Conceptual Mutation Testing for Student Programming Misconceptions

Context: Students often misunderstand programming problem descriptions. This can lead them to solve the wrong problem, which creates frustration, obstructs learning, and imperils grades. Researchers have found that students can be made to better understand the problem by writing examples before they start programming. These examples are checked against correct and wrong implementations -- analogous to mutation testing -- provided by course staff. Doing so results in better student understanding of the problem as well as better test suites to accompany the program, both of which are desirable educational outcomes. Inquiry: Producing mutant implementations requires care. If there are too many, or they are too obscure, students will end up spending a lot of time on an unproductive task and also become frustrated. Instead, we want a small number of mutants that each correspond to common problem misconceptions. This paper presents a workflow with partial automation to produce mutants of this form which, notably, are not those produced by mutation-testing tools. Approach: We comb through student tests that fail a correct implementation. The student misconceptions are embedded in these failures. We then use methods to semantically cluster these failures. These clusters are then translated into conceptual mutants. These can then be run against student data to determine whether we they are better than prior methods. Some of these processes also enjoy automation. Knowledge: We find that student misconceptions illustrated by failing tests can be operationalized by the above process. The resulting mutants do much better at identifying student misconceptions. Grounding: Our findings are grounded in a manual analysis of student examples and a quantitative evaluation of both our clustering techniques and our process for making conceptual mutants. The clustering evaluation compares against a ground truth using standard cluster-correspondence measures, while the mutant evaluation examines how conceptual mutants perform against student data. Importance: Our work contributes a workflow, with some automation, to reduce the cost and increase the effectiveness of generating conceptually interesting mutants. Such mutants can both improve learning outcomes and reduce student frustration, leading to better educational outcomes. In the process, we also identify a variation of mutation testing not commonly discussed in the software literature

Migratory Typing: Ten Years Later

In this day and age, many developers work on large, untyped code repositories. Even if they are the creators of the code, they notice that they have to figure out the equivalent of method signatures every time they work on old code. This step is time consuming and error prone. Ten years ago, the two lead authors outlined a linguistic solution to this problem. Specifically they proposed the creation of typed twins for untyped programming languages so that developers could migrate scripts from the untyped world to a typed one in an incremental manner. Their programmatic paper also spelled out three guiding design principles concerning the acceptance of grown idioms, the soundness of mixed-typed programs, and the units of migration. This paper revisits this idea of a migratory type system as implemented for Racket. It explains how the design principles have been used to produce the Typed Racket twin and presents an assessment of the project\u27s status, highlighting successes and failures

Thyroid cysts: a new extra-adrenal site of aldosterone synthase expression and increased aldosterone content

Abstract Background The rapid re-accumulation of fluid following aspiration of thyroid cystic lesions suggests that active transport of sodium and water may be involved in volume regulation of these lesions. In this study we address the possibility that aldosterone may take part in this process. Subjects and methods Thirty-one patients (29 women and two men), with a mean age of 52·7 ± 13·2 years (range: 27-77 years) underwent evaluation for thyroid nodules that had a sonographic cystic component. Cystic fluid obtained by FNA biopsy was sent for cytological examination and biochemical measurements. In 10 patients, material was collected for RNA extraction and determination of aldosterone synthase expression by RT-PCR amplification. Results All lesions were benign, cystic, colloid nodules. Cyst fluid aldosterone levels as measured by routine radioimmunoassay (RIA) were elevated above the normal plasma levels in all but five patients. Mean aldosterone levels were 27·1 ± 22·9 ng /dl (SD) (range: 5·9-117·5 ng/dl). In contrast, cyst cortisol values were in the low, low normal serum range (6·2 ± 2·9 µ g/dl, range: 0·2-10·2 µ g/dl). Sodium, chloride and potassium levels were 137 ± 4·7 mEq/l, 98 ± 5 mEq/l and 4·9 ± 1·4 mEq/l, respectively. Plasma aldosterone levels were normal in all patients tested. To confirm these results, 12 samples were assayed after extraction and chromatography using a highly specific antibody. Cyst aldosterone levels in this group were elevated above the normal serum range in all but one patient (mean concentration: 24·5 ± 14·6 ng/dl, range: 8·72-40·1 ng /dl). In this group, 18(OH)B levels were within the normal plasma range (12-55 ng /dl) in all but one patient (34·9 ± 17 ng/dl). Furthermore, aldosterone synthase mRNA expression was found in aspirates of four of 10 patients. Conclusions The increased aldosterone concentration and the presence of aldosterone synthase expression suggest that aldosterone may be locally produced and secreted in thyroid tissue. The pathophysiological implications of this finding remain to be established

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges

Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement

Introduction With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis

Advances in the treatment of prolactinomas

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases