High-speed Si/GeSi hetero-structure Electro Absorption Modulator.

The ever-increasing demand for integrated, low power interconnect systems is pushing the bandwidth density of CMOS photonic devices. Taking advantage of the strong Franz-Keldysh effect in the C and L communication bands, electro-absorption modulators in Ge and GeSi are setting a new standard in terms of device footprint and power consumption for next generation photonics interconnect arrays. In this paper, we present a compact, low power electro-absorption modulator (EAM) Si/GeSi hetero-structure based on an 800 nm SOI overlayer with a modulation bandwidth of 56 GHz. The device design and fabrication tolerant process are presented, followed by the measurement analysis. Eye diagram measurements show a dynamic ER of 5.2 dB at a data rate of 56 Gb/s at 1566 nm, and calculated modulator power is 44 fJ/bit.

A series of 38 novel germline and somatic mutations of NIPBL in Cornelia de Lange syndrome.

Cornelia de Lange syndrome is a multisystemic developmental disorder mainly related to de novo heterozygous NIPBL mutation. Recently, NIPBL somatic mosaicism has been highlighted through buccal cell DNA study in some patients with a negative molecular analysis on leukocyte DNA. Here, we present a series of 38 patients with a Cornelia de Lange syndrome related to a heterozygous NIPBL mutation identified by Sanger sequencing. The diagnosis was based on the following criteria: (i) intrauterine growth retardation and postnatal short stature, (ii) feeding difficulties and/or gastro-oesophageal reflux, (iii) microcephaly, (iv) intellectual disability, and (v) characteristic facial features. We identified 37 novel NIPBL mutations including 34 in leukocytes and 3 in buccal cells only. All mutations shown to have arisen de novo when parent blood samples were available. The present series confirms the difficulty in predicting the phenotype according to the NIPBL mutation. Until now, somatic mosaicism has been observed for 20 cases which do not seem to be consistently associated with a milder phenotype. Besides, several reports support a postzygotic event for those cases. Considering these elements, we recommend a first-line buccal cell DNA analysis in order to improve gene testing sensitivity in Cornelia de Lange syndrome and genetic counselling.

Ultra-compact III‒V-on-Si photonic crystal memory for flip-flop operation at 5 Gb/s.

We report on a photonic crystal (PhC) nanolaser based on the heterogeneous integration of a III-V PhC nanocavity on SOI, configured to operate as a Set-Reset Flip-Flop (SR-FF). The active layer is a nanobeam cavity made of a 650 nm × 285 nm InP-based wire waveguide evanescently coupled to 500 nm × 220 nm SOI wire waveguides, demonstrating a record-low footprint of only 6.2 µm2. Injection locking enables optical bistability allowing for memory operation with only 6.4 fJ/bit switching energies and <50 ps response times. Bit-level SR-FF memory operation was evaluated at 5 Gb/s with PRBS-resembling data patterns, revealing error free operation with a negative power penalty.

Molecular characterization of 39 de novo sSMC: contribution to prognosis and genetic counselling, a prospective study.

Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.

Modulation contrast optimization for wavelength conversion of a 20 Gbit/s data signal in hybrid InP/SOI photonic crystal nanocavity.

Photonic crystal cavity-based switching is studied both theoretically and experimentally in order to identify the best configuration to maximize "wavelength conversion" efficiency. In particular, it is shown that an enhanced contrast can be reached when the probe is blueshifted with respect to the resonance. The use of an InP/SOI hybrid photonic crystal nanocavity is reported for the first time for all-optical error-free "wavelength conversion" at 20 Gbit/s with a nonreturn to zero on-off keying signal.

A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes.

OBJECTIVE: The 22q11.2 deletion (del22q11.2) is one of the most common microdeletions. We performed a collaborative, retrospective analysis in France of prenatal diagnoses and outcomes of fetuses carrying the del22q11.2. METHODS: A total of 272 fetuses were included. Data on prenatal diagnosis, ultrasound findings, pathological features, outcomes and inheritance were analyzed. RESULTS: The mean time of prenatal diagnosis was 25.6 ± 6 weeks of gestation. Most of the diagnoses (86.8%) were prompted by abnormal ultrasound findings [heart defects (HDs), in 83.8% of cases]. On fetal autopsy, HDs were again the most common disease feature, but thymus, kidney abnormalities and facial dysmorphism were also described. The deletion was inherited in 27% of cases. Termination of pregnancy (TOP) occurred in 68.9% of cases and did not appear to depend on the inheritance status. However, early diagnosis was associated with a higher TOP rate. CONCLUSION: This is the largest cohort of prenatal del22q11.2 diagnoses. As in postnatally diagnosed cases, HDs were the most frequently observed abnormalities. However, thymus and kidney abnormalities and polyhydramnios should also be screened for in the prenatal diagnosis of del22q11.2. Only the time of diagnosis appeared to be strongly associated with the pregnancy outcome: the earlier the diagnosis, the higher the TOP rate.

[Facial nerve outcome after vestibular schwannoma surgery: About 89 patients]. / Fonction du nerf facial après chirurgie du schwannome vestibulaire: àpropos de 89 patients.

OBJECTIVES: We evaluated the postoperative facial nerve function after vestibular schwannoma (VS) surgery and analyzed factors causing it. MATERIAL AND METHODS: We included 89 consecutive patients undergoing surgical excision of unilateral VS. Patient and tumor characteristics, surgical approaches, facial nerve function, extent of tumor resection and complications were analyzed. RESULTS: Complete tumor resection was achieved in 85% of cases. Anatomic preservation of the facial nerve was achieved in 96% of patients. In all tumor stages, 88.2% of patients, have a normal or subnormal facial function within one year of the intervention, the rate was 100% in patients carrying a VS stage I or II. No severe complication or death was reported. CONCLUSION: Short- and long-term facial nerve outcome was comparable with results of other recent series reported in literature. The facial nerve function after surgery was better with small VS compared to large VS. The intraoperative decision of near-total excision of the tumor followed by adjuvant radiotherapy, in some cases, can prove to be a good option in the interest of better preservation of the facial nerve function. The adhesion of the facial nerve and its complex relationship with the tumor remain mysterious; RMI can bring significant refinements, helping to get the best preservation offacial function rate, in the coming years.

Uniformity of the lasing wavelength of heterogeneously integrated InP microdisk lasers on SOI.

We report a high lasing wavelength uniformity of optically pumped InP-based microdisk lasers processed with electron-beam lithography, heterogeneously integrated with adhesive bonding on silicon-on-insulator (SOI) waveguide circuits and evanescently coupled to an underlying waveguide. We study the continuous wave laser emission coupling out of the SOI via a grating coupler etched at one side of the waveguide, and demonstrate a standard deviation in lasing wavelength of nominally identical devices on the same chip lower than 500 pm. The deviation in the diameter of the microdisks as low as a few nanometers makes all-optical signal processing applications requiring cascadability possible.

Maternal transmission of interstitial 8p23.1 deletion detected during prenatal diagnosis.

We report on the first prenatally diagnosed interstitial 8p23.1 maternally inherited deletion. At 20 weeks of gestation (WG) the fetus was diagnosed with a complete atrioventricular canal. In infancy, the mother underwent a two-step cardiac surgery for an interrupted aortic arch type A associated to an inlet ventricular septal defect (VSD). A straddling of the tricuspid valve type B was confirmed during surgery. The outcome showed no cardiac failure or conduction anomalies. However, she presented with moderate intellectual disability. Classical and molecular cytogenetic studies on amniotic and maternal lymphocytes cells showed a nearly identical interstitial deletion of the 8p23.1 region encompassing the GATA4 gene locus (Mother: nt 6,913,337-12,580,828, fetus: nt 7,074,449-12,580,828) with no modification of the telomeric region. The relevance of our report is not only the maternal syndromic interstitial 8p23.1 deletion, but also maternal transmission which has never been reported before. The maternal and fetal phenotypes were not identical, however, even though they had the same cellular and molecular background: an alteration of the epithelial mesenchymal transition of the atrioventricular valvulo-septal complex where GATA4 plays a positive role in the regulation. We reviewed all cases of interstitial 8p23.1 deletions diagnosed either prenatally or postnatally.

Effect of single-unit transfusion in patients treated for haematological disease including acute leukemia: A multicenter randomized controlled clinical trial.

