Severe infantile-onset cardiomyopathy associated with a homozygous deletion in desmin

Desminopathy is a genetically heterogeneous disorder with autosomal dominant pattern of inheritance in most affected families; the age of disease onset is on average 30 years. We studied a patient with a history of recurrent episodes of syncope from infancy who later developed second-degree AV block and restrictive cardiomyopathy; she subsequently suffered several episodes of ventricular tachyarrhythmia requiring implantation of bicameral defibrillator. Neurological examination revealed rapidly progressive bilateral facial weakness, winging of the scapulae, symmetric weakness and atrophy of the trunk muscles, shoulder girdle and distal muscles of both upper and lower extremities. Muscle biopsy demonstrated signs of myofibrillar myopathy with prominent subsarcolemmal desmin-reactive aggregates. Molecular analysis identified a homozygous deletion in DES resulting in a predicted in-frame obliteration of seven amino acids (p.R173_E179del) in the 1B domain of desmin. We describe the youngest known desminopathy patient with severe cardiomyopathy and aggressive course leading to the devastation of cardiac, skeletal and smooth musculature at an early age

PK-guided switch between standard half-life and extended half-life factor VII products

P117 Introduction: Extended half-life (EHL) factor VIII (FVIII) requires improvements in half-life (t1/2) & area under the curve (AUC) of 1.3 & 1.25 times compared to standard half-life (SHL) products. The aim of this study is compare pharmacokinetics (PK) after the switch from SHL to EHL in patients with hemophilia A (HA). Methods: Multicenter comparative, cross-sectional, prospective study analyzing PK differences after switch from SHL to EHL (ef-moroctocog alfa [rFVIII-Fc] & rurioctocog alfa pegol [PEG-rFVIII]). WAPPS- Hemo® was used to analyze PK parameters with 2-3 samples: t1/2; AUC, peak level (PL); trough level at 24, 48 & 72 hours (TL24, TL48, TL72); & time to reach FVIII levels of 1, 2, 5% (T1%, T2%, T5%). Ratio of t1/2 & AUC, the number of weekly doses & the dose/kg/week before & after the switch were compared. Wilcoxon & Kruskal-Wallis tests (SPSS®) were used to compare the PK parameters. Results: Eightythree patients from 8 Spanish hospitals were analyzed (62 rFVIII-Fc; 21 PEG-rFVIII), 79 had severe HA & 4 moderate HA. Median age was 30 years (range = 3-64) & no differences in weight were observed between both periods.Dose/kg/week & weekly infusion frequency were reduced after the switch to EHL, & significant improvements were observed in all PK parameters after the change from SHL to EHL (Table 1). The median ratios of t1/2 & AUC were 1.3 (IQR:1.2-1.6) and 1.6 (IQR:1.3-2.2) in the entire cohort. In patients with =12 years ratios of t1/2 & AUC were 1.4 (IQR:1.3-1.6) & 1.7 (IQR:1.3-2.3), and in the cohort of 16 patients <12 years treated with rFVIII-Fc were 1.3 (IQR:0.9-1.5) and 1.4 (IQR:1.1- 2.1).After the switch to EHL, median weekly dose frequency (30%, IQR:0-33.3%) & dose/kg/week (16.9%, IQR:8.7-32.8%) were reduced. In a small subset of 15 younger patients the dose/kg/week was increased a median of 28.6% (IQR:11.7-40-7%). No differences were observed in any of the PK parameters & median ratios of t1/2 & AUC in patients aged =12 years treated with rFVIII-Fc vs. PEG-rFVIII (46 rFVIII-Fc; 21 PEG-rFVIII). Discussion/Conclusion: EHL FVIII have shown significant PK improvements in clinical real practice, allowing to reduce weekly infusion number & dose/kg/week. Outside the clinical trial setting, we have observed an increase in t1/2 & AUC ratios accordingly to EHL definition. Comparisons regarding clinical outcomes (bleeding rate after switch) will be performed after a follow-up of 1 year with EHL for the full cohort

In-band 16-QAM and multi-carrier SCM modulation to label DPSK payload signals for IP packet routing

