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Objectives: Scarce data are currently available on the kinetics of antibodies after vaccination with mRNA vaccines as a whole and, with mRNA-1273, in particular. We report here an ad-interim analysis of data obtained after a 6-month follow-up in a cohort of healthcare workers (HCWs) who received the mRNA-1273 vaccine. These new data provide more insight into whether and in whom a 3rd dose could be necessary. Methods: Our study compared the anti-S antibody kinetics at 2 weeks (T1), 3 months (T3) and 6 months (T4) after the first injection, and 2 weeks after the second injection (T2). The 201 participating HCWs were stratified according to their initial serological status. The vaccine effectiveness was also assessed through a medical questionnaire. Results: We report here a marked and statistically significant antibody decrease (P < 0.05) between T3 and T4, especially in naïve vaccinees. The analysis of potential confounding factors or known risk factors for severe COVID-19 disease did not reveal any influence on the drop observed. Six-month after vaccination, only one, symptomatic, infection was reported in our cohort. Conclusions: In a supply-limited environment, our results plead for reserving the 3rd dose scheme, in the upcoming months, to seronegative individuals prior to vaccination, especially when the serological status is easily accessible.

Attention-deficit hyperactivity disorder (ADHD), has been traditionally considered a neurodevelopmental disorder affecting children and adolescents characterized by inattention, hyperactivity, disruptive behavior, and impulsivity. Although still debated, it is evident that ADHD is also present in adulthood, but this diagnosis is rarely carried out, mainly for the frequent comorbidity with other psychiatric and/or substance abuse disorders. Given the need to shed more light on the pharmacological treatment of ADHD, we performed a naturalistic review to review and comment on the available literature of ADHD treatment across the lifespan. Indeed, stimulants are endowed of a prompt efficacy and safety, whilst non-stimulants, although requiring some weeks to be fully effective, are useful when a substance abuse history is detected. In any case, the pharmacological management of ADHD appears to be still largely influenced by the individual experience of the clinicians. Further longitudinal studies with a careful and detailed characterization of participants across different phases of the lifespan are also required to provide relevant confirmations (or denials) regarding pharmacological treatments amongst the different age groups.

Background: Air ions (AIs) are clusters of ionized particles present in the atmosphere, carrying an electrical charge of negative or positive polarity. Past speculations suggested that exposure to positive air ions may be harmful, while exposure to negative air ions (NAIs) may be associated with beneficial health effects. Increasing attention has been directed towards investigating the potential effect of NAIs on human brain activities since initial observations of their beneficial effects on some cognitive processes and mood. Aims: Given the paucity and scattered literature, our paper aims to review the available studies on potential positive effects of NAIs exposure on cognitive performances and depression. Discussion: The review of the literature seems to confirm the effects of NAIs on several brain functions. Indeed, a significant association between NAIs exposure and both well-being and high cognitive performances has been described. Furthermore, exposure to high concentrations of NAIs could be related to the improvement of depressive symptoms. Conclusion: A growing evidence of data, although not yet conclusive, would suggest that NAIs might improve cognitive processes. These findings require specific and urgent controlled trials adopting systems based on AIs release to possibly prevent and treat cognitive dysfunctions present in a broad range of neuropsychiatric conditions.

Background The field of mobile health (mHealth) is constantly expanding. Integrating mHealth apps and devices in clinical practice is a major and complex challenge. General practitioners (GPs) are an essential link in a patient’s care pathway. As they are patients’ preferred health care intermediaries, GPs play an important role in supporting patients’ transition to mHealth. Objective This study aims to identify the factors associated with the willingness of French GPs to prescribe mHealth apps and devices to their patients. Methods This study was part of the ApiAppS project whose overall objective was to help remove barriers GPs face when prescribing mHealth apps and devices by developing a custom-built platform to aid them. The study included GPs recruited from the general practice department of several medical faculties in France (Lyon, Nice, and Rouen) and mailing lists of academic GPs, health care professional associations, and social and professional networks. Participants were asked to complete a web-based questionnaire that collected data on various sociodemographic variables, indicators of their involvement in continued education programs and the amount of time they dedicated to promoting healthy behaviors during patient consultations, and indicators characterizing their patient population. Data on their perceptions of mHealth apps and devices were also collected. Finally, the questionnaire included items to measure GPs’ acceptability of prescribing mHealth apps and devices for several health-related dimensions. Results Of the 174 GPs, 129 (74.1%) declared their willingness to prescribe mHealth apps and devices to their patients. In multivariate analysis, involvement in continued education programs (odds ratio [OR] 6.17, 95% CI 1.52-28.72), a better patient base command of the French language (OR 1.45, 95% CI 1.13-1.88), GP-perceived benefits of mHealth apps and devices for both patients and their medical practice and GP-perceived drivers for mHealth apps and device implementation in their medical practice (OR 1.04, 95% CI 1.01-1.07), and validation of mHealth apps and devices through randomized clinical trials (OR 1.02, 95% CI 1.00-1.04) were all associated with GPs’ willingness to prescribe mHealth apps and devices. In contrast, older GPs (OR 0.95, 95% CI 0.91-0.98), female GPs (OR 0.26, 95% CI 0.09-0.69), and those who perceived risks for the patient or their medical practice (OR 0.96, 95% CI 0.94-0.99) were less inclined to prescribe mHealth apps and devices. Conclusions mHealth apps and devices were generally seen by GPs as useful in general medicine and were, for the most part, favorable to prescribing them. Their full integration in general medicine will be conditioned by the need for conclusive certification, transparency (reliable and precise data concerning mHealth app and device methods of construction and clinical validation), software aids to assist GPs prescribe them, and dedicated training programs.

Chronic hepatitis E virus (HEV) infection in hematopoietic stem cell transplantation (HSCT) recipients is an emerging threat. The aim of this study was to provide data on the HEV burden in an Italian cohort of HSCT recipients and analyze risk factors for HEV seropositivity. This retrospective study reports data from 596 HSCT recipients compiled between 2010 and 2019. It included patients who underwent transplantation between 2010 and 2015 for whom pretransplantation (n = 419) and post-transplantation (n = 161) serum samples were available and tested retrospectively, as well as patients in whom prospective HEV testing was performed during the standard care: pre-HSCT IgG screening in 144, pre-HSCT HEV-RNA screening in addition to IgG screening in 60, and HEV-RNA testing in case of clinical suspicion of HEV infection in 59 (26 of whom were also included in the IgG screening cohorts). The rate of pre-HSCT HEV-IgG positivity was 6.0% (34 of 563). Older age was an independent risk factor for seropositivity (P = .039). None of the 34 HEV-IgG-positive patients had detectable HEV-RNA. One case of transient HEV-RNA positivity pre-HSCT was identified through screening. Two patients were diagnosed with chronic HEV hepatitis, and 1 patient was successfully treated with ribavirin. The burden of HEV infection in HSCT recipients in Italy is limited, and pre-HSCT screening appears to be of no benefit. Timely diagnosis of HEV infection with HEV-RNA is mandatory in cases of clinical suspicion.

This paper reports the case of a 46‐year‐old woman suffering from bipolar disorder of type I with mixed features with initial fronto‐temporal atrophy. Although considered treatment‐resistant to conventional strategies, she successfully responded to a combination of rivastigmine, clozapine, and oxcarbazepine.

Monoallelic variants in the KIF1A gene are associated with a large set of clinical phenotypes including neurodevelopmental and neurodegenerative disorders, underpinned by a broad spectrum of central and peripheral nervous system involvement. In a multicenter study conducted in patients presenting spastic gait or complex neurodevelopmental disorders, we analyzed the clinical, genetic and neuroradiological features of 28 index cases harboring heterozygous variants in KIF1A. We conducted a literature systematic review with the aim to comparing our findings with previously reported KIF1A-related phenotypes. Among 28 patients, we identified nine novel monoallelic variants, and one a copy number variation encompassing KIF1A. Mutations arose de novo in most patients and were prevalently located in the motor domain. Most patients presented features of a continuum ataxia-spasticity spectrum with only five cases showing a prevalently pure spastic phenotype and six presenting congenital ataxias. Seventeen mutations occurred in the motor domain of the Kinesin-1A protein, but location of mutation did not correlate with neurological and imaging presentations. When tested in 15 patients, muscle biopsy showed oxidative metabolism alterations (6 cases), impaired respiratory chain complexes II + III activity (3/6) and low CoQ10 levels (6/9). Ubiquinol supplementation (1gr/die) was used in 6 patients with subjective benefit. This study broadened our clinical, genetic, and neuroimaging knowledge of KIF1A-related disorders. Although highly heterogeneous, it seems that manifestations of ataxia-spasticity spectrum disorders seem to occur in most patients. Some patients also present secondary impairment of oxidative metabolism; in this subset, ubiquinol supplementation therapy might be appropriate.

Surgical intervention within 48 h of hospital admission is the gold standard procedure for the management of elderly patients with femur fractures, since the increase in preoperative waiting time is correlated with the onset of complications and longer overall length of stay (LOS) in the hospital. However, national evidence demonstrates that there is still the need to provide timely intervention for this type of patient, especially in some regions of central southern Italy. Here we discuss the introduction of a diagnostic–therapeutic assistance pathway (DTAP) to reduce the preoperative LOS for patients undergoing femur fracture surgery in a university hospital. A Lean Six Sigma methodology, based on the DMAIC cycle (Define, Measure, Analyze, Improve, Control), is implemented to evaluate the effectiveness of the DTAP. Data were retrospectively collected and analyzed from two groups of patients before and after the implementation of DTAP over a period of 10 years. The statistics of the process measured before the DTAP showed an average preoperative LOS of 5.6 days (standard deviation of 3.2), thus confirming the need for corrective actions to reduce the LOS in compliance with the national guidelines. The influence of demographic and anamnestic variables on the LOS was evaluated, and the impact of the DTAP was measured and discussed, demonstrating the effectiveness of the improvement actions implemented over the years and leading to a significant reduction in the preoperative LOS, which decreased to an average of 3.5 days (standard deviation of 3.60). The obtained reduction of 39% in the average LOS proved to be in good agreement with previously developed DTAPs for femur fracture available in the literature.

We report the results of a study on the cumulative incidence of SARS-CoV-2 infections in about 6000 workers of the University Hospital of Modena, Northern Italy, in the period March 2020–January 2021, and the relations with some individual and occupational factors. Overall, in healthcare workers (HCW) the cumulative incidence of COVID-19 during the period was 13.8%. Results confirm the role of overweight and obesity as significant risk factors for SARS-CoV-2 infection. Chronic respiratory diseases, including asthma, also proved to be significantly associated with the infection rate. Considering occupational factors, the COVID-19 risk was about threefold (OR: 2.7, 95% CI 1.7–4.5) greater in nurses and nurse aides than in non-HCW, and about double (OR: 1.9, 95% CI 1.2–3.2) in physicians. Interestingly, an association was also observed between infection risk and nightshifts at work (OR: 1.8, 95% CI 1.4–2.3), significantly related to the total number of shifts in the whole eleven-month period. Even if the vaccination campaign has now greatly modified the scenario of SARS-CoV-2 infections among HCW, the results of this study can be useful for further development of health and policy strategies to mitigate the occupational risk related to the new variants of coronavirus, and therefore the evolution of the pandemic.

Several experimental databases of aeroelastic measurements performed on aircraft wing models are available for the validation of fluid-structure interaction (FSI) numerical methodologies. Most of these databases are used to model scaled systems focusing primarily on aerodynamic aspects, rather than on structural similitude with a full-scale model. To study flow regimes that replicate realistic operating conditions, wind tunnel test campaigns generate relatively high loads on models whose safe sizing forces the adoption of structural configurations that lose any similitude with typical wing box topologies. The aeroelastic measurements campaign conducted within the European Union "Radial basis functions at fluid Interface Boundaries to Envelope flow results for advanced Structural analysis"(RIBES) project was set up to shift attention to the structural similitude of aeroelastic mechanisms. The objective is to generate a database of loads, pressures, stresses, and deformations that is significant for a realistic aeronautical design problem. A wind tunnel model of a half wing that replicates a typical metallic wing box structure, instrumented with pressure taps and strain gauges, was designed and manufactured. This paper describes the experimental procedure and results by detailing the model design, its manufacture, and the measurements performed. All experimental data and numerical models are freely available online to the scientific community.

A serotonergic dysfunction has been largely postulated as the main cause of depression, mainly due to its effective response to drugs that increase the serotonergic tone, still currently the first therapeutic line in this mood disorder. However, other dysfunctional pathomechanisms are likely involved in the disorder, and this may in part explain why some individuals with depression are resistant to serotonergic therapies. Among these, emerging evidence suggests a role for the astrocytic inward rectifier potassium channel 4.1 (Kir4.1) as an important modulator of neuronal excitability and glutamate metabolism. To discuss the relationship between Kir4.1 dysfunction and depression, a systematic review was performed according to the PRISMA statement. Searches were conducted across PubMed, Scopus, and Web of Science by two independent reviewers. Twelve studies met the inclusion criteria, analyzing Kir4.1 relationships with depression, through in vitro, in vivo, and post-mortem investigations. Increasing, yet not conclusive, evidence suggests a potential pathogenic role for Kir4.1 upregulation in depression. However, the actual contribution in the diverse subtypes of the disorder and in the comorbid conditions, for example, the epilepsy-depression comorbidity, remain elusive. Further studies are needed to better define the clinical phenotype associated with Kir4.1 dysfunction in humans and the molecular mechanisms by which it contributes to depression and implications for future treatments.

SCOPUS: le.j, info:eu-repo/semantics/published

Objective The present paper compared vitamin D levels in adult patients with obsessive-compulsive disorder (OCD) and explored possible correlations with patients’ characteristics. Methods Fifty outpatients with OCD, according to DSM-5 criteria, were included and assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HRDS). Results All the patients except one showed lower vitamin D levels than normative values (>30 nm/L). Vitamin D values of the whole sample were negatively correlated with Y-BOCS total, compulsion subscale, and some items’ scores, specifically “interference from obsessions,” “distress associated with obsessions,” and “time spent on compulsions”. The same relationships were detected in men, while women showed negative correlations between vitamin D levels and Y-BOCS compulsion subscale and “resistance to compulsions,” “degree of control of compulsions,” “insight” item scores. Conclusions Our findings would indicate that vitamin D might be involved in the pathophysiology of OCD, and that it is possibly related to the severity of the disorder and to typical symptoms, with some sex-related peculiarities. Further studies are necessary to support or not our findings and to ascertain the effectiveness of vitamin D supplementation in patients with OCD.

A multidisciplinary analysis approach plays a very important role in the development of future transport aircraft, being able to interconnect all aircraft-related subjects and suppliers. A major issue, which has prevented aircraft manufacturers from implementing efficient and cost-effective design processes, is the loose integration of engine models into iterative aircraft design workflows. The continuous improvement of computer calculation capabilities over years has allowed the growth of a large family of software dedicated to aircraft preliminary design activities concerning also multi-disciplinary analyses, and optimizations. In this context, a new software for aircraft preliminary design, multi-disciplinary analyses and optimizations named JPAD (Java toolchain of Programs for Aircraft Design) has been developed at the University of Naples Federico II. The main purpose of this paper is to show the capabilities of the JPAD software applied to typical preliminary design problems. Thus, results of the activities carried out by means of JPAD in the scope of the Work Package 2 (WP2) of the European CleanSky2 project ADORNO will be shown. Those will concern trade factors and response surfaces related to environmental noise, DOC, and pollutant emissions (linked to the design mission block fuel) for a Rear-Mounted engines (RM) reference 2014 aircraft configuration.

Aircraft directional control effectiveness is analyzed through experiments in wind tunnel. Control surfaces on low aspect ratio lifting surfaces exhibit different lifting capabilities compared to those with high aspect ratio. Such behavior must be carefully considered in the preliminary design phase to avoid any overestimation in size, weight, costs and emissions. Traditional sizing methodologies are based on coupling the effects of the wing planform (e.g. aspect ratio) at low angles of control surface deflection with the effects of wing section (e.g. chord ratio) evaluated on section data in the full range of control surface deflection, so that the non-linear aerodynamics is inherited from 2D data, completely neglecting the different aerodynamic behavior of a low aspect ratio wing at high angles of deflection. To fill this gap, an experimental wind tunnel test campaign on a generic regional turboprop aircraft model with a modular vertical tail with rudder has been performed. Results indicate that the aircraft design methodologies present in public literature underestimate the control surface effectiveness at high angle of deflections by 15% to 25%, leading to an average overestimation of control surface size.

International audience; This paper presents methodological investigations performed in research activities in the field of Multi-disciplinary Design and Optimization (MDO) for overall aircraft design in the EU funded research project AGILE (2015–2018). In the AGILE project a team of 19 industrial, research and academic partners from Europe, Canada and Russia are working together to develop the next generation of MDO environment that targets significant reductions in aircraft development costs and time to market, leading to cheaper and greener aircraft. The paper introduces the AGILE project structure and describes the achievements of the 1st year that led to a reference distributed MDO system. A focus is then made on different novel optimization techniques studied during the 2nd year, all aiming at easing the optimization of complex workflows that are characterized by a high number of discipline interdependencies and a large number of design variables in the context of multi-level processes and multi-partner collaborative engineering projects. Three optimization strategies are introduced and validated for a conventional aircraft. First, a multi-objective technique based on Nash Games and Genetic Algorithm is used on a wing design problem. Then a zoom is made on the nacelle design where a surrogate-based optimizer is used to solve a mono-objective problem. Finally a robust approach is adopted to study the effects of uncertainty in parameters on the nacelle design process. These new capabilities have been integrated in the AGILE collaborative framework that in the future will be used to study and optimize novel unconventional aircraft configurations.

Timeliness in the treatment of fracture of the femur, through surgery, is crucial in the elderly patient as it reduces the risk of mortality and disability. Here we propose a Lean Six Sigma (LSS) approach to reduce the preoperative length of stay for patients with femur fracture. Through the LSS, a tailored Diagnostic Therapeutic Assistance Path (DTAP) for these has been implemented and monitored over time. In particular, through the analysis, based on the application of the DMAIC cycle conducted on data extrapolated from the information system of the “San Giovanni di Dio e Ruggi d’Aragona” University Hospital of Salerno, the new DTAP was designed and implemented. After the introduction of the DTAP, a significant reduction in the average length of hospital stay was observed, with a preoperative length of stay within 48 h in 65% cases (compared to the previous 9%). In particular, the most significant reduction (over 55%) is obtained for patients aged over 65 years old. Such a result reflects not only the improvement in the care process but it is also compliant with the guidelines of the Italian Ministry of Health, as reported in the New Guarantee System for monitoring the quality of care. © 2021, Springer Nature Switzerland AG.

Aeroelastic wind tunnel tests on a half-wing model have been performed at the University of Naples “Federico II” to acquire data about aerodynamic forces, section pressure coefficient, stress, strain, and model displacement, to validate high fidelity Fluid-Structure Interaction approaches based on Reynolds-Averaged Navier-Stokes and Finite Element Method solutions investigated at the University of Rome “Tor Vergata”. Most of the available experimental databases of aeroelastic measurements, performed on aircraft wings, model full scale systems, focusing primarily on aerodynamic aspects rather than on structural similitudes. To investigate flow regimes that replicate realistic operating conditions, wind tunnel test campaigns involve the generation of relative high loads on models whose safe dimensioning force the adoption of structural configurations that lose any similitude with typical wing box topologies. The objective of this work is to generate a database of loads, pressure, stress, and deformation measurements that is significant for a realistic aeronautical design problem. At this aim, a wind tunnel model of a half-wing that replicates a typical metallic wing box structure and instrumented with pressure taps and strain gages has been investigated. All experimental data and numerical models are freely available to the scientific community at the website www.ribes-project.eu.

Background: The pathophysiology of major depressive disorder (MDD), one of the major causes of worldwide disability, is still largely unclear, despite the increasing data reporting evidence of multiple alterations of different systems. Recently, there was a renewed interest in the signalling of gamma aminobutyric acid (GABA) - the main inhibitory neurotransmitter. Objective: The aim of this study was to review and comment on the available literature about the involvement of GABA in MDD, as well as on novel GABAergic compounds possibly useful as antidepressants. Methods: We carried out a narrative review through Pubmed, Google Scholar and Scopus, by using specific keywords. Results: The results, derived from various research tools, strongly support the presence of a deficiency of the GABA system in MDD, which appears to be restored by common antidepressant treatments. More recent publications would indicate the complex interactions between GABA and all the other processes involved in MDD, such as monoamine neurotransmission, hypothalamus-pituitary adrenal axis functioning, neurotrophism, and immune response. Taken together, all these findings seem to further support the complexity of the pathophysiology of MDD, possibly reflecting the heterogeneity of the clinical pictures. Conclusion: Although further data are necessary to support the specificity of GABA deficiency in MDD, the available findings would suggest that novel GABAergic compounds might constitute innovative therapeutic strategies in MDD.

Objective: Inappropriate use of the emergency department (ED) represents a major worldwide issue both in pediatric and adult age. Herein, we aim to describe features of pediatric visits to the ED of Salerno University Hospital and to evaluate parental reasons behind the decision to walk in.Materials and Methods: We performed a retrospective observational study evaluating ED encounters for children from January 2014 to December 2019. The appropriateness of visits was measured with a national tool assessing every ED encounter, namely, “the Mattoni method,” which consists of the combination of the triage code assigned, the diagnostic resources adopted, and the consultation outcomes. Moreover, 64 questionnaires were collected from a sample of parents in the waiting rooms in January 2020.Results: A total number of 42,507 visits were recorded during the study period (19,126 females; mean age ± SD: 4.3 ± 3.8 years), the majority of whom were inappropriate (75.8% over the considered period; 73.6% in 2014; 74.6% in 2015; 76.3% in 2016; 76.7% in 2017; 77.9% in 2018; 75.5% in 2019). Most of the inappropriate consultations arrived at the ED by their own vehicle (94.4%), following an independent decision of the parents (97.2%), especially in the evening and at night on Saturdays/Sundays/holidays (69.7%). A multivariate analysis revealed the following: patients of younger age (OR: 1.11, 95% C.I. 1.06–1.16; p < 0.0019), night visits (OR 1.39; 95% C.I.: 1.32–1.47; p < 0.001), patients living in the municipality of Salerno (OR 1.28; 95% C.I.: 1.22–1.34; p < 0.001), weekend day visits (OR 1.48; 95% C.I.: 1.41–1.56; p < 0.001), and independent parental decision without previous contact with primary care pediatrician (OR 3.01; 95% C.I.: 2.64–3.44; p < 0.001) were all significant independent predictors of inappropriate consultation. The most frequent trigger of ED encounters was fever (51.4%). Hospital admission made up 17.6% of all consultations. The questionnaire showed that most parents were aware of the lack of urgency (20.3%) or minor urgency (53.1%) of the visit. The reasons for walking in were the impossibility to receive a home consultation (70%), the difficulty of contacting their family pediatrician during weekends and holidays (54.4%), as well as the search for a quick, effective, diagnosis and therapy (48.4%).Conclusions: The study suggests a highly inappropriate use of ED for children in our region. This issue deserves considerable attention by health care system leaders in order to optimally integrate hospitals and primary care.

Background Late-presenting congenital diaphragmatic hernia (L-CDH) diagnosis is a challenge for its clinical various presentation. In literature radiologic misdiagnosis is up to 62%. The aim of this study is analyze clinical findings about our cases series in a particular setting of Pediatric Emergency Department (PED) and review of literature. Methods We retrospectively analyzed the medical records of children older than 1 month, operated for L-CDH from November 2009 to December 2019 presented to PED, with a total of 20 children (5 Morgagni and 15 Bochdaleck). Results The median age at diagnosis was 1,48 years. 50% patients had a history of previouses symtptoms with a mean duration of 243,75 days. In 30 % of cases associated anomalies were presented, mainly cardiovascular. 25% of patients had undergone to chest X-ray in past history with misdiagnosis of pneumonia, microganulia and broncovascular thickening. Misdiagnosis are manly among left sided Bochdaleck hernia. Respiratory distress alone or associated with vomiting is commonest acute symptom refered to PED. Respiratory symptoms were more common in younger children, while gastrointestinal ones in older children (not statistically differences p=0,8769). Post-operative recurrence were frequent only in cases of right sided CDH and comparing with left ones, there is a difference statistically significant (p=0.0476). Conclusions L-CDH should be suspected in cases of unexplained acute respiratory distress and vomiting, particulary when children are affected to associate cardiovascular malformation. In cases of patients with long previouses symptoms and various accesses to PED is important to emphasize history of respiratory distress, dysphagia and failure to thrive and should be considered a chest X-ray.

Aircraft directional stability and control are related to vertical tail design. The safety, performance, and flight qualities of an aircraft also depend on a correct empennage sizing. Specifically, the vertical tail is responsible for the aircraft yaw stability and control. If these characteristics are not well balanced, the entire aircraft design may fail. Stability and control are often evaluated, especially in the preliminary design phase, with semi-empirical methods, which are based on the results of experimental investigations performed in the past decades, and occasionally are merged with data provided by theoretical assumptions. This paper reviews the standard semi-empirical methods usually applied in the estimation of airplane directional stability derivatives in preliminary design, highlighting the advantages and drawbacks of these approaches that were developed from wind tunnel tests performed mainly on fighter airplane configurations of the first decades of the past century, and discussing their applicability on current transport aircraft configurations. Recent investigations made by the authors have shown the limit of these methods, proving the existence of aerodynamic interference effects in sideslip conditions which are not adequately considered in classical formulations. The article continues with a concise review of the numerical methods for aerodynamics and their applicability in aircraft design, highlighting how Reynolds-Averaged Navier-Stokes (RANS) solvers are well-suited to attain reliable results in attached flow conditions, with reasonable computational times. From the results of RANS simulations on a modular model of a representative regional turboprop airplane layout, the authors have developed a modern method to evaluate the vertical tail and fuselage contributions to aircraft directional stability. The investigation on the modular model has permitted an effective analysis of the aerodynamic interference effects by moving, changing, and expanding the available airplane components. Wind tunnel tests over a wide range of airplane configurations have been used to validate the numerical approach. The comparison between the proposed method and the standard semi-empirical methods available in literature proves the reliability of the innovative approach, according to the available experimental data collected in the wind tunnel test campaign.

Background and purpose Rehabilitation plays a central role in stroke recovery. Besides conventional therapy, technological treatments have become available. The effectiveness and appropriateness of technological rehabilitation are not yet well defined; hence, research focused on different variables impacting recovery is needed. Results from the literature identified cognitive reserve (CR) as a variable impacting on the cognitive outcome. In this paper, the aim was to evaluate whether CR influences the motor outcome in patients after stroke treated with conventional or robotic therapy and whether it may influence one treatment rather than another. Methods Seventy-five stroke patients were enrolled in five Italian neurological rehabilitation centres. Patients were assigned either to a robotic group, rehabilitation by means of robotic devices, or to a conventional group, where a traditional approach was used. Patients were evaluated at baseline and after rehabilitation treatment of 6 weeks through the Action Research Arm Test (ARAT), the Motricity Index (MI) and the Barthel Index (BI). CR was assessed at baseline using the Cognitive Reserve Index (CRI) questionnaire. Results Considering all patients, a weak correlation was found between the CRI related to leisure time and MI evolution (r = 0.276; P = 0.02). Amongst the patients who performed a robotic rehabilitation, a moderate correlation emerged between the CRI related to working activities and MI evolution (r = 0.422; P = 0.02). Conclusions Our results suggest that CR may influence the motor outcome. For each patient, CR and its subcategories should be considered in the choice between conventional and robotic treatment.

Women with chronic pelvic pain (CPP) frequently suffer from mood disturbances and reduced quality of life. Whether pain improvement ameliorates mood and quality of life is still unclear, and it was investigated in an observational prospective study performed in a cohort of 117 of the outpatient services for endometriosis and chronic pelvic pain at a University Hospital. Depending on disease, women were treated either by surgery or by the administration of an estrogen-progestin or a progestin alone. Pain during menses, between menses and at intercourse was evaluated by a 100 mm visual analog (VAS) scale. Quality of life was evaluated by the SF-36 questionnaire, state of anxiety by the Y-1 form of the State-Trait Anxiety Inventory (STAI-Y1) and depression the Self Evaluating Depression Scale (SDS). Women were 34.2 ± 8.1 years old. After a mean follow-up period of 10.0 ± 9.1 months, and independently on treatment (43.6% surgery), pain during menses (-28.2 ± 36.8; p.0001), between menses (-11.3 ± 37.1; p.002) and at intercourse (-8.3 ± 35.4; p.02) decreased. SF-36 increased (3.3 ± 16.2; p.03), STAI slightly decreased (-1.9 ± 8.6; p.02), while depression did not change (-0.7 ± 7.8; p=.36). Pain changes were not related to changes of SF-36 or mood scores. In women with CPP, prolonged pain amelioration, has little impact on mood, particularly on depression. The data support the need for a multidisciplinary approach to women with CPP.

International audience; Introduction: Tau protein misfolding and accumulation in toxic species is a critical pathophysiological process of Alzheimer's Disease (AD) and other neurodegenerative disorders (NDDs). Tau biomarkers, namely cerebrospinal fluid (CSF) total-tau (t-tau), 181-phosphorylated tau (p-tau) and tau-PET tracers, have been recently embedded in the diagnostic criteria for AD. Nevertheless, the role of tau as a diagnostic and prognostic biomarker for other NDDs remains controversial.Areas covered: We performed a systematical PubMed-based review of the most recent advances in tau-related biomarkers for NDDs. We focused on papers published from 2015 to 2020 assessing the diagnostic or prognostic value of each biomarker.Expert opinion: The assessment of tau biomarkers in alternative easily accessible matrices, through the development of ultrasensitive techniques, represents the most significant perspective for AD-biomarker research. In NDDs, novel tau isoforms (e.g., p-tau217) or proteolytic fragments (e.g., N-terminal fragments) may represent candidate diagnostic and prognostic biomarkers and may help monitoring disease progression. Protein misfolding amplification assays, allowing the identification of different tau strains (e.g. 3R- vs. 4R-tau) in CSF, may constitute a breakthrough for the in vivo stratification of NDDs. Tau-PET may help tracking the spatial-temporal evolution of tau pathophysiology in AD but its application outside the AD-spectrum deserves further studies.

Headache is the world's seventh most significant cause of disability-adjusted-life in people aged between 10 and 14 years. Therapeutic management is based on pharmacological approaches and lifestyle recommendations. Many studies show associations between each migraine-promoting lifestyle, behavioral triggers, frequency, and intensity of headaches. Nevertheless, the overall aspects of this topic lack any definitive evidence. Educational programs advise that pediatric patients who suffer from migraines follow a correct lifestyle and that this is of the utmost importance in childhood, as it will improve quality of life and assist adult patients in avoiding headache chronicity, increasing general well-being. These data are important due to the scarcity of scientific evidence on drug therapy for prophylaxis during the developmental age. The “lifestyle recommendations” described in the literature include a perfect balance between regular sleep and meal, adequate hydration, limited consumption of caffeine, tobacco, and alcohol, regular physical activity to avoid being overweight as well as any other elements causing stress. The ketogenic diet is a possible new therapeutic strategy for the control of headache in adults, however, the possible role of dietary factors requires more specific studies among children and adolescents. Educational programs advise that the improvement of lifestyle as a central element in the management of pediatric headache will be of particular importance in the future to improve the quality of life of these patients and reduce the severity of cephalalgic episodes and increase their well-being in adulthood. The present review highlights how changes in different aspects of daily life may determine significant improvements in the management of headaches in people of developmental age.

BackgroundThe SARS-CoV-2 pandemic has infected millions of people and has caused more than 2.30 million deaths worldwide to date. Several doubts arise about the role of asymptomatic carriers in virus transmission. During the first epidemic outbreak in Italy a large screening with nasopharyngeal swab (NS) was performed in those who were considered ‘suspect’ for infection.AimsTo report the results of the SARS-CoV-2 screening in a province in Southern Italy and to provide data on the COVID-19 epidemic and the burden of asymptomatic subjects.Patients and methodsA retrospective cohort study was set up in all healthcare facilities of the province (12 hospitals and 13 sanitary districts: primary, secondary and tertiary centres) with the aim to analyse the results of NS performed on all subjects suspected to be infected with SARS-CoV-2, either because they presented symptoms suggestive of SARS-CoV-2 infection, they were ‘contacts’ of positive subjects, they came from areas with high prevalence or they were healthcare workers. NS were performed and managed as indicated by international guidelines. The specimens were processed for SARS-CoV-2 detection by real-time PCR.ResultsA total of 20 325 NS were performed from 13 March to 9 May 2020. Of these, 638 (3.14%) were positive. 470 were asymptomatic, or 75.3% of persons who were positive. They were mostly among ‘contacts’ of symptomatic cases (428 of 470, 91%) and were in domiciliary isolation. Expression of three SARS-CoV-2 genes did not differ between asymptomatic and symptomatic subjects. The strict measures with regard to social distancing led to a continuous decrease in cases during phase 1.ConclusionsIn a large area in Southern Italy, 3.14% (638 of 20 325) of the total subjects tested were positive for SARS-CoV-2. Most of them were asymptomatic (470 of 624, 75.3%), and of these 91% (428 of 470) were ‘close contacts’ of symptomatic subjects. The combination of social distancing together with the systematic screening of close contacts of COVID-19-positive symptomatic subjects seems to be an efficacious approach to limit the spread of the epidemic.

The integration of on-board systems design within the aircraft design process is often considered only in the late part of the initial design. This is acceptable for civil aircraft using standard technology systems. However, facing with MEA and AEA concepts and different possible architectures, the systems design and the assessment of their effects on the overall aircraft should be moved up in the usual design process. This paper deals with evaluation of the effect of different on-board systems architecture, with a different electrification level, on the overall aircraft design. These effects have been evaluated using three different MDA workflows developed within the AGILE4.0 European research project. The workflows are defined with an increasing number of disciplines to show how the effect of a proper selection of a systems architecture is differently caught by each one. In this way it is possible to define which disciplines should be included for the systems architecture assessment. The results show a save of 1% of MTOM for the AEA applied to a small turboprop aircraft when only the OBS mass is assessed. Increasing workflow complexity, adding performance and engine design the save increase to 1.2%. Finally, the save increases to 1.3% when the effect on engine SFC is also considered. &nbsp

Background: Xia–Gibbs syndrome (XGS) is a rare disorder caused by de novo mutations in the AT-Hook DNA binding motif Containing 1 (AHDC1) gene, which is characterised by a wide spectrum of clinical manifestations, including global developmental delay, intellectual disability, structural abnormalities of the brain, global hypotonia, feeding problems, sleep difficulties and apnoea, facial dysmorphisms, and short stature. Methods: Here, we report on a girl patient who shows a peculiar cognitive and behavioural profile including high-functioning autism spectrum disorder (ASD) without intellectual disability and provide information on her developmental trajectory with the aim of expanding knowledge of the XGS clinical spectrum. On the basis of the current clinical case and the literature review, we also attempt to deepen understanding of behavioural and psychiatric manifestations associated with XGS. Results: In addition to the patient we described, a considerable rate of individuals with XGS display autistic symptoms or have been diagnosed with an autistic spectrum disorder. Moreover, the analysis of the few psychopathological profiles of patients with XGS described in the literature shows a frequent presence of aggressive and self-injurious behaviours that could be either an expression of autistic functioning or an additional symptom of the ASD evolution. A careful investigation of the abovementioned symptoms is therefore required, since they could represent a “red flag” for ASD.

Background Hepatitis E virus (HEV) is widely distributed worldwide and is endemic in developing countries. Travel-related HEV infection has been reported at national levels, but global data are missing. Moreover, the global availability of HEV diagnostic testing has not been explored so far. The aim of this study is to describe the epidemiology of HEV infections in returning travellers and availability of HEV diagnostic testing in the GeoSentinel surveillance network. Methods This was a multicentre retrospective cross-sectional study. All confirmed and probable HEV travel-related infections reported in the GeoSentinel Network between 1999 and 2018 were evaluated. GeoSentinel sites were asked to complete a survey in 2018 to assess the availability and accessibility of HEV diagnostic procedures (i.e. serology and molecular tests) throughout the study period. Results Overall, 165 travel-related HEV infections were reported, mainly since 2010 (60%) and in tourists (50%). Travellers were exposed to hepatitis E in 27 countries; most travellers (62%) were exposed to HEV in South Asia. One patient was pregnant at the time of HEV infection and 14 had a concomitant gastrointestinal infection. No deaths were reported. In the 51% of patients with information available, there was no pre-travel consultation. Among 44 GeoSentinel sites that responded to the survey, 73% have access to HEV serology at a local level, while 55% could perform (at a local or central level) molecular diagnostics. Conclusion Reported access to HEV diagnostic testing is suboptimal among sites that responded to the survey; this could negatively affect diagnosing HEV. Pre-travel consultations before travel to South Asia and other low-income and high-prevalence areas with a focus on food and water precautions could be helpful in preventing hepatitis E infection. Improved HEV diagnostic capacity should be implemented to prevent and correctly diagnose travel-related HEV infection.

Introduction: Schizophrenia is a very disabling condition that may result in a significant impairment of individual, professional, and social adjustments. Antipsychotics (APs), the first-line treatment for schizophrenia, in many cases modify the course of the disease, by reducing the institutionalization risk, at the price of severe and invalidating side effects. Cariprazine is one of the latest second-generation APs (SGAs) acting as a partial agonist of type 2 and 3 dopamine receptors, which was recently approved for the treatment of adult schizophrenia.Areas covered: The authors provide a critical review and commentary on the currently available data on the effectiveness and tolerability of cariprazine in schizophrenic patients, with a particular focus on its specific target symptoms.Expert opinion: Cariprazine appears significantly effective on both acute and maintenance treatment of schizophrenia, and in improving positive, negative, and cognitive symptoms, slightly more than other SGAs. It shows a good safety and tolerability profile, with akathisia being its most common side effect. Although further independent studies are needed to clarify its precise advantages over other SGAs, cariprazine seems a promising compound not only in schizophrenia, but also in a broad range of psychiatric conditions, including perhaps bipolar and addictive disorders.

Trailing edge modification is one of the most effective ways to achieve camber variations. Usual flaps and aileron implement this concept and allow facing the different needs related to take-off, landing, and maneuver operations. The extension of this idea to meet other necessities, less dramatic in terms of geometry change yet useful a lot to increase the aircraft performance, moves toward the so-called morphing architectures, a compact version of the formers and inserted within the frame of the smart structures’ design philosophy. Mechanic (whether compliant or kinematic), actuation and sensor systems, together with all the other devices necessary for its proper working, are embedded into the body envelope. After the successful experiences, gained inside the SARISTU (SmARt Intelligent Aircraft STrUctures) project where an adaptive trailing edge was developed with the aim of compensating the weight variations in a medium-size commercial aircraft (for instance, occurring during cruise), the team herein exploits the defined architecture in the wing of a typical airfoil, used on high-altitude long-endurance aircraft such as the Global Hawk. Among the peculiarities of this kind of aerial vehicle, there is the long endurance, in turn, associated with a massive fuel storage (approximately around 50% of the total weight). A segmented, finger-like, rib layout is considered to physically implement the transition from the baseline airfoil to the target configurations. This article deals with an extensive estimation of the possible benefits related to the implementation of this device on that class of planes. Parametric aerodynamic analyses are performed to evaluate the effects of different architectural layouts (in-plane geometry extension) and different shape envelopes (namely, the rotation boundaries). Finally, the expected improvements in the global high-altitude long-endurance aircraft performance are evaluated, following the implementation of the referred morphing device.

Dent disease 2 (DD2) is a rare X-Linked disorder characterized by proximal tubule dysfunction. It is considered as mild variant of Lowe Syndrome (LS) and both conditions are secondary to OCRL1 gene mutations.1Mutations in this gene drastically reduce (

This paper describes the powered wind tunnel tests setup of the innovative configuration of the IRON regional turboprop aircraft. The objective of the tests is the evaluation of propulsive effects on aircraft stability and control characteristics. During the setup process, several aerodynamic issues have been anticipated and here illustrated. A scaled engine deck has been derived from the full-scale data provided by the IRON powerplant consortium partner. From two representative flight conditions, the characteristics of the scaled motor as RPM, torque and power have been calculated, providing a choice for the electric motors to install in the test section. The motors’ operating voltage and current determined the sizing of the power, acquisition and control system. Similarly, the desired propeller coefficients were the target of a propeller design process, which was performed with XROTOR, MATLAB®, XFOIL and validated with RANS analyses. Finally, to directly evaluate the propeller thrust and normal force, motors’ supporting structures with load cells have been conceptually designed.

The paper presents a thorough conceptual design approach for a generic aircraft with conventional, hybrid-electric, or full-electric powertrain. It follows the steps of classic aircraft design methods, including the main aspects related to the hybridization of an aircraft: powertrain architectures, energy sources, aerodynamic-propulsive interactions, stability and control effects. Such aircraft is designed considering design and regulations requirements. Three are the main steps of the conceptual design approach presented: preliminary design, sizing, and analysis. The first step provides a statistical baseline, including both geometry and weight breakdown, moving from top-level requirements. The sizing activity provides the energetic requirements and the mass breakdown, by combining the free choice of the designer with aviation regulations and requirements. The subsequent analysis aims to choose the baseline for high-fidelity optimization. The first application of the presented workflow deals with regional turboprop aircraft and it is based on the ATR-42 design mission. However, in the present work, a further investigation of the possible concepts, based on different design missions, highlights that the competitiveness of hybrid-electric aircrafts cannot be based on the same mission profiles on which nowadays aircrafts have been designed.

Ultrasound (US) is the main imaging modality for the evaluation of pediatric patients with musculoskeletal diseases; particularly, it is an appropriate and reliable tool for diagnosis, follow-up and treatment of several musculoskeletal pathologies affecting the pediatric age. High-frequency (10–15 MHz) and high-resolution probes provide very lofty quality images, allowing a detailed study of the pediatric musculoskeletal system. Among the well-known advantages of this technique—such as the absence of ionizing radiations, its low cost and wide availability—US can as well rely on some intrinsic characteristics of the pediatric musculoskeletal system that can improve its diagnostic capability. The unossified portions of the pediatric skeleton and the absence of a thickened adipose tissue allow US to be highly effective and reliable in the study of muscles, tendons and cartilage. Lower-frequency sectoral transducers can be required in the study of some joints such as the shoulder or the hip, as well as in the examination of deep soft-tissue lesions. Furthermore, both color and spectral Doppler play an important role in the examination of soft-tissue lesions and synovial phlogosis. In this pictorial essay the main pathological conditions of pediatric musculoskeletal system will be examined, such as painful hip, evolutionary hip dysplasia, osteochondrosis, trauma-related pathologies and juvenile idiopathic arthritis.

The aim of this work is the development of a methodology to predict lift characteristics for transport aircraft in the whole flight envelope, useful in the preliminary aircraft design stage. The purpose is an attempt to improve the classical methodologies for wing load distribution and lift prediction, applicable to both clean and flapped configuration. This has been obtained considering the airfoils’ aerodynamic characteristics until stall and post-stall conditions during the process, and modifying 2D characteristics in the case of high-lift devices to take into account 3D effects introduced by the devices themselves. The method is a modification of standard vortex-lattice procedures which are capable of predicting wing aerodynamic characteristics. As regards the clean configuration, the enhanced method works by integrating airfoil characteristics, whereas as far as the high-lift devices’ effect is concerned, the improved method works by substituting clean airfoil aerodynamic characteristics for the flapped aerodynamics ones, and introducing a correction to evaluate the 3D effects induced by the high-lift devices’ geometrical discontinuities. The methodology is explained separately for these two configurations. The results of the developed method have been compared with CFD and experimental data showing good agreement, making available a fast and reliable method useful in preliminary aircraft design phase.

Introduction The quest for reliable fluid biomarkers tracking synaptic disruption is supported by the evidence of a tight association between synaptic density and cognitive performance in neurodegenerative diseases (NDD), especially Alzheimer's disease (AD). Areas covered Neurogranin (Ng) is a post-synaptic protein largely expressed in neurons involved in the memory networks. Currently, Ng measured in CSF is the most promising synaptic biomarker. Several studies show Ng elevated in AD dementia with a hippocampal phenotype as well as in MCI individuals who progress to AD. Ng concentrations are also increased in Creutzfeldt Jacob Disease where widespread and massive synaptic disintegration takes place. Ng does not discriminate Parkinson's disease from atypical parkinsonisms, nor is it altered in Huntington disease. CSF synaptosomal-associated protein 25 (SNAP-25) and synaptotagmin-1 (SYT-1) are emerging candidates. Expert opinion CSF Ng revealed a role as a diagnostic and prognostic biomarker in NDD. Ng increase seems to be very specific for typical AD phenotype, probably for a prevalent hippocampal involvement. Synaptic biomarkers may serve different context-of-use in AD and other NDD including prognosis, diagnosis, and tracking synaptic damage - a critical pathophysiological mechanism in NDD - thus representing reliable tools for a precision medicine-oriented approach to NDD.

Author(s): Della Vecchia, Jason; Blazar, Eric | Abstract: Introduction: Abdominal pain is a common complaint seen in the emergency department (ED). We report a case of celiac artery aneurysm (CAA) in a male patient presenting with abdominal pain to the ED on two separate occasions, approximately 24 hours apart.Case Report: On the initial visit the patient was discharged with undifferentiated abdominal pain after computed tomography imaging and laboratory investigations. On the repeat visit he was found to have a rapidly expanding CAA with rupture. He became unstable requiring intubation, blood transfusions, and emergent transfer to a tertiary care center for surgical management where, unfortunately, he died hours after failed operative management.Conclusion: Although rare, abdominal pain caused by CAAs can rapidly progress to rupture and have a high mortality.

Hormone receptor-positive (HR+, estrogen and/or progesterone receptor-positive) and HER2-negative breast cancer (BC) subtype is a biologically heterogeneous entity that comprises 70% of BCs. This subtype includes both luminal (Lum) A- and B-like subtypes, which have differences in prognosis and sensitivity to endocrine therapies. The development of biomarkers guiding treatment decisions in these settings is required. Tumor suppressor PDCD4 (programmed cell death 4), which can be found both in the nucleus (NPDCD4) or the cytoplasm (CPDCD4), inhibits tumor growth and metastasis, and its loss is associated with poor prognosis in solid tumors. To explore the clinical relevance of PDCD4 in BC, we analyzed its expression by immunohistochemistry in a cohort of 619 patients with primary invasive BC. We found that 34.7% of patients showed NPDCD4 and 21.3% showed CPDCD4. NPDCD4 positivity, but not CPDCD4, was associated with lower clinical stage (P = 0.0003), with presence of more differentiated tumors (P = 6.4x10-6), and with estrogen and progesterone receptor (PR) expression (P = 9.2x10-9 and P = 2.8x10-9, respectively). Kaplan-Meier analysis revealed that NPDCD4 expression was associated with a longer overall survival (OS) and disease-free survival (DFS) in LumA-like (P = 0.008 and P = 0.028, respectively) and LumB-like (P = 0.004 and P = 0.012, respectively) subtypes. Interestingly, patients with LumB-like tumors displaying NPDCD4 presented estimated OS and DFS rates similar to the ones observed in patients with LumA-like tumors also expressing NPDCD4, indicating that its presence improves the clinical outcome of LumB-like patients. Multivariate Cox regression analysis identified NPDCD4 as an independent predictor of good clinical outcome in both LumA-like (HR: 0.45, 95% CI 0.22-0.96, P = 0.038) and LumB-like (HR: 0.28, 95% CI 0.10-0.80, P = 0.018) subtypes. We validated our results by in silico analysis using expression data from the METABRIC cohort. Bioinformatics analysis of BC cells from the Cancer Cell Line Encyclopedia revealed a positive correlation between PDCD4 and PR expression (P = 0.015). Since LumB-like tumors present a higher risk of resistance to endocrine therapy and both PR and PDCD4 levels in this subtype are lower than in the LumA-like one, we postulated that the presence of PR may modulate PDCD4 expression. Silencing of PR expression in HR+ cells decreased PDCD4 protein levels while reconstitution of PR in a PR-null cell line increased them, confirming PR requirement for PDCD4 modulation. In line with PDCD4 physiological function, its knockdown increased cell migration capability of HR+ BC cells, whereas its restoration led to a decrease in cell migration of HR-negative BC models. Our findings identified NPDCD4 positivity as a novel biomarker of clinical outcome in LumA- and B-like subtypes and revealed PDCD4 reconstitution as a novel therapeutic strategy in BC.

Background: In patients with suspected stroke, brain imaging is recommended in the acute phase for appropriate management and treatment. Both computed tomography (CT) and magnetic resonance imaging (MRI) are considered reasonable choices for initial brain imaging. When both techniques are available, choosing one or the other might be associated with specific factors related either to patients, stroke symptoms, and severity or management organization. Methods: The study was performed within the STROKE 69 database, a population-based cohort of all adult patients with suspected stroke admitted in one of the emergency departments (ED), primary stroke center, or stroke center of the Rhône County, from November 2015 to December 2016. Patients were included if they were admitted within 24 h following either symptom onset or last known normal. To identify factors potentially associated with the choice of initial brain imaging, a multivariate logistic regression was performed. Results: Among the 3,244 patients with suspected stroke enrolled in the STROKE69 cohort, 3,107 (95.8%) underwent brain imaging within the first 24 h after admission. Among those 74.6% underwent CT as initial imaging while 25.4% had an MRI. In multivariate analyses, several factors were associated with a lower probability of having an MRI as initial brain imaging versus CT. These were either patient characteristics: older age (>80 years old, OR 0.39 [95% CI 0.28–0.54]), preexisting disability (OR 0.55 [95% CI 0.36–0.84]), use of anticoagulants (OR 0.52 [95% CI 0.33–0.81]), stroke characteristics: stroke of unknown onset (OR 0.42 [95% CI 0.31–0.58]) or factors associated with overall management: onset-to-door time (>6 h, OR 0.38 [95% CI 0.23–0.60]), initial admission to ED (OR 0.02 [95% CI 0.02–0.04]) or intensive care unit (OR 0.01 [95% CI 0.001–0.08]), personal transport (OR 0.66 [95% CI 0.45–0.96]), and admission during working hours (OR 0.65 [95% CI 0.51–0.84]). Conclusions: Besides CT or MRI availability, a number of other parameters could influence the choice of first imaging in case of stroke suspicion. These are related to patient characteristics, type of stroke symptoms, and type of organization.

Mounting evidence highlights the involvement of inflammatory/immune systems and their relationships with neurotransmitters and different metabolic processes in mood disorders. Nevertheless, there is a general agreement that available findings are still inconclusive. Therefore, further investigations are required, aimed at deepening the role of possible alterations of biomarkers in the pathophysiology of mood disorders that might lead to more focused and tailored treatments. The present study is a comprehensive review on these topics that seem to represent intriguing avenues for the development of real innovative therapeutic strategies of mood disorders.

INTRODUCTION: The postmortem examination still represents the reference standard for detecting the pathological nature of chronic neurodegenerative diseases (NDD). This approach displays intrinsic conceptual limitations since NDD represent a dynamic spectrum of partially overlapping phenotypes, shared pathomechanistic alterations that often give rise to mixed pathologies. AREAS COVERED: We scrutinized the international clinical diagnostic criteria of NDD and the literature to provide a roadmap toward a biomarker-based classification of the NDD spectrum. A few pathophysiological biomarkers have been established for NDD. These are time-consuming, invasive, and not suitable for preclinical detection. Candidate screening biomarkers are gaining momentum. Blood neurofilament light-chain represents a robust first-line tool to detect neurodegeneration tout court and serum progranulin helps detect genetic frontotemporal dementia. Ultrasensitive assays and retinal scans may identify Aβ pathology early, in blood and the eye, respectively. Ultrasound also represents a minimally invasive option to investigate the substantia nigra. Protein misfolding amplification assays may accurately detect α-synuclein in biofluids. EXPERT OPINION: Data-driven strategies using quantitative rather than categorical variables may be more reliable for quantification of contributions from pathophysiological mechanisms and their spatial-temporal evolution. A systems biology approach is suitable to untangle the dynamics triggering loss of proteostasis, driving neurodegeneration and clinical evolution.

The hormone receptor-positive (estrogen and/or progesterone receptor (PR)-positive) and HER2-negative breast cancer (BC) subtype is a biologically heterogeneous entity that includes luminal A-like (LumA-like) and luminal B-like (LumB-like) subtypes. Decreased PR levels is a distinctive biological feature of LumB-like tumors. These tumors also show reduced sensitivity to endocrine therapies and poorer prognosis than LumA-like tumors. Identification of biomarkers to accurately predict disease relapse in these subtypes is crucial in order to select effective therapies. We identified the tumor suppressor PDCD4 (programmed cell death 4), located in the nucleus (NPDCD4), as an independent prognostic factor of good clinical outcome in LumA-like and LumB-like subtypes. NPDCD4-positive LumB-like tumors presented overall and disease-free survival rates comparable to those of NPDCD4-positive LumA-like tumors, indicating that NPDCD4 improves the outcome of LumB-like patients. In contrast, NPDCD4 loss increased the risk of disease recurrence and death in LumB-like compared with LumA-like tumors. This, along with our results showing that LumB-like tumors present lower NPDCD4 positivity than LumA-like tumors, suggests that NPDCD4 loss contributes to endocrine therapy resistance in LumB-like BCs. We also revealed that PR induces PDCD4 transcription in LumB-like BC, providing a mechanistic explanation to the low PDCD4 levels in LumB-like BCs lacking PR. Finally, PDCD4 silencing enhanced BC cell survival in a patient-derived explant model of LumB-like disease. Our discoveries highlight NPDCD4 as a novel biomarker in LumA- and LumB-like subtypes, which could be included in the panel of immunohistochemical markers used in the clinic to accurately predict the prognosis of LumB-like tumors. Fil: Madera, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Chervo, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Chiauzzi, Violeta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Pereyra Matías G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Venturutti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Izzo, Franco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Roldán Deamicis, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Guzmán, Pablo. Universidad de La Frontera. Núcleo Científico y Tecnológico en Recursos Naturales; Chile Fil: Dupont, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Roa, Juan Carlos. Universidad de La Frontera. Núcleo Científico y Tecnológico en Recursos Naturales; Chile. Universidad Católica de Chile; Chile Fil: Cenciarini, Mauro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Barchuk, Sabrina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Figurelli, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Lopez Della Vecchia, Daniel Edgardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina Fil: Levit, Claudio. Sanatorio Sagrado Corazón. Servicio de Ginecología; Argentina Fil: Lebersztein, Gabriel. Sanatorio Sagrado Corazón. Servicio de Ginecología; Argentina Fil: Anfuso, Fabiana. Sanatorio Sagrado Corazón. Servicio de Ginecología; Argentina Fil: Castiglioni, Teresa. Centro de Patología Dr. Elsner; Argentina Fil: Cortese, Eduardo Mateo. Hospital Aeronáutico Central. Servicio de Ginecología; Argentina Fil: Ares, Sandra. Instituto Oncológico Henry Moore; Argentina Fil: Gil Deza, Ernesto. Instituto Oncológico Henry Moore; Argentina Fil: Gercovich, Felipe G.. Instituto Oncológico Henry Moore; Argentina Fil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Schillaci, Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Cordo Russo, Rosalía I.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina

Submarine buried pipelines interact with shallow soil layers that are often loose and prone to fluidization/liquefaction. Such occurrence is a possible consequence of pore pressure build-up induced by hydrodynamic loading, earthquakes, and/or structural vibrations. When liquefaction is triggered in sand, the soil tends to behave as a viscous solid–fluid mixture of negligible shear strength, possibly unable to constrain pipeline movements. Therefore, pipelines may experience excessive displacement, for instance, in the form of vertical flotation or sinking. To date, there are no well-established methods to predict pipe displacement in the event of liquefaction. To fill such a gap, this work proposes a computational fluid dynamics (CFD) framework enriched with soil mechanics principles. It is shown that the interaction between pipe and liquefied sand can be successfully analyzed via one-phase Bingham fluid modeling of the soil. Postliquefaction enhancement of rheological properties, viscosity, and yield stress can also be accounted for by linking soil–pipe CFD simulations to a separate analysis of the pore pressure dissipation. The proposed approach is thoroughly validated against the results of small-scale pipe flotation and pipe dragging tests from the literature.

La malattia metastatica in oncologia testa-collo.Il distretto testa e collo rappresenta una delle più comuni sedi di insorgenza di malattie oncologiche, con una percentuale di disseminazioni metastatiche elevata tanto a livello loco-regionale quanto a distanza. La prognosi di questi tumori è strettamente legata ad alcuni fattori principali: a) lo stadio della malattia; b) le recidive loco-regionali; c) le metastasi a distanza. Nei tumori della testa e del collo le metastasi a distanza sono presenti in circa il 10% dei casi al momento della prima diagnosi e si rendono evidenti nel corso della malattia in un ulteriore 20%-30% dei casi. Quando una metastasi a distanza a partenza da un tumore della testa e del collo si rende evidente, la prognosi viene usualmente considerata infausta, con una sopravvivenza media stimabile intorno ai 10 mesi. Scopo del presente lavoro è quello di fornire un up-todate aggiornato ed esaustivo in tema di metastasi a distanza in oncologia cervico-cefalica alla luce delle più recenti conoscenze. Concetti di recente acquisizione quali l’assetto molecolare dei tumori, le possibili interazioni tra cellule tumorali e tessuti, le peculiarità della malattia oligometastatica, il ruolo dell’immunoterapia… stanno profondamente cambiando l’approccio terapeutico in questi pazienti, con interessanti ricadute in tema di controllo di malattia. I primi capitoli sono dedicati alla storia naturale ed all’epidemiologia delle metastasi a distanza nei tumori della testa e del collo ed al loro inquadramento diagnostico anatomo-patologico e radiologico. Nei capitoli successivi vengono focalizzate le più rilevanti peculiarità cliniche con particolare attenzione agli argomenti di recente attualità quali le metastasi a distanza da tumori EBV ed HPV positivi ed il concetto di malattia oligometastatica. Ampio spazio viene destinato alle varie opzioni terapeutiche con particolare attenzione al sempre più rilevante ruolo dell’immunoterapia ed allo sviluppo di nuove tecnologie terapeutiche. In conclusione, vengono focalizzate le problematiche etico-cliniche legate al concetto di fragilità del paziente oncologico e le crescenti difficoltà di una sostenibile governance socio-economica.The head and neck district represents one of the most frequent sites of cancer, and the percentage of metastases is very high in both loco-regional and distant areas. Prognosis refers to several factors: a) stage of disease; b) loco-regional relapses; c) distant metastasis. At diagnosis, distant metastases of head and neck cancers are present in about 10% of cases with an additional 20-30% developing metastases during the course of their disease. Diagnosis of distant metastases is associated with unfavorable prognosis, with a median survival of about 10 months. The aim of the present review is to provide an update on distant metastasis in head and neck oncology. Recent achievements in molecular profiling, interaction between neoplastic tissue and the tumor microenvironment, oligometastatic disease concepts, and the role of immunotherapy have all deeply changed the therapeutic approach and disease control. Firstly, we approach topics such as natural history, epidemiology of distant metastases and relevant pathological and radiological aspects. Focus is then placed on the most relevant clinical aspects; particular attention is reserved to tumours with distant metastasis and positive for EBV and HPV, and the oligometastatic concept. A substantial part of the review is dedicated to different therapeutic approaches. We highlight the role of immunotherapy and the potential effects of innovative technologies. Lastly, we present ethical and clinical perspectives related to frailty in oncological patients and emerging difficulties in sustainable socio-economical governance.

The economic cuts suffered by public health have in many cases led to the reduction of beds. In order to optimize the available resources, the length of stay (LOS) can be used as an efficiency parameter. The objective of this study is to predict the value of LOS using the clinical information that is generally supplied by a patient who is hospitalized following a fracture of the neck of the femur and to make a comparison with results obtained after the implementation of the new diagnostic-therapeutic-assistance pathway (DTAP). The analysis was conducted on data extrapolated from the information system of the University Hospital “San Giovanni di Dio and Ruggi d’Aragona” of Salerno (Italy). The results show promising outcome in the use of the proposed prediction models as a tool for determining an estimate of the LOS and support the decision making process and the management of hospital resources in advance. In addition, the comparison of between the two models can be used as an indicator to assess the efficiency of the implemented DTAP.

Mandibular overdentures retained by 2 conventional implants have been considered the standard of care for complete edentulism, according to the McGill and York consensuses. However, many patients refuse this treatment modality due to the associated costs and postsurgical discomfort. Mini-implants have the chance to overcome these limitations due to their potentially lower costs and a relatively uncomplicated surgical technique. This study compared treatment costs and incremental cost-effectiveness following the insertion of mini-implants (2 or 4) or 2 standard-size implants for the retention of mandibular overdentures, by means of a randomized clinical trial. In total, 120 edentulous participants (mean age 59.5 ± 8.5 y) were randomly allocated into 3 groups according to treatment received: 4 mini-implants (group 1), 2 mini-implants (group 2), or 2 standard implants (group 3). Treatment costs and outcomes (Oral Health Impact Profile for Edentulous [OHIP-EDENT] and satisfaction with the dentures) were evaluated after 6 mo. Incremental cost-effectiveness ratios (ICERs) were calculated for each intervention in terms of cost per 1-point change in patient outcomes. A 1-way sensitivity analysis was performed considering a 95% confidence interval variation in cost and outcome parameters, represented in tornado diagrams. Overall treatment cost was the lowest for group 2 (average cost: US$318.08), followed by group 1 (US$510.75) and group 3 (US$566.13). Groups did not differ in terms of the length of unscheduled appointments and time spent by participants. In summary, our findings indicate that mandibular overdentures retained by 2 or 4 mini-implants are less costly compared to 2-implant overdentures. Despite the lower costs of overdentures retained by 2 mini-implants, those retained by 4 mini-implants showed further improvement in patient-reported outcomes and reduced costs compared to standard implants ( ClinicalTrials.gov NCT01411683). Knowledge Transfer Statement: This report shows that mini-implant retained overdentures are less costly than overdenture treatment on 2 standard-sized implants. Treatment with 2 mini-implants is an effective procedure to substantially save resources, whereas treatment with 4 mini-implants provides better results from a patient perspective combined with slightly reduced costs compared to the treatment with 2 standard implants. Therefore, mini-implant overdentures may be effective and more accessible than overdentures on 2 standard-size implants for those with limited incomes.

A reliable estimation of the aerodynamics of the fuselage of an airplane is crucial in order to carry out a well-designed aircraft. About 30% of an aircraft zero-lift drag source is due to the fuselage. Its aerodynamic instability is impacting wing and horizontal tail design, as well as aircraft directional stability characteristics. This paper proposes methods, developed through CFD analyses, to estimate fuselage aerodynamic drag, pitching, and yawing moment coefficients. These methods are focused on the regional turboprop aircraft category. Given the fuselage geometry, several charts allow to evaluate its aerodynamic characteristics. Numerical test cases are shown on several fuselage geometries and a comparison with typical semi-empirical methods is presented.