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Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.
Commission 4 was among the first set of commissions formed within the IAU at its founding in 1919. (Commissions were originally called “Standing Committees.”) During its 96 years of service to the IAU and astronomical community in general, the commission has been fortunate to have been led by many distinguished scientists — see the list of presidents below.
This study aimed to investigate pepsin as a marker of extra-oesophageal reflux disease by examining its presence in tracheal aspirates and correlating it with macroscopic changes on laryngobronchoscopy, along with the results of standard tests for gastro-oesophageal reflux disease and clinical features.
A retrospective review was undertaken of a cohort of 188 paediatric patients who underwent laryngobronchoscopy at a tertiary children's hospital and for whom pepsin assay results of tracheal aspirates were available. An association analysis was performed.
The mean patient age was 3.99 (3.40–4.58) years, with a male preponderance (55 per cent). Positive changes on laryngobronchoscopy were significantly associated with positive tracheal pepsin findings (p < 0.0001) but not with positive standard gastro-oesophageal reflux disease investigations. A positive pepsin assay was significantly associated with a history of recurrent croup (p = 0.0385) and a diagnosis of cystic fibrosis (p = 0.0232).
Macroscopic changes on laryngobronchoscopy were significantly associated with positive tracheal pepsin findings in this paediatric population, suggesting that extra-oesophageal reflux disease may be a contributing aetiology.
The Working Group on the Natural Planetary Satellites has been created to promote the development of high-quality ephemerides. The Working Group encourages theoretical studies, coordinated observations, and makes all data available to the users through the NSDC web site (http://www.imcce.fr/nsdc).
Anterior tongue reduction is indicated when macroglossia causes problems with oral hygiene, airway compromise, deglutition, articulation or orthognathic complications. Causes of macroglossia include hypothyroidism, mucopolysaccharide and lipid storage disease, lymphangioma, haemangioma, neurofibroma, and muscular macroglossia. This paper presents an 11-year experience of anterior tongue reduction at Great Ormond Street Hospital.
Retrospective study of patient medical records identified from the hospital ENT database. Anterior wedge resection was the preferred technique.
Anterior tongue reduction was performed on 18 patients, due to cystic hygroma with tongue involvement (nine patients), Beckwith–Wiedemann syndrome (eight) and Down's syndrome (one). Anterior wedge resection was preferred, using electrocautery in the majority, except for four cases involving CO2 laser. All but one patient had a good surgical outcome (i.e. tongue in mouth at rest). One patient subsequently required multiple laser procedures for recurrent macroglossia.
Anterior tongue reduction can be a safe procedure, with limited post-operative morbidity, consistently resulting in good surgical outcomes and improvement in macroglossia symptoms. Speech development does not appear to be adversely affected.
The electronic structure of Co (100 Å)/Cu (50 Å) bilayer film on Si(100) has been investigated using valence band photoemission at 50 eV. The aim is to understand the Co/Cu interface and the nature of intermixing in Co and Cu layers. The valence band of Co/Cu interface shows three features at −0.3, −1.17 and −1.9 eV binding energy. The experimental observations are explained with the help of calculations based on projected augmented wave pseudopotential method using density functional theory. The origin of −0.3 eV feature is mainly due to the Co 3d minority spin states while the features at −1.17 and −1.9 eV are due to the formation of Co and Co–Cu mixed nanoclusters at the interface.
The electronic structure of CeAg2Ge2 single crystal has been investigated by using resonant valence band photoemission and angle-resolved photoemission spectroscopy at different photon energies. Resonant photoemission has been observed near the 4d threshold of Ce at 121 eV. The constant initial state spectra show two photoemission features having 4f character near the Fermi level that exhibits Fano-like sharp resonance profile. Experimental energy bands have been mapped from the normal-emission photoelectron spectra of CeAg2Ge2 (001) surface along the Γ–Z direction. Four photoemission features are observed to show the dispersion related to the Ce 4f states and the hybridized Ag 4d with Ge 4p states. The experimental spectra have been interpreted with the help of calculations based on full potential linear augmented plane wave method using density functional theory.
Suboptimal vitamin D status among the South Asian UK population is widely reported; however, its impact on bone health is unclear. The aim of the present study was to conduct a comparative investigation of vitamin D status in postmenopausal South Asian (SA) and Caucasian (C) women and its relationship to parathyroid hormone (PTH) concentration, biochemical markers of bone turnover and bone quality. A cross-sectional study of community-dwelling women aged 50–66 years was carried out. A total of sixty-six SA women of Pakistani origin and forty-two C women living in the same community were recruited. Fasting blood was taken for the measurement of vitamin D, PTH and biochemical markers of bone turnover, including type-1 collagen β C-telopeptide (βCTX), procollagen type-1 amino-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (BAP) activity. Bone quality was assessed using broadband ultrasound attenuation (BUA). Total serum 25-hydroxyvitamin D (25(OH)D) was significantly lower in the SA women than the C women (medians: SA 10·5 v. C 47·1 nmol/l; P < 0·001) This was associated with a significantly elevated serum PTH concentration in the SA group (medians: SA 7·3 v. C 4·5 pmol/l; P < 0·01). BAP activity was also significantly higher in the SA group, indicating elevated osteoblast activity and bone turnover (medians: SA 23·0 v. C 20·0 U/l; P < 0·05). No significant differences were observed between the two groups for P1NP, βCTX or BUA. Although the SA women had significantly higher serum PTH and lower 25(OH)D concentrations than C women, this was not associated with significantly higher markers of bone resorption, or reduced bone quality in the SA women.
Ossicular chain damage from chronic ear disease is a significant problem in the Australian population. The ideal ossicular chain reconstruction prosthesis has yet to be defined. This paper examines, for the first time, the use of a titanium prosthesis for ossicular chain reconstruction in Australian patients.
Retrospective chart review.
Subjects and methods:
All patients undergoing ossicular chain reconstruction with a titanium prosthesis between 1 February 2002 and 31 March 2007.
Results showed a low complication rate, with only one extrusion out of 55 cases (1.8 per cent). Successful rehabilitation of conductive hearing loss (i.e. to ≤20 dB air–bone gap) was obtained in 85 per cent of the partial ossicular chain reconstruction group and 77 per cent of the total ossicular chain reconstruction group. Pure tone thresholds improved by an average 18 dB in the partial reconstruction group and 25 dB in the total reconstruction group.
Titanium is an ideal material for ossicular chain reconstruction due to its ease of insertion, low rate of extrusion and good functional results.
The occultation of a 9.1 magnitude star by asteroid (22) Kalliope and its satellite Linus was successfully observed in Japan in 2006 November 7.826 UT. This was the first definite observation of an occultation of a satellite of an asteroid that was discovered previously by other means. As a result the position of the satellite relative to Kalliope was obtained to be d = 0.246 ± 0.011 (arcsec), and P = 313.8 ± 2.7 (deg), where d is the angular distance and P is the position angle. The derived size for Kalliope is (209 ± 40)km × (136 ± 26)km (with the major axis in position angle of (8 ± 17) deg), and that for Linus is (33 ± 3) km. From the observations, the occulted star is also found to be a close double star whose separation is about 0.7 mas in position angle of about 300 deg, and the magnitudes of the components are found to be almost the same (~9.9 mag).
This triennial report from Commission 8 covers astrometry-related matters for objects ranging from Solar system bodies out to Milky Way stars and QSOs at cosmological distances. This enormous range of distances is needed to establish, maintain, and improve the metric of the visible Universe--a very challenging effort since everything is moving. The progress of astrometry in the last three years (2002-2005) is reflected here. To locate the references, the reader is advised to check the NASA ADS Astronomy Abstract Service and the expanded report posted at URL http://www.pha.jhu.edu/iau_comm8/comm8.html
Epitaxial thin films of PbZr0.52Ti0.48O3 (PZT) were synthesized successfully on SrRuO3/SrTiO3/MgO/TiN/Si heterostructures by pulsed laser deposition. The films were single phase and had (001) orientation. The deposition parameters were varied to obtain the best epitaxial layer for each of the compounds. Transmission electron microscopy indicated good epitaxy for the entire heterostructure and sharp interfaces between the epilayers. Dielectric and P–E hysteresis loop measurements were carried out with evaporated Ag electrodes. The dielectric constant for the films was found to be between 400–450. The value of saturation polarization Ps was between 55–60 μC/cm2, and the coercive field Ec varied from 60–70 kV/cm. Integration of PZT films with silicon will be useful for future memory and micromechanical devices.
The dielectric response of KNbO3 epitaxial ferroelectric thin films was measured as a function of bias, frequency, and temperature. Thin films with a thickness of 80 to 350 nm were deposited on spinel substrates by low-pressure metalorganic chemical vapor deposition. Bias dependence measurements showed hysteresis in the dielectric response. The dielectric constant decreased with bias, and the tunability was calculated to be between 35% and 42% for an applied field of 7 MV/cm. The frequency dependence of the dielectric constant followed a power law. A pronounced thickness effect was observed in the dielectric response, especially at the Curie temperature. With decreasing thickness, the dielectric constant and the loss tangent decreased. A diffuse ferroelectric phase transition was observed for films with a thickness less than 350 nm.
In this report, we explore the possibilities of the fabrication and characterization of ferroelectric nano-structures by various methods. Techniques include the self-assembly route and direct electron beam lithography. The chemical self-assembly route, which adopted the microemulsionmediated synthesis, appeared to be very encouraging for producing very small monodispersed nano particles and powders, with sizes of 10–60 nm. The possibility to form a two dimensional arrangement of these micro droplets was explored with a suitable choice of the substrate material, and the method of coating. For the patterns prepared by the e-beam technique, a strong coupling between two closely spaced nano elements was observed, the spacing between them was found to be the key factor in tailoring their interaction, i.e., whether they would arrange themselves in rod-like pattern or a two dimensional array of isolated squares or circles.
Uridine triphosphate (UTP) evoked inhibition of adrenaline-evoked cAMP accumulation in cultured equine epithelial cells (EC50, 1á8 ± 0á2 µM) and this effect was mimicked by 5-Br-UTP (EC50, 6á6 ± 1á8 µM) and uridine diphosphate (UDP; EC50, 96 ± 26 µM). This inhibitory action of UTP was abolished by pre-treating cells with pertussis toxin (10 ng ml-1, 24 h). UTP (EC50, 2á3 ± 0á3 µM) and 5-Br-UTP (EC50, 29á4 ± 9á4 µM) also increased intracellular free calcium ([Ca2+]i) whilst UDP did not; the two effects are thus differentially sensitive to these pyrimidine nucleotides. ATP evoked cAMP accumulation in control cells and this response was unaffected by pertussis toxin. There is, therefore, no indication that ATP activates the pertussis toxin-sensitive inhibitory pathway. The UTP-evoked inhibition of cAMP accumulation was abolished by isobutylmethylxanthine (IBMX, 5 mM) and so the negative control over cAMP levels appears to be mediated by receptors that are selectively activated by pyrimidine nucleotides and permit control over phosphodiesterase activity.
The stibiotantalite (ABO4) family includes a number of ferroelectrics and antiferroelectrics with excellent potential for applications. We report the deposition of phase-pure, polycrystalline thin films of BiNbO4 on Si(100) substrates using pulsed laser ablation. The deposition conditions were optimized with respect to substrate temperature, laser parameters, and the ambient oxygen pressure. The films were characterized by x-ray diffraction, energy dispersive x-ray analysis, and Raman spectroscopy, while their microstructure was studied by atomic force microscopy and scanning electron microscopy. Dielectric hysteresis studies indicated that films with a thickness below ≈250 nm are ferroelectric, while thicker ones are antiferroelectric.
A range of allophane samples (atomic AI/Si bulk ratios 1.1-1.9) from Silica Springs, New Zealand, has been characterized by X-ray photoelectron spectroscopy (XPS). Binding energies of Si 2s, Si 2p, Al 2p, O 1s, C 1s, and N 1s electrons, together with the kinetic energies of Al KL23L23 Auger electrons, at or near the surface of allophane aggregates, have been derived. The values for Al, Si and O electrons are similar to those for kaolinite but also to those for some framework silicates (feldspars) having 4-coordinate Al. Values for N electrons suggest that N occurs in organic structures. Comparison of XPS and bulk Al/Si ratios shows an enrichment of Al at or near the surface of allophane aggregates. The same is true for C and N. Extraction with citrate-dithionite-bicarbonate (CDB) reagent leaves the surfaces depleted in Al. The CDB extracts have higher Al/Si ratios than the bulk allophanes. Similarly, CDB treatment reduces the degree of surface enrichment of C and N. Small increases in the binding energies of Si electrons following CDB treatment suggest partial dissolution of the bulk structure though a concomitant removal of a separate phase or species cannot be ruled out. The results may be accounted for in terms of the structure previously suggested for the primary spherules of Silica Springs allophane (Childs et al., 1990) though the composition of the spherules at or near the surface of the allophane aggregates is different from those of the bulk.
The surface composition of some halloysites with different particle morphology has been investigated by X-ray photoelectron spectroscopy (XPS) before and after removal of external Fe. The Fe(III) 2p3/2 binding energy of external Fe is appreciably smaller than that of structural Fe. Particle morphology is influenced by structural Fe content. The long-tubular halloysite has very little surface Fe, and its concentration tends to increase with the proportion of non-tubular particles in the samples. The spheroidal sample contains the most structural Fe which, however, does not appear to influence particle shape directly. Study by XPS indicates that Fe substitutes for Al in octahedral positions in approximately 1 : 2 proportion. As a result, an increase in octahedral vacancies and cation exchange capacity would be predicted. Further, halloysite layers within a crystal are generally inhomogeneous in composition. Built up like “onion skins”, the surface layers would either be enriched or depleted in Fe depending on the chemical environment in which crystal growth occurs.
Resonance Raman spectroscopy has been used to observe the formation of cation radicals in the adsorption of N,N,N',N'-tetramethylbenzidine (TMBD), benzidine, N,Ndimethylaniline (DMA) and aniline on Na-, Cu- and Fe-montmorillonites. Cation radicals of benzidine and TMBD, and their dications were formed at acid sites on the montmorillonite surface, or through the reduction of Cu or Fe interlayer ions, and were adsorbed in the interlayer. Their structures are represented by biphenoquinone type structure, where the inter-ring CC bond and the ring C-N bond have double bond characters. It was demonstrated from Raman spectra that DMA and aniline adsorbed on Cu-montmorillonite from the vapour phase dimerize to form TMBD and benzidine dications.