The generation of transverse and longitudinal vortices in low speed wind tunnels

The present study documents an experimental and numerical investigation into the feasibility of generating longitudinal and transverse vortices in low speed wind tunnels. The longitudinal vortex system is that of a co-rotating vortex pair which, if substituted for a classical single tip vortex, may produce a beneficial modification to Blade Vortex Interaction. The transverse vortex mimics the tip vortex of a typical helicopter rotor and may be used to assess its effect when interacting with other aerofoils or fuselage components. Experiments have been conducted to investigate the flow field associated with two co-rotating vortices which represent the idealised vortex system associated with a novel rotor blade tip platform - the Westland Helicopters Vane Tip. These vortices were generated by two rectangular NACA 0015 half wings positioned upstream of the working section of a low speed wind tunnel. Hot-wire measurements were conducted downstream of the generators using x-wire probes to document the strength, position and size of the vortices. A numerical model was utilised to provide an accurate means of determining vortex strength, position and size. Finally, the model was successfully extended to consider the rotation of the vortex system. The transverse vortex was generated by a rotating blade placed in the contraction of a low speed wind tunnel. A numerical model was utilised in the conceptual design of the experimental facility to model the flow through the settling chamber, contraction, working section and diffuser. This numerical model consisted of a three dimensional source panel method, used to calculate the constrained flow through the low speed tunnel, and a free wake model representing the wake generated by the vortex generator. Convection of the wake was determined by superposition of the undisturbed tunnel velocity and the induced velocity components from the wake itself. Results, obtained via a parametric analysis, illustrate the relationship between the geometry of the wake and basic physical design parameters. On this basis, two possible operational strategies for the upstream rotor are examined with reference to development of the experimental facility. It is concluded that, while a short duration finite rotor traverse may be the optimum vortex generation strategy, a continuous running rotor is a more cost effective and viable option

Variability and change in the Canadian cryosphere

Abstract During the International Polar Year (IPY), comprehensive observational research programs were undertaken to increase our understanding of the Canadian polar cryosphere response to a changing climate. Cryospheric components considered were snow, permafrost, sea ice, freshwater ice, glaciers and ice shelves. Enhancement of conventional observing systems and retrieval algorithms for satellite measurements facilitated development of a snapshot of current cryospheric conditions, providing a baseline against which future change can be assessed. Key findings include: 1. surface air temperatures across the Canadian Arctic exhibit a warming trend in all seasons over the past 40 years. A consistent pan-cryospheric response to these warming temperatures is evident through the analysis of multi-decadal datasets; 2. in recent years (including the IPY period) a higher rate of change was observed compared to previous decades including warming permafrost, reduction in snow cover extent and duration, reduction in summer sea ice extent, increased mass loss from glaciers, and thinning and break-up of the remaining Canadian ice shelves. These changes illustrate both a reduction in the spatial extent and mass of the cryosphere and an increase in the temporal persistence of melt related parameters. The observed changes in the cryosphere have important implications for human activity including the close ties of northerners to the land, access to northern regions for natural resource development, and the integrity of northern infrastructure

Leadership in Improving Schools: A Qualitative Perspective

This article reports early case-study data gathered from 20 schools involved in the ‘Impact of School Leadership on Pupil Outcomes’ project. We present and discuss the perceptions of headteachers and other school leaders regarding leadership factors that directly and indirectly affect pupil outcomes in these improving schools. Included are issues relating to the pivotal role played by the headteacher in setting and communicating a strategic vision for the school; models of distributed leadership; and the building of leadership capacity so as to build a collective responsibility for the improvement of pupil outcomes

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/Vurea, a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome

De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial

BACKGROUND: Discontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic myeloid leukaemia (CML) with deep molecular responses, defined as stable MR4 (BCR-ABL1/ABL1 ratio 0.1%) on two consecutive samples. The study endpoint is the proportion of patients who lose their MMR on de-escalation and regain MMR on TKI resumption. The trial was registered at https://clinicaltrials.gov/ as NCT 01804985.FINDINGS: During the 12 months of half-dose therapy, 12 patients had molecular recurrence, all of whom regained MMR within 4 months of full dose TKI resumption. Recurrence was lower in the MR4 cohort (3 of 121 evaluable patients; 2.5%, 90% CI: 0.2-4.8%) than in the MMR cohort (9 of 48 evaluable patients; 18.8%, 90% CI: 9.5-28%) (p = 0.0007), but was unrelated to prior TKI or TKI therapy duration. Many adverse events improved during the first 3 months of de-escalation, though not thereafter. Overall, de-escalation saved 46.7% from an expected TKI budget (without de-escalation) of £4,156,969.INTERPRETATION: TKI de-escalation is safe for the vast majority of patients with excellent responses to TKI therapy, and is associated with improvement in symptoms and significant financial savings. The data imply that lower TKI doses may maintain responses in these patients

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes