The concept of nail psoriasis as an entheseal-driven disease has essentially been formulated on the basis of radiological findings because it is usually not possible to obtain the tissue directly ...from the joints. The aim of this retrospective study was to evaluate the histological features of isolated nail psoriasis with and without distal interphalangeal psoriatic arthritis (PsA), focusing on the question as to whether the fascia and adipose tissue surrounding the apex of the nail unit genuinely show an inflammatory infiltrate. In support of the nail-enthesitis theory, an ongoing inflammatory infiltrate could be expected. An immunohistochemical study was performed to evaluate the distribution and phenotype of the inflammatory infiltrate in nail psoriasis with and without PsA. This study did not show an inflammatory infiltrate in the fascia connecting the nail to the extensor tendon. CD8 and CD4 subsets were present in equal number in the nail dermis of nail psoriasis with or without PsA, which is a similar distribution to that seen in psoriatic synovium while skin psoriasis is characterized by a dermal predominance of CD4 T lymphocytes. Because of this study and recent microanatomic studies of the normal nail unit, it is possible to move away from a purely anatomic explanation of the strong association between nail psoriasis and PsA and to propose immunological factors as contributory. This study provides support for the hypothesis that CD8+ T cells play a crucial role in the pathogenesis of nail psoriasis through a pathogenic pathway similar to that of PsA and contrasting with that of the skin.
•Objective data collected in three naturalistic riding/driving studies were analyzed.•The analysis of acceleration and rotation rates allows to compare cars and PTWs.•Motorcyclists accelerate and ...brake more often and harder than motorists.•PTWs sometimes endure very high levels of yaw and roll rates.•Motorcyclists do not always drive faster than motorists.
The risk of serious crashes is much higher for motorcyclists than for motorists. While research into PTW safety is not as extensive as for other road users, there is a need for further understanding of fatal and injury crash patterns and causes, particularly in the critical pre-crash phase. Naturalistic Driving Studies (NDS) have been used to improve road safety and gain a better understanding of car crash mechanisms, but few studies have used this approach to examine PTW behavior. This paper aims to compare the actual use of PTW's dynamic capacities to that of passenger cars based on three Naturalistic Driving Studies conducted in France. A method designed to study the dynamic behavior of cars has been adapted to study the dynamic behavior of PTWs. This adaptation involves combining the longitudinal acceleration, not only with the lateral acceleration (which is adapted for cars), but also with the roll rate or the yaw rate. By doing so, it becomes possible to consider the specific behavior of PTWs in curves, and finally, to compare the dynamic demands experienced by cars and PTWs in all directions. It was found that there are significant differences in the distribution of accelerations, roll rate, yaw rate, and speeds between motorcycles and cars. Motorcycles were observed to endure higher levels of positive acceleration, experience more intense braking, and exhibit slightly higher levels of medium or high yaw rate values. The final analysis of speeds, with a 5 km/h interval, shows that motorcyclists travel at higher speeds than car drivers within a small fleet of equipped cars. However, when compared to a larger fleet of cars with speed data with a 10 km/h interval, car drivers were found to travel faster. Demand levels differ between fleets of cars and fleets of motorists, particularly where lateral demands are concerned. This can be attributed to various factors such as driving context, study duration, road type and weather conditions. Other NDS with more cars and PTWs should be analyzed with this method to complete the results.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A β-(1→6)–linked poly- N ...-acetyl- d -glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei , and sporozoites and blood-stage forms of Plasmodium falciparum . Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes , Streptococcus pneumoniae , Listeria monocytogenes , Neisseria meningitidis serogroup B, Candida albicans , and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae , and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Benefit of early awake prone positioning for COVID-19 patients hospitalised in medical wards and who need oxygen therapy remains to be demonstrated. The question was considered at the time of ...COVID-19 pandemic to avoid overloading the intensive care units. We aimed to determine whether prone position plus usual care could reduce the rate of non-invasive ventilation (NIV) or intubation or death as compared to usual care alone.
In this multicentre randomised clinical trial, 268 patients were randomly assigned to awake prone position plus usual care (N = 135) or usual care alone (N = 132). The primary outcome was the proportion of patients who underwent NIV or intubation or died within 28 days. Main secondary outcomes included the rates of NIV, of intubation or death, within 28 days.
