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Synchrotron radiation was used to obtain a high-resolution powder diffraction pattern of the high-density form of BeH2, a material whose unit-cell dimensions have not previously been determined. The observed d-spacing values were presented to three different computer indexing programs. All three programs returned as best solution a body-centered orthorhombic unit cell with a = 9.082, b = 4.160, c = 7.707 Å and V = 292 Å3. Interpretation of the three-dimensional Patterson led to 12 BeH2 molecules per unit cell; thus, the theoretical density is 0.755 g/cm3. The molecular structure is based on a network of corner-sharing BeH4 tetrahedra rather than flat, infinite chains with hydrogen bridges previously assumed.
Deutetrabenazine is approved for treating Huntington disease (HD) chorea and is being evaluated for tardive dyskinesia (TD).
To assess the effect of deutetrabenazine on cardiac repolarization.
A QT interval study was performed to evaluate effects of deutetrabenazine 12 and 24 mg on cardiac repolarization, as assessed by time-matched change from baseline, placebo-adjusted, in Fridericia-corrected QT interval (ΔΔQTcF). Moxifloxacin (400 mg) and tetrabenazine (50 mg) were the positive control and comparator, respectively. An exposure–response analysis was developed from this study to predict maximal effects on QTcF at maximum recommended dosing based on CYP2D6 status, an approach consistent with regulatory guidance at predicting QT interval effects.
Maximal ΔΔQTcF between the least-squares mean (90% two-sided confidence interval) of deutetrabenazine 12 and 24 mg (n=45 in each group) were 2.8 (0.7–4.8) ms and 4.5 (2.4–6.5) ms, respectively. The ΔΔQTcF increase with tetrabenazine (n=45) was 7.6 (5.6–9.5) ms. Assay sensitivity was verified with moxifloxacin (n=47), which produced a maximal effect on ΔΔQTcF of 14.0 (11.9–16.0) ms. A linear model was developed that described a correlation between plasma concentrations from pivotal HD andTD trials (n=101) and QT interval prolongation. Using that model and the individual predicted Cmax for HD and TD patients, the placebo-adjusted change from baseline inQTcF for deutetrabenazine at maximal recommended daily doses was found to be 5.4 (2.5–9.5) ms.
Patients receiving the maximal recommended doses of deutetrabenazine are predicted to have a QTcF increase below the level of regulatory concern.
Presented at: Psych Congress; September 16–19, 2017; New Orleans, Louisiana, USA.
This study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.
With specially computed detailed tables of equations of state and opacities, the instability strips for δ Scuti stars and Cepheids of population I and RR Lyrae and W Virginis stars of population II have been compared using the linear pulsation theory. Uncertainties in the observed strip locations and sometimes the mode of the observed pulsations do not allow high accuracy in fixing helium contents or the variables masses. Nevertheless, if masses close to those given by evolutionary theory are used, the helium content in population II objects is likely less than Y = 0.25. A helium content of close to zero would put the theoretical blue edge of the instability strip to the red of the observed red edge, and have all the hotter stars which are in the strip as non-pulsating. For population I, Y can be more than 0.3, (more than 0.4 if half evolutionary masses are used), but if a given star has Y less than about 0.2 (full mass) or 0.25 (half mass), it can appear in the dwarf and classical Cepheid strips as non-pulsating.
The model diatom Thalassiosira pseudonana is believed to be a single species with a global distribution, but it has not been confirmed previously whether isolates from different environmental and geographic origins are genotypically and phenotypically identical. In the present study, a polyphasic approach was employed to characterize nine clonal isolates, plus an additional replicate of one of the isolates, of the diatom T. pseudonana from culture collections to investigate whether there was any cryptic speciation in the publicly available strains of this species. Morphological analysis using scanning electron microscopy concluded that the strains were indistinguishable. Furthermore, conventional DNA barcoding genes (SSU rDNA, ITS1 and ITS2 rDNA and rbcL), revealed no nucleotide variation among the strains tested. On employing a whole genome fingerprinting technique, Amplified Fragment Length Polymorphism (AFLP), three clusters were revealed, although the level of variation between the clusters was surprisingly low. These findings indicate a low level of diversity among these cultured T. pseudonana strains, despite their wide spatial and temporal distribution and the salinity range of their original habitats. Based on the limited number of available strains, this suggests that T. pseudonana is a highly conserved diatom that nevertheless has an ability to tolerate wide ranges of salinity and populate varied geographic locations.
The miconia (Miconia calvescens) invasion of the East Maui Watershed (EMW) started from a single introduction over 40 yr ago, establishing a nascent patch network spread across 20,000 ha. In 2012, an accelerated intervention strategy was implemented utilizing the Herbicide Ballistic Technology (HBT) platform in a Hughes 500D helicopter to reduce target densities of seven nascent patches in the EMW. In a 14-mo period, a total of 48 interventions eliminated 4,029 miconia targets, with an estimated 33% increase in operations and 168% increase in recorded targets relative to the adjusted means from 2005 to 2011 data (prior to HBT adoption). This sequence of interventions covered a total net area of 1,138 ha, creating a field mosaic of overlapping search coverage (saturation) for each patch (four to eight interventions per patch). Target density reduction for each patch fit exponential decay functions (R2 > 0.88, P < 0.05), with a majority of the target interventions spatially assigned to the highest saturation fields. The progressive decay in target density led to concomitant reductions in search efficiency (min ha−1) and herbicide use rate (grams ae ha−1) in subsequent interventions. Mean detection efficacy (± SE) between overlapping interventions (n = 41) was 0.62 ± 0.03, matching closely with the probability of detection for a random search operation and verifying imperfect (albeit precise) detection. The HBT platform increases the value of aerial surveillance operations with 98% efficacy in target elimination. Applying coverage saturation with an accelerated intervention schedule to known patch locations is an adaptive process for compensating imperfect detection and building intelligence with spatial and temporal relevance to the next operation.
It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins.
The mid-infrared wavelength region offers a plethora of possible applications ranging from sensing, medical diagnostics and free space communications, to thermal imaging and IR countermeasures. Hence group IV mid-infrared photonics is attracting more research interest lately. Sensing is an especially attractive area as fundamental vibrations of many important gases are found in the 3 to 14 μm spectral region. To realise group IV photonic mid-infrared sensors several serious challenges need to be overcome. The first challenge is to find suitable material platforms for the mid-infrared. In this paper we present experimental results for passive mid-infrared photonic devices realised in silicon-on-insulator (SOI), silicon-on-sapphire (SOS), and silicon on porous silicon (SiPSi). Although silicon dioxide is lossy in most parts of the mid-infrared, we have shown that it has potential to be used in the 3-4 μm region. We have characterized SOI waveguides with < 1 dB/cm propagation loss. We have also designed and fabricated SOI passive devices such as MMIs and ring resonators. For longer wavelengths SOS or SiPSi structures could be used. An important active device for long wavelength group IV photonics will be an optical modulator. We present relationships for the free-carrier induced electro-refraction and electro-absorption in silicon in the mid-infrared wavelength range. Electro-absorption modulation is calculated from impurity-doping spectra taken from the literature, and a Kramers-Kronig analysis of these spectra is used to predict electro-refraction modulation. We have examined the wavelength dependence of electro-refraction and electro-absorption, and found that the predictions suggest longer-wave modulator designs will in many cases be different than those used in the telecom range.
To investigate the relative importance of specific health knowledge and taste on acceptance of Brassica vegetables (broccoli, red and green cabbages, broccolini, cauliflower, Brussels sprouts).
In a sample of adults all reporting medium–high physical activity (as a marker/control of health behaviour) and reporting either low (≤2 portions/d) or high (≥3 portions/d) vegetable intake, half of those with low vegetable consumption (Li group) and half of those with high vegetable consumption (Hi group) received cancer protection information, while the other half did not (Ln and Hn groups), before hedonic (9-point), perceived taste and flavour impact responses (100 mm scales) to samples of six Brassica vegetables were elicited. Additionally, attitudes towards foods for health, pleasure and reward, sociodemographics, intentions to consume the vegetables in the near future and recall of health information were also measured.
Adult males and females (n 200) aged 18–55 years.
Central location testing, Adelaide, Australia.
