Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation

Objective: Heavy post-transplant immunosuppression may contribute to long-term immunosuppression dependence by subverting tolerogenic mechanisms; thus, we sought to determine if this undesirable consequence could be mitigated by pretransplant lymphoid depletion and minimalistic post-transplant monotherapy. Study design: Lymphoid depletion in 17 unselected pediatric recipients of live (n = 14) or deceased donor kidneys (n = 3) was accomplished with antithymocyte globulin (ATG) (n = 8) or alemtuzumab (n = 9). Tacrolimus was begun post-transplantation with subsequent lengthening of intervals between doses (spaced weaning). Maintenance immunosuppression, morbidity, graft function, and patient/graft survival were collated. Results: Steroids were added temporarily to treat rejection in two patients (both ATG subgroup) or to treat hemolytic anemia in two others. After 16 to 31 months (mean 22), patient and graft survival was 100% and 94%, respectively. The only graft loss was in a nonweaned noncompliant recipient. In the other 16, serum creatinine was 0.85 ± 0.35 mg/dL and creatinine clearance was 90.8 ± 22.1 mL/1.73 m2. All 16 patients are on monotherapy (15 tacrolimus, one sirolimus), and 14 receive every other day or 3 times per week doses. There were no wound or other infections. Two patients developed insulin-dependent diabetes. Conclusion: The strategy of lymphoid depletion and minimum post-transplant immunosuppression appears safe and effective for pediatric kidney recipients. © 2006 Elsevier Inc. All rights reserved

A New Era in Extragalactic Background Light Measurements: The Cosmic History of Accretion, Nucleosynthesis and Reionization

(Brief Summary) What is the total radiative content of the Universe since the epoch of recombination? The extragalactic background light (EBL) spectrum captures the redshifted energy released from the first stellar objects, protogalaxies, and galaxies throughout cosmic history. Yet, we have not determined the brightness of the extragalactic sky from UV/optical to far-infrared wavelengths with sufficient accuracy to establish the radiative content of the Universe to better than an order of magnitude. Among many science topics, an accurate measurement of the EBL spectrum from optical to far-IR wavelengths, will address: What is the total energy released by stellar nucleosynthesis over cosmic history? Was significant energy released by non-stellar processes? Is there a diffuse component to the EBL anywhere from optical to sub-millimeter? When did first stars appear and how luminous was the reionization epoch? Absolute optical to mid-IR EBL spectrum to an astrophysically interesting accuracy can be established by wide field imagingat a distance of 5 AU or above the ecliptic plane where the zodiacal foreground is reduced by more than two orders of magnitude.Comment: 7 pages; Science White Paper for the US Astro 2010-2020 Decadal Survey. If interested in further community-wide efforts on this topic please contact the first autho

The Mock LISA Data Challenges: from Challenge 3 to Challenge 4

The Mock LISA Data Challenges are a program to demonstrate LISA data-analysis capabilities and to encourage their development. Each round of challenges consists of one or more datasets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants analyze the datasets and report best-fit solutions for the source parameters. Here we present the results of the third challenge, issued in Apr 2008, which demonstrated the positive recovery of signals from chirping Galactic binaries, from spinning supermassive--black-hole binaries (with optimal SNRs between ~ 10 and 2000), from simultaneous extreme-mass-ratio inspirals (SNRs of 10-50), from cosmic-string-cusp bursts (SNRs of 10-100), and from a relatively loud isotropic background with Omega_gw(f) ~ 10^-11, slightly below the LISA instrument noise.Comment: 12 pages, 2 figures, proceedings of the 8th Edoardo Amaldi Conference on Gravitational Waves, New York, June 21-26, 200

Radio Astronomy

Contains table of contents and reports on seven research projects.National Science Foundation (Grant AST 86-17172)National Aeronautics and Space AdministrationJet Propulsion LaboratoryNASA/Goddard Space Flight Center (Grant NAG5-10)SM Systems and Research, Inc.U.S. Navy Office of Naval Research (Contract N00014-86-C-2114)Center for Advanced Television StudiesNASA/Goddard Space Flight Center (Grant NAG5-537

