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Open-cell ceramic foams are widely used as filters for the purification of molten metals due to their high permeability and high efficiency for capturing non-metallic inclusions. With the consideration of manufacture and filtration behaviour, most filters are produced by replica methods. The intrinsic multiscale porous structure requires the ceramic foams to have sufficient strength. As a consequence, different processing approaches, material compositions and characterizations are investigated. Meanwhile, to further enhance the filtration performance, the functionalization of ceramic foam filters is often conducted with surface coating. This review summarizes the processing and characteristics of ceramic foam filters (CFFs), the nature and formation of non-metallic inclusions (NMIs), the filtration mechanism and applications of CFFs. The characterization of mechanical and filtration performance, as well as the corresponding strengthening and functionalization methods are also presented.

HJURP is overexpressed in several cancer types and strongly correlates with patient survival. However, the mechanistic basis underlying the association of HJURP with cancer aggressiveness is not well understood. HJURP promotes the loading of the histone H3 variant, CENP-A, at the centromeric chromatin, epigenetically defining the centromeres and supporting proper chromosome segregation. In addition, HJURP is associated with DNA repair but its function in this process is still scarcely explored. Here, we demonstrate that HJURP is recruited to DSBs through a mechanism requiring chromatin PARylation and promotes epigenetic alterations that favor the execution of DNA repair. Incorporation of HJURP at DSBs promotes turnover of H3K9me3 and HP1, facilitating DNA damage signaling and DSB repair. Moreover, HJURP overexpression in glioma cell lines also affected global structure of heterochromatin independently of DNA damage induction, promoting genome-wide reorganization and assisting DNA damage response. HJURP overexpression therefore extensively alters DNA damage signaling and DSB repair, and also increases radioresistance of glioma cells. Importantly, HJURP expression levels in tumors are also associated with poor response of patients to radiation. Thus, our results enlarge the understanding of HJURP involvement in DNA repair and highlight it as a promising target for the development of adjuvant therapies that sensitize tumor cells to irradiation.

Difficult airway is a major life-threatening complication during induction of general anesthesia. In thyroid surgery, intubation could be complicated by airway distortion because of the enlarged thyroid gland. Recently, ultrasonography has been proposed as a potential modality for airway assessment and management. The aim of the study is to evaluate ultrasound-based measurement of airway parameters in 13 selected patients with compressive goiter and tracheal deviation scheduled for thyroidectomy before induction of general anesthesia. Specifically, we detected the distance between the skin and retro-isthmic trachea (DSRIT) and the distance between the sub isthmic trachea and the carotid artery (DCSIT) at the side of the dominant lobe. We compared ultrasound measures before intubation with Cormack-Lehane laryngoscopes grades recorded during tracheal intubation.

Fluorescent proteins (FPs) have transformed cell biology through their use in fluorescence microscopy, enabling precise labeling of proteins via genetic fusion. A key advancement is altering primary sequences to customize their photophysical properties for specific imaging needs. A particularly notable family of engineered mutants is constituted by Reversible Switching Fluorescent Proteins (RSFPs), i.e. variant whose optical properties can be toggled between a bright and a dark state, thereby adding a further dimension to microscopy imaging. RSFPs have strongly contributed to the super-resolution (nanoscopy) revolution of optical imaging that has occurred in the last 20 years and afforded new knowledge of cell biochemistry at the nanoscale. Beyond high-resolution applications, the flexibility of RSFPs has been exploited to apply these proteins to other non-conventional imaging schemes such as photochromic fluorescence resonance energy transfer (FRET). In this work, we explore the origins and development of photochromic behaviors in FPs and examine the intricate relationships between structure and photoswitching ability. We also discuss a simple mathematical model that accounts for the observed photoswitching kinetics. Although we review most RSFPs developed over the past two decades, our main goal is to provide a clear understanding of key switching phenotypes and their molecular bases. Indeed, comprehension of photoswitching phenotypes is crucial for selecting the right protein for specific applications, or to further engineer the existing ones. To complete this picture, we highlight in some detail the exciting applications of RSFPs, particularly in the field of super-resolution microscopy.

Peridynamics is a robust theoretical framework for modelling a variety of phenomena in continuum mechanics. However, the same aspects of the peridynamic formulation that lend it versatility compound its computational complexity, and an efficient implementation of the method remains an open problem. Fortunately, peridynamics is very well-suited for parallelism, and the rapid improvement of GPU technology in recent years has provided new opportunities for acceleration. This work details an extension of the approach used by PeriPy, a recent bond-based GPU peridynamic modeller, to state-based peridynamics. Two additional methods are presented, a naive implementation based on prior work to serve as a comparison baseline, and a novel approach which aims to minimize GPU memory consumption and thereby maximize the problem size that can be executed on a given GPU. This novel memory-optimized method yields an acceleration of 3.6× relative to PeriPy, and a 10× increase in representable problem size. Additionally, results are included for a reduced version of this implementation using single-precision operations and removing damage calculations, which yields a further 63× speedup.

Nowadays, as an alternative to conventional mineral oils used for cooling in distribution transformers, environment-friendly ester oils are getting more attention. For this reason, the main objective of this work was to compare the cooling efficiency of both types of coolants in the medium-power distribution transformer under different ambient conditions. It was conducted by the development of a validated coupled numerical model that included all thermal, flow, and electromagnetic phenomena. Moreover, all the calculations were carried out for mineral, synthetic, and natural ester oils. As a result, the coupled computational fluid dynamics (CFD) model determined the hot-spot temperature within the transformer tank at three ambient temperatures on the basis of the local distribution of the power losses in windings and core that were delivered from the electromagnetic submodel. The investigated ambient temperatures of $- 10\,\,^{\circ} \text{C}$ , $20 ^{\circ} \text{C}$ , and $30 ^{\circ} \text{C}$ represented summertime and wintertime for two climate conditions. The numerical results also showed a satisfactory agreement with the measured temperature values recorded in the analyzed distribution transformer with mineral oil. In addition, it was presented that the highest hot-spot temperature of $94.6 ^{\circ} \text{C}$ was reached for the case of natural ester oil at $30 ^{\circ} \text{C}$ of the ambient temperature representing maximum monthly averaged Argentinian climate conditions. In these conditions, the hot-spot temperature transformer with mineral oil was only 1.6 K lower. Furthermore, one of the investigated synthetic ester oils allowed to reach even better cooling effectiveness than in the case of mineral oil. Therefore, more effective cooling connected with environment-friendly characteristics encourages to use of biodegradable oils for distribution transformers.

Nowadays, large amounts of unstructured data are available online. Such data often contain users' emotions and feelings about a variety of topics but their retrieval and selection on the basis of an emotional perspective are usually unfeasible through traditional search engines, which only rank web content according to its relevance with respect to a given search keyword. For this reason, in the present work we introduce the architecture of a novel emotion-aware search engine that can return search results ranked on the basis of seven human emotions. Using this system, users can benefit from a more advanced semantic search that also takes into account emotions. The system uses emotion recognition algorithms based on deep learning to extract emotion vectors from texts, images and videos and then populates an emotional index to allow users to visualise results related to given emotions. We also discuss and evaluate different deep learning models for building emotional indexes from texts, images and videos.

The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO2removal (ECCO2R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO2R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce VTfrom 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H2O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H2O after 24 hours, 48 hours, and at discontinuation of ECCO2R-plus-RRT (T3), respectively (p< 0.001). PaCO2and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively (p< 0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19–induced ARDS and AKI, ECCO2R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits.

ObjectivesThis study compared the burden of fatigue between treatment-nai¨ve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity.MethodsPretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML.ResultsPatients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI −8.6 to −6.4, p<0.001). Across AML disease risk categories, adjusted mean differences in fatigue compared with the general population ranged from 6.7 points worse (patients with favourable risk: 95% CI −8.6 to −4.8, p<0.001) to 8.9 points worse (patients with poor risk, 95% CI −10.5 to −7.2, p<0.001). Overall, 91% of patients with AML reported fatigue that was equal to or worse than the general population’s median fatigue score. Higher pretreatment fatigue was independently associated with female sex, WHO performance status ≥1 and lower platelet levels.ConclusionsPatients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue.

While stroke is one of the leading causes of disability, the prediction of upper limb (UL) functional recovery following rehabilitation is still unsatisfactory, hampered by the clinical complexity of post-stroke impairment. Predictive models leading to accurate estimates while revealing which features contribute most to the predictions are the key to unveil the mechanisms subserving the post-intervention recovery, prompting a new focus on individualized treatments and precision medicine in stroke. Machine learning (ML) and explainable artificial intelligence (XAI) are emerging as the enabling technology in different fields, being promising tools also in clinics. In this study, we had the twofold goal of evaluating whether ML can allow deriving accurate predictions of UL recovery in sub-acute patients, and disentangling the contribution of the variables shaping the outcomes. To do so, Random Forest equipped with four XAI methods was applied to interpret the results and assess the feature relevance and their consensus. Our results revealed increased performance when using ML compared to conventional statistical approaches. Moreover, the features deemed as the most relevant were concordant across the XAI methods, suggesting good stability of the results. In particular, the baseline motor impairment as measured by simple clinical scales had the largest impact, as expected. Our findings highlight the core role of ML not only for accurately predicting the individual outcome scores after rehabilitation, but also for making ML results interpretable when associated to XAI methods. This provides clinicians with robust predictions and reliable explanations that are key factors in therapeutic planning/monitoring of stroke patients.

In this work, refractory components based on alumina were produced by binder jetting using a large-scale 3D printer. The formulation contained several particle fractions up to a grain size of 3 mm, equal to the printer resolution. The binder system contained fine dead burnt magnesia, milled citric acid and reactive alumina, which were added to the aggregate mixture to create the powder bed. Deionized water was deposited from the printer's nozzles and triggered the binding reaction between the magnesia and citric acid. After 24 h, the printed samples were removed from the powder bed, dried and sintered at 1600 °C for 5 h. Reactive alumina contributed to the in situcreation of magnesium aluminate spinel at high temperature. The samples were characterized in terms of Young's modulus of elasticity, bending and compressive strength in 2 directions (parallel and perpendicular to the printing direction). The broken parts were used to investigate physical properties such as the open porosity and bulk density. The microstructure was studied by means of computed tomography. Finally, powder samples were used to determine the phase composition at different stages of production by means of XRD.

Recently, hydrogels have gained significant importance in different applications, such as tissue engineering and drug delivery. They are 3D structures of hydrophilic polymers held together through physical or chemical crosslinking. Important is their ability to swell in presence of solvents, forming elastic gels able to maintain their original shape. Furthermore, these scaffolds slowly degrade in the physiological environment, leading the growing tissue to replace the former filled site. In this work, hydrogels have been synthetized using branched polyacrylic acid (carbomer) cross-linked with an aliphatic polyetherdiamine (elastamine). In particular, we focused on the description of their equilibrium conditions in swollen state and the dynamic simulation of the swelling process. These hydrogels exhibited a peculiar swelling behaviour characterized by an overshoot of the volume increase before reaching the equilibrium. Notably, such behaviour was found at different pH values. In this manuscript, the swelling behaviour was studied by mathematical modelling. Moreover, the ability of these devices to release drugs was also examined through a literature model to understand the different operating transport mechanisms.

Graphical AbstractBig gamma-glutamyltransferase (b-GGT) and cardiovascular risk in the general population. b-GGT deriving from the bloodstream or released by macrophages (CD68+ cells) promotes oxidative stress within the plaque. This ultimately leads to plaque destabilization. ACS, acute coronary syndrome; CV, cardiovascular. Modified with permission from Emdin et al., 2005.26

Abstract:Paying tribute to Michiyo Fukaya, a mixed-race Asian American lesbian poet and feminist activist who died by suicide in 1987, this essay experiments with a reading practice that merges queer and feminist thought with poetics and autotheory. Throughout, the author interweaves details of Fukaya's life with their own, wading through Fukaya's writings to force attention onto the topics of sexual violence, anger, mental health, and U.S. imperialism. Fukaya—a contemporary of those who grace the pages of This Bridge Called My Back: Writings By Radical Women of Color and All The Women Are White, All The Blacks Are Men, But Some of Us Are Brave: Black Women's Studies—is largely absent in discussions of third world feminism, women of color feminism, and 1980s feminisms writ large. Attending to this absence, the essay models how one might touch and be touched by their dead, suggesting a turn inwards towards the feminist past as a prerequisite to survival.

A large body of evidence has demonstrated a connection between volunteering and improved well-being, especially among older adults, without fully considering the implications of transitioning out of volunteering. While volunteers represent an important resource for many organizations, working with older adult volunteers also presents a unique set of considerations for volunteer administrators and other staff. Building on previous findings, this qualitative study interviews older-adult hospital volunteers (age 65 and older) about their experiences, motivations, and plans for future volunteering. Findings suggest that older adults engage in diverse volunteering tasks, exhibit complex and multifaceted motivations for beginning and continuing to volunteer, and develop a sense of self and identity as a volunteer that they wish to preserve. Our findings contribute to the development of a nascent three-stage model to explain how older adults approach the possibility of volunteer retirement. Implications for policy and future research are discussed.

The 2017 version of the European LeukemiaNet (ELN) recommendations, by integrating cytogenetics and mutational status of specific genes, divides patients with acute myeloid leukemia into 3 prognostically distinct risk categories: favorable (ELN2017-FR), intermediate (ELN2017-IR), and adverse (ELN2017-AR). We performed a post hoc analysis of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) AML1310 trial to investigate the applicability of the ELN2017 risk stratification to our study population. In this trial, after induction and consolidation, patients in complete remission were to receive an autologous stem cell transplant (auto-SCT) if categorized as favorable risk or an allogeneic stem cell transplant (allo-SCT) if adverse risk. Intermediate-risk patients were to receive auto-SCT or allo-SCT based on the postconsolidation levels of measurable residual disease as measured by using flow cytometry. Risk categorization was originally conducted according to the 2009 National Comprehensive Cancer Network recommendations. Among 500 patients, 445 (89%) were reclassified according to the ELN2017 criteria: ELN2017-FR, 186 (41.8%) of 455; ELN2017-IR, 179 (40.2%) of 445; and ELN2017-AR, 80 (18%) of 455. In 55 patients (11%), ELN2017 was not applicable. Two-year overall survival (OS) was 68.8%, 51.3%, 45.8%, and 42.8% for the ELN2017-FR, ELN2017-IR, ELN2017-not classifiable, and ELN2017-AR groups, respectively (P < .001). When comparing the 2 different transplant strategies in each ELN2017 risk category, a significant benefit of auto-SCT over allo-SCT was observed among ELN2017-FR patients (2-year OS of 83.3% vs 66.7%; P = .0421). The 2 transplant procedures performed almost equally in the ELN2017-IR group (2-year OS of 73.9% vs 70.8%; P = .5552). This post hoc analysis of the GIMEMA AML1310 trial confirms that the ELN2017 classification is able to accurately discriminate patients with different outcomes and who may benefit from different transplant strategies. This trial was registered as EudraCT number 2010-023809-36 and at www.clinicaltrials.gov as #NCT01452646.

