High sensitivity Ge-on-Si single-photon avalanche diode detectors.

The performance of planar geometry Ge-on-Si single-photon avalanche diode detectors of 26µm diameter is presented. Record low dark count rates are observed, remaining less than 100 K counts per second at 6.6% excess bias and 125 K. Single-photon detection efficiencies are found to be up to 29.4%, and are shown to be temperature insensitive. These performance characteristics lead to a significantly reduced noise equivalent power (NEP) of 7.7×10-17WHz-12 compared to prior planar devices, and represent a two orders of magnitude reduction in NEP compared to previous Ge-on-Si mesa devices of a comparable diameter. Low jitter values of 134±10ps are demonstrated.

Postexposure Prophylaxis With rVSV-ZEBOV Following Exposure to a Patient With Ebola Virus Disease Relapse in the United Kingdom: An Operational, Safety, and Immunogenicity Report.

BACKGROUND: In October 2015, 65 people came into direct contact with a healthcare worker presenting with a late reactivation of Ebola virus disease (EVD) in the United Kingdom. Vaccination was offered to 45 individuals with an initial assessment of high exposure risk. METHODS: Approval for rapid expanded access to the recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine as an unlicensed emergency medicine was obtained from the relevant authorities. An observational follow-up study was carried out for 1 year following vaccination. RESULTS: Twenty-six of 45 individuals elected to receive vaccination between 10 and 11 October 2015 following written informed consent. By day 14, 39% had seroconverted, increasing to 87% by day 28 and 100% by 3 months, although these responses were not always sustained. Neutralizing antibody responses were detectable in 36% by day 14 and 73% at 12 months. Common side effects included fatigue, myalgia, headache, arthralgia, and fever. These were positively associated with glycoprotein-specific T-cell but not immunoglobulin (Ig) M or IgG antibody responses. No severe vaccine-related adverse events were reported. No one exposed to the virus became infected. CONCLUSIONS: This paper reports the use of the rVSV-ZEBOV vaccine given as an emergency intervention to individuals exposed to a patient presenting with a late reactivation of EVD. The vaccine was relatively well tolerated, but a high percentage developed a fever ≥37.5°C, necessitating urgent screening for Ebola virus, and a small number developed persistent arthralgia.

Virus-virus interactions impact the population dynamics of influenza and the common cold.

The human respiratory tract hosts a diverse community of cocirculating viruses that are responsible for acute respiratory infections. This shared niche provides the opportunity for virus-virus interactions which have the potential to affect individual infection risks and in turn influence dynamics of infection at population scales. However, quantitative evidence for interactions has lacked suitable data and appropriate analytical tools. Here, we expose and quantify interactions among respiratory viruses using bespoke analyses of infection time series at the population scale and coinfections at the individual host scale. We analyzed diagnostic data from 44,230 cases of respiratory illness that were tested for 11 taxonomically broad groups of respiratory viruses over 9 y. Key to our analyses was accounting for alternative drivers of correlated infection frequency, such as age and seasonal dependencies in infection risk, allowing us to obtain strong support for the existence of negative interactions between influenza and noninfluenza viruses and positive interactions among noninfluenza viruses. In mathematical simulations that mimic 2-pathogen dynamics, we show that transient immune-mediated interference can cause a relatively ubiquitous common cold-like virus to diminish during peak activity of a seasonal virus, supporting the potential role of innate immunity in driving the asynchronous circulation of influenza A and rhinovirus. These findings have important implications for understanding the linked epidemiological dynamics of viral respiratory infections, an important step towards improved accuracy of disease forecasting models and evaluation of disease control interventions.

DisCVR: Rapid viral diagnosis from high-throughput sequencing data.

High-throughput sequencing (HTS) enables most pathogens in a clinical sample to be detected from a single analysis, thereby providing novel opportunities for diagnosis, surveillance, and epidemiology. However, this powerful technology is difficult to apply in diagnostic laboratories because of its computational and bioinformatic demands. We have developed DisCVR, which detects known human viruses in clinical samples by matching sample k-mers (twenty-two nucleotide sequences) to k-mers from taxonomically labeled viral genomes. DisCVR was validated using published HTS data for eighty-nine clinical samples from adults with upper respiratory tract infections. These samples had been tested for viruses metagenomically and also by real-time polymerase chain reaction assay, which is the standard diagnostic method. DisCVR detected human viruses with high sensitivity (79%) and specificity (100%), and was able to detect mixed infections. Moreover, it produced results comparable to those in a published metagenomic analysis of 177 blood samples from patients in Nigeria. DisCVR has been designed as a user-friendly tool for detecting human viruses from HTS data using computers with limited RAM and processing power, and includes a graphical user interface to help users interpret and validate the output. It is written in Java and is publicly available from http://bioinformatics.cvr.ac.uk/discvr.php.

5.9 GHz graphene based q-switched modelocked mid-infrared monolithic waveguide laser.

A high repetition rate Q-switched modelocked ~2.1 µm monolithic waveguide laser is reported. Ultrafast laser inscription is used to fabricate 3D depressed cladding channel waveguides in holmium doped yttrium aluminium garnet. This results in a transversely single mode waveguide laser. With the use of a graphene based saturable output coupler, Q-switched modelocking was achieved with a pulse repetition frequency of 5.9 GHz and up to 170 mW of average output power. This first demonstration of multi-GHz repetition rate operation from a Ho3+:YAG laser provides a compact and convenient source for a number of applications.

Operation of Ho:YAG ultrafast laser inscribed waveguide lasers.

We report fabrication and operation of multi-watt level waveguide lasers utilizing holmium-doped yttrium aluminum garnet (Ho:YAG). The waveguides were fabricated using ultrafast laser inscription, which relies on a chirped pulse ytterbium fiber laser to create depressed cladding structures inside the material. A variety of waveguides were created inside the Ho:YAG samples. We demonstrate output powers of ∼2 W from both a single-mode 50 µm waveguide laser and a multimode 80 µm waveguide laser. In addition, laser action from a co-doped Yb:Ho:YAG sample under in-band pumping conditions was demonstrated.

Presence and Persistence of Zika Virus RNA in Semen, United Kingdom, 2016.

Zika virus RNA has been detected in semen collected several months after onset of symptoms of infection. Given the potential for sexual transmission of Zika virus and for serious fetal abnormalities resulting from infection during pregnancy, information regarding the persistence of Zika virus in semen is critical for advancing our understanding of potential risks. We tested serial semen samples from symptomatic male patients in the United Kingdom who had a diagnosis of imported Zika virus infection. Among the initial semen samples from 23 patients, Zika virus RNA was detected at high levels in 13 (56.5%) and was not detected in 9 (39.1%); detection was indeterminate in 1 sample (4.4%). After symptomatic infection, a substantial proportion of men have detectable Zika virus RNA at high copy numbers in semen during early convalescence, suggesting high risk for sexual transmission. Viral RNA clearance times are not consistent and can be prolonged.

The use of next generation sequencing in the diagnosis and typing of respiratory infections.

BACKGROUND: Molecular assays are the gold standard methods used to diagnose viral respiratory pathogens. Pitfalls associated with this technique include limits to the number of targeted pathogens, the requirement for continuous monitoring to ensure sensitivity/specificity is maintained and the need to evolve to include emerging pathogens. Introducing target independent next generation sequencing (NGS) could resolve these issues and revolutionise respiratory viral diagnostics. OBJECTIVES: To compare the sensitivity and specificity of target independent NGS against the current standard diagnostic test. STUDY DESIGN: Diagnostic RT-PCR of clinical samples was carried out in parallel with target independent NGS. NGS sequences were analyzed to determine the proportion with viral origin and consensus sequences were used to establish viral genotypes and serotypes where applicable. RESULTS: 89 nasopharyngeal swabs were tested. A viral pathogen was detected in 43% of samples by NGS and 54% by RT-PCR. All NGS viral detections were confirmed by RT-PCR. CONCLUSIONS: Target independent NGS can detect viral pathogens in clinical samples. Where viruses were detected by RT-PCR alone the Ct value was higher than those detected by both assays, suggesting an NGS detection cut-off - Ct=32. The sensitivity and specificity of NGS compared with RT-PCR was 78% and 80% respectively. This is lower than current diagnostic assays but NGS provided full genome sequences in some cases, allowing determination of viral subtype and serotype. Sequencing technology is improving rapidly and it is likely that within a short period of time sequencing depth will increase in-turn improving test sensitivity.