Search

Abstract Asthma-related mortality is high in low- and middle-income countries. Little is known about public perceptions of inhaled medicines. We conducted semi-structured interviews with asthma patients and healthcare workers at three secondary care facilities in The Gambia, between August and November 2022. Thematic analysis was used to interpret these data. A total of 20 patients and 15 healthcare workers were interviewed. Both groups noted limited access to inhalers was an issue resulting in continued use of oral medications. Some patients recognised the benefits of inhalers, yet beliefs that inhalers were dangerous were common. Reliance on oral short-acting beta agonists meant patients saw asthma as a recurrent acute condition resulting in an emphasis on hospital management with little awareness of inhaled preventative medicines. Increasing access to inhaled medicines has the potential to reduce costly avoidable admissions, but socio-cultural factors, in addition to medication supply, need addressing.

Abstract Background Cross-sectional studies suggest a relationship between diabetes status and weaker grip strength (GS) in adulthood and limited evidence from longitudinal studies has focussed on the association with average change in GS. We aimed to investigate whether diabetes status was related to membership of distinct GS trajectories in mid-to-late adulthood in 2,263 participants in the Medical Research Council National Survey of Health and Development. Methods Grip strength (kg) was measured at 53, 60–64 and 69 years. Pre-/diabetes was defined at 53 years based on HbA1c > 5.6% and/or doctor-diagnosis of diabetes. Sex-specific latent class trajectory models were developed and multinomial logistic regression was used to investigate the association between pre-/diabetes status and membership into GS trajectory classes. Results For both males and females, a 3-class solution (‘High’, ‘Intermediate’, ‘Low’) provided the best representation of the GS data and the most plausible solution. There was no evidence that pre-/diabetes status was associated with class membership in either sex: e.g., adjusted odds ratios of being in the ‘Low’ class (vs. ‘High’) for males with pre-/diabetes (vs. no-diabetes) was 1.07 (95% CI:0.45,2.55). Conclusion Using a flexible data-driven approach to identify GS trajectories between 53 and 69 years, we observed three distinct GS trajectories, all declining, in both sexes. There was no association between pre-/diabetes status at 53 years and membership into these GS trajectories. Understanding the diabetes status―GS trajectories association is vital to ascertain the consequences that projected increases in pre-/diabetes prevalence’s are likely to have.

This paper addresses the remote sensing challenging field of urban mixed pixels on a medium spatial resolution satellite data. The tentatively named Normalized Difference Built-up and Surroundings Unmixing Index (NDBSUI) is proposed by using Landsat-8 Operational Land Imager (OLI) bands. It uses the Shortwave Infrared 2 (SWIR2) as the main wavelength, the SWIR1 with the red wavelengths, for the built-up extraction. A ratio is computed based on the normalization process and the application is made on six cities with different urban and environmental characteristics. The built-up of the experimental site of Yaoundé is extracted with an overall accuracy of 95.51% and a kappa coefficient of 0.90. The NDBSUI is validated over five other sites, chosen according to Cameroon’s bioclimatic zoning. The results are satisfactory for the cities of Yokadouma and Kumba in the bimodal and monomodal rainfall zones, where overall accuracies are up to 98.9% and 97.5%, with kappa coefficients of 0.88 and 0.94 respectively, although these values are close to those of three other indices. However, in the cities of Foumban, Ngaoundéré and Garoua, representing the western highlands, the high Guinea savannah and the Sudano-sahelian zones where built-up is more confused with soil features, overall accuracies of 97.06%, 95.29% and 74.86%, corresponding to 0.918, 0.89 and 0.42 kappa coefficients were recorded. Difference of accuracy with EBBI, NDBI and UI are up to 31.66%, confirming the NDBSUI efficiency to automate built-up extraction and unmixing from surrounding noises with less biases.

Drought affects all human activities and ecosystems. Nearly 40 percent of the world’s population inhabit Drylands, and they depend on agriculture for their food, security and livelihoods. Among the remote sensing indices developed, the Land Surface General Drought Index (LSGDI) was recently proposed. This paper proposes an improved model of LSGDI to face the issue of drought in semi-arid and arid regions. The experiment was conducted for the Maga’s floodplain, in North-Cameroon. The method uses satellite images of Landsat in 1987, 2003 and 2018, for January and March or April, corresponding to the middle and the end of the dry season. A Vegetation Moisture Index (VMI) and a Normalized Difference Soil Drought Index (NDSoDI) are both developed. On an orthogonal plan, their projections give a drought line that expresses the improved LSGDI (LSGDI2) as the root sum square of the NDSoDI and the VMI. The LSGDI2 results are ranged in [0.09 – 0.14] interval, which is used to define the threshold and ease the qualifiers for drought classes. The visual patterns easily match the sandy areas of the original Landsat images with the highest values, while the vegetation and water areas match the lowest values. Compared with the LSGDI and Second Modified Perpendicular drought Index (MPDI1), the new index reflectance values are higher. Finally, although LSGDI2 curve’s evolution follows the NDSoDI one at 94%, the new spectral index values depends on the both components, helping to map highest values of drought and moisture in Maga’s floodplain, for a sustainable rice culture expansion.

