The Coronavirus Disease 2019 (COVID-19) has been placing severe strain on global healthcare systems and medical education programs, leading to growing demands for medical students to assume the role of preliminary healthcare providers.To assess the perception and attitudes of medical students about clinical clerkship training during the COVID-19 pandemic.A cross-sectional survey with web-based 3-fields/14-items questionnaire was conducted, from April 7 to 14, 2020, to evaluate their self-assessed perception and attitudes on clerkship training of hospital practice under the COVID-19 outbreak and spread among 161  medical students at Dankook University College of Medicine, Cheonan, Republic of Korea.P = 0.03), primarily because a clinical clerkship could not be replaced by an online class during the COVID-19 pandemic. In addition, their responses indicated, in order of significance, fear of not completing the clerkship course on time, willingness to participate as a preliminary healthcare provider in pandemic, the potential waste of tuition, and belief that a hospital is rather safe. The change in the academic calendar had not a positive impact on the lifestyles of many students.Of the 151 medical students who completed the survey, 81 students (53.7%) considered themselves familiar with COVID-19. Although the students were concerned about the spread of the virus during clinical clerkship training, 118 (78.1%) students preferred the clerkship training in a hospital practice. The students in the clinical clerkship program preferred this over those in the pre-clerkship program (85.7% vs. 70.2%, In circumstances such as the COVID-19 pandemic, educational strategies to clinical clerkship training for medical students should be developed to provide them with the opportunity to be actively involved in hospital practice under strict safety guidance focused on preventing virus infection and transmission. The Coronavirus Disease 2019 (COVID-19) is currently placing huge pressure on the medical community around the world. Since the outbreak of this novel infectious disease by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in Wuhan, China, in late 2019, the status of the disease has changed from ‘epidemic’ to ‘pandemic,’ putting countries on high alert to this menace to their national public health . Many coRecently, the availability of hospital-based roles for medical students during the COVID-19 pandemic has been recognized as an important issue –9. ReschWe enrolled a total of 161 medical students at Dankook University College of Medicine in this web-based, cross-sectional survey. The students represented four levels of training: 41 were in the first year of medical college, 37 in the second year, 44 in the third year, and 39 students were in the fourth year. Due to the outbreak of COVID-19, the first day of the new semester was postponed for a few weeks, so it began later than was originally scheduled on the academic calendar. The Dankook University authorities deemed it necessary to replace all face-to-face classes with online classes for students in the pre-clerkship stage (first year and second year); clinical clerkship training proceeded as usual for students in the clerkship stage (third year and fourth year). We conducted this survey over 2 weeks between April 7 and 21, 2020, during the 2 weeks following the start of the delayed semester. Due to the restrictions imposed by the COVID-19 pandemic, face-to-face surveys were not possible. Hence, all students were contacted by phone from the Administrative team of Dankook University College of Medicine and asked to participate using an online Google Docs survey. The link for the survey was informed by a text message. The principles of voluntary participation, no harm to the participants, anonymity and confidential assurances were announced at the beginning of the questionnaire.We developed the questionnaires to evaluate medical students’ thoughts on clinical clerkship training during the COVID-19 pandemic from the viewpoints of both preliminary healthcare providers and university students. We also prepared both Korean- and English-language versions of the questionnaire to enable the inclusion of international students in the survey, and conducted a pilot testing among six students: three pre-clerkship and three clinical clerkship students, with each group including one international student to reduce the likelihood of questions that could lead to misunderstandings or biased answers from participants. The study questionnaires were composed of the following three fields: 1) students’ knowledge and perception of COVID-19 (three questions); 2) students’ attitudes toward clinical clerkship training during the COVID-19 pandemic (six questions); and 3) the impact of the change in the academic calendar due to the COVID-19 pandemic on students’ routines and lifestyles (four questions). Enrolled students completely answered the questions addressing their own knowledge of COVID-19 based on self-assessment, and the questions about risk perception on the likelihood of contracting the novel coronavirus during the clinical clerkship training. The questions addressing students’ attitudes toward clinical clerkship training during the COVID-19 pandemic measured their willingness to participate and concerns regarding qualitative changes in the clinical clerkship. Furthermore, we evaluated their answers to questions about the impact of the changes to the academic calendar on students’ lifestyles by considering both the magnitude and significance of these lifestyle changes and the effectiveness of online classes at home. Most of the questionnaires consisted of closed-ended questions to facilitate categorization of the participants’ answers. Dichotomous questions were scored using a two-point scale, and questions with more than two options were scored based on a five-point Likert scale. Open-ended questions were also used to invite a variety of opinions from participants. The present study was approved by the Institutional Review Board of Dankook University Hospital (DKUH 2020–04-054-HE001).P < 0.05.We displayed all data in raw numbers with percentages and estimated the mean and standard deviation values. We analyzed, between two groups, continuous variables by the unpaired student-t-test and categorical variables by the χ2 test or Fisher’s exact test. All analyses were performed using SPSS version 25 software for Windows . Statistical signiﬁcance was determined at P = 0.001).Among the 161 medical students, 151 (93.8%) completed the survey. The baseline characteristics of participants are summarized in P = 0.086; transmission possible from students to patients, 51.3% vs. 50.6%, P = 0.129)  believed that their knowledge of COVID-19 was ‘above average’ or ‘far above average’; there was little difference between the pre-clerkship and clinical clerkship groups (48.7% vs. 58.4%). During the clerkship training, students’ perception of the SARS-CoV-2 transmissibility was higher in the pre-clerkship than in the clerkship group, but not significantly so  .P = 0.03). Of particular note, the willingness to participate in the clinical clerkship course was stronger in students in the third year than those in the fourth year (P = 0.441). In contrast, where students in the pre-clerkship and clinical clerkship groups were reluctant to participate in the clinical clerkship, the reasons were as follows: a need to follow national policies such as social distancing ; a fear of exposure to SARS-CoV-2 ; concerns about the deterioration of the clinical clerkship due to the spread of COVID-19 ; and a trust in online classes as a viable alternative to the clinical clerkship . These differences were statistically significant (P = 0.041)  . ApproxiP = 0.002). Lifestyle factors affected by the change of the academic calendar included sleep habits (58.9%), physical activity (54.3%), increased stress on academic achievement (43.0%), dietary patterns (42.4%), and alcohol consumption (15.2%). The majority of students believed that in cases where the clinical clerkship training was changed to an online class at home, participation in or understanding of the class would be significantly reduced (More than two thirds (69.5%) of the 151 medical students surveyed believed that the postponed academic calendar had a significant impact on their way of life. This belief was stronger, but not significantly so, for students in the pre-clerkship than those in the clinical clerkship course (75.7% vs. 63.6%). Although students generally believed the postponed academic calendar had a negative impact on their lifestyle, the students in the pre-clerkship course felt more positively about the situation  caused by the SARS-associated coronavirus in 2003 and of Middle East Respiratory Syndrome (MERS) caused by MERS coronavirus in 2015, measures of such changes to the academic schedule or partial school closures were implemented, but these were temporary and localized ,15. The In this survey, the majority of medical students showed a positive attitude toward hospital practices at this time, despite concerns that clerkship training during the COVID-19 pandemic could spread the virus. This demonstrates how important it is for students to complete the educational curriculum in a timely manner, as clinical clerkship training is irreplaceable. Additionally, it was possible to reaffirm their identities as doctors through their intention to take part in the COVID-19 crisis as a preliminary healthcare provider, not just as a student. It is particularly interesting to note that third-year students were most likely to express an interest in participating in clinical clerkship training, reaching 90%. In the Korean medical education curriculum, the third year is an introductory period for hospital practice through the clinical clerkship course. It is a difficult time for students in training due to the high intensity of coursework in major subjects, including internal medicine, general surgery, pediatrics, psychiatry, and obstetrics . TherefoDuring the COVID-19 pandemic, concerns about SARS-CoV-2 transmission from patients to students on clerkship and the reduced quality of clinical clerkship training appeared to be greater in the pre-clerkship group than in the clinical clerkship group. These results are likely due to the fact that students on the pre-clerkship course have had no opportunity to experience various clinical strategies for infection prevention and control within the hospital. However, the expectation of experiencing various clinical practices through the clinical clerkship during the COVID-19 pandemic was lower in the clinical clerkship group compared to pre-clerkship group. Students seemed to feel that restrictions on access to patients and on the use of hospital facilities or equipment resulting from changes in the hospital system designed to prevent the spread of SARS-CoV-2 were not suitable for proper education of students. Therefore, it is necessary to develop revised clinical clerkship programs that allow students to be involved in various medical scenarios that can still be experienced during the COVID-19 pandemic. In addition, these policies should encourage active participation in clinical clerkship training under the strict control of strengthened safety systems.In this study, a majority of medical students responded that their lifestyles were negatively affected by the postponement of the academic calendar due to COVID-19. With regard to the significance of that impact, students’ routine lifestyle was influenced more positively in the pre-clerkship group than the clinical clerkship group. The results demonstrate that although all face-to-face classes were replaced with online classes at home for the pre-clerkship group, the changes to the academic schedule did not have a great influence on their day-to-day routine. Conversely, even if clerkship training proceeded as usual, there would be many restrictions on social activities outside of training due to COVID-19. If the current academic schedule were to be replaced with online classes, students generally felt that their ability to participate and understand the classes would be poor. However, previous studies have shown that online classes were as useful, effective, and even as enjoyable as traditional didactics . TherefoThis study has several limitations. First, as a survey study, it depended on participants’ own subjective, rather than objective, views through self-assessment and self-reporting. However, on the other hand, it also demonstrated participants’ willingness and ability to be involved during these difficult circumstances. Second, this survey was conducted following the university’s decision regarding the clinical clerkship training of medical students; thus, there may have been a timing bias as students expressed their response to the hospital practice. However, this may also provide an opportunity to record their feelings while doing their own hospital practice. In addition, given that medical students taking this survey were selected from one university and the number of participants was relatively small, the generalizability of these findings to other medical students in Korea is limited.In conclusion, in the era of the COVID-19 pandemic, most medical students have a feeling of confidence in their understanding of COVID-19 and are concerned about its transmission to both themselves and patients during clinical clerkship training in hospitals. Nevertheless, they feel that clinical clerkship is necessary due to the difficulty of replacing hospital clerkships with online lectures, the need for timely achievement of academic goals with minimal disruption, and the desire for participation as required in clinical fields as a preliminary healthcare provider. Educational strategies to clinical clerkship training for medical students should be developed that provide the opportunity for active involvement in practical hospital training under strict safety guidance to prevent virus transmission.Click here for additional data file.


