Search

Background As diabetes is a chronic disease, patients must make adjustments to their lifestyle and self-care practices to live optimally with the disease and reduce associated morbidity. Their ability to make these adjustments is partly dependent on their coping capacity and resilience, which may enhance glycemic control. Materials and Methods A cross-sectional study involving 156 consented and randomly selected type 2 diabetes patients was conducted at Korle-Bu Teaching Hospital, a national health facility in Accra, Ghana. Structured questionnaires were used to extract information on sociodemographic characteristics and clinical parameters (including glycemic control), while the Africultural Coping Systems Inventory and the Adult Resilience Measure were administered to assess cultural variables and resilience. Stata version 16.1 was used to analyze the data, and the significance level was set at P ≤ 0.05. Results Ethnicity, age, and working status were significantly associated with glycemic control. Adjusted binary logistic regression revealed that the odds of good glycemic control among nonhypertensive patients was 2.8 times greater compared with hypertensive patients (adjusted odds ratio [aOR]: 2.80, 95% confidence interval [CI]: 1.02–7.69); while the odds of good glycemic control increase by 17% with every 1-point increase in the resilience caregiver arm score (aOR: 1.17, 95% CI: 1.01–1.37). Conclusions Efforts should be made toward implementing proactive measures aimed at enhancing income levels, coping strategies, and resilience among patients diagnosed with diabetes mellitus. Such initiatives are crucial for assisting individuals in adapting to the chronic nature of the condition and its associated treatment regimen, ultimately leading to improved glycemic control and treatment outcomes.

Abstract The standard method for identifying active Brown Adipose Tissue (BAT) is [18F]-Fluorodeoxyglucose ([18F]-FDG) PET/CT imaging, which is costly and exposes patients to radiation, making it impractical for population studies. These issues can be addressed with computational methods that predict [18F]-FDG uptake by BAT from CT; earlier population studies pave the way for developing such methods by showing some correlation between the Hounsfield Unit (HU) of BAT in CT and the corresponding [18F]-FDG uptake in PET. In this study, we propose training convolutional neural networks (CNNs) to predict [18F]-FDG uptake by BAT from unenhanced CT scans in the restricted regions that are likely to contain BAT. Using the Attention U-Net architecture, we perform experiments on datasets from four different cohorts, the largest study to date. We segment BAT regions using predicted [18F]-FDG uptake values, achieving 23% to 40% better accuracy than conventional CT thresholding. Additionally, BAT volumes computed from the segmentations distinguish the subjects with and without active BAT with an AUC of 0.8, compared to 0.6 for CT thresholding. These findings suggest CNNs can facilitate large-scale imaging studies more efficiently and cost-effectively using only CT.

Abstract Aims Right ventricular failure after left ventricular assist device (LVAD) implantation is a major concern that remains challenging to predict. We sought to investigate the relationship between preoperative pulmonary artery pulsatility index (PAPi) and mortality after LVAD implantation. Methods and results A retrospective analysis of the ASSIST‐ICD multicentre registry allowed the assessment of PAPi before LVAD according to the formula [(systolic pulmonary artery pressure − diastolic pulmonary artery pressure)/central venous pressure]. The primary endpoint was survival at 3 months, according to the threshold value of PAPi determined by the receiver operating characteristic (ROC) curve. A multivariate analysis including demographic, echographic, haemodynamic, and biological variables was performed to identify predictive factors for 2 year mortality. One hundred seventeen patients were included from 2007 to 2021. The mean age was 58.45 years (±13.16), with 15.4% of women (sex ratio 5.5). A total of 53.4% were implanted as bridge to transplant and 43.1% as destination therapy. Post‐operative right ventricular failure was observed in 57 patients (48.7%), with no significant difference between survivors and non‐survivors at 1 month (odds ratio 1.59, P = 0.30). The median PAPi for the whole study population was 2.83 [interquartile range 1.63–4.69]. The threshold value of PAPi determined by the ROC curve was 2.84. Patients with PAPi ≥ 2.84 had a higher survival rate at 3 months [PAPi

Abstract Background Interactions among cis-regulatory elements (CREs) play a crucial role in gene regulation. Various approaches have been developed to map these interactions genome-wide, including those relying on interindividual epigenomic variation to identify groups of covariable regulatory elements, referred to as chromatin modules (CMs). While CM mapping allows to investigate the relationship between chromatin modularity and gene expression, the computational principles used for CM identification vary in their application and outcomes. Results We comprehensively evaluate and streamline existing CM mapping tools and present guidelines for optimal utilization of epigenome data from a diverse population of individuals to assess regulatory coordination across the human genome. We showcase the effectiveness of our recommended practices by analyzing distinct cell types and demonstrate cell type specificity of CRE interactions in CMs and their relevance for gene expression. Integration of genotype information revealed that many non-coding disease-associated variants affect the activity of CMs in a cell type-specific manner by affecting the binding of cell type-specific transcription factors. We provide example cases that illustrate in detail how CMs can be used to deconstruct GWAS loci, assess variable expression of cell surface receptors in immune cells, and reveal how genetic variation can impact the expression of prognostic markers in chronic lymphocytic leukemia. Conclusions Our study presents an optimal strategy for CM mapping and reveals how CMs capture the coordination of CREs and its impact on gene expression. Non-coding genetic variants can disrupt this coordination, and we highlight how this may lead to disease predisposition in a cell type-specific manner.

Abstract Background We aimed to measure the variance due to examination conditions during the first sessions of objective structured clinical examinations (OSCEs) performed at a French medical school and identify factors associated with student success. Methods We conducted a retrospective, observational study using data from the first three OSCEs sessions performed at Paris-Saclay medical school in 2021 and 2022. For all sessions (each organized in 5 parallel circuits), we tested a circuit effect using a linear mixed-effects model adjusted for sex and the average academic level of students (according to written tests). Then, we studied the factors associated with student success at one station using a multivariate linear mixed-effects model, including the characteristics of students, assessors, and standardized patients. Results The study included three OSCEs sessions, with 122, 175, and 197 students and a mean (± SD) session score of 13.7(± 1.5)/20, 12.7(± 1.7)/20 and 12.7(± 1.9)/20, respectively. The percentage of variance due to the circuit was 6.5%, 18.2% (statistically significant), and 3.8%, respectively. For all sessions, the student’s average level and station scenario were significantly associated with the score obtained in a station. Still, specific characteristics of assessors or standardized patients were only associated with the student’s score in April 2021 (first session). Conclusion The percentage of the variance of students’ performance due to the examination conditions was significant in one out of three of the first OSCE sessions performed at Paris-Saclay medical school. This result seems more related to individual behaviors rather than specific characteristics of assessors or standardized patients, highlighting the need to continue training teaching teams. National clinical trial number Not applicable.

In severe skeletal muscle damage, muscle tissue regeneration process has to face the loss of resident muscle stem cells (MuSCs) and the lack of connective tissue necessary to guide the regeneration process. Biocompatible and standardized 3D structures that can be injected to the muscle injury site, conforming to the defect shape while actively guiding the repair process, holds great promise for skeletal muscle tissue regeneration. In this study, we explore the use of an injectable and porous lysine dendrimer/polyethylene glycol (DGL/PEG) hydrogel as an acellular support for skeletal muscle regeneration. We adjusted the DGL/PEG composition to achieve a stiffness conducive to the attachment and proliferation of murine immortalized myoblasts and human primary muscle stems cells, sustaining the formation and maturation of muscle fibers in vitro . We then evaluated the potential of one selected “myogenic-porous hydrogel” as a supportive structure for muscle repair in a large tibialis anterior muscle defect in rats. This injectable and porous formulation filled the defect, promoting rapid cellularization with the presence of endothelial cells, macrophages, and myoblasts, thereby supporting neo-myogenesis more specifically at the interface between the wound edges and the hydrogel. The selected porous DGL/PEG hydrogel acted as a guiding scaffold at the periphery of the defect, facilitating the formation and anchorage of aligned muscle fibers 21 days after injury. Overall, our results indicate DGL/PEG porous injectable hydrogel potential to create a pro-regenerative environment for muscle cells after large skeletal muscle injuries, paving the way for acellular treatment in regenerative muscle medicine.

Genome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability. Drosophila melanogaster is in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. The Drosophila Genetic Reference Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource. To address this, we created a web tool called DGRPool (dgrpool.epfl.ch), which aggregates phenotyping data of 1034 phenotypes across 135 DGRP studies in a common environment. DGRPool enables users to download data and run various tools such as genome-wide (GWAS) and phenome-wide (PheWAS) association studies. As a proof-of-concept, DGRPool was used to study the longevity phenotype and uncovered both established and unexpected correlations with other phenotypes such as locomotor activity, starvation resistance, desiccation survival, and oxidative stress resistance. DGRPool has the potential to facilitate new genetic and molecular insights of complex traits in Drosophila and serve as a valuable, interactive tool for the scientific community.

The value of artificial intelligence and machine learning applications for use in heritage research is increasingly appreciated. In specific areas, notably remote sensing, datasets have increased in extent and resolution to the point that manual interpretation is problematic and the availability of skilled interpreters to undertake such work is limited. Interpretation of the geophysical datasets associated with prehistoric submerged landscapes is particularly challenging. Following the Last Glacial Maximum, sea levels rose by 120 m globally, and vast, habitable landscapes were lost to the sea. These landscapes were inaccessible until extensive remote sensing datasets were provided by the offshore energy sector. In this paper, we provide the results of a research programme centred on AI applications using data from the southern North Sea. Here, an area of c. 188,000 km2 of habitable terrestrial land was inundated between c. 20,000 BP and 7000 BP, along with the cultural heritage it contained. As part of this project, machine learning tools were applied to detect and interpret features with potential archaeological significance from shallow seismic data. The output provides a proof-of-concept model demonstrating verifiable results and the potential for a further, more complex, leveraging of AI interpretation for the study of submarine palaeolandscapes.

Our objective is to achieve a new good-quality and mechanically durable high-transparency material that, when activated by rare earth ions, can be used as laser sources, scintillators, or phosphors. The best functional transparent ceramics are formed from high-symmetry systems, mainly cubic. Considering hexagonal hydroxyapatite, which shows anisotropy, the particle size of the initial powder is extremely important and should be of the order of several tens of nanometers. In this work, transparent micro-crystalline ceramics of non-cubic Ca10(PO4)6(OH)2 calcium phosphate were fabricated via Spark Plasma Sintering (SPS) from two types of nanopowders i.e., commercially available (COM. HA) and laboratory-made (LAB. HA) via the hydrothermal (HT) protocol. Our study centered on examining how the quality of sintered bodies is affected by the following parameters: the addition of LiF sintering agent, the temperature during the SPS process, and the quality of the starting nanopowders. The phase purity, microstructure, and optical transmittance of the ceramics were investigated to determine suitable sintering conditions. The best optical ceramics were obtained from LAB. HA nanopowder with the addition of 0.25 wt.% of LiF sintered at 1000 °C and 1050 °C.

Development of the continental shelf has accelerated significantly as nations around the world seek to harness offshore renewable energy. Many areas marked for development align with submerged palaeolandscapes. Poorly understood and difficult to protect, these vulnerable, prehistoric landscapes provide specific challenges for heritage management. Indeed, there now appears to be a schism between what underwater cultural heritage policy intends and what it is achieving in practice. Shortcomings in international and national legislature ensures that large parts of the continental shelf, including areas under development, may have little or no legal protection. Increasingly impacted by extensive development, these unique cultural landscapes are ever more at risk. However, heritage challenges posed by such development also create opportunities. An immense amount of data is being generated by development, and there is an opportunity to establish broader cooperative relationships involving industrial stakeholders, national curators, government bodies, and heritage professionals. As a matter of urgency, the archaeological community must better engage with the offshore sector and development process. If achieved, we may revolutionise our knowledge of submerged prehistoric settlement and land use. Otherwise, our capacity to reconstruct prehistoric settlement patterns, learn from past climate change, or simply manage what are among the best-preserved postglacial landscapes globally may be irreparably undermined.

Abstract As CMOS technologies face challenges in dimensional and voltage scaling, the demand for novel logic devices has never been greater, with spin-based devices offering scaling potential, at the cost of significantly high switching energies. Alternatively, magnetoelectric materials are predicted to enable low-power magnetization control, a solution with limited device-level results. Here, we demonstrate voltage-based magnetization switching and reading in nanodevices at room temperature, enabled by exchange coupling between multiferroic BiFeO3 and ferromagnetic CoFe, for writing, and spin-to-charge current conversion between CoFe and Pt, for reading. We show that, upon the electrical switching of the BiFeO3, the magnetization of the CoFe can be reversed, giving rise to different voltage outputs. Through additional microscopy techniques, magnetization reversal is linked with the polarization state and antiferromagnetic cycloid propagation direction in the BiFeO3. This study constitutes the building block for magnetoelectric spin-orbit logic, opening a new avenue for low-power beyond-CMOS technologies.

Descriptive clinical tools for characterizing burn scars are limited by between-user variability and unknown sensitivity to change over time. We previously described preclinical assessment of stereophotogrammetry as a valid measure of burn-related scars. Here, we compared the estimated vs. instrumented measurements of maximum height and total positive volume of 26 burn scars. The burn scars were imaged with the QuantifiCare LifeViz Micro 3D camera. Three experienced wound care therapists first estimated, then measured using 3D Track software, the imaged scars’ height and volume. Two-factor analysis without replication was performed to calculate intraclass correlation coefficients (ICCs) between assessors’ estimated scar height and volume, and measured height and volume. Two-sided Wilcoxon tests were performed comparing the mean estimated height and volume with the estimated and measured outputs. The estimated scar height’s ICC was 0.595, and for volume, it was 0.531. The measured scar height’s ICC was 0.933 and for volume, it was 0.890. The estimated and measured volume were significantly different (z = −2.87, p = 0.041), while the estimated and measured height were not (z = −1.39, p = 0.161). Stereophotogrammic measurement of scar height and volume is more reliable than clinical photograph assessment. Stereophotogrammetry should be utilized when assessing burn scar height and volume, rather than subjective estimates from clinical scar tools.

Occupational and environmental exposures, particularly those related to urban and suburban atmospheres, are increasingly linked to a range of pulmonary diseases. While diagnostic methods for these diseases are well established, analytical tools for assessing elemental contamination in lung tissue remain underutilized. This study introduces a novel framework based on laser‐induced breakdown spectroscopy (LIBS) for the in situ quantification of elemental titanium (Ti) in lung tissues from both animal models and human specimens. Rigorous validation is conducted using animal models exposed to TiO2 P25 nanoparticles and a comparative analysis with inductively coupled plasma mass spectrometry. The novel quantitative metric Svalue demonstrates robust correlation with elemental concentrations, expanding LIBS utility to volumetric organ analysis. This validated methodology is subsequently applied to human lung specimens preserved in paraffin. The research holds significant promise as a diagnostic tool for assessing exposure levels to environmental or occupational hazards, thereby offering valuable contributions to the fields of toxicology and respiratory medicine.

BackgroundPreoperative state anxiety (PSA) is distress and anxiety directly associated with perioperative events. PSA is associated with negative postoperative outcomes such as longer hospital length of stay, increased pain and opioid use, and higher rates of rehospitalization. Psychological prehabilitation, such as education, exposure to hospital environments, and relaxation strategies, has been shown to mitigate PSA; however, there are limited skilled personnel to deliver such interventions in clinical practice. Immersive virtual reality (VR) has the potential for greater accessibility and enhanced integration into an immersive and interactive experience. VR is rarely used in the preoperative setting, but similar forms of stress inoculation training involving exposure to stressful events have improved psychological preparation in contexts such as military deployment. ObjectiveThis study seeks to develop and investigate a targeted PSA intervention in patients undergoing oncological surgery using a single preoperative VR exposure. The primary objectives are to (1) develop a novel VR program for patients undergoing oncological surgery with general anesthesia; (2) assess the feasibility, including acceptability, of a single exposure to this intervention; (3) assess the feasibility, including acceptability, of outcome measures of PSA; and (4) use these results to refine the VR content and outcome measures for a larger trial. A secondary objective is to preliminarily assess the clinical utility of the intervention for PSA. MethodsThis study comprises 3 phases. Phase 1 (completed) involved the development of a VR prototype targeting PSA, using multidisciplinary iterative input. Phase 2 (data collection completed) involves examining the feasibility aspects of the VR intervention. This randomized feasibility trial involves assessing the novel VR preoperative intervention compared to a VR control (ie, nature trek) condition and a treatment-as-usual group among patients undergoing breast cancer surgery. Phase 3 will involve refining the prototype based on feasibility findings and input from people with lived experience for a future clinical trial, using focus groups with participants from phase 2. ResultsThis study was funded in March 2019. Phase 1 was completed in April 2020. Phase 2 data collection was completed in January 2024 and data analysis is ongoing. Focus groups were completed in February 2024. Both the feasibility study and focus groups will contribute to further refinement of the initial VR prototype (phase 3), with the final simulation to be completed by mid-2024. ConclusionsThe findings from this work will contribute to the limited body of research examining feasible and broadly accessible interventions for PSA. Knowledge gained from this research will contribute to the final development of a novel VR intervention to be tested in a large population of patients with cancer before surgery in a randomized clinical trial. Trial RegistrationClinicalTrials.gov NCT04544618; https://www.clinicaltrials.gov/study/NCT04544618 International Registered Report Identifier (IRRID)DERR1-10.2196/55692

Abstract Emulsions are widely used in many industrial applications, and the development of efficient techniques for synthesizing them is a subject of ongoing research. Vapor condensation is a promising method for energy‐efficient, high‐throughput production of monodisperse nanoscale emulsions. However, previous studies using this technique are limited to producing small volumes of water‐in‐oil dispersions. In this work, a new method for the continuous synthesis of nanoscale emulsions (water‐in‐oil and oil‐in‐water) is presented by condensing vapor on free‐flowing surfactant solutions. The viability of oil vaporization and condensation is demonstrated under mild heating/cooling using diverse esters, terpenes, aromatic hydrocarbons, and alkanes. By systematically investigating water vapor and oil vapor condensation dynamics on bulk liquid‐surfactant solutions, a rich diversity of outcomes, including floating films, nanoscale drops, and hexagonally packed microdrops is uncovered. It is demonstrated that surfactant concentration impacts oil spreading, self‐emulsification, and such behavior can aid in the emulsification of condensed oil drops. This work represents a critical step toward advancing the vapor condensation method's applications for emulsions and colloidal systems, with broad implications for various fields and the development of new emulsion‐based products and industrial processes.

Rational engineering of thin nanocomposite layers, deposited in reactive plasmas, requires knowledge on the plasma behavior in order to produce multifunctional deposits with tailored properties (structural, optical, electrical, etc.) This work presents an experimental study of nanoparticles synthesized in the plasma gas-phase and their subsequent use as building-blocks to form layer-by-layer nanostructures. The experiment is performed in a plasma process that successfully combines plasma polymerization of an organosilicon molecular precursor (hexamethyldisiloxane, HMDSO) and sputtering of a metallic (silver) target. Pulsed injection of the precursor is found to promote cyclic nanoparticle formation in Ar/HMDSO reactive plasmas. The plasma electron temperature is found to vary in the range 1.6—2.2 eV as derived from time-resolved optical emission spectroscopy of the plasma energetic conditions. This diagnostic method is also shown to provide a reliable tool for online monitoring of the nanoparticle synthesis process. Two types of layer-by-layer structured nanocomposites can be obtained depending on the type of nanoparticles synthesized: (i) organosilicon nanoparticles of size less than 100 nm in all studied plasma conditions for a large quantity of injected HMDSO and (ii) raspberry-like nanoparticles of size less than 150 nm when the quantity of injected HMDSO is reduced. The organosilicon nanoparticle growth follows a polydimethylsiloxane (PDMS)-like oligomerization scheme in which the R2-Si(-O)2 silicon bond tends towards the formation of polymeric structure in a R3-Si(-O)1 silicon chemical environment, containing Si-(CH2)-Si type bridges that are involved in cross-linking. The elemental composition of the raspberry-like nanoparticles is similar to that of the organosilicon nanoparticles, supplemented by the Ag component. The decorating silver nanoparticles are ∼15 nm of size, round in shape and polycrystalline. There is no evidence for silver oxides in the nanostructures. The Si-O-Ag bridges, revealed by infrared spectroscopy, suggest the presence of junction sites between the metallic and the organosilicon parts of the raspberry-like nanoparticles. The silver nanoparticles are found to decorate the organosilicon nanoparticles to form the raspberry-like nanoparticles in the plasma gas-phase, before being deposited. This reveals a very interesting phenomenon of simultaneous growth of the silver- and organosilicon-parts in the plasma without mixing during the nucleation phase.

