Dynamics of magnetization at infinite temperature in a Heisenberg spin chain.

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.

Tuning the Chemical and Electrochemical Properties of Paper-Based Carbon Electrodes by Pyrolysis of Polydopamine.

Electrochemical paper-based analytical devices represent an important platform for portable, low-cost, affordable, and decentralized diagnostics. For this kind of application, chemical functionalization plays a pivotal role to ensure high clinical performance by tuning surface properties and the area of electrodes. However, controlling different surface properties of electrodes by using a single functionalization route is still challenging. In this work, we attempted to tune the wettability, chemical composition, and electroactive area of carbon-paper-based devices by thermally treating polydopamine (PDA) at different temperatures. PDA films were deposited onto pyrolyzed paper (PP) electrodes and thermally treated in the range of 300-1000 °C. After deposition of PDA, the surface is rich in nitrogen and oxygen, it is superhydrophilic, and it has a high electroactive area. As the temperature increases, the surface becomes hydrophobic, and the electroactive area decreases. The surface modifications were followed by Raman, X-ray photoelectron microscopy (XPS), laser scanning confocal microscopy (LSCM), contact angle, scanning electron microscopy (SEM-EDS), electrical measurements, transmission electron microscopy (TEM), and electrochemical experiments. In addition, the chemical composition of nitrogen species can be tuned on the surface. As a proof of concept, we employed PDA-treated surfaces to anchor [AuCl4]- ions. After electrochemical reduction, we observed that it is possible to control the size of the nanoparticles on the surface. Our route opens a new avenue to add versatility to electrochemical interfaces in the field of paper-based electrochemical biosensors.

Development of the What Matters 2 Adults (WM2A) wellbeing measure for Aboriginal and Torres Strait Islander adults.

PURPOSE: As wellbeing is culturally bound, wellbeing measures for Aboriginal and Torres Strait Islander peoples must be culturally relevant and grounded in Aboriginal and Torres Strait Islander values and preferences. We describe the development of a nationally-relevant and culturally grounded wellbeing measure for Aboriginal and Torres Strait Islander adults: the What Matters to Adults (WM2A) measure. METHODS: We used a mixed methods approach to measure development, combining Indigenist methodologies and psychometric methods. Candidate items were derived through a large national qualitative study. Think-aloud interviews (n = 17) were conducted to assess comprehension, acceptability, and wording of candidate items. Two national surveys collected data on the item pool (n = 312, n = 354). Items were analysed using exploratory factor analysis (EFA), and item response theory (IRT) to test dimensionality, local dependence and item fit. A Collaborative Yarning approach ensured Aboriginal and Torres Strait Islander voices were privileged throughout. RESULTS: Fifty candidate items were developed, refined, and tested. Using EFA, an eight factor model was developed. All items met pre-specified thresholds for maximum endorsement frequencies, and floor and ceiling effects; no item redundancy was identified. Ten items did not meet thresholds for aggregate adjacent endorsement frequencies. During Collaborative Yarning, six items were removed based on low factor loadings (<0.4) and twelve due to conceptual overlap, high correlations with other items, endorsement frequencies, and/or low IRT item level information. Several items were retained for content validity. The final measure includes 32 items across 10 domains (Balance & control; Hope & resilience; Caring for others; Culture & Country; Spirit & identity; Feeling valued; Connection with others; Access; Racism & worries; Pride & strength). CONCLUSIONS: The unique combination of Indigenist and psychometric methodologies to develop WM2A ensures a culturally and psychometrically robust measure, relevant across a range of settings and applications.

Highly selective alkylcoumarates and diterpenoids isolated from leaves of Baccharis quitensis: a search for new hit compounds against Trypanosoma cruzi.

In the present work, the hexane extract of aerial parts of Baccharis quitensis Kunth. was subjected to chromatographic fractionation to afford two alkyl phenylpropanoids: n-docosyl (E)-p-coumarate (1) and n-tetracosyl (E)-p-coumarate (2) as well as five diterpenes: ent-kaurenoic acid (3), grandifloric acid (4), 15ß-senecioyl-oxy-ent-kaur-16-en-19-oic acid (5), and 15-oxo-ent-kaurenoic acid (6). Using an ex-vivo assay with macrophages infected with Trypanosoma cruzi, compounds 1 and 2 demonstrated high potency against intracellular amastigotes, with EC50 values of 7.5 and 6.9 µM, respectively. Compound 6 revealed a moderate potency against T. cruzi, with an EC50 of 25.6 µM, and compounds 3-5 showed no effectiveness. Additionally, compounds 1-6 compounds presented no toxicity for mammalian cells to the highest tested concentration of 200 µM. Based on potency and the selectivity indexes of 1, 2 and 6, these compounds could be future candidates for optimisation studies for the design of prototypes against Chagas disease.

