Search

Precise characterization of the mechanical properties of gelatin, a classic analog of the elastic crust, is necessary for scaling the mechanical models of the Earth's crust behavior in laboratory experiments. Here we reassess how to accurately calculate the Young modulus (E) of gelatin contained in experimental tanks. By means of dedicated analog experiments and finite element simulations, we estimate the bias introduced by using equations appropriate for a half-space to interpret the subsidence due to a cylindrical surface load applied on the gelatin. In the case of a standard experimental setup with gelatin adhering to the tank wall, we find E is overestimated by at least 5% for a box with lateral size smaller than 20 times the cylinder diameter. In addition, we deduce a correction factor to be applied when using an analytical formula. We confirm that measuring the shear velocity leads to accurate estimates for the rigidity of gelatin. We also propose a new method for in situ Young's modulus estimation, relying on the length of air-filled propagating crack. Indeed, for a given injected volume, this length depends only on the density contrast between air and gelatin and on the Young's modulus of the gelatin. The fracture toughness of the gelatin is estimated independently. Direct comparison between fracture toughness and Young's modulus shows that for a given Young's modulus, salted gelatin has a higher fracture toughness than unsalted gelatin.

SUMMARYBackgroundTocilizumab is a monoclonal antibody that binds to the receptor for interleukin (IL)-6, reducing inflammation, and is commonly used to treat rheumatoid arthritis. We evaluated the safety and efficacy of tocilizumab in adult patients admitted to hospital with COVID-19 with evidence of both hypoxia and systemic inflammation.MethodsThis randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation clinicaltrials.gov (NCT04381936).FindingsBetween 23 April 2020 and 24 January 2021, 4116 adults were included in the assessment of tocilizumab, including 562 (14%) patients receiving invasive mechanical ventilation, 1686 (41%) receiving non-invasive respiratory support, and 1868 (45%) receiving no respiratory support other than oxygen. Median CRP was 143 [IQR 107-204] mg/L and 3385 (82%) patients were receiving systemic corticosteroids at randomisation. Overall, 596 (29%) of the 2022 patients allocated tocilizumab and 694 (33%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·86; 95% confidence interval [CI] 0·77-0·96; p=0·007). Consistent results were seen in all pre-specified subgroups of patients. In particular, a clear mortality benefit was seen in those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital alive within 28 days (54% vs. 47%; rate ratio 1·22; 95% CI 1·12-1·34; pInterpretationIn hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the level of respiratory support and were additional to the benefits of systemic corticosteroids.FundingUK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).

Tacrolimus compared with cyclosporine A after haploidentical T-cell replete transplantation with post-infusion cyclophosphamide

Unmanipulated haploidentical transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy) represents an alternative for patients with high-risk diseases lacking HLA-identical donor. Although it provides low incidences of GVHD, the efficacy of Haplo-SCT is still questioned, especially for patients with myeloid malignancies. Thus, we analyzed 60 consecutive patients with refractory (n=30) or high-risk CR (n=30) AML or myelodysplastic syndromes (MDSs) who underwent PT-Cy Haplo-SCT. The median age was 57 years (22-73 years), hematopoietic cell transplantation comorbidity index was ⩾3 in 38 patients (63%) and Haplo-SCT was the second allogeneic transplantation for 10 patients (17%). Although most of patients received PBSC as graft source (n=48, 80%), we found low incidences of grade 3-4 acute (2%) and severe chronic GVHD (4%). Among patients with high-risk CR diseases, 1-year non-relapse mortality, cumulative incidence of relapse, progression-free and overall survivals were 20%, 32%, 47% and 62%, respectively. In patients with refractory disease, corresponding results were 34%, 35%, 32% and 37%, respectively. We conclude that PT-Cy Haplo-SCT could provide promising anti-leukemic effect even in the setting of very advanced diseases. Thus, it represents a viable alternative for high-risk AML/MDS patients without HLA-identical donor.

