Nonlinear pulse propagation in a quantum dot laser.

We investigate the nonlinear propagation of an ultra-short, 150 fs, optical pulse along the waveguide of a quantum dot (QD) laser operating above threshold. We demonstrate that among the various nonlinear processes experienced by the propagating pulse, four-wave mixing (FWM) between the pulse and the two oscillating counter-propagating cw fields of the laser is the dominant one. FWM has two important consequences. One is the creation of a spectral hole located in the vicinity of the cw oscillating frequency. The width of the spectral hole is determined by an effective carrier and gain relaxation time. The second is a modification of the shape of the trailing edge of the pulse. The wave mixing involves first and second order processes which result in a complicated interaction among several fields inside the cavity, some of which are cw while the others are time varying, all propagating in both directions. The nonlinear pulse propagation is analyzed using two complementary theoretical approaches. One is a semi-analytical model which considers only the wave mixing interaction between six field components, three of which propagate in each direction (two cw fields and four time-varying signals). This model predicts the deformation of the tail of the output signal by a secondary idler wave, produced in a cascaded FWM process, which co-propagates with the original injected pulse. The second approach is a finite-difference time-domain simulation, which considers also additional nonlinear effects, such as gain saturation and self-phase modulation. The theoretical results are confirmed by a series of experiments in which the time dependent amplitude and phase of the pulse after propagation are measured using the cross-frequency-resolved optical gating technique.

The novel anti-inflammatory agent VA694, endowed with both NO-releasing and COX2-selective inhibiting properties, exhibits NO-mediated positive effects on blood pressure, coronary flow and endothelium in an experimental model of hypertension and endothelial dysfunction.

Selective cyclooxygenase 2 (COX2) inhibitors (COXIBs) are effective anti-inflammatory and analgesic drugs with improved gastrointestinal (GI) safety compared to nonselective nonsteroidal anti-inflammatory drugs known as traditional (tNSAIDs). However, their use is associated with a cardiovascular (CV) hazard (i.e. increased incidence of thrombotic events and hypertension) due to the inhibition of COX2-dependent vascular prostacyclin. Aiming to design COX2-selective inhibitors with improved CV safety, new NO-releasing COXIBs (NO-COXIBs) have been developed. In these hybrid drugs, the NO-mediated CV effects are expected to compensate for the COXIB-mediated inhibition of prostacyclin. This study evaluates the potential CV beneficial effects of VA694, a promising NO-COXIB, the anti-inflammatory effects of which have been previously characterized in several in vitro and in vivo experimental models. When incubated in hepatic homogenate, VA694 acted as a slow NO-donor. Moreover, it caused NO-mediated relaxant effects in the vascular smooth muscle. The chronic oral administration of VA694 to young spontaneously hypertensive rats (SHRs) significantly slowed down the age-related development of hypertension and was associated with increased plasma levels of nitrates, stable end-metabolites of NO. Furthermore, a significant improvement of coronary flow and a significant reduction of endothelial dysfunction were observed in SHRs submitted to chronic administration of VA694. In conclusion, VA694 is a promising COX2-inhibiting hybrid drug, showing NO releasing properties which may mitigate the CV deleterious effects associated with the COX2-inhibition.

Active targeting of cancer cells by CD44 binding peptide-functionalized oil core-based nanocapsules.

Selectivity in tumor targeting is one of the major issues in cancer treatment. Therefore, surface functionalization of drug delivery systems with active moieties, able to selectively target tumors, has become a worldwide-recognized strategy. The CD44 receptor is largely used as a biomarker, being overexpressed in several tumors, and consequently as a target thanks to the identification of the CD44 binding peptide. Here we implemented the CD44 binding peptide logic onto an oil core-polymer multilayer shell, taking into account and optimizing all relevant features of drug delivery systems, such as small size (down to 100 nm), narrow size distribution, drug loading capability, antifouling and biodegradability. Besides promoting active targeting, the oil core-based system enables the delivery of natural and synthetic therapeutic compounds. Biological tests, using curcumin as a bioactive compound and fluorescent tag, demonstrated that CD44 binding peptide-functionalized nanocapsules selectively accumulate and internalize in cancer cells, compared to the control, thanks to ligand-receptor binding.

Eliminating congenital rubella: a seroepidemiological study on women of childbearing age and MMR vaccine coverage in newborns.

INTRODUCTION: Rubella can have particularly serious effects on the product of conception if contracted during pregnancy. Thus, the main aim of rubella vaccination programmes is to prevent infection during pregnancy. MATERIALS AND METHODS: A seroepidemiological study was conducted from July 2006 to December 2007 on 1000 women of childbearing age, 15 to 45 years old, using specific rubivirus antibody assays, IgG and IgM. A questionnaire administered at the same time allowed us to survey how much women knew about this disease. In addition, MMR vaccine coverage rates were analysed for cohorts born in the local health districts of Messina for the period 1993-2006. RESULTS: An analysis of the replies given to the questionnaire showed an estimated 42.8% of the women to have immunity from rubella, while the serological study showed an immunity coverage rate of80.6%. Vaccination coverage in the local health districts regarding the first dose of MMR was 81% (cohorts 1993-2005), while the rate was only 24% for the second dose (cohorts 1993-2002). CONCLUSIONS: Both immunity coverage in women of childbearing age and that for newborns (for the cohort considered)fall below the 95% target set by the National Elimination Plan for Measles and Congenital Rubella (PNEM). It is therefore necessary to provide women with adequate information about the risks of rubella during pregnancy and about the benefits of vaccination, as well as to recoup subjects at risk or those whose immune status is unknown. Public health authorities also need to make continued efforts to increase the number of MMR vaccinations throughout the region.

Direct observation of the coherent spectral hole in the noise spectrum of a saturated InAs/InP quantum dash amplifier operating near 1550 nm.

We demonstrate a direct observation of the coherent noise spectral hole in a saturated quantum dash amplifier. Its width 500-600 GHz is determined by the response time and is responsible for high speed regeneration properties.

Cross talk free multi channel processing of 10 Gbit/s data via four wave mixing in a 1550 nm InAs/InP quantum dash amplifier.

We demonstrate multi wavelength processing in a broad band 1550 nm quantum dash optical amplifier. Two 10 Gbit/s signals, spectrally separated by 30 nm are individually wavelength converted via four wave mixing (FWM) with no cross talk. High power signal levels cause depletion of high energy and wetting layer states resulting in some homogenizing of the gain medium and generation of cross FWM components near each channel due to FWM in the other channel. These do not affect the cross-talkless multichannel processing except when the two channels use equal detuning between signal and pump.

Treatment of de novo femoro-popliteal lesions with a new Drug Coated Balloon: early experience of a single Center in the first 50 patients.

Angioplasty with drug-coated balloon (DCB) is an emerging and reliable method for the treatment of femoro-popliteal lesions. We report our experience with the Stellarex™ DCB in the first 50 patients. METHODS: From July 2015 to November 2017, 50 patients (41 M, 9F), medium age (64 ± 7.4 year) were subject to 33 angioplasties (PTAs) for femoro-popliteal lesions with a paclitaxel-coated balloon (Stellarex™). Based upon clinical data sixteen patients had severe claudication (56% - Rutherford class 3); ten patients suffered from ischemic rest pain (34% - Rutherford class 4); and five presented minor tissue loss (10% - Rutherford class 5). 42% of patients showed femoro-popliteal lesion TASC-II B, and 58% presented lesions pertaining to TASC-II C. RESULTS: Immediate technical success was 100% without perioperative complications. Primary patency rate was 94% at twelve months. In three cases restenosis (6%) was detected within a year from procedure, and a further PTA DCB was performed with primary assisted patency rates of 100% at twelve months. Two patients underwent major lower limb amputation. Three patients died during follow-up and one patient was lost at follow-up. CONCLUSION: DCB angioplasty with Stellarex™ is a viable alternative to traditional endovascular procedures proving satisfactory primary patency rates at twelve months. Based on our experience, treatment with DCB is a first choice technique for non-complex de novo lesions of the femoro - popliteal tract.

Direct correlation between a highly damped modulation response and ultra low relative intensity noise in an InAs/GaAs quantum dot laser.

