From Soil Ecology to Human Nutrtition: Crop Symbiosis with Arbuscular Mycorrhizal Fungi in Agroecosystems

The Green Revolution helped us reduce global poverty, hunger, and malnutrition over the past 30 years. My research is part of an emerging Brown Revolution that is unlocking the power of living soil to sustainability provide human needs. We are losing soil more quickly than it is being replenished � worldwide, an area of farmland the size of half an Oklahoma erodes away every year; however, arbuscular mycorrhizal (AM) fungi are microorganisms that can stabilize and enhance soil, while benefitting most of our crops with increased water and nutrients. A teacup of healthy soil contains enough AM fungi to stretch across 30 football fields from end to end, but some agricultural practices reduce the abundance of AM fungi on farms. These practices degrade soil stability and fertility over time, resulting in a waste of water, a waste of fertilizers, and environmental damage. My research seeks to harness the benefits of AM fungi for sustainable food production and nutrition. We focused on sorghum and cowpea, because they are important in many developing countries, but their efficiency and drought-tolerance also make them ideal for places like Oklahoma. In the greenhouse and field, we assessed differences in plant response to AM fungi to discover which crop genotypes are the most effective partners. Then we examined how that partnership affected agricultural efficiency and seed (grain) nutritional contents, such as protein, zinc, and iron. We also assessed the impact of alternative fertility amendments (biochar, worm compost, reduced commercial fertilizers) and farm management practices (intercropping) on AM abundance, crop yield, and nutrition. More AM responsive genotypes and alternative amendments were shown to increase yield and/or key nutritional contents. Nearly 1 out of every 3 people on this planet are malnourished, and they often need more dietary protein, zinc, and iron; therefore, our results indicate that AM fungi improve soil health and human health as well. Crop genetics, alternative soil amendments, and farm management can enhance the benefits of AM fungi, and we can utilize them to help us regenerate our soils and nourish our growing population.Natural Resources and Ecology Managemen

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

The HumBug Challenge: ComParE 2022

This dataset can be found on Zenodo: https://doi.org/10.5281/zenodo.6478589A large-scale multi-species dataset of acoustic recordingsDataset compatible with two papers:The Computational Paralinguistics ChallengE (ComParE): Mosquito Event Detection Task https://github.com/EIHW/ComParE2022/tree/MOS-CAn update to: HumBugDB: a large-scale acoustic mosquito dataset: NeurIPS 2021 Paperhttps://github.com/HumBug-Mosquito/HumBugDB.A large-scale multi-species dataset containing recordings of mosquitoes collected from multiple locations globally, as well as via different collection methods. In total, we present 20 hours of labelled mosquito data with 15 hours of corresponding background noise, recorded at the sites of 8 experiments. Of these, 64,843 seconds contain species metadata, consisting of 36 species (or species complexes).This repository contains:Audio files to be extracted into audio/data/train and audio/data/dev/{a/b} respectivelyMetadata in csv format: neurips_2021_zenodo_0_0_2.csvFunding from the 2014 Google Impact Challenge Award, and The Bill and Melinda Gates Foundation (https://www.gatesfoundation.org/about/committed-grants/2019/07/opp1209888

HumBugDB : a large-scale acoustic mosquito dataset

This paper presents the first large-scale multi-species dataset of acoustic recordings of mosquitoes tracked continuously in free flight. We present 20 hours of audio recordings that we have expertly labelled and tagged precisely in time. Significantly, 18 hours of recordings contain annotations from 36 different species. Mosquitoes are well-known carriers of diseases such as malaria, dengue and yellow fever. Collecting this dataset is motivated by the need to assist applications which utilise mosquito acoustics to conduct surveys to help predict outbreaks and inform intervention policy. The task of detecting mosquitoes from the sound of their wingbeats is challenging due to the difficulty in collecting recordings from realistic scenarios. To address this, as part of the HumBug project, we conducted global experiments to record mosquitoes ranging from those bred in culture cages to mosquitoes captured in the wild. Consequently, the audio recordings vary in signal-to-noise ratio and contain a broad range of indoor and outdoor background environments from Tanzania, Thailand, Kenya, the USA and the UK. In this paper we describe in detail how we collected, labelled and curated the data. The data is provided from a PostgreSQL database, which contains important metadata such as the capture method, age, feeding status and gender of the mosquitoes. Additionally, we provide code to extract features and train Bayesian convolutional neural networks for two key tasks: the identification of mosquitoes from their corresponding background environments, and the classification of detected mosquitoes into species. Our extensive dataset is both challenging to machine learning researchers focusing on acoustic identification, and critical to entomologists, geo-spatial modellers and other domain experts to understand mosquito behaviour, model their distribution, and manage the threat they pose to humans