Outcomes of Hodgkin lymphoma patients who relapse after allogeneic stem cell transplantation

Outcomes remain poor for refractory severe aplastic anemia (SAA) patients. Alternative donor transplantation may be considered, but results from previous studies are not encouraging. We conducted a prospective nationwide phase 2 study to assess unrelated cord blood (CB) transplantation (CBT) efficacy and safety in refractory SAA patients (Aplastic Anemia and Cord Blood Transplantation protocol). To demonstrate a significant difference in 1-year survival from 20% (null hypothesis) to 50% (alternative hypothesis), we needed to include 25 transplanted patients and therefore included 26 (median age, 16 years). Eligibility criteria required 1 or 2 unrelated CB units, containing separately or together >4 × 107 frozen nucleated cells (NCs) per kilogram of recipient body weight. Conditioning regimen comprised fludarabine (FLU), cyclophosphamide (CY), antithymocyte globulin (ATG), and 2-Gy total body irradiation (TBI). With a median follow-up of 38.8 months, engraftment occurred in 23 patients (88%); cumulative incidences of grade II-IV acute and chronic graft-versus-host disease were 45.8% and 36%, respectively. Twenty-three patients were alive at 1 year, with an 88.5% overall survival (OS) rate, differing significantly from the expected 20% (P < .0001; 84% OS at 2 years). CBT with units containing ≥4 × 107 frozen NCs per kilogram is therefore a valuable curative option for young adults with refractory SAA and no available matched unrelated donors. This trial was registered at www.clinicaltrials.gov as #NCT01343953.

Background Patients with advanced B-cell non-Hodgkin's lymphoma (NHL) refractory to initial chemotherapy or relapsing after autologous stem-cell transplantation have a poor prognosis. Allogeneic stem-cell transplantation after reduced-intensity conditioning (RIC) regimen can be a therapeutic option. However, the high incidence of relapse remains a challenging issue. We speculated that the incorporation of 90Y-Ibritumomab tiuxetan into a fludarabine-based RIC regimen would improve the lymphoma control without overwhelming toxicity. Our aim was to evaluate the safety of 90Y-Ibritumomab tiuxetan in association with such a regimen in a prospective multicenter phase II trial. Patients and methods Thirty-one patients with advanced lymphoma from five distinct institutions were included between February 2008 and October 2010. Thirty patients in complete or partial response after failure of a median of 3 (range, 2–4) previous chemotherapy regimens including autologous transplant in 29 were evaluable for nonrelapse mortality (NRM) at day 100 post-transplant that was the primary end point. Results With a median follow-up of 32 months (range, 29–60 months), the 2-year event-free and overall survivals of the whole study group were both 80% [95 confidence interval (CI) 60.8% to 90.5%). The 100-day and 2-year post-transplant cumulative incidences of NRM were 3.3% (95% CI 0.2% to 14.9%) and 13.3% (95% CI 5.4% to 33.2%), respectively. The 2-year cumulative incidence of relapse was 6.7% (95% CI 1.7% to 25.4%). The cumulative incidences of grade II–IV and extensive chronic graft-versus-host disease were 27% and 14%, respectively. Conclusions For chemosensitive advanced high-risk B-cell lymphoma, the addition of 90Y-Ibritumomab tiuxetan to a RIC regimen based on fludarabine, busulfan and antithymocyte globulin followed by allogeneic transplant is safe and highly effective. clinicaltrials.gov : NCT00607854.

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.

Familial haploidentical challenging unrelated donor Allo-SCT in advanced non-Hodgkin lymphomas when matched related donor is not available

We performed a retrospective analysis on 421 adult patients who underwent unrelated cord blood transplantation (UCBT) for ALL. Median age was 32 years; 46% were in first CR (CR1), 32% in CR2 and 22% had advanced disease. Double UCBT was performed in 173 patients (41%). Myeloablative conditioning (MAC) was given to 314 patients (75%). Cumulative incidence (CI) of 60-day neutrophil recovery was 78%. CI of acute and chronic GVHD was 33 and 26%, respectively. Non-relapse mortality (NRM) at 2 years was 42%. Age >= 35 years (P < 0.0001), advanced disease at UCBT (P < 0.0001) and use of MAC (P < 0.0001) were associated with increased NRM. Relapse incidence (RI) at 2 years was 28%; use of reduced intensity conditioning (RIC) (P = 0.0002) was associated with increased RI. Two-year leukemia-free survival (LFS) was 39% for patients in CR1, 31% for CR2 and 8% for advanced disease. In multivariate analysis, factors associated with decreased LFS rate were: age >= 35 years (P = 0.034), use of MAC (P = 0.032) and advanced disease (P < 0.0001). These results show that UCBT is a valuable option to treat high-risk adult ALL when in remission. Strategies to decrease toxicity and relapse are needed to improve final outcomes.

