Rapidly accumulating data link the microbiome to severe neuropsychiatric disorders in humans, including schizophrenia, Alzheimer's and Parkinson's. Moreover, preclinical work has shown that perturbation of the microbiome is closely associated with social, cognitive and behavioural deficits. The potential of the microbiome as a diagnostic and therapeutic tool is currently undercut by a lack of clear mechanistic understanding of the microbiome–gut–brain axis. This review establishes the hypothesis that the mechanism by which this influence is carried out is synaptic plasticity – long‐term changes to the physical and functional neuronal structures that enable the brain to undertake learning, memory formation, emotional regulation and more. By examining the different constituents of the microbiome–gut–brain axis through the lens of synaptic plasticity, this review explores the diverse aspects by which the microbiome shapes the behaviour and mental wellbeing of the host. Key elements of this complex bi‐directional relationship include neurotransmitters, neuronal electrophysiology, immune mediators that engage with both the central and enteric nervous systems and signalling cascades that trigger long‐term potentiation of synapses. The importance of establishing mechanistic correlations along the microbiome–gut–brain axis cannot be overstated as they hold the potential for furthering current understanding regarding the vast fields of neuroscience and neuropsychiatry. This review strives to elucidate the promising theory of microbiome‐driven synaptic plasticity in the hope of enlightening current researchers and inspiring future ones.The microbiome influences the emotional and cognitive phenotype of its host, as well as the neurodevelopment and pathophysiology of various brain processes and disorders,  I.et al., et al., et al., et al., et al., et al., The microbiome–gut–brain axis refers to the way the resident gut microbiome communicates with and impacts the central nervous system. It has been firmly established , two systems that are engaged in constant bidirectional communication.Evidence links the microbiome to numerous phenomena . Therefore, we hypothesize that the most significant mechanistic relationship between the microbiome and the emotional, behavioural and cognitive phenotypes of the host is based on the microbiome's contribution to induction and maintenance of synaptic plasticity.The myriad ways in which the microbiome influences the ENS and CNS can be linked, to a great extent, to synaptic plasticity, both directly and indirectly . Gamma‐aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter and has been shown to induce either LTP or LTD, according to the varying postsynaptic signalling cascades recruited by the different GABAergic receptor subunits  animals are raised in a completely sterile environment, allowing them to serve as a platform for microbial transplants towards understanding causative effects of microbiome and host state on one another. While GF mice offer a blank slate for such studies, there is accumulating evidence that the GF condition is implicated in a range of health complications across the lifespan, which could make interpretation of findings more challenging  channels. These channels are thought to mediate the transmission of nociceptive signals, and capsaicin is a known irritant which activates these channels in a manner leading to increased intracellular calcium currents. Mice treated with L. reuteri exhibited a reduced capsaicin‐induced excitatory response, accompanied by decreased TRPV1 expression.There is thus a growing body of evidence that links the microbiome to the induction and maintenance of synaptic plasticity in both the ENS and CNS, suggesting that this crosstalk may be a key component of the microbiome–gut–brain axis.IV.et al., et al., via the vagus nerve. The microbiome is thought to influence the neuronal activity of the ENS and CNS by secretion of neuromodulatory molecules et al., et al., et al., et al., The importance of neurotransmitters in the microbiome–gut–brain axis is compounded by the importance of neurotransmitters to a host of CNS   and NA concentrations.Preclinical studies have demonstrated that the GF condition is characterized by increased plasma tryptophan concentrations which can be normalized following microbial colonization of mice immediately post‐weaning  are thought to exert their effects on gut 5‐HT in a manner that contributes to their anti‐depressant effects on the brain et al., Dopamine acts on both excitatory and inhibitory synapses distributed throughout the brain, but a high density of dopaminergic receptors in specific areas has led to the recognition of several major dopaminergic pathways implicated in a host of brain functions and neuropsychiatric disorders  in the brains of addiction‐prone mice and specific microbial alterations in the gut after alcohol exposure followed by a three‐month abstinence period  combined 16S sequencing with functional magnetic resonance imaging (fMRI) to connect microbial differences and dopaminergic‐transmission alteration in the striatum. The results showed increased et al.  , cerebral dopamine neurotrophic factor (CDNF) restored dopaminergic function in the nigrostriatal area of the brain   cells markedly reduced the beneficial behavioural effects of JB‐1. JB‐1 has been shown to exert mediating effects on anxiolytic and depressive behaviours in a vagus‐dependent manner  from the hypothalamus triggers adrenal adrenocorticotropic hormone (ACTH) release and subsequent cortisol secretion. Aside from metabolically affecting most organ systems in the body, cortisol has been specifically implicated in mental disorders and stress‐related gastrointestinal and immune disorders  activity in vagal afferents and the solitary tract nucleus, the prevention of beneficial effects of L. rhamnosus JB‐1 in vagotomized mice    and considerably rescued hippocampal EPSP response in the diabetic group. Also, the diabetic–probiotic group exhibited the greatest increase in LTP, which is significant due to the known phenomenon of diabetes‐induced learning and memory deficits  on the behavioural and electrophysiological aspects of diabetes‐induced learning and memory deficits in rats. Results of this study showed that diabetic animals that received probiotics exhibited markedly improved spatial memory, facilitated by an improved ability of the brain to perform LTP, a key element of synaptic plasticity.Another study  is an endotoxic, neurotoxic and inflammatory molecule found in gram‐negative bacterial membranes, capable of stimulating the expression of TNF‐α and interleukins IL‐1β and IL‐6  to mice. LJ corrected two detrimental effects caused by LPS: nuclear factor kappa B (NF‐κB)‐induced hippocampal neuroinflammation and reduced BDNF expression.A third study . As is clinically observed in preterm infants, the ‘induced preterm’ mice exhibited increased neuroinflammation as measured by increased Nos1 and Igfbp3 brain mRNA expression, altered insulin‐like growth factor 1 (IGF‐1) signalling and decreased circulating insulin‐like growth factor binding protein 3 (IGFBP3). A different study . Following introduction to the aversive WAS stimulus the C. rodentium‐infected mice exhibited decreased hippocampal BDNF and c‐Fos levels, which were ameliorated by probiotic treatment. Interestingly, it was only the combination of C. rodentium and WAS that produced the alterations in BDNF and c‐Fos expression.Correct gene expression in the CNS during neonatal development is critical for healthy maturation of countless brain functions, as evidenced in cases where the smallest alteration in gene expression results in complicated syndromes that affect an organism's entire well‐being , prebiotics (non‐digestible dietary fibre that serves as an energy source for the host's resident microbiome) and synbiotics (a combination of the two) have been increasingly used in a clinical setting by a variety of medical fields, exhibiting salubrious health effects, including normalization of neuropsychiatric symptoms (Moosmang, via the parasympathetic vagus nerve that connects the ENS the CNS and the systemic immune system or the HPA axis which are interconnected as well. Synaptic plasticity is one of the most fundamental processes occurring in the brain, implicated in learning and memory consolidation. Dysfunctions in induction of synaptic plasticity are implicated in severe neuropsychiatric disorders. The mechanisms of plasticity are highly complex and include many types of receptors and their trafficking across membranes, signalling and cell adhesion molecules. The presynaptic cell is stimulated by a neurotransmitter which in turn activates ionic channels on the presynaptic cell, altering its membrane potential and ionic permeability, thereby affecting its ability to fire an action potential. ENS plasticity is emerging as a vastly important research target due to the complex interconnectedness between the CNS and ENS, as well as the latter's substantial involvement in various physiological and pathological phenomena. Moreover, the ENS shares many similarities with the CNS – from its neuronal circuitry to the neurotransmitters activating it.The microbiome interacts extensively with the mucosal immune system and the enteric nervous system, which operate synergistically with effects spanning many organ systems, particularly the brain. Microbial metabolites affect the brain through several branches of the microbiome–gut–brain axis et al., et al., The microbiome has been shown to influence several plasticity inducers as well as homeostatic maintenance, through various neurotransmitters, BDNF, and expression of relevant genes. While research into the effects of the microbiome on synaptic plasticity is shifting to the ENS, very few studies have investigated the interplay between plasticity in the ENS and the CNS, under the influence of the microbiome and its metabolites Table . While cThe objective of this review was to highlight the multi‐factorial involvement of the microbiome with the vastly important process of synaptic plasticity, and to emphasize the need for a research paradigm shift, where the pathophysiology of complex neuropsychiatric and neurodegenerative disorders is involved Table . We beliX.The microbiome has been unequivocally shown to affect the mental, emotional and cognitive functionality of the host, including both phenotypic manifestations and neurophysiological aspects.Synaptic plasticity is a cardinal neurophysiological process occurring in both the CNS and ENS. It is responsible for the incorporation of long‐term functional changes to synaptic connectivity and structural integrity, and consequently, neuronal transmission. The consolidation of such plastic changes requires a host of molecular processes to occur, including alterations in gene expression and receptor trafficking, rapidly regulated signalling cascades, secretion of neurotransmitters and neurotrophic factors and more.The microbiome has been shown to influence various different neurophysiological aspects of synaptic plasticity, with direct correlations established between microbial perturbations and neurotransmitter secretion, immediate early gene expression, neuronal surface receptor trafficking, neurophysiological properties affecting neuronal transmission and more. These diverse effects of the microbiome on the different mechanisms underlying synaptic plasticity suggest that the influence of the microbiome on the mental, cognitive and emotional wellbeing of the host is achieved by affecting synaptic plasticity directly and indirectly, thereby allowing for long‐lasting changes to take place.


Gold and silver nanoparticles (NPs) are widely used in the biomedical research both in the therapeutic and the sensing/diagnostics fronts. Both metals share some common optical properties with surface plasmon resonance being the most widely exploited property in therapeutics and diagnostics. Au NPs exhibit excellent light‐to‐heat conversion efficiencies and hence have found applications primarily in precision oncology, while Ag NPs have excellent antibacterial properties which can be harnessed in biomaterials' design. Both metals constitute excellent biosensing platforms owing to their plasmonic properties and are now routinely used in various optical platforms. The utilization of Au and Ag NPs in the COVID‐19 pandemic was rapidly expanded mostly in biosensing and point‐of‐care platforms and to some extent in therapeutics. In this review article, the main physicochemical properties of Au and Ag NPs are discussed with selective examples from the recent literature.Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseDiagnostic Tools > In Vitro Nanoparticle‐Based SensingNanotechnology Approaches to Biology > Nanoscale Systems in BiologyThis article is categorized under: Properties and Applications of Gold and Silver Nanoparticles in Therapeutics, Diagnostics and Biosensing Applications. The research landscape of this research field has continued to expand in the last 5–10 years with increasing number of papers for both metals, while the number of research papers with more than 1000 citations as of February 2022 has now reached 270 for Au and Ag combined, testament of the relative maturity stage of the field Figure . ProportGiven the vast bοdy of literature and the relatively large number of excellent review articles that cover virtually all aspects of Au and Ag NPs and their biomedical applications, this review focuses on providing the reader with key recent examples ca. of the last 5–7 years that cover  emerging areas in the fields of therapeutics, medical imaging, and (bio‐)sensors with interest in (point‐of‐care) diagnostics. Key examples of bimetallic Au and Ag NPs that exert combinational properties are also discussed. Of great interest are examples of image‐guided drug delivery applications, which fully harness the unique optical and chemical properties of these NPs in the biomedical context and especially in precision medicine.+ release. The latter reason actually explains the intrinsic antibacterial properties via Ag+ release which induces disruption of the negatively charged bacterial cell wall, inhibition of DNA replication and blocking of respiratory enzyme activity, and hence their uses are mostly directed toward antibacterial therapeutics  but to give an overview of the most important properties of Au and Ag NPs in the context of the biomedical field by discussing examples from the recent literature, where possible. In the context of therapeutics, the two categories are described in different sections since their therapeutic applications are derived from different properties ; conversely, for biosensing applications the two classes of NPs are grouped together as they share common properties and are often combined. Examples from the recently emerging field of bimetallic Au–Ag NPs for therapeutics and diagnostics are also analyzed. Finally, recent examples on how these remarkable nanomaterials have been explored in the SARS‐CoV‐2 pandemic era are given.2λ (2r < <λ), the extinction cross‐section can be described by Equation (1)  = ε1 + iε2(ω) are the dielectric functions of the surrounding medium and the material itself, respectively  have a so‐called surface plasmon resonance (SPR) caused by the oscillation of the conduction electrons on the surface of the particles upon light irradiation Figure  Kelly e. The res) Figure , where VThe possibility to tune the plasmon resonance of Au NPs toward and beyond the NIR regime of the electromagnetic spectrum in combination of the aforementioned properties directed researchers to explore Au as a nanoplatform for photothermal therapeutics. More specifically, Au NPs in the form of nanoshells, nanorods, nanostars, nanocubes, and nanotriangles are now synthetically accessible by various synthetic routes allowing their biomedical use. The optical properties of these NPs are mainly controlled by their shape  Au nanoshells could induce lethal local hyperthermia at tumor sites. Encouraged by the results, the same group recently reported on the photothermal ablation of prostate tumors in human subjects in the first clinical pivot study utilizing Au nanoshells . Pulsed laser irradiation results in confined Au—S bond dissociation with negligible local heat buildup compared to continuous wave laser sources that induce DNA dehybridization as the main mechanism of nucleic acid release from plasmonic NPs  by NIR irradiation (980 nm)  , surface‐enhanced Raman scattering (SERS), with the use of a p‐mercaptobenzoic acid reporter molecule, as well as for two photon imaging by direct irradiation with a femtosecond Ti:Sapphire laser setup at 800 nm. It has been shown by several studies that particles with sharp edges  may constitute a superior drug delivery/photothermal platform as surface spikes tend to penetrate cell membranes more efficiently and the particles can be retained into the cytosol for prolonged timeframes  for augmented efficacy. Huang et al. used an efficient strategy to confine Au nanorod dimers with porphyrin‐functionalized upconverting NPs that generate cytotoxic singlet oxygen  Figure   Figure . The ens) Figure . In a si) Figure . It was ) Figure ; it was An alternative approach to red‐shift the SPR of Au NPs for NIR phototherapies and theranostics is to simply induce controlled aggregation of spherical Au NPs, resulting in interparticle plasmonic coupling  NPs has been demonstrated independently by several research groups  which could exert direct PDT by laser irradiation ; nevertheless there are several reports on the Ag+ release properties of Ag NPs to formulate nanomedicines not only for antibacterials' design but also for multimodal cancer therapy; Tang et al. coated Ag NPs with aggregation‐induced emission luminogens (AIEgen) forming a NIR absorbing formulation that was shown to have potent antitumor efficacy in vivo with simultaneous imaging capabilities owing to the X‐ray sensitization properties of the Ag metal core  to enhance the 1O2 generation efficiency due to local electric effects and (2) to trigger on‐demand Ag+ release confined at the area of irradiation. The proposed formulation was tested both for its antitumor properties against CT26 tumor bearing mice as well as for its bactericidal properties against Staphylococcus aureus  have focused on the synthesis of Ag NPs with anisotropic geometries  PLGA NPs to reduce Ag+ to metallic Ag NPs on the surface of the NPs   6]3−) that gradually etched the Ag shell and restored the Au plasmon band enabling for simultaneous NIR photoacoustic imaging of the bactericidal activity against MRSA  up to 8 days. The synergistic photothermal/Ag+ effects resulted in significantly faster wound healing timeframes compared to control subjects. Yang et al.  concentrations rendering them excellent transducer/signal motifs. Fu et al.  substrates on SNAs, on the enzyme trans‐cleavage activity of the enzymes; DNA strand density and length were found to be critical factors on the enzyme activity and by design optimization they could develop a SNA/CRISPR diagnostic for HPV‐16 detection with low detection limit down to picomolar range. Cao et al.  visualization . It remains to be seen whether our growing knowledge on the interactions of these remarkable nanomaterials with human tissue will accelerate their clinical translation. Finally, bimetallic NPs is still a relatively unexplored area which is rapidly expanding and may lead to novel applications that require confined and collective properties from both metals aiming to tackle unmet therapeutic and diagnostic needs.George Pasparakis: Conceptualization (lead); formal analysis (lead); funding acquisition (lead); methodology (lead); project administration (lead); writing – original draft (lead); writing – review & editing (lead).The author has declared no conflicts of interest for this article.Gold nanoparticle‐mediated photothermal therapy: applications and opportunities for multimodal cancer treatment


Understanding brain activity linked to built environment exposure is important, as it may affect underlying cognitive, perceptual, and emotional processes, which have a critical influence in our daily life. As our time spent inside buildings is rising, and mental health problems have become more prevalent, it is important we investigate how design characteristics of the built environment impact brain function. In this study, we utilized electroencephalography to understand whether the design elements of scale and color of interior built environments modulate functional brain connectivity . Using a Cave Automatic Virtual Environment, while controlling indoor environmental quality responsible for physiological comfort, healthy adult participants aged 18–55 years , were exposed to context‐neutral indoor room scenes presented for two‐minutes each. Our results show that both enlarging and reducing scale enhanced theta connectivity across the left temporoparietal region and right frontal region. We also found when reducing the built environment scale, there was a network exhibiting greater high‐gamma connectivity, over the right frontoparietal region. For color, the condition (blue) contrasted to our achromatic control (white) increased theta connectivity in the frontal hemispheres. These findings identify a link between theta and gamma oscillations during exposure to the scale and color of the built environment, showing that design characteristics of the built environment could affect our cognitive processes and mental health. This suggests that, through the design of buildings, we may be able to mediate performance and health outcomes, which could lead to major health and economic benefits for society. There is evidence emerging of the psychological impact of the built environment, but not the accompanying brain‐based evidence. As built environment exposure may have implications on our cognitive, attentional, perceptual, and emotional functioning, it is critical we understand and measure this impact. Here, we use a rigorous interdisciplinary approach using electroencephalography, virtual reality, and indoor environmental quality monitoring to understand if design elements of an interior room impact functional connectivity networks. The study confirmed that brain network activity is impacted by scale and color, demonstrating this approach is a viable method for investigating the health implications for time spent within built environments. This research raises the prospect that neuroscience methods could contribute an evidence base to guide building design and evaluation. While previous studies using EEG to investigate the impact of the built environment on brain activity have analyzed spectral power  or additional sensory inputs  are found to involve different processing mechanisms  participated in the scale component of this study, while 18 participants participated in both the scale and color component . All participants provided written, informed consent approved by the Deakin University Human Research Ethics Committee. No participants reported prior diagnosed psychiatric, neurological, or neurodevelopmental conditions, or previous training or work experience in built environment design. A healthy adult sample was selected due to the experimental nature of the study and to reduce confounding variables. All participants were able to speak and read English and had normal or corrected to normal visual acuity.2.2An eyes open resting‐state was incorporated at the start and between each of the scenes for two‐minutes. Participants were seated comfortably in the center of the CAVE and instructed to keep their eyes‐open and pay attention to the scene they would be presented with. They were then exposed to four randomized  achromatic built environment scenes, and one chromatic color condition at the end. Each scene was presented for two‐minutes, before the CAVE returned to the resting‐state display. This study used an eyes‐open resting‐state design due to the visual nature of the stimuli. Participants were exposed to varying built environment scenes using a standard sitting posture which is not uncommon for the type of study or real‐world behavior within the built environment. This helped minimize differences in head height