Telemetry without collars: performance of fur- and ear-mounted satellite tags for evaluating the movement and behaviour of polar bears.

The study of animal movement provides insights into underlying ecological processes and informs analyses of behaviour and resource use, which have implications for species management and conservation. The tools used to study animal movement have evolved over the past decades, allowing for data collection from a variety of species, including those living in remote environments. Satellite-linked radio and GPS collars have been used to study polar bear (Ursus maritimus) ecology and movements throughout the circumpolar Arctic for over 50 years. However, due to morphology and growth constraints, only adult female polar bears can be reliably collared. Collars have proven to be safe, but there has been opposition to their use, resulting in a deficiency in data across much of the species' range. To bolster knowledge of movement characteristics and behaviours for polar bears other than adult females, while also providing an alternative to collars, we tested the use of fur- and ear-mounted telemetry tags that can be affixed to polar bears of any sex and age. We tested three fur tag designs (SeaTrkr, tribrush and pentagon tags), which we affixed to 15 adult and 1 subadult male polar bears along the coast of Hudson Bay during August-September 2021-2022. Fur tags were compared with ear tags deployed on 42 subadult and adult male polar bears captured on the coast or the sea ice between 2016 and 2022. We used data from the tags to quantify the amount of time subadult and adult males spent resting versus traveling while on land. Our results show the three fur tag designs remained functional for shorter mean durations (SeaTrkr = 58 days; tribrush = 47 days; pentagon = 22 days) than ear tags (121 days), but positional error estimates were comparable among the Argos-equipped tags. The GPS/Iridium-equipped SeaTrkr fur tags provided higher resolution and more frequent location data. Combined, the tags provided sufficient data to model different behavioural states. Furthermore, as hypothesized, subadult and adult male polar bears spent the majority of their time resting while on land, increasing time spent traveling as temperatures cooled. Fur tags show promise as a short-term means of collecting movement data from free-ranging polar bears. Supplementary Information: The online version contains supplementary material available at 10.1186/s40317-024-00373-2.

Patient and provider medication preferences affect treatment outcomes among adolescents and young adults with opioid use disorder.

BACKGROUND: The opioid epidemic in the United States has not spared youth or young adults, as evidenced by a six-fold increase in opioid use disorder (OUD) diagnoses in the last two decades. Given this dramatic rise, a call for greater uptake and accessibility of medications for opioid use disorder (MOUDs) among youth and young adults has ensued, resulting in an increasing number of MOUD treatment pathways for this vulnerable population. METHODS: This secondary data analysis seeks to characterize patient and provider preferences for MOUD treatment pathways, and test for associations between baseline MOUD treatment preferences and opioid use and treatment adherence outcomes. Participants included 288 youth and young adults (age 15-21 years), recruited from a residential treatment program in Maryland. The study assessed patient preferences at baseline (n = 253) and provider preferences at patient treatment discharge (n = 224). Mixed-effects negative binomial regression models were conducted for opioid use outcomes, and logistic regressions were conducted for treatment adherence outcomes. RESULTS: Results indicate that congruence of treatment with patients' (Incidence Rate Ratio [IRR] = 0.65) and providers' (IRR = 0.66) preferences was significantly associated with reduced self-reported days of opioid use in the past 90 days, but only for patients receiving extended-release naltrexone (XR-NTX). Results also indicated that patients were less likely to switch medication treatment pathways (e.g., from XR-NTX to buprenorphine, or vice versa) during follow-up if they received their preferred treatment at baseline, a finding which held true for both XR-NTX (Odds Ratio [OR] = 0.32) and buprenorphine (OR = 0.22). CONCLUSIONS: Receipt of MOUD congruent with patient and provider preferences was associated with reduced opioid use and greater treatment adherence in this sample of youth and young adults with OUD.

Massively parallel single-cell sequencing of diverse microbial populations.