Median time spent each day in the prone position within 72 h of randomisation was 90 min (IQR 30-133). The proportion of NIV or intubation or death within 28 days was 14.1% (19/135) in the prone position group and 12.9% (17/132) in the usual care group odds ratio adjusted for stratification (aOR) 0.43; 95% confidence interval (CI) 0.14-1.35. The probability of intubation, or intubation or death (secondary outcomes) was lower in the prone position group than in the usual care group (aOR 0.11; 95% CI 0.01-0.89 and aOR 0.09; 95% CI 0.01-0.76, respectively) in the whole study population and in the prespecified subgroup of patients with SpO
≥ 95% on inclusion (aOR 0.11; 95% CI 0.01-0.90, and aOR 0.09; 95% CI 0.03-0.27, respectively).
Awake prone position plus usual care in COVID-19 patients in medical wards did not decrease the composite outcome of need for NIV or intubation or death. Trial registration ClinicalTrials.gov Identifier: NCT04363463 . Registered 27 April 2020.
Abstract
With the approval of new therapies targeting the PI3K pathway, the detection of PIK3CA mutations has become a key factor in treatment management for HR+/HER2− metastatic breast cancer (MBC). ...We developed multiplex digital PCR (dPCR) assays to detect and quantify PIK3CA mutations. A first screening assay allows the detection of 21 mutations, with a drop-off system targeting the 542–546 hotspot mutations combined with the simultaneous detection of N345K, C420R, H1047L and H1047R mutations. In the case of a positive result, a sequential strategy based on other assays that we have developped allows for precise mutation identification. Clinical validity was determined by analyzing plasma circulating free DNA (cfDNA) from 213 HR+/HER2− MBC samples, as well as DNA extracted from 97 available matched tumors from 89 patients. Our assays have shown reliable specificity, accuracy and reproducibility, with limits of blank of three and four droplets for the screening assay. Sixty-eight patients (32%) had at least one PIK3CA mutation detectable in their plasma, and we obtained 83.1% agreement between the cfDNA analysis and the corresponding tumors. The high sensitivity and robustness of these new dPCR assays make them well-suited for rapid and cost-effective detection of PIK3CA mutations in the plasma of MBC patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute-funded prospective sarcoma database NETSARC to report the management and ...oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level.
NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15-30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors.
Among 3,227 patients aged 15-30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) (p < 0.001). 3y-OS rates were 81.1% (95%CI 78.3-83.6) in AYA in RSC and 82.7% (95%CI 79.4-85.5) in AYA in non-RSC, respectively. Whereas no significant differences in OS was observed in AYAs treated in RSC and in non-RSC, LRFS and PFS were improved in AYAs treated in RSC compared to AYAs treated in non-RSC (Hazard Ratios (HR): 0.58 and 0.83, respectively).
This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
"Join up, they said! It’s a man’s life, they said!"Cartesian Lineage and Tradition in Being and Nothingness While Descartes is literally present in 27 of 722 pages that Being and Nothingness counts, ...Hegel appears in 43, Husserl in 46 and Heidegger in 47 of them. Without asserting, and thus without infirming the obvious influence of these three German thinkers on it, one year after his essay of phenomenological ontology, it is nevertheless the filiation and the manner of only the French philosopher that Sartre claims in front of Pierre Lorquet. So, which relative and which model is Descartes for him? And what relationship does Sartre exactly maintain with him? Following the track of the latter in the 1943 treatise, I want to ensure that “the individual of existentialism is Descartes’s true heir”.
This work focuses on the impact of sulfonated poly(ether ether ketone) (sPEEK) membrane pretreatments on fuel cell performance, starting from two different batches of Fumapem E730 from Fumatech, ...acquired in 2019 and in 2020. sPEEK membranes are possible lower cost alternatives to perfluorosulfonic acid (PFSA) membranes for proton exchange membrane fuel cells (PEMFC) applications. Before use, they must be pretreated to ensure a complete protonic substitution and removal of residual reagents/solvent: the simplest protocol consists in soaking the membrane in an acid solution followed by a rinsing step in water. In addition to this acidification step, hydrothermal (HT) treatments in water at high temperature for a few hours to a few days were also considered herein, as well as a hydro‐alcoholic (HA) step, because of their expected effects on membrane nanostructure. Overall, four different protocols were used. The membrane water uptake, water self‐diffusion, proton conductivity, and fuel cell performance—under H2/O2—were measured. It was found that in the best case—membranes from the 2020 batch subjected to HA followed by 72 h HT pretreatments—the fuel cell performances exceeded those obtained with a PFSA membrane (Nafion XL). This is explained by a higher protonic conductivity, probably resulting from a better sPEEK nano‐structuration.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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