**Background:** The association of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) with functional status in the general Medicare population are not well established. **Objectives:** This study examined patient-reported survey data linked with Medicare claims to describe the burden of these vision-threatening retinal diseases (VTRDs) among Medicare beneficiaries. **Methods:** Medicare Current Beneficiary Survey data linked with Medicare Fee-for-Service claims data from 2006 to 2018 were used in a nationally representative retrospective pooled cross-sectional population-based comparison study. Outcomes between community-dwelling beneficiaries with nAMD (n = 1228), DME (n = 101), or RVO (n = 251) were compared with community-dwelling beneficiaries without any VTRDs (n = 104 088), controlling for baseline demographic and clinical differences. Beneficiaries with a diagnosis of nAMD, DME, or RVO during the data year were included; those with other VTRDs were excluded. Outcomes included vision function and loss, overall functioning as assessed by difficulties with activities of daily living (ADLs) and instrumental ADLs (iADLs), anxiety/depression, falls, and fractures. Results: In patient cohorts with nAMD, DME, and RVO, approximately one-third (34.2%-38.3%) reported “a little trouble seeing” (vs 28.3% for controls), and 26%, 17%, and 9%, respectively, reported “a lot of trouble seeing/blindness” (vs 5% of controls). Difficulty walking and doing heavy housework were the most reported ADLs and iADLs, respectively. Compared with those without VTRDs, beneficiaries with nAMD had higher odds of diagnosed vision loss (odds ratio \[OR\], 5.39; 95% confidence interval, 4.06-7.16; P

Abstract Methane (CH4) is a powerful greenhouse gas with ongoing efforts aiming to quantify and map emissions from natural and managed ecosystems. Wetlands play a significant role in the global CH4 budget, but uncertainties in their total emissions remain large, due to a combined lack of CH4 data and fuzzy boundaries between mapped ecosystem categories. European floodplain meadows are anthropogenic ecosystems that originated due to traditional management for hay cropping. These ecosystems are seasonally inundated by river water, and straddle the boundary between grassland and wetland ecosystems; however, an understanding of their CH4 function is lacking. Here, we established a replicated outdoor floodplain‐meadow mesocosm experiment to test how water table depth (45, 30, 15 cm below the soil surface) and plant composition affect CH4 fluxes over an annual cycle. Water table was a major controller on CH4, with significantly higher fluxes (overall mean 9.3 mg m−2 d−1) from the high (15 cm) water table treatment. Fluxes from high water table mesocosms with bare soil were low (mean 0.4 mg m−2 d−1), demonstrating that vegetation drove high emissions. Larger emissions came from high water table mesocosms with aerenchymatous plant species (e.g. Alopecurus pratensis, mean 12.8 mg m−2 d−1), suggesting a role for plant‐mediated transport. However, at low (45 cm) water tables A. pratensis mesocosms were net CH4 sinks, suggesting that there is plasticity in CH4 exchange if aerenchyma are present. Plant cutting to simulate a hay harvest had no effect on CH4, further supporting a role for plant‐mediated transport. Upscaling our CH4 fluxes to a UK floodplain meadow using hydrological modelling showed that the meadow was a net CH4 source because oxic periods of uptake were outweighed by flooding‐induced anoxic emissions. Our results show that floodplain meadows can be either small sources or sinks of CH4 over an annual cycle. Their CH4 exchange appears to respond to soil temperature, moisture status and community composition, all of which are likely to be modified by climate change, leading to uncertainty around the future net contribution of floodplain meadows to the CH4 cycle.

Purpose: To evaluate anti-VEGF treatment patterns and the influence of patient demographic and clinical characteristics on up to 6-year vision outcomes in neovascular age-related macular degeneration. Design: Retrospective, multicenter, noninterventional registry study with up to 6 years of follow-up. Participants: A cohort of 254 655 eyes (226 767 patients) with first anti-VEGF injection and at least 2 years of follow-up; 160 423 eyes had visual acuity (VA) data. Methods: Anonymized patient data were collected in the United States through the IRIS® Registry (Intelligent Research in Sight). Main Outcome Measures: Changes in VA from baseline; frequency of and gaps between intravitreal anti-VEGF injections; treatment discontinuations; switching anti-VEGF agents; and influence of baseline clinical and demographic characteristics on VA. Results: After a mean VA increase of 3.0 ETDRS letters at year 1, annual decreases led to a net loss from baseline of 4.6 letters after 6 years. Patients with longer follow-ups had better baseline and follow-up VA. From a mean of 7.2 in year 1 and 5.6 in year 2, mean injections plateaued between 4.2 to 4.6 in years 3 through 6. Treatment was discontinued in 38.8% of eyes and switched in 32.3%. When adjusting for differences at baseline, every additional injection resulted in a 0.68 letter improvement from baseline to year 1; thus, multiple injections in a year have the potential to be clinically meaningful. Older age, male gender, Medicaid insurance, and not being treated by a retina specialist were associated with a higher likelihood of vision loss at year 1. Of the patients, 58.5% lost ≥ 10 letters VA at least once during follow-up, with 14.5% of patients experiencing sustained poor vision after a median of 3.4 years. Conclusions: After modest mean VA improvement with intravitreal anti-VEGF injections at year 1, patients netted a loss of VA by year 6. Injection frequency decreased over time, and this was paired with a relatively high rate of discontinuation. Modeling suggested that more frequent injections were associated with better VA. Difficulty with continuous adherence to frequent intravitreal injections may have contributed to undertreatment resulting in less-than-optimal vision outcomes. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract Background Living with HIV/AIDS is remarkably stressful and has an adverse effect on one’s physical and mental health. In Sub-Saharan Africa, the introduction of highly active anti-retroviral therapy has led to an increased number of children with perinatal acquired HIV who are living into adolescence and adulthood. Developing strategies to cope with HIV becomes imperative, especially among these adolescents. The study determined the factors that influence coping strategies among adolescents living with HIV. Methods An analytic cross-sectional design was used. A total of 154 adolescents aged 10–19 years living with HIV were systematically sampled at the Fevers Unit of Korle Bu Teaching Hospital from June to December, 2021. The adolescent version of the KidCope tool was used to assess the choice of coping strategies. Stata 16 was used to determine associations between independent variables and the coping strategies identified. Only variables that were significant at p = 0.1 or less in the crude model were used to run the adjusted regression model. The level of significance was set at p = 0.05 with a 95% confidence interval. Results The mean age of participants was 19.2 ± 0.45 years with 51.9% (80/154) of participants being males. A majority, 57.1% of the participants employed positive coping strategies with 87.0% (135/154) using cognitive restructuring strategy. In an adjusted linear regression model, participants coping strategies were significantly associated with their educational level (p = 0.04) and presence of both parents as caregivers (p = 0.02). Conclusion Participants largely adopted positive coping strategies in managing the disease. Factors that influenced the choice of coping strategies were higher levels of education and the presence of both parents as caregivers. The importance of a good social support structure and pursuing further education needs to be emphasized in counselling adolescents living with HIV as it promotes the choice of positive coping strategies.