Encryption is an important step for secure data transmission, and a true random number generator (TRNG) is a key building block in many encryption algorithms. Static random-access memory (SRAM) chips can be easily available sources of true random numbers, benefiting from noisy SRAM cells whose start-up values flip between different power-on cycles. Embarking from this phenomenon, a novel performance  improvement method of SRAM-based TRNG is proposed, and its implementation can be divided into two phases: irradiation exposure and hardware postprocessing. As the randomness of original SRAM power-on values is fairly low, ionization irradiation is utilized to enhance its randomness, and the min-entropy can increase from about 0.03 to above 0.7 in the total ionizing irradiation (TID) experiments. Additionally, while the data remanence effect hampers obtaining random bitstreams with high speed, the ionization irradiation can also weaken this impact and improve the throughput of TRNG. In the hardware postprocessing stage, Secure Hash Algorithm 256 (SHA-256) is implemented on a Field Programmable Gate Array (FPGA) with clock frequency of 200 MHz. It can generate National Institute of Standards and Technology (NIST) SP 800-22 compatible true random bitstreams with throughput of 178 Mbps utilizing SRAM chip with 1 Mbit memory capacity. Furthermore, according to different application scenarios, the throughput can be widely scalable by adjusting clock frequency and SRAM memory capacity, which makes the novel TRNG design applicable for various Internet of Things (IOT) devices. To keep the communication between Internet of Things (IOT) devices secure, the data often require encryption before being transmitted , and truThere also exists one common drawback of these TRNG designs in that they cannot reuse standard integrated circuit components and are usually used as single-purpose circuits, which increases the cost of production and decreases usage flexibility . EspeciaThe source of randomness of SRAM-based TRNGs is the noisy power-on values of SRAM cells . One SRAn represents the length (number of bits) of the start-up sequence. Unless otherwise specified, min-entropy hereinafter meansAssuming that every bit in the start-up sequence is independent, the average min-entropy of per bit can be defined as follows :(3)HminbLow min-entropy indicates that start-up values possess good repeatability and are suitable for extracting chip-specific fingerprints . On the Thorough simulations and measurements of SRAM cells reveal that the mismatch of threshold voltage between P1 and P2  cells ,25. The k) cells .As far as we know, studies on utilizing SRAM power-on values to construct TRNGs have newly risen in the last several years. Holcomb and Burleson et al.  first prAysu and Gulcan et al.  xored thIonization irradiation increases the min-entropy over 20 times, which is a remarkable randomness improvement upon the existing works. In other words, about only 5% of the SRAM cells are needed to generate the true random bitstreams of the same length as the ones before irradiation, which significantly promotes the utilization rate of memory cells and decreases the area and power consumption per random bit generation. Furthermore, putting SRAM chips that are powered off into the irradiation lab is the main operation in our randomness improvement scheme, and this has a much lower cost and is simpler to implement compared to designing a dedicated SRAM cell to enhance inherent noise sensitivity (as in ).Throughput is another obstacle for utilizing SRAM as a TRNG because the power-down time between two power-on cycles must be long enough to avoid the degradation of the randomness of power-on values by the remaining charge. Many researchers even give up optimizing throughput ,21,27,28The performance of SRAM-based TRNG is strengthened specifically by the following main contributions in this work:The rest of this paper is organized as follows: The entire TRNG design scheme is outlined in The procedure of the proposed TRNG is shown in s length ,29) by mIn order for the output string of SHA-256 to have full entropy (256 bits), the amount of entropy at the input of the hash function should be at least 256 bits ,30. ThisIn addition, throughput of the true random bitstreams is also in the scope of this work.It is obvious from Equation (6) that fast clock frequency  were randomly selected for testing. The experiment steps are shown in 2) doses, the chips were taken out to observe their power-on characteristics. To ensure that the normal read–write function of SRAM chips would not be damaged by the TID effect, 2 Mrad(SiO2) was chosen as the maximal irradiation dose.Every tested chip was powered on, and its start-up values were sampled 100 times before irradiation, for contrast with the postirradiation cases. Thereafter, the chips were powered off and suffered ionization irradiation iteratively; for each additional 500 Krad(SiO2) for all tested chips, which exceeds a 20-fold increase. Besides the improvement of randomness, the rising min-entropy can also help to decrease the block size , and 2) dose showed a great randomness improvement in behavior but still could not pass all the tests, needing postprocessing to improve the statistical properties [As depicted in operties .Actually, the raw random bits of many TRNGs become biased and cannot meet the NIST SP800-22 test standards ; therefo2), conditioned random bitstreams with throughput of 178 Mbps were generated, which were able to pass all NIST test items, as shown in 2). However, the conditioned bitstreams still could not pass all tests, as displayed in We performed SHA-256 on Xilinx XC7Z020  with clo2) could completely meet these two requirements and hence generate true random bitstreams with throughput up to 178 Mbps. However, power-on sequences without irradiation collected at such a small block size (370 bits) and short power-down period (3 ms) behave too poorly in terms of randomness due to large mismatches in SRAM cells and strong data remanence effect.It can be summarized from the above NIST test results that high throughput requires small block size  and short power-down period. The power-on sequences under 2 Mrad, the throughput is mainly constrained by block size . Besides, the minimal power-down period between two successive power-on cycles can decrease from approximately 250 ms to about 1.5 ms, which makes a great contribution to the throughput of a TRNG. In the subsequent hardware postprocessing, SRAM chip should be repeatedly powered up; during each power-on cycle, SRAM power-on values are conditioned into true random bitstreams by means of SHA-256. One implementation on FPGA can generate bitstreams with throughput of 178 Mbps, which can pass all NIST SP 800-22 tests.In our work, a novel SRAM-based TRNG is proposed; its implementation consists of two phases: irradiation exposure with zero voltage bias and hardware postprocessing. During the irradiation phase, the TID effect is utilized to make SRAM cells less mismatched and hence to obtain more random power-on values. The experiment results show that the min-entropy of SRAM power-on values can increase over 20 times as ionization dose is accumulated to 2 Mrad(SiO


Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2. It typically presents with respiratory symptoms such as fevers, cough, and shortness of breath. As the number of cases increases, however, COVID-19 is being increasingly recognized as being associated with a variety of other respiratory pathologies.We present the case of a 59-year-old man with COVID-19 pneumonia who acutely decompensated after having been on the medicine floor for two weeks. He was found to have a tension pneumothorax. This was treated with a needle decompression followed by a chest tube insertion. The patient subsequently recovered and was discharged.This case highlights the importance of considering tension pneumothorax as a possible cause of shortness of breath in patients with COVID-19 pneumonia. On March 11, 2020, coronavirus disease 2019 (COVID-19) was declared a global pandemic by the World Health Organization after it was identified in Wuhan, China in December 2019. As of September 1, 2020 there have been 169,419 deaths nationally.3In the context of a pandemic, many healthcare institutions have created protocols to efficiently address the most common presentations of this disease. Yet despite often presenting with similar symptoms, it is important to keep a wide differential when treating these patients as COVID-19 has been linked to a variety of pathologies. Reported complications secondary to COVID-19 include myocarditis, pulmonary embolism, large vessel cerebral vascular accidents, and acute respiratory distress syndrome.A 59-year-old male with no past medical history presented to the ED with cough, fevers, and shortness of breath. He was found to be hypoxic requiring 15 liters of oxygen on a non-rebreather mask to maintain an oxygen saturation above 90% on pulse oximetry. Computed tomography (CT) angiogram of the chest performed in the ED found pulmonary emboli within the segmental branches of the right upper and both lower lobe pulmonary arteries along with patchy areas of ground-glass opacities and consolidation. Polymerase chain reaction tests of nasal and pharyngeal swabs and sputum performed in the ED were positive for severe acute respiratory syndrome coronavirus 2 RNA. He was started on a therapeutic dose of enoxaparin and then admitted to the medicine floor for further treatment.His respiratory status improved and he was eventually weaned to one liter of oxygen via nasal cannula by day 10 of hospitalization. On day 11 of hospitalization the patient had a sudden desaturation to 60% on pulse oximetry. The rapid response team was called, and a portable chest radiograph (CXR) was performed, which found a large pneumothorax .Emergent needle decompression of the tension pneumothorax with an 18-gauge needle and subsequent 10 French chest tube placement were immediately performed. The patient had rapid clinical improvement after needle decompression with improvement of his oxygen saturation to 100% while on 15 liters of oxygen through a non-rebreather mask and re-expansion of his lung on CXR .On day 18 of hospitalization the patient’s hemoglobin dropped from 9.1 grams (g) per deciliter (dL) to 7.2 g/dL. Repeat CT was subsequently performed and showed bilateral loculated hemopneumothoraces. The patient was started on vancomycin and piperacillin/tazobactam due to concern for necrotizing pneumonia as the underlying cause of the new lung changes, and his anticoagulation was switched from therapeutic enoxaparin injections to a heparin infusion. He continued to clinically improve, and the chest tube was removed. He was eventually discharged from the hospital on apixaban, doxycycline hyclate, and amoxicillin/clavulanate potassium.CPC-EM CapsuleWhat do we already know about this clinical entity?Coronavirus disease 2019 (COVID-19) is known to present with respiratory symptoms such as cough, fevers, and shortness of breath.What makes this presentation of disease reportable?Pneumothorax is not a known complication of COVID-19. Here we present a patient whose pneumothorax occurred as a direct complication of COVID-19.What is the major learning point?Pneumothorax should be in the differential diagnosis of patients with COVID-19 who present with shortness of breath.How might this improve emergency medicine practice?Patients with COVID-19 and shortness of breath should have early evaluation with a chest radiograph or point-of-care ultrasound.We present a case of a healthy 59-year-old male, admitted to the hospital for COVID-19 pneumonia, who acutely decompensated secondary to a tension pneumothorax after having improved for 11 days on the medical floor. He had been improving from COVID-19 for three weeks prior to deteriorating. The patient subsequently improved with chest thoracostomy and antibiotics.Although the pneumothorax cannot definitively be considered a complication of COVID-19, our patient otherwise had no risk factors for developing a spontaneous pneumothorax. Multiple case reports from other sources have also documented spontaneous pneumothoraxes in healthy patients with COVID-19.COVID-19 often presents with hypoxia and shortness of breath with the diagnosis of pneumonia. Early mechanical ventilation has been suggested for acute hypoxemic respiratory failure in the context of COVID-19.Patients with COVID-19 should all have early radiological evaluation and repeat evaluation during any decompensation to evaluate for pneumothorax as the underlying cause of decompensation. This case highlights the importance of point-of-care ultrasound, which could have found the tension pneumothorax sooner and resulted in earlier placement of the chest tube. Making the diagnosis of a tension pneumothorax quickly is essential to early, lifesaving intervention.The emergency physician should include pneumothorax in the differential diagnosis of suspected COVID patients who present with shortness of breath. Tension pneumothorax is an easily reversible cause of shortness of breath but, if untreated, can be lethal.


Management of acute severe UC (ASUC) during the novel COVID-19 pandemic presents significant dilemmas. We aimed to provide COVID-19-specific guidance using current British Society of Gastroenterology (BSG) guidelines as a reference point.We convened a RAND appropriateness panel comprising 14 gastroenterologists and an IBD nurse consultant supplemented by surgical and COVID-19 experts. Panellists rated the appropriateness of interventions for ASUC in the context of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Median scores and disagreement index (DI) were calculated. Results were discussed at a moderated meeting prior to a second survey.Panellists recommended that patients with ASUC should be isolated throughout their hospital stay and should have a SARS-CoV-2 swab performed on admission. Patients with a positive swab should be discussed with COVID-19 specialists. As per BSG guidance, intravenous hydrocortisone was considered appropriate as initial management; only in patients with COVID-19 pneumonia was its use deemed uncertain. In patients requiring rescue therapy, infliximab with continuing steroids was recommended. Delaying colectomy because of COVID-19 was deemed inappropriate. Steroid tapering as per BSG guidance was deemed appropriate for all patients apart from those with COVID-19 pneumonia in whom a 4–6 week taper was preferred. Post-ASUC maintenance therapy was dependent on SARS-CoV-2 status but, in general, biologics were more likely to be deemed appropriate than azathioprine or tofacitinib. Panellists deemed prophylactic anticoagulation postdischarge to be appropriate in patients with a positive SARS-CoV-2 swab.We have suggested COVID-19-specific adaptations to the BSG ASUC guideline using a RAND panel. The British Society of Gastroenterology (BSG) has published evidence-based guidelines for the management of patients with acute severe UC (ASUC), but it is unknown whether these are appropriate in the setting of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.Currently there are limited data to inform clinicians in this area and there is no published guidance for the management of ASUC in the setting of the COVID-19 pandemic.The current BSG IBD guidelines provide a management pathway which remains largely appropriate during the COVID-19 pandemic.However, some treatment options were deemed uncertain or inappropriate in patients with established COVID-19 pneumonia.It is appropriate to involve COVID-19 specialists in decision-making for patients with ASUC who are SARS-CoV-2 positive.Steroid tapering as per BSG guidance was deemed appropriate for all patients apart from those with COVID-19 pneumonia in whom a 4–6 week taper was preferred.Prophylactic anticoagulation postdischarge is appropriate in patients with a positive SARS-CoV-2 swab.This paper summarises available evidence and provides expert opinion for the appropriate management of patients with ASUC during the COVID-19 pandemic.It also highlights areas of uncertainty which may help direct areas of future research.The novel coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first reported in December 2019 and its spread led to the declaration of a pandemic by the WHO on 11 March 2020. Infection varies in severity from asymptomatic carriage to an acute respiratory illness which, at its most severe, results in acute respiratory distress syndrome (ARDS) with hyperinflammation and cytokine storm syndrome.Acute severe UC (ASUC) occurs in up to 25% of patients with UC and is associated with a mortality of approximately 1%.www.prepareibd.org) is collecting data from patients with IBD who are admitted to hospital during the pandemic, as well as from those who develop confirmed or suspected SARS-CoV-2 infection. As of 8 May 2020, 19 patients with severe active UC including four with suspected or confirmed COVID-19 had been identified . The Surveillance Epidemiology of Coronavirus Under Research Exclusion-IBD registry (https://covidibd.org/) is collating data on patients with IBD with confirmed coronavirus, with 1074 patients included to date, the majority of whom have Crohn’s disease; details of how many in the cohort have ASUC are not yet available.While national and international registries continue to collate data regarding patients with IBD with COVID-19, very few cases relate to the management of ASUC. The PREPARE IBD (physician response to disease flares and patient adaptation in response to events in IBD during theCOVID-19 pandemic) study  guidelines were used as a reference point to highlight differences to current management.The RAND/UCLA  appropriateness method uses a modified Delphi panel approach and combines expert opinion with the best available evidence to determine the appropriateness of specific practices in certain clinical situations.The aim of this RAND panel was to provide clarity on the management of ASUC, as defined by Truelove and Witts criteria, in the context of the COVID-19 pandemic.We assembled a 15-person panel comprising representatives from the BSG IBD Section Committee, the BSG IBD Clinical Research Group (CRG) and other gastroenterologists, each from different IBD centres across the UK, as well as an IBD nurse consultant . A web-b10.1136/gutjnl-2020-321927.supp1Supplementary dataPanellists rated the appropriateness of management options at five different time points during the course of admission for ASUC  in the context of absence of, or varying severity of SARS-CoV-2 infection. They were asked to grade the appropriateness of specific interventions on a scale of 1–9 . The responses were summarised and anonymised before being presented at a virtual meeting in May 2020 with the aim of allowing discussion which ensured a common understanding of the questions and which focused on areas of disagreement, without trying to force consensus. Also present at the meeting were non-voting specialists who provided expert opinion with regards to IBD surgery , rheumatology (JG), intensive care (MG), respiratory medicine (FC) and infectious diseases (AU). In practice, several specialities may provide expert opinion in COVID-19 management, including intensivists, respiratory physicians and infectious disease physicians. We, therefore, used the encompassing term ‘COVID-19 specialist’ to represent this group. Finally, the Chairs of the BSG IBD Section Committee (IA) and the BSG IBD CRG (CAL) were also present. The moderators  neither expressed opinions on management nor voted, but were experts both in RAND panels and in the management of IBD. After the meeting, a second online survey comprising 91 questions, which had been slightly modified from the initial questionnaire following discussion at the meeting, was circulated for completion.Several assumptions were made for clarity. First, patients were assumed to have a confirmed diagnosis of UC with intercurrent gastrointestinal infection having been excluded. Second, if this was not an index presentation, patients were assumed to have received optimised 5-aminosalicylic acid therapy prior to admission and were also presumed to be biological-naive. In addition, where ciclosporin was suggested as an option, it was assumed that the patient was thiopurine-naive. Third, other than those areas addressed in the survey, the management of ASUC was assumed to be in line with BSG guidance.In addition, in the section about first-line medical therapy, panellists assumed patients were not steroid refractory. For the rescue therapy section, patients were assumed to have ongoing ASUC despite 3 days of intravenous corticosteroid therapy and had reached standard criteria for rescue therapy.For each scenario, median scores were calculated with a score of <3.5 being considered inappropriate, ≥3.5 but <6.5 uncertain and ≥6.5 appropriate. We used the validated RAND disagreement index (DI) to define disagreement among panellists using the equation outlined below.Of the 91 clinical scenarios, panellists rated 28 as appropriate, 19 as uncertain and 44 as inappropriate. After the second round of voting, agreement was present for all scenarios (DI<1). The key findings are summarised below and their relationship to current BSG guidance is highlighted in 10.1136/gutjnl-2020-321927.supp2Supplementary dataThe panellists agreed that all patients admitted to hospital with ASUC should have a SARS-CoV-2 swab performed on admission. If the result was negative it was deemed appropriate to repeat the swab at the point of requiring rescue therapy and/or surgery to exclude subclinical infection. It was also considered appropriate to isolate all patients throughout their hospital stay, irrespective of their COVID-19 status .It was rated appropriate to perform a flexible sigmoidoscopy within 24 hours of admission. If a patient had not had a flexible sigmoidoscopy on admission, it was considered appropriate that one should be performed prior to rescue therapy or colectomy. Repeating this test at these time points was deemed unnecessary in patients who had already had a flexible sigmoidoscopy performed.Routine CT scanning of the abdomen/pelvis on admission  was deemed inappropriate. However, the appropriateness of routine chest CT on admission was rated as uncertain. The one scenario in which a CT scan of the chest was felt to be appropriate for all patients irrespective of COVID-19 status was in the context of patients requiring colectomy.Throughout the scenarios, the panellists considered the appropriateness of discussion with COVID-19 specialists. In patients without symptoms or signs of COVID-19 and with a negative swab, this was deemed inappropriate if receiving first-line therapy but uncertain in patients requiring rescue therapy. However, it was considered appropriate in all patients with a positive swab, irrespective of the presence of symptoms or signs of COVID-19.As per BSG guidance, intravenous hydrocortisone, 100 mg, four times per day  was rated appropriate as the initial management of patients presenting with ASUC in the absence of symptoms and signs of COVID-19 pneumonia. In patients with COVID-19 pneumonia, use of