Science Research Program Research Articles

Дираковский синтез квантовой механики и специальной теории относительности: интертеоретический контекст

One of the key episodes of the history of modern physics – Paul Dirac’s 1928 contrivance of the relativistic theory of the electron – in the context of lucid epistemological model of mature theory change is elicited. The peculiar character of Dirac’s synthesis of special relativity and quantum mechanics is revealed by comparison with Einstein’s methodology of the Gen- eral Relativity creation. The structure of Dirac’s scientific research programme and first and foremost the three pivotal principles that put up its heuristics is scrutinized with special emphasis on the “mathematical beauty”. It is contended that it was the general relativity genesis elicited in Eddington’s masterpiece “The Mathematical Theory of Relativity” that constituted Dirac’s synthetic paradigm with its emphasis on mathematical speculation, continual modification and generalization of the basic axioms and with the Clifford algebra and Weyl’s bispinors playing the dual lead of Riemannian geometry and Einstein’s metrical tensor. It is punctuated that in spite of the relentless Dirac’s remarks underestimating the role of philosophy one can trace its indirect influence through Arthur Eddington’s whimsical philosophy of science grounded on Hermann Weyl’s quasi-Husserlian epistemology. The basic stages of realization of Dirac’s research programme are elicited with a special emphasis on the crossbred (dual) objects’ construction.

How Could Boltzmann Have Inspired the Early Wittgenstein?

In 1931, when writing about those who had inspired him, Wittgenstein singled out Boltzmann; nobody seems to know why, however. Most commentators have ignored this remark, while a few have tried to guess what the inspiration might have been by searching the popular and philosophical writings of Boltzmann. In this article, I hypothesize that Wittgenstein may have been inspired by Boltzmann’s scientific research program from his famous 1877 article. This hypothesis is not confirmed—or rejected—by any surviving documents. But to some extent (considering the role of Fleck’s creative misunderstandings) there are two explanations for the origins of the two strange theorems underlying the Tractatus’s ontology: (1) each situation can be the case or not the case while everything else remains the same; (2) the facts are not subject to the laws of nature. My hypothesis also makes it understandable why Wittgenstein developed his logical theory of probability. So, let’s keep it in mind.

Миф науки как источник прогресса

In the philosophy of science and technology, scientific progress has been usually considered in a logical-methodological way, namely, from the point of view of the capacity to solve problems, the theoretical and empirical success of a certain theory or scientific research program. These are the concepts of K. Popper, I. Lakatos, and L. Laudan. They are opposed by historical and sociological ap­proaches to the development of science by T. Kuhn, S. Toulmin, and P. Feyer­abend. The article proposes a variant of the second approach – socio-epistemo­logical and, in particular, value interpretation of scientific progress shifting the focus of the discourse on scientific progress to the world-view and ideological circumstances of the development of science not only as knowledge, but as a form of culture and social institution. There is a polemic with the thesis by A.L. Nikiforov about the dominant pragmatic need for science and the primacy of its applied results, as ifthe modern achievement of which science has al­legedly fulfilled as well as the purpose prescribed to it by F. Bacon, and even ex­hausted its progressive potential. Criticism of the position by A.L. Nikiforov is based on an alternative view on science, which follows from a different interpre­tation of the New Times scientific revolution and the purpose of science in gen­eral. Scientific progress is seen in the creation by science of a new image of the world, new ways of communication, new moral guidelines, the design of new ways of social order. Such a science does not fit into the narrow, logical-method­ological criteria of scientific rationality. However, it is precisely this culture-forming, socio-cultural function of science that allows us to talk about science as an enterprise that contributes to social progress and, if progressive, it is precisely because of this circumstance.

