Free Running Single Photon Detection based on a negative feedback InGaAs APD

InGaAs/InP-based semiconductor avalanche photodiode are usually employed for single-photon counting at telecom wavelength. However they are affected by afterpulsing which limits the diode performance. Recently, Princeton Lightwave has commercialised a diode integrating monolithically a feedback resistor. This solution effectively quenches the avalanche and drastically reduces afterpulsing. Here, we report the development and characterization of a detector module based on this diode, implementing an active hold-off circuit which further reduces the afterpulsing and notably improves the detector performances. We demonstrate free-running operation with 600 Hz dark count rate at 10% detection efficiency. We also improved the standard double-window technique for the afterpulsing characterization. Our algorithm implemented by a FPGA allows to put the APD in a well-defined initial condition and to measure the impact of the higher order afterpulses.Comment: 18 pages, 15 figures. Submitted to Journal of Modern Optic

Advances in InGaAs/InP single-photon detector systems for quantum communication

Single-photon detectors (SPDs) are the most sensitive instruments for light detection. In the near-infrared range, SPDs based on III–V compound semiconductor avalanche photodiodes have been extensively used during the past two decades for diverse applications due to their advantages in practicality including small size, low cost and easy operation. In the past decade, the rapid developments and increasing demands in quantum information science have served as key drivers to improve the device performance of single-photon avalanche diodes and to invent new avalanche quenching techniques. This Review aims to introduce the technology advances of InGaAs/InP single-photon detector systems in the telecom wavelengths and the relevant quantum communication applications, and particularly to highlight recent emerging techniques such as high-frequency gating at GHz rates and free-running operation using negative-feedback avalanche diodes. Future perspectives of both the devices and quenching techniques are summarized

High Fluence Increases the Antibacterial Efficacy of PACK Cross-Linking

PURPOSE Photoactivated chromophore for keratitis cross-linking (PACK-CXL) is used as an adjunct therapy to antibiotic medication in infectious keratitis. This experimental study aimed at quantifying the PACK-CXL efficacy as a function of UV fluence using several bacterial strains and irradiated volumes. METHODS Six distinct bacterial strains, including standardized strains and clinically isolated strains from patients with keratitis, were analyzed. Bacterial concentrations between 10 and 10 cells/mL were used (simulating small corneal ulcers). Volumes of either 11 μL (≈285 μm stromal thickness) or 40 μL (≈1000 μm stromal thickness) were irradiated within a microtiter plate at different fluences (5.4-27 J/cm) and irradiances (3, 9 and 18 mW/cm). The ratio of bacterial killing (B†) was determined to evaluate the antimicrobial efficacy of PACK-CXL. RESULTS B† was similar (51 ± 11%) in bacterial concentrations between 10 and 10 per ml. In 11 μL volume, Staphylococcus aureus (SA) 8325-4 ATCC 29213, Bacillus subtilis (BS) 212901, and Pseudomonas aeruginosa (PA) 2016-866624 were most sensitive to PACK-CXL at 5.4 J/cm (on average B† = 49 ± 8%), whereas Klebsiella oxytoca (KO) 2016-86624 (B† = 25%) was least sensitive. When irradiating a larger volume, B† was on average lower in 40 μL (19 ± 18%), compared with 11 μL (45 ± 17%, P < 0.001). By contrast, applying a higher UV fluence increased B† of SA ATCC 29213, from 50% at 5.4 J/cm to 92% at 10.8 J/cm, to 100% at 16.2 J/cm and above. CONCLUSIONS Applying higher UV fluences substantially increases the bacterial killing rates. Safety limits for clinical application require further investigation

Characterisation of clinical manifestations of and treatment strategies for invasive beta-haemolytic streptococcal infections in a Swiss tertiary hospital

