Reinventing discovery learning: a field-wide research program

© 2017, Springer Science+Business Media B.V., part of Springer Nature. Whereas some educational designers believe that students should learn new concepts through explorative problem solving within dedicated environments that constrain key parameters of their search and then support their progressive appropriation of empowering disciplinary forms, others are critical of the ultimate efficacy of this discovery-based pedagogical philosophy, citing an inherent structural challenge of students constructing historically achieved conceptual structures from their ingenuous notions. This special issue presents six educational research projects that, while adhering to principles of discovery-based learning, are motivated by complementary philosophical stances and theoretical constructs. The editorial introduction frames the set of projects as collectively exemplifying the viability and breadth of discovery-based learning, even as these projects: (a) put to work a span of design heuristics, such as productive failure, surfacing implicit know-how, playing epistemic games, problem posing, or participatory simulation activities; (b) vary in their target content and skills, including building electric circuits, solving algebra problems, driving safely in traffic jams, and performing martial-arts maneuvers; and (c) employ different media, such as interactive computer-based modules for constructing models of scientific phenomena or mathematical problem situations, networked classroom collective “video games,” and intercorporeal master–student training practices. The authors of these papers consider the potential generativity of their design heuristics across domains and contexts

Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study

<b>Objective</b>: To compare the analgesic efficacy and side effects of the synthetic cannabinoid nabilone with those of the weak opioid dihydrocodeine for chronic neuropathic pain. <b>Design</b>: Randomised, double blind, crossover trial of 14 weeks’ duration comparing dihydrocodeine and nabilone. <b>Setting</b>: Outpatient units of three hospitals in the United Kingdom. <b>Participants</b>: 96 patients with chronic neuropathic pain, aged 23-84 years. <b>Main outcome measures</b>: The primary outcome was difference between nabilone and dihydrocodeine in pain, as measured by the mean visual analogue score computed over the last 2 weeks of each treatment period. Secondary outcomes were changes in mood, quality of life, sleep, and psychometric function. Side effects were measured by a questionnaire. <b>Intervention</b>: Patients received a maximum daily dose of 240 mg dihydrocodeine or 2 mg nabilone at the end of each escalating treatment period of 6 weeks. Treatment periods were separated by a 2 week washout period. <b>Results</b>: Mean baseline visual analogue score was 69.6 mm (range 29.4-95.2) on a 0-100 mm scale. 73 patients were included in the available case analysis and 64 patients in the per protocol analysis. The mean score was 6.0 mm longer for nabilone than for dihydrocodeine (95% confidence interval 1.4 to 10.5) in the available case analysis and 5.6 mm (10.3 to 0.8) in the per protocol analysis. Side effects were more frequent with nabilone. <b>Conclusion</b>: Dihydrocodeine provided better pain relief than the synthetic cannabinoid nabilone and had slightly fewer side effects, although no major adverse events occurred for either drug

Data-Oblivious Stream Productivity

We are concerned with demonstrating productivity of specifications of infinite streams of data, based on orthogonal rewrite rules. In general, this property is undecidable, but for restricted formats computable sufficient conditions can be obtained. The usual analysis disregards the identity of data, thus leading to approaches that we call data-oblivious. We present a method that is provably optimal among all such data-oblivious approaches. This means that in order to improve on the algorithm in this paper one has to proceed in a data-aware fashion

Antibody localization in horse, rabbit, and goat antilymphocyte sera

The localization of antibodies was studied in rabbit, goat, and horse ALS raised by weekly immunization with canine or human spleen cells for 4 to 12 weeks. A combination of analytic techniques was used including column chromatography, electrophoresis, immunoelectrophoresis, determination of protein concentration, and measurement of antibody titers. In the rabbit and goat ALS, virtually all of the leukoagglutinins and lymphocytotoxins were in the easily separable IgG; accidentally induced thromboagglutinins were in the same location. In the rabbit hemagglutinins were found in both the IgG and IgM, whereas in the goat these were almost exclusively in the IgM. The antiwhite cell antibodies were most widely distributed in the horse. The cytotoxins were primarily in the IgG, but the leukoagglutinins were most heavily concentrated in the T-equine globulin which consists mostly of IgA. By differential ammonium sulfate precipitation of a horse antidoglymphocyte serum, fractions were prepared that were rich in IgG and IgA. Both were able to delay the rejection of canine renal homografts, the IgA-rich preparation to a somewhat greater degree. The findings in this study have been discussed in relation to the refining techniques that have been used for the production of globulin from heterologous ALS. © 1970

Rectification by charging -- the physics of contact-induced current asymmetry in molecular conductors

We outline the qualitatively different physics behind charging-induced current asymmetries in molecular conductors operating in the weakly interacting self-consistent field (SCF) and the strongly interacting Coulomb Blockade (CB) regimes. A conductance asymmetry arises in SCF because of the unequal mean-field potentials that shift a closed-shell conducting level differently for positive and negative bias. A very different current asymmetry arises for CB due to the unequal number of open-shell excitation channels at opposite bias voltages. The CB regime, dominated by single charge effects, typically requires a computationally demanding many-electron or Fock space description. However, our analysis of molecular Coulomb Blockade measurements reveals that many novel signatures can be explained using a {{simpler}} orthodox model that involves an incoherent sum of Fock space excitations and {\it{hence treats the molecule as a metallic dot or an island}}. This also reduces the complexity of the Fock space description by just including various charge configurations only, thus partially underscoring the importance of electronic structure, while retaining the essence of the single charge nature of the transport process. We finally point out, however, that the inclusion of electronic structure and hence well-resolved Fock space excitations is crucial in some notable examples.Comment: 12 pages, 10 figure

Three Cuts for Accelerated Interval Propagation

This paper addresses the problem of nonlinear multivariate root finding. In an earlier paper we described a system called Newton which finds roots of systems of nonlinear equations using refinements of interval methods. The refinements are inspired by AI constraint propagation techniques. Newton is competative with continuation methods on most benchmarks and can handle a variety of cases that are infeasible for continuation methods. This paper presents three "cuts" which we believe capture the essential theoretical ideas behind the success of Newton. This paper describes the cuts in a concise and abstract manner which, we believe, makes the theoretical content of our work more apparent. Any implementation will need to adopt some heuristic control mechanism. Heuristic control of the cuts is only briefly discussed here

Imipramine blue sensitively and selectively targets FLT3-ITD positive acute myeloid leukemia cells.

Aberrant cytokine signaling initiated from mutant receptor tyrosine kinases (RTKs) provides critical growth and survival signals in high risk acute myeloid leukemia (AML). Inhibitors to FLT3 have already been tested in clinical trials, however, drug resistance limits clinical efficacy. Mutant receptor tyrosine kinases are mislocalized in the endoplasmic reticulum (ER) of AML and play an important role in the non-canonical activation of signal transducer and activator of transcription 5 (STAT5). Here, we have tested a potent new drug called imipramine blue (IB), which is a chimeric molecule with a dual mechanism of action. At 200-300 nM concentrations, IB is a potent inhibitor of STAT5 through liberation of endogenous phosphatase activity following NADPH oxidase (NOX) inhibition. However, at 75-150 nM concentrations, IB was highly effective at killing mutant FLT3-driven AML cells through a similar mechanism as thapsigargin (TG), involving increased cytosolic calcium. IB also potently inhibited survival of primary human FLT3/ITD+ AML cells compared to FLT3/ITDneg cells and spared normal umbilical cord blood cells. Therefore, IB functions through a mechanism involving vulnerability to dysregulated calcium metabolism and the combination of fusing a lipophilic amine to a NOX inhibiting dye shows promise for further pre-clinical development for targeting high risk AML

Do GPs want or need formal support following a patient suicide?: a mixed methods study.

BACKGROUND: Patient suicide can be a devastating event for some general practitioners (GPs). Few guidelines exist to aid or support GPs in the aftermath of patient suicide. AIM: To explore GPs views on how they are affected by a patient suicide and the formal support available to them following a patient suicide. DESIGN: Questionnaires and semi-structured interviews. SETTING: General practices in the northwest of England. METHODS: About 198 semi-structured interviews were conducted as part of a retrospective study. Interviews were transcribed verbatim and analysed using descriptive statistics and a framework thematic approach. RESULTS: GPs were aged between 31 and 67 years, 144 (73%) were male and the number of years in practice varied between 8 and 40 years (median = 24 years). GPs were based at 133 (67%) urban and 65 (33%) rural practices, 30 (15%) were single-handed GP practices and 168 (85%) practices had two or more GPs. About 131 (66%) GPs reported being affected by patient suicide through feelings of grief, guilt and self-scrutiny. A greater number of years in practice may have been protective against these effects. About 54 (27%) GPs reported having mostly 'informal' support from peers or colleagues and support was less available to younger and single handed GPs. CONCLUSIONS: Our findings suggest that the majority of GPs are affected by patient suicide and most seek informal support from their peers and colleagues. Although many indicated that informal support systems were adequate and provided a protective environment, procedures should be developed to ensure the availability of guidelines for those who may require formal support

Capturing Hiproofs in HOL Light

Hierarchical proof trees (hiproofs for short) add structure to ordinary proof trees, by allowing portions of trees to be hierarchically nested. The additional structure can be used to abstract away from details, or to label particular portions to explain their purpose. In this paper we present two complementary methods for capturing hiproofs in HOL Light, along with a tool to produce web-based visualisations. The first method uses tactic recording, by modifying tactics to record their arguments and construct a hierarchical tree; this allows a tactic proof script to be modified. The second method uses proof recording, which extends the HOL Light kernel to record hierachical proof trees alongside theorems. This method is less invasive, but requires care to manage the size of the recorded objects. We have implemented both methods, resulting in two systems: Tactician and HipCam

Towards the Formal Reliability Analysis of Oil and Gas Pipelines

It is customary to assess the reliability of underground oil and gas pipelines in the presence of excessive loading and corrosion effects to ensure a leak-free transport of hazardous materials. The main idea behind this reliability analysis is to model the given pipeline system as a Reliability Block Diagram (RBD) of segments such that the reliability of an individual pipeline segment can be represented by a random variable. Traditionally, computer simulation is used to perform this reliability analysis but it provides approximate results and requires an enormous amount of CPU time for attaining reasonable estimates. Due to its approximate nature, simulation is not very suitable for analyzing safety-critical systems like oil and gas pipelines, where even minor analysis flaws may result in catastrophic consequences. As an accurate alternative, we propose to use a higher-order-logic theorem prover (HOL) for the reliability analysis of pipelines. As a first step towards this idea, this paper provides a higher-order-logic formalization of reliability and the series RBD using the HOL theorem prover. For illustration, we present the formal analysis of a simple pipeline that can be modeled as a series RBD of segments with exponentially distributed failure times.Comment: 15 page