Beyond Profiling: Using ADMET Models to Guide Decisions

ADMET Models, whether in silico or in vitro, are commonly used to ‘profile’ molecules, to identify potential liabilities or filter out molecules expected to have undesirable properties. While useful, this is the most basic application of such models. Here, we will show how models may be used to go ‘beyond profiling’ to guide key decisions in drug discovery. For example, selection of chemical series to focus resources with confidence or design of improved molecules targeting structural modifications to improve key properties. To prioritise molecules and chemical series, the success criteria for properties and their relative importance to a project's objective must be defined. Data from models (experimental or predicted) may then be used to assess each molecule's balance of properties against those requirements. However, to make decisions with confidence, the uncertainties in all of the data must also be considered. In silico models encode information regarding the relationship between molecular structure and properties. This is used to predict the property value of a novel molecule. However, further interpretation can yield information on the contributions of different groups in a molecule to the property and the sensitivity of the property to structural changes. Visualising this information can guide the redesign process. In this article, we describe methods to achieve these goals and drive drug‐discovery decisions and illustrate the results with practical examples.     

The teacher, the physician and the person: how faculty's teaching performance influences their role modelling

Objective

Previous studies identified different typologies of role models (as teacher/supervisor, physician and person) and explored which of faculty''s characteristics could distinguish good role models. The aim of this study was to explore how and to which extent clinical faculty''s teaching performance influences residents'' evaluations of faculty''s different role modelling statuses, especially across different specialties.

Methods

In a prospective multicenter multispecialty study of faculty''s teaching performance, we used web-based questionnaires to gather empirical data from residents. The main outcome measures were the different typologies of role modelling. The predictors were faculty''s overall teaching performance and faculty''s teaching performance on specific domains of teaching. The data were analyzed using multilevel regression equations.

Results

In total 219 (69% response rate) residents filled out 2111 questionnaires about 423 (96% response rate) faculty. Faculty''s overall teaching performance influenced all role model typologies (OR: from 8.0 to 166.2). For the specific domains of teaching, overall, all three role model typologies were strongly associated with “professional attitude towards residents” (OR: 3.28 for teacher/supervisor, 2.72 for physician and 7.20 for the person role). Further, the teacher/supervisor role was strongly associated with “feedback” and “learning climate” (OR: 3.23 and 2.70). However, the associations of the specific domains of teaching with faculty''s role modelling varied widely across specialties.

Conclusion

This study suggests that faculty can substantially enhance their role modelling by improving their teaching performance. The amount of influence that the specific domains of teaching have on role modelling differs across specialties.     

The Teaching of Photosynthesis in Secondary School: A History of the Science Approach

In this article we present a synthesis of the research affecting pupils' conceptions of photosynthesis and plant nutrition. The main false conceptions of the pupils identi?ed in this literature review are: that green plants ?nd their food in the soil; that water and mineral salts are suf?cient to the growth of a plant; the role of chlorophyll, where the transformation of luminous energy into chemical energy is never evoked; and air as a source of matter, which is never underlined. Secondly, we are going to see that several of these false conceptions have been developed during history. For example, the famous philosopher Aristotle (384–322 BC) thought that plants receive their food from the soil already elaborated. Several centuries later, the physician and chemist Van Helmont (1677–1644) added more precision to Aristotle’s conception while claiming that plants use only water for their growth. Finally, we will see that the analysis of the false theories developed during history will permit in a context of teaching to valorize the false conceptions of the pupils. Indeed, the history of sciences could incite a teacher to valorize his pupils’ false conceptions while considering them as an indication of difficulties that deserve particular pedagogical and didactic tools. The false conceptions constructed by the pupils don’t have to be ignored in a teaching context because they obey particular reasoning rules, sometimes similar to those that once guided some scientific steps. This view, drawing on false conceptions developed during history, gives a dynamic and human picture of the science very distant from the one sometimes carried on by dogmatic teaching.     

Annual Review

In recent years, the science teaching community and curriculum developers have emphasised the importance of teaching inquiry and teaching science as inquiry. One way of developing learners' skills for planning and carrying out scientific research is by allowing them to perform independent research, guided by a teacher. It was recently discovered that there are considerable differences between experiments conducted by scientists and those conducted by students, with regard to the cognitive processes that the experimenters go through. Developing inquiry study activities that emphasise authentic inquiry was suggested in order to introduce students to cognitive activity that more closely resembles that of scientific professionals. This article describes the Biomind programme, intended for students of Grades 11 and 12 (ages 16 to 18 years) majoring in biology. The curriculum, developed by biology teachers, enables students to conduct independent research under teacher guidance. The curriculum emphasises the learning process, not just the outcome, and so students must reflect upon the work in progress. Moreover, the Biomind curriculum follows the principles of authentic inquiry. Biomind may improve students' scientific thinking abilities, expand the guidance aspect of teachers' work, and inspire curriculum developers to further emphasise inquiry.     

