Particulate Matter (PM) emissions from passenger vehicles have attracted considerable interest over the last decade. In order to reduce PM emissions, improving maximum injection pressure has been a developing trend for new generation GDI engines. However, comparing gasoline and ethanol impingement spray characteristics from a GDI injector under high injection pressure is still unclear. In this paper, a comparative investigation on both the macroscopic and microscopic characteristics of impingement spray from a GDI injector fuelled with gasoline and ethanol was performed under injection pressure up to 50 MPa, providing new findings to promote a more homogeneous air–fuel mixture and reduce PM emissions. The experimental results show that under the same PI (injection pressure), rebound height of gasoline impingement spray is a bit higher than ethanol. AS (spray area) of gasoline is slightly higher than ethanol under PI=10MPa. However, under PI=30MPa and PI=50MPa, AS of gasoline is gradually exceeded by that of ethanol as time progresses. By increasing PI to 50 MPa, the difference in DN (diffusion distance of the near side) between gasoline and ethanol is greatly reduced, meantime DF (diffusion distance of the far side) becomes weaker than ethanol. For both gasoline and ethanol, with the increase PI from 10 MPa to 50 MPa, VN (average normal component of droplet velocity) and VT (average tangential component of droplet velocity) of incident droplets increase by around 1 m/s. Meantime, there is a slight decrease in the absolute value of VN and VT of reflected droplets. DSMD (Sauter mean diameter of droplets) presents a significant decreasing trend with the increase of PI. Besides, a smaller DSMD can be seen for the gasoline impingement spray compared to ethanol under the same PI.
Various design modifications have been proposed for tendon-driven continuum robots to improve their stiffness and workspace. One of them is using locking mechanisms to constrain the lengths of rods or passive backbones along the robot. However, physics-based models used to predict these robots' behaviour commonly assume that the curvature of the locked portion does not change during robot actuation or that the effects of friction and gravity are negligible. In addition, these models do not consider the variations in twist on force application. In this letter, we propose a 3D static model for tendon-driven continuum robots experiencing locking due to length constraints on rods along their backbone. The proposed model is evaluated on prototypes of length 240 mm, with up to three locking mechanisms and has an accuracy of 3.63% w.r.t. length. Using the proposed model, a compliance analysis is performed studying the evolution of the robot compliance with the position of the locking mechanisms. An actuation strategy is proposed that can allow the robot to achieve the same shape with different compliance.
The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This is the first guideline on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes published by the IWGDF. We followed the GRADE Methodology to devise clinical questions in the PACO (Population, Assessment, Comparison, Outcome) and PICO (Population, Intervention, Comparison, Outcome) format, conducted a systematic review of the medical literature, and developed recommendations with the rationale. The recommendations are based on the evidence from our systematic review, expert opinion when evidence was not available, and also taking into account weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to an intervention. We here present the 2023 Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus and also suggest key future topics of research.
Objectives: To describe the policies about parent visiting and involvement in care during admission to French PICUs. Design: A structured questionnaire was emailed to the chief of each of 35 French PICUs. Data about visiting policies, involvement in care, evolution of policies, and general characteristics were collected from April 2021 to May 2021. A descriptive analysis was conducted. Setting: Thirty-five PICUs in France. Patients: None. Interventions: None. Measurements and main results: Twenty-nine of 35 (83%) PICUs replied. Twenty-four-hour access for parents was reported for all PICUs responding. Other allowed visitors were grandparents (21/29, 72%) and siblings (19/29, 66%) with professional support. Simultaneous visits were restricted to two visitors in 83% (24/29) of PICUs. Family presence was always permitted during medical rounds for 20 of 29 (69%) PICUs. Most of the units rarely or never allowed parental presence during the most invasive procedures, such as central venous catheter placement (18/29, 62%) and intubation (22/29, 76%). Conclusions: Unrestricted access to the PICU, for both parents, was available in all responding French units. There were, however, restrictions on the number of visitors and the presence of other family members at the bedside. Moreover, permission for parental presence during care procedures was heterogenous, and mainly restricted. National guidelines and educational programs are needed to support family wishes and promote acceptance by healthcare providers in French PICUs.
