Frequency-Dependent Squeezed Vacuum Source for the Advanced Virgo Gravitational-Wave Detector.

In this Letter, we present the design and performance of the frequency-dependent squeezed vacuum source that will be used for the broadband quantum noise reduction of the Advanced Virgo Plus gravitational-wave detector in the upcoming observation run. The frequency-dependent squeezed field is generated by a phase rotation of a frequency-independent squeezed state through a 285 m long, high-finesse, near-detuned optical resonator. With about 8.5 dB of generated squeezing, up to 5.6 dB of quantum noise suppression has been measured at high frequency while close to the filter cavity resonance frequency, the intracavity losses limit this value to about 2 dB. Frequency-dependent squeezing is produced with a rotation frequency stability of about 6 Hz rms, which is maintained over the long term. The achieved results fulfill the frequency dependent squeezed vacuum source requirements for Advanced Virgo Plus. With the current squeezing source, considering also the estimated squeezing degradation induced by the interferometer, we expect a reduction of the quantum shot noise and radiation pressure noise of up to 4.5 dB and 2 dB, respectively.

Quantum Backaction on kg-Scale Mirrors: Observation of Radiation Pressure Noise in the Advanced Virgo Detector.

The quantum radiation pressure and the quantum shot noise in laser-interferometric gravitational wave detectors constitute a macroscopic manifestation of the Heisenberg inequality. If quantum shot noise can be easily observed, the observation of quantum radiation pressure noise has been elusive, so far, due to the technical noise competing with quantum effects. Here, we discuss the evidence of quantum radiation pressure noise in the Advanced Virgo gravitational wave detector. In our experiment, we inject squeezed vacuum states of light into the interferometer in order to manipulate the quantum backaction on the 42 kg mirrors and observe the corresponding quantum noise driven displacement at frequencies between 30 and 70 Hz. The experimental data, obtained in various interferometer configurations, is tested against the Advanced Virgo detector quantum noise model which confirmed the measured magnitude of quantum radiation pressure noise.

Increasing the Astrophysical Reach of the Advanced Virgo Detector via the Application of Squeezed Vacuum States of Light.

Current interferometric gravitational-wave detectors are limited by quantum noise over a wide range of their measurement bandwidth. One method to overcome the quantum limit is the injection of squeezed vacuum states of light into the interferometer's dark port. Here, we report on the successful application of this quantum technology to improve the shot noise limited sensitivity of the Advanced Virgo gravitational-wave detector. A sensitivity enhancement of up to 3.2±0.1 dB beyond the shot noise limit is achieved. This nonclassical improvement corresponds to a 5%-8% increase of the binary neutron star horizon. The squeezing injection was fully automated and over the first 5 months of the third joint LIGO-Virgo observation run O3 squeezing was applied for more than 99% of the science time. During this period several gravitational-wave candidates have been recorded.

Extracorporeal photochemotherapy for treatment of acute and chronic GVHD in childhood.

BACKGROUND: Extracorporeal photochemotherapy (EPC) has recently been proposed for the treatment of adults with either acute or chronic GVHD. However, data on children given this therapy are scarce. A Phase I-II study was carried out on EPC in children experiencing GVHD after allogeneic transplantation of HPCs. STUDY DESIGN AND METHODS: Nine patients with steroid-resistant, grade II-IV acute GVHD and 14 with chronic GVHD, all of whom had been refractory to at least one line of treatment, were enrolled in this study and analyzed. The median age was 10.3 years (range, 5.4-18.1), and the median body weight was 35 kg (range, 17-89). RESULTS: Seven of the nine patients with acute GVHD showed a response to EPC, whereas the disease progressed in the remaining two children (both with skin, gastrointestinal, and liver GVHD), and they died of grade IV acute GVHD. Among the seven children who responded to EPC, it was possible to completely discontinue immunosuppressive treatment in three. In the 14 children with chronic GVHD, 4 and 5 patients experienced complete and partial response to EPC, respectively, whereas the remaining 5 patients, all with extensive chronic GVHD, had stable disease or disease that progressed during EPC. Among these latter 5 patients, 3 died. In 6 of the 9 patients with chronic GVHD responding to EPC, immunosuppressive therapy was discontinued. CONCLUSION: EPC is safe, feasible, and effective in children with either acute or chronic GVHD occurring after an allograft.

Feasibility and safety of a new technique of extracorporeal photochemotherapy: experience of 240 procedures.