The effect of psychiatric decision unit services on inpatient admissions and mental health presentations in emergency departments: an interrupted time series analysis from two cities and one rural area in England.

AIMS: High-quality evidence is lacking for the impact on healthcare utilisation of short-stay alternatives to psychiatric inpatient services for people experiencing acute and/or complex mental health crises (known in England as psychiatric decision units [PDUs]). We assessed the extent to which changes in psychiatric hospital and emergency department (ED) activity were explained by implementation of PDUs in England using a quasi-experimental approach. METHODS: We conducted an interrupted time series (ITS) analysis of weekly aggregated data pre- and post-PDU implementation in one rural and two urban sites using segmented regression, adjusting for temporal and seasonal trends. Primary outcomes were changes in the number of voluntary inpatient admissions to (acute) adult psychiatric wards and number of ED adult mental health-related attendances in the 24 months post-PDU implementation compared to that in the 24 months pre-PDU implementation. RESULTS: The two PDUs (one urban and one rural) with longer (average) stays and high staff-to-patient ratios observed post-PDU decreases in the pattern of weekly voluntary psychiatric admissions relative to pre-PDU trend (Rural: -0.45%/week, 95% confidence interval [CI] = -0.78%, -0.12%; Urban: -0.49%/week, 95% CI = -0.73%, -0.25%); PDU implementation in each was associated with an estimated 35-38% reduction in total voluntary admissions in the post-PDU period. The (urban) PDU with the highest throughput, lowest staff-to-patient ratio and shortest average stay observed a 20% (-20.4%, CI = -29.7%, -10.0%) level reduction in mental health-related ED attendances post-PDU, although there was little impact on long-term trend. Pooled analyses across sites indicated a significant reduction in the number of voluntary admissions following PDU implementation (-16.6%, 95% CI = -23.9%, -8.5%) but no significant (long-term) trend change (-0.20%/week, 95% CI = -0.74%, 0.34%) and no short- (-2.8%, 95% CI = -19.3%, 17.0%) or long-term (0.08%/week, 95% CI = -0.13, 0.28%) effects on mental health-related ED attendances. Findings were largely unchanged in secondary (ITS) analyses that considered the introduction of other service initiatives in the study period. CONCLUSIONS: The introduction of PDUs was associated with an immediate reduction of voluntary psychiatric inpatient admissions. The extent to which PDUs change long-term trends of voluntary psychiatric admissions or impact on psychiatric presentations at ED may be linked to their configuration. PDUs with a large capacity, short length of stay and low staff-to-patient ratio can positively impact ED mental health presentations, while PDUs with longer length of stay and higher staff-to-patient ratios have potential to reduce voluntary psychiatric admissions over an extended period. Taken as a whole, our analyses suggest that when establishing a PDU, consideration of the primary crisis-care need that underlies the creation of the unit is key.

Highly selective alkylcoumarates and diterpenoids isolated from leaves of Baccharis quitensis: a search for new hit compounds against Trypanosoma cruzi

In the present work, the hexane extract of aerial parts of Baccharis quitensis Kunth. was subjected to chromatographic fractionation to afford two alkyl phenylpropanoids: n-docosyl (E)-p-coumarate (1) and n-tetracosyl (E)-p-coumarate (2) as well as five diterpenes: ent-kaurenoic acid (3), grandifloric acid (4), 15β-senecioyl-oxy-ent-kaur-16-en-19-oic acid (5), and 15-oxo-ent-kaurenoic acid (6). Using an ex-vivo assay with macrophages infected with Trypanosoma cruzi, compounds 1 and 2 demonstrated high potency against intracellular amastigotes, with EC50 values of 7.5 and 6.9 µM, respectively. Compound 6 revealed a moderate potency against T. cruzi, with an EC50 of 25.6 µM, and compounds 3–5 showed no effectiveness. Additionally, compounds 1–6 compounds presented no toxicity for mammalian cells to the highest tested concentration of 200 µM. Based on potency and the selectivity indexes of 1, 2 and 6, these compounds could be future candidates for optimisation studies for the design of prototypes against Chagas disease.

