University of East Anglia

Magnaporthe oryzae is the causal agent of rice blast, one of the most serious diseases affecting rice cultivation around the world. During plant infection, M. oryzae forms a specialised infection structure called an appressorium. The appressorium forms in response to the hydrophobic leaf surface and relies on multiple signalling pathways, including a MAP kinase phosphorelay and cAMP‐dependent signalling, integrated with cell cycle control and autophagic cell death of the conidium. Together, these pathways regulate appressorium morphogenesis.The appressorium generates enormous turgor, applied as mechanical force to breach the rice cuticle. Re‐polarisation of the appressorium requires a turgor‐dependent sensor kinase which senses when a critical threshold of turgor has been reached to initiate septin‐dependent re‐polarisation of the appressorium and plant infection. Invasive growth then requires differential expression and secretion of a large repertoire of effector proteins secreted by distinct secretory pathways depending on their destination, which is also governed by codon usage and tRNA thiolation. Cytoplasmic effectors require an unconventional Golgi‐independent secretory pathway and evidence suggests that clathrin‐mediated endocytosis is necessary for their delivery into plant cells. The blast fungus then develops a transpressorium, a specific invasion structure used to move from cell‐to‐cell using pit field sites containing plasmodesmata, to facilitate its spread in plant tissue. This is controlled by the same MAP kinase signalling pathway as appressorium development and requires septin‐dependent hyphal constriction. Recent progress in understanding the mechanisms of rice infection by this devastating pathogen using live cell imaging procedures are presented.

Agriculture is an essential component of human sustenance in this world. These days, with a growing population, we must significantly increase agricultural productivity to meet demand. Agriculture moved toward technologies as a result of the demand for higher yields with less resources. Increasing awareness of the significance and influence of agricultural practices in global climate change has made the use of energy-efficient innovations a vital aspect of the agriculture sector. The use of greenhouses to provide controlled environments that encourage effective plant growth is one of the current associated approaches. If not properly maintained, the energy used to run the greenhouses’ chillers, heaters, humidifiers, carbon dioxide (CO₂) generators, and carbon emissions becomes expensive. The goal of this research is to create a sustainable greenhouse model while achieving the best plant growth requirements with minimal use of energy. In order to achieve the lowest possible amount of energy consumption, the optimization model considered temperature, humidity, CO₂ levels, and sunlight as essential parameters in the environment. The Artificial Bee Colony (ABC) optimization technique was utilized for setting the environmental parameters for plant growth, considered for the suggested system. The system’s inputs were plant-preferred factors, and plant comfort was achieved by applying ABC to boost the parameters’ efficiency. A fuzzy controller was utilized to regulate different devices, including humidifiers, heaters, chillers, and CO₂ generators, by entering the introduced values. The overall efficacy of the fuzzy controllers that switch On/Off the actuators was obtained by minimizing the error between the best estimates of environmental factors and the ABC optimized values. Additionally, the suggested method was contrasted with other effective algorithms, such as Genetic Algorithm (GA), Firefly Algorithm (FA), and Ant Colony Optimization (ACO). Based on the results of the comparison analysis between the ABC algorithm and current practices, present procedures do not minimize the fluctuations in the inaccuracy between the target and actual environmental parameters, which is a necessary step towards increasing energy efficiency. The suggested method used 162.19 kWh for temperature control, 84.65405 kWh for Humidity, 131.2013 kWh for Sunlight, and 603.55208 kWh for CO₂ management, indicating the maximum energy efficiency. ACO needed 172.2621 kWh, 88.269 kWh, 175.7127 kWh, and 713.2125 kWh, in contrast to FA 169.7983 kWh, 86.04496 kWh, 155.8442 kWh, and 743.7986 kWh. Temperature, Humidity, Sunlight, and CO₂ were measured by GA at 164.1609 kWh, 86.19566 kWh, 174.6429 kWh, and 734.9514 kWh, respectively. In terms of Plant comfort, the suggested approach also outperformed 0.986770848 ACO (0.944043), FA (0.949832), and GA (0.946076). It is important to note that the research being done has the potential to minimize operating costs and maximize the amount of energy needed for plant growth, thereby creating a model for sustainable greenhouse agriculture.

Banana is sensitive to cold stress and often suffers from chilling injury with browning peel and failure to normal ripening. We have previously reported that banana chilling injury is accompanied by a reduction of miR528 accumulation, alleviating the degradation of its target gene MaPPO and raising ROS levels that cause peel browning. Here, we further revealed that the miR528-MaPPO cold-responsive module was regulated by miR156-targeted SPL transcription factors, and the miR156c-MaSPL4 module was also responsive to cold stress in banana. Transient overexpression of miR156c resulted in a more severe chilling phenotype by decreasing the expression of MaSPL4 and miR528. Conversely, the browning was alleviated in STTM-miR156c silencing and OE-MaSPL4 samples. Furthermore, DNA affinity purification sequencing and MaSPL4-overexpressing transcriptome jointly revealed that MaSPL4 may mediate the transcription of genes related to lipid metabolism and antioxidation, in addition to the miR528-MaPPO module, demonstrating MaSPL4 as a master regulator in the fruit cold response network. In summary, our results suggest that the miR156c-MaSPL4 module can mediate the chilling response in banana by regulating the miR528-MaPPO module and multiple other pathways, which provides evidence for the crosstalk between TFs and miRNAs that can be used for the molecular breeding of fruit cold tolerance. Supplementary Information The online version contains supplementary material available at 10.1186/s43897-024-00115-1.

Fungi are the most important group of plant pathogens, responsible for many of the world’s most devastating crop diseases. One of the reasons they are such successful pathogens is because several fungi have evolved the capacity to breach the tough outer cuticle of plants using specialized infection structures called appressoria. This is exemplified by the filamentous ascomycete fungus Magnaporthe oryzae , causal agent of rice blast, one of the most serious diseases affecting rice cultivation globally. M. oryzae develops a pressurized dome-shaped appressorium that uses mechanical force to rupture the rice leaf cuticle. Appressoria form in response to the hydrophobic leaf surface, which requires the Pmk1 MAP kinase signalling pathway, coupled to a series of cell-cycle checkpoints that are necessary for regulated cell death of the fungal conidium and development of a functionally competent appressorium. Conidial cell death requires autophagy, which occurs within each cell of the spore, and is regulated by components of the cargo-independent autophagy pathway. This results in trafficking of the contents of all three cells to the incipient appressorium, which develops enormous turgor of up to 8.0 MPa, due to glycerol accumulation, and differentiates a thickened, melanin-lined cell wall. The appressorium then re-polarizes, re-orienting the actin and microtubule cytoskeleton to enable development of a penetration peg in a perpendicular orientation, that ruptures the leaf surface using mechanical force. Re-polarization requires septin GTPases which form a ring structure at the base of the appressorium, which delineates the point of plant infection, and acts as a scaffold for actin re-localization, enhances cortical rigidity, and forms a lateral diffusion barrier to focus polarity determinants that regulate penetration peg formation. Here we review the mechanism of regulated cell death in M. oryzae , which requires autophagy but may also involve ferroptosis. We critically evaluate the role of regulated cell death in appressorium morphogenesis and examine how it is initiated and regulated, both temporally and spatially, during plant infection. We then use this synopsis to present a testable model for control of regulated cell death during appressorium-dependent plant infection by the blast fungus.

Aim We describe activity, outcomes, and benefits after streaming low urgency attenders to G eneral practice services at D oor of A ccident and E mergency departments (GDAE). Background Many attendances to A&Es are for non-urgent health problems that could be better met by primary care rather than urgent care clinicians. It is valuable to monitor service activity, outcomes, service user demographics, and potential benefits when primary care is co-located with A&E departments. Methods As a service evaluation, we describe and analyse GDAE users, reasons for presentation, wait times, outcomes, and co-located A&E wait times at two hospitals in eastern England. Distributions of outcomes, wait times, reasons for attendance, deprivation, and age groups were compared for GDAE and usual A&E attenders at each site using Pearson chi-square tests and accelerated time failure modelling. Performance in a four-hour key performance indicator was descriptively compared for co-located and similar emergency departments. Findings Each GDAE saw about 1025 patients per month. Wait times for usual accident and emergency (A&E) care are relatively short at only one site. Reattendances were common (about 11% of unique patients), 75% of GDAE attenders were seen within 1 hour of arrival, 7% of patients initially allocated to GDAE were referred back to A&E for further investigations, and 59% of GDAE patients were treated and discharged with no further treatment or referral required. Pain, injury, infection, or feeling generally unwell each comprised > 10% of primary reasons for attendance. At James Paget University Hospital, 4.3%, and at Queen Elizabeth Hospital, 16.1% of GDAE attendances led to referral to specialist health services. GDAE attenders were younger and more socially deprived than attenders to co-located A&Es. Patients were seen quickly at both GDAE sites, but there were differences in counts of specialist referrals and wait times. Process evaluation could illuminate reasons for differences between study sites.

Metaphor comprehension has been investigated in neurodevelopmental disorders, but studies devoted to adults with dyslexia are few and present inconsistent results. The present study sought to investigate how adults with dyslexia process novel metaphors. Individual differences in vocabulary, working memory, and Theory of Mind were also assessed. An online metaphor comprehension task based on the Visual World Paradigm was carried out with eye-tracking. Metaphors and corresponding literal sentences were aurally presented in isolation, and participants were asked to select a picture that best corresponded to the sentence they heard. Our results indicated that participants with dyslexia chose metaphor interpretations at a similar rate as did the control group. However, online processing data indicated generally slower response times, with a particular delay in processing metaphorical utterances. Eye movement analyses provided further insights into the underlying nature of the processing slowdowns, highlighting specific challenges encountered by individuals with dyslexia when interpreting figurative language.

This chapter deals with quoting practices in the German COVID-19 debate, specifically with polemical misrepresentations of statements by the Health Minister Karl Lauterbach. Both he and the scientist Christian Drosten had to defend themselves against biased quoting practises of the media and other politicians who selectively (mis)quoted historical statements to show that in the light of later pandemic developments these two speakers had been wrong or mendacious. The chapter first analyzes in detail the metapragmatic counter-argumentation that Lauterbach (assisted by Drosten) developed in order to counter the anachronistic misconstruction of his own earlier statements as having been proven wrong by later pandemic events. Then I investigate the exploitation of such misquotations by extremist parties and politicians who use them to “prove” conspiracist narratives of the pandemic as a hoax or a conspiracy against the people. The analysis shows that “vilification-by-misquotation” can lead to serious threats against the safety of the quoted speakers and to general confusion. In conclusion, this type of anachronistic misquotation is defined as a special case of deceitful metarepresentation.

Objectives Berlinia confusa is used as wound healing agent in folklore medicine. However, this has not been scientifically validated and there is dearth of information on its bioactive metabolites. The current research aimed at evaluating the wound healing, antioxidant and antimicrobial activities of the stem bark of the plant and track down some of its metabolites. Methods The dermal excision model in Sprague Dawley rats was used for the in vivo wound healing activity of the 70% ethanol extract (formulated as 1% and 2% cream). The DPPH radical scavenging and in-vivo lipid peroxidation assays were used to assess the antioxidant activity whereas the agar well and broth-dilution assays were used for the antimicrobial activity evaluation. The PrestoBlue cell viability in keratinocytes and acute dermal toxicity assays were used for the safety assessment. Results The 1% w/w extract showed over 70% wound surface closure from day 13-23 whereas the 2% w/w exhibited similar effect from day 15-23. The activity of the extract was comparable to 1% silver sulphadiazine (SSD) used as reference agent. The extract (1% w/w) also significantly reduced malondialdehyde (MDA) levels (455.2 ± 11.91) compared to the negative control group (739.8 ± 44.93) and was also superior to silver sulphadiazine (MDA level 548.4 ± 10.73). The extract again showed a considerable antimicrobial activity against pathogenic microorganisms with MIC's in the range of 5-10 mg/mL. The 2% extract did not show any skin irritation and were mildly toxic (88.2 ± 3.76% viability) to keratinocytes. Purification of the extract yielded two (2) major known wound healing metabolites including betulinic acid and catechin. Conclusion Berlinia confusa has demonstrated considerable wound healing in vivo and also mitigated healing modifying factors such as microbes and reactive oxygen species.