Rare pathogenic variants in WNK3 cause X-linked intellectual disability

Purpose: WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown. Method: We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID). Results: We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.Pro204Arg, p.Leu300Ser, p.Glu607Val) in WNK3 in 14 male individuals from 6 unrelated families. Affected individuals had ID with variable presence of epilepsy and structural brain defects. WNK3 variants cosegregated with the disease in 3 different families with multiple affected individuals. This included 1 large family previously diagnosed with X-linked Prieto syndrome. WNK3 pathogenic missense variants localize to the catalytic domain and impede the inhibitory phosphorylation of the neuronal-specific chloride cotransporter KCC2 at threonine 1007, a site critically regulated during the development of synaptic inhibition. Conclusion: Pathogenic WNK3 variants cause a rare form of human X-linked ID with variable epilepsy and structural brain abnormalities and implicate impaired phospho-regulation of KCC2 as a pathogenic mechanism.</p

Report of the first seven agents in the I-SPY COVID trial: a phase 2, open label, adaptive platform randomised controlled trial

BackgroundAn urgent need exists to rapidly screen potential therapeutics for severe COVID-19 or other emerging pathogens associated with high morbidity and mortality.MethodsUsing an adaptive platform design created to rapidly evaluate investigational agents, hospitalised patients with severe COVID-19 requiring ≥6&nbsp;L/min oxygen were randomised to either a backbone regimen of dexamethasone and remdesivir alone (controls) or backbone plus one open-label investigational agent. Patients were enrolled to the arms described between July 30, 2020 and June 11, 2021 in 20 medical centres in the United States. The platform contained up to four potentially available investigational agents and controls available for randomisation during a single time-period. The two primary endpoints were time-to-recovery (&lt;6&nbsp;L/min oxygen for two consecutive days) and mortality. Data were evaluated biweekly in comparison to pre-specified criteria for graduation (i.e., likely efficacy), futility, and safety, with an adaptive sample size of 40-125 individuals per agent and a Bayesian analytical approach. Criteria were designed to achieve rapid screening of agents and to identify large benefit signals. Concurrently enrolled controls were used for all analyses. https://clinicaltrials.gov/ct2/show/NCT04488081.FindingsThe first 7 agents evaluated were cenicriviroc (CCR2/5 antagonist; n&nbsp;=&nbsp;92), icatibant (bradykinin antagonist; n&nbsp;=&nbsp;96), apremilast (PDE4 inhibitor; n&nbsp;=&nbsp;67), celecoxib/famotidine (COX2/histamine blockade; n&nbsp;=&nbsp;30), IC14 (anti-CD14; n&nbsp;=&nbsp;67), dornase alfa (inhaled DNase; n&nbsp;=&nbsp;39) and razuprotafib (Tie2 agonist; n&nbsp;=&nbsp;22). Razuprotafib was dropped from the trial due to feasibility issues. In the modified intention-to-treat analyses, no agent met pre-specified efficacy/graduation endpoints with posterior probabilities for the hazard ratios [HRs] for recovery ≤1.5 between 0.99 and 1.00. The data monitoring committee stopped Celecoxib/Famotidine for potential harm (median posterior HR for recovery 0.5, 95% credible interval [CrI] 0.28-0.90; median posterior HR for death 1.67, 95% CrI 0.79-3.58).InterpretationNone of the first 7 agents to enter the trial met the prespecified criteria for a large efficacy signal. Celecoxib/Famotidine was stopped early for potential harm. Adaptive platform trials may provide a useful approach to rapidly screen multiple agents during a pandemic.FundingQuantum Leap Healthcare Collaborative is the trial sponsor. Funding for this trial has come from: the COVID R&amp;D Consortium, Allergan, Amgen Inc., Takeda Pharmaceutical Company, Implicit Bioscience, Johnson &amp; Johnson, Pfizer Inc., Roche/Genentech, Apotex Inc., FAST Grant from Emergent Venture George Mason University, The DoD Defense Threat Reduction Agency (DTRA), The Department of Health and Human ServicesBiomedical Advanced Research and Development Authority (BARDA), and The Grove Foundation. Effort sponsored by the U.S. Government under Other Transaction number W15QKN-16-9-1002 between the MCDC, and the Government

Lessons learned from the eMERGE Network: balancing genomics in discovery and practice

The Electronic Medical Records and Genomics (eMERGE) Network, established in 2007, is a consortium of academic and integrated health systems conducting discovery and implementation research in translational genomics. Here, we outline the history of the network, highlight major impacts and lessons learned, and present the tools and resources developed for large-scale genomic analyses and translation into a clinical setting. The network developed methods to extract phenotypes from the electronic medical record to perform genome-wide and phenome-wide association studies. Recruited cohorts were clinically sequenced off a custom panel for targeted sequencing of variants and monogenic disease risks and returned to participants to investigate the impact of return of genomic results. After generating a 105,000 participant-imputed genome-wide association study (GWAS) dataset for discovery, the network enrolled and sequenced 24,998 participants. Integration of these results into the medical record and the effects of results on participants provided key lessons to the field. These learned lessons inform genetic research in diverse populations and provide insights into the clinical impact of return and implementation of genomic medicine using the electronic medical record. The lessons produced by the eMERGE Network can be utilized by other consortia as translational genomic medicine research evolves