Povidone-iodine intra-abdominal irrigation versus no irrigation in pediatric perforated appendicitis: A secondary economic analysis of a Bayesian randomized controlled trial.

BACKGROUND: A pilot randomized controlled trial (RCT) conducted in children (2-17 â€‹y) with perforated appendicitis demonstrated an 89% probability of reduced intra-abdominal abscess (IAA) rate with povidone-iodine (PVI) irrigation, compared with no irrigation (NI). We hypothesized that PVI also reduced 30-day hospital costs. METHODS: We conducted a retrospective economic analysis of a pilot RCT. Hospital costs, inflated to 2019 U.S. dollars, were obtained for index admissions and 30-day emergency visits and readmissions. Cost differences between groups were assessed using frequentist and Bayesian generalized linear models. RESULTS: We observed a 95% Bayesian probability that PVI reduced 30-day mean total hospital costs ($16,555 [PVI] versus $18,509 [NI]; Bayesian cost ratio: 0.90, 95% CrI, 0.78-1.03). The mean absolute difference per patient was $1,954 less with PVI (95% CI, -$4,288 to $379). CONCLUSIONS: PVI likely reduced the IAA rate and 30-day hospital costs, suggesting the intervention is both clinically superior and cost saving.

Observation of interplay between phonon chirality and electronic band topology.

The recently demonstrated chiral modes of lattice motion carry angular momentum and therefore directly couple to magnetic fields. Notably, their magnetic moments are predicted to be strongly influenced by electronic contributions. Here, we have studied the magnetic response of transverse optical phonons in a set of Pb1-xSnxTe films, which is a topological crystalline insulator for x > 0.32 and has a ferroelectric transition at an x-dependent critical temperature. Polarization-dependent terahertz magnetospectroscopy measurements revealed Zeeman splittings and diamagnetic shifts, demonstrating a large phonon magnetic moment. Films in the topological phase exhibited phonon magnetic moment values that were larger than those in the topologically trivial samples by two orders of magnitude. Furthermore, the sign of the effective phonon g-factor was opposite in the two phases, a signature of the topological transition according to our model. These results strongly indicate the existence of interplay between the magnetic properties of chiral phonons and the topology of the electronic band structure.

A qualitative evaluation of internet information on hip and knee osteoarthritis.

BACKGROUND: Hip and knee arthritis are two of the most common conditions that result in referral to orthopaedic outpatient clinics. Many patients now use the internet to research their condition and to inform their decision about treatment options. This has implications for the process of informed consent. AIM: To assess the quality of patient information on the internet regarding hip and knee arthritis. METHODS: 'Hip arthritis' and 'Knee arthritis' were entered as search terms into a popular search engine. To adjust for temporal variation, the process was repeated one month and one year later. Of the 200 results analysed, 83 websites met the inclusion criteria. The quality of patient information presented on these websites was assessed using a validated scoring instrument by two independent observers. RESULTS: Most websites assessed were of poor quality; nearly half of all websites did not mention any risks or complications associated with surgical intervention for these conditions. CONCLUSIONS: As part of their professional obligation to provide a robust process of informed consent, clinicians should be aware of the variable quality of patient information available on the internet. As such, they should be prepared to advise their patients about quality websites where reliable information can be sought.

Generation and Manipulation of Rat Intestinal Organoids.

When using organoids to assess physiology and cell fate decisions, it is important to use a model that closely recapitulates in vivo contexts. Accordingly, patient-derived organoids are used for disease modeling, drug discovery, and personalized treatment screening. Mouse intestinal organoids are commonly utilized to understand aspects of both intestinal function/physiology and stem cell dynamics/fate decisions. However, in many disease contexts, rats are often preferred over mice as a model due to their greater physiological similarity to humans in terms of disease pathophysiology. The rat model has been limited by a lack of genetic tools available in vivo, and rat intestinal organoids have proven fragile and difficult to culture long-term. Here, we build upon previously published protocols to robustly generate rat intestinal organoids from the duodenum and jejunum. We provide an overview of several downstream applications utilizing rat intestinal organoids, including functional swelling assays, whole mount staining, the generation of 2D enteroid monolayers, and lentiviral transduction. The rat organoid model provides a practical solution to the need of the field for an in vitro model which retains physiological relevance to humans, can be quickly genetically manipulated, and is easily obtained without the barriers involved in procuring human intestinal organoids.

