High-temporal resolution profiling reveals distinct immune trajectories following the first and second doses of COVID-19 mRNA vaccines.

Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high-temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency sampling protocols in profiling vaccine-elicited immune responses.

Overcrowding in Emergency Department: Causes, Consequences, and Solutions-A Narrative Review.

Overcrowding in Emergency Departments (EDs) is a phenomenon that is now widespread globally and causes a significant negative impact that goes on to affect the entire hospital. This contributes to a number of consequences that can affect both the number of resources available and the quality of care. Overcrowding is due to a number of factors that in most cases lead to an increase in the number of people within the ED, an increase in mortality and morbidity, and a decrease in the ability to provide critical services in a timely manner to patients suffering from medical emergencies. This phenomenon results in the Emergency Department reaching, and in some cases exceeding, its optimal capacity. In this review, the main causes and consequences involving this phenomenon were collected, including the effect caused by the SARS-CoV-2 virus in recent years. Finally, special attention was paid to the main operational strategies that have been developed over the years, strategies that can be applied both at the ED level (microlevel strategies) and at the hospital level (macrolevel strategies).

Offline Evaluation of Recommender Systems in a User Interface With Multiple Carousels.

Many video-on-demand and music streaming services provide the user with a page consisting of several recommendation lists, i.e., widgets or swipeable carousels, each built with specific criteria (e.g., most recent, TV series, etc.). Finding efficient strategies to select which carousels to display is an active research topic of great industrial interest. In this setting, the overall quality of the recommendations of a new algorithm cannot be assessed by measuring solely its individual recommendation quality. Rather, it should be evaluated in a context where other recommendation lists are already available, to account for how they complement each other. The traditional offline evaluation protocol however does not take this into account. To address this limitation, we propose an offline evaluation protocol for a carousel setting in which the recommendation quality of a model is measured by how much it improves upon that of an already available set of carousels. We also propose to extend ranking metrics to the two-dimensional carousel setting in order to account for a known position bias, i.e., users will not explore the lists sequentially, but rather concentrate on the top-left corner of the screen. Finally, we describe and evaluate two strategies for the ranking of carousels in a scenario where the technique used to generate the two-dimensional layout is agnostic on the algorithms used to generate each carousel. We report experiments on publicly available datasets in the movie domain to show how the relative effectiveness of several recommendation models compares. Our results indicate that under a carousel setting the ranking of the algorithms changes sometimes significantly. Furthermore, when selecting the optimal carousel layout accounting for the two dimensional layout of the user interface leads to very different selections.

Evaluating the job shop scheduling problem on a D-wave quantum annealer.

Job Shop Scheduling is a combinatorial optimization problem of particular importance for production environments where the goal is to complete a production task in the shortest possible time given limitations in the resources available. Due to its computational complexity it quickly becomes intractable for problems of interesting size. The emerging technology of Quantum Annealing provides an alternative computational architecture that promises improved scalability and solution quality. However, several limitations as well as open research questions exist in this relatively new and rapidly developing technology. This paper studies the application of quantum annealing to solve the job shop scheduling problem, describing each step required from the problem formulation to the fine-tuning of the quantum annealer and compares the solution quality with various classical solvers. Particular attention is devoted to aspects that are often overlooked, such as the computational cost of representing the problem in the formulation required by the quantum annealer, the relative qubits requirements and how to mitigate chain breaks. Furthermore, the impact of advanced tools such as reverse annealing is presented and its effectiveness discussed. The results indicate several challenges emerging at various stages of the experimental pipeline which bring forward important research questions and directions of improvement.

Feature Selection for Recommender Systems with Quantum Computing.

The promise of quantum computing to open new unexplored possibilities in several scientific fields has been long discussed, but until recently the lack of a functional quantum computer has confined this discussion mostly to theoretical algorithmic papers. It was only in the last few years that small but functional quantum computers have become available to the broader research community. One paradigm in particular, quantum annealing, can be used to sample optimal solutions for a number of NP-hard optimization problems represented with classical operations research tools, providing an easy access to the potential of this emerging technology. One of the tasks that most naturally fits in this mathematical formulation is feature selection. In this paper, we investigate how to design a hybrid feature selection algorithm for recommender systems that leverages the domain knowledge and behavior hidden in the user interactions data. We represent the feature selection as an optimization problem and solve it on a real quantum computer, provided by D-Wave. The results indicate that the proposed approach is effective in selecting a limited set of important features and that quantum computers are becoming powerful enough to enter the wider realm of applied science.

Prospective validation study of prognostic biomarkers to predict adverse outcomes in patients with COVID-19: a study protocol.

INTRODUCTION: Accurate triage is an important first step to effectively manage the clinical treatment of severe cases in a pandemic outbreak. In the current COVID-19 global pandemic, there is a lack of reliable clinical tools to assist clinicians to perform accurate triage. Host response biomarkers have recently shown promise in risk stratification of disease progression; however, the role of these biomarkers in predicting disease progression in patients with COVID-19 is unknown. Here, we present a protocol outlining a prospective validation study to evaluate the biomarkers' performance in predicting clinical outcomes of patients with COVID-19. METHODS AND ANALYSIS: This prospective validation study assesses patients infected with COVID-19, in whom blood samples are prospectively collected. Recruited patients include a range of infection severity from asymptomatic to critically ill patients, recruited from the community, outpatient clinics, emergency departments and hospitals. Study samples consist of peripheral blood samples collected into RNA-preserving (PAXgene/Tempus) tubes on patient presentation or immediately on study enrolment. Real-time PCR (RT-PCR) will be performed on total RNA extracted from collected blood samples using primers specific to host response gene expression biomarkers that have been previously identified in studies of respiratory viral infections. The RT-PCR data will be analysed to assess the diagnostic performance of individual biomarkers in predicting COVID-19-related outcomes, such as viral pneumonia, acute respiratory distress syndrome or bacterial pneumonia. Biomarker performance will be evaluated using sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operating characteristic curve. ETHICS AND DISSEMINATION: This research protocol aims to study the host response gene expression biomarkers in severe respiratory viral infections with a pandemic potential (COVID-19). It has been approved by the local ethics committee with approval number 2020/ETH00886. The results of this project will be disseminated in international peer-reviewed scientific journals.

Transformation of a Ferry Ship into a Ship Hospital for COVID-19 Patients.

Liguria is a northwestern region of Italy that, since the WHO has declared COVID-19 as a pandemic (11 March 2020), presented 108 patients hospitalized, 34 of which were in the intensive care unit. Due to this serious epidemiological emergency, the transformation of a long-distance ferry ship into a hospital ship for COVID-19 patients who were still positive after the acute phase of the illness was carried out to free up hospital beds for patients in the acute phase. The ship was moored in the port of Genoa, the capital of Liguria. The conversion was localized to a single deck, where designated healthcare areas were identified. From 23 March to 18 June 2020, 191 patients were admitted onto the ship; they were provided with high-level healthcare guaranteed by the multi-disciplinary nature of clinical competencies available. Patients had a favorable outcome in all cases, confirmed by their recovery and negative swab results. Moreover, no cases of voluntary discharge were recorded. To the best of our knowledge, this is the only example in the world in which a passenger ship was transformed into a ship hospital for COVID patients.

Evaluation of novel coronavirus disease (COVID-19) using quantitative lung CT and clinical data: prediction of short-term outcome.

BACKGROUND: Computed tomography (CT) enables quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, helping in outcome prediction. METHODS: From 1 to 22 March 2020, patients with pneumonia symptoms, positive lung CT scan, and confirmed SARS-CoV-2 on reverse transcription-polymerase chain reaction (RT-PCR) were consecutively enrolled. Clinical data was collected. Outcome was defined as favourable or adverse (i.e., need for mechanical ventilation or death) and registered over a period of 10 days following CT. Volume of disease (VoD) on CT was calculated semi-automatically. Multiple linear regression was used to predict VoD by clinical/laboratory data. To predict outcome, important features were selected using a priori analysis and subsequently used to train 4 different models. RESULTS: A total of 106 consecutive patients were enrolled (median age 63.5 years, range 26-95 years; 41/106 women, 38.7%). Median duration of symptoms and C-reactive protein (CRP) was 5 days (range 1-30) and 4.94 mg/L (range 0.1-28.3), respectively. Median VoD was 249.5 cm3 (range 9.9-1505) and was predicted by lymphocyte percentage (p = 0.008) and CRP (p < 0.001). Important variables for outcome prediction included CRP (area under the curve [AUC] 0.77), VoD (AUC 0.75), age (AUC 0.72), lymphocyte percentage (AUC 0.70), coronary calcification (AUC 0.68), and presence of comorbidities (AUC 0.66). Support vector machine had the best performance in outcome prediction, yielding an AUC of 0.92. CONCLUSIONS: Measuring the VoD using a simple CT post-processing tool estimates SARS-CoV-2 burden. CT and clinical data together enable accurate prediction of short-term clinical outcome.

