Biology subjects

Wilson, N.

Publications and source records attributed to Wilson, N..

16 recordsLinked to original sources

bioRxiv2026

Antibiotic condensates activate magnesium signaling to drive drug tolerance

The spatial distribution of small molecules within cells shapes their biological activity, yet these distributions are generally assumed to be governed passively by reaction-driven electrochemical gradients. Here we show that aminoglycoside antibiotics actively control their own subcellular organization by undergoing phase separation with RNAs. Combining in vitro reconstitution, bacterial assays, and molecular dynamics simulations, we discovered that aminoglycosides coacervate with RNA through multivalent electrostatic interactions, displacing and releasing RNA-bound Mg2+. This condensate-dependent Mg2+ release remodels the cytosolic labile Mg2+ pool and activates magnesium signaling. This effect dampens the magnesium-starvation regulation, sustains ribosome activity, and shifts the cellular electrochemical state, promoting bacterial fitness. Because condensation occurs only above a defined concentration threshold, it generates a non-monotonic dose-response in which higher antibiotic concentrations paradoxically enhance bacterial survival. This antibiotic condensate-dependent Mg2+ signaling confers tolerance to multiple ribosome-targeting antibiotics simultaneously even in cells lacking resistance gene, while condensate dissolution restores antibiotic efficacy. Our findings establish antibiotic-driven phase separation as a previously unrecognized mechanism to encode cellular signaling and identify antibiotic condensates as a distinct functional unit underlying drug tolerance.

microbiology↗

bioRxiv2026

AMPK senses cellular levels of nicotinamide adenine dinucleotide

The electron shuttle and coenzyme nicotinamide adenine nucleotide (NAD) is essential for cellular metabolism and homeostasis. NAD levels significantly fluctuate in cells, whilst several age-related diseases are associated with depletion of this metabolite. However, how NAD changes are monitored by nutrient/energy sensing signalling pathways remains poorly understood. We found that at physiological concentrations NAD controls the activity of the AMP-activated protein kinase (AMPK) in vitro and in human cells. Mechanistically, NAD binds gamma subunit of AMPK, and mutagenesis of the putative binding site renders the holoenzyme insensitive to NAD inhibition. Hyperactivation of AMPK in response to NAD depletion suppresses metabolic pathways including mammalian Target of Rapamycin Complex I (mTORC1) and autophagy. These results demonstrate that in addition to monitoring cellular energy levels AMPK functions as a NAD sensor, providing novel insight into how cells and tissues detect and respond to metabolic fluctuations with implications for stress resistance and ageing.

molecular biology↗

bioRxiv2026

Unsupervised anomaly detection for tumor delineation in a preclinical model of glioblastoma using CEST MRI

IntroductionGlioblastoma is characterized by heterogeneous tumor characteristics and infiltrative tumor boundaries, making accurate delineation difficult with extensive manual annotations. Chemical exchange saturation transfer (CEST) is a non-invasive MRI technique used for in vivo assessment of metabolic and macromolecular information through a Z-spectrum. CEST may provide insight into metabolic changes present in early-stage disease that are not visible in routine clinical imaging, thereby improving tumor delineation. In this work, we use an unsupervised anomaly detection (UAD) strategy to learn the distribution of features present in Z-spectra of healthy tissue and capture their deviations in pathology, foregoing the need for extensive labels. The approach leverages the metabolic information provided by CEST to improve the detection and delineation of glioblastoma and inform further treatment planning. MethodsA 1D convolutional autoencoder (CAE) was implemented to reconstruct Z-spectra from individual tissue voxels. The network was trained on Z-spectra acquired at 9.4T from healthy Sprague-Dawley rats and tested on data acquired from F98 glioma-bearing rats post Gd-administration. For baseline comparisons, Isolation Forest and Local Outlier Factor, which have shown success in anomaly detection, were implemented. For the CAE, our anomaly score was determined to be the mean squared reconstruction error. To facilitate clinical translation and evaluate the robustness of our model for under sampled Z-spectra, acceleration factors of 2x and 7x were performed with two sampling schemes: uniformly skipping frequency offsets and selecting offsets based on feature importance identified by Shapley value analysis and Integrated Gradients (IG). Binarization was performed by determining an optimal anomaly threshold, followed by comparison to ground truth tumor masks. Metrics related to model performance were assessed for baseline anomaly detectors on the fully sampled dataset and for the CAE on fully and under sampled datasets. ResultsThe best baseline anomaly detector was Isolation Forest, with an ROC-AUC of 0.967 and an F1-score of 0.584. Our method, the CAE, accurately reconstructed Z-spectral features, achieving Dice scores of up to 0.72 and outperforming the baseline model with an ROC-AUC of 0.968 and F1-score of 0.642. This model performance remained robust across sampling schemes and acceleration factors, with ROC-AUCs of [~]0.96 and similar Dice scores (up to 0.7). Feature importance analysis indicated that offsets in the range of {+/-}3.0 to 5.0ppm contributed most to the anomaly score. DiscussionThis study successfully demonstrated a UAD pipeline utilizing the Z-spectrum from CEST MRI for metabolically informed tumor delineation. The framework captures biochemical deviations that may precede or extend beyond morphologic abnormalities, enabling sensitive detection of tumor regions and intra-tumoral heterogeneity that previous methods may fail to capture. The offsets from the feature analysis indicated a strong contribution from the magnetization transfer (MT) pool to the spectral deviations captured by the model, with additional contributions from relayed nuclear Overhauser effect (rNOE) and amide proton transfer (APT). Model robustness with under sampling further highlights the pipelines potential in accelerated acquisitions, thus improving clinical practicality. While there is a need for validation on larger cohorts and clinical datasets, the current results demonstrate that this label-free, Z-spectral anomaly mapping can serve as an interpretable and scalable tool for monitoring tumor heterogeneity and progression, with potential applicability to other diffuse or metabolically subtle pathologies.

