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BackgroundWearable activity trackers, including fitness bands and smartwatches, offer the potential for disease detection by monitoring physiological parameters. However, their accuracy as specific disease diagnostic tools remains uncertain. ObjectiveThis systematic review and meta-analysis aims to evaluate whether wearable activity trackers can be used to detect disease and medical events. MethodsTen electronic databases were searched for studies published from inception to April 1, 2023. Studies were eligible if they used a wearable activity tracker to diagnose or detect a medical condition or event (eg, falls) in free-living conditions in adults. Meta-analyses were performed to assess the overall area under the curve (%), accuracy (%), sensitivity (%), specificity (%), and positive predictive value (%). Subgroup analyses were performed to assess device type (Fitbit, Oura ring, and mixed). The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Diagnostic Test Accuracy Studies. ResultsA total of 28 studies were included, involving a total of 1,226,801 participants (age range 28.6-78.3). In total, 16 (57%) studies used wearables for diagnosis of COVID-19, 5 (18%) studies for atrial fibrillation, 3 (11%) studies for arrhythmia or abnormal pulse, 3 (11%) studies for falls, and 1 (4%) study for viral symptoms. The devices used were Fitbit (n=6), Apple watch (n=6), Oura ring (n=3), a combination of devices (n=7), Empatica E4 (n=1), Dynaport MoveMonitor (n=2), Samsung Galaxy Watch (n=1), and other or not specified (n=2). For COVID-19 detection, meta-analyses showed a pooled area under the curve of 80.2% (95% CI 71.0%-89.3%), an accuracy of 87.5% (95% CI 81.6%-93.5%), a sensitivity of 79.5% (95% CI 67.7%-91.3%), and specificity of 76.8% (95% CI 69.4%-84.1%). For atrial fibrillation detection, pooled positive predictive value was 87.4% (95% CI 75.7%-99.1%), sensitivity was 94.2% (95% CI 88.7%-99.7%), and specificity was 95.3% (95% CI 91.8%-98.8%). For fall detection, pooled sensitivity was 81.9% (95% CI 75.1%-88.1%) and specificity was 62.5% (95% CI 14.4%-100%). ConclusionsWearable activity trackers show promise in disease detection, with notable accuracy in identifying atrial fibrillation and COVID-19. While these findings are encouraging, further research and improvements are required to enhance their diagnostic precision and applicability. Trial RegistrationProspero CRD42023407867; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=407867

Poor youth mental health is an area of global concern. Summer holiday programs may provide environments that support mental health when the structures and supports of school are not available. The aim of this review was to determine the effectiveness of summer holiday programs in improving the mental health, social–emotional well-being, and cognitive (non-academic) outcomes of children and adolescents. Studies of summer holiday programs for school-aged children (5–18 years) were included if they measured any mental, socio-emotional or cognitive (non-academic) outcome. Studies were excluded if they were published prior to 2000, targeted clinical populations or lasted less than five days. Six databases were searched (April 2023). Risk of bias was assessed using the PEDro tool. Study outcomes were grouped according to three main constructs: mental health (psychological well-being, anxiety, depression, distress, and self-perception including self-esteem, self-worth, self-concept, confidence, and competence); social–emotional well-being (behavior and social skills, e.g., communication, bullying, conflict resolution, empathy, and social skills); and cognitive function (memory, selective attention, and executive function). A fourth “other” group captured substance use, personality traits, character skills, and values. Effect sizes were calculated as the standardized mean difference between pre- and post-intervention scores. The synthesis involved a random-effects meta-analysis (presented in forest plots), where possible, with the remaining outcomes narratively synthesized. Twenty-six studies (n = 6812 participants) were included. The results of the meta-analysis suggested that summer programs showed a statistically non-significant trend toward reducing symptoms of anxiety and depression (k = 2 studies, SMD = −0.17, 95% CI −2.94, 2.60), psychological distress (k = 2 studies, SMD −0.46, 95% CI –1.71, 0.79), and no effect on self-esteem (k = 6 studies, SMD = 0.02, 95% CI −0.02, 0.06) or self-worth (k = 3 studies, SMD = 0.05, 95% CI 0.00, 0.11). Narrative syntheses indicated a pattern toward improvements in general mental health, self-perception, social–emotional outcomes, and cognition. Studies were generally small, with a high risk of bias. Summer holiday programs for children and adolescents show trends toward improving mental, social, emotional, and cognitive outcomes. Programs targeting disadvantaged children showed stronger patterns of improvement related to mental health and self-perception than programs targeting the general population. While effect sizes are small to negligible, they consistently indicate improvements. Summer programs present a promising avenue to promote mental health in children; however, further rigorously designed, clearly reported control-group studies are required to more fully understand their effects.

