Search results for: William F. Christensen

Authors: Amber Dhoot, Tarush Gupta, Andrea Gurr, William Jenkins, Sandro Pietrunti, Alexis Tang

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Background: The COVID-19 pandemic has driven pharmacovigilance towards a new paradigm. Nowadays, more people than ever before are recognising and reporting adverse reactions from medications, treatments, and vaccines. In the modern era, with over 3.8 billion users, social media has become the most accessible medium for people to voice their opinions and so provides an opportunity to engage with more patient-centric and accessible pharmacovigilance. However, the pharmaceutical industry has been slow to incorporate social media into its modern pharmacovigilance strategy. This project aims to make social media a more effective tool in pharmacovigilance, and so reduce drug costs, improve drug safety and improve patient outcomes. This will be achieved by firstly uncovering and categorising the barriers facing the widespread adoption of social media in pharmacovigilance. Following this, the potential opportunities of social media will be explored. We will then propose realistic, practical recommendations to make social media a more effective tool for pharmacovigilance. Methodology: A comprehensive systematic literature review was conducted to produce a categorised summary of these barriers. This was followed by conducting 11 semi-structured interviews with pharmacovigilance experts to confirm the literature review findings whilst also exploring the unpublished and real-life challenges faced by those in the pharmaceutical industry. Finally, a survey of the general public (n = 112) ascertained public knowledge, perception, and opinion regarding the use of their social media data for pharmacovigilance purposes. This project stands out by offering perspectives from the public and pharmaceutical industry that fill the research gaps identified in the literature review. Results: Our results gave rise to several key analysis points. Firstly, inadequacies of current Natural Language Processing algorithms hinder effective pharmacovigilance data extraction from social media, and where data extraction is possible, there are significant questions over its quality. Social media also contains a variety of biases towards common drugs, mild adverse drug reactions, and the younger generation. Additionally, outdated regulations for social media pharmacovigilance do not align with new, modern General Data Protection Regulations (GDPR), creating ethical ambiguity about data privacy and level of access. This leads to an underlying mindset of avoidance within the pharmaceutical industry, as firms are disincentivised by the legal, financial, and reputational risks associated with breaking ambiguous regulations. Conclusion: Our project uncovered several barriers that prevent effective pharmacovigilance on social media. As such, social media should be used to complement traditional sources of pharmacovigilance rather than as a sole source of pharmacovigilance data. However, this project adds further value by proposing five practical recommendations that improve the effectiveness of social media pharmacovigilance. These include: prioritising health-orientated social media; improving technical capabilities through investment and strategic partnerships; setting clear regulatory guidelines using multi-stakeholder processes; creating an adverse drug reaction reporting interface inbuilt into social media platforms; and, finally, developing educational campaigns to raise awareness of the use of social media in pharmacovigilance. Implementation of these recommendations would speed up the efficient, ethical, and systematic adoption of social media in pharmacovigilance.

Keywords: adverse drug reaction, drug safety, pharmacovigilance, social media

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Authors: Karlee J. Hall, Mark Laylor, Jessy Varghese, Paula Polastri, Karen Van Ooteghem, William McIlroy

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Balance training is a common part of physiotherapy treatment and often involves a set of proprioceptive exercises which the patient carries out in the clinic and as part of their exercise program. Understanding all contributing factors to altered balance is of utmost importance to the clinical success of treatment of balance dysfunctions. A critical role for the autonomic nervous system (ANS) in the control of balance reactions has been proposed previously, with evidence for potential involvement being inferred from the observation of phasic galvanic skin responses (GSR) evoked by external balance perturbations. The current study explored whether the coupling between ANS reactivity and balance reactions would be observed during spontaneously occurring instability while standing, including standard positions typical of physiotherapy balance assessments. It was hypothesized that time-varying changes in GSR (ANS reactivity) would be associated with time-varying changes in the mediolateral center of pressure (ML-COP) (somatomotor reactivity). Nine individuals (5 females, 4 males, aged 19-37 years) were recruited. To induce varying balance demands during standing, the study compared ML-COP and GSR data across different task conditions varying the availability of vision and width of the base of support. Subjects completed 3, 30-second trials for each of the following stance conditions: standard, narrow, and tandem eyes closed, tandem eyes open, tandem eyes open with dome to shield visual input, and restricted peripheral visual field. ANS activity was evaluated by measures of GSR recorded from Ag-AgCl electrodes on the middle phalanges of digits 2 and 4 on the left hand; balance measures include ML-COP excursion frequency and amplitude recorded from two force plates embedded in the floor underneath each foot. Subjects were instructed to stand as still as possible with arms crossed in front of their chest. When comparing mean task differences across subjects, there was an expected increase in postural sway from tasks with a wide stance and no sensory restrictions (least challenging) to those with a narrow stance and no vision (most challenging). The correlation analysis revealed a significant positive relationship between ML-COP variability and GSR variability when comparing across tasks (r=0.94, df=5, p < 0.05). In addition, correlations coincided within each subject and revealed a significant positive correlation in 7 participants (r= 0.47, 0.57, 0.62, 0.62, 0.81, 0.64, 0.69 respectively, df=19, p < 0.05) and no significant relationship in 2 participants (r=0.36, 0.29 respectively, df=19, p > 0.05). The current study revealed a significant relationship between ML-COP and GSR during balance tasks, revealing the ANS reactivity associated with naturally occurring instability when standing still, which is proportional to the degree of instability. Understanding the link between ANS activity and control of COP is an important step forward in the enhancement of assessment of contributing factors to poor balance and treatment of balance dysfunctions. The next steps will explore the temporal association between the time-varying changes in COP and GSR to establish if the ANS reactivity phase leads or lags the evoked motor reactions, as well as exploration of potential biomarkers for use in screening of ANS activity as a contributing factor to altered balance control clinically.