BACKGROUND: Retrospective studies in hematological unit have suggested that single red blood cell (1-RBC) unit transfusion policy may reduce the number of RBC used without negative clinical impact. METHOD: Acute leukemia patients requiring intensive chemotherapy or patients receiving autologous or allogeneic transplantation were randomly assigned to receive either single RBC (1-RBC arm) or double RBC (2-RBC arm) per transfusion with a hemoglobin trigger of 8 g/dL. The primary composite endpoint was the percentage of patients experiencing serious complications, such as a non-hematological adverse event grade ≥ 3 or intensive care admission or death. FINDINGS: A total of 981 and 592 RBC transfusions were required in the 1-RBC arm (n = 125) and the 2-RBC arm (n = 120), respectively. The mean pre-transfusion hemoglobin levels were 7.49 ± 0.83 g/dL in the 1-RBC arm and 7.46 ± 0.67 g/dL in the 2-RBC arm (p = 0.275). The predefined non-inferiority criteria was achieved with 28/125 patients reaching the primary endpoint in the 1-RBC arm (22.4 %) and 28/120 patients in the 2-RBC arm (23.3 %) (Risk difference 0.009; 95 %, Confidence interval [-0.0791 to 0.0978], p = 0.021). The median (IQR) of RBC units transfused per patient was 7 (4-12) in the 1-RBC arm and 8 (4-12) in 2-RBC arm. Hemoglobin levels at discharge were also comparable in both arms. INTERPRETATION: The results of this trial indicate that a single RBC transfusion policy is not inferior to a double RBC transfusion policy for patients receiving a bone marrow transplant or intensive chemotherapy in a hematological intensive care unit. However, the single RBC transfusion policy did not reduce the number of RBC units transfused per stay. FUNDING: This trial was funded by a grant from the French Ministry of Health.

Trisomy 7 mosaicism prenatally misdiagnosed and maternal uniparental disomy in a child with pigmentary mosaicism and Russell- Silver syndrome.

Prenatal diagnosis of true mosaic trisomy 7 is rare in amniotic fluid and can be misinterpreted as pseudomosaic. The phenotype is highly variable and may be modified by a maternal uniparental disomy of chromosome 7 leading to mild Russell-Silver syndrome (RSS). We report here the third postnatal case of mosaic trisomy 7 with maternal uniparental disomy of chromosome 7 in a boy presenting a mild RSS. Fetal karyotype performed in amniocentesis for intrauterine growth retardation was considered normal. Mosaic trisomy 7 was diagnosed after birth, on fibroblasts karyotype performed for blaschkolinear pigmentary skin anomalies and failure to thrive. Maternal uniparental disomy of chromosome 7 was observed in blood sample. Retrospectively, trisomic 7 cells were identified in one prenatal long-term flask culture revealing a prenatal diagnosis failure. This report emphasizes the difficulty of assessing fetal mosaicism and distinguishing it from pseudomosaicism in cultured amniocytes. It is important to search for uniparental disomy as an indirect clue of trisomy 7 mosaicism and a major prognosis element. Although there are only few prenatal informative cases, detection of trisomy 7 in amniocentesis appears to be associated with a relatively good outcome when maternal uniparental disomy has been ruled out.

High quality beaming and efficient free-space coupling in L3 photonic crystal active nanocavities.

We report on far-field measurements of L3 photonic crystal (PhC) cavities with high quality beaming. This is achieved by means of the so-called "band folding" technique, in which a modulation of the radius of specific holes surrounding the cavity is introduced. Far-field patterns are measured from photoluminescence of quantum wells embedded in the PhC. A very good agreement between experimental results and simulated radiation patterns has been found. Laser effect is demonstrated in the beaming cavity with a threshold comparable to the regular one. In addition, free-space input coupling to this cavity has been achieved. In order to fully analyze the coupling efficiency, we generalize the approach developed in S. Fan, et al., [J. Opt. Soc. Am. A 20, 569 (2003)], relaxing the hypothesis of mirror symmetry. The obtained coupling efficiencies are about 15% with quality factors (Q) exceeding 10(4). These results further validate the "folding" technique on L3 cavities for nanocavity realization with efficient free-space coupling and high Q factors.

Occupational hepatitis C seroconversions in a Brazilian hospital.

BACKGROUND: There are six known cases of occupational human immunodeficiency virus (HIV) seroconversion in Brazil. However, there are neither published cases of occupational hepatitis C virus (HCV) seroconversion nor systematic studies of blood and body fluid exposures (BBFE) that could estimate the risk of HCV or HIV occupational seroconversion in Brazil. AIMS: To describe the outcomes of BBFEs in a Brazilian hospital over 12 years and 2 months. METHODS: Statistical analysis of a computerized database of exposure events recorded on printed forms. Incidence rates (IR) were calculated as the number of BBFE per 100 full-time equivalent worker-years. RESULTS: There were 1457 BBFE, 87% being percutaneous and 561 (38%) recurring in health care workers (HCWs) who reported having previous exposures. The highest IRs occurred in laboratory technicians (9.7), medical students (9.5), cleaning staff (9.5) and nursing aids (9.2). The IR in temporary employees was 13.0. Two HCWs, a nursing aid and a surgeon, seroconverted to hepatitis C after HCV exposures involving 13 G catheter needles. The risk of acquiring a HCV infection was 2 in 38 percutaneous HCV exposures, i.e. 5% (95% CI: 0.89-16.3). There were no seroconversions to HIV despite 80 percutaneous HIV exposures. CONCLUSIONS: HCV has a higher potential for occupational transmission than HIV. Measures to reduce the risks of BBFE and occupational transmission of blood-borne viral infections should be improved in Brazil.

Hybrid III-V semiconductor/silicon nanolaser.

Heterogeneous integration of III-V compound semiconductors on Silicon on Insulator is one the key technology for next-generation on-chip optical interconnects. In this context, the use of photonic crystals lasers represents a disruptive solution in terms of footprint, activation energy and ultrafast response. In this work, we propose and fabricate very compact laser sources integrated with a passive silicon waveguide circuitry. Using a subjacent Silicon-On-Insulator waveguide, the emitted light from a photonic crystal based cavity laser is efficiently captured. We study experimentally the evanescent wave coupling responsible for the funneling of the emitted light into the silicon waveguide mode as a function of the hybrid structure parameters, showing that 90% of coupling efficiency is possible.

Hypersensitivity reactions to blood components: document issued by the allergy committee of the French medicines and healthcare products regulatory agency.

These guidelines represent a consensus among experts on hypersensitivity reactions occurring after transfusion of blood components. They cover recognition, investigation, treatment, and prevention of such reactions. Implemented in France under the auspices of the French Medicines and Healthcare Products Regulatory Agency (AFSSAPS) and based on current knowledge, research, and experience, they aim to provide effective and easily teachable means of further improving the quality of hemovigilance databases, promote interest in this field, and help identify possible mechanisms and at-risk patient groups.

Prenatal diagnosis of 18q-syndrome: a case of fetal mosaicism with a normal karyotype in chorionic villi.

We report a case of fetoplacental discrepancy with normal karyotype on chorionic villi and deletion of the long arm of chromosome 18 on amniotic fluid. Cytogenetic tests were repeated because of a short corpus callosum on ultrasound examination. This 18q-syndrome has been reported to be associated with poor neurodevelopmental outcome.

Efficacy of microsurgical vascular decompression in trigeminal neuralgia.

OBJECTIVES: Analysis of the long-term efficacy of microvascular decompression surgery in trigeminal neuralgia. MATERIAL AND METHODS: A single-center retrospective study included patients undergoing microvascular decompression surgery for trigeminal neuralgia after failure of well-conducted medical or complementary therapy, with visualization of nerve compression syndrome on MRI. RESULTS: Eighty-seven patients were included. Nerve compression was alleviated without interposition of polytetrafluoroethylene in 79.3% of cases. Postoperative efficacy on pain was immediate in 97.7% of cases. There were no postoperative deaths, and the rate of severe complications was low (2.3%). The efficacy of microvascular decompression surgery was total at 2 years in 90.8% of cases and at 10 years in 92.3%, without resumption of medical treatment. The failure rate was 10.3%; 26.3% of these patients had been previously treated by a lesional technique (P: 0.043) and 33.3% by interposition of polytetrafluoroethylene (P: 0.003). CONCLUSIONS: With confirmed clinical and radiological diagnosis, microvascular decompression surgery for trigeminal nerve compression was safe, with total effectiveness in the immediate, short and long terms. It should be considered in first line in case of failure or intolerance of well-conducted medical treatment.

Hearing preservation and facial nerve function after microsurgery for intracanalicular vestibular schwannomas: comparison of middle fossa and retrosigmoid approaches.