BACKGROUND AND OBJECTIVE: Extracorporeal photochemotherapy (ECP) is a therapeutic approach based on the biological effects of ultraviolet light (UV) - A and psoralens on mononuclear cells collected by apheresis. Recently, ECP has been under investigation as an alternative treatment for various immune and autoimmune diseases. The aim of this study was to evaluate the safety and feasibility of a new three-step ECP technique, in terms of reproducibility, acceptance, tolerability, and short and long term side effects. DESIGN AND METHODS: Seventeen patients affected by acute or chronic graft-versus-host disease (GvHD), pemphigus vulgaris, or interferon-resistant chronic hepatitis C and one patient being treated for prevention of heart transplant rejection underwent 240 ECP procedures. MNC collection and processing parameters were recorded, biological effects of UV-A/8 methoxy-psoralen (8-MOP) were evaluated, and short and long term side effects were monitored. RESULTS: At a mean follow up of 7 months (range 2-19) 240 ECP had been completed, a mean of 7,136 mL (range 1,998-10,591) of whole blood having beenprocessed per procedure. The mean of total nucleated cells collected per procedure was 6.5x109 (range 0.65-23.8), with a mean MNC percentage of 85% (41. 4-98%) in a mean final volume of 115.5 mL (37-160). No severe side effects were documented and no infectious episodes occurred throughout the course of the treatment. INTERPRETATION AND CONCLUSIONS: The new ECP technique was highly reproducible as regards the collection and each processing step. Short and long term side effects were mild. No increase in infectious episodes was recorded. All patients willingly underwent ECP, demonstrating an excellent tolerability for the procedure even after several courses.

Acute promyelocytic leukemia toluidine blue subtype.

In the hypergranular group of acute promyelocytic leukemia (APL) a rare subvariant with basophilic granules, metachromatic for toluidine blue, is recognizable. To evaluate the incidence as well as the biological and clinical significance of this subtype, we studied 53 consecutive untreated patients with APL with morphological, cytochemical, immunological and cytogenetic methods. In 10 cases (19% of the total) granules stained metachromatically in percentages of promyelocytes ranging from 16 to 60. In these cases peroxidase positivity was weaker than in the classic hypergranular and microgranular M3 and activities of esterases were usually present; at the ultrastructural level granules contained particulate material. Immunophenotypic and cytogenetic characteristics seemed not to differ from those of other M3 cases. Coagulopathy was usually life-threatening, notwithstanding the low white cell count, and the median survival was short. Hyperhistaminemia-related symptoms were not observed. Cytochemical, immunologic and cytogenetic findings are useful to differentiate this form from M2 with basophilic differentiation and from mast cell leukemia.

Acute promyelocytic leukemia: morphological and clinical features.

BACKGROUND AND METHODS: Acute promyelocytic leukemia (APL) is not a morphologically homogeneous entity: to verify whether there is any relationship between this heterogeneity and other biological and clinical aspects, we studied 43 cases of APL with morphological, cytochemical, cytogenetic and immunological methods. RESULTS: Three morphological categories were present: a classic hypergranular type (30 cases), a microgranular type (6 cases) and a form with basophilic granules (M3b) that stained metachromatically with toluidine blue (7 cases). In all these groups there were cases with cytochemical features of both myeloid and monocytic type (alpha-naphthyl-acetate esterase positive). No immunological and cytogenetic differences were observed; the morphological variant with basophilic granules was more frequent in females; age distribution was not related to the morphological subtype; organomegaly was extremely rare in M3b. A low white blood cell count was constant in M3b, whereas no differences were observed in hemoglobin and platelet values. Severity of bleeding was worst in the group with toluidine blue metachromasia; this and the microgranular type had poor prognosis. CONCLUSIONS: Our study confirms the importance of identifying different cytologic categories in APL. In particular we focused our attention on a new variant with basophilic granules.

Transient aplasia preceding adult acute lymphoblastic leukemia.

A 62-year-old woman developed common acute lymphoblastic leukemia (ALL) after spontaneous recovery from transient marrow aplasia. Although the mechanisms underlying bone marrow suppression in acute leukemia are obscure, it is important to know that transient aplasia may be observed as a prodromal feature in ALL in adult patients as well as in children.

Accidents in the school environment in Milan, a five year survey.

Data regarding 11,541 cases of school accidents (from kindergarten to senior high school) that required hospital attention for treatment were examined. The information was obtained from the records of the "School Medicine Service of the City of Milan", and covered five school years (from 1980-81 to 1984-85). The surveyed population included over 160,000 subjects for each year. After computer processing, data regarding type of school, year, age of the victim, place of the accident and type of lesions were obtained. The frequency of accidents was highest (about 2%) among kindergarten pupils, while in senior high school the lowest frequency (less than 1%) was accompanied by the greatest percentage of hospitalizations (about 6%). From our results it appears that most accidents occur in school gyms (around 50%), and that the percentage of sprains and fractures is also highest in this area. School gyms can therefore be considered as a primary target for any prevention activity.

Epidemic of breast enlargement in an Italian school.

An outbreak of breast enlargement in girls and boys attending a school in Milan, first noted in November, 1977, was followed up until the end of 1978. 213 boys aged 3-14 years and 110 girls aged 3-7 years were studied; control children attending five other schools were also examined. In total 1647 boys and 476 girls were examined. Breast enlargement was significantly more common in boys (29.0%) and girls (21.6%) aged 3-5 years, boys (58.0%) aged 6-10, and girls (67.1%) aged 6-7 from the school in Milan, than in age and sex matched children at control schools. Breast enlargement was not pronounced and disappeared within 8 months. Hormonal determinations were within normal limits except for 17 beta-oestradiol which was slightly raised. Although oestrogen contamination was not detected when samples of school meals were tested, an uncontrolled supply of poultry and beef was suspected as being the cause of this outbreak.