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Centanafadine (CTN) is a potential first-in-class norepinephrine/dopamine/serotonin triple reuptake inhibitor (NDSRI). The efficacy, safety, and tolerability of CTN sustained release (SR) for adults with ADHD was demonstrated in 2 pivotal phase 3 trials (Adler LA, et al. J Clin Psychopharmacol. 2022;42:429-39).
Methods
Adults (18–55 years) meeting DSM-5 criteria for ADHD enrolled in these double-blind, multicenter, placebo-controlled trials and randomized to treatment if ADHD Investigator Symptom Rating Scale (AISRS) score was ≥28 at screening (if not receiving pharmacologic treatment for ADHD) or ≥22 at screening and ≥28 at baseline (BL) (if receiving treatment). Having had no prior benefit from ≥2 ADHD therapies of 2 different classes, taking prohibited medications, and positive alcohol/drug screen were exclusionary. Trials had 4 periods: (1) screening and washout (≤28 days), (2) single-blind placebo run-in (1 week), (3) double-blind treatment (6 weeks), and (4) follow-up (10 days after last dose). Patients with ≥30% improvement in the Adult ADHD Self-report Scale (ASRS) from start to end of screening were screen failures; those with ≥30% ASRS improvement from start to end of placebo run-in were terminated early. Patients were randomized 1:1:1 to twice-daily CTN SR (200 or 400 mg total daily dose [TDD]) or matching placebo. The 200 mg/d group received CTN SR 200 mg TDD from days 1–42; the 400 mg/d group received 200 mg TDD on days 1–7, and increased to 400 mg TDD on day 8. This analysis assessed CTN SR effects based on median BL AISRS severity score (<38 or ≥38) using a mixed model for repeated measures analysis. Least squares mean (LSM) differences (95% CI) from BL at day 42 were compared between individual CTN SR dose groups and placebo, tested at a 2-sided significance level of 0.05.
Results
In total, 859 patients were randomized (200 mg TDD, n=287; 400 mg TDD, n=287; placebo, n=285). Significant LSM differences on the AISRS were observed vs placebo in the overall population (200 mg TDD and 400 mg TDD, P<0.0001 for each), in the low BL severity (200 mg TDD [P=0.016]; 400 mg TDD [P=0.019]), and in the high BL severity (200 mg TDD [P=0.005]; 400 mg TDD [P=0.003]) populations at day 42. Significant LSM differences vs placebo (P<0.01) began at day 7 (200 mg) and day 14 (400 mg) overall, remaining significant to day 42. Significant LSM differences were observed vs placebo (P<0.05) from day 14 (400 mg TDD) and day 21 (200 mg) in the low severity populations, and from day 21 (400 mg TDD) and day 7 (200 mg TDD) in the high severity population, remaining significant (P<0.05) to day 42.
Conclusions
CTN SR, a potential first-in-class NDSRI, is efficacious for patients with adult ADHD of low or high BL symptom severity, with significant improvements observed vs placebo within the first 3 weeks.
The new species Caloplaca tswaluensis is described from Tswalu Kalahari Reserve, Northern Cape Province, South Africa. Caloplaca tswaluensis occurs on the trunks of Vachellia erioloba (camelthorn) trees and is characterized by its 3-septate to quadrilocular ascospores. Molecular data indicate that the new species is placed in the subfamily Teloschistoideae but cannot be assigned to any existing genus and, because its systematic position is unclear, we choose to describe it in Caloplaca s. lat. Caloplaca tswaluensis is compared with other crustose Teloschistaceae species with plurilocular ascospores.
OBJECTIVES/GOALS: Early diagnosis of congenital sensorineural hearing loss (SNHL) is of paramount importance in preventing speech and language impairment.Diffusion tensor imaging (DTI) MRI can identify brain microstructural changes that may potentially contribute towards prognosticating rehabilitation. METHODS/STUDY POPULATION: We retrospectively reviewed pediatric patients with SNHL who obtained DTI MRI between 2011 and 2019, identifying 16 pediatric patients (age <18 years) with at least moderate asymmetric/bilateral SNHL., and gender-matched controlswithout neurological, developmental, or MRI-based brain macrostructural abnormalities. The following brainstem regions and tracts of the auditory pathway were assessed: superior olivary nucleus (SON), inferior colliculus (IC), ipsilateral tracts between the inferior colliculus and superior olivary nucleus (IC-SON). Diffusion values for bilateral regions and tracts were generated, then averaged to calculate a mean value for fractional anisotropy (FA) and mean diffusivity (MD) for each subject. RESULTS/ANTICIPATED RESULTS: Significant differences were identified in FA values of the SON between the SNHL cohort and controls (0.377±0.056 vs 0.422±0.052; p=0.009). No other FA or MD values were significantly different. In children £5 years, MD was significantly decreased in the SNHL cohort compared to controls in the IC (0.918±0.051 vs 1.120±0.142; p<0.001). In children >5 years, there were no significant differences in MD (1.124±0.198 vs 0.997±0.103; p = 0.119). There were no significant differences in MD or FA in the white matter fibers of the IC-SON tract [applewebdata%3A//720AAF0C-C4CF-459C-A42A-6BAA56C4E4CA#_msocom_2]. DISCUSSION/SIGNIFICANCE: This is the first study to assess microstructural changes in brainstem auditory pathway regions among children with SNHL. Longitudinal studies are warranted to assess the predictive value of DTI imaging for long-term outcomes and prognosticating intervention.
OBJECTIVES/GOALS: Diffusion MRI can identify microstructural brain changes and can provide insight into neural development and to potentially prognosticate speech and language outcomes in children with SNHL. The goal of our study was to investigate MRI-based microstructural changes along the brainstem regions of the auditory pathway in pediatric patients with SNHL. METHODS/STUDY POPULATION: We reviewed cohort of pediatric patients with SNHL who obtained MRI at 3T between 2011 and 2019. We identified 16 pediatric patients (age RESULTS/ANTICIPATED RESULTS: We identified significant differences in FA values of the SON between the SNHL cohort and controls (0.377 ± 0.056 vs 0.422 ± 0.052; p=0.009). No other FA or MD values were significantly different between the two groups. Among younger children (ï‚£5 years), MD was significantly decreased in the SNHL cohort compared to controls in the IC (0.918 ± 0.051 vs 1.120 ± 0.142; p5 years), there were no significant differences in MD (1.124 ± 0.198 vs 0.997 ± 0.103; p = 0.119). There were no significant differences in MD or FA in the white matter fibers of the IC-SON tract. DISCUSSION/SIGNIFICANCE: This study is the first to assess microstructural changes in brainstem auditory pathway regions among children with SNHL. Longitudinal studies are warranted to assess the predictive value of these MRI-based findings for long-term outcomes and the efficacy of intervention.
The Very High Frequency (VHF) Data Exchange System (VDES) is a new radio communication system being developed by the international maritime community, with the principal objectives to safeguard existing Automatic Identification System (AIS) core functions and enhance maritime communication applications, based on robust, efficient and secure data transmission with wider bandwidth than the AIS. VDES is also being considered as a potential component of the R-mode concept, where the same signals used for communication are also used for ranging, thus mitigating the impact of disruptions to satellite positioning services. This paper establishes statistical performance bounds on the ranging precision of VDES R-mode, assuming an additive white Gaussian noise propagation channel. Modified Cramér-Rao bounds on the pseudorange estimation error are provided for all waveforms currently proposed for use in terrestrial VDES communications. These are then used to estimate the maximum usable ranges for AIS/VDES R-mode stations. The results show that, under the assumed channel conditions, all of the new VDES waveforms provide better ranging performance than the AIS waveform, with the best performance being achieved using the 100 kHz bandwidth terrestrial VDE waveforms.
Integrated pest management (IPM) initially focused on insect pest control. More recently, IPM encompasses a broader concept of management, one which crosses several disciplinary boundaries. This article reports results of research dealing with four integrated management decisions for alfalfa (cultivar selection, inset control, weed control, and end-of-season harvest options).
We have begun a series of laboratory experiments focused on understanding how coronal mass ejections (CME) interact and evolve in the solar wind. The experiments make use of the Helicon-Cathode (HelCat) plasma facility, and the Plasma Bubble eXperiment (PBeX). PBeX can generate CME-like structures (sphereomak geometry) that propagate into the high-density, magnetized background plasma of the HelCat device. The goal of the current research is to compare CME evolution under conditions where there is sheared flow in the background plasma, versus without flow; observations suggest that CME evolution is strongly influenced by such sheared flow regions. Results of these studies will be used to validate numerical simulations of CME evolution, in particular the 3D BATS-R-US MHD code of the University of Michigan. Initial studies have characterized the plasma bubble as it evolves into the background field with and without plasma (no shear).
Originally published in 1985, this book is concerned with the housing and service needs of the poor in Latin America and how they are articulated and satisfied. It examines the aims and implementation of government policies towards low-income housing dwellers and tries to relate those policies to the wider interests of the state. It discusses how the poor perceive the constraints on barrio servicing and improvement, their involvement in community organisations and the role the community and its leaders play in influencing state action. Since housing and servicing issues directly impinge on the interests of politicians, bureaucrats, landowners and real-estate developers, as well as on those of the poor, patterns of provision mirror closely the nature of the relationships between the poor and the wider urban society. The main theme of this book is thus the allocation of resources within urban society and the operation of political and administrative power at city level. The book will interest not only those concerned with housing and planning but also those who wish to understand social and economic policies towards the poor in most kinds of Third World city.