This article presents an overall examination of how small temperature fluctuations affect P-wave velocity (Vp) measurements and their uncertainties in concrete using embedded piezoelectric transducers. This study highlights the fabrication of custom transducers tailored for long-term concrete monitoring. Accurate and reliable estimation of ultrasonic wave velocities is challenging, since they can be impacted by multiple experimental and environmental factors. In this work, a reliable methodology incorporating correction models is introduced for the quantification of uncertainties in ultrasonic absolute and relative velocity measurements. The study identifies significant influence quantities and suggests uncertainty estimation laws, enhancing measurement accuracy. Determining the onset time of the signal is very time-consuming if the onset is picked manually. After testing various methods to pinpoint the onset time, we selected the Akaike Information Criterion (AIC) due to its ability to produce sufficiently reliable results. Then, signal correlation was used to determine the influence of temperature (20 °C to 40 °C) on Vp in different concrete samples. This technique proved effective in evaluating velocity changes, revealing a persistent velocity decrease with temperature increases for various concrete compositions. The study demonstrated the capability of ultrasonic measurements to detect small variations in the state of concrete under the influence of environmental variables like temperature, underlining the importance of incorporating all influencing factors.

The deposition of a thin LixSny alloy layer by plasma vapor deposition (PVD) on the surface of a Li foil is reported. The formation of a Li-rich alloy is confirmed by the volume expansion (up to 380%) of the layer and by the disappearance of metallic Sn peaks in the X-ray diffractogram. The layer has a much higher hardness than bare Li and can withstand aggressive cycling at 1C. Post-mortem scanning electron microscope observations revealed that the alloy layer remains intact even after fast cycling for hundreds of cycles. A concept of double modification by adding a thin ceramic/polymer layer deposited by a doctor blade on top of the LixSny layer was also reported to be efficient to reach long-term stability for 500 cycles at C/3. Finally, a post-treatment after Sn deposition consisting of a plasma cleaning of the LixSny alloy layer led to a strong improvement in the cycling performance at 1C. The surface is smoother and less oxidized after this treatment. The combination of a Li-rich alloy interlayer, the increase in hardness at the electrolyte/Li interface, and the absence of dissolution of the layer during cycling at high C-rates are reasons for such an improvement in electrochemical performance.

Order of Authorship [...]

During the last twenty years, minimal white spotting associated with blue eyes was selected by feline breeders to create the Altai, Topaz, and Celestial breeds. Additionally, certain breeders introduced this trait in their lineages of purebred cats. The trait has been called “dominant blue eyes (DBE)” and was confirmed to be autosomal dominant in all lineages. DBE was initially described in outbred cats from Kazakhstan and Russia and in two purebred lineages of British cats from Russia, as well as in Dutch Maine Coon cats, suggesting different founding effects. We have previously identified two variants in the Paired Box 3 (PAX3) gene associated with DBE in Maine Coon and Celestial cats; however, the presence of an underlying variant remains undetermined in other DBE breeding lines. Using a genome-wide association study, we identified a single region on chromosome C1 that was associated with DBE in British cats. Within that region, we identified PAX3 as the strongest candidate gene. Whole-genome sequencing of a DBE cat revealed an RD-114 retrovirus LTR (long terminal repeat) insertion within PAX3 intron 4 (namely NC_018730.3:g.206975776_206975777insN[433]) known to contain regulatory sequences. Using a panel of 117 DBE cats, we showed that this variant was fully associated with DBE in two British lineages, in Altai cats, and in some other DBE lineages. We propose that this NC_018730.3:g.206975776_206975777insN[433] variant represents the DBEALT (Altai Dominant Blue Eye) allele in the domestic cat. Finally, we genotyped DBE cats from 14 lineages for the three PAX3 variants and showed that they were not present in four lineages, confirming genetic heterogeneity of the DBE trait in the domestic cat.

Abstract Structural anisotropy in crystals is crucial for controlling light propagation, particularly in the infrared spectral regime where optical frequencies overlap with crystalline lattice resonances, enabling light-matter coupled quasiparticles called phonon polaritons (PhPs). Exploring PhPs in anisotropic materials like hBN and MoO3 has led to advancements in light confinement and manipulation. In a recent study, PhPs in the monoclinic crystal β-Ga2O3 (bGO) were shown to exhibit strongly asymmetric propagation with a frequency dispersive optical axis. Here, using scanning near-field optical microscopy (s-SNOM), we directly image the symmetry-broken propagation of hyperbolic shear polaritons in bGO. Further, we demonstrate the control and enhancement of shear-induced propagation asymmetry by varying the incident laser orientation and polariton momentum using different sizes of nano-antennas. Finally, we observe significant rotation of the hyperbola axis by changing the frequency of incident light. Our findings lay the groundwork for the widespread utilization and implementation of polaritons in low-symmetry crystals.

Abstract Despite advances in cardioprotection, new therapeutic strategies capable of preventing ischemia-reperfusion injury of patients are still needed. Here, we discover that sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2) phosphorylation at serine 663 is a clinical and pathophysiological event of cardiac function. Indeed, the phosphorylation level of SERCA2 at serine 663 is increased in ischemic hearts of patients and mouse. Analyses on different human cell lines indicate that preventing serine 663 phosphorylation significantly increases SERCA2 activity and protects against cell death, by counteracting cytosolic and mitochondrial Ca2+ overload. By identifying the phosphorylation level of SERCA2 at serine 663 as an essential regulator of SERCA2 activity, Ca2+ homeostasis and infarct size, these data contribute to a more comprehensive understanding of the excitation/contraction coupling of cardiomyocytes and establish the pathophysiological role and the therapeutic potential of SERCA2 modulation in acute myocardial infarction, based on the hotspot phosphorylation level of SERCA2 at serine 663 residue.

BackgroundScoliosis constitutes a prevalent comorbidity in adolescents with polyhandicap and frequently leads to other severe impairments, impacting abilities and requiring complex caregiving strategies. Therefore, spinal fusion surgeries are commonly performed to alleviate pain and provide more comfort. However, spine stabilization has not previously been proven to improve the severity health status of adolescents with polyhandicap according to specific clinical scales.ObjectiveThis study describes and compares the severity health status of adolescents with polyhandicap before and after they underwent spinal fusion.MethodsA monocentric retrospective observational study was conducted in the university hospital centre of Saint-Etienne, France. We included between 2009 to 2020, 30 scoliotic adolescents with polyhandicap who underwent spinal fusion performed with the same surgical technique and the same surgeon. The main outcome was the variation in the Polyhandicap Severity Scale (PSS) score after surgery. Secondary outcomes were variations in PSS subscores, quality of life scores, fronto-sagittal X-ray parameters, and measures of surgical complication rates and lengths of stay.ResultsAmong 30 adolescents, 27 PSS analyses were performed. We found a significant improvement between pre- and postoperative PSS scores, mainly for pain and respiratory, digestive, and skin disabilities. These improvements were accompanied by significant reductions in pelvic obliquity, in frontal and sagittal curves. The mean hospital length of stay was 45 days. During postoperative period, patients received a personalized postoperative rehabilitation procedure with spasticity and pain treatments, physiotherapy, and verticalization (wheelchair sitting and positioning devices such as contoured seat intended to increase postural stability). The mortality rate was estimated at 7%. At least 1 complication per patient occurred.ConclusionsWe show that spinal fusion surgeries confer a significant improvement in the severity health status in scoliotic adolescents with polyhandicap.

