Minimizing Energy Consumption for 5G NR Beam Management for RedCap Devices

In 5G New Radio (NR), beam management entails periodic and continuous transmission and reception of control signals in the form of synchronization signal blocks (SSBs), used to perform initial access and/or channel estimation. However, this procedure demands continuous energy consumption, which is particularly challenging to handle for low-cost, low-complexity, and battery-constrained devices, such as RedCap devices to support mid-market Internet of Things (IoT) use cases. In this context, this work aims at reducing the energy consumption during beam management for RedCap devices, while ensuring that the desired Quality of Service (QoS) requirements are met. To do so, we formalize an optimization problem in an Indoor Factory (InF) scenario to select the best beam management parameters, including the beam update periodicity and the beamwidth, to minimize energy consumption based on users' distribution and their speed. The analysis yields the regions of feasibility, i.e., the upper limit(s) on the beam management parameters for RedCap devices, that we use to provide design guidelines accordingly

Définition de valeurs normales de testostérone libre chez la femme (influence de l'indice de masse corporelle et application dans le diagnostic du syndrome des ovaires polykystiques)

Nous nous proposons dans cette étude de déterminer des valeurs normales de testostérone libre chez la femme d après une méthode de calcul se basant sur les concentrations de testostérone totale et de Sex Hormone Binding Globulin (SHBG), et utilisant la loi d action de masse. Nous avons mis en évidence l intérêt d adapter ces valeurs normales au statut métabolique du sujet puisque nous avons démontré une corrélation significative entre l indice de masse corporelle (BMI) et la valeur de la testostérone libre calculée.Nous proposons donc les intervalles de référence suivants: Femmes non obèses (BMI = 30) : de 6.0 à 36.1 pmol/L avec une médiane à 17.8 pmol/L.L étude de l apport de la testostérone libre dans l aide au diagnostic du syndrome des ovaires polykystiques fait ressortir des performances médiocres mais toutefois supérieures à celles de la testostérone totale. Cette étude permet cependant de souligner encore l importance de l adaptation du seuil décisionnel au BMI de la patiente. En effet nous avons mis en évidence que l utilisation d un seuil commun à toutes les patientes conduisait à un tiers de valeurs faussement élevées chez les patientes obèsesLILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Applicability and Efficiency of NGS in Routine Diagnosis: In-Depth Performance Analysis of a Complete Workflow for CFTR Mutation Analysis.

BACKGROUND:Actually, about 2000 sequence variations have been documented in the CFTR gene requiring extensive and multi-step genetic testing in the diagnosis of cystic fibrosis and CFTR-related disorders. We present a two phases study, with validation and performance monitoring, of a single experiment methodology based on multiplex PCR and high throughput sequencing that allows detection of all variants, including large rearrangements, affecting the coding regions plus three deep intronic loci. METHODS:A total of 340 samples, including 257 patients and 83 previously characterized control samples, were sequenced in 17 MiSeq runs and analyzed with two bioinformatic pipelines in routine diagnostic conditions. We obtained 100% coverage for all the target regions in every tested sample. RESULTS:We correctly identified all the 87 known variants in the control samples and successfully confirmed the 62 variants identified among the patients without observing false positive results. Large rearrangements were identified in 18/18 control samples. Only 17 patient samples showed false positive signals (6.6%), 12 of which showed a borderline result for a single amplicon. We also demonstrated the ability of the assay to detect allele specific dropout of amplicons when a sequence variation occurs at a primer binding site thus limiting the risk for false negative results. CONCLUSIONS:We described here the first NGS workflow for CFTR routine analysis that demonstrated equivalent diagnostic performances compared to Sanger sequencing and multiplex ligation-dependent probe amplification. This study illustrates the advantages of NGS in term of scalability, workload reduction and cost-effectiveness in combination with an improvement of the overall data quality due to the simultaneous detection of SNVs and large rearrangements

Clinical interpretation of SPINK1 and CTRC variants in pancreatitis

International audienceSince the description of the SPINK1 gene encoding the serine protease inhibitor Kazal type 1 and the CTRC gene encoding the Chymotrypsin C as being involved in chronic pancreatitis, more than 56 SPINK1 and 87 CTRC variants have been reported. Assessing the clinical relevance of SPINK1 and CTRC variants is often complicated in the absence of functional evidence and interpretation of rare variants is not very easy in clinical practice. The aim of this study was to review the different variants identified in these two genes and to classify them according to their degree of damaging effect. This classification was based on the results of in vitro experiments, in silico analysis using different prediction tools, and on population data, in comparing the allelic frequency of each variant in patients with pancreatitis and in unaffected control individuals. This review should help geneticists and clinicians in charge of patient's care and genetic counseling to interpret the results of genetic studies

Clinical interpretation of PRSS1 variants in patients with pancreatitis

International audienceSince the description of the PRSS1 gene encoding the cationic trypsinogen as being involved in dominant hereditary pancreatitis, more than 50 PRSS1 variants have been reported. Among the PRSS1 variants that have been classified as pathogenic, some have a high penetrance and others have a low penetrance. Assessing the clinical relevance of PRSS1 variants is often complicated in the absence of functional evidence and interpretation of rare variants is not very easy in clinical practice. The aim of this study was to review the different variants identified in the PRSS1 gene and to classify them according to their degree of deleterious effect. This classification was based on the results of several in vitro experiments and on population data, in comparing the allelic frequency of each variant in patients with pancreatitis and in unaffected individuals. This review should help geneticists and clinicians in charge of patient's care and genetic counseling to interpret molecular results

Novel ADGRG2 truncating variants in patients with X‐linked congenital absence of vas deferens

International audienceBACKGROUND:Congenital absence of vas deferens (CAVD) represents a major cause of obstructive azoospermia and is mainly related to biallelic alteration of the CFTR gene, also involved in cystic fibrosis. Using whole exome sequencing, we recently identified hemizygous loss-of-function mutations in the Adhesion G Protein-coupled Receptor G2 gene (ADGRG2) as responsible of isolated CAVD in the absence of associated unilateral renal agenesis.OBJECTIVES:The objective of this study was to retrospectively perform ADGRG2 sequencing on a large cohort of patients with CAVD, and 0 or only 1 CFTR defective allele identified after comprehensive testing in order to (a) define more precisely the spectrum and the frequency of ADGRG2 mutations within Caucasian population (b) explore the possibility of co-occurrence of CFTR and ADGRG2 mutations.MATERIALS AND METHODS:We collected 53 DNA samples from CAVD patients with 0 (n = 23) or 1 (n = 30) alteration identified after comprehensive CFTR testing in order to perform ADGRG2 sequencing. Twenty patients had normal ultrasonographic renal examination, and renal status was not documented for 33 patients.RESULTS:We identified six new truncating ADGRG2 mutations in 8 patients including two twin brothers: c.251C > G (p.Ser84*), c.1013delC (p.Pro338Hisfs*4), c.1460delG (p.Gly487Alafs*9), c.2096dupT (p.Phe700Ilefs*29), c.2473C > T (p.Arg825*), and c.1731_1839 + 373del (p.Asn578Thrfs*12), which is a 596 base pair deletion affecting the last five bases of exon 21 and the whole exon 22. Five of the eight patients also harbored an heterozygous CFTR mutation which we consider as incidental regarding the high penetrance expected for ADGRG2 truncating variants. The frequency of ADGRG2 truncating mutation was 26% (5/19 unrelated patients) when presence of both kidneys was attested by ultrasonography and 6.1% (2/33) among patients with unknown renal status.DISCUSSION & CONCLUSION:Our results confirm the interest of ADGRG2 sequencing in patients with CAVD not formerly related to CFTR dysfunction, especially in the absence of associated unilateral renal agenesis

Genotypes tested in validation phase (phase 1).

<p>Genotypes tested in validation phase (phase 1).</p

Impact of primer trimming on variant calling.

<p>(A) Overestimation of WT allele at variant A locus due to the presence of the primers sequence in the sequencing reads of Amplicon 2 as observed for c.1000C>T (the same principle applies to c.2583del and c.2589_2599del, which are located under the R2 primer of Amplicon 1). When no allele drop-out occurred, variant A is present in 3/12 reads in R1 direction (3/6 from Amplicon1 and 0/6 from Amplicon2) and 3/6 reads in R2 direction for Amplicon1 for a total VAF of 6/18 = 33%. There is a risk of false negative for variant A if the depth of coverage of Amplicon2 is superior to Amplicon1, resulting in a VAF under the detection threshold. In the case of an allele drop-out of Amplicon 2 due to the presence of variant A, then variant A is present in 3/9 reads in R1 direction (3/6 from Amplicon1 and 0/3 from Amplicon2) and 3/6 reads in R2 direction for Amplicon1 for a total VAF of 6/15 = 40%. In this case there is also a risk of false negative if a second variant is associated in cis with variant A (as illustrated by variant B). (B) Impact of primer trimming to limit the risk of false negative results. When primer sequences are removed from the reads, the VAF for variant A is 50% independently of the risk of allele drop-out. In the case of a complex allele involving variant A and B, the risk of false negative result for variant B due to allele drop-out of Amplicon 2 is still present and can be addressed by concomitant CNVs detection followed by Sanger sequencing with a different primer set.</p

CNVs analysis of Phase 2 samples.

<p>RPC_CNV for (1) every amplicon of 3 negative samples verified by MLPA, (2) deleted amplicons for CFTRdele2_3 (n = 14) and CFTRdele1_24 (n = 1) positive controls, (3) apparently deleted amplicons in false positive samples (n = 6 samples for 15 amplicons), (4) duplicated amplicons for CFTRdup4_10 controls (n = 2) and (5) apparently duplicated amplicons in false positive samples (n = 14 samples for 20 amplicons). Three samples showed false positive signals for both deletion and amplification. Dot lines indicate thresholds for deletion (0.7) and duplication (1.3).</p

Variants identified in the performance monitoring phase (Phase 2).

<p>Variants identified in the performance monitoring phase (Phase 2).</p