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Evaluate the safety and tolerability of aripiprazole once-monthly (ARI-OM) initiation in patients stabilized on oral antipsychotics other than aripiprazole. Previous pivotal Phase III trials have evaluated initiating ARI-OM in patients stabilized on oral aripiprazole1.
Eligible patients were treated with oral atypical antipsychotics other than aripiprazole with a history of oral aripiprazole tolerability. The study included a screening phase (30 days) and a treatment phase (28 days). Patients were stabilized per investigator's judgment for ≥14 days on risperidone, olanzapine, quetiapine, or ziprasidone, before administration of ARI-OM (400 mg). Current oral antipsychotic was co-administered with ARI-OM for 2 weeks to determine safety and tolerability of a single ARI-OM dose following treatment initiation. Safety assessments were adverse events (AEs); extrapyramidal symptoms (EPSs) using standard objective rating scales; Columbia-Suicide Severity Rating Scale; clinical laboratory measures; and weight changes.
60 patients initiated ARI-OM, while continuing treatment for ≤2 weeks with oral risperidone (n=24), quetiapine (n=28), ziprasidone (n=5) or olanzapine (n=3). Treatment-emergent (TE) AEs (≥5%) were fatigue, injection-site pain, and restlessness (risperidone); insomnia, dystonia, injection-site pain, and toothache (quetiapine); and muscle spasm, tooth abscess, and toothache (ziprasidone). Prior olanzapine did not cause any AEs. Incidence of TE-EPSs were similar in all groups (< 5%). There were no unusual changes in objective EPS rating scales, suicidality, weight, laboratory values or fasting metabolic parameters across all groups.
The AE profile of patients receiving ARI-OM concomitant with oral atypical antipsychotics other than aripiprazole was consistent with prior reports1.
Evaluate the effectiveness of investigational aripiprazole once-monthly (ARI-OM) for maintenance treatment in schizophrenia.
Detailed methodology has been published previously1. Briefly, the study consisted of 4 phases: oral conversion to aripiprazole (Phase 1); oral aripiprazole stabilization (Phase 2); ARI-OM stabilization (Phase 3), with co-administration of oral aripiprazole for the first 2 weeks; and an ARI-OM maintenance phase (Phase 4). Effectiveness assessments included Investigator's Assessment Questionnaire (IAQ) scores, a scale that evaluates effectiveness of current treatment vs. pre-trial medication, where a negative change in score signals improvement, and Personal and Social Performance (PSP) scale scores, where negative change in score signals worsening.
710 patients entered Phase 2, 576 Phase 3 and 403 Phase 4 (ARI-OM=269, placebo once-monthly [placebo- OM]=134). Mean IAQ Total scores remained stable in Phase 2 (31.3) and Phase 3 (30.6). During Phase 4, the mean change in IAQ Total score was +1.3 for ARI-OM vs. +3.8 for placebo-OM (p< 0.0001). Mean changes in PSP Total scale scores showed improvement during Phase 2 (3.0) and Phase 3 (2.6). Mean change in PSP scores during Phase 4 showed greater functional stability with ARI-OM (−1.7) compared with placebo-OM (−6.2) (p=0.0002 vs. placebo-OM).
Improvements in effectiveness, as assessed by the IAQ and PSP Total scale scores, in the Phases 2 & 3 were maintained in Phase 4 for ARI-OM compared with placebo-OM. Treatment with ARI-OM improved symptoms, overall response to treatment and functioning.
Modern humans evolved in Africa approximately 200,000 years ago (Campbell and Tishkoff 2010). As groups migrated out of Africa they underwent bottlenecks leading to sharp reductions in population size and genetic diversity (Amos and Hoffman 2010; Harpending and Rogers 2000; Ramachandran et al. 2005). To this day, African populations retain the most genetic diversity globally (Auton et al. 2015). In order to survive both within and out of Africa, early human populations had to adapt to their novel environments, including new food resources, colder climates, higher altitudes, and, especially, infectious diseases (Balaresque et al. 2007; Fumagalli et al. 2011). These adaptive requirements, facilitated by natural selection, led to an increased frequency of alleles that were beneficial in that environment. Due to the fact that these adaptive requirements were driven by local environmental pressures, some of these evolutionarily advantageous alleles display geographic and ancestral specificity, as observed in the genomes of present-day humans (Fumagalli et al. 2011).
Glucose intolerance during pregnancy – a major driver of gestational diabetes mellitus (GDM) – has significant short- and long-term health consequences for both the mother and child. As GDM prevalence continues to escalate, there is growing need for preventative strategies. There is limited but suggestive evidence that myo-inositol (MI) and probiotics (PB) could improve glucose tolerance during pregnancy. The present study tested the hypothesis that MI and/or PB supplementation would reduce the risk of glucose intolerance during pregnancy. Female C57BL/6 mice were randomised to receive either no treatment, MI, PB (Lactobacillus rhamnosus and Bifidobacterium lactis) or both (MIPB) for 5 weeks. They were then provided with a high-fat diet for 1 week before mating commenced and throughout mating/gestation, while remaining on their respective treatments. An oral glucose tolerance test occurred at gestational day (GD) 16·5 and tissue collection at GD 18·5. Neither MI nor PB, separately or combined, improved glucose tolerance. However, MI and PB both independently increased adipose tissue expression of Ir, Irs1, Akt2 and Pck1, and PB also increased Pparγ. MI was associated with reduced gestational weight gain, whilst PB was associated with increased maternal fasting glucose, total cholesterol and pancreas weight. These results suggest that MI and PB may improve insulin intracellular signalling in adipose tissue but this did not translate to meaningful differences in glucose tolerance. The absence of fasting hyperglycaemia or insulin resistance suggests this is a very mild model of GDM, which may have affected our ability to assess the impact of these nutrients.
The geomagnetic field extending outward beyond Earth’s solid surface encounters a strong, highly variable flow of hot ionized gas from the Sun called the solar wind. This compresses and shapes the dayside of Earth’s magnetic field. On the night (anti-sunward) side of the Earth, the magnetic field gets drawn out into a long, comet-like tail. Present evidence is that this magnetotail region extends to hundreds or thousands of Earth radii. Research over the past six decades has revealed much about the various current systems that shape the Earth’s "magnetosphere". This chapter is devoted to providing a broad overview of the individual current systems that, acting together, generate the complex and fascinating geomagnetic field.
Computational acceleration of performance metric-based materials discovery via high-throughput screening and machine learning methods is becoming widespread. Nevertheless, development and optimization of the opto-electronic properties that depend on dilute concentrations of point defects in new materials have not significantly benefited from these advances. Here, the authors present an informatics and simulation suite to computationally accelerate these processes. This will enable faster and more fundamental materials research, and reduce the cost and time associated with the materials development cycle. Analogous to the new avenues enabled by current first-principles-based property databases, this type of framework will open entire new research frontiers as it proliferates.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Official counts of deaths attributed to disasters are often under-reported, thus adversely affecting public health messaging designed to prevent further mortality. During the Oklahoma (USA) May 2013 tornadoes, Oklahoma State Health Department Division of Vital Records (VR; Oklahoma City, Oklahoma USA) piloted a flagging procedure to track tornado-attributed deaths within its Electronic Death Registration System (EDRS). To determine if the EDRS was capturing all tornado-attributed deaths, the Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) evaluated three event fatality markers (EFM), which are used to collate information about deaths for immediate response and retrospective research efforts.
Oklahoma identified 48 tornado-attributed deaths through a retrospective review of hospital morbidity and mortality records. The Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) analyzed the sensitivity, timeliness, and validity for three EFMs, which included: (1) a tornado-specific flag on the death record; (2) a tornado-related term in the death certificate; and (3) X37, the International Classification of Diseases, 10th Revision (ICD-10) code in the death record for Victim of a Cataclysmic Storm, which includes tornadoes.
The flag was the most sensitive EFM (89.6%; 43/48), followed by the tornado term (75.0%; 36/48), and the X37 code (56.2%; 27/48). The most-timely EFM was the flag, which took 2.0 median days to report (range 0-10 days), followed by the tornado term (median 3.5 days; range 1-21), and the X37 code (median >10 days; range 2-122). Over one-half (52.1%; 25/48) of the tornado-attributed deaths were missing at least one EFM. Twenty-six percent (11/43) of flagged records had no tornado term, and 44.1% (19/43) had no X37 code. Eleven percent (4/36) of records with a tornado term did not have a flag.
The tornado-specific flag was the most sensitive and timely EFM. Using the flag to collate death records and identify additional deaths without the tornado term and X37 code may improve immediate response and retrospective investigations. Moreover, each of the EFMs can serve as quality controls for the others to maximize capture of all disaster-attributed deaths from vital statistics records in the EDRS.
Issa AN, Baker K, Pate D, Law R, Bayleyegn T, Noe RS. Evaluation of Oklahoma’s Electronic Death Registration System and event fatality markers for disaster-related mortality surveillance – Oklahoma USA, May 2013. Prehosp Disaster Med. 2019;34(2):125–131
This article presents an analysis of how activists, politicians, and the media framed youth involvement in the sex trade during the 1970s, the 1990s, and the 2000s in the United States. Across these periods of public concern about the issue, similar framing has recurred that has drawn upon gendered and racialized notions of victimization and perpetration. This frame has successfully brought attention to this issue by exploiting public anxieties at historical moments when social change was threatening white male dominance. Using intersectional feminist theory, I argue that mainstream rhetoric opposing the youth sex trade worked largely within neoliberal logics, ignoring histories of dispossession and structural violence and reinforcing individualistic notions of personhood and normative ideas about subjectivity and agency. As part of the ongoing project of racial and gender formation in US society, this discourse has shored up neoliberal governance, particularly the build-up of the prison industrial complex, and it has obscured the state's failure to address the myriad social problems that make youth vulnerable to the sex trade.
Here we present the synthesis of porous platinum–palladium macrobeams templated from high aspect ratio Magnus’ salt needle derivatives. The combination of [PtCl4]2− and/or [PdCl4]2− with [Pt(NH3)4]2+ ions results in salt needles ranging from 15 to 300 µm in length. Electrochemical reduction of the salt templates results in porous macrobeams with a square cross-section. Porous side wall texture and elemental composition was controlled with initial platinum to palladium salt ratio. Macrobeam free-standing films exhibited a specific capacitance up to 11.73 F/g and a solvent accessible surface area of 26.6 m2/g. These salt-templated porous platinum–palladium macrobeams offer a promising material for fuel cell catalysis.