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.

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.

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.

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.

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.

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'.

Zoonotic Influenza and Human Health-Part 1: Virology and Epidemiology of Zoonotic Influenzas.

PURPOSE OF REVIEW: Zoonotic influenza viruses are those that cross the animal-human barrier and can cause disease in humans, manifesting from minor respiratory illnesses to multiorgan dysfunction. They have also been implicated in the causation of deadly pandemics in recent history. The increasing incidence of infections caused by these viruses worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. In this first part of a two-part review, we describe the structure of zoonotic influenza viruses, the relationship between mutation and pandemic capacity, pathogenesis of infection, and also discuss history and epidemiology. RECENT FINDINGS: We are currently witnessing the fifth and the largest wave of the avian influenza A(H7N9) epidemic. Also in circulation are a number of other zoonotic influenza viruses, including avian influenza A(H5N1) and A(H5N6); avian influenza A(H7N2); and swine influenza A(H1N1)v, A(H1N2)v, and A(H3N2)v viruses. Most recently, the first human case of avian influenza A(H7N4) infection has been documented. By understanding the virology and epidemiology of emerging zoonotic influenzas, we are better prepared to face a new pandemic. However, continued effort is warranted to build on this knowledge in order to efficiently combat the constant threat posed by the zoonotic influenza viruses.

Zoonotic Influenza and Human Health-Part 2: Clinical Features, Diagnosis, Treatment, and Prevention Strategies.

PURPOSE OF REVIEW: Zoonotic influenza viruses are those influenza viruses that cross the animal-human barrier and can cause disease in humans, manifesting from minor respiratory illnesses to multiorgan dysfunction. The increasing incidence of infections caused by these viruses worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. In this second part of a two-part review, we discuss the clinical features, diagnostic modalities, and treatment of zoonotic influenza, and provide an overview of prevention strategies. RECENT FINDINGS: Illnesses caused by novel reassortant avian influenza viruses continue to be detected and described; most recently, a human case of avian influenza A(H7N4) has been described from China. We continue to witness increasing rates of A(H7N9) infections, with the latest (fifth) wave, from late 2016 to 2017, being the largest to date. The case fatality rate for A(H7N9) and A(H5N1) infections among humans is much higher than that of seasonal influenza infections. Since the emergence of the A(H1N1) 2009 pandemic, and subsequently A(H7N9), testing and surveillance for novel influenzas have become more effective. Various newer treatment options, including peramivir, favipiravir (T-705), and DAS181, and human or murine monoclonal antibodies have been evaluated in vitro and in animal models. Armed with robust diagnostic modalities, antiviral medications, vaccines, and advanced surveillance systems, we are today better prepared to face a new influenza pandemic and to limit the burden of zoonotic influenza than ever before. Sustained efforts and robust research are necessary to efficiently deal with the highly mutagenic zoonotic influenza viruses.

Photoionization in the time and frequency domain.

Ultrafast processes in matter, such as the electron emission after light absorption, can now be studied using ultrashort light pulses of attosecond duration (10-18 seconds) in the extreme ultraviolet spectral range. The lack of spectral resolution due to the use of short light pulses has raised issues in the interpretation of the experimental results and the comparison with theoretical calculations. We determine photoionization time delays in neon atoms over a 40-electron volt energy range with an interferometric technique combining high temporal and spectral resolution. We spectrally disentangle direct ionization from ionization with shake-up, in which a second electron is left in an excited state, and obtain excellent agreement with theoretical calculations, thereby solving a puzzle raised by 7-year-old measurements.

Comparative analysis of viral shedding in pediatric and adult subjects with central nervous system-associated enterovirus infections from 2013 to 2015 in Switzerland.

BACKGROUND: Several enterovirus (EV) genotypes can result in aseptic meningitis, but their routes of access to the central nervous system remain to be elucidated and may differ between the pediatric and adult populations. OBJECTIVE: To assess the pattern of viral shedding in pediatric and adult subjects with acute EV meningitis and to generate EV surveillance data for Switzerland. STUDY DESIGN: All pediatric and adult subjects admitted to the University Hospitals of Geneva with a diagnosis of EV meningitis between 2013 and 2015 were enrolled. A quantitative EV real-time reverse transcriptase (rRT)-PCR was performed on the cerebrospinal fluid (CSF), blood, stool, urine and respiratory specimens to assess viral shedding and provide a comparative analysis of pediatric and adult populations. EV genotyping was systematically performed. RESULTS: EV positivity rates differed significantly between pediatric and adult subjects; 62.5% of pediatric cases (no adult case) were EV-positive in stool and blood for subjects for whom these samples were all collected. Similarly, the EV viral load in blood was significantly higher in pediatric subjects. Blood C-reactive protein levels were lower and the number of leucocytes/mm3 in the CSF were higher in non-viremic than in viremic pediatric subjects, respectively. A greater diversity of EV genotypes was observed in pediatric cases, with a predominance of echovirus 30 in children ≥3 years old and adults. CONCLUSION: In contrast to adults, EV-disseminated infections are predominant in pediatric subjects and show different patterns of EV viral shedding. This observation may be useful for clinicians and contribute to modify current practices of patient care.

Sub-cycle ionization dynamics revealed by trajectory resolved, elliptically-driven high-order harmonic generation.

The sub-cycle dynamics of electrons driven by strong laser fields is central to the emerging field of attosecond science. We demonstrate how the dynamics can be probed through high-order harmonic generation, where different trajectories leading to the same harmonic order are initiated at different times, thereby probing different field strengths. We find large differences between the trajectories with respect to both their sensitivity to driving field ellipticity and resonant enhancement. To accurately describe the ellipticity dependence of the long trajectory harmonics we must include a sub-cycle change of the initial velocity distribution of the electron and its excursion time. The resonant enhancement is observed only for the long trajectory contribution of a particular harmonic when a window resonance in argon, which is off-resonant in the field-free case, is shifted into resonance due to a large dynamic Stark shift.

Design and test of a broadband split-and-delay unit for attosecond XUV-XUV pump-probe experiments.

We present the design of a split-and-delay unit for the production of two delayed replicas of an incident extreme ultraviolet (XUV) pulse. The device features a single grazing incidence reflection in combination with attenuation of remaining infrared light co-propagating with the XUV beam, offering a high throughput without the need of introducing additional optics that would further decrease the XUV flux. To achieve the required spatial and temporal stabilities, the device is controlled by two PID-controllers monitoring the delay and the beam pointing using an optical reference laser beam, making collimation of the beam by additional optics unnecessary. Finally, we demonstrate the stability of the split-and-delay unit by performing all-reflective autocorrelation measurements on broadband few-cycle laser pulses.

Spectral phase measurement of a Fano resonance using tunable attosecond pulses.

Electron dynamics induced by resonant absorption of light is of fundamental importance in nature and has been the subject of countless studies in many scientific areas. Above the ionization threshold of atomic or molecular systems, the presence of discrete states leads to autoionization, which is an interference between two quantum paths: direct ionization and excitation of the discrete state coupled to the continuum. Traditionally studied with synchrotron radiation, the probability for autoionization exhibits a universal Fano intensity profile as a function of excitation energy. However, without additional phase information, the full temporal dynamics cannot be recovered. Here we use tunable attosecond pulses combined with weak infrared radiation in an interferometric setup to measure not only the intensity but also the phase variation of the photoionization amplitude across an autoionization resonance in argon. The phase variation can be used as a fingerprint of the interactions between the discrete state and the ionization continua, indicating a new route towards monitoring electron correlations in time.

Enterovirus and Parechovirus viraemia in young children presenting to the emergency room: Unrecognised and frequent.

BACKGROUND: Human Enterovirus (EV) and Parechovirus (HPeV) are well recognised as agents causing disease in neonates, but their importance is poorly described in the general paediatric population consulting with a suspicion of infection. OBJECTIVE: We investigated the prevalence of EV- or HPeV-associated infections in children presenting to a paediatric emergency department with a suspicion of infection. STUDY DESIGN: Plasma specimens collected in our paediatric emergency room for clinical reasons were screened by specific real-time RT-PCR for the presence of EV and HPeV. RESULTS: Based on an analyses of 233 plasma specimens, up to 6.9% and 2.6% were positive for EV and HPeV, respectively. Amongst the population <3y.o, prevalence of EV and HPeV viraemia was 11% and 3.7%, respectively. Importantly, 56.3% of positive EV specimens were detected in infants >3 months of age. CONCLUSION: The prevalence of EV and HPeV viraemia in children <3 years old is largely underestimated. Our results confirm that EV should be suspected and included in the work-up in children >3 months of age and not restricted to neonates.

Survival of rhinoviruses on human fingers.

Rhinovirus is the main cause of the common cold, which remains the most frequent infection worldwide among humans. Knowledge and understanding of the rhinovirus transmission route is important to reduce morbidity as only preventive measures are effective. In this study, we investigated the potential of rhinovirus to survive on fingers. Rhinovirus-B14 was deposited on fingers for 30, 60, 90 and 120 min. Survival was defined as the ability of the virus to grow after 7 days, confirmed by immunofluorescence. Rhinovirus survival was not dependent on incubation time on fingers. Droplet disruption had no influence on survival. Survival was frequent with high rhinovirus concentrations, but rare with low-concentration droplets, which corresponded to the usual rhinovirus concentrations in mucus observed in children and adults, respectively. Our study confirms that rhinovirus infectiousness is related to the viral concentration in droplets and suggests that children represent the main transmission source, which occurs only rarely via adults. It confirms also that rhinovirus hand-related transmission is possible and supports hand hygiene as a key prevention measure.

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.

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.

A high-flux high-order harmonic source.

We develop and implement an experimental strategy for the generation of high-energy high-order harmonics (HHG) in gases for studies of nonlinear processes in the soft x-ray region. We generate high-order harmonics by focusing a high energy Ti:Sapphire laser into a gas cell filled with argon or neon. The energy per pulse is optimized by an automated control of the multiple parameters that influence the generation process. This optimization procedure allows us to obtain energies per pulse and harmonic order as high as 200 nJ in argon and 20 nJ in neon, with good spatial properties, using a loose focusing geometry (f#≈400) and a 20 mm long medium. We also theoretically examine the macroscopic conditions for absorption-limited conversion efficiency and optimization of the HHG pulse energy for high-energy laser systems.