A high efficiency 10W MMIC PA for K-b and satellite communications

This paper discusses the design steps and experimental characterization of a monolithic microwave integrated circuit (MMIC) power amplifier developed for the next generation of K-band 17.3–20.2 GHz very high throughput satellites. The technology used is a commercially available 100-nm gate length gallium nitride on silicon process. The chip was developed taking into account the demanding constraints of the spacecraft and, in particular, carefully considering the thermal constraints of such technology, in order to keep the junction temperature in all devices below 160°C in the worst-case condition (i.e., maximum environmental temperature of 85°C). The realized MMIC, based on a three-stage architecture, was first characterized on-wafer in pulsed regime and, subsequently, mounted in a test-jig and characterized under continuous wave operating conditions. In 17.3–20.2 GHz operating bandwidth, the built amplifier provides an output power >40 dBm with a power added efficiency close to 30% (peak >40%) and 22 dB of power gain

The healthcare professionals’ support towards organ donation. An analysis of current practices, predictors, and consent rates in Apulian hospitals

Introduction. The paper investigates the critical care staff’s support towards organ donation by analysing how their attitude, knowledge, confidence, engagement, and training can act as predictors of donation consent rates. Our study focused on hospitals in the Apulia Region, Italy. Material and methods. The study employs a quantitative methodology based on a survey of healthcare professionals. The rate of consent to organ and tissue donation at the hospital level, given as a ratio of the permissions received to the proposals performed, was extracted from GEDON software related to the year 2019 report. For each Apulian participating hospital, we calculated a median score for each of the five predictors (namely, attitude, knowledge, confidence, engagement, and training) and investigated the association with hospital consent rates. Results. The results highlight that the engagement of the intensive care units’ healthcare personnel stands as the only influential predictor of the consent rate. Discussion. In Italy’s Apulia Region, efforts are needed to increase consent rates for organ donation. Strategies should concentrate on continuous support, as well as specific training of hospital staff involved in the donation process

A novel homozygous KCNQ3 loss-of-function variant causes non-syndromic intellectual disability and neonatal-onset pharmacodependent epilepsy

OBJECTIVE: Heterozygous variants in KCNQ2 or, more rarely, KCNQ3 genes are responsible for early-onset developmental/epileptic disorders characterized by heterogeneous clinical presentation and course, genetic transmission, and prognosis. While familial forms mostly include benign epilepsies with seizures starting in the neonatal or early-infantile period, de novo variants in KCNQ2 or KCNQ3 have been described in sporadic cases of early-onset encephalopathy (EOEE) with pharmacoresistant seizures, various age-related pathological EEG patterns, and moderate/severe developmental impairment. All pathogenic variants in KCNQ2 or KCNQ3 occur in heterozygosity. The aim of this work was to report the clinical, molecular, and functional properties of a new KCNQ3 variant found in homozygous configuration in a 9-year-old girl with pharmacodependent neonatal-onset epilepsy and non-syndromic intellectual disability. METHODS: Exome sequencing was used for genetic investigation. KCNQ3 transcript and subunit expression in fibroblasts was analyzed with quantitative real-time PCR and Western blotting or immunofluorescence, respectively. Whole-cell patch-clamp electrophysiology was used for functional characterization of mutant subunits. RESULTS: A novel single-base duplication in exon 12 of KCNQ3 (NM_004519.3:c.1599dup) was found in homozygous configuration in the proband born to consanguineous healthy parents; this frameshift variant introduced a premature termination codon (PTC), thus deleting a large part of the C-terminal region. Mutant KCNQ3 transcript and protein abundance was markedly reduced in primary fibroblasts from the proband, consistent with nonsense-mediated mRNA decay. The variant fully abolished the ability of KCNQ3 subunits to assemble into functional homomeric or heteromeric channels with KCNQ2 subunits. SIGNIFICANCE: The present results indicate that a homozygous KCNQ3 loss-of-function variant is responsible for a severe phenotype characterized by neonatal-onset pharmacodependent seizures, with developmental delay and intellectual disability. They also reveal difference in genetic and pathogenetic mechanisms between KCNQ2- and KCNQ3-related epilepsies, a crucial observation for patients affected with EOEE and/or developmental disabilities

Yield, quality and antioxidants of peeled tomato as affected by genotype and industrial processing in southern Italy

Research was carried out on processing tomato in San Severo (Tavoliere delle Puglie, Foggia, Italy) in order to compare four long-type fruit hybrids oriented to peeled produce (Abbundo, Umex, Superpeel, Taylor), using a randomized complete block design with three replicates. The hybrid Superpeel reached the highest marketable yield due to the highest fruit number and mean weight; along the peeling chain, Umex and Taylor showed the highest processing efficiency. Titratable acidity and sodium were highest in Taylor fruits, whereas the highest fiber content was detected in Abbundo fruits. Compared to pre-processing fruits, peeled tomatoes showed increased values of total and soluble solids as well as reducing sugars, but decreased sugar ratio and colour. The highest concentrations of antioxidants in processed fruits were recorded in Umex for lycopene and in Superpeel for β-carotene. Compared to pre-processing fruits, in peeled tomatoes lycopene and β-carotene concentrations remained stable and polyphenols increased referring to fresh weight. The hybrids examined did not show univocal trends in terms of sensorial features

