Spray-dried dispersions (SDDs) of low-solubility drugs have been prepared using the polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS). For a variety of drug structures, these SDDs ...provide supersaturation in in vitro dissolution determinations and large bioavailability increases in vivo. In bile-salt/lecithin in vitro solutions, these SDDs provide amorphous drug/polymer colloids and an increased concentration of free drug and drug in micelles relative to crystalline or amorphous drug. As dry powders, the SDDs are a single amorphous phase in which the drug remains amorphous and dispersed and does not crystallize over storage times relevant for practical drug products. A melting temperature (T m)/glass-transition temperature (T g) (K/K) versus log P map for 139 compounds formulated as SDDs provides a perspective on an appropriate formulation strategy for low-solubility drugs with various physical properties.
We have modelled Atacama Large Millimetre/sub-millimetre Array (ALMA) long baseline imaging of the strong gravitational lens system H-ATLAS J090311.6+003906 (SDP.81). We have reconstructed the ...distribution of band 6 and 7 continuum emission in the z = 3.042 source and determined its kinematic properties by reconstructing CO(5–4) and CO(8–7) line emission in bands 4 and 6. The continuum imaging reveals a highly non-uniform distribution of dust with clumps on scales of ∼200 pc. In contrast, the CO line emission shows a relatively smooth, disc-like velocity field which is well fitted by a rotating disc model with an inclination angle of (40 ± 5)° and an asymptotic rotation velocity of 320 km s−1. The inferred dynamical mass within 1.5 kpc is (3.5 ± 0.5) × 1010 M⊙ which is comparable to the total molecular gas masses of (2.7 ± 0.5) × 1010 M⊙ and (3.5 ± 0.6) × 1010 M⊙ from the dust continuum emission and CO emission, respectively. Our new reconstruction of the lensed Hubble Space Telescope near-infrared emission shows two objects which appear to be interacting, with the rotating disc of gas and dust revealed by ALMA distinctly offset from the near-infrared emission. The clumpy nature of the dust and a low value of the Toomre parameter of Q ∼ 0.3 suggest that the disc is in a state of collapse. We estimate a star formation rate in the disc of 470 ± 80 M⊙ yr−1 with an efficiency ∼65 times greater than typical low-redshift galaxies. Our findings add to the growing body of evidence that the most infrared luminous, dust obscured galaxies in the high-redshift Universe represent a population of merger-induced starbursts.
We have determined the mass density radial profiles of the first five strong gravitational lens systems discovered by the Herschel Astrophysical Terahertz Large Area Survey. We present an enhancement ...of the semilinear lens inversion method of Warren & Dye which allows simultaneous reconstruction of several different wavebands and apply this to dual-band imaging of the lenses acquired with the Hubble Space Telescope. The five systems analysed here have lens redshifts which span a range 0.22 ≤ z ≤ 0.94. Our findings are consistent with other studies by concluding that: (1) the logarithmic slope of the total mass density profile steepens with decreasing redshift; (2) the slope is positively correlated with the average total projected mass density of the lens contained within half the effective radius and negatively correlated with the effective radius; (3) the fraction of dark matter contained within half the effective radius increases with increasing effective radius and increases with redshift. PUBLICATION ABSTRACT
Body mass index (BMI) (weight per height
) is the most widely used marker of childhood obesity and total body fatness (BF). However, its validity is limited, especially in children of South Asian and ...Black African origins. We aimed to quantify BMI adjustments needed for UK children of Black African and South Asian origins so that adjusted BMI related to BF in the same way as for White European children.
We used data from four recent UK studies that made deuterium dilution BF measurements in UK children of White European, South Asian and Black African origins. A height-standardized fat mass index (FMI) was derived to represent BF. Linear regression models were then fitted, separately for boys and girls, to quantify ethnic differences in BMI-FMI relationships and to provide ethnic-specific BMI adjustments.
We restricted analyses to 4-12 year olds, to whom a single consistent FMI (fat mass per height
) could be applied. BMI consistently underestimated BF in South Asians, requiring positive BMI adjustments of +1.12 kg m
(95% confidence interval (CI): 0.83, 1.41 kg m
; P<0.0001) for boys and +1.07 kg m
(95% CI: 0.74, 1.39 kg m
; P<0.0001) for girls of all age groups and FMI levels. BMI overestimated BF in Black Africans, requiring negative BMI adjustments for Black African children. However, these were complex because there were statistically significant interactions between Black African ethnicity and FMI (P=0.004 boys; P=0.003 girls) and also between FMI and age group (P<0.0001 for boys and girls). BMI adjustments therefore varied by age group and FMI level (and indirectly BMI); the largest adjustments were in younger children with higher unadjusted BMI and the smallest in older children with lower unadjusted BMI.
BMI underestimated BF in South Asians and overestimated BF in Black Africans. Ethnic-specific adjustments, increasing BMI in South Asians and reducing BMI in Black Africans, can improve the accuracy of BF assessment in these children.
Acoustic radiation force impulse (ARFI) imaging techniques were used to monitor radiofrequency (RF) ablation of ovine cardiac tissue in vivo. Additionally, ARFI M-mode imaging methods were used to ...interrogate both healthy and ablated regions of myocardial tissue. Although induced cardiac lesions were not visualized well in conventional B-mode images, ARFI images of ablation procedures allowed determination of lesion location, shape, and relative size through time. The ARFI M-mode images were capable of distinguishing differences in behavior through the cardiac cycle between healthy and damaged tissue regions. As conventional sonography is often used to guide ablation catheters, ARFI imaging, which requires no additional equipment, may be a convenient modality for monitoring lesion formation in vivo.
The National Child Measurement Programme (NCMP) records weight and height and assesses overweight-obesity patterns in English children using body mass index (BMI), which tends to underestimate body ...fatness in South Asian children and overestimate body fatness in Black children of presumed African ethnicity. Using BMI adjustments to ensure that adjusted BMI was similarly related to body fatness in South Asian, Black and White children, we reassessed population overweight and obesity patterns in these ethnic groups in NCMP.
Analyses were based on 2012-2013 NCMP data in 582 899 children aged 4-5 years and 485 362 children aged 10-11 years. Standard centile-based approaches defined weight status in each age group before and after applying BMI adjustments for English South Asian and Black children derived from previous studies using the deuterium dilution method.
Among White children, overweight-obesity prevalences (boys, girls) were 23% and 21%, respectively, in 4-5 year olds and 33% and 30%, respectively, in 10-11 year olds. Before adjustment, South Asian children had lower overweight-obesity prevalences at 4-5 years (19%, 19%) and slightly higher prevalences at 10-11 years (42%, 34%), whereas Black children had higher overweight-obesity prevalences both at 4-5 years (31%, 29%) and 10-11 years (42%, 45%). Following adjustment, overweight-obesity prevalences were markedly higher in South Asian children both at 4-5 years (39%, 35%) and at 10-11 years (52%, 44%), whereas Black children had lower prevalences at 4-5 years (11%, 12%); at 10-11 years, prevalences were slightly lower in boys (32%) but higher in girls (35%).
BMI adjustments revealed extremely high overweight-obesity prevalences among South Asian children in England, which were not apparent in unadjusted data. In contrast, after adjustment, Black children had lower overweight-obesity prevalences except among older girls.
British Heart Foundation, NIHR CLAHRC (South London), NIHR CLAHRC (North Thames).
Based on research on cermet inert anodes for aluminium production, it has been suggested that nickel ferrite spinel might be suitable for use as a sidewall refractory in Hall-Héroult cells. A ...corrosion resistant sidewall would allow elimination of the frozen bath ledge, and has potentially huge benefits in terms of energy savings and increased productivity. However, little work has been done to assess nickel ferrite's suitability as a refractory.
Dense nickel ferrite samples were prepared and characterized, and corrosion tests in cryolite based baths were conducted. Results confirm that the spinel does have good corrosion resistance. The corrosion mechanism is complex, involving grain boundary attack and formation of a Ni–Fe alloy. This alloy could pose a risk in terms of contamination of the aluminium. The use of additives to restrict penetration of grain boundaries may be the key to development of a successful spinel based refractory.
Oxidative stress has an important role in the pathogenesis of asthma. 8-Isoprostane is a prostaglandin (PG)-F2-like compound belonging to the F2 isoprostane class that is produced in vivo by the free ...radical-catalyzed peroxidation of arachidonic acid. 8-Isoprostane is a biomarker of oxidative stress, and its concentration is increased in the bronchoalveolar lavage fluid of patients with interstitial lung diseases. We measured 8-isoprostane concentrations in exhaled breath condensate in healthy subjects and in patients with mild (steroid naive, n = 12), moderate (inhaled steroid treatment, n = 17), and severe asthma (oral steroid treatment, n = 15). We also measured exhaled carbon monoxide (CO) and nitric oxide (NO), which may also reflect oxidative stress in the airways. 8-Isoprostane was detectable in breath condensate of normal subjects (15.8 +/- 1.6 pg/ml), and was increased in the breath condensate of patients with mild (33.7 +/- 2.8, p < 0.001), moderate (38.3 +/- 3.7 pg/ml, p < 0. 001), and severe asthma (48.9 +/- 5.0 pg/ml, p < 0.001). There was a positive correlation (r = 0.68, p < 0.05) of 8-isoprostane with NO, but not with CO, in the exhaled air of patients with mild asthma, but not in that of patients with moderate or severe asthma. There was no correlation between 8-isoprostane and lung function tests in any group of patients. Our study shows that oxidative stress is increased in asthmatic subjects as reflected by 8-isoprostane concentrations in breath condensate.
These international clinical practice guidelines were developed with detailed input from 29 invited international consultants, who provided content as well as detailed feedback on draft versions. The ...final draft of the guidelines was ratified by the Executive of the International Early Psychosis Association and presented and formally endorsed at the Third International Conference on Early Psychosis held in Copenhagen, September 2002. They have been revised slightly to include medications that were not available in 2002, although a fully comprehensive process of update has not yet been conducted. The final version is published in this Supplement with the aim of encouraging further discussion as well as providing practical guidance to clinicians and researchers. A second edition is planned for publication in 2008.
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