AIMS OF THE STUDY Invasive streptococcal infections affect more than half a million patients worldwide every year and have a high lethality. Little is known about the epidemiology and microbiological characteristics of streptococcal infections in Switzerland. This case series study aims to describe the demographics, known risk factors for streptococcal skin and soft tissue infections, clinical presentations, treatment and outcomes of patients admitted to the University Hospital Zurich between 2000 and 2014 with invasive streptococcal infections caused by Streptococcus pyogenes (group A Streptococcus), Streptococcus dysgalactiae ssp. equisimilis or the Streptococcus anginosus group, as well as the microbiological characteristics of the clinical isolates. METHODS Data collected retrospectively from patients hospitalised between 2000 and 2014 with invasive streptococcal infections were analysed. M protein gene (emm) typing of the bacterial clinical isolates was carried out according to the Centers for Disease Control and Prevention guidelines. RESULTS A total of 86 patients with invasive beta-haemolytic streptococcal infections were included in this study, of which 49% presented with necrotising fasciitis. The median age was 44 years and half were female. The most common risk factor was acute skin lesions. C-reactive protein levels were significantly higher in patients with necrotising fasciitis, as were acute renal failure and distributive shock. Beta-lactam antibiotics were given to most patients, and intravenous immunoglobulins were given to 18% of patients within the first 24 hours. All patients suffering from necrotising fasciitis underwent surgery. The overall case fatality rate was 8.1% at 30 days post admission. All Group A Streptococcus strains were susceptible to penicillin and clindamycin, and we found resistance to tetracycline in 11.9% of strains. The most common emm-type isolated was emm1 (44.4%). CONCLUSIONS Invasive beta-haemolytic streptococcal infections, the most severe presentation of which is necrotising fasciitis, remain a serious clinical issue and require rapid diagnosis and treatment. This is the first representative analysis monitoring clinical and microbiological characteristics of patients with a severe invasive beta-haemolytic streptococcal infection and treated in Zurich, Switzerland. In addition to the detailed reporting of various clinical and microbiological characteristics, we show that C-reactive protein levels, acute renal failure and distributive shock were higher in the patients with necrotising fasciitis. We also found a low case fatality rate compared to other reports. The detailed clinical data and microbiological characteristics depicted in this study will lead to a better understanding of regional differences in severe invasive streptococcal infections

Deleting a UBE3A substrate rescues impaired hippocampal physiology and learning in Angelman syndrome mice

In humans, loss-of-function mutations in the UBE3A gene lead to the neurodevelopmental disorder Angelman syndrome (AS). AS patients have severe impairments in speech, learning and memory, and motor coordination, for which there is currently no treatment. In addition, UBE3A is duplicated in &gt; 1-2% of patients with autism spectrum disorders-a further indication of the significant role it plays in brain development. Altered expression of UBE3A, an E3 ubiquitin ligase, is hypothesized to lead to impaired levels of its target proteins, but identifying the contribution of individual UBE3A targets to UBE3A-dependent deficits remains of critical importance. Ephexin5 is a putative UBE3A substrate that has restricted expression early in development, regulates synapse formation during hippocampal development, and is abnormally elevated in AS mice, modeled by maternally-derived Ube3a gene deletion. Here, we report that Ephexin5 can be directly ubiquitylated by UBE3A. Furthermore, removing Ephexin5 from AS mice specifically rescued hippocampus-dependent behaviors, CA1 physiology, and deficits in dendritic spine number. Our findings identify Ephexin5 as a key driver of hippocampal dysfunction and related behavioral deficits in AS mouse models. These results demonstrate the exciting potential of targeting Ephexin5, and possibly other UBE3A substrates, to improve symptoms of AS and other UBE3A-related developmental disorders

Spontaneous reversal of stenosis in tissue-engineered vascular grafts

We developed a tissue-engineered vascular graft (TEVG) for use in children and present results of a U.S. Food and Drug Administration (FDA)-approved clinical trial evaluating this graft in patients with single-ventricle cardiac anomalies. The TEVG was used as a Fontan conduit to connect the inferior vena cava and pulmonary artery, but a high incidence of graft narrowing manifested within the first 6 months, which was treated successfully with angioplasty. To elucidate mechanisms underlying this early stenosis, we used a data-informed, computational model to perform in silico parametric studies of TEVG development. The simulations predicted early stenosis as observed in our clinical trial but suggested further that such narrowing could reverse spontaneously through an inflammation-driven, mechano-mediated mechanism. We tested this unexpected, model-generated hypothesis by implanting TEVGs in an ovine inferior vena cava interposition graft model, which confirmed the prediction that TEVG stenosis resolved spontaneously and was typically well tolerated. These findings have important implications for our translational research because they suggest that angioplasty may be safely avoided in patients with asymptomatic early stenosis, although there will remain a need for appropriate medical monitoring. The simulations further predicted that the degree of reversible narrowing can be mitigated by altering the scaffold design to attenuate early inflammation and increase mechano-sensing by the synthetic cells, thus suggesting a new paradigm for optimizing next-generation TEVGs. We submit that there is considerable translational advantage to combined computational-experimental studies when designing cutting-edge technologies and their clinical management