Deciphering exome sequencing data: Bringing mitochondrial DNA variants to light

The expanding use of exome sequencing (ES) in diagnosis generates a huge amount of data, including untargeted mitochondrial DNA (mtDNA) sequences. We developed a strategy to deeply study ES data, focusing on the mtDNA genome on a large unspecific cohort to increase diagnostic yield. A targeted bioinformatics pipeline assembled mitochondrial genome from ES data to detect pathogenic mtDNA variants in parallel with the "in-house" nuclear exome pipeline. mtDNA data coming from off-target sequences (indirect sequencing) were extracted from the BAM files in 928 individuals with developmental and/or neurological anomalies. The mtDNA variants were filtered out based on database information, cohort frequencies, haplogroups and protein consequences. Two homoplasmic pathogenic variants (m.9035T>C and m.11778G>A) were identified in 2 out of 928 unrelated individuals (0.2%): the m.9035T>C (MT-ATP6) variant in a female with ataxia and the m.11778G>A (MT-ND4) variant in a male with a complex mosaic disorder and a severe ophthalmological phenotype, uncovering undiagnosed Leber\u27s hereditary optic neuropathy (LHON). Seven secondary findings were also found, predisposing to deafness or LHON, in 7 out of 928 individuals (0.75%). This study demonstrates the usefulness of including a targeted strategy in ES pipeline to detect mtDNA variants, improving results in diagnosis and research, without resampling patients and performing targeted mtDNA strategies

Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples

Mobile element insertions (MEIs) are a known cause of genetic disease but have been underexplored due to technical limitations of genetic testing methods. Various bioinformatic tools have been developed to identify MEIs in Next Generation Sequencing data. However, most tools have been developed specifically for genome sequencing (GS) data rather than exome sequencing (ES) data, which remains more widely used for routine diagnostic testing. In this study, we benchmarked six MEI detection tools (ERVcaller, MELT, Mobster, SCRAMble, TEMP2 and xTea) on ES data and on GS data from publicly available genomic samples (HG002, NA12878). For all the tools we evaluated sensitivity and precision of different filtering strategies. Results show that there were substantial differences in tool performance between ES and GS data. MELT performed best with ES data and its combination with SCRAMble increased substantially the detection rate of MEIs. By applying both tools to 10,890 ES samples from Solve-RD and 52,624 samples from Radboudumc we were able to diagnose 10 patients who had remained undiagnosed by conventional ES analysis until now. Our study shows that MELT and SCRAMble can be used reliably to identify clinically relevant MEIs in ES data. This may lead to an additional diagnosis for 1 in 3000 to 4000 patients in routine clinical ES

Tracking with heavily irradiated silicon detectors operated at cryogenic temperatures

In this work we show that a heavily irradiated double-sided silicon microstrip detector recovers its performance when operated at cryogenic temperatures. A DELPHI microstrip detector, irradiated to a fluence of $\sim\,4\times 10^{14}$ p/cm$^2$, no longer operational at room temperature, cannot be distinguished from a non-irradiated one when operated at $T<120$~K. Besides confirming the previously observed `Lazarus effect' in single diodes, these results establish for the first time, the possibility of using standard silicon detectors for tracking applications in extremely demanding radiation environments

YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse.

Miller-Dieker syndrome is caused by a multiple gene deletion, including PAFAH1B1 and YWHAE. Although deletion of PAFAH1B1 causes lissencephaly unambiguously, deletion of YWHAE alone has not clearly been linked to a human disorder. Cases with YWHAE variants were collected through international data sharing networks. To address the specific impact of YWHAE loss of function, we phenotyped a mouse knockout of Ywhae. We report a series of 10 individuals with heterozygous loss-of-function YWHAE variants (3 single-nucleotide variants and 7 deletions &lt;1 Mb encompassing YWHAE but not PAFAH1B1), including 8 new cases and 2 follow-ups, added with 5 cases (copy number variants) from literature review. Although, until now, only 1 intragenic deletion has been described in YWHAE, we report 4 new variants specifically in YWHAE (3 splice variants and 1 intragenic deletion). The most frequent manifestations are developmental delay, delayed speech, seizures, and brain malformations, including corpus callosum hypoplasia, delayed myelination, and ventricular dilatation. Individuals with variants affecting YWHAE alone have milder features than those with larger deletions. Neuroanatomical studies in Ywhae &lt;sup&gt;-/-&lt;/sup&gt; mice revealed brain structural defects, including thin cerebral cortex, corpus callosum dysgenesis, and hydrocephalus paralleling those seen in humans. This study further demonstrates that YWHAE loss-of-function variants cause a neurodevelopmental disease with brain abnormalities

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

PURPOSE: Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. METHODS: Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. RESULTS: We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). CONCLUSION: The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock