Efficacy and safety of once-monthly Risperidone ISM ® in schizophrenic patients with an acute exacerbation

Funding: This study was funded by Laboratorios Farmacéuticos Rovi, S.A. Madrid, Spain. It was supported also in part by a grant from Center for the Development of Industrial Technology (Expedient No. IDI-20160109).To evaluate the efficacy and safety of Risperidone ISM ® against placebo in patients with acute exacerbation of schizophrenia. A multicenter, randomized, double-blind, placebo-controlled study was conducted between June 2017 and December 2018 (NCT03160521). Eligible patients received once-monthly intramuscular injections of Risperidone ISM ® (75 or 100 mg) or placebo for 12 weeks. The primary efficacy outcome was change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 12. The key secondary efficacy outcome was change from baseline in Clinical Global Impressions-Severity of Illness scale (CGI-S) score. Altogether, 438 patients were randomized (1:1:1) and 390 included in the modified ITT efficacy set. The PANSS total score (mean difference, 95% CI) improved significantly from baseline to day 85 with Risperidone ISM ® 75 and 100 mg, with placebo-adjusted differences of −13.0 (95% CI, −17.3 to −8.8); (p < 0.0001), and −13.3 (−17.6 to −8.9); (p < 0.0001), respectively. Significantly improved mean changes were also obtained for CGI-S score from baseline to day 85 for both doses of Risperidone ISM ® compared with placebo −0.7 (−1.0 to −0.5); p < 0.0001, for both doses. The statistically significant improvement for both efficacy outcomes were observed as early as 8 days after first injection. The most frequently reported treatment-emergent adverse events were increased blood prolactin (7.8%), headache (7.3%), hyperprolactinemia (5%), and weight increase (4.8%). Neither new nor unexpected relevant safety information was recorded. Risperidone ISM ® provided rapid and progressive reduction of symptoms in patients with acutely exacerbated schizophrenia without need of oral risperidone supplementation or loading doses. Both doses were safe and well tolerated

Use of peptide antibodies to probe for the mitoxantrone resistance-associated protein MXR/BCRP/ABCP/ABCG2

AbstractRecent studies have characterized the ABC half-transporter associated with mitoxantrone resistance in human cancer cell lines. Encoded by the ABCG2 gene, overexpression confers resistance to camptothecins, as well as to mitoxantrone. We developed four polyclonal antibodies against peptides corresponding to four different epitopes on the mitoxantrone resistance-associated protein, ABCG2. Three epitopes localized on the cytoplasmic region of ABCG2 gave rise to high-affinity antibodies, which were demonstrated to be specific for ABCG2. Western blot analysis of cells with high levels of ABCG2 showed a single major band of the expected 72-kDa molecular size of ABCG2 under denaturing conditions. Immunoblot analysis performed under non-reducing conditions and after treatment with cross-linking reagents demonstrated a molecular weight shift from 72 kDa to several bands of 180 kDa and higher molecular weight, suggesting detection of dimerization products of ABCG2. Evidence of N-linked glycosylation was also obtained using tunicamycin and N-glycosidase F. Finally, both by light, fluorescence and electron microscopic immunohistochemical staining, we demonstrate cytoplasmic and predominantly plasma membrane localization of ABCG2 in cell lines with high levels of expression. Plasma membrane staining was observed on the surface of the chorionic villi in placenta. These results support the hypothesis that ABCG2 is an ABC half-transporter that forms dimers in the plasma membrane, functioning as an ATP-dependent outward pump for substrate transport

Governing urban accessibility: moving beyond transport and mobility

Access to people, goods, ideas and services is the basis of economic development in cities. The better this access, the greater the economic benefits through economies of scale, agglomeration effects and networking advantages. The way in which cities facilitate accessibility also impacts directly on other key aspects of human development, social inclusion and well-being. Accessibility is created through a complex interplay of urban form and transport systems. Thus, governing urban accessibility requires moving beyond conventional urban transport considerations linked to mobility and movement. Such a re-framing implies a far greater recognition of urban form characteristics like land use, distribution of densities and urban design, in addition to transport characteristics like infrastructures, service levels and travel speeds. A new interface between these characteristics has emerged as a result of shared mobility systems, putting additional pressure on city governments to act as system integrators. Based on a literature review, empirical insights from a global survey and the case-study cities of London, NYC and Berlin, this paper explores the institutional capacities of shifting from governing urban transport to urban accessibility. The evidence shows that there are entrenched misalignments which may impact negatively on the capacity to pair planning and policies essential for delivering better accessibility. Furthermore, it is clear that “hierarchies” and “networks” are not mutually exclusive when it comes to integrated governance of accessibility. The findings also suggest that cities may be better equipped to integrate shared mobility and consider mobility as a service than to pursue more wide-ranging metropolitan accessibility policies

The MATCH Corpus: A Corpus of Older and Younger Users' Interactions With Spoken Dialogue Systems.

We present the MATCH corpus, a unique data set of 447 dialogues in which 26 older and 24 younger adults interact with nine different spoken dialogue systems. The systems varied in the number of options presented and the confirmation strategy used. The corpus also contains information about the users’ cognitive abilities and detailed usability assessments of each dialogue system. The corpus, which was collected using a Wizard-of-Oz methodology, has been fully transcribed and annotated with dialogue acts and ‘‘Information State Update’’ (ISU) representations of dialogue context. Dialogue act and ISU annotations were performed semi-automatically. In addition to describing the corpus collection and annotation, we present a quantitative analysis of the interaction behaviour of older and younger users and discuss further applications of the corpus. We expect that the corpus will provide a key resource for modelling older people’s interaction with spoken dialogue systems