Conformable Euler's theorem on homogeneous functions Martínez, Francisco; Martínez‐Vidal, Inmaculada; Paredes, Silvestre
Computational and mathematical methods,
September 2019, 2019-09-00, 20190901, Volume:
1, Issue:
5
Journal Article
Peer reviewed
Open access
Recently, the conformable derivative and its properties have been introduced. In this paper, we propose and prove some new results on the conformable multivariable fractional calculus. We introduce a ...conformable version of classical Euler's theorem on homogeneous functions. Furthermore, we are extending the aforementioned result for higher‐order partial derivatives.
SARS-CoV-2 is an RNA virus causing COVID-19. The clinical characteristics and epidemiology of COVID-19 have been extensively investigated, however, only one study so far focused on the patient's ...nasopharynx microbiota. In this study we investigated the nasopharynx microbial community of patients that developed different severity levels of COVID-19. We performed 16S ribosomal DNA sequencing from nasopharyngeal swab samples obtained from SARS-CoV-2 positive (56) and negative (18) patients in the province of Alicante (Spain) in their first visit to the hospital. Positive SARS-CoV-2 patients were observed and later categorized in mild (symptomatic without hospitalization), moderate (hospitalization), and severe (admission to ICU). We compared the microbiota diversity and OTU composition among severity groups and built bacterial co-abundance networks for each group.
Statistical analysis indicated differences in the nasopharyngeal microbiome of COVID19 patients. 62 OTUs were found exclusively in SARS-CoV-2 positive patients, mostly classified as members of the phylum Bacteroidota (18) and Firmicutes (25). OTUs classified as
were found to be significantly more abundant in patients that developed more severe COVID-19. Furthermore, co-abundance analysis indicated a loss of network complexity among samples from patients that later developed more severe symptoms.
Our study shows that the nasopharyngeal microbiome of COVID-19 patients showed differences in the composition of specific OTUs and complexity of co-abundance networks. Taxa with differential abundances among groups could serve as biomarkers for COVID-19 severity. Nevertheless, further studies with larger sample sizes should be conducted to validate these results.
Although the Coronavirus disease 2019 (COVID-19) pandemic has generated a large amount of studies, the patient-perceived quality of care (PQ) in this context is still not well known, so more studies ...intending to focus on this issue are strongly needed. This study assesses changes on PQ in patients hospitalized in Spain during the first month of the COVID-19 pandemic and investigates differences between those admitted for this cause and the rest a descriptive study using the “Net Promoters Score” and the hospital regular monitoring plan. Due to this point of view, ethical approval is not applicable. Four PQ dimensions (nurse, physician, and nurse assistant actions NA, and discharge information DI) were measured in all COVID patients (57) and in a sample of non-COVID patients (60) discharged at home during the first month of the pandemic, and also compared with another sample (384) from an immediately previous period. The COVID patients scored worse (8.2) than non-COVID ones (9.0; P < .0001), especially in NA and DI, and were more likely to be detractors (odds ratio OR: 3.05, P < .0001) and less to be promoters (OR: 0.64, P < .05). Global and DI net promoters score values before the pandemic were higher than afterward. In conclusion, the COVID-19 pandemic negatively and significantly influenced the health care quality as perceived by inpatients, both in COVID and in non-COVID ones, but more intensely in the former. As a health care organization, this knowledge meant an opportunity from improvement and to be better qualified to face the pandemic.
TNFα overexpression has been associated with several chronic inflammatory diseases, including psoriasis, lichen planus, rheumatoid arthritis, and inflammatory bowel disease. Paradoxically, numerous ...studies have reported new-onset psoriasis and lichen planus following TNFα antagonist therapy. Here, we show that genetic inhibition of Tnfa and Tnfr2 in zebrafish results in the mobilization of neutrophils to the skin. Using combinations of fluorescent reporter transgenes, fluorescence microscopy, and flow cytometry, we identified the local production of dual oxidase 1 (Duox1)-derived H₂O₂ by Tnfa- and Tnfr2-deficient keratinocytes as a trigger for the activation of the master inflammation transcription factor NF-κB, which then promotes the induction of genes encoding pro-inflammatory molecules. In addition, pharmacological inhibition of Duox1 completely abrogated skin inflammation, placing Duox1-derived H₂O₂ upstream of this positive feedback inflammatory loop. Strikingly, DUOX1 was drastically induced in the skin lesions of psoriasis and lichen planus patients. These results reveal a crucial role for TNFα/TNFR2 axis in the protection of the skin against DUOX1-mediated oxidative stress and could establish new therapeutic targets for skin inflammatory disorders.
We aimed to assess the percentage of azole resistance in Aspergillus fumigatus in Spain.
Thirty participating Spanish hospitals stored all morphologically identified A. fumigatus sensu lato clinical ...isolates—regardless their clinical significance—from 15 February to 14 May 2019. Isolates showing azole resistance according to the EUCAST 9.3.2 methodology were molecularly identified and the cyp51A gene was studied in A. fumigatus sensu stricto isolates.
Eight hundred and forty-seven isolates from 725 patients were collected in 29 hospitals (A. fumigatus sensu stricto (n = 828) and cryptic species (n = 19)). Isolates were mostly from the lower respiratory tract (94.0%; 797/847). Only cryptic species were amphotericin B resistant. Sixty-three (7.4%) out of the 847 isolates were resistant to ≥1 azole(s). Azole resistance was higher in cryptic species than in A. fumigatus sensu stricto (95%, 18/19 vs. 5.5%, 45/828); isavuconazole was associated to the lowest number of non-wild type isolates. The dominant mechanism of resistance was the presence of TR34-L98H substitutions (n = 24 out of 63). Out of the 725 patients, 48 (6.6%) carried either cryptic species (n = 14) or A. fumigatus sensu stricto (n = 34; 4.7%) resistant isolates. Aspergillus fumigatus sensu stricto harbouring either the TR34-L98H (n = 19) or TR46/Y121F/T289A (n = 1) mutations were detected in patients in hospitals located at 7/24 studied cities.
Of the patients, 6.6% carry azole-resistant A. fumigatus sensu lato isolates in Spain. TR34-L98H is the dominant cyp51A gene substitutions, although its presence is not widespread.
The main goal of this study was to accurately detect azole resistance in species of the Aspergillus fumigatus complex by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry ...(MALDI-TOF MS).
Identification of isolates (n = 868) was done with MALDI-TOF MS using both commercial and in-house libraries. To determine azole susceptibility, the EUCAST E.Def. 9.3.2 method was applied as the reference standard. Identification of resistant isolates was confirmed by DNA sequence analysis. Protein spectra obtained by MALDI-TOF MS were analysed to differentiate species within the A. fumigatus complex and to detect azole-resistant A. fumigatus sensu stricto isolates.
Correct discrimination of A. fumigatus sensu stricto from cryptic species was accomplished in 100% of the cases applying principal component analysis (PCA) to protein spectra generated by MALDI-TOF MS. Furthermore, a specific peak (4586 m/z) was found to be present only in cryptic species. The application of partial least squares (PLS) discriminant analysis allowed 98.43% (±0.038) discrimination between susceptible and azole-resistant A. fumigatus sensu stricto isolates. Finally, based on PLS and SVM, A. fumigatus sensu stricto isolates with different cyp51A gene mutations were correctly clustered in 91.5% of the cases.
MALDI-TOF MS combined with peak analysis is a novel tool that allows the differentiation of A. fumigatus sensu stricto from other species within the A. fumigatus complex, as well as the detection of azole-resistant A. fumigatus sensu stricto. Although further studies are still needed, the results reported here show the great potential of MALDI-TOF and machine learning for the rapid detection of azole-resistant Aspergillus fumigatus isolates from clinical origins.
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The EUCAST EDef 9.3.2 procedure recommends visual readings of azole and amphotericin B MICs against
spp. Visual determination of MICs may be challenging. In this work, we aim to obtain and compare ...visual and spectrophotometric MIC readings of azoles and amphotericin B against
isolates. A total of 847
isolates (
= 828 and cryptic species
= 19) were tested against amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole using the EUCAST EDef 9.3.2 procedure. Isolates were classified as susceptible or resistant/non-wild type according to the 2020 updated breakpoints. The area of technical uncertainty for the azoles was defined in the updated breakpoints. Visual and spectrophotometric (fungal growth reduction of >95% compared to the control, read at 540 nm) MICs were compared. Essential (±1 2-fold dilution) and categorical agreements were calculated. Overall, high essential (97.1%) and categorical (99.6%) agreements were found. We obtained 100% categorical agreements for amphotericin B, itraconazole, and posaconazole, and consequently, no errors were found. Categorical agreements were 98.7 and 99.3% for voriconazole and isavuconazole, respectively. Most of the misclassifications for voriconazole and isavuconazole were found to be associated with MIC results falling either in the area of technical uncertainty or within one 2-fold dilution above the breakpoint. The resistance rate was slightly lower when the MICs were obtained by spectrophotometric readings. However, all relevant
mutants were correctly classified as resistant. Spectrophotometric determination of azole and amphotericin B MICs against
isolates may be a convenient alternative to visual endpoint readings.
Pressure ulcers are a major burden to patients because they affect health, well-being, and health-related quality of life. Thus, prevention and early treatment of pressure ulcers is a major challenge ...for health care professionals.
To compare the efficacy of hydrocellular and hydrocolloid dressings after 8 weeks of treatment of category II pressure ulcers.
A prospective multicenter clinical trial with blinded outcome assessors.
Adult patients with category II pressure ulcers from primary and long-term care institutions on Majorca island.
Category II ulcers were treated with ALLEVYN Adhesive® dressings or VARIHESIVE® GEL CONTROL dressings, with the primary outcome being healing of the ulcers in 8 weeks. Blinded confirmation of ulcer healing was performed by a treatment-group assessment committee. Estimates of cumulative survival probabilities were determined using the Kaplan-Meier method and analyses of effectiveness were performed using the chi-squared test.
A total of 169 patients with pressure ulcers were enrolled, 84 of whom received hydrocellular dressings and 85 of whom received hydrocolloid dressings. A total of 58% were women and 56% were from primary care institutions. The hydrocellular dressing group had a higher percentage of healed pressure ulcers at 8 weeks (90.7% vs. 77.1%, p = 0.039) and a shorter average healing time (3 weeks vs. 4 weeks, p = 0.015). Analysis of safety outcomes at 8 weeks indicated that the hydrocellular dressing group had a smaller proportion of ulcers that were unhealed (3.9% vs. 7.1%) and a smaller proportion of ulcers that progressed to a higher category or infection (5.3% vs. 15.7%), although these differences were not statistically significant.
This study of patients with category II pressure ulcers indicated that hydrocellular dressings were superior to hydrocolloid dressings in terms of healing at 8 weeks and time required for healing, although these two dressings had similar safety profiles.
Background
Azole resistance screening in Aspergillus fumigatus isolates can be routinely carried out by using azole‐containing plates (E.Def 10.2 method), that requires filtering conidial suspensions ...prior inoculum adjustment.
Objectives
We evaluated whether skipping the filtration step of conidial suspensions negatively influences the performance of the E.Def 10.2.
Patients/Methods
A. fumigatus sensu stricto isolates (n = 92), classified as azole‐susceptible or azole‐resistant according to the EUCAST microdilution E.Def 9.4 method, were studied. Azole‐resistant isolates had either wild type cyp51A gene sequence (n = 3) or the TR34‐L98H (n = 26), G54R (n = 5), TR46‐Y121F‐T289A (n = 1), F46Y‐M172V‐N248T‐D255E‐E427K (n = 1), F165L (n = 1) or G448S (n = 1) cyp51A gene substitutions. In‐house azole‐containing agar plates were prepared according to the EUCAST E.Def 10.2 procedure. Conidial suspensions were obtained by adding distilled water (Tween 20 0.1%). Subsequently, the suspensions were either filtered or left unfiltered prior to inoculum adjustment to 0.5 McFarland. Using microdilution as the gold standard, agreement, sensitivity and specificity of the agar plates inoculated with two inoculums were assessed.
Results
Agreements for the agar screening method with either unfiltered or filtered conidial suspensions were high for itraconazole (100%), voriconazole (100%) and posaconazole (97.8%). Sensitivity (100%) and specificity (98.2%) of the procedure to rule in or out resistance when unfiltered suspensions were used were also high. Isolates harbouring the TR34‐L98H, G54R and TR46‐Y121F‐T289A substitutions were detected with the modified method.
Conclusions
Unfiltered conidial suspensions does not negatively influence the performance of the E.Def 10.2 method when screening for A. fumigatus sensu stricto.
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