Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder

BackgroundDespite 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.MethodsIn 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.ResultsFour 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.ConclusionIn 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 registrationClinical Trial Numbers: NCT00334880 and NCT01070394Clinical Trial Registry: clinicaltrials.govURLshttp://www.clinicaltrials.gov/show/NCT00334880http://www.clinicaltrials.gov/ct2/show/NCT01070394?term=NCT01070394&rank=

ALICE: The Ultraviolet Imaging Spectrograph aboard the New Horizons Pluto-Kuiper Belt Mission

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.Comment: 24 pages, 29 figures, 2 tables; To appear in a special volume of Space Science Reviews on the New Horizons missio

Short tandem repeat profiling: part of an overall strategy for reducing the frequency of cell misidentification

The role of cell authentication in biomedical science has received considerable attention, especially within the past decade. This quality control attribute is now beginning to be given the emphasis it deserves by granting agencies and by scientific journals. Short tandem repeat (STR) profiling, one of a few DNA profiling technologies now available, is being proposed for routine identification (authentication) of human cell lines, stem cells, and tissues. The advantage of this technique over methods such as isoenzyme analysis, karyotyping, human leukocyte antigen typing, etc., is that STR profiling can establish identity to the individual level, provided that the appropriate number and types of loci are evaluated. To best employ this technology, a standardized protocol and a data-driven, quality-controlled, and publically searchable database will be necessary. This public STR database (currently under development) will enable investigators to rapidly authenticate human-based cultures to the individual from whom the cells were sourced. Use of similar approaches for non-human animal cells will require developing other suitable loci sets. While implementing STR analysis on a more routine basis should significantly reduce the frequency of cell misidentification, additional technologies may be needed as part of an overall authentication paradigm. For instance, isoenzyme analysis, PCR-based DNA amplification, and sequence-based barcoding methods enable rapid confirmation of a cell line’s species of origin while screening against cross-contaminations, especially when the cells present are not recognized by the species-specific STR method. Karyotyping may also be needed as a supporting tool during establishment of an STR database. Finally, good cell culture practices must always remain a major component of any effort to reduce the frequency of cell misidentification

Colonial Archives and the Arts of Governance

Anthropologists engaged inpost-colonial studies are increasingly adoptingan historical perspective and using archives. Yet their archival activity tends to remain morean extractive than an ethnographic one.Documents are thus still invokedpiecemeal to confirm the colonial invention ofcertain practices or to underscore culturalclaims, silent. Yet such mining of the content of government commissions,reports, and other archival sources rarely paysattention to their peculiar placement and form .Scholars need to move fromarchive-as-source to archive-as-subject. Thisarticle, using document production in the DutchEast Indies as an illustration, argues thatscholars should view archives not as sites ofknowledge retrieval, but of knowledgeproduction, as monuments of states as well assites of state ethnography. This requires asustained engagement with archives as culturalagents of ``fact'' production, of taxonomies inthe making, and of state authority. What constitutes thearchive, what form it takes, and what systemsof classification and epistemology signal atspecific times are (and reflect) critical featuresof colonial politics and state power. The archive was the supreme technology of thelate nineteenth-century imperial state, arepository of codified beliefs that clustered(and bore witness to) connections betweensecrecy, the law, and power.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41825/1/10502_2004_Article_5096461.pd

Between Commerce and Empire: David Hume, Colonial Slavery, and Commercial Incivility

Eighteenth-century Enlightenment thought has recently been reclaimed as a robust, albeit short-lived, cosmopolitan critique of European imperialism. This essay complicates this interpretation through a study of David Hume’s reflections on commerce, empire and slavery. I argue that while Hume condemned the colonial system of monopoly, war and conquest, his strictures against empire did not extend to colonial slavery in the Atlantic. This was because colonial slavery represented a manifestly uncivil institution when judged by enlightened metropolitan sensibilities, yet also a decisively commercial institution pivotal to the eighteenth-century global economy. Confronted by the paradoxical ‘commercial incivility’ of modern slavery, Hume opted for disavowing the link between slavery and commerce, and confined his criticism of slavery to its ancient, feudal and Asiatic incarnations. I contend that Hume’s disavowal of the commercial barbarism of the Atlantic economy is part of a broader ideological effort to separate the idea of commerce from its imperial origins and posit it as the liberal antithesis of empire. The implications of analysis, I conclude, go beyond the eighteenth-century debates over commerce and empire, and more generally pertain to the contradictory entwinement of liberalism and capitalism

Pedestrian Crossings and Safety on Four Anishinaabe Reservations in Minnesota

The Minnesota Department of Transportation (MnDOT) has identified Native American as one of six priority populations in the state that face disproportionate risks as pedestrians. This report summarizes results from observations of pedestrian crossing behaviors on four Anishinaabe reservations in northern Minnesota. The University of Minnesota Traffic Observatory (MTO) video-taped and classified pedestrian crossings at 10 intersections identified by Tribal transportation managers as high priority because of perceived risks. Across the intersections, pedestrian crossing volumes during daylight hours ranged from 3 per day to 136 per day. The percent of pedestrian crossings that involved interactions with vehicles ranged from 9% to 54%. Tribal transportation managers from the Bois Forte, Fond du Lac, Grand Portage, and Mille Lacs Bands, MnDOT, county engineers, and the investigators collaborated to identify countermeasures to address risks to pedestrians. Proposed countermeasures varied by intersection and included vegetation removal and line-of-sight improvements, new lighting, crosswalk improvements, Rectangular Rapid Flashing Beacons with advanced warning signs, ADA-compliant ramps, pedestrian education programs, realignment of intersections, and at one intersection a Pedestrian Hybrid Beacon. Prospects for implementation of countermeasures vary by intersection and reservation and are contingent on Tribal and transportation agency budgets, state and county plans for roadway improvements, and categorical grant programs such as Minnesota's Transportation Alternatives Program. Some countermeasures are being implemented, and MnDOT is extending the approach to additional reservations