Multiphoton Atom Interferometry via Cavity-Enhanced Bragg Diffraction.

We present a novel atom interferometer configuration that combines large momentum transfer with the enhancement of an optical resonator for the purpose of measuring gravitational strain in the horizontal directions. Using Bragg diffraction and taking advantage of the optical gain provided by the resonator, we achieve momentum transfer up to 8ℏk with mW level optical power in a cm-sized resonating waist. Importantly, our experiment uses an original resonator design that allows for a large resonating beam waist and eliminates the need to trap atoms in cavity modes. We demonstrate inertial sensitivity in the horizontal direction by measuring the change in tilt of our resonator. This result paves the way for future hybrid atom or optical gravitational wave detectors. Furthermore, the versatility of our method extends to a wide range of measurement geometries and atomic sources, opening up new avenues for the realization of highly sensitive inertial atom sensors.

A control hardware based on a field programmable gate array for experiments in atomic physics.

Experiments in Atomic, Molecular, and Optical (AMO) physics require precise and accurate control of digital, analog, and radio frequency (RF) signals. We present control hardware based on a field programmable gate array core that drives various modules via a simple interface bus. The system supports an operating frequency of 10 MHz and a memory depth of 8 M (223) instructions, both easily scalable. Successive experimental sequences can be stacked with no dead time and synchronized with external events at any instructions. Two or more units can be cascaded and synchronized to a common clock, a feature useful to operate large experimental setups in a modular way.

A fibered laser system for the MIGA large scale atom interferometer.

We describe the realization and characterization of a compact, autonomous fiber laser system that produces the optical frequencies required for laser cooling, trapping, manipulation, and detection of 87Rb atoms - a typical atomic species for emerging quantum technologies. This device, a customized laser system from the Muquans company, is designed for use in the challenging operating environment of the Laboratoire Souterrain à Bas Bruit (LSBB) in France, where a new large scale atom interferometer is being constructed underground - the MIGA antenna. The mobile bench comprises four frequency-agile C-band Telecom diode lasers that are frequency doubled to 780 nm after passing through high-power fiber amplifiers. The first laser is frequency stabilized on a saturated absorption signal via lock-in amplification, which serves as an optical frequency reference for the other three lasers via optical phase-locked loops. Power and polarization stability are maintained through a series of custom, flexible micro-optic splitter/combiners that contain polarization optics, acousto-optic modulators, and shutters. Here, we show how the laser system is designed, showcasing qualities such as reliability, stability, remote control, and flexibility, while maintaining the qualities of laboratory equipment. We characterize the laser system by measuring the power, polarization, and frequency stability. We conclude with a demonstration using a cold atom source from the MIGA project and show that this laser system fulfills all requirements for the realization of the antenna.

Exploring gravity with the MIGA large scale atom interferometer.

We present the MIGA experiment, an underground long baseline atom interferometer to study gravity at large scale. The hybrid atom-laser antenna will use several atom interferometers simultaneously interrogated by the resonant mode of an optical cavity. The instrument will be a demonstrator for gravitational wave detection in a frequency band (100 mHz-1 Hz) not explored by classical ground and space-based observatories, and interesting for potential astrophysical sources. In the initial instrument configuration, standard atom interferometry techniques will be adopted, which will bring to a peak strain sensitivity of [Formula: see text] at 2 Hz. This demonstrator will enable to study the techniques to push further the sensitivity for the future development of gravitational wave detectors based on large scale atom interferometers. The experiment will be realized at the underground facility of the Laboratoire Souterrain à Bas Bruit (LSBB) in Rustrel-France, an exceptional site located away from major anthropogenic disturbances and showing very low background noise. In the following, we present the measurement principle of an in-cavity atom interferometer, derive the method for Gravitational Wave signal extraction from the antenna and determine the expected strain sensitivity. We then detail the functioning of the different systems of the antenna and describe the properties of the installation site.

Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia.

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.

Serum autoimmune gastritis markers, pepsinogen I and parietal cell antibodies, in patients with type 1 diabetes mellitus: a 5-year prospective study.

BACKGROUND AND AIM: To determine the temporal evolution of serum markers of autoimmune gastritis, mainly pepsinogen I (PI) and parietal cell antibodies (PCA), in patients with Type 1 diabetes mellitus (DM1). MATERIALS AND METHODS: A 5-yr prospective follow-up study of 168 DM1 patients (87 men, aged 31 ± 9.3 yr) attending the endocrinology outpatient clinic of a university hospital evaluated in 2001 and 2006. Serum PI, gastrin, hemoglobin, cobalamin concentrations, PCA and antibodies to intrinsic factor were measured. RESULTS: In 2001, 11 patients had low PI concentrations and positive PCA (group I), 11 had only low PI concentrations (group II), and 33 had only positive PCA (group III). After 5 yr, PI remained low and PCA positive in all patients from group I. In group II, PI remained low in 4 and normalized in 7. In group III, 4 patients presented low PI concentrations after 5 yr, which remained normal in the other 29 subjects. PCA became negative in 17 patients from group III. In 2001, 3 of the 11 patients of group I had low cobalamin concentrations. In 2006, 2 additional patients from this group presented low cobalamin concentrations. CONCLUSIONS: These results show the importance of determining PI together with PCA, since the presence of abnormal results in both tests, that is low PI and positive PCA, is the association that best identifies patients with a higher risk to decrease cobalamin concentrations during follow-up.

Immunophenotype of acute myeloid leukemia with NPM mutations: prognostic impact of the leukemic compartment size.

NPM mutations are the most common genetic abnormalities found in non-promyelocytic AML. NPM-positive patients usually show a normal karyotype, a peculiar morphologic appearance with frequent monocytic traits and good prognosis in the absence of an associated FLT3 mutation. This report describes the immunophenotypic and genetic characteristics of a consecutive series of NPM-mutated de novo AML patients enroled in the CETLAM trial. Eighty-three patients were included in the study. Complete immunophenotype was obtained using multiparametric flow cytometry. Associated genetic lesions (FLT3, MLL, CEBPA and WT1 mutations) were studied by standardized methods. Real-time PCR was employed to assess the minimal residual status. The most common pattern was CD34-CD15+ and HLA-DR+. Small CD34 populations with immunophenotypic aberrations (CD15 and CD19 coexpression, abnormal SSC) were detected even in CD34 negative samples. Nearly all cases expressed CD33 (strong positivity), CD13 and CD117, and all were CD123+. The stem cell marker CD110 was also positive in most cases. Biologic parameters such as a high percentage of intermediate CD45+ (blast gate) (>75% nucleated cells), CD123+ and FLT3-ITD mutations were associated with a poor outcome. Quantitative PCR positivity had no prognostic impact either after induction or at the end of chemotherapy. Only PCR positivity (greater than 10 copies) detected in patients in haematological remission was associated with an increased relapse rate. Further studies are required to determine whether the degree of leukemic stem cell expansion (CD45+CD123+cells) increases the risk of acquisition of FLT3-ITD and/or provides selective advantages.

Surgical excision of retrorectal tumour using transanal endoscopic microsurgery.

Abstract Surgical excision is the best therapeutic option for tumours in the retrorectal space. Classically, surgery in this area required an abdominal or posterior approach, or a combination of the two methods. We report the use of transanal endoscopic microsurgery for the treatment of retrorectal tumours as an alternative to classical procedures.

The prevalence of parastomal hernia after formation of an end colostomy. A new clinico-radiological classification.

INTRODUCTION: Parastomal hernia (PH) is a common complication of end colostomy, found in over 50% of patients. Abdominal computerized tomography (CT) may help diagnosis. The prevalence of PH may be higher than previously reported. We present a new CT classification for use in clinical practice. METHOD: A cross-sectional, descriptive observational study was carried out, assessing the clinical and radiological prevalence of PH in 75 patients with an end colostomy operated on since 1997. Clinical examinations were performed by a single surgeon. Abdominal CTs were assessed by a single radiologist. RESULTS: PH was observed clinically in 33 (44%) of 75 patients and 27 (82%) were symptomatic. Using the classification 0 (Normal), I (Hernial sac containing stoma loop), II (Sac containing omentum), III (Sac containing a loop other than stoma), radiological PH was observed in 35 (47%) patients. Clinical/radiological concordance (Kappa index = 0.4) increased proportionally with sac size. All type-III PHs (n = 9) were symptomatic. The combined prevalence of PH detected by one or other method was 60.8%. CONCLUSION: Clinical and radiological prevalence of PH is high. As there is no gold standard for PH detection, we recommend a combination of the two methods. A new classification for use in clinical practice is proposed.

Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)].

Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level >0.1% at the end of treatment than in patients with < or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of >10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR >10 compared to 21% for patients with RQ-PCR levels < or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.

Adverse prognostic impact of CD36 and CD2 expression in adult de novo acute myeloid leukemia patients.

BACKGROUND AND OBJECTIVES: A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytometry. DESIGN AND METHODS: Two hundred and sixty-six bone marrow (BM) samples from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were studied by multiparametric flow cytometry. Immunophenotyping studies were performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells was analyzed using triple stainings with fluorochrome-conjugated combinations of monoclonal antibodies. RESULTS: CD2 was positive in 21 cases (8%); an associated inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS) rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)- patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+ patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+ (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2; p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS. CONCLUSIONS: CD2+ patients had a very poor OS when CD2/inv(16)+ cases were excluded. CD36 and CD2 expression at diagnosis can provide prognostically important information in adult de novo AML.

CXCR4 and SDF-1 expression in B-cell chronic lymphocytic leukemia and stage of the disease.

The pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) has been linked to an overexpression of the chemokine receptor CXCR4 and increased in vitro functional response to its natural ligand CXCL12 (SDF-1). The CXCR4/SDF-1 system appears to be important for tissue localization and increased survival of B-CLL cells. The aim of our study was to examine if CXCR4 expression and SDF-1 blood levels were correlated to clinical and pathological stage of B-CLL. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) techniques were used to determine CXCR4 expression and SDF-1 plasma levels, respectively, in a cohort of 51 patients diagnosed with B-CLL to correlate these measurements with several parameters that define the clinical stage of the disease. We confirmed that CXCR4 was consistently expressed on circulating B-CLL cells with a fluorescence intensity that was five-fold greater than in cells from healthy volunteers. There was a correlation between CXCR4 expression and leukocyte count ( r: 0.55, p<0.01), and CD19(+)/CD5(+ )cells ( r: 0.63, p<0.01). Interestingly, the group of B-CLL patients showed lower SDF-1 plasma levels compared to the control group. However, there was no correlation between CXCR4 or SDF-1 expression and the clinical stage of disease or the pattern of bone marrow infiltration. The results obtained suggest that other factors, and not only alteration in the SDF-1/CXCR4 chemokine system, must account for marrow infiltration of neoplastic cells observed in B-CLL and that CXCR4 could be involved in other features that exhibit malignant B cells, such as increased survival, rather than in their homing or migration to the bone marrow.

Characterization of a new hemoglobin variant: Hb Badalona (beta31[B13]Leu-->Val).

Hemoglobin (Hb) Badalona was identified in a 35-year-old Spanish female and two other family members. All affected subjects presented erythrocytosis and increased oxygen affinity (P(50): 21 mmHg). Hemoglobinopathy was not detected with electrophoretic methods. It was, however, separated and quantified by cation exchange and reverse-phase high-performance liquid chromatography. Hb Badalona accounted for 35% of the total Hb. No significant clinical symptoms were found to be related to this hemoglobinopathy. This is the first case of a Leu-->Val replacement at position beta31(B13) reported in the world literature.

Homocysteine and lipid peroxidation in haemodialysis: role of folinic acid and vitamin E.

BACKGROUND: Cardiovascular diseases are the leading cause of death in haemodialysis patients. Hyperhomocysteinaemia is an independent risk factor. Basic research has provided strong evidence that oxidation of low-density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. Oxidative stress, lipid metabolism alterations, and hyperhomocysteinaemia observed in haemodialysis patients could induce increases in LDL oxidation. This study was designed to determine the effect of folinic acid on hyperhomocysteinaemia and to assess the antioxidant efficacy of folinic acid. The antioxidant effect of folinic acid was compared with that of vitamin E. METHODS: Sixteen stable patients (11 men, five women; mean age 54.3+/-6.32 years) on standard haemodialysis received 400 mg of vitamin E, orally, at the end of each haemodialysis session for 3 months. After a 1-month wash-out, they received 10 mg of folinic acid, intravenously, at the end of each haemodialysis session for an additional 3 months. Blood samples were drawn in the morning after an overnight fast and before dialysis. Plasma vitamin E was analysed by high-pressure liquid chromatography. Malondialdehyde (MDA) was determined using a fluorimetric method and plasma copper oxidized anti-LDL antibodies (Ab-LDLox) were measured with an ELISA method using native LDL and oxLDL as antigens. Plasma homocysteine was determined by an FPIA method. RESULTS: Folinic acid supplements significantly reduced hyperhomocysteinaemia (-44%), MDA concentrations (-40%), and IgG-LDLox titres (-13%). CONCLUSIONS: Treatment with folinic acid lowers plasma homocysteine levels and, like vitamin E, affords antioxidant protection, which prevents lipid peroxidation. This lowering of lipid peroxidation may reduce the risk of atherosclerosis and prevent or delay cardiovascular complications in HD patients.