Keywords: autonomic nervous system, balance control, center of pressure, somatic nervous system

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Authors: John D. Sanderson

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The popularity of American cinema worldwide has contributed to the development of sociolects related to specific film genres in other cultural contexts by means of screen translation, in many cases eluding norms of usage in the target language, a process whose result has come to be known as 'dubbese'. A consequence for the reception in countries where local audiovisual fiction consumption is far lower than American imported productions is that this linguistic construct is preferred, even though it differs from common everyday speech. The iconography of film genres such as science-fiction, western or sword-and-sandal films, for instance, generates linguistic expectations in international audiences who will accept more easily the sociolects assimilated by the continuous reception of American productions, even if the themes, locations, characters, etc., portrayed on screen may belong in origin to other cultures. And the non-normative language (e.g., calques, semantic loans) used in the preferred mode of linguistic transfer, whether it is translation for dubbing or subtitling, has diachronically evolved in many cases into a status of canonized sociolect, not only accepted but also required, by foreign audiences of American films. However, a remarkable step forward is taken when this typology of artificial linguistic constructs starts being used creatively by nationals of these target cultural contexts. In the case of Spain, the success of American sitcoms such as Friends in the 1990s led Spanish television scriptwriters to include in national productions lexical and syntactical indirect borrowings (Anglicisms not formally identifiable as such because they include elements from their own language) in order to target audiences of the former. However, this commercial strategy had already taken place decades earlier when Spain became a favored location for the shooting of foreign films in the early 1960s. The international popularity of the then newly developed sub-genre known as Spaghetti-Western encouraged Spanish investors to produce their own movies, and local scriptwriters made use of the dubbese developed nationally since the advent of sound in film instead of using normative language. As a result, direct Anglicisms, as well as lexical and syntactical borrowings made up the creative writing of these Spanish productions, which also became commercially successful. Interestingly enough, some of these films were even marketed in English-speaking countries as original westerns (some of the names of actors and directors were anglified to that purpose) dubbed into English. The analysis of these 'back translations' will also foreground some semantic distortions that arose in the process. In order to perform the research on these issues, a wide corpus of American films has been used, which chronologically range from Stagecoach (John Ford, 1939) to Django Unchained (Quentin Tarantino, 2012), together with a shorter corpus of Spanish films produced during the golden age of Spaghetti Westerns, from una tumba para el sheriff (Mario Caiano; in English lone and angry man, William Hawkins) to tu fosa será la exacta, amigo (Juan Bosch, 1972; in English my horse, my gun, your widow, John Wood). The methodology of analysis and the conclusions reached could be applied to other genres and other cultural contexts.

Keywords: dubbing, film genre, screen translation, sociolect

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Authors: William Michael Short

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Semantic Web’ technologies such as the Unified Medical Language System Metathesaurus, SNOMED-CT, and MeSH have been touted as transformational for the way users access online medical and health information, enabling both the automated analysis of natural-language data and the integration of heterogeneous healthrelated resources distributed across the Internet through the use of standardized terminologies that capture concepts and relationships between concepts that are expressed differently across datasets. However, the approaches that have so far characterized ‘semantic bioinformatics’ have not yet fulfilled the promise of the Semantic Web for medical and health information retrieval applications. This paper argues within the perspective of cognitive linguistics and cognitive anthropology that four features of human meaning-making must be taken into account before the potential of semantic technologies can be realized for this domain. First, many semantic technologies operate exclusively at the level of the word. However, texts convey meanings in ways beyond lexical semantics. For example, transitivity patterns (distributions of active or passive voice) and modality patterns (configurations of modal constituents like may, might, could, would, should) convey experiential and epistemic meanings that are not captured by single words. Language users also naturally associate stretches of text with discrete meanings, so that whole sentences can be ascribed senses similar to the senses of words (so-called ‘discourse topics’). Second, natural language processing systems tend to operate according to the principle of ‘one token, one tag’. For instance, occurrences of the word sound must be disambiguated for part of speech: in context, is sound a noun or a verb or an adjective? In syntactic analysis, deterministic annotation methods may be acceptable. But because natural language utterances are typically characterized by polyvalency and ambiguities of all kinds (including intentional ambiguities), such methods leave the meanings of texts highly impoverished. Third, ontologies tend to be disconnected from everyday language use and so struggle in cases where single concepts are captured through complex lexicalizations that involve profile shifts or other embodied representations. More problematically, concept graphs tend to capture ‘expert’ technical models rather than ‘folk’ models of knowledge and so may not match users’ common-sense intuitions about the organization of concepts in prototypical structures rather than Aristotelian categories. Fourth, and finally, most ontologies do not recognize the pervasively figurative character of human language. However, since the time of Galen the widespread use of metaphor in the linguistic usage of both medical professionals and lay persons has been recognized. In particular, metaphor is a well-documented linguistic tool for communicating experiences of pain. Because semantic medical knowledge-bases are designed to help capture variations within technical vocabularies – rather than the kinds of conventionalized figurative semantics that practitioners as well as patients actually utilize in clinical description and diagnosis – they fail to capture this dimension of linguistic usage. The failure of semantic technologies in these respects degrades the efficiency and efficacy not only of medical research, where information retrieval inefficiencies can lead to direct financial costs to organizations, but also of care provision, especially in contexts of patients’ self-management of complex medical conditions.

Keywords: ambiguity, bioinformatics, language, meaning, metaphor, ontology, semantic web, semantics

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Authors: Mian Huang, Chi Ma, Junyu Lin, William Lu

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Introduction: Bone health attracts more attention recently and an intelligent question and answer (QA) chatbot for osteoporosis is helpful for science popularization. With Generative Pretrained Transformer (GPT) technology developing, we build an osteoporosis corpus dataset and then fine-tune LLaMA, a famous open-source GPT foundation large language model(LLM), on our self-constructed osteoporosis corpus. Evaluated by clinical orthopedic experts, our fine-tuned model outperforms vanilla LLaMA on osteoporosis QA task in Chinese. Three-dimensional quantitative computed tomography (QCT) measured bone mineral density (BMD) is considered as more accurate than DXA for BMD measurement in recent years. We develop an automatic Phantom-less QCT(PL-QCT) that is more efficient for BMD measurement since no need of an external phantom for calibration. Combined with LLM on osteoporosis, our PL-QCT provides efficient and accurate BMD measurement for our chatbot users. Material and Methods: We build an osteoporosis corpus containing about 30,000 Chinese literatures whose titles are related to osteoporosis. The whole process is done automatically, including crawling literatures in .pdf format, localizing text/figure/table region by layout segmentation algorithm and recognizing text by OCR algorithm. We train our model by continuous pre-training with Low-rank Adaptation (LoRA, rank=10) technology to adapt LLaMA-7B model to osteoporosis domain, whose basic principle is to mask the next word in the text and make the model predict that word. The loss function is defined as cross-entropy between the predicted and ground-truth word. Experiment is implemented on single NVIDIA A800 GPU for 15 days. Our automatic PL-QCT BMD measurement adopt AI-associated region-of-interest (ROI) generation algorithm for localizing vertebrae-parallel cylinder in cancellous bone. Due to no phantom for BMD calibration, we calculate ROI BMD by CT-BMD of personal muscle and fat. Results & Discussion: Clinical orthopaedic experts are invited to design 5 osteoporosis questions in Chinese, evaluating performance of vanilla LLaMA and our fine-tuned model. Our model outperforms LLaMA on over 80% of these questions, understanding ‘Expert Consensus on Osteoporosis’, ‘QCT for osteoporosis diagnosis’ and ‘Effect of age on osteoporosis’. Detailed results are shown in appendix. Future work may be done by training a larger LLM on the whole orthopaedics with more high-quality domain data, or a multi-modal GPT combining and understanding X-ray and medical text for orthopaedic computer-aided-diagnosis. However, GPT model gives unexpected outputs sometimes, such as repetitive text or seemingly normal but wrong answer (called ‘hallucination’). Even though GPT give correct answers, it cannot be considered as valid clinical diagnoses instead of clinical doctors. The PL-QCT BMD system provided by Bone’s QCT(Bone’s Technology(Shenzhen) Limited) achieves 0.1448mg/cm2(spine) and 0.0002 mg/cm2(hip) mean absolute error(MAE) and linear correlation coefficient R2=0.9970(spine) and R2=0.9991(hip)(compared to QCT-Pro(Mindways)) on 155 patients in three-center clinical trial in Guangzhou, China. Conclusion: This study builds a Chinese osteoporosis corpus and develops a fine-tuned and domain-adapted LLM as well as a PL-QCT BMD measurement system. Our fine-tuned GPT model shows better capability than LLaMA model on most testing questions on osteoporosis. Combined with our PL-QCT BMD system, we are looking forward to providing science popularization and early morning screening for potential osteoporotic patients.

Keywords: GPT, phantom-less QCT, large language model, osteoporosis

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