hydrocortisone was deemed uncertain. Other possible treatments  were considered inappropriate. The exception was infliximab (without steroids) which was considered uncertain in patients with a positive swab for SARS-CoV-2, either with or without signs of COVID-19 pneumonia. Ambulatory outpatient management with daily intravenous methylprednisolone was rated as inappropriate in all patients with ASUC regardless of SARS-CoV-2 status, as was management by immediate colectomy unless complications mandating emergency surgery were present such as toxic megacolon, perforation or severe haemorrhage .In patients meeting criteria for escalation of management at day 3, it was considered inappropriate to avoid rescue therapy by continuing monotherapy with intravenous corticosteroids, irrespective of COVID-19 status. Instead, the panellists deemed that following standard BSG guidance by initiating infliximab and continuing steroids was appropriate, whereas treatment with infliximab in conjunction with immediate steroid withdrawal was deemed uncertain. The BSG guidelines also recommend ciclosporin as an alternative rescue therapy. However, the RAND panel voted that ciclosporin, either with or without ongoing steroids, was inappropriate in all scenarios other than in patients with a negative SARS-CoV-2 swab in whom it was rated uncertain. Finally, colectomy without rescue therapy was deemed inappropriate in all the scenarios considered by the panel. However, once colectomy became necessary, for example where rescue therapy had failed or when complications had occurred, it was deemed inappropriate to delay surgery, even in patients with COVID-19 pneumonia .The ongoing management of patients who had responded to intravenous corticosteroids and were ready for discharge on oral steroids was also considered. In patients with a negative SARS-CoV-2 swab, or with a positive swab but without signs or symptoms of pneumonia, steroid tapering over 6–8 weeks as per BSG guidance was deemed appropriate. However, in patients with COVID-19 pneumonia it was rated uncertain. Accelerated steroid withdrawal over 4–6 weeks was rated appropriate regardless of COVID-19 status. More rapid withdrawal over 4 weeks was deemed inappropriate except in patients with COVID-19 pneumonia, in whom it was rated uncertain. The use of poorly bioavailable oral steroids as an alternative to a standard steroid taper was rated as inappropriate in all scenarios .Initiation of additional therapy prior to or soon after discharge to prevent relapse was also considered. Following BSG guidance by initiating a thiopurine was rated uncertain in SARS-CoV-2 swab-negative patients and inappropriate in swab-positive patients. Use of biological therapy (anti-tumour necrosis factor (TNF), ustekinumab or vedolizumab) was deemed appropriate in swab-negative patients. In all other patients, the appropriateness of biological therapy was uncertain, except for anti-TNF therapy in patients with a positive swab but without pneumonia in whom treatment was rated as appropriate. Tofacitinib was generally rated as inappropriate except in swab-negative patients in whom it was rated uncertain.Finally, panellists were asked whether patients should be discharged with a period of ongoing prophylactic anticoagulation. This was deemed appropriate in patients who had a positive SARS-CoV-2 swab regardless of whether they had pneumonia but was rated uncertain in those who had negative swabs.The recent International Organisation For the Study of Inflammatory Bowel Disease RAND appropriateness panel addressing the use of medications to treat IBD in the COVID-19 era did not specifically address the management of patients with ASUC.SARS-CoV-2 is found in the gut and RNA is measurable in the stool significantly longer than in serum or respiratory samplesCurrently, it is not clear whether IBD-specific factors lead to worse outcomes in patients who develop COVID-19. In the Italian series of 79 patients with IBD and COVID-19, active disease was associated with the risk of COVID-19 pneumonia even after controlling for other risk factors.Of concern to most clinicians caring for patients with IBD is the possible risk of the drugs used to manage ASUC in the context of the COVID-19 pandemic. Intravenous corticosteroids remain the most widely used induction therapy in ASUC,We used an established methodology, a RAND appropriateness panel, to produce guidance in this challenging clinical area. Regarding initial management, there was agreement that all patients with ASUC should be managed as inpatients. Ambulatory care was considered inappropriate, since patients with ASUC need regular monitoring and involvement of a multidisciplinary team, this type of complex care being difficult to deliver in the outpatient setting. While there was some support for ambulatory management to avoid patients being admitted, thereby decreasing the risk of nosocomial acquisition of SARS-CoV-2, the risks of managing ASUC as an outpatient were considered to outweigh this possible benefit. Furthermore, in scenarios in which patients had confirmed SARS-CoV-2 infection, no such benefit existed. Nevertheless, in view of the acknowledged risk of contracting SARS-CoV-2 infection in hospital, it is perhaps unsurprising that the panel considered it appropriate to isolate patients with ASUC in a side room wherever possible.The panel deemed it uncertain whether a CT chest should be performed in all patients on admission. While a CT chest is more sensitive than a chest X-ray (CXR) in detecting signs of early or limited infection, the COVID-19 specialists advised that a CXR would suffice in asymptomatic patients on admission. However, the Royal College of Radiologists has advised a low-dose CT chest should be performed in patients who are having a CT abdomen as part of the investigation of an abdominal emergency.It was considered appropriate to involve a COVID-19 specialist in all scenarios in the presence of a positive SARS-CoV-2 swab, regardless of signs or symptoms of COVID-19 pneumonia. The panel was uncertain whether this was required in patients with a negative SARS-CoV-2 swab who required rescue therapy. During the meeting, concern was expressed by some panellists about the possible effects of corticosteroids and rescue therapies on SARS-CoV-2 infection and COVID-19 pneumonia driving the need to seek clarification from COVID-19 experts and highlighting the need for further research.It was considered appropriate to follow the BSG guidelines on the initial management of ASUC in patients without signs or symptoms of COVID-19, regardless of SARS-CoV-2 swab results. Only in patients with COVID-19 pneumonia was there uncertainty among the panel regarding the appropriateness of conventional therapy with intravenous corticosteroids, largely driven by concerns of possible harm. However, it should be noted that in this challenging condition in which there is scant experience and almost no published data in relation to COVID-19, of all suggested treatments, intravenous corticosteroids were given the highest median score by the panel. Regarding the ongoing uncertainty about the benefits or harms of corticosteroids in patients with COVID-19 pneumonia and the inconclusive data emerging from the current coronavirus pandemic, the results of the adaptive trial, RECOVERY, which includes a dexamethasone arm, are eagerly awaited.The panel was uncertain whether infliximab, without concurrent corticosteroids, should be used as a first-line therapy in patients who are SARS-CoV-2 positive, regardless of whether they had COVID-19. As with corticosteroids, the risk of anti-TNF in the context of the pandemic is unknown. In addition, there is no high-quality evidence for infliximab in ASUC other than as a rescue therapy following corticosteroid failure. Anti-TNF agents are known to increase the risk of respiratory tract and other opportunistic infections,Up to half of patients with ASUC fail first-line medical therapy with corticosteroids.There is little evidence regarding the risks of surgical management in patients with COVID-19. Preliminary data demonstrate a substantial increase in morbidity and mortality among patients infected with SARS-CoV-2 undergoing surgery. In one report, 34 patients underwent elective surgery in Wuhan, China, with all developing COVID-19 pneumonia, 7 of whom (20%) died.The BSG IBD guidelines recommend corticosteroid tapering over 6–8 weeks which was considered appropriate by the panel, except in the context of COVID-19 pneumonia where an accelerated taper over 4–6 weeks was considered appropriate instead. A more accelerated taper, over fewer than 4 weeks, was generally deemed inappropriate due to the high risk of relapse in this cohort.Thiopurines and tofacitinib were not considered appropriate at any stage during the scenarios. This is despite the BSG recommendation that thiopurines should be initiated at or soon after discharge following successful treatment of ASUC.Tofacitinib is a non-selective Janus kinase inhibitor which is associated with herpes zoster viral reactivation and, like COVID-19, is also associated with an increased risk of deep vein thrombosis.Prophylactic anticoagulation was considered appropriate beyond discharge among patients with a positive SARS-CoV-2 swab, although this strategy was deemed uncertain in people with negative swabs. Like ASUC, COVID-19 is strongly linked to a hypercoagulable state with substantially increased risk of microthrombi and venous thromboembolism (VTE).Clostridium difficile prior to colectomy in view of higher exposure to antibiotics in the COVID-19 era was not addressed. The outcomes should, therefore, be considered an adjunct to multidisciplinary decision-making rather than a replacement. Finally, knowledge within the field remains fast moving such that it will be important to stay abreast of new developments as they arise.The strengths of our study include the inclusion of a diverse group of IBD experts drawn from a wide range of UK centres as well as non-gastroenterology specialists with experience in managing patients with COVID-19. In addition, we used the RAND methodology which is a validated technique to guide decision-making in the absence of a robust evidence base. It is not necessarily an attempt to reach consensus but rather to guide clinicians as to the appropriateness or inappropriateness of interventions, while accepting that uncertainty is also a valid outcome, which was highly appropriate in this setting. It was impossible for our scenarios to encompass fully all cases encountered in clinical practice. We, therefore, focused on principles that may help to guide decision-making in most cases of ASUC in the context of COVID-19. We appreciate that by doing so, this guidance may not be directly applicable to more nuanced cases where decision-making may be influenced by a myriad of factors. Nor was every aspect of care considered; for example, the question of repeating testing for By combining clinical expertise from the BSG CRG and IBD Section Committee in conjunction with other medical and surgical IBD and COVID-19 experts, we have provided guidance to clinicians regarding the appropriate management of ASUC during the COVID-19 pandemic, highlighting where current BSG guidance may need adaptation. Population-based studies are needed to clarify the risks and benefits of interventions used in the management of ASUC during the pandemic. Until then, we consider the results of the panel, which largely support following the well-established and evidence-based BSG guideline, will help guide clinicians in this challenging and evolving area.


Individual differences and age-related normal and pathological changes in mental abilities require the use of cognitive screening and assessment tools. However, simultaneously occurring deficits in sensory processing, whose prevalence increases especially in old age, may negatively impact cognitive-test performance and thus result in an overestimation of cognitive decline. This hypothesis was tested using an impairment-simulation approach. Young normal-hearing university students performed three memory tasks, using auditorily presented speech stimuli that were either unprocessed or processed to mimic some of the perceptual consequences of age-related hearing loss (ARHL). Both short-term-memory and working-memory capacities were significantly lower in the simulated-hearing-loss condition, despite good intelligibility of the test stimuli. The findings are consistent with the notion that, in case of ARHL, the perceptual processing of auditory stimuli used in cognitive assessments requires additional (cognitive) resources that cannot be used toward the execution of the cognitive task itself. Researchers and clinicians would be well advised to consider sensory impairments as a confounding variable when administering cognitive tasks and interpreting their results. Over the past decades, there has been increasing interest in the role of cognition in (the decline of) speech processing across the adult lifespan see . Indeed,Presumably for reasons of convenience and universal usability, most cognitive tests require the administrator to provide verbal instructions, and a substantial number use at least some auditorily presented stimuli  to establish that none had any hearing impairment. The test consists of listening to diotically presented triple digits  in a fixed-level speech-shaped background noise  with the pure-tone average (PTA) for octave frequencies between 0.5 and 4 kHz  native-English-speaking volunteers were recruited from the undergraduate student population of Loughborough University (United Kingdom), and received course credit for participating in the study. All participants completed the internet version of the hearing-screening test offered by the British hearing charity “Action on Hearing Loss” (SD) = 1.1] formed the “normal-hearing” (NH) group that listened to unprocessed stimuli, and (ii) 26 participants  with a mean age of 19.3 years (SD = 1.3) formed the “simulated hearing loss” (SHL) group that listened to degraded speech. The small age difference between groups was not significant .Participants were randomly assigned to one of two experimental groups: (i) 30 participants  with a mean age of 19.1 years .All SHL participants correctly recognized the nine digits, but six of them (23%) failed to recognize two to four target words, representing 4 to 7% of the total number of words to be remembered in the LS test. Hence, all results of the LS test were reanalyzed, excluding those participants . However, there is converging evidence that sensitivity to temporal fine structure worsens with age and hearing loss  controlling experimentally  or (ib) statistically (by measuring sensory performance and using this information as a covariant) the effect of sensory decline, (ii) compensating for sensory deficits , and (iii) using a visual version of cognitive tests originally including auditory-based tasks  Sub-Committee. The participants provided written informed consent prior to participation in the study.CF designed the study, analyzed and plotted the data, and wrote the manuscript.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Vegetation Types (VTs) are important managerial units, and their identification serves as essential tools for the conservation of land covers. Despite a long history of Earth observation applications to assess and monitor land covers, the quantitative detection of sparse VTs remains problematic, especially in arid and semiarid areas. This research aimed to identify appropriate multi-temporal datasets to improve the accuracy of VTs classification in a heterogeneous landscape in Central Zagros, Iran. To do so, first the Normalized Difference Vegetation Index (NDVI) temporal profile of each VT was identified in the study area for the period of 2018, 2019, and 2020. This data revealed strong seasonal phenological patterns and key periods of VTs separation. It led us to select the optimal time series images to be used in the VTs classification. We then compared single-date and multi-temporal datasets of Landsat 8 images within the Google Earth Engine (GEE) platform as the input to the Random Forest classifier for VTs detection. The single-date classification gave a median Overall Kappa (OK) and Overall Accuracy (OA) of 51% and 64%, respectively. Instead, using multi-temporal images led to an overall kappa accuracy of 74% and an overall accuracy of 81%. Thus, the exploitation of multi-temporal datasets favored accurate VTs classification. In addition, the presented results underline that available open access cloud-computing platforms such as the GEE facilitates identifying optimal periods and multitemporal imagery for VTs classification. VegetatDespite the advantages of using EO data, processing satellite data to map VTs in heterogeneous landscapes poses multiple challenges . GeneralMulti-temporal Landsat image analyses have increased substantially since 2008. When it comes to vegetation mapping, all available Landsat images can be used to increase the number of good quality observations in a year . ExploitOverall, while using satellite imagery has been addressed relatively well in image classification, the process of vegetation cover classification is a more challenging and complex process. This is especially the case where VTs as a subclass of rangeland cover are concerned. Subclasses of vegetation cover are more spectrally similar than that of a higher hierarchical land cover types. To overcome this, images acquired at different dates during VTs growth periods are required to accurately identify and discriminate VTs. Our analysis provides insights into whether the use of an optimal multi-temporal dataset of Landsat OLI-8 images is sufficient to accurately classify VTs across heterogeneous rangelands at the landscape level. We chose a heterogeneous landscape in the southwest of Iran as our study area to cover different distinguishable VTs and their ecological significance. This research focuses on the VTs classification process using an optimal time series dataset derived from the NDVI temporal profiles and plant species' spectral behavior for the period of 2018, 2019, and 2020. In addition, we applied the machine learning classifier Random Forest to compare the VTs classification accuracy of the single-date and multi-temporal Landsat 8 images. This study will eventually provide insights into selecting the time series dataset for optimized VTs mapping in heterogeneous landscapes.22.1The semi-steppe Marjan rangelands is located within the Chaharmahal-Va Bakhtiari province in southwest Iran. The area covers 7736 ha, extending from 32º07’40” to 32º0’20”N and 51º17’30” to 51º23’00”E . This ar2.2Astragalus verus Olivier), (2) VT2 (Bromus tomentellus Boiss), (3) VT3 , and (4) VT4 . The canopy cover data could potentially be used to identify VTs from structural, compositional, or a combination of both, the so-called physiognomic-floristic classification, to have a sound and accurate perspective on VTs. We sampled the four identified VTs using three replicates, in each of which the canopy cover was sampled along three transects of 100 m that were evenly distributed throughout the study area  to accurately identify and classify VTs. Within GEE we selected Top of Atmosphere (TOA) reflectance (ee. Image Collection (‘LAND-SAT/LC08/C01/T1_SR')) and less than 5% cloud coverage ) Landsat 8 images. So, only images with less than 5% cloud cover are included. Thereby, some months of the year are excluded due to persistent cloudiness. A total of 36 cloudless dates were extracted for this study .We processed all the available collection of the Landsat 8 time-series images in the GEE to generate the NDVI spectral curve . The NDVred band .In this research, by analyzing the NDVI temporal profile and plant species’ spectral behavior at different growth periods, we identified a dataset of an optimal combination of multi-temporal images (time-series dataset) as input for classification. In other words, we only used this index to identify optimal multi-time images for vegetation classification and did not use the NDVI as input for classification.To determine the NDVI values for each VT, the NDVI values were extracted from the canopy cover sampling plots . The cor2.42.4.1After distinguishing the dominant VTs within the area, for each identified VT, 75 sample points were recorded by field excursion. The XY position of each representative VTs point was recorded using a Garmin eTrex 32× Handheld GPS . In tota2.4.2Multiple classification algorithms have been applied in land cover mapping studies, such as decision trees , artific2.4.3For the classification process, the mapping accuracy was evaluated by means of the confusion matrix resulting from crossing the ground truth image of the “verification samples” and the outcome map of the classification process. Other accuracy indices to assess the performance of the classification include the Overall Accuracy (OA), Overall Kappa (OK), Kappa Index of Agreement (KIA), User’s Accuracy (UA), and Producer’s Accuracy (PA). As the confusion matrix only gives the performances of VTs maps based on validation samples, we additionally computed the Friedman test. This test enabled us to assess whether there was a statistically significant difference between single-date images and multi-temporal images in VTs classification. 3.13.2Using the NDVI temporal profile for specified time intervals, the plant species spectral behavior can be analyzed at different growth periods, and an optimal combination of multi-temporal images (time series dataset) can be selected to improve the VTs classification. The NDVI temporal profile and error bars for each VT class are shown in In general, the highest NDVI value change occurs every three years between April and June. This multi-temporal time window is then used to optimize the classification of different VTs.3.3As shown in After selecting the dataset of an optimal combination of multi-temporal images and creating an image collection  using the RF algorithm, VTs classification was performed . The sin3.4Using the multi-temporal images led to the improvement of VTs classification accuracies. The performance of the multi-temporal images showed an overall kappa accuracy of 74% and an overall accuracy of 81%. The side-by-side comparison of the performance of single-date images and multi-temporal images revealed that multi-temporal images improved the OA by 17% and OK accuracy by 23% .3.5p < 0.05).The statistical comparisons of multi-temporal images and single-data images for VTs classification using the Friedman test are shown in 4As ve), VT2 is a tallgrass species (Br to), VT3 is semi-shrub species (Sc or), and VT4 is the combination of shrub and tallgrass species (As ve-Br to).The construction of a fast, accurate, and simple model for extracting land cover information and VTs maps is of concern to natural resources managers and ecologists . This stField methods are a useful tool for accurate identification and classification of VTs, but these methods face limitations, and due to personnel, logistical, and budgetary limitations, field measurement methods cannot make repeated and simultaneous in situ observations of the heterogeneous landscapes . The incstudy area. This issue is particularly relevant to VTs, thus phenological data become important in the land cover mapping of the VTs distribution and subsequently in their classification, while single-date image assessments may not accurately represent annual changes and discriminate vegetation .4.1As vr), semi-shrubs (Sc or), and grasses (Br to), shrub species, due to their higher canopy cover percentage, have a higher NDVI value than the grasses and semi-shrubs species in the three years of 2018, 2019, and 2020.According to the NDVI temporal profile in Br to) is not drought resistant and shows the lowest vegetative growth rate, leading to the lowest NDVI value. Other VTs (As ve and Sc or) are more resistant to drought due to shrubby and semi-shrub species dominance or compositional variation, and have maintained their canopy cover, thus maintaining a higher NDVI value than the VT2. The amount of precipitation somewhat increased in 2019 and 2020 , which meant that the VT2 dominant grass species had better vegetative growth than semi-shrubs and had a higher NDVI value in early spring. However, the high palatability of these grass species, as opposed to shrubby and semi-shrub species, favors intensive grazing, and the canopy cover starts to decrease starting from late spring onwards. Likewise, the grazing provoked a decrease in NDVI values , VT2 with dominant grass species  from Landsat OLI-8 images with an RF classifier. The overall classification accuracy (64%) and overall kappa (51%) were obtained in the first model .The second model is based on the optimal multi-temporal images  from Landsat OLI-8 images with an RF classifier. While development of a multi-temporal dataset is often time consuming and requires optimization of the plant species’ phenological behavior, it is the most important step to identifying an optimal multi-temporal dataset to represent the different VTs between different kinds of land cover. This research introduces an optimal multi-temporal dataset, which is valuable in improving VTs classification accuracy. The results of the second model showed that combinations of distinct multi-temporal datasets can improve the OA (17%) and OK (23%).The usage of multi-temporal satellite imagery provides important information for VTs mapping and classification. In the multi-temporal satellite images, using plant species’ phenological behavior during the growing season can be selected as the best feature space in the temporal domain, so that the separation degree increases as much as possible between different VTs. In a related study about using multi-temporal images in classification, Stumpf  found thThe produced maps were validated against ground truth data, the so-called verification samples, by computing the OA . The res5The identification and classification of VTs in a spectrally heterogeneous landscape is among the most challenging tasks in satellite image classification. In this study, we conducted a detailed experiment on how to improve image classification accuracy by integrating multi-temporal images. The presented results suggested that single-date images do not lead to a proper identification of VTs. Instead, our results underpin that the development of an accurate VTs map is feasible in a heterogeneous landscape when a dataset of an optimal combination of multi-temporal images is entered into an RF machine learning classifier. To do so, stacking and filtering the multi-temporal images based on the cloud cover threshold are required. By analyzing the NDVI temporal profile and plant species’ spectral behavior at different growth periods, we identified the multi-temporal images with the most distinct spectral response as input for RF classification. The classification results revealed that multi-temporal satellite imagery provides important information for VTs detection and mapping. Compared to single-date images, it led to an OA and OK improvement of 17% and 23%, respectively.When it comes to perspectives for future work, cloud-computing platforms such as the GEE opened opportunities to quickly identify optimal periods and time series dates for VTs classification. While the multi-temporal images dataset is most promising for VTs classification, further research should focus on the exploration of the relationships between novel EO data processing techniques and dynamic VTs mapping.


IL-1β is considered one of the most impactful cytokines in OA disease and therefore, its blockage offers a promising approach for the modulation of OA. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory protein belonging to the IL-1 family that competes with IL-1β for occupancy of its receptors, without triggering the same downstream inflammatory response. Because of its natural anti-inflammatory properties, different methods have been proposed to use IL-1Ra therapeutically in OA. Autologous conditioned serum (ACS) and autologous protein solution (APS) are blood-derived products produced with the use of specialized commercial kits. These processes result in hemoderivatives with high concentrations of IL-1Ra and other cytokines and growth factors with potential modulatory effects on OA progression. Several studies have demonstrated potential anti-inflammatory effect of these therapies with promising clinical results. However, as with any hemoderivatives, clinical outcomes may vary. For optimal therapeutic use, further research is warranted for a more comprehensive understanding of the product's composition and interaction of its components in joint inflammation. Additionally, differences between ACS and APS treatments may not be clear for many clients and clinicians. Thus, the objective of this narrative review is to guide the reader in important aspects of ACS and APS therapies,  Osteoarthritis is a common cause of lameness observed in horses , and hasBiological therapies such as platelet-rich plasma (PRP), autologous protein solution (APS), and autologous conditioned serum (ACS) provide a more physiological alternative to conventional treatments capable of modulating inflammation in OA –8. These2), IL-6 and IL-8 propagate OA  preparation method (Orthokine®) , was devstration .During incubation, platelets degranulate and mononuclear cells are stimulated to produce various cytokines and growth factors such as; IL-1Ra, IL-4, TNF-α, IL-10, IL-6, and basic fibroblast growth factor (FGFb) among various other anabolic factors stated on Despite the aforementioned studies, the ratio between anti-inflammatory cytokines and pro-inflammatory cytokines  should still be sufficient to justify therapeutic use . In fact4)  .Different studies suggested that the chemical-cell interaction would be essential for cytokine expression in monocytes , 38. Ini4-treated glass beads may not be necessary to produce an enriched serum , transferred to a separation device and centrifuged for 15 min , 46. TheIn horses, APS presented significantly more white blood cells, platelets and significantly less erythrocytes compared with the whole blood . DiffereCytokines in APS seem to correlate to the cellular content within the product. For instance, a negative correlation has already been determined between WBC and TGF-β concentrations . PlateleThe general condition of the patients did not seem to interfere significantly with the cytokine composition of APS. Similar concentrations of anti-inflammatory cytokines and anabolic growth factors were observed in APS from patients with OA and controls .Although not extensively studied as other hemoderivatives, APS has been successfully used as a symptom modifying option for the treatment of OA. This treatment seems to be safe and its side-effects  are commonly associated with other intraarticular injections .The use of APS has provided optimistic results for OA treatment in different species , 48, 49.In fact, one single injection of APS demonstrated significant improvement in Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scores in OA patients after 2 weeks post-injection compared with baseline . Pain scIn horses with naturally occurring OA, APS significantly improved lameness, pain-in-flexion, gait analysis and range of motion up to 14 days after treatment compared with baseline and controls . In equiPromising results with APS use were justified due to its favorable cytokine content. A IL-1Ra:IL-1 ratio >1,000 in APS seemed to predict the inhibition of inflammation in human OA patients . AdditioAlthough positive results were observed with clinical use of ACS and APS, others demonstrated that ACS did not have a direct effect on cartilage metabolism compared with unstimulated serum. This may justify the lack of disease modifying effects observed clinically with the use of these products , 42.in vivo may be attributed to the reduction of therapeutic cytokine concentrations in the synovial fluid after injection, suggesting that new intra-articular therapies should focus on the prolonged presence of the cytokines in the joint space. For this reason, some authors opted for a protocol of multiple serial ACS injections separated by short periods of time  and collagen type II (COL2-A1) expression in cartilage  effect in different tissues within the joint, may reveal other potential treatment routes equally or more important than IL-1 blockage. For instance, in horses with mild osteoarthritis, clinical improvement was statistically associated with content of not only IL-1Ra but also IGF-1 in ACS . In vivoAs with other biological therapies, the optimization of protocols for preparation and application of ACS and APS in different OA scenarios is warranted. Considering the autologous nature of the product, cytokine variability is an inevitable issue with this treatment, which can lead to inconsistent modulatory and clinical effects . The devAutologous protein solution currently offers a more user-friendly approach since it requires shorter preparation and no incubation times, unlike ACS which requires a minimum laboratory setting . Autologous protein solution can be prepared using a portable centrifugation equipment and is a very basic and undemanding technique . The intDespite the limited number of clinical studies using ACS and APS and the lack of knowledge in relation to its composition, these therapies provide a symptom-modifying option of treatment in early OA cases , 9. ThesRecent studies presented in this review provided important information regarding to the lack of disease modifying effect associated with the use of these therapies. This information may help researchers direct investigations into learning how conditioned serum and protein solution composite can modulate inflammation and enhance improvement in lameness in selected cases.The promising anecdotal results with the use of APS and the practicality of the treatment compared with ACS may lead clinicians