A general framework for quantifying the effects of DNA repair inhibitors on radiation sensitivity as a function of dose

Purpose. Current methods for quantifying effects of DNA repair modifiers on radiation sensitivity assume a constant effect independent of the radiation dose received. The aim of this study was to develop and evaluate a modelling strategy by which radiation dose dependent effects of DNA repair inhibitors on clonogenic survival might be identified and their significance assessed. Methods. An indicator model that allowed quantification of the Sensitiser Effect on Radiation response as a function of Dose (SERD) was developed. This model was fitted to clonogenic survival data derived from human tumour and rodent fibroblast cell lines irradiated in the presence and absence of chemical inhibitors of poly(ADP-ribose) polymerase (PARP) activity. Results. PARP inhibition affected radiation response in a cell cycle and radiation dose dependent manner, and was also associated with significant radiation-independent effects on clonogenic survival. Application of the SERD method enabled identification of components of the radiation response that were significantly affected by PARP inhibition and indicated the magnitude of the effects on each component. Conclusion. The proposed approach improves on current methods of analysing effects of DNA repair modification on radiation response. Furthermore, it may be generalised to account for other parameters such as proliferation or dose rate to enable its use in the context of fractionated or continuous radiation exposures

Interactive film scenes for tutor training in problem-based learning (PBL): dealing with difficult situations

<p>Abstract</p> <p>Background</p> <p>In problem-based learning (PBL), tutors play an essential role in facilitating and efficiently structuring tutorials to enable students to construct individual cognitive networks, and have a significant impact on students' performance in subsequent assessments. The necessity of elaborate training to fulfil this complex role is undeniable. In the plethora of data on PBL however, little attention has been paid to tutor training which promotes competence in the moderation of specific difficult situations commonly encountered in PBL tutorials.</p> <p>Methods</p> <p>Major interactive obstacles arising in PBL tutorials were identified from prior publications. Potential solutions were defined by an expert group. Video clips were produced addressing the tutor's role and providing exemplary solutions. These clips were embedded in a PBL tutor-training course at our medical faculty combining PBL self-experience with a non-medical case. Trainees provided pre- and post-intervention self-efficacy ratings regarding their PBL-related knowledge, skills, and attitudes, as well as their acceptance and the feasibility of integrating the video clips into PBL tutor-training (all items: 100 = completely agree, 0 = don't agree at all).</p> <p>Results</p> <p>An interactive online tool for PBL tutor training was developed comprising 18 video clips highlighting difficult situations in PBL tutorials to encourage trainees to develop and formulate their own intervention strategies. In subsequent sequences, potential interventions are presented for the specific scenario, with a concluding discussion which addresses unresolved issues.</p> <p>The tool was well accepted and considered worth the time spent on it (81.62 ± 16.91; 62.94 ± 16.76). Tutors considered the videos to prepare them well to respond to specific challenges in future tutorials (75.98 ± 19.46). The entire training, which comprised PBL self-experience and video clips as integral elements, improved tutor's self-efficacy with respect to dealing with problematic situations (pre: 36.47 ± 26.25, post: 66.99 ± 21.01; p < .0001) and significantly increased appreciation of PBL as a method (pre: 61.33 ± 24.84, post: 76.20 ± 20.12; p < .0001).</p> <p>Conclusions</p> <p>The interactive tool with instructional video clips is designed to broaden the view of future PBL tutors in terms of recognizing specific obstacles to functional group dynamics and developing individual intervention strategies. We show that this tool is well accepted and can be successfully integrated into PBL tutor-training. Free access is provided to the entire tool at <url>http://www.medizinische-fakultaet-hd.uni-heidelberg.de/fileadmin/PBLTutorTraining/player.swf</url>.</p

The effect of sediment grain properties and porewater flow on microbial abundance and respiration in permeable sediments

Sandy sediments cover 50–60% of the continental shelves and are highly efficient bioreactors in which organic carbon is remineralized and inorganic nitrogen is reduced to N2. As such they seem to play an important role, buffering the open ocean from anthropogenic nitrogen inputs and likely remineralizing the vast amounts of organic matter formed in the highly productive surface waters. To date however, little is known about the interrelation between porewater transport, grain properties and microbial colonization and the consequences for remineralization rates in sandy sediments. To constrain the effect of theses factors on remineralization in silicate sands, we incubated North Sea sediments in flow-through reactors after separating into five different grain size fractions. Bulk sediment and sediment grain properties were measured along with microbial colonization and cell abundances, oxygen consumption and denitrification rates. Volumetric oxygen consumption ranged from 14 to 77 µmol O2 l−1 h−1 while nitrogen-loss via denitrification was between 3.7 and 8.4 µmol N l−1 h−1. Oxygen consumption and denitrification rates were linearly correlated to the microbial cell abundances, which ranged from 2.9 to 5.4·108 cells cm−3. We found, that cell abundance and consumption rates in sandy sediments are influenced (i) by the surface area available for microbial colonization and (ii) by the exposure of these surfaces to the solute-supplying porewater flow. While protective structures such as cracks and depressions promote microbial colonization, the oxygen demand is only met by good ventilation of these structures, which is supported by a high sphericity of the grains. Based on our results, spherical sand grains with small depressions, i.e. golf ball like structures, provide the optimal supporting mineral structure for microorganisms on continental shelves

Photometric Variability in Kepler Target Stars: The Sun Among Stars -- A First Look

The Kepler mission provides an exciting opportunity to study the lightcurves of stars with unprecedented precision and continuity of coverage. This is the first look at a large sample of stars with photometric data of a quality that has heretofore been only available for our Sun. It provides the first opportunity to compare the irradiance variations of our Sun to a large cohort of stars ranging from vary similar to rather different stellar properties, at a wide variety of ages. Although Kepler data is in an early phase of maturity, and we only analyze the first month of coverage, it is sufficient to garner the first meaningful measurements of our Sun's variability in the context of a large cohort of main sequence stars in the solar neighborhood. We find that nearly half of the full sample is more active than the active Sun, although most of them are not more than twice as active. The active fraction is closer to a third for the stars most similar to the Sun, and rises to well more than half for stars cooler than mid K spectral types.Comment: 13 pages, 4 figures, accepted to ApJ Letter

Regulation of benthic oxygen fluxes in permeable sediments of the coastal ocean

Large areas of the oceanic shelf are composed of sandy sediments through which reactive solutes are transported via porewater advection fueling active microbial communities. The advective oxygen transport in permeable sands of the North Sea was investigated under in situ conditions using a new benthic observatory to assess the dynamic interaction of hydrodynamics, sediment morphodynamics, and oxygen penetration depth. During 16 deployments, concurrent measurement of current velocity, sediment topography, and porewater oxygen concentration were carried out. In all cases the oxyclines were found at depths of 1–6 cm, correlating with the topography of stationary and migrating bedforms (ripples). Different conditions in terms of bottom water currents and bedform migration led to fluctuating oxygen penetration depths and, hence, highly variable redox conditions in up to 2.5 cm thick layers beneath the surface. Volumetric oxygen consumption rates of surface sediments were measured on board in flow-through reactors. Bedform migration was found to reduce consumption rates by up to 50%, presumably caused by the washout of organic carbon that is otherwise trapped in the pore space of the sediment. Based on the observations we found oxygen penetration depths to be largely controlled by oxygen consumption rates, grain size, and current velocity. These controlling variables are summarized by an adapted Damköhler number which allows for prediction of oxygen penetretion depths based on a simple scaling law. By integrating the oxygen consumption rates over the oxygen penetration depth, oxygen fluxes of 8–34 mmol m−2 d−1 were estimate

Nurse practitioner interactions in acute and long-term care : an exploration of the role of knotworking in supporting interprofessional collaboration

BACKGROUND: Interprofessional care ensures high quality healthcare. Effective interprofessional collaboration is required to enable interprofessional care, although within the acute care hospital setting interprofessional collaboration is considered suboptimal. The integration of nurse practitioner roles into the acute and long-term care settings is influencing enhanced care. What remains unknown is how the nurse practitioner role enacts interprofessional collaboration or enables interprofessional care to promote high quality care. The study aim was to understand how nurse practitioners employed in acute and long-term care settings enable interprofessional collaboration and care. METHOD: Nurse practitioner interactions with other healthcare professionals were observed throughout the work day. These interactions were explored within the context of "knotworking" to create an understanding of their social practices and processes supporting interprofessional collaboration. Healthcare professionals who worked with nurse practitioners were invited to share their perceptions of valued role attributes and impacts. RESULTS: Twenty-four nurse practitioners employed at six hospitals participated. 384 hours of observation provided 1,284 observed interactions for analysis. Two types of observed interactions are comparable to knotworking. Rapid interactions resemble the traditional knotworking described in earlier studies, while brief interactions are a new form of knotworking with enhanced qualities that more consistently result in interprofessional care. Nurse practitioners were the most common initiators of brief interactions. CONCLUSIONS: Brief interactions reveal new qualities of knotworking with more consistent interprofessional care results. A general process used by nurse practitioners, where they practice a combination of both traditional (rapid) knotworking and brief knotworking to enable interprofessional care within acute and long-term care settings, is revealed