Ferroelectric Behavior in Exfoliated 2D Aurivillius Oxide Flakes of Sub‐Unit Cell Thickness

Ferroelectricity in ultrasonically exfoliated flakes of the layered Aurivillius oxide Bi5Ti3Fe0.5Co0.5O15 with a range of thicknesses is studied. These flakes have relatively large areas (linear dimensions many times the film thickness), thus classifying them as 2D materials. It is shown that ferroelectricity can exist in flakes with thicknesses of only 2.4 nm, which equals one‐half of the normal crystal unit cell. Piezoresponse force microscopy (PFM) demonstrates that these very thin flakes exhibit both piezoelectric effects and that the ferroelectric polarization can be reversibly switched. A new model is presented that permits the accurate modeling of the field‐on and field‐off PFM time domain and hysteresis loop responses from a ferroelectric during switching in the presence of charge injection, storage, and decay through a Schottky barrier at the electrode–oxide interface. The extracted values of spontaneous polarization, 0.04(±0.02) C m−2 and electrostrictive coefficient, 2(±0.1) × 10−2 m4 C−2 are in good agreement with other ferroelectric Aurivillius oxides. Coercive field scales with thickness, closely following the semi‐empirical scaling law expected for ferroelectric materials. This constitutes the first evidence for ferroelectricity in a 2D oxide material, and it offers the prospect of new devices that might use the useful properties associated with the switchable ferroelectric spontaneous polarization in a 2D materials format

Direct and indirect control of the initiation of meiotic recombination by DNA damage checkpoint mechanisms in budding yeast

Meiotic recombination plays an essential role in the proper segregation of chromosomes at meiosis I in many sexually reproducing organisms. Meiotic recombination is initiated by the scheduled formation of genome-wide DNA double-strand breaks (DSBs). The timing of DSB formation is strictly controlled because unscheduled DSB formation is detrimental to genome integrity. Here, we investigated the role of DNA damage checkpoint mechanisms in the control of meiotic DSB formation using budding yeast. By using recombination defective mutants in which meiotic DSBs are not repaired, the effect of DNA damage checkpoint mutations on DSB formation was evaluated. The Tel1 (ATM) pathway mainly responds to unresected DSB ends, thus the sae2 mutant background in which DSB ends remain intact was employed. On the other hand, the Mec1 (ATR) pathway is primarily used when DSB ends are resected, thus the rad51 dmc1 double mutant background was employed in which highly resected DSBs accumulate. In order to separate the effect caused by unscheduled cell cycle progression, which is often associated with DNA damage checkpoint defects, we also employed the ndt80 mutation which permanently arrests the meiotic cell cycle at prophase I. In the absence of Tel1, DSB formation was reduced in larger chromosomes (IV, VII, II and XI) whereas no significant reduction was found in smaller chromosomes (III and VI). On the other hand, the absence of Rad17 (a critical component of the ATR pathway) lead to an increase in DSB formation (chromosomes VII and II were tested). We propose that, within prophase I, the Tel1 pathway facilitates DSB formation, especially in bigger chromosomes, while the Mec1 pathway negatively regulates DSB formation. We also identified prophase I exit, which is under the control of the DNA damage checkpoint machinery, to be a critical event associated with down-regulating meiotic DSB formation

Genetic Crossovers Are Predicted Accurately by the Computed Human Recombination Map

Hotspots of meiotic recombination can change rapidly over time. This instability and the reported high level of inter-individual variation in meiotic recombination puts in question the accuracy of the calculated hotspot map, which is based on the summation of past genetic crossovers. To estimate the accuracy of the computed recombination rate map, we have mapped genetic crossovers to a median resolution of 70 Kb in 10 CEPH pedigrees. We then compared the positions of crossovers with the hotspots computed from HapMap data and performed extensive computer simulations to compare the observed distributions of crossovers with the distributions expected from the calculated recombination rate maps. Here we show that a population-averaged hotspot map computed from linkage disequilibrium data predicts well present-day genetic crossovers. We find that computed hotspot maps accurately estimate both the strength and the position of meiotic hotspots. An in-depth examination of not-predicted crossovers shows that they are preferentially located in regions where hotspots are found in other populations. In summary, we find that by combining several computed population-specific maps we can capture the variation in individual hotspots to generate a hotspot map that can predict almost all present-day genetic crossovers

Performance indicators for clinical practice management in primary care in Portugal : consensus from a Delphi study

Early OnlineBackground: Performance indicators assessing the quality of medical care and linked to pay for performance may cause disagreement. Portuguese indicators included in recent health care reform are controversial. Objectives: To obtain consensus from opinion leaders in family medicine regarding the performance indicators for practice management used in the evaluation of Family Health Units in Portugal. Methods: Eighty-nine specialists in primary care were invited to answer the following question in an online Delphi study: 'Which performance indicators should be assessed regarding the organization and management of clinical practice in primary care in Portugal?' A Likert scale was used to evaluate validity, reliability, feasibility and sensitivity to change. Twenty-seven experts participated in the second round and achieved a high degree of consensus. Eight categories were created for analysis. Results: The experts suggested the use of existing indicators as well as new indicators. Thirty-nine indicators suggested by the experts are currently in use in Portugal. The assessment of the number of clinical acts performed, the number of administrative acts, and evaluation of the clinical demographic profile achieved a high degree of consensus. The expert panel suggested fifty new indicators. Five categories of these new indicators had a high degree of consensus, and three categories had a low degree of consensus. Conclusion: The expert panel recommended that performance indicators of practice management should first assess the quantity of clinical and administrative activities undertaken. These indicators must take into account the human and financial resources available to the clinic and its demographic context

Warming Can Boost Denitrification Disproportionately Due to Altered Oxygen Dynamics

Background: Global warming and the alteration of the global nitrogen cycle are major anthropogenic threats to the environment. Denitrification, the biological conversion of nitrate to gaseous nitrogen, removes a substantial fraction of the nitrogen from aquatic ecosystems, and can therefore help to reduce eutrophication effects. However, potential responses of denitrification to warming are poorly understood. Although several studies have reported increased denitrification rates with rising temperature, the impact of temperature on denitrification seems to vary widely between systems. Methodology/Principal Findings: We explored the effects of warming on denitrification rates using microcosm experiments, field measurements and a simple model approach. Our results suggest that a three degree temperature rise will double denitrification rates. By performing experiments at fixed oxygen concentrations as well as with oxygen concentrations varying freely with temperature, we demonstrate that this strong temperature dependence of denitrification can be explained by a systematic decrease of oxygen concentrations with rising temperature. Warming decreases oxygen concentrations due to reduced solubility, and more importantly, because respiration rates rise more steeply with temperature than photosynthesis. Conclusions/Significance: Our results show that denitrification rates in aquatic ecosystems are strongly temperature dependent, and that this is amplified by the temperature dependencies of photosynthesis and respiration. Our result

Interactive Actor Analysis for Rural Water Management in The Netherlands

Recent developments in the policy sciences emphasize the social environment in which decisions are made. The ‘network metaphor’ is often used to describe the key role of interactions between interdependent actors involved in decision making. These interactions take place in a policy arena drawn up by actors with an interest in and control over decisions on the issues addressed. Interdependencies, caused by the need for actors to increase their means of realizing objectives, are the driving force behind these interactions. Dependency relations are of special interest to water management and river basin management because of the fundamental asymmetrical interdependencies that exist in river basins between upstream and downstream stakeholders. Coleman’s linear system of action models decision making process involving dependencies between multiple stakeholders as exchange of control over issues, while interactions are required to negotiate exchanges of control. We developed an interactive method for actor analysis based on Coleman’s linear system of action and applied it to the national rural water management policy domain in The Netherlands. The method is firmly rooted in mathematical sociology and defies the criticism that methods for actor and stakeholder analysis do not specify a theoretical basis explaining the causal relations between the variables analyzed and policy change. With the application to the rural water management policy arena we intended to increase our insight into the practical applicability of this analyticmethod in an interactive workshop, the acceptability of the approach for the participating actors, its contribution to the process of decision making and our understanding of the rural water management policy arena in The Netherlands. We found that the Association of Water Authorities, the Ministry of Public Works and the Ministry of Agriculture are the most powerful actor in the policy domain, while governance and cost and benefits of rural water management are the most salient issues. Progress in policy development for rural water management is probably most promising for the issues governance, costs and benefits, safety and rural living conditions through improved interaction between the Association of Water Authorities, the Ministry of Agriculture and the Rural Credit Bank. Besides these analytic results the interactive approach implemented increased the participants understanding of their dependency on other actors in the rural water management policy domain and supported them in developing a sound perspective on their dependency position. We concluded that the method developed is acceptable to real-world policy decision makers, can successfully be applied in an interactive setting, potentially contributes to the process of decision making by increasing the participants understanding of their dependency position, has the potential to delivers valuable advice for future decision-making and increases our understanding of policy development for rural water management in general

Development of a practice guideline for dietary counselling of children with IgE-mediated food allergy

Purpose The incidence of food allergy is increasing globally and whilst there is consensus that dietitians should be involved in its management, the roles that dietitians should fulfill differ between different guidelines and the description of tasks remains unclear. Currently, no Swiss guideline exists to assist dietitians in counselling children with food allergies. There is a need for recommendations that will guide dietitians through the counselling process. The aim of this project was to create a practice guideline for dietary counselling of children with food allergy. Methods Practice guidelines were developed following the Academy of Nutrition and Dietetics stepwise approach. The process consisted of six steps: (1) Determine the scope oft he guideline. (2) Conduct a systematic review. (3) Draft the guideline recommendations using the Nutrition Care Process (NCP) as a framework. (4) Finalise the guideline during a face-to-face meeting. (5) Conduct internal and external review and revise accordingly. (6) Publish guideline. Results The process resulted in 25 recommendations for dietary counselling. Most recommendations are based on expert opinion only, due to the lack of studies in this field and showed similar levels of consensus between the expert group and external review by allergists. However, there were nine recommendations where the consensus differed. Conclusion This guideline provides a comprehensive guide to dietary counselling for food allergy by dietitians in Switzerland. It will inform best practice and improve patient-centred care and encourage a consistent approach, but it will need to be reviewed and updated as more robust evidence is produced

BRIT1/MCPH1 Is Essential for Mitotic and Meiotic Recombination DNA Repair and Maintaining Genomic Stability in Mice

BRIT1 protein (also known as MCPH1) contains 3 BRCT domains which are conserved in BRCA1, BRCA2, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. BRIT1 mutations or aberrant expression are found in primary microcephaly patients as well as in cancer patients. Recent in vitro studies suggest that BRIT1/MCPH1 functions as a novel key regulator in the DNA damage response pathways. To investigate its physiological role and dissect the underlying mechanisms, we generated BRIT1−/− mice and identified its essential roles in mitotic and meiotic recombination DNA repair and in maintaining genomic stability. Both BRIT1−/− mice and mouse embryonic fibroblasts (MEFs) were hypersensitive to γ-irradiation. BRIT1−/− MEFs and T lymphocytes exhibited severe chromatid breaks and reduced RAD51 foci formation after irradiation. Notably, BRIT1−/− mice were infertile and meiotic homologous recombination was impaired. BRIT1-deficient spermatocytes exhibited a failure of chromosomal synapsis, and meiosis was arrested at late zygotene of prophase I accompanied by apoptosis. In mutant spermatocytes, DNA double-strand breaks (DSBs) were formed, but localization of RAD51 or BRCA2 to meiotic chromosomes was severely impaired. In addition, we found that BRIT1 could bind to RAD51/BRCA2 complexes and that, in the absence of BRIT1, recruitment of RAD51 and BRCA2 to chromatin was reduced while their protein levels were not altered, indicating that BRIT1 is involved in mediating recruitment of RAD51/BRCA2 to the damage site. Collectively, our BRIT1-null mouse model demonstrates that BRIT1 is essential for maintaining genomic stability in vivo to protect the hosts from both programmed and irradiation-induced DNA damages, and its depletion causes a failure in both mitotic and meiotic recombination DNA repair via impairing RAD51/BRCA2's function and as a result leads to infertility and genomic instability in mice

Conducting Online Expert panels: a feasibility and experimental replicability study

<p>Abstract</p> <p>Background</p> <p>This paper has two goals. First, we explore the feasibility of conducting online expert panels to facilitate consensus finding among a large number of geographically distributed stakeholders. Second, we test the replicability of panel findings across four panels of different size.</p> <p>Method</p> <p>We engaged 119 panelists in an iterative process to identify definitional features of Continuous Quality Improvement (CQI). We conducted four parallel online panels of different size through three one-week phases by using the RAND's ExpertLens process. In Phase I, participants rated potentially definitional CQI features. In Phase II, they discussed rating results online, using asynchronous, anonymous discussion boards. In Phase III, panelists re-rated Phase I features and reported on their experiences as participants.</p> <p>Results</p> <p>66% of invited experts participated in all three phases. 62% of Phase I participants contributed to Phase II discussions and 87% of them completed Phase III. Panel disagreement, measured by the mean absolute deviation from the median (MAD-M), decreased after group feedback and discussion in 36 out of 43 judgments about CQI features. Agreement between the four panels after Phase III was fair (four-way kappa = 0.36); they agreed on the status of five out of eleven CQI features. Results of the post-completion survey suggest that participants were generally satisfied with the online process. Compared to participants in smaller panels, those in larger panels were more likely to agree that they had debated each others' view points.</p> <p>Conclusion</p> <p>It is feasible to conduct online expert panels intended to facilitate consensus finding among geographically distributed participants. The online approach may be practical for engaging large and diverse groups of stakeholders around a range of health services research topics and can help conduct multiple parallel panels to test for the reproducibility of panel conclusions.</p