and reduced movement artifact in recordings; however, it is worth noting subject positioning can alter the neurophysiological activity  and a floor (2.4 m wide × 3 m long), each with Barco Galaxy NW‐12 stereoscopic projectors. Projectors connected to a series of image generators consisting of Nvidia Quadro P6000 graphic cards, synced using Quadro Sync II cards at 120 Hz (60 Hz per eye) to render images at the same time. An optical‐based tracking system connected back to a Virtual Reality Peripheral Network (VRPN) Server  tracked used movement through active LED markers located on the stereoscopic glasses. These were calibrated to ensure there was no conflict between eye height and postural cue  at one‐minute intervals which were date and time stamped. We then averaged the one‐minute recordings of each session to create an average per participant session, and then average across all participant sessions. Variables recorded included interval sound pressure levels, overall mean air and wet‐bulb globe temperature, carbon dioxide concentration, and relative humidity. These were all within acceptable range for optimal performance as previously reported in Bower et al.  and Bowe2.4EEG data were acquired using a 64‐channel EEG system (Philips Hydrocel Geodesic Sensor Net 64‐channel HCGSN) and recorded using Net Station 5 Geodesic EEG software, version 5.4.2  using a sampling rate of 1000 Hz, with Cz as the online reference. We created a continuous recording with manual time stamps at the start and end of each two‐minute scene exposure using markers for each participant. We preprocessed the EEG data using EEGLab v2019.1)  to return the complex Fourier spectra for each subject/electrode across each EEG frequency band in 1 Hz steps: delta (1–3 Hz), theta (4–7 Hz), alpha (8–12 Hz), beta (13–30 Hz), low‐gamma (30–45 Hz), and high‐gamma (55–80 Hz). We compared phase‐based connectivity between all electrodes for each frequency band using the weighted phase lag index (wPLI) in FieldTrip toolbox for EEG/MEG‐analysis , and 3.4 for color  conditions. The secondary significant threshold was set to p = .025 (two‐tailed) for family‐wise corrected cluster analysis (5000 permutations). BrainNet Viewer v1.7  was used for visualizing the results. We also extracted the average connectivity strength across the significant subnetworks identified through NBS for each participant and condition. We then averaged these values to visually compare the difference in connectivity strength which we exported to RStudio (Version 1.3.959) for analysis and visualization.The analysis was performed using the Network‐Based Statistic (NBS) Toolbox v1.2 . When comparing the control to the small condition, NBS identified a significant network of increased theta connectivity . The identified network encompassed left temporal and parietal regions, as well as bilateral frontal regions. We also found a significant network of increased theta activity when comparing the control to the large condition . This was asymmetrically spread across the brain, in the left hemisphere and across the midline from the left temporal to right frontal region. We also observed between‐condition effects in the theta range with increased connections when comparing the small to the large condition . The network identified by NBS for small to large predominantly comprises frontal activity in the right hemisphere, connecting to the left temporal region . This activity was concentrated in the right frontoparietal region  was widespread, comprising electrodes over frontal, central and posterior regions. Although widespread, there was significant clustered activity in the right temporo‐occipital region. In the low‐gamma range, the NBS identified increased connectivity networks when comparing the resting‐state to the control condition . This was largely confined to the right occipital region. We did not detect any significant connectivity changes within the delta, beta, or low‐gamma frequencies . This network consisted of interhemispheric activity across the frontoparietal region. We did not detect differences between the resting‐state and white control condition, suggesting the presentation of the achromatic built environment scene itself did not affect functional connectivity. The NBS also revealed a significant network of increased activity in the low‐gamma range when comparing the resting‐state to the color condition . This was clustered in the right occipital region. No significant changes were detected in the remaining delta, alpha, or high‐gamma bandwidths  and increasing  the scale of the built environment resulted in theta connectivity enhancement. We also detected increased high‐gamma connectivity comparing the control to small condition. Differences in alpha and low‐gamma connectivity were also found, but these were between the control and eyes‐open restingstate rather than scale conditions. When analyzing color, theta functional connectivity was also found to increase between the control (white) and color (blue) condition. Significant low‐gamma connectivity also increased from the resting‐state to the color condition. These findings are indicative of an association between exposure to different elements of the built environment and patterns of functional connectivity within the brain. Although further investigation is required to replicate this finding and understand the precise neural mechanisms involved, the application of these findings may have implications for several underlying processes such as cognitive, attentional, perceptual, and emotional functioning.This initial study was interested in examining the neural correlates of changes to the scale and color of interior built environments, and future work will attempt extend these initial findings by exploring brain behavior relationships between the neural response and emotional, cognitive, and social behaviors. A key strength of this study is the use of the CAVE with EEG and IEQ monitoring to ensure ecological validity. Only a handful of studies worldwide have combined EEG measurement with an immersive CAVE environment  which could improve spatial resolution while also enabling the participant to have greater immersion through a virtual projection. The development of optically pumped magnetometer‐based MEG also has the potential to progress the field further , or a cognitive response to the environment . Crucially, debate is required to unravel the ethical implications and responsibilities of policy makers, planners, and building designers to ensure built environments are supportive and have a positive effect on mental health of the public. We believe it is important that we further interrogate the impact of building design on a broader subset of the population to further untangle whether built environment design is one of the underpinning elements of environmental enrichment which can serve as a neuroprotective factor for both healthy and clinical subsets of the population. This research will help us predict and evaluate the effect of the built environments we inhabit on brain and body functioning, so we can work towards designing buildings for optimal cognitive function and mental health.The authors declare no conflict of interests.APPENDIX S1 Supporting InformationClick here for additional data file.


Culture is widely accepted as an important social factor present across a wide range of species. Bears have a culture as defined as behavioral traditions inherited through social learning usually from mothers to offspring. Successful bear cultures can enhance fitness and resource exploitation benefits. In contrast, some bear cultures related to response to humans and human‐related foods can be maladaptive and result in reduced fitness and direct mortality. In environments with minimal human influence most bear culture has evolved over generations to be beneficial and well adapted to enhance fitness. However, most bears across the world do not live in areas with minimal human influence and in these areas, bear culture is often changed by bear interactions with humans, usually to the detriment of bear survival. We highlight the importance of identifying unique bear cultural traits that allow efficient use of local resources and the value of careful management to preserve these adaptive cultural behaviors. It is also important to select against maladaptive cultural behaviors that are usually related to humans in order to reduce human–bear conflicts and high bear mortality. We use examples from Yellowstone National Park to demonstrate how long‐term management to reduce maladaptive bear cultures related to humans has resulted in healthy bear populations and a low level of human–bear conflict in spite of a high number of Yellowstone National Park visitors in close association with bears. Bears have a culture as defined as behavioral traditions inherited through social learning usually from mothers to offspring. Successful bear cultures can enhance fitness and resource exploitation benefits. We highlight the importance of identifying unique bear cultural traits that allow efficient use of local resources and the value of careful management to preserve these adaptive cultural behaviors. They genotyped parents and their offspring and compared the frequency of problem (conflicts with humans or depredation on livestock) and non‐problem offspring from problem and non‐problem parents. They found no evidence that offspring from problem fathers were more likely to be involved in conflicts. In contrast, they documented that offspring of problem mothers were likely to also be conflict bears, whereas offspring of non‐problem mothers were not likely to be problem bears. Since young bears spend so much time with their mothers, social mother–offspring learning is the primary cause of problem behaviors related to human conflicts in young bears. Morehouse et al.'s     providing YNP visitors with information on how to hike, camp, recreate, and store anthropogenic bear attractants in a manner that reduces the chances of bear–human conflicts; (2) providing YNP visitors with bear‐resistant infrastructure  so that food and garbage storage regulations are easy and convenient to comply with; (3) rigorously enforcing food and garbage storage regulations through campground food security patrols and backcountry campsite patrols; and (4) removing (killing or sending to zoos) rather than translocating bears that intentionally seek out and damage property or injure people while attempting to obtain anthropogenic foods (in benign incidents where bears inadvertently happen upon unsecured foods they are left to roam free on the landscape).YNP managers attempt to break the chain of learned conflict behavior passed from mothers to offspring and adult female offspring to future offspring Cole, . BreakinUrsus americanus) was also low in Yosemite, Sequoia, and Kings Canyon National Parks  period in YNP when relocation of conflict bears was common, to a 22‐year (2000–2012) period when relocation was rarely used, provides opportunity to compare the efficacy of each management practice. High numbers of human‐caused grizzly bear mortalities in the early 1970s  incidents in the park where grizzly bears obtained human foods or damaged property while attempting to access anthropogenic attractants. Of those 29 incidents, 7 were benign and involved bears consuming anthropogenic foods that were left out and not stored in a bear‐proof manner. In 22 incidents, bears aggressively sought human foods or garbage and damaged property in the process. In response to those 22 incidents, 3 (x¯= 0.3 ± 0.5 SD/year) independent age grizzly bears were removed (2 killed and 1 sent to a zoo) in management actions. It is important to note that limiting lethal management removals of bears to sustainable rates while operating under YNP's aggressive bear management strategy requires significant investment of resources in conflict prevention.The YNP management strategy has been highly successful at reducing grizzly bear–human conflicts and management removals of grizzly bears on national park lands where humans are temporary visitors and their activities are highly controlled  calves or cutthroat trout in late spring and early summer, and feed on the seeds of whitebark pine  in late summer and fall ; Data curation (supporting); Formal analysis (supporting); Investigation ; Methodology ; Writing – original draft (lead); Writing – review & editing . Kerry A. Gunther: Conceptualization (supporting); Data curation (lead); Formal analysis (lead); Investigation ; Methodology ; Writing – original draft (supporting); Writing – review & editing .


Posterior basal (S10) segmentectomy is one of the most challenging (and uncommon) types of pulmonary segmentectomy. Here, we present two key tips for facilitating a uniportal operation. The first is a full understanding of the relative locations of the pulmonary vessels and bronchi , and the other is the use of “suction‐guided stapling” to dissect and divide the peripheral pulmonary vessels and bronchi. We describe the successful postoperative course of a patient who was so treated. Posterior basal (S10) segmentectomy is one of the most challenging (and uncommon) types of pulmonary segmentectomy. We here present two key tips, which are a full understanding of the relative locations of the pulmonary vessels and bronchi by preoperative three‐dimensional computed tomography/broncho‐angiography and the use of “suction‐guided stapling”, facilitating a uniportal operation. The results of JCOG0802/WJOG4607 by Saji et al. indicated that segmentectomy will become one of the standard procedures for lung cancer in the future.A 74‐year‐old man with a history of colorectal cancer visited us because chest computed tomography (CT) revealed an approximately 20‐mm diameter solid nodular shadow in the posterior basal S10) segment . Careful anatomical evaluation pre‐ and perioperatively is essential. In our department, we confirmed the location of pulmonary vessels and bronchi from several viewing by rotating the 3DCTBA data which was very helpful. The second tip is appropriate dissection and division of the peripheral pulmonary vessels and bronchi. When using a uniportal approach, it is sometimes difficult to dissect these tissues because it is not easy to grasp the surrounding tissues. Stapler insertion is also difficult (for the same reason). We highly recommend our “suction‐guided stapling” method for division of the pulmonary vein and bronchi.Compared to our previously described “intersegmental tunneling” method, a posterior approach is not contraindicated by a dense fissure. We removed the chest drainage tube on postoperative day 1 because no dense fissure was dissected, and there was no air leakage. A uniportal posterior approach facilitates unidirectional dissection of intrathoracic structures; we earlier found that such dissection was easy even via a uniport.None declared.Video S1 Uniportal thoracoscopic left posterior basal segmentectomy using a posterior approach.Click here for additional data file.


The COVID‐19 pandemic forced health care systems globally to adapt quickly to remote modes of health care delivery, including for routine asthma reviews. A core component of asthma care is supporting self‐management, a guideline‐recommended intervention that reduces the risk of acute attacks, and improves asthma control and quality of life.We aimed to explore context and mechanisms for the outcomes of clinical effectiveness, acceptability and safety of supported self‐management delivery within remote asthma consultations.The review followed standard methodology for rapid realist reviews. An External Reference Group (ERG) provided expert advice and guidance throughout the study. We systematically searched four electronic databases and, with ERG advice, selected 18 papers that explored self‐management delivery during routine asthma reviews.Health care professional delivery of supported self‐management for asthma patients during remote  consultations.Data were extracted using Context‐Mechanism‐Outcome (C‐M‐O) configurations and synthesised into overarching themes using the PRISMS taxonomy of supported self‐management as a framework to structure the findings.The review findings identified how support for self‐management delivered remotely was acceptable (often more acceptable than in‐person consultations), and was a safe and effective alternative to face‐to‐face reviews. In addition, remote delivery of supported self‐management was associated with; increased patient convenience, improved access to and attendance at remote reviews, and offered continuity of care.Remote delivery of supported self‐management for asthma was generally found to be clinically effective, acceptable, and safe with the added advantage of increasing accessibility. Remote reviews could provide the core content of an asthma review, including remote completion of asthma action plans.Our findings support the option of remote delivery of routine asthma care for those who have this preference, and offer healthcare professionals guidance on embedding supported self‐management into remote asthma reviews.Patient and public contribution was provided by a representative of the Asthma UK Centre for Applied Research (AUKCAR) patient and public involvement (PPI) group. The PPI representative reviewed the findings, and feedback and comments were considered. This lead to further interpretations of the data which were included in the final manuscript. Given the changing clinical context and national/international recommendations for implementing supported self‐management,1.21.Identify and synthesize studies that evaluated and/or explored remote asthma consultations and the delivery of supported self‐management.2.Explore the context and mechanisms that have contributed to clinically effective, safe and acceptable delivery of supported self‐management during remote asthma consultations.3.Produce recommendations for best practices in the delivery of supported self‐management during remote consultations for people with asthma.Using realist methodology, we aimed to:22.1Following Realist Review methodology2.2Devised by Pawson and Tilly,2.3For this review, we used the rapid realist review approach described by Saul et al.2.4The review took place between August 2020 and March 2021. One reviewer (E. K.) initially scoped relevant literature exploring the delivery of routine asthma reviews via remote consultations. From this initial broad search, the research group created a preliminary programme theory. This process defined the scale of the research and ensured that the review focussed appropriately on the research questions. Although not an essential element of a rapid realist review, the creation of programme theory is a recognized step in realist approaches.2.5The following databases were searched in October 2020 by E. K.: MEDLINE, Embase, PsychINFO and the Cochrane Library. Key search terms that were likely to identify studies relevant to the research questions and to address the purpose of the review were used File . We sear2.6Titles/abstracts and potentially eligible full texts were independently screened by two reviewers (E. K. and  I. S.), and disagreements were resolved by discussion.It was during this stage, that the first External Reference Group Meeting took place (November 2020) to review the list of full‐text articles and provide feedback on the importance of included papers and suggest any other publications or research that might contribute data to the review. During this stage, there was also an emphasis on grey literature or ‘difficult to find’ documents which may have not otherwise be identified. From the feedback provided by the group, any gaps in the literature were addressed by iteratively modifying the search terms/inclusion and exclusion criteria to capture any further relevant documents.2.7To begin the data extraction phase, a template was devised focusing on C–M–O configurations that explored components of support for self‐management, as defined by the Practical Systematic Review of Self‐Management Support (PRISMS).C–M–O configurations were then extracted from all full‐text articles. Quantitative, qualitative or contextual data could be extracted from any part of selected papers. We continuously considered the relevance and rigour of each included C–M–O, and regularly discussed within the core research team  how individual extracts should be used to ensure appropriate inferences were made. Data extraction was completed by E. K.  resulted in the same C–M–O configurations being extracted by both authors, that is, each author identified the same outcome related to remote delivery of SSM in all papers and also connected the same context and mechanism to each outcome for all papers. How to optimally present the data  and the interpretation of each C–M–O was discussed in detail until a consensus was reached.2.8We used the PRISMS taxonomyTo synthesise the findings, all extracted C–M–Os were mapped against the PRISMS taxonomy components. We considered C–M–Os for each component of self‐management and identified key themes within and across each component. Further, we considered whether there was variance in the frequency of delivery of each component. Following this, we considered the association of C–M–Os to the outcomes of acceptability, clinical effectiveness and safety. Key themes were created from all C–M–O and taxonomy components until data saturation was reached. As External Reference Group members included clinicians currently delivering supported asthma self‐management, their feedback ensured that the final findings and themes addressed any gaps in practice that the analysis had not represented.33.1A total of 1519 articles were identified in the search, of which 153.2n = 10), the United States of America and Canada (n = 7) and Italy (n = 1). Eight of the included papers were systematic reviews (n = 5) or meta‐reviews (n = 3), including data from a total of (n = 366) unique primary studies represented within these systematic reviews. Eleven papers had the primary aim of exploring the use of remote consultations in routine asthma reviews. Of the three papers provided by the External Reference Group, one was a feasibility study and two were systematic reviews. Detailed study characteristics can be found in File All 18 included studies were published between 2003 and 2020 and were undertaken in the United Kingdom .Video consultations: In addition to enabling feedback on monitored asthma symptoms or behaviours, video consultations had particular advantages for monitoring a patient's condition through systems, such as ‘document camera’ or ‘picture‐in‐picture’ functions, which facilitated patients and professionals reviewing the contents of documents  together.Telephone consultations: A number of articles supported telephone reviews as an efficient way of maintaining contact with asthma patients.3.3.2Patient: Video and telephone consultations were a safe and effective mechanism to facilitate the delivery of individualized information about asthma and its management, resulting in increased patient understanding of their conditionProfessional: Use of video and telephone consultations were both recognized as effective communication strategies for healthcare professionals to provide individualized information, instructions, education and signposting of other essential resources to patients.Video consultations: Patients found video consultation technology visually appealing and engaging, enhancing understanding and asthma education .Telephone consultations: Several studies supported the use of telephone consultations as an effective tool to deliver individualized information to patients.3.3.3Patients: Remote consultations provided more convenient and flexible access to advice and support for patients with asthma, compared to attending a face‐to‐face review.Professionals: Healthcare professionals may have more availability to conduct a remote video or telephone review, enabling them to respond more promptly than a face‐to‐face appointment may have offered.Video and telephone consultations: For some patients, telephone and video consultations were a preferred method of consultation, and patients were more likely to attend this type of review, leading to increased engagement.3.3.4Patients: Patients whose reviews were conducted with the same clinician each time , reported better health‐related outcomes and greater satisfaction with the consultation..Professionals: A number of studies suggested that