Radio Astronomy

Contains reports on nine research projects.National Science Foundation (Grant AST 86-17172)National Aeronautics and Space Administration (Contract NAS7-918)Jet Propulsion Laboratory (Contract 958048)U.S. Navy - Office of Naval Research (Contract N00014-84-C-2082)U.S. Navy - Office of Naval Research (Contract N00014-86-C-2114)SM Systems and Research, Inc.National Aeronautics and Space Administration/Goddard Space Flight Center (Grant NAG5-10)Center for Advanced Television StudiesBrazil, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Grant 300.832-82)National Aeronautics and Space Administration/Goddard Space Flight Center (Grant NAG5-537

Tolerogenic immunosuppression for organ transplantation

Background: Insight into the mechanisms of organ engraftment and acquired tolerance has made it possible to facilitate these mechanisms, by tailoring the timing and dosage of immunosuppression in accordance with two therapeutic principles: recipient pretreatment, and minimum use of post-transplant immunosuppression. We aimed to apply these principles in recipients of renal and extrarenal organ transplants. Methods: 82 patients awaiting kidney, liver, pancreas, or intestinal transplantation were pretreated with about 5 mg/kg of a broadly reacting rabbit antithymocyte globulin during several hours. Post-transplant immunosuppression was restricted to tacrolimus unless additional drugs were needed to treat breakthrough rejection. After 4 months, patients on tacrolimus monotherapy were considered for dose-spacing to every other day or longer intervals. Findings: We frequently saw evidence of immune activation in graft biopsy samples, but unless this was associated with graft dysfunction or serious immune destruction, treatment usually was not intensified. Immunosuppression-related morbidity was virtually eliminated. 78 (95%) of 82 patients survived at 1 year and at 13-18 months. Graft survival was 73 (89%) of 82 at 1 year and 72 (88%) of 82 at 13-18 months. Of the 72 recipients with surviving grafts, 43 are on spaced doses of tacrolimus monotherapy: every other day (n=6), three times per week (11), twice per week (15), or once per week (11). Interpretation: The striking ability to wean immunosuppression in these recipients indicates variable induction of tolerance. The simple therapeutic principles are neither drug-specific nor organ-specific. Systematic application of these principles should allow improvements in quality of life and long-term survival after organ transplantation

The views and experiences of fathers regarding their young child's intellectual and developmental disability diagnosis: Findings from a qualitative study

AIMS AND OBJECTIVES: To report the views and experiences of fathers following their child's diagnosis of an intellectual and developmental disability (IDD). BACKGROUND: There is a growing interest in understanding the experiences of fathers of children with IDD given the transformation of the structural change of fathers' roles within the family and wider society. DESIGN: A qualitative design was used to elicit the view and experiences of fathers. METHODS: A total of ten Irish fathers participated in face-to-face interviews. The data were thematically analysed. The COREQ guidelines for reporting qualitative studies were used in the development of this paper. RESULTS: The key themes that emerged were (a) the confirmation of the child's diagnosis (b) the impact of the diagnosis and (c) father's motivation to participate in disability research. CONCLUSIONS: This study informs and develops a further understanding of the international evidence base of fathers receiving a confirmation of a child's diagnosis of an intellectual and developmental disability, the impact of the diagnosis on fathers and their motivation to share their stories to add to the disability research. Health and social care practitioners have important contributions to make in meeting the needs of fathers. There are specific areas to consider in terms of practice, education and research that require further attention and development to ensure fathers' distinct needs regarding their child's diagnosis of IDD are known and responded to effectively. RELEVANCE TO CLINICAL PRACTICE: This study highlights that when the child's disability is confirmed, fathers experience a diverse range of mixed emotions. Health and social care practitioners including nurses need to be aware of the impact of the diagnosis upon fathers. There is scope to develop the knowledge, skills and confidence of health and social care practitioners regarding the experiences of fathers and how they can further support fathers and their families during the critical time of a disability disclosure

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi