Ultrabroadband flying-focus using an axiparabola-echelon pair.

Flying-focus pulses promise to revolutionize laser-driven secondary sources by decoupling the trajectory of the peak intensity from the native group velocity of the medium over distances much longer than a Rayleigh range. Previous demonstrations of the flying focus have either produced an uncontrolled trajectory or a trajectory that is engineered using chromatic methods that limit the duration of the peak intensity to picosecond scales. Here we demonstrate a controllable ultrabroadband flying focus using a nearly achromatic axiparabola-echelon pair. Spectral interferometry using an ultrabroadband superluminescent diode was used to measure designed super- and subluminal flying-focus trajectories and the effective temporal pulse duration as inferred from the measured spectral phase. The measurements demonstrate that a nearly transform- and diffraction-limited moving focus can be created over a centimeter-scale-an extended focal region more than 50 Rayleigh ranges in length. This ultrabroadband flying-focus and the novel axiparabola-echelon configuration used to produce it are ideally suited for applications and scalable to >100 TW peak powers.

Erratum: Dephasingless Laser Wakefield Acceleration [Phys. Rev. Lett. 124, 134802 (2020)].

This corrects the article DOI: 10.1103/PhysRevLett.124.134802.

Nonlinear Thomson scattering with ponderomotive control.

In nonlinear Thomson scattering, a relativistic electron reradiates the photons of a laser pulse, converting optical light to x rays or beyond. While this extreme frequency conversion offers a promising source for probing high-energy-density materials and driving uncharted regimes of nonlinear quantum electrodynamics, conventional nonlinear Thomson scattering has inherent trade-offs in its scaling with laser intensity. Here we discover that the ponderomotive control afforded by spatiotemporal pulse shaping enables regimes of nonlinear Thomson scattering that substantially enhance the scaling of the radiated power, emission angle, and frequency with laser intensity. By appropriately setting the velocity of the intensity peak, a spatiotemporally shaped pulse can increase the power radiated by orders of magnitude. The enhanced scaling with laser intensity allows for operation at significantly lower electron energies or intensities.

Vacuum acceleration of electrons in a dynamic laser pulse.

A planar laser pulse propagating in vacuum can exhibit an extremely large ponderomotive force. This force, however, cannot impart net energy to an electron: As the pulse overtakes the electron, the initial impulse from its rising edge is completely undone by an equal and opposite impulse from its trailing edge. Here we show that planarlike "flying focus" pulses can break this symmetry, imparting relativistic energies to electrons. The intensity peak of a flying focus-a moving focal point resulting from a chirped laser pulse focused by a chromatic lens-can travel at any subluminal velocity, forward or backward. As a result, an electron can gain enough momentum in the rising edge of the intensity peak to outrun and avoid the trailing edge. Accelerating the intensity peak can further boost the momentum gain. Theory and simulations demonstrate that these dynamic intensity peaks can backwards accelerate electrons to the MeV energies required for radiation and electron diffraction probes of high energy density materials.

Dephasingless Laser Wakefield Acceleration.

Laser wakefield accelerators (LWFAs) produce extremely high gradients enabling compact accelerators and radiation sources but face design limitations, such as dephasing, occurring when trapped electrons outrun the accelerating phase of the wakefield. Here we combine spherical aberration with a novel cylindrically symmetric echelon optic to spatiotemporally structure an ultrashort, high-intensity laser pulse that can overcome dephasing by propagating at any velocity over any distance. The ponderomotive force of the spatiotemporally shaped pulse can drive a wakefield with a phase velocity equal to the speed of light in vacuum, preventing trapped electrons from outrunning the wake. Simulations in the linear regime and scaling laws in the bubble regime illustrate that this dephasingless LWFA can accelerate electrons to high energies in much shorter distances than a traditional LWFA-a single 4.5 m stage can accelerate electrons to TeV energies without the need for guiding structures.

Evolution of the Electron Distribution Function in the Presence of Inverse Bremsstrahlung Heating and Collisional Ionization.

The picosecond evolution of non-Maxwellian electron distribution functions was measured in a laser-produced plasma using collective electron plasma wave Thomson scattering. During the laser heating, the distribution was measured to be approximately super-Gaussian due to inverse bremsstrahlung heating. After the heating laser turned off, collisional ionization caused further modification to the distribution function while increasing electron density and decreasing temperature. Electron distribution functions were determined using Vlasov-Fokker-Planck simulations including atomic kinetics.

