Brushing Up on Cartilage Lubrication: Polyelectrolyte-Enhanced Tribological Rehydration.

This study presents new insights into the potential role of polyelectrolyte interfaces in regulating low friction and interstitial fluid pressurization of cartilage. Polymer brushes composed of hydrophilic 3-sulfopropyl methacrylate potassium salt (SPMK) tethered to a PEEK substrate (SPMK-g-PEEK) are a compelling biomimetic solution for interfacing with cartilage, inspired by the natural lubricating biopolyelectrolyte constituents of synovial fluid. These SPMK-g-PEEK surfaces exhibit a hydrated compliant layer approximately 5 µm thick, demonstrating the ability to maintain low friction coefficients (µ ∼ 0.01) across a wide speed range (0.1-200 mm/s) under physiological loads (0.75-1.2 MPa). A novel polyelectrolyte-enhanced tribological rehydration mechanism is elucidated, capable of recovering up to ∼12% cartilage strain and subsequently facilitating cartilage interstitial fluid recovery, under loads ranging from 0.25 to 2.21 MPa. This is attributed to the combined effects of fluid confinement within the contact gap and the enhanced elastohydrodynamic behavior of polymer brushes. Contrary to conventional theories that emphasize interstitial fluid pressurization in regulating cartilage lubrication, this work demonstrates that SPMK-g-PEEK's frictional behavior with cartilage is independent of these factors and provides unabating aqueous lubrication. Polyelectrolyte-enhanced tribological rehydration can occur within a static contact area and operates independently of known mechanisms of cartilage interstitial fluid recovery established for converging or migrating cartilage contacts. These findings challenge existing paradigms, proposing a novel polyelectrolyte-cartilage tribological mechanism not exclusively reliant on interstitial fluid pressurization or cartilage contact geometry. The implications of this research extend to a broader understanding of synovial joint lubrication, offering insights into the development of joint replacement materials that more accurately replicate the natural functionality of cartilage.

Protocol implementation during the COVID-19 pandemic: experiences from a randomized trial of stress ulcer prophylaxis.

BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.

Effects of food supplementation and helminth removal on space use and spatial overlap in wild rodent populations.

Animal space use and spatial overlap can have important consequences for population-level processes such as social interactions and pathogen transmission. Identifying how environmental variability and inter-individual variation affect spatial patterns and in turn influence interactions in animal populations is a priority for the study of animal behaviour and disease ecology. Environmental food availability and macroparasite infection are common drivers of variation, but there are few experimental studies investigating how they affect spatial patterns of wildlife. Bank voles (Clethrionomys glareolus) are a tractable study system to investigate spatial patterns of wildlife and are amenable to experimental manipulations. We conducted a replicated, factorial field experiment in which we provided supplementary food and removed helminths in vole populations in natural forest habitat and monitored vole space use and spatial overlap using capture-mark-recapture methods. Using network analysis, we quantified vole space use and spatial overlap. We compared the effects of food supplementation and helminth removal and investigated the impacts of season, sex and reproductive status on space use and spatial overlap. We found that food supplementation decreased vole space use while helminth removal increased space use. Space use also varied by sex, reproductive status and season. Spatial overlap was similar between treatments despite up to threefold differences in population size. By quantifying the spatial effects of food availability and macroparasite infection on wildlife populations, we demonstrate the potential for space use and population density to trade-off and maintain consistent spatial overlap in wildlife populations. This has important implications for spatial processes in wildlife including pathogen transmission.

Impact of Opioid Use on Duration of Therapy and Overall Survival for Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) have significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). We evaluated the effect of opioid use on outcomes in patients receiving ICI either alone or with chemotherapy. We conducted a retrospective review of 209 patients with advanced NSCLC who received an ICI at the University of Virginia between 1 February 2015 and 1 January 2020. We performed univariate and multivariate analyses to evaluate the impact of opioid use on duration of therapy (DOT) and overall survival (OS). Patients with no or low opioid use (n = 172) had a median DOT of 12.2 months (95% CI: 6.9-17.4) compared to 1.9 months (95% CI: 1.8-2.0) for those with high opioid use (n = 37, HR 0.26 95% CI: 0.17-0.40, p < 0.001). Patients with no or low opioid use had a median OS of 22.6 months (95% CI: 14.8-30.4) compared to 3.8 months (95% CI: 2.7-4.9) for those with high opioid use (HR 0.26 95% CI: 0.17-0.40 p < 0.001). High opioid use was associated with a shorter DOT and worse OS. This difference remained significant when accounting for possible confounding variables. These data warrant investigation of possible mechanistic interactions between opioids, tumor progression, and ICIs, as well as prospective evaluation of opioid-sparing pain management strategies, where possible.

Extreme heat reduces host and parasite performance in a butterfly-parasite interaction.

Environmental temperature fundamentally shapes insect physiology, fitness and interactions with parasites. Differential climate warming effects on host versus parasite biology could exacerbate or inhibit parasite transmission, with far-reaching implications for pollination services, biocontrol and human health. Here, we experimentally test how controlled temperatures influence multiple components of host and parasite fitness in monarch butterflies (Danaus plexippus) and their protozoan parasites Ophryocystis elektroscirrha. Using five constant-temperature treatments spanning 18-34°C, we measured monarch development, survival, size, immune function and parasite infection status and intensity. Monarch size and survival declined sharply at the hottest temperature (34°C), as did infection probability, suggesting that extreme heat decreases both host and parasite performance. The lack of infection at 34°C was not due to greater host immunity or faster host development but could instead reflect the thermal limits of parasite invasion and within-host replication. In the context of ongoing climate change, temperature increases above current thermal maxima could reduce the fitness of both monarchs and their parasites, with lower infection rates potentially balancing negative impacts of extreme heat on future monarch abundance and distribution.

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175.

BACKGROUND: Combination chemotherapy and immunotherapy regimens have significantly improved survival for patients with previously untreated advanced non-small cell lung cancer (NSCLC). Improvements in overall survival (OS) in two separate pembrolizumab trials have demonstrated survival improvements over chemotherapy alone, regardless of PD-L1 status. The optimal chemotherapy backbone for combination with immunotherapy is unknown. We hypothesized nab-paclitaxel may be a well-suited platinum partner to use in combination with checkpoint inhibitor therapy for both adenocarcinoma and squamous histology and conducted a phase I/II trial to assess the efficacy of this regimen in advanced NSCLC. METHODS: Adult patients with previously untreated, stage IIIB/IV NSCLC (any histology) with an Eastern Cooperative Oncology Group performance status of 0-1, any PD-L1 expression, and no EGFR mutations or ALK translocations, received carboplatin area under the curve (AUC) 6 day 1, nab-paclitaxel 100 mg/m2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3w. Co-primary endpoints were progression-free survival (PFS) and overall response rate (ORR). RESULTS: Forty-six evaluable patients enrolled, 14 in phase I and 32 in phase II, from June 2015 to July 2018 with a median duration of follow-up of 35.4 months. Median time from enrollment to data lock was 42 months. In the ITT population, the ORR was 35%, median PFS was 5.6 months (95% CI, 4.6-8.2), and median OS was 15.4 months (CI, 12.4-28.1). There were no statistical differences in PFS or OS by PD-L1 status. The 2- and 3-year landmark OS rates were 33% and 24%, respectively. CONCLUSION: Carboplatin, nab-paclitaxel, and pembrolizumab are a safe and effective regimen for patients with both squamous and nonsquamous NSCLC. Although this study did not meet the prespecified endpoints, the median and landmark OS results are consistent with durable benefit of this regimen as seen in phase III trials for first-line treatment of advanced NSCLC.

DNA Polymerase Diversity Reveals Multiple Incursions of Polintons During Nematode Evolution.

Polintons are double-stranded DNA, virus-like self-synthesizing transposons widely found in eukaryotic genomes. Recent metagenomic discoveries of Polinton-like viruses are consistent with the hypothesis that Polintons invade eukaryotic host genomes through infectious viral particles. Nematode genomes contain multiple copies of Polintons and provide an opportunity to explore the natural distribution and evolution of Polintons during this process. We performed an extensive search of Polintons across nematode genomes, identifying multiple full-length Polinton copies in several species. We provide evidence of both ancient Polinton integrations and recent mobility in strains of the same nematode species. In addition to the major nematode Polinton family, we identified a group of Polintons that are overall closely related to the major family but encode a distinct protein-primed DNA polymerase B (pPolB) that is related to homologs from a different group of Polintons present outside of the Nematoda. Phylogenetic analyses on the pPolBs support the evolutionary scenarios in which these extrinsic pPolBs that seem to derive from Polinton families present in oomycetes and molluscs replaced the canonical pPolB in subsets of Polintons found in terrestrial and marine nematodes, respectively, suggesting interphylum horizontal gene transfers. The pPolBs of the terrestrial nematode and oomycete Polintons share a unique feature, an insertion of an HNH nuclease domain, whereas the pPolBs in the marine nematode Polintons share an insertion of a VSR nuclease domain with marine mollusc pPolBs. We hypothesize that horizontal gene transfer occurs among Polintons from widely different but cohabiting hosts.

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial.

BACKGROUND: The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. OBJECTIVE: To outline the statistical analysis plan for the REVISE trial. METHODS: REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated. RESULTS: The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment. CONCLUSIONS: This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT03374800. November 21, 2017.

Enabling synthesis in fragment-based drug discovery (FBDD): microscale high-throughput optimisation of the medicinal chemist's toolbox reactions.

Miniaturised high-throughput experimentation (HTE) is widely employed in industrial and academic laboratories for rapid reaction optimisation using material-limited, multifactorial reaction condition screening. In fragment-based drug discovery (FBDD), common toolbox reactions such as the Suzuki-Miyaura and Buchwald-Hartwig cross couplings can be hampered by the fragment's intrinsic heteroatom-rich pharmacophore which is required for ligand-protein binding. At Astex, we are using microscale HTE to speed up reaction optimisation and prevent target down-prioritisation. By identifying catalyst/base/solvent combinations which tolerate unprotected heteroatoms we can rapidly optimise key cross-couplings and expedite route design by avoiding superfluous protecting group manipulations. However, HTE requires extensive upfront training, and this modern automated synthesis technique largely differs to the way organic chemists are traditionally trained. To make HTE accessible to all our synthetic chemists we have developed a semi-automated workflow enabled by pre-made 96-well screening kits, rapid analytical methods and in-house software development, which is empowering chemists at Astex to run HTE screens independently with minimal training.

DNA polymerase diversity reveals multiple incursions of Polintons during nematode evolution.

Polintons are dsDNA, virus-like self-synthesizing transposons widely found in eukaryotic genomes. Recent metagenomic discoveries of Polinton-like viruses are consistent with the hypothesis that Polintons invade eukaryotic host genomes through infectious viral particles. Nematode genomes contain multiple copies of Polintons and provide an opportunity to explore the natural distribution and evolution of Polintons during this process. We performed an extensive search of Polintons across nematode genomes, identifying multiple full-length Polinton copies in several species. We provide evidence of both ancient Polinton integrations and recent mobility in strains of the same nematode species. In addition to the major nematode Polinton family, we identified a group of Polintons that are overall closely related to the major family, but encode a distinct protein-primed B family DNA polymerase (pPolB) that is related to homologs from a different group of Polintons present outside of the Nematoda . Phylogenetic analyses on the pPolBs support the evolutionary scenarios in which these extrinsic pPolBs that seem to derive from Polinton families present in oomycetes and molluscs replaced the canonical pPolB in subsets of Polintons found in terrestrial and marine nematodes, respectively, suggesting inter-phylum horizontal gene transfers. The pPolBs of the terrestrial nematode and oomycete Polintons share a unique feature, an insertion of a HNH nuclease domain, whereas the pPolBs in the marine nematode Polintons share an insertion of a VSR nuclease domain with marine mollusc pPolBs. We hypothesize that horizontal gene transfer occurs among Polintons from widely different but cohabiting hosts.

Highly lubricious SPMK-g-PEEK implant surfaces to facilitate rehydration of articular cartilage.

To enable long lasting osteochondral defect repairs which preserve the native function of synovial joint counter-face, it is essential to develop surfaces which are optimised to support healthy cartilage function by providing a hydrated, low friction and compliant sliding interface. PEEK surfaces were modified using a biocompatible 3-sulfopropyl methacrylate potassium salt (SPMK) through UV photo-polymerisation, resulting in a ∼350 nm thick hydrophilic coating rich in hydrophilic anionic sulfonic acid groups. Characterisation was done through Fourier Transformed Infrared Spectroscopy, Focused Ion Beam Scanning Electron Microscopy, and Water Contact Angle measurements. Using a Bruker UMT TriboLab, bovine cartilage sliding tests were conducted with real-time strain and shear force measurements, comparing untreated PEEK, SPMK functionalised PEEK (SPMK-g-PEEK), and Cobalt Chrome Molybdenum alloy. Tribological tests over 2.5 h at physiological loads (0.75 MPa) revealed that SPMK-g-PEEK maintains low friction (µ< 0.024) and minimises equilibrium strain, significantly reducing forces on the cartilage interface. Post-test analysis showed no notable damage to the cartilage interfacing against the SPMK functionalised surfaces. The application of a constitutive biphasic cartilage model to the experimental strain data reveals that SPMK surfaces increase the interfacial permeability of cartilage in sliding, facilitating fluid and strain recovery. Unlike previous demonstrations of sliding-induced tribological rehydration requiring specific hydrodynamic conditions, the SPMK-g-PEEK introduces a novel mode of tribological rehydration operating at low speeds and in a stationary contact area. SPMK-g-PEEK surfaces provide an enhanced cartilage counter-surface, which provides a highly hydrated and lubricious boundary layer along with supporting biphasic lubrication. Soft polymer surface functionalisation of orthopaedic implant surfaces are a promising approach for minimally invasive synovial joint repair with an enhanced bioinspired polyelectrolyte interface for sliding against cartilage. These hydrophilic surface coatings offer an enabling technology for the next generation of focal cartilage repair and hemiarthroplasty implant surfaces.

Use of poxvirus display to select antibodies specific for complex membrane antigens.

Antibody discovery against complex antigens is limited by the availability of a reproducible pure source of concentrated properly folded antigen. We have developed a technology to enable direct incorporation of membrane proteins such as GPCRs and into the membrane of poxvirus. The protein of interest is correctly folded and expressed in the cell-derived viral membrane and does not require any detergents or refolding before downstream use. The poxvirus is selective in which proteins are incorporated into the viral membrane, making the antigen poxvirus an antigenically cleaner target for in vitro panning. Antigen-expressing virus can be readily purified at scale and used for antibody selection using any in vitro display platform.

mRNA Transfection of S. mediterranea for Luminescence Analysis.

Planarians have become a powerful model system for stem cell research and regeneration. While the tool kit for mechanistic investigations has been steadily expanding over the last decade, robust genetic tools for transgene expression are still lacking. We describe here methods for in vivo and in vitro mRNA transfection of the planarian species Schmidtea mediterranea. These methods utilize the commercially available TransIT-mRNA transfection reagent to efficiently deliver mRNA encoding a synthetic nanoluciferase reporter. Using a luminescent reporter overcomes the bright autofluorescent background of planarian tissues and allows quantitative measurements of protein expression levels. Collectively, our methods provide the means for heterologous reporter expression in planarian cells and the basis for future development of transgenic techniques.

An automated system for polymer wear debris analysis in total disc arthroplasty using convolution neural network.

Introduction: Polymer wear debris is one of the major concerns in total joint replacements due to wear-induced biological reactions which can lead to osteolysis and joint failure. The wear-induced biological reactions depend on the wear volume, shape and size of the wear debris and their volumetric concentration. The study of wear particles is crucial in analysing the failure modes of the total joint replacements to ensure improved designs and materials are introduced for the next generation of devices. Existing methods of wear debris analysis follow a traditional approach of computer-aided manual identification and segmentation of wear debris which encounters problems such as significant manual effort, time consumption, low accuracy due to user errors and biases, and overall lack of insight into the wear regime. Methods: This study proposes an automatic particle segmentation algorithm using adaptive thresholding followed by classification using Convolution Neural Network (CNN) to classify ultra-high molecular weight polyethylene polymer wear debris generated from total disc replacements tested in a spine simulator. A CNN takes object pixels as numeric input and uses convolution operations to create feature maps which are used to classify objects. Results: Classification accuracies of up to 96.49% were achieved for the identification of wear particles. Particle characteristics such as shape, size and area were estimated to generate size and volumetric distribution graphs. Discussion: The use of computer algorithms and CNN facilitates the analysis of a wider range of wear debris with complex characteristics with significantly fewer resources which results in robust size and volume distribution graphs for the estimation of the osteolytic potential of devices using functional biological activity estimates.

Genomic analysis of the population structure of Paenibacillus larvae in New Zealand.

New Zealand is a remote country in the South Pacific Ocean. The isolation and relatively late arrival of humans into New Zealand has meant there is a recorded history of the introduction of domestic species. Honey bees (Apis mellifera) were introduced to New Zealand in 1839, and the disease American foulbrood was subsequently found in the 1870s. Paenibacillus larvae, the causative agent of American foulbrood, has been genome sequenced in other countries. We sequenced the genomes of P. larvae obtained from 164 New Zealand apiaries where American foulbrood was identified in symptomatic hives during visual inspection. Multi-locus sequencing typing (MLST) revealed the dominant sequence type to be ST18, with this clonal cluster accounting for 90.2% of isolates. Only two other sequence types (with variants) were identified, ST5 and ST23. ST23 was only observed in the Otago area, whereas ST5 was limited to two geographically non-contiguous areas. The sequence types are all from the enterobacterial repetitive intergenic consensus I (ERIC I) genogroup. The ST18 and ST5 from New Zealand and international P. larvae all clustered by sequence type. Based on core genome MLST and SNP analysis, localized regional clusters were observed within New Zealand, but some closely related genomes were also geographically dispersed, presumably due to hive movements by beekeepers.

Abundant dsRNA picobirnaviruses show little geographic or host association in terrestrial systems.

Picobirnaviruses are double-stranded RNA viruses known from a wide range of host species and locations but with unknown pathogenicity and host relationships. Here, we examined the diversity of picobirnaviruses from cattle and gorillas within and around Bwindi Impenetrable Forest National Park (BIFNP), Uganda, where wild and domesticated animals and humans live in relatively close contact. We use metagenomic sequencing with bioinformatic analyses to examine genetic diversity. We compared our findings to global Picobirnavirus diversity using clustering-based analyses. Picobirnavirus diversity at Bwindi was high, with 14 near-complete RdRp and 15 capsid protein sequences, and 497 new partial viral sequences recovered from 44 gorilla samples and 664 from 16 cattle samples. Sequences were distributed throughout a phylogenetic tree of globally derived picobirnaviruses. The relationship with Picobirnavirus diversity and host taxonomy follows a similar pattern to the global dataset, generally lacking pattern with either host or geography.

Direct haplotype-resolved 5-base HiFi sequencing for genome-wide profiling of hypermethylation outliers in a rare disease cohort.

Long-read HiFi genome sequencing allows for accurate detection and direct phasing of single nucleotide variants, indels, and structural variants. Recent algorithmic development enables simultaneous detection of CpG methylation for analysis of regulatory element activity directly in HiFi reads. We present a comprehensive haplotype resolved 5-base HiFi genome sequencing dataset from a rare disease cohort of 276 samples in 152 families to identify rare (~0.5%) hypermethylation events. We find that 80% of these events are allele-specific and predicted to cause loss of regulatory element activity. We demonstrate heritability of extreme hypermethylation including rare cis variants associated with short (~200 bp) and large hypermethylation events (>1 kb), respectively. We identify repeat expansions in proximal promoters predicting allelic gene silencing via hypermethylation and demonstrate allelic transcriptional events downstream. On average 30-40 rare hypermethylation tiles overlap rare disease genes per patient, providing indications for variation prioritization including a previously undiagnosed pathogenic allele in DIP2B causing global developmental delay. We propose that use of HiFi genome sequencing in unsolved rare disease cases will allow detection of unconventional diseases alleles due to loss of regulatory element activity.

Mixed-species assemblages and disease: the importance of differential vector and parasite attraction in transmission dynamics.

Individuals from multiple species often aggregate at resources, group to facilitate defense and foraging, or are brought together by human activity. While it is well-documented that host-seeking disease vectors and parasites show biases in their responses to cues from different hosts, the influence of mixed-species assemblages on disease dynamics has received limited attention. Here, we synthesize relevant research in host-specific vector and parasite bias. To better understand how vector and parasite biases influence infection, we provide a conceptual framework describing cue-oriented vector and parasite host-seeking behaviour as a two-stage process that encompasses attraction of these enemies to the assemblage and their choice of hosts once at the assemblage. We illustrate this framework, developing a case study of mixed-species frog assemblages, where frog-biting midges transmit trypanosomes. Finally, we present a mathematical model that investigates how host species composition and asymmetries in vector attraction modulate transmission dynamics in mixed-species assemblages. We argue that differential attraction of vectors by hosts can have important consequences for disease transmission within mixed-species assemblages, with implications for wildlife conservation and zoonotic disease. This article is part of the theme issue 'Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes'.

A four-decade profile of apicultural demographics and production in New Zealand, 1980-2020.

The demand for honey and pollination services has continued to grow in many countries worldwide, including New Zealand. This has influenced changes in the demographics of the managed population of honey bees (Apis mellifera). We examined historical data to describe how the apicultural demographics in New Zealand have changed temporally and geographically in the four decades to 2020. We also describe trends in honey production and the economic value of pure honey exported from New Zealand between 2000 and 2020. Our findings suggest that commercial apiculture has been key to the intensification of beekeeping in New Zealand during the study period. This is supported by evidence showing pronounced expansion of beekeeping operations among those with more than 1,000 colonies. The intensification has resulted in the density of apiaries increasing threefold across New Zealand during the four decades. While higher numbers of colonies per area produced higher volumes of honey, there was no corresponding improvement in production efficiency. Honey yields per apiary or colony, as indicators of production efficiency, appear to decline from the mid-2000s. The volume of pure honey export increased over 40-fold, a magnitude approximately ten times higher than that of production increase. This reflects a substantial increase in returns from honey exports, mostly driven by the price of manuka honey. Our findings add to a pool of information to support evidence-based decision making to enhance honey bee health and develop the apicultural industry in New Zealand.