Factors influencing the rating of low-rise wooden houses as “green” buildings

The article presents a program of scientific and practical research on the assessment of “green” technologies in wooden low-rise housing construction in the field of energy efficiency and resource conservation. The objects of research are two identical experimental buildings built in 2020 in Murmansk and Petrozavodsk using different technologies of wooden housing construction and various thermal insulation materials. Attention is focused on assessing the factors affecting the energy efficiency class and the internal microclimate of a wooden building, taking into account the changing environmental conditions and operating modes of buildings in cold climates. The stages of the study were determined, the tasks for each type of experiment and the expected results were formulated. Methods fixed in the regulatory documents of the Russian Federation are considered as the main ones. A method for monitoring the parameters of the internal microclimate, environment and temperature and humidity in the layers of the enclosing structures of model objects is proposed and implemented. The implementation of the research program will allow assessing the influence of the factors under study on the energy efficiency class of a wooden building and developing recommendations for the design, construction and operation of low-rise wooden buildings in a cold climate, taking into account the criteria of “green” construction.

<b>T</b>he <b>A</b>rtificial i <b>NT</b>elligence-Assisted sm <b>A</b>ll bow <b>L</b> caps <b>U</b>le endo <b>S</b>copy ( <b>TANTALUS</b>), Multicentre Study – AI in Capsule Well within Our Reach

Objective: Reading small bowel capsule endoscopy (SBCE) is a tedious task. We aim to evaluate the performance of a Convolutional Neural Network (CNN) algorithm (SmartScan)-assisted reading in the setting of real-life clinical care. Design: A total of 5,825 SBCE examinations (comprising 295,314,067 images) performed in 51 Chinese medical centres were collected. 2,927 SBCE examinations from 29 medical centres were used to train SmartScan to detect 17 CEST findings. SmartScan was later validated in 2,898 SBCE examinations collected from 22 medical centres. All 2,898 SBCE examinations were read with both Conventional Reading (CR) and SmartScan-Assisted Reading (SSAR) by eight specialist gastroenterologists. If finding(s)/results by both types of reading in a patient were concordant, the result was taken as the Combined Agreed Comparator (CAC) for that case. In discordant cases, the consensus result by three expert readers was taken as the CAC for the case. Results: SSAR achieved an overall higher detection rate (79.30%) for CEST findings compared to CR (70.67%); from a total of 6,084 SB findings, SSAR detected 95.89%, significantly higher compared to CR (76.10%). Furthermore, SSAR achieved overall higher sensitivity (98.80%), for the 17 CEST subtypes of findings, 10.75% higher than CR (88.05%). With SSAR, the number of images requiring review per SB CE video was reduced to 779.17 ±337.18, with reading time was shortened to 5.37 ±1.51min. C Conclusion: A commercially available CNN algorithm (SmartScan) can increase the detection rate of SB findings while reducing SB CE reading times. Trial Registration: This clinical trial study was registered in the Chinese Clinical Trial Registry (reg no. CHiCTR2100042455). Funding: This work was supported by the National Key Research and Development Program (NO. 2016YFC0107000) and Special project of National Health Committee (NO. 201502013). Declaration of Interest: The authors declare no competing interests. Ethical Approval: The whole study was performed in accordance with guidelines approved by Medical Ethics Committee of Second Affiliated Hospital of the Third Medical University (NO.2020-yan-134-01).

Участие АО «Российские космические системы» в реализации отечественных космических программ исследования дальнего космоса

The article describes the role of Joint Stock Company “Russian Space Systems” in realization of national space programs, in study of space and planets of the solar system by automatic spacecraft and interplanetary complexes. The history of the creation of the national ground control system for long-range spacecraft in realization of the program of scientific research in deep space is briefly described. The main scientific results of these studies are given.

The Nasal Symbiont <i>Staphylococcus Epidermidis</i> Restricts the Transcription of SARS-CoV-2 Entry Factors in Human Nasal Epithelium

Emerging evidence indicates that severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) targets the human nasal epithelium via the principal entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), which are highly expressed in the nasal epithelium. However, little is known about suppressive biologics against SARS-CoV-2 entry factors. Here, we show that the nasal commensal Staphylococcus epidermidis altered the host transcriptional response against SARS-CoV-2 by reducing ACE2 and TMPRSS2 gene expression in concert with an increase in serine protease inhibitors. Our data reveal that ACE2 was more abundantly expressed in nasal epithelial (NHNE) cells than bronchial epithelial cells, and inoculation with S. epidermidis reduced ACE2 transcription in NHNE cells. TMPRSS2 mRNA was significantly decreased in NHNE cells and S. epidermidis colony number in human nasal mucus was inversely correlated with ACE2 and TMPRSS2 gene expression in nasal mucosa. In addition, levels of the serine protease inhibitors SERPINE1 and SERPINE2 were significantly increased by S. epidermidis , and this accompanied reduction of TMPRSS2 transcription in nasal epithelial cells. These results characterize the S. epidermidis -regulated host transcriptional response restricting SARS-CoV-2 entry to the nasal epithelium via downregulation of cellular receptors and principal host protease of SARS-CoV-2 coupled with SERPINE1 and SERPINE2 induction.Funding: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2016R1D1A1B01014116 and 2019M3C9A6091945 to HJK). This research was also supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare of the Republic of Korea (HI20C0546 to HJK).Declaration of Interest: The authors declare that the research was conducted in the absence of anycommercial or financial relationships that could be construed as potential conflicts ofinterest.Ethical Approval: Participation was voluntary, with written informed consent obtained from all subjects.This study was approved by the Institutional Review Board (IRB) of the SeoulNational University College of Medicine (no. 1709-049-883).

Artificial Intelligence for Intraoperative Guidance: Using an Object Detection Model in Conjunction With Data Augmentation to Detect Parathyroid Glands During Thyroidectomy

Background: Postoperative hypoparathyroidism is a major complication of thyroidectomy that occurs when the parathyroid glands are inadvertently damaged during surgery. Although intraoperative images are rarely used to train AI because of its complex nature, our group recognized the potential of training AI to intraoperatively detect parathyroid glands using various augmentation methods. The aim of the present study was to train an effective artificial intelligence (AI) model to detect parathyroid glands during thyroidectomy and evaluate its accuracy. Methods: Video clips of the parathyroid gland were collected during thyroid lobectomy procedures. Confirmed parathyroid images were used to form three types of datasets according to augmentation status: baseline, geometric transformation, and generative adversarial network-based image inpainting. The average precision was set as the primary outcome regarding the performance of parathyroid detection performance. Findings: The performance of the AI model in detecting parathyroid glands based on baseline data was 77%. This performance was enhanced by applying both geometric transformation and image inpainting augmentation methods. Between the two, the geometric transformation data augmentation dataset demonstrated superior results compared to that of the image inpainting model. The average precision was 79% in the transformation dataset vs. 78.6% in the inpainting dataset. However, when the model was subjected to images of a completely different thyroidectomy approach, image inpainting methods proved to be more effective compared to both geometric transformation and baseline (46% vs. 37% vs. 33%). Conclusions: Our study demonstrated the utility of our AI model, which, when aided with appropriate augmentation methods, is potentially an effective and generalizable tool for intraoperative identification of parathyroid glands during thyroidectomy. Furthermore, this technology has significant potential to be easily extended to identifying important structures during other surgical procedures in general. Funding Information: Basic Science Research Program of the National Research Foundation of Korea [NRF-2019R1C1C1008384]. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: Institutional review board approval was acquired (GDIRB2019-359), and research was conducted in accordance with the Declaration of Helsinki in its latest form.

Nasal Symbiont <i>Staphylococcus Epidermidis</i> Promotes the Cellular Environment Lacking Airway Proteases to Restrict the Cellular Entry of Influenza a Virus in the Nasal Epithelium

Background: Our recent study presented that human nasal commensal Staphylococcus Epidermidis could potentiate antiviral immunity in the nasal mucosa through interferon-related innate responses. Here, we found that human nasal commensal S. epidermidis promoted protease–protease inhibitor balance in favor of the host and prevented influenza A virus (IAV) replication in the nasal mucosa and lungs. Methods: We examined the contribution of intranasal administration of human nasal S. epidermidis in controlling IAV infection using murine model and culture nasal epithelial cells. IAV mRNA, viral titer, nucleoprotein levels, and histopathologic findings were evaluated. The induction of S. epidermidis-regulated serine protease inhibitors and correlation of serine proteases were also determined. Findings: A relatively higher induction of Serpine1 exhibited in S. epidermidis-inoculated nasal epithelium and S. epidermidis-induced Serpine1 significantly decreased the expression of serine proteases. Furthermore, the transcription of urokinase plasminogen activator (uPA) and Serpine1 was biologically relevant in S. epidermidis-inoculated nasal epithelium, and the induction of uPA might be related with the sequential increase of Serpine1 in human nasal epithelium. Interpretation: Our findings reveal that human nasal commensal S. epidermidismanipulates the cellular environment lacking serine proteases in the nasal epithelium through Serpine1 induction and disturbs IAV spread to the lungs at the level of the nasal mucosa. Funding: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education 2016R1D1A1B01014116, 2019M3C9A6091945, 2017M3A9F3041233) and was also supported by a grant from the Korean Health Technology R&D Project through the Korean Health Industry Development Institute, funded by the Ministry of Health & Welfare of the Republic of Korea (HI20C0546). Declaration of Interest: None to declare. Ethical Approval: The institutional review board (IRB) of the Seoul National University College of Medicine approved the protocol for this study (IRB #C2012248 [943]). In vivo experiments with C57BL/6J mice were carried out according to guidelines approved by the IRB of the Seoul National University College of Medicine (IACUC #2016-0093).

Effect of the Age of the Surgeon on Postoperative Complications and Mortality: A Systematic Review and Meta-Analysis of Cohort Studies

Objective: The surgical workforce, like the rest of the population, is ageing. This has raised concerns about the association between the age of the surgeon and their surgical outcomes; however, this association has not been widely studied. We performed a systematic review and meta-analysis of cohort studies published as full articles on postoperative mortality and major adverse outcome (MAO) according to the surgeons' age. Design: Ten retrospective cohort studies on 29 various surgeries were considered.Setting: The search was performed on 2 February 2021 using the Embase and Medline databases.Participants: This meta-analysis involved 1,666,108 patients who were drawn from 10 cohort studies and were subjected to 29 types of surgeries. Main outcome measures: This meta-analysis categorised surgeons into young, middle-aged, and old-aged groups and evaluated the influence of the surgeons' age on the clinical outcomes, like postoperative mortality and MAO. Results: The risk of death in the patients undergoing surgery by young surgeons was 1.02 (1.00–1.04, P = 0.07) compared to those by middle-aged surgeon. The mortality risk in patients undergoing surgery by old-aged surgeons was 1.14 (1.02–1.28, P < 0.001) compared to those by middle-aged surgeons. The MAO risk in the patients undergoing surgery by young surgeons was 1.04 (0.92–1.18, P = 0.48) compared to those by middle-aged surgeons. The MAO risk in the patients undergoing surgery by older surgeons was 1.01 (0.88–1.16, P = 0.93) compared to those by middle-aged surgeons. Conclusion: This meta-analysis indicated that surgeries performed by oldaged surgeons had a higher risk of postoperative mortality than those by middle-aged surgeons. Thus, it necessitates the introduction of a multidisciplinary approach to evaluate the performance of senior surgeons. Funding: This work was supported by the Medical Research Center (MRC) Program [grant number: NRF-2018R1A5A2023879], the Basic Science Research Program [grant number: NRF-2020R1A2C1102433], and the Collaborative Genome Program for Fostering New Post-Genome Industry (grant number: NRF-2017M3C9A6047610) through a National Research Foundation of Korea Grant funded by the Korean government. Declaration of Interest: The authors have none to declare.

Correction to “Classification of β-Thalassemia Carriers From Red Blood Cell Indices Using Ensemble Classifier”

In the above article [1] , the funding information should read “This work was supported in part by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education under Grant NRF-2019R1A2C1006159, and in part by the Ministry of Science and ICT (MSIT), South Korea, under the Information Technology Research Center (ITRC) support program supervised by the Institute for Information Communications Technology Promotion (IITP), under Grant IITP-2020-2016-0-00313.”

Virus Blocking Textile for SARS-CoV-2 Using Human Body Triboelectric Energy Harvesting

Efficient mitigation strategies to prevent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are required before achieving population immunity through vaccines. Inspired by the negatively charged nature of SARS-CoV-2 aerosols, in the present study, we demonstrate a virus blocking textile (VBT) which repulse SARS-CoV-2 respiratory particles based on Coulomb force. Also, we demonstrate that human body triboelectric energy harvesting can be a promising powering source for continuous, highly efficient blocking of VBT. We found that contact and separation between human body and surround materials can generate a peak-to-peak current of 259.6 μA at most and it charges VBT and a 0.25-μF capacitor to 180 V in 134 seconds. Further, through acrylic chamber study which mimics respiratory contact using SARS-CoV-2 aerosols, we found that VBT repulses SARS-CoV-2 aerosols and virus copies in VBT is 13-times reduced. As a result, 99.95% of SARS-CoV-2 is blocked at the flow rate of 0.5 m/s. These findings provide the first technology that prevents spread of virus based on repulsive Coulomb force and triboelectric energy harvesting.Funding Information: This work was financially supported by the Nano Material Technology Development Program (2020M3H4A1A03084600), the Basic Science Research Program (2021R1A2C2010990) and the Bio & Medical Technology Development Program (2021M3A9I2080490) through the National Research Foundation of Korea (NRF) funded by Ministry of Science and ICT.Declaration of Interests: The authors declare no competing interests.

The Burden of Neurological Diseases in Asia: An Analysis for the Global Burden of Disease Study 2019

Background: The global burden of diseases (GBD) of neurological disorders is increasing worldwide. The purpose of this study is to determine the burden of neurological disorders between 1990 and 2019 in Asian regions. Methods: The GBD study is updated every year, and the most recent version provides the burden of diseases according to age, gender, and region from 1990 to 2019. The burden of neurological disorders was totally and separately evaluated as incidence, prevalence, death, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability. Findings: In 2019, DALYs of neurological diseases were 64.4 million in South-East Asia (95% UI 45 ∙2-94∙2) and 85∙0 million in Western pacific regions (95% UI 63∙0-118∙5). The three neurological diseases with the highest DALYs in WHO South-East Asia and WHO Western pacific regions in 2019 were stroke, migraine, Alzheimer's disease and other dementias. DALYs of stroke and Alzheimer's disease and other dementia, Parkinson’s disease, brain and central nervous system cancer, multiple sclerosis, migraine, and tension type headache increased in both regions in 2019 compared to 1990. Infectious diseases such as tetanus, meningitis, encephalitis decreased in both regions. DALYs of idiopathic epilepsy and motor neuron disease increased in the WHO South-East Asia region and decreased in the WHO Western Pacific region. Interpretation: This study demonstrated the burden of neurological diseases in Asia. To reduce the burden of neurologic disease, a strategy suited to the reality of each country will be needed, and this study can serve as the cornerstone of the strategy. Funding: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1F1A1048113 to T-JS). Declaration of Interest: None to declare.

Association of Benzodiazepines with SARS-CoV-2 Infection and Clinical Outcomes: A Nationwide Cohort Study

The evidence for the impact of benzodiazepine (BZD) use on infection or clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited. We evaluated the association of BZD use with SARS-CoV-2 infection and the clinical outcomes of coronavirus disease 2019 (COVID-19) using a nationwide COVID-19 database from South Korea. This nationwide cohort study was performed using the COVID-19 database from the Health Insurance Review and Assessment Service of Korea, and SARS-CoV-2 positivity was investigated according to BZD use. SARS-CoV-2-positive adult patients were assessed in three groups, those who needed hospitalization, those with severe symptoms requiring intensive care, and those who died. A multivariate logistic regression model was used for all the analyses. After adjusting for potential confounding factors, there was no association between BZD use and SARS-CoV-2 positivity. SARS-CoV-2-positive patients with BZD use showed an increased risk of need for hospitalization from COVID-19 compared to those without BZD use (odds ratio [OR]: 1·33, 95% confidence interval [CI]: 1·07–1·65). In addition, there was a higher risk for long-term users (OR: 2·64, 95% CI: 1·08–6·47).Chronic BZD use contributed to a higher risk of the need for hospitalization among COVID-19 patients, whereas BZD use did not increase the risk of SARS-CoV-2 test positivity, severe outcomes, or mortality.Funding: Basic Science Research Program (grant number 2017R1A2B3008214) through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning, Republic of Korea.Declaration of Interest: There are no conflicts of interest to declare.Ethical Approval: The Yonsei University Institutional Review Board approved this study (Approval number: 4-2020-1240).

The Prognostic&amp;nbsp;Significance&amp;nbsp;of&amp;nbsp;Extranodal&amp;nbsp;Extension&amp;nbsp;in&amp;nbsp;Papillary Thyroid Cancer: A Real-World Study

Background: The prognostic significance of extranodal extension in papillary thyroid cancer remains controversial. Methods: Seven hundred and thirty-eight PTC patients were enrolled in the study from January 2016 to December 2019. Patients were dichotomized with or without ENE. Univariate and multivariate logistic analyses were used to compare differences between the two groups. Kaplan-Meier (K-M) curve and propensity score matching analysis were used for recurrence-free survival comparison. Result: Thirty patients (4.07%) had associated extranodal extension. Univariate analysis demonstrated age, tumor size, extrathyroidal extension, nodal staging to be associated with ENE. Further logistic regression analysis showed age, extrathyroidal extension and nodal staging remained statistically significant. Evaluation of K-M curves demonstrated a statistically significant difference was found between two groups before and after propensity score matching. Conclusions: Age≥55years, extrathyroidal extension, and lateral cervical lymph node metastasis have been identified as independent risk factors of ENE. PTC patients with ENE have worse recurrence-free survival. Funding: This work is supported by Science Research Program of Hangzhou(20180533B39), the Project of Medical Scientific and Technology Program in Hangzhou (grant number A20200432), and the Medical and Health Research Program of Zhejiang Province (2019RC240). Declaration of Interest: The authors declare no conflict of interests. Ethical Approval: The present study was approved by the Ethics Committee of our institution (Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine).

The First Meta-Analysis of the M129V Single Nucleotide Polymorphism (SNP) of the Prion Protein Gene ( &lt;i&gt;PRNP&lt;/i&gt; ) with sporadic Creutzfeldt-Jako disease &lt;i&gt;PRNP&lt;/i&gt;) with Sporadic Creutzfeldt-Jakob Disease

Background: Prion diseases are fatal, chronic and incurable neurodegenerative diseases caused by pathogenic forms of prion protein (PrPSc) derived from the endogenous forms of prion protein (PrPC). Several case-control and genome-wide association studies have reported that the M129V polymorphism of the human prion protein gene (PRNP) is significantly associated with susceptibility to sporadic Creutzfeldt-Jakob disease (CJD). However, since some case-control studies have not shown these associations, the results remain controversial. Methods: We collected data that contain the genotype and allele frequencies of the M129V single nucleotide polymorphism (SNP) of the PRNP gene and information on ethnic backgrounds from sporadic CJD patients. We performed a meta-analysis by collecting data from eligible studies to evaluate the association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD. Interpretation: We found a very strong association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD using meta-analysis for the first time. We validated the eligibility of existing reports and found severe heterogeneity in some previous studies. We also found the strongest association with the risk of sporadic CJD in the heterozygote comparison model (MM vs. MV, odds ratio = 5.1354, 95% confidence interval: 3.6622; 7.2012, P=0). To the best of our knowledge, this was the first meta-analysis assessment of the relationship between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD. Funding: This research was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education (2017R1A6A1A03015876). This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MSIT) (2021R1A2C1013213). Declaration of Interests: The authors declared no conflicts of interest.

