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Fracture injection/shut-in tests are commonly used to measure the state of stress in the subsurface. Injection creates a hydraulic fracture (or in some cases, opens a preexisting fracture), and then the pressure after shut-in is monitored to identify fracture closure. Different interpretation procedures have been proposed for estimating closure, and the procedures sometimes yield significantly different results. In this study, direct, in-situ strain measurements are used to observe fracture reopening and closure. The tests were performed as part of the EGS Collab project, a mesoscale project performed at 1.25 and 1.5 km depth at the Sanford Underground Research Facility. The tests were instrumented with the SIMFIP tool, a double-packer probe with a high-resolution three-dimensional borehole displacement sensor. The measurements provide a direct observation of the fracture closure signature, enabling a high-fidelity estimate of the fracture closure stress (ie, the normal stress on the fracture). In two of the four tests, injection created an opening mode fracture, and so the closure stress can be interpreted as the minimum principal stress. In the other two tests, injection probably opened preexisting natural fractures, and so the closure stress can be interpreted as the normal stress on the fractures. The strain measurements are compared against different proposed methods for estimating closure stress from pressure transients. The shut-in transients are analyzed with two techniques that are widely used in the field of petroleum engineering – the ‘tangent’ method and the ‘compliance’ method. In three of the four tests, the tangent method significantly underestimates the closure stress. The compliance method is reasonably accurate in all four tests. Closure stress is also interpreted using two other commonly-used methods – ‘first deviation from linearity’ and the method of (Hayashi and Haimson, 1991). In comparison with the SIMFIP data, these methods tend to overestimate the closure stress, evidently because they identify closure from early-time transient effects, such as near-wellbore tortuosity. In two of the tests, microseismic imaging provides an independent estimate of the size of the fracture created by injection. When combined with a simple mass balance calculation, the SIMFIP stress measurements yield predictions of fracture size that are reasonably consistent with the estimates from microseismic. The calculations imply an apparent fracture toughness 2-3x higher than typical laboratory-derived values.

IntroductionIn 2018, the National Cancer Institute of Naples has launched the GLUBREAST Trial to verify the efficacy of cyanoacrylate sealing glue to prevent or reduce seroma after axillary dissection in breast surgery. The glue is a synthetic sealant (N-Butyl-2-CyanoAcrylate+Metacryloxisulfolane) biocompatible, CE approved for internal human uses and surgical procedures. The assumed mechanism of action in breast surgery is that the glue would create a seal coating in the operative field to occlude lymphatic leaks and limit seroma formation.Materials and methodsThe trial included 180 patients scheduled for breast-conserving surgery or for radical modified mastectomy without reconstruction. Out of 180 patients, 91 were randomized to receive suction drain and sealant glue after axillary dissection (Experimental Arm), whereas 89 patients (Control Arm) received suction drain without glue.StatisticsA multivariable mixed effect model on presence of liquid drained and volume drained was calculated. Stratified models by visits were performed.ResultsThe trial ended in June 2022. Older age was associated with a higher volume of seroma drained per day (β 0.30; 95% CI: 0.00–0.60). A 5-U increase in body mass index was associated with higher daily drained seroma volume in patients who underwent breast-conserving surgery (β 5.0; 95% CI: 0.62–9.4), but not in patients who underwent mastectomy (β 2.5; 95% CI: −3.6–8.6). We did not find statistically significant differences in presence of liquid drained and volume drained among the study groups. An advantage for the Experimental Arm was observed from third and fourth to fifth outpatient visits without reaching a statistical significance (p=0.069 and p=0.072, respectively); so far, 5% of patients in the Experimental Group had clinical benefit from the glue.ConclusionsThe vast majority of data in the literature come from case series, and surgeons need a higher level of evidence to drive surgical decision-making and choose proper devices to increase patient quality of life. The GLUBREAST randomized trial tested the efficacy of cyanoacrylate sealing glue to prevent postoperative seroma in breast surgery. Although only a small number of patients benefited from sealant application, we regret to say this trial has some limitation, i.e., the prolonged presence of suction drain. Further research is warranted to better clarify the benefit of cyanoacrylate glue in breast surgery.

The Epithelial Science Expert Group convened on 18–19 October 2023, in Naples, Italy, to discuss the current understanding of the fundamental role of the airway epithelium in asthma and other respiratory diseases and to explore the future direction of patient care. This review summarises the key concepts and research questions that were raised. As an introduction to the epithelial era of research, the evolution of asthma management throughout the ages was discussed and the role of the epithelium as an immune-functioning organ was elucidated. The role of the bronchial epithelial cells in lower airway diseases beyond severe asthma was considered, as well as the role of the epithelium in upper airway diseases such as chronic rhinosinusitis. The biology and application of biomarkers in patient care was also discussed. The Epithelial Science Expert Group also explored future research needs by identifying the current knowledge and research gaps in asthma management and ranking them by priority. It was identified that there is a need to define and support early assessment of asthma to characterise patients at high risk of severe asthma. Furthermore, a better understanding of asthma progression is required. The development of new treatments and diagnostic tests as well as the identification of new biomarkers will also be required to address the current unmet needs. Finally, an increased understanding of epithelial dysfunction will determine if we can alter disease progression and achieve clinical remission.

Fault slip is a complex natural phenomenon involving multiple spatiotemporal scales from seconds to days to weeks. To understand the physical and chemical processes responsible for the full fault slip spectrum, a multidisciplinary approach is highly recommended. The Near Fault Observatories (NFOs) aim at providing high-precision and spatiotemporally dense multidisciplinary near-fault data, enabling the generation of new original observations and innovative scientific products. The Alto Tiberina Near Fault Observatory is a permanent monitoring infrastructure established around the Alto Tiberina fault (ATF), a 60 km long low-angle normal fault (mean dip 20°), located along a sector of the Northern Apennines (central Italy) undergoing an extension at a rate of about 3 mm yr−1. The presence of repeating earthquakes on the ATF and a steep gradient in crustal velocities measured across the ATF by GNSS stations suggest large and deep (5–12 km) portions of the ATF undergoing aseismic creep. Both laboratory and theoretical studies indicate that any given patch of a fault can creep, nucleate slow earthquakes, and host large earthquakes, as also documented in nature for certain ruptures (e.g., Iquique in 2014, Tōhoku in 2011, and Parkfield in 2004). Nonetheless, how a fault patch switches from one mode of slip to another, as well as the interaction between creep, slow slip, and regular earthquakes, is still poorly documented by near-field observation. With the strainmeter array along the Alto Tiberina fault system (STAR) project, we build a series of six geophysical observatory sites consisting of 80–160 m deep vertical boreholes instrumented with strainmeters and seismometers as well as meteorological and GNSS antennas and additional seismometers at the surface. By covering the portions of the ATF that exhibits repeated earthquakes at shallow depth (above 4 km) with these new observatory sites, we aim to collect unique open-access data to answer fundamental questions about the relationship between creep, slow slip, dynamic earthquake rupture, and tectonic faulting.

Introduction: Childhood maltreatment, particularly emotional abuse (EA), has been identified as a significant risk factor for the development of eating disorders (EDs). This study investigated the association between EA and ED symptoms while considering multiple potential mediators. Methods: Participants included 151 individuals with Anorexia Nervosa (AN), 115 with Bulimia Nervosa (BN), and 108 healthy controls. The Childhood trauma questionnaire, the Toronto Alexithymia scale, the Behavioral inhibition System, and the Eating Disorder Inventory 2 scale were completed before treatment. A mediator path model was conducted in each group: EA was set as independent variable, eating symptoms as dependent variables and ineffectiveness, sensitivity to punishment, alexithymia, and impulsivity as mediators. Results: In individuals with AN, impulsivity emerged as a significant mediator between EA and desire for thinness and bulimic behaviors. Conversely, in individuals with BN, sensitivity to punishment was found to mediate the association between EA and dissatisfaction with one's body.Ineffectiveness and difficulty identifying emotions were identified as transdiagnostic mediators in both clinical groups. No mediation effect was found in healthy individuals. Discussion: The simultaneous assessment of multiple mediators in a unique model outlines the complex interplay between childhood EA and ED psychopathology. Improving ineffectiveness, emotion identification, sensitivity to punishment and impulsivity and exploring their relations with early emotional abuse may represent treatment targets in individuals with EDs and childhood trauma.

BackgroundNeutrophils (polymorphonuclear leukocytes, PMNs) are the most abundant subtype of white blood cells and are among the main actors in the inflammatory response. Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting both the axial and peripheral joints. Typically associated with psoriasis, PsA can also affect multiple systems and organs, including the nails and entheses. Despite the involvement of PMNs in PsA, their specific role in the disease remains poorly understood. This study aimed to characterize the biological functions of PMNs and neutrophil-related mediators in PsA patients.Materials and methods31 PsA patients and 22 healthy controls (HCs) were prospectively recruited. PMNs were isolated from peripheral blood and subjected to in vitro stimulation with lipopolysaccharide (LPS), N-Formylmethionyl-leucyl-phenylalanine (fMLP), tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate (PMA), or control medium. Highly purified peripheral blood PMNs (>99%) were evaluated for activation status, reactive oxygen species (ROS) production, phagocytic activity, granular enzyme and neutrophil extracellular traps (NETs) release. Serum levels of matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), TNF, interleukin 23 (IL-23), and interleukin 17 (IL-17) were measured by ELISA. Serum Citrullinated histone H3 (CitH3) was measured as a NET biomarker.ResultsActivated PMNs from PsA patients displayed reduced activation, decreased ROS production, and impaired phagocytic activity upon stimulation with TNF, compared to HCs. PMNs from PsA patients also displayed reduced granular enzyme (MPO) and NET release. Serum analyses revealed elevated levels of MMP-9, MPO, TNF, IL-23, IL-17, and CitH3 in PsA patients compared to HCs. Serum CitH3 levels positively correlated with MPO and TNF concentrations, and IL-17 concentrations were positively correlated with IL-23 levels in PsA patients. These findings indicate that PMNs from PsA patients show reduced in vitro activation and function, and an increased presence of neutrophil-derived mediators (MMP-9, MPO, TNF, IL-23, IL-17, and CitH3) in their serum.ConclusionsTaken together, our findings suggest that PMNs from PsA patients exhibit an “exhausted” phenotype, highlighting their plasticity and multifaceted roles in PsA pathophysiology.

The increasing incidence of organophosphate (OP) pesticide poisoning and the use of OP chemical warfare agents (CWA) in conflicts and terrorist acts need sustainable methods for sensing, decontamination, and detoxification of OP compounds. Enzymes can serve as specific, cost-effective biosensors for OPs. We will report on recent advancements in the use of carboxylesterases from the Hormone-Sensitive Lipase for the detection of OP compounds. In addition, enzymatic-based OP detoxification and decontamination offer long-term, environmentally friendly benefits compared to conventional methods such as chemical treatment, incineration, neutralization, and volatilization. Enzymatic detoxification has gained attention as an alternative to traditional OP-detoxification methods. This review provides an overview of the latest research on enzymatic sensing and detoxification of OPs, by exploiting enzymes, isolated from thermophilic/extremophilic Bacteria and Archaea that show exceptional thermal stability and stability in other harsh conditions. Finally, we will make examples of integration between sensing and decontamination systems, including protein engineering to enhance OP-degrading activities and detailed characterization of the best variants.

Urban parks and cemeteries constitute hot spots of bird diversity in urban areas. However, the seasonal dynamics of their bird communities have been scarcely explored at large scales. This study aims to analyze the drivers of urban bird assemblage seasonality in urban parks and cemeteries comparing assemblages during breeding and non-breeding seasons in the Neotropical Region. Since cemeteries have less human disturbance than urban parks, we expected differences in bird community seasonality between habitats. The seasonal change of species composition was partitioned into species turnover and nestedness. At large scales, the seasonal change of species composition was positively related to temperature seasonality and was higher in the Northern Hemisphere. At the landscape scale, the seasonal change of composition decreased in sites located in the most urbanized areas. At the local scale, sites with the highest habitat diversity and pedestrian traffic had the lowest seasonal change of composition. The species turnover was higher in the Northern Hemisphere, augmented with increasing annual temperature range, and decreased in urban parks. The species nestedness was positively related to habitat diversity. Our results showed that a multi-scale framework is essential to understand the seasonal changes of bird communities. Moreover, the two components of seasonal composition dissimilarity showed contrasting responses to environmental variables. Although the surrounding urbanization lowered the seasonal dynamics of urban green areas, cemeteries seem to conserve more seasonal changes than urban parks. Thus, urban cemeteries help to conserve the temporal dynamics of bird communities in cities.

CD28 provides the prototypical costimulatory signal required for productive T-cell activation. Known molecular consequences of CD28 costimulation are mostly based on studies of protein signaling molecules. The microRNA cluster miR-17∼92 is induced by T cell receptor stimulation and further enhanced by combined CD28 costimulation. We demonstrate that transgenic miR-17∼92 cell-intrinsically largely overcomes defects caused by CD28 deficiency. Combining genetics, transcriptomics, bioinformatics, and biochemical miRNA:mRNA interaction maps we empirically validate miR-17∼92 target genes that include several negative regulators of T cell activation. CD28-deficient T cells exhibit derepressed miR-17∼92 target genes during activation. CRISPR/Cas9-mediated ablation of the miR-17∼92 targets Pten and Nrbp1 in naive CD28-/- CD4+ T cells differentially increases proliferation and expression of the activation markers CD25 and CD44, respectively. Thus, we propose that miR-17∼92 constitutes a central mediator for T cell activation, integrating signals by the TCR and CD28 costimulation by dampening multiple brakes that prevent T cell activation.

IntroductionThe Janus kinase (JAK) family includes four cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) constitutively bound to several cytokine receptors. JAKs phosphorylate downstream signal transducers and activators of transcription (STAT). JAK-STAT5 pathways play a critical role in basophil and mast cell activation. Previous studies have demonstrated that inhibitors of JAK-STAT pathway blocked the activation of mast cells and basophils.MethodsIn this study, we investigated the in vitro effects of ruxolitinib, a JAK1/2 inhibitor, on IgE- and IL-3-mediated release of mediators from human basophils, as well as substance P-induced mediator release from skin mast cells (HSMCs).ResultsRuxolitinib concentration-dependently inhibited IgE-mediated release of preformed (histamine) and de novo synthesized mediators (leukotriene C4) from human basophils. Ruxolitinib also inhibited anti-IgE- and IL-3-mediated cytokine (IL-4 and IL-13) release from basophils, as well as the secretion of preformed mediators (histamine, tryptase, and chymase) from substance P-activated HSMCs.DiscussionThese results indicate that ruxolitinib, inhibiting the release of several mediators from human basophils and mast cells, is a potential candidate for the treatment of inflammatory disorders.

ABSTRACT Objective The aim of this observational, cross-sectional study was to investigate physicians’ preferences for radioiodine (RAI) treatment in patients with differentiated thyroid cancer (DTC) in Brazil and the factors influencing RAI indications. Materials and methods A survey was distributed to physicians potentially involved in DTC care in Brazil to understand the factors influencing RAI indications. The survey collected information on the profiles of the physicians, along with the characteristics of their workplaces and their preferences regarding RAI indications in three hypothetical clinical cases. Cases 1, 2, and 3 described the cases of patients with DTC and variations to the case that included different scenarios to assess how the respondents would change their RAI recommendations. The analysis included the RAI indications across different medical specialties. Results A total of 175 physicians answered the survey. There was considerable variability in RAI recommendations in all three cases. The training background influenced the respondents' preferences for RAI indications and their approaches to preparing patients for RAI treatment. Conclusion The findings of this study reaffirm the need for a Brazilian consensus among physicians across multiple specialties to help guide health care professionals treating patients with DTC in Brazil.

In recent years, age management practices and strategies have become widely diffused since today the valorization of people according to their age represents, a fundamental aspect for organisations, which are required to understand in depth the dynamics of generational belonging for a correct definition of their work and training policies. Population ageing is a phenomenon shared by many countries, especially those in Europe. In health care contexts, the ageing of workers and their co-habitation of organisational contexts with colleagues belonging to other generations demands effective equal opportunities for training and skills development policies to improve both the quality of work and the quality of services offered. To this purpose, communities of practice, including virtual ones, become a training device to be explored, especially looking at the latest developments in artificial intelligence. Age management e formazione intergenerazionale in medicina. Intelligenza artificiale e comunità di pratica virtuali. Negli ultimi anni, le pratiche e le strategie di age management si sono largamente diffuse poiché la valorizzazione delle persone in funzione della loro età rappresenta, oggi, un aspetto fondamentale per le organizzazioni, chiamate a comprendere in modo approfondito le dinamiche dell’appartenenza generazionale per una corretta definizione e valorizzazione delle proprie politiche di lavoro e formazione. L’invecchiamento della popolazione è un fenomeno che accomuna molti paesi, soprattutto quelli europei. Nei contesti sanitari, l’invecchiamento degli operatori e la loro co-abitazione dei contesti organizzativi con colleghi appartenenti ad altre generazioni richiede politiche efficaci di pari opportunità e di formazione e sviluppo delle competenze per migliorare sia la qualità del lavoro sia la qualità dei servizi offerti. A tale scopo, le comunità di pratica, anche quelle virtuali, divengono un dispositivo formativo da esplorare, soprattutto guardando ai più recenti sviluppi dell’intelligenza artificiale.