Compact tunable 80 MHz repetition rate vacuum ultraviolet light source up to 10 eV: intracavity high harmonic generation by nonlinear reflection on a AlN nanofilm in a mode locked Ti:sapphire oscillator.

We report the realization of an intra-oscillator high harmonic source based on a Kerr lens mode locked Ti:sapphire laser running at 80 MHz repetition rate. A nonlinear medium consisting of an AlN nanofilm on a thin sapphire substrate is placed inside the oscillator cavity. The harmonics are generated, in reflection geometry, on the AlN nanofilm, directing the harmonic beam out of the cavity. Exploiting the benefits of this approach, a compact size, tunable, high repetition rate and coherent vacuum ultraviolet light source with a spectrum up to the 7th harmonic has been achieved. In particular, the powerful 5th harmonic covering the 145-163 nm range aims to be an attractive tunable light source for spectroscopical applications.

Parametric attosecond pulse amplification far from the ionization threshold from high order harmonic generation in He.

Parametric amplification of attosecond coherent pulses around 100 eV at the single-atom level is demonstrated for the first time by using the 3D time-dependent Schrödinger equation in high-harmonic generation processes from excited states of He+. We present the attosecond dynamics of the amplification process far from the ionization threshold and resolve the physics behind it. The amplification of a particular central photon energy requires the seed XUV pulses to be perfectly synchronized in time with the driving laser field for stimulated recombination to the He+ ground state and is only produced in a few specific laser cycles in agreement with the experimental measurements. Our simulations show that the amplified photon energy region can be controlled by varying the peak intensity of the laser field. Our results pave the way to the realization of compact attosecond pulse intense XUV lasers with broad applications.

All-solid-state VUV frequency comb at 160 nm using high-harmonic generation in nonlinear femtosecond enhancement cavity.

We realized a solid-state-based vacuum ultraviolet frequency comb by harmonics generation in an external enhancement cavity. Optical conversions were so far reported by only using gaseous media. We present a theory that allows the most suited solid generation medium to be selected for specific target harmonics by adapting the material's bandgap. We experimentally use a thin AlN film grown on a sapphire substrate to realize a compact frequency comb high-harmonic source in the Deep Ultraviolet (DUV) / Vacuum Ultraviolet (VUV) spectral range. By extending our earlier VUV source [Opt. Express26, 21900 (2018)] with the enhancement cavity, a sub-Watt level Ti:sapphire femtosecond frequency comb is enhanced to 24 W stored average power, its 3rd, 5th, and 7th harmonics are generated, and the targeted 5th harmonic's power at 160 nm increased by two orders of magnitude. The emerging nonlinear effects in the solid medium, together with suitable intra-cavity dispersion management, support optimal enhancement and stable locking. To demonstrate the realized frequency comb's spectroscopic ability, we report on the beat measurement between the 3rd harmonic beam and a 266 nm CW laser reaching about 1 MHz accuracy.

Non-perturbative generation of DUV/VUV harmonics from crystal surfaces at 108 MHz repetition rate.

We demonstrate non-perturbative 3rd (267 nm) and 5th (160 nm) harmonic generation in solids from a Ti:sapphire frequency comb (800 nm) at 108 MHz repetition rate. The experiments show that non-perturbative low harmonics are dominantly generated on the surface and on the interface between solids, and that they are not produced by bulk processes from the near-surface layer of the material. Measurements reveal that due to the lack of phase matching, the generated harmonics in bulk are suppressed by orders of magnitude compared to the signal generated on the surface. Our results pave the way for the development of all-solid-state high repetition rate harmonic sources for vacuum ultraviolet spectroscopy and high precision frequency comb metrology.

PET/MRI and PET/MRI/SISCOM coregistration in the presurgical evaluation of refractory focal epilepsy.

We aimed to investigate the usefulness of coregistration of positron emission tomography (PET) and magnetic resonance imaging (MRI) findings (PET/MRI) and of coregistration of PET/MRI with subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) (PET/MRI/SISCOM) in localizing the potential epileptogenic zone in patients with drug-resistant epilepsy. We prospectively included 35 consecutive patients with refractory focal epilepsy whose presurgical evaluation included a PET study. Separately acquired PET and structural MRI images were coregistered for each patient. When possible, ictal SPECT and SISCOM were obtained and coregistered with PET/MRI. The potential location of the epileptogenic zone determined by neuroimaging was compared with the seizure onset zone determined by long-term video-EEG monitoring and with invasive EEG studies in patients who were implanted. Structural MRI showed no lesions in 15 patients. In these patients, PET/MRI coregistration showed a hypometabolic area in 12 (80%) patients that was concordant with seizure onset zone on EEG in 9. In 7 patients without MRI lesions, PET/MRI detected a hypometabolism that was undetected on PET alone. SISCOM, obtained in 25 patients, showed an area of hyperperfusion concordant with the seizure onset zone on EEG in 7 (58%) of the 12 of these patients who had normal MRI findings. SISCOM hyperperfusion was less extensive than PET hypometabolism. A total of 19 patients underwent surgery; 11 of these underwent invasive-EEG monitoring and the seizure onset zone was concordant with PET/MRI in all cases. PET/MRI/SISCOM coregistration, performed in 4 of these patients, was concordant in 3 (75%). After epilepsy surgery, 13 (68%) patients are seizure-free after a mean follow-up of 4.5 years. PET/MRI and PET/MRI/SISCOM coregistration are useful for determining the potential epileptogenic zone and thus for planning invasive EEG studies and surgery more precisely, especially in patients without lesions on MRI.

High-harmonic generation and parametric amplification in the soft X-rays from extended electron trajectories.

We report, for the first time, the generation of high-order harmonics in a spectral range between 200 eV and 1 keV with an unusual spectral property: only every 4(th) (4i + 1, i∈ℵ) harmonic line appears, whereas the usual high-harmonic spectra consist of every odd (2i + 1) harmonic. We attribute this unique property to the quantum path interference of two extended electron trajectories that experience multiple re-scattering. In the well-established theory, electrons emitted via tunnel ionisation are accelerated by a laser field, return to the ion and recombine. The acceleration typically lasts for less than one optical cycle, and the electrons radiate in the extreme ultraviolet range at recombination. In contrast, for extended trajectories, electrons are accelerated over two or more optical cycles. Here, we demonstrate that two sets of trajectories dominate and provide substantial contributions to the generated soft X-ray radiation because they fulfil the resonance condition for X-ray parametric amplification.

Parametric amplification of attosecond pulse trains at 11†nm.

We report the first experimental demonstration of the parametric amplification of attosecond pulse trains at around 11 nm. The helium amplifier is driven by intense laser pulses and seeded by high-order harmonics pulses generated in a neon gas jet. Our measurements suggest that amplification takes place only if the seed pulse-trains are perfectly synchronized in time with the driving laser field in the amplifier. Varying the delay, we estimate the durations of the individual extreme ultraviolet pulses within the train to be on the order of 0.2 fs. Our results demonstrate that strong-field parametric amplification can be a suitable tool to amplify weak attosecond pulses from non-destructive pump-probe experiments and it is an important step towards designing amplifiers for realization of energetic XUV pulses with sub-femtosecond duration using compact lasers fitting in university laboratories.

Optical platelet aggregometry does not appear useful as a means of assessing the risk of recurrent vascular events in aspirin-treated patients.

OBJECTIVES: To investigate whether the results of optical platelet aggregometry indicate the risk of recurrent ischemic events. MATERIALS AND METHODS: Cerebro- and cardiovascular patients taking aspirin for at least 30 days were studied retrospectively. Ischemic vascular events occurring prior to testing and the presence of vascular risk factors were recorded. RESULTS: 241 subjects were included. Among the 78 patients (32.4%) who displayed recurrent vascular episodes, the age (62.5 +/- 10.6 vs. 58.4 +/- 11.6, P = 0.009) and the proportion of hypertensives (80.8% vs. 68.1%, P = 0.040) were significantly higher when compared with the participants who exhibited single events. The degree of platelet aggregation did not differ significantly between the patients with and those without recurrent episodes. Logistic regression analysis identified only age (OR 1.033, 95% CI 1.008-1.058, P = 0.010), and not aggregation values, as a risk condition for recurrent vascular episodes. CONCLUSIONS: Results of optical platelet aggregometry were not indicative of the risk of recurrent vascular events. The role of conventional risk factors appeared to be more important.

The norepinephrine level is decreased in the lymphocytes of long-term interferon-beta-treated multiple sclerosis patients.

The mutual involvement of dopamine and its metabolites in the nervous and immune systems has the potential to provide information on the interaction of these two systems. During a 24-hour period, we used capillary electrophoresis with electrochemical detection to repeatedly measure the intracellular catecholamine concentrations in the peripheral blood lymphocytes of relapsing-remitting multiple sclerosis (RRMS) patients receiving interferon (IFN)-beta-1b (n = 13), and those of IFN-naïve RRMS patients receiving their first IFN-beta-1a injection (n = 19) during this study, and compared them with the levels in healthy controls (n = 12). At baseline, the norepinephrine level was significantly decreased (P =0.003) in the long-term IFN MS patients compared with the controls. The Time x Group interactions for dopamine (P=0.5854) and norepinephrine (P=0.6192) were not significant. The group effects for the individual drugs were P=0.3529 and 0.1282, respectively. The lower norepinephrine level at baseline in the long-term IFN MS group suggests an immunologically stable phase, in line with our previous findings. This is the first report of the effects of IFN-beta administration on intracellular catecholamines in MS patients. Further studies are necessary to elucidate the immune reactions affected by the catecholamines in MS and to evaluate the roles of these potential immunotransmitters.

Interferon-beta affects the tryptophan metabolism in multiple sclerosis patients.

Tryptophan and its metabolites are of great interest in understanding the pathogenesis of multiple sclerosis (MS). The total levels of tryptophan and its metabolites, kynurenine and kynurenic acid were determined in plasma by capillary liquid chromatography electrospray ionisation tandem mass spectrometry. This is the first report of the plasma levels of these analytes in healthy controls and relapsing-remitting MS patients receiving long-term and acute interferon-beta (IFN-beta) treatment. Twenty-four hours post-administration increased kynurenine levels (first IFN MS versus healthy, P = 0.042) and kynurenine/tryptophan ratio (K/T; first IFN MS versus healthy, P =0.027; first IFN MS versus long-term IFN MS, P = 0.036) were found. The long-term IFN MS group had higher K/T ratios at 4 and 12 h post-administration (P = 0.015 and 0.009, respectively). The increase of K/T ratio in the first IFN MS group indicate an induction of the enzyme indolamine-2,3-dioxygenase (IDO), as reported earlier in experimental allergic encephalomyelitis. As IDO is participating in both inflammatory and neurodegenerative processes, further knowledge of its involvement in the pathogenesis of MS is of great importance.

Laser technology: source of coherent kiloelectronvolt X-rays.

Generating X-rays that have the properties of laser light has been a long-standing goal for experimental science. Here we describe the emission of highly collimated, spatially coherent X-rays, at a wavelength of about 1 nanometre and at photon energies extending to 1.3 kiloelectronvolts, from atoms that have been ionized by a 5-femtosecond laser pulse. This means that a laboratory source of laser-like, kiloelectronvolt X-rays, which will operate on timescales relevant to many chemical, biological and materials problems, is now within reach.

Familial multiple sclerosis: case study of three affected siblings.

We report on three sisters with new-onset multiple sclerosis (MS). The symptoms of the eldest sister began in 1993 with lower-limb weakness and paraesthesia. In 1998, she had limb weakness, nystagmus and ataxia. Magnetic resonance imaging (MRI) of the brain, the cerebrospinal fluid (CSF) examinations, and evoked potentials verified MS. The middle sister exhibited left-side optic neuritis in 1998. All findings pointed to MS. The third sister had subjective complaints such as paraesthesias and vertigo. MRI and CSF results supported the diagnosis. Both parents and all four grandparents are without neurological signs; the brain MRI examinations on the parents were negative. The prevalence of familial MS in first-degree relatives is 5-10%, while that in twins is 20-30%. In this case, environmental factors seem to play the crucial role. Although the anamnesis as concerns MS proved negative in the other family members examined here, further genetic examination of the sisters is needed.

Injury risks among chimpanzees in three housing conditions.

Meeting the psychological needs of chimpanzees (Pan troglodytes) can be a challenge given their aggressiveness on the one hand and the complexity of their social lives on the other. It is unclear how to balance the need to provide opportunities for species-appropriate behavior against potential risks of injury chimpanzees may inflict on each other. This study evaluates the suggestion that simpler social environments protect chimpanzees from wounding. Over a two-year period all visible injuries to 46 adult males, 64 adult females, and 25 immature chimpanzees were recorded at the Yerkes Regional Primate Research Center. Approximately half of the subjects were mother-reared, and the rest were nursery-reared. Housing included compounds containing about 20 chimpanzees, interconnected indoor-outdoor runs for groups of up to 12 individuals, and smaller indoor-outdoor runs for pairs and trios. Annual wounding rates were calculated for serious wounds (extensive injuries and all those requiring veterinary intervention) as well as for minor wounds. Compound-housed chimpanzees incurred the highest level of minor wounding, but serious wounding levels were not affected by housing condition. Even with a period of dominance instability and elevated levels of wounding in one compound, compound chimpanzees were not injured more than those in smaller social groups over the long term. Nursery-reared females in moderate-sized groups were wounded more than mother-reared females. Also, nursery-reared males and females were wounded less often when paired with mother-reared companions. Overall, this study indicates that maintaining chimpanzees in pairs and trios would not be an effective means for reducing injuries. The management of wounding in chimpanzee colonies is influenced more by the sex and rearing composition of a colony.

Amino acids in the saliva of patients with migraine.

There are a number of hypotheses concerning the pathogenesis of migraine, but they are frequently conflicting. In addition to the vascular hypothesis, clinical data are available that excitatory amino acids may play an important role in the development of the disease. In this study, free amino acid concentrations were measured by RP-HPLC in the saliva of 23 migraineurs without aura, 14 migraineurs with aura, and 20 healthy subjects. Significantly higher concentrations of glutamic acid, serine, glycine, arginine, and tyrosine were found in the saliva samples of both groups of migraineurs relative to the control group. It is suggested that amino acids causing hyperexcitability in the central nervous system may be linked to the pathogenesis of migraine.

[Diagnostic studies of cerebrospinal fluid in patients with multiple sclerosis]. / Liquordiagnosztikai vizsgálatok sclerosis multiplexes betegekben.

The diagnostic criteria postulated by Poser necessitate clinical and laboratory CSF analysis for establishment of the diagnosis of definitive multiple sclerosis. The present paper reports methods for CSF examinations relating to multiple sclerosis with regard to the examinations suggested by the Charcot Foundation. In the course of CSF analysis, it is important to discriminate between the immunoglobulins present in normal amounts, those synthesized locally in pathological quantities and those penetrating across the damaged blood-CSF barrier. Normally, a parallel assay of CSF and serum specimens is carried out in the course of quantitative and qualitative protein analysis. In 37 patients with clinical multiple sclerosis, we determined the albumin and the immunoglobulin classes IgG, IgA and IgM, using laser nephelometry. An elevated IgG index was found in 76% of the cases, which points to local IgG snythesis and might be proof of the humoral immune response. The albumin quotient, which is suitable for examination of the integrity of the blood-CSF barrier, was within the reference range. Qualitative protein analysis was performed by means of electrophoresis on agarose-gel and isoelectric focusing. Agarose-gel electrophoresis revealed oligoclonal gammopathy in 68%, in contrast with the 91% demonstrated by isoelectric focusing. Comparison of the two kids of qualitative protein analyses indicated that isoelectric focusing was more sensitive for the detection of oligoclonal bands, in support of the literature finding.

Supernumerary nipples and renal anomalies.

The authors found a total of 504 supernumerary nipples in healthy newborn infants, schoolchildren and patients in the paediatric ward and outpatient clinic. The prevalence of supernumerary nipples was 4.29% among newborn infants and 5.86% among schoolchildren; 496 children with supernumerary nipples were examined with ultrasound for renal malformations and 410 acutely ill patients served as controls. The other control group consisted of 1957 newborn infants routinely screened by ultrasound. The prevalence of renal anomalies was 3.74% in children with supernumerary nipples, 3.17% in the control group, 2.86% in newborn infants with supernumerary nipples and 1.89% in control newborn infants. The differences are not significant.

[Polythelia and renal malformation]. / Polythelia és vese fejlödési rendellenesség.

The authors found 241 polythelia (5.86) among 4113 schoolchildren (aged 6-14 years). They investigated 236 of the 241 with ultrasound and found 10 renal malformations (4.24%). Among 280 controls with respiratory infection, accident or tonsillectomy they found 9 renal malformations (3.21%). With screening of 1635 neonates they found 66 with accessory nipples (4.05%). Two of the 66 had renal malformations (3.03%), while among the 1957 control neonates 37 had renal malformations (1.89%). In the hospital and ambulancy the authors found 106 polythelia, five of them had renal abnormalities (4.72%). The authors did not found association of polythelia and renal malformation with ultrasound investigation of 408 children with polythelia.