Teaching and Assessing Science Process Skills in Physics: THE “BUBBLES” TASK

In the following article, Dr. Seuss's children's books are creatively integrated with science activities through the creation of take-home activity kits. The kits provide families an opportunity to read at home while connecting the enjoyable experience to science content and skill development through associated activities. The kits should be constructed using easy-reading books and aligned to developmentally appropriate academic science standards. Most importantly, they should be designed in a manner so that all family members are participants rather than expecting the adults to teach the expected outcomes. The activity kits can be completed as stand-alone experiences for interested students, used by students who are ready for an additional challenge, or adapted for an entire classroom of students as part of a teacher's normal curriculum.     

Using stage‐based system dynamics modeling for demographic management of captive populations

Management of captive populations relies on a complex synthesis of genetic and demographic analyses to guide populations toward sustainability. Demographic analyses of captive populations currently utilize age‐based matrix projections to predict a population's trajectory. An alternate approach is to use a stage‐based, system dynamics model for captive systems. Such models can more easily incorporate complex captive systems in which population dynamics are dependent on a combination of management and a species' biology. By linking these two areas, population managers can gain a more accurate understanding of how management decisions impact captive populations and which aspects of a species' demography should be of special concern in the future. We present a general stage‐based system dynamics model that has been developed for use with captive populations. The utility of the model is then illustrated by applying it to three captive bear populations: spectacled bears (Tremarctos ornatus), sloth bears (Melursus ursinus), and sun bears (Helarctos malayanus). Zoo Biol 22:45–64, 2003. © 2003 Wiley‐Liss, Inc.     

An ecological energetics field course for sixth forms

the field course described has recently been piloted with a sixth-form group and is currently undergoing a more extensive evaluation. It consists of written materials for students and a teacher's booklet giving all the necessary techniques, lists of apparatus, and practical hints. The course aims to estimate the energy flows in a woodland ecosystem by means of a series of practical sessions involving field and laboratory investigations and calculation.

It is hoped the course will eventually be published and made generally available. designed with the non-ecologist teacher in mind. By using the supporting materials any teacher should be able to run the course.     

Designed to Sell

The purpose of this study was to construct a profile of K–12 music teachers in the United States and develop a model to predict their retention, turnover, and attrition. Responses to the Schools and Staffing Survey from 47,857 K–12 public and private school teachers, including 1,903 music teachers, were analyzed using comparative statistics, factor analysis, logistic regression, and structural equation modeling. Results indicated that music teachers were far more likely than other types of teachers to hold itinerant or part-time positions, and were less likely to receive support for working with special needs students. Music teachers changed teaching positions because of dissatisfaction with workplace conditions and for better teaching assignments. Music teachers left the teaching profession for better salary or benefits, and were generally more satisfied in their new field. Music teachers’ perceived level of administrative support had the most prominent influence on both music teacher satisfaction and retention.     

Looking Backwards to Reach Forward: A Strategic Architecture for Professional Development in Music Education

The article analyzes professional development in music education considering the ways in which policy change depends on conditions where renewed practice can become self supporting. The authors situate professional development amid the current politico-educational climate while offering an interpretive framework based on key issues and actions identified by other authors in this issue of Arts Education Policy Review. Further, they suggest a pragmatic policy agenda focused on the notion of a strategic architecture for professional development in music education, arguing that it may bring (1) greater confidence in teacher's capacity to adapt, engender concepts, intervene in instructional patterns, and establish positive feedback loops; and (2) improvement in teacher retention and productivity. The article calls for a professional development agenda that sees teachers as capable change agents and that is jointly incentivized by union leaders, government, and institutions of higher learning.     

Hibernacula selection by Townsend's big-Eared bat in southwestern Colorado

In western United States, both mine reclamations and renewed mining at previously abandoned mines have increased substantially in the last decade. This increased activity may adversely impact bats that use these mines for roosting. Townsend's big-eared bat (Corynorhinus townsendii) is a species of conservation concern that may be impacted by ongoing mine reclamation and renewed mineral extraction. To help inform wildlife management decisions related to bat use of abandoned mine sites, we used logistic regression, Akaike's information criterion, and multi-model inference to investigate hibernacula use by Townsend's big-eared bats using 9 years of data from surveys inside abandoned mines in southwestern Colorado. Townsend's big-eared bats were found in 38 of 133 mines surveyed (29%), and occupied mines averaged 2.6 individuals per mine. The model explaining the most variability in our data included number of openings and portal temperature at abandoned mines. In southwestern Colorado, we found that abandoned mine sites with more than one opening and portal temperatures near 0°C were more likely to contain hibernating Townsend's big-eared bats. However, mines with only one opening and portal temperatures of ≥10°C were occasionally occupied by Townsend's big-eared bat. Understanding mine use by Townsend's big-eared bat can help guide decisions regarding allocation of resources and placement of bat-compatible closures at mine sites scheduled for reclamation. When feasible we believe that surveys should be conducted inside all abandoned mines in a reclamation project at least once during winter prior to making closure and reclamation recommendations. © 2010 The Wildlife Society.     

Attempting to break the code in student comprehension of genetic concepts

Conducted in Israel, this research probes students' understanding of the relationships between genetic concepts. Four populations were examined: 9th graders (14–15 year olds), who were exposed to genetics for the first time (n = 184); 12th graders (17–18 year olds), who were studying biology as their main subject (n = 121); college pre-service teachers, who had not yet earned a degree (n = 29); and university pre-service teachers, who had earned biology degrees and were seeking teacher certification (n = 22). Three research instruments were used: a written questionnaire, interviews, and concept maps. The questions were open-ended to enable the identification of students' patterns of comprehensive thinking and understanding, not identifiable in multiple choice testing. Alternative conceptions and compartmentalisation between related concepts were identified. Based on these findings, genetic instruction in 9th and 12th grade and in college needs improvement.     

Assessing the use of vibrations and strobe lights at fish screens as enhanced deterrents for two estuarine fishes

The role of vision and the lateral-line system in fish-screen avoidance behaviours was investigated in shiner surfperch Cymatogaster aggregata and staghorn sculpin Leptocottus armatus. Avoidance experiments were conducted in front of water-diversion-type wedge-wire fish screens in a laboratory flume with a 0.3 m s⁻¹ water velocity. Fish contacted the screens less frequently during the day than night, indicating that fish screen avoidance is visually mediated during the day. Input from the fishes' lateral-line systems was also blocked with streptomycin-sulphate treatments during the night to determine if these fishes use mechanoreceptive cues to guide screen avoidance in darkened conditions. Streptomycin-treated and untreated fish had similar contact rates suggesting that mechanoreceptive guidance was not increasing the fishes' abilities to avoid contact with non-vibrating screens at night. Fishes were stained with 2-(4-(dimethylamino)styryl)-N-ethylpyridinium iodide (DASPEI) to assess the streptomycin treatment's effectiveness. We also tested the fishes' ability to avoid contact with the screens at night, when a strobe light or industrial vibrator was operated on the screens, to respectively increase the screen's visual and mechanoreceptory guidance potential. Cymatogaster aggregata contacted the screens significantly less frequently when they were vibrating, compared with their night-time controls, suggesting useful mechanoreceptive guidance. Leptocottus armatus contacted the screens significantly less frequently under strobe-light illumination, compared with their night-time controls, suggesting useful visual guidance. This research should benefit fishery and water-resource managers, regarding the development of future fish-protection decisions at screened water diversions.     

Fetal tissue transplantation and abortion decisions: a survey of urban women.

OBJECTIVE: To describe women''s attitudes and predicted behaviour regarding the potential for fetal tissue transplantation (FTT) to influence abortion decisions. DESIGNS: Self-administered questionnaire survey by mail. SETTING: Academic family practice in Toronto. PARTICIPANTS: Random sample of 475 women 18 to 40 years of age selected from the family practice registry of an urban teaching hospital. Family physicians were blind to their patients'' participation, and investigators were blind to the subjects'' identity. Forty questionnaires were undeliverable. Of the remaining 435, 272 (62.5%) were completed. Six of the women were over 40 years of age or did not indicate their age and were excluded, which left 266 (61.1%) questionnaires for analysis. OUTCOME MEASURES: Number of women who would (a) be more likely to have an abortion if they could donate tissue for FTT and (b) feel better or worse about choosing abortion if FTT were an option, and open-ended comments about the potential for FTT to influence abortion decisions. RESULTS: Of the 266 respondents 32 (12.0%) reported that they would be more likely to have an abortion if they could donate tissue for FTT, 178 (66.9%) stated that they would not be more likely to do so, and 56 (21.1%) were uncertain. Of the 122 who indicated that they would consider an abortion if they were pregnant, 21 (17.2%) stated that they would be more likely to have an abortion if they could donate tissue for FTT, 77 (63.1%) replied that they would not be more likely to do so, and 24 (19.7%) were uncertain. The women 25 to 33 years of age were more likely to be influenced by FTT than the younger or older women, and the women 18 to 24 years were more uncertain about the influence of FTT on abortion decisions than the older women. In written responses some of the women felt that FTT might make abortion decisions easier; many were troubled that FTT might be used to justify a morally problematic abortion decision and felt that FTT should not be used to justify abortion. CONCLUSION: The data, the first of their kind gathered from from women, suggest that some women''s abortion decisions may be influenced by the option to donate tissue for FTT. Further research is necessary to explore the mechanism of influence.     

Multi‐model comparison highlights consistency in predicted effect of warming on a semi‐arid shrub

A number of modeling approaches have been developed to predict the impacts of climate change on species distributions, performance, and abundance. The stronger the agreement from models that represent different processes and are based on distinct and independent sources of information, the greater the confidence we can have in their predictions. Evaluating the level of confidence is particularly important when predictions are used to guide conservation or restoration decisions. We used a multi‐model approach to predict climate change impacts on big sagebrush (Artemisia tridentata), the dominant plant species on roughly 43 million hectares in the western United States and a key resource for many endemic wildlife species. To evaluate the climate sensitivity of A. tridentata, we developed four predictive models, two based on empirically derived spatial and temporal relationships, and two that applied mechanistic approaches to simulate sagebrush recruitment and growth. This approach enabled us to produce an aggregate index of climate change vulnerability and uncertainty based on the level of agreement between models. Despite large differences in model structure, predictions of sagebrush response to climate change were largely consistent. Performance, as measured by change in cover, growth, or recruitment, was predicted to decrease at the warmest sites, but increase throughout the cooler portions of sagebrush's range. A sensitivity analysis indicated that sagebrush performance responds more strongly to changes in temperature than precipitation. Most of the uncertainty in model predictions reflected variation among the ecological models, raising questions about the reliability of forecasts based on a single modeling approach. Our results highlight the value of a multi‐model approach in forecasting climate change impacts and uncertainties and should help land managers to maximize the value of conservation investments.     

A View of Current Evaluative Practices in Instrumental Music Teacher Education

The purpose of this study was to examine how instrumental music educator skills are being evaluated in current undergraduate programs. While accrediting organizations mandate certain elements of these programs, they provide limited guidance on what evaluative approaches should be used. Instrumental music teacher educators in the College Music Society (n = 303) supplied data about their respective programs through an online survey. Participants reported using written and verbal feedback, self-evaluation, and rubrics most frequently. Similar evaluation processes used across program courses or experiences, such as rubrics and ePortfolios, were described by 35 percent of the music teacher educators. Most programs culminated in a semester-long student teaching period, during which preservice teachers were observed and evaluated by university supervisors three to four times. Weak correlations were indicated between some evaluative practices and music teacher educators’ expectations for program graduates’ music educator skills. Implications for music teacher education programs and suggestions for establishing evaluation policies are discussed.     

A model for change: An approach for forecasting well-being from service-based decisions

Every community decision incorporates a “forecasting” strategy (whether formal or implicit) to help visualize expected results and evaluate the potential “feelings/responses” that people living in that community may have about those results. With more communities seeking to make decisions based on sustainable alternatives, forecasting efforts that examine potential impacts of decisions on overall community well-being may prove to be valuable for not only gauging future benefits and trade-offs, but also for recognizing a community's affective response to the outcomes of those decisions. This paper describes a forecasting approach based on concepts introduced in the development of the U.S. Environmental Protection Agency's (US EPA) Human Well-Being Index (HWBI) (Smith et al., 2014, Summers et al., 2014). The approach examines the relationships among selected economic, environmental and social services that can be directly impacted by community decisions and eight domains of human well-being. Using models developed from constructed- or fixed-effect step-wise and multiple regressions and 11 years of data (2000–2010), these relationship functions may be used to characterize likely direct impacts of decisions on future well-being, as well as the possible intended and unintended secondary and tertiary effects relative to any main decision effects.     

M.S. Gilyarov's Scientific School of Soil Zoology

The role of M.S. Gilyarov's scientific school in the development of the subject and methodology of a new complex discipline formed in the mid 20th century—soil zoology—was considered. The establishment and evolution of the proper scientific school was periodized. The creative continuity and development of the basic laws and technical approaches included in the teacher's scientific program was demonstrated by scientific historical analysis.