Abstract Body Adults with ADHD describe self-medicating with cannabis. A small number of psychiatrists in the US prescribe cannabis medication for ADHD, despite there being no evidence from trials. The EMA-C trial (Experimental Medicine in ADHD-Cannabinoids) was a pilot randomised placebo-controlled experimental study of a cannabinoid medication, Sativex Oromucosal Spray, in 30 adults with ADHD. The primary outcome was cognitive performance and activity level using the QbTest. Secondary outcomes included ADHD and emotional lability (EL) symptoms. From 17.07.14-18.06.15, 30 participants were randomly assigned to the active (n=15) or placebo (n=15) group. For the primary outcome, no significant difference was found in the intent-to-treat analysis although the overall pattern of scores was such that the active group usually had scores that were better than the placebo group (Est=-0.17,95%CI-0.40-0.07, p=0.16, n=15/11 active/placebo). For secondary outcomes Sativex was associated with a nominally significant improvement in hyperactivity/impulsivity (p=0.03) and a cognitive measure of inhibition (p=0.05), and a trend towards improvement for inattention (p=0.10) and EL (p=0.11). Per-protocol effects were higher. Results did not meet significance following adjustment for multiple testing. One serious (muscular seizures/spasms) and three mild adverse events occurred in the active group and one serious (cardiovascular problems) adverse event in the placebo group. Adults with ADHD may represent a subgroup of individuals who experience a reduction of symptoms and no cognitive impairments following cannabinoid use. While not definitive, this study provides preliminary evidence supporting the self-medication theory of cannabis use in ADHD and the need for further studies of the endocannabinoid system in ADHD. Disclosure During this work-RC was a Ph.D. student funded by a grant to PA from Vifor Pharma. PA received funds (consultancy/sponsored talks/research/education) from Shire, Lilly, Novartis, Janssen, PCMScientific, Vifor Pharma, QBTech. Sativex was free from GW Pharm

The potential of advanced tree-based models and optimized deep learning algorithms to predict fluvial bedload transport was explored, identifying the most flexible and accurate algorithm, and the optimum set of readily available and reliable inputs. Using 926 datasets for 20 rivers, the performance of three groups of models was tested: (1) standalone tree-based models Alternating Model Tree (AMT) and Dual Perturb and Combine Tree (DPCT); (2) ensemble tree-based models Iterative Absolute Error Regression (IAER), ensembled with AMT and DPCT; and (3) optimized deep learning models Long Short-Term Memory (LSTM) and Recurrent Neural Network (RNN) ensembled with Grey Wolf Optimizer. Comparison of the predictive performance of the models with that of commonly used empirical equations and sensitivity analysis of the driving variables revealed that: (i) the coarse grain-size percentile D90 was the most effective variable in bedload transport prediction (where Dx is the xth percentile of the bed surface grain size distribution), followed by D84, D50, flow discharge, D16, and channel slope and width; (ii) all tree-based models and optimized deep learning algorithms displayed ‘very good’ or ‘good’ performance, outperforming empirical equations; and (iii) all algorithms performed best when all input parameters were used. Thus, a range of different input variable combinations must be considered in the optimization of these models. Overall, ensemble algorithms provided more accurate predictions of bedload transport than their standalone counterpart. In particular, the ensemble tree-based model IAER-AMT performed most strongly, displaying great potential to produce robust predictions of bedload transport in coarse-grained rivers based on a few readily available flow and channel variables.

Abstract Autophagy plays an important role in determining stem‐cell differentiation. During the osteogenic differentiation of mesenchymal stem cells (MSCs), autophagosome formation is upregulated but the reason is unknown. A long‐standing quest in the autophagy field is to find the membrane origin of autophagosomes. In this study, cytoplasmic coat protein complex II (COPII) vesicles, endoplasmic reticulum‐derived vesicles responsible for the transport of storage proteins to the Golgi, are demonstrated to be a critical source of osteoblastic autophagosomal membrane. A significant correlation between the number of COPII vesicle and the autophagy level is identified in the rat bone tissues. Disruption of COPII vesicles restrained osteogenesis and decreased the number and size of autophagosomes. SEC31a (an outer coat protein of COPII vesicle) is found to be vital to regulate COPII vesicle‐dependent autophagosome formation via interacting with ATG9a of autophagosomal seed vesicles. The interference of Sec31a inhibited autophagosome formation and osteogenesis in vitro and in vivo. These results identified a novel mechanism of autophagosome formation in osteogenic differentiation of stem cells and identified SEC31a as a critical protein that mediates the interplay between COPII and ATG9a vesicles. These findings broaden the understanding of the regulatory mechanism in the osteogenic differentiation of MSCs.

Este trabajo presenta un estudio sobre la caracterización de las propiedades mecánicas de uniones soldadas con alambre tubular autoprotegido, de acero API 5L-X80. En este sentido, se evalúa la influencia de la temperatura de precalentamiento, manteniendo el aporte de calor uniforme. Todas las uniones soldadas se realizaron en la posición plana (IG), con la antorcha fíja y la tubería girando. Se utilizó un tubo de 762 mm de diámetro exterior y 16 mm de espesor. Las soldaduras se aplicaron sobre una unión de tope con bisel en V simple, utilizando 6 pasadas, con tres niveles de temperatura de precalentamiento (ambiente, 100 °C y 160 °C). Estas temperaturas se mantuvieron como temperatura entre pasadas. El metal de aporte, del tipo E71T8-K6, se utilizó en la condición undermatched. La caracterización de las uniones se presenta en función de los resultados de los ensayos mecánicos de resistencia a la tracción, dureza e impacto. Estos ensayos se realizaron de acuerdo a las normas API 1104, AWS y ASTM. Las normas API 1104 y API 5L se emplearon como criterio de aceptación. A partir de los análisis realizados fue posible observar que se pueden soldar tuberías de acero API 5L-X80 con alambre tubular autoprotegido, atendiendo a los requisitos 4e calidad especificados por las normas de referencia, sin necesidad de utilizar temperatura de precalentamiento.

Abstract Background Human dental pulp stem cells (hDPSCs) have received widespread attention in the fields of tissue engineering and regenerative medicine. Although amphiregulin (AREG) has been shown to play a vital function in the biological processes of various cell types, its effects on DPSCs remain largely unknown. The aim of this study was to explore the specific role of AREG as a biologically active factor in the regeneration of dental pulp tissue. Methods The growth of hDPSCs, together with their proliferation and apoptosis, in response to AREG was examined by CCK-8 assay and flow cytometry. We explored the effects of AREG on osteo/odontogenic differentiation in vitro and investigated the regeneration and mineralization of hDPSCs in response to AREG in vivo. The effects of AREG gain- and loss-of-function on DPSC differentiation were investigated following transfection using overexpression plasmids and shRNA, respectively. The involvement of the mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the mineralization process and the expression of odontoblastic marker proteins after AREG induction were investigated by using Alizarin Red S staining and Western blotting, respectively. Results AREG (0.01–0.1 µg/mL) treatment of hDPSCs from 1 to 7 days increased hDPSCs growth and affected apoptosis minimally compared with negative controls. AREG exposure significantly promoted hDPSC differentiation, shown by increased mineralized nodule formation and the expression of odontoblastic marker protein expression. In vivo micro-CT imaging and quantitative analysis showed significantly greater formation of highly mineralized tissue in the 0.1 μg/mL AREG exposure group in DPSC/NF-gelatin-scaffold composites. AREG also promoted extracellular matrix production, with collagen fiber, mineralized matrix, and calcium salt deposition on the composites, as shown by H&E, Masson, and Von Kossa staining. Furthermore, AREG overexpression boosted hDPSC differentiation while AREG silencing inhibited it. During the differentiation of hDPSCs, AREG treatment led to phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and PI3K/Akt. Notably, a specific inhibitor of ERK, JNK, and PI3K/Akt signaling markedly reduced AREG-induced differentiation, as well as levels of phosphorylated ERK and JNK in hDPSCs. Conclusions The data indicated that AREG promoted odontoblastic differentiation and facilitated regeneration and mineralization processes in hDPSCs.

