Profiling of the anti-malarial drug candidate SC83288 against artemisinins in Plasmodium falciparum

Background: The increased resistance of the human malaria parasite Plasmodium falciparum to currently employed drugs creates an urgent call for novel anti-malarial drugs. Particularly, efforts should be devoted to developing fast-acting anti-malarial compounds in case clinical resistance increases to the first-line artemisinin-based combination therapy. SC83288, an amicarbalide derivative, is a clinical development candidate for the treatment of severe malaria. SC83288 is fast-acting and able to clear P. falciparum parasites at low nanomolar concentrations in vitro, as well as in a humanized SCID mouse model system in vivo. In this study, the antiplasmodial activity of SC83288 against artemisinins was profiled in order to assess its potential to replace, or be combined with, artemisinin derivatives. Results: Based on growth inhibition and ring survival assays, no cross-resistance was observed between artemisinins and SC83288, using parasite lines that were resistant to either one of these drugs. In addition, no synergistic or antagonistic interaction was observed between the two drugs. This study further confirmed that SC83288 is a fast acting drug in several independent assays. Combinations of SC83288 and artesunate maintained the rapid parasite killing activities of both components. Conclusion: The results obtained in this study are consistent with artemisinins and SC83288 having distinct modes of action and different mechanisms of resistance. This study further supports efforts to continue the clinical development of SC83288 against severe malaria as an alternative to artemisinins in areas critically affected by artemisinin-resistance. Considering its fast antiplasmodial activity, SC83288 could be combined with a slow-acting anti-malarial drug

Spatially and temporally resolved temperature measurements of plasma generated in percussion drilling with a diode-pumped Nd:YAG laser

Results of spectroscopic temperature measurements of the laser-induced plasma generated during percussion drilling with a high power diode-pumped, pulsed Nd:YAG laser are presented. SAE 52100 steel was drilled with varying average powers. Helium and oxygen were each used as the shield gas. Emission spectra were collected with a monochrometer and an intensified charge coupled detector connected to the optical multichannel analyzer. The plasma electron temperatures were calculated from the relative intensities of the spectral lines. The spatial and temporal temperature distributions are presented. Both drilling times and spatial distributions indicate energy absorption by the plasma. © 1998 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71333/2/JAPIAU-84-8-4122-1.pd

On the use of low-cost computer peripherals for the assessment of motor dysfunction in Parkinson’s disease – Quantification of bradykinesia using target tracking tasks

The potential of computer games peripherals to measure the motor dysfunction in Parkinson’s diseases is assessed. Of particular interest is the quantification of bradykinesia. Previous studies used modified or custom haptic interfaces, here an unmodified force feedback joystick and steering wheel are used with a laptop. During testing an on screen cursor moves in response to movements of the peripheral, the user has to track a continuously moving target (pursuit tracking), or move to a predetermined target (step tracking). All tasks use movement in the horizontal axis, allowing use of joystick or steering wheel. Two pursuit tracking tasks are evaluated, pseudo random movement, and a swept frequency task. Two step tracking tasks are evaluated, movement between two or between two of five fixed targets. Thirteen patients and five controls took part on a weekly basis. Patients were assessed for bradykinesia at each session using standard clinical measures. A range of quantitative measures was developed to allow comparison between and within patients and controls using ANOVA. Both peripherals are capable of discriminating between controls and patients, and between patients with different levels of bradykinesia. Recommendations for test procedures and peripherals are given

High-contrast Doppler-free transmission spectroscopy

By applying Doppler-free saturated absorption spectroscopy in the regime of high integrated sample absorption, high-contrast Doppler-free laser transmission signals can be obtained as demonstrated in experiments on the sodium D lines. Natural linewidth background-free signals are observed

S02-3 Physical activity policies and good practices in Europe

Background The establishment of the EU physical activity (PA) guidelines and the HEPA monitoring framework has had an impact on policy development and implementation across the region from 2015. This works presents results from the third round of monitoring in 2021 and discusses trends since 2015. Methods A questionnaire was distributed in 2021 to all EU Member States of the WHO European Region through the network of PA Focal Points, who were requested to collect data from national colleagues and complete the questionnaire. All EU Member States (27 in 2021) responded to the survey on the implementation of the 23 indicators of the HEPA monitoring framework. Results The results of the 2021 round of data collection on HEPA indicators showed an overall stabilization of the implementation of PA promotion policies. Besides important increases in several indicators, such as indicators 15 (HEPA in the training of physical education teachers), 20 (Schemes to promote physical activity at the workplace) and 21 (Schemes for community interventions to promote physical activity in older adults), many others decreased and others showed no progress. Most national physical activity policies or action plans were multi-sectoral, with good coverage of the sectors recognized as important for HEPA promotion. While some methodological aspects may have affected the results, this round also reflected policy implementation during the COVID-19 pandemic (2019–2021). COVID-19 has had a significant impact on all sectors of society but especially on health, sports, education and mobility, which are major areas for PA promotion and policy implementation. Conclusions There seems to be an overall stabilization of the implementation of PA promotion policies since 2015. Public health experts and decision makers could utilise the increase in public awareness of the health benefits of physical activity kindled by the COVID-19 crisis to implement new health-promoting policies. Policy design, development and implementation of HEPA promotion must be strengthened for post-COVID-19 social and economic recovery

Laser spectroscopy using beam-overlap modulation

A new Doppler-free laser spectroscopy method is demonstrated that employs modulation of the position of a laser beam rather than the commonly used intensity or polarization modulation. The technique is applicable in saturated absorption as well as fluorescence measurements, as is illustrated in experiments on sodium and iodine lines. A particular feature of the method is that Doppler- and background-free fluorescence spectra can be recorded without using intermodulation techniques

Dynamic buckling of containments: The influence of damping

The seismic buckling capacities of representative thin, unstiffened elastic containment shells are investigated to evaluate the sensitivity of buckling to the damping level. The finite element method with transient time integration is utilized with both actual earthquake acceleration-time signals and artificial time histories generated from regulatory spectra. The dynamic response and subsequent buckling of the selected containment shells are found to be highly dependent on both damping level and the degree to which the input signal excites the fundamental shear-bending mode of the shell. Transient stresses and buckling levels for the two containment shells induced by the seismic inputs were reduced in the range of 12% to 111% by increasing the damping level from 1% to 4% of critical