Additive manufacturing of metal parts in the motorsport industry is becoming a decisive technology for producing lightweight and rigid parts, with increasing applications as the costs decrease. Among ...the available metal alloys, AlSi10Mg is one of the most widely used. In this paper, the corrosion resistance of additively manufactured AlSi10Mg is compared with that of other traditionally manufactured aluminium alloys widespread in the automotive industry. Several potentially corrosive agents, typical of vehicle applications, were used: salty water, motor oil, suspension oil, cooling fluid and gasoline. Corrosion tests were conducted at both room temperature and 90 °C. The effects of heat and surface treatments were evaluated separately. The samples were visually inspected and weighed to evaluate the corrosion rate with the aid of SEM and EDS analysis. Additively manufactured AlSi10Mg generally showed better corrosion resistance in the stress-relieved condition as compared to the T6-treated state, with slightly better results for the polished samples. Motor oil, suspension oil, cooling fluid and gasoline did not significantly corrode the specimens, except for the T6-treated AlSi10Mg samples at 90 °C. However, the corrosion rate was always higher than traditionally manufactured aluminium alloys tested for comparison.
The Laser Powder Bed Fusion (L-PBF) process is recognized for high-end industrial applications due to its ability to produce parts with high geometric complexity. If lightweighting is one of the main ...strengths of L-PBF, a weakness is still the trade-off between high mechanical properties and competitive productivity. This objective can be targeted through a fine tuning of the process parameters within the manufacturing window. The paper pursues the combined optimization of part quality and process productivity for AlSi10Mg by going beyond the commonly used approach based solely on volumetric energy density. The effects of hatch distance and scan speed on the two targets were analyzed in detail. The best results were achieved by the adoption of a high scan speed and a low hatch distance, with notably different outcomes for nearly the same energy density.
We aimed to report on previously unappreciated clinical features associated with
-related intellectual disability (ID) syndrome, a rare neurodevelopmental disorder characterized by global ...developmental delay, intellectual disability, and language delay, with or without autistic features.
We performed whole-exome sequencing (WES) to molecularly characterize an individual presenting with ID, epilepsy, autism spectrum disorder, behavioral problems, and facial dysmorphisms as major features.
WES allowed us to identify a previously unreported
splice site variant, c.1429-1G>T (NM_032682.6), in the
gene (OMIM
605515) as the causative event underlying the phenotype. Clinical reassessment of the patient and revision of the literature allowed us to refine the phenotype associated with
haploinsufficiency, including hyperkinetic movement disorder and flat angiomas as associated features. Interestingly, the patient also has an asymmetric face and choanal atresia and a novel
variant of the
gene.
We suggest that
-related ID syndrome may also predispose to the development of hyperkinetic movement disorders and flat angiomas. These features could therefore require specific management of this condition.
After a suspected allergic reaction to first dose of mRNA COVID‐19 vaccine, given the PEG skin tests negativity and tolerance in vivo to PEG containing drugs, five patients were vaccinated with the ...second dose of Pfizer‐Biontech undergoing a fractional protocol, with antihistamine premedication, without presenting immediate or delayed reactions.
Our aim was to strengthen that, after an allergological valuation, a fractionated administration of undiluted vaccine seems to be safe and secure in patients with a suspected previous nonsevere allergic reaction to Pfizer‐BioNTech COVID‐19 vaccine.
A graded challenge with adalimumab could be safe in case of a delayed allergic reaction to golimumab, after a detailed allergological evaluation and the exclusion of allergic sensitization using skin ...tests.
A graded challenge with adalimumab could be safe in case of a delayed allergic reaction to golimumab, after a detailed allergological evaluation and the exclusion of allergic sensitization using skin tests.
Inactivating
mutations causing Sotos syndrome have been previously associated with a specific genome-wide DNA methylation (DNAm) pattern. Sotos syndrome is characterized by phenotypic overlap with ...other overgrowth syndromes, and a definite diagnosis might not be easily reached due to the high prevalence of variants of unknown significance (VoUS) that are identified in patients with a suggestive phenotype.
we performed microarray DNAm profiling in a set of 11 individuals with a clinical suspicion of Sotos syndrome and carrying an
VoUS or previously unreported variants to solve uncertainty in defining pathogenicity of the observed variants. The impact of the training cohort size on sensitivity and prediction confidence of the classifier was assessed.
The Sotos syndrome-specific DNAm signature was validated in six individuals with a clinical diagnosis of Sotos syndrome and carrying
pathogenic
variants. Applying this approach to the remaining 11 individuals with
variants, we succeeded in confirming pathogenicity in eight subjects and excluding the diagnosis of Sotos syndrome in three. The sensitivity and prediction confidence of the classifier based on the different sizes of the training sets did not show substantial differences, though the overall performance was improved by using a data balancing strategy.
The present approach solved uncertainty in cases with
VoUS, further demonstrating the clinical utility of DNAm profiling.
Gain of function pathogenic variants in MRAS have been found in a small subset of pediatric subjects presenting with Noonan syndrome (NS) associated with hypertrophic cardiomyopathy (HCM) and ...moderate to severe intellectual disability. These variants are considered to confer a high‐risk for the development of severe HCM with poor prognosis and fatal outcome. We report on the natural history of the first adult subject with NS carrying the recurrent pathogenic p.Thr68Ile amino acid substitution. Different from what had previously been observed, he presented with a mild, late‐onset left ventricular hypertrophy, and a constellation of additional symptoms rarely seen in NS. The present case provides evidence that HCM does not represent an obligatory, early‐onset and severe complication in subjects with MRAS variants. It also adds new data about late‐onset features suggesting that other unexpected complications might be observed in adult subjects providing anticipatory guidance for individuals of all age.
BACKGROUND AND AIMSDiagnosis of fish may represent an important challenge for the allergists. This study aimed to evaluate the diagnostic sensitivity of an in vitro multiplex assay using a ...comprehensive panel of fish allergens and the cross-reactivity patterns between different molecular components. METHODS56 subjects with fish allergy were enrolled. All patients underwent specific IgE measurement using the Allergy Explorer-Alex 2™ multiplex assay (Macroarray Diagnostics, Vienna, Austria) RESULTS: The single ß-parvalbumins Clu h 1, Cyp c 1, Gad m 1, Sal s 1, Sco s 1, Thu a 1 and Xyp g 1 scored positive in 75.0%, 67.8%, 62.5%, 80.3%,80.3%, 78.8% and 73,2% patients, respectively. 14.3% scored positive for the α-parvalbumin (Raj c-parvalbumin), and 16.1% for the aldolase + enolase (Gad m 2 + 3) components. 92.8% reacted to at least one ß-parvalbumin and 96.4% to at least one of the allergens tested. Overall sensitivity was higher than that obtained using commercial extracts of cod, salmon and tuna for skin prick test (75.8%) and IgE detection (92.3%). CONCLUSIONSThe Alex 2 showed high diagnostic sensitivity and it might be used as an additional assay to investigate the cross-reactivity patterns between different molecular components, looking for potentially safe fish species.
Autosomal dominant Kabuki syndrome (KS) is a rare multiple congenital anomalies/neurodevelopmental disorder caused by heterozygous inactivating variants or structural rearrangements of the ...lysine-specific methyltransferase 2D (KMT2D) gene. While it is often recognizable due to a distinctive gestalt, the disorder is clinically variable, and a phenotypic scoring system has been introduced to help clinicians to reach a clinical diagnosis. The phenotype, however, can be less pronounced in some patients, including those carrying postzygotic mutations. The full spectrum of pathogenic variation in KMT2D has not fully been characterized, which may hamper the clinical classification of a portion of these variants. DNA methylation (DNAm) profiling has successfully been used as a tool to classify variants in genes associated with several neurodevelopmental disorders, including KS. In this work, we applied a KS-specific DNAm signature in a cohort of 13 individuals with KMT2D VUS and clinical features suggestive or overlapping with KS. We succeeded in correctly classifying all the tested individuals, confirming diagnosis for three subjects and rejecting the pathogenic role of 10 VUS in the context of KS. In the latter group, exome sequencing allowed to identify the genetic cause underlying the disorder in three subjects. By testing five individuals with postzygotic pathogenic KMT2D variants, we also provide evidence that DNAm profiling has power to recognize pathogenic variants at different levels of mosaicism, identifying 15% as the minimum threshold for which DNAm profiling can be applied as an informative diagnostic tool in KS mosaics.