Information groups Li and Hi reported specific cancer protection information knowledge, in contrast to Ln and Hn groups (P < 0·000). Information independently influenced responses to (the least liked) Brussels sprouts only. Multivariate regression analysis found sensory perception tended to predict liking and intentions to consume Brassica vegetables. For example, broccoli hedonics (adjusted R2 = 0·37) were predicted (P < 0·05) by bitterness (β = −0·38), flavour (β = 0·31), sweetness (β = 0·17) and female gender (β = 0·19) and intentions to consume (adjusted R2 = 0·20) were predicted (P < 0·05) by bitterness (β = −0·38), flavour (β = 0·24), female gender (β = 0·20) and vegetable intake (β = 0·14).
Addressing taste dimensions (while retaining healthy compounds) may be more important than promoting health information in order to increase the popularity of Brassica vegetables.
To examine whether parents offering a sticker reward to their child to taste a vegetable the child does not currently consume is associated with improvements in children's liking and consumption of the vegetable.
A randomized controlled trial evaluated the effectiveness of exposure only (EO) and exposure plus reward (E + R), relative to a control group, on children's liking and consumption of a target vegetable. Assessments were conducted at baseline and 2 weeks from baseline (post-intervention). Follow-up assessments were conducted at 4 weeks and 3 months from baseline.
The study took place in Adelaide, South Australia. Participants were self-selected in response to local media advertisements seeking to recruit parents finding it difficult to get their children to eat vegetables.
Participants were 185 children (110 boys, seventy-five girls) aged 4–6 years and their primary caregiver/parent (172 mothers, thirteen fathers).
The E + R group was able to achieve more days of taste exposure. Both EO and E + R increased liking at post-intervention compared with control and no further change occurred over the follow-up period. All groups increased their intake of the target vegetable at post-intervention. Target vegetable consumption continued to increase significantly over the follow-up period for E + R and control but not for EO.
The findings provide support for the effectiveness of using a sticker reward with a repeated exposure strategy. In particular, such rewards can facilitate the actual tastings necessary to change liking.
The present study aimed to define the complexity of the relationships between the family environment, health behaviours and obesity. A conceptual model that quantifies the relationships and interactions between parent factors, family environment, and certain aspects of children's behaviour and weight status is presented.
Exploratory structural equation modelling was used to quantitatively model the relationships between parent, child and family environmental factors.
Adelaide, South Australia.
Families (n 157) with children aged 5–10 years completed self-reported questionnaires, providing data on parents’ knowledge, diet quality and activity habits; child feeding and general parenting styles; and the food and physical activity environments. Outcome variables included children's fruit and vegetable intake, activity and sedentary habits and weight status.
The proposed model was an acceptable fit (normed fit index = 0·457; comparative fit index = 0·746; root-mean-squared error associated = 0·044). Parents’ BMI (β = 0·32) and nutrition and physical activity knowledge (β = 0·17) had the strongest direct associations with children's BMI Z-score. Parents’ dietary intake and energy expenditure behaviours were indirectly associated with children's behaviour through the creation of the home environment. The physical activity and food environments were associated with children's sedentary (β = −0·44) and activity habits (β = 0·29), and fruit and vegetable intake (β = 0·47), respectively.
A conceptual model that quantifies the complex network of family environment factors influencing children's behaviour and weight status is presented. The model provides a basis for future research on larger representative samples with a view to guiding obesity prevention interventions.
The temperature dependent structural evolutions of RbxC60 (x = 3, 5, 6) and K4C60 were studied using both in-house andsynchrotron x-ray powder diffraction and thermal analysis techniques over a temperature range of 10K - 673K. The superconducting face centered-cubic (fcc) Rb3C60 and the body centered-tetragonal (bct) M4C60(M = K, Rb) phases are found to be line compounds in this temperature range, while the body centered-cubic (bcc) phase forms a solid solution in which the solubility of vacant M sites increases with temperature. The orientation of the C60 molecules in the K4C60 phase was analyzed. A crystalline fcc Rb1C60 phase is stable only above room temperature.
The ligament structure of several open-cell carbon foams was examined by optical and electron microscopy. The arrangement, sizes, and shapes of the ligaments were measured and analyzed according to the cell sizes. The ligament lengths and cross-sections vary with the cell sizes in a simply scaled fashion. A models based on the observed dodecahedral-like arrangement of ligaments was constructed consisting of 12-, 14-, and 15-faced polyhedra with five-edged faces dominating.