Treatment response and remission in a double-blind, randomized, head-to-head study of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit hyperactivity disorder

The Author(s) 2014. This article is published with open access at Springerlink.com Objectives A secondary objective of this head-to-head study of lisdexamfetamine dimesylate (LDX) and ato-moxetine (ATX) was to assess treatment response rates in children and adolescents with attention-deficit hyperactiv-ity disorder (ADHD) and an inadequate response to methylphenidate (MPH). The primary efficacy and safety outcomes of the study, SPD489-317 (ClinicalTrials.gov NCT01106430), have been published previously. Methods In this 9-week, double-blind, active-controlled study, patients aged 6–17 years with a previous inadequate response to MPH were randomized (1:1) to dose-optimized LDX (30, 50 or 70 mg/day) or ATX (patients \70 kg: 0.5–1.2 mg/kg/day, not to exceed 1.4 mg/kg/day; patients C70 kg: 40, 80 or 100 mg/day). Treatment response was a secondary efficacy outcome and was predefined as a reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score of at least 25, 30 or 50 %. Sustained response was predefined as a reduction from baseline in ADHD-RS-IV total score (C25, C30 or C50 %) or a Clinical Global Impressions (CGI)–Improvement (CGI–I) score of 1 or 2 throughout weeks 4–9. CGI– Severity (CGI–S) scores were also assessed, as an indicator of remission. Results A total of 267 patients were enrolled (LDX, n = 133; ATX, n = 134) and 200 completed the study (LDX, n = 99; ATX, n = 101). By week 9, significantly (p \ 0.01) greater proportions of patients receiving LDX than ATX met the response criteria of a reduction from baseline in ADHD-RS-IV total score of at least 25 % (90.5 vs. 76.7 %), 30 % (88.1 vs. 73.7 %) or 50 % (73.0 vs. 50.4 %). Sustained response rates were also signifi-cantly (p \ 0.05) higher among LDX-treated patient

CD98hc facilitates B cell proliferation and adaptive humoral immunity.

The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

Evaluation and Validation of a Real-Time PCR Assay for Detection and Quantitation of Human Adenovirus 14 from Clinical Samples

In 2007, the Centers for Disease Control and Prevention (CDC) reported that Human adenovirus type 14 (HAdV-14) infected 106 military personnel and was responsible for the death of one U.S. soldier at Lackland Air Force Base in Texas. Identification of the responsible adenovirus, which had not previously been seen in North America and for which rapid diagnostic tools were unavailable, required retrospective analysis at reference laboratories. Initial quarantine measures were also reliant on relatively slow traditional PCR analysis at other locations. To address this problem, we developed a real-time PCR assay that detects a 225 base pair sequence in the HAdV-14a hexon gene. Fifty-one oropharyngeal swab specimens from the Naval Health Research Center, San Diego, CA and Advanced Diagnostic Laboratory, Lackland AFB, TX were used to validate the new assay. The described assay detected eight of eight and 19 of 19 confirmed HAdV-14a clinical isolates in two separate cohorts from respiratory disease outbreaks. The real-time PCR assay had a wide dynamic range, detecting from 102 to 107 copies of genomic DNA per reaction. The assay did not cross-react with other adenoviruses, influenza, respiratory syncytial virus, or common respiratory tract bacteria. The described assay is easy to use, sensitive and specific for HAdV-14a in clinical throat swab specimens, and very rapid since turnaround time is less than four hours to obtain an answer

Prevalence of adult ADHD in an all-female prison unit.