cancer biology↗

bioRxiv2025

Frequent Whole-Genome Duplication Events Drive the Genomic Evolution of Triple-Negative Breast Cancer During Neoadjuvant Chemotherapy

BackgroundTriple-negative breast cancer (TNBC) is associated with poor survival rate and high genomic instability, generating complex tumour genomes. However, the processes that generate this complexity are poorly studied in longitudinal samples. Here, we study the temporal dynamics of TNBC somatic mutations, revealing major transitions in tumour genome evolution, from diagnostic biopsies, through treatment, to cancer remission or recurrence. MethodsDeep whole exome sequencing and CUTseq, a reduced representation whole genome sequencing approach, were performed in parallel, to comprehensively identify short nucleotide variants (SNVs), copy number alterations (CNAs) and aneuploidies. Tumour samples (N=74) from 22 patients were profiled before and after neoadjuvant chemotherapy (NACT), and encompassed spatially diverse samples from multiple primary breast tumours, to allow tracking of the gain and loss of candidate driver variants over time. ResultsGenome-wide SNV mutational burden remained stable across disease progression and RCB classes. However, recurrent SNVs were identified in several known TNBC driver genes in response to treatment, with TP53, MICA, CYP2D6, BRCA1, and BRCA2 being frequently altered. The candidate driver variants in these genes frequently exhibited dynamic changes throughout the course of a patients treatment, with the original SNVs in pre-treatment samples often lost, while novel variants in the same genes emerged at subsequent time points. In contrast to the stable genome-wide SNV burdens, dramatic changes in chromosome structure were seen in all tumours, with abundant CNAs and chromosome arm aneuploidies seen in pre-treatment samples, followed by frequent loss of these alterations post-treatment, and their re-emergence at recurrence. Whole genome duplication (WGD) events appear to drive these dynamics, with a higher frequency of pre-treatment WGD seen in patients with the best response to NACT. ConclusionsComprehensive longitudinal profiling of the TNBC genome demonstrates the complex interplay of SNVs and structural alterations during tumour progression, leading to diverse evolutionary trajectories impacting patient outcomes. Complex mutational patterns encompassing entire chromosomes emerge during progression, with WGD events making major contributions to intra-tumour heterogeneity, and emerging as a potential candidate biomarker of response at both tumour establishment and recurrence.

genomics↗

bioRxiv2025

A subset of Haematopoietic Stem Cells resists Plasmodium infection-induced stress by uncoupling interferon sensing and metabolic activation

Hematopoietic stem cells (HSCs) sustain lifelong haematopoiesis as their progeny differentiate into all blood cell lineages. Homeostatic HSCs are mostly quiescent and only rarely divide, however their proliferation and differentiation rates can be modulated by external factors. Acute and chronic infections from a wide range of pathogens are known to challenge HSCs at the population level, being forced to respond to inflammation-mediated organismal demand to replenish the myeloid cell pool. However, less is known about the degree of heterogeneity in the HSCs response to inflammation at the single cell level. Here, using a natural murine malaria model and an NHS-ester biotin dilution assay we identify two subsets of HSCs, BiotinLo and BiotinHi, with distinct proliferation kinetics. Using combined functional, single-cell transcriptomics and phenotypic analyses, we uncover that BiotinHi HSCs remain highly functional despite expressing strong interferon response signatures. These infection-resistant HSCs express high levels of MHC II and are metabolically distinct from the remaining HSCs as they maintain less active mitochondria. These findings demonstrate that a likely reserve pool of HSCs remains highly functional during Plasmodium infection not because cells are shielded, but because they maintain a stemness associated metabolic profile despite effectively sensing inflammation.

cell biology↗

bioRxiv2025

Delayed Trp53 activation protects Dnmt3a-mutant hematopoietic stem cells from inflammatory attrition.

Hematopoietic stem cells (HSCs) accumulate somatic mutations over time, some conferring a fitness advantage that can lead to clonal hematopoiesis (CH). Mutations in DNMT3A, particularly at hotspot R882, are the most prevalent in CH and carry an increased risk of acute myeloid leukemia (AML). Although DNMT3A R882 mutations are linked to global DNA hypomethylation, the mechanisms underlying their selective advantage remain unclear. Here, we show that Dnmt3a-R882H mutant HSCs exhibit resilience under inflammatory and genotoxic stress. During IL-1{beta}-induced emergency granulopoiesis, Dnmt3a R882H/+ HSCs uncouple increased proliferation from stem cell exhaustion. In contrast, wild-type HSCs rapidly progress to terminal differentiation. We link this phenotype to a delayed activation of the p53-p21-DREAM axis, that allows mutant HSCs to avoid attrition, despite increased replication stress. Similarly, mutant HSCs exhibit delayed Trp53 activation following irradiation, but eventually recover a physiological Trp53 response. Analysis of patient data reveals shared phenotypic features between DNMT3A and monoallelic TP53 mutations in CH and myeloid neoplasms, highlighting potential functional similarities. Collectively, these findings suggest that the expansion of DNMT3A-mutant clones is affected by impaired TP53 signaling, which confers resilience against stressors. Therapeutic strategies targeting inflammatory pathways or the p53-p21-DREAM axis may reduce DNMT3A-CH expansion and/or progression and its associated risks.

molecular biology↗

bioRxiv2024

Concomitant suppression of COX-1 and COX-2 is insufficient to induce enteropathy associated with chronic NSAID use

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used medications for the management of chronic pain; however, they are associated with numerous gastrointestinal (GI) adverse events. Although many mechanisms have been suggested, NSAID-induced enteropathy has been thought to be primarily due to inhibition of both cyclooxygenases (COX) -1 and -2, which results in suppression of prostaglandin synthesis. Yet surprisingly, we found that concomitant postnatal deletion of Cox-1 and -2 over 10 months failed to cause intestinal injury in mice unless they were treated with naproxen or its structural analog, phenylpropionic acid, which is not a COX inhibitor. Cox double knockout mice exhibit a distinct gut microbiome composition and cohousing them with controls rescues their dysbiosis and delays the onset of NSAID-induced GI bleeding. In both the UK Biobank and All of Us human cohorts, coadministration of antibiotics with NSAIDs is associated with an increased frequency of GI bleeding. These results show that prostaglandin suppression plays a trivial role in NSAID-induced enteropathy. However, Cox deletion causes dysbiosis of the gut microbiome that amplifies the enteropathic response to NSAIDs.

pharmacology and toxicology↗

bioRxiv2024

High-throughput DNA engineering by mating bacteria

To reduce the operational friction and scale DNA engineering, we report here an in vivo DNA assembly technology platform called SCRIVENER (Sequential Conjugation and Recombination for In Vivo Elongation of Nucleotides with low ERrors). SCRIVENER combines bacterial conjugation, in vivo DNA cutting, and in vivo homologous recombination to seamlessly stitch blocks of DNA together by mating E. coli in large arrays or pools. This workflow is simpler, cheaper, and higher throughput than current DNA assembly approaches that require DNA to be moved in and out of cells at different procedural steps. We perform over 5,000 assemblies with two to 13 DNA blocks that range from 240 bp to 8 kb and show that SCRIVENER is capable of assembling constructs as long as 23 kb at relatively high throughput and fidelity. Most SCRIVENER errors are deletions between long interspersed repeats. However, SCRIVENER can overcome these errors by enabling assembly and sequence verification at high replication at a nominal additional cost per replicate. We show that SCRIVENER can be used to build combinatorial libraries in arrays or pools, and that DNA blocks onboarded into the platform can be repurposed and reused with any other DNA block in high throughput without a PCR step. Because of these features, DNA engineering with SCRIVENER has the potential to accelerate design-build-test-learn cycles of DNA products.

synthetic biology↗

bioRxiv2024

Maintenance of haematopoietic stem cells by JAK inhibition and increased tyrosine-unphosphorylated STAT5

Normal and malignant hematopoietic stem cells (HSCs) are controlled by extracellular cues including cytokine signalling through the JAK/STAT pathway. Here, we show that STAT5-deficient HSCs exhibit an unusual phenotype: while reduced multi-lineage repopulation and reduced self-renewal are commonly associated with overproliferation and exhaustion, they are instead associated with reduced cell-cycle progression and increased differentiation in STAT5-deficient HSCs. Mechanistic studies show that unphosphorylated-STAT5 (uSTAT5) contributes to this phenotype by constraining HSC differentiation, promoting HSC maintenance and upregulating transcriptional programs associated with stemness. The JAK1/2 inhibitor ruxolitinib increases levels of uSTAT5, constrains differentiation and proliferation of murine HSCs, promotes their maintenance and upregulates transcriptional programs associated with stemness. Ruxolitinib also enhances clonogenicity of normal human HSPCs, CALR-mutant murine HSCs and HSPCs from patients with myelofibrosis. Our results therefore reveal a previously unrecognized role for uSTAT5 in controlling HSC function, highlight JAK inhibition as a strategy for enhancing HSC function and provide insights into the failure of JAK inhibitors to eradicate myeloproliferative neoplasms.

cell biology↗

bioRxiv2023

Systematic characterisation of perturbations in complex developing cell populations reveals mechanisms underpinning development and disease

Perturbation studies using gene knockouts have become a key tool for understanding the roles of regulatory genes in development and disease. Here we systematically characterise the knockout effects of the key developmental regulators T and Mixl1 in chimeric mouse embryos during gastrulation and organogenesis. We present a comprehensive and effective suite of statistical tools for systematic characterisation of effects at the level of differential abundance of cell types, lineage development, and gene dysregulation. Applying our computational approach to a novel chimera data set with Mixl1 knockout reveals a disruption in Epicardium development in the absence of Mixl1, characterized by lack of upregulation of the key transcription factor Tbx18 and the Wnt regulator Sfrp5, and by dysregulation of the recently identified juxta-cardiac field. Finally, we demonstrate the wider utility of our framework by applying it to published acute myeloid leukemia (AML) patient data, and show how different responses to therapy are reflected in changes in gene expression along the myeloid trajectory between healthy and AML patients.

genomics↗

bioRxiv2022

CXCR2 inhibition enables NASH-HCC immunotherapy

ObjectiveHepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor may sensitise NASH-HCC to ICI therapy. DesignNeutrophil infiltration was characterised in human HCC and mouse models of HCC. Late-stage intervention with anti-PD1 and/or a CXCR2 inhibitor was performed in murine models of NASH-HCC. The tumour immune microenvironment was characterised by imaging mass cytometry, RNA-seq and flow cytometry. ResultsNeutrophils expressing CXCR2, a receptor crucial to neutrophil recruitment in acute-injury, are highly represented in human NASH-HCC. In models of NASH-HCC lacking response to ICI, the combination of a CXCR2 antagonist with anti-PD1 suppressed tumour burden and extended survival. Combination therapy increased intratumoral XCR1+ dendritic cell activation and CD8+ T cell numbers which are associated with anti-tumoral immunity, this was confirmed by loss of therapeutic effect upon genetic impairment of myeloid cell recruitment, neutralisation of the XCR1-ligand XCL1 or depletion of CD8+ T cells. Therapeutic benefit was accompanied by an unexpected increase in tumour-associated neutrophils (TANs) which switched from a pro-tumor to anti-tumour progenitor-like neutrophil phenotype. Reprogrammed TANs were found in direct contact with CD8+ T cells in clusters that were enriched for the cytotoxic anti-tumoural protease granzyme B. Neutrophil reprogramming was not observed in the circulation indicative of the combination therapy selectively influencing TANs. ConclusionCXCR2-inhibition induces reprogramming of the tumour immune microenvironment that promotes ICI in NASH-HCC. Significance of this studyWhat is already known on this subject? O_LIImmune checkpoint inhibition therapy is emerging as a promising new therapy for the treatment of advanced hepatocellular carcinoma (HCC). C_LIO_LIOnly a minority of HCC patients will respond to immune checkpoint inhibition (ICI) therapy and recent data suggest that HCC on the background of NASH may have reduced sensitivity to this treatment strategy. C_LIO_LINeutrophils are a typical myeloid component of the liver in NASH and are found either within the HCC tumour microenvironment or in a peritumoural location. C_LIO_LINeutrophils have considerable phenotypic plasticity and can exist in both tumour promoting and tumour suppressing states. C_LIO_LINeutrophils may have the ability to influence ICI therapy. C_LI What are the new findings? O_LICXCR2+ neutrophils are found in human NASH and within the tumour of both human and mouse models of NASH-HCC. C_LIO_LIThe resistance of NASH-HCC to anti-PD1 therapy is overcome by co-treatment with a CXCR2 small molecule inhibitor, with evidence of reduced tumour burden and extended survival. C_LIO_LIAnti-PD1 and CXCR2 inhibitor combine to selectively reprogramme tumour-associated neutrophils (TANs) from a pro- to an anti-tumour phenotype. C_LIO_LIReprogrammed TANs proliferate locally within Granzyme B+ immune clusters that contain physically associating CD8+ T cells and antigen presenting cells. C_LIO_LIConventional XCR1+ dendritic cells (cDC1s) are found to be elevated in anti-PD1 and CXCR2 inhibitor treated HCCs and together with CD8+ T cells are required for therapeutic benefit. C_LI How might it impact on clinical practice in the foreseeable future? O_LITANs can be selectively manipulated to adopt an anti-tumour phenotype which unlocks their potential for cancer therapy. The ability of CXCR2 antagonism to combine with ICI therapy to bring about enhanced therapeutic benefit in NASH-HCC (and potentially in HCC of other aetiologies) warrents clinical investigation. C_LI

cancer biology↗

bioRxiv2021

Endothelial-specific Gata3 expression is required for haematopoietic stem cell generation

To generate sufficient numbers of transplantable haematopoietic stem cells (HSCs) in vitro, a detailed understanding of how this process takes place in vivo is essential. The endothelial-to-haematopoietic transition (EHT), which culminates in the production of the first HSCs, is a highly complex process during which key regulators are switched on and off at precise moments and which is embedded into a myriad of microenvironmental signals from surrounding cells and tissues. We have previously demonstrated an HSC-supportive function for Gata3 within the sympathetic nervous system and the sub-aortic mesenchyme, but show here that it also plays a cell-intrinsic role during the EHT. It is expressed in haemogenic endothelial cells and early HSC precursors, where its expression correlates with a more quiescent state. Importantly, endothelial-specific deletion of Gata3 shows that it is functionally required for these cells to mature into HSCs, placing Gata3 at the core of the EHT regulatory network.

developmental biology↗

bioRxiv2021

p57Kip2 regulates embryonic haematopoietic stem cell numbers by controlling the size of the sympathoadrenal progenitor pool

Haematopoietic stem cells (HSCs) are of major clinical importance, and finding methods for their in vitro generation is a prime research focus. We demonstrate that the cell cycle inhibitor p57Kip2/Cdkn1c limits HSC numbers by restricting the size of the sympathetic nervous system (SNS) and the amount of HSC-supportive catecholamines secreted by these cells, specifically in the aorta-gonads-mesonephros (AGM) region via {beta}2-adrenergic receptor signalling. This regulation occurs at the SNS progenitor level and is in contrast to the cell-intrinsic function of p57Kip2 in maintaining adult HSCs. Using single-cell RNA-Seq we dissect the differentiation pathway of neural crest cells into SNS cells in the AGM and reveal that they are able to take an alternative differentiation pathway, giving rise to a subset of mesenchymal cells expressing HSC-supportive factors. Neural crest cells thus appear to contribute to the AGM HSC niche via two different mechanisms: SNS-mediated catecholamine secretion and HSC-supportive mesenchymal cell production.

developmental biology↗

bioRxiv2021

Evaluating host to host transplants as a method to study plant bacterial assembly

The ability to predict plant microbiome assembly will enable new bacterial-based technologies for agriculture. A major step towards this is quantifying the roles of ecological processes on community assembly. This is challenging, in part because individual plants are colonised by different communities of soil bacteria and it is difficult to estimate if the absence of a given species was a) because it was not present in the soil to colonise a given plant or b) it went locally extinct from competition, predation or similar. To minimise this uncertainty, the authors develop a mesocosm system to study bacterial communities of individual plants by replicated transplantation to a recipient host plant population, ensuring new hosts receive a homogenous species pool for colonisation. We sought to understand which factors affected the transplant and, what the main drivers of variation in the model communities were. A nested factorial design was used to investigate the transplantation of cultured or total, root or leaf associated bacterial communities from donor host species to surrogate host species. Specific metrics were developed to quantify colonisation efficiency of communities. The results show the root communities were more effectively transplanted than leaf communities, with leaf communities more susceptible to contamination. For root communities the strongest driver of beta diversity was the donor host species, and for leaves it was the surrogate host species. Overall, the results reveal that root, but not leaf communities are amenable to transplant reflecting their differing ecological drivers. This work provides the basis to develop a plant microbiome transplant system.

ecology↗

bioRxiv2018

Diversification of retinoblastoma protein function associated with cis and trans adaptations

Retinoblastoma proteins are eukaryotic transcriptional co-repressors that play central roles in cell cycle control, among other functions. Although most metazoan genomes encode a single retinoblastoma protein, gene duplications have occurred at least twice: in the vertebrate lineage, leading to three genes encoding Rb, p107, and p130, while separately in the Drosophila lineage an ancestral Rbf1 gene and a derived Rbf2 gene. Structurally, Rbf1 resembles p107 and p130 most closely, and mutation of the gene is lethal, while Rbf2 is more divergent, and is not essential for development. Rbf1 has been demonstrated to be a potent repressor of canonical cell-cycle promoters, unlike Rbf2. The retention of Rbf2 over 60 million years in the entire Drosophila lineage points to essential functions, however. We show here that Rbf2 regulates a broad set of cell growth control related genes, and can antagonize Rbf1 on specific sets of promoters. Rbf2 null mutants exhibit abnormal development of the female reproductive tract, with reduced egg laying, while heterozygous null mutants exhibit an increased rate of egg deposition, suggesting that the normal function of this protein is critical for optimal control of fertility. The structural alterations found in conserved regions of the Rbf2 gene suggest that this gene was sub- or neofunctionalized to develop specific regulatory specificity and activity. We define cis regulatory features of Rbf2 target genes that allow preferential repression by this protein, indicating that it is not merely a weaker version of the ancestral protein. The specialization of retinoblastoma function in Drosophila may reflect a parallel evolution found in vertebrates, and raises the possibility that cell growth control is equally important to cell cycle function for this conserved family of transcriptional corepressors.

developmental biology↗

bioRxiv2018

Mass media promotion of a smartphone smoking cessation app: Modeled health and cost impacts

BackgroundSmartphones are increasingly available and some high quality apps are available for smoking cessation. However, the cost-effectiveness of promoting such apps has never been studied.\n\nObjectiveTo estimate the health gain, inequality impacts and cost-utility from a five-year promotion campaign of a smoking cessation smartphone app compared to business-as-usual (no app use for quitting).\n\nMethodsA well-established Markov macro-simulation model utilising a multi-state life-table was adapted to the intervention (lifetime horizon, 3% discount rate). The setting was the New Zealand (NZ) population (N = 4.4 million). The intervention effect size was from a multi-country randomised trial: relative risk for quitting at six months = 2.23 (95%CI: 1.08 to 4.77). Intervention costs were based on NZ mass media promotion data and the NZ cost of attracting a smoker to smoking cessation services ($NZ64 per person).\n\nResultsThe five-year intervention was estimated to generate 6760 QALYs (95%UI: 5420 to 8420) over the remaining lifetime of the population. For M[a]ori (Indigenous population) there was 2.8 times the per capita age-standardized QALYs relative to non-M[a]ori. The intervention was also estimated to be cost-saving to the health system (saving NZ$115, 95%UI: 72.5 million [m] to 171m; US$81.8m). The cost-saving aspect of the intervention was maintained in scenario and sensitivity analyses where the discount rate was doubled to 6%, the effect size halved, and the intervention run for just one year.\n\nConclusionsThis study provides modelling-level evidence that mass-media promotion of a smartphone app for smoking cessation is likely to generate health gain, reduce ethnic inequalities in health and save health system costs. Nevertheless, there are other tobacco control which generate considerably larger health gains and cost-savings such as raising tobacco taxes.

epidemiology↗