Robust Isolated Attosecond Pulse Generation with Self-Compressed Subcycle Drivers from Hollow Capillary Fibers.

High-order harmonic generation (HHG) arising from the nonperturbative interaction of intense light fields with matter constitutes a well-established tabletop source of coherent extreme-ultraviolet and soft X-ray radiation, which is typically emitted as attosecond pulse trains. However, ultrafast applications increasingly demand isolated attosecond pulses (IAPs), which offer great promise for advancing precision control of electron dynamics. Yet, the direct generation of IAPs typically requires the synthesis of near-single-cycle intense driving fields, which is technologically challenging. In this work, we theoretically demonstrate a novel scheme for the straightforward and compact generation of IAPs from multicycle infrared drivers using hollow capillary fibers (HCFs). Starting from a standard, intense multicycle infrared pulse, a light transient is generated by extreme soliton self-compression in a HCF with decreasing pressure and is subsequently used to drive HHG in a gas target. Owing to the subcycle confinement of the HHG process, high-contrast IAPs are continuously emitted almost independently of the carrier-envelope phase (CEP) of the optimally self-compressed drivers. This results in a CEP-robust scheme which is also stable under macroscopic propagation of the high harmonics in a gas target. Our results open the way to a new generation of integrated all-fiber IAP sources, overcoming the efficiency limitations of usual gating techniques for multicycle drivers.

A realist process evaluation of an intervention to promote competencies in interprofessional collaboration among interdisciplinary integrated care teams for older people: Study protocol.

Background: International policy is increasingly committed to placing interdisciplinary team-working at the centre of health and social care integration across the lifespan. The National Clinical Programme for Older People in Ireland has a critical role in the design and implementation of the National Older Person's Service Model, which aims to shift the delivery of care away from acute hospitals towards community-based care. Interdisciplinary Community Specialist Teams for older persons (CST-OPs) play an important role in this service model. To support the development of competencies for interprofessional collaboration and an interdisciplinary team-based approach to care integration, a culture shift will be required within care delivery. Design:This study builds upon a collaborative partnership project which co-designed a framework describing core competencies for interprofessional collaboration in CST-OPs. A realist-informed process evaluation of the framework will be undertaken as the competencies described in the framework are being fostered in newly developed CST-OPs under the national scale-up of the service model. Realist evaluation approaches reveal what worked, why it worked (or did not), for whom and under what circumstances. Three iterative and integrated work packages are proposed which combine multiple methods of data collection, analysis and synthesis. Prospective data collection will be undertaken within four CST-OPs, including qualitative exploration of the care experiences of older people and family carers. Discussion: The realist explanatory theory will provide an understanding of how interprofessional collaboration can be fostered and sustained in various contexts of care integration for older people. It will underpin curriculum development for team-based education and training of health and social care professionals, a key priority area in the national Irish health strategy. It will provide healthcare leaders with knowledge of the resources and supports required to harness the benefits of interprofessional collaboration and to realise the goals of integrated care for older people.

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.

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.

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.

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.

Spectroscopic application of few-femtosecond deep-ultraviolet laser pulses from resonant dispersive wave emission in a hollow capillary fibre.

We exploit the phenomenon of resonant dispersive wave (RDW) emission in gas-filled hollow capillary fibres (HCFs) to realize time-resolved photoelectron imaging (TRPEI) measurements with an extremely short temporal resolution. By integrating the output end of an HCF directly into a vacuum chamber assembly we demonstrate two-colour deep ultraviolet (DUV)-infrared instrument response functions of just 10 and 11 fs at central pump wavelengths of 250 and 280 nm, respectively. This result represents an advance in the current state of the art for ultrafast photoelectron spectroscopy. We also present an initial TRPEI measurement investigating the excited-state photochemical dynamics operating in the N-methylpyrrolidine molecule. Given the substantial interest in generating extremely short and highly tuneable DUV pulses for many advanced spectroscopic applications, we anticipate our first demonstration will stimulate wider uptake of the novel RDW-based approach for studying ultrafast photochemistry - particularly given the relatively compact and straightforward nature of the HCF setup.

Near-zero-index ultra-fast pulse characterization.

Transparent conducting oxides exhibit giant optical nonlinearities in the near-infrared window where their linear index approaches zero. Despite the magnitude and speed of these nonlinearities, a "killer" optical application for these compounds has yet to be found. Because of the absorptive nature of the typically used intraband transitions, out-of-plane configurations with short optical paths should be considered. In this direction, we propose an alternative frequency-resolved optical gating scheme for the characterization of ultra-fast optical pulses that exploits near-zero-index aluminium zinc oxide thin films. Besides the technological advantages in terms of manufacturability and cost, our system outperforms commercial modules in key metrics, such as operational bandwidth, sensitivity, and robustness. The performance enhancement comes with the additional benefit of simultaneous self-phase-matched second and third harmonic generation. Because of the fundamental importance of novel methodologies to characterise ultra-fast events, our solution could be of fundamental use for numerous research labs and industries.

Testing the feasibility of a primary-care exercise intervention to prevent and reverse early frailty and build resilience in community-dwelling older adults.

Background: Resistance exercises have been shown to prevent and reverse frailty but their application in clinical practice is low. We wished to test the feasibility of an optimised exercise intervention for mild or pre-frailty in a primary-care setting and inform the design of a definitive randomised control trial. Methods: The intervention was co-designed with eighteen older adults in two group workshops, informed by systematic review and meta-analysis. Eligible patients aged 65+, mildly frail or less, presenting to an Irish primary-care centre over 6 months from January 2020 were invited to participate. They were offered an exercise guide and educational discussion. Demographics, health indicators and frailty scores were recorded. Feasibility was assessed using the Bowen model for acceptability; participation; demand; implementation; practicality; adaptation; integration; expansion; and limited-efficacy. Half of the randomly selected participants were telephoned after one month, and all the participants were called after two to measure effects on adherence. Findings: 94 of 107 eligible people (88%) participated (average age 77, 59 women (63%)). Only 15% had previously considered resistance exercises. The intervention satisfied all Bowen feasibility criteria. At one month, 65% of participants were exercising. At two months, adherence amongst those previously called was higher: 78%. 87% described exercises as 'very easy' or 'somewhat easy'. 66% felt 'much better' or 'slightly better'. Interpretation: Frailty intervention uptake and adherence were high. A single telephone call appeared to help increase adherence. Participants reported meaningful physical and mental health benefits. Funding: Roman Romero-Ortuno is funded by a grant from Science Foundation Ireland (SFI), grant number 18/FRL/6188.

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.

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.

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.

Primary care interventions to address physical frailty among community-dwelling adults aged 60 years or older: A meta-analysis.

INTRODUCTION: The best interventions to address frailty among older adults have not yet been fully defined, and the diversity of interventions and outcome measures makes this process challenging. Consequently, there is a lack of guidance for clinicians and researchers regarding which interventions are most likely to help older persons remain robust and independent. This paper uses meta-analysis to assess effectiveness of primary care interventions for physical frailty among community-dwelling adults aged 60+ and provides an up-to-date synthesis of literature in this area. METHODS: PubMed, CINAHL, Cochrane Register of Controlled Trials, and PEDro databases were searched, and RCTs, controlled pilot studies, or trials with similar study designs addressing frailty in the primary care setting among persons aged 60+ were chosen. Study data was abstracted following PRISMA guidelines, then meta-analysis was performed using the random effects model. RESULTS: 31 studies with a total of 4794 participants were analysed. Interventions using predominantly resistance-based exercise and nutrition supplementation seemed to improve frailty status versus control (RR = 0.62 (CI 0.48-0.79), I2 = 0%). Exercise plus nutrition education also reduced frailty (RR = 0.69 (CI 0.58-0.82), I2 = 0%). Exercise alone seemed effective in reducing frailty (RR = 0.63 (CI 0.47-0.84), I2 = 0%) and improving physical performance (RR = 0.43 (CI 0.18-0.67), I2 = 0%). Exercise alone also appeared superior to control in improving gait speed (SMD = 0.36 (CI 0.10-0.61, I2 = 74%), leg strength (SMD = 0.61 (CI 0.09-1.13), I2 = 87%), and grip strength (Mean Difference = 1.08 (CI 0.02-2.15), I2 = 71%) though a high degree of heterogeneity was observed. Comprehensive geriatric assessment (RR = 0.77 (CI 0.64-0.93), I2 = 0%) also seemed superior to control in reducing frailty. CONCLUSION: Exercise alone or with nutrition supplementation or education, and comprehensive geriatric assessment, may reduce physical frailty. Individual-level factors and health systems resource availability will likely determine configuration of future interventions.

Protocol for a randomised controlled trial of a primary care intervention to Reverse Frailty and Enhance Resilience through Exercise and dietary protein Education (REFEREE) in community-dwelling adults aged 65 and over.

Introduction: Resistance exercises and dietary protein have been shown to reverse frailty, yet they are not commonly offered in clinical practice. We aim to measure changes in health outcomes, including physical frailty status (SHARE-FI), clinical frailty status (CFS) and muscle mass, as a result of an optimised exercise and dietary intervention versus usual care in a primary care (PC) setting. The intervention has been derived from our systematic review and meta-analysis findings and optimised through patient and public involvement and multidisciplinary team input. Methods: This study is a multicentre randomised controlled parallel arm trial with a three month follow up. 210 eligible people aged 65 and over, no more than mildly frail, will be recruited in seven PC practices in Ireland and randomly assigned to 'intervention' or 'usual care'. Intervention participants will be provided a leaflet with strength exercises, protein dietary guidance and educational discussion. Baseline measurements will include demographics, health indicators, comorbidities, malnutrition universal screening tool (MUST), frailty status (SHARE-FI, CFS) and muscle mass (bioelectrical impedance). Primary outcome will be frailty status measured by SHARE-FI at three months. Secondary outcomes include CFS, muscle mass, in-patient hospitalisation, long term care admission, and subjective ease of intervention and difference to general health. Statistical analysis will be undertaken by an independent statistician. Discussion: The diversity of tested frailty interventions and lack of clear guidance may contribute to low implementation rates. The REFEREE trial focusses on an optimised intervention for a syndrome that poses growing individual and societal challenges. It is hoped results can encourage mainstream adoption of interventions to reverse clinical frailty and build resilience in primary care. Trial registration: ClinicalTrials.gov ID NCT04628754; registered on 13 November 2020.

Quantitative assessment of left atrial scar using high-density voltage mapping and a novel automated voltage analysis tool.

PURPOSE: Left atrial (LA) fibrosis plays an important role in the pathogenesis and perpetuation of atrial fibrillation (AF). It may be identified by bipolar voltage (BiV) mapping, but quantification of fibrosis which previously relied on visual estimation of scar has been shown to be inaccurate. Our aim was to use a novel automated voltage histogram analysis (VHA) tool to quantify LA scar burden accurately in patients with AF. METHODS: LA voltage was assessed in 100 consecutive patients undergoing first pulmonary vein isolation (PVI) for paroxysmal or persistent AF using a circular multielectrode catheter to create high-density LA BiV maps which were analysed using the VHA tool after the procedure. RESULTS: High-density electro-anatomic maps took 10 min to create and contained a median of 1049 points. The VHA algorithm accurately quantified the burden of Diseased LA Tissue (≤ 0.5 mV) and Dense LA Scar (≤ 0.2 mV) with a median of 17.8% and 3.5% respectively. A quartile classification was applied based on diseased LA tissue burden. Patients in class IV with the highest diseased LA burden were older (p < 0.0001), more likely female (p = 0.0095), had higher CHA2DS2-VASc scores (p = 0.0024) and were more likely to have persistent rather than paroxysmal AF (p = 0.0179) than those in classes I-III. CONCLUSIONS: The VHA algorithm is able to quantify percentage surface area voltage rapidly and according to preset ranges for the first time. The algorithm offers the potential for classification of patients undergoing AF ablation into different classes of diseased LA burden, which may have diagnostic, therapeutic and prognostic implications.

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).

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.

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.