Beyond the pill: New medication delivery options for ADHD

Successful treatment of pediatric disorders has necessitated the development of alternative medication formulations, as children may prefer alternative dosage forms to tablets or capsules. This is especially true for attention-deficit/hyperactivity disorder (ADHD), which is one of the most common chronic pediatric conditions and often involves children with a variety of overlapping physical, psychological, or neurodevelopmental disorders. A special challenge for developing alternative dosage forms for ADHD treatment is the incorporation of a once-daily long-acting formulation. Traditional ADHD medication formulations have been limited, and issues surrounding prescribed dosing regimens—including poor medication adherence, difficulty swallowing, and the lack of dosing titration options—persist in ADHD treatment. In other disease areas, the development of alternative formulations has provided options for patients who have issues with consuming solid dosage forms, particularly children and individuals with developmental disorders. In the light of these new developments, several alternative formulations for ADHD medications are under development or have recently become available. This article reviews the various strategies for developing alternative dosage forms in other disease areas and discusses the application of these strategies in ADHD treatment. Alternative dosage forms may increase medication adherence, compliance, and patient preference and, therefore, improve the overall treatment for ADHD.</jats:p

Public knowledge about polar regions increases while concerns remain unchanged

The authors of this brief conduct the first comparative analysis of the polar questions that were part of the National Opinion Research Center\u27s 2006 and 2010 General Social Survey. Developed by scientists at the National Science Foundation\u27s Office of Polar Programs, these questions covered topics such as climate change, melting ice and rising sea levels, and species extinction. The authors report that the public\u27s knowledge about the north and south polar regions significantly improved between 2006 and 2010--before and after the International Polar Year. In addition, respondents who know more about science in general, and polar facts specifically, tend to be more concerned about polar changes. More knowledgeable respondents also tend to favor reserving the Antarctic for science, rather than opening it for commercial development

Sensitivity to speech rhythm explains individual differences in reading ability independently of phonological awareness

This study considered whether sensitivity to speech rhythm can predict concurrent variance in reading attainment after individual differences in age, vocabulary and phonological awareness have been controlled. Five to six-year-old English-speaking children completed a battery of phonological processing assessments and reading assessments, along with a simple word stress manipulation task. The results showed that performance on the stress manipulation measure predicted a significant amount of variance in reading attainment after age, vocabulary, and phonological processing had been taken into account. These results suggest that stress sensitivity is an important, yet neglected aspect of English-speaking children?s phonological representations, which needs to be incorporated into theoretical accounts of reading development

Fuel-Air Mixing and Combustion in Scramjets

At flight speeds, the residence time for atmospheric air ingested into a scramjet inlet and exiting from the engine nozzle is on the order of a millisecond. Therefore, fuel injected into the air must efficiently mix within tens of microseconds and react to release its energy in the combustor. The overall combustion process should be mixing controlled to provide a stable operating environment; in reality, however, combustion in the upstream portion of the combustor, particularly at higher Mach numbers, is kinetically controlled where ignition delay times are on the same order as the fluid scale. Both mixing and combustion time scales must be considered in a detailed study of mixing and reaction in a scramjet to understand the flow processes and to ultimately achieve a successful design. Although the geometric configuration of a scramjet is relatively simple compared to a turbomachinery design, the flow physics associated with the simultaneous injection of fuel from multiple injector configurations, and the mixing and combustion of that fuel downstream of the injectors is still quite complex. For this reason, many researchers have considered the more tractable problem of a spatially developing, primarily supersonic, chemically reacting mixing layer or jet that relaxes only the complexities introduced by engine geometry. All of the difficulties introduced by the fluid mechanics, combustion chemistry, and interactions between these phenomena can be retained in the reacting mixing layer, making it an ideal problem for the detailed study of supersonic reacting flow in a scramjet. With a good understanding of the physics of the scramjet internal flowfield, the designer can then return to the actual scramjet geometry with this knowledge and apply engineering design tools that more properly account for the complex physics. This approach will guide the discussion in the remainder of this section

Current and future nonstimulants in the treatment of pediatric ADHD: Monoamine reuptake inhibitors, receptor modulators, and multimodal agents

Attention-deficit/hyperactivity disorder (ADHD), the single most common neuropsychiatric disorder with cognitive and behavioral manifestations, often starts in childhood and usually persists into adolescence and adulthood. Rarely seen alone, ADHD is most commonly complicated by other neuropsychiatric disorders that must be factored into any intervention plan to optimally address ADHD symptoms. With more than 30 classical Schedule II (CII) stimulant preparations available for ADHD treatment, only three nonstimulants (atomoxetine and extended-release formulations of clonidine and guanfacine) have been approved by the United States Food and Drug Administration (FDA), all of which focus on modulating the noradrenergic system. Given the heterogeneity and complex nature of ADHD in most patients, research efforts are identifying nonstimulants which modulate pathways beyond the noradrenergic system. New ADHD medications in clinical development include monoamine reuptake inhibitors, monoamine receptor modulators, and multimodal agents that combine receptor agonist/antagonist activity (receptor modulation) and monoamine transporter inhibition. Each of these pipeline ADHD medications has a unique chemical structure and differs in its pharmacologic profile in terms of molecular targets and mechanisms. The clinical role for each of these agents will need to be explored with regard to their potential to address the heterogeneity of individuals struggling with ADHD and ADHD-associated comorbidities. This review profiles alternatives to Schedule II (CII) stimulants that are in clinical stages of development (Phase 2 or 3). Particular attention is given to viloxazine extended-release, which has completed Phase 3 studies in children and adolescents with ADHD

Impact of small-scale vegetation structure on tephra layer preservation.

The factors that influence tephra layer taphonomy are poorly understood, but vegetation cover is likely to play a role in the preservation of terrestrial tephra deposits. The impact of vegetation on tephra layer preservation is important because: 1) the morphology of tephra layers could record key characteristics of past land surfaces and 2) vegetation-driven variability in tephra thickness could affect attempts to infer eruption and dispersion parameters. We investigated small- (metre-) scale interactions between vegetation and a thin (<10 cm), recent tephra layer. We conducted surveys of vegetation structure and tephra thickness at two locations which received a similar tephra deposit, but had contrasting vegetation cover (moss vs shrub). The tephra layer was thicker and less variable under shrub cover. Vegetation structure and layer thickness were correlated on the moss site but not under shrub cover, where the canopy reduced the influence of understory vegetation on layer morphology. Our results show that vegetation structure can influence tephra layer thickness on both small and medium (site) scales. These findings suggest that some tephra layers may carry a signal of past vegetation cover. They also have implications for the sampling effort required to reliably estimate the parameters of initial deposits

Serdexmethylphenidate/dexmethylphenidate effects on sleep in children with attention-deficit/hyperactivity disorder

IntroductionSleep-related problems are common in children with attention-deficit/hyperactivity disorder (ADHD). Sleep disorders are also side effects of all stimulant ADHD medications. Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is a once-daily treatment approved for patients age 6 years and older with ADHD. In this analysis, sleep behavior was assessed during SDX/d-MPH treatment in children with ADHD.MethodsIn a 12-month, dose-optimized, open-label safety study in 6- to 12-year-old participants (NCT03460652), a secondary endpoint was assessment of sleep behavior based on the Children’s Sleep Habits Questionnaire (CSHQ) consisting of 8 sleep domains (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness). This post hoc analysis examined the individual sleep domains in the 12-month safety study.ResultsOf 282 participants enrolled, 238 were included in the sleep analysis. At baseline, mean (SD) CSHQ total sleep disturbance score was 53.4 (5.9). After 1 month of treatment, the mean (SD) CSHQ total score significantly decreased to 50.5 (5.4); least-squares mean change from baseline was −2.9 (95% CI: −3.5 to −2.4; p &lt; 0.0001) and remained decreased up to 12 months. Mean sleep-score improvements from baseline to 12 months were statistically significant (p &lt; 0.0001) for 5 of 8 sleep domains, including bedtime resistance, sleep anxiety, night wakings, parasomnias, and daytime sleepiness. Parasomnias and daytime sleepiness sleep domains showed the greatest mean improvement from baseline to 12 months. Sleep onset delay and sleep duration scores increased from baseline to 12 months. No statistically significant worsening occurred from baseline in sleep duration and sleep-disordered breathing domains; however, worsening of sleep onset delay was statistically significant.ConclusionIn this analysis of children taking SDX/d-MPH for ADHD, sleep problems did not worsen based on the mean CSHQ total sleep disturbance score. Statistically significant improvements in most CSHQ sleep domains were observed after 1 month and lasted for up to 12 months of treatment

