We report the final results of the Phase II SIMPLE measurements, comprising two run stages of 15 superheated droplet detectors each, the second stage including an improved neutron shielding. The analyses includes a refined signal analysis, and revised nucleation efficiency based on reanalysis of previously-reported monochromatic neutron irradiations. The combined results yield a contour minimum of σp = 5.7 × 10 −3 pb at 35 GeV/c 2 in the spin-dependent sector of WIMP-proton interactions, the most restrictive to date for MW ≤ 60 GeV/c 2 from a direct search experiment and overlapping for the first time results previously obtained only indirectly. In the spin-independent sector, a minimum of 4.7 × 10 −6 pb at 35 GeV/c 2 is achieved, with the exclusion contour challenging a significant part of the light mass WIMP region of current interest.The search for weakly interacting massive particle (WIMP) dark matter remains at the forefront of modern physics activity. Estimated to comprise ∼ 23% of the Universe mass, it is the role of direct detection efforts to elaborate its nature, and whether its interaction with nucleons is spin-independent (SI) or spin-dependent (SD). SIMPLE (Superheated Instrument for Massive ParticLe Experiments) [1] is a direct search activity using superheated liquid detectors, and one of only a few in the international panorama with sensitivity to the WIMPproton sector of the SD phase space. It is operated at the 1500 mwe level of the Low Noise Underground Laboratory (LSBB) in southern France.In [1], we reported the first results of a two stage Phase II measurement, comprising a 14.1 kgd Stage 1 exposure of 15 superheated droplet detectors (SDDs) [2-4] with a total active mass of 0.208 kg. We here provide the results of the full Phase II measurement, including a 13.67 kgd Stage 2 exposure of a second 15 SDD set, together with improved neutron shielding and a refined analysis of the individual detector run signals, sensitivities, and nucleation efficiency.A SDD consists of a dispersion of superheated liquid droplets homogeneously distributed within a gel matrix, which may undergo a transition to the gas phase upon energy deposition by incident radiation. Two conditions are required for the nucleation of the gas phase of the superheated droplets [5]: (i) the energy deposited must be greater than a thermodynamic minimum, and (ii) this * criodets@cii.fc.ul.pt energy must be deposited within a thermodynamicallydefined minimum distance (Λr c ) inside the droplet, where Λ is the nucleation parameter and r c = the thermodynamic critical bubble radius. Adjustment of the two conditions results in the necessity of depositions of order ≥ 150 keV/µm for a bubble nucleation, rendering the SDD effectively insensitive to the majority of traditional detector backgrounds (including electrons, γ's and cosmic muons) which complicate more conventional dark matter search detectors, leaving only α-and neutron-induced events.The 15 Stage 2 SDDs were fabricated as described in [1], each containing between 11-19 g of C 2 ...
Background SCID is a syndrome characterized by profound T cell deficiency. BCG vaccine is contraindicated in SCID patients. Because most countries encourage BCG vaccination at birth, a high percent of SCID patients are vaccinated before their immune defect is detected. Objectives To describe the complications and risks associated with BCG vaccination in SCID patients. Methods An extensive standardized questionnaire evaluating complications, therapeutics, and outcome regarding BCG in patients diagnosed with SCID was widely distributed. Summary statistics and association analysis was performed. Results Data on 349 BCG vaccinated SCID patients from 28 centers in 17 countries was analyzed. Fifty-one percent of the patients developed BCG complications, 34% disseminated and 17% localized (a 33,000 and 400 fold increase, respectively, over the general population). Patients receiving early vaccination (≤ 1 month) showed an increased prevalence of complications (p=0.006) and death due to BCG complications (p<0.0001). The odds of experiencing complications among patients with T cells ≤ 250/uL at diagnosis was 2.1 times higher (95% CI, 1.4-3.4; p = 0.001) than among those with T cells > 250/uL. BCG complications were reported in 2/78 patients who received anti-mycobacterial therapy while asymptomatic and no deaths due to BCG complications occurred in this group. In contrast 46 BCG-associated deaths were reported among 160 patients treated with anti-mycobacterial therapy for a symptomatic BCG infection (p<0.0001). Conclusions BCG vaccine has a very high rate of complications in SCID patients, which increase morbidity and mortality rates. Until safer and more efficient anti-tuberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.
FOXN1 deficiency is a primary immunodeficiency characterized by athymia, alopecia totalis, and nail dystrophy. Two infants with FOXN1 deficiency were transplanted with cultured postnatal thymus tissue. Subject 1 presented with disseminated Bacillus Calmette-Guérin infection and oligoclonal T cells with no naive markers. Subject 2 had respiratory failure, human herpes virus 6 infection, cytopenias, and no circulating T cells. The subjects were given thymus transplants at 14 and 9 months of life, respectively. Subject 1 received immunosuppression before and for 10 months after transplantation. With follow up of 4.9 and 2.9 years, subjects 1 and 2 are well without infectious complications. The pretransplantation mycobacterial disease in subject 1 and cytopenias in subject 2 resolved. Subject 2 developed autoimmune thyroid disease 1.6 years after transplantation. Both subjects developed functional immunity. Subjects 1 and 2 have 1053/mm3 and 1232/mm3 CD3+ cells, 647/mm3 and 868/mm3 CD4+ T cells, 213/mm3 and 425/mm3 naive CD4+ T cells, and 10 200 and 5700 T-cell receptor rearrangement excision circles per 100 000 CD3+ cells, respectively. They have normal CD4 T-cell receptor β variable repertoires. Both subjects developed antigen-specific proliferative responses and have discon-tinued immunoglobulin replacement. In summary, thymus transplantation led to T-cell reconstitution and function in these FOXN1 deficient infants.
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Forkhead box N1 (FOXN1) is a transcription factor crucial for thymic epithelium development and prevention of its involution. Investigation of a patient with a rare homozygous FOXN1 mutation (R255X), leading to alopecia universalis and thymus aplasia, unexpectedly revealed non-maternal circulating T-cells, and, strikingly, large numbers of aberrant double-negative αβ T-cells (CD4negCD8neg, DN) and regulatory-like T-cells. These data raise the possibility that a thymic rudiment persisted, allowing T-cell development, albeit with disturbances in positive/negative selection, as suggested by DN and FoxP3+ cell expansions. Although regulatory-like T-cell numbers normalized following HLA-mismatched thymic transplantation, the αβDN subset persisted 5 years post-transplantation. Involution of thymus allograft likely occurred 3 years post-transplantation based on sj/βTREC ratio, which estimates intrathymic precursor T-cell divisions and, consequently, thymic explant output. Nevertheless, functional immune-competence was sustained, providing new insights for the design of immunological reconstitution strategies based on thymic transplantation, with potential applications in other clinical settings.
We report the isolation of Borrelia lusitaniae from a 13-year-old female child presenting with a vasculitis syndrome. The patient was treated with doxycycline, 100 mg bid for 20 days, and is in remission after a follow-up of 2 years. These results should alert clinicians to the fact that B. lusitaniae may be pathogenic in humans, highlighting that patients may be seronegative or present with minimal positive antibody titres and clinical signs that are not specific for Lyme borreliosis. In order to prevent the occurrence of more serious disease manifestations via timely treatment, the analysis by molecular methods may be a useful approach when antibody titres are uninformative.
PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenitis) is a benign sporadic syndrome of unknown cause. We report 2 siblings diagnosed with this syndrome. The second case started crisis simultaneously with recurrence of crisis after a 3-year free interval in her brother. This temporal relation suggests environmental factor acting in genetically predisposed children.
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