Vincent Gaffney (born in 1958) is a British archaeologist. In his 40-year career he has worked as a contract field archaeologist, museum curator, researcher and university professor at both Birmingham and Bradford. His expertise includes landscape archaeology, marine landscapes, remote sensing, GIS, computer visualization and communication. He has been awarded several prizes for his outstanding research achievements, among them the British Archaeological Award for the Best Book (2010) and European Archaeological Heritage Prize of the European Association of Archaeologists (2013), as well as an MBE in 2018, making him a Member of the Most Excellent Order of the British Empire. His close collaboration with Slovene and Croatian archaeology dates from the mid-1980s and is still continuing.

Introduction: The Remote First Aid Self-Efficacy Scale was originally developed as a 30-item self-report instrument designed as an evaluation tool for training providers and a reflection tool for course participants. Remote first aid training courses and programs are designed for remote communities, worksites, and other wilderness contexts involving activities such as recreation, education, and therapy. Self-efficacy refers to the strength of the beliefs a person has in their capacity to organize and take the necessary actions towards any given attainment. The purpose of our study was to measure the reliability and validity of the 15-Item Remote First Aid Self-Efficacy Scale (RFA SES) in French and English populations. Methods: Alumni from SIRIUSMEDx wilderness first aid courses were invited via email to complete either a French or English online questionnaire at two different time periods (T1 & T2). Data collection involved using online questionnaires containing demographic questions, the 15-Item RFA SES, and the 10-Item Generalized Self-Efficacy Scale (GSES). Data analysis involved assessing the scale for internal consistency, test re-test reliability, and concurrent validity. Results: There were 58 French and 47 English alumni respondents from SIRIUSMEDx courses for a total of 105 respondents. Internal consistency was high amongst the French group (alpha = .95) and the English group (alpha = .92). Test re-test reliability was high amongst the French group, (r = 0.78, p < .01), and the English group (r = .92, p < .01). The correlations between the RFS SES and GSES were positive and moderate in the French group (r = 0.53, p < .01), as well as in the English group (r = 0.32, p = .03). Conclusions: Results from this study suggest that both the French and English 15-Item RFA SES are reliable and valid. This shorter 15-item version is now available for use, along with the original validated 30-Item version of the RFA SES. Future research should focus on validation of the scale in other contexts and populations, using the scale as a participant reflection tool, and using it for evaluation of training programs and courses.

Summary:. Clinical trials (CTs) are crucial for evidence-based surgical care. Despite growing interest in plastic and reconstructive surgery (PRS) research, the status of PRS CTs remains unknown. We obtained PRS CTs from ClinicalTrials.gov and WHO’s International Clinical Trials Registry Platform (November 2022). Topic modeling identified research themes and machine learning models generated CT-publication pairs. Kaplan-Meier curves visualized CT discontinuation and nonpublication. Of the 4685 PRS CTs identified, 79% were interventional and 81% recruited adults. Most were single-center-led (67%) and academic-funded (77%). Male investigators led 77% of CTs. Female-only patient CTs outnumbered male-only (31% versus 1%). The United States led with 41% of CTs, followed by France, Canada, and China. Industry-funded CTs were higher in the USA, Germany, and Belgium, and academic-funded in France, Canada, and China. PRS CTs clustered into aesthetics (43%), reconstructive (20%), wound healing (8%), peripheral nerve (6%), tumor excision (5%), craniofacial (5%), perioperative pain (5%), and burns (4%). Industry preferred funding aesthetics, whereas academia and industry co-funded wound healing. Publication rates of completed (24%) and terminated (10%) CTs varied by cluster, with perioperative pain CTs exhibiting higher rates. Industry-funded CTs had lower publication rates (hazard ratio: 0.64, 95% confidence interval: 0.5–0.81) and higher discontinuation (hazard ratio: 1.34, confidence interval: 1.06–1.68) driven by sponsors’ decision to terminate prematurely. Global growth in PRS trialome reflects rising interest in evidence-based plastic surgery. Yet, imbalances in participant age, geography, funding source, and trial design influence likelihood of CT discontinuation and publication. Key research gaps include pediatric CTs, accountability in industry-funded research, and multicenter collaborations with underrepresented regions.

Caenorhabditis elegans is a model system widely used in fundamental research. Even though, nematodes are easy to maintain in the laboratory, obtaining large populations of worms require a lot of work and is time consuming. Furthermore, because C. elegans are mainly hermaphrodite it is even more complicated to obtain large amounts of males which make high-throughput experiments using C. elegans males very challenging.In order to overcome these limitations, we developed affordable and rapid methods to:(1) grow large synchronous worm populations(2) easily obtain large amounts of malesWe developed a culture method on plates to grow big synchronized worm populations with the standard incubators used on all worm labs. We also established an easy filtration method allowing to obtain large male populations in an hour. After filtering, the worm population contains more than 90% of adult males and no adult hermaphrodites since all the contaminants are larva and embryos.The culture and the filtering methods we developed are easy to implement and require a very limited investment in equipment and consumables beside the standard one present in worm labs. In addition, this filtering method could be applied to nematode's species similar in size to C. elegans.

The use of smartphones has greatly increased in the last decade and has revolutionized the way that health data are being collected and shared. Mobile applications leverage the ubiquity and technological sophistication of modern smartphones to record and process a variety of metrics relevant to human health, including behavioral measures, clinical data, and disease symptoms. Information processed by mobile applications may have significant utility for increasing biomedical knowledge, both through conventional research and emerging discovery paradigms such as citizen science. However, the ways in which smartphone-collected data may be used in nontraditional modes of biomedical discovery are not well understood, such as using data to train artificially intelligent algorithms and for product development purposes. This paper argues that the use of mobile health data for algorithm training and product development is (a) likely to become a prominent fixture in medicine, (b) likely to raise significant ethical and legal challenges, and (c) warrants immediate scrutiny by policymakers and scholars. We introduce the concept of “smartphone-crowdsourced medical data,” or SCMD, and set out a broad research agenda for addressing concerns associated with this new and potentially momentous practice. We conclude that SCMD for algorithm training raises a number of ethical and legal issues which require further scholarly attention to ensure that individual interests are protected and that emerging health information sources can be used in ways that maximally, and safely, promote medical innovation.

Abstract Background and Aim Patients living with diabetes mellitus have a high burden of psychological distress such as depression and anxiety as well as impaired quality of life, which may negatively impact their adherence to medications, glucose control, and health‐related costs. This study assessed the impact of quality of life and depression on medication adherence among patients with type 2 diabetes (type 2 diabetes mellitus [T2DM]) in a tertiary care setting in Ghana Methods The study was a cross‐sectional study involving 238 patients with diabetes aged 18 years and above. Validated tools were used to assess medication adherence, depressive symptoms, and quality of life. Structural Equation Modeling was adopted to examine the mediation effect of quality of life on the relationship between depression and medication adherence among participants. Results The mean age of the participants was 58.82 ± 13.49, and 169 (71.0%) out of a total of 238 respondents were females. Depression had a significant direct relationship with the quality of life of respondents [aβ (95% confidence interval, CI) = −0.20 (−0.03, −0.00), p

Lymph nodes in various locations of the body differ in their cell composition and gene expression signatures. Here authors show that the rapid postnatal expansion of lymph nodes is governed by CD34 + stromal cells and fibroblastic reticular stromal cell progenitors, distinguished by intrinsic, microbiome-independent core epigenetic blueprints.