Abstract This study quantifies the association between the COVID‐19 economic downturn and 2020 tropospheric ozone anomalies above Europe and western North America, and their impact on long‐term trends. Anomaly detection for an atmospheric time series is usually carried out by identifying potentially aberrant data points relative to climatological values. However, detecting ozone anomalies from sparsely sampled ozonesonde profiles (once per week at most sites) is challenging due to ozone's high temporal variability. We first demonstrate the challenges for summarizing regional trends based on independent time series from multiple nearby ozone profiling stations. We then propose a novel regional‐scale anomaly detection framework based on generalized additive mixed models, which accounts for the sampling frequency and inherent data uncertainty associated with each vertical profile data set, measured by ozonesondes, lidar or commercial aircraft. This method produces a long‐term monthly time series with high vertical resolution that reports ozone anomalies from the surface to the middle‐stratosphere under a unified framework, which can be used to quantify the regional‐scale ozone anomalies during the COVID‐19 economic downturn. By incorporating extensive commercial aircraft data and frequently sampled ozonesonde profiles above Europe, we show that the complex interannual variability of ozone can be adequately captured by our modeling approach. The results show that free tropospheric ozone negative anomalies in 2020 are the most profound since the benchmark year of 1994 for both Europe and western North America, and positive trends over 1994–2019 are diminished in both regions by the 2020 anomalies.

Objective: The aim of this observational study was to determine the optimal timing of interleukin-6 receptor inhibitor (IL6ri) administration for coronavirus disease 2019 (COVID-19). Methods: Patients with COVID-19 were given an IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients with lower oxygen requirements. Patients were divided into two groups: those requiring ≤45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. The main outcomes were all-cause mortality, discharge alive from hospital, and extubation. Results: A total of 255 COVID-19 patients were treated with IL6ri (149 stage IIB and 106 stage III). Patients treated in stage IIB had lower mortality than those treated in stage III (adjusted hazard ratio (aHR) 0.24, 95% confidence interval (CI) 0.08–0.74). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR 1.43, 95% CI 1.06–1.93) and were less likely to be intubated (aHR 0.43, 95% CI 0.24–0.79). Conclusions: IL6ri administration prior to >45% FiO2 requirement was associated with improved COVID-19 outcomes. This can guide clinical management pending results from randomized controlled trials.

Flooding and erosion will pose increasing challenges to urban settlements and critical infrastructure, such as roads and power grids in the future. Improved projections on the impact of climate change to critical infrastructure are essential to assist future planning. This paper uses hydro-sedimentary modelling to predict river erosion threats to electricity transmission infrastructure in an urbanised river valley under multiple increasing flow magnitude scenarios. We use a coupled hydrodynamic and landscape evolution model, CAESAR-Lisflood, to simulate river channel changes along a reach of the River Mersey, UK from the present day to 2050. A range of synthetic flow scenarios, based on recent hydrological records, was used in the model ranging from ‘no change’ up to a flow with 50% higher magnitude. The results revealed: (1) riverbank erosion will pose significant threats to several transmission towers located along the river, requiring intervention to avoid destabilisation by the moving channel; (2) the total area of floodplain erosion and deposition ≥ 0.5 m deep was positively related to increasing projected flow magnitudes. However, through running a ‘low’ and ‘high’ erosion version of the model, the simulations revealed these threats were most sensitive to the calibration of the erosion component of the model, illustrating the challenges and uncertainty in forecasting long-term river channel change; and (3) how long-term simulations can assist in adaptation planning for electricity transmission towers. Further reach- and catchment-scale modelling will be necessary to determine the timings of large floods more accurately, which produce the most significant erosion and deposition events, and to evaluate the efficacy of protections to transmission towers.

In recent years it has become understood that quantum oscillations of the magnetization as a function of magnetic field, long recognized as phenomena intrinsic to metals, can also manifest in insulating systems. Theory has shown that in certain simple band insulators, quantum oscillations can appear with a frequency set by the area traced by the minimum gap in momentum space, and are suppressed for weak fields by an intrinsic "Dingle damping" factor reflecting the size of the bandgap. Here we examine quantum oscillations of the magnetization in excitonic and Kondo insulators, for which interactions play a crucial role. In models of these systems, self-consistent parameters themselves oscillate with changing magnetic field, generating additional contributions to quantum oscillations. In the low-temperature, weak-field regime, we find that the lowest harmonic of quantum oscillations of the magnetization are unaffected, so that the zero-field bandgap can still be extracted by measuring the Dingle damping factor of this harmonic. However, these contributions dominate quantum oscillations at all higher harmonics, thereby providing a route to measure this interaction effect.