Variations in tephra stratigraphy created by small-scale surface features in sub-polar landscapes

Financial support for this work was provided by NERC Doctoral Training Partnership Ph.D. studentship NE/L002558/1 to Polly I. J. Thompson.We explore the effect small-scale surface features have on influencing the morphology and grain-size distribution (GSD) of tephra layers within the Quaternary stratigraphy of sub-polar landscapes. Icelandic thúfur, small cryogenic earth mounds, are used to assess how and why the morphology and GSD of tephra layers vary over such formations. Through measurement of tephra layer thickness and GSD, Hekla 1947 and Grímsvötn 2011 tephra layers are analysed. Results indicate that such microtopographic features do indeed alter the form of tephra deposits and therefore the tephra layer that is preserved in the stratigraphy. Tephra thickness is significantly greater in hollows than on the thúfur crests. There is greater variation in tephra thickness measurements from thúfur in comparison to control measurements from a surface where thúfur are absent. Thúfur crests contain larger grain sizes than hollows, for both H1947 and G2011 tephras; however this was only statistically significant for the G2011 tephra. Such morphological patterns are thought to arise from an interplay of tephra characteristics, altered topography from the thúfur formations and earth surface processes operating at the sites. This study provides insight into the potential of tephra layer morphology and internal structures as indicators of Quaternary landforms and processes. Additionally, it provides important context for the appropriate sampling of tephra layers to infer volcanological processes, as the characteristics of preserved layers do not necessarily reflect those of the original fall-out.Publisher PDFPeer reviewe

Collisions of boosted black holes: perturbation theory prediction of gravitational radiation

We consider general relativistic Cauchy data representing two nonspinning, equal-mass black holes boosted toward each other. When the black holes are close enough to each other and their momentum is sufficiently high, an encompassing apparent horizon is present so the system can be viewed as a single, perturbed black hole. We employ gauge-invariant perturbation theory, and integrate the Zerilli equation to analyze these time-asymmetric data sets and compute gravitational wave forms and emitted energies. When coupled with a simple Newtonian analysis of the infall trajectory, we find striking agreement between the perturbation calculation of emitted energies and the results of fully general relativistic numerical simulations of time-symmetric initial data.Comment: 5 pages (RevTex 3.0 with 3 uuencoded figures), CRSR-107

How does tephra deposit thickness change over time? A calibration exercise based on the 1980 Mount St Helens tephra deposit

Tephra layers are frequently used to reconstruct past volcanic activity. Inferences made from tephra layers rely on the assumption that the preserved tephra layer is representative of the initial deposit. However, a great deal can happen to tephra after it is deposited; thus, tephra layer taphonomy is a crucial but poorly understood process. The overall goal of this research was to gain greater insight into the taphonomy of terrestrial tephra layers. We approached this by a) conducting a new survey of the tephra layer from the recent, well-studied eruption of Mount St Helens on May 18th, 1980 (MSH1980); b) modelling the tephra layer thickness using an objective mathematical technique and c) comparing our results with an equivalent model based on measurements taken immediately after the eruption. In this way, we aimed to quantify any losses and transformations that have occurred. During our study, we collected measurements of tephra layer thickness from 86 locations ranging from 600 km from the vent. Geochemical analysis was used to verify the identity of tephra of uncertain origin. Our results indicated that the extant tephra layer at undisturbed sites was representative of the original deposit: overall, preservation in these locations (in terms of thickness, stratigraphy and geochemistry) had been remarkably good. However, isopach maps generated from our measurements diverged from isopachs derived from the original survey data. Furthermore, our estimate of the quantity of tephra produced during eruption greatly exceeded previous estimates of the fallout volume. In this case, inaccuracies in the modelled fallout arose from issues of sampling strategy, rather than taphonomy. Our results demonstrate the sensitivity of volcanological reconstructions to measurement location, and the great importance of reliably measured low/zero values in reconstructing tephra deposits