136 research outputs found

    Human-AI Teaming During an Ongoing Disaster: How Scripts Around Training and Feedback Reveal this is a Form of Human-Machine Communication

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    Humans play an integral role in identifying important information from social media during disasters. While human annotation of social media data to train machine learning models is often viewed as human-computer interaction, this study interrogates the ontological boundary between such interaction and human-machine communication. We conducted multiple interviews with participants who both labeled data to train machine learning models and corrected machine-inferred data labels. Findings reveal three themes: scripts invoked to manage decision-making, contextual scripts, and scripts around perceptions of machines. Humans use scripts around training the machine—a form of behavioral anthropomorphism—to develop social relationships with them. Correcting machine-inferred data labels changes these scripts and evokes self-doubt around who is right, which substantiates the argument that this is a form of human-machine communication

    fMRI Response During Figural Memory Task Performance in College Drinkers [pre-print]

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    Rationale: 18-25-year-olds show the highest rates of alcohol use disorders (AUD) and heavy drinking, which may have critical neurocognitive implications. Regions subserving memory may be particularly susceptible to alcohol-related impairments. Objective: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the neural correlates of visual encoding and recognition among heavy drinking college students. We predicted that heavy drinkers would show worse memory performance and increased frontal/parietal activation and decreased hippocampal response during encoding. Methods: Participants were 23 heavy drinkers and 33 demographically matched light drinkers, ages 18-20, characterized using quantity/frequency of drinking and AUD diagnosis. Participants performed a figural encoding and recognition task during fMRI. BOLD response during encoding was modeled based on whether each stimulus was subsequently recognized or forgotten (i.e., correct vs. incorrect encoding). Results: There were no group differences in behavioral performance. Compared to light drinkers, heavy drinkers showed: 1) greater BOLD response during correct encoding in right hippocampus/medial temporal, right dorsolateral prefrontal, left inferior frontal, and bilateral posterior parietal cortices; 2) less left inferior frontal activation and greater bilateral precuneus deactivation during incorrect encoding; and 3) less bilateral insula response during correct recognition (clusters \u3e10,233ul, p Conclusions: This is the first investigation of the neural substrates of figural memory among heavy drinking older adolescents. Heavy drinkers demonstrated compensatory hyperactivation of memory-related areas during correct encoding, greater deactivation of default mode regions during incorrect encoding, and reduced recognition-related response. Results could suggest use of different encoding and recognition strategies among heavy drinkers

    Challenges and opportunities for increasing patient involvement in heart failure self-care programs and self-care in the post–hospital discharge period

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    Background: People living with heart failure (HF) are particularly vulnerable after hospital discharge. An alliance between patient authors, clinicians, industry, and co-developers of HF programs can represent an effective way to address the unique concerns and obstacles people living with HF face during this period. The aim of this narrative review article is to discuss challenges and opportunities of this approach, with the goal of improving participation and clinical outcomes of people living with HF. Methods: This article was co-authored by people living with HF, heart transplant recipients, patient advocacy representatives, cardiologists with expertise in HF care, and industry representatives specializing in patient engagement and cardiovascular medicine, and reviews opportunities and challenges for people living with HF in the post–hospital discharge period to be more integrally involved in their care. A literature search was conducted, and the authors collaborated through two virtual roundtables and via email to develop the content for this review article. Results: Numerous transitional-care programs exist to ease the transition from the hospital to the home and to provide needed education and support for people living with HF, to avoid rehospitalizations and other adverse outcomes. However, many programs have limitations and do not integrally involve patients in the design and co-development of the intervention. There are thus opportunities for improvement. This can enable patients to better care for themselves with less of the worry and fear that typically accompany the transition from the hospital. We discuss the importance of including people living with HF in the development of such programs and offer suggestions for strategies that can help achieve these goals. An underlying theme of the literature reviewed is that education and engagement of people living with HF after hospitalization are critical. However, while clinical trial evidence on existing approaches to transitions in HF care indicates numerous benefits, such approaches also have limitations. Conclusion: Numerous challenges continue to affect people living with HF in the post–hospital discharge period. Strategies that involve patients are needed, and should be encouraged, to optimally address these challenges

    Enhancing students’ motivation to learn software engineering programming techniques: a collaborative and social interaction approach

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    To motivate students to study advanced programming techniques, including the use of architectural styles such as the model–view–controller pattern, we have con-ducted action research upon a project based-learning approach. In addition to collabo-ration, the approach includes students’ searching and analysis of scientific documents and their involvement in communities of practice outside academia. In this paper, we report the findings of second action research cycle, which took place throughout the fourth semester of a six-semester program. As with the previous cycle during the pre-vious academic year, students did not satisfactorily achieve expected learning out-comes. More groups completed the assigned activities, but results continue to reflect poor engagement in the communities of practice and very low performance in other learning tasks. From the collected data we have identified new approaches and recom-mendations for subsequent research.Fundação para a Ciência e Tecnologia (FCT), Portugal, for Ph.D. Grants SFRH/BD/91309/2012 and SFRH/BD/87815/201

    Intra- and Inter-clade Cross-reactivity by HIV-1 Gag Specific T-Cells Reveals Exclusive and Commonly Targeted Regions: Implications for Current Vaccine Trials

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    The genetic diversity of HIV-1 across the globe is a major challenge for developing an HIV vaccine. To facilitate immunogen design, it is important to characterize clusters of commonly targeted T-cell epitopes across different HIV clades. To address this, we examined 39 HIV-1 clade C infected individuals for IFN-γ Gag-specific T-cell responses using five sets of overlapping peptides, two sets matching clade C vaccine candidates derived from strains from South Africa and China, and three peptide sets corresponding to consensus clades A, B, and D sequences. The magnitude and breadth of T-cell responses against the two clade C peptide sets did not differ, however clade C peptides were preferentially recognized compared to the other peptide sets. A total of 84 peptides were recognized, of which 19 were exclusively from clade C, 8 exclusively from clade B, one peptide each from A and D and 17 were commonly recognized by clade A, B, C and D. The entropy of the exclusively recognized peptides was significantly higher than that of commonly recognized peptides (p = 0.0128) and the median peptide processing scores were significantly higher for the peptide variants recognized versus those not recognized (p = 0.0001). Consistent with these results, the predicted Major Histocompatibility Complex Class I IC50 values were significantly lower for the recognized peptide variants compared to those not recognized in the ELISPOT assay (p<0.0001), suggesting that peptide variation between clades, resulting in lack of cross-clade recognition, has been shaped by host immune selection pressure. Overall, our study shows that clade C infected individuals recognize clade C peptides with greater frequency and higher magnitude than other clades, and that a selection of highly conserved epitope regions within Gag are commonly recognized and give rise to cross-clade reactivities

    Ovarian cancer immunotherapy: opportunities, progresses and challenges

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    Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer

    Mutations in TOP3A Cause a Bloom Syndrome-like Disorder

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    Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic testing. Here, we describe biallelic mutations in TOP3A in ten individuals with prenatal-onset growth restriction and microcephaly. TOP3A encodes topoisomerase III alpha (TopIIIα), which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination. We also identify a homozygous truncating variant in RMI1, which encodes another component of the BTRR complex, in two individuals with microcephalic dwarfism. The TOP3A mutations substantially reduce cellular levels of TopIIIα, and consequently subjects’ cells demonstrate elevated rates of SCE. Unresolved DNA recombination and/or replication intermediates persist into mitosis, leading to chromosome segregation defects and genome instability that most likely explain the growth restriction seen in these subjects and in Bloom syndrome. Clinical features of mitochondrial dysfunction are evident in several individuals with biallelic TOP3A mutations, consistent with the recently reported additional function of TopIIIα in mitochondrial DNA decatenation. In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis

    Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa

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    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants, respectively1-3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity

    Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: A comparative risk assessment

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    Background: High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods: We used data for exposure to risk factors by country, age group, and sex from pooled analyses of population-based health surveys. We obtained relative risks for the effects of risk factors on cause-specific mortality from meta-analyses of large prospective studies. We calculated the population attributable fractions for each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the effects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specific population attributable fractions by the number of disease-specific deaths. We obtained cause-specific mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the final estimates. Findings: In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10·8 million deaths, 95% CI 10·1-11·5) of deaths from these diseases in 2010 were attributable to the combined effect of these four metabolic risk factors, compared with 67% (7·1 million deaths, 6·6-7·6) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined effects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation: The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing effect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the global response to non-communicable diseases. Funding: UK Medical Research Council, US National Institutes of Health. © 2014 Elsevier Ltd
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