This review article discusses the definition and implementation of brain–computer interface (BCI) system relying on brain connectivity (BC) and machine learning/deep learning (DL) for motor imagery (MI)-based applications. During the past few years, many approaches have been explored in terms of types of neurological sources of information, feature extraction, and intention prediction for BCI applications. Two novel aspects are becoming increasingly interesting for the BCI community: BC modeling and DL. The former aims at describing the interactions among different brain regions as connectivity patterns that reflect the dynamics of information flow either at rest or when performing a task. The latter is becoming pervasive for its capability of modeling and predicting complex data, where a huge amount of information is involved. In this scenario, we conducted a systematic literature review on BCI studies that led to the selection of 34 articles meeting all the required criteria. This provides evidence of the rapid growth of the topic over the past few years, though being still in its infancy. The last part of this article is dedicated to this new frontier of BCI that we call MI BC-based computer interfaces highlighting the potential of BC features. This, jointly with DL as enabling technology, has the potential of improving the performance of electroencephalography-based systems.

Objectives: To assess the prevalence of delirium (DEL) among older patients living at home and periodically visited by their General Practitioners (GPs). Design: Observational study. Setting: In Italy, programmed home visits by the GPs are regularly scheduled for their vulnerable and frail patients who are often on poly-drug regimens and suffering from dementia. Participants: N= 102 patients among those receiving programmed home visits by n= 6 GP based in the Brianza area (Lombardy). Measurements: Patients were screened for delirium with the Italian version of the 4AT, with a score ≥ 4 considered as a positive indicator for DEL. The Charlson Comorbidity Index (CCI), the Short Physical Performance Battery (SPPB), the presence of dementia, and benzodiazepine (BZD) use were recorded. Results: DEL+ was detected in almost half of the recruited sample (44.1%), and it was clearly associated with increased comorbidity and decreased motor abilities. Pre-existing dementia was documented in most of DEL+ patients (71.1%), while this was the case for only a minority of DEL- (5.2%, p&lt; 0.00001). Analogously, BZD use was over-represented in the DEL+ group with respect to the DEL− one (73.3% vs.22.8%, p&lt; 0.00001). Conclusions: DEL prevalence as detected by GP during programmed home visits is surprisingly high, and related to motor impairment, comorbidities (among which dementia), and BZD use. DEL prompt recognition should be one of the goals of GP-programmed home visits, since this treatable and preventable condition is associated to an elevated burden of frailty and risk of death.

Peridynamics has been developed over the past 2 decades as an approach to engineering simulation that offers an alternative to discretizing the partial differential equations produced by traditional continuum models. The peridynamic constitutive model assumes a material point lies in the bulk of the material; points near a body’s surface are known to exhibit an erroneous “surface effect,” appearing softer than points in the bulk. Le and Bobaru (Comput Mech61:499–518, 2018) proposed a fictitious node method for eliminating the surface effect artifacts for bodies with simple, axis-aligned boundaries. In this paper, we present a generalization of this approach that can be applied to arbitrary boundary geometries. Additionally, the approach presented provides a method for more strict enforcement of boundary conditions than what is available in typical peridynamic boundary treatments. The correction method is tested on a set of canonical elasticity problems and shows suppression of the surface effect comparable to the levels of suppression obtained by Le and Bobaru, while removing the geometrical constraints limiting the applicability of Le and Bobaru’s method.

Background: Childhood overweight and obesity are a global concern, with prevalence rising dramatically over the last decades. The condition is caused by an increase in energy intake and reduction of physical activity, leading to excessive fat accumulation, followed by systemic chronic inflammation and altered function of immune cell responses. This study aimed at providing new insights regarding sex-specificity on the inflammatory response to obesity in the young patient. Design: Forty-three Brazilian obese adolescents (Female = 22 and Male=21, BMI (body mass index) Z-score average = 2.78 ± 0.51) and forty-nine eutrophic adolescents (Female = 24 and Male = 25, BMI Z-score average = −0.35 ± 0.88) were enrolled in the study. Anthropometrical analyses and blood cell counts were carried out. Using Luminex®xMAP™ technology, circulating serum cytokines, chemokines, and inflammatory biomarkers were analyzed. Two-way ANOVA test, Tukey’s test, and Spearman’s correlation coefficient were employed, with a significance threshold set at p&lt; 0.05. Results: We identified increased levels of serum amyloid A (SAA), platelets, and leukocytes solely in male obese patients. We found a noteworthy sex-dependent pattern in regard to inflammatory response: obese boys showed higher TNFβ, IL15, and IL2 and lower IL10 and IL13, while obese girls showed increased TNFα, CCL3, CCL4, and IP10 content in the circulation. BMI Z-score was significantly linearly correlated with neutrophils, leukocytes, platelets, SAA, TNFα, CCL3, CCL4, IP10, and IL13 levels within the entire cohort (non-sex-dependent). Conclusions: Our data support a complex relationship between adiposity, blood cell count, and circulating inflammatory cytokine content. High SAA levels suggest that this factor may play a critical role in local and systemic inflammation. In the eutrophic group, females presented a lower status of inflammation, as compared to males. Both obese boys and girls showed an increased inflammatory response in relation to eutrophic counterparts. Taken together, results point out to clear sex dimorphism in the inflammatory profile of obese adolescents.

