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This retrospective study investigates the histopathological outcomes, upgrade rates, and disease-free survival (DFS) of high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. The study addresses the challenge posed by these lesions due to their association with synchronous or adjacent Breast Cancer (BC) and increased future BC risk. The research, comprising 320 patients who underwent stereotactic VABB, focuses on 246 individuals with a diagnosis of ADH (120) or LIN (126) observed at follow-up. Pathological assessments, categorized by the UK B-coding system, were conducted, and biopsy samples were compared with corresponding excision specimens to determine upgrade rates for in situ or invasive carcinoma. Surgical excision was consistently performed for diagnosed ADH or LIN. Finally, patient follow-ups were assessed and compared between LIN and ADH groups to identify recurrence signs, defined as histologically confirmed breast lesions on either the same or opposite side. The results reveal that 176 (71.5%) patients showed no upgrade post-surgery, with ADH exhibiting a higher upgrade rate to in situ pathology than LIN1 (Atypical Lobular Hyperplasia, ALH)/LIN2 (Low-Grade Lobular in situ Carcinoma, LCIS) (38% vs. 20%, respectively, p-value = 0.002). Considering only patients without upgrade, DFS at 10 years was 77%, 64%, and 72% for ADH, LIN1, and LIN2 patients, respectively (p-value = 0.92). The study underscores the importance of a multidisciplinary approach, recognizing the evolving role of VABB. It emphasizes the need for careful follow-up, particularly for lobular lesions, offering valuable insights for clinicians navigating the complex landscape of high-risk breast lesions. The findings advocate for heightened awareness and vigilance in managing these lesions, contributing to the ongoing refinement of clinical strategies in BC care.

Purpose: To compare the diagnostic performance (detection, assessment of correct disease extent and multifocality/centricity) of Contrast-Enhanced Mammography (CEM) Versus Breast Magnetic Resonance (MRI) in the study of lobular neoplasms. Methods: We retrospectively selected all the patients who underwent surgery for a lobular breast neoplasm, either an in situ or an invasive tumor, and had undergone both breast CEM and MRI examinations during the pre-surgical planning. Wilcoxon Signed Rank test was performed to assess the differences between size measurements using the different methods and the post-surgical pathological measurements, considered the gold standard. The agreement in identifying multifocality/multicentricity among the different methods and the pathology was assessed using the Kappa statistics. Results: We selected 19 patients, of which one presented a bilateral neoplasm. Then, the images of these 19 patients were analyzed, for a total of 52 malignant breast lesions. We found no significant differences between the post-surgical pathological size of the lesions and the calculated size with CEM and MRI (p-value of the difference respectively 0.71 and 0.47). In all 20 cases, neoplasm detection was possible both with CEM and MRI. CEM and MRI showed an excellent ability to identify multifocal and multicentric cases (K statistic equal to 0.93 for both the procedures), while K statistic was 0.11 and 0.59 for FFDM and US, respectively. Conclusion: The findings of this study suggest that CEM is a reliable imaging technique in the preoperative setting of patients with lobular neoplasm, with comparable results to breast MRI.

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

OBJECTIVE: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. METHODS: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. RESULTS: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. CONCLUSION: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

While mitigation and adaptation will help to protect us from climate change, there are harms that are beyond our ability to adapt. Some of these harms, which may have been instigated from historical emissions, plausibly give rise to duties of compensation. This chapter discusses several principles that have been discussed about how to divide climate duties – the polluter pays principle, the beneficiary pays principle, the ability to pay principle, and a new one, the polluter pays, then receives principle. The chapter introduces several challenges to these principles from the literature, before discussing which policies and institutions might be relevant to compensation, whether internationally (e.g., the Green Climate Fund) or intergenerationally (e.g., Broome and Foley’s World Climate Bank). It also describes some recent successful climate cases that require both the Dutch government and a private firm to act in accordance with climate targets to avoid potential rights violations. Finally, it discusses one of the most important international concepts with respect to compensation: the Loss & Damage pillar of climate policy.

While mitigation and adaptation will help to protect us from climate change, there are harms that are beyond our ability to adapt. Some of these harms, which may have been instigated from historical emissions, plausibly give rise to duties of compensation. This chapter discusses several principles that have been discussed about how to divide climate duties – the polluter pays principle, the beneficiary pays principle, the ability to pay principle, and a new one, the polluter pays, then receives principle. The chapter introduces several challenges to these principles from the literature, before discussing which policies and institutions might be relevant to compensation, whether internationally (e.g., the Green Climate Fund) or intergenerationally (e.g., Broome and Foley’s World Climate Bank). It also describes some recent successful climate cases that require both the Dutch government and a private firm to act in accordance with climate targets to avoid potential rights violations. Finally, it discusses one of the most important international concepts with respect to compensation: the Loss & Damage pillar of climate policy.

Cyber Security

This chapter addresses an under investigated issue of climate ethics: the duty of adaptation, i.e., a standard of moral behavior required of duty bearers due to their violation of the no harm principle which involves a practical commitment to rectify consequent harmful impacts. This chapter, after framing the duty of adaptation within a harm-centered perspective, first identifies its constitutive moral features: the duty bearers, i.e., the agent who should bear the burdens required of the duty of adaptation; the forms in which the duty of adaptation abides by its moral mandate; the scope, i.e., the morally-pertinent harm that the duty of adaptation should financially rectify; and the duty-recipients, i.e., the agents entitled to rectification and the modality of the allocation of the rectificatory actions among them. It goes on to examine the empirical features of the duty of adaptation dictated by its moral articulation: the structure through which the duty of adaptation should be attained; and the currency and magnitude of its required rectification actions. Finally, the chapter provides an overview of why and how other agents have a second-order duty to ensure the bearers of the duty of adaptation meet their commitments.

Background Magnetoencephalography (MEG) is a widely used non-invasive tool to estimate brain activity with high temporal resolution. However, due to the ill-posed nature of the MEG source imaging (MSI) problem, the ability of MSI to identify accurately underlying brain sources along the cortical surface is still uncertain and requires validation. Method We validated the ability of MSI to estimate the background resting state activity of 45 healthy participants by comparing it to the intracranial EEG (iEEG) atlas (https://mni-open-ieegatlas.research.mcgill.ca/). First, we applied wavelet-based Maximum Entropy on the Mean (wMEM) as an MSI technique. Next, we converted MEG source maps into intracranial space by applying a forward model to the MEG-reconstructed source maps, and estimated virtual iEEG (ViEEG) potentials on each iEEG channel location; we finally quantitatively compared those with actual iEEG signals from the atlas for 38 regions of interest in the canonical frequency bands. Results The MEG spectra were more accurately estimated in the lateral regions compared to the medial regions. The regions with higher amplitude in the ViEEG than in the iEEG were more accurately recovered. In the deep regions, MEG-estimated amplitudes were largely underestimated and the spectra were poorly recovered. Overall, our wMEM results were similar to those obtained with minimum norm or beamformer source localization. Moreover, the MEG largely overestimated oscillatory peaks in the alpha band, especially in the anterior and deep regions. This is possibly due to higher phase synchronization of alpha oscillations over extended regions, exceeding the spatial sensitivity of iEEG but detected by MEG. Importantly, we found that MEG-estimated spectra were more comparable to spectra from the iEEG atlas after the aperiodic components were removed. Conclusion This study identifies brain regions and frequencies for which MEG source analysis is likely to be reliable, a promising step toward

Introduction: The impact of COVID-19 pandemic represents a serious challenge for ‘frail’ patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic. Patients and method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines. Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evalu

Objectives: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation). Methods: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc. Results: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features. Conclusions: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.

Objective. There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. Methods. A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. Results. The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. Conclusion. Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

We report a hitherto undocumented causal mechanism of how patent protection affects exports. The empirical analysis leverages unique data on the worldwide patenting and exporting activities at the product level for the universe of French firms. Exploiting heterogeneity of patent coverage within firm-product-country destinations, we find evidence of a patent premium. Goods protected by patents in a destination country are associated with higher export quantities, ceteris paribus. The effect ranges between four and eleven percent. The causality of the finding is confirmed using rejected patent applications, which are exogenous to the firm. Exports collapse when firms lose patent protection.

This paper examines the effect of persistence in product and process innovations on the employment dynamics of a representative sample of Spanish manufacturing firms observed over more than 20 years. We build a conceptual framework that links innovation, its persistence, and different trajectories of employment growth. This framework suggests that firms might show different responses in terms of their employment growth and its persistence depending on the degree of persistence in their product and process innovations. We construct a synthetic indicator of innovation persistence at the firm-level and link this indicator to different employment trajectories. We find that persistence in product innovation affects both employment growth and the sustainability of job creation over time significantly, whilst persistence in process innovation does not play any relevant role. Also, the positive effect of persistence in product innovation is particularly strong for SMEs. The evidence we provide supports the notion that product innovation is more effective in spurring sustained employment growth when carried out systematically.

Inflammatory bowel disease (IBD) pathogenesis has been linked to the aberrant activation of the Gut-associated lymphoid tissues against components of the intestinal microbiota. Although the contribution of CD4+ T helper cells to inflammatory processes is being increasingly acknowledged, the functional engagement of human invariant natural killer T (iNKT) cells is still poorly defined. Here, we evaluated the functional characteristics of intestinal iNKT cells during IBD pathogenesis and to exploit the role of mucosa-associated microbiota recognition in triggering iNKT cells’ pro-inflammatory responses in vivo. Lamina propria iNKT cells, isolated from surgical specimens of active ulcerative colitis and Crohn’s disease patients and non-IBD donors, were phenotypically and functionally analyzed ex vivo, and stable cell lines and clones were generated for in vitro functional assays. iNKT cells expressing a pro-inflammatory cytokine profile were enriched in the lamina propria of IBD patients, and their exposure to the mucosa-associated microbiota drives pro-inflammatory activation, inducing direct pathogenic activities against the epithelial barrier integrity. These observations suggest that iNKT cell pro-inflammatory functions may contribute to the fuelling of intestinal inflammation in IBD patients.

While the extant innovation literature has provided extensive evidence of the so-called “demand-pull” effect, the possible diverse impact of demand evolution on product vs process innovation activities has not been yet investigated. This paper develops a formal model predicting a larger inducing impact of past sales in fostering product rather than process innovation. This prediction is then tested through a dynamic microeconometric model, controlling for R&D persistence, sample selection, observed and unobservable individual firm effects and time and sectoral peculiarities. Results are consistent with the model and suggest that an expansionary economic policy may benefit the diffusion of new products or even the emergence of entire new sectors.

The present document provides the take of innovation economists on the COVID-19 pandemic. It targets the general public and focuses on questions related to the Science, Technology, and Innovation ecosystem. It provides a reading of current real-world developments using economic reasoning and relying on existing economic research.

This paper examines how firm age can affect a firm’s perception of the obstacles (deterring vs. revealed) that hamper and delay innovation. Using a comprehensive panel of Spanish firms for the period 2004–2011, the empirical analysis conducted shows that distinct types of obstacle are perceived differently by firms of different ages. First, a clear-cut negative relationship is identified between firm age and a firm’s assessment of both the internal and external shortages of financial resources. Second, young firms seem to be less sensitive to the lack of qualified personnel when initiating an innovative project than when they are already engaged in such activities. By contrast, the attempts of mature firms to engage in innovation activity are significantly affected by the lack of qualified personnel. Finally, mature incumbents appear to attach greater importance to obstacles related to market structure and demand than is the case of firms with less experience.

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Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern. Objective: We explored the clinical management of inpatients with COVID-19 in Italy. Methods: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed. Results: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%. Conclusions: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.

Human aging is currently defined as a physiological decline of biological functions in the body with a continual adaptation to internal and external damaging. The endocrine system plays a major role in orchestrating cellular interactions, metabolism, growth, and aging. Several in vivo studies from worms to mice showed that downregulated activity of the GH/IGF-1/insulin pathway could be beneficial for the extension of human life span, whereas results are contradictory in humans. In the present review, we discuss the potential role of the IGF-1 system in modulation of longevity, hypothesizing that the endocrine and metabolic adaptation observed in centenarians and in mammals during caloric restriction may be a physiological strategy for extending lifespan through a slower cell growing/metabolism, a better physiologic reserve capacity, a shift of cellular metabolism from cell proliferation to repair activities and a decrease in accumulation of senescent cells. Therefore, understanding of the link between IGF-1/insulin system and longevity may have future clinical applications in promoting healthy aging and in Rehabilitation Medicine.

Human aging is currently defined as a physiological decline of biological functions in the body with a continual adaptation to internal and external damaging. The endocrine system plays a major role in orchestrating cellular interactions, metabolism, growth, and aging. Several in vivo studies from worms to mice showed that downregulated activity of the GH/IGF-1/insulin pathway could be beneficial for the extension of human life span, whereas results are contradictory in humans. In the present review, we discuss the potential role of the IGF-1 system in modulation of longevity, hypothesizing that the endocrine and metabolic adaptation observed in centenarians and in mammals during caloric restriction may be a physiological strategy for extending lifespan through a slower cell growing/metabolism, a better physiologic reserve capacity, a shift of cellular metabolism from cell proliferation to repair activities and a decrease in accumulation of senescent cells. Therefore, understanding of the link between IGF-1/insulin system and longevity may have future clinical applications in promoting healthy aging and in Rehabilitation Medicine.

Interstitial lung diseases (ILDs) may be complicated by chronic respiratory failure (CRF), especially in the advanced stages. Aim of this narrative review is to evaluate the current evidence in management of CRF in ILDs.Many physiological mechanisms underlie CRF in ILDs, including lung restriction, ventilation/perfusion mismatch, impaired diffusion capacity and pulmonary vascular damage. Intermittent exertional hypoxemia is often the initial sign of CRF, evolving, as ILD progresses, into continuous hypoxemia. In the majority of the cases, the development of CRF is secondary to the worsening of the underlying disease; however, associated comorbidities may also play a role. When managing CRF in ILDs, the need for pulmonary rehabilitation, the referral to lung transplant centers and palliative care should be assessed and, if necessary, promptly offered. Long-term oxygen therapy is commonly prescribed in case of resting or exertional hypoxemia with the purpose to decrease dyspnea and improve exercise tolerance. High-Flow Nasal Cannula oxygen therapy may be used as an alternative to conventional oxygen therapy for ILD patients with severe hypoxemia requiring both high flows and high oxygen concentrations. Non-Invasive Ventilation may be used in the chronic setting for palliation of end-stage ILD patients, although the evidence to support this application is very limited.

Interstitial lung diseases (ILDs) may be complicated by chronic respiratory failure (CRF), especially in the advanced stages. Aim of this narrative review is to evaluate the current evidence in management of CRF in ILDs.Many physiological mechanisms underlie CRF in ILDs, including lung restriction, ventilation/perfusion mismatch, impaired diffusion capacity and pulmonary vascular damage. Intermittent exertional hypoxemia is often the initial sign of CRF, evolving, as ILD progresses, into continuous hypoxemia. In the majority of the cases, the development of CRF is secondary to the worsening of the underlying disease; however, associated comorbidities may also play a role. When managing CRF in ILDs, the need for pulmonary rehabilitation, the referral to lung transplant centers and palliative care should be assessed and, if necessary, promptly offered. Long-term oxygen therapy is commonly prescribed in case of resting or exertional hypoxemia with the purpose to decrease dyspnea and improve exercise tolerance. High-Flow Nasal Cannula oxygen therapy may be used as an alternative to conventional oxygen therapy for ILD patients with severe hypoxemia requiring both high flows and high oxygen concentrations. Non-Invasive Ventilation may be used in the chronic setting for palliation of end-stage ILD patients, although the evidence to support this application is very limited.

© 2019 The Author(s). Background: Despite the limited number of articles dedicated to its use, augmented reality (AR) is an emerging technology that has shown to have increasing applications in multiple different medical sectors. These include, but are not limited to, the Maxillo-facial and Dentistry disciplines of medicine. In these medical specialties, the focus of AR technology is to achieve a more visible surgical field during an operation. Currently, this goal is brought about by an accurate display of either static or dynamic diagnostic images via the use of a visor or specific glasses. The objective of this study is to evaluate the feasibility of using a virtual display for dynamic navigation via AR. The secondary outcome is to evaluate if the use of this technology could affect the accuracy of dynamic navigation. Case presentation: Two patients, both needing implant rehabilitation in the upper premolar area, were treated with flapless surgery. Prior to the procedure itself, the position of the implant was virtually planned and placed for each of the patients using their previous scans. This placement preparation contributed to a dynamic navigation system that was displayed on AR glasses. This, in turn, allowed for the use of a computer-aided/image-guided procedure to occur. Dedicated software for surface superimposition was then used to match the planned position of the implant and the real one obtained from the postoperative scan. Accuracies, using this procedure were evaluated by way of measuring the deviation between real and planned positions of the implants. For both surgeries it was possible to proceed using the AR technology as planned. The deviations for the first implant were 0.53 mm at the entry point and 0.50 mm at the apical point and for the second implant were 0.46 mm at the entry point and 0.48 mm at the apical point. The angular deviations were respectively 3.05° and 2.19°. Conclusions: From the results of this pilot study, it seems that AR c

AIM:The objective of this prospective pilot clinical study was to evaluate the accuracy of a new dynamic navigation system and postoperative clinical outcomes. MATERIALS AND METHODS:Ten patients were recruited and 18 implants were placed. The surgery was performed with the navigation system and according to the virtual planning. Ten implants were placed using a flapless technique and eight implant sites were prepared with a combined piezo-drill method. The deviation between the real implant position obtained from the postoperative cone beam computed tomography (CBCT) scan and the planned implant position was measured. RESULT:The average deviation was 1.19 ± 0.54 mm. The mean deviation measured at the insertion point was 1.04 ± 0.47 mm and at the apical point it was 1.35 ± 0.56 mm. The depth error was 0.43 ± 0.34 mm. The axis deviation was 6.46 ± 3.95 degrees. No significant differences were found between the flapless and the open-flap approaches and between the conventional and piezoelectric techniques. No complications occurred. CONCLUSION:The accuracy values reported in this study are comparable, although not superior, to the literature data regarding dynamic and static computer-guided surgery. Dynamic navigation could increase the quality and safety of interventions and may reduce morbidity when compared with freehand insertion techniques. Deviation at the entry point (mm) Deviation at the apex (mm) Depth deviation (mm) Angular deviation (degrees) Mean 1.04 1.35 0.43 6.46 SD 0.47 0.56 0.34 3.95 Maximum 2.21 2.28 1.41 6.46 Minimum 0.45 0.59 0.03 3.95 Deviation at the entry point (mm)Deviation at the apex (mm)Depth deviation (mm)Angular deviation (degrees)OF0.96 ± 0.331.45 ± 0.600.35 ± 0.227.93 ± 5.15FL1.10 ± 0.581.27 ± 0.570.49 ± 0.425.28 ± 2.60Data are shown as mean ± SDOF = open-flap surgery; FL = flapless surgery Deviation at the entry point (mm)Deviation at the apex (mm)Depth deviation (mm)Angular deviation (degrees)P1.01 ± 0.251.37 ± 0.480.44 ± 0.267.63 ± 4.3

© 2019 The Author(s). Background: Despite the limited number of articles dedicated to its use, augmented reality (AR) is an emerging technology that has shown to have increasing applications in multiple different medical sectors. These include, but are not limited to, the Maxillo-facial and Dentistry disciplines of medicine. In these medical specialties, the focus of AR technology is to achieve a more visible surgical field during an operation. Currently, this goal is brought about by an accurate display of either static or dynamic diagnostic images via the use of a visor or specific glasses. The objective of this study is to evaluate the feasibility of using a virtual display for dynamic navigation via AR. The secondary outcome is to evaluate if the use of this technology could affect the accuracy of dynamic navigation. Case presentation: Two patients, both needing implant rehabilitation in the upper premolar area, were treated with flapless surgery. Prior to the procedure itself, the position of the implant was virtually planned and placed for each of the patients using their previous scans. This placement preparation contributed to a dynamic navigation system that was displayed on AR glasses. This, in turn, allowed for the use of a computer-aided/image-guided procedure to occur. Dedicated software for surface superimposition was then used to match the planned position of the implant and the real one obtained from the postoperative scan. Accuracies, using this procedure were evaluated by way of measuring the deviation between real and planned positions of the implants. For both surgeries it was possible to proceed using the AR technology as planned. The deviations for the first implant were 0.53 mm at the entry point and 0.50 mm at the apical point and for the second implant were 0.46 mm at the entry point and 0.48 mm at the apical point. The angular deviations were respectively 3.05° and 2.19°. Conclusions: From the results of this pilot study, it seems that AR c

AIM:The objective of this prospective pilot clinical study was to evaluate the accuracy of a new dynamic navigation system and postoperative clinical outcomes. MATERIALS AND METHODS:Ten patients were recruited and 18 implants were placed. The surgery was performed with the navigation system and according to the virtual planning. Ten implants were placed using a flapless technique and eight implant sites were prepared with a combined piezo-drill method. The deviation between the real implant position obtained from the postoperative cone beam computed tomography (CBCT) scan and the planned implant position was measured. RESULT:The average deviation was 1.19 ± 0.54 mm. The mean deviation measured at the insertion point was 1.04 ± 0.47 mm and at the apical point it was 1.35 ± 0.56 mm. The depth error was 0.43 ± 0.34 mm. The axis deviation was 6.46 ± 3.95 degrees. No significant differences were found between the flapless and the open-flap approaches and between the conventional and piezoelectric techniques. No complications occurred. CONCLUSION:The accuracy values reported in this study are comparable, although not superior, to the literature data regarding dynamic and static computer-guided surgery. Dynamic navigation could increase the quality and safety of interventions and may reduce morbidity when compared with freehand insertion techniques. Deviation at the entry point (mm) Deviation at the apex (mm) Depth deviation (mm) Angular deviation (degrees) Mean 1.04 1.35 0.43 6.46 SD 0.47 0.56 0.34 3.95 Maximum 2.21 2.28 1.41 6.46 Minimum 0.45 0.59 0.03 3.95 Deviation at the entry point (mm)Deviation at the apex (mm)Depth deviation (mm)Angular deviation (degrees)OF0.96 ± 0.331.45 ± 0.600.35 ± 0.227.93 ± 5.15FL1.10 ± 0.581.27 ± 0.570.49 ± 0.425.28 ± 2.60Data are shown as mean ± SDOF = open-flap surgery; FL = flapless surgery Deviation at the entry point (mm)Deviation at the apex (mm)Depth deviation (mm)Angular deviation (degrees)P1.01 ± 0.251.37 ± 0.480.44 ± 0.267.63 ± 4.3

In this work, we test the employment impact of distinct types of innovative investments using a representative sample of Spanish manufacturing firms over the period 2002–2013. Our GMM-SYS estimates generate various results, which are partially in contrast with the extant literature. Indeed, estimations carried out on the entire sample do not provide statistically significant evidence of the expected labor-friendly nature of innovation. More in detail, neither R&D nor investment in innovative machineries and equipment (the so-called embodied technological change, ETC) turn out to have any significant employment effect. However, the job-creation impact of R&D expenditures becomes highly significant when the focus is limited to the high-tech firms. On the other hand - and interestingly - ETC exhibits its labor-saving nature when SMEs are singled out.

The paper analyzes the effect of financial, knowledge, demand, market structure and regulation barriers to innovation on firms’ economic performance. It contributes to the literature on barriers to innovation by accounting for the heterogeneous effects that each barrier has on firms across the productivity distribution. We do so by employing both quantile regression techniques and matching estimators on this UK CIS panel 2002–2010 merged with the Business Structure Database. While we find evidence that both the cost and also the availability of finance negatively affect productivity across the whole distribution, the lack of qualified personnel mostly hinders high productivity firms. Moreover, quantile regression reveals some interesting variation in effect sizes across the (conditional) productivity distribution.

This article discusses macroeconomic policies in a low interest rate environment, the central theme of the 2017 edition of the Melbourne Institute Macroeconomic Policy Meeting. After reviewing possible causes of the decline in interest rates observed since the 1990s, we present and discuss some of the challenges that monetary and fiscal policy face in a ‘new normal’ environment characterised by a real natural interest rate close to zero. Proposals by leading researchers on how to operate in such an environment are presented and discussed. We conclude by outlining some research questions that are highly relevant from a policy perspective.

© 2018, by Quintessence Publishing Co. Inc. Zygomatic implant site preparation could be considered a challenging procedure because of the use of a very long twist drill that could sometimes be difficult to control due to the need for drilling the malar bone on an oblique surface. Ultrasound was recently suggested to achieve better control, but the specific long tips required are not readily available, and the elongated tip also tends to reduce the efficacy. This technical note describes a proposal of a novel computer-aided technique to simplify the procedure of zygomatic implant site preparation. This method uses a standard-length ultrasonic tip to prepare the crestal bone and the zygomatic bone in two individual steps. The desired implant trajectory can be achieved during preparation using a real-time tracking navigation system. The combined use of the navigation system and the ultrasonic tips could aid the surgeon, during the first steps, in achieving optimal control of the instruments employed for the implant site preparation and keeping the planned zygomatic implant position. If the efficacy of the procedure is confirmed through clinical trials, this technique could also contribute to reducing the invasiveness of the procedure, promoting a smaller flap, and reducing the soft tissue damage.

This article explores the relations between firm growth and a set of four innovation indicators (inhouse R & D, external sourcing, product innovation, and process innovation) that capture the different sources, modes, and outcomes of the innovative strategies adopted by firms. While existing studies tend to focus on the individual effects on growth of each innovation activity, we stress that firms adopt heterogeneous innovation strategies, choosing to perform different combinations of the basic innovation activities. We directly address the empirical question as to whether jointly performing two basic innovation activities boosts sales growth above and beyond the separate contribution of each innovation activity when performed individually. Exploiting a panel of Spanish manufacturing firms observed between 2004 and 2011, we document instances of super-modularity of the growth function, and reveal the presence of complementarities between internal R & D and product innovation, and between product and process innovations. As such, the combination of these three basic innovation activities appears to be the most effective strategy for sustaining growth and market shares, while external sourcing does not appear to make any systematic contribution.

In amyotrophic lateral sclerosis (ALS), respiratory muscle weakness leads to respiratory failure and death. Non-invasive positive pressure ventilation (NIPPV) appears to reduce lung function decline, thus improving survival and quality-of-life of patients affected by the disease. Unfortunately, clinical features and timing to start NIPPV are not well defined. Starting from recent findings, we examine established and novel tests of respiratory muscle function that could help clinicians decide whether and when to start NIPPV in ALS. Non-invasive tests estimate the function of inspiratory, expiratory, and bulbar muscles, whereas clinical examination allows to assess the overall neurologic and respiratory symptoms and general conditions. Most of the studies recommend that together with a thorough clinical evaluation of the patient according to current guidelines, vital capacity, maximal static and sniff nasal inspiratory pressures, maximal static expiratory pressures and peak cough expiratory flow, and nocturnal pulse oximetry be measured. A sound understanding of physiology can guide the physician also through the current armamentarium for additional supportive treatments for ALS, such as symptomatic drugs and new treatments to manage sialorrhea and thickened saliva, cough assistance, air stacking, and physiotherapy. In conclusion, careful clinical and functional evaluation of respiratory function and patient's preference are key determinants to decide "when" and "to whom" respiratory treatments can be provided.

Background: Interstitial lung diseases (ILDs) are a heterogeneous group of diseases characterized by widespread fibrotic and inflammatory abnormalities of the lung. Respiratory failure is a common complication in advanced stages or following acute worsening of the underlying disease. Aim of this review is to evaluate the current evidence in determining the best management of acute respiratory failure (ARF) in ILDs. Methods: A literature search was performed in the Medline/PubMed and EMBASE databases to identify studies that investigated the management of ARF in ILDs (the last search was conducted on November 2017). Results: In managing ARF, it is important to establish an adequate diagnostic and therapeutic management depending on whether the patient has an underlying known chronic ILD or ARF is presenting in an unknown or de novo ILD. In the first case both primary causes, such as acute exacerbations of the disease, and secondary causes, including concomitant pulmonary infections, fluid overload and pulmonary embolism need to be investigated. In the second case, a diagnostic work-up that includes investigations in regards to ILD etiology, such as autoimmune screening and bronchoalveolar lavage, should be performed, and possible concomitant causes of ARF have to be ruled out. Oxygen supplementation and ventilatory support need to be titrated according to the severity of ARF and patients' therapeutic options. High-Flow Nasal oxygen might potentially be an alternative to conventional oxygen therapy in patients requiring both high flows and high oxygen concentrations to correct hypoxemia and control dyspnea, however the evidence is still scarce. Neither Non-Invasive Ventilation (NIV) nor Invasive Mechanical Ventilation (IMV) seem to change the poor outcomes associated to advanced stages of ILDs. However, in selected patients, such as those with less severe ARF, a NIV trial might help in the early recognition of NIV-responder patients, who may present a better short-ter

© 2018, by Quintessence Publishing Co. Inc. Zygomatic implant site preparation could be considered a challenging procedure because of the use of a very long twist drill that could sometimes be difficult to control due to the need for drilling the malar bone on an oblique surface. Ultrasound was recently suggested to achieve better control, but the specific long tips required are not readily available, and the elongated tip also tends to reduce the efficacy. This technical note describes a proposal of a novel computer-aided technique to simplify the procedure of zygomatic implant site preparation. This method uses a standard-length ultrasonic tip to prepare the crestal bone and the zygomatic bone in two individual steps. The desired implant trajectory can be achieved during preparation using a real-time tracking navigation system. The combined use of the navigation system and the ultrasonic tips could aid the surgeon, during the first steps, in achieving optimal control of the instruments employed for the implant site preparation and keeping the planned zygomatic implant position. If the efficacy of the procedure is confirmed through clinical trials, this technique could also contribute to reducing the invasiveness of the procedure, promoting a smaller flap, and reducing the soft tissue damage.

We consider dynamic group services, where outputs based on small samples of privacy-sensitive user inputs are repetitively computed. The leakage of user input data is analysed, caused by producing multiple outputs, resulting from inputs of frequently changing sets of users. A cryptographic technique, known as random user selection, is investigated. We show the effect of random user selection, given different types of output functions, thereby disproving earlier work. A new security measure is introduced, which provably improves the privacy-preserving effect of random user selection, irrespective of the output function. We show how this new security measure can be implemented in existing cryptographic protocols. To investigate the effectiveness of our security measure, we conducted a couple of statistical simulations with large user populations, which show that it forms a key ingredient, at least for the output function addition. Without it, an adversary is able to determine a user input, with increasing accuracy when more outputs become available. When the security measure is implemented, an adversary remains oblivious of user inputs, even when thousands of outputs are collected. Therefore, our new security measure assures that random user selection is an effective way of protecting the privacy of dynamic group services. © 2017, The Author(s).

We consider dynamic group services, where outputs based on small samples of privacy-sensitive user inputs are repetitively computed. The leakage of user input data is analysed, caused by producing multiple outputs, resulting from inputs of frequently changing sets of users. A cryptographic technique, known as random user selection, is investigated. We show the effect of random user selection, given different types of output functions, thereby disproving earlier work. A new security measure is introduced, which provably improves the privacy-preserving effect of random user selection, irrespective of the output function. We show how this new security measure can be implemented in existing cryptographic protocols. To investigate the effectiveness of our security measure, we conducted a couple of statistical simulations with large user populations, which show that it forms a key ingredient, at least for the output function addition. Without it, an adversary is able to determine a user input, with increasing accuracy when more outputs become available. When the security measure is implemented, an adversary remains oblivious of user inputs, even when thousands of outputs are collected. Therefore, our new security measure assures that random user selection is an effective way of protecting the privacy of dynamic group services., Cyber Security, Optimization

We consider dynamic group services, where outputs based on small samples of privacy-sensitive user inputs are repetitively computed. The leakage of user input data is analysed, caused by producing multiple outputs, resulting from inputs of frequently changing sets of users. A cryptographic technique, known as random user selection, is investigated. We show the effect of random user selection, given different types of output functions, thereby disproving earlier work. A new security measure is introduced, which provably improves the privacy-preserving effect of random user selection, irrespective of the output function. We show how this new security measure can be implemented in existing cryptographic protocols. To investigate the effectiveness of our security measure, we conducted a couple of statistical simulations with large user populations, which show that it forms a key ingredient, at least for the output function addition. Without it, an adversary is able to determine a user input, with increasing accuracy when more outputs become available. When the security measure is implemented, an adversary remains oblivious of user inputs, even when thousands of outputs are collected. Therefore, our new security measure assures that random user selection is an effective way of protecting the privacy of dynamic group services., Cyber Security, Discrete Mathematics and Optimization

Flowers of the Mediterranean orchid genus Serapias L. form small, dark tubes that vary among taxa in diameter and depth. Visiting insects use the floral tube as shelter and act as pollinators if they touch the sticky viscidium at the rear of the tube and remove the pollinarium. It has been assumed that floral tube size and shape limit access to the flowers and thus may act as a barrier to gene flow between different Serapias species. Here we investigated floral characters and nuclear microsatellite markers in populations belonging to three morphologically similar Serapias species to test whether these species show evidence for floral or reproductive isolation. We found strong overlap of floral traits between two species, suggesting that floral isolation is nonexistent between them. Microsatellite markers applied to the same populations were highly polymorphic and revealed clear genetic differentiation among all three species. These results suggest that reproductive isolation exists, despite the lack of floral isolation between two of the species. In contrast to morphological characters, diagnostic microsatellite alleles were found for all Serapias species. The microsatellite markers could thus provide a useful tool to identify Serapias species and further investigate evolutionary relationships in this fascinating orchid lineage

