Ultra-low threshold deep ultraviolet generation in a hollow-core fiber.

Tunable ultrashort pulses in the ultraviolet spectral region are in great demand for a wide range of applications, including spectroscopy and pump-probe experiments. While laser sources capable of producing such pulses exist, they are typically very complex. Notably, resonant dispersive-wave (RDW) emission has emerged as a simple technique for generating such pulses. However, the required pulse energy used to drive the RDW emission, so far, is mostly at the microjoule level, requiring complicated and expensive pump sources. Here, we present our work on lowering the pump energy threshold for generating tuneable deep ultraviolet pulses to the level of tens of nanojoules. We fabricated a record small-core antiresonant fiber with a hollow-core diameter of just 6 µm. When filled with argon, the small mode area enables higher-order soliton propagation and deep ultraviolet (220 to 270 nm) RDW emission from 36 fs pump pulses at 515 nm with the lowest pump energy reported to date (tens of nanojoules). This approach will allow the use of low-cost and compact laser oscillators to drive nonlinear optics in gas-filled fibers for the first time to our knowledge.

Effect of rotational Raman response on ultra-flat supercontinuum generation in gas-filled hollow-core photonic crystal fibers.

We experimentally and numerically investigate flat supercontinuum generation in gas-filled anti-resonant guiding hollow-core photonic crystal fiber. By comparing results obtained with either argon or nitrogen we determine the role of the rotational Raman response in the supercontinuum formation. When using argon, a supercontinuum extending from 350 nm to 2 µm is generated through modulational instability. Although argon and nitrogen exhibit similar Kerr nonlinearity and dispersion, we find that the energy density of the continuum in the normal dispersion region is significantly lower when using nitrogen. Using numerical simulations, we find that due to the closely spaced rotational lines in nitrogen, gain suppression in the fundamental mode causes part of the pump pulse to be coupled into higher-order modes which reduces the energy transfer to wavelengths shorter than the pump.

On-target delivery of intense ultrafast laser pulses through hollow-core anti-resonant fibers.

We report the flexible on-target delivery of 800 nm wavelength, 5 GW peak power, 40 fs duration laser pulses through an evacuated and tightly coiled 10 m long hollow-core nested anti-resonant fiber by positively chirping the input pulses to compensate for the anomalous dispersion of the fiber. Near-transform-limited output pulses with high beam quality and a guided peak intensity of 3 PW/cm2 were achieved by suppressing plasma effects in the residual gas by pre-pumping the fiber with laser pulses after evacuation. This appears to cause a long-term removal of molecules from the fiber core. Identifying the fluence at the fiber core-wall interface as the damage origin, we scaled the coupled energy to 2.1 mJ using a short piece of larger-core fiber to obtain 20 GW at the fiber output. This scheme can pave the way towards the integration of anti-resonant fibers in mJ-level nonlinear optical experiments and laser-source development.

Efficient and compact source of tuneable ultrafast deep ultraviolet laser pulses at 50 kHz repetition rate.

Deep ultraviolet (DUV) laser pulses with tuneable wavelength and very short duration are a key enabling technology for next-generation technology and ultrafast science. Their generation has been the subject of extensive experimental effort, but no technique demonstrated thus far has been able to meet all requirements in one light source. Here we demonstrate a bright, efficient, and compact source of tuneable DUV ultrafast laser pulses based on resonant dispersive wave emission in hollow capillary fiber. In a total footprint of only 120cm×75cm, including the ytterbium-based drive laser, we generate pulses between 208nm and 363nm at 50kHz repetition rate with a total efficiency of up to 3.6%. Down-scaling of the DUV generation reduces the required energy sufficiently to enable the generation of two-color few-femtosecond DUV pulses.

Generation and characterization of frequency tunable sub-15-fs pulses in a gas-filled hollow-core fiber pumped by a Yb:KGW laser.

We investigate soliton self-compression and photoionization effects in an argon-filled antiresonant hollow-core photonic crystal fiber pumped with a commercial Yb:KGW laser. Before the onset of photoionization, we demonstrate self-compression of our 220 fs pump laser to 13 fs in a single and compact stage. By using the plasma driven soliton self-frequency blueshift, we also demonstrate a tunable source from 1030 to ∼700 nm. We fully characterize the compressed pulses using sum-frequency generation time-domain ptychography, experimentally revealing the full time-frequency plasma-soliton dynamics in hollow-core fiber for the first time.

Building resilience and reversing frailty: a randomised controlled trial of a primary care intervention for older adults.

BACKGROUND: There is a need for effective primary care interventions that help older people combat frailty and build resilience. OBJECTIVE: To study the effectiveness of an optimised exercise and dietary protein intervention. DESIGN: Multicentre, randomised-controlled, parallel-arm trial. SETTING: Six primary care practices, Ireland. METHODS: Six general practitioners enrolled adults aged 65+ with Clinical Frailty Scale score ≤5 from December 2020 to May 2021. Participants were randomised to intervention or usual care with allocation concealed until enrolment. Intervention comprised a 3-month home-based exercise regime, emphasising strength, and dietary protein guidance (1.2 g/kg/day). Effectiveness was measured by comparing frailty levels, based on the SHARE-Frailty Instrument, on an intention-to-treat basis. Secondary outcomes included bone mass, muscle mass and biological age measured by bioelectrical impedance analysis. Ease of intervention and perceived health benefit were measured on Likert scales. RESULTS: Of the 359 adults screened, 197 were eligible and 168 enrolled; 156 (92.9%) attended follow-up (mean age 77.1; 67.3% women; 79 intervention, 77 control). At baseline, 17.7% of intervention and 16.9% of control participants were frail by SHARE-FI. At follow-up, 6.3 and 18.2% were frail, respectively. The odds ratio of being frail between intervention and control groups post-intervention was 0.23 (95% confidence interval: 0.07-0.72; P = 0.011), adjusting for age, gender and site. Absolute risk reduction was 11.9% (CI: 0.8%-22.9%). Number needed to treat was 8.4. Grip strength (P < 0.001) and bone mass (P = 0.040) improved significantly. 66.2% found the intervention easy, 69.0% reported feeling better. CONCLUSION: A combination of exercises and dietary protein significantly reduced frailty and improved self-reported health.

Involving older people in co-designing an intervention to reverse frailty and build resilience.

BACKGROUND: An essential consideration in health research is to conduct research with members of the public rather than for them. Public and patient involvement (PPI) of older people in research can improve enrolment, relevance and impact. However, few studies with PPI in frailty research have been identified. PPI has fallen during the Covid-19 pandemic. OBJECTIVE: We aimed to involve older people in co-designing a randomised control trial (RCT) intervention to reverse frailty and build resilience. We also wished to encourage wider use of PPI with older people by outlining our approach. METHODS: Involvement of older people was undertaken in three stages. Eighteen over 65-year-olds helped co-design an exercise intervention in two group discussions using the Socratic education method. Ninety-four contributed intervention feedback in one-on-one telephone interviews over nine months. Ten contributors helped optimise the intervention in three online workshops. Multidisciplinary team input and systematic review supported co-design. RESULTS: Eleven home-based resistance exercises were co-designed by group discussion contributors (mean age 75, 61% female). Frailty intervention format, gender balance and GP follow-up were shaped in telephone interviews (mean age 77, 63% female). Dietary guidance and patient communication were co-designed in workshops (mean age 71, 60% females). Technology proved no barrier to PPI. The co-designed frailty intervention is being evaluated in a definitive RCT. CONCLUSIONS: We enabled meaningful the involvement of 112 older people in the co-design of an intervention to reverse frailty and build resilience in diverse ways. Inclusive involvement can be achieved during a pandemic. Feedback enhanced intervention feasibility for real-world primary-care.

