Flow leaks normalization

Flow leaks are small devices generating a well-determined flow when subject to a pressure differential (feed pressure). Though, they need to be calibrated against a reference flow based on the feed pressure and fluid density through a complex relation derived from the modified Darcy law, therefore results of a calibration performed in a given condition are not necessarily valid when the leak is used in different conditions. In this paper we will describe a correct renormalization of the calibration results allowing to compute precisely the actual flow rate generated by the leak. A mathematical description of the renormalization will be presented and a method for the experimental determination of the permeability will be discussed. It will be shown that the calibration uncertainty can be reduced by applying the correct normalization, and that the in-use uncertainty can be brought to be of the same order of magnitude as the calibration uncertainty

Gender matter in isotretinoin therapy for acne vulgaris? A retrospective study

Introduction: Gender differences have been recently highlighted for several aspects of acne vulgaris such as epidemiology, pathogenesis, clinical course, quality of life and treatment outcome. In particular a shorter but more severe clinical course has been reported in males than in females; nevertheless, usually men have their quality of life less affected. Aim: To determine if the response and the adverse events to 1 cycle of oral isotretinoin therapy can be influenced by gender. Methods: A retrospective study was conducted on consecutive patients affected by acne vulgaris and treated with oral isotretinoin. Global acne grading system (GAGS), acne-related quality of life (AQoL) and isotretinoin-related adverse events were considered as outcome measures and were evaluated before (T0), every month during administration and 4 weeks after the withdrawal (T1) of oral isotretinoin therapy. Mann-Whitney U test and Wilcoxon signed-rank test were used for quantitative parameters and Fisher exact test for qualitative ones. Results: Forty-nine acneic patients were retrospectively selected (33 males 67.3% and 16 females -32.7%; median age: 19 years). Patients had received a median dosage of isotretinoin of 0.4 mg/kg/die for a median period of 5 months; no differences in outcome measures among genders were reported. Limitations: The study is retrospective and the sample is small and not homogenously distributed among genders, as males are double in number than females. Conclusions: In our study population gender didn't influence neither the clinical and the quality of life outcome measures nor the occurrence of adverse events to oral isotretinoin therapy for acne

Correlation between Dermatology Life Quality Index and Minor Test and Differences in Their Levels over Time in Patients with Axillary Hyperhidrosis Treated with Botulinum Toxin Type A

Hyperhidrosis is an idiopathic condition of exaggerated sweat production resulting in dramatic impairments of daily activities, social interactions and occupational activities. The aim of the present study was to evaluate correlation between a subjective (Dermatology Life Quality Index) and an objective (Minor test) criterion and to assess difference in their levels over time in patients affected by axillary hyperhidrosis treated with botulinum toxin type A. Nineteen patients received injections of 50 U of botulinum toxin type A per axilla. Patients were observed for 9 months after treatment. All patients showed great improvement of hyperhidrosis by Minor test and Dermatology Life Quality Index following treatment with botulinum toxin type A, with the effect persisting for 6-9 months. All patients demonstrated direct relationship between objective improvement documented by Minor test and quality of live improvement documented by Dermatology Life Quality Index after treatment with botulinum toxin type A

Cardiovascular Risk Evaluation through Heart Rate Variability (HRV) Analysis in Patients with Psoriasis before and after 12 Weeks of Etanercept Therapy: A Preliminary Prospective Study

Background The association between psoriasis and cardiovascular diseases is suggested by epidemiological studies. The sub-inflammatory systemic state that characterizes both psoriasis and atherosclerosis has been proposed as the link between these conditions; it cannot, however, explain the increased incidence of sudden cardiac death reported in young patients with severe psoriasis without common cardiovascular risk factors. In a previous study we reported higher levels of autonomic dysregulation in psoriatic patients, concluding that the prevalence of the sympathetic arm over the para-sympathetic one could increase cardiovascular risk. Objectives To assess the influence of etanercept, an anti-TNFα agent, on the autonomic cardiovascular regulation in young patients with moderate-to-severe psoriasis without cardiovascular risk factors. Methods Five-minute ECG recordings were collected at rest conditions before and after 12 weeks of therapy with etanercept in 19 young psoriatic patients without cardiovascular risk factors. The Cardiolab CE pocket PC ECG system was used for linear methods of heart rate variability (HRV) analysis. Results No significant change in HRV analysis parameters was apparent after 12 weeks of etanercept therapy. Conclusion Our data suggest that treatment with etanercept in patients with moderate-to-severe psoriasis doesn\u27t affect cardiovascular autonomic regulation, and subsequently the cardiovascular risk.</p

Probing black hole accretion tracks, scaling relations, and radiative efficiencies from stacked X-ray active galactic nuclei

