Background Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. Conclusions Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693 .
Human vision requires us to analyze the visual periphery to decide where to fixate next. In the present study, we investigated this process in people with age-related macular degeneration (AMD). In particular, we examined viewing biases and the extent to which visual salience guides fixation selection during free-viewing of naturalistic scenes. We used an approach combining generalized linear mixed modeling (GLMM) with a-priori scene parcellation. This method allows one to investigate group differences in terms of scene coverage and observers’ well-known tendency to look at the center of scene images. Moreover, it allows for testing whether image salience influences fixation probability above and beyond what can be accounted for by the central bias. Compared with age-matched normally sighted control subjects (and young subjects), AMD patients’ viewing behavior was less exploratory, with a stronger central fixation bias. All three subject groups showed a salience effect on fixation selection—higher-salience scene patches were more likely to be fixated. Importantly, the salience effect for the AMD group was of similar size as the salience effect for the control group, suggesting that guidance by visual salience was still intact. The variances for by-subject random effects in the GLMM indicated substantial individual differences. A separate model exclusively considered the AMD data and included fixation stability as a covariate, with the results suggesting that reduced fixation stability was associated with a reduced impact of visual salience on fixation selection.
Existing evidence suggest that SME exporting is affected by a combination of environmental, firm-level, and owner-level drivers. However, it is not yet clear what constitute the profile of exporting SMEs and whether innovation orientation plays a role. To fill this important gap, our study adopts a configurational approach contending that a specific set of drivers makeup the profiles of exporting SMEs. Using the Classification and Regression Trees (CART) algorithm, we empirically show three distinctive exporting profiles for product, service, and process innovators, with varying magnitude and importance of export drivers. Our results show the most important export drivers for product, service and process innovators. While process innovators’ profile excludes process innovation, product and service innovators’ profiles include product and service innovation respectively. These results lead to major policy and managerial implications in relation to promoting exporting among SMEs given that the UK has left the European Union.
With the growing rate of energy, depletion of natural resources, and the impact issues of conventional energy sources on the global climate changes, there is a growing demand for heat recovery that saves over 90% of the lost energy in terms of saving wasted energy. Throughout the research, it is noticed that hybrid heat recovery systems, which means employing more than one heat recovery system into one single system, are showing great potential in many applications, where the recovery systems exceed 28% and the coefficient of performance reaches 2.2 times the conventional system. At this point, the current study presents a comprehensive review of hybrid heat recovery systems and gives a rich and useful summary of previous works. The main aim here is to (1) classify energy recovery systems into specific methods, (2) provide an overview of hybrid energy recovery systems, (3) demonstrate a detailed description of each method, (4) point out their applications, (5) present innovative systems, and (6) show the pros and cons of each system alone and each system combined into a hybrid heat recovery system. Finally, this review shows that hybrid heat recovery is a promising solution, especially when combined with thermoelectric generators (TEG), where 60% of the studies involve TEG in a hybrid heat recovery system. Moreover, this review answers the main question which is: does the rise in the percent of heat recovery in a hybrid heat recovery system is worthy of employing a complement or new heat recovery system, or may it cost more than it recovers?
Cryptosporidium parvum is a leading cause of diarrheal illness worldwide being a significant threat to young children and immunocompromised patients but the pathogenesis caused by this parasite remains poorly understood. C. parvum was recently linked with oncogenesis. Notably, the mechanisms of gene expression regulation are unexplored in Cryptosporidium and little is known about how the parasite impact host genome regulation. Here, we investigated potential histone lysine methylation, a dynamic epigenetic modification, during the life cycle of the parasite. We identified SET-domain containing proteins, putative lysine methyltransferases (KMTs), in the C. parvum genome and classified them phylogenetically into distinct subfamilies (namely CpSET1, CpSET2, CpSET8, CpKMTox and CpAKMT). Our structural analysis further characterized CpSET1, CpSET2 and CpSET8 as histone lysine methyltransferases (HKMTs). The expression of the CpSET genes varies considerably during the parasite life cycle and specific methyl-lysine antibodies showed dynamic changes in parasite histone methylation during development (CpSET1:H3K4; CpSET2:H3K36; CpSET8:H4K20). We investigated the impact of C. parvum infection on the host histone lysine methylation. Remarkably, parasite infection led to a considerable decrease in host H3K36me3 and H3K27me3 levels, highlighting the potential of the parasite to exploit the host epigenetic regulation to its advantage. This is the first study to describe epigenetic mechanisms occurring throughout the parasite life cycle and during the host-parasite interaction. A better understanding of histone methylation in both parasite and host genomes may highlight novel infection control strategies.
