docid: jlzncyax

title: Inflammation Profiling of Critically Ill Coronavirus Disease 2019 Patients

text: OBJECTIVES: Coronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019. DESIGN: Daily blood inflammation profiling with immunoassays. SETTING: Tertiary care ICU and academic laboratory. SUBJECTS: All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative), or until ICU day 7 if the patient was positive (coronavirus disease 2019 positive). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age- and sex-matched healthy controls and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. We measured 57 inflammatory analytes and then analyzed with both conventional statistics and machine learning. Twenty inflammatory analytes were different between coronavirus disease 2019 positive patients and healthy controls (p < 0.01). Compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had 17 elevated inflammatory analytes on one or more of their ICU days 1–3 (p < 0.01), with feature classification identifying the top six analytes between cohorts as tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2. While tumor necrosis factor, granzyme B, heat shock protein 70, and interleukin-18 were elevated for all seven ICU days, interferon-gamma-inducible protein 10 transiently elevated on ICU days 2 and 3 and elastase 2 increased over ICU days 2–7. Inflammation profiling predicted coronavirus disease 2019 status with 98% accuracy, whereas elevated heat shock protein 70 was strongly associated with mortality. CONCLUSIONS: While many inflammatory analytes were elevated in coronavirus disease 2019 positive ICU patients, relative to healthy controls, the top six analytes distinguishing coronavirus disease 2019 positive ICU patients from coronavirus disease 2019 negative ICU patients were tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2.


title: The Epidemiology of Respiratory Failure in the United States 2002–2017: A Serial Cross-Sectional Study

text: OBJECTIVES: Respiratory failure with mechanical ventilation is a limited labor-intensive resource that is associated with high mortality. Understanding the longitudinal national epidemiology is essential for the organization of healthcare resources. DESIGN: Serial cross-sectional study. SETTING: The 2002–2017 Healthcare Utilization Project’s National Inpatient Sample datasets. INTERVENTIONS: None. MEASUREMENTS: We use six diagnosis codes and five procedural codes from International Classification of Diseases, 9th Revision, Clinical Modification, and 19 diagnosis codes and 15 procedures codes from International Classification of Diseases, 10th Revision, Clinical Modification to examine national epidemiology of different case definitions for respiratory failure. RESULTS: In the United States in 2017, there were an estimated 1,146,195 discharges with a diagnosis of respiratory failure and procedural code for mechanical ventilation, with an average length of stay of 10.5 days and hospital charge of $158,443. Over the study period, there was an 83% increase in incidence from 249 to 455 cases per 100,000 adults with a 48% decrease in hospital mortality from 34% to 23%. Exploring a case definition that captures only diagnosis codes for respiratory failure, there was a 197% increase in annual incidence, from 429 to 1,275 cases per 100,000 adults with a 57% decrease in hospital mortality from 28% to 12%. For invasive mechanical ventilation without a requisite diagnosis code, there was no change in incidence over the study period, with the 2017 incidence at 359 cases per 100,000 adults, but a 19% decrease in hospital mortality from 37% to 30%. For the noninvasive mechanical ventilation procedural codes, there was a 437% increase in incidence from 41 to 220 cases per 100,000 adults, with a 38% decrease in hospital mortality from 16% to 10%. CONCLUSIONS: Examining different case definitions for respiratory failure, there was a large increase in the population incidence and decrease in the hospital mortality for respiratory failure diagnosis codes with more modest changes procedural codes for invasive mechanical ventilation. There was a large increase in incidence of noninvasive mechanical ventilation.


Cardiovascular and cardiometabolic prevention: high-level priority in the era of COVID-19


title: Impact of Fiber-Based Enteral Nutrition on the Gut Microbiome of ICU Patients Receiving Broad-Spectrum Antibiotics: A Randomized Pilot Trial

text: OBJECTIVES: Dietary fiber increases the abundance of bacteria that metabolize fiber into short-chain fatty acids and confers resistance against gut colonization with multidrug-resistant bacteria. This pilot trial estimated the effect of fiber on gut short-chain fatty acid–producing bacteria in the ICU. DESIGN: Randomized, controlled, open label trial. SETTING: Medical ICU. PATIENTS: Twenty ICU adults receiving broad-spectrum IV antibiotics for sepsis. INTERVENTION: 1:1 randomization to enteral nutrition with mixed soy- and oat-derived fiber (14.3 g fiber/L) versus calorie- and micronutrient-identical enteral nutrition with 0 g/L fiber. MEASUREMENTS: Rectal swabs and whole stools were collected at baseline and on study Days 3, 7, 14, and 30. The primary outcome was within-individual change in the cumulative relative abundance of short-chain fatty acid–producing taxa from baseline to Day 3 based on 16S sequencing of rectal swabs. The secondary outcome was Day 3 cumulative short-chain fatty acid levels based on mass spectrometry of whole stools. Analyses were all intent to treat. MAIN RESULTS: By Day 3, the fiber group received a median of 32.1 g fiber cumulatively (interquartile range, 17.6–54.6) versus 0 g fiber (interquartile range, 0–4.0) in the no fiber group. The median within-individual change in short-chain fatty acid producer relative abundance from baseline to Day 3 was +61% (interquartile range −51 to +1,688) in the fiber group versus −46% (interquartile range, −78 to +13) in the no fiber group (p = 0.28). Whole stool short-chain fatty acid levels on Day 3 were a median of 707 μg short-chain fatty acids/g stool (interquartile range, 190–7,265) in the fiber group versus 118 μg short-chain fatty acids/g stool (interquartile range, 22–1,195) in the no fiber group (p = 0.16). CONCLUSIONS: Enteral fiber was associated with nonsignificant trends toward increased relative abundance of short-chain fatty acid–producing bacteria and increased short-chain fatty acid levels among ICU patients receiving broad-spectrum IV antibiotics. Larger studies should be undertaken and our results can be used for effect size estimates.


title: Framework and Outcomes of a Critical Care Pharmacy Visiting Clinical Professor Program

text: OBJECTIVES: Experiences with utilizing a visiting clinical professor program to mentor institutions and collaborate on best practices in critical care pharmacy are described to provide a framework for these services and a synopsis of key outcomes. DESIGN: The Society of Critical Care Medicine Clinical Pharmacy and Pharmacology Section implemented a visiting clinical professor program to address the need for collaboration, idea-sharing, mentorship, and diffusion of innovation to clinicians in critical care practice. SETTING: Critical care pharmacy departments at 12 medical centers. SUBJECTS: Twelve visiting clinical professors and host institutions from 2007-2018. INTERVENTION: After an application is submitted to the section steering committee, an experienced clinician is paired with an institution, and a site visit is planned in collaboration with the visiting clinical professor program coordinators. The expert clinician visits the institution to share their insights and best practices based on visit goals and objectives. Reflective debriefing with both the host institution and the visiting clinical professor occurs after the visit. MEASUREMENTS AND MAIN RESULTS: The program has demonstrated numerous benefits including shared best practices related to critical care clinical services, expansion and refinement of care delivery models, development and optimization of research programs, and advancement of new training programs including specialty pharmacy residencies. Both the site and visiting professor find these partnerships beneficial, which has resulted in sustained success of the program over an 11-year period. Key resultant deliverables after visits have included new pharmacist positions, advancement of pharmacy services, and expanded access to academic opportunities. CONCLUSIONS: A professional organization led visiting clinical professor program is viable, sustainable, and yields clear benefit for critical care pharmacy programs across the country. Application of this framework to other areas of pharmacy practice may be an avenue to share best practices and advance pharmacy services.


title: Gender Difference Is Associated With Severity of Coronavirus Disease 2019 Infection: An Insight From a Meta-Analysis

text: OBJECTIVES: Coronavirus disease 2019 is a novel infection now causing pandemic around the world. The gender difference in regards to the severity of coronavirus disease 2019 infection has not been well described thus far. Our aim was to investigate how gender difference can affect the disease severity of coronavirus disease 2019 infection. DATA SOURCES: A comprehensive literature search of PubMed and Embase databases was conducted from December 1, 2019, to March 26, 2020. An additional manual search of secondary sources was conducted to minimize missing relevant studies. There were no language restrictions. STUDY SELECTION: Studies were included in our meta-analysis if it was published in peer-reviewed journals and recorded patient characteristics of severe versus nonsevere or survivor versus nonsurvivor in coronavirus disease 2019 infection. DATA EXTRACTION: Two investigators independently screened the search, extracted the data, and assessed the quality of the study. DATA SYNTHESIS: Our search identified 15 observational studies with a total of 3,494 patients (1,935 males and 1,559 females) to be included in our meta-analysis. Males were more likely to develop severe coronavirus disease 2019 infection compared with females (odds ratio, 1.31; 95% CI, 1.07–1.60). There was no significant heterogeneity (I(2) = 12%) among the studies. CONCLUSIONS: This meta-analysis suggests that the male gender may be a predictor of more severe coronavirus disease 2019 infection. Further accumulation of evidence from around the world is warranted to confirm our findings.


docid: adepbywq

title: Pediatric Sepsis Definition—A Systematic Review Protocol by the Pediatric Sepsis Definition Taskforce

text: OBJECTIVES: Sepsis is responsible for a substantial proportion of global childhood morbidity and mortality. However, evidence demonstrates major inaccuracies in the use of the term “sepsis” in clinical practice, coding, and research. Current and previous definitions of sepsis have been developed using expert consensus but the specific criteria used to identify children with sepsis have not been rigorously evaluated. Therefore, as part of the Society of Critical Care Medicine’s Pediatric Sepsis Definition Taskforce, we will conduct a systematic review to synthesize evidence on individual factors, clinical criteria, or illness severity scores that may be used to identify children with infection who have or are at high risk of developing sepsis-associated organ dysfunction and separately those factors, criteria, and scores that may be used to identify children with sepsis who are at high risk of progressing to multiple organ dysfunction or death. DATA SOURCES: We will identify eligible studies by searching the following databases: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. STUDY SELECTION: We will include all randomized trials and cohort studies published between January 1, 2004, and March 16, 2020. DATA EXTRACTION: Data extraction will include information related to study characteristics, population characteristics, clinical criteria, and outcomes. DATA SYNTHESIS: We will calculate sensitivity and specificity of each criterion for predicting sepsis and conduct a meta-analysis if the data allow. We will also provide pooled estimates of overall hospital mortality. CONCLUSIONS: The potential risk factors, clinical criteria, and illness severity scores from this review which identify patients with infection who are at high risk of developing sepsis-associated organ dysfunction and/or progressing to multiple organ dysfunction or death will be used to inform the next steps of the Pediatric Sepsis Definition Taskforce.