Vitamin C is crucial for physical well-being, and its deficiency can lead to severe health consequences. Biofortification has been used to address this deficiency by enhancing vitamin C in plants. Additionally, soilless agriculture has been used to conserve and optimize water use in comparison to conventional agriculture. While hydrogels have been shown to improve water conservation and are used for biofortification in crops, their application has only been explored in soil-based and hydroponic farming. The aeroponics system is a plant-growing method that has shown potential for increasing yields and biomass while conserving water and nutrients. In this paper, we have developed an aeroponic-compatible medium to grow romaine lettuce (Lactuca sativa L.) with eggshell powder (ESP) mixed with calcium-alginate hydrogel as a substrate and nutrient source aiming to conserve water and incorporate vitamin C through biofortification. Herein, lower water spray time and higher intervals, with varied gel types and ESP concentrations, resulted in healthy lettuce growth. Plants treated with 0.5% ascorbic acid-absorbed ESP-mixed alginate hydrogel for biofortification showed higher levels of vitamin C compared to the traditional method. This study suggests using an alginate hydrogel–ESP-based substrate in aeroponics to reduce water usage and enhance plant biofortification of vitamin C.

Background: Effective therapeutics given early to high-risk ambulatory patients with coronavirus disease 2019 (COVID-19) could improve outcomes and reduce overall healthcare burden. However, conducting site visits in non-hospitalised patients, who should remain isolated, is problematic. Aim: To evaluate the feasibility of a purely remote (virtual) study in non-hospitalised patients with COVID-19; and the efficacy and safety of nebulised recombinant interferon-β1a (SNG001) in this setting. Design & setting: Randomised, double-blind, parallel-group study, which was conducted remotely. Method: Eligible patients aged ≥65 years (or ≥50 years with risk factors) with COVID-19 and not requiring hospital admission were recruited remotely. They were randomised to SNG001 or placebo once-daily via nebuliser for 14 days. The main outcomes were assessments of feasibility and safety, which were all conducted remotely. Results: Of 114 patients treated, 111 (97.4%) completed 28 days of follow-up. Overall compliance to study medication was high, with ≥13 doses taken by 89.7% and 92.9% of treated patients in the placebo and SNG001 groups, respectively. Over the course of the study, only two patients were hospitalised, both in the placebo group; otherwise there were no notable differences between treatments for the efficacy parameters. No patients withdrew owing to an adverse event, and a similar proportion of patients experienced on-treatment adverse events in the two treatment groups (64.3% and 67.2% with SNG001 and placebo, respectively); most were mild or moderate and not treatment-related. Conclusion: This study demonstrated that it is feasible to conduct a purely virtual study in community-based patients with COVID-19, when the study included detailed daily assessments and with medication administered via nebuliser.