We describe modulation responses and relative intensity noise (RIN) spectra of an InAs/GaAs quantum dot laser operating near 1300 nm. A very large nonlinear gain compression coefficient yields a highly damped modulation response with a maximum 3 dB bandwidth of ~6.5 GHz and flat RIN spectra which reach as low a level as -158/-160 dB/Hz at frequencies up to 10 GHz.

Neuroendoscopic management of hydrocephalus secondary to midline and pineal lesions.

AIM: In patients with space-occupying lesions of the pineal region, increased intracranial pressure is due to direct compression of the sylvian aqueduct. Based on results of the recent literature, neuroendoscopic management of obstructive hydrocephalus, secondary to tumors of the pineal gland, has gained a preeminent role respect to shunting procedures. METHODS: In 14 select cases, hydrocephalus was secondary to midline and pineal lesions. The patient's age ranged from 1 to 56 years (mean 47.3+/-12.5), with a follow-up ranged from 3 months to 5 years after discharge. In 9 cases the endoscopic procedure represented the only surgical treatment. In 5 cases, microsurgical removal of the lesions and/or ventriculo-peritoneal shunts placement were performed, as additional treatment, while adjuvant radiotherapy was utilized in 4 cases; high dose chemotherapy followed by bone marrow transplantation was performed in 3 cases. RESULTS: In our series, obstructive hydrocephalus secondary to midline and pineal lesions, was successful treated by neuroendoscopic approach alone in 9 cases, with an unremarkable course and good outcome, except in 1 case. CONCLUSIONS: Neuroendoscopic approach affords a minimally invasive way to obtain 4 objectives by one-step surgical approach, such as resolution of obstructive hydrocephalus by endoscopic third ventriculostomy (ETV), cerebrospinal fluid sample to detect tumor markers and to perform cytological analysis, biopsy specimens and tissue diagnosis, associated to absence of shunt-related complications. Therefore, in experienced hands, ETV should be the treatment of first choice, in cases of hydrocephalus secondary to lesions of the pineal gland.

Pharmacological purging of syngeneic bone marrow ex vivo: effect of treatment with doxorubicin and lonidamine on normal and leukaemic cells of DBA/2 mice.

The in vivo effect of in vitro treatment with doxorubicin plus lonidamine on normal and leukaemic cells was investigated in a mouse model of syngeneic bone marrow transplantation. Different numbers of L5178Y tumour cells or normal bone marrow cells alone, or mixtures of bone marrow and leukaemic cells were incubated with doxorubicin (0.25, 0.5, 0.75, 1 microgram/ml) and/or lonidamine (50 micrograms/ml) and reinfused in DBA/2 mice. Lonidamine potentiated the cytotoxic effect of doxorubicin dependent on doxorubicin dosage and tumour cell concentration. Survival after injection of 10(4) in vitro-treated tumour cells was 42% for doxorubicin 0.75 micrograms/ml alone versus 100% for the combination with lonidamine and 50% for doxorubicin 1 microgram/ml alone versus 100% combination. Reinfusion of normal bone marrow incubated with doxorubicin alone or in combination with lonidamine in lethally irradiated mice did not occur in 12-14% of mice injected, indicating that the repopulating ability of stem cells was spared. These data suggest the potential usefulness of lonidamine in ex vivo purging of bone marrow before autologous bone marrow transplants in haemopoietic malignancies.

Fractionated total body irradiation in allogeneic bone marrow transplantation in leukemia patients: analysis of prognostic factors and results in 136 patients.

BACKGROUND AND PURPOSE: The results of a single-institution series of patients with chronic and acute leukemias are analyzed with regard to literature-reported predictor variables. MATERIALS AND METHODS: Between 1985 and 1994, 136 patients, 82 patients with chronic myeloid leukemia (CML) and 54 with acute leukemia (AL), received a uniform preparatory regimen of fractionated total body irradiation (TBI; 12 Gy in 3 days) plus different chemotherapy regimens before bone marrow transplantation. Eighty-six patients were considered to be in early phase of disease (CML in chronic phase or AL in first complete remission) and 50 in advanced phase (all those beyond first remission or first chronic phase). Ninety-five patients received unmanipulated allogeneic BM, and 41 T-lymphocyte-depleted BM. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) of the whole series were 43% and 31%, and median survival was 43 and 10 months, respectively. A Cox proportional hazard model identified variables related to overall and disease-free survival. For OS, graft versus host disease (GVHD) was the first independent variable (P < 0.0001), followed by age (P < 0.001), T-depletion (P < 0.01), disease status (P < 0.05) and type of leukemia (P < 0.05). With regard to DFS, only T-depletion (P < 0.0001), disease status (P < 0.01) and GVHD (P < 0.01) resulted predictor factors. Early complications after BMT were reported in 59 patients, TBI-induced delayed toxicity in 9 patients, and 16 patients suffered late complications. CONCLUSIONS: Our results confirm the curability of early phase leukemias with standard fractionated TBI-induced Allogeneic bone marrow transplantation (ABMT). With an homogeneous fractionated TBI schedule as employed in our series, T-cell depletion negatively affected the outcome.

Role of ultrasonography in the diagnosis and follow-up of hemorrhagic cystitis after bone marrow transplantation.

The role of ultrasonographic examination of the bladder has been retrospectively evaluated in 12 patients with hemorrhagic cystitis occurring after BMT. Three sonographic patterns of bladder abnormalities have been observed: type 1, circumscribed thickening of the wall protruding into the lumen (4 patients); type 2, diffuse thickening of the wall (3 patients); type 3, intraluminal lobulated bulky mass reducing the capacity (5 patients). Sonographic follow-up showed a progressive trend of bladder abnormalities: type 3 lesions were always preceded by type 1 or type 2 abnormalities. In 10 of 12 patients the cystoscopic findings proved the correlation between the sonographic aspects and the progressive stages of bladder wall damage. Patients were treated initially by hyperhydration and blood products transfusions in order to stop hematuria. The median duration of bleeding was significantly longer (p < 0.01) in patients showing type 3 lesions (90 days) than in the combined groups with types 1 or 2 lesions (14 days). All 5 patients with type 3 abnormalities failed treatment and required endoscopic removal of clots; hemorrhagic cystitis was the major cause of death in 3 patients in this group. Ultrasonography may therefore be considered an accurate investigation for assessing the extent of bladder damage and monitoring the effectiveness of treatment for this complication.

Multicentre experience with combined hyperthermia and radiation therapy in the treatment of superficially located non-Hodgkin's lymphomas.

The combination of Radiation Therapy (RT) and Hyperthermia (HT) has proved to be an effective treatment for a wide variety of superficially located recurrences of different tumors, particularly those arising in previously irradiated areas. Few studies on the use of HT in the management of lymphomatous diseases have so far obtained interesting results. Eight patients with Non Hodgkin Lymphomas (LNH) - 4 with cutaneous lymphomas and 4 with nodal recurrences after RT-Chemotherapy (CHT) treatment treated in three different Italian institutions with combined RT and HT are here reported. Rt dose ranged from 15 to 40 Gy with different fractionations, on the basis of previously received treatment. Hyperthermia was delivered using 432 or 915 MHz external microwave applicators, according to extension and depth of the lesions and available equipment. All patients tolerated well the HT treatment, and in all cases average intratumoral temperatures were >42 degrees, with 3 out of 10 treated sites achieving the goal of average temperatures >42.5%. One patient, with recurrent NHL, is disease-free after 24 months from completion of combined therapy. Our results seem to confirm previous experiences, suggesting a role of HT/RT not only for palliative purposes in cutaneous lymphomas, but also as an adjunct to radiotherapy alone in selected patients with superficially located recurrences.

Glycosylations of inosine and uridine nucleoside bases and synthesis of the new 1-(beta-D-glucopyranosyl)-inosine-5',6"-diphosphate.

Gluco- and ribosylation of the bases of sugar protected inosine and uridine were investigated, obtaining only adducts with beta-configuration at the new glycosidic carbon; stereospecific insertion of a sugar moiety at the 1-N of inosine was achieved either using a Mitsunobu approach (for ribosylation) or by direct coupling of 1-alpha-bromoglucose 13 with 2',3',5'-tri-O-acetylinosine for glucosylation. 1-(beta-D-glucosyl)-inosine, chosen as starting substrate for glucosylated analogs of cyclic IDP-ribose, was phosphorylated at the primary hydroxyls and tested in intramolecular pyrophosphate bond formation.

[Post-traumatic subperiosteal chondroma of the hand. Clinical case]. / Condroma sottoperiosteo post-traumatico della mano. Caso clinico.

The authors report a case of rapidly developing periosteal chondroma of the fifth metacarpal. No erosion of the bone cortex could be observed radiographically. The development of the tumor appears to follow a violent trauma without skeletal lesions occurred seven months before.

[Intraoperative electron radiotherapy (IOERT) in the QUART sequence: a phase I study]. / Radioterapia intraoperatoria con elettroni (IOERT) nella sequenza QUART: studio di fase I.

We evaluated the tolerance of a single dose of 800-1500 cGy, delivered with an electron beam from an IOERT-dedicated linear accelerator to the tumour bed in patients with breast cancer undergoing conservative treatment, instead of the traditional boost. We enrolled 27 patients (cT1-2, cN0). The first 6 received a dose of 800 cGy, 6 1000 cGy, 10 1200 cGy and 5 1500 cGy. External beam radiation therapy (EBRT) with a conventional schedule, 4000 cGy total dose, was performed after wound healing. The median gap between IOERT and EBRT was 8 weeks. Three patients with adverse prognostic factors undergoing chemotherapy, including doxorubicin or taxanes, received EBRT after completion of chemotherapy. One patient with a prosthesis implant had yielding of the surgical scar 8 months after IOERT (after 4 cycles of doxorubicin and 4 cycles of CMF complicated by frequent mastitis). Another patient with a large serum collection in the axilla manifested delayed scar formation. In the others no significant increase in healing time or surgery-related morbidity was observed. Another 4 patients developed mastitis. The cosmetic outcome was good in 26/27 patients. This treatment is well tolerated at all IOERT doses delivered. In the follow-up, to date, there have been no local relapses.

Coherent control in a semiconductor optical amplifier operating at room temperature.

Quantum decoherence times in semiconductors are extremely short, particularly at room temperature where the quantum phase is completely erased in a fraction of a picosecond. However, they are still of finite duration during which the quantum phase is well defined and can be tailored. Recently, we demonstrated that quantum coherent phenomena can be easily accessed by examining the phase and amplitude of an optical pulse following propagation along a room temperature semiconductor optical amplifier. Taking the form of Rabi oscillations, these recent observations enabled to decipher the time evolution of the ensemble states. Here we demonstrate the Ramsey analogous experiment known as coherent control. Remarkably, coherent control occurs even under room temperature conditions and enables to directly resolve the dephasing times. These results may open a new way for the realization of room temperature semiconductor-based ultra-high speed quantum processors with all the advantages of upscaling and low-cost manufacturing.

Covalently immobilized RGD gradient on PEG hydrogel scaffold influences cell migration parameters.

Understanding the influence of a controlled spatial distribution of biological cues on cell activities can be useful to design "cell instructive" materials, able to control and guide the formation of engineered tissues in vivo and in vitro. To this purpose, biochemical and mechanical properties of the resulting biomaterial must be carefully designed and controlled. In this work, the effect of covalently immobilized RGD peptide gradients on poly(ethylene glycol) diacrylate hydrogels on cell behaviour was studied. We set up a mechanical device generating gradients based on a fluidic chamber. Cell response to RGD gradients with different slope (0.7, 1 and 2 mM cm(-1)) was qualitatively and quantitatively assessed by evaluating cell adhesion and, in particular, cell migration, compared to cells seeded on hydrogels with uniform distribution of RGD peptides. To evaluate the influence of RGD gradient and to exclude any concentration effect on cell response, all analyses were carried out in a specific region of the gradients which displayed the same average concentration of RGD (1.5 mM). Results suggest that cells recognize the RGD gradient and adhere onto it assuming a stretched shape. Moreover, cells tend to migrate in the direction of the gradient, as their speed is higher than that of cells migrating on hydrogels with a uniform distribution of RGD and increases by increasing RGD gradient steepness. This increment is due to an augmentation of bias speed component of the mean squared speed, that is, the drift of the cell population migrating on the anisotropic surface provided by the RGD gradient.