There is increasing evidence suggesting a link between ADHD and criminality, including a strong association between ADHD symptoms and the likelihood of being on probation or in prison. Most studies investigating the prevalence of ADHD in prison populations have focused on adult male offenders. In the current study, 69 female prisoners were screened for both childhood and adult ADHD symptoms using the Barkley Adult ADHD Rating Scale-IV. The results indicate that 41 % of the prisoners met the diagnostic criteria for ADHD in childhood and continued to meet criteria for ADHD as adults. More importantly, young female prisoners (aged 18-25) were significantly more likely to report symptoms of ADHD than older prisoners. Prisoners who reported symptoms of ADHD also reported high levels of impairment associated with these symptoms. A better understanding of the prevalence of ADHD in female prison units can highlight specific areas for intervention during rehabilitation, as well as the management of serious incidents within prison

Introduction:strategy in EU foreign policy

The point of departure for the special collection is provided by the observation that the growing complexity of the crises in the neighbourhood and the internal ones faced by the Union provides a sense of urgency to any type of strategic thinking that the EU might embrace. Against this backdrop, the recent shift towards geopolitics and strategic thinking is contextualized and the understanding of key aspects of ways in which the shift is translated into strategies by EU actors is put forward. The analysis recognizes the recent developments within the institutional dimension of EU’s foreign and security policy, yet it confirms the fundamental meaning of the member states’ willingness to invest resources and harmonize their foreign policy strategies at the EU level

Gene Expression Disruptions of Organism versus Organ in Drosophila Species Hybrids

Hybrid dysfunctions, such as sterility, may result in part from disruptions in the regulation of gene expression. Studies of hybrids within the Drosophila simulans clade have reported genes expressed above or below the expression observed in their parent species, and such misexpression is associated with male sterility in multigenerational backcross hybrids. However, these studies often examined whole bodies rather than testes or had limited replication using less-sensitive but global techniques. Here, we use a new RNA isolation technique to re-examine hybrid gene expression disruptions in both testes and whole bodies from single Drosophila males by real-time quantitative RT-PCR. We find two early-spermatogenesis transcripts are underexpressed in hybrid whole-bodies but not in assays of testes alone, while two late-spermatogenesis transcripts seem to be underexpressed in both whole-bodies and testes alone. Although the number of transcripts surveyed is limited, these results provide some support for a previous hypothesis that the spermatogenesis pathway in these sterile hybrids may be disrupted sometime after the expression of the early meiotic arrest genes

GABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Naïve P and NP Rats

BACKGROUND:By performing identical studies in humans and rats, we attempted to distinguish vulnerability factors for addiction from neurobiological effects of chronic drug exposure. We focused on the GABAergic system within the hippocampus, a brain region that is a constituent of the memory/conditioning neuronal circuitry of addiction that is considered to be important in drug reinforcement behaviors in animals and craving and relapse in humans. METHODOLOGY:Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, alcohol preferring (P) and non-preferring (NP) rats selectively bred for extremes of alcohol-seeking behavior that also show a general addictive tendency. A pathway-targeted analysis of 25 GABAergic genes encoding proteins implicated in GABA synthesis, metabolism, synaptic transmission and re-uptake was undertaken. PRINCIPAL FINDINGS:Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10⁻¹⁴, 7×10⁻¹¹ respectively). Principal FDR-corrected findings were that GABBR1 was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in NSF, implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. GABRG2, encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with GPHN, encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (GAD1, GAD2), alcoholics (GABRA2) and P rats (ABAT, GABRG3). CONCLUSIONS/SIGNIFICANCE:Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA input in cocaine addiction. Congruent findings in human addicts and P rats provide clues to predisposing factors for alcohol and drug addiction. Finally, the results of this study have therapeutic implications

On Being Negative

This paper investigates the pragmatic expressions of negative evaluation (negativity) in two corpora: (i) comments posted online in response to newspaper opinion articles; and (ii) online reviews of movies, books and consumer products. We propose a taxonomy of linguistic resources that are deployed in the expression of negativity, with two broad groups at the top level of the taxonomy: resources from the lexicogrammar or from discourse semantics. We propose that rhetorical figures can be considered part of the discourse semantic resources used in the expression of negativity. Using our taxonomy as starting point, we carry out a corpus analysis, and focus on three phenomena: adverb + adjective combinations; rhetorical questions; and rhetorical figures. Although the analysis in this paper is corpus-assisted rather than corpus-driven, the final goal of our research is to make it quantitative, in extracting patterns and resources that can be detected automatically