Predicting critical power in elite cyclists: questioning validity of the 3-min All-out test

Purpose: New applications of the critical power concept, such as the modelling of intermittent work capabilities, are exciting prospects for elite cycling. However, accurate calculation of the required parameters is traditionally time invasive and somewhat impractical. An alternative single test protocol (3-min All-out) has recently been proposed, but validation in an elite population is lacking. The traditional approach for parameter establishment, but with fewer tests, could also prove an acceptable compromise. Methods: Six senior Australian endurance track cycling representatives completed six efforts to exhaustion on two separate days over a three week period. These included 1, 4, 6, 8 and 10 minute self-paced efforts, plus the 3-min All-out protocol. Traditional work versus time calculations of CP and W’ using the five self-paced efforts were compared to calculations from the 3-min All-out protocol. The impact of using just two or three self-paced efforts for traditional CP and W’ estimation were also explored using thresholds of agreement (8W, 2.0kJ respectively). Results: CP estimated from the 3-min All-out approach was significantly higher than from the traditional approach (402±33W, 351±27W, p<0.001), whilst W’ was lower (15.5±3.0kJ, 24.3±4.0kJ, p=0.02). Five different combinations of two or three self-paced efforts led to CP estimates within the threshold of agreement, with only one combination deemed accurate for W’. Conclusions: In elite cyclists the 3-min All-out approach is not suitable to estimate CP when compared to the traditional method. However, reducing the number of tests used in the traditional method lessens testing burden whilst maintaining appropriate parameter accuracy.Jason C Bartram, Dominic Thewlis, David T Martin, Kevin I Norto

Influence of Context on Item Parameters in Forced-Choice Personality Assessments

A fundamental assumption in computerized adaptive testing (CAT) is that item parameters are invariant with respect to context – items surrounding the administered item. This assumption, however, may not hold in forced-choice (FC) assessments, where explicit comparisons are made between items included in the same block. We empirically examined the influence of context on item parameters by comparing parameter estimates from two FC instruments. The first instrument was compiled of blocks of three items, whereas in the second, the context was manipulated by adding one item to each block, resulting in blocks of four. The item parameter estimates were highly similar. However, a small number of significant deviations were observed, confirming the importance of context when designing adaptive FC assessments. Two patterns of such deviations were identified, and methods to reduce their occurrences in a FC CAT setting were proposed. It was shown that with a small proportion of violations of the parameter invariance assumption, score estimation remained stable

Inhibition of IGF1-R overcomes IGFBP7-induced chemotherapy resistance in T-ALL

Background T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease with the need for treatment optimization. Previously, high expression of Insulin-like growth factor binding protein 7 (IGFBP7), a member of the IGF system, was identified as negative prognostic factor in adult T-ALL patients. Since aberrant IGFBP7 expression was observed in a variety of neoplasia and was relevant for prognosis in T-ALL, we investigated the functional role of IGFBP7 in Jurkat and Molt-4 cells as in vitro models for T-ALL. Methods Jurkat and Molt-4 cells were stably transfected with an IGFBP7 over-expression vector or the empty vector as control. Proliferation of the cells was assessed by WST-1 assays and cell cycle status was measured by flow-cytometry after BrDU/7-AAD staining. The effect of IGFBP7 over-expression on sensitivity to cytostatic drugs was determined in AnnexinV/7-AAD assays. IGF1-R protein expression was measured by Western Blot and flow-cytometric analysis. IGF1-R associated gene expression profiles were generated from microarray gene expression data of 86 T-ALL patients from the Microarrays Innovations in Leukemia (MILE) multicenter study. Results IGFBP7-transfected Jurkat cells proliferated less, leading to a longer survival in a nutrient–limited environment. Both IGFBP7-transfected Jurkat and Molt-4 cells showed an arrest in the G0/G1 cell cycle phase. Furthermore, Jurkat IGFBP7-transfected cells were resistant to vincristine and asparaginase treatment. Surface expression and whole protein measurement of IGF1-R protein expression showed a reduced abundance of the receptor after IGFBP7 transfection in Jurkat cells. Interestingly, combination of the IGF1-R inhibitor NPV-AEW541 restored sensitivity to vincristine in IGFBP7-transfected cells. Additionally, IGF1-R associated GEP revealed an up-regulation of important drivers of T-ALL pathogenesis and regulators of chemo-resistance and apoptosis such as NOTCH1, BCL-2, PRKCI, and TP53. Conclusion This study revealed a proliferation inhibiting effect of IGFBP7 by G0/G1 arrest and a drug resistance-inducing effect of IGFBP7 against vincristine and asparaginase in T-ALL. These results provide a model for the previously observed association between high IGFBP7 expression and chemotherapy failure in T-ALL patients. Since the resistance against vincristine was abolished by IGF1-R inhibition, IGFBP7 could serve as biomarker for patients who may benefit from therapies including IGF1-R inhibitors in combination with chemotherapy

Experimental Investigation of Rotorcraft Outwash in Ground Effect

The wake characteristics of a rotorcraft are affected by the proximity of a rotor to the ground surface, especially during hover. Ground effect is encountered when the rotor disk is within a distance of a few rotor radii above the ground surface and results in an increase in thrust for a given power relative to that same power condition with the rotor out of ground effect. Although this phenomenon has been highly documented and observed since the beginning of the helicopter age, there is still a relatively little amount of flow-field data existing to help understand its features. Joint Army and NASA testing was conducted at NASA Langley Research Center using a powered rotorcraft model in hover at various rotor heights and thrust conditions in order to contribute to the complete outwash data set. The measured data included outwash velocities and directions, rotor loads, fuselage loads, and ground pressures. The researchers observed a linear relationship between rotor height and percent download on the fuselage, peak mean outwash velocities occurring at radial stations between 1.7 and 1.8 r/R regardless of rotor height, and the measurement azimuthal dependence of the outwash profile for a model incorporating a fuselage. Comparisons to phase-locked PIV data showed similar contours but a more contracted wake boundary for the PIV data. This paper describes the test setup and presents some of the averaged results

Does global progress on sanitation really lag behind water? An analysis of global progress on community- and household-level access to safe water and sanitation.

Safe drinking water and sanitation are important determinants of human health and wellbeing and have recently been declared human rights by the international community. Increased access to both were included in the Millennium Development Goals under a single dedicated target for 2015. This target was reached in 2010 for water but sanitation will fall short; however, there is an important difference in the benchmarks used for assessing global access. For drinking water the benchmark is community-level access whilst for sanitation it is household-level access, so a pit latrine shared between households does not count toward the Millennium Development Goal (MDG) target. We estimated global progress for water and sanitation under two scenarios: with equivalent household- and community-level benchmarks. Our results demonstrate that the "sanitation deficit" is apparent only when household-level sanitation access is contrasted with community-level water access. When equivalent benchmarks are used for water and sanitation, the global deficit is as great for water as it is for sanitation, and sanitation progress in the MDG-period (1990-2015) outstrips that in water. As both drinking water and sanitation access yield greater benefits at the household-level than at the community-level, we conclude that any post-2015 goals should consider a household-level benchmark for both

γδβ-thalassaemias 1 and 2 are the result of a 100 kpb deletion in the human β-globin cluster.

The DNA spanning two large deletions in the human beta-globin gene cluster (gamma beta-thalassaemia 1 and 2) has been cloned by cosmid cloning and chromosomal walking. The entire region was mapped and analyzed for the presence of repetitive sequences. The results show that the affected loci have lost almost 100 kb of DNA in a deletion event not involving homologous or repetitive sequences

FLT3 mutations in Early T-Cell Precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup

Navier-Stokes Simulation of a Heavy Lift Slowed-Rotor Compound Helicopter Configuration

Time accurate numerical simulations were performed using the Reynolds-averaged Navier-Stokes (RANS) flow solver OVERFLOW for a heavy lift, slowed-rotor, compound helicopter configuration, tested at the NASA Langley 14- by 22-Foot Subsonic Tunnel. The primary purpose of these simulations is to provide support for the development of a large field of view Particle Imaging Velocimetry (PIV) flow measurement technique supported by the Subsonic Rotary Wing (SRW) project under the NASA Fundamental Aeronautics program. These simulations provide a better understanding of the rotor and body wake flows and helped to define PIV measurement locations as well as requirements for validation of flow solver codes. The large field PIV system can measure the three-dimensional velocity flow field in a 0.914m by 1.83m plane. PIV measurements were performed upstream and downstream of the vertical tail section and are compared to simulation results. The simulations are also used to better understand the tunnel wall and body/rotor support effects by comparing simulations with and without tunnel floor/ceiling walls and supports. Comparisons are also made to the experimental force and moment data for the body and rotor

Examining the effects of Lighting Effects on Peripheral Devices for Visual User Notifications

The ubiquitous and pervasive use of lighting effects embedded into peripheral hardware has gained popularity through it’s use in Triple-A video game titles such as Call of Duty and the availability of software development kits (SDK) from leading manufacturers. A preliminary NASA TLX experiment was performed to examine the effect that notifications displayed on a peripheral device has, in comparison to traditional dialog notifications. This research will prove useful to create notification design guidance for these devices

Mechanisms of Active Aerodynamic Load Reduction on a Rotorcraft Fuselage With Rotor Effects

The reduction of the aerodynamic load that acts on a generic rotorcraft fuselage by the application of active flow control was investigated in a wind tunnel test conducted on an approximately 1/3-scale powered rotorcraft model simulating forward flight. The aerodynamic mechanisms that make these reductions, in both the drag and the download, possible were examined in detail through the use of the measured surface pressure distribution on the fuselage, velocity field measurements made in the wake directly behind the ramp of the fuselage and computational simulations. The fuselage tested was the ROBIN-mod7, which was equipped with a series of eight slots located on the ramp section through which flow control excitation was introduced. These slots were arranged in a U-shaped pattern located slightly downstream of the baseline separation line and parallel to it. The flow control excitation took the form of either synthetic jets, also known as zero-net-mass-flux blowing, and steady blowing. The same set of slots were used for both types of excitation. The differences between the two excitation types and between flow control excitation from different combinations of slots were examined. The flow control is shown to alter the size of the wake and its trajectory relative to the ramp and the tailboom and it is these changes to the wake that result in a reduction in the aerodynamic load