Two phase-matching regimes in high-order harmonic generation.

High-order harmonic generation (HHG) provides scalable sources of coherent extreme ultraviolet radiation with pulse duration down to the attosecond time scale. Efficient HHG requires the constructive interplay between microscopic and macroscopic effects in the generation volume, which can be achieved over a large range of experimental parameters from the driving field properties to those of the generating medium. Here, we present a systematic study of the harmonic yield as a function of gas pressure and medium length. Two regimes for optimum yield are identified, supporting the predictions of a recently proposed analytical model. Our observations are independent on the focusing geometry and, to a large extent, on the pulse duration and laser intensity, providing a versatile approach to HHG optimization.

Single-shot d-scan technique for ultrashort laser pulse characterization using transverse second-harmonic generation in random nonlinear crystals.

We demonstrate a novel dispersion-scan (d-scan) scheme for single-shot temporal characterization of ultrashort laser pulses. The novelty of this method relies on the use of a highly dispersive crystal featuring antiparallel nonlinear domains with a random distribution and size. This crystal, capable of generating a transverse second-harmonic signal, acts simultaneously as the dispersive element and the nonlinear medium of the d-scan device. The resulting in-line architecture makes the technique very simple and robust, allowing the acquisition of single-shot d-scan traces in real time. The retrieved pulses are in very good agreement with independent frequency-resolved optical grating measurements. We also apply the new single-shot d-scan to a terawatt-class laser equipped with a programmable pulse shaper, obtaining an excellent agreement between the applied and the d-scan retrieved dispersions.

Accuracy and precision of the RABBIT technique.

One of the most ubiquitous techniques within attosecond science is the so-called reconstruction of attosecond beating by interference of two-photon transitions (RABBIT). Originally proposed for the characterization of attosecond pulses, it has been successfully applied to the accurate determination of time delays in photoemission. Here, we examine in detail, using numerical simulations, the effect of the spatial and temporal properties of the light fields and of the experimental procedure on the accuracy of the method. This allows us to identify the necessary conditions to achieve the best temporal precision in RABBIT measurements. This article is part of the theme issue 'Measurement of ultrafast electronic and structural dynamics with X-rays'.

Electron localization following attosecond molecular photoionization.

For the past several decades, we have been able to directly probe the motion of atoms that is associated with chemical transformations and which occurs on the femtosecond (10(-15)-s) timescale. However, studying the inner workings of atoms and molecules on the electronic timescale has become possible only with the recent development of isolated attosecond (10(-18)-s) laser pulses. Such pulses have been used to investigate atomic photoexcitation and photoionization and electron dynamics in solids, and in molecules could help explore the prompt charge redistribution and localization that accompany photoexcitation processes. In recent work, the dissociative ionization of H(2) and D(2) was monitored on femtosecond timescales and controlled using few-cycle near-infrared laser pulses. Here we report a molecular attosecond pump-probe experiment based on that work: H(2) and D(2) are dissociatively ionized by a sequence comprising an isolated attosecond ultraviolet pulse and an intense few-cycle infrared pulse, and a localization of the electronic charge distribution within the molecule is measured that depends-with attosecond time resolution-on the delay between the pump and probe pulses. The localization occurs by means of two mechanisms, where the infrared laser influences the photoionization or the dissociation of the molecular ion. In the first case, charge localization arises from quantum mechanical interference involving autoionizing states and the laser-altered wavefunction of the departing electron. In the second case, charge localization arises owing to laser-driven population transfer between different electronic states of the molecular ion. These results establish attosecond pump-probe strategies as a powerful tool for investigating the complex molecular dynamics that result from the coupling between electronic and nuclear motions beyond the usual Born-Oppenheimer approximation.

Attosecond pulse walk-off in high-order harmonic generation.

We study the influence of the generation conditions on the group delay of attosecond pulses in high-order harmonic generation in gases. The group delay relative to the fundamental field is found to decrease with increasing gas pressure in the generation cell, reflecting a temporal walk-off due to the dispersive properties of the nonlinear medium. This effect is well reproduced using an on-axis phase-matching model of high-order harmonic generation in an absorbing gas.

Macroscopic effects in noncollinear high-order harmonic generation.

We study two-color high-order harmonic generation using an intense driving field and its weak second harmonic, crossed under a small angle in the focus. Employing sum- and difference-frequency generation processes, such a noncollinear scheme can be used to measure and control macroscopic phase matching effects by utilizing a geometrical phase mismatch component, which depends on the noncollinear angle. We further show how spatial phase effects in the generation volume are mapped out into the far field allowing a direct analogy with temporal carrier envelope effects in attosecond pulse generation.

Highly versatile, two-color setup for high-order harmonic generation using spatial light modulators.

We present a novel, interferometric, two-color, high-order harmonic generation setup based on a turn-key Ytterbium-doped femtosecond laser source and its second harmonic. Each interferometer arm contains a spatial light modulator with individual capabilities to manipulate the spatial beam profiles and to stabilize the relative delay between the fundamental and the second harmonic. In addition, separate control of the relative power and focusing geometries of the two color beams is implemented to conveniently perform automated scans of multiple parameters. A live diagnostics system gives continuous information during ongoing measurements.

Probing time-dependent molecular dipoles on the attosecond time scale.

Photoinduced molecular processes start with the interaction of the instantaneous electric field of the incident light with the electronic degrees of freedom. This early attosecond electronic motion impacts the fate of the photoinduced reactions. We report the first observation of attosecond time scale electron dynamics in a series of small- and medium-sized neutral molecules (N(2), CO(2), and C(2)H(4)), monitoring time-dependent variations of the parent molecular ion yield in the ionization by an attosecond pulse, and thereby probing the time-dependent dipole induced by a moderately strong near-infrared laser field. This approach can be generalized to other molecular species and may be regarded as a first example of molecular attosecond Stark spectroscopy.

Rational Use of Microbiological Tests in the Diagnosis of Central Nervous System Infections Using Restrictive Criteria: a Retrospective Study.

Central nervous infections, mostly represented by meningitis and encephalitis, remain a diagnostic challenge despite substantial advances in microbiological tools in recent years. Meanwhile, extensive microbiological workups, which often prove to be irrelevant retrospectively, continue to be processed on a large scale, therefore leading to unnecessary costs. The main goal of this study was to evaluate a systematic approach enabling more rational use of microbiological tools in the setting of community-acquired central nervous system infection diagnosis. In this single-center descriptive study, the modified Reller criteria were retrospectively extended to all neuropathogens tested in cerebrospinal fluid (CSF) samples with the FilmArray meningitis/encephalitis panel (BioFire Diagnostics, LLC) and bacterial culture. The inclusion period was 30 months. In total, 1,714 fluid (CSF) samples analyzed from 1,665 patients over 2 and a half years were reported. According to the retrospective application of the modified Reller criteria, microbiological testing was considered unnecessary in 544 CSF samples. Fifteen positive microbiological results were found among these samples, interpreted either as inherited chromosomally integrated human herpesvirus 6 (HHV-6), a false-positive result, or a true microbial detection without clinical relevance. No CNS infection case would have been missed if these analyses were not carried out, while about one-third of all meningitis/encephalitis multiplex PCR panels would have been saved. Our retrospective analysis suggests that the modified Reller criteria could be safely applied to all microbiological tests performed in CSF, thereby saving substantial costs. IMPORTANCE Microbiological testing in general and in the setting of central nervous system (CNS) infection in particular are often excessive, leading to superfluous laboratory work and costs. In this regard, restrictive criteria, named Reller criteria, have been developed to reduce unnecessary CSF herpes simplex virus 1 (HSV-1) PCR testing when suspecting encephalitis. These criteria were then adapted for increased safety to become the modified Reller criteria. This retrospective study aims at evaluating the safety of these criteria when applied to CSF microbiological testing in general, including multiplex PCR, direct examination, and bacterial culture. The postulate was that a CNS infection can be excluded if none of these criteria is present. According to our data set, no CNS infection would have been missed if the modified Reller criteria would have been applied to save microbiological tests. This study therefore proposes a simple way to reduce unnecessary microbiological testing in the context of CNS infection suspicion.

Impaired antibody memory to varicella zoster virus in HIV-infected children: low antibody levels and avidity*.

OBJECTIVE: HIV-infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV-infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV-infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response. METHODS: In a prospective, cross-sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV-infected children and 78 HIV-infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age-matched healthy children. We also tested antibody avidity in HIV-infected and healthy children. RESULTS: Median anti-VZV immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36-72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV-infected children. Anti-VZV antibodies did not decline more rapidly in HIV-infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in HIV-infected than in healthy children (median 1151 IU/L; P<0.001). Antibody avidity was lower in HIV-infected than healthy children (P<0.001). A direct correlation between anti-VZV IgG level and avidity was present in HIV-infected children (P=0.001), but not in healthy children. CONCLUSION: Failure to maintain anti-VZV IgG levels in HIV-infected children results from failure to reactivate memory responses. Further studies are required to investigate long-term protection and the potential benefits of immunization.

Digital in-line holography on amplitude and phase objects prepared with electron beam lithography.

We report on the fabrication and characterization of amplitude and phase samples consisting of well defined Au or Al features formed on ultrathin silicon nitride membranes. The samples were manufactured using electron beam lithography, metallization and a lift-off technique, which allow precise lateral control and thickness of the metal features. The fabricated specimens were evaluated by conventional microscopy, atomic force microscopy and with the digital in-line holography set-up at the Lund Laser Centre. The latter uses high-order harmonic generation as a light source, and is capable of recovering both the shape and phase shifting properties of the samples. We report on the details of the sample production and on the imaging tests with the holography set-up.

Successful serology-based intervention to increase protection against vaccine-preventable diseases in liver-transplanted children: a 19-yr review of the Swiss national reference center.

As children referred for OLT in Switzerland were not vaccinated optimally, new guidelines were developed and recommended to base catch-up immunization on serum antibody titers against vaccine-preventable diseases, before and after OLT. We measure the results of this serology-based intervention by comparing vaccine coverage and antibody titers in the pre- (1990-2002, P1) and post-intervention (2003-2008, P2) cohorts in a quality control project. Forty-four P1 and 30 P2 children were evaluated. At pre-OLT visit, D, T, SPn, and MMR serologies were checked more frequently in P2 than P1 (p < 0.05). More P2 children were up-to-date for DTaP and MMR (p < 0.05) or had received ≥1 dose of HBV, HAV, SPn, and VZV vaccines (p < 0.05). One yr post-OLT, DT, SPn, MMR, and VZV serologies were more frequently checked (p < 0.05), and antibody titers were higher for DT and HAV (p < 0.05) in P2. Gender, age, or diagnosis did not explain these differences. Among P2 patients, pre- and post-OLT titers for D, T, Hib, HBV, SPn14, and SPn19 were correlated (p < 0.05 for all). Protection against vaccine-preventable diseases of high-risk children like OLT patients can be significantly improved by serology-based intervention for vaccine-preventable diseases.

High-speed carrier-envelope phase drift detection of amplified laser pulses.

An instrument for measuring carrier-envelope phase (CEP) drift of amplified femtosecond laser pulses at repetition rates up to the 100-kHz regime is presented. The device can be used for real-time pulse labeling and it could also enable single-loop CEP control of future high-repetition rate laser amplifiers. The scheme is demonstrated by measuring the CEP drift of a 1-kHz source.

Spectrally resolved maker fringes in high-order harmonic generation.

We investigate macroscopic interference effects in high-order harmonic generation using a Ti:sapphire laser operating at a 100 kHz repetition rate. The structure and behavior of spectral and spatial interference fringes are explained and analytically described by transient phase matching of the long electron trajectory contribution. Time-frequency mapping due to the temporal chirp of the harmonic emission allows us to observe Maker fringes directly in the spectral domain.

Probing single-photon ionization on the attosecond time scale.

We study photoionization of argon atoms excited by attosecond pulses using an interferometric measurement technique. We measure the difference in time delays between electrons emitted from the 3s(2) and from the 3p(6) shell, at different excitation energies ranging from 32 to 42 eV. The determination of photoemission time delays requires taking into account the measurement process, involving the interaction with a probing infrared field. This contribution can be estimated using a universal formula and is found to account for a substantial fraction of the measured delay.

Phase measurement of resonant two-photon ionization in helium.

We study resonant two-color two-photon ionization of helium via the 1s3p (1)P(1) state. The first color is the 15th harmonic of a tunable Ti:sapphire laser, while the second color is the fundamental laser radiation. Our method uses phase-locked high-order harmonics to determine the phase of the two-photon process by interferometry. The measurement of the two-photon ionization phase variation as a function of detuning from the resonance and intensity of the dressing field allows us to determine the intensity dependence of the transition energy.

Attosecond electron spectroscopy using a novel interferometric pump-probe technique.

We present an interferometric pump-probe technique for the characterization of attosecond electron wave packets (WPs) that uses a free WP as a reference to measure a bound WP. We demonstrate our method by exciting helium atoms using an attosecond pulse (AP) with a bandwidth centered near the ionization threshold, thus creating both a bound and a free WP simultaneously. After a variable delay, the bound WP is ionized by a few-cycle infrared laser precisely synchronized to the original AP. By measuring the delay-dependent photoelectron spectrum we obtain an interferogram that contains both quantum beats as well as multipath interference. Analysis of the interferogram allows us to determine the bound WP components with a spectral resolution much better than the inverse of the AP duration.

Attosecond timing of electron emission from a molecular shape resonance.

Shape resonances in physics and chemistry arise from the spatial confinement of a particle by a potential barrier. In molecular photoionization, these barriers prevent the electron from escaping instantaneously, so that nuclei may move and modify the potential, thereby affecting the ionization process. By using an attosecond two-color interferometric approach in combination with high spectral resolution, we have captured the changes induced by the nuclear motion on the centrifugal barrier that sustains the well-known shape resonance in valence-ionized N2. We show that despite the nuclear motion altering the bond length by only 2%, which leads to tiny changes in the potential barrier, the corresponding change in the ionization time can be as large as 200 attoseconds. This result poses limits to the concept of instantaneous electronic transitions in molecules, which is at the basis of the Franck-Condon principle of molecular spectroscopy.

Α 10-gigawatt attosecond source for non-linear XUV optics and XUV-pump-XUV-probe studies.

The quantum mechanical motion of electrons and nuclei in systems spatially confined to the molecular dimensions occurs on the sub-femtosecond to the femtosecond timescales respectively. Consequently, the study of ultrafast electronic and, in specific cases, nuclear dynamics requires the availability of light pulses with attosecond (asec) duration and of sufficient intensity to induce two-photon processes, essential for probing the intrinsic system dynamics. The majority of atoms, molecules and solids absorb in the extreme-ultraviolet (XUV) spectral region, in which the synthesis of the required attosecond pulses is feasible. Therefore, the XUV spectral region optimally serves the study of such ultrafast phenomena. Here, we present a detailed review of the first 10-GW class XUV attosecond source based on laser driven high harmonic generation in rare gases. The pulse energy of this source largely exceeds other laser driven attosecond sources and is comparable to the pulse energy of femtosecond Free-Electron-Laser (FEL) XUV sources. The measured pulse duration in the attosecond pulse train is 650 ± 80 asec. The uniqueness of the combined high intensity and short pulse duration of the source is evidenced in non-linear XUV-optics experiments. It further advances the implementation of XUV-pump-XUV-probe experiments and enables the investigation of strong field effects in the XUV spectral region.