There is growing evidence that cytonuclear incompatibilities (i.e. disruption of cytonuclear coadaptation) might contribute to the speciation process. In a former study, we described the possible involvement of plastid-nuclear incompatibilities in the reproductive isolation between four lineages of Silene nutans (Caryophyllaceae). Because organellar genomes are usually cotransmitted, we assessed whether the mitochondrial genome could also be involved in the speciation process, knowing that the gynodioecious breeding system of S. nutans is expected to impact the evolutionary dynamics of this genome. Using hybrid capture and high-throughput DNA sequencing, we analyzed diversity patterns in the genic content of the organellar genomes in the four S. nutans lineages. Contrary to the plastid genome, which exhibited a large number of fixed substitutions between lineages, extensive sharing of polymorphisms between lineages was found in the mitochondrial genome. In addition, numerous recombination-like events were detected in the mitochondrial genome, loosening the linkage disequilibrium between the organellar genomes and leading to decoupled evolution. These results suggest that gynodioecy shaped mitochondrial diversity through balancing selection, maintaining ancestral polymorphism and, thus, limiting the involvement of the mitochondrial genome in evolution of hybrid inviability between S. nutans lineages.
The loss of pancreatic β-cell identity emerges as an important feature of type 2 diabetes development, but the molecular mechanisms are still elusive. Here, we explore the cellautonomous role of the cell cycle regulator and transcription factor E2F1 in the maintenance of β-cell identity, insulin secretion and glucose homeostasis. We show that the β-cell-specific loss of E2f1 function in mice triggers glucose intolerance associated with defective insulin secretion, an altered endocrine cell mass, a downregulation of many β-cell genes and a concomitant increase of non-β-cell markers. Mechanistically, the epigenomic profiling of promoters of these non-β-cell upregulated genes identified an enrichment of bivalent H3K4me3/H3K27me3 or H3K27me3 marks. Conversely, promoters of downregulated genes were enriched in active chromatin H3K4me3 and H3K27ac histone marks. We find that specific E2f1 transcriptional, cistromic and epigenomic signatures are associated with these β-cell dysfunctions, with E2F1 directly regulating several β-cell genes at the chromatin level. Finally, the pharmacological inhibition of E2F transcriptional activity in human islets also impairs insulin secretion and the expression of β-cell identity genes. Our data suggest that E2F1 is critical for maintaining β-cell identity and function through a sustained control of β-cell and non β-cell transcriptional programs.
Background: West African Economic and Monetary Union (UEMOA) countries are characterised by a high prevalence of informal use of medicinal plants and traditional medicines by their population for health care, requiring the establishment of pharmacovigilance, in order to monitor the associated health risks. However, the state of implementation of pharmacovigilance for traditional medicines in UEMOA countries is not known. Objective: This study aimed to assess the state of implementation of pharmacovigilance for traditional medicines in the eight UEMOA countries, describing the relevant community provisions, assessing the integration of traditional medicines monitoring into national pharmacovigilance systems and identifying related national challenges. Methods: This was a cross-sectional study using questionnaires, conducted between 1 May and 31 August 2022. A face-to-face questionnaire was administered to officials responsible for the issue within UEMOA and the West African Health Organisation (WAHO). A second online questionnaire was specifically sent to the pharmacovigilance focal points of the eight UEMOA countries. Questionnaires were designed using the WHO indicators for pharmacovigilance. The face-to-face questionnaire collected two types of data, namely community policies and regulations on pharmacovigilance and technical and financial support from sub-regional organisations to countries. The online questionnaire sent to countries collected four categories of data on the study issue: structural data, process data, impact data and data on national challenges. Results: As a community provision, WAHO has a harmonised regulatory framework for phytovigilance. The monitoring of traditional medicines is not effectively implemented in the pharmacovigilance systems of UEMOA countries. Only two reports of adverse events due to traditional medicines have so far been recorded in the Union. The countries have neither funding nor sufficient human resources for pharmacovigilance in general. Monitoring of traditional medicines in the unregulated market, training of stakeholders, risk communication, and integration of traditional health practitioners in reporting systems are the main challenges of countries for the development of pharmacovigilance for traditional medicines. Conclusion: The effective compliance of WAHO's harmonised phytovigilance regulatory framework by UEMOA countries and addressing the challenges identified by the countries constitute the basis for the development of pharmacovigilance for traditional medicines within UEMOA.