PURPOSE: Therapeutic options for vestibular schwannomas (VS) include microsurgery, stereotactic radiosurgery and conservative management. Early treatment of intracanalicular vestibular schwannomas (IVS) may be advisable because their spontaneous course will show hearing loss in most cases. Advanced microsurgical techniques and continuous intraoperative monitoring of cranial nerves may allow hearing preservation (HP) without facial nerve damage. However, there are still controversies about the definition of hearing preservation, and the best surgical approach that should be used. METHODS: In this study, we reviewed the main data from the recent literature on IVS surgery and compared hearing, facial function and complication rates after the retrosigmoid (RS) and middle fossa (MF) approaches, respectively. RESULTS: The results showed that the average HP rate after IVS surgery ranged from 58% (RS) to 62% (MF). HP varied widely depending on the audiometric criteria that were used for definition of serviceable hearing. There was a trend to show that the MF approach offered a better quality of postoperative hearing (not statistically significant), whereas the RS approach offered a better facial nerve preservation and fewer complications (not statistically significant). CONCLUSIONS: We believe that the timing of treatment in the course of the disease and selection between radiosurgical versus microsurgical procedure are key issues in the management of IVS. Preservation of hearing and good facial nerve function in surgery for VS is a reasonable goal for many patients with intracanalicular tumors and serviceable hearing. Once open surgery has been decided, selection of the approach mainly depends on individual anatomical considerations and experience of the surgeon.

[Nocardia brain abscess: features, therapeutic strategies and outcome]. / Abcès cérébraux àNocardia: caractéristiques radiocliniques et prise en charge thérapeutique.

BACKGROUND AND PURPOSE: Nocardia species is an aerobic soil-saprophyte bacterium, responsible for rare opportunistic infections, mainly reported in immunocompromised patients. Nocardia brain abscess accounts for 1 to 2% of cerebral abscesses. Prognosis is poor. METHODS: We describe clinical, radiological and bacteriological findings along with therapeutic aspects for five patients and review the literature on Nocardia cerebral abscess. RESULTS: The clinical features of Nocardia brain abscess are insidious and nonspecific, occurring frequently with a medical background of obvious or latent immunodeficiency; fever, if any, is observed subordinate to extracerebral nocardiosis. Computerized tomography scan and conventional magnetic resonance (MR) scan show lesions with a necrotic core and multilobed thick walls enhancing after injection of gadolinium or iodine. Abscesses are mainly located in the brain stem, basal ganglia and cerebral cortex of the frontal, parietal and occipital lobes; cerebellar and spinal locations are uncommon. MR diffusion-weighted imaging with calculation of apparent diffusion coefficient and proton MR spectroscopy can provide additional data for accurate differential diagnosis between abscess and other necrotic lesions, such as tumor and cyst formations. Bacteriological identification has progressed with advances in molecular microbiology: 16S rRNA sequencing, allowing a more rapid routine identification of Nocardia strains from clinical samples. Clinical management of patients with a Nocardia brain abscess relies upon early use of intravenous antibiotics adapted to the strains identified and their susceptibility. Most Nocardia strains display susceptibility to cotrimoxazol, amikacin and linezolid, but develop beta-lactamase activity. CONCLUSIONS: Early pus samples, obtained by biopsy or surgical resection, are needed to establish a certain bacteriological diagnosis and initiate appropriate intravenous antibiotics.

Drilling and control of the internal auditory canal by fixed endoscope.

Preservation of vestibular structures, particularly the posterior semicircular canal, is essential to ensure hearing preservation in addition to complete tumour resection during retrosigmoid surgical resection of a vestibular schwannoma. Drilling of the internal auditory canal (IAC) is a delicate step, during which these structures can be accidentally perforated. The orientation of the IAC results in the formation of poorly visible zones that can predispose to perforation of these structures when drilling is performed with a microscope. Hand-held endoscopy exposes all of the operative field, but immobilizes one of the surgeon's hands, making this surgery even more delicate. Fixed endoscopy is a solution that gives the surgeon greater freedom of movement, while ensuring precise control of the surgical procedure. It allows identification and avoidance of vestibular structures, while allowing resection as close as possible to the tumour. The schwannoma can be entirely cleaved when the fundus of the IAC is correctly controlled, while sparing the facial and cochlear nerves.