Invasive fungal infections (IFIs) such as candidiasis and mold infections have caused significant morbidity and mortality among immunocompromised patients in recent years. Micafungin, a new echinocandin, inhibits fungal cell wall β-glucan synthesis, with potent activity against most species of Candida and Aspergillus. The aim of this observational study was to investigate the efficacy and safety of micafungin in prophylaxis of IFIs in 26 high-risk adult patients with various hematological diseases receiving haplo-identical Allo-SCT. Only two patients had a history of possible aspergillosis before transplant treated by voriconazole. The patients received a median of four lines (2-7) of treatment before Allo-SCT. Thirteen patients (50%) received at least one prior Auto-SCT; and eight patients (31%) received a previous Allo-SCT. Patients received a median of 29 infusions (range, 15-85) of micafungin (50 mg/day i.v. as a 1-h infusion). The treatment was initiated at the beginning of the transplant conditioning regimen until the hospital discharge. None of our patients discontinued the treatment for drug-related adverse events. Micafungin was not associated with any hepatotoxicity. Only one patient (4%) discontinued the treatment because of early disease progression. In all patients no Candida and/or Aspergillus species was documented after 3 and 6 months from transplant. None of our patients presented a positive galactomannan antigenemia0.5. Nine patients (35%) presented a CMV reactivation. Four patients presented an acute GVHD grade II and two patients presented a chronic GVHD. The median follow-up was 11 months (3-23). At the last follow-up, there were 20 patients (77%) who were alive; four patients (12%) died because of disease progression and two patients because of graft failure. Micafungin has a good safety and tolerability profile, with an efficacy in preventing IFI in this high-risk population. Our data provide support for an efficacy study in a prophylaxis setting, but prospective and comparative clinical trials using micafungin are urgently needed to define the role of this drug in prophylaxis after haplo-identical Allo-SCT.

The calcineurin inhibitor and the intensity of the conditioning regimen may affect the occurrence of polyomavirus-associated hemorrhagic cystitis after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide

The patient’s CMV serological status affects clinical outcome after T-cell replete haplo-HSCT and post-transplant cyclophosphamide

Micro-ring lasers, with a minimum bend radius of 10 $\mu{\rm m}$ , are presented that exhibit directional bistability and output powers up to 1.5 mW. In order to achieve devices with low threshold currents, mW output powers and directional bistability, the confilicting design constraints on the device are highlighted. Optimized adiabatic waveguide bends, bi-level evanescent couplers, and deeply etched ridge waveguide designs are presented in order to meet the stringent device design requirements. The optimized micro-ring laser devices exhibit directional extinction ratios of 25 dB and side-mode suppression ratios ${>}{\rm 25}~{\rm dB}$ .

Allo-SCT is used to exploit GVL effect in high-risk relapsed non-Hodgkin's lymphoma (NHL). Here, we retrospectively analyzed 34 high-risk NHL patients who underwent auto-SCT followed closely by reduced-intensity allo-SCT ('tandem auto-allo') from January 2002 to November 2010. The search for an allogeneic donor was started at the beginning of salvage regimen. Median patients' age was 47 (27-68) years; histotypes were: diffuse large B-cell n=5, follicular n=14, transformed follicular n=4, mantle-cell n=5, plasmocytoid lymphoma n=1, anaplastic large T-cell n=2, peripheral T-cell n=3. Donors were HLA-identical siblings (n=29) or 10/10-matched unrelated individuals (n=5). Median interval between auto-SCT and allo-SCT was 77 days (36-197). At a median follow-up of 46 (8-108) months since allo-SCT, 5-year OS is 77% (61-93) and PFS is 68% (51-85). Disease relapse or progression occurred in six patients, 100-day TRM was 0%, 2-year TRM incidence was 6%. In conclusion, tandem transplantation is feasible in high-risk NHL patients having a HLA-identical donor. This approach could represent a suitable therapeutic option for those patients with high-risk NHL potentially benefitting from further therapy after auto-SCT. Donor searches should be started promptly whenever such an approach is chosen.

Rituximab is one of the most commonly used drugs in the treatment of B-cell non-Hodgkin lymphoma. Because of its ability to target CD20 + lymphocytes, its use before allogeneic stem cell transplantation seemed to reduce risk of graft-vs.-host disease (GVHD) occurrence. We retrospectively analyzed the outcomes of adult patients diagnosed with CD20 + lymphoproliferative disease undergoing allogeneic stem cell transplantation and receiving, or not receiving, rituximab up to 3 months before transplantation. Analysis on a cohort of 57 patients showed a protective role of rituximab on the occurrence of acute GVHD for those receiving anti-thymocyte globulin during conditioning (n = 39). Grade 2 to 4 and 3 to 4 acute GVHD occurred in 10% vs. 48% ( p = 0.03) and 0% vs. 24% ( p = 0.08) in the rituximab and no-rituximab groups, respectively. No impact on chronic GVHD was observed. These results confirm a protective role of rituximab on the occurrence of GVHD and enhance further investigation on future studies aimed at reducing GVHD incidence.

In this retrospective study, 63 patients >60 years with hematological malignancies and treated with allo-SCT and with reduced-intensity conditioning (RIC) were reviewed. A total of 51% of patients suffered from AML or myelodysplastic syndromes. Disease status before transplantation was CR or PR 71 with 29% transplanted with active disease. Patients were classified according to three published prognostic indexes: (1) hematopoietic cell transplantation comorbidity index (HCT-CI); (2) European BMT (EBMT) score; and (3) Pretransplantation Assessment of Mortality (PAM) score. The 100-day and 1-year treatment-related mortality (TRM) were 6 and 22%, respectively, for the entire group. The 2-year OS and PFS were 60 and 58%, respectively. The incidence of grade II-IV acute GVHD (aGVHD) and extensive chronic GVHD was 46 and 48%, respectively. In a univariate analysis, neither the HCT-CI nor the EBMT score, nor the PAM score were predictive of TRM and OS. Only the occurrence of aGVHD affected the TRM and OS. ALLO-RIC is feasible in elderly patients. Even if those prognostic scores were not adapted to elderly patients, they did not predict for TRM and OS. aGVHD is the main cause of TRM and more efforts should be made to reduce its incidence without sacrificing graft vs tumor effect.

This corrects the article DOI: 10.1038/bmt.2012.225.

We investigated the use of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of advanced Hodgkin lymphoma (HL). Sixty-two consecutive HL patients underwent haplo-HSCT. Unmanipulated stem cells and post-transplant cyclophosphamide were given to all patients as GVHD prophylaxis. At 100 days, the cumulative incidence of grades 2-3 and grades 3-4 acute GVHD was 23% and 4%, respectively. The chronic GVHD (cGVHD) cumulative incidence was 16%, with one patient experiencing severe cGVHD. The 3-year OS, PFS, relapse rates and 1-year non-relapse mortality (NRM) were 63%, 59%, 21% and 20%, respectively. Uncontrolled disease status and high hematopoietic cell transplantation comorbidity index (HCT-CI) were associated with lower OS, whereas PBSC was an independent protective factor. Uncontrolled disease and HCT-CI >2 was predictive for NRM. Finally, disease status other than CR was predictive of relapse. In conclusion, haplo-HSCT is a valid treatment in advanced HL, offering excellent rates of survival and acceptable toxicities.