Background Studies that report an association between anticholinergic medications and dementia often suffer from confounding by indication and rarely consider gender effects. We estimated the association between recurrent prescriptions for anticholinergic overactive bladder (OAB) medications and incident dementia, separately in men and women. Method We studied patients aged ≥50 years first prescribed an anticholinergic OAB drug (e.g. oxybutynin, solifenacin, tolterodine) during 1998‐2019 in England using the Clinical Practice Research Datalink Aurum (CPRD) linked to hospital admissions data. To reduce confounding by indication, we compared patients receiving a second prescription to those only prescribed one during the first year. To reduce protopathic bias, we began follow‐up for incident dementia (first diagnosis in CPRD, hospital data or prescription for a cognitive enhancer) first prescription, and censored patients at death, leaving the practice, one month before last data collection, or 31/3/2020. We excluded patients with history of dementia, cognitive impairment, serious central nervous system disorders, severe mental illness, alcohol abuse, or <12 months registration with their GP. We used Cox regression, with age as the time‐scale, to estimate hazard ratios (HR) for recurrent OAB prescription and incident dementia adjusted for many socio‐demographic and health‐related covariates, comorbidities, and concomitant medications, separately in men and women. We also examined risks by drug and cumulative defined daily doses (DDDs). Result We included 80,874 men and 149,930 women who initiated bladder anticholinergics with ≥3 years of subsequent follow‐up. Of these, 83,718 (received only one prescription during the first year. Receiving a second prescription was associated with a greater increased dementia incidence in men (HR = 1.23, 95%CI 1.17‐1.29) than women (HR = 1.11, 95%CI 1.08‐1.15; p = 0.002 for gender interaction). Associations increased with greater cumulative exposure, with HRs (95%CI) of 1.32 (1.24‐1.40) and 1.16 (1.11‐1.21) for >6 months of DDDs (vs ≤1 month) for men and women. Conclusion We observed greater increased rates of dementia for men with recurrent OAB anticholinergic prescriptions than women, and associations were dose‐dependent. Prescribers should exercise additional caution in men, and aim for alternative management options or the lowest effective dose and a limited period where possible.

Background Reported effects of Hormone Replacement Therapy (HRT) on late‐life neurodegenerative disease are inconsistent. Variability in the timing and formulation of HRT, plus whether an individual carries an Apolipoprotein (APOE) e4 genetic risk variant for Alzheimer’s Disease (AD), likely contribute to conflicting results. Additionally, whilst many studies have focused exclusively on the effects of exogenous oestrogen, the inclusion of testosterone in HRT appears protective against AD pathology, specifically in APOE e4 carriers. This project will investigate whether the introduction of HRT affects cognition in mid‐life, including whether benefits are influenced by HRT formulation, timing of initiation, and APOE genotype. Methods Peri and early postmenopausal women (minimum n = 500) being newly prescribed HRT will be recruited from Newson Health specialist menopause clinics. Participants will complete a suite of online cognitive tasks targeting domains sensitive to preclinical AD (e.g., perceptual discrimination, spatial navigation), alongside questionnaires capturing cognitive, physical, and behavioural menopause symptoms, at baseline, 4‐months, and 12‐months. A tissue sample will be collected for APOE genotype analysis. HRT prescription and circulating blood‐hormone levels will also be available from clinic records. Results Existing cohort data (n = 10,222) from Newson Health indicates 97% patients present at clinic with memory or concentration complaints. Pilot data for this study (n = 85, mean age 56.48 years, peri/postmenopausal women) showed HRT users (relative to non‐users) were significantly quicker on a perceptual 'odd‐one‐out’ task (p = .025) and trended to show better lure discrimination on an object mnemonic similarity task (p = .064). This project builds on this by testing whether the introduction of HRT influences cognition longitudinally, including whether effects differ by HRT formulation (estrogen/+progesterone/+testosterone), timing of initiation relative to menopause, and APOE genotype. Exploratory analysis will consider whether predicted benefits of HRT are moderated by non‐cognitive menopause symptoms, cardiovascular health, and wider lifestyle factors. Conclusions Exploring the impact of HRT on cognition, specifically in interaction with the leading genetic risk factor for AD, will further research into how we can promote women’s brain health from mid‐life. Additionally, this research will inform best‐practices for HRT prescription, considering possible effects on late‐life neurodegenerative disease.