Abstract Within healthcare settings, physicians use antibiograms, which offer information on local susceptibility rates, as an aid in selecting empirical antibiotic therapy and avoiding the prescription of potentially ineffective drugs. While antibiograms display susceptibility and resistance data at hospital, city, or region-specific levels and ultimately enable the initiation of antibiogram-based empirical antibiotic treatment, AST reports at the individual patient level and guides treatments away from broad-spectrum antibiotics towards narrower-spectrum antibiotics or the removal of antibiotics entirely. Despite these advantages, AST traditionally requires a 48- to 72-h turn-around; this window of time can be critical for some antimicrobial therapeutic interventions. Herein, we present a direct-from-specimen AST to reduce the time between patient sampling and receipt of lab AST results. The biggest challenge of performing AST directly from unprocessed clinical specimens with an unknown microbial load is aligning the categorical susceptibility report with CLSI reference methods, which start from a fixed inoculum of 0.5 McFarland units prepared using colonies from a sub-culture. In this pilot clinical feasibility study using de-identified remnant specimens collected from MCW, we observed the high and low ends of microbial loads, demonstrating a final categorical agreement of 87.5% for ampicillin, 100% for ciprofloxacin, and 100% for sulfamethoxazole-trimethoprim.

Liquid organic hydrogen carriers (LOHCs) are an interesting alternative for hydrogen storage as the method is based on the reversibility of hydrogenation and dehydrogenation reactions to produce liquid and safe components at room temperature. As hydrogen storage involves a large amount of hydrogen and pure compounds, the design of a three-phase reactor requires the study of gas and liquid-phase kinetics. The gas-phase hydrogenation kinetics of LOHC γ-butyrolactone/1,4-butanediol on a copper-zinc catalyst are investigated here. The experiments were performed with data, taken from the literature, in the temperature and pressure ranges 200–240 °C and 25–35 bar, respectively, for a H2/γ-butyrolactone molar ratio at the reactor inlet of about 90. The best kinetic law takes into account the thermodynamic chemical equilibrium, is based on the associative hydrogen adsorption and is able to simulate temperature and pressure effects. For this model, the confidence intervals are at most 28% for the pre-exponential factors and 4% for the activation energies. Finally, this model will be included in a larger reactor model in order to evaluate the selectivity of the reactions, which may differ depending on whether the reaction takes place in the liquid or gas phase.

Real-time PCRs were developed to characterize Fomes fomentarius lineages occurring in the beech forests of the Ardennes (southern Belgium). A collection of F. fomentarius sensu lato isolates was built up in 2020 and 2021 from basidiocarps developing on beech trunks, stumps, or logs. Two of the 148 isolates tested (monokaryotic and dikaryotic) belonged to the species Fomes inzengae, while the other isolates corresponded to the species Fomes fomentarius sensu stricto. As far as we know, this is the first record of Fomes inzengae in Belgium. This fungus was also found in a mature tree not showing any signs of decay. This demonstrates its endophytic nature. Growth tests at different temperatures, as well as wood degradation tests in accordance with standard NBN EN113 showed different behavior between both species. Passive sticky traps were installed during two growing seasons at the two sites where F. inzengae had been reported. Spores were detected at all collection times between April and July, using the specific molecular test developed. Moreover, in 2023, the DNA concentrations measured were 100 times higher than in 2022. The implications of this new species in Belgium is discussed in the context of climate change.

Stem cells, particularly human iPSCs, constitute a powerful tool for tissue engineering, notably through spheroid and organoid models. While the sensitivity of stem cells to the viscoelastic properties of their direct microenvironment is well-described, stem cell differentiation still relies on biochemical factors. Our aim is to investigate the role of the viscoelastic properties of hiPSC spheroids’ direct environment on their fate. To ensure that cell growth is driven only by mechanical interaction, bioprintable alginate–gelatin hydrogels with significantly different viscoelastic properties were utilized in differentiation factor-free culture medium. Alginate–gelatin hydrogels of varying concentrations were developed to provide 3D environments of significantly different mechanical properties, ranging from 1 to 100 kPa, while allowing printability. hiPSC spheroids from two different cell lines were prepared by aggregation (⌀ = 100 µm, n > 1 × 104), included and cultured in the different hydrogels for 14 days. While spheroids within dense hydrogels exhibited limited growth, irrespective of formulation, porous hydrogels prepared with a liquid–liquid emulsion method displayed significant variations of spheroid morphology and growth as a function of hydrogel mechanical properties. Transversal culture (adjacent spheroids-laden alginate–gelatin hydrogels) clearly confirmed the separate effect of each hydrogel environment on hiPSC spheroid behavior. This study is the first to demonstrate that a mechanically modulated microenvironment induces diverse hiPSC spheroid behavior without the influence of other factors. It allows one to envision the combination of multiple formulations to create a complex object, where the fate of hiPSCs will be independently controlled by their direct microenvironment.

Introduction and Objectives: Ablation of multifocal premature ventricular complexes (PVCs) is challenging. Activation mapping can be performed for the predominant morphology, but may be useless for other less prevalent ones. We aimed to describe the efficacy of an automated pace-mapping software-based ablation strategy for ablating the site of origin of multiple PVC locations. Methods: Consecutive patients referred for ablation of multifocal PVCs were prospectively enrolled. Spontaneous PVC templates were recorded and a detailed pace-mapping map was generated to spot the site of origin of PVCs. Results: A total of 47 PVCs were targeted in 21 patients (five and 16 patients with three or two PVCs morphologies each, respectively). Detailed pace-mapping comprising 73.5±41.6 different pacing locations was performed (best matching 97.2% [IQR 95.9-98.3%] similar to the clinical PVC). Activation points were acquired if possible, although ablation was only based on pace-mapping in 13 (27.6%) foci. Complete acute procedural success was obtained in 14 (66.7%) patients, while one PVC morphology was deliberately not ablated in five patients (23.8%). After 12.3±9.4 months of follow-up, PVC burden decreased from 24.4±10.4% to 5.6±5.0% (p