title: Obese communities among the best predictors of COVID-19-related deaths

text: INTRODUCTION: Coronavirus disease 2019 (COVID-19) is the largest outbreak to strike the world since the Spanish flu in 1918. Visual examination of the world map shows a wide variation of death tolls between countries. The main goal of our series is to determine the best predictors of such discrepancy. METHODS: This is a retrospective study in which the rate of COVID-19 deaths was correlated with each of the following independent variables: total tests per 1 million population, gross domestic product (GDP), average temperatures per country, ultraviolet index, median age, average BMI per country, food supply, Bacille Calmette-Guerin compulsory status, and passenger traffic. RESULTS: BMI per country proved to be the second best predictor of death rate with an R value of 0.43, and GDP being the best predictor with R = 0.65. CONCLUSION: This article shows a tight correlation between average BMI, food supply per country, and COVID-19-related deaths. Such predisposing factors might operate by upregulating the inflammation pathway in heavily struck countries, leading to easier triggering of the infamous cytokine storm syndrome. Obesity also increases cardiovascular and respiratory morbidities, which are coupled to increased ICU demand and deaths among infected cases. Video abstract: http://links.lww.com/CAEN/A25.


title: The Efficacy of Albumin Dialysis in the Reversal of Refractory Vasoplegic Shock Due to Amlodipine Toxicity

text: OBJECTIVES: Calcium channel blockers are highly protein-bound medications frequently used in the management of hypertension. Overdose results in severe hypotension and is the fourth most common cause of toxicity-related deaths in the United States. Management is mostly supportive, with currently no standard role for targeted drug removal. The protein-bound nature of these medications presents the option of utilizing albumin dialysis for their removal and for the reversal of associated shock. DESIGN AND SUBJECTS: We present two cases of life-threatening intentional amlodipine overdoses successfully treated with albumin dialysis. Both patients experienced profound distributive shock in the setting of preserved cardiac contractility that was refractory to maximal vasoactive agent support. INTERVENTIONS AND RESULTS: After initiation of albumin dialysis, the patients showed rapid hemodynamic improvement and were able to be weaned off vasopressor support. CONCLUSIONS: These cases demonstrate the safety and efficacy of albumin dialysis in the management of near-fatal calcium channel blocker overdoses related to amlodipine and offer an additional therapeutic option apart from conventional supportive care. Importantly, these cases were not associated with impaired cardiac contractility, thereby making venoarterial extracorporeal membrane oxygenation a less preferable option. Furthermore, this therapeutic benefit of albumin dialysis can potentially be extended to the management of toxicity related to other highly protein-bound drugs and toxins.


title: Recombinant Human Proteoglycan-4 Mediates Interleukin-6 Response in Both Human and Mouse Endothelial Cells Induced Into a Sepsis Phenotype

text: OBJECTIVES: Sepsis is a leading cause of death in the United States. Putative targets to prevent systemic inflammatory response syndrome include antagonism of toll-like receptors 2 and 4 and CD44 receptors in vascular endothelial cells. Proteoglycan-4 is a mucinous glycoprotein that interacts with CD44 and toll-like receptor 4 resulting in a blockade of the NOD-like receptor pyrin domain-containing-3 pathway. We hypothesized that endothelial cells induced into a sepsis phenotype would have less interleukin-6 expression after recombinant human proteoglycan 4 treatment in vitro. DESIGN: Enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction to measure interleukin-6 protein and gene expression. SETTING: Research laboratory. SUBJECTS: Human umbilical vascular endothelial cells, human lung microvascular endothelial cells, and transgenic mouse (wild type) (Cd44(+/+)/Prg4(+/+)), Cd44(–/–) (Cd44(tm1Hbg)Prg4(+/+)), Prg4(GT/GT) (Cd44(+/+) Prg4(tm2Mawa/J)), and double knockout (Cd44(tm1Hbg) Prg4(tm2Mawa/J)) lung microvascular endothelial cells. INTERVENTIONS: Cells were treated with 100 or 250 ng/mL lipopolysaccharide-Escherichia coli K12 and subsequently treated with recombinant human proteoglycan 4 after 30 minutes. Interleukin-6 levels in conditioned media were measured via enzyme-linked immunosorbent assay and gene expression was measured via reverse transcriptase-quantitative polymerase chain reaction with ΔΔ–Ct analysis. Additionally, human umbilical vascular endothelial cells and human lung microvascular endothelial cells were treated with 1:10 diluted plasma from 15 patients with sepsis in culture media. After 30 minutes, either 50 or 100 µg/mL recombinant human proteoglycan 4 was administered. Interleukin-6 protein and gene expression were assayed. Proteoglycan 4 levels were also compared between control and sepsis patient plasma. MEASUREMENTS AND MAIN RESULTS: Human umbilical vascular endothelial cell, human lung microvascular endothelial cell, and mouse lung microvascular endothelial cell treated with lipopolysaccharide had significantly increased interleukin-6 protein compared with controls. Recombinant human proteoglycan-4 significantly reduced interleukin-6 in human and mouse endothelial cells. Interleukin-6 gene expression was significantly increased after lipopolysaccharide treatment compared with controls. This response was reversed by 50 or 100 µg/mL recombinant human proteoglycan-4 in 80% of sepsis samples in human umbilical vascular endothelial cells and in 60–73% in human lung microvascular endothelial cells. In Cd44(–/–) genotypes of the mouse lung microvascular endothelial cells, recombinant human proteoglycan-4 significantly reduced interleukin-6 protein levels after lipopolysaccharide treatment, indicating that Cd44 is not needed for recombinant human proteoglycan-4 to have an effect in a toll-like receptor 4 agonist inflammation model. Patient sepsis samples had higher plasma levels of native proteoglycan-4 than controls. INTERPRETATION AND CONCLUSIONS: Recombinant human proteoglycan-4 is a potential adjunct therapy for sepsis patients and warrants future in vivo model studies.


title: Mechanical Ventilation, Sedation and Neuromonitoring of Patients with Aneurysmal Subarachnoid Hemorrhage in Germany: Results of a Nationwide Survey

text: OBJECTIVE: Current evidence-based guidelines for the management of aneurysmal subarachnoid hemorrhage (aSAH) focus primarily on timing, modality and technique of aneurysm occlusion, and on prevention and treatment of delayed cerebral ischemia. Significant aspects of management in the intensive care unit (ICU) during the later course of aSAH such as ventilation and sedation (VST) remain unaddressed. aSAH patients present unique challenges not accounted for in general ICU recommendations and guidelines, which is why we attempted to further characterize ICU practices in aSAH patients in Germany. METHODS: We conducted a nationwide survey on ICU practices in aSAH in Germany. Secondarily, we assessed the existence of and compliance with current guidelines regarding ICU practices. The questionnaire was designed in interdisciplinary fashion and distributed online through the kwiksurvey(®) platform (Bristol, UK). RESULTS: A total of 50 responses were received, accounting for a response rate of 49%. Twenty-one were university hospitals (UH), 23 high-volume centers (HVC), 6 low-volume centers (LVC). Half of the participating centers do not take into consideration WFNS at presentation to indicate ventilation. While 42% of centers rely on the P/F ratio to indicate ventilation, 62% of them have a cutoff value of < 200, and 38% of < 100. While most UH and HVC used propofol for the first phase of sedation (95%), LVC employed benzodiazepines (100%). Sedation deepening was done with ketamine in UH (75%) and HVC (60%), whereas LVC used predominantly clonidine (100%). CONCLUSIONS: Our study clearly demonstrates that attitudes and practices pertaining to ICU management in aSAH are enormously heterogeneous, reflecting the lack of good quality evidence and differing interpretations thereof. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-020-01029-8) contains supplementary material, which is available to authorized users.


Anita Zaidi


Jacques Acar


The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polyps


News Article


Editor’s note: “family business scholars, lead the charge!”


Global shortage of personal protective equipment


Acute respiratory distress syndrome during a pandemic—an obvious diagnosis?


JCF Year in Review


title: The pattern of neonatal gastro-intestinal perforation in upper Egypt

text: BACKGROUND: Neonatal gastro-intestinal perforation [NGIP] is one of the major problems in pediatric surgical practice. Although the outcomes of neonatal surgery have improved markedly over the past decade the mortality rates of neonates with NGIP are still high. The aim of this study was to present the possible etiological factors, clinical findings, and operative procedures of NIP in our locality. RESULTS: A total of 34 neonates with NGIP were included in this study. The median age at presentation was (15.8 ± 7.0 SD) days. The median interval between presentation and surgical interference was (2.0 ± 1.1 SD).Necrotizing enterocolitis [NEC] was the commonest cause of neonatal gastro-intestinal perforation. The commonest site of perforation was the colon [11cases]. The overall mortality rate was 11 cases [32.4%]. The main cause of mortality was neonatal NEC [6 cases]. Eight cases [40 %] died out of 20 cases which the interval between the presentation and interference were more than one day. CONCLUSIONS: Neonatal gastro-intestinal perforations are still associated with high mortality rate in our institutions, and delayed diagnosis with increased interval between the presentation and surgical intervention are associated with increased mortality. In our locality, although NEC is the commonest cause of NGIP, the iatrogenic cause is relatively higher than reported.