We present an experimental demonstration of the feasibility of in-band subcarrier multiplexing (SCM) for labeling of differential phase shift keying (DPSK) payload signals. We show that by proper selection of the value of the subcarrier frequency the effect of the superimposed SCM label on the performance of the DPSK signal is minimized. Furthermore, we show experimentally the advantages of using alternative modulation formats such as 16-QAM and multi-carrier SCM for optical labeling of a 10 Gb/s DPSK payload signal

RF bandwidth capacity and SCM in a radio-over-fibre link employing optical frequency multiplication

We demonstrate the feasibility of generating two 24Mbps 64-QAM radio signals simultaneously at 17.3GHz and 17.8GHz after 4.4km of multimode fibre in an OFM radio-over-fibre link for wireless multistandard support at the antenna site

In-band 16-QAM and multi-carrier SCM modulation to label DPSK payload signals for IP packet routing

We present an experimental demonstration of the feasibility of in-band subcarrier multiplexing (SCM) for labeling of differential phase shift keying (DPSK) payload signals. We show that by proper selection of the value of the subcarrier frequency the effect of the superimposed SCM label on the performance of the DPSK signal is minimized. Furthermore, we show experimentally the advantages of using alternative modulation formats such as 16-QAM and multi-carrier SCM for optical labeling of a 10 Gb/s DPSK payload signal

Asynchronous, self-controlled, all-optical label and payload separator using nonlinear polarization rotation in a semiconductor optical amplifier

We demonstrate an all-optical label and payload separator based on nonlinear polarization rotation in a semiconductor optical amplifier (SOA). The proposed scheme uses a packet format composed of a label and payload information signal combined with a control signal by using polarization division multiplexing. The control signal is employed to separate the label from the payload signal by exploiting nonlinear polarization rotation in a SOA. Experimental results show a label from payload suppression factor of 22 dB. This scheme operates asynchronously and does not need external control signal. Clean and wide open eye diagrams are obtained for both the payload and the label signal operating at bit-rates of 10 Gbit/s and 625 Mbit/s, respectively

Asynchronous, self-controlled, all-optical label and payload separator using nonlinear polarization rotation in a semiconductor optical amplifier

We demonstrate an all-optical label and payload separator based on nonlinear polarization rotation in a semiconductor optical amplifier (SOA). The proposed scheme uses a packet format composed of a label and payload information signal combined with a control signal by using polarization division multiplexing. The control signal is employed to separate the label from the payload signal by exploiting nonlinear polarization rotation in a SOA. Experimental results show a label from payload suppression factor of 22 dB. This scheme operates asynchronously and does not need external control signal. Clean and wide open eye diagrams are obtained for both the payload and the label signal operating at bit-rates of 10 Gbit/s and 625 Mbit/s, respectively

An all-optical time-serial label and payload separator generating a synchronization pulse

We demonstrate an all-optical label and payload processor based on nonlinear optical processing with semiconductor optical amplifiers. The processor separates the label and the payload, and generates a synchronization pulse

An All-Optical Time-Serial Label and Payload Separator Generating a

We demonstrate an all-optical label and payload processor based on nonlinear optical processing with semiconductor optical amplifiers. The processor separates the label and the payload, and generates a synchronization pulse

Severe infantile-onset cardiomyopathy associated with a homozygous deletion in desmin

Desminopathy is a genetically heterogeneous disorder with autosomal dominant pattern of inheritance in most affected families; the age of disease onset is on average 30 years. We studied a patient with a history of recurrent episodes of syncope from infancy who later developed second-degree AV block and restrictive cardiomyopathy; she subsequently suffered several episodes of ventricular tachyarrhythmia requiring implantation of bicameral defibrillator. Neurological examination revealed rapidly progressive bilateral facial weakness, winging of the scapulae, symmetric weakness and atrophy of the trunk muscles, shoulder girdle and distal muscles of both upper and lower extremities. Muscle biopsy demonstrated signs of myofibrillar myopathy with prominent subsarcolemmal desmin-reactive aggregates. Molecular analysis identified a homozygous deletion in DES resulting in a predicted in-frame obliteration of seven amino acids (p.R173_E179del) in the 1B domain of desmin. We describe the youngest known desminopathy patient with severe cardiomyopathy and aggressive course leading to the devastation of cardiac, skeletal and smooth musculature at an early age