) includes 7 P50 Centers that are interested in broad measures of impact. We provide an overview of the approach underway within the ISC3 consortium to identify health and social impacts.
Methods:
ISC3 adapted and applied the Translational Science Benefits Model (TSBM) to identify the impact on the discipline of D&I science and to consider dissemination and implementation (D&I) impacts in the four original TSBM domains: (1) clinical; (2) community; (3) economic; and (4) policy. To collect data from all Centers, we: (1) co-developed a set of detailed impact indicators with examples; (2) created a data collection template; and (3) summarized the impact data from each center.
Results:
Based on data from 48 ISC3 pilot studies, cores, or consortium activities, we identified 84 distinct benefits. The most common impacts were shown for implementation science (43%), community (28%), and clinical (18%). Frequent audiences included primary care providers, public health practitioners, and community partners. ISC3 members highlighted the need for product feedback, and storytelling assistance to advance impact.
Conclusions:
The ISC3 consortium is using a participatory approach to successfully apply the TSBM, thus seeking to maximize the real-world impacts of D&I science. The D&I field needs to prioritize ways to more fully document and communicate societal impacts.
Jellyfishes have ecological and societal value, but our understanding of taxonomic identity of many jellyfish species remains limited. Here, an approach integrating morphological and molecular (16S ribosomal RNA and cytochrome oxidase I) data enables taxonomic assessment of the blubber jellyfish found in the Philippines. In this study, we aimed to resolve doubt on the taxonomy of Acromitoides purpurus, a valid binomen at the time of our research. Our morphological findings confirm that this jellyfish belongs to the genus Catostylus, and is distinct from known species of the genus inhabiting the Western Pacific, such as Catostylus ouwensi, Catostylus townsendi, and Catostylus mosaicus. Detailed morphological and molecular analyses of the type specimens from the Philippines with the other Catostylus species revive the binomen Catostylus purpurus and invalidate A. purpurus. Genetic analysis also distinguishes this Philippine jellyfish from C. townsendi and C. mosaicus. Through this study, we arranged several Catostylidae taxa into species inquirendae (Catostylus tripterus, Catostylus turgescens, and Acromitoides stiphropterus) and one genus inquirenda (Acromitoides) and provided an identification key for species of Catostylus. This comprehensive study confirms the blubber jellyfish as C. purpurus, enriching our understanding of jellyfish biodiversity. The integration of morphological and genetic analyses proves vital in resolving taxonomic ambiguities within the Catostylidae family and in the accurate identification of scyphozoan jellyfishes.