At a time when legislative powers are being undermined by strengthened executives, oversight has become a core function of parliaments throughout the democratic world. In the European Parliament ( ep ), whose legislative role has been enhanced throughout the integration process, a significant proportion of the activities of its members is devoted to their broad ‘functions of political control’ on the EU’s executive institutions (art. 14 teu ). The ways in which Members of the European Parliament ( mep s) exercise these functions and how the EU political system is impacted in turn remains, however, an under-researched topic. Focusing specifically on parliamentary questions, this article investigates the day-to-day interactions between the ep and one major EU institution, namely the European Central Bank ( ecb ). It seeks to establish what motivates mep s questions concerning monetary and financial policies. Relying on a new dataset, we find evidence that mep s’ questions to the ecb are subject to both strategic and partisan considerations.
Introduction and hypothesisProlapse is a common condition seen in women and its therapeutical management consists first and foremost of surgery. Postoperative pain is one of the most common side effects seen after surgery. The objective of this study was to identify risk factors for postoperative pain after cystocele repair with mesh.Methods This is a secondary analysis of the multicenter randomized trial PROSPERE, which compared cystocele repair with mesh according to the vaginal or laparoscopic approach. The presence of postoperative pain was assessed by a pain-specific self-reported questionnaire (Questionnaire de Baudelocque). The statistical analysis is based on the Wilcoxon, Chi-squared, and Fisher’s tests.ResultsThe prevalence of postoperative pain (pain persisting more than 6 months) was 39% (80 out of 205, 95% CI 32.4–46.1), with 6.3% (13 out of 205) of chronic pain reports. Preoperative pain was the only statistically significant risk factor OR = 2.32 (p = 0,007; 95% CI 1.24–4.36).Conclusions Surgeons must be careful with preoperative painful prolapse and should inform their patient of the risk of developing postoperative chronic pain.
Objectives: To assess the reliability and diagnostic accuracy of new radiographic definitions for calcium pyrophosphate deposition (CPPD) identification, developed by an international multidisciplinary working group. Methods: Patients with knee osteoarthritis scheduled for knee replacement were enrolled. Two radiologists and two rheumatologists assessed twice the images for presence/absence of CPPD on menisci, hyaline cartilage, tendons, joint capsule, synovial membrane, using the new definitions. In case of disagreement, a consensus decision was taken and considered for the assessment of diagnostic performance. Histological examination of specimens under compensated polarized light microscopy was the reference standard. Prevalence-adjusted bias-adjusted kappa (PABAK) was used to assess the reliability. Diagnostic performance statistics were calculated. Results: Sixty-seven participants were enrolled for the reliability study. The inter-observer reliability was substantial in most of the assessed structures when considering all 4 readers (kappa range 0.59 - 0.90), substantial to almost perfect among radiologists (kappa range 0.70-0.91), and moderate to almost perfect among rheumatologists (kappa range 0.46 - 0.88). The intra-observer reliability was substantial to almost perfect for all the observers (kappa range 0.70 - 1). Fifty-one patients were enrolled for the accuracy study. Radiography demonstrated to be specific for CPPD (92%), but sensitivity remained low in all sites and in the overall diagnosis (54%). Conclusion: The new imaging definitions of CPPD are highly specific against the gold standard of histological diagnosis; when described findings are present these definitions allow for a definite diagnosis of CPPD, rather than other calcium-containing crystal depositions; instead a negative finding does not exclude the diagnosis.
Background Ventilator-associated pneumonia (VAP) is common in patients with severe SARS-CoV-2 pneumonia. The aim of this ancillary analysis of the coVAPid multicenter observational retrospective study is to assess the relationship between adjuvant corticosteroid use and the incidence of VAP. Methods Planned ancillary analysis of a multicenter retrospective European cohort in 36 ICUs. Adult patients receiving invasive mechanical ventilation for more than 48 h for SARS-CoV-2 pneumonia were consecutively included between February and May 2020. VAP diagnosis required strict definition with clinical, radiological and quantitative microbiological confirmation. We assessed the association of VAP with corticosteroid treatment using univariate and multivariate cause-specific Cox’s proportional hazard models with adjustment on pre-specified confounders. Results Among the 545 included patients, 191 (35%) received corticosteroids. The proportional hazard assumption for the effect of corticosteroids on the incidence of VAP could not be accepted, indicating that this effect varied during ICU stay. We found a non-significant lower risk of VAP for corticosteroid-treated patients during the first days in the ICU and an increased risk for longer ICU stay. By modeling the effect of corticosteroids with time-dependent coefficients, the association between corticosteroids and the incidence of VAP was not significant (overall effect p = 0.082), with time-dependent hazard ratios (95% confidence interval) of 0.47 (0.17–1.31) at day 2, 0.95 (0.63–1.42) at day 7, 1.48 (1.01–2.16) at day 14 and 1.94 (1.09–3.46) at day 21. Conclusions No significant association was found between adjuvant corticosteroid treatment and the incidence of VAP, although a time-varying effect of corticosteroids was identified along the 28-day follow-up.
In Italy, 2021 has been a year marking a turning point in the struggle against the COVID‐19 pandemic, and a time of economic, political and social transition. The country has reaped several important successes, policy‐wise, both with regard to the efficacy of its vaccination campaign and to the drafting of its National Recovery and Resilience Plan (NRRP). All this was achieved after a quite troubled start of the year, with the fall of the Conte II government and the arrival in office of the new Prime Minister, Mario Draghi. The effects of the pandemic and the advent of the Draghi government affected both the dynamic of competition in the Italian party system and the intra‐party conflicts. The 2021 round of Italian local elections, involving thousands of municipalities, triggered a surprising victory for the centre left and marked an important shift in the electoral balance of power between Italian parties.
We have developed deep learning models for automatic identification of the maternal heart rate (MHR) and, more generally, false signals (FSs) on fetal heart rate (FHR) recordings. The models can be used to preprocess FHR data prior to automated analysis or as a clinical alert system to assist the practitioner. Three models were developed and used to detect (i) FSs on the MHR channel (the FSMHR model), (ii) the MHR and FSs on the Doppler FHR sensor (the FSDop model), and (iii) FSs on the scalp ECG channel (the FSScalp model). The FSDop model was the most useful because FSs are far more frequent on the Doppler FHR channel. All three models were based on a multilayer, symmetric, GRU, and were trained on data recorded during the first and second stages of delivery. The FSMHR and FSDop models were also trained on antepartum recordings. The training dataset contained 1030 expert-annotated periods (mean duration: 36 min) from 635 recordings. In an initial evaluation of routine clinical practice, 30 fully annotated recordings for each sensor type (mean duration: 5 h for MHR and Doppler sensors, and 3 h for the scalp ECG sensor) were analyzed. The sensitivity, positive predictive value (PPV) and accuracy were respectively 62.20%, 87.1% and 99.90% for the FSMHR model, 93.1%, 95.6% and 99.68% for the FSDop model, and 44.6%, 87.2% and 99.93% for the FSScalp model. We built a second test dataset with a more solid ground truth by selecting 45 periods (lasting 20 min, on average) on which the Doppler FHR and scalp ECG signals were recorded simultaneously. Using scalp ECG data, the experts estimated the true FHR value more reliably and thus annotated the Doppler FHR channel more precisely. The models achieved a sensitivity of 53.3%, a PPV of 62.4%, and an accuracy of 97.29%. In comparison, two experts (blinded to the scalp ECG data) respectively achieved a sensitivity of 15.7%, a PPV of 74.3%, and an accuracy of 96.91% and a sensitivity of 60.7%, a PPV of 83.5% and an accuracy of 98.24%. Hence, the models performed at expert level (better than one expert and worse than the other), although a well-trained expert with good knowledge of FSs could probably do better in some cases. The models and datasets have been included in the Fetal Heart Rate Morphological Analysis open-source MATLAB toolbox and can be used freely for research purposes.
Purpose: Adolescent idiopathic scoliosis (AIS) is associated with perturbation of orthostatic postural control. In humans, orthostatic postural control is organized around the gravitational vertical (GV). Perception of the GV involves a bottom-up process (central integration of multisensorial information) and a top-down process that uses cognitive mechanisms relying on body image. This study hypothesized that AIS would be associated with an erroneous central representation of verticality. The objective was to demonstrate an altered top-down process of sense of verticality in AIS. Methods: This multicenter, single-blind, case-control study evaluated 63 adolescent girls with AIS divided into two groups (major AIS (n = 31) and minor AIS (n = 32)) and 30 matched non-scoliotic adolescents. Participants scored their perception of trunk appearance in an upright position using a pictographic scale. The outcome measure was the difference between perception score and real trunk deformity. Results: Participants with major AIS presented with misperception of their trunk appearance in an upright position when compared with those with minor AIS or controls. Conclusion: Adolescents with major AIS underestimate their trunk deformity in an upright position. This suggests an altered representation of body image, affecting top-down control of sense of verticality.
Hospitals and other healthcare settings use various simulation methods to improve their operations, management, and training. The COVID-19 pandemic, with the resulting necessity for rapid and remote assessment, has highlighted the critical role of modeling and simulation in healthcare, particularly distributed simulation (DS). DS enables integration of heterogeneous simulations to further increase the usability and effectiveness of individual simulations. This article presents a DS system that integrates two different simulations developed for a hospital intensive care unit (ICU) ward dedicated to COVID-19 patients. AnyLogic has been used to develop a simulation model of the ICU ward using agent-based and discrete event modeling methods. This simulation depicts and measures physical contacts between healthcare providers and patients. The Unity platform has been utilized to develop a virtual reality simulation of the ICU environment and operations. The high-level architecture, an IEEE standard for DS, has been used to build a cloud-based DS system by integrating and synchronizing the two simulation platforms. While enhancing the capabilities of both simulations, the DS system can be used for training purposes and assessment of different managerial and operational decisions to minimize contacts and disease transmission in the ICU ward by enabling data exchange between the two simulations.
Background Systemic inflammatory and autoimmune diseases (SIADs) occur in 10–20% of patients with myelodysplastic syndrome (MDS). Recently identified VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, associated with somatic mutations in UBA1 (Ubiquitin-like modifier-activating enzyme 1), encompasses a range of severe inflammatory conditions along with hematological abnormalities, including MDS. The pathophysiological mechanisms underlying the association between MDS and SIADs remain largely unknown, especially the roles of different myeloid immune cell subsets. The aim of this study was to quantitatively evaluate peripheral blood myeloid immune cells (dendritic cells (DC) and monocytes) by flow cytometry in MDS patients with associated SIAD (n = 14, most often including relapsing polychondritis or neutrophilic dermatoses) and to compare their distribution in MDS patients without SIAD (n = 23) and healthy controls (n = 7). Most MDS and MDS/SIAD patients had low-risk MDS. Eight of 14 (57%) MDS/SIAD patients carried UBA1 somatic mutations, defining VEXAS syndrome.Compared with MDS patients, most DC and monocyte subsets were significantly decreased in MDS/SIAD patients, especially in MDS patients with VEXAS syndrome. Our study provides the first overview of the peripheral blood immune myeloid cell distribution in MDS patients with associated SIADs and raises several hypotheses: possible redistribution to inflammation sites, increased apoptosis, or impaired development in the bone marrow.
When receiving personalized rather than population-based information, agents improve their knowledge about their probability of experiencing adverse events (e.g. health shocks). Being revealed as high or low risk, they may revise their willingness to pay (WTP) for prevention programs. If the WTP changes of the high- and low-risk individuals go in opposite directions, the overall impact on the WTP for prevention depends on whether the relationship between WTP and the initial probability of damage is convex or concave. We address this question in a laboratory experiment. Participants received an endowment and were exposed to a non-financial damage—consisting in electrical shocks—with a certain probability. We elicit subjects’ WTP for self-protection and self-insurance, i.e. actions reducing respectively the probability and the number of shocks, using the Becker-DeGroot-Marschak mechanism. Our results suggest that WTP for self-protection is insensitive to the baseline probability to undergo pain, but reveal that WTP for self-insurance increases at a decreasing rate with this probability. This implies that the diffusion of personalized information should reduce the demand for self-insurance programs.
The goal of this study is to examine the food and oil price nexus from January 1993 to September 2020. To have a broader aspect, we decompose oil prices into demand and supply shocks and food price index into sub-indices such as Meat, Dairy, Cereal, and sugar price indices. The findings show that the association between the food prices and indices with oil prices is bidirectional. Also, results show that the oil prices, demand, and supply shocks are the main contributors to volatility transmission compared to food prices and their sub-indices. The outcome of this study will help the agricultural sector's policymakers develop reliable and sound policy designs that will help control the influence of oil prices on food prices.
With the widespread popularity of green and environmental protection concepts, customer satisfaction with green marketing in the green supply chain is particularly important, and channel green marketing is an important part of the green supply chain. Thus, this paper studies competition and cooperation strategies in the pricing and green marketing of a dual-channel supply chain while considering customer satisfaction. Using a two-stage optimization method and the Stackelberg game, we explore two cooperation models. In the first model, two retailers cooperate and compete with the manufacturer; in the second model, retailer 1 cooperates with the manufacturer and competes with retailer 2. It finds that because of the influence of customer satisfaction, the optimal price is not always proportional to green marketing efforts, and retailers with a higher market share may not necessarily have higher profits. The manufacturer, even if it is in competition with retailers, in some cases should actively help retailers improve green marketing to increase profits. Finally, we note that the cooperation strategy in a green supply chain is influenced by the relationship between green marketing and customer satisfaction.
Background Recent studies have shown a lack of implementation of gout recommendations in primary care. In this context of therapeutic inertia, the French Society of Rheumatology (SFR) published its first recommendations on gout in 2020, which were deliberately simple and concise. Objectives The objectives were to determine the profile of patients referred to French gout expert centres, and to examine the results of their management and the factors leading to those results. Methods Three hundred patients attending a first visit for gout management in three French referral centres were retrospectively and randomly included in this multicentre observational study.Visits were performed at baseline (M0) and scheduled for month 6 (M6), month 12 (M12), and month 24 (M24). Data collected included: patient profile; disease activity and treatments; serum urate (SU) level; estimated glomerular filtration rate (eGFR). Results Patients were 81% male and mean age 62.2 ± 15.2 years. Only 15,3% of them had difficult-to-treat gout at baseline. Management followed French recommendations after the baseline visit in 94.9% of cases. SU levels were below 6.0mg/dL in 59.4% of patients at M6, 67.9% at M12, and 78.6% at M24, with increasing clinical improvement (i.e. flare decrease) over 2 years of follow-up. At M24, 50% of patients were treated with allopurinol (313 ± 105 mg/d), which exceeded renal restrictions of doses in 61.5% of them, and 48.2% received febuxostat (84 ± 36mg/d). The need for a sufficient dosage of ULT was the only predictive factor found for successful reach SU levels <6.0mg/dL at a given visit. Overall, 50 patients (16.7%) received off-label anakinra for flare treatment or flare prophylaxis. Conclusion Simple application of gout management guidelines is feasible in clinical practice, and is efficient with a majority of patients achieving SU targets and clinical improvement.
Electronic health records (EHRs) involve heterogeneous data types such as binary, numeric and categorical attributes. As traditional clustering approaches require the definition of a single proximity measure, different data types are typically transformed into a common format or amalgamated through a single distance function. Unfortunately, this early transformation step largely pre-determines the cluster analysis results and can cause information loss, as the relative importance of different attributes is not considered. This exploratory work aims to avoid this premature integration of attribute types prior to cluster analysis through a multi-objective evolutionary algorithm called MVMC. This approach allows multiple data types to be integrated into the clustering process, explore trade-offs between them, and determine consensus clusters that are supported across these data views. We evaluate our approach in a case study focusing on systemic sclerosis (SSc), a highly heterogeneous auto-immune disease that can be considered a representative example of an EHRs data problem. Our results highlight the potential benefits of multi-view learning in an EHR context. Furthermore, this comprehensive classification integrating multiple and various data sources will help to understand better disease complications and treatment goals.
Background In patients with septic shock, the impact of the mean arterial pressure (MAP) target on the course of mottling remains uncertain. In this post hoc analysis of the SEPSISPAM trial, we investigated whether a low-MAP (65 to 70 mmHg) or a high-MAP target (80 to 85 mmHg) would affect the course of mottling and arterial lactate in patients with septic shock. Methods The presence of mottling was assessed every 2 h from 2 h after inclusion to catecholamine weaning. We compared mottling and lactate time course between the two MAP target groups. We evaluated the patient’s outcome according to the presence or absence of mottling. Results We included 747 patients, 374 were assigned to the low-MAP group and 373 to the high-MAP group. There was no difference in mottling and lactate evolution during the first 24 h between the two MAP groups. After adjustment for MAP and confounding factors, the presence of mottling ≥ 6 h during the first 24 h was associated with a significantly higher risk of death at day 28 and 90. Patients without mottling or with mottling < 6 h and lactate ≥ 2 mmol/L have a higher probability of survival than those with mottling ≥ 6 h and lactate < 2 mmol/L. Conclusion Compared with low MAP target, higher MAP target did not alter mottling and lactate course. Mottling lasting for more than 6 h was associated with higher mortality. Compared to arterial lactate, mottling duration appears to be a better marker of mortality.
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