ZD1839 (‘Iressa’), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model

The effect of ZD1839 (‘Iressa’), a specific inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor, on the radiation response of human tumour cells (LoVo colorectal carcinoma) was evaluated in vitro and in vivo. ZD1839 (0.5 μM, incubated days 1–5) significantly increased the anti-proliferative effect of fractionated radiation treatment (2 Gy day−1, days 1–3) on LoVo cells grown in vitro (P=0.002). ZD1839 combined with either single or fractionated radiotherapy in mice bearing LoVo tumour xenografts, also produced a highly significant increase in tumour growth inhibition (P⩽0.001) when compared to treatment with either modality alone. The radio-potentiating effect of ZD1839 was more apparent when radiation was administered in a fractionated protocol. This phenomenon may be attributed to an anti proliferative effect of ZD1839 on tumour cell re-population between radiotherapy fractions. These data suggest radiotherapy with adjuvant ZD1839 could enhance treatment response. Clinical investigation of ZD1839 in combination with radiotherapy is therefore warranted

A Composite HST Spectrum of Quasars

We construct a composite quasar spectrum from 284 HST FOS spectra of 101 quasars with redshifts z > 0.33. The spectrum covers the wavelengths between 350 and 3000 A in the rest frame. There is a significant steepening of the continuum slope around 1050 A. The continuum between 1050 and 2200 A can be modeled as a power law with alpha = -0.99. For the full sample the power-law index in the extreme ultraviolet (EUV) between 350 and 1050 A is alpha = -1.96. The continuum flux in the wavelengths near the Lyman limit shows a depression of about 10 percent. The break in the power-law index and the slight depression of the continuum near the Lyman limit are features expected in Comptonized accretion-disk spectra.Comment: 10 figures To appear in the February 1, 1997, issue of the Ap.

From Service to Experience: Understanding and Defining the Hospitality Business

Failure adequately to define or understand hospitality as a commercial phenomenon has created a fragmented academic environment and a schizophrenia in the industry that has the potential to limit its development as a global industry. This article suggests that, by redefining hospitality as behaviour and experience, a new perspective emerges that has exciting implications for the management of hospitality businesses. A framework to describe hospitality in the commercial domain is proposed. This framework suggests a focus on the host–guest relationship, generosity, theatre and performance, ‘lots of little surprises’, and the security of strangers – a focus that provides guests with experiences that are personal, memorable and add value to their lives

Psychometric Analysis of the Adult Sickle Cell Quality of Life Measurement Information System (ACSQ-Me) in a UK Population

Background: The Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) has been shown to be a reliable and valid questionnaire measuring health-related quality of life (HRQoL) in the US sickle cell disease (SCD) population. The study objective was to test the validity and reliability of the ASCQ-Me for use in the UK. Methods: The US ASCQ-Me, Hospital Anxiety and Depression Scale (HADS), self-reported symptoms, and Medical Outcome Survey Short Form 36 (SF-36) were administered to 173 patients with SCD. Clinical severity was assessed by the number of painful episodes indicated by hospital admissions. Results: The results showed that the item banks of the UK ASCQ-Me had good internal consistency. Anxiety and depression were strongly correlated with the emotional, and social item banks of the UK ASCQ-Me, with moderate correlations between the UK ASCQ-Me item banks and SF-36 components suggesting convergent validity. A confirmatory factor analysis confirmed the conceptual framework of the scale as being the same as the US ASCQ-Me, indicating construct validity. Known groups validity was found, with the ASCQ-Me being able to differentiate by SCD severity groups. Conclusion: The analysis of the sample shows evidence of both validity and reliability of the ACCQ-Me for use in the UK SCD population

Highly Ionized Collimated Outflow from HE 0238 - 1904

We present a detailed analysis of a highly ionized, multiphased and collimated outflowing gas detected through O V, O VI, Ne VIII and Mg X absorption associated with the QSO HE 0238 - 1904 (z_em ~ 0.629). Based on the similarities in the absorption line profiles and estimated covering fractions, we find that the O VI and Ne VIII absorption trace the same phase of the absorbing gas. Simple photoionization models can reproduce the observed N(Ne VIII), N(O VI) and N(Mg X) from a single phase whereas the low ionization species (e.g. N III, N IV, O IV) originate from a different phase. The measured N(Ne VIII)/N(O VI) ratio is found to be remarkably similar (within a factor of ~ 2) in several individual absorption components kinematically spread over ~ 1800 km/s. Under photoionization this requires a fine tuning between hydrogen density (nH) and the distance of the absorbing gas from the QSO. Alternatively this can also be explained by collisional ionization in hot gas with T > 10^{5.7} K. Long-term stability favors the absorbing gas being located outside the broad line region (BLR). We speculate that the collimated flow of such a hot gas could possibly be triggered by the radio jet interaction.Comment: Minor revision (accepted for publication in MNRAS letter

The Glasgow-Maastricht foot model, evaluation of a 26 segment kinematic model of the foot