Report of consensus panel 7 from the 11th international workshop on Waldenström macroglobulinemia on priorities for novel clinical trials.

Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have impacted the development of effective novel agents and improved our knowledge of how the genomic background of WM may influence selection of therapy. Consensus Panel 7 (CP7) of the 11th International Workshop on WM was convened to examine the current generation of completed and ongoing clinical trials involving novel agents, consider updated data on WM genomics, and make recommendations on the design and prioritization of future clinical trials. CP7 considers limited duration and novel-novel agent combinations to be the priority for the next generation of clinical trials. Evaluation of MYD88, CXCR4 and TP53 at baseline in the context of clinical trials is crucial. The common chemoimmunotherapy backbones, bendamustine-rituximab (BR) and dexamethasone, rituximab and cyclophosphamide (DRC), may be considered standard-of-care for the frontline comparative studies. Key unanswered questions include the definition of frailty in WM; the importance of attaining a very good partial response or better (≥VGPR), within stipulated time frame, in determining survival outcomes; and the optimal treatment of WM populations with special needs.

Determinants of exposure to endocrine disruptors following hurricane Harvey.

Hurricane Harvey was a category four storm that induced catastrophic flooding in the Houston metropolitan area. Following the hurricane there was increased concern regarding chemical exposures due to damage caused by flood waters and emergency excess emissions from industrial facilities. This study utilized personal passive samplers in the form of silicone wristbands in Houston, TX to both assess chemical exposure to endocrine disrupting chemicals (EDCs) immediately after the hurricane and determine participant characteristics associated with higher concentrations of exposure. Participants from the Houston-3H cohort (n = 172) wore a wristband for seven days and completed a questionnaire to determine various flood-related and demographic variables. Bivariate and multivariate analysis indicated that living in an area with a high Area Deprivation Index (ADI) (indicative of low socioeconomic status), identifying as Black/African American or Latino, and living in the Houston neighborhoods of Baytown and East Houston were associated with increased exposure to EDCs. These results provide evidence of racial/ethnic and socioeconomic injustices in exposure to EDCs in the Houston Metropolitan Area. Since the multiple regression models conducted did not fully explain exposure (0.047 < R2 < 0.34), more research is needed on the direct sources of EDCs within this area to create effective exposure mitigation strategies.

Regulatory mechanisms of stem cell differentiation: Biotechnological applications for neurogenesis.

The world population's life expectancy is growing, and neurodegenerative disorders common in old age require more efficient therapies. In this context, neural stem cells (NSCs) are imperative for the development and maintenance of the functioning of the nervous system and have broad therapeutic applicability for neurodegenerative diseases. Therefore, knowing all the mechanisms that govern the self-renewal, differentiation, and cell signaling of NSC is necessary. This review will address some of these aspects, including the role of growth and transcription factors, epigenetic modulators, microRNAs, and extracellular matrix components. Furthermore, differentiation and transdifferentiation processes will be addressed as therapeutic strategies showing their significance for stem cell-based therapy.

Strategic use of organoids and organs-on-chip as biomimetic tools.

Organoid development and organ-on-a-chip are technologies based on differentiating stem cells, forming 3D multicellular structures resembling organs and tissues in vivo. Hence, both can be strategically used for disease modeling, drug screening, and host-pathogen studies. In this context, this review highlights the significant advancements in the area, providing technical approaches to organoids and organ-on-a-chip that best imitate in vivo physiology.

Development of an x-ray radiography platform to study laser-direct-drive energy coupling at the National Ignition Facility.

A platform has been developed to study laser-direct-drive energy coupling at the National Ignition Facility (NIF) using a plastic sphere target irradiated in a polar-direct-drive geometry to launch a spherically converging shock wave. To diagnose this system evolution, eight NIF laser beams are directed onto a curved Cu foil to generate Heα line emission at a photon energy of 8.4 keV. These x rays are collected by a 100-ps gated x-ray imager in the opposing port to produce temporally gated radiographs. The platform is capable of acquiring images during and after the laser drive launches the shock wave. A backlighter profile is fit to the radiographs, and the resulting transmission images are Abel inverted to infer radial density profiles of the shock front and to track its temporal evolution. The measurements provide experimental shock trajectories and radial density profiles that are compared to 2D radiation-hydrodynamic simulations using cross-beam energy transfer and nonlocal heat-transport models.

New derivatives from dehydrodieugenol B and its methyl ether displayed high anti-Trypanosoma cruzi activity and cause depolarization of the plasma membrane and collapse the mitochondrial membrane potential.

In the present work, dehydrodieugenol B (1) and its methyl ether (2), isolated from Nectandra leucantha twigs, were used as starting material for the preparation of two new derivatives (1a and 2a) containing an additional methoxycarbonyl unit on allyl side chains. Compounds 1a and 2a demonstrated activity against trypomastigotes (EC50 values of 13.5 and 23.0 µM, respectively) and against intracellular amastigotes (EC50 values of 10.2 and 6.1 µM, respectively). Additionally, compound 2a demonstrated no mammalian cytotoxicity up to 200 µM whereas compound 1a exhibited a CC50 value of 139.8 µM. The mechanism of action studies of compounds 1a and 2a demonstrated a significant depolarization of the plasma membrane potential in trypomastigotes, followed by a mitochondrial membrane potential collapse. Neither calcium level nor reactive oxygen species alterations were observed after a short-time incubation. Considering the potential of compound 2a against T. cruzi and its simple preparation from the natural product 2, isolated from N. leucantha, this compound could be considered a new hit for future drug design studies in Chagas disease.

Comparison of treatment outcome definitions in drug-resistant tuberculosis patients with high incidence of acquired second-line drug resistance.

Background: Simplified drug-resistant tuberculosis (DR-TB) treatment outcome definitions, mostly centred around receipt of treatment and sputum culture status at 6 months after treatment initiation, have been proposed, but have not been widely evaluated in resource-limited settings. Objectives: To compare DR-TB treatment outcomes, as defined by the World Health Organization (WHO) at the time of treatment, with simplified definitions. Methods: We performed retrospective folder reviews of a cohort of 246 South African DR-TB patients, most of whom developed second-line drug resistance. Sequential treatment outcomes were assigned retrospectively using both simplified Tuberculosis Network European Trials Group (TBNET)-based and 2013 WHO-based definitions. Results: Of 246 patients, 40% were HIV-positive, and 88% developed second-line drug resistance. Patients were observed for a median of 38 (interquartile range 24 - 63) months from DR-TB treatment initiation. Using WHO-based definitions, 93% of patients had >1 sequential outcome, whereas with simplified definitions, 25% of patients had >1 outcome. Fewer outcomes of cure (3% v. 9%) and more outcomes of treatment failure (42% v. 22%) were assigned using simplified definitions. Conclusion: Simplified outcome definitions applied to real-world patients with long, often complex treatment histories resulted in underestimating cures and overestimating treatment failures compared with WHO-based definitions. Simplified definitions may identify more individuals at higher risk for treatment failure than WHO-based definitions, but without consistent programmatic follow-up it may be difficult to distinguish cure, failure and loss to follow-up.

Ionizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes.

Introduction: Gene therapy is a promising approach to be applied in cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies. However, cardiomyocytes are crucial cell types that are considered hard-to-transfect. The entrapment of nucleic acids in non-viral vectors, such as lipid nanoparticles (LNPs), is an attractive approach for safe and effective delivery. Methods: Here, a mini-library of engineered LNPs was developed for pDNA delivery in cardiomyocytes. LNPs were characterized and screened for pDNA delivery in cardiomyocytes and identified a lead LNP formulation with enhanced transfection efficiency. Results: By varying lipid molar ratios, the LNP formulation was optimized to deliver pDNA in cardiomyocytes with enhanced gene expression in vitro and in vivo, with negligible toxicity. In vitro, our lead LNP was able to reach a gene expression greater than 80%. The in vivo treatment with lead LNPs induced a twofold increase in GFP expression in heart tissue compared to control. In addition, levels of circulating myeloid cells and inflammatory cytokines remained without significant changes in the heart after LNP treatment. It was also demonstrated that cardiac cell function was not affected after LNP treatment. Conclusion: Collectively, our results highlight the potential of LNPs as an efficient delivery vector for pDNA to cardiomyocytes. This study suggests that LNPs hold promise to improve gene therapy for treatment of cardiovascular disease.