Reduced-intensity conditioning regimen with in vivo T-cell depletion for patients with haematological malignancies: results using unrelated and sibling donors

Allo-SCT is regularly performed in advanced lymphoma. Haploidentical family donors are a valuable source of hematopoietic stem cells and transplants from these donors, using T-repleted grafts, has recently been successfully reported. We report on 49 patients with refractory lymphoma who received T-repleted haploidentical SCT with a non-myeloablative regimen and post-transplant CY. The median time to recover ANC >0.5 × 10e9/L and transfusion independent plt count >20 × 10e9/L was 20 days (range 14-38) and 26 days (range 14-395). The probability to reach ANC >0.5 × 10e9/L at 30 days was 87% and transfusion independent plt count >20 × 10e9/L at 100 days was 87%. The cumulative incidence of grade 2-4 acute GVHD (aGVHD) was 25.6% (95% confidence interval (CI): 12.9-38.3%) and the cumulative incidence of chronic GVHD (cGVHD) was 5.2% (95% CI: 0-12.4%). The median follow-up is 20.6 months (range 12-54), and the projected 2-year OS and PFS were 71 and 63%. The relapse rate was 18.7% (95% CI: 7.6-29.8%) and the median time to relapse was 4.4 months (range 1.1-8.3). At 2 years, cumulative incidence of NRM was 16.3% (95% CI: 5.9-26.8%). T-repleted Haploidentical transplantation with post-infusion CY is a feasible and effective therapy in the poor prognosis of advanced lymphoma patients.

We report on room-temperature continuous-wave operation and single-mode lasing of microdisk and microring lasers with radii as small as 7 mum. The waveguide sidewall roughness was minimized by an optimized fabrication process using hydrogen silsesquioxane e-beam resist and Cl 2-CH 3-H 2 inductively coupled plasma etching. The devices show unidirectional bistability between the counterpropagating modes for radii larger than 30 mu m and a strong hybrid output polarization for radii smaller than 15 mum with a transverse-magnetic component of approximately 30%.

Outcome after reduced-intensity conditioning allogeneic SCT for AML in first complete remission: comparison of two regimens

We report on cavity-enhanced four-wave mixing (FWM) in 1.55-mum semiconductor ring lasers (SRLs). External optical injection into one of the cavity modes of the ring laser induces a FWM signal up to detuning frequencies of 1.5 THz. Mode-locked signals at 34.5 GHz with a linewidth as small as 5 kHz were measured. Initial results show similar characteristics with a distributed feedback laser monolithically integrated next to the SRL.

Long-term graft-versus-Waldenstrom macroglobulinemia effect following reduced intensity conditioning allogeneic stem cell transplantation

Objective: To determine whether exposure to angiotensin-converting enzyme (ACE) inhibitors prior to the onset of scleroderma renal crisis (SRC) leads to worse outcomes of SRC. Methods: Prospective cohort study of incident SRC subjects. The exposure of interest was ACE inhibitors prior to the onset of SRC. The outcomes of interest were death or dialysis during the first year after the onset of SRC. Results: A total of 87 subjects with incident SRC were identified and 1-year follow-up data were obtained in 75 (86%) subjects. Overall, 27 (36%) subjects died within the first year and an additional 19 (25%) remained on dialysis 1 year after the onset of SRC. In adjusted analyses, exposure to ACE inhibitors prior to the onset of SRC was associated with an increased risk of death (hazard ratio 2.42, 95% CI 1.02, 5.75, p < 0.05 in the primary analysis and 2.17, 95% CI 0.88, 5.33, p = 0.09 after post-hoc adjustment for pre-existing hypertension). Conclusion: Overall, the 1-year outcomes of SRC were poor. Prior exposure to ACE inhibitors was associated with an increased risk of death after the onset of SRC, although there was uncertainty around the magnitude of the risk and the possibility of residual confounding could not be ruled out. Further studies will be needed to confirm these findings. © 2014 Elsevier Inc.

This paper surveys the relationships between the chemical structures and pharmacological activities of natural or semisynthetic 4,5a­ epoxymorphinans, synthetic morphinans and benzomorphans. Substitution . of the N-methyl group affords strong analgesics, opioid antagonists and mixed agonist-antagonists respectively. The role of opioid agonists and antagonists in the development of opioid receJ:>tor models is also discussed.