Background: Although many acute exacerbations of COPD (AECOPD) are triggered by non-bacterial causes, they are often treated with antibiotics. Preliminary research suggests that the Chinese herbal medicine “Shufeng Jiedu” (SFJD), may improve recovery and therefore reduce antibiotic use in patients with AECOPD.Aims: To assess the feasibility of conducting a randomised placebo-controlled clinical trial of SFJD for AECOPD in UK primary care.Methods: GPs opportunistically recruited patients experiencing an AECOPD. Participants were randomised 1:1 to usual care plus SFJD or placebo for 14 days. Participants, GPs and research nurses were blinded to treatment allocation. GPs could prescribe immediate, delayed or no antibiotics, with delayed prescribing encouraged where appropriate. Participants were asked to complete a participant diary, including EXACT-PRO and CAT™ questionnaires for up to 4 weeks. Outcomes included recruitment rate and other measures of study feasibility described using only descriptive statistics and with no formal comparisons between groups. We also conducted qualitative interviews with recruited and non-recruited COPD patients and clinicians, analysed using framework analysis.Results: Over 6 months, 19 participants (6 SFJD, 13 placebo) were recruited. Sixteen (84%) participants returned diaries or provided a diary by recall. Overall, 1.3 participants were recruited per 1,000 patients on the COPD register per month open. Median duration of treatment was 9.8 days in the intervention group vs 13.3 days in the placebo group. The main reason for discontinuation in both groups was perceived side-effects. in both groups. Point estimates for both the EXACT-PRO and CAT™ outcomes suggested possible small benefits of SFJD. Most patients and clinicians were happy to try SFJD as an alternative to antibiotics for AECOPD. Recruitment was lower than expected because of the short recruitment period, the lower incidence of AECOPD during the COVID-19 pandemic, patients starting antibiotics from “rescue packs” before seeing their GP, and workforce challenges in primary care.Conclusion: Recruitment was impaired by the COVID-19 pandemic. Nevertheless, we were able to demonstrate the feasibility of recruiting and randomising participants and identified approaches to address recruitment challenges such as including the trial medication in COPD patients’ “rescue packs” and delegating recruitment to a central trials team.Clinical Trial Registration: Identifier, ISRCTN26614726

The Hub Global Labour Conflicts provides scholars, students, activists, and other interested audiences with historical and contemporary data on workers’ collective actions. The project is hosted by the International Institute of Social History in Amsterdam and aims to be a central resource for freely accessible labour conflict data from all over the world. By discussing how the Hub has evolved since its launch in 2015, this article reviews its accomplishments so far, its current limitations and potential areas for expansion. From this, we outline the ambition to make the Hub more global and thus even more strongly embedded within ongoing debates in global labour history. Thereby, we hope to introduce new audiences to the available data or enthuse you to contribute to the project.

Peat is one of the most commonly used substrates in soilless cultivation. However, peat mining produces a negative carbon footprint, which raises the need for alternative sustainable substrate media. To address this, we studied the impact of peat replacement with a combination of various biochars and cotton burr compost on the growth and yield of cucumber (Cucumis sativus L.), and nutrient concentration of media, plant leaf, and fruit in greenhouse conditions. Two experiments were conducted from Nov 2020 through Jan 2021 (Trial 1) and from Feb to Apr 2021 (Trial 2). The treatments were control (peat, vermiculite, and perlite at 2:1:1) and in the control peat was either fully replaced (hardwood biochar+compost, softwood biochar+compost, and hemp biochar+compost) or partially replaced up to 50% (v/v) (hardwood biochar+compost, softwood biochar+compost, and hemp biochar+compost). The control media was more acidic with lowest electrical conductivity than the other treatments. The leaf chlorophyll content and the photosynthetic assimilation rate varied among the treatments in both trials. The final dry shoot biomass was lowest in peat-dominated control treatment suggesting biochar-compost in the substrate media contributed in increased dry biomass of the cucumber plant. The total number of fruits per plant and total yield per plant was significantly increased in all the treatments with the highest in hardwood biochar+compost, compared with the control. The nutrient concentration of media, leaf, and fruit indicates that biochar-compost enhances the nutritional status of the media, which supplies essential nutrients to the plant leaf and fruit while growing in different substrate compositions. Our results suggest that the replacement of peat with full or partial proportions of biochar-compost can produce similar and, in some cases, even better growth, yield, and physiology in potted cucumber than in the unamended control treatment.

Abstract Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major reason for consultations in primary care, hospital admissions, deterioration in function, and mortality. Despite the majority of exacerbations not being caused by bacteria, as many as 70% of patients who present in UK primary care with AECOPD are prescribed antibiotics as part of standard care. However, finding effective non-antibiotic treatments for COPD exacerbations is a priority to reduce antibiotic use. The Chinese herbal medicine Shufeng Jiedu® (SFJD) has the potential to reduce treatment failure and duration of hospital stay. This study aims to determine the feasibility of conducting a fully powered randomised, double blind, placebo-controlled clinical trial on SFJD for AECOPD in UK primary care. Methods This study is a phase III, two-arm individually double blind, randomised, placebo-controlled feasibility trial with nested qualitative study, coordinated by the Southampton Clinical Trial Unit (SCTU). Patients aged ≥ 40 years, with a current AECOPD, presenting with increased sputum purulence/volume, or breathlessness, and for whom the GP is considering use of antibiotics, will be eligible to participate. We aim to recruit seven eligible participants per month and randomise them to receive either the patent Chinese herbal medicine SFJD capsules or placebo for 14 consecutive days and to follow-up for 12 weeks. The primary outcomes include the feasibility of recruitment, study retention, and the percentage of diary completion. Discussion If this trial demonstrates the feasibility of recruitment, delivery, and follow-up, we will seek funding for a fully powered placebo-controlled trial of SFJD for the treatment of AECOPD in primary care. Trial registration This trial is registered via ISRCTN on 1 July 2021, identifier: ISRCTN26614726.

Abstract Vitamin C (Vit C) is an essential micronutrient and antioxidant for human health. Unfortunately, Vit C cannot be produced in humans and is ingested through diet while severe deficiencies can lead to scurvy. However, consumption is often inconsistent, and foods vary in Vit C concentrations. Biofortification, the practice of increasing micronutrient or mineral concentrations, can improve the nutritional quality of crops and allow for more consistent dietary levels of these nutrients. Of the three leading biofortification practices (i.e., conventional, transgenic, and agronomical), the least explored approach to increase Vit C in microgreens is agronomically, especially through the supplemental application of ascorbic acid. In this study, biofortification of Vit C in microgreens through supplemental ascorbic acid was attempted and proven achievable. Arugula (Eruca sativa 'Astro') microgreens were irrigated with four concentrations of ascorbic acid and a control. Total Vit C (T-AsA) and ascorbic acid increased in microgreens as supplementary concentrations increased. In conclusion, biofortification of Vit C in microgreens through supplemental ascorbic acid is achievable, and consumption of these bio-fortified microgreens could help fulfill the daily Vit C requirements for humans, thereby reducing the need for supplemental vitamins.

The consumption of plants plays an important role in human health. In addition to providing macro and micronutrients, plants are the sole sources of several phytonutrients that play a major role in disease prevention. However, in modern diets, increased consumption of cheaper, processed foods with poor nutritional value over fruits and vegetables leads to insufficient consumption of essential nutrients such as vitamin C. Taking supplements can address some of the insufficient nutrients in a diet. However, supplements are not as diverse or bioavailable as the nutrients in plants. Improving the abundance of nutrients in plants will reduce the amounts that need to be consumed, thereby reducing the price barrier and use of supplements. In this study, broccoli (Brassica oleracea var. italica) microgreens grown in a controlled environment were biofortified for increased vitamin C content. The microgreens grown on growing pads were treated with supplemental nutrient solutions. Treatments were applied four to five days after germination and included four different concentrations of ascorbic acid specifically, 0% (control), 0.05%, 0.1%, 0.25% and 0.5%, added to the nutrient solution. Microgreens with turgid cotyledons and appearance of tip of first true leaves were harvested about 14 days after germination and were analyzed for biomass, chlorophylls, carotenoids, vitamin C and other minerals content. The ascorbic acid improved the microgreens’ fresh biomass, percent dry matter, chlorophylls, carotenoids, vitamin C, and potassium content. Moreover, this study also mapped out the correlation between ascorbic acid, phytochemicals, and broccoli microgreens’ mineral composition. The total vitamin C was positively correlated to K and negatively correlated to chlorophylls, N, P, Mg, Ca, S, and B (p < 0.01). These relationships can be applied in future vitamin C biofortification research across different microgreens. In conclusion, vitamin C was increased up to 222% by supplemental ascorbic acid without being detrimental to plant health and mineral composition.

Abstract In pulmonary artery hypertension (PAH), emerging evidence suggests that metabolic abnormalities may be contributing to cellular dysfunction in PAH. Metabolic abnormalities such as glycolytic shift have been observed intracellularly in several cell types in PAH, including microvacular endothelial cells (MVECs). Concurrently, metabolomics of human PAH samples has also revealed a variety of metabolic abnormalities; however the relationship between the intracellular metabolic abnormalities and the serum metabolome in PAH remains under investigation. In this study, we utilize the sugen/hypoxia (SuHx) rodent model of PAH to examine the RV, LV and MVEC intracellular metabolome (using targeted metabolomics) in normoxic and SuHx rats. We additionally validate key findings from our metabolomics experiments with data obtained from cell culture of normoxic and SuHx MVECs, as well as metabolomics of human serum samples from two different PAH patient cohorts. Taken together, our data, spanning rat serum, human serum and primary isolated rat MVECs reveal that: (1) key classes of amino acids (specifically, branched chain amino acids—BCAA) are lower in the pre‐capillary (i.e., RV) serum of SuHx rats (and humans); (2) intracellular amino acid levels (in particular BCAAs) are increased in SuHx‐MVECs; (3) there may be secretion rather than utilization of amino acids across the pulmonary microvasculature in PAH and (4) an oxidized glutathione gradient is present across the pulmonary vasculature, suggesting a novel fate for increased glutamine uptake (i.e., as a source of glutathione). in MVECs in PAH. In summary, these data reveal new insight into the shifts in amino acid metabolism occurring across the pulmonary circulation in PAH.

Colored shading nets have been increasingly studied in semi-arid crop production systems, primarily because of their ability to reduce solar radiation with the attendant reductions in air, plant, and soil temperatures. However, there is a paucity of research concerning the impact of colored shading nets on various crops grown under semi-arid environments, particularly the sweet pepper (Capsicum annum) production system. This study aimed to investigate the effects of three colored shading net treatments (i.e., white, green, and black shading nets with 50% shading intensity and control with unshaded conditions) on the growth and instantaneous water use efficiency (WUE) of sweet pepper. The results showed that all colored shading nets exhibited significantly lower daytime air temperatures and light intensity (22 to 28 °C and 9992 lx, respectively) compared with the control (32 to 37 °C and 24,973 lx, respectively). There were significant differences in sweet pepper growth performance among treatments, including plant height, shoot dry weight, leaf area, leaf chlorophyll content, and vitamin C in ripened fruit. The enhanced photosynthetic rates were observed in sweet pepper plants under the colored shading nets compared with control plants. WUE increased among the colored shading net treatments in the following order: control ≤ white < black < green. Overall, the application of green and black shading nets to sweet pepper production systems under semi-arid environments significantly enhanced plant growth responses and WUE.

In arid and semi-arid climates, water scarcity and nutrient availability are major constraints for food production. Excess fertilization to make up for the limited nutrient availability in dry soils leads to nitrogen runoff and groundwater contamination. Reducing nitrogen leaching into surface water while providing adequate nutrition remains a major challenge. Superabsorbent polymers (SAPs) can reduce water loss and improve nutrient retention and therefore minimize leaching and increase crop yields. SAPs are made from petroleum or natural products, but plant-based SAPs have been gaining popularity because they have fewer long-term effects on the environment. However, there is little known about how SAPs made from cornstarch effect plant growth and production in tomatoes. So, we evaluated total nitrogen and water retention in SAP-treated soils and evaluated their effects on growth and development of tomatoes (Solanum lycopersicum). Soils were amended with different rates of cornstarch-based SAP (i.e., 0 kg SAP, 0 kg SAP+N, 0.5 kg SAP+N, 1 kg SAP+N, 1.5 kg SAP+N, and 2 kg SAP+N). Results indicate that the mean volume of water and nitrates retained in the soils amended with cornstarch-based SAPs increased with increasing rate of SAP. The treatment containing the highest dose (i.e., 2 kg SAP) decreased the amount of leachate and nitrates from soil 79.34% and 93.11% at 3 days after fertilization (DAF) and 78.84% and 81.58% at 9 DAF in comparison with the soil-only and fertilizer-only treatments, respectively. The results also indicate cornstarch-based SAP significantly improved plant growth and yield parameters compared with the treatments without SAP. Furthermore, the greatest number of leaves, flowers, fruits, and dry matter production were found in the 1-kg SAP treatment. Therefore, application of cornstarch-based SAPs can improve tomato production in times of drought stress by retaining more water and nutrients in the active rooting zone and can reduce environmental pollution by reducing nitrogen runoff.

Abstract Background There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. Methods/design AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol can be adapted for each candidate based on prior knowledge of the candidate (i.e. population, primary endpoint and sample size can be amended). This information is detailed in each candidate specific trial protocol of the master protocol. Discussion Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tocilizumab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. Trial registration EudraCT Number: 2020-001860-27 14 March 2020 ClinicalTrials.gov Identifier: NCT04746183 19 February 2021 ISRCTN reference: 27106947

Abstract Background Pelargonium sidoides DC (Geraniaceae) root extract, EPs®7630 or “Kaloba®”, is a widely used herbal remedy for respiratory infections, with some evidence of effectiveness for acute bronchitis. However, it is not yet widely recommended by medical professionals in the UK. There is a need to undertake appropriately designed randomised trials to test its use as an alternative to antibiotics. The aim was to assess the feasibility of conducting a double-blind randomised controlled trial of Pelargonium sidoides root extract for treatment of acute bronchitis in UK primary care, investigating intervention compliance, patient preference for dosage form and acceptability of patient diaries. Study design Feasibility double-blind randomised placebo-controlled clinical trial. Methods We aimed to recruit 160 patients with cough (≤ 21 days) caused by acute bronchitis from UK general practices. Practices were cluster-randomised to liquid or tablet preparations and patients were individually randomised to Kaloba® or placebo. We followed participants up for 28 days through self-reported patient diaries with telephone support and reviewed medical records at one month. Outcomes included recruitment, withdrawal, safety, reconsultation and symptom diary completion rates. We also assessed treatment adherence, antibiotic prescribing and consumption, mean symptom severity (at days 2–4 after randomisation) and time to symptom resolution. We interviewed 29 patients and 11 health professionals to identify barriers and facilitators to running such a randomised trial. Results Of 543 patients screened, 261 were eligible, of whom 134 (51%) were recruited and 103 (77%) returned a completed diary. Overall, 41% (41/100) of patients took antibiotics (Kaloba® liquid group: 48% [15/31]; placebo liquid group: 23% [6/26]; Kaloba® tablet group: 48% [9/21]; placebo tablet group: 50% [11/22]). Most patients adhered to the study medication (median 19 out of 21 doses taken in week 1, IQR 18–21 - all arms combined). There were no serious adverse events relating to treatment. Most patients interviewed found study recruitment to be straightforward, but some found the diary too complex. Conclusions It was feasible and acceptable to recruit patients from UK primary care to a double-blind placebo-controlled trial of herbal medicine (Kaloba®) for the treatment of acute bronchitis, with good retention and low data attrition. Trial registration HATRIC was registered on the ISRCTN registry ( ISRCTN17672884 ) on 16 August 2018, retrospectively registered. The record can be found at http://www.isrctn.com/ISRCTN17672884 .

Semiarid pasture management strategies can affect soil hydraulic and thermal properties that determine water fluxes and storage, and heat flow in unsaturated soils. We evaluated long-term (>10 years) perennial and annual semiarid pasture system effects on saturated hydraulic conductivity (ks), soil water retention curves (SWRCs), soil water thresholds (i.e., volumetric water content (θv) at saturation, field capacity (FC), and permanent wilting point (PWP); plant available water (PAW)), thermal conductivity (λ), and diffusivity (Dt) within the 0–20 cm soil depth. Forage systems included: Old World bluestem (Bothriochloa bladhii) + legumes (predominantly alfalfa (Medicago sativa)) (OWB-legume), native grass-mix (native), alfalfa + tall wheatgrass (Thinopyrum ponticum) (alfalfa-TW), and annual grass-mix (annual) pastures on a clay loam soil; and native, teff (Eragrostis tef), OWB-grazed, and OWB-ungrazed pastures on a sandy clay loam soil. The perennial OWB-legume and native pastures had increased soil organic matter (SOM) and reduced bulk density (ρb), improving ks, soil water thresholds, λ, and Dt, compared to annual teff and alfalfa-TW (P < 0.05). Soil λ, but not Dt, increased with increasing θv. Grazed pastures decreased ks and water retention compared to other treatments (P < 0.05), yet did not affect λ and Dt (P > 0.05), likely due to higher ρb and contact between particles. Greater λ and Dt at saturation and PWP in perennial versus annual pastures may be attributed to differing SOM and ρb, and some a priori differences in soil texture. Overall, our results suggest that perennial pasture systems are more beneficial than annual systems for soil water storage and heat movement in semiarid regions.

Abstract Background Acute lower respiratory tract infection is a common acute infection managed in primary care. The current dominant management strategy in the UK is antibiotics, despite widespread publicity regarding antimicrobial resistance and evidence that the small benefits of antibiotics do not outweigh the harms. There is a need to address the rising problem of antibiotic resistance by providing credible alternative strategies, which reduce symptom burden. There is sufficient evidence to recommend the use of Pelargonium sidoides root extract in order to warrant undertaking an independent clinical trial. We propose a feasibility study to demonstrate our ability to recruit and retain patients and conduct a placebo-controlled trial of Pelargonium sidoides extract EPs®7630 in lower respiratory tract infection where pneumonia is not suspected. Both the tablet and liquid formulations will be included. Methods The HATRIC trial is a double-blind randomised placebo-controlled feasibility study aiming to determine the potential to conduct a fully powered trial of Pelargonium sidoides root extract as an alternative to the inappropriate use of antibiotics for acute bronchitis in UK primary care. Primary care sites will be equally randomised to one of two formulation groups (tablet or liquid preparation). Additionally, within each site, patients will be evenly randomised to active or placebo treatment. Antibiotic consumption will be monitored during the trial, but the use of a delayed prescription strategy is encouraged. The target sample size for this study is 160 patients overall or 40 per arm, recruited from approximately 20 primary care sites. The analysis will be descriptive focusing on estimation with no formal comparison of groups taking place. Discussion If this trial demonstrates the feasibility of recruitment and delivery, we will seek funding for a fully powered placebo-controlled trial of Pelargonium sidoides root extract for the treatment of lower respiratory tract infections in primary care. Trial registration HATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018.

IL-23 is considered a critical regulator of IL-17 in Th17 cells; however, its requirement for inducing IL-17 production in other human immune subsets remains incompletely understood. Mucosal associated invariant T (MAIT) cells uniformly express retinoic acid receptor-related orphan receptor gamma t (RORγt) but only a minor population have been shown to produce IL-17A. Here we show that IL-17F is the dominant IL-17 isoform produced by MAIT cells, not IL-17A. For optimal MAIT cell derived IL-17A and IL-17F production, T cell receptor (TCR) triggering, IL-18 and monocyte derived IL-12 signaling is required. Unlike Th17 cells, this process is independent of IL-23 signaling. Using an in vitro skin cell activation assay, we demonstrate that dual neutralization of both IL-17A and IL-17F resulted in greater suppression of inflammatory proteins than inhibition of IL-17A alone. Finally, we extend our findings by showing that other innate-like lymphocytes such as group 3 innate lymphoid cells (ILC3) and gamma delta (γδ) T cells are also capable of IL-23 independent IL-17A and IL-17F production. These data indicate both IL-17F and IL-17A production from MAIT cells may contribute to tissue inflammation independently of IL-23, in part explaining the therapeutic disconnect between targeting IL-17 or IL-23 in certain inflammatory diseases.

Increasing costs and environmental issues regarding excessive use of peat moss is impacting the horticultural industry. Biochar is a valuable substrate additive that has the potential to reduce the use of peatmoss in greenhouse production. However, its varying effects on ornamentals requires that individual species and cultivars of crops must be evaluated to determine the threshold for benefits. Viola cornuta is a high value ornamental crop; however, information on how different rates of biochar rates affect productivity and physiology of Viola cultivars in container production is not known. To determine if biochar rates could increase the productivity of Viola, we mixed a peat-based substrate with 10, 25, and 50% (w:w) hardwood biochar in two studies on four cultivars. Without fertilizers, 10 and 25% biochar improved plant biomass, growth, root length, and flowering, but 50% biochar was found to have negative effects on plant growth and flowering. Cultivars varied in their response to biochar rates. When fertilizer was applied in the second experiment, biochar rates did not impact growth parameters or flowering. These results suggest that up to 25% biochar can be used in Viola production without detrimental impacts. However, 50% biochar can be used with the addition of fertilizer without negatively affecting plant growth. Biochar can have a short-term impact on the growth characteristics of Viola plants in container production, but fertilization and growing period of Viola may influence these effects. These results indicate that biochar could be the suitable replacement for peat moss, with up to 50% biochar rate in Viola production reducing the environmental and economic burden for peat moss.

