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The High Beta Tokamak-Extended Pulse has recently incorporated a tangential multi-energy extreme ultraviolet and soft x-ray diagnostic system. This system enables measurements of the electron temperature and the examination of mode dynamics within the tokamak. While other systems have been built for poloidal views over similar temperature ranges, this is the first multi-energy tangential-view system designed to work in a temperature range below 200 eV in a tokamak. To facilitate these measurements, a filter wheel comprising five distinct groups of dual-filters has been developed and implemented. By employing a combination of 0.1 μm aluminum and 0.2 μm titanium filters, the system allows estimation of electron temperature profiles through reconstruction of the emission profile using the standard "double-foil" technique. The influence of impurities and filter oxide layers on measurement outcomes is examined. Results reveal that, while the absolute electron temperature values may exhibit some deviations, key characteristics like the electron temperature profile shape and inversion radius during sawtooth events remain consistent. This consistency confirms the system's suitability for core plasma studies. This system has proven effective in detecting and analyzing internal magnetohydrodynamic phenomena, such as sawteeth. [ABSTRACT FROM AUTHOR]

Low-activation ferritic steels are leading material candidates for use in next-generation fusion development experiments such as a prospective component test facility and DEMO power reactor. Understanding the interaction of plasmas with a ferromagnetic wall will provide crucial physics for these facilities. In order to study ferromagnetic effects in toroidal geometry, a ferritic wall upgrade was designed and installed in the High Beta Tokamak-Extended Pulse (HBT-EP). Several material options were investigated based on conductivity, magnetic permeability, vacuum compatibility, and other criteria, and the material of choice (high-cobalt steel) is characterized. Installation was accomplished quickly, with minimal impact on existing diagnostics and overall machine performance, and initial results demonstrate the effects of the ferritic wall on plasma stability. [ABSTRACT FROM AUTHOR]

High-resolution active and passive kink mode studies are conducted in a tokamak with an adjustable ferromagnetic wall near the plasma surface. Ferritic tiles made from 5.6 mm thick Hiperco® 50 alloy have been mounted on the plasma-facing side of half of the in-vessel movable wall segments in the High Beta Tokamak-Extended Pulse device [D. A. Maurer et al., Plasma Phys. Controlled Fusion 53, 074016 (2011)] in order to explore ferritic resistive wall mode stability. Low-activation ferritic steels are a candidate for structural components of a fusion reactor, and these experiments examine MHD stability of plasmas with nearby ferromagnetic material. Plasma-wall separation for alternating ferritic and non-ferritic wall segments is adjusted between discharges without opening the vacuum vessel. Amplification of applied resonant magnetic perturbations and plasma disruptivity are observed to increase when the ferromagnetic wall is close to plasma surface instead of the standard stainless steel wall. Rapidly rotating m/n=3/1 external kink modes have higher growth rates with the nearby ferritic wall. Feedback suppression of kinks is still as effective as before the installation of ferritic material in vessel, in spite of increased mode growth rates. [ABSTRACT FROM AUTHOR]

We present high-resolution detection and control of the 3D magnetic boundary in the High Beta Tokamak-Extended Pulse (HBT-EP) device. Measurements of non-axisymmetric radial andpoloidal fields are made using 216 magnetic sensors positioned near the plasma surface. Control of 3D fields is accomplished using 40 independent saddle coils attached to the passive stabilizing wall. The control coils are energized with high-power solid-state amplifiers, and massively parallel, high-throughput feedback control experiments are performed using low-latency connections between PCI Express analogue input and output modules and a graphics processing unit. The time evolution of unstable and saturated wall-stabilized external kink modes are studied with and without applying magnetic perturbations using the control coils. The 3D dynamic structure of the magnetic field surrounding the plasma is determined through biorthogonal decomposition using the full set of magnetic sensors without the need to fit either a Fourier or a model-based basis. Naturally occurring external kinks are composed of multiple independent helical modes. Smooth transitions between dominant poloidal mode numbers are observed for simultaneous n = 1 and n = 2 modes as the edge safety factor changes. Relative amplitudes of coexistent m/n = 3/1 and 6/2 modes depend on the plasma's major radius and edge safety factor. When stationary 3/1 magnetic perturbations are applied, the resonant response can be linear, saturated, or disruptive, depending upon the perturbation amplitude and the edge safety factor; increased plasma-wall interactions from the perturbed plasma are proposed as a saturation mechanism. Initial feedback experiments have used 40 sensors and 40 control coils, producing mode amplification or suppression, and acceleration or deceleration depending on the feedback phase angle. [ABSTRACT FROM AUTHOR]

A unique in situ calibration technique has been used to spatially calibrate and characterize the extensive new magnetic diagnostic set and close-fitting conducting wall of the High Beta Tokamak-Extended Pulse (HBT-EP) experiment. A new set of 216 Mirnov coils has recently been installed inside the vacuum chamber of the device for high-resolution measurements of magnetohydrodynamic phenomena including the effects of eddy currents in the nearby conducting wall. The spatial positions of these sensors are calibrated by energizing several large in situ calibration coils in turn, and using measurements of the magnetic fields produced by the various coils to solve for each sensor's position. Since the calibration coils are built near the nominal location of the plasma current centroid, the technique is referred to as an 'artificial plasma' calibration. The fitting procedure for the sensor positions is described, and results of the spatial calibration are compared with those based on metrology. The time response of the sensors is compared with the evolution of the artificial plasma current to deduce the eddy current contribution to each signal. This is compared with simulations using the VALEN electromagnetic code, and the modeled copper thickness profiles of the HBT-EP conducting wall are adjusted to better match experimental measurements of the eddy current decay. Finally, the multiple coils of the artificial plasma system are also used to directly calibrate a non-uniformly wound Fourier Rogowski coil on HBT-EP. [ABSTRACT FROM AUTHOR]

Mobilization and collection of haemopoietic stem and progenitor cells (HSPC) is the cornerstone of autologous and allogeneic stem cell transplantation for a wide variety of haematological and some non-haematological malignancies. Centres providing this service face the challenge of optimizing the likelihood of successful collection of transplantable doses of cells, while maximizing the efficiency of the apheresis unit and minimizing the risk of toxicity as well as mobilization failure. Recent developments in the understanding of the molecular mechanisms of mobilization have led to the emergence of novel strategies for HSPC mobilization, which may assist in meeting these imperatives. The task for clinicians is how to incorporate the use of these strategies into practice, in the light of emerging evidence for efficacy and safety of these agents. Herein, the literature is reviewed, and a proposed algorithm for HSPC mobilization is presented. [ABSTRACT FROM AUTHOR]

The Thomson scattering diagnostic on the High Beta Tokamak-Extended Pulse (HBT-EP) is routinely used to measure electron temperature and density during plasma discharges. Avalanche photodiodes in a five-channel interference filter polychromator measure scattered light from a 6 ns, 800 mJ, 1064 nm Nd:YAG laser pulse. A low cost, high-power spatial filter was designed, tested, and added to the laser beamline in order to reduce stray laser light to levels which are acceptable for accurate Rayleigh calibration. A detailed analysis of the spatial filter design and performance is given. The spatial filter can be easily implemented in an existing Thomson scattering system without the need to disturb the vacuum chamber or significantly change the beamline. Although apertures in the spatial filter suffer substantial damage from the focused beam, with proper design they can last long enough to permit absolute calibration. [ABSTRACT FROM AUTHOR]

While high harmonic generation from atoms is relatively well understood, the ability to align gas-phase molecules opens an opportunity to more deeply understand the underlying physics. Many assumptions, such as the single active electron approximation, neglect of the Coulomb potential, the strong field approximation, and the assumption of plane waves, are being challenged by new experimental observations. We study high harmonic emission from aligned molecules such as N2, O2 and CO2. We present experimental measurements of the amplitude of the emission as a function of molecular angle, as well as the polarization state. [ABSTRACT FROM AUTHOR]

Endolyn (CD164) is a sialomucin that functions as an adhesion molecule and a negative regulator of CD34+ CD38– human haematopoietic precursor cell proliferation. The 105A5 and 103B2/9E10 CD164 monoclonal antibodies (mAbs), which act as surrogate ligands, recognize distinct glycosylation-dependent classes I and II epitopes located on domain I of the native and recombinant CD164 proteins. Here, we document five new CD164 mAbs, the 96 series, that rely on conformational integrity, but not glycosylation, of exons 2- and 3-encoded CD164 domains, thereby resembling the class III mAbs, N6B6 and 67D2. Although all the 96 series class III mAbs labelled both the 105A5+ and 103B2/9E10+ cells, cross-competition and immunoblotting studies allow them to be categorized into two distinct class III subgroups, i.e. the N6B6-like subgroup that only recognizes 80–100 kDa proteins and the 67D2-like subgroup that also recognizes a higher molecular weight (>220 kDa) form. To more closely define the reactivity patterns of mAbs to the classes I and II epitopes, the global glycosylation patterns of the soluble human (h) CD164 proteins were determined using lectin binding, high-performance liquid chromatography (HPLC) and mass spectrometry. hCD164 recombinant proteins bound to the lectins,Galanthus nivalisagglutinin,Datura stramoniumagglutinin,Sambucus nigraagglutinin,Maackia amurensisagglutinin and peanut agglutinin, indicating the presence of high mannose and complex N-glycans, in addition to core 1 O-glycans (the Tn antigen) andα2-3 andα2-6 sialic acid moieties. Our HPLC and mass spectrometry results revealed both high mannose and complex N-glycosylation with various numbers of branches increasing the complexity of the glycosylation pattern. Most O-glycans were small, core 1 or 2 based. High levels of sialylation inα2-3 andα2-6 linkages, without sialyl-Lewis X, indicate that the majority of these hCD164 recombinant proteins are unable to bind to selectins in our assay system, but may interact with Siglec molecules. [ABSTRACT FROM AUTHOR]

Single-electron wavefunctions, or orbitals, are the mathematical constructs used to describe the multi-electron wavefunction of molecules. Because the highest-lying orbitals are responsible for chemical properties, they are of particular interest. To observe these orbitals change as bonds are formed and broken is to observe the essence of chemistry. Yet single orbitals are difficult to observe experimentally, and until now, this has been impossible on the timescale of chemical reactions. Here we demonstrate that the full three-dimensional structure of a single orbital can be imaged by a seemingly unlikely technique, using high harmonics generated from intense femtosecond laser pulses focused on aligned molecules. Applying this approach to a series of molecular alignments, we accomplish a tomographic reconstruction of the highest occupied molecular orbital of N2. The method also allows us to follow the attosecond dynamics of an electron wave packet. [ABSTRACT FROM AUTHOR]

Exact (non-Born-Oppenheimer) numerical solutions of the time-dependent Schrödinger equation for a 1-D model of the one-electron systems $ \rm H^+ _2 $ , HD + and HT + have been obtained in a two-colour laser control scheme, ω + 2 ω, of dissociation and dissociative ionization. Calculations have been performed at wavelengths λCO 2 = 10.3 µm and λ YAG = 1.064 µm. It is found that the phase sensitivity of the asymmetric nuclear dissociation is completely different in the two wavelength regimes. Quasistatic models of the dissociation process are used to interpret the results and the effect of ionization is investigated at high intensities ( I ≥ 10 14 W cm -2 ). [ABSTRACT FROM AUTHOR]

Active feedback control in magnetic confinement fusion devices is desirable to mitigate plasma instabilities and enable robust operation. Optical high-speed cameras provide a powerful, non-invasive diagnostic and can be suitable for these applications. In this study, we process high-speed camera data, at rates exceeding 100 kfps, on in situ field-programmable gate array (FPGA) hardware to track magnetohydrodynamic (MHD) mode evolution and generate control signals in real time. Our system utilizes a convolutional neural network (CNN) model, which predicts the n = 1 MHD mode amplitude and phase using camera images with better accuracy than other tested non-deep-learning-based methods. By implementing this model directly within the standard FPGA readout hardware of the high-speed camera diagnostic, our mode tracking system achieves a total trigger-to-output latency of 17.6 μs and a throughput of up to 120 kfps. This study at the High Beta Tokamak-Extended Pulse (HBT-EP) experiment demonstrates an FPGA-based high-speed camera data acquisition and processing system, enabling application in real-time machine-learning-based tokamak diagnostic and control as well as potential applications in other scientific domains. [ABSTRACT FROM AUTHOR]

Investigations of biasing induced H-mode discharges on HBT-EP show that the edge turbulence is consistent with the ion temperature gradient) mode and have allowed for the controlled observation of the effect of applied flow shear on the turbulence. Measurements of the radial wavenumber spectrum of floating potentials at the edge show that the turbulence intensity decreases with increasing shift in the spectrum average ⟨ k r ⟩ when increasing amounts of bias probe voltage (and increasing amounts of flow shear) is applied. This is in agreement with the spectral shift model [Staebler et al., Phys. Rev. Lett. 110, 055003 2013] for turbulence suppression via sheared flow. A shift in the wavenumber spectrum occurs at applied electrode voltages and currents below the threshold needed for an L–H transition, and a dithering transition is obtained when biasing near the threshold. Suppression of blob-filament turbulence in the scrape-off layer (SOL) precedes the L–H transition, with the SOL turbulence remaining low throughout the dithering phase, despite the modulation of turbulence levels in the nearby edge. This demonstrates that the SOL turbulence "decouples" from the edge turbulence. The spectral shift in the measured radial wavenumber is corroborated by the direct measurement of eddy tilt angle using a novel time delay analysis technique first developed for Doppler reflectometry [Pinzón et al., Plasma Phys. Controlled Fusion 61, 105009 (2019)] but adapted here for floating potential measurements. [ABSTRACT FROM AUTHOR]

Background: Disparities in access to primary care (PC) have been demonstrated within and between health systems. However, few studies have assessed the factors associated with multiple barriers to access occurring along the care-seeking process in different healthcare systems. Methods: In this secondary analysis of the 2016 Commonwealth Fund International Health Policy Survey of Adults, access was represented through participant responses to questions relating to access barriers either before or after reaching the PC practice in 11 countries (Australia, Canada, France, Germany, Norway, the Netherlands, New Zealand, Sweden, Switzerland, the United Kingdom, and United States). The number of respondents in each country ranged from 1000 to 7000 and the response rates ranged from 11% to 47%. We used multivariable logistic regression models within each of eleven countries to identify disparities in response to the access barriers by age, sex, immigrant status, income and the presence of chronic conditions. Results: Overall, one in five adults (21%) experienced multiple barriers before reaching PC practices. After reaching care, an average of 16% of adults had two or more barriers. There was a sixfold difference between nations in the experience of these barriers to access. Vulnerable groups experiencing multiple barriers were relatively consistent across countries. People with lower income were more likely to experience multiple barriers, particularly before reaching primary care practices. Respondents with mental health problems and those born outside the country displayed substantial vulnerability in terms of barriers after reaching care. Conclusion: A greater understanding of the multiple barriers to access to PC across the stages of the care-seeking process may help to inform planning and performance monitoring of disparities in access. Variation across countries may reveal organisational and system drivers of access, and inform efforts to improve access to PC for vulnerable groups. The cumulative nature of these barriers remains to be assessed. [ABSTRACT FROM AUTHOR]

Inertial confinement fusion (ICF) and high-energy density (HED) physics experiments experience complicated forcing for instability growth and mix due to the ubiquitous presence of multiple shocks interacting with perturbations on multiple material interfaces. One common driver of instability growth is successive shocks from the same direction. However, there is a severe lack of analytic work and modeling validation for same-sided successive shocks since they are extremely difficult to achieve with conventional (non-HED) drivers. Successive shocks access a large instability parameter space; idealized fluid theory [K. O. Mikaelian, Phys. Rev. A 31, 410 (1985)] predicts 15 different interface evolution scenarios for a sinusoidal perturbation. Growth becomes more complex for multi-mode, compressible HED systems. The Mshock campaign is the first experiment in any fluid regime to probe a wide portion of successive shock parameter space. This is enabled by our development of a hybrid direct/indirect drive platform capable of creating independently controllable successive shocks on the National Ignition Facility. These experiments have delivered the first data capable of rigorously challenging our models and their ability to accurately capture Richtmyer–Meshkov growth under successive shocks. Single-mode and two-mode experiments have successfully demonstrated the ability to access and control the various growth scenarios of the shocked interface, including re-inversion, freeze out, and continued growth. Simulations and theoretical modeling are shown to accurately capture the experimental observations in the linear growth phase, giving us confidence in our ICF/HED design codes. [ABSTRACT FROM AUTHOR]

In this study, an analysis of elastic residual stress in Inconel ® 718 (IN 718) linear friction welds (LFWs) was carried out. In particular, the suitability of LFW for manufacturing and repair of aero engine components was emulated by joining virgin and in-service (extracted from a turbine disk) materials. The evolution in the residual strains and stresses in the heat-affected zone (HAZ), thermomechanically affected zone (TMAZ) and dynamically recrystallized zone (DRX) of the weld was characterized using the neutron diffraction and contour methods. The results provided insight into diverse challenges in quantitative analysis of residual stresses in welded IN 718 using diffraction techniques. Specifically, judicious selection of the beam width, height and stress-free lattice spacing were seen to be crucial to minimize measurement error and increase accuracy. Further, the contour method – a destructive technique relying on capturing the stress relaxation after electrical discharge machining – was used to characterize the residual stress distribution on two-dimensional plane sections of the welds. Both techniques suggested an increasing magnitude of residual stress originating from the base metal that reached a peak at the weld interface. Both methods indicated that the peak magnitude of residual stresses were below the yield stress of IN 718. [ABSTRACT FROM AUTHOR]

Asymmetric halo currents (HCs) can exert large net forces on the vacuum vessel and other components during disruptions on tokamaks. The displacements caused by these forces can then be amplified if these asymmetric forces rotate at frequencies resonant with the vessel. This paper reports on the investigation of a recently proposed scaling law for the disruption HC rotation frequency [Saperstein et al., "Halo current rotation scaling in post-disruption plasmas," Nucl. Fusion 62, 026044 (2022)] that combines measurements on Alcator C-Mod with those on HBT-EP. We find that a new non-circular version of the scaling law [ ⟨ f rot ⟩ m / ⟨ m ⟩ ∝ 1 B T (S / π) ] takes into consideration the dependence of frot on the poloidal structure of the MHD instability (m) driving the asymmetry and describes the disruption-averaged rotation frequency on C-Mod. Disruption rotation is also found to be insensitive to the vertical position and impurity content of the plasma at the onset of the disruption. However, a stagnation in the time evolution of frot is occasionally observed. Observations are consistent with the dominance of poloidal rotation during the disruption, which is motivated by the poloidal drift nature of the scaling law. [ABSTRACT FROM AUTHOR]

An abstract is presented of the article "Prognosis Following Acute Whiplash Associated Disorder: Development of a New Clinical Tool."

The article presents information related to the "Journal of Youth & Adolescence." The current editorial staff has carefully thought through the transition and addressed all critical technicalities. In addition, the Journal already enjoys a secure base and stature. The Journal holds the distinction of being the most established and most cited journal that is devoted to the study of adolescence. The Journal will need to move toward electronic management and will need to carve a place for itself among several successful journals that have emerged in recent years.

Background: While comorbidities and types of road users are known to influence survival in people hospitalised with injury, few studies have examined the association between comorbidities and survival in people injured in road traffic crashes. Further, few studies have examined outcomes across different types of road users with different types of pre-existing comorbidities. This study aims to examine differences in survival within 30 days of admission among different road user types with and without different pre-existing comorbidities.Method: Retrospective cohort study using data for all major road trauma cases were extracted from the NSW Trauma Registry Minimum Dataset (1 January 2013 - 31 July 2019) and linked to the NSW Admitted Patient Data Collection, and the NSW Registry of Births, Deaths and Marriages - death dataset. Pre-existing comorbidities and road user types were identified by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes and Charlson Comorbidity Index in the Trauma Registry, hospital admission, and death datasets. Logistic regression was used to assess the associations between six types of road users (pedestrian, pedal cycle, two- and three-wheel motorcycle, car and pick-up truck, heavy vehicle and bus, and other types of vehicle) and death within 30 days of hospital admission while controlling for comorbidities. All models used 'car and pick-up truck driver/passenger' as the road user reference group and adjusted for demographic variables, injury severity, and level of impaired consciousness.Results: Within 6253 traffic injury person-records (all aged ≥15 years old, ISS>12), and in final models, injured road users with major trauma who had a history of cardiovascular diseases (including stroke), diabetes mellitus, and higher Charlson Comorbidity Index score, were more likely to die, than those without pre-existing comorbidities. Furthermore, in final models, pedestrians were more likely to die than car occupants (OR: 1.68 - 1.77, 95CI%: 1.26 - 2.29 depending on comorbidity type).Conclusions: This study highlights the need to prioritize enhanced management of trauma patients with comorbidities, given the increasing prevalence of chronic medical conditions globally, together with actions to prevent pedestrian crashes in strategies to reach Vision Zero. [ABSTRACT FROM AUTHOR]

An advanced adaptive control algorithm is used to study the control of external kink modes that are excited in the HBT-EP tokamak and have a natural toroidal rotation frequency near 8 kHz. The controller's system model is parametrized and the parameters are adjusted in real-time to match the measured plasma evolution. Depending upon a programmed phase angle, active feedback control is shown to either suppress or amplify the controlled amplitude by an amount comparable to the variations observed over a variety of plasma discharges. With negative feedback, the maximum amplitude is reduced to 40% of the uncontrolled value. With positive feedback, the amplitude increases to 155%. Intermediate feedback phases lead to an acceleration or deceleration of the mode rotation frequency in addition to changes in mode amplitude. As the feedback gain increases, the level of both mode suppression and mode amplification also increases. However, for sufficiently high gain, kink mode suppression becomes limited by the excitation of an additional, slowly rotating 1.4 kHz mode having the same helical structure as the uncontrolled kink. High gain amplification is limited by disruptive loss of plasma current. Experimental results are compared with numerical simulations based on a single helicity model, and qualitative agreement is found. [ABSTRACT FROM AUTHOR]

Generating attosecond pulses has required a radically different approach from previous ultrafast optical methods. The technology of attosecond measurement, however, is built on established methods of characterizing femtosecond pulses: the pulse is measured after it has left the region where it was produced. We offer a completely different approach: in situ measurement. That is, we integrate attosecond-pulse production and measurement in a manner that can be applied to many high-order nonlinear interactions. To demonstrate this approach, we combine a low-intensity (<10−3) second-harmonic beam with the fundamental beam, to gently perturb the production process without significantly modifying it. The attosecond-pulse duration is read from the modulation of the even-harmonic signal as a function of the two-field delay. Increasing the second-harmonic intensity slightly (<10−2), we extend measurement to control. We demonstrate control by manipulating the high-harmonic spectrum with high efficiency. [ABSTRACT FROM AUTHOR]

Rotation of the plasma and MHD modes in tokamaks has been shown to stabilize resistive wall and tearing modes as well as improve confinement through suppression of edge turbulence. In this work, we control mode rotation with a biased electrode inserted into the plasma of the High Beta Tokamak-Extended Pulse's facility in conjunction with its active GPU (Graphical Processing Unit) feedback system. We first characterize a negative linear relationship between the electrode voltage and mode rotation. Using this relationship, we design, simulate, and implement a proof-of-concept, GPU-based active-control system, which shows consistent success in controlling mode rotation in both feedforward and feedback operation. Controllability is limited by operating conditions, the electrode's voltage range, and by the electrode's proximity to the vessel's walls. The final control system has a 15 μs cycle time, but the addition of various signal filters results in a full cycle latency of 200 μs. [ABSTRACT FROM AUTHOR]

Leading-edge infrastructure renovation is driven by innovations in materials processing to optimize desired properties. The immediate challenge for the metal industry is the development of effective and efficient materials quality-control practices. At present, mechanical and sheet forming properties are assessed using standard tensile tests to measure yield and ultimate tensile strengths, as well as the total elongation to failure. The resulting stress-strain data is used as a “pass-fail” test to ensure that the product meets industry specifications. We report a new method of constitutive relation analyses (CRA) that can extract fundamental information regarding the underlying crystalline mechanisms of deformation and failure from standard stress-strain data. The CRA method is applied to industrial extrusion product made from AA6063 aluminum alloy to demonstrate how this type of forensic examination can be used to direct changes to thermo-mechanical processing to optimize desired material properties. The CRA prediction of point-defect generation and nano-void formation leading to ductile failure during plastic flow was validated by small angle X-ray scattering (SAXS) studies. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor (HIF)-1α accumulation promotes hematopoietic stem cells' quiescence and is necessary to maintain their self-renewal. However, the role of HIF-2α in hematopoietic cells is less clear. We investigated the role of HIF-2α in leukemia and lymphoma cells. HIF-2α expression was high in subsets of human and mouse leukemia and lymphoma cells, whereas it was low in normal bone marrow leukocytes. To investigate the role of HIF-2α, we transduced human HIF-2α cDNA in mouse syngeneic models of myeloid preleukemia and a transgenic model of B lymphoma. Ectopic expression of HIF-2α accelerated leukemia cell proliferation in vitro. Mice transplanted with cells transduced with HIF-2α died significantly faster of leukemia or B lymphoma than control mice transplanted with empty vector-transduced cells. Conversely, HIF-2α knockdown in human myeloid leukemia HL60 cells decreased proliferation in vitro and significantly prolonged animal survival following transplantation. In human acute myeloid leukemia (AML), HIF-2α mRNA was significantly elevated in several subsets such as the t(15;17), inv(16), complex karyotype and favorable cytogenetic groups. However, patients with high HIF-2α expression had a trend to higher disease-free survival in univariate analysis. The different effects of HIF-2α overexpression in mouse models of leukemia and human AML illustrates the complexity of this mutliclonal disease. [ABSTRACT FROM AUTHOR]

Many patients with hematological neoplasms fail to mobilize sufficient numbers of hematopoietic stem cells (HSCs) in response to granulocyte colony-stimulating factor (G-CSF) precluding subsequent autologous HSC transplantation. Plerixafor, a specific antagonist of the chemokine receptor CXCR4, can rescue some but not all patients who failed to mobilize with G-CSF alone. These refractory poor mobilizers cannot currently benefit from autologous transplantation. To discover alternative targetable pathways to enhance HSC mobilization, we studied the role of hypoxia-inducible factor-1α (HIF-1α) and the effect of HIF-1α pharmacological stabilization on HSC mobilization in mice. We demonstrate in mice with HSC-specific conditional deletion of the Hif1a gene that the oxygen-labile transcription factor HIF-1α is essential for HSC mobilization in response to G-CSF and Plerixafor. Conversely, pharmacological stabilization of HIF-1α with the 4-prolyl hydroxylase inhibitor FG-4497 synergizes with G-CSF and Plerixafor increasing mobilization of reconstituting HSCs 20-fold compared with G-CSF plus Plerixafor, currently the most potent mobilizing combination used in the clinic. [ABSTRACT FROM AUTHOR]

Many patients with hematological neoplasms fail to mobilize sufficient numbers of hematopoietic stem cells (HSCs) in response to granulocyte colony-stimulating factor (G-CSF) precluding subsequent autologous HSC transplantation. Plerixafor, a specific antagonist of the chemokine receptor CXCR4, can rescue some but not all patients who failed to mobilize with G-CSF alone. These refractory poor mobilizers cannot currently benefit from autologous transplantation. To discover alternative targetable pathways to enhance HSC mobilization, we studied the role of hypoxia-inducible factor-1α (HIF-1α) and the effect of HIF-1α pharmacological stabilization on HSC mobilization in mice. We demonstrate in mice with HSC-specific conditional deletion of the Hif1a gene that the oxygen-labile transcription factor HIF-1α is essential for HSC mobilization in response to G-CSF and Plerixafor. Conversely, pharmacological stabilization of HIF-1α with the 4-prolyl hydroxylase inhibitor FG-4497 synergizes with G-CSF and Plerixafor increasing mobilization of reconstituting HSCs 20-fold compared with G-CSF plus Plerixafor, currently the most potent mobilizing combination used in the clinic. [ABSTRACT FROM AUTHOR]

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be corroborated in humans. [ABSTRACT FROM AUTHOR]

Mobilized blood has supplanted bone marrow (BM) as the primary source of hematopoietic stem cells for autologous and allogeneic stem cell transplantation. Pharmacologically enforced egress of hematopoietic stem cells from BM, or mobilization, has been achieved by directly or indirectly targeting the CXCL12/CXCR4 axis. Shortcomings of the standard mobilizing agent, granulocyte colony-stimulating factor (G-CSF), administered alone or in combination with the only approved CXCR4 antagonist, Plerixafor, continue to fuel the quest for new mobilizing agents. Using Protein Epitope Mimetics technology, a novel peptidic CXCR4 antagonist, POL5551, was developed. In vitro data presented herein indicate high affinity to and specificity for CXCR4. POL5551 exhibited rapid mobilization kinetics and unprecedented efficiency in C57BL/6 mice, exceeding that of Plerixafor and at higher doses also of G-CSF. POL5551-mobilized stem cells demonstrated adequate transplantation properties. In contrast to G-CSF, POL5551 did not induce major morphological changes in the BM of mice. Moreover, we provide evidence of direct POL5551 binding to hematopoietic stem and progenitor cells (HSPCs) in vivo, strengthening the hypothesis that CXCR4 antagonists mediate mobilization by direct targeting of HSPCs. In summary, POL5551 is a potent mobilizing agent for HSPCs in mice with promising therapeutic potential if these data can be corroborated in humans. [ABSTRACT FROM AUTHOR]

Feedback control has become a crucial tool in the research on magnetic confinement of plasmas for achieving controlled nuclear fusion. We present the first experimental results from a novel feedback control system that, for the first time, employs a graphics processing unit (GPU) for microsecond-latency, real-time control computations. The system was tested on the HBT-EP tokamak using an adaptive control algorithm for control of rotating magnetic perturbations. The algorithm assumes that perturbations of known shape are rotating rigidly, but dynamically derives and updates the rotation frequency to improve phase and gain accuracy of the control signals. Experiments were set up to control four rotating n = 1 perturbations at different poloidal angles. The perturbations are treated as coupled in frequency but independent of amplitude and phase, so that the system effectively controls a helical n = 1 perturbation with unknown poloidal spectrum. The control system suppresses the amplitude of the dominant 8 kHz mode by up to 60%. Deviation from the optimal feedback phase combines suppression with a speed up or slow down of the mode rotation frequency. The feedback performance is found to exceed previous results obtained with an FPGA- and Kalman-filter based control system without requiring any tuning of system model parameters. [ABSTRACT FROM AUTHOR]

Introduction: We sought to assess the care experience of primary health care users, to determine whether users' assessments of their experience vary according to the geographical context in which services are obtained, and to determine whether the observed variations are consistent across all components of the care experience. Methods: We examined the experience of 3389 users of primary care in 5 administrative regions in Quebec, focusing on accessibility, continuity, responsiveness and reported use of health services. Results: We found significant variations in users' assessments of the specific components of the care experience. Access to primary health care received positive evaluations least frequently, and continuity of information received the approval of the highest percentage of users. We also found significant variations among geographical contexts. Positive assessments of the care experience were more frequently made by users in remote rural settings; they became progressively less frequent in near-urban rural and near-urban settings, and were found least often in urban settings. We observed these differences in almost all of the components of the care experience. Conclusion: Given the relatively greater supply of services in urban areas, this analysis has revealed a rural-urban paradox in the care experience of primary health care users. [ABSTRACT FROM AUTHOR]

Objective: Given the increasing evidence that vertebral fractures are underdiagnosed and not acted on, Osteoporosis Canada and the Canadian Association of Radiologists initiated a project to develop and publish a set of recommendations to promote and facilitate the diagnosis and reporting of vertebral fractures. Options: The identification of spinal fractures is not uniform. More than 65% of vertebral fractures cause no symptoms. It is also apparent that vertebral fractures are inadequately recognized when the opportunity for diagnosis arises fortuitously. It is to patients' benefit that radiologists report vertebral fractures evident on a chest or other radiograph, no matter how incidental to the immediate clinical indication for the examination. Outcomes: The present recommendations can help to close the gap in care in recognizing and treating vertebral fractures, to prevent future fractures and thus reduce the burden of osteoporosis-related morbidity and mortality, as well as fracture-related costs to the health care system. Evidence: Several studies indicate that a gap exists in regard to the diagnosis of vertebral fractures and the clinical response following such diagnosis. All recommendations presented here are based on consensus. Values: These recommendations were developed by a multidisciplinary working group under the auspices of the Scientific Advisory Council of Osteoporosis Canada and the Canadian Association of Radiologists. Benefits, Harm, and Costs: Prevalent vertebral fractures have important clinical implications in terms of future fracture risk. Recognizing and reporting fractures incidental to radiologic examinations done for other reasons has the potential to reduce health care costs by initiating further steps in osteoporosis diagnosis and appropriate therapy. Recommendations: Physicians should be aware of the importance of vertebral fracture diagnosis in assessing future osteoporotic fracture risk. Vertebral fractures incidental to radiologic examinations done for other reasons should be identified and reported. Vertebral fractures should be assessed from lateral spinal or chest radiographs according to the semiquantitative method of Genant and colleagues. Grade II and Grade III fractures as classified by this method should be given the greatest emphasis. Semiquantitative fracture recognition should include the recognition of changes such as loss of vertebral end-plate parallelism, cortical interruptions, and quantitative changes in the anterior, midbody, and posterior heights of vertebral bodies. When spine radiographs are performed to assess the presence of vertebral fractures, anteroposterior examinations may assist in the initial evaluation. The standard follow-up need only consist of single lateral views of the thoracic and lumbar spine that include T4 to L4 vertebrae. The radiographic technique described in this paper, or a technique of comparable efficacy, should be used. Dual X-ray absorptiometry examinations that include lateral spinal morphological assessments (vertebral fracture assessment) may contribute to fracture recognition. Educational material about the clinical importance of vertebral fracture recognition as a potential indicator of future osteoporotic fracture risk with its associated morbidity and mortality should be directed to all physicians. [ABSTRACT FROM AUTHOR]

Abstract: A vertex detector that can measure particles with charm or bottom quarks would dramatically expand the physics capability of the STAR detector at RHIC. To accomplish this, we are proposing to build the Heavy Flavor Tracker (HFT) using 2×2cm Active Pixels Sensors (APS). Ten of these APS chips will be arranged on a ladder (0.28% of a radiation length) at radii of 1.5 and at 5.0cm. We have examined several properties of APS chips, so that we can characterize the performance of this detector. Using 1.5GeV/c electrons, we have measured the charge collected and compared it to the expected charge. To achieve high efficiency, we have considered two different cluster finding algorithms and found that the choice of algorithm is dependent on noise level. We have demonstrated that a Scanning Electron Microscope can probe properties of an APS chip. In particular, we studied several position resolution algorithms. Finally, we studied the properties of pixel pitches from 5 to 30μm. [Copyright &y& Elsevier]

Limited data are available concerning sexual behaviour of Hispanic women. A total of 318 Hispanic women were surveyed concerning extra-relational sex and their condom-related attitudes. Fifteen per cent of the sample had a secondary sex partner (apart from the first partner) during the three months preceding the survey. Of these women, 77 and 53% used condoms with their secondary and primary partners, respectively. Among women in monogamous relationships, condom use was low (17%), and nearly two-thirds (61%) of those with a high-risk partner did not use condoms. The most common concerns about condom use among these Hispanic women were a reduction in pleasurable sensations and embarrassment associated with buying condoms. Women with concurrent partners as compared to those with a single partner felt more at risk for HIV and STDs, were less likely to believe condoms have side effects or are unacceptable to their male partners and were more able to use condoms in long-term relations. In conclusion, extra-relational sex among Hispanic women may be higher than previously reported, although more favourable attitudes to condom use are seen among women with concurrent than those with a single partner. HIV/STD programmes in the Hispanic community should tailor to the sexual behaviour of their participants. [ABSTRACT FROM AUTHOR]

Background: Clinical evidence shows knee arthroscopy has little benefit for degenerative conditions and considerable variation in the incidence of knee arthroscopy in Australia has been identified. This study aimed to evaluate a clinician-led evidence-based policy which was implemented in one local health district in New South Wales (NSW) in 2012 to reduce the use of knee arthroscopy for patients aged 50 years or over.Methods: Trends in rates and volume of knee arthroscopy for patients 50 years or over in NSW between 2004 and 2015 by district were examined. Changes at four hospitals that adopted the policy were assessed by a quasi-experimental before and after study design with control groups, using the generalised estimating equations (GEE) Poisson model. Each case hospital was matched with four control hospitals in terms of the volume of knee arthroscopy surgeries performed in the five years prior to the intervention.Results: Between 2004 and 2015, the number of knee arthroscopies in NSW initially increased and then decreased after 2011, with considerable variation across districts. While an overall reducing trend in NSW was observed between 2011 and 2015 (39%), a 58% reduction (95% CI: 55-62%) was found in the intervention district, including the private sector, being the greatest reduction found in all districts. The GEE Poisson results show that, compared with control hospitals, the number of knee arthroscopy was significantly reduced by 56% (95% CI: 11%-79%) at four hospitals that adopted the policy during the follow-up period (p = 0.02).Conclusions: Clinicians in one local health district initiated a policy to restrict knee arthroscopy for patients aged 50 years or over, which may explain the greater reduction seen in that district compared to all others, despite an overall decrease noted in the state. A significant reduction found at intervened hospitals proved the effect of the policy, suggesting that the implementation of a simple clinical governance process may help reduce inappropriate surgery. [ABSTRACT FROM AUTHOR]