Refractory chronic GVHD (cGVHD) remains a major cause of morbidity after transplantation. Many drugs are used but there is no consensus on the standard of care. We investigated the efficacy of TLI in corticosteroid-refractory cGVHD. We analyzed retrospectively 31 patients receiving one or more TLI session for refractory cGVHD from 2000 to 2007. The main objective was to evaluate the response rate after TLI. Decreased corticosteroid doses and/or discontinued immunosuppressive agents were considered to be surrogate markers of response. All but one patient presented with severe cGVHD at the time of TLI. The median number of previous immunosuppressive treatment lines was 3 (range: 2–4). Fourteen patients (45%) achieved an objective response after TLI and 8 (25%) were cGVHD free at long-term follow-up. In all, 5 (29%) of the 17 nonresponsive patients did not show the features of progressive cGVHD and could decrease the amount of immunosuppressive drugs taken. Response after TLI significantly improved 5-year GVHD-related mortality (14% vs 42%, P=0.038) but not OS (58%vs 64% P=0.27). Regarding the promising response rate in this heavily pretreated population, we reasoned that TLI could be an alternative treatment for corticosteroid-refractory cGVHD.

We analyzed 113 patients with lymphoma who underwent allogeneic transplantation with reduced-intensity conditioning (allo-RIC) regimens at a single institution, from February 2001 through November 2009, searching for factors predictive of the outcome. At the time of transplantation, 60% of patients were in CR, 29% in PR and 11% had progressive or stable disease. At a median follow-up of 34 months (confidence interval (CI) 17-45), the 3-year OS and PFS were 59% (CI 48-68%) and 51% (CI 41-61%), respectively. The 100-day and 2-year nonrelapse mortalities (NRM) were 6% and 28% (CI 20-35%), respectively. Grade II-IV acute GVHD (aGVHD) incidence was 38%, and the global incidence of chronic GVHD was 33%. In univariate analysis, OS was influenced by disease status before allo-RIC; aGVHD negatively affected on survival. Similarly, PFS was influenced only by disease status. Histological subtype did not affect OS or PFS. We conclude that disease status at the time of transplantation significantly influences survival in patients receiving allo-RIC for lymphoma, whereas histological subtype does not. This reinforces the need to administer more effective debulking treatments to lymphoma patients, for optimal benefit of allogeneic immune recognition of minimal residual disease, independently from lymphoma histology.

We previously reported that reduced intensity conditioning (RIC) regimen with fludarabine, BU and 2.5 mg/kg of rabbit anti-thymocyte globulin (r-ATG) was effective but associated with a high rate of acute and chronic GVHD. Therefore, we increased the dose of r-ATG to 5 mg/kg. In this report, we analyzed 87 patients with AML or myelodysplastic syndrome (MDS) undergoing allo-SCT from an HLA-identical sibling donor from 2000 to 2010. RIC consisted of fludarabine, BU and r-ATG 2.5 mg/kg on 1 day (r-ATG1; n=53) or 2.5 mg/kg per day over 2 days (r-ATG2; n=22). Grade 2–4 acute GVHD incidence at day 100 was 30.2% and 8.8% in the r-ATG1 and r-ATG2 groups, respectively (P=0.038). Extensive chronic GVHD incidence was 60.4% and 12% in the r-ATG1 and r-ATG2 groups, respectively (P

3 pages, 7 figures.-- PACS: 42.55.Px, 42.60.By, We have experimentally and theoretically analyzed the modal properties of semiconductor ring lasers and the wavelength jumps that occur in connection with directional switching above the threshold., We acknowledge financial support from the IOLOS 034743 project funded by the European Union’s Sixth Framework Program (EU FP6-2005-IST-5), the PhoDeCC (TEC2006-10009/MIC) project funded by the Spanish Ministerio de Educación y Ciencia MIC , the QULMI (PROGECIB-5A) project funded by the Spanish Govern Balear, and the TEC2006-13887-C05-03 project funded by the Spanish Ministerio de Educación y Ciencia.

The frequency response and alpha factor of monolithic semiconductor ring lasers (SRLs) with 150 micron radius are measured using an all-optical modulation technique, yielding a -3 dB, frequency of 11 GHz and alpha factor of 2.4.

ISLC 2008. IEEE 21st International 14-18 Sept. 2008, We have experimentally and theoretically analyzed the modal properties of semiconductor ring lasers and the wavelength jumps that occur in connection with directional switching above threshold, This work was funded by the European project IOLOS IST- 2005-34743, Spanish project PhoDeCC TEC2006-10009/MIC and Balear Government project QULMI PROGECIB-5A. A.S. acknowledges Ram´on y Cajal program by Spanish MEC. S.B. and J.J. acknowledge financial support from project TEC2006- 13887-C05-03. J.J. acknowledges support from the Juan de La Cierva program by the Spanish MEC.

We report on the monolithical integration of a semiconductor ring laser and a Bragg reflector to achieve very fast wavelength tunability. Stable and digital wavelength switching with a speed below 1 ns is demonstrated.

A monolithic semiconductor ring laser (SRL) is demonstrated to operate as an all-optical flip-flop that is triggered by optical pulses of 400 ps and 5 ps duration, showing a response time of 130 ps.

We fabricated micro-sized semiconductor ring and disk lasers. Devices operate continuous wave down to a radius of 7 mum, with robust directional switching exhibited to a radius of 30 mum. Additionally, polarisation rotation is reported.

A semiconductor ring laser all-optical flip-flop is used to realize all-optical label swapping. Old address is erased by blocking the switching optically and new address is inserted by modulating the output from SRL.

The optical spectrum of monolithic Semiconductor Ring Lasers (SRLs) is measured simultaneously for both lasing directions with a grating-based OSA, in the regimes of bidirectional and unidirectional operation. In the unidirectional operation regime the SMSR is larger than 25 dB, and the directional extinction ratio (i.e., the ratio of the power emitted in the two opposite directions) is larger than 20 dB. The influence of the current injected in the active output waveguides that act as SOAs is outlined. In the unidirectional regime the linewidth of the SRL is measured by an heterodyne technique, revealing linewidth values around 2 MHz., This research was founded by he EU-FP6 ‘IOLOS’ project.

We have analyzed experimentally and theoretically the modal properties of a semiconductor ring laser and the wavelength jumps that occur in connection with directional switching above threshold. A transfer matrix analysis allow us to explain the transfer function measurements when amplified spontaneous emission in the cavity is accounted for. Moreover the transfer matrix analysis permits to determine the threshold condition for the laser modes, which split in two branches due to the symmetry breaking imposed by the output coupler and output waveguides. The wavelength jumps displayed by the device above threshold are interpreted with the frequency splitting and threshold difference between these two branches of solutions, together with the redshift of the material gain., We acknowledge financial support from project IOLOS, FP6-2005-IST-5. S. B. acknowledges financial support from project TEC2006-13887-C05-03. A.P. and A.S. acknowledge Balear Government project QULMI PROGECIB-5A. A.S. acknowledges Ram´on y Cajal program by Spanish MEC

Monolithic Semiconductor Ring Lasers (SRLs) are promising devices for all-optical memory and all-optical switching applications, as they can operate in a directional bistable regime where only one directional mode (clockwise or anti-clockwise) is active at one time. The unidirectional bistable regime can be naturally associated to a binary logic, and the SRL represents an elementary digital memory cell that can be written all-optically, realising the function of an all-optical flip-flop. In fact, the direction of operation can be switched by injecting an external optical signal pulse into the SRL through one of the 4 input/output ports. Directional switching of the SRL-based all-optical flip-flop has been demonstrated by injecting optical pulses with 5 ps duration into one of the four input/output ports. The required switching energy is around 100 fJ, and the swiching time is between 100 and 200 ps. The same function has been demonstrated by injecting 400 ps pulses as optical trigger.

A monolithic semiconductor ring laser (SRL) is demonstrated as a fully all-optical flip-flop that can be triggered by optical pulses of 400 ps duration, showing 130 ps response time.

(1990). Richard F. Sterba 1898–1989. The Psychoanalytic Quarterly: Vol. 59, No. 3, pp. 451-454.