Patient perspectives on the unwanted effects of multidisciplinary pain management programmes: A qualitative study.

OBJECTIVE: This study aimed to understand the impact of pain management programmes, focusing on the unwanted effects and their influence on patients' long-term use of self-management strategies. DESIGN: Qualitative study. SETTING: Specialist musculoskeletal hospital in North London, England. PARTICIPANTS: Patients with chronic musculoskeletal pain that have completed a pain management programme. INTERVENTION: Multidisciplinary pain management programmes. MAIN MEASURES: Data were collected regarding patients' experiences and unwanted effects from the pain management programme using semi-structured interviews. Data were analysed using thematic analysis. RESULTS: Fourteen participant interviews were included in the analysis (median age 54 years, 12 females). Four themes were generated from the data: Benefits and burdens, Pain management programme and real life, Social support and Healthcare interventions. Unwanted effects included heightened anxiety related to negative interactions with peers, being in a new environment, worries about ability to cope with the programme, social anxiety from being in a group, the strain on families due to participants being away from home and a sense of abandonment at end of the programme. Burdens associated with implementing pain management strategies were identified, including the emotional burden of imposing their self-management on close family and competing demands with time and energy spent on self-management at the expense of work or home commitments. CONCLUSIONS: Pain management programmes have an important role in helping patients to learn how to self-manage chronic pain. Their unwanted effects and the treatment burdens associated with long-term self-management may be an important consideration in improving the longevity of their beneficial effects.

Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting.

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

Assessing the contribution of plastic-associated obesogenic compounds to cardiometabolic diseases.

PURPOSE OF REVIEW: To present recent evidence that strengthens the concept that exogenous pollutants contribute to adipose dysfunction and increased rates of disease and to highlight the ineffective regulation of this risk as industry switches to related but similarly toxic variants. RECENT FINDINGS: Substitutes for common phthalates and the highly regulated bisphenol A (BPA) show similar deleterious effects on adipocytes. The well tolerated limit for BPA exposure has been reduced in Europe to below the level detected in recent population studies. Additionally, the role for BPA-induced inflammation mediated by interleukin 17a has been described in animal and human studies. SUMMARY: Despite experimental and associative evidence that supports plastics and plastic associated chemicals deleteriously influencing adipose homeostatasis and contributing to metabolic diseases, structurally related alternate chemicals are being substituted by manufacturers to circumvent trailing regulatory actions.

Rethinking egocentric bias: A computer mouse-tracking study of adult belief processing.

Several theories of belief processing assume that processing another's false belief requires overcoming an egocentric bias toward one's current knowledge. The current evidence in support of this claim, however, is limited. In order to investigate the presence of egocentric bias in adult belief processing, computer mouse tracking was used across three experiments to measure attraction toward response options reflecting one's current knowledge while reporting a false belief. Participants viewed scenarios in which an agent either had a true belief or a false belief about the location of a set of keys. Participants used a mouse to answer reality questions "where are the keys currently hidden?" and belief questions "where does she think the keys are?" Mouse-tracking measures indexing attraction toward response options during decision making were measured, along with time taken to make a response and accuracy. Experiment 1 found no evidence, in any measures, that participants showed a bias toward their own knowledge when reporting another's false belief. Experiment 2 investigated whether differences in event timings between true belief and false belief scenarios in Experiment 1 masked an egocentric bias. Experiment 3 investigated whether the lack of egocentric bias could be explained by participants prioritizing encoding the other's beliefs. Neither follow-up experiment found evidence supporting the presence of an egocentric bias. Overall, contrary to many theories of belief processing, our results suggest that adults are readily able to process other people's beliefs without having to overcome a default bias toward their own knowledge. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Out-of-plane arrivals recorded by drifting hydrophones during the Northern Ocean Rapid Surface Evolution Experiment.

This paper reports on an observation of three-dimensional (3D) arrivals for which the change in the direction of horizontally refracted sound is nearly 180°. The experimental site is Jan Mayen Channel (JMCh), which connects the Greenland and Norwegian Seas. During the experiment, signals from a moored source transmitting a 500-1500 Hz sweep every 4 h were recorded by three surface drifters equipped with hydrophone arrays. Over a 3-day period, the drifters moved north across JMCh toward the moored source. In each recording, an in-plane arrival is identified. In a subset of these recordings, a second arrival is observed, having travel time consistent with propagation from the moored source, turning at the ridge on the south side of the channel, and arriving at the drifters. In a smaller subset of recordings, a third arrival is also observed having travel time consistent with a turning point on the face of the bathymetric rise on the west end of the channel that forms the Jan Mayen volcano. A 3D ray trace is employed to show the change in direction results from repeated reflections from the seafloor such that it is classified as horizontal refraction and not a single-bounce reflection.

Disordered Quantum Critical Fixed Points from Holography.

Using holographic duality, we present an analytically controlled theory of quantum critical points without quasiparticles, at finite disorder and finite charge density. These fixed points are obtained by perturbing a disorder-free quantum critical point with relevant disorder whose operator dimension is perturbatively close to Harris marginal. We analyze these fixed points both using field theoretic arguments, and by solving the bulk equations of motion in holography. We calculate the critical exponents of the IR theory, together with thermoelectric transport coefficients. Our predictions for the critical exponents of the disordered fixed point are consistent with previous work, both in holographic and nonholograpic models.

Observations and simulations of caustic formation due to oceanographic fine structure.

An at-sea experiment in deep water was conducted to explore the impact of small-scale sound-speed variability on mid-frequency (1-10 kHz) acoustic propagation. Short-range (1-5 km) acoustic transmissions were sent through the upper ocean (0-200 m) while oceanographic instruments simultaneously measured the ocean environment within 2 km of the single upper turning points of the acoustic transmissions. During these transmissions, acoustic receptions over a 7.875 m vertical line array show closely spaced, sometimes interfering arrivals. Ray and full-wave simulations of the transmissions using nearby sound-speed profiles are compared deterministically to the received acoustic signals. The sensitivity of the acoustic arrivals to the vertical scales of ocean sound speed is tested by comparing the observed and simulated arrival intensity where the sound-speed profile used by the simulation is smoothed to varying scales. Observations and modeling both suggest that vertical fine-scale structures (1-10 m) embedded in the sound-speed profile have strong second derivatives which allow for the formation of acoustic caustics as well as potentially interfering acoustic propagation multipaths.

Speed limits and locality in many-body quantum dynamics.

We review the mathematical speed limits on quantum information processing in many-body systems. After the proof of the Lieb-Robinson Theorem in 1972, the past two decades have seen substantial developments in its application to other questions, such as the simulatability of quantum systems on classical or quantum computers, the generation of entanglement, and even the properties of ground states of gapped systems. Moreover, Lieb-Robinson bounds have been extended in non-trivial ways, to demonstrate speed limits in systems with power-law interactions or interacting bosons, and even to prove notions of locality that arise in cartoon models for quantum gravity with all-to-all interactions. We overview the progress which has occurred, highlight the most promising results and techniques, and discuss some central outstanding questions which remain open. To help bring newcomers to the field up to speed, we provide self-contained proofs of the field's most essential results.

Prethermalization and the Local Robustness of Gapped Systems.

We prove that prethermalization is a generic property of gapped local many-body quantum systems, subjected to small perturbations, in any spatial dimension. More precisely, let H_{0} be a Hamiltonian, spatially local in d spatial dimensions, with a gap Δ in the many-body spectrum; let V be a spatially local Hamiltonian consisting of a sum of local terms, each of which is bounded by ε≪Δ. Then, the approximation that quantum dynamics is restricted to the low-energy subspace of H_{0} is accurate, in the correlation functions of local operators, for stretched exponential timescale τ∼exp[(Δ/ε)^{a}] for any a<1/(2d-1). This result does not depend on whether the perturbation closes the gap. It significantly extends previous rigorous results on prethermalization in models where H_{0} was frustration-free. We infer the robustness of quantum simulation in low-energy subspaces, the existence of athermal "scarred" correlation functions in gapped systems subject to generic perturbations, the long lifetime of false vacua in symmetry broken systems, and the robustness of quantum information in non-frustration-free gapped phases with topological order.

Dinoflagellate vertical migration fuels an intense red tide.