The masses of supermassive black holes at the centres of local galaxies appear to be tightly correlated with the mass and velocity dispersions of their galactic hosts. However, the local Mbh–Mstar relation inferred from dynamically measured inactive black holes is up to an order-of-magnitude higher than some estimates from active black holes, and recent work suggests that this discrepancy arises from selection bias on the sample of dynamical black hole mass measurements. In this work, we combine X-ray measurements of the mean black hole accretion luminosity as a function of stellar mass and redshift with empirical models of galaxy stellar mass growth, integrating over time to predict the evolving Mbh–Mstar relation. The implied relation is nearly independent of redshift, indicating that stellar and black hole masses grow, on average, at similar rates. Matching the de-biased local Mbh–Mstar relation requires a mean radiative efficiency ε ≳ 0.15, in line with theoretical expectations for accretion on to spinning black holes. However, matching the ‘raw’ observed relation for inactive black holes requires ε ∼ 0.02, far below theoretical expectations. This result provides independent evidence for selection bias in dynamically estimated black hole masses, a conclusion that is robust to uncertainties in bolometric corrections, obscured active black hole fractions, and kinetic accretion efficiency. For our fiducial assumptions, they favour moderate-to-rapid spins of typical supermassive black holes, to achieve ε ∼ 0.12–0.20. Our approach has similarities to the classic Soltan analysis, but by using galaxy-based data instead of integrated quantities we are able to focus on regimes where observational uncertainties are minimized

Bowel preparation for elective colorectal resection: multi-treatment machine learning analysis on 6241 cases from a prospective Italian cohort

background current evidence concerning bowel preparation before elective colorectal surgery is still controversial. this study aimed to compare the incidence of anastomotic leakage (AL), surgical site infections (SSIs), and overall morbidity (any adverse event, OM) after elective colorectal surgery using four different types of bowel preparation. methods a prospective database gathered among 78 Italian surgical centers in two prospective studies, including 6241 patients who underwent elective colorectal resection with anastomosis for malignant or benign disease, was re-analyzed through a multi-treatment machine-learning model considering no bowel preparation (NBP; No. = 3742; 60.0%) as the reference treatment arm, compared to oral antibiotics alone (oA; No. = 406; 6.5%), mechanical bowel preparation alone (MBP; No. = 1486; 23.8%), or in combination with oAB (MoABP; No. = 607; 9.7%). twenty covariates related to biometric data, surgical procedures, perioperative management, and hospital/center data potentially affecting outcomes were included and balanced into the model. the primary endpoints were AL, SSIs, and OM. all the results were reported as odds ratio (OR) with 95% confidence intervals (95% CI). results compared to NBP, MBP showed significantly higher AL risk (OR 1.82; 95% CI 1.23-2.71; p = .003) and OM risk (OR 1.38; 95% CI 1.10-1.72; p = .005), no significant differences for all the endpoints were recorded in the oA group, whereas MoABP showed a significantly reduced SSI risk (OR 0.45; 95% CI 0.25-0.79; p = .008). conclusions MoABP significantly reduced the SSI risk after elective colorectal surgery, therefore representing a valid alternative to NBP

Abdominal drainage after elective colorectal surgery: propensity score-matched retrospective analysis of an Italian cohort

background: In italy, surgeons continue to drain the abdominal cavity in more than 50 per cent of patients after colorectal resection. the aim of this study was to evaluate the impact of abdominal drain placement on early adverse events in patients undergoing elective colorectal surgery. methods: a database was retrospectively analysed through a 1:1 propensity score-matching model including 21 covariates. the primary endpoint was the postoperative duration of stay, and the secondary endpoints were surgical site infections, infectious morbidity rate defined as surgical site infections plus pulmonary infections plus urinary infections, anastomotic leakage, overall morbidity rate, major morbidity rate, reoperation and mortality rates. the results of multiple logistic regression analyses were presented as odds ratios (OR) and 95 per cent c.i. results: a total of 6157 patients were analysed to produce two well-balanced groups of 1802 patients: group (A), no abdominal drain(s) and group (B), abdominal drain(s). group a versus group B showed a significantly lower risk of postoperative duration of stay &gt;6 days (OR 0.60; 95 per cent c.i. 0.51-0.70; P &lt; 0.001). a mean postoperative duration of stay difference of 0.86 days was detected between groups. no difference was recorded between the two groups for all the other endpoints. conclusion: this study confirms that placement of abdominal drain(s) after elective colorectal surgery is associated with a non-clinically significant longer (0.86 days) postoperative duration of stay but has no impact on any other secondary outcomes, confirming that abdominal drains should not be used routinely in colorectal surgery

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an “end-on” manner. uSTA-guided modeling and a high-resolution cryo–electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis