Perceptually-based language to simplify sketch recognition user interface development

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2007.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 473-495).Diagrammatic sketching is a natural modality of human-computer interaction that can be used for a variety of tasks, for example, conceptual design. Sketch recognition systems are currently being developed for many domains. However, they require signal-processing expertise if they are to handle the intricacies of each domain, and they are time-consuming to build. Our goal is to enable user interface designers and domain experts who may not have expertise in sketch recognition to be able to build these sketch systems. We created and implemented a new framework (FLUID - f acilitating user interface development) in which developers can specify a domain description indicating how domain shapes are to be recognized, displayed, and edited. This description is then automatically transformed into a sketch recognition user interface for that domain. LADDER, a language using a perceptual vocabulary based on Gestalt principles, was developed to describe how to recognize, display, and edit domain shapes. A translator and a customizable recognition system (GUILD - a generator of user interfaces using ladder descriptions) are combined with a domain description to automatically create a domain specific recognition system.(cont.) With this new technology, by writing a domain description, developers are able to create a new sketch interface for a domain, greatly reducing the time and expertise for the task Continuing in pursuit of our goal to facilitate UI development, we noted that 1) human generated descriptions contained syntactic and conceptual errors, and that 2) it is more natural for a user to specify a shape by drawing it than by editing text. However, computer generated descriptions from a single drawn example are also flawed, as one cannot express all allowable variations in a single example. In response, we created a modification of the traditional model of active learning in which the system selectively generates its own near-miss examples and uses the human teacher as a source of labels. System generated near-misses offer a number of advantages. Human generated examples are tedious to create and may not expose problems in the current concept. It seems most effective for the near-miss examples to be generated by whichever learning participant (teacher or student) knows better where the deficiencies lie; this will allow the concepts to be more quickly and effectively refined.(cont.) When working in a closed domain such as this one, the computer learner knows exactly which conceptual uncertainties remain, and which hypotheses need to be tested and confirmed. The system uses these labeled examples to automatically build a LADDER shape description, using a modification of the version spaces algorithm that handles interrelated constraints, and which also has the ability to learn negative and disjunctive constraints.by Tracy Anne Hammond.Ph.D

Mechanix: An Intelligent Web Interface for Automatic Grading of Sketched Free-Body Diagrams

Sketching free body diagrams is an essential skill that students learn in introductory physics and engineering classes; however, university class sizes are growing and often have hundreds of students in a single class. This situation creates a grading challenge for instructors as there is simply not enough time nor resources to provide adequate feedback on every problem. We have developed a web-based application called Mechanix to provide automated real-time feedback on hand-drawn free body diagrams for students. The system is driven by novel sketch recognition algorithms developed for recognizing and comparing trusses, general shapes, and arrows in diagrams. We have discovered students perform as well as paper homework or other online homework systems which only check the final answer through deployment to five universities with 450 students completing homework on the system over the 2018 and 2019 school years. Mechanix has reduced the amount of manual grading required for instructors in those courses while ensuring students can correctly draw the free body diagram

Sketchtivity, an Intelligent Tutoring Software: Broadening Applications and Impact

Freehand sketching is an essential skill for engineers. Sketching enables designers to represent ideas rapidly and offload working memory. Sketches in the design process also correlate with positive design outcomes. Teaching sketching to engineers, however, presents many challenges in engineering curriculums. Sketching is most often taught in large entry-level courses where individualized feedback, which is vital to learning sketching, is not possible. Sketchtivity is an intelligent tutoring software designed to aid in the practice and feedback on freehand sketching skills. Sketchtivity teaches the basics of two-point perspective sketching providing lessons, feedback, and tips on how to improve. The goal of this project is to implement Sketchtivity at a broader range of universities, to expand on the software functionality, and to understand more about the implications of improving sketching skill. Sketchtivity is currently being implemented in classrooms at three diverse universities across the United States. Our research has shown that the tablet interface does not negatively impact students’ sketching skill development. We are currently conducting further experiments to better understand how students are learning from the feedback the software provides. Beyond measuring current impact, this project seeks to expand the functionality of Sketchtivity to offer lessons on more complex sketching tasks and more poignant feedback to learners. The main research goal is focused on improving sketching skills. The remaining goals turn outward toward the implications for improved sketching skill for engineers. It is essential to understand how to measure sketching skill effectively, and what role sketching skill plays in engineering design. Sketching skill has been measured in many different ways in many different fields and there seems to be no consensus on measurement strategy or validity. As a part of this project, we are conducting a systematic literature review of sketching evaluation. This literature review aims to compile the different methods of measurement to remove some of the ambiguity around evaluating sketching skill in engineering research and education. There has been much research on the role of sketching in engineering design, but the research around sketching skill has been limited. Essential to improving skill in any task is understanding how confidence in the skill is affected. Engineers’ self-efficacy can enable or limit their application of skills. We are also looking at how sketching skill is related to drawing self-efficacy. Sketching has the largest impact in the early stages of design. The final research goal of this project is to investigate the relationship between sketching and creativity in the early stages of design. Through experiments of idea generation and sketching abilities, we hope to better understand to what degree sketching enables creativity in design. To summarize, this project seeks to improve sketching skill through Sketchtivity. We are accomplishing this through expanding reach at multiple universities and expanding the capabilities of the software. It is also essential to understand the implications of improving sketching skill. This is being investigated through improved evaluation of sketching and investigations of sketching’s relationship to drawing self-efficacy and creativity

Impact of a sketch-based tutoring system at multiple universities

Large class sizes in engineering programs often prevent instructors from providing detailed and meaningful feedback to students on their homework problems. While the literature shows that frequent and immediate formative feedback has several benefits in terms of knowledge gain and academic motivation, several instructors struggle to provide any feedback. Motivated by this inability, a sketch-based virtual tutoring system, named Mechanix, has been developed and implemented. Mechanix lets the students to sketch their freebody diagram on a virtual interface and the process involved is very close to using a pencil and paper. The system provides real-time feedback on the accuracy of their Freebody diagrams and the solution to the problem. This paper reports the implementation of Mechanix at two large public universities in the United States - Georgia Institute of Technology and Texas State University. Mechanix is used to solve specific assignments from each school that involve the use of freebody diagrams. Pre- and post- concept inventories are used to measure the improvements in the conceptual understanding of the students. The results show that students who solve their homework using Mechanix outperform their peers who do not in one school, whereas the results are similar across the two groups in the second school. The evaluation of the concept inventories shows that the students who used Mechanix has the same level of improvement in their conceptual knowledge compared to the control group

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Sketch Recognition User Interface Development

Diagrammatic sketching is a natural modality of human-computer interaction that can be used for a variety of tasks, for example, conceptual design. Sketch recognition systems are currently being developed for many domains. However, they require signal-processing expertise if they are to handle the intricacies of each domain, and they are time-consuming to build. Our goal is to enable user interface designers and domain experts who may not have expertise in sketch recognition to be able to build these sketch systems. We created and implemented a new framework (FLUID- facilitating user interface development) in which developers can specify a domain description indicating how domain shapes are to be recognized, displayed, and edited. This description is then automatically transformed into a sketch recognition user interface for that domain. LADDER, a language using a perceptual vocabulary based on Gestalt principles, was developed to describe how to recognize, display, and edit domain shapes. A translator and a customizable recognition system (GUILD- a generator of user interfaces usin

Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques

Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIV SF162P3 . On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8 + T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs