Explore the vast range of titles available.

The ALICE instrument is a lightweight (4.4 kg), low-power (4.4 watt) imaging spectrograph aboard the New Horizons mission to the Pluto system and the Kuiper Belt. Its primary job is to determine the relative abundances of various species in Pluto’s atmosphere. ALICE will also be used to search for an atmosphere around Pluto’s moon, Charon, as well as the Kuiper Belt Objects (KBOs) that New Horizons is expected to fly by after Pluto-Charon, and it will make UV surface reflectivity measurements of all of these bodies, as well as of Pluto’s smaller moons Nix and Hydra. The instrument incorporates an off-axis telescope feeding a Rowland-circle spectrograph with a 520–1870 Å spectral passband, a spectral point spread function of 3–6 Å FWHM, and an instantaneous spatial field-of-view that is 6 degrees long. Two different input apertures that feed the telescope allow for both airglow and solar occultation observations during the mission. The focal plane detector is an imaging microchannel plate (MCP) double delay-line detector with dual solar-blind opaque photocathodes (KBr and CsI) and a focal surface that matches the instrument’s 15-cm diameter Rowland-circle. In this paper, we describe the instrument in greater detail, including descriptions of its ground calibration and initial in flight performance. New Horizons launched on 19 January 2006.

The New Horizons ALICE instrument is a lightweight (4.4 kg), low-power (4.4 Watt) imaging spectrograph aboard the New Horizons mission to Pluto/Charon and the Kuiper Belt. Its primary job is to determine the relative abundances of various species in Pluto's atmosphere. ALICE will also be used to search for an atmosphere around Pluto's moon, Charon, as well as the Kuiper Belt Objects (KBOs) that New Horizons hopes to fly by after Pluto-Charon, and it will make UV surface reflectivity measurements of all of these bodies as well. The instrument incorporates an off-axis telescope feeding a Rowland-circle spectrograph with a 520-1870 angstroms spectral passband, a spectral point spread function of 3-6 angstroms FWHM, and an instantaneous spatial field-of-view that is 6 degrees long. Different input apertures that feed the telescope allow for both airglow and solar occultation observations during the mission. The focal plane detector is an imaging microchannel plate (MCP) double delay-line detector with dual solar-blind opaque photocathodes (KBr and CsI) and a focal surface that matches the instrument's 15-cm diameter Rowland-circle. In what follows, we describe the instrument in greater detail, including descriptions of its ground calibration and initial in flight performance.

Background Despite the overall high degree of response to pharmacotherapy, consensus is lacking on how to judge clinical response or define optimal treatment/remission when treating adults with attention-deficit/hyperactivity disorder (ADHD). This study examined clinical response and symptomatic remission in analyses of 2 studies of lisdexamfetamine dimesylate (LDX) in adults with ADHD. Methods In a 4-week, double-blind, forced-dose trial, adults with ADHD were randomized to LDX 30, 50, and 70 mg/day (mg/d) or placebo. In a second, open-label, follow-up trial, adults entering from the 4-week study were titrated to an “optimal” LDX dose (30 mg/d [n=44], 50 mg/d [n=112], and 70 mg/d [n=171]) over 4 weeks, and maintained for 11 additional months. The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts and the Clinical Global Impressions-Improvement (CGI-I) scale assessed efficacy. Clinical response was defined, post hoc, as ≥30% reduction from baseline in ADHD-RS-IV and CGI-I rating of 1 or 2; symptomatic remission was defined as ADHD-RS-IV total score ≤18. Log rank analysis examined overall significance among the treatment groups in time to response or remission. Results Four hundred and fourteen participants in the 4-week study and 345 in the open-label, extension study were included in the efficacy populations. All LDX groups improved by ADHD-RS-IV and CGI-I scores in both studies. In the 4-week study (n=414), 69.3% responded and 45.5% achieved remission with LDX (all doses); 37.1% responded and 16.1% achieved remission with placebo; time (95% CI) to median clinical response (all LDX doses) was 15.0 (15.0, 17.0) days and to remission was 31.0 (28.0, 37.0) days ( P <.0001 overall). In the open-label study, with LDX (all doses), 313 (95.7%) and 278 (85.0%) of 327 participants with evaluable maintenance-phase data met criteria for response and remission, respectively. Of participants who completed dose optimization, 75.2% remained responders and 65.7% remained in remission in the 12-month study. Overall, 285 (82.6%) and 227 (65.8%) of 345 participants were responders and remitters, respectively, at their final visits. Conclusion In the long-term study, with open-label, dose-optimized LDX treatment, most adults with ADHD achieved clinical response and/or symptomatic remission; almost two-thirds maintained symptomatic remission over the remaining 11 months. Trial registration Clinical Trial Numbers: NCT00334880 and NCT01070394 Clinical Trial Registry: clinicaltrials.gov URLs http://www.clinicaltrials.gov/show/NCT00334880 http://www.clinicaltrials.gov/ct2/show/NCT01070394?term=NCT01070394&rank=1

Glioblastoma (GBM) is an incurable brain cancer that lacks effective therapies. Here we show that EAG2 and Kvβ2, which are predominantly expressed by GBM cells at the tumor-brain interface, physically interact to form a potassium channel complex due to a GBM-enriched Kvβ2 isoform. In GBM cells, EAG2 localizes at neuron-contacting regions in a Kvβ2-dependent manner. Genetic knockdown of the EAG2-Kvβ2 complex decreases calcium transients of GBM cells, suppresses tumor growth and invasion and extends the survival of tumor-bearing mice. We engineered a designer peptide to disrupt EAG2-Kvβ2 interaction, thereby mitigating tumor growth in patient-derived xenograft and syngeneic mouse models across GBM subtypes without overt toxicity. Neurons upregulate chemoresistant genes in GBM cells in an EAG2-Kvβ2-dependent manner. The designer peptide targets neuron-associated GBM cells and possesses robust efficacy in treating temozolomide-resistant GBM. Our findings may lead to the next-generation therapeutic agent to benefit patients with GBM.

Objective To compare the incidence of tuberculosis over two years in infants vaccinated at birth with intradermal BCG or with percutaneous BCG.Design Randomised trial.Setting South Africa.Participants 11 680 newborn infants.Interventions Infants were randomised by week of birth to receive Tokyo 172 BCG vaccine through the percutaneous route (n=5775) or intradermal route (n=5905) within 24 hours of birth and followed up for two years.Main outcome measures The primary outcome measure was documented Mycobacterium tuberculosis infection or radiological and clinical evidence of tuberculosis disease. Secondary outcome measures were rates of adverse events, all cause and tuberculosis specific admissions to hospital, and mortality.Results The difference in the cumulative incidence of definite, probable, and possible tuberculosis between the intradermal group and the percutaneous group, as defined using study definitions based on microbiological, radiological, and clinical findings was −0.36% (95.5% confidence interval −1.27% to 0.54%). No significant differences were found between the routes in the cumulative incidence of tuberculosis using a range of equivalence of “within 25%.” Additionally, no significant differences were found between the routes in the cumulative incidence of adverse events (risk ratio 0.98, 95% confidence interval 0.91 to 1.06), including deaths (1.19, 0.89 to 1.58).Conclusion Equivalence was found between intradermal BCG vaccine and percutaneous BCG in the incidence of tuberculosis in South African infants vaccinated at birth and followed up for two years. The World Health Organization should consider revising its policy of preferential intradermal vaccination to allow national immunisation programmes to choose percutaneous vaccination if that is more practical.Trial registration ClinicalTrials.gov NCT00242047.