title: The impact of tracheostomy timing on clinical outcomes and adverse events in intubated patients with infratentorial lesions: early versus late tracheostomy

text: We evaluated the association between the timing of tracheostomy and clinical outcomes in patients with infratentorial lesions. We performed a retrospective observational cohort study in a neurosurgical intensive care unit (ICU) at a tertiary academic medical center from January 2014 to December 2018. Consecutive adult patients admitted to the ICU who underwent resection of infratentorial lesions as well as tracheostomy were included for analysis. Early tracheostomy was defined as performed on postoperative days 1–10 and late tracheostomy on days 10–20 after operation. Univariate and multivariate analyses were used to compare the characteristics and outcomes between both cohorts. A total of 143 patients were identified, and 96 patients received early tracheostomy. Multivariable analysis identified early tracheostomy as an independent variable associated with lower occurrence of pneumonia (odds ratio, 0.25; 95% CI, 0.09–0.73; p = 0.011), shorter stays in ICUs (hazard ratio, 0.4; 95% CI, 0.3–0.6; p = 0.03), and earlier decannulation (hazard ratio, 0.5; 95% CI, 0.4–0.8; p = 0.003). However, no significant differences were observed between the early and late tracheostomy groups regarding hospital mortality (p > 0.999) and the modified Rankin scale after 6 months (p = 0.543). We also identified postoperative brainstem deficits, including cough, swallowing attempts, and extended tongue as well as GCS < 8 at ICU admission as the risk factors independently associated with patients underwent tracheostomy. There is a significant association between early tracheostomy and beneficial clinical outcomes or reduced adverse event occurrence in patients with infratentorial lesions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10143-020-01339-7) contains supplementary material, which is available to authorized users.


title: Epistemic Consultants and the Regulation of Policy Knowledge in the Obama Administration

text: The agencies of the government of the United States of America, such as the Food and Drug Administration or the Environmental Protection Agency, intervene in American society through the collection, processing, and diffusion of information. The Presidency of Barack Obama was notable for updating and redesigning the US government’s information infrastructure. The White House enhanced mass consultation through open government and big data initiatives to evaluate policy effectiveness, and it launched new ways of communicating with the citizenry. In this essay we argue that these programs spelled out an emergent epistemology based on two assumptions: dispersed knowledge and a critique of judgment. These programs have redefined the evidence required to justify and design regulatory policy and conferred authority to a new kind of expert, which we call epistemic consultants.


Proceedings from the Editorial Board Meeting of The AJC in 2019


title: Regime Change: Education to Work Transitions in England, 1980s–2020s

text: Abstract This paper argues the case for viewing a country’s transition regime as a totality in which different career steps and routes assign significance and value to one another. Following the destruction of major sections of Britain’s transition regime in the 1970s and 1980s, the paper explains how the regime has subsequently been reconstructed following the 1988 Education Reform Act, replacing the vocational education and training schemes of the 1980s with government-supported apprenticeships, almost uninterrupted employment growth since 1992, and the financialization of the corporate economy alongside uncapped expansion of higher education. England’s current transition regime keeps rates of youth unemployment and NEET below the European Union averages and delivers the fastest transitions in Europe. However, the reconstructed regime also locks-in features that may well become long-term problems, namely an expensive higher education system which leaves graduates with debts that many do not expect to repay in full, and substantial low wage, low skill, low productivity sectors in the economy and workforce.


Existential Returns


Trainee award announcement


Geographies of risk: Emerging infectious diseases and travel health data


The authors reply: Study selection for meta-analyses


title: The Glasgow Subgraph Solver: Using Constraint Programming to Tackle Hard Subgraph Isomorphism Problem Variants

text: The Glasgow Subgraph Solver provides an implementation of state of the art algorithms for subgraph isomorphism problems. It combines constraint programming concepts with a variety of strong but fast domain-specific search and inference techniques, and is suitable for use on a wide range of graphs, including many that are found to be computationally hard by other solvers. It can also be equipped with side constraints, and can easily be adapted to solve other subgraph matching problem variants. We outline its key features from the view of both users and algorithm developers, and discuss future directions.


title: A Flexible and Easy-to-Use Library for the Rapid Development of Graph Tools in Java

text: We present a programming library for the rapid development of graph tools, with applications in graph transformation and related fields. Features include working with graphs, graph morphisms, basic categorical constructions such as computing pushouts and pushout complements or enumerating all morphisms with certain properties, but also applications such as executing graph transformation steps. Additionally, we offer graphical user interface widgets for visualization and manipulation of graphs, morphisms and categorical diagrams. Our objective is to allow users to quickly develop graph tools for both simple and complex problems, to allow easy embedding into existing software, and to have comprehensible code especially for the main algorithms. Existing tools that demonstrate the versatility and ease of use of the library include: DPOdactic (a didactic tool for teaching double-pushout graph transformation), DrAGoM (a tool to handle multiply annotated type graphs for abstract graph rewriting), and Grez (termination analysis of graph transformation systems).


title: Computing Embeddings of Directed Bigraphs

text: Directed bigraphs are a meta-model which generalises Milner’s bigraphs by taking into account the request flow between controls and names. A key problem about these bigraphs is that of bigraph embedding, i.e., finding the embeddings of a bigraph inside a larger one. We present an algorithm for computing embeddings of directed bigraphs, via a reduction to a constraint satisfaction problem. We prove soundness and completeness of this algorithm, and provide an implementation in jLibBig, a general Java library for manipulating bigraphical reactive systems, together with some experimental results.


title: A Simulator for Probabilistic Timed Graph Transformation Systems with Complex Large-Scale Topologies

text: Future cyber-physical systems, like networks of autonomous vehicles, will result in a huge number of collaborating systems acting together on large-scale topologies. Modeling them requires capturing timed and probabilistic behavior as well as structure dynamics. In [9], we introduced Probabilistic Timed Graph Transformation Systems (PTGTSs) as a means of modeling a high-level view of these systems of systems and provided model checking support. However, given the scale of emerging systems of systems and their often complex topologies, analyzing only small or medium size models using model checking is insufficient. To close this gap, we developed a simulator for PTGTSs that can import real-world topologies, automatically detect violations of state properties, and handle the graph pattern matching as well as time and probabilities efficiently so that complex large-scale topologies can be considered.


title: Conditional Bigraphs

text: Bigraphs are a universal graph based model, designed for analysing reactive systems that include spatial and non-spatial (e.g. communication) relationships. Bigraphs evolve over time using a rewriting framework that finds instances of a (sub)-bigraph, and substitutes a new bigraph. In standard bigraphs, the applicability of a rewrite rule is determined completely by a local match and does not allow any non-local reasoning, i.e. contextual conditions. We introduce conditional bigraphs that add conditions to rules and show how these fit into the matching framework for standard bigraphs. An implementation is provided, along with a set of examples. Finally, we discuss the limits of application conditions within the existing matching framework and present ways to extend the range of conditions that may be expressed.


docid: eenftvew

title: Initial Conflicts for Transformation Rules with Nested Application Conditions

text: We extend the theory of initial conflicts in the framework of [Formula: see text]-adhesive categories to transformation rules with ACs. We first show that for rules with ACs, conflicts are in general neither inherited from a bigger context any more, nor is it possible to find a finite and complete subset of finite conflicts as illustrated for the category of graphs. We define initial conflicts to be special so-called symbolic transformation pairs, and show that they are minimally complete (and in the case of graphs also finite) in this symbolic way. We show that initial conflicts represent a proper subset of critical pairs again. We moreover demonstrate that (analogous to the case of rules without ACs) for each conflict a unique initial conflict exists representing it. We conclude with presenting a sufficient condition illustrating important special cases for rules with ACs, where we do not only have initial conflicts being complete in a symbolic way, but also find complete (and in the case of graphs also finite) subsets of conflicts in the classical sense.


title: Multiscale Graph Grammars Can Generate Cayley Graphs of Groups and Monoids

text: A graph grammar with parallel replacement of subgraphs, based on the single-pushout approach in graph rewriting, was designed which constructs Cayley graphs of monoids of transformations of a finite set, with permutation groups as a special case. As input, graph-based representations of a finite number of generating transformations have to be specified; they will then correspond to the edge types of the Cayley graph which is the final result of the rewriting process. The grammar has [Formula: see text] rules, where d is the number of generators, and operates at two scale levels. The fine-scale level is the level of elements on which the transformations act and where their composition is calculated by parallel subgraph replacement. The coarse-scale level corresponds to the transformations themselves which are organized in the Cayley graph in a sequential rule application process. Both scale levels are represented in a single graph. The graph grammar was implemented in the programming language XL on the software platform GroIMP, a graph rewriting tool which was originally designed for simulating the growth of plants.


title: Unfolding Symbolic Attributed Graph Grammars

text: Attributed graph grammars can specify the transformation of complex data and object structures within a natural rule-based model of concurrency. This is crucial to their use in modelling interfaces of services and components as well as the evolution of complex systems and networks. However, the established concurrent semantics of graph grammars by unfolding does not cover attributed grammars. We develop a theory of unfolding for attributed graph grammars where attribution is represented symbolically, via logical constraints. We establish a functorial representation (a coreflection) of unfolding which guarantees it to be correct, complete and fully abstract. As a case study and running example we demonstrate the use of visual contracts to specify an escrow smart contract.


title: Confluence up to Garbage

text: The transformation of graphs and graph-like structures is ubiquitous in computer science. When a system is described by graph-transformation rules, it is often desirable that the rules are both terminating and confluent so that rule applications in an arbitrary order produce unique resulting graphs. However, there are application scenarios where the rules are not globally confluent but confluent on a subclass of graphs that are of interest. In other words, non-resolvable conflicts can only occur on graphs that are considered as “garbage”. In this paper, we introduce the notion of confluence up to garbage and generalise Plump’s critical pair lemma for double-pushout graph transformation, providing a sufficient condition for confluence up to garbage by non-garbage critical pair analysis. We apply our results to language recognition by backtracking-free graph reduction, showing how to establish that a graph language can be decided by a system which is confluent up to garbage. We present two case studies with backtracking-free graph reduction systems which recognise a class of flow diagrams and a class of labelled series-parallel graphs, respectively. Both systems are non-confluent but confluent up to garbage.


title: Hypergraph Basic Categorial Grammars

text: This work is an attempt to generalize categorial grammars, which deal with string languages, to hypergraphs. We consider a particular approach called basic categorial grammar (BCG) and introduce its natural extension to hypergraphs — hypergraph basic categorial grammar (HBCG). We show that BCGs can be naturally embedded in HBCGs. It turns out that, as BCGs are equivalent to context-free grammars, HBCGs are equivalent to hyperedge replacement grammars in generalized Greibach normal form. We also present several structural properties of HBCGs. From practical point of view, we show that HBCGs can be used to describe semantics of sentences of natural languages. We incorporate the lambda semantics into the new mechanism in the same way as it is done for BCGs and show that such an embedding allows one to describe semantics of sentences with cross-serial dependencies.


title: Graph Consistency as a Graduated Property: Consistency-Sustaining and -Improving Graph Transformations

text: Where graphs are used for modelling and specifying systems, consistency is an important concern. To be a valid model of a system, the graph structure must satisfy a number of constraints. To date, consistency has primarily been viewed as a binary property: a graph either is or is not consistent with respect to a set of graph constraints. This has enabled the definition of notions such as constraint-preserving and constraint-guaranteeing graph transformations. Many practical applications—for example model repair or evolutionary search—implicitly assume a more graduated notion of consistency, but without an explicit formalisation only limited analysis of these applications is possible. In this paper, we introduce an explicit notion of consistency as a graduated property, depending on the number of constraint violations in a graph. We present two new characterisations of transformations (and transformation rules) enabling reasoning about the gradual introduction of consistency: while consistency-sustaining transformations do not decrease the consistency level, consistency-improving transformations strictly reduce the number of constraint violations. We show how these new definitions refine the existing concepts of constraint-preserving and constraint-guaranteeing transformations. To support a static analysis based on our characterisations, we present criteria for deciding which form of consistency ensuring transformations is induced by the application of a transformation rule. We illustrate our contributions in the context of an example from search-based model engineering.


title: Single Pushout Rewriting in Comprehensive Systems

text: The elegance of the single-pushout (SPO) approach to graph transformations arises from substituting total morphisms by partial ones in the underlying category. Thus, SPO’s applicability depends on the durability of pushouts after this transition. There is a wide range of work on the question when pushouts exist in categories with partial morphisms starting with the pioneering work of Löwe and Kennaway and ending with an essential characterisation in terms of an exactness property (for the interplay between pullbacks and pushouts) and an adjointness condition (w.r.t. inverse image functions) by Hayman and Heindel. Triple graphs and graph diagrams are frameworks to synchronize two or more updatable data sources by means of internal mappings, which identify common sub-structures. Comprehensive systems generalise these frameworks, treating the network of data sources and their structural inter-relations as a homogeneous comprehensive artifact, in which partial maps identify commonalities. Although this inherent partiality produces amplified complexity, Heindel’s characterisation still yields cocompleteness of the category of comprehensive systems equipped with closed partial morphisms and thus enables computing by SPO graph transformation.


title: A Categorical Semantics for Guarded Petri Nets

text: We build on the correspondence between Petri nets and free symmetric strict monoidal categories already investigated in the literature, and present a categorical semantics for Petri nets with guards. This comes in two flavors: Deterministic and with side-effects. Using the Grothendieck construction, we show how the guard semantics can be internalized in the net itself.


title: Patch Graph Rewriting

text: The basic principle of graph rewriting is the stepwise replacement of subgraphs inside a host graph. A challenge in such replacement steps is the treatment of the patch graph, consisting of those edges of the host graph that touch the subgraph, but are not part of it. We introduce patch graph rewriting, a visual graph rewriting language with precise formal semantics. The language has rich expressive power in two ways. First, rewrite rules can flexibly constrain the permitted shapes of patches touching matching subgraphs. Second, rules can freely transform patches. We highlight the framework’s distinguishing features by comparing it against existing approaches.


title: Algebras for Tree Decomposable Graphs

text: Complex problems can be sometimes solved efficiently via recursive decomposition strategies. In this line, the tree decomposition approach equips problems modelled as graphs with tree-like parsing structures. Following Milner’s flowgraph algebra, in a previous paper two of the authors introduced a strong network algebra to represent open graphs (up to isomorphism), so that homomorphic properties of open graphs can be computed via structural recursion. This paper extends this graphical-algebraic foundation to tree decomposable graphs. The correspondence is shown: (i) on the algebraic side by a loose network algebra, which relaxes the restriction reordering and scope extension axioms of the strong one; and (ii) on the graphical side by Milner’s binding bigraphs, and elementary tree decompositions. Conveniently, an interpreted loose algebra gives the evaluation complexity of each graph decomposition. As a key contribution, we apply our results to dynamic programming (DP). The initial statement of the problem is transformed into a term (this is the secondary optimisation problem of DP). Noting that when the scope extension axiom is applied to reduce the scope of the restriction, then also the complexity is reduced (or not changed), only so-called canonical terms (in the loose algebra) are considered. Then, the canonical term is evaluated obtaining a solution which is locally optimal for complexity. Finding a global optimum remains an NP-hard problem.


title: Optimistic and Pessimistic On-the-fly Analysis for Metric Temporal Graph Logic

text: The nonpropositional Metric Temporal Graph Logic (MTGL) specifies the behavior of timed dynamic systems given by timed graph sequences (TGSs), which contain typed attributed graphs representing system states and the elapsed time between states. MTGL satisfaction can be analyzed for finite TGSs by translating its satisfaction problem to the satisfaction problem of nested graph conditions using a folding operation (aggregating a TGS into a graph with history) and a reduction operation (translating an MTGL condition into a nested graph condition). In this paper, we introduce an analysis procedure for MTGL to allow for an on-the-fly analysis of finite/infinite TGSs. To this end, we introduce a further (optimistic) reduction of MTGL conditions, which leads to violations during the on-the-fly analysis only when non-satisfaction is guaranteed in the future whereas the former (pessimistic) reduction leads to violations when satisfaction is not guaranteed in the future. We motivate the relevance of our analysis procedure, which uses both reduction operations, by means of a running example. Finally, we discuss prototypical support in the tool AutoGraph.


title: Multilevel Typed Graph Transformations

text: Multilevel modeling extends traditional modeling techniques with a potentially unlimited number of abstraction levels. Multilevel models can be formally represented by multilevel typed graphs whose manipulation and transformation are carried out by multilevel typed graph transformation rules. These rules are cospans of three graphs and two inclusion graph homomorphisms where the three graphs are multilevel typed over a common typing chain. In this paper, we show that typed graph transformations can be appropriately generalized to multilevel typed graph transformations improving preciseness, flexibility and reusability of transformation rules. We identify type compatibility conditions, for rules and their matches, formulated as equations and inequations, respectively, between composed partial typing morphisms. These conditions are crucial presuppositions for the application of a rule for a match—based on a pushout and a final pullback complement construction for the underlying graphs in the category [Image: see text] —to always provide a well-defined canonical result in the multilevel typed setting. Moreover, to formalize and analyze multilevel typing as well as to prove the necessary results, in a systematic way, we introduce the category [Image: see text] of typing chains and typing chain morphisms.


title: Rewriting Theory for the Life Sciences: A Unifying Theory of CTMC Semantics

text: The Kappa biochemistry and the MØD organo-chemistry frameworks are amongst the most intensely developed applications of rewriting theoretical methods in the life sciences to date. A typical feature of these types of rewriting theories is the necessity to implement certain structural constraints on the objects to be rewritten (a protein is empirically found to have a certain signature of sites, a carbon atom can form at most four bonds, ...). In this paper, we contribute to the theoretical foundations of these types of rewriting theory a number of conceptual and technical developments that permit to implement a universal theory of continuous-time Markov chains (CTMCs) for stochastic rewriting systems. Our core mathematical concepts are a novel rule algebra construction for the relevant setting of rewriting rules with conditions, both in Double- and in Sesqui-Pushout semantics, augmented by a suitable stochastic mechanics formalism extension that permits to derive dynamical evolution equations for pattern-counting statistics.


title: Graph Parsing as Graph Transformation: Correctness of Predictive Top-Down Parsers

text: Hyperedge replacement (HR) allows to define context-free graph languages, but parsing is NP-hard in the general case. Predictive top-down (PTD) is an efficient, backtrack-free parsing algorithm for subclasses of HR and contextual HR grammars, which has been described and implemented in earlier work, based on a representation of graphs and grammar productions as strings. In this paper, we define PTD parsers for HR grammars by graph transformation rules and prove that they are correct.


title: Formal Verification of Invariants for Attributed Graph Transformation Systems Based on Nested Attributed Graph Conditions

text: The behavior of various kinds of dynamic systems can be formalized using typed attributed graph transformation systems (GTSs). The states of these systems are then modelled using graphs and the evolution of the system from one state to another is described by a finite set of graph transformation rules. GTSs with small finite state spaces can be analyzed with ease but analysis is intractable/undecidable for GTSs inducing large/infinite state spaces due to the inherent expressiveness of GTSs. Hence, automatic analysis procedures do not terminate or return indefinite or incorrect results. We propose an analysis procedure for establishing state-invariants for GTSs that are given by nested graph conditions (GCs). To this end, we formalize a symbolic analysis algorithm based on k-induction using Isabelle, apply it to GTSs and GCs over typed attributed graphs, develop support to single out some spurious counterexamples, and demonstrate the feasibility of the approach using our prototypical implementation.


Tussen wal en schip


In het kort


title: Unravelling the regio- and stereoselective synthesis of bicyclic N,O-nucleoside analogues within the molecular electron density theory perspective

text: The [3 + 2] cycloaddition (32CA) reactions of 1-pyrroline-1-oxide with N-vinyl nucleobases leading to bicyclic N,O nucleoside analogues have been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These non-polar zwitterionic type 32CA reactions take place through a one-step mechanism with minimal global electron density transfer (GEDT) at the TSs and the exo/ortho approach mode as the energetically favoured reaction path. The 32CA reactions of N-vinyl nucleobases with thymine and cytosine substituents respectively show the activation enthalpies of 15.2 and 12.5 kcal mol(−1) in toluene. The reactions are irreversible due to strong exothermic character of − 35.4–− 26.4 kcal mol(−1) in toluene. The bonding evolution theory (BET) study suggests that these 32CA reactions take place through the coupling of pseudoradical centres with earlier C–C bond formation and the formation of new C–C and C–O covalent bonds has not been started in the TSs. Non-covalent interactions (NCI) are predicted at the TSs from the visualization of NCI gradient isosurfaces. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11224-020-01569-x) contains supplementary material, which is available to authorized users.


title: Coupling between financing and innovation in a startup: embedded in networks with investors and researchers

text: Innovation may be a basis for starting a business, and financing is typically needed for starting. Innovation and financing may conceivably be negatively related, or be unrelated, or plausibly be beneficially related. These possible scenarios frame the questions: What is the coupling between innovation and financing at inception, and what is the embeddedness of coupling in networks around the entrepreneur, specifically networks with investors and researchers? These questions are addressed with a globally representative sample of entrepreneurs interviewed at inception of their business. Innovation and financing are found to be decoupled, typically; less frequently to be loosely coupled, and rarely to be tightly coupled. Coupling is promoted by networking with both investors and researchers, with additive effects and with a synergy effect. By ascertaining coupling and its embeddedness in networks as a way for building capability in a startup, the study contributes to empirically supported theorizing about capability building.