Our research paper describes how we involved 112 older adults in the co-design of an intervention aiming to reverse frailty and build resilience. Involving participants in research can improve its feasibility and impact. However, there have been few studies involving older people in frailty research and involvement has fallen further during the Covid-19 pandemic. Involvement of older people was undertaken in three stages. Eighteen over 65-year-olds helped co-design an exercise intervention in two group discussions. Ninety-four older adults contributed intervention feedback in one-on-one telephone interviews over nine months. Ten contributors helped optimise the intervention in three online workshops. The co-designed intervention involved resistance exercises and dietary guidance and will be tested in a full randomised control trial. We enabled the meaningful involvement of 112 older people in our research in diverse ways. Inclusive involvement can be achieved during a pandemic.

Ultrafast circularly polarized pulses tunable from the vacuum to deep ultraviolet.

We experimentally demonstrate the efficient generation of circularly polarized pulses tunable from the vacuum to deep ultraviolet (160-380 nm) through resonant dispersive wave emission from optical solitons in a gas-filled hollow capillary fiber. In the deep ultraviolet, we measure up to 13 µJ of pulse energy, and from numerical simulations, we estimate the shortest output pulse duration to be 8.5 fs. We also experimentally verify that simply scaling the pulse energy by 3/2 between linearly and circularly polarized pumping closely reproduces the soliton and dispersive wave dynamics. Based on previous results with linearly polarized self-compression and resonant dispersive wave emission, we expect our technique to be extended to produce circularly polarized few-fs pulses further into the vacuum ultraviolet, and few to sub-fs circularly polarized pulses in the near infrared.

Resonant dispersive wave emission in hollow capillary fibers filled with pressure gradients.

Resonant dispersive wave (RDW) emission in gas-filled hollow waveguides is a powerful technique for the generation of bright few-femtosecond laser pulses from the vacuum ultraviolet to the near infrared. Here, we investigate deep-ultraviolet RDW emission in a hollow capillary fiber filled with a longitudinal gas pressure gradient. We obtain broadly similar emission to the constant-pressure case by applying a surprisingly simple scaling rule for the gas pressure and study the energy-dependent dispersive wave spectrum in detail using simulations. We further find that in addition to enabling dispersion-free delivery to experimental targets, a decreasing gradient also reduces the pulse stretching within the waveguide itself, and that transform-limited pulses with 3 fs duration can be generated by using short waveguides. Our results illuminate the fundamental dynamics underlying this frequency conversion technique and will aid in fully exploiting it for applications in ultrafast science and beyond.

Generation of broadband circularly polarized deep-ultraviolet pulses in hollow capillary fibers.

We demonstrate an efficient scheme for the generation of broadband, high-energy, circularly polarized femtosecond laser pulses in the deep ultraviolet through seeded degenerate four-wave mixing in stretched gas-filled hollow capillary fibers. Pumping and seeding with circularly polarized 35 fs pulses centered at 400 nm and 800 nm, respectively, we generate idler pulses centered at 266 nm with 27 µJ of energy and over 95% spectrally averaged ellipticity. Even higher idler energies and broad spectra (27 nm bandwidth) can be obtained at the cost of reduced ellipticity. Our system can be scaled in average power and used in different spectral regions, including the vacuum ultraviolet.

Generation of 1.5 cycle pulses at 780 nm at oscillator repetition rates with stable carrier-envelope phase.

We demonstrate a spectral broadening and compression setup for carrier-envelope phase (CEP) stable sub-10-fs Ti:sapphire oscillator pulses resulting in 3.9 fs pulses spectrally centered at 780 nm. Pulses from the oscillator with 2 nJ energy are launched into a 1 mm long all-normal dispersive solid-core photonic crystal fiber and spectrally broadened to more than one octave. Subsequent pulse compression is achieved with a phase-only 4f pulse shaper. Second harmonic frequency resolved optical gating with a ptychographic reconstruction algorithm is used to obtain the spectral phase, which is fed back as a phase mask to the shaper display for pulse compression. The compressed pulses are CEP stable with a long term standard deviation of 0.23 rad for the CEP noise and 0.32 rad for the integrated rms phase jitter. The high total throughput of 15% results in a remaining pulse energy of about 300 pJ at 80 MHz repetition rate. With these parameters and the ability to tailor the spectral phase, the system is well suited for waveform sensitive photoemission experiments with needle tips or nanostructures and can be easily adapted to other sub-10 fs ultra-broadband Ti:sapphire oscillators.

High-energy ultraviolet dispersive-wave emission in compact hollow capillary systems.

We demonstrate high-energy resonant dispersive-wave emission in the deep ultraviolet (218 to 375 nm) from optical solitons in short (15 to 34 cm) hollow capillary fibers. This down-scaling in length compared to previous results in capillaries is achieved by using small core diameters (100 and 150 µm) and pumping with 6.3 fs pulses at 800 nm. We generate pulses with energies of 4 to 6 µJ across the deep ultraviolet in a 100 µm capillary and up to 11 µJ in a 150 µm capillary. From comparisons to simulations we estimate the ultraviolet pulse to be 2 to 2.5 fs in duration. We also numerically study the influence of pump duration on the bandwidth of the dispersive wave.

Highly efficient deep UV generation by four-wave mixing in gas-filled hollow-core photonic crystal fiber.

We report on a highly efficient experimental scheme for the generation of deep-ultraviolet (UV) ultrashort light pulses using four-wave mixing in gas-filled kagomé-style photonic crystal fiber. By pumping with ultrashort, few microjoule pulses centered at 400 nm, we generate an idler pulse at 266 nm and amplify a seeded signal at 800 nm. We achieve remarkably high pump-to-idler energy conversion efficiencies of up to 38%. Although the pump and seed pulse durations are ∼100 fs, the generated UV spectral bandwidths support sub-15 fs pulses. These can be further extended to support few-cycle pulses. Four-wave mixing in gas-filled hollow-core fibers can be scaled to high average powers and different spectral regions such as the vacuum UV (100-200 nm).

Direct characterization of tuneable few-femtosecond dispersive-wave pulses in the deep UV.

Dispersive wave emission (DWE) in gas-filled hollow-core dielectric waveguides is a promising source of tuneable coherent and broadband radiation, but so far the generation of few-femtosecond pulses using this technique has not been demonstrated. Using in-vacuum frequency-resolved optical gating, we directly characterize tuneable 3 fs pulses in the deep ultraviolet generated via DWE. Through numerical simulations, we identify that the use of a pressure gradient in the waveguide is critical for the generation of short pulses.

Effects of low-dose aspirin on clinical outcome and disease progression in patients with gastroenteropancreatic neuroendocrine neoplasm.

Objective: The chemopreventive effect of aspirin (ASA) has been observed in the setting of colorectal cancer and other solid neoplasms. Recently, ASA has demonstrated a promising anti-proliferative effect on GEP-NENs in vitro. However, the direct anti-neoplastic impact of ASA on GEP-NEN clinical outcome is yet to be clarified. Materials and methods: All the GEP-NEN patients followed up in three European Centers from January 2005 to September 2016 were retrospectively enrolled. Patients taking ASA in doses of 75-100 mg daily for cardiovascular prevention for at least six months were evaluated. The possible association between ASA and disease grading, staging, primary site, OS and PFS were evaluated. Results: Two hundred fifty one patients were included (117 males, median age 63 years). Of these, 64 patients were prescribed with ASA. No clear impact on OS or PFS was observed in GEP-NEN patients taking ASA compared to those not taking it. ASA intake was related with the patients' older age. At Cox multivariate analysis, stage IV and Ki-67 resulted independent predictors for OS and PFS. In the setting of intestinal NENs, a suggestive, but not statistically significant, protective role of ASA on PFS was observed [HR 0.41 (95% CI: 0.13-1.29)]. Conclusions: Despite ASA showed promising anti-proliferative effects in vitro and a chemopreventive action in NENs has been reported, a clear impact of ASA on survival in NENs has not emerged from the present study. However, in the subgroup of patients with small-intestine NENs, ASA showed a trend toward a protective role.

Generation of broadband mid-IR and UV light in gas-filled single-ring hollow-core PCF.

We report generation of an ultrafast supercontinuum extending into the mid- infrared in gas-filled single-ring hollow-core photonic crystal fiber (SR-PCF) pumped by 1.7 µm light from an optical parametric amplifier. The simple fiber structure offers shallow dispersion and flat transmission in the near and mid-infrared, enabling the generation of broadband spectra extending from 270 nm to 3.1 µm, with a total energy of a few µJ. In addition, we demonstrate the emission of ultraviolet dispersive waves whose frequency can be tuned simply by adjusting the pump wavelength. SR-PCF thus constitutes an effective means of compressing and delivering tunable ultrafast pulses in the near and mid-infrared spectral regions.

Continuously wavelength-tunable high harmonic generation via soliton dynamics.

We report the generation of high harmonics in a gas jet pumped by pulses self-compressed in a He-filled hollow-core photonic crystal fiber through the soliton effect. The gas jet is placed directly at the fiber output. As the energy increases, the ionization-induced soliton blueshift is transferred to the high harmonics, leading to emission bands that are continuously tunable from 17 to 45 eV.

Coherent octave-spanning mid-infrared supercontinuum generated in As2S3-silica double-nanospike waveguide pumped by femtosecond Cr:ZnS laser.

A more than 1.5 octave-spanning mid-infrared supercontinuum (1.2 to 3.6 µm) is generated by pumping a As2S3-silica "double-nanospike" waveguide via a femtosecond Cr:ZnS laser at 2.35 µm. The combination of the optimized group velocity dispersion and extremely high nonlinearity provided by the As2S3-silica hybrid waveguide enables a ~100 pJ level pump pulse energy threshold for octave-spanning spectral broadening at a repetition rate of 90 MHz. Numerical simulations show that the generated supercontinuum is highly coherent over the entire spanning wavelength range. The results are important for realization of a high repetition rate octave-spanning frequency comb in the mid-infrared spectral region.

Characterization of few-fs deep-UV dispersive waves by ultra-broadband transient-grating XFROG.

A multi-shot transient-grating cross-correlation frequency-resolved optical gating (FROG) is implemented for the characterization of nanojoule-scale, few-femtosecond, deep-ultraviolet pulses. In theory, the system can characterize pulses with a bandwidth extending from below 200 nm to above 1.5 µm. It is experimentally shown that a 200 THz (50 nm) wide dispersive wave centered at 275 nm, generated in a gas-filled HC-PCF, has a temporal duration of 4 fs. The numerical simulations agree well with the experiment. The results confirm that dispersive wave emission in a gas-filled HC-PCF can be used as a novel source of ultrashort UV pulses in a range of applications, for example, ultrafast UV pump-probe spectroscopy.

Supercontinuum generation in ZBLAN glass photonic crystal fiber with six nanobore cores.

Photonic crystal fibers (PCFs) made from ZBLAN glass are of great interest for generating broadband supercontinua extending into the ultraviolet and mid-infrared regions. Precise sub-micrometer structuring makes it possible to adjust the modal dispersion over a wide range, making the generation of new frequencies more efficient. Here we report a novel ZBLAN PCF with six cores, each containing a central nanobore of a diameter ∼330 nm. Each nanobore core supports several guided modes, and the presence of the nanobore significantly modifies the dispersion, strongly influencing the dynamics and the extent of supercontinuum generation. Spectral broadening is observed when a single core is pumped in the fundamental and first higher order core modes with 200 fs long pulses at a wavelength of 1042 nm. Frequency-resolved optical gating is used to characterize the output pulses when pumping in the lowest order mode. The results are verified by numerical simulations.