The task of network traffic monitoring has evolved drastically with the ever-increasing amount of data flowing in large scale networks. The automated analysis of this tremendous source of information often comes with using simpler models on aggregated data (e.g. IP flow records) due to time and space constraints. A step towards utilizing IP flow records more effectively are stream learning techniques. We propose a method to collect a limited yet relevant amount of data in order to learn a class of complex models, finite state machines, in real-time. These machines are used as communication profiles to fingerprint, identify or classify hosts and services and offer high detection rates while requiring less training data and thus being faster to compute than simple models., Accepted author manuscript, Cyber Security

Contains fulltext : 141646.pdf (publisher's version ) (Closed access), Damage to the human ventromedial prefrontal cortex (vmPFC) leads to profound changes in everyday social interactions [1, 2]. Yet, in the lab, vmPFC patients show surprising proficiency in reasoning about other agents [3-8]. These conflicting observations suggest that what vmPFC patients lack in everyday social interactions might be the ability to guide their decisions with knowledge about a social partner [9-13], despite preserved access to that knowledge [2, 14]. Quantification of socially relevant decisions during live interaction with different partners offers the possibility of testing this hypothesis. Eight patients with vmPFC damage, eight patients with brain damage elsewhere, and 15 healthy participants were asked to communicate non-verbally with two different addressees, an adult or a child, in an experimentally controlled interactive setting [15, 16]. In reality, a confederate blindly performed the role of both adult and child addressee, with matched performance and response times, such that the two addressees differed only in terms of the communicator's beliefs. Patients with vmPFC damage were able-and motivated-to generate communicatively effective behaviors. However, unlike patient and healthy controls, vmPFC patients failed to adjust their communicative decisions to the presumed abilities of their addressee. These findings indicate that the human vmPFC is necessarily involved in social interactions, insofar as those interactions need to be tailored toward knowledge about a social partner. In this perspective, the known contribution of this region to disparate domains like value-based decision-making [17-19], schema-based memory-processing [20-22], and person-specific mentalizing [11-13] might be instances of decisions based on contingently updated conceptual knowledge.

Contains fulltext : 141646.pdf (publisher's version ) (Closed access), Damage to the human ventromedial prefrontal cortex (vmPFC) leads to profound changes in everyday social interactions [1, 2]. Yet, in the lab, vmPFC patients show surprising proficiency in reasoning about other agents [3-8]. These conflicting observations suggest that what vmPFC patients lack in everyday social interactions might be the ability to guide their decisions with knowledge about a social partner [9-13], despite preserved access to that knowledge [2, 14]. Quantification of socially relevant decisions during live interaction with different partners offers the possibility of testing this hypothesis. Eight patients with vmPFC damage, eight patients with brain damage elsewhere, and 15 healthy participants were asked to communicate non-verbally with two different addressees, an adult or a child, in an experimentally controlled interactive setting [15, 16]. In reality, a confederate blindly performed the role of both adult and child addressee, with matched performance and response times, such that the two addressees differed only in terms of the communicator's beliefs. Patients with vmPFC damage were able-and motivated-to generate communicatively effective behaviors. However, unlike patient and healthy controls, vmPFC patients failed to adjust their communicative decisions to the presumed abilities of their addressee. These findings indicate that the human vmPFC is necessarily involved in social interactions, insofar as those interactions need to be tailored toward knowledge about a social partner. In this perspective, the known contribution of this region to disparate domains like value-based decision-making [17-19], schema-based memory-processing [20-22], and person-specific mentalizing [11-13] might be instances of decisions based on contingently updated conceptual knowledge.

This chapter provides application developers with a presentation of the implemented reference implementation of the ABC4Trust architecture and protocols as well as a presentation on how to get started using the reference implementation. The reference implementation includes the ABC-Engines of the different entities, namely the User, Issuer, Verifier, Inspector, and Revocation Authority, and the smart card implementation for the User. This chapter also presents results of a perturbation analysis of the reference implementation. Even though the ABC4Trust focused on a server-desktop environment, we have done some proof of concept implementations and analysis of the feasibility of using smart phones for the user side of a Privacy-ABC setup; these results are also presented in this chapter. © Springer International Publishing Switzerland 2015.

The isolation among physically co-located virtual machines is an important prerequisite for ensuring the security in a virtualized environment (VE). The VE should prevent from exploitation of sidechannels stemming from the usage of shared resources, being hardware or software. However, despite the presumed secure logical isolation, a possible information leakage beyond the boundaries of a virtual machine due to side-channel exploits is a key concern in the VE. Such exploits have been demonstrated in the academic world during the last years. This paper takes into consideration the side-channel attacks threat, and points out that the feasibility of a SCA strongly depends on the specific context of the execution environment. The paper proposes a framework for feasibility assessment of SCAs using cache-based exploits as an example scenario. Furthermore, we provide a proof of concept to show how the feasibility of cache-based SCAs can be assessed using the proposed approach. © Springer International Publishing Switzerland 2015.