The Impact of Metabolic Activity of Vertebra and Amygdala on Stroke Recurrence

Background: We investigated whether the metabolic activities of the vertebrae and amygdala are related to future vascular events after cerebral infarction. Methods: Between August 1, 2015 and February 28, 2020 patients admitted with acute cerebral infarction and carotid atherosclerosis were included. They underwent whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG PET). We compared the FDG uptake in the internal carotid artery, vertebrae, spleen and amygdala between patients with and without stroke recurrence. Cox proportional hazards model was used to identify factors related to stroke recurrence. Findings: A total of 110 stroke patients were included (mean age=73 years, 43 female). During the median follow-up period of 18 months, 15 patients experienced stroke recurrence. Patients with recurrent stroke were more likely to have diabetes mellitus, lower estimated glomerular filtration rate, and a higher degree of internal carotid artery stenosis than in those without. Patients with recurred stroke also had a significantly higher glucose uptake in the vertebrae (1·14±0·28 versus 1·36±0·40, p=0·009 by t-test) and amygdala (1·01±0·11 versus 1·09±0·14, p=0·017) than those without. The vertebral FDG uptake correlated with bone mineral density and C-peptide level. The FDG uptake in the amygdala was correlated with the monocyte lymphocyte ratio, but not with the vertebral FDG uptake. The Cox proportional hazard model showed that a higher FDG uptake in the vertebrae was independently associated with stroke recurrence (hazard ratio=4·94, 95% confidence interval=1·29 – 18·9), and a higher FDG uptake in the amygdala with overall vascular events (hazard ratio=3·11, 95% confidence interval=1·11 – 8·70). Interpretation: The increased metabolic activities of the vertebrae and amygdala are related to stroke recurrence and overall vascular event, possibly by elevated insulin resistance and innate immune response. Funding Statement: The study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF- 2019R1F1A1059455). Declaration of Interests: None. Ethics Approval Statement: This study was reviewed and approved by the institutional review board of Chung-Ang University Hospital (C2015061) and was registered in the Clinical Research Information Service (Registration no.: 170602-001) as a part of the International clinical Trials Registry Platform of the World Health Organization supported by Korea centers for Disease Control and Prevention.

Analysis of research programs: a sociological perspective

The origins and content of the methodology of scientific research programs of I. Lakatos are considered taking into account the problems and tasks of the history of sociology. The reception of the methodology of research programs in sociology can be explained by the relevance of the analytical model of the structure and dynamics of the research program in the analysis of sociological knowledge. Within the framework of sociological knowledge, metatheoretical, theoretical and empirical structural levels are analytically distinguished. Certain structural analogies are observed: between the “hard core” and “negative heuristics” of the research program, on the one hand, and metatheory, on the other; between the “protective belt” and the “positive heuristic” of the research program, on the one hand, and theory, on the other; between the empirical content of the research program, on the one hand, and the empirical basis of sociology, on the other. One can observe a number of analogies in the dynamics of functional connections between the structural components of the research program, on the one hand, and the dynamics of functional connections between metatheorizing, theorizing, and empirical analysis in sociology, on the other.

Ethical, Legal, and Social Issues (ELSI) in Clinical Genetics Research.

ELSI (Ethical, Legal, and Social Issues) is a widely used acronym in the bioethics literature that encompasses a broad range of research examining the various impacts of science and technology on society. In Canada, GE3LS (Genetics, Ethical, Economic, Environmental, Legal, Social issues) is the term used to describe ELSI studies in the context of genetics and genomics research. It is intentionally more expansive in that GE3LS explicitly brings economic and environmental issues under its purview. ELSI/GE3LS research is increasingly relevant in recent years as there has been a greater emphasis on "translational research" that moves genomic discoveries from the bench to the clinic. The purpose of this chapter is to outline a range of ELSI-related work that might be conducted as part of a large scale genetics or genomics research project, and to provide some practical insights on how a scientific research team might incorporate a strong and effective ELSI program within its broader research mandate. We begin by describing the historical context of ELSI research and the development of GE3LS research in the Canadian context. We then illustrate how some ELSI research might unfold by outlining a variety of GE3LS research questions or content domains and the methodologies that might be employed in studying them. We conclude with some practical suggestions about how to build an effective ELSI/GE3LS team and focus within a broader scientific research program.

Methodology of model development in the applied sciences

The formulation and validation of mathematical models in the applied sciences are largely consistent with the methodology of scientific research programmes (MSRP), however an essential modification is necessary: The domain of calibration has to be defined. The ranking and systematic improvement of mathematical models based on objective criteria are described and illustrated by an example. The methodology outlined in this paper provides a framework for the evolutionary development of a large class of mathematical models.