Large eddy simulation of plume dispersion behind an aircraft in the take-off phase

The aim of this paper is to provide an investigation, using large eddy simulation, into plume dispersion behind an aircraft in co-flowing take-off conditions. Validation studies of the computational model were presented by Aloysius and Wrobel (Environ Model Softw 24:929–937, 2009) and a study of the flow and dispersion properties of a double-engine aircraft jetwas presented by Aloysius et al. EEC/SEE/2007/001,EUROCONTROLExperimentalCentre, http://www.eurocontrol.int/eec/gallery/content/public/document/eec/report/2007/ 032_ALAQS_comparison_of_CFD_and_Lagrangian_dispersion_methods.pdf), in which only the engine was modelled. In this paper, the complete geometry of a Boeing 737 is modelled and investigated. The currentwork represents a contribution towards a better understanding of the source dynamics behind an airplane jet engine during the take-off and landing phases. The information provided from these simulations will be useful for future improvements of existing dispersion models

Impact of PTEN abnormalities on outcome in pediatric patients with T-cell acute lymphoblastic leukemia treated on the MRC UKALL2003 trial.

PTEN gene inactivation by mutation or deletion is common in pediatric T-cell acute lymphoblastic leukemia (T-ALL), but the impact on outcome is unclear, particularly in patients with NOTCH1/FBXW7 mutations. We screened samples from 145 patients treated on the MRC UKALL2003 trial for PTEN mutations using heteroduplex analysis and gene deletions using single nucleotide polymorphism arrays, and related genotype to response to therapy and long-term outcome. PTEN loss-of-function mutations/gene deletions were detected in 22% (PTEN(ABN)). Quantification of mutant level indicated that 67% of mutated cases harbored more than one mutant, with up to four mutants detected, consistent with the presence of multiple leukemic sub-clones. Overall, 41% of PTEN(ABN) cases were considered to have biallelic abnormalities (mutation and/or deletion) with complete loss of PTEN in a proportion of cells. In addition, 9% of cases had N- or K-RAS mutations. Neither PTEN nor RAS genotype significantly impacted on response to therapy or long-term outcome, irrespective of mutant level, and there was no evidence that they changed the highly favorable outcome of patients with double NOTCH1/FBXW7 mutations. These results indicate that, for pediatric patients treated according to current protocols, routine screening for PTEN or RAS abnormalities at diagnosis is not warranted to further refine risk stratification.Leukemia advance online publication, 21 August 2015; doi:10.1038/leu.2015.206

Metastasis-inducing proteins are widely expressed in human brain metastases and associated with intracranial progression and radiation response

Background:Understanding the factors that drive recurrence and radiosensitivity in brain metastases would improve prediction of outcomes, treatment planning and development of therapeutics. We investigated the expression of known metastasis-inducing proteins in human brain metastases.Methods:Immunohistochemistry on metastases removed at neurosurgery from 138 patients to determine the degree and pattern of expression of the proteins S100A4, S100P, AGR2, osteopontin (OPN) and the DNA repair marker FANCD2. Validation of significant findings in a separate prospective series with the investigation of intra-tumoral heterogeneity using image-guided sampling. Assessment of S100A4 expression in brain metastatic and non-metastatic primary breast carcinomas.Results:There was widespread staining for OPN, S100A4, S100P and AGR2 in human brain metastases. Positive staining for S100A4 was independently associated with a shorter time to intracranial progression after resection in multivariate analysis (hazard ratio for negative over positive staining=0.17, 95% CI: 0.04-0.74, P=0.018). S100A4 was expressed at the leading edge of brain metastases in image guided sampling and overexpressed in brain metastatic vs non-brain metastatic primary breast carcinomas. Staining for OPN was associated with a significant increase in survival time after post-operative whole-brain radiotherapy in retrospective (OPN negative 3.43 months, 95% CI: 1.36-5.51 vs OPN positive, 11.20 months 95% CI: 7.68-14.72, Log rank test, P<0.001) and validation populations.Conclusions:Proteins known to be involved in cellular adhesion and migration in vitro, and metastasis in vivo are significantly expressed in human brain metastases and may be useful biomarkers of intracranial progression and radiosensitivity

Effect of Phosphorus and Strontium Additions on Formation Temperature and Nucleation Density of Primary Silicon in Al-19 Wt Pct Si Alloy and Their Effect on Eutectic Temperature

The influence of P and Sr additions on the formation temperature and nucleation density of primary silicon in Al-19 wt pct Si alloy has been determined, for small volumes of melt solidified at cooling rates _T of ~0.3 and 1 K/s. The proportion of ingot featuring primary silicon decreased progressively with increased Sr addition, which also markedly reduced the temperature for first formation of primary silicon and the number of primary silicon particles per unit volume �Nv: When combined with previously published results, the effects of amount of P addition and cooling rate on �Nv are in reasonable accord with �Nv� _T ¼ ðp=6fÞ1=2 109 [250 � 215 (wt pct P)0.17]�3, where �Nv is in mm�3, _T is in K/s, and f is volume fraction of primary silicon. Increased P addition reduces the eutectic temperature, while increased Sr appears to generate a minimum in eutectic temperature at about 100 ppmw Sr

Allostatic load as a predictor of grey matter volume and white matter integrity in old age: The Whitehall II MRI study

The allostatic load index quantifies the cumulative multisystem physiological response to chronic everyday stress, and includes cardiovascular, metabolic and inflammatory measures. Despite its central role in the stress response, research of the effect of allostatic load on the ageing brain has been limited. We investigated the relation of mid-life allostatic load index and multifactorial predictors of stroke (Framingham stroke risk) and diabetes (metabolic syndrome) with voxelwise structural grey and white matter brain integrity measures in the ageing Whitehall II cohort (N = 349, mean age = 69.6 (SD 5.2) years, N (male) = 281 (80.5%), mean follow-up before scan = 21.4 (SD 0.82) years). Higher levels of all three markers were significantly associated with lower grey matter density. Only higher Framingham stroke risk was significantly associated with lower white matter integrity (low fractional anisotropy and high mean diffusivity). Our findings provide some empirical support for the concept of allostatic load, linking the effect of everyday stress on the body with features of the ageing human brain

Getting it right: a model for compliance assessment

Compliance is important for organisations but models and tools to aid understanding of compliance behaviour is limited. This paper argues that the understanding of the interaction between subjects and objects and their intention to comply with requirements of rules and regulations may be a predictor of compliance behaviour. Thus, a Conceptual Compliance Assessment Model (CAM) is developed by extension of Technology Acceptance Model and Activity theory for assessment of compliance behaviour. Data collected and evaluated showed that the awareness and understanding of the mediational tool is critical in realizing the outcome. It also showed that other factors like the perceived usefulness, perceived ease of use, the community and the management set up also affected compliance behaviour. Essentially, the use of CAM will be useful in assessing the compliance activities of subjects which may aid in formulation of behaviour support systems to improve compliance behaviour

Natural equilibrium states for multimodal maps

This paper is devoted to the study of the thermodynamic formalism for a class of real multimodal maps. This class contains, but it is larger than, Collet-Eckmann. For a map in this class, we prove existence and uniqueness of equilibrium states for the geometric potentials $-t \log|Df|$, for the largest possible interval of parameters $t$. We also study the regularity and convexity properties of the pressure function, completely characterising the first order phase transitions. Results concerning the existence of absolutely continuous invariant measures with respect to the Lebesgue measure are also obtained

The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism

Adherence of bacteria to biotic or abiotic surfaces is a prerequisite for host colonization and represents an important step in microbial pathogenicity. This attachment is facilitated by bacterial adhesins at the cell surface. Because of their size and often elaborate multidomain architectures, these polypeptides represent challenging targets for detailed structural and functional characterization. The multifunctional fibrillar adhesin CshA, which mediates binding to both host molecules and other microorganisms, is an important determinant of colonization by Streptococcus gordonii, an oral commensal and opportunistic pathogen of animals and humans. CshA binds the high-molecular-weight glycoprotein fibronectin (Fn) via an N-terminal non-repetitive region, and this protein-protein interaction has been proposed to promote S. gordonii colonization at multiple sites within the host. However, the molecular details of how these two proteins interact have yet to be established. Here we present a structural description of the Fn binding N-terminal region of CshA, derived from a combination of X-ray crystallography, small angle X-ray scattering, and complementary biophysical methods. In vitro binding studies support a previously unreported two-state “catch-clamp” mechanism of Fn binding by CshA, in which the disordered N-terminal domain of CshA acts to “catch” Fn, via formation of a rapidly assembled but also readily dissociable pre-complex, enabling its neighboring ligand binding domain to tightly clamp the two polypeptides together. This study presents a new paradigm for target binding by a bacterial adhesin, the identification of which will inform future efforts toward the development of anti-adhesive agents that target S. gordonii and related streptococci

Effect of Using the Same vs Different Order for Second Readings of Screening Mammograms on Rates of Breast Cancer Detection A Randomized Clinical Trial

Importance Interpreting screening mammograms is a difficult repetitive task that can result in missed cancers and false-positive recalls. In the United Kingdom, 2 film readers independently evaluate each mammogram to search for signs of cancer and examine digital mammograms in batches. However, a vigilance decrement (reduced detection rate with time on task) has been observed in similar settings. Objective To determine the effect of changing the order for the second film reader of batches of screening mammograms on rates of breast cancer detection. Design, Setting, and Participants A multicenter, double-blind, cluster randomized clinical trial conducted at 46 specialized breast screening centers from the National Health Service Breast Screening Program in England for 1 year (all between December 20, 2012, and November 3, 2014). Three hundred sixty readers participated (mean, 7.8 readers per center)—186 radiologists, 143 radiography advanced practitioners, and 31 breast clinicians, all fully qualified to report mammograms in the NHS breast screening program. Interventions The 2 readers examined each batch of digital mammograms in the same order in the control group and in the opposite order to one another in the intervention group. Main Outcomes and Measures The primary outcome was cancer detection rate; secondary outcomes were rates of recall and disagreements between readers. Results Among 1 194 147 women (mean age, 59.3; SD, 7.49) who had screening mammograms (596 642 in the intervention group; 597 505 in the control group), the images were interpreted in 37 688 batches (median batch size, 35; interquartile range [IQR]; 16-46), with each reader interpreting a median of 176 batches (IQR, 96-278). After completion of all subsequent diagnostic tests, a total of 10 484 cases (0.88%) of breast cancer were detected. There was no significant difference in cancer detection rate with 5272 cancers (0.88%) detected in the intervention group vs 5212 cancers (0.87%) detected in the control group (difference, 0.01% points; 95% CI, −0.02% to 0.04% points; recall rate, 24 681 [4.14%] vs 24 894 [4.17%]; difference, −0.03% points; 95% CI, −0.10% to 0.04% points; or rate of reader disagreements, 20 471 [3.43%] vs 20 793 [3.48%]; difference, −0.05% points; 95% CI, −0.11% to 0.02% points). Conclusions and Relevance Interpretation of batches of mammograms by qualified screening mammography readers using a different order vs the same order for the second reading resulted in no significant difference in rates of detection of breast cancer. Trial Registration isrctn.org Identifier: ISRCTN4660337