BACKGROUND: Accurately measuring of intrinsic foot kinematics using skin mounted markers is difficult, limited in part by the physical dimensions of the foot. Existing kinematic foot models solve this problem by combining multiple bones into idealized rigid segments. This study presents a novel foot model that allows the motion of the 26 bones to be individually estimated via a combination of partial joint constraints and coupling the motion of separate joints using kinematic rhythms. METHODS: Segmented CT data from one healthy subject was used to create a template Glasgow-Maastricht foot model (GM-model). Following this, the template was scaled to produce subject-specific models for five additional healthy participants using a surface scan of the foot and ankle. Forty-three skin mounted markers, mainly positioned around the foot and ankle, were used to capture the stance phase of the right foot of the six healthy participants during walking. The GM-model was then applied to calculate the intrinsic foot kinematics. RESULTS: Distinct motion patterns where found for all joints. The variability in outcome depended on the location of the joint, with reasonable results for sagittal plane motions and poor results for transverse plane motions. CONCLUSIONS: The results of the GM-model were comparable with existing literature, including bone pin studies, with respect to the range of motion, motion pattern and timing of the motion in the studied joints. This novel model is the most complete kinematic model to date. Further evaluation of the model is warranted

Associations between environmental factors and hospital admissions for sickle cell disease

Sickle cell disease (SCD) is an increasing global health burden. This inherited disease is characterised by a remarkable phenotypic heterogeneity, which can only partly be explained by genetic factors. Environmental factors are likely to play an important role but studies of their impact on disease severity are limited and their results are often inconsistent. This study investigated associations between a range of environmental factors and hospital admissions of young patients with SCD in London and in Paris between 2008 and 2012. Specific analyses were conducted for sub-groups of patients with different genotypes and for the main reasons of admissions. Generalized additive models and distributed lag non-linear models were used to assess the magnitude of the associations and to calculate relative risks. Some environmental factors significantly influence the numbers of hospital admissions of children with SCD, although the associations identified are complicated. Our study suggests that meteorological factors are more likely to be associated with hospital admissions for SCD than air pollutants. It confirms previous reports of risks associated with wind speed (RR: 1.06/SD [95% confidence interval (CI): 1.00-1.12]) and also with rainfall (RR: 1.06/SD [95%CI: 1.01-1.12]). Maximum atmospheric pressure was found to be a protective factor (RR: 0.93/SD [95%CI: 0.88-0.99]). Weak or no associations were found with temperature. Divergent associations were identified for different genotypes or reasons of admissions, which could partly explain the lack of consistency in earlier studies. Advice to patients with SCD usually includes avoiding a range of environmental conditions that are believed to trigger acute complications, including extreme temperatures and high altitudes. Scientific evidence to support such advice is limited and sometimes confusing. This study shows that environmental factors do explain some of the variations in rates of admission to hospital with acute symptoms in SCD, but the associations are complex, and likely to be specific to different environments and the individual's exposure to them. Furthermore, this study highlights the need for prospective studies with large numbers of patients and standardised protocols across Europe

Performance of the Center-Of-Curvature Optical Assembly During Cryogenic Testing of the James Webb Space Telescope

The James Webb Space Telescope (JWST) primary mirror (PM) is 6.6 meters in diameter and consists of 18 hexagonal segments, each 1.5 meters point-to-point. Each segment has a 6 degree-of-freedom hexapod actuation system and a radius-of-curvature (ROC) actuation system. The full telescope was tested at its cryogenic operating temperature at Johnson Space Center (JSC) in 2017. This testing included center-of-curvature measurements of the PM wavefront error using the Center-of-Curvature Optical Assembly (COCOA), along with the Absolute Distance Meter Assembly (ADMA). The COCOA included an interferometer, a reflective null, an interferometer-null calibration system, coarse and fine alignment systems, and two displacement measuring interferometer systems. A multiple-wavelength interferometer was used to enable alignment and phasing of the PM segments. By combining measurements at two laser wavelengths, synthetic wavelengths up to 15 millimeters could be achieved, allowing mirror segments with millimeter-level piston errors to be phased to the nanometer level. The ADMA was used to measure and set the spacing between the PM and the focus of the COCOA null (i.e., the PM center-of-curvature) for determination of the ROC. This paper describes the COCOA, the PM test setup, the testing performed, the test results, and the performance of the COCOA in aligning & phasing the PM segments and measuring the final PM wavefront error

Cosmic Hydrogen Was Significantly Neutral a Billion Years After the Big Bang

The ionization fraction of cosmic hydrogen, left over from the big bang, provides crucial fossil evidence for when the first stars and quasar black holes formed in the infant universe. Spectra of the two most distant quasars known show nearly complete absorption of photons with wavelengths shorter than the Ly-alpha transition of neutral hydrogen, indicating that hydrogen in the intergalactic medium (IGM) had not been completely ionized at a redshift z~6.3, about a billion years after the big bang. Here we show that the radii of influence of ionizing radiation from these quasars imply that the surrounding IGM had a neutral hydrogen fraction of tens of percent prior to the quasar activity, much higher than previous lower limits of ~0.1%. When combined with the recent inference of a large cumulative optical depth to electron scattering after cosmological recombination from the WMAP data, our result suggests the existence of a second peak in the mean ionization history, potentially due to an early formation episode of the first stars.Comment: 14 Pages, 2 Figures. Accepted for publication in Nature. Press embargo until publishe