Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.

Abstract OBJECTIVE: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. METHODS: Multicenter retrospective study of 16 children with NMO/NMOSD receiving 652 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 6510 7 10(6) cells/L). RESULTS: The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 7 10(6) cells/L, 10 had inadequate monitoring ( 641 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. CONCLUSION: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses

Operative Intervention Does Not Change Pain Perception in Patients With Diabetic Foot Ulcers

Researchers investigated pain perception in patients with diabetic foot ulcers (DFUs) by analyzing pre- and postoperative physical function (PF), pain interference (PI), and depression domains of the Patient-Reported Outcome Measurement Information System (PROMIS). They hypothesized that 1) because of painful diabetic peripheral neuropathy (DPN), a majority of patients with DFUs would have high PROMIS PI scores unchanged by operative intervention, and 2) the initially assessed PI, PF, and depression levels would be correlated with final outcomes. Seventy-five percent of patients with DFUs reported pain, most likely because of painful DPN. Those who reported high PI and low PF were likely to report depression. PF, PI, and depression levels were unchanged after operative intervention or healing of DFUs

Ecological immunogenetics of life-history traits in a model amphibian

Major histocompatibility complex (MHC) genes determine immune repertoires and social preferences of vertebrates. Immunological regulation of microbial assemblages associated with individuals influences their sociality, and should also affect their life-history traits. We exposed Xenopus laevis tadpoles to water conditioned by adult conspecifics. Then, we analysed tadpole growth, development and survivorship as a function of MHC class I and class II peptide-binding region amino acid sequence similarities between tadpoles and frogs that conditioned the water to which they were exposed. Tadpoles approached metamorphosis earlier and suffered greater mortality when exposed to immunogenetically dissimilar frogs. The results suggest that developmental regulatory cues, microbial assemblages or both are specific to MHC genotypes. Tadpoles may associate with conspecifics with which they share microbiota to which their genotypes are well adapted

The upgrade of GEO600

The German / British gravitational wave detector GEO 600 is in the process of being upgraded. The upgrading process of GEO 600, called GEO-HF, will concentrate on the improvement of the sensitivity for high frequency signals and the demonstration of advanced technologies. In the years 2009 to 2011 the detector will undergo a series of upgrade steps, which are described in this paper.Comment: 9 pages, Amaldi 8 conference contributio

The path to the enhanced and advanced LIGO gravitational-wave detectors

We report on the status of the Laser Interferometric Gravitational-Wave Observatory (LIGO) and the plans and progress towards Enhanced and Advanced LIGO. The initial LIGO detectors have finished a two year long data run during which a full year of triple-coincidence data was collected at design sensitivity. Much of this run was also coincident with the data runs of interferometers in Europe, GEO600 and Virgo. The joint analysis of data from this international network of detectors is ongoing. No gravitational wave signals have been detected in analyses completed to date. Currently two of the LIGO detectors are being upgraded to increase their sensitivity in a program called Enhanced LIGO. The Enhanced LIGO detectors will start another roughly one year long data run with increased sensitivity in 2009. In parallel, construction of Advanced LIGO, a major upgrade to LIGO, has begun. Installation and commissioning of Advanced LIGO hardware at the LIGO sites will commence at the end of the Enhanced LIGO data run in 2011. When fully commissioned, the Advanced LIGO detectors will be ten times as sensitive as the initial LIGO detectors. Advanced LIGO is expected to make several gravitational wave detections per year.Comment: 11 pages, 5 figure

Aadi in situ hypoxia monitoring solutions applied in the framework of the eu fp7 project hypox

Peer Reviewe

Mobility of thorium ions in liquid xenon

We present a measurement of the $^{226}$Th ion mobility in LXe at 163.0 K and 0.9 bar. The result obtained, 0.240$\pm$0.011 (stat) $\pm$0.011 (syst) cm$^{2}$/(kV-s), is compared with a popular model of ion transport.Comment: 6.5 pages,

LOOC UP: Locating and observing optical counterparts to gravitational wave bursts

Gravitational wave (GW) bursts (short duration signals) are expected to be associated with highly energetic astrophysical processes. With such high energies present, it is likely these astrophysical events will have signatures in the EM spectrum as well as in gravitational radiation. We have initiated a program, "Locating and Observing Optical Counterparts to Unmodeled Pulses in Gravitational Waves" (LOOC UP) to promptly search for counterparts to GW burst candidates. The proposed method analyzes near real-time data from the LIGO-Virgo network, and then uses a telescope network to seek optical-transient counterparts to candidate GW signals. We carried out a pilot study using S5/VSR1 data from the LIGO-Virgo network to develop methods and software tools for such a search. We will present the method, with an emphasis on the potential for such a search to be carried out during the next science run of LIGO and Virgo, expected to begin in 2009.Comment: 11 pages, 2 figures; v2) added acknowledgments, additional references, and minor text changes v3) added 1 figure, additional references, and minor text changes. v4) Updated references and acknowledgments. To be published in the GWDAW 12 Conf. Proc. by Classical and Quantum Gravit