The phase 3 GIMEMA-MMY-3006 trial, which compared bortezomib, thalidomide, and dexamethasone (VTD) combination therapy with thalidomide and dexamethasone (TD) as induction therapy before and consolidation therapy after double autologous haematopoietic stem-cell transplantation (HSCT) for newly diagnosed multiple myeloma, showed the superiority of the triplet regimen over the doublet in terms of increased complete response rate and improved progression-free survival. We report the results from the final analysis of the study.

IMPORTANCE: Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU). OBJECTIVE: To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase–polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020. EXPOSURES: Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission. MAIN OUTCOMES AND MEASURES: Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression. RESULTS: Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao2:Fio2 ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29). CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high.

Assessment of consciousness following severe brain-injury is challenging. Our hypothesis is that electroencephalography (EEG) can provide information on awareness, in terms of oscillatory activity and network task–related modifications, in people with disorders of consciousness. Similar results were obtained with neuroimaging techniques; we aim at demonstrating the use of EEG, which is low cost and routinely implemented, to the same goal. Nineteen-channel EEG was recorded in 7 persons with unresponsive wakefulness syndrome (UWS) and in 10 healthy subjects during the execution of active (attempted movement) and passive motor tasks as well as 2 mental imagery tasks. Event-related synchronization/desynchronization (ERS/ERD), coherence and network parameters were calculated in delta (1-4 Hz), theta (4-8 Hz), alpha1 (8-10 Hz), alpha2 (10-12 Hz), and beta (13-30 Hz) ranges. In UWS subjects, passive movement induced a weak alpha2 ERD over contralateral sensorimotor area. During motor imagery, ERD was detected over the frontal and motor contralateral brain areas; during spatial imagery, ERS in lower alpha band over the right temporo-parietal regions was missing. In UWS, functional connectivity provided evidence of network disruption and isolation of the motor areas, which cannot dialog with adjacent network nodes, likely suggesting a diffuse structural alteration. Our findings suggest that people with a clinical diagnosis of UWS were able to modulate their brain activity when prompted to perform movement tasks and thus suggest EEG as a potential tool to support diagnosis of disorders of consciousness.

Emulsion polymerization of the three‐monomer system butyl acrylate–styrene–methacrylic acid was performed in batch using a commercial maltodextrin derived from starch degradation as stabilizer. Stable latexes with narrow particle size distributions were obtained in all examined cases. A method was developed to analyze and quantify the partitioning of the maltodextrin between the continuous phase (supernatant) and the particle phase. Significant differences between the polysaccharides adsorbed onto particles with or without emulsion polymerization reaction were observed. The possible reactions of maltodextrin in presence of a radical initiator were studied in aqueous phase, thus confirming maltodextrin degradation. The formation of copolymers involving the original monomers and the stabilizer according to two different reactive pathways was also confirmed. In terms of adsorbed maltodextrin, two different contributions were observed: maltodextrin physically adsorbed and maltodextrin chemically grafted and/or physically incorporated into the polymer. Commercially available maltodextrin is employed as a stabilizer in an emulsion polymerization process instead of a conventional emulsifier. An in‐depth study allows to fully characterize maltodextrin behavior as a stabilizer: it is evaluated the maltodextrin distribution between supernatant, adsorbed onto polymer surface and grafted/incorporated. It is discovered that the radical activation of the maltodextrin during the polymerization leads to copolymer formation and the consequent grafting of the maltodextrin and its incorporation into polymer latex.

ABSTRACTThe novel coronavirus (COVID-19) began in China in early December 2019 and rapidly has spread to many countries around the globe, with the number of confirmed cases increasing every day. An epidemic has been recorded since February 20 in a middle province in Northern Italy (Lodi province, in the low Po Valley). The first line hospital had to redesign its logistical and departmental structure to respond to the influx of COVID-19-positive patients who needed hospitalization. Logistical and structural strategies were guided by the crisis unit, managing in 8 days from the beginning of the epidemic to prepare the hospital to be ready to welcome more than 200 COVID-19-positive patients with different ventilatory requirements, keeping clean emergency access lines, and restoring surgical interventions and deferred urgent, routine activity.

Multiple myeloma is the second most frequent hematological cancer after lymphoma and remains an incurable disease. The pervasive support provided by the bone marrow microenvironment to myeloma cells is crucial for their survival. Here, an unbiased assessment of receptor tyrosine kinases overexpressed in myeloma identified ROR2, a receptor for the WNT noncanonical pathway, as highly expressed in myeloma cells. Its ligand, WNT5A is the most abundant growth factor in the bone marrow of myeloma patients. ROR2 mediates myeloma cells interactions with the surrounding bone marrow and its depletion resulted in detachment of myeloma cells from their niche in an in vivo model, triggering apoptosis and thus markedly delaying disease progression. Using in vitro and ex vivo 3D-culture systems, ROR2 was shown to exert a pivotal role in the adhesion of cancer cells to the microenvironment. Genomic studies revealed that the pathways mostly deregulated by ROR2 overexpression were PI3K/AKT and mTOR. Treatment of cells with specific PI3K inhibitors already used in the clinic reduced myeloma cell adhesion to the bone marrow. Together, our findings support the view that ROR2 and its downstream targets represent a novel therapeutic strategy for the large subgroup of MM patients whose cancer cells show ROR2 overexpression.

Living materials, which are composites of living cells residing in a polymeric matrix, are designed to utilize the innate functionalities of the cells to address a broad range of applications such as fermentation and biosensing. Herein, we demonstrate the additive manufacturing of catalytically active living materials (AMCALM) for continuous fermentation. A multi-stimuli-responsive yeast-laden hydrogel ink, based on F127-dimethacrylate, was developed and printed using a direct-write 3D printer. The reversible stimuli-responsive behaviors of the polymer hydrogel inks to temperature and pressure are critical, as they enabled the facile incorporation of yeast cells and subsequent fabrication of 3D lattice constructs. Subsequent photo-cross-linking of the printed polymer hydrogel afforded a robust elastic material. These yeast-laden living materials were metabolically active in the fermentation of glucose into ethanol for 2 weeks in a continuous batch process without significant reduction in efficiency (∼90% yield of ethanol). This cell immobilization platform may potentially be applicable toward other genetically modified yeast strains to produce other high-value chemicals in a continuous biofermentation process.

Polymer electrolyte membrane fuel cells are widely employed for transport applications due to the beneficial aspects of the proton-conducting polymer membrane, which reduces the chance of leakages compared to liquid electrolytes as well as efficiently prevents the flow of electrons. This membrane is characterized by a polymeric framework that is often produced by free radical emulsion copolymerization of perfluorinated monomers, the most abundant of which are typically tetrafluoroethylene and perfluoro-sulfonyl vinyl ether. Therefore, the proper description of monomer partitioning in the multiphase reaction environment is crucial for the development of a predictive kinetic model for polymerization and the optimization of the process. In this study, monomer solubility data have been collected for different combinations of all four phases of the reactive system, namely, gas phase, water phase, droplets of a water-immiscible liquid comonomer, and polymer particles. A thermodynamic partitioning model has been developed to describe these data, exploiting the Sanchez and Lacombe theory for the characterization of the monomer–monomer and monomer–polymer interactions. The comparison with the experimental measurements allowed to estimate important parameters, such as the solubility of the monomers in the different phases and interaction parameters with the polymer, which ultimately allowed evaluation of the monomer mixture composition in the reaction locus. Finally, the developed partitioning model has been validated for the multiphase system and exploited to estimate the reactivity ratios for the two monomers.

In this study, we investigated the effects of oxygen toxicity on brain activity and functional connectivity (FC) in divers using a closed-circuit oxygen breathing apparatus. We acquired and analyzed electroencephalographic (EEG) signals from a group of normal professional divers (PD) and a group that developed oxygen intolerance, i.e., oxygen-intolerant professional divers (OPD), to evaluate the potential risk of a dive and understand the physiological mechanisms involved. The results highlighted a significant difference in the baseline levels of αrhythm between PD and OPD, with PD exhibiting a lower level to counteract the effects of increased O2inhalation, while OPD showed a higher level that resulted in a pathological state. Connectivity analysis revealed a strong correlation between cognitive and motor regions, and high levels of αsynchronization at rest in OPDs. Our findings suggest that a pathological condition may underlie the higher αlevels observed in these individuals when facing the stress of high O2inhalation. These findings support the hypothesis that oxygen modulates brain networks, and have important implications for understanding the neural mechanisms involved in oxygen toxicity. The study also provides a unique opportunity to investigate the impact of neurophysiological activity in simulated critical scenarios, and opens up new perspectives in the screening and monitoring of divers.

Due to the complex interaction among the process operating parameters originated by the two refluxes in dual reflux pressure swing adsorption, to foresee the influence of changes in the main operating parameters is not trivial. On one hand, the reliable rules of thumb effective to design such a process are not available. On the other hand, multi-objective optimization (MOO) algorithms coupled with detailed modeling of the process are also not viable to be used as a daily design tool since the aforementioned complexity can result in huge CPU time demand to achieve cyclic steady-state conditions. In this work, a design tool based on MOO using a properly simplified model of the unit was used to identify suitable relationships between selected target parameters (typically, product purity and energy demand) and the main operating parameters, as suggested by the equilibrium theory. These relationships allowed building a Master plot summarizing the effect of changing such operating parameters on separation performance as well as quickly identifying a small enough operating window where both the target parameters achieve the desired values. The whole procedure has been investigated and validated with reference to the separation of the binary mixture CO2–N2as a case study.

Thrust wedge evolution is typically characterized by out‐of‐sequence thrusting, which can occur in both submarine and subaerial conditions to maintain the balance between gravitational and tectonic forces. The Gran Sasso Massif, in Central Italy, is a high topography region where the kinematics and environmental conditions of deformation of some fault zones are still controversial, and this bears important implications for the Central Apennines orogenic wedge evolution. To obtain further constraints on fault activity in the Gran Sasso Massif, we studied the Monte Camicia and Vado di Ferruccio thrusts using structural, petrographical, and geochemical analyses. Such dataset allowed us to constrain the structural‐diagenetic evolution of the studied faults, which has first‐order implications in the characterization of their paleo‐hydraulic properties. Our results indicate that in the Vado di Ferruccio out‐of‐sequence thrust, pressure solution‐mediated mass transfer promoted low‐permeability conditions in the fault core that led to a semiclosed fluid circulation, pore fluid overpressuring, and dolomite crystallization in submarine conditions. In contrast, the Monte Camicia out‐of‐sequence thrust was characterized by dominant cataclasis in subaerial conditions, which facilitated meteoric fluid infiltration. By considering both fault zones as belonging to the same thrust system at crustal scale, we interpret these differences as indicating the occurrence of multiple pulses of thrusting during the exhumation of this sector of the Central Apennines, up to Quaternary times, when extensional faulting eventually dissected the thrust stack. This caused extensional reactivation of the Monte Camicia Thrust and related alteration in vadose zone conditions, leading to porosity enhancement, dolomite dissolution, and calcitization. Structural diagenetic evolution of adjacent out‐of‐sequence thrusts was determined by contrasting deformation mechanisms and timingOut‐of‐sequence thrusting developed to restore orogenic wedge critical taper, while abundant syntectonic sedimentation occurred at wedge toeInherited contractional deformation structures affected the late‐stage extensional architecture and were partially reactivated

AbstractThe abundance and composition of parasitic faunas are influenced by morphological and environmental characteristics. Environments with distinct climatic characteristics, such as the semiarid Caatinga domain and coastal Restinga ecosystem of Brazil, have particular humidity, rainfall, and temperature conditions that can influence parasitism in lizard communities. We evaluated the effects of geographic distribution and body size on the abundance and composition of endo- and ectoparasites of a lizard species representing each of the habitats: Ameivula ocelliferaand A. nigrigula. Body size did not influence parasitic infestations. Both lizard species showed aggregate distribution patterns of the mite Eutrombicula alfreddugesi. Four endoparasite species were found: Oochoristica, Raillietiellasp., Pharyngodon cesarpintoi, and Physaloptera. The principal endoparasites recorded in A. ocelliferaand A. nigrigulawere heteroxenous parasites, which are usually indirectly ingested by lizards through their diets (mainly arthropods). The discrepancy indices of endoparasite distributions were similar between the two host species, and showed aggregated distribution patterns. Geographic distributions, substrate temperatures, and the interaction between geographic distribution and air and substrate temperatures influenced ectoparasite abundance in both species, although endoparasite abundance was not explained by these variables. Temperature, precipitation, and humidity during the rainy season in both the Caatinga and Restinga habitats affected parasite abundance, distribution, survival, and development, and contributed to the observed variations in parasitic infestation levels in these lizard species.

We designed a trial in which postremission therapy of young patients with de novo acute myeloid leukemia (AML) was decided combining cytogenetics/genetics and postconsolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (AlloSCT). Intermediate-risk patients (IR) were to receive AuSCT or AlloSCT depending on the postconsolidation levels of MRD. Three hundred sixty-one of 500 patients (72%) achieved a complete remission, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to AlloSCT (122 PR, 43 IR MRD-positive) plus 23 rescued after salvage therapy, for a total of 188 candidates; 150 (44%) to AuSCT (115 FR, 35 IR MRD-negative) plus 27 IR patients (8%) with no leukemia-associated phenotype, for a total of 177 candidates. Overall, 110/177 (62%) and 130/188 (71%) AuSCT or AlloSCT candidates received it, respectively. Two-year overall (OS) and disease-free survival (DFS) of the whole series was 56% and 54%, respectively. Two-year OS and DFS were 74% and 61% in the FR category, 42% and 45% in the PR category, 79% and 61% in the IR MRD-negative category, and 70% and 67% in the IR MRD-positive category. In conclusion, AuSCT may still have a role in FR and IR MRD-negative categories. In the IR MRD-positive category, AlloSCT prolongs OS and DFS to equal those of the FR category. Using all the available sources of stem cells, AlloSCT was delivered to 71% of the candidates.This trial was registered at www.clinicaltrials.gov as #NCT01452646 and EudraCT as #2010-023809-36.

We designed a trial in which postremission therapy of young patients with de novo acute myeloid leukemia (AML) was decided combining cytogenetics/genetics and postconsolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (AlloSCT). Intermediate-risk patients (IR) were to receive AuSCT or AlloSCT depending on the postconsolidation levels of MRD. Three hundred sixty-one of 500 patients (72%) achieved a complete remission, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to AlloSCT (122 PR, 43 IR MRD-positive) plus 23 rescued after salvage therapy, for a total of 188 candidates; 150 (44%) to AuSCT (115 FR, 35 IR MRD-negative) plus 27 IR patients (8%) with no leukemia-associated phenotype, for a total of 177 candidates. Overall, 110/177 (62%) and 130/188 (71%) AuSCT or AlloSCT candidates received it, respectively. Two-year overall (OS) and disease-free survival (DFS) of the whole series was 56% and 54%, respectively. Two-year OS and DFS were 74% and 61% in the FR category, 42% and 45% in the PR category, 79% and 61% in the IR MRD-negative category, and 70% and 67% in the IR MRD-positive category. In conclusion, AuSCT may still have a role in FR and IR MRD-negative categories. In the IR MRD-positive category, AlloSCT prolongs OS and DFS to equal those of the FR category. Using all the available sources of stem cells, AlloSCT was delivered to 71% of the candidates.This trial was registered at www.clinicaltrials.govas #NCT01452646 and EudraCT as #2010-023809-36.

We report our efforts toward 3D printing of polyether ether ketone (PEEK) at room temperature by direct-ink write technology. The room-temperature extrusion printing method was enabled by a unique formulation comprised of commercial PEEK powder, soluble epoxy-functionalized PEEK (ePEEK), and fenchone. This combination formed a Bingham plastic that could be extruded using a readily available direct-ink write printer. The initial green body specimens were strong enough to be manipulated manually after drying. After printing, thermal processing at 230 °C resulted in crosslinking of the ePEEK components to form a stabilizing network throughout the specimen, which helped to preclude distortion and cracking upon sintering. A final sintering stage was conducted at 380 °C. The final parts were found to have excellent thermal stability and solvent resistance. The Tgof the product specimens was found to be 158 °C, which is 13 °C higher than commercial PEEK as measured by DSC. Moreover, the thermal decomposition temperature was found to be 528 °C, which compares well against commercial molded PEEK samples. Chemical resistance in trifluoroacetic acid and 8 common organic solvents, including CH2Cl2and toluene, were also investigated and no signs of degradation or weight changes were observed from parts submerged for 1 week in each solvent. Test specimens also displayed desirable mechanical properties, such as a Young’s modulus of 2.5 GPa, which corresponds to 63% of that of commercial PEEK (reported to be 4.0 GPa).

In the frame of dual-reflux pressure swing adsorption processes, design strategies applicable to the complete separation of binary gas mixtures are available only in the case of linear adsorption isotherms. Therefore, in this work we propose a simple and efficient design procedure which enables the selection of suitable operating conditions when sharp separation is required and Langmuir adsorption isotherms are involved. Starting from the available strategy for the linear adsorption case, we adapt it to the nonlinear case tuning properly the pressure ratio. Then, the resulting design strategy is validated by application to selected study cases involving different values of key parameters such as different levels of nonlinearity of the isotherms, but also different values of the pressure ratio, feed composition, and selectivity.

The plasma membrane of cells has a complex architecture based on the bidimensional liquid-crystalline bilayer arrangement of phospho- and sphingolipids, which in turn embeds several proteins and is connected to the cytoskeleton. Several studies highlight the spatial membrane organization into more ordered (Loor lipid raft) and more disordered (Ld) domains. We here report on a fluorescent analog of the green fluorescent protein chromophore that, when conjugated to a phospholipid, enables the quantification of the Loand Lddomains in living cells on account of its large fluorescence lifetime variation in the two phases. The domain composition is straightforwardly obtained by the phasor approach to confocal fluorescence lifetime imaging, a graphical method that does not require global fitting of the fluorescence decay in every spatial position of the sample. Our imaging strategy was applied to recover the domain composition in human oligodendrocytes at rest and under treatment with galactosylsphingosine (psychosine). Exogenous psychosine administration recapitulates many of the molecular fingerprints of a severe neurological disease, globoid cell leukodystrophy, better known as Krabbe disease. We found out that psychosine progressively destabilizes plasma membrane, as witnessed by a shrinking of the Lofraction. The unchanged levels of galactosyl ceramidase, i.e., the enzyme lacking in Krabbe disease, upon psychosine treatment suggest that psychosine alters the plasma membrane structure by direct physical effect, as also recently demonstrated in model membranes.