Photon Acceleration in a Flying Focus.

A high-intensity laser pulse propagating through a medium triggers an ionization front that can accelerate and frequency upshift the photons of a second pulse. The maximum upshift is ultimately limited by the accelerated photons outpacing the ionization front or the ionizing pulse refracting from the plasma. Here, we apply the flying focus-a moving focal point resulting from a chirped laser pulse focused by a chromatic lens-to overcome these limitations. Theory and simulations demonstrate that the ionization front produced by a flying focus can frequency upshift an ultrashort optical pulse to the extreme ultraviolet over a centimeter of propagation. An analytic model of the upshift predicts that this scheme could be scaled to a novel tabletop source of spatially coherent x rays.

Ionization Waves of Arbitrary Velocity.

Flying focus is a technique that uses a chirped laser beam focused by a highly chromatic lens to produce an extended focal region within which the peak laser intensity can propagate at any velocity. When that intensity is high enough to ionize a background gas, an ionization wave will track the intensity isosurface corresponding to the ionization threshold. We report on the demonstration of such ionization waves of arbitrary velocity. Subluminal and superluminal ionization fronts were produced that propagated both forward and backward relative to the ionizing laser. All backward and all superluminal cases mitigated the issue of ionization-induced refraction that typically inhibits the formation of long, contiguous plasma channels.

Renal Pseudoaneurysms and Arteriovenous Fistulas as a Complication of Nephron-Sparing Partial Nephrectomy: Technical and Functional Outcomes of Patients Treated With Selective Microcoil Embolization During a Ten-Year Period.

PURPOSE: The aim of this study was to evaluate the clinical and functional outcomes in patients who underwent selective interventional embolization of renal pseudoaneurysms or arteriovenous fistulas at our center. MATERIALS AND METHODS: Our retrospective analysis included all consecutive patients who received selective transcatheter embolization of renal pseudoaneurysms or arteriovenous fistulas after partial nephrectomy in our department from January, 2003 to September, 2013. The technical and clinical success rate and functional outcome of every procedure was collected and analyzed. Furthermore, the change in renal parenchymal volume before and after embolization was determined in a subgroup. RESULTS: A total of 1425 patients underwent partial nephrectomy at our hospital. Of these, 39 (2.7 %) were identified with a pseudoaneurysm or an arteriovenous fistula after partial nephrectomy. The diagnosis of the vascular lesions was made by means of biphasic CT or CEUS. Technical success by means of selective microcoil embolization was achieved in all 39 patients (100 %). Clinical success, defined as no need for further operation or nephrectomy during follow-up, was achieved in 35 of 39 patients (85.7 %). Renal function, as measured by eGFR before and after the intervention, did not change significantly. However, a mean loss of parenchymal volume of 25.2 % was observed in a subgroup. No major or minor complications were attributable to the embolization procedure. CONCLUSION: Transcatheter embolization is a promising method for treating vascular complications which may occur after partial nephrectomy. We confirm the high success rate of this technique while discussing renal functional outcomes and potential safety aspects. KEY POINTS: Arterial pseudoaneurysms and arteriovenous fistulas are rare but severe complications after partial nephrectomy. Selective microcoil embolization is a safe and effective kidney-preserving procedure for treating these complications. Embolization leads to a significant loss of renal parenchymal volume but not to a loss of renal function.

Tobramycin once- vs thrice-daily for elective intravenous antipseudomonal therapy in pediatric cystic fibrosis patients.

PURPOSE: We hypothesized that a single intravenous (iv) tobramycine infusion (treatment B) would have equivalent anti-infectious efficacy in chronic Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) as the commonly performed treatment of three doses (treatment A) . Toxicity and practicability may even be improved in the single-dose regimen. METHODS: This was a randomized crossover study comparing outcome after 14 and 35 days. The primary end-point was a decrease in the leukocyte count, and the secondary end-points were clinical and lung function parameters, Pseudomonas quantification in sputum, and inflammation markers (immunoglobulin G, C-reactive protein) in serum. 30 patients (20 female, mean age 11.2 years, mean age range 1.7-18.1 years) received elective 14-day courses of treatments A or B, followed by the alternative treatment after a mean interval of 37 (+/- 21) weeks. RESULTS: With the exception of PA density, there were no significant differences between both treatment strategies after 14 days of treatment. After 35 days of treatment, there were no significant changes in the leukocyte count and inflammation markers. Both treatment strategies reduced the bacterial load in the airways, as reflected by a decreased PA density in sputum. Nephrotoxicity was equal in both groups, with a transient slight elevation of urinary N-acetyl-beta-glucosaminidase concentrations. Standard audiometry tests revealed no evidence of a hearing impairment in any patient following therapy. Mean body weight increased during the study period by 0.5 kg. Forced expiratory volume increased by approximately 5% of the predicted volume, forced vital capacity increased by 2% of predicted capacity, and forced mid expiratory flow rate increased by 7% (A) or 4% (B) of the predicted normal value, although these changes were not statistically significant. CONCLUSION: We conclude that tobramycin given in a daily single dose (with the advantage of being more practical in a home environment) has an efficacy equal to that of three daily doses in terms of elective antipseudomonal therapy in clinically stable patients with CF.

Continuous vs thrice-daily ceftazidime for elective intravenous antipseudomonal therapy in cystic fibrosis.

BACKGROUND/AIM: We hypothesized that a continuous 24-h infusion of 100 mg/kg per day ceftazidime (treatment C) would result in equivalent or even superior anti-infectious efficacy in chronic Pseudomonus aeruginosa (PA) infection in patients with cystic fibrosis (CF) in comparison to the usual application of 200 mg/kg per day ceftazidime in three doses (treatment T). METHODS: This was a randomized crossover study comparing outcome after 14 days and 35 days. Tobramycin administered once daily (10 mg/kg per day) was administered concomitantly in both groups. The primary end-point was a decrease in the leukocyte count, and the secondary endpoints were clinical and lung function parameters, Pseudomonas quantification in sputum, and inflammation markers (immunogloblulin [Ig] G, C-reactive protein [CRP]) in serum. All patients received antibiotics electively as 14-day courses on a regular basis, not for acute exacerbations. RESULTS: Fifty-six patients (29 females, mean patient age 14.4 years, age range 5-37) initially received treatments C or T, followed by the alternative treatment after a mean interval of 37 (+/- 21) weeks. After 2 weeks of antibiotic treatment, the overall study group showed significant improvements compared to baseline for body weight, leukocyte counts, CRP, forced expiratory volume in 1 s (FEV(1)), FVC (forced vital capacity), and bacterial load in the airways, with no significant differences between treatment groups. Both regimens were well tolerated. Three weeks after cessation of antimicrobial therapy, leukocytes and PA density had returned to pre-treatment values. CONCLUSION: We conclude that continuous or thrice-daily dosing of intravenous ceftazidime, both combined with once-daily tobramycin, are equally effective application regimens for elective antipseudomonal therapy in clinically stable patients with CF.

Experimental investigation of nasal airflow.

The airway geometry of the nasal cavity is manifestly complex, and the manner in which it controls the airflow to accomplish its various physiological functions is not fully understood. Since the complex morphology and inaccessibility of the nasal passageways precludes detailed in-vivo measurements, either computational simulation or in-vitro experiments are needed to determine how anatomical form and function are related. The fabrication of a replica model of the nasal cavity, of a high optical clarity and derived from in-vivo scan data is described here, together with characteristics of the flow field investigated using particle image velocimetry (PIV) and flow visualization. Flow visualization is shown to be a capable and convenient technique for identifying key phenomena. Specifically the emergence of the jet from the internal nasal valve into the main cavity, how it impacts on the middle turbinate, and the large enhancement of dispersion that accompanies the initial appearance of flow instability are revealed as particularly significant features. The findings from the visualization experiments are complemented by PIV imaging, which provides quantitative detail on the variations in velocity in different regions of the nasal cavity. These results demonstrate the effectiveness of the cavity geometry in partitioning the flow into high shear zones, which facilitate rapid heat transfer and humidification from the nasal mucosa, and slower zones affording greater residence times to facilitate olfactory sensing. The experimental results not only provide a basis for comparison with other computational modelling but also demonstrate an alternative and flexible means to investigate complex flows, relevant to studies in different parts of the respiratory or cardiovascular systems.

Rgs 2 gene polymorphisms as modulators of anxiety in humans?

Rgs2 (regulator of G-protein signalling 2) gene recently was reported as a quantitative trait gene for anxious behaviour in mice and male Rgs2 knockout mice have been shown to be more anxious than wildtype mice. Therefore we investigated four non-coding single nucleotide polymorphisms in a sample of 173 patients with panic disorder and 173 matched controls of German descent. At the genotype level all four SNPs were associated with panic disorder (p = 0.02-0.05). At the haplotype level the strongest association was observed for a haplotype containing SNP3 and SNP 4 (subgroup men and men with agoraphobia: p = 0.01 and 0.03). This points towards a functional polymorphism at the 3' end of the gene. Our results support the hypothesis that variations of the Rgs2 gene play a role also for the development of anxiety in humans.

Genetic analysis of the biosynthesis of non-ribosomal peptide- and polyketide-like antibiotics, iron uptake and biofilm formation by Bacillus subtilis A1/3.

The Bacillus subtilis strain A1/3 shows exceptionally diverse antibiotic capacities compared to other B. subtilis strains. To analyze this phenomenon, mutants for the putative pantotheinyltransferase gene (pptS), and for several genes involved in non-ribosomal peptide synthesis and polyketide synthesis were constructed and characterized, using bioassays with blood cells, bacterial and fungal cells, and mass spectrometry. Among at least nine distinct bioactive compounds, five antibiotics and one siderophore activity were identified. The anti-fungal and hemolytic activities of strain A1/3 could be eliminated by mutation of the fen and srf genes essential for the synthesis of fengycins and surfactins. Both pptS- and dhb -type mutants were defective in iron uptake, indicating an inability to produce a 2,3-dihydroxybenzoate-type iron siderophore. Transposon mutants in the malonyl CoA transacylase gene resulted in the loss of hemolytic and anti-fungal activities due to the inhibition of bacillomycin L synthesis, and this led to the discovery of bmyLD-LA-LB* genes. In mutants bearing disruption mutations in polyketide (pksM- and/or pksR -like) genes, the biosynthesis of bacillaene and difficidins, respectively, was inactivated and was accompanied by the loss of discrete antibacterial activities. The formation of biofilms (pellicles) was shown to require the production of surfactins, but no other lipopeptides, indicating that surfactins serve specific developmental functions.

Cholecystokinin- and cholecystokinin-B-receptor gene polymorphisms in panic disorder.

Panic disorder like other neuropsychiatric disorders is believed to be caused by multiple psychosocial and biological factors. Several lines of evidence point to a role for the peptide neurotransmitter cholecystokinin in the pathogenesis of panic disorder. We therefore determined the allele and genotype frequencies of a single nucleotide polymorphism in the CCK gene (-36C>T) and one CT repeat polymorphism in the CCK-B-receptor gene in a German panic disorder sample (n = 115 for CCK gene polymorphism, n = 111 for CCK-B-receptor polymorphism) and compared them with gender and age matched controls. The length of the polymorphic CT repeat alleles varies between 146 bp and 180 bp. We first analysed the results by a permutation test which provided evidence for heterogeneity between patients and controls (p=0.002). We then analysed the data as a di-allelic polymorphism with a short (146-162bp) and a long (164-180bp) allele and as a tetra-allelic polymorphism with 4 alleles (146-154bp, 156-162bp, 164-170bp, 172-180bp). In the di-allelic analysis as well as in the tetra-allelic analysis there was an excess of the longer allele (p = 0.001) or the two longer alleles (p = 0.041) respectively in patients with panic disorder. No difference between groups was observed for the -36C > T polymorphism. Our findings are consistent with the notion that genetic variation in the CCK neurotransmitter system contributes to the pathogenesis of panic disorder.

Association study of serotonin-2A receptor gene polymorphism and panic disorder in patients from Canada and Germany.

The T102C serotonin-2A (5-HT2A) receptor gene polymorphism has been studied extensively in a number of complex psychiatric conditions with mixed results. Recently a genetic association has been described between this polymorphism and panic disorder in a Japanese sample. To evaluate the impact of the T102C polymorphism in panic disorder we genotyped triad families (panic disorder patient and parents), and cases with controls in Canadian and German samples. No significant transmission disequilibrium was observed between the alleles of the T102C 5-HT2A receptor gene polymorphism and panic disorder, nor was a significant excess of either allele found in the case control analysis. Our data suggest thus that this polymorphism is unlikely to play a major role in the pathogenesis of panic disorder.