Pandemic 2020: A View from Chicago


Hydroxychloroquine retinal toxicity: The bull's eye in the human eye


ETIOLOGICAL AND CLINICAL PROFILE OF VIRUS-ASSOCIATED COMMUNITY-ACQUIRED PNEUMONIA IN ADULTS


LUNG TRANSPLANTATION FOR AN ARDS PATIENT POST-COVID-19 INFECTION


docid: lufcimeh

title: THE PREVALENCE AND PATTERN OF PNEUMONIA AMONG HAJJ PILGRIMS: A STUDY OF TWO SUCCESSIVE HAJJ SEASONS


Classification of Viruses


Microorganisms


Acute Viral Hepatitis


Epidemiology of Disease in the Tropics


Otorhinolaryngology


Acute respiratory failure in chronic obstructive pulmonary disease


Diseases of the Liver and Biliary Tract


Molecular pathology


Infections


Acute Lung Injury


Inflammatory and Purpuric Eruptions


Chest Imaging


Severe acute respiratory syndrome (SARS) vaccines


Armamentarium and Sterilization


Diarrhoea Caused by Viruses


Multifocal Ill-Defined Opacities


Lung Infections


title: The impact of delayed time to first CT head in traumatic brain injury

text: PURPOSE: Trauma team activation (TTA) criteria trigger early mobilization of resources for the sickest trauma patients. Patients with moderately depressed GCS who do not trigger the highest level activation are at risk for adverse outcomes, potentially from delayed time to intervention. The study objective was to define the impact of time to first CT Head (CTH) on outcomes among blunt trauma patients with moderately depressed GCS. METHODS: Patients from the Trauma Quality Improvement Program (TQIP) databank (2013–2016) with first ED GCS 9–12 were included. Transfers, penetrating mechanisms, death < 24 h, AIS = 6 in any body region, and patients with severe associated injuries were excluded. Study groups were defined by time to first CTH after ED arrival: immediate (≤ 1 h) vs. delayed (1–6 h). Primary outcomes were time to neurosurgical intervention and time to ED discharge. RESULTS: After exclusions, 4997 patients were identified. Of these, 79% (n = 3,954) underwent immediate CTH and 21% (n = 1,043) had delayed CTH. Median GCS was 11 [10–12] in both groups and there was no difference in median Head AIS (4 [3–4] vs. 4 [3–4], p = 0.586). Time to craniotomy and ICP monitor insertion were longer in the delayed group (4.2 h [3.0–7.6] vs. 3.1 h [2.1–8.7], p = 0.001; and 5.7 h [3.8–13.0] vs. 4.4 h [2.6–12.0], p = 0.008), as was time in the ED (4.3 h [2.7–6.5] vs. 2.1 h [1.2–3.7], p < 0.001). There was no difference in need for craniotomy (11% vs. 10%, p = 0.287), need for ICP monitor (12% vs. 12%, p = 0.899), or mortality (11% vs. 9%, p = 0.160). On multivariate analysis, age > 65 (OR 2.813, p < 0.001), SBP < 90 mmHg (OR 2.934, p < 0.001), ED intubation (OR 1.486, p = 0.001), and Head AIS scores of 4 (OR 1.884, p < 0.001) and 5 (OR 6.729, p < 0.001) were independently associated with death. CONCLUSIONS: Immediate CTH for blunt trauma patients with moderately depressed GCS decreases time to intervention and reduces ED time. A protocol to shorten time to CTH may be beneficial for both patients and hospitals.


Towards a new cosmopolitan social contract: social trends and political challenges: Daniel Innerarity: Política para Perplexos. Lisboa: Porto Editora, 2019, 214pp, € 14,94, ISBN 978-972-0-03253-4 PB


title: “They Kept Away”: Social Isolation of Cisgender Women Living with HIV in Hyderabad, India

text: Social isolation of cisgender women living with HIV has been recognized as a barrier to early detection of the virus, disclosure of HIV status to partners, and access to healthcare and social work services. The goal of this study is to explore how social isolation and depression affect cisgender women living with HIV in Hyderabad, India. Sixteen cisgender women living with HIV were asked to complete in-depth interviews regarding their experiences with HIV stigma and depression. All interviews were digitally audio-recorded in Hindi or Telugu, then translated, transcribed, and analyzed using thematic content analysis by two to three coders. Three main themes emerged from the qualitative interviews among these cisgender women living with HIV: (1) “They kept away”: Experiences with social isolation; (2) “I thought people would think badly about me”: Perceived experiences of discrimination; and (3) “I will live till I die”: Suicidality, resilience, and gaining hope. Our findings reinforce the need for emphasis on culturally appropriate interventions for depression for cisgender women living with HIV in India, including greater access to mental health resources, greater availability of trained counselors that share the same gender and are native speakers of Hindi or Telugu, and increased family and community support for socially isolated individuals.


title: Impact of Human Microbiome on Health

text: The human genome in the recent years, by the advent of technological advancements, has emerged as a major prolocutor for reciprocity between the human body and the food consumed. As known, microbiome comprises all the genetic materials within a microbiota and can thereby be also referred to as metagenome of the microbiota. Contemporary researches have revealed the influence of microbiome not only on human mind and health status, but also in wide range of disease switching, ranging from cardio-metabolic diseases, allergies and obesities to life-threatening diseases such as cancer. Though the complete mechanism of many diseases is yet unclear, research works have revealed that the metabolites, nutrients and microbes can be regarded as the key players for such physiological state. The major approach of this chapter is to enlighten the interrelationship of the microbiome on the human health either in a synergistic or in an antagonistic manner.


title: Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment

text: [Image: see text] While remdesivir has garnered much hope for its moderate anti-Covid-19 effects, its parent nucleoside, GS-441524, has been overlooked. Pharmacokinetic analysis of remdesivir evidences premature serum hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs. With its synthetic simplicity and in vivo efficacy in the veterinary setting, we contend that GS-441524 is superior to remdesivir for Covid-19 treatment.


Mitteilungen der DGKJ


title: Popular Geopolitics

text: Long derided as an inferior form of geography, there is now a recognition that if we want to understand geography and war, we can no longer depend on elite texts and elite actors. There has been an acceptance and expectation that there is some form of relationship between civil society and policy formation (and therefore decisions over war and peace) but the exact nature of this relationship has been difficult to determine. A summary of attempts to better understand this through television, cinema, cartoons and comics will be presented. However, the case will be made that this does not go far enough. Accordingly, new work from Japan will be presented, as will a case study on the use of Twitter to show how modern social media break down the traditional elite/pluralist divides.


To solve our new emergency care crisis, let's start with the old one


Successful use of COVID-19 convalescent plasma in a patient recently treated for follicular lymphoma


title: Spatial Structure in Disease Transmission Models

text: With the advent of substantial intercontinental air travel, it is possible for diseases to move from one location to a completely separate location very rapidly. This was an essential aspect of modeling SARS during the epidemic of 2002–2003, and has become a very important part of the study of the spread of epidemics. Mathematically, it has led to the study of metapopulation models or models with patchy environments and movement between patches.


The authors' response: A diagnostic confusion between serotonin syndrome and neuroleptic malignant syndrome


3 Tips for Pharma Startup Success


title: Epidemiological Models Incorporating Mobility, Behavior, and Time Scales

text: The work of Eubank et al., Sara del Valle et al., Chowell et al., and Castillo-Chavez and Song have highlighted the impact of modified modeling approaches that incorporate heterogeneous modes of mobility within variable environments in order to study their impact on the dynamics of infectious diseases. Castillo-Chavez and Song, for example, proceeded to highlight a Lagrangian perspective, that is, the use of models that keep track at all times of the identity of each individual. This approach was used to study the consequences of deliberate efforts to transmit smallpox in a highly populated city, involving transient sub-populations and the availability of massive modes of public transportation.


A pragmatic tool for Drug Discovery


docid: msohpcoy

title: Simple Compartmental Models for Disease Transmission

text: Communicable diseases that are endemic (always present in a population ) cause many deaths). For example, in 2011 tuberculosis caused an estimated 1,400,000 deaths and HIV/AIDS caused an estimated 1,200,000 deaths worldwide. According to the World Health Organization there were 627,000 deaths caused by malaria, but other estimates put the number of malaria deaths at 1,2000,000. Measles, which is easily treated in the developed world, caused 160,000 deaths in 2011, but in 1980 there were 2,600,000 measles deaths. The striking reduction in measles deaths is due to the availability of a measles vaccine. Other diseases such as typhus, cholera, schistosomiasis, and sleeping sickness are endemic in many parts of the world. The effects of high disease mortality on mean life span and of disease debilitation and mortality on the economy in afflicted countries are considerable. Most of these disease deaths are in less developed countries, especially in Africa, where endemic diseases are a huge barrier to development.


title: Models for Influenza

text: Influenza causes more morbidity and more mortality than all other respiratory diseases together. There are annual seasonal epidemics that cause about 500,000 deaths worldwide each year. During the twentieth century there were three influenza pandemics. The World Health Organization estimates that there were 40,000,000–50,000,000 deaths worldwide in the 1918 pandemic, 2,000,000 deaths worldwide in the 1957 pandemic, and 1,000,000 deaths worldwide in the 1968 pandemic. There has been concern since 2005 that the H5N1 strain of avian influenza could develop into a strain that can be transmitted readily from human to human and develop into another pandemic, together with a widely held belief that even if this does not occur there is likely to be an influenza pandemic in the near future. More recently, the H1N1 strain of influenza did develop into a pandemic in 2009, but fortunately its case mortality rate was low and this pandemic turned out to be much less serious than had been feared. There were 18,500 confirmed deaths, but the actual number of deaths caused by the H1N1 influenza may have been as many as 200,000. This history has aroused considerable interest in modeling both the spread of influenza and comparison of the results of possible management strategies.


title: Endemic Disease Models

text: In this chapter, we consider models for disease that may be endemic. In the preceding chapter we studied SIS models with and without demographics and SIR models with demographics. In each model, the basic reproduction number [Formula: see text] determined a threshold. If [Formula: see text] the disease dies out, while if [Formula: see text] the disease becomes endemic. The analysis in each case involves determination of equilibria and determining the asymptotic stability of each equilibrium by linearization about the equilibrium. In each of the cases studied in the preceding chapter the disease-free equilibrium was asymptotically stable if and only if [Formula: see text] and if [Formula: see text] there was a unique endemic equilibrium that was asymptotically stable. In this chapter, we will see that these properties continue to hold for many more general models, but there are situations in which there may be an asymptotically stable endemic equilibrium when [Formula: see text] , and other situations in which there is an endemic equilibrium that is unstable for some values of [Formula: see text] .


docid: xohwssct

title: Impacts of Modifiable Factors on Ambient Air Pollution: A Case Study of COVID-19 Shutdowns

text: [Image: see text] COVID-19-related closures offered a novel opportunity to observe and quantify the impact of activity levels of modifiable factors on ambient air pollution in real time. We use data from a network of low-cost Real-time Affordable Multi-Pollutant (RAMP) sensor packages deployed throughout Pittsburgh, Pennsylvania, along with data from Environmental Protection Agency regulatory monitors. The RAMP locations were divided into four site groups based on land use. Concentrations of PM(2.5), CO, and NO(2) following the COVID-related closures at each site group were compared to measurements from “business-as-usual” periods. Overall, PM(2.5) concentrations decreased across the domain by ∼3 μg/m(3). The morning rush-hour-induced CO and NO(2) concentrations at the high-traffic sites were both reduced by ∼50%, which is consistent with observed reductions in commuter traffic (∼50%). The morning rush-hour PM(2.5) enhancement from traffic emissions was reduced nearly 100%, from 1.4 to ∼0 μg/m(3) across all site groups. There was no significant change in the industry-related intraday variability of CO and PM(2.5) at the industrial sites following the COVID-related closures. If PM(2.5) National Ambient Air Quality Standards (NAAQS) are tightened, this natural experiment sheds light on the extent to which reductions in traffic-related emissions can aid in meeting more stringent regulations.


title: Human Behaviour and Humanitarian Work

text: This chapter illustrates parallels and similarities between the interplay that links and shapes the four internal dimensions, and the interaction between individuals (micro-level), their close environment, including the institutions they work in (meso), society (macro) and the planet (meta). This perspective is applied to the working of humanitarian organizations with an overview of options for using this logic to optimize the full potential that is inherent to the mandate of these institutions. It is shown how the proposed paradigm shift can be started, expanded and maintained, from individuals to institutions and vice versa. The outline of Compassion for Change (C4C) proposes a concrete way for using the paradigm-shift that this book is based up to transform the internal culture of humanitarian and development organizations in order to reanimate and expand their external influence.


title: Blood and Neoplastic Disorders

text: Blood Disorders covers disorders of red blood cells, white blood cells, platelets, and coagulation including congenital and acquired disorders. Neoplastic Disorders covers both Hematopoietic and Solid Tumors with information on epidemiology, clinical presentation, diagnosis, and treatment of these disorders.


title: Data Privacy Issues with RFID in Healthcare

text: Radio frequency identification (RFID) provides a means to implement the “last-mile” connection in a connected world, often referred to as the Internet of Things (IoT). RFID has been widely used in the retail and construction sectors for supply-chain management, and has provided significant benefits to those sectors. RFID has also been employed by healthcare to improve supply-chain management and monitor the locations of patients and providers to improve service offerings. The wireless and low-cost aspects of RFID introduce privacy concerns. However, there are some privacy issues related to the use of RFID, including tracking and the ability of an attacker to obtain sensitive data that is stored in the RFID tag. This chapter will explore the use of RFID in healthcare and identify issues relating to privacy that need to be addressed in these use-cases. An overview of RFID technology is presented followed by an overview of applications of RFID in healthcare. The privacy issues are then identified and potential solutions described. The privacy issues identified can be addressed using proven and standard security practices, many of which are already implemented by healthcare providers. A discussion of how to extend these practices to include RFID technology is provided.


title: Simulation-based training programme and preparedness testing for COVID-19 using system integration methodology

text: BACKGROUND: COVID-19 pandemic is presenting serious challenges to the world’s healthcare systems. The high communicability of the COVID-19 necessitates robust medical preparedness and vigilance. OBJECTIVE: To report on the simulation-based training and test preparedness activities to prepare healthcare workers (HCWs) for effective and safe handling of patients with COVID-19. METHODOLOGY: Two activities were conducted: simulation-based training to all HCWs and a full-scale unannounced simulation-based disaster exercise at King Fahad Medical City (KFMC). The online module was designed to enhance the knowledge on COVID-19. This module was available to all KFMC staff. The five hands-on practical part of the course was available to frontliner HCWs. The unannounced undercover simulated patients’ full-scale COVID-19 simulation-based disaster exercise took place in the emergency department over 3 hours. Six scenarios were executed to test the existing plan in providing care of suspected COVID-19 cases. RESULTS: 2620 HCWs took the online module, 17 courses were conducted and 337 frontliner HCWs were trained. 94% of learners were satisfied and recommended the activity to others. The overall compliance rate of the full-scale COVID-19 disaster drill with infection control guidelines was 90%. Post-drill debriefing sessions recommended reinforcing PPE training, ensuring availability of different sizes of PPEs and developing an algorithm to transfer patients to designated quarantine areas. CONCLUSION: Simulation-based training and preparedness testing activities are vital in identifying gaps to apply corrective actions immediately. In the presence of a highly hazardous contagious disease like COVID-19, such exercises are a necessity to any healthcare institution.


title: Efficacy and safety of umbilical cord mesenchymal stem cells in treatment of cesarean section skin scars: a randomized clinical trial

text: BACKGROUND: Pathological skin scars, caused by cesarean section, affected younger mothers esthetically and psychosocially and to some extent frustrated obstetricians and dermatologists. Umbilical cord mesenchymal stem cells (UC-MSCs), as a population of multipotent cells, are abundant in human tissues, providing several possibilities for their effects on skin scar tissues. Herein, we performed a randomized, double-blind, placebo-controlled, three-arm clinical trial, aiming to assess the efficacy and safety of UC-MSCs in the treatment of cesarean section skin scars among primiparous singleton pregnant women. METHODS: Ninety primiparous singleton pregnant women undergoing elective cesarean section were randomly allocated to receive placebo, low-dose (3 × 10(6) cells), or high-dose (6 × 10(6) cells) transdermal hydrogel UC-MSCs on the surface of the skin incision. The primary outcome was cesarean section skin scars followed after the sixth month, assessed by the Vancouver Scar Scale (VSS). RESULTS: All the participants completed their trial of the primary outcome according to the protocol. The mean score of estimated total VSS was 5.52 in all participants at the sixth-month follow-up, with 6.43 in the placebo group, 5.18 in the low-dose group, and 4.71 in the high-dose group, respectively. No significant difference was found between-group in the mean scores for VSS at the sixth month. Additional prespecified secondary outcomes were not found with significant differences among groups either. No obvious side effects or adverse effects were reported in any of the three arms. CONCLUSION: This randomized clinical trial showed that UC-MSCs did not demonstrate the effects of improvement of cesarean section skin scars. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02772289. Registered on 13 May 2016.


title: Getting a head start: turn-of-the-month submission effect for accepted papers in management journals

text: Intriguing unforced regularities in human behaviors have been reported in varied research domains, including scientometrics. In this study we examine the manuscript submission behavior of researchers, with a focus on its monthly pattern. With a large and reliable dataset which records the submission history of articles published on 10 multidisciplinary journals and 10 management journals over a five-year period (2013–2017), we observe a prominent turn-of-the-month submission effect for accepted papers in management journals but not multidisciplinary journals. This effect gets more pronounced in submissions to top-tier journals and when the first day of a month happens to be a Saturday or Sunday. Sense of ceremony is proposed as a likely explanation of this effect, since the first day of a month is a fundamental temporal landmark which has a ‘fresh start effect’ on researchers. To conclude, an original and interesting day-of-the-month effect in the academia is reported in this study, which calls for more research attention.


docid: qzvzutqi

title: Expanding access to radiotherapy in sub-Saharan Africa


docid: htykcyfk

title: Offline: The second wave


Aletha Maybank: AMA's Chief Health Equity Officer


Correction to Lancet Infect Dis 2020; published online June 15. https://doi.org/10.1016/S1473-3099(20)30466-7


Nature and nowness under lockdown


Evaluating case definitions for Ebola virus disease


Access to health care under threat in Afghanistan


Generation coronavirus?


Research in Brief


The ongoing torture and medical neglect of Julian Assange


"We have to consider the return on investment"


New Opportunities


The Hydrogen Engine is on its Way


A Paradigm Shift in China - The New Powertrain Mix


title: Global molecular diversity of RSV – the “INFORM RSV” study

text: BACKGROUND: Respiratory syncytial virus (RSV) is a global cause of severe respiratory morbidity and mortality in infants. While preventive and therapeutic interventions are being developed, including antivirals, vaccines and monoclonal antibodies, little is known about the global molecular epidemiology of RSV. INFORM is a prospective, multicenter, global clinical study performed by ReSViNET to investigate the worldwide molecular diversity of RSV isolates collected from children less than 5 years of age. METHODS: The INFORM study is performed in 17 countries spanning all inhabited continents and will provide insight into the molecular epidemiology of circulating RSV strains worldwide. Sequencing of > 4000 RSV-positive respiratory samples is planned to detect temporal and geographical molecular patterns on a molecular level over five consecutive years. Additionally, RSV will be cultured from a subset of samples to study the functional implications of specific mutations in the viral genome including viral fitness and susceptibility to different monoclonal antibodies. DISCUSSION: The sequencing and functional results will be used to investigate susceptibility and resistance to novel RSV preventive or therapeutic interventions. Finally, a repository of globally collected RSV strains and a database of RSV sequences will be created.


title: Dynamics of anti-malarial antibodies in non-immune patients during and after a first and unique Plasmodium falciparum malaria episode

text: BACKGROUND: Malaria is a major travel medicine issue. Retrospective confirmation of a malaria episode diagnosed in an endemic area can have relevant implications in transfusional medicine in Europe, where blood donors are excluded from donation on the basis of positive malaria serology. However, there is scarce evidence on the dynamics of anti-malarial antibodies after a first malaria episode in non-immune individuals. The first aim of this study was to describe the dynamics of anti-malarial antibodies in a first malaria episode in non-immune travellers. Secondary objectives were to assess the sensitivity of serology for a retrospective diagnosis in non-immune travellers diagnosed while abroad and to discuss the implications in transfusional medicine. METHODS: Retrospective analysis of the results of an indirect fluorescence antibody test (IFAT) for malaria available for patients with a first malaria episode by Plasmodium falciparum and admitted at the IRCCS Sacro Cuore Don Calabria hospital in a 14-year period. The antibody titres were collected at baseline and during further follow up visits. Epidemiological, demographic and laboratory test results (including full blood count and malaria parasite density) were anonymously recorded in a study specific electronic Case Report Form created with OpenClinica software. Statistical analysis was performed with SAS software version 9.4. RESULTS: Thirty-six patients were included. Among them, all but two were Europeans (one African and one American). Median length of fever before diagnosis was 2 days (IQR 1–3). Thirty-five patients had seroconversion between day 1 and day 4 from admission, and the titre showed a sharply rising titre, often to a very high level in a few days. Only a single patient remained negative in the first 5 days from admission, after which he was no more tested. Six patients were followed up for at least 2 months, and they all showed a decline in IFAT titre, tending to seroreversion (confirmed in one patient with the longest follow up, almost 4 years). CONCLUSIONS: Serology demonstrated reliable for retrospective diagnosis in non-immune travellers. The decline in the anti-malarial titre might be included in the screening algorithms of blood donors, but further studies are needed.


title: Localization of Cell Receptor-Related Genes of SARS-CoV-2 in the Kidney through Single-Cell Transcriptome Analysis

text: BACKGROUND: The new coronavirus (SARS-CoV-2), which has been responsible for the recent coronavirus disease 2019 (COVID-19) pandemic, uses the cell receptor angiotensin converting enzyme-2 (ACE2) for entry and the serine protease TMPRSS2 for spike (S) protein priming. Meanwhile, the presence of B0AT1 (SLC6A19) may prevent TMPRSS2 from accessing the cutting position on ACE2. Identifying the expression of these cell receptor-related genes of SARS-CoV-2 is critical for understanding the pathogenesis of SARS-CoV-2 in various tissues, especially in the kidney. METHODS: The single-cell transcription datasets of the human cell landscape (HCL) and other relevant single-cell transcription databases were used to analyze the expression of ACE2, TMPRSS2, and SLC6A19 in various organs and tissues, but mainly in the kidney. RESULTS: ACE2 was significantly expressed in the S1, S2, and S3 segments of proximal tubule (PT) cells. TMPRSS2 was widely expressed in several renal tubule populations extending from the PT cells to the collection system cell type, of which intercalated cells and the distal convoluted tubule cells showed more significant expression than PT cells. Unexpectedly, although expressed on various renal tubule populations, SLC6A19 was mainly enriched in PT cells, in line with ACE2 expression. Although alveolar-type (AT) 2 cells of the lung and intestinal epithelial cells expressed ACE2 as well as PT cells, AT 2 cells significantly expressed TMPRSS2 but not SLC6A19, while all 3 genes were significantly expressed in intestinal epithelial cells. CONCLUSIONS: ACE2 was widely expressed in specific cell subgroups of various human tissues, especially in intestinal epithelial cells, kidney PT cells, and also AT 2 cells of the lung. These 3 types of cells demonstrated significant differences in the distribution of the cell receptor-related genes of SARS-CoV-2, which may indicate the diversity of cell surface structures and differences in the affinity between SARS-CoV-2 and cells.


title: Aggressive Quarantine Measures Reduce the High Morbidity of COVID-19 in Patients on Maintenance Hemodialysis and Medical Staff of Hemodialysis Facilities in Wuhan, China

text: INTRODUCTION: Maintenance hemodialysis (MHD) patients are highly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Medical staff of dialysis facilities without sufficient biosecurity protection are susceptible once exposed to asymptomatic coronavirus disease 2019 (COVID-19) patients. This study evaluated the epidemiological characteristics of COVID-19 in all MHD patients and medical staff of dialysis facilities in Wuhan, China. METHODS: We collected COVID-19 morbidity and mortality data from MHD patients and medical staff from 52 hemodialysis centers in Wuhan. Then, we analyzed the symptoms and signs of patients and staff in our hospital (Tongji Hospital in Wuhan), and chest CT, SARS-CoV-2 nucleic acid detection and laboratory tests were performed. After aggressive quarantine of the COVID-19 patients, we followed up on the prognosis of them. RESULTS: We analyzed the hemodialysis data from Wuhan and found that 10% of MHD patients and 6.0% of medical staff were suspected of COVID-19. Further detection of SARS-CoV-2 nucleic acid showed that 1.7% of MHD patients and 2.9% of medical staff were confirmed as having COVID-19. In our facility, 18.9% (46/244) of patients and 9.5% (6/63) of medical staff were suspected of COVID-19. Among them, 2.9% (7/244) of MHD patients and 4.8% (3/63) of medical staff tested positive for SARS-CoV-2 were confirmed as having COVID-19. Interestingly, 87.0% of MHD patients suspected of COVID-19 did not have obvious symptoms, but the CT screening showed features of viral pneumonia. There were no significant differences in symptoms, CT findings, comorbidity and laboratory findings of SARS-CoV-2 nucleic-acid-positive and -negative patients. We followed up these patients and found that 57 patients with COVID-19 died (COVID-19 mortality 8.9%). Two patients from our dialysis center with COVID-19 (mortality 4.3%) died. No new infections occurred in our dialysis center after aggressive quarantine was initiated. CONCLUSIONS: The SARS-CoV-2 infection rates in MHD patients and medical staff in dialysis facilities were both high in Wuhan. Frequent chest CT and SARS-CoV-2 nucleic acid detection were needed to screen COVID-19 patients in dialysis facilities. Through the lessons of this experience on the aggressive diagnosis and quarantine measures of COVID-19 patients, we hope medical staff avoid more infections in serious epidemic areas.


title: Yersinia Enterocolitis May Mimic Appendicitis: 12 Years of Experience in a Single Tertiary Center

text: INTRODUCTION: Yersinia enterocolitica infection is a zoonotic disease that varies from self-limited gastroenteritis to more severe forms. Its propensity to affect the terminal ileum and to spread to regional lymph nodes explains the potential misdiagnosis with appendicitis. METHODS: We reviewed the Y. enterocoliticainfection cases in a pediatric population for the last 12 years. RESULTS: There were 11 cases of Y. enterocolitica infection in the selected period. Four patients had a suspected surgical diagnosis: 1 intussusception, 3 acute appendicitis. Patients who presented with appendicitis-like features were older, whereas younger children most commonly presented with diarrhea and fever. Ultrasound and abdominal computed tomography (CT) were performed in appendicitis-like patients and ruled out appendicitis in 2 of the 3 cases. The only patient submitted to surgery had abnormal CT findings and an important risk factor for this infection that was not recognized at presentation. CONCLUSION: This condition should be considered in patients with known risk factors (such as iron overload) and with the right epidemiological setting when presenting with abdominal symptoms. The suspicion of this diagnosis in these particular cases might obviate unnecessary surgical interventions.


Antibacterials/isavuconazole/voriconazole: Lack of efficacy: case report


Multiple drugs overdose: Various toxicities: case report


Methylprednisolone/prednisone: Accelerated viral replication following an off-label treatment: case report


Immunosuppressants: COVID-19 pneumonia: 10 case reports


Multiple drugs: Various toxicities and off-label use: case report


Norepinephrine: Severe acute dried gangrene: case report


Remote Psychosocial Rehabilitation (rPSR): A Broad View


Hydroxychloroquine: QTc prolongation: case report.


Stay Put—Undoing Screens and Oceans


title: Transformation of the mathematics classroom with the internet

text: Growing use of the internet in educational contexts has been prominent in recent years. In this survey paper, we describe how the internet is transforming the mathematics classroom and mathematics teacher education. We use as references several reviews of use of the internet in mathematics education settings made in recent years to determine how the field has evolved. We identify three domains in which new approaches are being generated by mathematic educators: principles of design of new settings; social interaction and construction knowledge; and tools and resources. The papers in this issue reflect different perspectives developed in the last decade in these three domains, providing evidence of the advances in theoretical frameworks and support in the generation of new meanings for old constructs such as ‘tool’, ‘resources’ or ‘learning setting’. We firstly highlight the different ways in which the use of digital technologies generates new ways of thinking about mathematics and the settings in which it is learnt, and how mathematics teacher educators frame the new initiatives of initial training and professional development. In this survey paper, we identify trends for future research regarding theoretical and methodological aspects, and recognise new opportunities requiring further engagement.


Put your Own Oxygen Mask Before Helping Others


docid: bwpuqiww

title: Strategies for the Prevention and Treatment of Iatrogenic Withdrawal from Opioids and Benzodiazepines in Critically Ill Neonates, Children and Adults: A Systematic Review of Clinical Studies

text: BACKGROUND: Critically ill patients are at high risk of iatrogenic withdrawal syndrome (IWS), due to exposure to high doses or prolonged periods of opioids and benzodiazepines. PURPOSE: To examine pharmacological management strategies designed to prevent and/or treat IWS from opioids and/or benzodiazepines in critically ill neonates, children and adults. METHODS: We included non-randomised studies of interventions (NRSI) and randomised controlled trials (RCTs), reporting on interventions to prevent or manage IWS in critically ill neonatal, paediatric and adult patients. Database searching included: PubMed, CINAHL, Embase, Cochrane databases, TRIP, CMA Infobase and NICE evidence. Additional grey literature was examined. Study selection and data extraction were performed in duplicate. Data collected included: population, definition of opioid, benzodiazepine or mixed IWS, its assessment and management (drug or strategy, route of administration, dosage and titration), previous drug exposures and outcomes measures. Methodological quality assessment was performed by two independent reviewers using the Cochrane risk of bias tool for RCTs and the ROBINS-I tool for NRSI. A qualitative synthesis of the results is provided. For the subset of studies evaluating multifaceted protocolised care, we meta-analysed results for 4 outcomes and examined the quality of evidence using GRADE post hoc. RESULTS: Thirteen studies were eligible, including 10 NRSI and 3 RCTs; 11 of these included neonatal and paediatric patients exclusively. Eight studies evaluated multifaceted protocolised interventions, while 5 evaluated individual components of IWS management (e.g. clonidine or methadone at varying dosages, routes of administration and duration of tapering). IWS was measured using an appropriate tool in 6 studies. Ten studies reported upon occurrence of IWS, showing significant reductions (n = 4) or no differences (n = 6). Interventions failed to impact duration of mechanical ventilation, ICU length of stay, and adverse effects. Impact on opioid and/or benzodiazepine total doses and duration showed no differences in 4 studies, while 3 showed opioid and benzodiazepine cumulative doses were significantly reduced by 20–35% and 32–66%, and treatment durations by 1.5–11 and 19 days, respectively. Variable effects on intervention drug exposures were found. Weaning durations were reduced by 6–12 days (n = 4) for opioids and/or methadone and by 13 days (n = 1) for benzodiazepines. In contrast, two studies using interventions centred on transition to enteral routes or longer tapering durations found significant increases in intervention drug exposures. Interventions had overall non-significant effects on additional drug requirements (except for one study). Included studies were at high risk of bias, relating to selection, detection and reporting bias. CONCLUSION: Interventions for IWS management fail to impact duration of mechanical ventilation or ICU length of stay, while effect on occurrence of IWS and drug exposures is inconsistent. Heterogeneity in the interventions used and methodological issues, including inappropriate and/or subjective identification of IWS and bias due to study design, limited the conclusions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40265-020-01338-4) contains supplementary material, which is available to authorized users.


Views from around the world


Doing our best


IOTECH in times of COVID-19


Richard Sennett: Building and dwelling: ethics for the city: Penguin Books, 2019, 368 pp., ISBN: 9780141022116


title: Ventilator-associated pneumonia in neonates: the role of point of care lung ultrasound

text: No consensus exists regarding the definition of ventilator-associated pneumonia (VAP) in neonates and reliability of chest X-ray (CXR) is low. Lung ultrasound (LU) is a potential alternative diagnostic tool. The aim was to define characteristics of VAP in our patient population and propose a multiparameter score, incorporating LU, for VAP diagnosis. Between March 25, 2018, and May 25, 2019, infants with VAP were identified. Clinical, laboratory and microbiology data were collected. CXRs and LU scans were reviewed. A multiparameter VAP score, including LU, was calculated on Day 1 and Day 3 for infants with VAP and for a control group and compared with CXR. VAP incidence was 10.47 episodes/1000 ventilator days. LU and CXR were available for 31 episodes in 21 infants with VAP, and for six episodes in five patients without VAP. On Day 1, a VAP score of > 4, and on Day 3 a score of > 5 showed sensitivity of 0.94, and area under the curve of 0.91 and 0.97, respectively. AUC for clinical information only was 0.88 and for clinical and CXR 0.85. Conclusion: The multiparameter VAP score including LU could be useful in diagnosing VAP in neonates with underlying lung pathology.


title: Study design of the DAS-OLT trial: a randomized controlled trial to evaluate the impact of dexmedetomidine on early allograft dysfunction following liver transplantation

text: BACKGROUND: Perioperative ischemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction (EAD), graft loss, and mortality. Hepatic I/R injury also causes remote damage to other organs including the renal and pulmonary systems. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist which is used as an adjuvant to general anesthesia, has been shown in preclinical studies to provide organ protection by ameliorating the effects of I/R injury in a range of tissues (including the liver). However, prospective clinical evidence of any potential benefits in improving outcomes in liver transplantation is lacking. This study aimed to verify the hypothesis that the application of dexmedetomidine during the perioperative period of liver transplantation can reduce the incidence of EAD and primary graft non-function (PNF). At the same time, the effects of dexmedetomidine application on perioperative renal function and lung function were studied. METHODS: This is a prospective, single-center, randomized, parallel-group study. Two hundred participants (18–65 years) scheduled to undergo liver transplantation under general anesthesia will be included in this study. For participants in the treatment group, a loading dose of DEX will be given after induction of anesthesia (1 μg/kg over 10 min) followed by a continuous infusion (0.5 μg/kg /h) until the end of surgery. For participants in the placebo group, an equal volume loading dose of 0.9% saline will be given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. All other supplements, e.g., opioids, sedatives, and muscle relaxant, will be identical in both arms and administered according to routine clinical practice. DISCUSSION: The present trial will examine whether DEX confers organoprotective effects in the liver, in terms of reducing the incidence of EAD and PNF in orthotopic liver transplantation recipients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03770130. Registered on 10 December 2018. https://clinicaltrials.gov/ct2/show/NCT03770130


Mining Medical Isotopes from Nuclear Waste


docid: fgigvhpt

title: Die Coronavirus Structural Task Force


title: Contingent reflections on coronavirus and priorities for educational planning and development

text: The COVID-19 pandemic has dramatically shifted education and development priorities. The tragic death toll and high rates of morbidity across many countries are an unprecedented setback and a calamity for those affected physically and mentally. The economic and social effects of lockdowns, loss of production and business confidence, and global recession will cast a long shadow over education systems. Despite the 435 million items that Google already indexes under “COVID-19 education”, many things remain unknown. No one has a clear idea of how the current pandemic will unravel over anything but the short term. The challenge is to strengthen the mechanisms to separate evidence from opinion and to balance popularism with speaking truth to power—especially when political systems can find it difficult to distinguish fact from convenient fiction. This paper advances ten propositions that will shape policy dialogue and whatever iteration of the Sustainable Development Goals is needed to ensure they remain fit for purpose. Testing these propositions over the next year will open the door to an evidence-based approach to reconstruction and sustainable development and juxtapose immediate concerns of the present with aspirations for the future. More than ever the need is to see beyond the exigencies of COVID-19 and act to secure the educational gains of the recent past. UNESCO and other development agencies can play a key role in sharing how to manage revitalised and resilient learning systems that allow the community of practice to stay focussed on development that is economically, socially, medically, and educationally sustainable. Spaceship Earth has to be secured for future generations through the knowledge, skill and attitudes of its crew and passengers. Seriously revisiting SDG4, its targets and indicators, and its relationships with other SDGs, would be a start.


Rekombinante, vollständig humane Antikörper zur Behandlung akuter COVID-19


title: Multiklonale Antikörper als Ersatz für Zweitantikörper aus Seren

text: Today, recombinant antibodies can replace animal-derived primary antibodies in almost all applications. Due to their monoclonal origin and always known sequence, they offer optimal reproducibility. In contrast, almost all secondary antibodies are still made from animal sera. Multiclonal antibodies made by animal-free recombinant methods here offer a higher quality replacement for serum-derived secondary antibodies.


Corona und Forschungsförderung: Unterstützung und Impulse im Zeichen der Pandemie


title: Dynamische Preisgestaltung in der digitalisierten Welt

text: Digital technologies favor the use of dynamic pricing, i.e., prices that vary unannounced for a product that basically remains unchanged. However, different forms of dynamic pricing are often mixed in the public discussion, which makes a meaningful analysis of the advantages and disadvantages of dynamic pricing difficult. The aim of this paper is to present the economic foundations of dynamic pricing as well as to discuss and to classify its design options. In addition, the paper assesses dynamic pricing from a buyer and seller perspective. Finally, the paper discusses implications for business research.


title: Maßgeschneiderte Polyketidsynthasen zur Herstellung von Polyketid-Derivaten

text: Polyketides (PKs) are secondary metabolites with valuable properties, including antibiotic, antifungal, antiviral, anticancer, and immunosuppressive activity. The biosynthesis of PKs is accomplished by multifunctional megaenzymes, the polyketide synthases (PKSs). The molecular architecture of those remarkable assembly lines provides opportunities for their engineering and generation of PK derivatives with potentially improved pharmacokinetics and/or expanded spectrum of bioactivity.


docid: bltitaal

title: Gemeinschaftlich in Krisenzeiten: NMR-Strukturbiologie gegen COVID-19


title: A stochastic analysis for a triple delayed SIQR epidemic model with vaccination and elimination strategies

text: In this paper, a delayed SIQR epidemic model with vaccination and elimination hybrid strategies is analysed under a white noise perturbation. We prove the existence and the uniqueness of a positive solution. Afterwards, we establish a stochastic threshold [Formula: see text] in order to study the extinction and persistence in mean of the stochastic epidemic system. Then we investigate the existence of a stationary distribution for the delayed stochastic model. Finally, some numerical simulations are presented to support our theoretical results.


Infections and Collapsing Glomerulopathy


Ultrasound-guided central venous catheterization amid the COVID-19 outbreak: ‘Revisiting protocols’


What Should We be Studying Regarding COVID-19?


Evaluation of interference effects from hemolysis, icterus and lipemia on the Roche Elecsys® Anti-SARS-CoV-2 assay


How should the political animals of the 21st century feel?: Comment on “The sense of should: A biologically-based framework for modelling social pressure” by J.E. Theriault et al.


title: Lung Cytopathology (Bronchial and Aspiration Cytology)

text: This chapter is focused on the discussion and review of cytomorphological features of benign and malignant respiratory lesions. The respiratory system can be divided into upper and lower tract, thus, the variety of sampling and preparation methods are also reviewed, since the cytomorphology of the lesion may reveal differently depending on the sampling and preparation techniques. In addition, the critical information regarding molecular tests of lung carcinomas are also reviewed.