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This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury.
203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8–18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1–11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (∼4 months) phase.
Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not.
The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.
During and after the Crimean annexation in March 2014, Russia witnessed a huge increase in support for President Vladimir Putin (Hale, 2018). More importantly for events on the ground, however, this rally was not limited to changes in political approval: it extended to the mobilization of large numbers of volunteers, donors and sympathizers in support of military action outside the country’s borders. Both online and offline, a surge of activism was unleashed to strengthen, militarily and ideologically, the claim that Crimea and eastern Ukraine were somehow a natural part of Russia that had been accidentally and wrongly alienated by the idiosyncrasies of the collapse of the USSR (Matveeva, 2018). Two names that came to be adopted by the movement, “Russian Spring”/“Novorossiya,” reflect the intertwined ideas of a revival of ethnic Russian consciousness, the return of a previously dormant Russia back onto the international stage, and the tsarist-era basis of the Russian claim to much of what is today southern and eastern Ukraine.
Although lignin has been negatively correlated with neutral-detergent fibre (NDF) digestibility (NDFD) in ruminants and used to predict potential extent of NDF digestion of forages, selection of an analysis, Klason lignin (KL) or acid-detergent lignin (ADL), to describe that the nutritionally relevant lignin has not been resolved. Dismissed as an artifact is the difference between KL and ADL (ΔL). A question is whether ΔL influences NDFD. We evaluated the relationships of ΔL, KL and ADL with NDFD in order to determine the nutritionally homogeneous or heterogeneous nature of KL. Data sets from two laboratories (DS1 and DS2) were used that included ADL, KL and in vitro NDFD at 48 h (NDFD48). DS1 contained seven C3 grasses, seventeen C4 maize forages and nineteen alfalfas, and DS2 had fifteen C3 grasses, eight C4 forages and six alfalfas. Mean ΔL was greater than ADL in C3 and C4 samples and less in alfalfas. Within forage type and laboratory, ΔL was not correlated with NDFD48 (r −0·34–0·49; all P > 0·17). ADL was more consistently correlated with NDFD48 (r −0·47–−0·95; P < 0·01–0·21) than with KL (r 0·03–−0·91; P < 0·01–0·94). ΔL as a proportion of KL was correlated with NDFD48 in C3 and C4 samples (r 0·44–0·76; P < 0·01–0·08). The differing behaviours of ΔL and ADL relative to NDFD48 indicate that KL is a nutritionally heterogeneous fraction, the behaviour of which may vary by forage type and ratios of ADL and ΔL present.
GXR, a selective α2A-adrenergic agonist, is a non-stimulant treatment for ADHD (approved in the USA for children and adolescents and in Canada for children).
To assess the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD.
To evaluate the efficacy (symptom and function) and safety of GXR for the treatment of ADHD. An atomoxetine (ATX) arm was included to provide reference data against placebo (NCT01244490).
Patients (6–17 years) were randomly assigned at baseline to dose-optimized GXR (6–12 years, 1–4 mg/day; 13–17 years, 1–7 mg/day), ATX (10–100mg/day) or placebo for 4 or 7 weeks. The primary efficacy measure is change from baseline in ADHD-Rating Scale-version IV (ADHD-RS-IV). Key secondary measures were defined as Clinical Global Impressions-Improvement (CGI-I) and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P). Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs.
Of 338 patients randomized, 272 (80.5%) completed the study. Placebo-adjusted differences in least squares (LS) mean in ADHD-RS-IV total score, percent improvement versus placebo for CGI-I, placebo-adjusted differences in LS mean change from baseline in WFIRS-P score (family and learning and school domains) are shown in the Table. The most common TEAEs for GXR were somnolence, headache, and fatigue; 8 (7%) TEAEs were severe.
GXR was effective and well tolerated in children and adolescents with ADHD.
Placebo-adjusted difference in LS mean change from baseline in ADHD-RS-IV total score (95% Cl, p-value; effect size)
−8.9 (−11.9, −5.8, p<0.001; 0.76)
−3.8 (−6.8, −0.7, p<0.05; 0.32)
Difference in improvement from placebo for CGI-I (95% Cl, p-value)
23.7% (11.1, 36.4; p<0.001)
12.1% (−0.9, 25.1; p<0.05)
Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; learning and school domain score (95%CI, p-value; effect size)
−0.22 (−0.36, −0.08, p<0.01; 0.42)
−0.16 (−0.31, −0.02, p<0.05; 0.32)
Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; family domain score (95%CI, p-value; effect size)
GXR, a selective α2A-adrenergic agonist, is a non-stimulant ADHD treatment approved in the USA for children and adolescents, and in Canada for children.
To evaluate long-term maintenance of efficacy of GXR in children and adolescents with ADHD who respond to an initial open-label, short-term trial.
To determine if there is a higher rate of treatment failure for placebo vs GXR during the double-blind randomised-withdrawal phase (RWP) (NCT01081145).
Patients (6–17 years) meeting DSM-IV-TR criteria for ADHD, baseline ADHD Rating Scale-IV (ADHD-RS-IV) ≥32 and Clinical Global Impressions-Severity (CGI-S) ratings ≥4 were enrolled. Following 7-week dose optimization and 6-week maintenance periods on open-label GXR (1–7 mg/day), eligible patients entered a 26-week, double-blind, RWP with GXR or placebo. The primary endpoint was rate of treatment failure (≥50% increase in ADHD-RS-IV total score and ≥2-point increase in CGI-S at two consecutive visits, compared to the RWP baseline). The key secondary endpoint was time-to-treatment failure. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms and vital signs.
Of 528 patients enrolled, 316 (60.0%) entered the RWP. At study end, 49.3% (GXR) and 64.9% (placebo) (95%CI; −26.6, −4.5, p<0.01) of patients had relapsed (Figure). Time-to-treatment failure was 56 days (placebo) versus 218 days (GXR), p=0.003. During the RWP, the most common GXR TEAEs (≥5% patients) were headache, somnolence and nasopharyngitis.
GXR demonstrated long-term maintenance of efficacy versus placebo in children and adolescents with ADHD.
This anthology is the first sustained examination of American involvement in World War II through an environmental lens. World War II was a total and global war that involved the extraction, processing, and use of vast quantities of natural resources. The wartime military-industrial complex, the 'Arsenal of Democracy,' experienced tremendous economic growth and technological development, employing resources at a higher intensity than ever before. The war years witnessed transformations in American agriculture; the proliferation of militarized landscapes; the popularization of chemical and pharmaceutical products; a rapid increase in energy consumption and the development of nuclear energy; a remaking of the nation's transportation networks; a shift in population toward the Sunbelt and the West Coast; a vast expansion in the federal government, in conjunction with industrial firms; and the emergence of environmentalism. World War II represented a quantitative and qualitative leap in resource use, with lasting implications for American government, science, society, health, and ecology.