Human nuclear transcription factor gene CREM: genomic organization, mutation screening, and association analysis in panic disorder.

Panic disorder is an anxiety disorder with an estimated heritability of 48%. Variation in the gene of the nuclear transcription factor "cAMP-responsive element modulator" (CREM) might contribute to its pathogenesis. CREM knock-out mice exhibit significantly less anxiety behavior than wild-type mice and the alternative CREM gene product "inducible cAMP early repressor" (ICER) plays a pivotal role in the hypothalamo-pituitary-adrenal (HPA) axis, which is disturbed in panic disorder. We characterized the genomic organization of the human CREM gene and performed a systematic mutation screening by means of single stranded conformational analysis (SSCA) in a sample of 40 German patients with panic disorder (DSM-III-R). Four novel single nucleotide polymorphisms in CREM promoters P 1 and P 4, one trinucleotide (ATT)-repeat polymorphism in CREM promoter P 2-generating the ICER isoform-and a rare amino acid substitution in CREM exon glut 2 were identified. Association analysis in an extended sample of German patients (n = 88) revealed a significant excess of the shorter CREM P 2 promoter eight-repeat trinucleotide allele and of genotypes containing the eight-repeat trinucleotide allele in panic disorder (P = 0.02), in particular in panic disorder without agoraphobia (P = 0.001). A replication study in independent Italian (n = 76) and Spanish (n = 62) samples, however, failed to confirm this observation. This suggests that the CREM P 2 promoter trinucleotide polymorphism is not a major susceptibility factor in the pathogenesis of panic disorder. Functional analysis of the observed CREM P 2 promoter polymorphism as well as studies in independent panic disorder samples are necessary.

[Psychiatric comorbidity in risk groups of opioid addiction: a comparison between opioid dependent and non-opioid dependent prisoners (in jail due to the German narcotics law)]. / Psychiatrische Komorbidität in Risikogruppen für Opiatabhängigkeit: eine Untersuchung an opiatabhängigen und nichtopiatabhängigen BtmG-Inhaftierten.

Individuals who do not develop opioid dependence although they have access to opioids might differ with regard to psychiatric risk factors from opioid-exposed subjects who developed opioid dependence. To test this assumption, the present investigation compared individuals who were in jail due to the German "Dangerous Drugs Act" (i. e. particular risk group due to facilitated opioid availability) according to presence or absence of opioid dependence and psychiatric comorbidity in each group. This study design is in line with the assumption that in addition to the (postulated) environmental risk factor of facilitated availability of opioids, psychiatric risk factors enhance the likelihood for the development of opioid dependence. Opioid addicts represent a risk group, not only for other forms of substance dependence, but also psychiatric disorders like anxiety disorders, suicide attempts and specific forms of personality disorders. However the difference between opioid dependent subjects and non-opioid dependent controls was less marked than initially postulated. Alcoholism of non-opioid dependent prisoners also was associated with depressive episodes, anxiety disorders as well as cocaine dependence. Despite the high frequency of life-time psychiatric comorbidity in the opioid dependent sample, this increased comorbidity was not paralleled by psychiatric treatment. In general, the sample of prisoners investigated here, was characterized by a high frequency of psychiatric disorders including substance dependence.

Norepinephrine transporter gene (NET) variants in patients with panic disorder.

Several lines of evidence suggest that catecholamines, especially norepinephrine, are implicated in the etiology and/or symptomatology of panic disorder (PD). At the cellular level, functional noradrenergic neurotransmission depends on synaptic reuptake of norepinephrine as mediated by the norepinephrine transporter (NET). A pharmacological target of agents with an established anti-panic efficacy, e.g. tricyclic antidepressants, the NET is of particular interest in PD. We investigated the NET gene for the presence of 6 naturally occurring exonic sequence variants, 5 of which give rise to amino acid substitutions (Val69Ile, Thr99Ile, Val245Ile, Val449Ile and Gly478Ser) in a population of 87 patients with PD and 89 healthy controls. Except for a silent substitution (G1287A), overall frequencies of variant alleles were low (< or =0.016). None of the variants under study was found to be associated with PD regardless of an additional diagnosis of agoraphobia.