title: Remote Access

text: Driven in large part by the globalization of technology, focus on a healthier work-life balance, and an increase in the number of millennials entering the workforce, we are increasingly seeing companies across the globe offer their employees the option to work remotely. Not surprisingly, a recent survey from Bayt.com found that 79% of professionals in the Middle East and North Africa (MENA) region would actually prefer to work for companies that offer a remote working option. Offering employees the opportunity to work remotely can actually work to the advantage of the organization. According to Gartner, “by 2020, organizations that support a ‘choose-your-own-work-style’ culture will boost employee retention rates by more than 10%.”


title: Ransomware and Privileges

text: Let me get this out right off the bat: no one solution is 100% effective in mitigating the risk of ransomware. Some technologies are claiming to have tested hundreds of samples, and that their tool is perfect in stopping all types of attacks. I’m sorry, but that is a falsehood. Why? If any single vendor had a solution that could solve the problem completely, ransomware would not be such a problem.


title: Expanding the Options Through Nine Steps

text: The nine levels of Stepped Care 2.0 are designed to maximize choice. They also facilitate care adaptations as needs, motivation and readiness evolve. Their arrangement on dimensions of stakeholder engagement, and both treatment intensity and client autonomy, enables full transparency. Providers and help-seekers are able to see the forest and the trees. The steps support more meaningful organization of both new and existing resources. They can be tailored to the needs and unique circumstances of any jurisdiction. Each of the nine steps is defined to incorporate recovery values and principles in order to maximize efficiency and client empowerment.


title: Hantavirus Infection and the Renal Syndrome

text: Fever with renal syndrome is currently endemic in Eurasia, where the main etiological agents are the Hantaan and Seoul viruses in Asia (China, South Korea, and the Far East of Russia), in addition to the Seoul, Puumala, and Dobrava viruses in Europe (central, northern, Alpine Massif, Balkans, and western Russia). Lethality rates are higher with Hantaan and Dobrava virus infections (5–10%) when compared to the Puumala and Seoul viruses (1%). With the expansion and geographical migration of the urban rodent (Rattus norvegicus) from the “Old World,” the Seoul virus was introduced into the Americas and is now considered a virus with a cosmopolitan distribution. On the American continent, the presence of the Seoul virus has been confirmed in Brazil, Argentina, and the United States. The hantavirus transmission to humans occurs by inhalation of aerosol-dispersed viral particles present in rodent droppings and saliva. This disease should be clinically differentiated from leptospirosis and other viral hemorrhagic fevers that occur in the same areas of occurrence of hantavirus infections. There is no treatment with antiviral drugs specific for hantavirus. Faced to a suspected hantavirus case, it should be communicated to the local health authorities and provide an eventually intensive care unit support.


title: Adapting for Unique Settings

text: Although Stepped Care 2.0 is a new model, programming and principles are familiar to many. What is new, are the processes for system building and adjustment discussed in Chap. 10.1007/978-3-030-48055-4_6. Equipped with these processes many institutions are adopting variations of the model to suit their unique ecosystems. Specifically, post-secondary counselling centres across North America and publicly funded mental health care systems in Canadian provinces and territories are now implementing Stepped Care 2.0. A comprehensive case study, based on an amalgamation of implementation experiences, illustrates the co-design process, emphasizing strategies for working through conflict and ensuring maximum stakeholder buy-in.


title: Assessment of spontaneous breathing during pressure controlled ventilation with superimposed spontaneous breathing using respiratory flow signal analysis

text: Integrating spontaneous breathing into mechanical ventilation (MV) can speed up liberation from it and reduce its invasiveness. On the other hand, inadequate and asynchronous spontaneous breathing has the potential to aggravate lung injury. During use of airway-pressure-release-ventilation (APRV), the assisted breaths are difficult to measure. We developed an algorithm to differentiate the breaths in a setting of lung injury in spontaneously breathing ewes. We hypothesized that differentiation of breaths into spontaneous, mechanical and assisted is feasible using a specially developed for this purpose algorithm. Ventilation parameters were recorded by software that integrated ventilator output variables. The flow signal, measured by the EVITA® XL (Lübeck, Germany), was measured every 2 ms by a custom Java-based computerized algorithm (Breath-Sep). By integrating the flow signal, tidal volume (V(T)) of each breath was calculated. By using the flow curve the algorithm separated the different breaths and numbered them for each time point. Breaths were separated into mechanical, assisted and spontaneous. Bland Altman analysis was used to compare parameters. Comparing the values calculated by Breath-Sep with the data from the EVITA® using Bland–Altman analyses showed a mean bias of − 2.85% and 95% limits of agreement from − 25.76 to 20.06% for MV(total). For respiratory rate (RR) RR(set) a bias of 0.84% with a SD of 1.21% and 95% limits of agreement from − 1.53 to 3.21% were found. In the cluster analysis of the 25th highest breaths of each group RR(total) was higher using the EVITA®. In the mechanical subgroup the values for RR(spont) and MV(spont) the EVITA® showed higher values compared to Breath-Sep. We developed a computerized method for respiratory flow-curve based differentiation of breathing cycle components during mechanical ventilation with superimposed spontaneous breathing. Further studies in humans and optimizing of this technique is necessary to allow for real-time use at the bedside. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-020-00545-4) contains supplementary material, which is available to authorized users.


title: Functional investigation of the chromosomal ccdAB and hipAB operon in Escherichia coli Nissle 1917

text: Toxin-antitoxin systems (TASs) have attracted much attention due to their important physiological functions. These small genetic factors have been widely studied mostly in commensal Escherichia coli strains, whereas the role of TASs in the probiotic E. coli Nissle 1917 (EcN) is still elusive. Here, the physiological role of chromosomally encoded type II TASs in EcN was examined. We showed that gene pair ECOLIN_00240-ECOLIN_00245 and ECOLIN_08365-ECOLIN_08370 were two functional TASs encoding CcdAB and HipAB, respectively. The homologs of CcdAB and HipAB were more conserved in E. coli species belonging to pathogenic groups, suggesting their important roles in EcN. CRISPRi-mediated repression of ccdAB and hipAB significantly reduced the biofilm formation of EcN in the stationary phase. Moreover, ccdAB and hipAB were shown to be responsible for the persister formation in EcN. Biofilm and persister formation of EcN controlled by the ccdAB and hipAB were associated with the expression of genes involved in DNA synthesis, SOS response, and stringent response. Besides, CRISPRi was proposed to be an efficient tool in annotating multiple TASs simultaneously. Collectively, our results advance knowledge and understanding of the role of TASs in EcN, which will enhance the utility of EcN in probiotic therapy. Key points • Two TASs in EcN were identified as hipAB and ccdAB. • Knockdown of HipAB and CcdAB resulted in decreased biofilm formation of EcN. • Transcriptional silencing of hipAB and ccdAB affected the persister formation of EcN. • An attractive link between TASs and stress response was unraveled in EcN. • CRISPRi afforded a fast and in situ annotation of multiple TASs simultaneously. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-020-10733-6) contains supplementary material, which is available to authorized users.


Announcement of Humanities and Medicine pages (PU from 58/4)


title: EU-ASEAN relations in the 2020s: pragmatic inter-regionalism?

text: The world in the late 1990s and early 2000s witnessed a proliferation of region-to-region institutional frameworks. There was a recognition that scale and leverage could create an advantage for economic relations, that security could benefit from cross-region dialogue and initiatives, and that some of the many global challenges, from global climate change to resource depletion, could be addressed more effectively at regional and even inter-regional levels. The EU-ASEAN dialogue itself presents an important model for inter-regional cooperation at the heart of these tangled institutional webs. This article assesses the ways in which the changing multilateral landscape and intra-regional crises within ASEAN and the EU have altered the relevance of inter-regional dialogue and initiatives.


Treatment of the COVID-19 pandemic: Preventing a missed opportunity()


Acute coronary syndrome and shock in the context of acute COVID-19 infection


title: NCI Workshop on Artificial Intelligence in Radiation Oncology: Training the Next Generation

text: Artificial intelligence (AI) is about to touch every aspect of radiotherapy from consultation, treatment planning, quality assurance, therapy delivery, to outcomes modeling. There is an urgent need to train radiation oncologists and medical physicists in data science to help shepherd AI solutions into clinical practice. Poorly trained personnel may do more harm than good when attempting to apply rapidly developing and complex technologies. As the amount of AI research expands in our field, the radiation oncology community needs to discuss how to educate future generations in this area. The National Cancer Institute (NCI) Workshop on AI in Radiation Oncology (Shady Grove, MD, April 4-5, 2019) was the first (https://dctd.cancer.gov/NewsEvents/20190523_ai_in_radiation_oncology.htm) of two data science workshops in radiation oncology hosted by the NCI in 2019. During this workshop, the Training and Education Working Group was formed by volunteers among the invited attendees. Its members represent radiation oncology, medical physics, radiology, computer science, industry, and the NCI. In this perspective article written by members of the Training and Education Working Group, we provide and discuss Action Points relevant for future trainees interested in radiation oncology AI: (1) creating AI awareness and responsible conduct; (2) implementing a practical didactic curriculum; (3) creating a publicly available database of training resources; and (4) accelerate learning and funding opportunities. Together, these Action Points can facilitate the translation of AI into clinical practice.


docid: nzpyptpm

title: Necrotizing tracheobronchitis with endotracheal tube obstruction in COVID-19 patients()


A French emergency department organisation in a coronavirus hotspot


title: Oral Complementary Medicine Use among People with Inflammatory Arthritis: An Australian Rheumatology Association Database Analysis

text: OBJECTIVES: To describe oral complementary medicine (CM) use in people with inflammatory arthritis, associations with use, and changes in use over time. METHODS: Demographic, clinical, and patient-reported outcome data from 5,630 participants with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) were extracted from the Australian Rheumatology Association Database (ARAD), a national observational database. CM use at entry into ARAD was ascertained for participants recruited between 2002 and 2018. CM was categorised according to the NIH/Cochrane schema (fatty acids, herbs, or supplements). Logistic regression was used to assess associations between demographic characteristics and CM use. Change in CM use between 2006 and 2016 was investigated using a nonparametric test for trend of rate by year. RESULTS: 2,156 (38.3%) ARAD participants were taking CM at enrolment (RA: 1,502/3,960 (37.9%), AS: 281/736 (38.2%), PsA: 334/749 (44.6%), and JIA: 39/185 (21.1%)). CM use was more prevalent in women (OR 1.3; 95% CI: 1.13-1.50), those with tertiary education (OR 1.32; 95% CI: 1.13-1.55), private health insurance (OR 1.26; (95% CI: 1.10-1.44), drinking alcohol sometimes (OR 1.22; 95% CI: 1.05-1.43), poorer function (HAQ) (OR 1.13; 95% CI: 1.02-1.24), use of NSAID (OR 1.32; 95% CI 1.17-1.50), weak (OR 1.21; 95% CI 1.05-1.41) but not strong opioids, and less prevalent in current smokers (OR 0.76; 95%: CI 0.63-0.91). CM use was not associated with pain, disease activity, or quality of life. The most common CMs were fish oils (N = 1,489 users) followed by glucosamine (N = 605). Both declined in use over time between 2006 and 2016 (27.5% to 21.4%, trend p = 0.85 and 15.5% to 6.4%, trend p < 0.01), respectively. CONCLUSION: Oral CM use is common among Australians with inflammatory arthritis. Its use is greater among women and those with tertiary education. Fish oil and glucosamine, the most common CMs, both declined in use over time.


title: Green polymeric nanomaterials for the photocatalytic degradation of dyes: a review

text: Pure and drinkable water will be rarer and more expensive as the result of pollution induced by industrialisation, urbanisation and population growth. Among the numerous sources of water pollution, the textile industry has become a major issue because effluents containing dyes are often released in natural water bodies. For instance, about two years are needed to biodegrade dye-derived, carcinogenic aromatic amines, in sediments. Classical remediation methods based upon physicochemical reactions are costly and still generate sludges that contain amine residues. Nonetheless, recent research shows that nanomaterials containing biopolymers are promising to degrade organic pollutants by photocatalysis. Here, we review the synthesis and applications of biopolymeric nanomaterials for photocatalytic degradation of azo dyes. We focus on conducting biopolymers incorporating metal, metal oxide, metal/metal oxide and metal sulphide for improved biodegradation. Biopolymers can be obtained from microorganisms, plants and animals. Unlike fossil-fuel-derived polymers, biopolymers are carbon neutral and thus sustainable in the context of global warming. Biopolymers are often biodegradable and biocompatible.


title: Estimating, monitoring and minimizing the travel footprint associated with the development of the Athena X-ray Integral Field Unit: An on-line travel footprint calculator released to the science community

text: Global warming imposes us to reflect on the way we carry research, embarking on the obligation to minimize the environmental impact of our research programs, with the reduction of our travel footprint being one of the easiest actions to implement, thanks to the advance of digital technology. The X-ray Integral Field Unit (X-IFU), the cryogenic spectrometer of the Athena space X-ray observatory of the European Space Agency will be developed by a large international consortium, currently involving 240 members, split over 13 countries, 11 in Europe, Japan and the United States. The travel footprint associated with the development of the X-IFU is to be minimized. For that purpose, a travel footprint calculator has been developed and released to the X-IFU consortium members. The calculator uses seven different emission factors and methods leading to estimates that differ by up to a factor of 5 for the same flying distance. These differences illustrate the lack of standards and regulations for computing the footprint of flight travels and are explained primarily, though partly, by different accounting of non- CO2 effects. When accounting for non-CO2 effects, the flight emission is estimated as a multiple of the direct CO2 emission from burning fuel, expressed in CO2-equivalent (CO2eq), with a multiplication factor ranging from 2 to 3. Considering or ignoring this multiplication factor is key when comparing alternative modes of transportation to flying. The calculator enables us to compute the travel footprint of a large set of travels and can help identify a meeting place that minimizes the overall travel footprint for a large set of possible city hosts, e.g. cities with large airports. The calculator also includes the option for a minimum distance above which flying is considered the most suitable transport option; below that chosen distance, the emission of train journeys are considered. To demonstrate its full capabilities, the calculator is first run on one of the largest scientific meetings; the fall meeting of the American Geoscience Union (AGU) gathering some 24000 participants and the four meetings of the lead authors of the working group I of the Intergovernmental Panel on Climate Change (IPCC) preparing its sixth assessment report. In both examples, the calculator is used to compute the location of the meetings that would minimize the travel footprint. Then, the travel footprint of a representative set of X-IFU related meetings is estimated to be 500 tons of CO2eq per year (to place this number in perspective, it is equivalent to 2 billion kilometers driven by an average passenger vehicle). Of this amount, each annual consortium meeting accounts for 100 tons, being located at a site of minimum emission and for a minimum distance for flying of 700 km. Actions to reduce the X-IFU travel footprint are being implemented, e.g., the number of large consortium meetings has been reduced to one per year and face-to-face working meetings are progressively replaced by video conferences. As the on-line travel footprint calculator may be used to all scientific collaborations and meetings, the calculator and its methodology described in this paper are made freely available to the science communitycommunity (https://travel-footprintcalculator.irap.omp.eu).


title: Effects of self-employment on hospitalizations: instrumental variables analysis of social security data

text: The importance of self-employment and small businesses raises questions about their health effects and public policy implications, which can only be addressed with suitable data. We explore the relationship between self-employment and health by drawing on comprehensive longitudinal administrative data to explore variation in individual work status and by applying novel instrumental variables. We focus on an objective outcome—hospital admissions—that is not subject to recall or other biases that may affect previous studies. Our main findings, based on a sample of about 6,500 individuals followed monthly from 2005 to 2011 and who switch between self-employment and wage work along that period, suggest that self-employment has a positive effect on health as it reduces the likelihood of hospital admission by at least half.


title: Verantwoordelijkheid

text: “Verbaasd heb ik in de periode van maart tot nu (de 1(e) week van mei) gekeken naar het gedrag van mensen in deze crisistijd. Veel mensen verwijten anderen steeds dat iets niet in orde is, maar komen zelf niet met goede raad en daad. In de politiek bijvoorbeeld. Op het moment dat het land in een crisis is en alle hulp en ideeën welkom zijn, gaan we urenlang verwijten over en weer horen. Vervolgens krijg je ook nog ruzies in kleine partijen zoals DENK en 50PLUS. Is dit onze beschaving?


title: Vaknieuws

text: Dit blijkt uit onderzoek van de Universiteit van Amsterdam, Cardiologie Centra Nederland en Amsterdam uMC. Onderzoekers vroegen gezonde proefpersonen om te spreken en te hoesten. Ze fotografeerden met laserlichttechnieken de druppeltjes die daarbij vrijkwamen. Ze namen zowel bij het spreken als bij het hoesten grote hoeveelheden kleine druppeltjes waar.


title: ‘Ik heb geleerd mijn tijd goed te bewaken’

text: Op bezoek in coronatijd. Dat betekent niet alleen anderhalve meter afstand, maar ook een lege salon. Bij BeautyCorner in Geertruidenberg komen tijdens het interview vooral klanten langs voor een tubetje crème. Een enkele keer zijn er klanten voor een medische voetbehandeling. “De crisis duurt lang, erg lang”, zegt eigenaar Arlette de Jongh.


Science education during times of crisis: calling for reflections, responses, and forward thinking from the CSSE community


title: Current Strategies in Development of New Chromone Derivatives with Diversified Pharmacological Activities: A Review

text: Chromone derivatives possess a spectrum of biological activities. Chromone has been recognized as a privileged structure for new drug invention and development. Substitution pattern of chromone scaffold determines different type of biological activities. The type, number and position of substituents connected to the chromone core play a vital role in determining pharmacological activities. In the present review, we have discussed new chromone derivatives as anticancer, anti-diabetic, antimicrobial, anti-inflammatory, antioxidant and as anti-Alzheimer agents. This review deals with the chromone derivatives prepared by combining chromone molecule with various natural and synthetic pharmacophores and pharmacological activities presented by them. The main aim is to highlight the diversified pharmacological activities exhibited by chromone hybrid molecules during the last eight to ten years.


Redeployment: creating value through diversity


Der Unterschied


Is amalgam more suitable?


Successfully protecting staff


Hydroxychloroquine shortage


A Renowned Indian Physicst, an Obituary of Prof. S. K. Joshi


Beards and masks


Repurposing the 7Ps


Povidone iodine development


docid: jlfuuwkm

title: Urgent hub data


Antibody testing


Incredulity and disappointment


The future for dental events


Consent during a pandemic


Guidelines published to enable confident return to dental practice


Team adapt elements of the Spitfire to design new PPE for dentistry


Rebooting dentistry


Age-appropriate antibiotics


Altered exodontia techniques


A DCT on a trauma and orthopaedic ward


Undergraduate uncertainty


Spotlight on teledentistry


Mitteilungen der DGSM


Knocked out!


Events of Interest


title: Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis: results of a multicenter randomized placebo-controlled clinical trial

text: BACKGROUND: Surgical site infections (SSIs) are common complications after colorectal surgery. Oral non-absorbable antibiotic prophylaxis (OAP) can be administered preoperatively to reduce the risk of SSIs. Its efficacy without simultaneous mechanical cleaning is unknown. METHODS: The Precaution trial was a double-blind, placebo-controlled randomized clinical trial conducted in six Dutch hospitals. Adult patients who underwent elective colorectal surgery were randomized to receive either a three-day course of preoperative OAP with tobramycin and colistin or placebo. The primary composite endpoint was the incidence of deep SSI or mortality within 30 days after surgery. Secondary endpoints included both infectious and non-infectious complications at 30 days and six months after surgery. RESULTS: The study was prematurely ended due to the loss of clinical equipoise. At that time, 39 patients had been randomized to active OAP and 39 to placebo, which reflected 8.1% of the initially pursued sample size. Nine (11.5%) patients developed the primary outcome, of whom four had been randomized to OAP (4/39; 10.3%) and five to placebo (5/39; 12.8%). This corresponds to a risk ratio in the intention-to-treat analysis of 0.80 (95% confidence interval (CI) 0.23–2.78). In the per-protocol analysis, the relative risk was 0.64 (95% CI 0.12–3.46). CONCLUSIONS: Observational data emerging during the study provided new evidence for the effectiveness of OAP that changed both the clinical and medical ethical landscape for infection prevention in colorectal surgery. We therefore consider it unethical to continue randomizing patients to placebo. We recommend the implementation of OAP in clinical practice and continuing monitoring of infection rates and antibiotic susceptibilities. TRIAL REGISTRATION: The PreCaution trial is registered in the Netherlands Trial Register under NL5932 (previously: NTR6113) as well as in the EudraCT register under 2015–005736-17.


title: Rapid decline of Zika virus NS1 antigen-specific antibody responses, northeastern Brazil

text: Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family. After decades of circulation in Asia, ZIKV was introduced to Brazil in 2014–2015, associated with a rise in congenital malformations. Unlike the genetically related dengue virus (DENV), ZIKV constitutes only one serotype. Although assumed that ZIKV infection may engender lifelong immunity, the long-term kinetics of ZIKV antibody responses are unclear. We assessed long-term kinetics of ZIKV NS1-IgG response in 144 individuals from 3 different subpopulations: HIV patients, tuberculosis patients and healthy individuals first tested in 2016 and retested 1.5–2 years after the 2015–2016 ZIKV epidemic in Salvador de Bahia, Brazil, using a widely distributed NS1-based commercial ELISA. The seropositivity in 2016 reached 59.0% (85/144, 95% confidence interval (CI) 50.7–66.7%), and decreased to 38.6% (56/144, CI 31.3–47.0%) 1.5–2 years later. In addition, the median ZIKV NS1-ELISA reactivity for individuals that remained positive in both timepoints significantly decreased from a ratio of 4.4 (95% CI 3.8–5.0) to 1.6 (95% CI 1.6–1.9) over the 2-year interval (Z: − 6.1; p < 0.001) irrespective of the subpopulation analyzed. Initial 2016 DENV antibody response was non-significant between groups, suggesting comparable DENV background. The high 20.6% seroreversion suggest that widely used serologic tests may fail to account a considerable proportion of past ZIKV infections in flavivirus endemic countries. In addition, ZIKV immunity might be shorter-lived than previously thought, which may contribute to local ZIKV resurgence once individual immune responses wane sufficiently to reduce community protective immunity in addition to birth and migration.


docid: qnmqflpa

title: Editorial to the Second Issue of Childhood Vulnerability Journal


title: Dental management of patients with substance use disorder

text: Substance use disorder (SUD) is a relapsing brain disorder characterized by compulsion and chronicity. SUD has detrimental effects on oral health. Drugs and alcohol negatively impact oral health by inducing a myriad of orofacial conditions including xerostomia, dental caries, periodontal disease, bruxism, pre-cancer and cancer, to name a few. Limited recommendations are available for dental professionals on how best to manage patients afflicted with SUD. The aim of this article is to review the oral health consequences of alcohol and commonly abused drugs to provide guidelines for the public health community and dental professionals. The United Nations estimates that a quarter billion people, representing five per cent of the global adult population, used drugs at least once in 2015. Developing public health interventions that include the participation of dental professionals and access to dental services for persons afflicted with SUD could play a critical role in improving their quality of life, their recovery, and their reintroduction into society.


title: Variations in killer-cell immunoglobulin-like receptor and human leukocyte antigen genes and immunity to malaria

text: Malaria is one of the deadliest infectious diseases in the world. Immune responses to Plasmodium falciparum malaria vary among individuals and between populations. Human genetic variation in immune system genes is likely to play a role in this heterogeneity. Natural killer (NK) cells produce inflammatory cytokines in response to malaria infection, kill intraerythrocytic Plasmodium falciparum parasites by cytolysis, and participate in the initiation and development of adaptive immune responses to plasmodial infection. These functions are modulated by interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigens (HLAs). Therefore, variations in KIR and HLA genes can have a direct impact on NK cell functions. Understanding the role of KIRs and HLAs in immunity to malaria can help to better characterize antimalarial immune responses. In this review, we summarize the different KIRs and HLAs associated with immunity to malaria thus far.


title: Leishmaniosis

text: Leishmania spp. affecting cats include L. infantum, L. mexicana, L. venezuelensis, L. amazonensis, and L. braziliensis. Leishmania infantum is the species most frequently reported in cats and causes feline leishmaniosis (FeL). Cats exposed to L. infantum are able to mount a cell-mediated immune response that does not parallel antibody production. Cats with L. infantum-associated clinical disease have positive blood PCR and low to very high antibody levels. About half of the clinical cases of FeL are diagnosed in cats with impaired immunocompetence. Skin or mucocutaneous lesions are the most common clinical findings; however, FeL is a systemic disease. Skin or mucocutaneous lesions and lymph node enlargement are seen in at least half of cases, ocular or oral lesions and some aspecific signs (weight loss, anorexia, lethargy) in about 20–30% of cases, and many other clinical signs (e.g., respiratory, gastrointestinal) are sporadically observed. Ulcerative and nodular lesions due to diffuse granulomatous dermatitis are the most frequent skin manifestations, mainly distributed on the head or symmetrically on the distal limbs. Diagnosis can be obtained by cytology and histology, and immunohistochemistry is useful to confirm the causative role of Leishmania infection in the dermopathological manifestations; however, other skin diseases may coexist with FeL. Polymerase chain reaction is used in case of suggestive lesions with lack of parasites and for Leishmania speciation. Comorbidities, coinfections, and chronic renal disease influence the prognosis and should be investigated. Treatment is currently based on the same drugs used for canine leishmaniosis, and generally clinical cure is obtained; however recurrence is possible.


Addressing PA burnout


Reperfusion of ST-Segment–Elevation Myocardial Infarction in the COVID-19 Era: Business as Usual?


title: Application of median lethal concentration (LC(50)) of pathogenic microorganisms and their antigens in vaccine development

text: OBJECTIVE: Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms. Hence, the modified arithmetical formula of Reed and Muench has been integrated with other formulas and used to determine bacterial colony forming unit/viral concentration, virulence and immunogenicity. RESULTS: Microorganisms’ antigens tested are Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa in mice and rat, Edwardsiella ictaluri, Aeromonas hydrophila, Aeromonas veronii in fish, New Castle Disease virus in chicken, Sheep Pox virus, Foot-and-Mouth Disease virus and Hepatitis A virus in vitro, respectively. The LC(50)s for the pathogens using different routes of administrations are 1.93 × 10(3)(sheep poxvirus) and 1.75 × 10(10) for Staphylococcus aureus (ATCC29213) in rat, respectively. Titer index (TI) equals N log(10) LC(50) and provides protection against lethal dose in graded fashion which translates to protection index. N is the number of vaccine dose that could neutralize the LC(50). Hence, parasite inoculum of 10(3) to 10(11) may be used as basis for determination of LC(50) and median bacterial concentrations (BC(50)).Pathogenic dose for immune stimulation should be sought at concentration about LC(10).


Adapting Scientific Conferences to the Realities Imposed by COVID-19


title: Radiological Society of North America Chest CT Classification System for Reporting COVID-19 Pneumonia: Interobserver Variability and Correlation with RT-PCR

text: PURPOSE: To evaluate the Radiological Society of North America (RSNA) chest CT classification system for reporting COVID-19 pneumonia. MATERIALS AND METHODS: Chest CT scans of consecutive patients with suspected COVID-19 were retrospectively and independently evaluated by two chest radiologists and a fifth-year radiology resident using the RSNA chest CT classification system for reporting COVID-19 pneumonia. Interobserver agreement was evaluated by calculating weighted kappa (ĸ) coefficients. Proportion of patients with real-time reverse transcriptase polymerase chain reaction (RT-PCR) confirmed COVID-19 in each of the four chest CT categories ("typical", "indeterminate", "atypical", and "negative" features for COVID-19) was calculated. RESULTS: Ninety-six patients (61 males, median age 70 years [range 29-94]) were included, of whom 45 had RT-PCR confirmed COVID-19. The number of patients assigned to chest CT categories "typical", "indeterminate", "atypical", and "negative" by the three readers ranged from 18-29, 26-43, 19-31, and 5-8 respectively. □ coefficient between the chest radiologists was 0.663 (95% confidence interval [CI]: 0.565-0.761). □ coefficients between the chest radiologists and the fifth-year radiology resident were 0.570 (95% CI: 0.443-0.696) and 0.564 (95% CI: 0.451-0.678). Proportion of patients with RT-PCR confirmed COVID-19 in the chest CT categories "typical", "indeterminate", "atypical", and "negative" for the three readers ranged from 76.9%-96.6%, 51.2%-64.1%, 2.8%-5.3%, and 20-25%, respectively. CONCLUSION: The RSNA chest CT classification system for reporting COVID-19 pneumonia has moderate to substantial interobserver agreement. However, the proportion of RT-PCR confirmed COVID-19 cases in the categories "atypical appearance" and "negative for pneumonia" is non-negligible.


title: Development of a Large-Scale Cyanation Process Using Continuous Flow Chemistry En Route to the Synthesis of Remdesivir

text: [Image: see text] The implementation of cyanation chemistry at manufacturing scales using batch equipment can be challenging because of the hazardous nature of the reagents employed and the tight control of reaction parameters, including cryogenic temperatures, that help to afford acceptable selectivity and conversion for the desired reaction. Application of continuous flow chemistry offers a means to mitigate the risk associated with handling large amounts of hazardous reagents and to better control the reaction parameters. A case study describing the cyanation of a glycoside using continuous flow chemistry toward the synthesis of the drug candidate remdesivir is presented.


Checking in with Women Materials Scientists During a Global Pandemic: May 2020


title: Possible SARS-coronavirus 2 inhibitor revealed by simulated molecular docking to viral main protease and host toll-like receptor

text: Aim: SARS-coronavirus 2 main protease (Mpro) and host toll-like receptors (TLRs) were targeted to screen potential inhibitors among traditional antiviral medicinal plants. Materials & methods: LeDock software was adopted to determine the binding energy between candidate molecules and selected protein pockets. Enrichment analyses were applied to illustrate potential pharmacology networks of active molecules. Results: The citrus flavonoid rutin was identified to fit snugly into the Mpro substrate-binding pocket and to present a strong interaction with TLRs TLR2, TLR6 and TLR7. One-carbon metabolic process and nitrogen metabolism ranked high as potential targets toward rutin. Conclusion: Rutin may influence viral functional protein assembly and host inflammatory suppression. Its affinity for Mpro and TLRs render rutin a potential novel therapeutic anti-coronavirus strategy.


title: Hepatobiliary and Pancreatic Manifestations of Coronavirus Disease 2019

text: Coronavirus disease 2019 (COVID-19) is a new infectious disease that has spread rapidly throughout the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a member of the Coronaviridae family. Though the pulmonary involvement is a major cause of morbidity and mortality, involvement of the gastrointestinal tract, liver, and pancreas has been explained in these patients. The literature is rapidly changing because of influx of new information with every passage of time. The most common hepatic presentation is mild elevation of aspartate transaminase and alanine transaminase, which does not require specific treatment. Occasionally, patients can have severe liver injury. Because of underlying predisposing factors such as diabetes mellitus, hypertension, and obesity, patients with nonalcoholic liver disease may be at risk of severe disease. Patients with decompensated liver disease may also be vulnerable to severe disease. Behavior of SARS-CoV-2 in patients with chronic hepatitis B and C, autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis is yet to be seen. The prevalence and severity of COVID-19 patients with the aforementioned diseases may be different. The effect of SARS-CoV-2 on an underlying liver disease is not known. COVID-19 may complicate the peritransplant period and throw new challenges in these patients. Drugs used to treat severe COVID-19 may cause liver injury and may have an effect on the underlying disease activity. Both hepatic and pancreatic involvement is related to the severity of COVID-19 disease. Serum amylase and lipase levels may be elevated in patients with severe COVID-19 disease. The involvement of pancreatic islet cells may lead to deranged blood sugar levels and potentially predispose to future diabetes mellitus. There are many unknown facts that will unfold with the passage of time.


Der festliegende Esel – Wie Sie subtile Symptome richtig interpretieren


COVID-19: Beyond Respiratory Tract


title: Disinfection of Endoscopy and Reusability of Accessories

text: Corona viruses are a group of medium-sized positive-sense single-stranded RNA viruses with crown-like structure due to projections noted over the surface of the virus. The infection has been declared as a pandemic by the world health organization (WHO) in March 2020. Health care professionals in endoscopy are at high risk of infection by novel corona virus disease 2019 (COVID-19) from inhalation of droplets, conjunctival contact, feces, and touch contamination. Upper gastrointestinal (GI) endoscopy is considered to be a high-risk aerosol-generating procedures (AGPs) and the live virus has been found in patient stool. Flexible endoscopes when contaminated have been considered as the vector for transmission of infections. Infections related to the side viewing endoscopes and endoscopic ultrasound scopes are more frequent than upper GI scope and colonoscopes. Stratifying patients needing endoscopy and deferral of elective procedures will help to decrease the virus spread. Planning and revision of workflows is necessary for safety of patient and staff and to successfully provide infection prevention and control measures, for this a “three zones and two passages” concept should be followed. Manual cleaning followed by high-level disinfection (HLD), effectively eliminates nearly all microorganisms from endoscopes during reprocessing. Transmission of viral infections during endoscopy is quite rare and, it is usually the result of noncompliance from the essential steps of reprocessing. Reuse of any disposable GI endoscopic device is strongly discouraged. Environmental decontamination is essential to reduce the risk of fomite transmission. Noncritical environmental surfaces frequently touched by hands (e.g., bedside tables and bed rails) and endoscopy furniture and floor should be considered heavily contaminated in patients with intermediate or high risk of COVID-19 and should be thoroughly disinfected at the end of each procedure. If available, negative pressure rooms are preferred for endoscopy, as has been advised by Centers for Disease Control and Prevention (CDC). Staff involved in reprocessing and the cleaning of endoscopy rooms should utilize personal protective equipment (PPE) including N95 mask. Reprocessing staff should undergo necessary training and ongoing annual assessment of competency.


title: 2019 Novel Coronavirus Infection: Gastrointestinal Manifestations

text: The world is witnessing a major public health crisis in the wake of the third coronavirus strain pandemic, a novel coronavirus (severe acute respiratory syndrome coronavirus 2). Although initially thought to be a pure respiratory pathogen, recent reports have highlighted not only the extrapulmonary effects of the virus but also, importantly, the gastrointestinal tract (GIT) effects. Various studies have looked into the effects of this novel coronavirus infection (coronavirus-19 disease [COVID-19]) on GIT involvement with reports of more frequent involvement than previously expected. With feco-oral transmission, debate being conclusively proven with fecal samples testing positive for COVID-19 and longer shedding time, it only underlines the importance of GIT involvement. Moreover, the presence of other GI diseases, such as inflammatory bowel disease, with COVID-19 infection might wreak havoc leading to poor patient outcomes.


Emerging Medico-legal Issues Novel to COVID Era


COVID-2019 and Its Shadow on Gastrointestinal Endoscopy


title: Being Legally Sound in the COVID-19 Era

text: All the three Indian gastroenterology societies (Society of Gastrointestinal Endoscopy of India, Indian Society of Gastroenterology, and Indian National Association for the Study of the Liver) jointly recommend to consider only emergency and urgent endoscopy procedures for the next 1 month or till the current threat due to coronavirus disease 2019 (COVID-19) is over. Two laws that are penal in nature are now applicable in the current pandemic, namely the Epidemics Diseases Act 1897 and the Indian Penal Code 1860. No act of an endoscopist should be seen to be in contravention of any of the aforementioned laws, and the sections thereunder as provisions of the Indian Penal Code can be attracted in the current scenario for spreading an infectious disease either knowingly (Section 270) or unknowingly or negligently (Section 269). Section 4 of the Epidemics Disease Act 1897 gives legal protection to every person who has acted under this Act or the directions issued under this Act subject to only one condition, that is, the act must have been done in good faith. Though the hospitals are obliged to ensure personal safety of its staff legally, morally and ethically, because of the huge gap in demand and supply of personal protective equipment (PPE), it is advisable to arrange PPE on one’s own to first protect oneself and then, by extension, to prevent the spread to others. The dictum is “take care of yourself.” Self-preservation is a supreme law. In the current COVID-19 pandemic conditions, certain additional information, to be agreed upon by the patient, needs to be incorporated in the consent. It should be incorporated in the consent that: • While all the necessary precautions are being taken, there is a finite though small risk that the patient may contract the infection from the hospital. • He/she indemnifies the hospital and the endoscopist against any such liability arising out of any action taken while doing the procedure. • Furthermore, to protect the patient him/herself, he/she agrees to get the preprocedural test for COVID-19 as well as bear the additional cost of the PPE used by the endoscopist and support staff. Several of those who have undergone an endoscopy would require a follow-up consultation. As it is difficult to have physical interaction, teleconsultation may be done as per the telemedicine practice guidelines issued by the Medical Council of India (MCI).


title: Navigating Through the Financial Crisis that may Occur during and after the COVID-19 Pandemic for Gastroenterologists

text: Introduction Considering the specific set of gastrointestinal endoscopy practitioners, it is witnessed that the number of patients forelective procedures are being deferred by the patients amid various concerns ranging from financial constraint to the fear of infection from the dreaded coronavirus. With Routine endoscopy procedures recommended to be safely postponed, the impact on the practice of Gastrointestinal Endoscopists shall be magnified. Assessment and Strategy The article discusses impact and remedial actions that may be taken by Gastrointestinal Endoscopists, which classified into: - Anindependent practitioner - A consultant - An employee The article further touches upon the difficulties that might be envisaged by the Gastrointestinal Endoscopists, and obtain a financial understanding of what could potentially lead to an existential crisis? Those with cash reserves sit in a pleasant position i.e. they can buy assets at an attractive price, experiment with new ideas, research and development, etc. It is imperative in these times to understand the uncertainty cast on operations of Gastrointestinal Endoscopists and prepare a response plan for coming out of this economic crisis. A roadmap also has been devised which provides a possible outline of a plan that can be implemented for handling the economic crisis. It is also important to answer these two questions: 1. Who do I want to be during the crisis? 2. Who do I want to be when this is over?


The Corona Blitzkrieg: The Developed World on its Knees


Exploring COVID-19 Therapies: An Extraordinary Global Challenge


Personal Protective Equipment use for Gastrointestinal Endoscopy: Are we Ready?


docid: wccwqxbu

title: Triaging: A New Algorithm for Endoscopy


title: Physiotherapie bei erwachsenen Patienten mit Verdacht oder Nachweis von COVID-19 an der Charité Universitätsmedizin Berlin

text: Die physikalisch-therapeutische Versorgung von Patienten im Rahmen der aktuellen Corona-Pandemie ist auch für die Physikalische Medizin eine neue Erfahrung.( Tab. 1 )


title: Systemrelevanz der Pflegeberufe in Zeiten von Corona – und darüber hinaus

text: Die Corona-Pandemie stellt die Gesellschaft vor unvorhergesehene Herausforderungen: Beschränkungen zur Reduktion der sozialen Kontakte werden angeordnet, um eine Ausbreitung des Virus zumindest zu verlangsamen. Das Gesundheitswesen ist mit einem dramatischen Mangel an Schutzausrüstung konfrontiert. Die Anzahl an (Intensiv-)Betten wird deutlich erhöht, um der zunehmenden Zahl an intensivpflichtigen Patientinnen und Patienten gerecht werden zu können. Parallel zu diesen neuen Herausforderungen wird in der aktuellen Situation der bereits seit längerem bestehende Fachkräftemangel in der Pflege vollends ersichtlich.


Osteopathie für Kleintiere: Der sanfte Weg zu mehr Beweglichkeit und Ausgeglichenheit


Artgerecht! – Wie gesund ist die vegetarische und vegane Ernährung von Hund und Katze?


Gastrointestinal Endoscopy during COVID: Do Some, Leave Most


Welche Schutzmaske schützt vor COVID-19? Was ist evidenzbasiert?


Epidemiology of COVID-19: Implications for a Gastroenterologist


Be Aware, Be Alert, Be Prepared: Endoscopy during the COVID-2019 Pandemic


Atypischer Hypoadrenokortizismus (Morbus Addison) beim Hund: Ein Fall für internistische Detektivarbeit!


title: Emerging Treatment and Prevention Strategies against COVID-19: A Brief Update

text: Patients with novel coronavirus disease 2019 (COVID-19) are at significantly increased risk for mortality and morbidity. Current management remains supportive care, ranging from symptomatic outpatient management to full–intensive care support, including intravenous fluids, invasive, and non-invasive oxygen supplementation. In patients with septic shock, treatment with antibiotics and vasopressors are recommended to keep mean arterial pressure (MAP) ≥ 65 mm Hg and lactate < 2 mmol/L. Because of the lack of effectiveness and possible adverse effects, routine corticosteroids should be avoided unless they are indicated for another reason (exacerbation of asthma or chronic obstructive pulmonary disease [COPD], and septic shock in whom fluids and vasopressors do not restore hemodynamic stability). There is currently no sufficient evidence of efficacy of hydroxychloroquine/chloroquine, remdesivir, and other antivirals in the treatment or prevention of COVID-19. Limited evidence shows that COVID-19 convalescent plasma can be used as a treatment of COVID-19 without the occurrence of severe adverse events. Drug regulatory agencies granted an emergency-use authorization of chloroquine/hydroxychloroquine and remdesivir to treat patients when a clinical trial is not available or participation is not feasible. Chloroquine and hydroxychloroquine are associated with QT interval prolongation and life-threatening cardiac arrhythmia in patients with pre-existing cardiovascular disease. Guidelines are issued for use of convalescent plasma in patients with serious or immediately life-threatening COVID-19. Data from several ongoing randomized controlled trials will provide further evidence regarding the safety and efficacy of these drugs for the treatment of COVID-19.


CAPNETZ fokussiert auf COVID-19


Phacoemulsification and pars plana vitrectomy: no evidence of an increased risk of aerosol transmission


title: Scalable Hierarchical Aggregation and Reduction Protocol (SHARP)(TM) Streaming-Aggregation Hardware Design and Evaluation

text: This paper describes the new hardware-based streaming-aggregation capability added to Mellanox’s Scalable Hierarchical Aggregation and Reduction Protocol in its HDR InfiniBand switches. For large messages, this capability is designed to achieve reduction bandwidths similar to those of point-to-point messages of the same size, and complements the latency-optimized low-latency aggregation reduction capabilities, aimed at small data reductions. MPI_Allreduce() bandwidth measured on an HDR InfiniBand based system achieves about 95% of network bandwidth. For medium and large data reduction this also improves the reduction bandwidth by a factor of 2–5 relative to host-based (e.g., software-based) reduction algorithms. Using this capability also increased DL-Poly and PyTorch application performance by as much as 4% and 18%, respectively. This paper describes SHARP Streaming-Aggregation hardware architecture and a set of synthetic and application benchmarks used to study this new reduction capability, and the range of data sizes for which Streaming-Aggregation performs better than the low-latency aggregation algorithm.


title: FASTHash: FPGA-Based High Throughput Parallel Hash Table

text: Hash table is a fundamental data structure that provides efficient data store and access. It is a key component in AI applications which rely on building a model of the environment using observations and performing lookups on the model for newer observations. In this work, we develop FASTHash, a “truly” high throughput parallel hash table implementation using FPGA on-chip SRAM. Contrary to state-of-the-art hash table implementations on CPU, GPU, and FPGA, the parallelism in our design is data independent, allowing us to support p parallel queries ([Formula: see text]) per clock cycle via p processing engines (PEs) in the worst case. Our novel data organization and query flow techniques allow full utilization of abundant low latency on-chip SRAM and enable conflict free concurrent insertions. Our hash table ensures relaxed eventual consistency - inserts from a PE are visible to all PEs with some latency. We provide theoretical worst case bound on the number of erroneous queries (true negative search, duplicate inserts) due to relaxed eventual consistency. We customize our design to implement both static and dynamic hash tables on state-of-the-art FPGA devices. Our implementations are scalable to 16 PEs and support throughput as high as 5360 million operations per second with PEs running at 335 MHz for static hashing and 4480 million operations per second with PEs running at 280 MHz for dynamic hashing. They outperform state-of-the-art implementations by 5.7x and 8.7x respectively.


docid: axfoktwu

title: Predicting Job Power Consumption Based on RJMS Submission Data in HPC Systems

text: Power-aware scheduling is a promising solution to the resource usage monitoring of High-Performance Computing facility electrical power consumption. This kind of solution needs a reliable estimation of job power consumption to feed the Resources and Jobs Management System at submission time. Available data for inference is restricted in practice because unavailable or even untrustworthy. We propose in this work an instance-based model using only the submission logs and user provided job data. GID and the number of tasks per node appears to be good features for prediction of a job’s average power consumption. Moreover, we extant this model to production context with online computation to make a practical global power prediction from job submission data using instances re-weighting. The performance of the online model are excellent on COBALT’s data. With any doubt this model will be a good candidate for the achievement of consistent power-aware scheduling for other computing centers with similar informative inputs.


title: Load-Balancing Parallel Relational Algebra

text: Relational algebra (RA) comprises a basis of important operations, sufficient to power state-of-the-art reasoning engines for Datalog and related logic-programming languages. Parallel RA implementations can thus play a significant role in extracting parallelism inherent in a wide variety of analytic problems. In general, bottom-up logical inference can be implemented as fixed-point iteration over RA kernels; relations dynamically accumulate new tuples of information according to a set of rules until no new tuples can be discovered from previously inferred tuples and relevant rules (RA kernels). While this strategy has been quite successful in single-node contexts, it poses unique challenges when distributed over many-node, networked clusters—especially regarding how the work-load is balanced across available compute resources. In this paper, we identify two fundamental kinds of load imbalance and present a strategy to address each. We investigate both spatial load imbalance—imbalance across each relation (across compute nodes)—and temporal load imbalance–imbalance in tuples produced across fixed-point iterations. For spatial balancing, we implement refinement and consolidation procedures. For temporal balancing, we implement a technique that permits the residual workload from a busy iteration to roll over to a new iteration. In sum, these techniques permit fully dynamic load-balancing of relational algebra that is robust to changes across time.


title: Pattern-Aware Staging for Hybrid Memory Systems

text: The ever increasing demand for higher memory performance and—at the same time—larger memory capacity is leading the industry towards hybrid main memory designs, i.e., memory systems that consist of multiple different memory technologies. This trend, however, naturally leads to one important question: how can we efficiently utilize such hybrid memories? Our paper proposes a software-based approach to solve this challenge by deploying a pattern-aware staging technique. Our work is based on the following observations: (a) the high-bandwidth fast memory outperforms the large memory for memory intensive tasks; (b) but those tasks can run for much longer than a bulk data copy to/from the fast memory, especially when the access pattern is more irregular/sparse. We exploit these observations by applying the following staging technique if the accesses are irregular and sparse: (1) copying a chunk (few GB of sequential data) from large to fast memory; (2) performing a memory intensive task on the chunk; and (3) writing it back to the large memory. To check the regularity/sparseness of the accesses at runtime with negligible performance impact, we develop a lightweight pattern detection mechanism using a helper threading inspired approach with two different Bloom filters. Our case study using various scientific codes on a real system shows that our approach achieves significant speed-ups compared to executions with using only the large memory or hardware caching: 3[Formula: see text] or 41% speedups in the best, respectively.


title: Understanding HPC Benchmark Performance on Intel Broadwell and Cascade Lake Processors

text: Hardware platforms in high performance computing are constantly getting more complex to handle even when considering multicore CPUs alone. Numerous features and configuration options in the hardware and the software environment that are relevant for performance are not even known to most application users or developers. Microbenchmarks, i.e., simple codes that fathom a particular aspect of the hardware, can help to shed light on such issues, but only if they are well understood and if the results can be reconciled with known facts or performance models. The insight gained from microbenchmarks may then be applied to real applications for performance analysis or optimization. In this paper we investigate two modern Intel x86 server CPU architectures in depth: Broadwell EP and Cascade Lake SP. We highlight relevant hardware configuration settings that can have a decisive impact on code performance and show how to properly measure on-chip and off-chip data transfer bandwidths. The new victim L3 cache of Cascade Lake and its advanced replacement policy receive due attention. Finally we use DGEMM, sparse matrix-vector multiplication, and the HPCG benchmark to make a connection to relevant application scenarios.


docid: tdeveikn

title: Shared-Memory Parallel Probabilistic Graphical Modeling Optimization: Comparison of Threads, OpenMP, and Data-Parallel Primitives

text: This work examines performance characteristics of multiple shared-memory implementations of a probabilistic graphical modeling (PGM) optimization code, which forms the basis for an advanced, state-of-the art image segmentation method. The work is motivated by the need to accelerate scientific image analysis pipelines in use by experimental science, such as at x-ray light sources, and is motivated by the need for platform-portable codes that perform well across many different computational architectures. The primary focus of this work and its main contribution is an in-depth study of shared-memory parallel performance of different implementations, which include those using alternative parallelization approaches such as C11-threads, OpenMP, and data parallel primitives (DPPs). Our results show that, for this complex data-intensive algorithm, the DPP implementation exhibits better runtime performance, but also exhibits less favorable scaling characteristics than the C11-threads and OpenMP counterparts. Based upon a set of experiments that collect hardware performance counters on multiple platforms, the reason for the runtime performance difference appears to be due primarily to algorithmic efficiency gains: the reformulation from the traditional C11-threads and OpenMP expression of the solution into that of data parallel primitives results in significantly fewer instructions being executed. This study is the first of its type to do performance analysis using hardware counters for comparing methods based on VTK-m-based data-parallel primitives with those based on more traditional OpenMP or threads-based parallelism. It is timely, as there is increasing awareness of the need for platform portability in light of increasing node-level parallelism and increasing device heterogeneity.


title: Embedding Algorithms for Quantum Annealers with Chimera and Pegasus Connection Topologies

text: We propose two new algorithms – Spring-Based MinorMiner (SPMM) and Clique-Based MinorMiner (CLMM) – which take as input the connectivity graph of a Quadratic Unconstrained Binary Optimization (QUBO) problem and produce as output an embedding of the input graph on a host graph that models the topology of a quantum computing device. As host graphs, we take the Chimera graph and the Pegasus graph, which are the topology graphs of D-Wave’s 2000 qubit (first introduced in 2017) and 5000 qubit (expected 2020) quantum annealer devices, respectively. We evaluate our algorithms on a large set of random graph QUBO inputs (Erdős-Rényi [Formula: see text], Barabási-Albert and d-regular graphs) on both host topologies against other embedding algorithms. For the Pegasus topology, we find that CLMM outperforms all other algorithms at edge densities larger than 0.08, while SPMM wins at edge densities smaller than 0.08 for Erdős-Rényi graphs, with very similar transition densities for the other graph classes. Surprisingly, the standard D-Wave MinorMiner embedding algorithm – while also getting slightly outperformed by SPMM for sparse and very dense graphs on Chimera – does not manage to extend its overall good performance on Chimera to Pegasus as it fails to embed even medium-density graphs on 175–180 nodes which are known to have clique embeddings on Pegasus.


title: Offsite Autotuning Approach: Performance Model Driven Autotuning Applied to Parallel Explicit ODE Methods

text: Autotuning (AT) is a promising concept to minimize the often tedious manual effort of optimizing scientific applications for a specific target platform. Ideally, an AT approach can reliably identify the most efficient implementation variant(s) for a new platform or new characteristics of the input by applying suitable program transformations and analytic models. In this work, we introduce Offsite, an offline AT approach that automates this selection process at installation time by rating implementation variants based on an analytic performance model without requiring time-consuming runtime tests. From abstract multilevel description languages, Offsite automatically derives optimized, platform-specific and problem-specific code of possible variants and applies the performance model to these variants. We apply Offsite to parallel numerical methods for ordinary differential equations (ODEs). In particular, we investigate tuning a specific class of explicit ODE solvers, PIRK methods, for four different initial value problems (IVPs) on three different shared-memory systems. Our experiments demonstrate that Offsite can reliably identify the set of most efficient implementation variants for different given test configurations (ODE solver, IVP, platform) and effectively handle important AT scenarios.


title: Time Series Mining at Petascale Performance

text: The mining of time series data plays an important role in modern information retrieval and analysis systems. In particular, the identification of similarities within and across time series has garnered significant attention and effort over the last few years. For this task, the class of matrix profile algorithms, which create a generic structure that encodes correlations among records and dimensions—the matrix profile—is a promising approach, as it allows simplified post-processing and analysis steps by examining the resulting matrix profile structure. However, it is expensive to create a matrix profile: it requires significant computational power to evaluate the distance among all subsequence pairs in a time series, especially for very long and multi-dimensional time series with a large dimensionality. Existing approaches are limited in their scalability, as they do not target High Performance Computing systems, and—for most realistic problems—are suited only for datasets with a small dimensionality. In this paper, we introduce a novel MPI-based approach for the calculation of a matrix profile for multi-dimensional time series that pushes these limits. We evaluate the efficiency of our approach using an analytical performance model combined with experimental data. Finally, we demonstrate our solution on a 128-dimensional time series dataset of 1 million records, solving 274 trillion sorts at a sustained 1.3 Petaflop/s performance on the SuperMUC-NG system.


docid: wdzruhor

title: Opportunities for Cost Savings with In-Transit Visualization

text: We analyze the opportunities for in-transit visualization to provide cost savings compared to in-line visualization. We begin by developing a cost model that includes factors related to both in-line and in-transit which allows comparisons to be made between the two methods. We then run a series of studies to create a corpus of data for our model. We run two different visualization algorithms, one that is computation heavy and one that is communication heavy with concurrencies up to 32, 768 cores. Our primary results are in exploring the cost model within the context of our corpus. Our findings show that in-transit consistently achieves significant cost efficiencies by running visualization algorithms at lower concurrency, and that in many cases these efficiencies are enough to offset other costs (transfer, blocking, and additional nodes) to be cost effective overall. Finally, this work informs future studies, which can focus on choosing ideal configurations for in-transit processing that can consistently achieve cost efficiencies.


title: Scaling Genomics Data Processing with Memory-Driven Computing to Accelerate Computational Biology

text: Research is increasingly becoming data-driven, and natural sciences are not an exception. In both biology and medicine, we are observing an exponential growth of structured data collections from experiments and population studies, enabling us to gain novel insights that would otherwise not be possible. However, these growing data sets pose a challenge for existing compute infrastructures since data is outgrowing limits within compute. In this work, we present the application of a novel approach, Memory-Driven Computing (MDC), in the life sciences. MDC proposes a data-centric approach that has been designed for growing data sizes and provides a composable infrastructure for changing workloads. In particular, we show how a typical pipeline for genomics data processing can be accelerated, and application modifications required to exploit this novel architecture. Furthermore, we demonstrate how the isolated evaluation of individual tasks misses significant overheads of typical pipelines in genomics data processing.


title: TeaMPI—Replication-Based Resilience Without the (Performance) Pain

text: In an era where we can not afford to checkpoint frequently, replication is a generic way forward to construct numerical simulations that can continue to run even if hardware parts fail. Yet, replication often is not employed on larger scales, as naïvely mirroring a computation once effectively halves the machine size, and as keeping replicated simulations consistent with each other is not trivial. We demonstrate for the ExaHyPE engine—a task-based solver for hyperbolic equation systems—that it is possible to realise resiliency without major code changes on the user side, while we introduce a novel algorithmic idea where replication reduces the time-to-solution. The redundant CPU cycles are not burned “for nothing”. Our work employs a weakly consistent data model where replicas run independently yet inform each other through heartbeat messages whether they are still up and running. Our key performance idea is to let the tasks of the replicated simulations share some of their outcomes, while we shuffle the actual task execution order per replica. This way, replicated ranks can skip some local computations and automatically start to synchronise with each other. Our experiments with a production-level seismic wave-equation solver provide evidence that this novel concept has the potential to make replication affordable for large-scale simulations in high-performance computing.


title: HyPar-Flow: Exploiting MPI and Keras for Scalable Hybrid-Parallel DNN Training with TensorFlow

text: To reduce the training time of large-scale Deep Neural Networks (DNNs), Deep Learning (DL) scientists have started to explore parallelization strategies like data-parallelism, model-parallelism, and hybrid-parallelism. While data-parallelism has been extensively studied and developed, several problems exist in realizing model-parallelism and hybrid-parallelism efficiently. Four major problems we focus on are: 1) defining a notion of a distributed model across processes, 2) implementing forward/back-propagation across process boundaries that requires explicit communication, 3) obtaining parallel speedup on an inherently sequential task, and 4) achieving scalability without losing out on a model’s accuracy. To address these problems, we create HyPar-Flow—a model-size and model-type agnostic, scalable, practical, and user-transparent system for hybrid-parallel training by exploiting MPI, Keras, and TensorFlow. HyPar-Flow provides a single API that can be used to perform data, model, and hybrid parallel training of any Keras model at scale. We create an internal distributed representation of the user-provided Keras model, utilize TF’s Eager execution features for distributed forward/back-propagation across processes, exploit pipelining to improve performance and leverage efficient MPI primitives for scalable communication. Between model partitions, we use send and recv to exchange layer-data/partial-errors while allreduce is used to accumulate/average gradients across model replicas. Beyond the design and implementation of HyPar-Flow, we also provide comprehensive correctness and performance results on three state-of-the-art HPC systems including TACC Frontera (#5 on Top500.org). For ResNet-1001, an ultra-deep model, HyPar-Flow provides: 1) Up to 1.6[Formula: see text] speedup over Horovod-based data-parallel training, 2) 110[Formula: see text] speedup over single-node on 128 Stampede2 nodes, and 3) 481[Formula: see text] speedup over single-node on 512 Frontera nodes.


title: Enabling Execution of a Legacy CFD Mini Application on Accelerators Using OpenMP

text: We describe the process and outcome of our efforts to port a legacy Fortran benchmark code to heterogeneous GPU-accelerated computing architectures using OpenMP. The benchmark code is one of the multi-zone NAS Parallel Benchmarks (NPB-MZ) called SP-MZ. This “mini-app” mimics the computation and data movement that is found in popular legacy and modern implicit computational fluid dynamics (CFD) solvers. Our objective was to examine how efficiently legacy Fortran codes can be ported to accelerators by leveraging OpenMP directives. We describe the development and optimization process and demonstrate the performance impact of various code modifications. We show select profiling results from the NVIDIA Visual Profiler (nvpp) to help others diagnose and overcome performance issues in their own applications. We present results for two compute systems endowed with NVIDIA V100 accelerators.


docid: oneshodu

title: DGEMM Using Tensor Cores, and Its Accurate and Reproducible Versions

text: This paper proposes a method for implementing dense matrix multiplication on FP64 (DGEMM) and FP32 (SGEMM) using Tensor Cores on NVIDIA’s graphics processing units (GPUs). Tensor Cores are special processing units that perform [Formula: see text] matrix multiplications on FP16 inputs with FP32 precision, and return the result on FP32. The proposed method adopts the Ozaki scheme, an accurate matrix multiplication algorithm based on error-free transformation for matrix multiplication. The proposed method has three prominent advantages: first, it can be built upon the cublasGemmEx routine using Tensor Core operations; second, it can achieve higher accuracy than standard DGEMM, including the correctly-rounded result; third, it ensures bit-level reproducibility even for different numbers of cores and threads. The achievable performance of the method depends on the absolute-value range of each element of the input matrices. For example, when the matrices were initialized with random numbers over a dynamic range of 1E+9, our DGEMM-equivalent implementation achieved up to approximately 980 GFlops of FP64 operation on the Titan RTX GPU (with 130 TFlops on Tensor Cores), although cublasDgemm can achieve only 539 GFlops on FP64 floating-point units. Our results reveal the possibility of utilizing hardware with limited FP32/FP64 resources and fast low-precision processing units (such as AI-oriented processors) for general-purpose workloads.


title: Solving Acoustic Boundary Integral Equations Using High Performance Tile Low-Rank LU Factorization

text: We design and develop a new high performance implementation of a fast direct LU-based solver using low-rank approximations on massively parallel systems. The LU factorization is the most time-consuming step in solving systems of linear equations in the context of analyzing acoustic scattering from large 3D objects. The matrix equation is obtained by discretizing the boundary integral of the exterior Helmholtz problem using a higher-order Nyström scheme. The main idea is to exploit the inherent data sparsity of the matrix operator by performing local tile-centric approximations while still capturing the most significant information. In particular, the proposed LU-based solver leverages the Tile Low-Rank (TLR) data compression format as implemented in the Hierarchical Computations on Manycore Architectures (HiCMA) library to decrease the complexity of “classical” dense direct solvers from cubic to quadratic order. We taskify the underlying boundary integral kernels to expose fine-grained computations. We then employ the dynamic runtime system StarPU to orchestrate the scheduling of computational tasks on shared and distributed-memory systems. The resulting asynchronous execution permits to compensate for the load imbalance due to the heterogeneous ranks, while mitigating the overhead of data motion. We assess the robustness of our TLR LU-based solver and study the qualitative impact when using different numerical accuracies. The new TLR LU factorization outperforms the state-of-the-art dense factorizations by up to an order of magnitude on various parallel systems, for analysis of scattering from large-scale 3D synthetic and real geometries.


title: Communication-Aware Hardware-Assisted MPI Overlap Engine

text: Overlap of computation and communication is critical for good application-level performance. Modern high-performance networks offer Hardware-assisted tag matching and rendezvous offload to enable communication progress without involving the host CPU. However, hardware based offload cannot be used in many situations due to various hardware limitations and performance issues. Furthermore, hardware-based designs cannot provide good overlap for common communication patterns involving unexpected messages or non-contiguous datatypes. In this paper, we address these limitations by designing a communication-aware overlap engine for MPI that uses novel hardware-assisted and software-based solutions to extract overlap for both expected and unexpected messages. The proposed design adapts to the application’s communication requirements including message size, datatype, and relative timing of processes using heuristics and history-driven predictions. We evaluate the proposed designs against state-of-the-art MPI libraries and show up to 41% and 22% reduction in latency for collective operations and stencil-based application kernels on 1024 and 128 nodes, respectively, as well as 23% improvement in communication performance of the P3DFFT application.


title: Using High-Level Synthesis to Implement the Matrix-Vector Multiplication on FPGA

text: This work presents how to implement the Matrix-Vector Multiplication (MVM) onto FPGA through the QuickPlay High-Level Synthesis flow. The motivations arise from the Adaptive Optics field, where the MVM is the core of the real-time control algorithm which controls the mirrors of a telescope to compensate for the effects of the atmospheric turbulence. The proposed implementation of the MVM exploits four different levels of parallelism: spatial and pipeline parallelism are used both at the fine (scalar instructions) and at the coarse (vector instructions) levels. To characterize the architecture being developed, a performance model has been developed and validated through the actual results obtained from runs on a prototype board based on the Intel ARRIA10 FPGA. Some details are given to describe how the algorithm has been implemented using the QuickPlay HLS flow. Performance results are presented, in terms of sustained computational speed and resources used in the hardware implementation.


title: Running a Pre-exascale, Geographically Distributed, Multi-cloud Scientific Simulation

text: As we approach the Exascale era, it is important to verify that the existing frameworks and tools will still work at that scale. Moreover, public Cloud computing has been emerging as a viable solution for both prototyping and urgent computing. Using the elasticity of the Cloud, we have thus put in place a pre-exascale HTCondor setup for running a scientific simulation in the Cloud, with the chosen application being IceCube’s photon propagation simulation. I.e. this was not a purely demonstration run, but it was also used to produce valuable and much needed scientific results for the IceCube collaboration. In order to reach the desired scale, we aggregated GPU resources across 8 GPU models from many geographic regions across Amazon Web Services, Microsoft Azure, and the Google Cloud Platform. Using this setup, we reached a peak of over 51k GPUs corresponding to almost 380 PFLOP32s, for a total integrated compute of about 100k GPU hours. In this paper we provide the description of the setup, the problems that were discovered and overcome, as well as a short description of the actual science output of the exercise.


title: Semi-automatic Assessment of I/O Behavior by Inspecting the Individual Client-Node Timelines—An Explorative Study on [Formula: see text] Jobs

text: HPC applications with suboptimal I/O behavior interfere with well-behaving applications and lead to increased application runtime. In some cases, this may even lead to unresponsive systems and unfinished jobs. HPC monitoring systems can aid users and support staff to identify problematic behavior and support optimization of problematic applications. The key issue is how to identify relevant applications? A profile of an application doesn’t allow identifying problematic phases during the execution but tracing of each individual I/O is too invasive. In this work, we split the execution into segments, i.e., windows of fixed size and analyze profiles of them. We develop three I/O metrics to identify three relevant classes of inefficient I/O behaviors, and evaluate them on raw data of 1,000,000 jobs on the supercomputer Mistral. The advantages of our method is that temporal information about I/O activities during job runtime is preserved to some extent and can be used to identify phases of inefficient I/O. The main contribution of this work is the segmentation of time series and computation of metrics (Job-I/O-Utilization, Job-I/O-Problem-Time, and Job-I/O-Balance) that are effective to identify problematic I/O phases and jobs.


docid: sgofnocp

title: Sparse Linear Algebra on AMD and NVIDIA GPUs – The Race Is On

text: Efficiently processing sparse matrices is a central and performance-critical part of many scientific simulation codes. Recognizing the adoption of manycore accelerators in HPC, we evaluate in this paper the performance of the currently best sparse matrix-vector product (SpMV) implementations on high-end GPUs from AMD and NVIDIA. Specifically, we optimize SpMV kernels for the CSR, COO, ELL, and HYB format taking the hardware characteristics of the latest GPU technologies into account. We compare for 2,800 test matrices the performance of our kernels against AMD’s hipSPARSE library and NVIDIA’s cuSPARSE library, and ultimately assess how the GPU technologies from AMD and NVIDIA compare in terms of SpMV performance.


title: Footprint-Aware Power Capping for Hybrid Memory Based Systems

text: High Performance Computing (HPC) systems are facing severe limitations in both power and memory bandwidth/capacity. By now, these limitations have been addressed individually: to improve performance under a strict power constraint, power capping, which sets power limits to components/nodes/jobs, is an indispensable feature; and for memory bandwidth/capacity increase, the industry has begun to support hybrid main memory designs that comprise multiple different technologies including emerging memories (e.g., 3D stacked DRAM or Non-Volatile RAM) in one compute node. However, few works look at the combination of both trends. This paper explicitly targets power managements on hybrid memory based HPC systems and is based on the following observation: in spite of the system software’s efforts to optimize data allocations on such a system, the effective memory bandwidth can decrease considerably when we scale the problem size of applications. As a result, the performance bottleneck component changes in accordance with the footprint (or data) size, which then also changes the optimal power cap settings in a node. Motivated by this observation, we propose a power management concept called [Image: see text] and a profile-driven software framework to realize it. Our experimental result on a real system using HPC benchmarks shows that our approach is successful in correctly setting power caps depending on the footprint size while keeping around 93/96% of performance/power-efficiency compared to the best settings.


title: Simplifying Communication Overlap in OpenSHMEM Through Integrated User-Level Thread Scheduling

text: Overlap of communication with computation is a key optimization for high performance computing (HPC) applications. In this paper, we explore the usage of user-level threading to enable productive and efficient communication overlap and pipelining. We extend OpenSHMEM with integrated user-level thread scheduling, enabling applications to leverage fine-grain threading as an alternative to non-blocking communication. Our solution introduces communication-aware thread scheduling that utilizes the communication state of threads to minimize context switching overheads. We identify several patterns common to multi-threaded OpenSHMEM applications, leverage user-level threads to increase overlap of communication and computation, and explore the impact of different thread scheduling policies. Results indicate that user-level threading can enable blocking communication to meet the performance of highly-optimized, non-blocking, single-threaded codes with significantly lower application-level complexity. In one case, we observe a 28.7% performance improvement for the Smith-Waterman DNA sequence alignment benchmark.


docid: pgkgfrwx

title: Desynchronization and Wave Pattern Formation in MPI-Parallel and Hybrid Memory-Bound Programs

text: Analytic, first-principles performance modeling of distributed-memory parallel codes is notoriously imprecise. Even for applications with extremely regular and homogeneous compute-communicate phases, simply adding communication time to computation time does often not yield a satisfactory prediction of parallel runtime due to deviations from the expected simple lockstep pattern caused by system noise, variations in communication time, and inherent load imbalance. In this paper, we highlight the specific cases of provoked and spontaneous desynchronization of memory-bound, bulk-synchronous pure MPI and hybrid MPI+OpenMP programs. Using simple microbenchmarks we observe that although desynchronization can introduce increased waiting time per process, it does not necessarily cause lower resource utilization but can lead to an increase in available bandwidth per core. In case of significant communication overhead, even natural noise can shove the system into a state of automatic overlap of communication and computation, improving the overall time to solution. The saturation point, i.e., the number of processes per memory domain required to achieve full memory bandwidth, is pivotal in the dynamics of this process and the emerging stable wave pattern. We also demonstrate how hybrid MPI-OpenMP programming can prevent desirable desynchronization by eliminating the bandwidth bottleneck among processes. A Chebyshev filter diagonalization application is used to demonstrate some of the observed effects in a realistic setting.


title: Reinit[Formula: see text]: Evaluating the Performance of Global-Restart Recovery Methods for MPI Fault Tolerance

text: Scaling supercomputers comes with an increase in failure rates due to the increasing number of hardware components. In standard practice, applications are made resilient through checkpointing data and restarting execution after a failure occurs to resume from the latest checkpoint. However, re-deploying an application incurs overhead by tearing down and re-instating execution, and possibly limiting checkpointing retrieval from slow permanent storage. In this paper we present Reinit[Formula: see text], a new design and implementation of the Reinit approach for global-restart recovery, which avoids application re-deployment. We extensively evaluate Reinit[Formula: see text] contrasted with the leading MPI fault-tolerance approach of ULFM, implementing global-restart recovery, and the typical practice of restarting an application to derive new insight on performance. Experimentation with three different HPC proxy applications made resilient to withstand process and node failures shows that Reinit[Formula: see text] recovers much faster than restarting, up to 6[Formula: see text], or ULFM, up to 3[Formula: see text], and that it scales excellently as the number of MPI processes grows.


title: Timemory: Modular Performance Analysis for HPC

text: HPC has undergone a significant transition toward heterogeneous architectures. This transition has introduced several issues in code migration to support multiple frameworks for targeting the various architectures. In order to cope with these challenges, projects such as Kokkos and LLVM create abstractions which map a generic front-end API to the backend that supports the targeted architecture. This paper presents a complementary framework for performance measurement and analysis. Several performance measurement and analysis tools in existence provide their capabilities through various methods but the common theme among these tools are prohibitive limitations in terms of user-level extensions. For this reason, software developers commonly have to learn multiple tools and valuable analysis methods, such as the roofline model, are frequently required to be generated manually. The timemory framework provides complete modularity for performance measurement and analysis and eliminates all restrictions on user-level extensions. The timemory framework also provides a highly-efficient and intuitive method for handling multiple tools/measurements (i.e., “components”) concurrently. The intersection of these characteristics provide ample evidence that timemory can serve as the common interface for existing performance measurement and analysis tools. Timemory components are developed in C++ but includes multi-language support for C, Fortran, and Python codes. Numerous components are provided by the library itself – including, but not limited to, timers, memory usage, hardware counters, and FLOP and instruction roofline models. Additionally, analysis of the intrinsic overhead demonstrates superior performance in comparison with popular tools.


Calling algorithms by their name (and engineers’ and philosophers’ novel teamwork): Serge Abiteboul and Gilles Dowek: The age of algorithms, translated by K-Rae Nelson. Cambridge: Cambridge University Press, 2020, 166 pp, £ 14.99 PB


title: A patient with severe polytrauma with massive pulmonary contusion and hemorrhage successfully treated with multiple treatment modalities: a case report

text: BACKGROUND: The mortality rate is very high for patients with severe multiple trauma with massive pulmonary contusion containing intrapulmonary hemorrhage. Multiple treatment modalities are needed not only for a prevention of cardiac arrest and quick hemostasis against multiple injuries, but also for recovery of oxygenation to save the patient’s life. CASE PRESENTATION: A 48-year-old Japanese woman fell down stairs that had a height of approximately 4 m. An X-ray showed pneumothorax, pulmonary contusion in her right lung, and an unstable pelvic fracture. A chest drain was inserted and preperitoneal pelvic packing was performed to control bleeding, performing resuscitative endovascular balloon occlusion of the aorta. A computed tomography scan revealed massive lung contusion in the lower lobe of her right lung, pelvic fractures, and multiple fractures and hematoma in other areas. An emergency thoracotomy was performed, and then we performed wide wedge resection of the injured lung, clamping proximal to suture lines with two Satinsky blood vessel clamps. The vessel clamps were left in the right thoracic cavity. The other hemorrhagic areas were embolized by transcatheter arterial embolization. However, since her respiratory functions deteriorated in the intensive care unit, veno-venous extracorporeal membrane oxygenation was used for lung assist. Planned reoperation under veno-venous extracorporeal membrane oxygenation was performed on day 2. Since her respiratory condition improved gradually, the veno-venous extracorporeal membrane oxygenation circuit was withdrawn on day 7. She was transferred to the psychiatric ward of our hospital on day 75. CONCLUSION: Utilizing multiple treatment modalities such as resuscitative endovascular balloon occlusion of the aorta, damage control surgery, transcatheter arterial embolization, and veno-venous extracorporeal membrane oxygenation with appropriate timing saves a patient with severe polytrauma with massive pulmonary contusion including intrapulmonary hemorrhage.


La Neurología en tiempos de COVID


Contents page 2


Reivindicando la validez del oftalmólogo general. Homenaje al Dr. Li Wenliang (1986-2020)


Functioning During a Pandemic


Inside This Issue


Table of Contents & Bacode


Green endoscopy: a call for sustainability in the midst of COVID-19


Small but mighty: A newfound respect for brief research communications


Advisory Board and Contents


Letter from Editor


New Precedents


JACC: Case Reports: Moving to a Multimedia Educational Vehicle


title: Apocalypse Now

text: Wilhelm von Humboldts Bildungsideal, das zu einem autonomen Individuum und Weltbürger führen soll, ist u. a. das Ergebnis seiner Auseinandersetzung mit Philosophen der Aufklärung wie z. B. mit Immanuel Kant. Die Schriften von Kant sollen Wilhelm von Humboldt schon in jungen Jahren beeinflusst haben. Immanuel Kant ist einer der bedeutendsten Philosophen der Aufklärung.


title: Threats and opportunities in remote learning of mathematics: implication for the return to the classroom

text: Australian schools, like schools elsewhere, have been through a period of closure. The closure creates both threats and opportunities for teachers and students. In the context of a project exploring approaches to teaching in early years, we outline some considerations and offer advice to teachers and educators on strategies for welcoming students back to school.


The View From the Cusp of the “Third Act”


title: Avoidance of vitamin D deficiency to slow the COVID-19 pandemic

text: Vitamin D deficiency, which impedes good immune function, is common during winter and spring in regions of high latitude. There is good evidence that vitamin D deficiency contributes to the seasonal increase of virus infections of the respiratory tract, from the common cold to influenza, and now possibly also COVID-19. This communication explores key factors that make it more likely, particularly in combination, that individuals are vitamin D deficient. These factors include old age, obesity, dark skin tone and common genetic variants that impede vitamin D status. Precision nutrition is an approach that aims to consider known personal risk factors and health circumstances to provide more effective nutrition guidance in health and disease. In regard to avoiding vitamin D deficiency, people with excess body fat, a dark skin tone or older age usually need to use a moderately dosed daily vitamin D supplement, particularly those living in a high-latitude region, getting little ultraviolet B exposure due to air pollution or staying mostly indoors. Carriers of the GC (group-specific component) rs4588 AA genotype also are more likely to become deficient. Very high-dosed supplements with more than 4000 IU vitamin D are rarely needed or justified. A state-by-state Mendelian randomisation analysis of excess COVID-19 mortality of African-Americans in the USA shows a greater disparity in northern states than in southern states. It is conceivable that vitamin D adequacy denies the virus easy footholds and thereby slows spreading of the contagion. This finding should drive home the message that vitamin D supplementation is particularly important for individuals with dark skin tones. Vitamin D deficiency, even for a few months during the winter and spring season, must be rigorously remedied because of its many adverse health impacts that include decreased life expectancy and increased mortality. Slowing the spread of COVID-19 would be an added bonus.


title: Nutrition, immunity and COVID-19

text: The immune system protects the host from pathogenic organisms (bacteria, viruses, fungi, parasites). To deal with this array of threats, the immune system has evolved to include a myriad of specialised cell types, communicating molecules and functional responses. The immune system is always active, carrying out surveillance, but its activity is enhanced if an individual becomes infected. This heightened activity is accompanied by an increased rate of metabolism, requiring energy sources, substrates for biosynthesis and regulatory molecules, which are all ultimately derived from the diet. A number of vitamins (A, B(6), B(12), folate, C, D and E) and trace elements (zinc, copper, selenium, iron) have been demonstrated to have key roles in supporting the human immune system and reducing risk of infections. Other essential nutrients including other vitamins and trace elements, amino acids and fatty acids are also important. Each of the nutrients named above has roles in supporting antibacterial and antiviral defence, but zinc and selenium seem to be particularly important for the latter. It would seem prudent for individuals to consume sufficient amounts of essential nutrients to support their immune system to help them deal with pathogens should they become infected. The gut microbiota plays a role in educating and regulating the immune system. Gut dysbiosis is a feature of disease including many infectious diseases and has been described in COVID-19. Dietary approaches to achieve a healthy microbiota can also benefit the immune system. Severe infection of the respiratory epithelium can lead to acute respiratory distress syndrome (ARDS), characterised by excessive and damaging host inflammation, termed a cytokine storm. This is seen in cases of severe COVID-19. There is evidence from ARDS in other settings that the cytokine storm can be controlled by n-3 fatty acids, possibly through their metabolism to specialised pro-resolving mediators.


Non-Human Animal Trauma During the Pandemic


title: Untargeted Metabolomic Analysis of the Effects and Mechanism of Nuciferine Treatment on Rats With Nonalcoholic Fatty Liver Disease

text: Metabolomic analysis has been used to characterize the effects and mechanisms of drugs for nonalcoholic fatty liver disease (NAFLD) at the metabolic level. Nuciferine is an active component derived from folium nelumbinis and has been demonstrated to have beneficial effects on a high-fat diet (HFD) induced hepatic steatosis model. However, the effect of the altered metabolites of nuciferine on NAFLD has not yet been elucidated. In this study, we established a NAFLD rat model using HFD and treated with nuciferine. The lipid content levels, pro-inflammatory cytokines, and oxidative stress were investigated to access the therapeutic effects of nuciferine. Additionally, the metabolic regulatory mechanisms of nuciferine on NAFLD were analyzed using untargeted metabolomics. Gene expression of the key enzymes related to the changed metabolic pathways following nuciferine intervention was also investigated. The results showed that nuciferine treatment significantly reduced the body weight, levels of lipids, and liver enzymes in the blood and improved the hepatic steatosis in the NAFLD rat model. Nuciferine treatment also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the levels of methane dicarboxylic aldehyde (MDA) in the liver. Nuciferine treatment decreased the serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) and upregulated the gene expression of IL-6, IL-1β, and TNF-α in the liver. Metabolomic analysis indicated a metabolism disorder in the NAFLD rat model reflected in a dysfunction of the glycerophospholipid, linoleic acid, alpha-linolenic acid, arginine and proline metabolism. Conversely, treatment with nuciferine improved the metabolic disorder in the NAFLD rat model. Nuciferine treatment also regulated the gene expression of key enzymes related to the glycerophospholipid, linoleic acid, and alpha-linolenic acid metabolism pathways in the liver. In conclusion, our study demonstrated an amelioration of the metabolic disorders following nuciferine treatment in NAFLD rat model. Our study contributes to the understanding of the effects and mechanisms of drugs for complex diseases using metabolomic analysis and experimental approaches.