HLA‐DRB1*14:255 differs from HLA‐DRB1*14:54:01 by one nucleotide substitution in codon 205 in exon 4.
Due to the constant expansion of China’s industrial sector, environmental pollution has become a major issue that requires urgent and continuous government intervention. We use a panel of 239 Chinese cities for 2007 – 2019 and a system Generalized Method of Moments (GMM) model to estimate the impact of fiscal expenditures on industrial pollution levels. Our results suggest that local fiscal expenditures have a positive and significant impact on industrial wastewater generation, sulfur dioxide emissions, and smoke and dust pollution levels, as well as on pollution intensity. Conversely, expanding environmental protection initiatives helps significantly improve environmental quality. In addition, government expenditure on education has a negative and statistically significant influence on both industrial wastewater and smoke and dust pollution, while higher spending on research and development (R&D) helps curb sulfur dioxide emissions and pollution intensity. We also demonstrate that green financing initiatives can strengthen the negative relationship between education expenditure and R&D spending on the one hand and pollution level and its intensity on the other. Hence, our results offer suggestions for improving the composition of government expenditures and therefore better controlling pollution levels, which can be achieved by increasing investment in environmental protection, spending more on education and R&D, and promoting the spread of green financing initiatives.
Balancing selection is a form of natural selection maintaining diversity at the sites it targets and at linked nucleotide sites. Due to selection favouring heterozygosity, it has the potential to facilitate the accumulation of a “sheltered” load of tightly linked recessive deleterious mutations. However, precisely evaluating the extent of these effects has remained challenging. Taking advantage of plant self-incompatibility as one of the best-understood examples of long-term balancing selection, we provide a highly resolved picture of the genomic extent of balancing selection on the sheltered genetic load. We used targeted genome resequencing to reveal polymorphism of the genomic region flanking the self-incompatibility locus in three sample sets in each of the two closely related plant species Arabidopsis halleri and A. lyrata, and used 100 control regions from throughout the genome to factor out differences in demographic histories and/or sample structure. Nucleotide polymorphism increased strongly around the S-locus in all sample sets, but only over a limited genomic region, as it became indistinguishable from the genomic background beyond the first 25-30 kb. Genes in this chromosomal interval exhibited no excess of mutations at 0-fold degenerated sites relative to putatively neutral sites, hence revealing no detectable weakening of the efficacy of purifying selection even for these most tightly linked genes. Overall, our results are consistent with the predictions of a narrow genomic influence of linkage to the S-locus, and clarify how natural selection in one genomic region affects the evolution of the adjacent genomic regions.
Background: Diffusion-weighted imaging lesion reversal (DWIR) is frequently observed after mechanical thrombectomy for acute ischemic stroke, but little is known about age-related differences and impact on outcome. We aimed to compare, in patients <80 versus ≥80 years old, (1) the effect of successful recanalization on DWIR and (2) the impact of DWIR on functional outcome. Methods: We retrospectively analyzed data of patients treated for an anterior circulation acute ischemic stroke with large vessel occlusion in 2 French hospitals, who underwent baseline and 24-hour follow-up magnetic resonance imaging, with baseline DWI lesion volume ≥10 cc. The percentage of DWIR (DWIR%), was calculated as follows: DWIR%=(DWIR volume/baseline DWI volume)×100. Data on demographics, medical history, and baseline clinical and radiological characteristics were collected. Results: Among 433 included patients (median age, 68 years), median DWIR% after mechanical thrombectomy was 22% (6-35) in patients ≥80, and 19% (interquartile range, 10-34) in patients <80 (P=0.948). In multivariable analyses, successful recanalization after mechanical thrombectomy was associated with higher median DWIR% in both ≥80 (P=0.004) and <80 (P=0.002) patients. In subgroup analyses performed on a minority of subjects, collateral vessels status score (n=87) and white matter hyperintensity volume (n=131) were not associated with DWIR% (P>0.2). In multivariable analyses, DWIR% was associated with increased rates of favorable 3-month outcomes in both ≥80 (P=0.003) and <80 (P=0.013) patients; the effect of DWIR% on outcome was not influenced by the age group (P interaction=0.185) Conclusions: DWIR might be an important and nonage-dependent effect of arterial recanalization, as it seems to beneficially impact 3-month outcomes of both younger and older subjects treated with mechanical thrombectomy for acute ischemic stroke and large vessel occlusion.
Whether the LSC17 gene expression can improve risk stratification in the context of NGS-based risk stratification and measurable residual disease (MRD) in AML patients treated intensively has not been explored. We analyzed LSC17 in 504 adult patients prospectively treated in the ALFA-0702 trial. Multiple (cyto)genetic alterations were associated with changes in LSC17, such as higher LSC17 in patients with RUNX1 or TP53 mutations, and lower scores in those with CEBPA and NPM1 mutations. LSC17-high patients had a lower rate of complete response (CR) or CR with incomplete platelet recovery (CRp) after one induction course in a multivariable analysis (OR=0.41, p=0.0007) accounting for European LeukemiaNet 2022 (ELN22) risk groups, age, and white blood cell (WBC) count. The LSC17-high status was associated with shorter overall survival (OS) (3-year OS: 70.0% versus 52.7% in LSC17-low patients, p<0.0001). In a multivariable analysis considering ELN22, age and WBC count, LSC17-high patients had shorter disease-free survival (DFS) (HR=1.36, p=0.048) compared to LSC17-low patients. In 123 NPM1-mutated patients in CR/CRp with available MRD data, LSC17-high status predicted poorer DFS (HR=2.34, p=0.01) independently of age, WBC count, ELN22 risk, and NPM1-MRD. Combining MRD and LSC17 status identified a subset of 48% of NPM1 patients with LSC17-low status and negative NPM1-MRD with a 3-year OS from CR/CRp of 93.1% compared to 60.7% in those with LSC17-high status and/or positive NPM1-MRD (p=0.0001). Overall, LSC17 assessment refines genetic risk stratification in adult AML patients treated intensively. Combined with MRD, LSC17 identifies a subset of NPM1-mutated AML patients with excellent clinical outcome.
Androgens have represented the historical therapeutic backbone of bone marrow failure (BMF) syndromes. However, their role has been rarely analyzed in prospective setting and systematic and long-term data are currently unavailable regarding their usage, effectiveness and toxicity in both acquired and inherited BMF. Here, taking advantage of a unique disease-specific international dataset, we retrospectively analyzed the so far largest cohort of BMF patients who received androgens before or in absence of an allogeneic hematopoietic cell transplantation (HCT), reappraising their current use in these disorders. We identified 274 patients across 82 EBMT affiliated centers, 193 with acquired (median age of 32) and 81 with inherited BMF (median age of 8 years). With a median duration of androgen treatment of 5.6 and 20 months respectively, complete/partial remission rates at 3 months were of 6%/29% in acquired and 8%/29% in inherited disorders. Five-year overall survival and failure free survival (FFS) were respectively 63% and 23% in acquired and 78% and 14% in inherited contexts. Androgen initiation after second line treatments for acquired, and after > 12 months post-diagnosis for inherited group were identified as factors associated with improved FFS in multivariable analysis. Androgen use was associated with a manageable incidence of organ-specific toxicity and low rates of solid and hematological malignancies. Sub-analysis of transplant-related outcomes after exposure to these compounds showed probabilities of survival and complications similar to other transplanted BMF cohorts. This study delivers a unique opportunity to track androgen use in BMF syndromes and represents the basis for general recommendations on their use on behalf of the SAAWP of the EBMT.
Objectives: To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). Methods: An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. Results: A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3 T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5 min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. Conclusions: While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. Clinical relevance statement: Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. Key points: • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.
Follow-up of patients with type 2 diabetes mellitus (T2DM) involves several healthcare professionals. The quality of their communication is crucial for optimizing care. This exploratory work aims to characterize those communications and their problems. Interviews were performed with general practitioners (GP), patients and other professionals. Data were analyzed deductively, and results were structured through a people map. We performed 25 interviews. GP, patients, nurses, community pharmacists, medical specialists and diabetologists are the main actors of the T2DM patients' follow-up. Three communication issues were identified: difficulties in reaching the hospital diabetologist, delays in receiving reports, and difficulties for patient to transmit information. Results were discussed in terms of tools, care pathways and new roles to support communications during T2DM patients' follow-up.
Sharing health data could avoid duplication of effort in data collection, reduce unnecessary costs in future studies, and encourage collaboration and data flow within the scientific community. Several repositories from national institutions or research teams have making their datasets available. These data are mainly aggregated at spatial or temporal level, or dedicated to a specific field. The objective of this work is to propose a standardized storage and description of open datasets for research purposes. For this, we selected 8 publicly accessible datasets, covering the fields of demographics, employment, education and psychiatry. Then, we studied the format, nomenclature (i.e., files and variables names, modalities of recurrent qualitative variables) and descriptions of these datasets and we proposed on common and standardized format and description. We made available these datasets in an open gitlab repository. For each dataset, we proposed the raw data file in its original format, the cleaned data file in csv format, the variables description, the data management script and the descriptive statistics. Statistics are generated according to the type of variables previously documented. After one year of use, we will evaluate with the users if the standardization of the data sets is relevant and how they use the dataset in real life.
The French Professional Suicidal Helpline 3114 was launched on October 1st, 2021. The objective of this study was to implement automated reports of the activity of the suicidal helpline. We developed automated reports and presentations with Rmarkdown. Two formats were developed, national reports to present for a funding agency and regional reports for each calling center. These reports fulfill a critical need to adjust call distribution patterns, identify problems, adjust communication across the territory and ensure that 3114 is delivering the service it is supposed to provide.
The release of a book denouncing mistreatment in French nursing home triggered a scandal which was conveyed on social networks. The objectives of this study were to study the temporal trends and dynamics of publication on Twitter during the scandal as well as to identify the main topics of discussion.The first one is spontaneous and completely aligned with the actuality and fed by media and family of residents, while the second one is out of step with current events and fed by the company involved in the scandal.
In France, the prevalence of treated diabetes has been estimated at 4.6%, or more than 3 million people and 5.2% in Northern France. The reuse of primary care data allows to study outpatient clinical data such as laboratory results and drug prescriptions, which are not documented in claims and hospital databases. In this study, we selected the population of treated diabetics from the Wattrelos primary care data warehouse, in North of France. Firstly, we studied the laboratory results of diabetics by identifying whether the recommendations of the French National Authority for Health (HAS) were respected. In a second step, we studied the prescriptions of diabetics by identifying the oral hypoglycemic agents treatments and insulins treatments. The diabetic population represents 690 patients of the health care center. The recommendations on labortatory are respected for 84% of diabetics. The majority of diabetics are treated with oral hypoglycemic agents 68.6%. As recommended by the HAS, metformin is the first-line treatment in the diabetic population.
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