when a relationship is already established between patient and professional, telephone and video technologies are a suitable platform to engage in shared decision‐making and discussion of self‐management strategies. The existing relationship ensures the professional recognizes changes in a person's condition due to their prior awareness of personal circumstances.Video consultation: Patients were able to discuss their asthma action plan with their health professional during remote reviews. Video‐facilitated collaboration through technologies, such as ‘screening sharing’ and ‘editing documents’, allowed the patient and professional to work together to personalize their action plan.3.3.5Patients: Specific practical asthma self‐management strategies can be effectively communicated, delivered and discussed during remote asthma reviews. An individualized, written asthma action plan can be successfully discussed via telephone or video consultation. Remote provision/discussion of an action plan leads to positive patient outcomes, such as increased patient understanding,Professionals: The use of video and telephone consultations is an effective alternative for discussing a patient's asthma plan compared to face‐to‐face reviews. Discussion of individualized action plan information and medications can be safely reviewed to increase patient understanding of their condition, medication adherence and how to recognize symptom deterioration. Professionals were able to demonstrate inhaler technique and provide education using the visual aids and tools of video consultation technologies effectively and safely.Video consultation: When professionals are communicating and demonstrating practical strategies, such as inhaler technique via video consultation, patients were able to understand and learn from the instructions when the professional's video camera was positioned from the waist up .Telephone consultation: Telephone consultations are a safe and effective alternative to face‐to‐face reviews to discuss and provide practical self‐management advice and support. Individual asthma action plans can be discussed over the telephone and then converted into written versions and sent to patients after the consultation. This technique of discussions and provision of action plans were seen to significantly improve asthma control.3.3.6Patient: Through the increased engagement with a remote consultation and prompt clinical input, patients felt more empowered and had up‐to‐date strategies to manage their condition.3.4The overarching synthesis from the six key themes identified that, in relation to the review's key aims , remote consultations were overall, more highly accepted than in‐person consultations by many patients and professionals, and were an equally safe and effective alternative to face‐to‐face reviews. In only one instance were concerns raised about remote consulting,44.1We identified six themes using data from 18 articles to describe how supported self‐management is delivered during remote asthma consultations. We identified positive benefits associated with remote asthma care, including increased convenience, improved access (including for some vulnerable groups) and attendance at reviews, ability to assess the core content of asthma remotely , completion of asthma action plans (screen sharing or discussed with documents sent postconsultation) and continuity of care. Typically, these overrode any challenges associated with distance imposed by remote consultations, and patient's concerns about the quality of the interaction. Overall, our data suggest that for many patients and healthcare professionals, remote consultations are more highly accepted than in‐person consultations, and were equally as effective and safe as face‐to‐face reviews.4.2Guidelines for asthma managementProviding patients with information and guidance for self‐management of their asthma is an essential aspect of all routine reviews. Our findings highlight that the use of telephone and video consultations is an acceptable, effective and safe alternative to face‐to‐face consultations for providing patients with this information. Importantly, the partnership between the patient and professional should enable information to be discussed, understood and agreed upon between both the patient and professional. Such ‘shared decision‐making’ can improve clinical outcomes and quality of life by actively engaging them in managing their own health.Asthma is a variable condition and some people with asthma may be well controlled and need very little support for many months. However, when symptoms are triggered, access to professional care needs to be flexible in timing and mode of delivery.The provision of a personalized asthma action plan is an essential strategy in supporting people with asthma to take the right actions at the right time.Kew and Cates‘ do things differently’ in their approach to LTCs and the delivery of supported self‐management. The report concludes that it is critical to plan carefully for the use of remote technologies and to identify the best practice of self‐management delivery at scale and in a sustainable way. The findings of our review provide the context and mechanisms for effective remote asthma‐supported self‐management delivery.Kearney4.3To our knowledge, we have conducted the first rapid realist review in the area of asthma supported self‐management delivery via remote consultation. Our review is timely given the shift to remote care driven by the COVID‐19 pandemic, and we explored the (rapidly expanding) use of video and/or telephone consultations, and systematically identified the perceived benefits and challenges of each mode of delivery in relation to each theme. Additionally, the findings are explored through the perspective of both the health professional and the patient. A final strength is that we utilized a robust realist methodology, which is gaining recognition for its contribution to healthcare research.A weakness of our study was the time constraints that we overcame by the use of a rapid realist review. By design, our review was ‘rapid’, and we recognize that a more detailed approach such as a traditional realist synthesis may have revealed, challenged or confirmed some of the themes presented in the findings of this study, due to its ability to test presented theories. However, we believe our findings have been systematically constructed, and all feedback provided by the multidisciplinary External Reference Group was considered and actioned. Additionally, the use of the PRISMS taxonomyTo increase the reliability of findings, we involved a second reviewer in the data extraction phase. The research team regularly discussed potential findings to ensure different perspectives were considered and resulted in a balanced interpretation of the data. The aim was to reach a consensus in interpretation, and this was achieved for all findings.This review was completed during the COVID‐19 pandemic period, but all studies included in the data predated the pandemic. Post‐COVID research may present different findings as healthcare adapts to new models of asthma care. Additionally, we were dependent on the completeness of the included studies, so some potentially important contexts may not have been evaluated. For example, we did not have evidence to inform the role of remote support for self‐management in the context of people living with disabilities, or ethnic minority groups potentially with language barriers. Future research should specifically explore remote supported self‐management delivery for such groups.We also acknowledge that although the review findings indicate either equivalence or greater benefit of remote self‐management delivery, there will be individuals for whom face‐to‐face reviews are a preferred mode of healthcare delivery and communication. Additionally, we recognize that the ‘safety’ variable measured within this review has not been tested within a controlled trial. Although we found no indication that remote delivery of supported self‐management caused harm, we would recommend future studies to explore this further.4.42ART programme of work has developed evidence‐based, practical strategies to promote the delivery of supported self‐management in routine primary care.2ART programme.Future research should explore how telecommunication can be implemented in ways that are most valued by patients and clinicians, to fit within the organisational and technical infrastructure of healthcare services and embrace the culture of delivering supported self‐management.5Even when the COVID‐19 pandemic recedes, remote technologies will remain in everyday healthcare. This paper highlights new knowledge through the use of realist methodology by understanding the existing mechanisms and the interplay within differing contexts, and has revealed how and why remote supported self‐management for asthma can be effectively delivered. A core component of asthma care is supporting self‐management, a guideline‐recommended intervention that reduces the risk of acute attacks, and improves asthma control and quality of life. Across a broad range of contexts, remote consultations are highly accepted by both patients and professionals, and are as clinically effective and safe as face‐to‐face reviews to provide self‐management support. Specific groups advantaged by remote consulting included those living in rural communities, or who had to fit their healthcare around work or domestic responsibilities, and those with reduced mobility. The findings of this rapid realist review can inform the conduct of remote asthma reviews, and implementation of supported self‐management techniques into asthma care.The authors declare that there are no conflict of interests.Emma Kinley undertook the data collection, extraction and synthesis. Imogen Skene independently screened the data search and extracted 25% of the data to ensure reliability and validity. All authors  contributed to data interpretation and critically revised the manuscript. All authors read and approved the final manuscript.Supplementary information.Click here for additional data file.Supplementary information.Click here for additional data file.Supplementary information.Click here for additional data file.


Children with Autism Spectrum Disorder (ASD) struggle with communication, sensory sensitivities and social interaction. These difficulties can make hospital visits challenging. Every child with ASD is unique, and as such, some children can do well in clinical settings with minimal supports while others may require environmental modifications to achieve optimal care. ASD is prevalent worldwide and cultural differences can lead to varied care. Several hospitals, including Boston Medical Center in USA and Sidra Medicine and Research Center in Qatar, have attempted to address these challenges by developing strategies to create an ‘Autism Friendly’ environment.This workshop will 1. Describe the 4 domains of an “Autism Friendly” environment 2. Describe practical steps for successful implementation of interventions and modifications to consider based on setting and culture.Didactic section 1 will describe the 4 domains for greating an ‘Autism Friendly environment’. Didactic section 2 will describe implementation in an inpatient and outpatient setting focusing on modifications based on environmental differences. These didactic presentations will be followed by a hands on, interactive section where participants will break out in small groups to learn specific implementation skills.Participants will learn how to improve care offered to children with ASD during hospital visits. Participants will develop the skills to implement similar interventions in their home institutions.Hospitals can create an Autism Friendly environment by using 4 domains of intervention which could help improve provider skills and patient and family experience.


Building rural health workforce research capacity is critical to addressing rural health inequalities. Research training is a mainstay research capacity building strategy. This paper describes the delivery and evaluation of a research training program for rural and regional allied health professions (AHPs).A mentored research training program was delivered to AHPs employed public health services in rural and regional Victoria, Australia. The program was evaluated using the Evidence‐Based Practice Knowledge Attitudes and Practice (EBP‐KAP) tool at baseline and 3 months post‐training. Semi‐structured interviews undertaken at 3 and 16 months post‐training explored participants' perspectives of the training, their development and application of EBP and research skills. Survey data were analysed descriptively, and interview data were analysed using a framework approach.Thirty‐four individuals from 14 organisations attended the first workshop and 31 attended the second. Thirty‐one participants completed the survey at baseline and nine at 3 months post‐training. Sixteen interviews were undertaken with 11 participants, five participating at both time points. Participants had positive EBP attitudes at both time points. Overall, participants' knowledge and incorporation of EBP into their practice, and retrieval of evidence was unchanged 3 months post‐training. Themes identified in the interview data were as follows: (1) individual research capacity enhanced through supported practice, (2) organisational factors influence individuals' progression of research and (3) individual contributions towards research capacity within the organisation.A mentored rural research training program promoted the application of EBP skills at the individual level and contributed to organisational research capacity. Research led by health professionals and health services influences evidence‐based practice, improves service‐user outcomes, and health workforce recruitment and retentionRural health services and health professionals have less access to research capacity building initiatives and opportunities than those in metropolitan areasInvestment in rural health research capacity building is a key policy directive and strategy to reduce geographic location‐related health disparitiesA mentored and applied research training for allied health professionals led to several individual outcomes beyond increased research and evidence‐based practice knowledge. It led to the development of rural research networks, new opportunities and ways of thinking about and approaching clinical practice changesOrganisational research capacity and culture influenced the outcomes for individual allied health professionals that engaged in research trainingAlthough targeted at the individual allied health professional level, the training impacted on organisation‐level research capacity1Allied health incorporates numerous disciplines such as occupational therapy, physiotherapy and dietetics.Embedding research as core business in health services is essential for the delivery of evidence‐based practice (EBP) and effective health care that improves service‐user outcomes, and promotes health workforce recruitment and retention.In Victoria, Allied health incorporates 27 professions, including disciplines such as occupational therapy, physiotherapy and dietetics.Promoting health service‐led research in rural areas is critical to ensuring relevant evidence is generated to improve service delivery and, in turn, the health outcomes of people living in these communities.Delivering high‐quality research training, skills development and research support to local health professionals, supervisors, students and broader community stakeholdersref. 21, p. 28Developing regional consultative mechanisms to identify and respond to local research needs’.Effective RCB initiatives encompass a range of integrated strategies targeted at the policy or systems, organisational, team and individual level.‘Recommendation 15 Through the RHMT program, universities be required to demonstrate that they are supporting rural research through the RCS and UDRH network by:This paper describes a research training program developed and delivered in a rural setting to AHPs and the outcomes of the evaluation.1.1measure the effect of the research training program on participants' knowledge, attitudes and practice regarding evidence‐based practice;explore the outcomes and impacts (if any) of the research training program on participants' individual EBP and research activity;explore the factors that influenced the outcomes and impacts of the training program on individual EBP and research activity; andexplore any potential influence of the research training program on research capacity within participants' health organisations.This evaluation study aimed to:22.1To address current evidence and practice gaps, a research training program targeting point‐of‐care AHPs in rural and regional health settings was developed in 2019. AHPs from 27 public health organisations located in rural and regional settingsThe overarching aim of the program was to support novice researchers to enhance participants' EBP knowledge, skills and attitudes and to develop a small‐scale study protocol relevant to their practice setting. Training consisted of two face‐to‐face full‐day workshops at a rural health service held 6 weeks apart, with mentoring by experienced researchers, between workshops. It was anticipated that the protocols developed throughout the training would be submitted as part of research ethics applications to enable participants to progress their research activity.close to practice research skills.Active pedagogies were employed in both training workshops to maximise participants' engagement with the training content and its application to their identified research problem during, between and beyond the workshops.2.2A sequential mixed‐methods study design was used to address the aims of the study. Although the workshop aimed to support participants to develop a research protocol as a tangible outcome, the evaluation focused on measuring the development and application of EBP skills through the quantitative survey and used interviews to explore more deeply, the outcomes and application of EBP in health settings. All AHPs who participated in the research training program were invited to take part in the evaluation.2.3To quantitatively measure participants' EBP knowledge, attitudes and practice, the 23‐item EBP‐Knowledge Attitudes Practice (EBP‐KAP)The survey was administered in hard copy form at baseline (prior to the training) and then again electronically 3 months post‐training.Semi‐structured telephone interviews were conducted by a researcher (OK) who has extensive qualitative interview and research experience and was not involved in the delivery of the training. The interviews explored the outcomes and impacts of the training program more broadly and to understand whether the training or other factors influenced participants' research and EBP capacity development, the application of these skills, research progress and any other organisational impacts (see Interviews were conducted at two time points: (1) August 2019 (3 months post‐training) and (2) September 2020 (16 months post‐training). The 12‐month interviews were delayed due to COVID‐19‐related disruptions. The semi‐structured interview guide was informed by the RCB literature, the researchers' knowledge and experiences of the intended outcomes of research training: the improvement in, and application of participants' EBP and research skills. Interviews were audio‐recorded and professionally transcribed verbatim.2.4Survey data were analysed using IBM SPSS Statistics (version 27). Mean scores for the knowledge, attitudes and practices subscales were calculated by calculating the individual mean score for the subscale and then taking an average of those scores as a summary measure for the whole group. Negatively worded items were reverse scored for subscale score calculations. Differences on the knowledge, attitudes and practices subscales baseline scores were analysed using a within‐subjects ANOVA. Differences in knowledge, attitudes and practices subscales pre‐ and post‐training were analysed using a Wilcoxon signed rank test.Interview data (3 months post‐training) were analysed according to a team‐based framework thematic analysis approach, using both inductive and deductive techniques.Quantitative and qualitative data were analysed separately. Analysis of the survey results  was completed prior to the interviews. Findings from the survey were explored in greater depth through the interviews. The interview questions were determined prior to the completion of the quantitative component.3The training program included 13 project teams from 14 health organisations, with 34 participants attending the first workshop and 31 the second workshop.3.1n = 33, 82.5%). Half of the participants were aged between 30 and 39 years (range 20–60+ years). A third of participants had been working for <5 years. Thirteen disciplines were represented including nine Allied Health professions. Within‐subjects' comparisons of the subscale scores resulted in a significant main effect (F (3) = 13.068, p < 0.001). Respondents' scores on knowledge  were significantly higher than scores on both information retrieval practices  and professional practice and learning  subscales. The two practice subscales were not significantly different from one another (p = 1.000). The knowledge and attitudes  were not significantly different from one another (p = 0.378). The attitudes subscale mean score was significantly different from information retrieval practices (p = 0.028), however not significantly different from the professional practice and learning subscale (p = 0.055).Thirty‐one participants 91.2%) completed the 23‐item EBP‐KAP survey at baseline  completed both the baseline and 3‐month surveys. There were no significant differences in mean scores for the factors: knowledge pre‐analysis  and post‐analysis , practice information retrieval pre‐analysis  and post‐analysis , professional practice and learning pre‐analysis  and post‐analysis , and attitudes about EBP  and post‐analysis . This pre–post analysis is under powered due to the small sample size.A small number of participants , with 11 participants. Interviews lasted between 11 and 30 min in duration. Five participated at both the 3‐ and 16‐month time points. Through thematic framework analysis of the combined three‐ and 16‐month post‐training interview data, we identified three key themes: (1) individual research capacity enhanced through supported practice, (2) organisational factors influence individuals' progression of research and (3) individual contributions towards research capacity within the organisation.3.2.1Participant 2, 16 months post‐trainingrealising that research is achievable and it's not just something that imaginary people do at universities. So seeing it as being something that clinicians can do and that you don't need special powers. Obviously you need support to be able to do it, but that is a realistic goalThe outcomes of the training program described by participants varied from ceased project initiatives to finalised study protocols. Of the interview participants representing 11 teams, four had developed a study protocol by the 16‐month post‐training timepoint, two reported that their protocols were undergoing ethics and governance review, one study was in progress, and one had completed their study and were now preparing a manuscript. Despite the variation in terms of progress, participants appreciated gaining basic research skills and an understanding of ‘how to get started’ on their research journey, and there was a sense that the research training provided much more than research knowledge and skills. The practical nature of the training and interactive learning environment provided opportunities for participants to apply the workshop content, using their own research idea, so that it was able to be taken forward in a structured and systematic way. Through practical application of research knowledge, participants were able to experience and demystify the research process:Participant 5, three months post‐trainingIt's great to see other people's designs and ideas and some of their input … questions were really helpful because things that were clear in our minds were clearly not understandable to people who were not embedded in our project the same way we were.The mentoring component of the training further promoted the practical application of the content and was a frequently reported and somewhat novel highlight for participants:Participant 2, three months post‐trainingthey [mentor] were highly qualified … super supportive and super enthusiastic that made us more enthusiastic about the project which helped … She was just there to help … she gets back to you as quickly as possible. You felt really supported. That's something that you don't get ever really.The practical nature of the training program coupled with the mentoring meant participants could apply the knowledge and skills they learned in the workshops and guided them through the challenges faced between and beyond the workshop context. In this sense, the workshops provided the starting point or springboard for participants. Although it was not an expectation of the program, mentorship extended beyond the defined training period for some and enabled the novice researchers to continue journey in a support way.References to the practical, applied nature of the training were made frequently and described as a valued feature of the program. Linked to this were the social and collaborative characteristics of the workshops, where participants shared and contributed to one another's projects. This facilitated peer learning, lateral thinking and the refinement of research ideas3.2.2Participant 10, three months post‐training[Health Organisation] is very supportive of clinical research and they've got [Name] as the research manager, so it's just part of the culture here as well about researching and new program development and that's just very well supported.An enabler to their research progression was their ease of access to the helpful health service embedded researcher for guidance; however, the same participant described a barrier to the progress was the lack of response from the person required to support and sign‐off on their ethics application. The same participant describes several other organisational influences on research progress:Participant 10, three months post‐trainingwe haven't even got it [ethics application] in yet. I've sought [Embedded researcher's] support to try and get some information about the next steps. [Embedded researcher] was really good, but it went to the next person at the hospital and I can't get people to call me back or answer my emails … after a few attempts, I stop and then it goes off my radar again.The above participant quote illustrates how organisational factors and barriers combined with limited time for AHPs to dedicate to research result in research endeavours being abandoned. A lack of time and competing priorities are well‐documented barriers to health professional‐led research, and this was further reinforced by data generated in this study.On describing the factors that influenced the progress of their research project, participants referred to a range of organisational factors including team‐related factors, research infrastructure and organisational research culture. Participants referred to supportive managers and team leaders as key factors enabling and promoting research progress:Participant 5, three months post‐trainingShe [manager] was definitely supportive of us quarantining some time and extending our supervision time that we usually have from a clinical perspective, to also incorporate some research time … that's an enabler, otherwise I don't think we would have got there.In the case described above, the manager provided the participant with the scope to be flexible in their use of clinical supervision time and allowed them to dedicate that ‘quarantined’ time to their research. On the flip side, some participants felt that research was not valued by their organisation, which limited their ability to dedicate the time required to progress their research idea:Participant 2, 16 months post‐trainingOne of our clinicians' hours got reduced which meant then she had more time available to ‐ in her own time to work the other project, which is not ideal … the barriers are definitely getting approval to do that in your work time and for the organisation to see it as a priority.Other organisation‐related factors included staff turnover which led to the ‘stop‐starting’ of research projects:Participant 8, 16 months post‐trainingall of our research work has been put on hold. Following the end of the training, it was [put] on hold because we had shifting priorities due to staff members leaving, so we were redistributing all of the projects.Staffing shortages are a recognised barrier to progressing new health service initiatives; however, this is arguably more critical in rural and regional health services where it is more difficult to recruit and retain staff.COVID‐19 negatively impacted the progress of each of the 16‐month interview participants' research projects, due to staff being redeployed to manage outbreaks and related changes to clinical programs and practice. Nonetheless, this next participant describes a creative approach to providing time to be allocated to facilitate research progress:3.2.3Participant 3, three months post‐trainingit [training] was a really good chance to network and liaise with other clinicians across different health settings, who are working on similar projects, or even working on completely different projects. Just to know that those other research projects are happening and are out there … One of the people that we were meeting with on the day actually has ended up being involved in our study.The above quote illustrates that training is about more than research knowledge, skills and outputs, and it is also about establishing and fostering research networks, which are pivotal for all novice researchers, arguably even more so for researchers working in organisations that have less research infrastructure or an immature research culture.The training was designed as an RCB initiative targeted at the individual level; however, the interview data indicated that individuals were contributing their organisations' research capacity. This was evident in several ways. The social learning environment provided opportunities for participants to connect with peers from within their organisation and across the region, and some of those wider connections were then sustained post‐training:Participant 6, 16 months post‐trainingMy manager is really excited to keep doing research now that we've done it once and he said if you come back next year then we would be really keen to write that into your project plan and KPIs [key performance indicators], so there's definitely potential there.Research training focused on the individual level makes research ‘accessible’ for novice AHP researcher and has the potential to light ‘a spark’ in some:Participant 2, 16 months post‐trainingmaking that research scene accessible just for your average clinician. I know particularly for that one member in our team, she's seriously considering whether she goes and does further research and does her PhD. So, for her it really lit a spark.This illustrates that providing opportunities for individuals to access and participate in research activity can be the first step in longer‐term and higher‐level engagement with research. A less frequent, yet important outcome for participants was the identification of health service research employment opportunities. For this next participant, having ‘that mindset about research being an accessible thing, I have actually just applied for a research assistant position at my workplace’ . This once again speaks to the development of organisational research infrastructure including a positive research capacity and career structure for AHP researchers.In other cases, managers were able to fully appreciate the benefits of the training on individual team members that participated, and took action to embed research in their core business:Participant 5, 16 months post‐trainingI have done two in‐services to our OT department since the training scheme. We've just recently applied to be part of our annual research symposium that's happening this year.The quote above illustrates how individual RCB directly influences the organisational capacity and, indeed, the development of team and organisational research resources and infrastructure.Several participants reported sharing their learnings from the research training with colleagues within their teams and organisations. A combination of informal or ad hoc opportunities to share their learnings, and more structured inservices and presentations at team meetings were described. For example, this next participant has taken multiple opportunities to share their learnings with their team and wider network:4Turning Ideas into Proposals research training program aimed to facilitate novice researcher participants' completion of a research protocol, and in the process, improve their EBP knowledge, attitudes and practices. Although these aims were not fully achieved, due to multiple factors including COVID‐19‐related disruptions, the interview data illustrated that the training program led to more important and yet less quantifiable impacts. It is recognised that ‘stand‐alone’ research training is limited in its ability to produce tangible research outputs, particularly where organisational research capacity and access to research resources, is a local challenge.The The individual‐level outcomes of the training are demonstrated via the EBP‐KAP, which indicated that training participants had positive attitudes towards EBP at both baseline and 3 months post‐training. These positive attitudes are not unexpected, given that training participants prepared and submitted an expression of interest for the training program, secured manager approval and took 2 days out of their regular work, with many travelling considerable distance to participate. The significant differences between AHPs' knowledge and attitudes, compared with their evidence‐based practices , were similar to those reported in a study evaluating EBP in nursing and AHP students.Participants' knowledge of EBP, incorporation of EBP into their professional practice and retrieval of evidence were also unchanged at the three‐month post‐training mark. Other authors have noted imperceptible changes to participants' EBP knowledge and practices post‐RCB intervention and attributed this to the short duration of the intervention.The interviews enabled exploration of individuals' application of their EBP skills in their research endeavours and clinical practice. It was found that the training‐related factors that most cogently influenced AHPs' confidence to embark on research activity and utilise research to guide clinical practice (i.e. engage in EBP) were the practical nature of the training, and the support of an experienced and accessible research mentor. Indeed, the evaluation highlighted that some mentorships continued beyond formal training period, despite this not being expected of the mentors or the program. The value that experienced and accessible research mentors bring to the novice researcher journey is well‐established and now considered core component of individual‐level RCB strategies.Similarly, the importance of the social, collaborative nature of the workshop activities, the peer connection and networks facilitated by the training cannot be underestimated. This social connection aspect is particularly important for novice researchers and those in rural and regional settings.Nonetheless, organisational factors seemed to supersede the practical nature of the training with respect to influencing the outcomes and impacts of the training. This was evident in both the positive and negative sense. Through the expression of interest process, manager support for the participants' research ideas was evident. When managerial and organisational support was combined with key research resources, for example access to embedded researchers and other research infrastructure, participants described their ability to progress their research to varying extents. The opposite was apparent in the absence of organisational support and infrastructure. There is a need for greater engagement with managers and organisations in the early stages of the training program and throughout, to support, progress and sustain AHP‐led research activity. Further, there might be merit in supporting potential AHP research training participants to identify organisational barriers to conducting research and to address these pre‐emptively, for example by using the Capability, Opportunity, Motivation—Behaviour Framework.interrelatedness of RCB strategies and levels of influence, and call on those concerned with RCB appreciate the unquantifiable benefits of providing a ‘catalyst for releasing potential research energies from within individuals and organisations’ .Data S1Click here for additional data file.


To identify trusted sources of contraception information among pregnancy‐capable individuals with opioid use disorder (OUD).We conducted interviews between October 2018 and January 2019 at Boston Medical Center, a university‐based tertiary care center.Data were drawn from semi‐structured qualitative interviews with a convenience sample of 20 pregnant or recently pregnant individuals with OUD. We used the Ottawa Decision Support Framework, a health decision making conceptual model, to structure our interviews. We analyzed the data using inductive and deductive coding.Not applicable.Pregnancy‐capable individuals who use opioids value friends who are not actively using opioids, including peers in recovery homes, as trusted sources of contraception information. They also value internet resources, including websites recommended by clinicians and social media posts, and established clinical providers as reliable sources of contraception information in ways that emulate individuals with other chronic medical conditions. These sources of contraception information may explain some trends in contraceptive use among individuals with OUD, inform nonstigmatizing contraceptive counseling, and serve as a foundation for improved decision support. People with chronic conditions are at increased risk of having unintended pregnanciesExisting research suggests that persons with opioid use disorder have unique patterns of contraception useKnowledge on contraception information sources valued by persons with opioid use disorder is limitedPersons with opioid use disorder value peers who were not actively using opioids as trusted sources of contraception informationPersons with opioid use disorder value contraceptive counseling in which clinicians center their lived contraception experiences and personal goals1People with chronic conditions are at increased risk of having unintended pregnancies. Yet these individuals often require multidisciplinary and proactive pregnancy planning for optimal maternal and fetal health.Contraceptive use patterns differ between people with chronic conditions, including diabetes, cardiovascular disease, asthma, HIV, and OUD and those without.Patients make contraceptive decisions informed by the recommendation of medical professionals, but also with the input of partners, friends, family, and social media networks.2As part of our broader exploration of contraceptive decision making among pregnancy capable individuals with OUD, we conducted semi‐structured qualitative interviews between October 2018 and January 2019 at Boston Medical Center, a university‐based care center.We recruited our sample from Project RESPECT , a specialized outpatient obstetric clinic for patients with substance use disorder (SUD), the SOFAR (Supporting Our Families through Addiction and Recovery) program, an outpatient clinic for parents in SUD recovery and their children, and an inpatient maternal fetal medicine service, where patients are admitted for inpatient medication for OUD titration. Participants were recruited via provider referral, self‐referral in response to flyers, and referral by prior participants. Eligibility criteria were (1) currently pregnant or pregnant within one year regardless of outcome, (2) self‐identified OUD, (3) 18 years old or older, and able to consent, and (4) English speaking. We continued recruitment until we reached thematic saturation. We provided a $50 gift card for participation.We obtained written informed consent prior to each interview. Interviewers (LS and YWL) both identified as female and were an OB‐GYN resident and OB‐GYN medical student with prior qualitative interviewing experience. They were not directly involved in the participants' medical care. They conducted in person interviews in the clinical environment. Interviews were audio recorded and professionally transcribed. Interviewers took field notes after the conclusion of each interview.We structured our interview guide around the Ottawa Decision Support Framework, an internationally recognized conceptual model describing health decision making.LS and EWP independently analyzed five transcripts using inductive and deductive coding to develop a codebook. Each subsequent transcript was coded by LS and either EWP or YWL. They met regularly to ensure coding consistency, resolve discrepancies through consensus, and iteratively revise the codebook. We used NVivo 11 software to manage our data and facilitate coding. The Boston University Institutional Review Board approved this study.3We screened 131 individuals and approached 58 for study participation. Twenty‐two individuals ultimately completed interviews. Patients most often declined participation due to time constraints or withdrawal symptoms. Two interviews were not included in the final analysis because the identified their primary substance use to be cocaine or alcohol rather than opioids. . They also described that friends who regularly engaged with social media were less likely to be actively using opioids: “A lot of my Facebook friends will post about their experiences with [contraception]… not everyone is on Facebook. Not friends [who use opioids]—they're not gonna post on Facebook.” (Participant 19) Given these attitudes, participants viewed contraceptive experiences shared on social media as a reliable source of contraception information.Participants commonly cited friends as sources of contraception information. They noted that friends who had never used opioids, as well as those who were stable in their recovery, modeled admirable preventative health care behaviors. This resulted in more value being placed on the health information they provided: 3.2“I remember at the program I was at before this one – a nurse came in and talked to us about all the different [contraception] options.” (Participant 16) More commonly, participants described peers in their recovery home sharing both negative and positive contraception experiences. They also noted that some recovery homes had contraception trends based on the shared experiences: “I mean, everyone in the house had Nexplanon. So I knew that was kind of like a trending thing… A girl came home with a bandage on her arm and I was like, what's that from? And she's like oh, it's uh, the implant. I was like, what's the implant? And she told me about it and then I was like wow, that sounds great.” (Participant 21)Multiple participants cited recovery home peers as trusted sources of contraception information. Recovery homes are group living arrangements that provide a structured environment for individuals in the immediate postacute phase of substance use as a transition into independent living.3.3“And also [my daughter's] pediatrician will ask me [about birth control] because she knows us… I don't mind talking to her about it at all.” (Participant 16). Yet, even among clinicians they identified as trusted sources of contraception information, they questioned their ability to counsel on contraceptive side‐effects and interactions in the context of their chronic condition. “Doctors… just kind of know how it works… but like they don't really get the side effects that the patients like us get.” (Participant 19). The side effects, most commonly referred to, included weight gain with contraception use, which for some can trigger a relapse, personal hygiene related to bleeding patterns in the setting of housing instability, and interactions with mood stabilizing medications.Participants identified their obstetrician/ gynecologists, addiction medicine specialists, and their child's pediatrician with whom they often had long‐standing relationships as reliable sources of contraception information, regardless of their training in contraception counseling: 3.4I've tried pretty much all of the birth control that there is out there. I can tell you what my body has done for each birth control, so, that's kind of where I've gotten most of my information.” (Participant 18). They valued their ability to identify evidence‐based information sources and recognize misinformation. They also appreciated when clinicians recommended reliable contraception information sources: “I don't look at posts where people aren't of some kind of [medical] background… I like to go on the websites my doctors tell me” (Participant 4). When participants felt clinicians did not value their research and experience, they described less trust in the medical information provided: “If we were to talk about breastfeeding with my [Hepatitis] C, I would shut a doctor down if they told me it's not a good idea and not trust them on anything else because I've done a ton of online research about it.” (Participant 2).Participants strongly desired that their clinicians understood the importance of both their personal contraceptive experiences and their own research. Participants drew from their personal experience with contraception in the context of their chronic disease: “4Understanding the contraception information sources valued by persons with OUD provides a foundation for improved patient‐centered and nonstigmatizing counseling, as well as multiple points for evidence‐based interventions.Clinicians use a variety of communication strategies when engaging in contraception counseling. Directive counseling can lead to experiences with clinician‐based reproductive coercion to use highly effective contraceptive methods, which contributes to health care system distrust.People with chronic conditions often seek condition‐specific contraceptive counseling. Thus, after acknowledging the expertise of the patient, the role of the clinician is to contribute information on each method contextualized by data specific to OUD. While participants feel clinicians who provide contraception counseling are generally familiar with the mechanism of action and common side‐effects of each method, they often feel that they are unable to ground their discussion in the unique needs and preferences of persons with OUD.Our data highlight that regardless of specialty, the development of a trusting contraception counseling relationship is predicated on the clinician providing contraceptive information in the context of this chronic disease, as well as demonstrating the knowledge of pertinent reproductive health topics specific to OUD. To our knowledge, there is only one contraception information resource developed by professional societies specific to individuals with OUD.One sequela of this lack of contraception information specific to individuals with OUD is that information sources outside the health care system are highly valued by this population. Individuals with chronic conditions are commonly excluded from contraception clinical trials, yet they are often actively engaged in disease‐specific internet threads and forums.Our study also highlights the recovery home environment as a valued source of contraception information. Unlike other chronic conditions, individuals with OUD can exchange experiences and information on medical topics such as fertility, infectious disease, and medications by virtue of living together during the immediate postacute phase of substance use. Efforts to promote the dissemination of accurate information in the recovery home environment present a unique opportunity for intervention. Colocation of reproductive health services with OUD treatment has been successfully implemented in many outpatient treatment settings to meet the contraceptive information needs for individuals with OUD.Study strengths include being the first qualitative study to describe contraceptive information sources valued by persons with OUD, which is paramount to providing patient‐centered preventative reproductive health care. Additionally, qualitative interviews enabled us to obtain rich and nuanced perspectives from patients with OUD on their contraceptive experiences and preferred information sources. Our study does have limitations. Interviews were conducted in Massachusetts, where all Food and Drug Administration‐approved contraceptive methods are covered by Medicaid. Thus, our findings may not be generalizable to pregnancy‐capable individuals with OUD who have more limited contraceptive access. Additionally, our convenience sample may not reflect the perspectives of those who do not speak English or are not engaged in care. Our predominantly White non‐Hispanic patient population is reflective of ethnic disparities in the utilization of medication for opioid use disorder among pregnant individuals.In conclusion, an understanding of the contraception information sources valued by individuals with OUD may have significant implications for building therapeutic relationships and for the dissemination of accessible, evidence‐based, and trusted contraception information among individuals with OUD.This work was supported by a 2018 Society of Family Planning Emerging Scholars in Family Planning Grant [SFPRF12‐ES19].