Single-cell genetic heterogeneity is ubiquitous in microbial populations and an important aspect of microbial biology; however, we lack a broadly applicable and accessible method to study this heterogeneity in microbial populations. Here, we show a simple, robust and generalizable method for high-throughput single-cell sequencing of target genetic loci in diverse microbes using simple droplet microfluidics devices (droplet targeted amplicon sequencing; DoTA-seq). DoTA-seq serves as a platform to perform diverse assays for single-cell genetic analysis of microbial populations. Using DoTA-seq, we demonstrate the ability to simultaneously track the prevalence and taxonomic associations of >10 antibiotic-resistance genes and plasmids within human and mouse gut microbial communities. This workflow is a powerful and accessible platform for high-throughput single-cell sequencing of diverse microbial populations.

Single-cell analysis of multiple invertible promoters reveals differential inversion rates as a strong determinant of bacterial population heterogeneity.

Population heterogeneity can promote bacterial fitness in response to unpredictable environmental conditions. A major mechanism of phenotypic variability in the human gut symbiont Bacteroides spp. involves the inversion of promoters that drive the expression of capsular polysaccharides, which determine the architecture of the cell surface. High-throughput single-cell sequencing reveals substantial population heterogeneity generated through combinatorial promoter inversion regulated by a broadly conserved serine recombinase. Exploiting control over population diversification, we show that populations with different initial compositions converge to a similar composition over time. Combining our data with stochastic computational modeling, we demonstrate that the differential rates of promoter inversion are a major mechanism shaping population dynamics. More broadly, our approach could be used to interrogate single-cell combinatorial phase variable states of diverse microbes including bacterial pathogens.

Spatio-temporal patterning of extensile active stresses in microtubule-based active fluids.

Microtubule-based active fluids exhibit turbulent-like autonomous flows, which are driven by the molecular motor powered motion of filamentous constituents. Controlling active stresses in space and time is an essential prerequisite for controlling the intrinsically chaotic dynamics of extensile active fluids. We design single-headed kinesin molecular motors that exhibit optically enhanced clustering and thus enable precise and repeatable spatial and temporal control of extensile active stresses. Such motors enable rapid, reversible switching between flowing and quiescent states. In turn, spatio-temporal patterning of the active stress controls the evolution of the ubiquitous bend instability of extensile active fluids and determines its critical length dependence. Combining optically controlled clusters with conventional kinesin motors enables one-time switching from contractile to extensile active stresses. These results open a path towards real-time control of the autonomous flows generated by active fluids.

A systematic review of typologies on aged care system components to facilitate complex comparisons.

Objectives: Typologies are frequently utilised in analyses of the quality, funding, and efficiency of aged care systems. This review aims to provide a comprehensive resource identifying and critiquing existing aged care typologies. Methods: Systematic search of MEDLINE, Econlit, Google Scholar, greylit.org and Open Grey databases from inception to July 2020, including typologies of national, regional or provider aged care systems. Article screening, data extraction, and quality appraisal were conducted in duplicate. Results: 14 aged care typologies were identified; five applied to residential care, two to home care and seven to mixed settings; eight examined national systems and seven regional or provider systems. Five typologies classifying national financing or home care services, provider financing of staff and services and quality of residential care were considered high quality. The schematic provided summarises the focus area and aids in typology selection. Discussion: The aged care typologies identified cover a wide range of areas and contexts of aged care provision. This schematic, summary and critique will aid researchers, providers, and aged care policy makers to examine their own setting, compare it to other approaches to aged care provision and assist in identifying alternatives and important considerations, when undertaking aged care reform.

Programming bacteria for multiplexed DNA detection.

DNA is a universal and programmable signal of living organisms. Here we develop cell-based DNA sensors by engineering the naturally competent bacterium Bacillus subtilis (B. subtilis) to detect specific DNA sequences in the environment. The DNA sensor strains can identify diverse bacterial species including major human pathogens with high specificity. Multiplexed detection of genomic DNA from different species in complex samples can be achieved by coupling the sensing mechanism to orthogonal fluorescent reporters. We also demonstrate that the DNA sensors can detect the presence of species in the complex samples without requiring DNA extraction. The modularity of the living cell-based DNA-sensing mechanism and simple detection procedure could enable programmable DNA sensing for a wide range of applications.

The Microbiome-TIME Axis: A Host of Possibilities.

Cancer continues to be a significant source of mortality and morbidity worldwide despite progress in cancer prevention, early detection, and treatment. Fortunately, immunotherapy has been a breakthrough in the treatment of many cancers. However, the response to immunotherapy treatment and the experience of associated side effects varies significantly between patients. Recently, attention has been given to understanding the role of the tumor immune microenvironment (TIME) in the development, progression, and treatment response of cancer. A new understanding of the role of the microbiota in the modulation of the TIME has further complicated the story but also unlocked a new area of adjuvant therapeutic research. The complex balance of tumor-permissive and tumor-suppressive immune environments requires further elucidation in order to be harnessed as a therapeutic target. Because both the TIME and the microbiome show importance in these areas, we propose here the concept of the "microbiome-TIME axis" to review the current field of research and future directions.

Motor processivity and speed determine structure and dynamics of microtubule-motor assemblies.

Active matter systems can generate highly ordered structures, avoiding equilibrium through the consumption of energy by individual constituents. How the microscopic parameters that characterize the active agents are translated to the observed mesoscopic properties of the assembly has remained an open question. These active systems are prevalent in living matter; for example, in cells, the cytoskeleton is organized into structures such as the mitotic spindle through the coordinated activity of many motor proteins walking along microtubules. Here, we investigate how the microscopic motor-microtubule interactions affect the coherent structures formed in a reconstituted motor-microtubule system. This question is of deeper evolutionary significance as we suspect motor and microtubule type contribute to the shape and size of resulting structures. We explore key parameters experimentally and theoretically, using a variety of motors with different speeds, processivities, and directionalities. We demonstrate that aster size depends on the motor used to create the aster, and develop a model for the distribution of motors and microtubules in steady-state asters that depends on parameters related to motor speed and processivity. Further, we show that network contraction rates scale linearly with the single-motor speed in quasi-one-dimensional contraction experiments. In all, this theoretical and experimental work helps elucidate how microscopic motor properties are translated to the much larger scale of collective motor-microtubule assemblies.

Ray Optics for Gliders.

Control of self-propelled particles is central to the development of many microrobotic technologies, from dynamically reconfigurable materials to advanced lab-on-a-chip systems. However, there are few physical principles by which particle trajectories can be specified and can be used to generate a wide range of behaviors. Within the field of ray optics, a single principle for controlling the trajectory of light─Snell's law─yields an intuitive framework for engineering a broad range of devices, from microscopes to cameras and telescopes. Here we show that the motion of self-propelled particles gliding across a resistance discontinuity is governed by a variant of Snell's law, and develop a corresponding ray optics for gliders. Just as the ratio of refractive indexes sets the path of a light ray, the ratio of resistance coefficients is shown to determine the trajectories of gliders. The magnitude of refraction depends on the glider's shape, in particular its aspect ratio, which serves as an analogue to the wavelength of light. This enables the demixing of a polymorphic, many-shaped, beam of gliders into distinct monomorphic, single-shaped, beams through a friction prism. In turn, beams of monomorphic gliders can be focused by spherical and gradient friction lenses. Alternatively, the critical angle for total internal reflection can be used to create shape-selective glider traps. Overall our work suggests that furthering the analogy between light and microscopic gliders may be used for sorting, concentrating, and analyzing self-propelled particles.

Examining the Effectiveness of the FaCES Adolescent SBIRT Intervention.

PURPOSE: The Facilitating Change for Excellence in SBIRT (FaCES) is a service package for adolescent primary care that was developed based on best practices and evidence, but was empirically untested. The aim of this study is to compare the FaCES intervention to treatment as usual (TAU) for rural adolescent primary care patients. METHODS: In this modified cluster-randomized stepped wedge design, providers who completed at least 20 adolescent TAU visits received training in the FaCES package in random order. Adolescent patients (N = 1,226) waiting for appointments were continuously recruited into the study and completed a baseline assessment before their scheduled appointment and an on-line 3-month follow-up. Participants received either FaCES or TAU, depending on whether their provider had been trained in FaCES. Due to COVID-19 disruptions, only 14 of the 29 providers were trained before study recruitment activities ceased. RESULTS: More than 80% of the sample indicated no prior use of tobacco, alcohol, or marijuana at study entry. The Arm × Time interaction failed to reach significance for the substance use outcomes considered. In the FaCES condition, the group with no prior use had an increased probability of substance use at 3-month follow-up, while the group reporting prior use had a decreased probability of use at follow-up. Participants who reported no use at baseline had an increased probability of use at follow-up, whether they received the FaCES intervention or TAU. DISCUSSION: This study was unable to demonstrate the effectiveness of FaCES. Findings suggest some natural movement in substance use risk over time.

Patients with substance use disorders receiving continued care in skilled nursing facilities following hospitalization.

Background: As hospitals in the US face pressures to reduce lengths of stay, healthcare systems are increasingly utilizing skilled nursing facilities (SNFs) to continue treating patients stable enough to leave the hospital, but not to return home. Substance use disorder (SUD) can complicate care of patients transferred to SNFs. The objective of this paper is to understand SNF experiences for this population of patients with comorbid SUD transferred to SNFs and examine care experiences in these facilities. Methods: This secondary mixed-methods analysis focuses on SNF experiences from a clinical trial of patient navigation services for medically-hospitalized adults with comorbid opioid, cocaine, and/or alcohol use disorder. This study compared baseline assessments and medical record review for participants (N = 400) with vs. without SNF transfer, and analyzed semi-structured qualitative interviews with a subsample of 15 participants purposively selected based on their transfer to a SNF. Results: Over 1 in 4 participants had a planned discharged to a SNF (26.8% sub-acute, 3.3% acute). Compared to participants with other types of discharge, participants discharged to a SNF had longer initial hospitalizations (4.9 vs. 11.8 days, p < 0.001), and were more likely to be White (38.6 vs. 50.8%; p = 0.02), female (38.9 vs. 52.5%; p = 0.01), have opioid use disorder (75.7 vs. 85.0%, p = 0.03), and be hospitalized for infection (43.6 vs. 58.3%; p = 0.007), and less likely to have worked prior to hospitalization (24.3 vs. 12.5%; p = 0.006). Qualitative narratives identified several themes from the SNF experience, including opioid analgesic dosing issues, challenges to the use of opioid agonist treatment of OUD, illicit opioid dealing/use, and limited access to addiction recovery support services during and following the SNF stay. Conclusions: SNFs are a common disposition for patients in need of subacute services following hospitalization but may be ill-equipped to properly manage patients in need of new or continuing SUD treatment.

The neuropsychological profile of delirium vulnerability: A systematic review and meta-analysis.

Delirium is a common neurocognitive disorder in hospitalised older adults with substantial negative consequences. Impaired global cognition is a well-established delirium risk factor. However, poor performance on attention tests and higher intra-subject variability may be more sensitive delirium risk factors, given the disorder is characterised by a fluctuating course and attentional deficits. We systematically searched databases (Embase, PsycINFO, MEDLINE) and 44 studies satisfied inclusion criteria. Random-effects meta-analysis models showed poor performance in all cognitive domains except perception was significantly associated with incident delirium. Largest effects were for orientation (g=-1.20) and construction and motor performance (g=-0.60). These effects were no longer significant in the subgroup without pre-existing cognitive impairment, where executive functions and verbal functions and language skills were associated with incident delirium. A small, non-significant association between intra-subject variability and incident delirium was found (g=0.42). Cognitive domain specific tests may be quicker and more sensitive predictors of incident delirium. This pattern of neuropsychological findings supports the proposition that vulnerability for delirium manifests as a dysfunction of whole-brain information integration.

Organizational Acceptability of Implementing SBIRT for Adolescents in Primary Care.

INTRODUCTION: Adolescent illicit drug, tobacco, and alcohol use can result in sudden and long-term negative health consequences. Primary care environments present the optimal opportunity for screening and brief interventions that target prevention and curtailing use. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a service delivery method that could potentially be well-integrated into primary care settings and used to serve a high volume of adolescents. Methods: This qualitative analysis of clinic staff interviews (N = 20), collected during a large cluster-randomized trial to implement two models of adolescent SBIRT, examined barriers and facilitating factors to overall acceptability of SBIRT. This study was conducted in a large, urban Federally Qualified Health Center (FQHC) at 7 sites throughout Baltimore City, Maryland, USA. Participants from each clinic included a range of various roles and responsibilities including: medical assistants (n = 3), nurses (n = 3), primary care providers (n = 4), behavioral health counselors (n = 4), and administrators (n = 6). Results: Results indicate both barriers and facilitating factors for acceptability of SBIRT in terms of (1) universal screening, (2) provider time demands, (3) behavioral health collaboration, and (4) behavioral health caseloads. Discussion: Universal screening was acceptable to participants across organizational roles, but brief interventions and referrals to treatment were found substantially less acceptable.

The effects of anticholinergic medications on cognition in children: a systematic review and meta-analysis.

Cognitive side effects of anticholinergic medications in older adults are well documented. Whether these poor cognitive outcomes are observed in children has not been systematically investigated. We aimed to conduct a systematic review and meta-analysis on the associations between anticholinergic medication use and cognitive performance in children. Systematic review was conducted using Medline, PsychInfo, and Embase, identifying studies testing cognitive performance relative to the presence versus absence of anticholinergic medication(s) in children. We assessed effects overall, as well as relative to drug class, potency (low and high), cognitive domain, and duration of administration. The systematic search identified 46 articles suitable for meta-analysis. For the most part, random effects meta-analyses did not identify statistically significant associations between anticholinergic exposure and cognitive performance in children; the one exception was a small effect of anticholinergic anti-depressants being associated with better cognitive function (Hedges' g = 0.24, 95% CI 0.06-0.42, p = 0.01). Anticholinergic medications do not appear to be associated with poor cognitive outcomes in children, as they do in older adults. The discrepancy in findings with older adults may be due to shorter durations of exposure in children, differences in study design (predominantly experimental studies in children rather than predominantly epidemiological in older adults), biological ageing (e.g. blood brain barrier integrity), along with less residual confounding due to minimal polypharmacy and comorbidity in children.

Investigating how electroencephalogram measures associate with delirium: A systematic review.

Delirium is a common neurocognitive disorder in hospital settings, characterised by fluctuating impairments in attention and arousal following an acute precipitant. Electroencephalography (EEG) is a useful method to understand delirium pathophysiology. We performed a systematic review to investigate associations between delirium and EEG measures recorded prior, during, and after delirium. A total of 1,655 articles were identified using PsycINFO, Embase and MEDLINE, 31 of which satisfied inclusion criteria. Methodological quality assessment was undertaken, resulting in a mean quality score of 4 out of a maximum of 5. Qualitative synthesis revealed EEG slowing and reduced functional connectivity discriminated between those with and without delirium (i.e. EEG during delirium); the opposite pattern was apparent in children, with cortical hyperexcitability. EEG appears to have utility in differentiating those with and without delirium, but delirium vulnerability and the long-term effects on brain function require further investigation. Findings provide empirical support for the theory that delirium is a disorder of reduced functional brain integration.

Risk Factors for Delirium and Cognitive Decline Following Coronary Artery Bypass Grafting Surgery: A Systematic Review and Meta-Analysis.

Background Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer-reviewed, English publications reporting post-CABG delirium or cognitive decline data, for at least one risk factor. Random-effects meta-analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety-seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1-6 months) post-CABG cognitive decline. Conclusions This meta-analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable. Registration URL: https://www.crd.york.ac.uk/prosp​ero/; Unique identifier: CRD42020149276.

The HIF target ATG9A is essential for epithelial barrier function and tight junction biogenesis.

Intestinal epithelial cells (IECs) exist in a metabolic state of low oxygen tension termed "physiologic hypoxia." An important factor in maintaining intestinal homeostasis is the transcription factor hypoxia-inducible factor (HIF), which is stabilized under hypoxic conditions and mediates IEC homeostatic responses to low oxygen tension. To identify HIF transcriptional targets in IEC, chromatin immunoprecipitation (ChIP) was performed in Caco-2 IECs using HIF-1α- or HIF-2α-specific antibodies. ChIP-enriched DNA was hybridized to a custom promoter microarray (termed ChIP-chip). This unbiased approach identified autophagy as a major HIF-1-targeted pathway in IEC. Binding of HIF-1 to the ATG9A promoter, the only transmembrane component within the autophagy pathway, was particularly enriched by exposure of IEC to hypoxia. Validation of this ChIP-chip revealed prominent induction of ATG9A, and luciferase promoter assays identified a functional hypoxia response element upstream of the TSS. Hypoxia-mediated induction of ATG9A was lost in cells lacking HIF-1. Strikingly, we found that lentiviral-mediated knockdown (KD) of ATG9A in IECs prevents epithelial barrier formation by >95% and results in significant mislocalization of multiple tight junction (TJ) proteins. Extensions of these findings showed that ATG9A KD cells have intrinsic abnormalities in the actin cytoskeleton, including mislocalization of the TJ binding protein vasodilator-stimulated phosphoprotein. These results implicate ATG9A as essential for multiple steps of epithelial TJ biogenesis and actin cytoskeletal regulation. Our findings have novel applicability for disorders that involve a compromised epithelial barrier and suggest that targeting ATG9A may be a rational strategy for future therapeutic intervention.

Meta-Analysis of Prevalence and Risk Factors for Cognitive Decline and Improvement After Transcatheter Aortic Valve Implantation.

Changes to cognition, both decline and improvement, are commonly reported after transcatheter aortic valve implantation (TAVI). However, previous systematic reviews and meta-analyses have missed these subgroups by assessing whole-group-averages for cognitive outcomes. We sought to pool estimates to identify the prevalence of cognitive decline and improvement after TAVI, as well as associated factors for these outcomes. A systematic review identified 15 articles appropriate for meta-analysis. When robust cognitive change definitions were employed, the pooled prevalence of incident cognitive impairment up to 1-, 1 to 6-, and ≥6-months post-TAVI was 7%, 14%, and 12%, respectively. For cognitive improvement, the prevalence from 1 to 6 months and ≥6 months after TAVI was estimated to be 19% and 11%, respectively. Two factors were associated with these cognitive outcomes: (1) using a cerebral embolic protection device was associated with decreased prevalence of cognitive decline up to 1-week post-TAVI; (2) baseline cognitive impairment had a large association with post-TAVI cognitive improvement. In conclusion, cognitive decline and cognitive improvement are experienced by approximately 7% to 19% of patients after TAVI, respectively. Those with the lowest cognitive performance pre-TAVI appear to have the most to gain in terms of cognitive improvement post-TAVI. Identifying further predictive factors for cognitive decline and improvement post-TAVI will facilitate a personalized-medicine approach for cognitive care and prognosis.

Investigating the dynamics of microbial consortia in spatially structured environments.

The spatial organization of microbial communities arises from a complex interplay of biotic and abiotic interactions, and is a major determinant of ecosystem functions. Here we design a microfluidic platform to investigate how the spatial arrangement of microbes impacts gene expression and growth. We elucidate key biochemical parameters that dictate the mapping between spatial positioning and gene expression patterns. We show that distance can establish a low-pass filter to periodic inputs and can enhance the fidelity of information processing. Positive and negative feedback can play disparate roles in the synchronization and robustness of a genetic oscillator distributed between two strains to spatial separation. Quantification of growth and metabolite release in an amino-acid auxotroph community demonstrates that the interaction network and stability of the community are highly sensitive to temporal perturbations and spatial arrangements. In sum, our microfluidic platform can quantify spatiotemporal parameters influencing diffusion-mediated interactions in microbial consortia.