Decolonisation is redressing colonial legacies and reaffirming self-determination. Understandings of decolonisation in social work field education literature were examined using a social justice lens. This scoping review combined systematic database searching with decolonising methods including relational searches. Data synthesis included thematic and deductive analysis to critical frameworks. The 43 studies included were primarily English-speaking and post-2010. Themes emphasised integrating Indigenous knowledge, challenging White dominance, reconstructing spaces, promoting critical reflection, and understanding socio-political contexts. Analysis highlighted the need for ameliorative and transformative change. Cultural and epistemic injustices embedded in social work field education marginalise non-White social work students. If unaddressed, harmful practices will be perpetuated.

Manipulation and reduction (M&R) of an injured limb is often required to reduce pain, bleeding and restore anatomical alignment, typically using procedural sedation and analgesia (PSA). Inhaled methoxyflurane (IMF) may be a suitable alternative that is simple to administer, does not require intravenous access, and has a favourable side effect profile. The objective of this systematic review and meta-analysis was to determine the effectiveness of IMF compared to PSA for M&R in acute traumatic limb injury. The primary outcome measure was procedural success rate. The secondary outcomes were to compare the length of stay, adverse events, patient satisfaction and cost-effectiveness. Methods This systematic review was planned, conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and is registered on PROSPERO CRD42024561087. A literature search was conducted and included studies from database inception to the search date (22 February 2024), using MEDLINE, EMBASE, Cochrane, CINAHL and PubMed platforms. All studies involving the use of IMF for M&R of acute traumatic limb injuries were included. Animal studies, case-reports, non-English language publications and opinion articles were excluded. The risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analysis was undertaken for the primary outcome of procedural success. Narrative synthesis was undertaken for the themes of length of stay, adverse events, patient satisfaction and cost-effectiveness. Results Fifty one abstracts were screened through a database search, reference review, and search of the grey literature. Following full-text review and exclusions, a total of six studies were included, with two suitable for meta-analysis. No significant differences in performance were observed between IMF and PSA (RR 0.90, 95% confidence interval 0.77–1.04, p = 0.16). Patients receiving IMF had a shorter emergency department length of stay, a low incidence of adverse events, and overall positive patient satisfaction. There may be cost-savings associated with the use of IMF. Conclusion Inhaled methoxyflurane was observed to perform no differently to procedural sedation for the successful manipulation and reduction of acute traumatic limb injuries in the emergency department. The overall quality of the evidence is poor, and further higher-level evidence is required.

Aim We aimed to identify enablers and barriers of using primary care routine data for healthcare research, to formulate recommendations for improving efficiency in knowledge discovery. Background Data recorded routinely in primary care can be used for estimating the impact of interventions provided within routine care for all people who are clinically eligible. Despite official promotion of ‘efficient trial designs’, anecdotally researchers in the Asthma UK Centre for Applied Research (AUKCAR) have encountered multiple barriers to accessing and using routine data. Methods Using studies within the AUKCAR portfolio as exemplars, we captured limitations, barriers, successes, and strengths through correspondence and discussions with the principal investigators and project managers of the case studies. Results We identified 14 studies (8 trials, 2 developmental studies and 4 observational studies). Investigators agreed that using routine primary care data potentially offered a convenient collection of data for effectiveness outcomes, health economic assessment and process evaluation in one data extraction. However, this advantage was overshadowed by time-consuming processes that were major barriers to conducting efficient research. Common themes were multiple layers of information governance approvals in addition to the ethics and local governance approvals required by all health service research; lack of standardisation so that local approvals required diverse paperwork and reached conflicting conclusions as to whether a study should be approved. Practical consequences included a trial that over-recruited by 20% in order to randomise 144 practices with all required permissions, and a 5-year delay in reporting a trial while retrospectively applied regulations were satisfied to allow data linkage. Conclusions Overcoming the substantial barriers of using routine primary care data will require a streamlined governance process, standardised understanding/application of regulations and adequate National Health Service IT (Information Technology) capability. Without policy-driven prioritisation of these changes, the potential of this valuable resource will not be leveraged.

Globally scarce and ecologically valuable, the lowland chalk streams of southern and eastern England experience extensive eutrophication pressures arising from intensive agriculture. Mitigation measures are required to restore natural chalk stream functioning and the reintroduction of the Eurasian beaver (Castor fiber) could provide a solution. Here, we investigated the impact upon chalk stream hydrochemistry of the reintroduction of beavers to a 6-ha enclosure on the headwaters of the River Glaven, Norfolk. Over a two-year period (March 2022-May 2024), 190 river water samples were collected across control and impact sites displaying minor-to-major hydrological disturbance from beaver activity, with samples analysed for nitrate (NO 3), phosphate (PO 4), and dissolved organic carbon (DOC). Results revealed significant reductions in nutrient concentrations downstream of the beaver enclosure (NO 3 =-43%; PO 4 =-51%), as well as significantly lower concentrations relative to the agricultural control site (NO 3 =-64%; PO 4 =-86%). Conversely, DOC concentrations were significantly higher downstream of the enclosure (+ 94%) and compared to the control (+ 272%). Greater reductions in nitrate and phosphate during the summer (NO 3 =-47%; PO 4 =-61%) compared to winter (NO 3 =-37%; PO 4 =-38%) indicated biological assimilation within the beaver wetland as a likely causal mechanism, whilst lower dissolved oxygen concentrations within the beaver ponds indicated a role for denitrification in nitrate removal. Overall, these results demonstrate that beaver wetlands can significantly mitigate eutrophication risk in agriculturally impacted chalk streams and provides further evidence in support of their wider reintroduction to English catchments.

Rationale There is limited guidance on the best ways to stop using nicotine‐containing vapes (otherwise known as e‐cigarettes) and ensure long‐term abstinence, whilst minimising the risk of tobacco smoking and other unintended consequences. Treatments could include pharmacological interventions, behavioural interventions, or both. Objectives To conduct a living systematic review assessing the benefits and harms of interventions to help people stop vaping compared to each other or to placebo or no intervention. To also assess how these interventions affect the use of combustible tobacco, and whether the effects vary based on participant characteristics. Search methods We searched the following databases from 1 January 2004 to 24 April 2024: CENTRAL; MEDLINE; Embase; PsycINFO; ClinicalTrials.gov (through CENTRAL); World Health Organization International Clinical Trials Registry Platform (through CENTRAL). We also searched the references of eligible studies and abstracts from the Society for Research on Nicotine and Tobacco 2024 conference, and contacted study authors. Eligibility criteria Randomised controlled trials (RCTs) recruiting people of any age using nicotine‐containing vapes, regardless of tobacco smoking status. Studies had to test an intervention designed to support people to quit vaping, and plan to measure at least one of our outcomes. Outcomes Critical outcomes: vaping cessation; change in combustible tobacco use at six months or longer; number of participants reporting serious adverse events (SAEs) at one week or longer. Risk of bias We used the Cochrane RoB 1 tool to assess bias in the included studies. Synthesis methods We followed standard Cochrane methods for screening and data extraction. We grouped studies by comparisons and outcomes reported, and calculated individual study and pooled effects, as appropriate. We used random‐effects Mantel‐Haenszel methods to calculate risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. We used random‐effects inverse variance methods to calculate mean differences and 95% CI for continuous outcomes. We assessed the certainty of the evidence using the GRADE approach. Included studies Nine RCTs, representing 5209 participants motivated to stop using nicotine‐containing vapes at baseline, are included. In six studies, participants were abstinent from smoking tobacco cigarettes at baseline, although most studies included some participants who had previously smoked. Eight studies included participants aged 18 or older, three included only young adults (18 to 24 years), and one included 13‐ to 17‐year‐olds only. We judged three studies at low risk, three at high risk, and three at unclear risk of bias. Synthesis of results Pharmacological interventions for quitting nicotine vaping Studies assessed combination nicotine replacement therapy (NRT), cytisine, and varenicline as pharmacological interventions for quitting vaping in comparison to placebo or no/minimal support (control). The point estimate for combination NRT indicated possible benefit, but the CI incorporated the possibility of no benefit and a potential benefit of control (very low‐certainty evidence due to imprecision and risk of bias; RR 2.57, 95% CI 0.29 to 22.93; 1 study, 16 participants). The one study investigating cytisine did not report vaping cessation rates at six months or longer. Varenicline increased vaping cessation rates at six months, but the evidence was low certainty due to imprecision (RR 2.00, 95% CI 1.09 to 3.68; 1 study, 140 participants). Zero participants reported SAEs in the studies of combination NRT versus no/minimal support (1 study, 508 participants; low‐certainty evidence due to imprecision) and cytisine versus placebo (1 study, 159 participants; low‐certainty evidence due to imprecision). Three studies investigating varenicline measured the number of participants reporting SAEs. However, only one study reported an SAE (in the intervention arm); therefore, the effect estimate was calculated based on that single study (RR 2.60, 95% CI 0.11 to 62.16; 95 participants; low‐certainty evidence due to imprecision). Behavioural interventions for quitting nicotine vaping Studies assessed reducing nicotine concentration and vaping behaviour (1 study) and text message‐based interventions (3 studies) as behavioural interventions for stopping vaping in comparison to no/minimal support (control). In one study, the point estimate suggested nicotine/vaping reduction increased vaping cessation compared to minimal support at six‐month follow‐up, but the CI incorporated the possibility of no intervention effect and higher cessation rates in the control arm (RR 3.38, 95% CI 0.43 to 26.30; 17 participants; very low‐certainty due to imprecision and risk of bias). There was low‐certainty evidence (downgraded two levels due to indirectness) that text message‐based interventions may have increased vaping cessation rates compared to control in 13‐ to 24‐year‐olds (RR 1.32, 95% CI 1.19 to 1.47; I² = 0%; 2 studies, 4091 participants). The one study investigating nicotine/vaping behaviour reduction did not report on SAEs. One of the studies investigating text message‐based interventions did report on SAEs; however, zero events were reported in both study arms (508 participants; low‐certainty evidence due to imprecision). No studies reported change in combustible tobacco smoking at six‐month follow‐up or longer. Authors' conclusions There is low‐certainty evidence that text message‐based interventions designed to help people stop nicotine vaping may help more youth and young adults to successfully stop than no/minimal support, and low‐certainty evidence that varenicline may also help people quit vaping. Data exploring the effectiveness of combination NRT, cytisine, and nicotine/vaping behaviour reduction are inconclusive due to risk of bias and imprecision. Most studies that measured SAEs reported none; however, more data are needed to draw clear conclusions. Of note, data from studies investigating these interventions for quitting smoking have not demonstrated serious concerns about SAEs. No studies assessed the change in combustible tobacco smoking, including relapse to or uptake of tobacco smoking, at six‐month follow‐up or longer. It is important that future studies measure this so the complete risk profile of relevant interventions can be considered. We identified 20 ongoing RCTs. Their incorporation into the evidence base and the continued identification of new studies is imperative to inform clinical and policy guidance on the best ways to stop vaping. Therefore, we will continue to update this review as a living systematic review by running searches monthly and updating the review when relevant new evidence that will strengthen or change our conclusions emerges. Funding Cancer Research UK (PRCPJT‐Nov22/100012). National Institute of Health Research (NIHR206123) Registration Protocol available via DOI: 10.1002/14651858.CD016058.

Plants lack specialized and mobile immune cells. Consequently, any cell type that encounters pathogens must mount immune responses and communicate with surrounding cells for successful defence. However, the diversity, spatial organization and function of cellular immune states in pathogen-infected plants are poorly understood¹. Here we infect Arabidopsis thaliana leaves with bacterial pathogens that trigger or supress immune responses and integrate time-resolved single-cell transcriptomic, epigenomic and spatial transcriptomic data to identify cell states. We describe cell-state-specific gene-regulatory logic that involves transcription factors, putative cis-regulatory elements and target genes associated with disease and immunity. We show that a rare cell population emerges at the nexus of immune-active hotspots, which we designate as primary immune responder (PRIMER) cells. PRIMER cells have non-canonical immune signatures, exemplified by the expression and genome accessibility of a previously uncharacterized transcription factor, GT-3A, which contributes to plant immunity against bacterial pathogens. PRIMER cells are surrounded by another cell state (bystander) that activates genes for long-distance cell-to-cell immune signalling. Together, our findings suggest that interactions between these cell states propagate immune responses across the leaf. Our molecularly defined single-cell spatiotemporal atlas provides functional and regulatory insights into immune cell states in plants.

In this study, a robust adaptive control strategy using a ${{\mathcal {L}}}$1 theory is applied to fulfil the motion control of a four-wheel electric vehicle. The dynamic model includes longitudinal velocity, lateral velocity, and yaw rate. To develop the proposed control strategy, the vehicle dynamics are decomposed into linear and nonlinear components. The linear part is controlled by fine-tuned state feedback, with its steady-state error addressed by a feedforward control block. The nonlinear part is addressed based on nonlinear adaptive laws and ${{\mathcal {L}}}$1 theory to mitigate adverse effects on the linear dynamics, unwanted parameter changes, and external disturbances. An essential component of the proposed approach is the incorporation of a reference model that dictates the desired system responses. A projection algorithm is used to instantly estimate the nonlinear part of the vehicle dynamics. The performance of the closed-loop system is thoroughly evaluated over a range of vehicle manoeuvres, assessing factors such as steady-state accuracy, transient response, and power consumption. In addition, the effectiveness of the proposed method is compared with conventional model reference adaptive control and a recent robust control approach, particularly in terms of robustness to uncertainties inherent in the nonlinear aspects of vehicle dynamics.

Migratory birds depend on a suite of sites across their annual cycles, making them vulnerable to a wide variety of anthropogenic pressures. Current area‐based conservation measures have been found inadequate to safeguard migratory birds, in part due to a lack of consideration for the connectivity between sites mediated by the movements of individuals. To address this issue, we develop a network analysis integrating different types of individual movement data for a migratory shorebird, the Black‐tailed Godwit (Limosa limosa), across the East Atlantic Flyway. Leveraging metal‐ring recoveries, colour‐ring re‐sightings and satellite tracking from over 10,000 individual godwits, we quantify variation in connectivity between sites across the migratory range, using two weighted metrics to address sampling biases. Colour‐ring re‐sightings provided the largest number of sites (70%) and links (60% and 43% per season) overall, followed by tracking data (50% of sites, 49% and 63% of links per season) and ring recoveries (25% of sites, <1% of links per season), with clear regional variation in datatype contributions. Sampling completeness of the network structure varied with longitude, with information particularly lacking in central and eastern countries of both Europe and Africa. We identified 49 sites playing a disproportionate role in the site network, each with direct connections to 48 (interquartile range 32–84) other sites, on average. Just 23 (47%) top sites are formally recognized for their international importance for Black‐tailed Godwits, and 33 (67%) were robust to sampling incompleteness. Across all 1058 sites, 20% lacked protected area coverage, and per site, 44% (44% ± SD) of bird relocations fell within protected areas. Integrating multiple sources of data improved geographical coverage and completeness of the site network, allowing us to quantify the importance of sites in terms of connectivity across the flyway. Our results highlight shortcomings of existing area‐based conservation measures and add value to ongoing efforts to identify important sites for migratory birds. Policy implications. The increasing availability of individual movement data provides valuable opportunities to reveal the inter‐dependence of sites used by migratory species, which can help identify priority areas and facilitate flyway‐scale management.