As a novel alternative to established surface display or combinatorial chemistry approaches for the discovery of therapeutic peptides, we present a method for the isolation of small, cysteine-rich domains from bovine antibody ultralong complementarity-determining regions (CDRs). We show for the first time that isolated bovine antibody knob domains can function as autonomous entities by binding antigen outside the confines of the antibody scaffold. This yields antibody fragments so small as to be considered peptides, each stabilised by an intricate, bespoke arrangement of disulphide bonds. For drug discovery, cow immunisations harness the immune system to generate knob domains with affinities in the picomolar to low nanomolar range, orders of magnitude higher than unoptimized peptides from naïve library screening. Using this approach, knob domain peptides that tightly bound Complement component C5 were obtained, at scale, using conventional antibody discovery and peptide purification techniques.

Abstract Background Women with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use. Methods/design Adult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below: Group 1 – Uva-ursi + advice to take ibuprofen Group 2 – Placebo + advice to take ibuprofen Group 3 – Uva-ursi + no advice to take ibuprofen Group 4 – Placebo + no advice to take ibuprofen Patients and physicians will be blinded to the randomised group for the herb. The main outcome is symptom severity at days 2–4 recorded in a validated, self-report diary used in previous studies. Secondary outcomes include antibiotic use and symptom duration. In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint. In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package. Discussion The outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics. Trial registration ISRCTN registry, ID: ISRCTN43397016 . Registered on 11 February 2015.

Huanglongbing (HLB) and Phytophthora foot and root rot are diseases that affect citrus production and profitability. The symptoms and physiological changes associated with these diseases are diagnosed through expensive and time-consuming field measurements. Unmanned aerial vehicles (UAVs) using red/green/blue (RGB, true color) imaging, may be an economic alternative to diagnose diseases. A methodology using a UAV with a RGB camera was developed to assess citrus health. The UAV was flown in April 2018 on a grapefruit field infected with HLB and foot rot. Ten trees were selected for each of the following disease classifications: (HLB-, foot rot−), (HLB+, foot rot−), (HLB-, foot rot+) (HLB+, foot rot+). Triangular greenness index (TGI) images were correlated with field measurements such as tree nutritional status, leaf area, SPAD (leaf greenness), foot rot disease severity and HLB. It was found that 61% of the TGI differences could be explained by Na, Fe, foot rot, Ca, and K. This study shows that diseased citrus trees can be monitored using UAVs equipped with RGB cameras, and that TGI can be used to explain subtle differences in tree health caused by multiple diseases.

Ror2 is a Wnt ligand receptor that is overexpressed in a variety of tumors including clear cell renal cell carcinoma (ccRCC). Here we demonstrate that expression of wild type Ror2 results in increased tumorigenic properties in in vitro cell culture and in vivo xenograft models. In addition, Ror2 expression produced positive changes in both cell migration and invasion, which were dependent on matrix metalloprotease 2 (MMP2) activity. Mutations in key regions of the kinase domain of Ror2 resulted in the abrogation of increased tumor growth, cell migration, and cell invasion observed with expression of wild-type Ror2. Finally, we examined Ror2 expression as a prognostic biomarker for ccRCC utilizing the TCGA ccRCC dataset. High expression of Ror2 showed a significant correlation with higher clinical stage, nuclear grade, and tumor stage. Furthermore, high expression of Ror2 in ccRCC patients correlated with significant lower overall survival, cancer specific survival, and recurrence free survival. Together, these findings suggest that Ror2 plays a central role in influencing the ccRCC phenotype, and can be considered as a negative prognostic biomarker and potential therapeutic target in this cancer.

In this study I explored the reported effects of Literacy Collaborative, a whole-school literacy reform model, on teacher turnover through in-depth telephone interviews with 16 randomly sampled teachers. Although 8 of the teachers said Literacy Collaborative would have no effect on whether they stayed at or left their respective schools, the interviews suggested that Literacy Collaborative had professional implications. Eight teachers attributed a stronger and more supportive professional community to Literacy Collaborative, and 12 teachers said their teaching skills and their students' academic outcomes had improved because of the model. The strongest negative themes that were reported by 5 teachers were feelings of disempowerment and increased workload attributed to the model. These negative feelings did not independently drive teachers out but instead interacted with already extant feelings of dissatisfaction and disempowerment. Finally, 5 teachers reported that the school and district administration's understanding of Literacy Collaborative and the level of support teachers felt they received in implementing the model mattered in how teachers perceived their work environment and considered their career decisions.