Nonlinear pulse compression to sub-two-cycle, 1.3†mJ pulses at 1.9†µm wavelength with 132†W average power.

We report the nonlinear pulse compression of a high-power, thulium-doped fiber laser system using a gas-filled hollow-core fiber. The sub-two cycle source delivers 1.3 mJ pulse energy with 80 GW peak power at a central wavelength of 1.87 µm and an average power of 132 W. This is, so far, to the best of our knowledge, the highest average power of a few-cycle laser source reported in the short-wave infrared region. Given its unique combination of high pulse energy and high average power, this laser source is an excellent driver for nonlinear frequency conversion, toward terahertz, mid-infrared, and soft X-ray spectral regions.

Continuously tunable high photon flux high harmonic source.

In this work, a continuously tunable extreme ultraviolet source delivering a state-of-the-art photon flux of >1011 ph/s/eV spanning from 50 eV to 70 eV is presented. The setup consists of a high-power fiber laser with a subsequent multipass cell followed by a waveguide-based high harmonic generation setup. Spectral tuning over the full line spacing is achieved by slightly adjusting the lasers driving pulse energy, utilizing nonlinear propagation effects and pulse chirping. The presented method enables a high tuning speed while delivering reproducible and reliable results due to a simple experimental realization. For possible future experiments, a method for continuous, on-demand pulse-to-pulse switching of the generated XUV radiation with full spectral coverage is conceived.

Inband-pumped, high-power thulium-doped fiber amplifiers for an ultrafast pulsed operation.

We investigate the influence of the pump wavelength on the high-power amplification of large-mode area, thulium-doped fibers which are suitable for an ultrashort pulsed operation in the 2 µm wavelength region. By pumping a standard, commercially available photonic crystal fiber in an amplifier configuration at 1692 nm, a slope efficiency of 80 % at an average output power of 60 W could be shown. With the help of simulations we investigate the effect of cross-relaxations on the efficiency and the thermal behavior. We extend our investigations to a rod-type, large-pitch fiber with very large mode area, which is exceptionally suited for high-energy ultrafast operation. Pumping at 1692 nm leads to a slope efficiency of 74 % with a average output power of 67 W, instead of the 38 % slope efficiency obtained when pumping at 793 nm. These results pave the way to highly efficient 2 µm fiber-based CPA systems.

Ultrafast Tm-doped fiber laser system delivering 1.65-mJ, sub-100-fs pulses at a 100-kHz repetition rate.

High-energy, ultrafast, short-wavelength infrared laser sources with high average power are important tools for industrial and scientific applications. Through the coherent combination of four ultrafast thulium-doped rod-type fiber amplifiers, we demonstrate a Tm-doped chirped pulse amplification system with a compressed pulse energy of 1.65 mJ and 167 W of average output power at a repetition rate of 101 kHz. The system delivers 85 fs pulses with a peak power of 15 GW. Additionally, the system presents a high long- and short-term stability. To the best of our knowledge, this is the highest average output power short wavelength IR, mJ-class source to date. This result shows the potential of coherent beam combining techniques in the short wavelength infrared spectral region for the power scalability of these systems.

Transverse mode instability and thermal effects in thulium-doped fiber amplifiers under high thermal loads.

We experimentally analyze the average-power-scaling capabilities of ultrafast, thulium-doped fiber amplifiers. It has been theoretically predicted that thulium-doped fiber laser systems, with an emission wavelength around 2 µm, should be able to withstand much higher heat-loads than their Yb-doped counterparts before the onset of transverse mode instability (TMI) is observed. In this work we experimentally verify this theoretical prediction by operating thulium doped fibers at very high heat-load. In separate experiments we analyze the performance of two different large-core, thulium-doped fiber amplifiers. The first experiment aims at operating a short, very-large core, thulium-doped fiber amplifier at extreme heat-load levels of more than 300 W/m. Even at this extreme heat-load level, the onset of TMI is not observed. The second experiment maximizes the extractable average-output power from a large-core, thulium-doped, fiber amplifier. We have achieved a pump-limited average output power of 1.15 kW without the onset of TMI. However, during a longer period of operation at this power level the amplifier performance steadily degraded and TMI could be observed for average powers in excess of 847 W thereafter. This is the first time, to the best of our knowledge, that TMI has been reported in a thulium-doped fiber amplifier.

Investigation of spatiotemporal output beam profile instabilities from differentially pumped capillaries.

Differentially pumped capillaries, i.e., capillaries operated in a pressure gradient environment, are widely used for nonlinear pulse compression. In this work, we show that strong pressure gradients and high gas throughputs can cause spatiotemporal instabilities of the output beam profile. The instabilities occur with a sudden onset as the flow evolves from laminar to turbulent. Based on the experimental and numerical results, we derive guidelines to predict the onset of those instabilities and discuss possible applications in the context of nonlinear flow dynamics.

Watt-scale super-octave mid-infrared intrapulse difference frequency generation.

The development of high-power, broadband sources of coherent mid-infrared radiation is currently the subject of intense research that is driven by a substantial number of existing and continuously emerging applications in medical diagnostics, spectroscopy, microscopy, and fundamental science. One of the major, long-standing challenges in improving the performance of these applications has been the construction of compact, broadband mid-infrared radiation sources, which unify the properties of high brightness and spatial and temporal coherence. Due to the lack of such radiation sources, several emerging applications can be addressed only with infrared (IR)-beamlines in large-scale synchrotron facilities, which are limited regarding user access and only partially fulfill these properties. Here, we present a table-top, broadband, coherent mid-infrared light source that provides brightness at an unprecedented level that supersedes that of synchrotrons in the wavelength range between 3.7 and 18 µm by several orders of magnitude. This result is enabled by a high-power, few-cycle Tm-doped fiber laser system, which is employed as a pump at 1.9 µm wavelength for intrapulse difference frequency generation (IPDFG). IPDFG intrinsically ensures the formation of carrier-envelope-phase stable pulses, which provide ideal prerequisites for state-of-the-art spectroscopy and microscopy.

Trends in human immunodeficiency virus diagnoses among men who have sex with men in North America, Western Europe, and Australia, 2000-2014.

PURPOSE: The aim of the article was to investigate recent trends in human immunodeficiency virus (HIV) diagnosis rates among men who have sex with men (MSM) in high-income countries in North America, Western Europe, and Australia. METHODS: Data on annual rates of HIV diagnoses among MSM aged 15 to 65 years from 2000 to 2014 were collected from 13 high-income countries. Joinpoint regression software was used to empirically determine country-specific trend periods. Trends in HIV diagnosis rates and in the proportion of diagnoses occurring in young MSM aged 15 to 24 years were analyzed using Poisson regression and log-binomial regression, respectively. RESULTS: Six countries experienced an increasing trend from 2000 to 2007-08 followed by either a stable or declining trend through 2014. Five countries had recently increasing trends, and two countries had one stable trend from 2000 to 2014. All 13 countries experienced increases in the proportion of diagnoses occurring in young MSM. CONCLUSIONS: Since 2008, half of the 13 high-income countries examined experienced stable or decreasing trends. Still, some countries continue to experience increasing HIV trends, and young MSM are increasingly represented among new diagnoses. Efforts to support early sexual health promotion, reduce barriers to pre-exposure prophylaxis, and improve care engagement for young MSM are critical to addressing current HIV trends.

Carbon chloride-core fibers for soliton mediated supercontinuum generation.

We report on soliton-fission mediated infrared supercontinuum generation in liquid-core step-index fibers using highly transparent carbon chlorides (CCl4, C2Cl4). By developing models for the refractive index dispersions and nonlinear response functions, dispersion engineering and pumping with an ultrafast thulium fiber laser (300 fs) at 1.92 µm, distinct soliton fission and dispersive wave generation was observed, particularly in the case of tetrachloroethylene (C2Cl4). The measured results match simulations of both the generalized and a hybrid nonlinear Schrödinger equation, with the latter resembling the characteristics of non-instantaneous medium via a static potential term and representing a simulation tool with substantially reduced complexity. We show that C2Cl4 has the potential for observing non-instantaneous soliton dynamics along meters of liquid-core fiber opening a feasible route for directly observing hybrid soliton dynamics.

Hybrid soliton dynamics in liquid-core fibres.

The discovery of optical solitons being understood as temporally and spectrally stationary optical states has enabled numerous innovations among which, most notably, supercontinuum light sources have become widely used in both fundamental and applied sciences. Here, we report on experimental evidence for dynamics of hybrid solitons-a new type of solitary wave, which emerges as a result of a strong non-instantaneous nonlinear response in CS2-filled liquid-core optical fibres. Octave-spanning supercontinua in the mid-infrared region are observed when pumping the hybrid waveguide with a 460 fs laser (1.95 µm) in the anomalous dispersion regime at nanojoule-level pulse energies. A detailed numerical analysis well correlated with the experiment uncovers clear indicators of emerging hybrid solitons, revealing their impact on the bandwidth, onset energy and noise characteristics of the supercontinua. Our study highlights liquid-core fibres as a promising platform for fundamental optics and applications towards novel coherent and reconfigurable light sources.Here, Chemnitz et al. report experimental evidence for hybrid solitons - a type of solitary wave, which emerges as a result of a strong non-instantaneous nonlinear response in CS2-filled liquid-core optical fibres, demonstrating efficient soliton-driven supercontinuum generation.

Decreasing Proportion of Recent Infections among Newly Diagnosed HIV-1 Cases in Switzerland, 2008 to 2013 Based on Line-Immunoassay-Based Algorithms.

BACKGROUND: HIV surveillance requires monitoring of new HIV diagnoses and differentiation of incident and older infections. In 2008, Switzerland implemented a system for monitoring incident HIV infections based on the results of a line immunoassay (Inno-Lia) mandatorily conducted for HIV confirmation and type differentiation (HIV-1, HIV-2) of all newly diagnosed patients. Based on this system, we assessed the proportion of incident HIV infection among newly diagnosed cases in Switzerland during 2008-2013. METHODS AND RESULTS: Inno-Lia antibody reaction patterns recorded in anonymous HIV notifications to the federal health authority were classified by 10 published algorithms into incident (up to 12 months) or older infections. Utilizing these data, annual incident infection estimates were obtained in two ways, (i) based on the diagnostic performance of the algorithms and utilizing the relationship 'incident = true incident + false incident', (ii) based on the window-periods of the algorithms and utilizing the relationship 'Prevalence = Incidence x Duration'. From 2008-2013, 3'851 HIV notifications were received. Adult HIV-1 infections amounted to 3'809 cases, and 3'636 of them (95.5%) contained Inno-Lia data. Incident infection totals calculated were similar for the performance- and window-based methods, amounting on average to 1'755 (95% confidence interval, 1588-1923) and 1'790 cases (95% CI, 1679-1900), respectively. More than half of these were among men who had sex with men. Both methods showed a continuous decline of annual incident infections 2008-2013, totaling -59.5% and -50.2%, respectively. The decline of incident infections continued even in 2012, when a 15% increase in HIV notifications had been observed. This increase was entirely due to older infections. Overall declines 2008-2013 were of similar extent among the major transmission groups. CONCLUSIONS: Inno-Lia based incident HIV-1 infection surveillance proved useful and reliable. It represents a free, additional public health benefit of the use of this relatively costly test for HIV confirmation and type differentiation.

Impact of atmospheric molecular absorption on the temporal and spatial evolution of ultra-short optical pulses.

We present a rigorous study on the impact of atmospheric molecular absorption on the linear propagation of ultrashort pulses in the mid-infrared wavelength region. An ultrafast thulium-based fiber laser was employed to experimentally investigate ultrashort-pulse propagation through the atmosphere in a spectral region containing several strong molecular absorption lines. The atmospheric absorption profile causes a significant degradation of the pulse quality in the time domain as well as a distortion of the transverse beam profile in the spatial domain. Numerical simulations carried out in the small signal limit accurately reproduce the experimental observations in the time domain and reveal that the relative loss in peak power after propagation can be more than twice as high as the relative amount of absorbed average power. Although their nature is purely linear (i.e. the intensities considered are sufficiently low) the discussed effects represent significant challenges to performance-scaling of mid-infrared ultrafast lasers operating in spectral regions with molecular absorption bands. Guidelines for an efficient mitigation of the pulse quality degradation and the beam profile distortion are discussed.

Tm-based fiber-laser system with more than 200 MW peak power.

Tm-based fiber-laser systems are an attractive concept for the development of high-performance laser sources in the spectral region around 2 µm wavelength. Here we present a system delivering a pulse-peak power higher than 200 MW in combination with 24 W average power and 120 µJ pulse energy. Key components enabling this performance level are a Tm-doped large-pitch fiber with a mode-field diameter of 65 µm, highly efficient dielectric gratings, and a Tm-based fiber oscillator operating in the stretched-pulse regime.

152 W average power Tm-doped fiber CPA system.

A high-power thulium (Tm)-doped fiber chirped-pulse amplification system emitting a record compressed average output power of 152 W and 4 MW peak power is demonstrated. This result is enabled by utilizing Tm-doped photonic crystal fibers with mode-field diameters of 35 µm, which mitigate detrimental nonlinearities, exhibit slope efficiencies of more than 50%, and allow for reaching a pump-power-limited average output power of 241 W. The high-compression efficiency has been achieved by using multilayer dielectric gratings with diffraction efficiencies higher than 98%.

High peak-power mid-infrared ZnGeP2 optical parametric oscillator pumped by a Tm:fiber master oscillator power amplifier system.

We report on the utilization of a novel Tm:fiber laser source for mid-IR ZnGeP2 (ZGP) optical parametric oscillator (OPO) pumping. The pump laser is built in a master oscillator power-amplifier configuration delivering up to 3.36 W of polarized, diffraction limited output power with 7 ns pulse duration and 4 kHz repetition rate. This corresponds to a peak power of ∼121 kW and a pulse energy of ∼0.84 mJ. With this source, we generated 27.9 kW of total mid-IR peak power in a doubly resonant oscillator (DRO) configuration. This is, to the best of our knowledge, the highest ever demonstrated mid-IR peak power from a directly Tm:fiber laser pumped ZGP OPO. Moreover, a DRO output with about 284 µJ of total mid-IR pulse energy was demonstrated using 100 ns pump pulses. The wavelength tuning of the idler was extended to 6 µm with lower output power in another OPO experiment.

Simple estimation of incident HIV infection rates in notification cohorts based on window periods of algorithms for evaluation of line-immunoassay result patterns.

BACKGROUND: Tests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods. METHODS: We classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship 'Prevalence = Incidence x Duration' in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship 'incident = true incident + false incident' and also to the IIR derived from the BED incidence assay. RESULTS: Window periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R(2) = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods. CONCLUSIONS: IIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.

Amplification of nanosecond pulses to megawatt peak power levels in Tm3+-doped photonic crystal fiber rod.

We report amplification of sub-10-100 ns pulses with repetition rates from 1 to 20 kHz in a rod-type thulium-doped photonic crystal fiber with 80 µm core diameter. The rod is pumped with a 793 nm laser diode and produces the highest peak power at 1 kHz repetition rate with 6.5 ns pulse duration and more than 7 W average output power. This result exemplifies the potential of this fiber design to scale pulse peak powers and pulse energies to the megawatt and multi-millijoule range in the 2 µm wavelength regime.

Resurgence of HIV infection among men who have sex with men in Switzerland: mathematical modelling study.

BACKGROUND: New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. METHODOLOGY/PRINCIPAL FINDINGS: The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995-1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. CONCLUSIONS/SIGNIFICANCE: The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.

Diagnostic performance of line-immunoassay based algorithms for incident HIV-1 infection.

BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have previously demonstrated that a patient's antibody reaction pattern in a confirmatory line immunoassay (INNO-LIA™ HIV I/II Score) provides information on the duration of infection, which is unaffected by clinical, immunological and viral variables. In this report we have set out to determine the diagnostic performance of Inno-Lia algorithms for identifying incident infections in patients with known duration of infection and evaluated the algorithms in annual cohorts of HIV notifications. METHODS: Diagnostic sensitivity was determined in 527 treatment-naive patients infected for up to 12 months. Specificity was determined in 740 patients infected for longer than 12 months. Plasma was tested by Inno-Lia and classified as either incident (< = 12 m) or older infection by 26 different algorithms. Incident infection rates (IIR) were calculated based on diagnostic sensitivity and specificity of each algorithm and the rule that the total of incident results is the sum of true-incident and false-incident results, which can be calculated by means of the pre-determined sensitivity and specificity. RESULTS: The 10 best algorithms had a mean raw sensitivity of 59.4% and a mean specificity of 95.1%. Adjustment for overrepresentation of patients in the first quarter year of infection further reduced the sensitivity. In the preferred model, the mean adjusted sensitivity was 37.4%. Application of the 10 best algorithms to four annual cohorts of HIV-1 notifications totalling 2'595 patients yielded a mean IIR of 0.35 in 2005/6 (baseline) and of 0.45, 0.42 and 0.35 in 2008, 2009 and 2010, respectively. The increase between baseline and 2008 and the ensuing decreases were highly significant. Other adjustment models yielded different absolute IIR, although the relative changes between the cohorts were identical for all models. CONCLUSIONS: The method can be used for comparing IIR in annual cohorts of HIV notifications. The use of several different algorithms in combination, each with its own sensitivity and specificity to detect incident infection, is advisable as this reduces the impact of individual imperfections stemming primarily from relatively low sensitivities and sampling bias.

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease.

BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA < 50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥ 50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.