An Italian registry of chest pain patients in the emergency department: clinical predictors of acute coronary syndrome.

BACKGROUND: The aim of this study was to describe the population of patients arriving in several Italian Emergency Departments (EDs) complaining of chest pain suggestive of acute coronary syndrome (ACS) in order to evaluate the incidence of ACS in this cohort and the association between ACS and different clinical parameters and risk factors. METHODS: This is an observational prospective study, conducted from the 1st January to the 31st December 2014 in 11 EDs in Italy. Patients presenting to ED with chest pain, suggestive of ACS, were consecutively enrolled. RESULTS: Patients with a diagnosis of ACS (N.=1800) resulted to be statistically significant older than those without ACS (NO ACS; N.=4630) (median age: 70 vs. 59, P<0.001), and with a higher prevalence of males (66.1% in ACS vs. 57.5% in NO ACS, P<0.001). ECG evaluation, obtained at ED admission, showed new onset alterations in 6.2% of NO ACS and 67.4% of ACS patients. Multiple logistic regression analysis showed that the following parameters were predictive for ACS: age, gender, to be on therapy for cardio-vascular disease (CVD), current smoke, hypertension, hypercholesterolemia, heart rate, ECG alterations, increased BMI, reduced SaO2. CONCLUSIONS: Results from this observational study strengthen the importance of the role of the EDs in ruling in and out chest pain patients for the diagnosis of ACS. The analysis put in light important clinical and risk factors that, if promptly recognized, can help Emergency Physicians to identify patients who are more likely to be suffering from ACS.

Angioedema in the emergency department: a practical guide to differential diagnosis and management.

BACKGROUND: Angioedema is a common presentation in the emergency department (ED). Airway angioedema can be fatal; therefore, prompt diagnosis and correct treatment are vital. OBJECTIVE OF THE REVIEW: Based on the findings of two expert panels attended by international experts in angioedema and emergency medicine, this review aims to provide practical guidance on the diagnosis, differentiation, and management of histamine- and bradykinin-mediated angioedema in the ED. REVIEW: The most common pathophysiology underlying angioedema is mediated by histamine; however, ED staff must be alert for the less common bradykinin-mediated forms of angioedema. Crucially, bradykinin-mediated angioedema does not respond to the same treatment as histamine-mediated angioedema. Bradykinin-mediated angioedema can result from many causes, including hereditary defects in C1 esterase inhibitor (C1-INH), side effects of angiotensin-converting enzyme inhibitors (ACEis), or acquired deficiency in C1-INH. The increased use of ACEis in recent decades has resulted in more frequent encounters with ACEi-induced angioedema in the ED; however, surveys have shown that many ED staff may not know how to recognize or manage bradykinin-mediated angioedema, and hospitals may not have specific medications or protocols in place. CONCLUSION: ED physicians must be aware of the different pathophysiologic pathways that lead to angioedema in order to efficiently and effectively manage these potentially fatal conditions.

The Robustness and Effectiveness of the Triage System at Times of Overcrowding and the Extra Costs due to Inappropriate Use of Emergency Departments.

BACKGROUND: Overcrowding is one of the most harmful problems for Emergency Department (ED) management and the correct estimation of time resource absorption by each type of patient plays a strategic role in dealing with overcrowding and correctly programming ED activity. OBJECTIVE: We aimed to investigate how overcrowding may affect urgent patients' waiting times (i.e., the robustness of the triage patient priority system) and to evaluate the extra costs due to inappropriate use of EDs. METHODS: Data referring to 54,254 patients who accessed the ED of a major Italian hospital in 2011 were analyzed to study patient flows and overcrowding. To define an average per-patient cost, according to the severity of his or her health condition, the 2010 profit and loss account of the aforementioned hospital was studied and the time devoted by physicians to each type of patient was estimated by means of a self-reported survey. RESULTS: Empirical findings confirm a positive correlation between overcrowding and the time a patient has to wait before receiving treatment. This effect is relevant only for non-urgent patients who are responsible for the overcrowding itself. However, urgent patients' waiting times do not increase in the presence of overcrowding, confirming that the triage priority system is robust against the overcrowding situation. The analysis estimates, using 2010 data, that the actual per patient cost incurred by the hospital when treating white-coded patients is, on average, 36.54 euros; a green code costs 93.17, yellow 170.62, and red 227.62. It emerges that 4% of all the personnel costs are attributable to white color-code assistance, 67% to green codes, 23% to yellow codes, and the remaining 6% to red codes. CONCLUSION: The implementation of effective policies intended to improve both efficiency and quality in providing emergency health services has to deal with the systemic problem of inappropriate use of EDs. Policy-makers should be aware of the fact that there is a considerable portion of ED demand for assistance that is inappropriate and that oversizing EDs with respect to the true, appropriate, urgent patients' demands, could bring about a further and undesirable rise in inappropriate assistance demands and, therefore, an increase in ED costs that are not consistent with their objectives.

Potent cholesteryl ester transfer protein inhibitors of reduced lipophilicity: 1,1'-spiro-substituted hexahydrofuroquinoline derivatives.

A series of 1,1'-spiro-substituted hexahydrofuroquinoline derivatives exhibiting potent cholesteryl ester transfer protein (CETP) inhibition at reduced lipophilicity was identified. A focused structure-activity relationship (SAR) exploration led to the potent and comparatively polar CETP inhibitor 26 showing robust high density lipoprotein-cholesterol (HDL-C) elevation and low density lipoprotein-cholesterol (LDL-C) reduction in transgenic hCETP/hApoB-100 mice. Compound 26 was also shown to positively differentiate from highly lipophilic CETP inhibitors in its complete elimination from fat tissue in hCETP transgenic mice as evident within 21 days after cessation of treatment. In addition, compound 26 showed no significant effects on aldosterone secretion from H295R cells, as well as no significant effects on blood pressure and electrocardiogram parameters in telemetrized cynomolgus monkeys.

Guidance for diagnosis and treatment of acute angioedema in the emergency department: consensus statement by a panel of Italian experts.

Angioedema attacks, characterized by the transient swelling of the skin and mucosae, are a frequent cause of visits to the emergency department. Swellings of the oral cavity, tongue, or larynx can result in life-threatening airway obstruction, while abdominal attacks can cause severe pain and often lead to unnecessary surgery. The underlying pathophysiologic process resulting in increased vascular permeability and plasma extravasation is mediated by vasoactive molecules, most commonly histamine and bradykinin. Based on the mediator involved, distinct angioedema forms can be recognized, calling for distinct therapeutic approaches. Prompt recognition is challenging for the emergency physician. The low awareness among physicians of the existence of rare forms of angioedema with different aetiologies and pathogenesis, considerably adds to the problem. Also poorly appreciated by emergency personnel may be the recently introduced bradykinin-targeted treatments. The main objective of this consensus statement is to provide guidance for the management of acute angioedema in the emergency department, from presentation to discharge or hospital admission, with a focus on identifying patients in whom new treatments may prevent invasive intervention.

[The utility of assaying the N-terminal of brain natriuretic peptide precursor (NT pro-BNP) to predict the clinical outcome in patients with supraventricular tachyarrhythmias observed and treated in the emergency room]. / Utilità del dosaggio del precursore del peptide natriuretico cerebrale come predittore di cardioversione efficace nei pazienti con tachicardie e tachiaritmie sopraventricolari, osservati e trattati in Pronto Soccorso.

Many patients arrive at the emergency room (ER) with recent-onset atrial fibrillation or other forms of supraventricular tachyarrhythmia (SV Ta) or tachycardia. The restoration of sinus rhythm (SR) is always desirable and, in addition, can enable many hospitalisations to be avoided, thereby achieving considerable savings in financial and healthcare resources. Even in haemodynamically stable cases, it is clearly useful to be able to evaluate which subjects will benefit most from attempts to restore SR, even when few truly diagnostic means are on hand (such as echocardiography, which is not always promptly available in the ER setting). We evaluated the brain natriuretic peptide precursor (N terminal pro-BNP) in 105 patients arriving at the ER. We observed that SR was restored in a low percentage of patients with values > 4500, while the vast majority of those with values < 1500 was normalised even by means of antiarrhythmic drugs alone. It is therefore probable that a medium-low value of the hormone indicates only an acute response to the distension of the atrial tissue induced by the arrhythmia; by contrast, decidedly elevated values are probably also caused by ventricular dysfunction and therefore indicate a lesser likelihood of restoring SR. The routine evaluation of NT pro-BNP could be used as an alternative to echocardiography in order to rapidly select patients in whom cardioversion should be attempted in the ER or Brief Observation Unit.