A systematic review of the safety of lisdexamfetamine dimesylate

BACKGROUND: Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). RESULTS: In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX. CONCLUSIONS: The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants

Continuous symmetry of C60 fullerene and its derivatives

Conventionally, the Ih symmetry of fullerene C60 is accepted which is supported by numerous calculations. However, this conclusion results from the consideration of the molecule electron system, of its odd electrons in particular, in a close-shell approximation without taking the electron spin into account. Passing to the open-shell approximation has lead to both the energy and the symmetry lowering up to Ci. Seemingly contradicting to a high-symmetry pattern of experimental recording, particularly concerning the molecule electronic spectra, the finding is considered in the current paper from the continuous symmetry viewpoint. Exploiting both continuous symmetry measure and continuous symmetry content, was shown that formal Ci symmetry of the molecule is by 99.99% Ih. A similar continuous symmetry analysis of the fullerene monoderivatives gives a reasonable explanation of a large variety of their optical spectra patterns within the framework of the same C1 formal symmetry exhibiting a strong stability of the C60 skeleton.Comment: 11 pages. 5 figures. 6 table

Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder:results from a randomized, controlled trial

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6–17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners’ Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment − placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours)

A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance

Mitochondrial energy metabolism plays an important role in the pathophysiology of insulin resistance. Recently, a missense N437S variant was identified in the MRPP3 gene, which encodes a mitochondrial RNA processing enzyme within the RNase P complex, with predicted impact on metabolism. We used CRISPR-Cas9 genome editing to introduce this variant into the mouse Mrpp3 gene and show that the variant causes insulin resistance on a high-fat diet. The variant did not influence mitochondrial gene expression markedly, but instead, it reduced mitochondrial calcium that lowered insulin release from the pancreatic islet β cells of the Mrpp3 variant mice. Reduced insulin secretion resulted in lower insulin levels that contributed to imbalanced metabolism and liver steatosis in the Mrpp3 variant mice on a high-fat diet. Our findings reveal that the MRPP3 variant may be a predisposing factor to insulin resistance and metabolic disease in the human population

Toward a global description of the nucleus-nucleus interaction

Extensive systematization of theoretical and experimental nuclear densities and of optical potential strengths exctracted from heavy-ion elastic scattering data analyses at low and intermediate energies are presented.The energy-dependence of the nuclear potential is accounted for within a model based on the nonlocal nature of the interaction.The systematics indicate that the heavy-ion nuclear potential can be described in a simple global way through a double-folding shape,which basically depends only on the density of nucleons of the partners in the collision.The poissibility of extracting information about the nucleon-nucleon interaction from the heavy-ion potential is investigated.Comment: 12 pages,12 figure

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

Improved dd+4^4He potentials by inversion, the tensor force and validity of the double folding model

Improved potential solutions are presented for the inverse scattering problem for $d$+$^4$He data. The input for the inversions includes both the data of recent phase shift analyses and phase shifts from RGM coupled-channel calculations based on the NN Minnesota force. The combined calculations provide a more reliable estimate of the odd-even splitting of the potentials than previously found, suggesting a rather moderate role for this splitting in deuteron-nucleus scattering generally. The approximate parity-independence of the deuteron optical potentials is shown to arise from the nontrivial interference between antisymmetrization and channel coupling to the deuteron breakup channels. A further comparison of the empirical potentials established here and the double folding potential derived from the M3Y effective NN force (with the appropriate normalisation factor) reveals strong similarities. This result supports the application of the double folding model, combined with a small Majorana component, to the description even of such a loosely bound projectile as the deuteron. In turn, support is given for the application of iterative-perturbative inversion in combination with the double folding model to study fine details of the nucleus-nucleus potential. A $d$-$^4$He tensor potential is also derived to reproduce correctly the negative $^6$Li quadrupole moment and the D-state asymptotic constant.Comment: 22 pages, 12 figures, in Revte

Socially impaired robots: Human social disorders and robots’ socio-emotional intelligence

© Springer International Publishing Switzerland 2014. Social robots need intelligence in order to safely coexist and interact with humans. Robots without functional abilities in understanding others and unable to empathise might be a societal risk and they may lead to a society of socially impaired robots. In this work we provide a survey of three relevant human social disorders, namely autism, psychopathy and schizophrenia, as a means to gain a better understanding of social robots’ future capability requirements.We provide evidence supporting the idea that social robots will require a combination of emotional intelligence and social intelligence, namely socio-emotional intelligence. We argue that a robot with a simple socio-emotional process requires a simulation-driven model of intelligence. Finally, we provide some critical guidelines for designing future socio-emotional robots

Stability-indicating liquid chromatographic and UV spectrophotometric methods for the quantification of ciprofibrate in capsules and tablets

This study describes the development and evaluation of stability-indicating liquid chromatographic (LC) and UV spectrophotometric methods for the quantification of ciprofibrate (CPF) in tablets and capsules. Isocratic LC separation was achieved on a RP18 column using a mobile phase of o-phosphoric acid (0.1% v/v), adjusted to pH 3.0 with triethylamine (10% v/v) and acetonitrile (35:65 v/v), with a flow rate of 1.0 mL min-1. Detection was achieved with a photodiode array detector at 233 nm. For the spectrophotometric analysis, ethanol and water were used as the solvent and a wavelength of 233 nm was selected for the detection. The methods were validated according to International Conference on Harmonization (ICH) guidelines for validating analytical procedures. Statistical analysis showed no significant difference between the results obtained by the two methods. The proposed methods were successfully applied to the CPF quality-control analysis of tablets and capsules

Sensory over-responsivity: parent report, direct assessment measures, and neural architecture

BACKGROUND: Sensory processing difficulties are common across neurodevelopmental disorders. Thus, reliable measures are needed to understand the biological underpinnings of these differences. This study aimed to define a scoring methodology specific to auditory (AOR) and tactile (TOR) over-responsivity. Second, in a pilot cohort using MRI Diffusion Tensor Imaging, we performed a proof of concept study of whether children with AOR showed measurable differences in their white matter integrity. METHODS: This study included children with AOR and TOR from a mixed neurodevelopmental disorder cohort including autism and sensory processing dysfunction (n = 176) as well as neurotypical children (n = 128). We established cohorts based on sensory over-responsivity using parent report (Short Sensory Profile (SSP)) and direct assessment (Sensory Processing-Three Dimensions: Assessment (SP-3D:A)) measures. With a subset of the children (n = 39), group comparisons, based on AOR phenotype, were conducted comparing the white matter fractional anisotropy in 23 regions of interest. RESULTS: Using direct assessment, 31% of the children with neurodevelopmental disorders had AOR and 27% had TOR. The inter-test agreement between SSP and SP-3D:A for AOR was 65% and TOR was 50%. Children with AOR had three white matter tracts showing decreased fractional anisotropy relative to children without AOR. CONCLUSIONS: This study identified cut-off scores for AOR and TOR using the SSP parent report and SP-3D:A observation. A combination of questionnaire and direct observation measures should be used in clinical and research settings. The SSP parent report and SP-3D:A direct observation ratings overlapped moderately for sensory related behaviors. Based on these preliminary structural neuroimaging results, we suggest a putative neural network may contribute to AOR