D. Harter

Ultrashort-pulse second-harmonic generation with longitudinally nonuniform quasi-phase-matching gratings: pulse compression and shaping

We present a theory of ultrashort-pulse second-harmonic generation (SHG) in materials with longitudinally nonuniform quasi-phase-matching (QPM) gratings. We derive an expression for the output second-harmonic field generated in an arbitrary QPM grating from an arbitrary fundamental field, valid for arbitrary material dispersion in the undepleted-pump approximation. In the case when group-velocity dispersion can be neglected, a simple transfer-function relationship describes the SHG process. This SHG transfer function depends only on material properties and on the QPM grating design. We use this SHG transfer function to show that nonuniform QPM gratings can be designed to generate nearly arbitrarily shaped second-harmonic output pulses. We analyze in detail a technologically important example of pulse shaping: the generation of compressed second-harmonic pulses from linearly chirped fundamental input pulses. The efficiency of these interactions as well as the limits imposed by higher-order material dispersion are discussed.

Ultrawide tunable Er soliton fiber laser amplified in Yb-doped fiber.

A Raman-shifted and frequency-doubled high-power Er-fiber soliton laser for seeding an efficient high-power Yb fiber femtosecond amplifier is demonstrated. The Raman-shifted and frequency-doubled Er-soliton laser is tunable from 1.00 to 1.070microm and produces bandwidth-limited 24-pJ pulses at a repetition rate of 50 MHz with a FWHM pulse width of 170 fs at 1.040microm . The Yb(3+) amplifier has a slope efficiency of 52% and generates 3-ps linearly chirped pulses with an average power of 0.8 W at 1.05microm . After pulse compression, 74-fs bandwidth-limited pulses with an average power of 0.4 W and a pulse energy of 8 nJ are generated.

Glioblastoma multiforme: State of the art and future therapeutics

Background: Glioblastoma multiforme (GBM) is the most common and lethal primary malignancy of the central nervous system (CNS). Despite the proven benefit of surgical resection and aggressive treatment with chemo- and radiotherapy, the prognosis remains very poor. Recent advances of our understanding of the biology and pathophysiology of GBM have allowed the development of a wide array of novel therapeutic approaches, which have been developed. These novel approaches include molecularly targeted therapies, immunotherapies, and gene therapy. Methods: We offer a brief review of the current standard of care, and a survey of novel therapeutic approaches for treatment of GBM. Results: Despite promising results in preclinical trials, many of these therapies have demonstrated limited therapeutic efficacy in human clinical trials. Thus, although survival of patients with GBM continues to slowly improve, treatment of GBM remains extremely challenging. Conclusion: Continued research and development of targeted therapies, based on a detailed understanding of molecular pathogenesis can reasonably be expected to yield improved outcomes for patients with GBM.

Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas

BACKGROUND Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA. METHODS Key eligibility criteria included age ≥ 2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m(2)/dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available. RESULTS Eleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1-31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma. CONCLUSIONS Sorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.

High-energy femtosecond pulse amlification in a quasi-phase-matched parametric amplifier

A new type of solid-state femtosecond amplifier is demonstrated that is based on quasi-phase-matched parametric amplification. Such gain media are different from conventional solid-state amplifiers in that their amplification bandwidths and pump and signal wavelengths can be engineered. Furthermore, high gain is characteristic of parametric amplification, permitting extraction of high energies without the need to resort to multiple-pass configurations. We report a parametric chirped pulse amplification system in which femtosecond pulses from a mode-locked Er-doped fiber laser system are amplified to 1-mJ energies in a single pass by use of a 5-mm-long periodically poled LiNbO(3) (PPLN) crystal. This amplifier is pumped by 5-mJ and 0.5-ns pulses at 786 nm, demonstrating that limitations associated with a low optical-damage threshold for long pump pulses can be overcome because of the high nonlinearity of PPLN and that relatively simple Q -switched lasers can be used with such parametric amplifiers.

ENGINEERABLE FEMTOSECOND PULSE SHAPING BY SECOND-HARMONIC GENERATION WITH FOURIER SYNTHETIC QUASI-PHASE-MATCHING GRATINGS

We describe a pulse-shaping technique that uses second-harmonic generation with Fourier synthetic quasi-phase-matching gratings. We demonstrate both amplitude and phase tailoring by generating a picosecond squarelike pulse as well as trains of femtosecond pulses with a terahertz-range repetition rate from either a compressed or a chirped pump pulse.

Bevacizumab in recurrent high-grade pediatric gliomas†

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m(2). Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonalds criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference.

Chirped-pulse-amplification circuits for fiber amplifiers, based on chirped-period quasi-phase-matching gratings.

A new type of compact chirped-pulse-amplification circuit for high-power amplification of femtosecond pulses in an optical fiber is demonstrated. This circuit is based on a novel pulse compressor, chirped-period quasi-phase-matching gratings in electric-field-poled lithium niobate. The main advantages of this circuit are simplicity, the small number of components, compactness, and wavelength conversion of Er-doped fiber output to the technologically important 780-nm wavelength region.

Pulse shaping by difference-frequency mixing with quasi-phase-matching gratings

We present a theory of ultrashort-pulse difference-frequency generation (DFG) with quasi-phase-matching (QPM) gratings in the undepleted-pump, unamplified-signal approximation. In the special case of a cw (or quasi-cw) pump, the spectrum of the generated idler is related to the spectrum of the signal through a transfer-function relation that is valid for arbitrary dispersion in the medium. The engineerability of this QPM-DFG transfer function establishes the basis for arbitrary pulse shaping. Experimentally we demonstrate QPM-DFG devices operating in a frequency-degenerate type II configuration and producing pulse-shaped output at 1550 nm from 220-fs pulses at 1550 nm.

Equivalence of fusion rates after rigid internal fixation of the occiput to C-2 with or without C-1 instrumentation

OBJECT The object of this study was to assess a multiinstitutional experience with pediatric occipitocervical constructs to determine whether a difference exists between the fusion and complication rates of constructs with or without direct C-1 instrumentation. METHODS Seventy-seven cases of occiput-C2 instrumentation and fusion, performed at 9 childrens hospitals, were retrospectively analyzed. Entry criteria included atlantooccipital instability with or without atlantoaxial instability. Any case involving subaxial instability was excluded. Constructs were divided into 3 groups based on the characteristics of the anchoring spinal instrumentation: Group 1, C-2 instrumentation; Group 2, C-1 and C-2 instrumentation without transarticular screw (TAS) placement; and Group 3, any TAS placement. Groups were compared based on rates of fusion and perioperative complications. RESULTS Group 1 consisted of 16 patients (20.8%) and had a 100% rate of radiographically demonstrated fusion. Group 2 included 22 patients (28.6%), and a 100% fusion rate was achieved, although 2 cases were lost to follow-up before documented fusion. Group 3 included 39 patients (50.6%) and demonstrated a 100% radiographic fusion rate. Complication rates were 12.5, 13.7, and 5.1%, respectively. There were 3 vertebral artery injuries, 1 (4.5%) in Group 2 and 2 (5.1%) in Group 3. CONCLUSIONS High fusion rates and low complication rates were achieved with each configuration examined. There was no difference in fusion rates between the group without (Group 1) and those with (Groups 2 and 3) C-1 instrumentation. These findings indicated that in the pediatric population, excellent occipitocervical fusion rates can be accomplished without directly instrumenting C-1.