Objective: To evaluate high-frequency (10-kHz) spinal cord stimulation (SCS) treatment in refractory painful diabetic neuropathy. Patients and Methods: A prospective, multicenter randomized controlled trial was conducted between Aug 28, 2017 and March 16, 2021, comparing conventional medical management (CMM) with 10-kHz SCS+CMM. The participants had hemoglobin A1c level of less than or equal to 10% and pain greater than or equal to 5 of 10 cm on visual analog scale, with painful diabetic neuropathy symptoms 12 months or more refractory to gabapentinoids and at least 1 other analgesic class. Assessments included measures of pain, neurologic function, and health-related quality of life (HRQoL) over 12 months with optional crossover at 6 months. Results: The participants were randomized 1:1 to CMM (n=103) or 10-kHz SCS+CMM (n=113). At 6 months, 77 of 95 (81%) CMM group participants opted for crossover, whereas none of the 10-kHz SCS group participants did so. At 12 months, the mean pain relief from baseline among participants implanted with 10-kHz SCS was 74.3% (95% CI, 70.1-78.5), and 121 of 142 (85%) participants were treatment responders (≥50% pain relief). Treatment with 10-kHz SCS improved HRQoL, including a mean improvement in the EuroQol 5-dimensional questionnaire index score of 0.136 (95% CI, 0.104-0.169). The participants also reported significantly less pain interference with sleep, mood, and daily activities. At 12 months, 131 of 142 (92%) participants were “satisfied” or “very satisfied” with the 10-kHz SCS treatment. Conclusion: The 10-kHz SCS treatment resulted in substantial pain relief and improvement in overall HRQoL 2.5- to 4.5-fold higher than the minimal clinically important difference. The outcomes were durable over 12 months and support 10-kHz SCS treatment in patients with refractory painful diabetic neuropathy. Trial registration: clincaltrials.gov Identifier: NCT03228420

Abstract A significant proportion of carbon (C) captured by terrestrial primary production is buried in lacustrine ecosystems, which have been substantially affected by anthropogenic activities globally. However, there is a scarcity of sedimentary organic carbon (OC) accumulation information for lakes surrounded by highly productive rainforests at warm tropical latitudes, or in response to land cover and climate change. Here, we combine new data from intensive campaigns spanning 13 lakes across remote Amazonian regions with a broad literature compilation, to produce the first spatially-weighted global analysis of recent OC burial in lakes (over ~50-100-years) that integrates both biome type and forest cover. We find that humid tropical forest lake sediments are a disproportionately important global OC sink of 7.4 Tg C yr−1 with implications for climate change. Further, we demonstrate that temperature and forest conservation are key factors in maintaining massive organic carbon pools in tropical lacustrine sediments.

IntroductionThe synovial membrane is the main site of inflammation in rheumatoid arthritis (RA). Here several subsets of fibroblasts and macrophages, with distinct effector functions, have been recently identified. The RA synovium is hypoxic and acidic, with increased levels of lactate as a result of inflammation. We investigated how lactate regulates fibroblast and macrophage movement, IL-6 secretion and metabolism via specific lactate transporters.MethodsSynovial tissues were taken from patients undergoing joint replacement surgery and fulfilling the 2010 ACR/EULAR RA criteria. Patients with no evidence of degenerative or inflammatory disease were used as control. Expression of the lactate transporters SLC16A1 and SLC16A3 on fibroblasts and macrophages was assessed by immunofluorescence staining and confocal microscopy. To test the effect of lactate in vitro we used RA synovial fibroblasts and monocyte-derived macrophages. Migration was assessed via scratch test assays or using trans-well inserts. Metabolic pathways were analysed by Seahorse analyser. IL-6 secretion was determined by ELISA. Bioinformatic analysis was performed on publicly available single cell and bulk RNA sequencing datasets.ResultsWe show that: i) SLC16A1 and SLC16A3 which regulate lactate intake and export respectively, are both expressed in RA synovial tissue and are upregulated upon inflammation. SLC16A3 is more highly expressed by macrophages, while SLC16A1 was expressed by both cell types. ii) This expression is maintained in distinct synovial compartments at mRNA and protein level. iii) Lactate, at the concentration found in RA joints (10 mM), has opposite effects on the effector functions of these two cell types. In fibroblasts, lactate promotes cell migration, IL-6 production and increases glycolysis. In contrast macrophages respond to increases in lactate by reducing glycolysis, migration, and IL-6 secretion.DiscussionIn this study, we provide the first evidence of distinct functions of fibroblasts and macrophages in presence of high lactate levels, opening new insights in understanding the pathogenesis of RA and offering novel potential therapeutic targets.

Cardiac resynchronisation therapy (CRT) has an established role in the management of patients with heart failure, reduced left ventricular ejection fraction (LVEF 130 msec). Despite the complex pathophysiology of left ventricular (LV) dyssynchrony and the increasing evidence supporting the identification of specific electromechanical substrates that are associated with a higher probability of CRT response, the assessment of LVEF is the only imaging-derived parameter used for the selection of CRT candidates.This review aims to (1) provide an overview of the evolution of cardiac imaging for the assessment of LV dyssynchrony and its role in the selection of patients undergoing CRT; (2) highlight the main pitfalls and advantages of the application of cardiac imaging for the assessment of LV dyssynchrony; (3) provide some perspectives for clinical application and future research in this field.Conclusionthe road for a more individualized approach to resynchronization therapy delivery is open and imaging might provide important input beyond the assessment of LVEF.

Refractory hypoxemia in patients with acute respiratory distress syndrome treated with mechanical ventilation is one of the most challenging conditions in human and veterinary intensive care units. When a conventional lung protective approach fails to restore adequate oxygenation to the patient, the use of recruitment maneuvers and positive end-expiratory pressure to maximize alveolar recruitment, improve gas exchange and respiratory mechanics, while reducing the risk of ventilator-induced lung injury has been suggested in people as the open lung approach. Although the proposed physiological rationale of opening and keeping open previously collapsed or obstructed airways is sound, the technique for doing so, as well as the potential benefits regarding patient outcome are highly controversial in light of recent randomized controlled trials. Moreover, a variety of alternative therapies that provide even less robust evidence have been investigated, including prone positioning, neuromuscular blockade, inhaled pulmonary vasodilators, extracorporeal membrane oxygenation, and unconventional ventilatory modes such as airway pressure release ventilation. With the exception of prone positioning, these modalities are limited by their own balance of risks and benefits, which can be significantly influenced by the practitioner's experience. This review explores the rationale, evidence, advantages and disadvantages of each of these therapies as well as available methods to identify suitable candidates for recruitment maneuvers, with a summary on their application in veterinary medicine. Undoubtedly, the heterogeneous and evolving nature of acute respiratory distress syndrome and individual lung phenotypes call for a personalized approach using new non-invasive bedside assessment tools, such as electrical impedance tomography, lung ultrasound, and the recruitment-to-inflation ratio to assess lung recruitability. Data available in human medicine provide valuable insights that could, and should, be used to improve the management of veterinary patients with severe respiratory failure with respect to their intrinsic anatomy and physiology.

Abstract This study aims to examine the trends in the sustainability performance indicators disclosed in sustainability reports by Canadian companies. Our sample is comprised of eight companies in four sectors and our observations cover a 19-year period. The results of our analysis show a general increase over time of sustainability performance indicators disclosed, as well as varying degrees of coverage of the three sustainability dimensions. While the focus was more on environmental performance in the early 2000s, social performance indicators, such as employment practices and human rights, have now gained more traction. In addition, the scope of sustainability performance indicators disclosed in sustainability reports reached a plateau around 2010. Our results highlight the need for a standardised approach to sustainability reporting that would help overcome the shortcomings of voluntary initiatives and improve the overall comparability of voluntary reporting mechanisms.

Non-coding variants can regulate transcription factor binding and gene expression at variable chromatin modules. Here, the authors show that a germline variant induces transcription factor nucleation through chromatin compaction leading to AXIN2 up-regulation and is associated to better prognosis in chronic lymphocytic leukaemia.