to prefer its use , 48. HowLCG was responsible for the literature search and preparation of the manuscript. MJM contributed with the literature search and edition of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Machine learning, particularly classification algorithms, constructs mathematical models from labeled data that can predict labels for new data. Using its capability to identify distinguishing patterns among multi-dimensional data, we investigated the impact of three factors on the observation of architectural scenes: individuality, education, and image stimuli. An analysis of the eye-tracking data revealed that (1) a velocity histogram was unique to individuals, (2) students of architecture and other disciplines could be distinguished via endogenous parameters, but (3) they were more distinct in terms of seeking structural versus symbolic elements. Because of the reverse nature of the classification algorithms that automatically learn from data, we could identify relevant parameters and distinguishing eye-tracking patterns that have not been reported in previous studies. In the design research community, the benefit of using eye-trackingis distinct: it provides quantifiable information about a viewer’svisual attention in a non-intrusive manner. Its significance is based onthe fact that the visual appearance of a product plays a critical rolein consumer response  and on tEye-tracking is subject to certain restrictions though: processingeye-tracking data computationally has no universal standard , thelinEye-tracking data have been linked to design problems through layersof mediating parameters. Human eye movement consists primarily of twophenomena: 1) fixation—a relatively stationary period of eye movementand 2) saccades—rapid movements between fixations. The low-levelparameters, e.g., fixation duration, fixated positions, and saccadeamplitude, have been combined as quantitative indicators of a specifieddesign problem. For example, changes in fixated positions were relatedto the specified task , and theThe limitation of this practice is that the determination of thecriterion parameters for a specified problem is not alwaysstraightforward or successful. That is, the selected eye-trackingparameters were often not effective indicators of the target effect. Theconsequence is the lack of agreement on the mapping between parametersand design problems , and stuAccording to Arthur Samuel, machine learning is a field of study thatgives computers the ability to learn without being explicitly programmed . By virtMotivated by the opportunities that machine learning offers, ourstudy intends to evaluate the impact of three factors associated withviewing architectural scenes: individuality, education, and stimuli.Among the factors exogenous and endogenous to the participatingindividual, we designed the experiment such that eye-tracking dataconstituted the combined effect of natural tendency, architecturaltraining, and image content. First, the presence of eye-trackingparameters unique to an individual has been studied extensively , 25, 26.In art and design research, eye-tracking data have been used as aquantifiable measure, an objective indicator, and scientific evidence ofvarious aesthetic rules and design heuristics. In art research, oneprimary question was the manner in which trained artists behavedifferently from novices. According to Berlyne’s  notion oIn design discipline, the eye-tracking research diversified by itssub-disciplines. In the product design domain, researchers have exploredthe use of the eye-tracker as a tool for understanding user preferencewithin the entire product development cycle. Using the effectiveness ofthe eye-tracker for measuring user attention , KukkoneOccasionally, design research that used eye-tracking data exhibitedvariance in the level of success, i.e., differences in the number ofobjectively verified hypotheses and proposed hypotheses. Thecharacteristics of these studies are the absence of analysis on theproposed questions, lack of quantitative reasoning, and high rate ofunexpected findings. For example, Koivunen et al.  initiallRecently, two papers have reported controversial opinions on theobservation of Yarbus  that theIn this study, we aimed to evaluate the impact of three factors,i.e., individuality, educational background, and image stimuli, by usingmachine learning to explore multi-dimensional data. Regardingindividuality, the question has been whether endogenous eye-trackingparameters consistent across different viewing conditions exist. Themotivation was to know (1) the extent to which endogenous factors affecteye-tracking patterns, and (2) the potential connection with neuralsubstrates, such as ADHD, dementia, memory , visual http://bit.ly/2eqb4TV), as input data. To observe the effect of architectural training on visual attention, they recorded 10-s eye-tracking patterns of 71major/non-major participants (39 majors and 32 non-majors) on 14 imageswith certain architectural elements (Appendix). The data consist of eyepositions sampled with a frequency of 60 Hz in normalized coordinates: ascreen space with a size of 1.0 (width) by 0.74 (height). A fixation wasdefined as a group of sample points whose diameter does not exceed 0.02in normalized length and 300 ms in time between the first and last one.All other events, such as glissades and smooth pursuits as well assaccades in the traditional sense were collected into single ‘saccade’category in our study, following the Identification by Dispersion Threshold algorithm  . Hence, Rather than establishing candidate parameters and verifying theirstatistical significance, we applied machine learning to identify thedistinguishing parameters and their patterns that characterizeindividuals and majors/non-majors. Regarding the data features fordecoding individuals and majors/non-majors, we considered characteristicpatterns such as oscillating movements and the extent of fixation overtime proposed by Lee et al. (19), as well as well-established endogenousparameters such as total fixations, mean fixation duration, and meansaccade amplitude . To unde(1) Fixation data comprising average fixation duration, totalfixation count, average saccade length, and total saccade count(2) Fixation histogram data whose bins represent different ranges offixation duration(3) Saccade histogram data whose bins indicate ranges of saccadelengths(4) Velocity histogram data whose bins are ranges of normalizedlengths between adjacent points sampled at 60 Hz(5) Fixation map data representing cumulative fixation durations on a10 × 10 gridv (s-1) can beconverted to a degree in the visual angle by using 2 tan-1( v/2 × 24.98/50) (deg/s). The histogram consisted of 14bins, 1 special bin reserved for zero velocity, and 13 bins for therest. The ranges of 13 bins were determined by first sorting the dataand then dividing them into 13 groups of equal sizes. Fixation and thesaccade histogram consisted of 10 bins of equal sizes with no specialbin.Velocity histograms store normalized lengths traveled in 1/60 of asecond. Because a 24.98 cm × 18.61 cm screen was placed 50 cm from theparticipant, velocity www.scikit-learn.org).While SVM with a linear kernel was the choice of previous eye-trackingresearch with high-dimensional data  into 70/30, i.e., 70% for thetraining dataset and 30% for the validation dataset. As with individualdecoding, we compared the performance of different classifiers averagedover 14 iterations. To estimate the statistical significance, we adoptedone-way ANOVA using 14 data samples against the chance level (50%) inaccordance with Greene et al.  against the randomchance level . Different classifiers werecompared to determine the most optimum result. To split the entire datainto training and validation datasets, we adopted the leave-N-outselection scheme; 71 samples from the individual-image pairs formed thevalidation set and the remaining (14 - 1) × 71 samples formed thetraining set. With each of the 14 iterations, we chose one image out of14 images to form a validation set. This folding scheme allowed nosample in the testing set see the target image of the validation set,ensuring that the prediction of validation set is based solely onendogenous factor  by excluding the effect of exogenousfactor (image). An exhaustive alternative would have been to iterateover all the 14e et al. . Please Finally, in order to investigate the effects of image stimuli, weclassified 71 participants’ data for each image into major/non-majorgroups and identified the image content that contributed to high correctprediction rates. We ran 71 iterations per image; in each case, one ofthe 71 data samples formed the validation dataset and the remainingformed the training dataset. Decoding an individual per image was notfeasible because there was only one sample from each participant perimage, preventing division into training/validation datasets.Before matching various classifiers with different data features, weapplied a decision tree classifier to obtain the relative importance ofdata features. The overall results indicated that the fixation data andvelocity histogram were more effective for individual decoding than theothers , with a higher correction prediction rate (967/7100 =13.62%) than the chance level (1/71 = 1.41%). Figure 2 visualizes thatthe velocity histogram data (yellow), particularly the earlier bins,exerted the highest importance, followed by the fixation data (lightblue). The importance of the fixation histogram (orange) and saccadehistogram (gray) were lower than these two features. The fixation mapdata (dark blue) displays 10 peaks, whose maxima are higher near themiddle (third to seventh peaks) than both ends. Each peak represents thelongest fixation duration of each row in a 10 × 10 cell grid. The higherpeaks near the middle indicate that cells around the center of an imagewere a better indicator of the identity of the individual.Table 2 presents the results of different classifiers obtained byusing feature selection and hyper-parameter tuning on all data features.Whereas the decision tree exhibited an average correctness ofapproximately 14%, the LinearSVC classifier performed better, and theSVC classifier generated the highest correct prediction rate. Thefeatures chosen by feature selection over 14 iterations matched wellwith those having high importance in the preliminary testing run usingthe histogram ranges averaged over all folds . The top-five correct prediction rate with the SVC classifier was65.29%, implying that the prediction rate doubles if we permit up tofive guesses per individual.Using the classification results with the best options (SVM.SVCclassifier), we compared the correct prediction rate of each individual.Figure 3 (left) shows that the majority of the participants had acorrect prediction rate higher than random chance (1.41%). The averagecorrect prediction rate of the non-majors (33.3%) was higher than thatof the majors (29.3%). Figure 3 (right) shows a confusion matrix thatvisualizes the correct and incorrect predictions. The x- andy-coordinates or each dot represent true and predicted individual for aspecified data, and the bright diagonal line indicates the overallsuccess of individual decoding. A few dots off the diagonal line areincorrect predictions, and the higher density of warm dots in the lowerright quadrant is indicative of the high prediction rates of non-majorsthan majors.Figure 4 is a graph showing the velocity histogram per individual forall the images. It represents eight participants’ data with the highestand lowest correct prediction rates. The highest rates were 92.86%), 85.71% ), and 71.43% ); thelowest were 7.14% ) and 0% ). Each Figurecontains 14 colored lines, representing data from all the 14 images. Themost prominent difference between the two groups was the consistencyacross images; the first four participants, particularly Figure 4(b),tend to have more narrowly clustered lines than the others. Moreover, asthe early bins exert larger impact for individual decoding ,the level of convergence at bin 1 appears to have contributed to thehigher prediction rate of Figure 4(d) than that of Figure 4notwithstanding their overall similarity. The highest performance inFigure 4(a) seems to be explained by its uniqueness of pattern among theparticipants; this is further supported by the fixation data ).We could observe such consistency from the scanpath visualization aswell. Figure 6 shows the actual eye-tracking patterns of the twoparticipants ), whose lines with identical colorsrepresent the same bin in the velocity histogram. We can infer from thisthat for each individual, the ratio between the numbers of the lineswith the same color is more or less stable across the images. Moreover,as a unique sequence of colored lines repeats, it seems that it is notjust the distribution of the lengths of these lines but also the orderof their occurrence of them that carries individual character. Forexample, whereas a long red line and a set of shorter blue linesalternate in Figure 6 (left), there are numerous green dots inconjunction with the adjacent blue lines between the longer red lines inFigure 6 (right). Such an observation implies that we can have a bettermeasure representing an individual character by incorporating bothtemporal  and spatial properties.A preliminary run of the decision tree classifier for major/non-majordecoding revealed that the distribution of importance over all the datafeatures is similar to that of individual decoding . However,the standard deviation over 100 iterations exceeds the average values,indicating the unavailability of clear feature(s) containing the uniqueproperties of the majors/non-majors.p = 2.73e-38) against the chance level(50%), non-majors exhibited significantly lower performance (57.32%)than majors (70.39%). When we plotted a 2D graph using the two featureswith the highest importance , the majors were more narrowlyclustered than the non-majors with substantial overlap. We can inferthat the shared area had been labeled as majors’ territory, and only thenon-majors outside this territory were correctly predicted asnon-majors.Next, we matched three classifiers with different data features. Thebest result (64.5 ± 7.16%) was from the SVM.SVC run with featureselection and hyper-parameter tuning on all data features, as inindividual decoding. Whereas t-test verified a statistically meaningfuldifference  or green (non-major dominant)with transparency . The larger the difference, the brighterand more transparent the color became. We also marked the fixation timeon each cell to differentiate between cells with equally high and lowattention.In Figure 10(a), both the majors and non-majors focused on humanfigures, but the non-majors exhibited marginally higher concentration(green box). We could observe larger differences at architecturalelements with complex forms: conjunction between a column and a beam,the space between the stairs and a column, and the setback of theceiling slab around a column. It appears that majors spend more timeprocessing and interpreting structural ambiguities.In Figure 10(b), it is noticeable that the non-majors focused more onthe commercial signboards, particularly those in the brighter upperarea. The strength of focus tended to get intensified toward thevanishing point. On the other hand, the majors spread more to the darkerregion right below the commercial signboards and paid more attention tothe complex shape of the stair rails.In Figure 10(c), both the majors and non-majors paid attention to theLED display. However, the majors stayed longer near the larger screen,whereas more non-majors tended to read the direction sign. A subtlealbeit visible difference was the uneven attention toward the roof trussstructure. Whereas the non-majors concentrated most on the brighterside, where the window wall and the ceiling meet, some majors focused onthe ill-lighted deeper area.Overall, the majors exhibited a tendency to focus more on thestructural elements, whereas the non-majors were attracted to signboardsor human figures. The lighting condition and complexity of the shapeappeared to play a role in the division of attention in that the darkerand more complex a target element was, the longer the majors stayed thannon-majors. However, an exception was that the majors paid strongerattention to the large LED screen area.To investigate the impact of different endogenous and exogenousparameters on how we view architectural scenes, we applied aclassification algorithm to multi-dimensional eye-tracking data obtainedfrom students of architecture and other disciplines. We verified theeffect of three factors, namely individuality, major/non-major, andimage stimuli, on visual attention. The individual identity of theeye-tracking data was encoded in the velocity histogram, representingthe distribution of the speed of eye movement measured at a fixed framerate (60 Hz). The separation between the major and non-major groups wasenabled using endogenous parameters, although it could be betterexplained by the differing sensitivities toward structural and symbolicimage features.Regarding individual decoding, the classification was successfulusing velocity histogram when the impact of other factors such asfixation duration and count was not as much significant. This isinconsistent with previous findings where the fixation duration andsaccade length were consistent across different images  and the The visual analysis of the velocity histogram revealed that asequence of spatiotemporal pattern, rather than only the distribution ofspeed, was unique to each individual. Whereas a histogram could capturean aspect of such a pattern, it is not straightforward to determinewhich parameter can summarize such a feature more effectively. Itappears challenging to (1) define the length of a sequence, (2)determine the tolerance of the variation, and (3) completely accommodatespatial disposition in a smaller parameter space. We consider that thisvenue of exploration has a potential for future research.It is not evident why certain individuals exhibit strongercharacteristics than others; in particular, the group of non-majorsincluded a higher number of similar individuals than that of majors. The question is whether endogenous eye-tracking parametersare innate or acquired. Previous research has concluded that fixationand saccadic measures are natural properties determined by physical,neural, developmental, and psychological constraints  and thatRegarding decoding majors/non-majors, the classification wasstatistically significant using similar data features for individualdecoding. However, the prediction rate was substantially higher formajors than for non-majors, as revealed by a 2D map whosex- and y-axes are two data features with the highestimportance. The areas occupied by the two groups exhibited a largeoverlap, but because the majors were more narrowly clustered, the sharedarea had been marked as majors’ territory. It resulted in the incorrectprediction of non-majors in that area as majors. The map itself is adiscovery of data features characterizing the randomness of a moreheterogeneous group, but its level of distinction does not appearsignificant.The analysis of image stimuli revealed that the level of attention ofthe majors and non-majors to certain elements differed. Whereas bothgroups tended to fixate on visually dense areas, the majors focused moreon architectural elements  and the non-majors focused more on non-structural elements. It is noteworthy that thedivision was prominent where a feature exhibited a complex shape or wasin low lighting condition. To summarize, whereas the majors aimed toresolve structural uncertainty, the non-majors were affected more bydirect symbolic cue , 10. ItsA limitation of the process here is that the classificationperformance depends highly on the resolution of the grid. In theory, ahigher granularity always yields better classification results becauseit essentially creates more room for boundaries between differentgroups. Meanwhile, we also noticed a significant number of imagefeatures lying on the boundary. We recommend that a classificationanalysis based on boundary construction be interpreted and supplementedby other visual inspection methods. Another important point is that thereproducibility of our results will depend on the accuracy or precisionof the measurement. We used raw data whose positions in normalizedcoordinates had a resolution in the order of 10e-4, and a timing in theorder of 2.5e-6 ms, well below the frequency of the recording . In our study, the first bin of the velocity histogramrepresents the “zero” distance between adjacent eye positions, and theexistence itself along with its low to high variability across andwithin an individual is one proof of the soundness of the small scaledata .In conclusion, the application of machine learning to eye-trackingdata revealed more data features unique to an individual and providedobjective measures indicating the uneven attention between groups withand without educational training. Unlike previous forward-basedapproaches that test the effectiveness of the selected parameters,machine learning could automatically identify the distinguishingpatterns from the candidate features in high dimensional spaces.However, it is also true that machine learning is not a panacea that canreveal all the hidden eye-tracking parameters. Not only did previousstudies show the effectiveness of various parameterizations, but alsohistogram features in our study depended largely on researchers’insights rather than blind application of machine learning. The problemproposed as future research – investigation of better methods forcapturing the spatiotemporal nature and spatial distribution of eyemovement – will also require trial and error of multiple hypotheses. Inconclusion, the practice of forward-based searches of eye-trackingparameters will continue to exist in the near future, but the machinelearning community will keep offering strong alternatives for exploringeye-tracking parameters more effectively and these alternatives would beworthwhile to consider.http://biblio.unibe.ch/portale/elibrary/BOP/jemr/ethics.htmland that there is no conflict of interest regarding the publication ofthis paper.The author(s) declare(s) that the contents of the article are inagreement with the ethics described inThis research was supported in part by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014S1A5A8012349).