Harmful algal blooms (HABs) are increasing globally, causing economic, human health, and ecosystem harm. In spite of the frequent occurrence of HABs, the mechanisms responsible for their exceptionally high biomass remain imperfectly understood. A 50-y-old hypothesis posits that some dense blooms derive from dinoflagellate motility: organisms swim upward during the day to photosynthesize and downward at night to access deep nutrients. This allows dinoflagellates to outgrow their nonmotile competitors. We tested this hypothesis with in situ data from an autonomous, ocean-wave-powered vertical profiling system. We showed that the dinoflagellate Lingulodinium polyedra's vertical migration led to depletion of deep nitrate during a 2020 red tide HAB event. Downward migration began at dusk, with the maximum migration depth determined by local nitrate concentrations. Losses of nitrate at depth were balanced by proportional increases in phytoplankton chlorophyll concentrations and suspended particle load, conclusively linking vertical migration to the access and assimilation of deep nitrate in the ocean environment. Vertical migration during the red tide created anomalous biogeochemical conditions compared to 70 y of climatological data, demonstrating the capacity of these events to temporarily reshape the coastal ocean's ecosystem and biogeochemistry. Advances in the understanding of the physiological, behavioral, and metabolic dynamics of HAB-forming organisms from cutting-edge observational techniques will improve our ability to forecast HABs and mitigate their consequences in the future.

Subset-specific Retention of Donor Myeloid Cells After Major Histocompatibility Complex-matched and Mismatched Liver Transplantation.

BACKGROUND: During solid organ transplantation, donor leukocytes, including myeloid cells, are transferred within the organ to the recipient. Both tolerogenic and alloreactive roles have been attributed to donor myeloid cells; however, their subset-specific retention posttransplantation has not been investigated in detail. METHODS: Major histocompatibility complex (MHC)-matched and mismatched liver transplants were performed in mice, and the fate of donor and recipient myeloid cells was assessed. RESULTS: Following MHC-matched transplantation, a proportion of donor myeloid cells was retained in the graft, whereas others egressed and persisted in the blood, spleen, and bone marrow but not the lymph nodes. In contrast, after MHC-mismatched transplantation, all donor myeloid cells, except Kupffer cells, were depleted. This depletion was caused by recipient T and B cells because all donor myeloid subsets were retained in MHC-mismatched grafts when recipients lacked T and B cells. Recipient myeloid cells rapidly infiltrated MHC-matched and, to a greater extent, MHC-mismatched liver grafts. MHC-mismatched grafts underwent a transient rejection episode on day 7, coinciding with a transition in macrophages to a regulatory phenotype, after which rejection resolved. CONCLUSIONS: Phenotypic and kinetic differences in the myeloid cell responses between MHC-matched and mismatched grafts were identified. A detailed understanding of the dynamics of immune responses to transplantation is critical to improving graft outcomes.

Investigation of the pharmacokinetic properties of synthetic heparan sulfate oligosaccharides.

Heparan sulfate (HS) is a sulfated polysaccharide with a wide range of biological activities. There is an increasing interest in the development of structurally homogeneous HS oligosaccharides as therapeutics. However, the factors influencing the pharmacokinetic properties of HS-based therapeutics remain unknown. Here, we report the pharmacokinetic properties of a panel of dodecasaccharides (12-mers) with varying sulfation patterns in healthy mice and uncover the pharmacokinetic properties of an octadecasaccharide (18-mer) in acutely injured mice. In the 12-mer panel, 1 12-mer, known as dekaparin, is anticoagulant, and 3 12-mers are nonanticoagulant. The concentrations of 12-mers in plasma and urine were determined by the disaccharide analysis using liquid chromatography coupled with tandem mass spectrometry. We observed a striking difference between anticoagulant and nonanticoagulant oligosaccharides in the 12-mer panel, showing that anticoagulant dekaparin had a 4.6-fold to 8.6-fold slower clearance and 4.4-fold to 8-fold higher plasma exposure compared to nonanticoagulant 12-mers. We also observed that the clearance of HS oligosaccharides is impacted by disease. Using an antiinflammatory 18-mer, we discovered that the clearance of 18-mer is reduced 2.8-fold in a liver failure mouse model compared to healthy mice. Our results suggest that oligosaccharides are rapidly cleared renally if they have low interaction with circulating proteins. We observed that the clearance rate of oligosaccharides is inversely associated with the degree of binding to target proteins, which can vary in response to pathophysiological conditions. Our findings uncover a contributing factor for the plasma and renal clearance of oligosaccharides which will aid the development of HS-based therapeutics.

Absence of hyperfibrinolysis may explain lack of efficacy of tranexamic acid in hypoproliferative thrombocytopenia.

The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT, NCT02578901) demonstrated no superiority of TXA over placebo in preventing World Health Organization (WHO) grade 2 or higher bleeding in patients with severe thrombocytopenia requiring supportive platelet transfusion following myeloablative therapy for hematologic disorders. In this ancillary study, we sought to determine whether this clinical outcome could be explained on the basis of correlative assays of fibrinolysis. Plasma was collected from A-TREAT participants (n = 115) before the initiation of study drug (baseline) and when TXA was at steady-state trough concentration (follow-up). Global fibrinolysis was measured by 3 assays: euglobulin clot lysis time (ECLT), plasmin generation (PG), and tissue-type plasminogen activator (tPA)-challenged clot lysis time (tPA-CLT). TXA was quantified in follow-up samples by tandem mass spectrometry. Baseline samples did not demonstrate fibrinolytic activation by ECLT or tPA-CLT. Furthermore, neither ECLT nor levels of plasminogen activator inhibitor-1, tPA, plasminogen, alpha2-antiplasmin, or plasmin-antiplasmin complexes were associated with a greater risk of WHO grade 2+ bleeding. TXA trough concentrations were highly variable (range, 0.7-10 µg/mL) and did not correlate with bleeding severity, despite the fact that plasma TXA levels correlated strongly with pharmacodynamic assessments by PG (Spearman r, -0.78) and tPA-CLT (r, 0.74). We conclude that (1) no evidence of fibrinolytic activation was observed in these patients with thrombocytopenia, (2) trough TXA concentrations varied significantly between patients receiving the same dosing schedule, and (3) tPA-CLT and PG correlated well with TXA drug levels.

The patient acceptability of a remotely delivered pain management programme for people with persistent musculoskeletal pain: A qualitative evaluation.

Introduction: Remotely delivered pain management programmes have been offered in place of in-person programmes by many chronic pain services since the onset of the COVID-19 pandemic. There is a lack of evidence regarding the acceptability of these programmes. In this evaluation, we have explored patients' acceptability of a remotely delivered pain management programme for patients with persistent musculoskeletal pain. Methods: Qualitative data were collected using focus groups with participants who had previously attended the remote pain management programme. Data were analysed using abductive analysis. Results: Three focus groups were conducted with a total of 13 participants. The programmme was either entirely acceptable, had some acceptable components or was not acceptable to patients. Factors leading to the programme being acceptable include learning to manage pain from home, receiving high quality care from home, enhancing the potential of rehabilitation using technology, enabling attendance on a pain management programme from home, overcoming social distancing requirements of COVID-19 using technology, and virtual peer support. Factors leading to the programme not being acceptable include having an inappropriate home environment for virtual therapy, communication challenges with virtual therapy, technological issues and concerns regarding the quality of care. Conclusions: There is a spectrum of acceptability with respect to the remote programme. The factors that influence this are dynamic, individual and situational. Hybrid programmes have the potential to enhance access to pain management programmes and improve patient experience and programme outcomes in the future.

Fracton Hydrodynamics without Time-Reversal Symmetry.

We present an effective field theory for the nonlinear fluctuating hydrodynamics of a single conserved charge with or without time-reversal symmetry, based on the Martin-Siggia-Rose formalism. Applying this formalism to fluids with only charge and multipole conservation, and with broken time-reversal symmetry, we predict infinitely many new dynamical universality classes, including some with arbitrarily large upper critical dimensions. Using large scale simulations of classical Markov chains, we find numerical evidence for a breakdown of hydrodynamics in quadrupole-conserving models with broken time-reversal symmetry in one spatial dimension. Our framework can be applied to the hydrodynamics around stationary states of open systems, broadening the applicability of previously developed ideas and methods to a wide range of systems in driven and active matter.

A Modified Murine Heterotopic Heart Transplant Protocol Matching Contemporary Standards of Aseptic Technique, Anesthesia, and Analgesia.

The development of experimental models of cardiac transplantation in animals has contributed to many advances in the fields of immunology and solid organ transplantation. While the heterotopic vascularized murine cardiac transplantation model was initially utilized in studies of graft rejection using combinations of mismatched inbred mouse strains, access to genetically modified strains and therapeutic modalities can provide powerful new preclinical insights. Fundamentally, the surgical methodology for this technique has not changed since its development, especially with respect to important factors such as aseptic technique, anesthesia, and analgesia, which make material impacts on postsurgical morbidity and mortality. Additionally, improvements in perioperative management are expected to provide improvements in both animal welfare and experimental outcomes. This paper reports upon a protocol developed in collaboration with a subject matter expert in veterinary anesthesia and describes the surgical technique with an emphasis on perioperative management. Additionally, we discuss the implications of these refinements and provide details on troubleshooting critical surgical steps for this procedure.

Imaging the Breakdown of Ohmic Transport in Graphene.

Ohm's law describes the proportionality of the current density and electric field. In solid-state conductors, Ohm's law emerges due to electron scattering processes that relax the electrical current. Here, we use nitrogen-vacancy center magnetometry to directly image the local breakdown of Ohm's law in a narrow constriction fabricated in a high mobility graphene monolayer. Ohmic flow is visible at room temperature as current concentration on the constriction edges, with flow profiles entirely determined by sample geometry. However, as the temperature is lowered below 200 K, the current concentrates near the constriction center. The change in the flow pattern is consistent with a crossover from diffusive to viscous electron transport dominated by electron-electron scattering processes that do not relax current.

Nonequilibrium phase transitions in competitive markets caused by network effects.

Network effects are the added value derived solely from the popularity of a product in an economic market. Using agent-based models inspired by statistical physics, we propose a minimal theory of a competitive market for (nearly) indistinguishable goods with demand-side network effects, sold by statistically identical sellers. With weak network effects, the model reproduces conventional microeconomics: there is a statistical steady state of (nearly) perfect competition. Increasing network effects, we find a phase transition to a robust nonequilibrium phase driven by the spontaneous formation and collapse of fads in the market. When sellers update prices sufficiently quickly, an emergent monopolist can capture the market and undercut competition, leading to a symmetry- and ergodicity-breaking transition. The nonequilibrium phase simultaneously exhibits three empirically established phenomena not contained in the standard theory of competitive markets: spontaneous price fluctuations, persistent seller profits, and broad distributions of firm market shares.

Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B-cells that accumulate in the lung adjacent to areas of active fibrosis. We have shown previously a requirement for B-cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B-cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B-cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20 B-cell ablation did not reduce fibrosis in this model; however, immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20-treated mice retained a high frequency of CD19+ CD138+ plasma cells. Interestingly, high levels of CD138+ cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes plasma cells, reduced the level of Blm-induced lung fibrosis, implicating plasma cells as important effector cells in the development and progression of pulmonary fibrosis.

Hidden quasiconservation laws in fracton hydrodynamics.

We show that the simplest universality classes of fracton hydrodynamics in more than one spatial dimension, including isotropic theories of charge and dipole conservation, can exhibit hidden quasiconservation laws, in which certain higher multipole moments can only decay due to dangerously irrelevant corrections to hydrodynamics. We present two simple examples of this phenomenon. First, an isotropic dipole-conserving fluid in the infinite plane conserves an infinite number of harmonic multipole charges within linear response; we calculate the decay or growth of these charges due to dangerously irrelevant nonlinearities. Second, we consider a model with xy and x^{2}-y^{2} quadrupole conservation, in addition to dipole conservation, which is described by isotropic fourth-order subdiffusion, yet has dangerously irrelevant sixth-order corrections necessary to relax the harmonic multipole charges. We confirm our predictions for the anomalously slow decay of the harmonic conserved charges in each setting by using numerical simulations, both of the nonlinear hydrodynamic differential equations, and in quantum automaton circuits on a square lattice.