Silicate bonding of sapphire to SESAMs: adjustable thermal lensing for high-power lasers.

Silicate bonding is a flexible bonding method that enables room-temperature bonding of many types of materials with only moderate flatness constraints. It is a promising approach for bonding components in high power laser systems, since it results in a thin and low-absorption interface layer between the bonded materials. Here we demonstrate for the first time silicate bonding of a sapphire window to a SEmiconductor Saturable Absorber Mirror (SESAM) and use the composite structure to mode-lock a high-power thin-disk laser. We characterize the fabricated devices both theoretically and experimentally and show how the thermally induced lens of the composite structure can be tuned both in magnitude and sign via the thickness of the sapphire window. We demonstrate mode-locking of a high-power thin-disk laser oscillator with these devices. The altered thermal lens allows us to increase the output power to 233 W, a 70-W-improvement compared to the results achieved with a state-of-the-art SESAM in the same cavity.

Power scaling of ultrafast oscillators: 350-W average-power sub-picosecond thin-disk laser.

We report a semiconductor saturable absorber mirror (SESAM)-modelocked thin-disk laser oscillator delivering a record 350-W average output power with 940-fs, 39-µJ pulses at 8.88-MHz repetition rate and 37-MW peak power. This oscillator is based on the Yb:YAG gain material and has a large pump spot on the disk. The cavity design includes an imaging scheme, which results in multiple reflections on the disk gain medium to enable a larger output coupling rate compared to those used in thin-disk oscillators with a single reflection on the disk. This reduces the intracavity power for a given output power, thus decreasing the stress on the intracavity components. We operate the laser in a low-pressure environment in order to limit the disk's thermal lensing and drastically reduce the nonlinearity picked up in the intracavity air medium. The combination of the imaging scheme and low-pressure operation paves the way to further power scaling of ultrafast thin-disk oscillators toward the kW milestone.

Gas-lens effect in kW-class thin-disk lasers.

We unveil a gas-lens effect in kW-class thin-disk lasers, which accounts in our experiments for 33% of the overall disk thermal lensing. By operating the laser in vacuum, the gas lens vanishes. This leads to a lower overall thermal lensing and hence to a significantly extended power range of optimal beam quality. In our high-power continuous-wave (cw) thin-disk laser, we obtain single-transverse-mode operation, i.e. M2 < 1.1, in a helium or vacuum environment over an output-power range from 300 W to 800 W, which is 70% broader than in an air environment. In order to predict the magnitude of the gas-lens effect in different thin-disk laser systems and gain a deeper understanding of the effect of the heated gas in front of the disk, we develop a new numerical model. It takes into account the heat transfer between the thin disk and the surrounding gas and calculates the lensing effect of the heated gas. Using this model, we accurately reproduce our experimental results and additionally predict, for the first time by means of a theoretical tool, the existence of the known gas-wedge effect due to gas convection. The gas-lens and gas-wedge effects are relevant to all high-power thin-disk systems, both oscillators and amplifiers, operating in cw as well as pulsed mode. Specifically, canceling the gas-lens effect becomes crucial for kW power scaling of thin-disk oscillators because of the larger mode area on the disk and the resulting higher sensitivity to the disk thermal lens.

Modelocking of a thin-disk laser with the frequency-doubling nonlinear-mirror technique.

We demonstrate a frequency-doubling nonlinear-mirror (NLM) modelocked thin-disk laser. This modelocking technique, composed of an intracavity second harmonic crystal in combination with a dichroic output coupler, offers robust operation decoupled from cavity stability (as in semiconductor saturable absorber mirror (SESAM) modelocking) combined with an ultrafast saturable loss and high modulation depth (as in Kerr-lens modelocking (KLM)). With our NLM diode-pumped Yb:YAG thin-disk laser we achieve 21 W of average power at 323-fs pulse duration, which is an order of magnitude shorter than the previously obtained duration with the same technique in bulk lasers. Using these first results, we present a theoretical model for the NLM technique, which accurately predicts its loss modulation properties and the shortest achievable pulse duration without relying on any fitting parameters. Based on this simulation, we expect that the NLM technique will enable thin-disk lasers with average power of more than 100 W, with potentially sub-200 fs pulses. This could potentially solve the pulse duration limitations with SESAM modelocked Yb:YAG thin-disk lasers without imposing strong cavity stability constraints such as in KLM.

Allogeneic cellular gene therapy in hemoglobinopathies--evaluation of hematopoietic SCT in sickle cell anemia.

Many patients with thalassemia have been cured with BMT since the first successful transplant in 1981. Allogeneic stem cell gene therapy is the only treatment option for patients with sickle cell anemia (SCA). A total of 11 patients with a median age of 12 years (range, 2-16), affected by SCA, received hematopoietic SCT from HLA-identical, related donors following a myeloablative-conditioning regimen. Indications for transplantation were vaso-occlusive crisis, acute chest syndrome, avascular bone necrosis, chronic RBC transfusions, or hemorrhagic stroke. All patients had sustained engraftment. One patient became a stable mixed chimera with 25% of donor cells at 4 years after transplantation. One patient died at 1 year after transplantation. The probability of survival, SCA-free survival and TRM at 5 years after transplant were 90, 90 and 10%, respectively. All 10 surviving patients remained free of any SCA-related events after transplantation. In conclusion, these data confirm SCT from a suitable HLA-matched, related donor should become the primary option for curing children with SCA. There is an excellent survival rate and a return to normal life, free of SCA-related events.

Higher CD3(+) and CD34(+) cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia.

We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3(+) and CD34(+) cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P=0.005 and 46 vs 23%, P=0.021, respectively). In multivariate analysis, high CD3(+) (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P=0.010) and CD34(+) (HR 4.3; 95% CI 1.4-12.7; P=0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3(+) and CD34(+) cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3(+) (38 × 10(6)/kg) and CD34(+) (4 × 10(6)/kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3(+) and CD34(+) cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD.

High rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myeloma.

Novel agents are increasingly used during induction therapy for multiple myeloma (MM), but there is concern about their potential impact on stem cell mobilization. Regimens containing either thalidomide or cyclophosphamide have little or no impact on stem cell collection. In this retrospective review of 136 patients with newly diagnosed MM, we show that the combination of thalidomide and oral CY with dexamethasone (CTD) during induction therapy impaired stem cell mobilization substantially. Compared with VAD (vincristine, doxorubicin, dexamethasone) and a VAD-like induction regimen, the stem cell collection yield after CTD was decreased by 49% (median 5.0 vs 9.8 × 10(6) CD34+cells/kg, P<0.001). Following CTD, more patients failed to mobilize enough stem cells for one (25.4 vs 5.8%, P=0.002) or two (39.4 vs 15.9%, P=0.002) transplants. These results demonstrate that the combination of thalidomide and oral CY impairs stem cell mobilization and indicate that drugs with no previously reported relevant effect on stem cell mobilization can have a substantial impact when given in combination.

[The Sikorskj HH-3F in rescue activities and in air medical transport]. / Il Sikorskj HH-3F nell'attività di soccorso e trasporto sanitario per via aerea.

Technical and medical problems arising out of air rescue and transport operations are examined through an overview of the activities of the 15th S.A.R. Wing, Italian Air Force. The particular engineering, radio, and S.A.R. features of the Sikorskj HH-3F, currently used for this purpose, make it a sound and effective choice. A specially trained medical, health and nursing unit able to operate on the aircraft under all-weather conditions, coupled with a wide range of medical material, provide the best comment on the series of pathologies illustrated in the tables. Behind this matter, however, there increasingly lies the equally important question of the desirability or otherwise of imposing a strict control to make sure that the use of helicopters on S.A.R. tasks is not indiscriminate, but governed by clearly defined conditions.