The purpose of the present research was to examine the perceptions of risk regarding falling held by older adults and their adult children. Using a focused ethnographic approach, older adults and adult children were interviewed in depth. Thematic analysis was conducted to identify themes within groups and to compare the perspectives of older adults and adult children. Findings highlighted differences in perceptions and approaches to action between older adults and their adult children. There were three approaches to action adopted by these families, which focused around whose actions were dominant: parents' actions, shared actions, and children's secret actions. The results emphasize the value placed on independence by older adults and the impact of multiple family relations taking action to prevent falls. The present study points to the importance of including multiple family perspectives in research concerning injury prevention for older adults.
Eating Out, first published in 2000, is a fascinating study of the consumption of food outside the home, based on extensive original research carried out in England in the 1990s. Reflecting the explosion of interest in food, ranging from food scares to the national obsession with celebrity chefs, the practice of eating out has increased dramatically over recent years. Through surveys and intensive interviews, the authors have collected a wealth of information into people's attitudes towards, and expectations of, eating out as a form of entertainment and an expression of taste and status. Amongst other topics they examine social inequalities in access to eating out, social distinction, interactions between customers and staff, and the economic and social implications of the practice. Eating Out will be a valuable resource to academics, advanced students and practitioners in the sociology of consumption, cultural studies, social anthropology, tourism and hospitality, home economics, marketing, and the general reader.
Versions of this paper were first presented at the Royal Institute of Navigation GNSS Vulnerabilities and Solutions Conference held at Baska, Croatia in September 2008 and the Royal Institute of Navigation NAV 08 Conference held at Church House, Westminster, London in October 2008.
The US Global Positioning System (GPS) is currently the primary source of Position, Navigation and Timing (PNT) information in maritime applications, whether stand-alone or augmented with additional systems. This situation will continue in the future with GPS, possibly together with other Global Navigation Satellite Systems (GNSS) e.g. Galileo, being the core PNT technology for e-Navigation – the future digital maritime architecture. GPS signals, measured at the surface on the Earth, are very weak. As such, the system is vulnerable to unintentional interference and jamming, resulting in possible denial of service over large geographical areas. The result of such interference could be the complete failure of the mariner's GPS receiver or, possibly worse, the presentation to the mariner of hazardously misleading information (HMI) for navigation and situational awareness, depending on how the GPS receiver reacts to the jamming incident. Recognising this, the General Lighthouse Authorities of the United Kingdom and Ireland (GLA), in collaboration with the UK Ministry of Defence (MOD) Defence Science and Technology Laboratory (DSTL), have conducted a series of sea-trials with the aim of identifying the full effects of GPS jamming on safe navigation at sea.
This paper presents the key findings of these trials and provides important information on the effect of GPS denial. The GLA are playing a pivotal role in the establishment of eLoran as an independent source of PNT, taking advantage of eLoran's complementary nature, having dissimilar failure modes to GPS and the future GNSS. This paper provides information on the performance of an eLoran receiver in an area of GPS service denial. The paper presents the rationale for the work, details the system architecture employed, the data gathering efforts and finally the data analysis procedures, results and conclusions.
This paper examines a town in northwest England and a particular set of conditions that inhibited the growth of working-class politics during the twentieth century. The paradox of class politics in Lancaster is that despite a proletarian population, the labour movement locally remained extremely weak. Ironically, it was only upon the deindustrialisation of the town in the later 1960s that labour showed any collective strength. Explanation of quiescence in terms of paternalism and deference is rejected. Rather an account is given in terms of powerlessness. Local structural conditions rendered Lancaster workers so highly dependent that resistance to political domination was precluded.
The maritime radiobeacon differential GNSS service in Europe has recently been reorganised with the aim of having at least two of the 162 stations serve each critical coastal location. Maritime administrations have now set specifications for the availability and continuity of the service. The paper analyses these requirements, noting incompatibilities between them. It proposes a method of predicting the performance of beacons, employing IALA standards. This takes into account each beacon's own availability, and propagation factors that include groundwave signal attenuation, interference, and skywave fading at night. Availability, continuity and coverage maps produced by the new programs are presented in the paper.
This Note uses the British Household Panel Study (BHPS) to consider the changing volume and distribution of voluntary association membership (and hence social capital) in Great Britain. We aim to supplement Hall's study of trends in social capital published in this Journal with more recent and longitudinal data. This allows us to show that whilst the volume of social capital is not declining, it is becoming increasingly class specific, and that its relative aggregate stability masks considerable turnover at the individual level. These findings are significant for current debates on social capital.