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Many scholars have highlighted the individual, organizational and inter-organizational causes of organizational wrongdoing; others have focused on its (negative) consequences or have analyzed how it can persist and spread between organizations. An underlining assumption shared by many of those studies is that organizational wrongdoing is a deviant, society-damaging phenomenon originating from individual and organizational actors’ pursuit of undue advantages. We argue that, at least in some cases, actors may also have “organizational reasons” for wrongdoing, besides self-interest. This article aims at analyzing the organizational reasons for wrongdoing in the CSM affair, a scandal that shed light on the deviant practices for career paths within the Italian judiciary system. By relying on documents and several semi-structured interviews to judges, public prosecutors, and experts in the field, we reconstructed actual practices for career advancement (extra-legal governance) and compared them with formal policies (legal governance). Our analysis shows that deviant practices were not merely occasional episodes of favoritism, but were part of an extra-legal governance system that involved virtually all of Italy’s judges. We also found that the CSM decoupled formal policies from actual practices to manage two organizational trade-offs – bureaucratic rules vs. efficiency, and independence vs. accountability. Therefore, besides individual gain, actors had two major “organizational reasons” for wrongdoing: first, they needed to cope with a lack of organizational capabilities and resources; second, they needed to address calls for greater accountability. In the light of our findings, we conclude with some considerations about organizational learning and the relation between law, organizations, and wrongdoing.

Background: Patients with programmed cell death-ligand 1 (PD-L1) ≥50% metastatic non-small cell lung cancer (mNSCLC) and ECOG performance status (PS) of 2 treated with first-line immunotherapy have heterogeneous clinical assessment and outcomes. Methods: To explore the role of immune-inflammatory surrogates by the validated lung immuno-oncology prognostic score (LIPS) score, including the neutrophil-to-lymphocyte ratio (NLR) and the pretreatment use of steroids, alongside other prognostic variables. A retrospective analysis of 128 patients with PS2 and PD-L1 ≥50% mNSCLC treated between April 2018 and September 2019 with first-line pembrolizumab in a real-world setting was performed. Results: With a median follow-up of 15.3 months, the 1-year overall survival (OS) and median progression-free survival (PFS) were 32.3% (95% CI: 30.9–33.9) and 3.3 months (95% CI: 1.8–4.7), respectively. The NLR, lactate dehydrogenase (LDH) and pretreatment steroids results were the only significant prognostic factors on the univariate analysis and independent prognostic factors by the multivariate analysis on both OS and PFS. The LIPS score, including the NLR and pretreatment steroids, identified 29 (23%) favourable-risk patients, with 0 factors, 1-year OS of 67.6% and median PFS of 8.2 months; 57 (45%) intermediate-risk patients, with 1 factor, 1-year OS 32.1% and median PFS 2.7 months; 42 (33%) poor-risk patients, with both factors, 1-year OS of 10.7% and median PFS of 1.2 months. Conclusions: The assessment of pre-existing imbalance of the host immune response by combined blood and clinical immune-inflammatory markers may represent a way to unravel the heterogeneous outcome and assessment of patients with mNSCLC and poor PS in the immune-oncology setting.

At its focal point, this work attempts to reveal the cultural and social characteristics of the Porticoes of Bologna. The research is conducted in three classes of the Comprehensive Institute of Pianoro’s Lower Secondary School, and targets children with cognitive characteristics, behaviors and interests that usually lead them to distance themselves from school. The laboratory approach managed to make such children demonstrate the motivation to learn and evince the sense of belonging to a group. In this project, the architecture of the city is deemed as a stimulus for stories, illustrations, songs and artifacts that have led to the acquisition of a collective consciousness and identity. In so doing, landscape, territorial and environmental instruction becomes strongly connected to active citizenship education, which paves the way for the training of responsible, reflective and participatory subjects, with attitudes, behaviors and activities that characterize citizens aware of their rights and duties.

Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking stat

BACKGROUND: A method of measurement of voluntary activation (VA, percent of full muscle recruitment) during isometric and isokinetic concentric contractions of the quadriceps femoris (QF) at 60s and 120s was previously validated. OBJECTIVE: This study aimed to quantify the test-retest minimal real difference (MRD) of VA during isometric (ISOM) and isokinetic concentric contractions of QF (100s, ISOK) in a sample of healthy individuals. METHODS: VA was measured through the interpolated twitch technique. Pairs of electrical stimuli were delivered to the QF at 40 of knee flexion during maximal voluntary contractions. Twenty-five healthy participants (20-38 years, 12 women, 13 men) completed two testing sessions with a 14-day interval. VA values were linearized through logit transformation (VAl). The MRD was estimated from intraclass correlation coefficients (model 2.1). RESULTS: The VA (median, range) was 84.20% (38.2-99.9%) in ISOM and 94.22% (33.8-100%) in ISOK. MRD was 0.78 and 1.12 logit for ISOM and ISOK, respectively. As an example, in terms of percent VA these values correspond to a change from 76% to 95% and from 79% to 98% in ISOM and in ISOK, respectively. CONCLUSIONS: The provided MRD values allow to detect significant individual changes in VA, as expected after training and rehabilitation programs.

While walking on split-belt treadmills (two belts running at different speeds), the slower limb shows longer anterior steps than the limb dragged by the faster belt. After returning to basal conditions, the step length asymmetry is transiently reversed (after-effect). The lower limb joint dynamics, however, were not thoroughly investigated. In this study, 12 healthy adults walked on a force-sensorised split-belt treadmill for 15 min. Belts rotated at 0.4 m s−1 on both sides, or 0.4 and 1.2 m s−1 under the non-dominant and dominant legs, respectively. Spatiotemporal step parameters, ankle power and work, and the actual mean velocity of the body’s centre of mass (CoM) were computed. On the faster side, ankle power and work increased, while step length and stance time decreased. The mean velocity of the CoM slightly decreased. As an after-effect, modest converse asymmetries developed, fading within 2–5 min. These results may help to decide which belt should be assigned to the paretic and the unaffected lower limb when split-belt walking is applied for rehabilitation research in hemiparesis.

During walking, falling is most likely to occur towards the side of the supporting lower limb during the single stance. Timely lateral redirection of the centre of mass (CoM) preceding the no-return position is necessary for balance. We analysed the curvature peaks (the inverse of the radius of curvature) of the three-dimensional path of the CoM during the entire stride. Twelve healthy adults walked on a force-sensorized treadmill at constant velocities from 0.4 to 1.2 m s−1, in 0.2 m s−1 increments. The three-dimensional displacements of the CoM, the muscular power sustaining the CoM motion with respect to the ground, and the efficiency of the pendulum-like transfer of the CoM were computed via the double integration of the ground reaction forces. The curvatures of the CoM trajectory were measured (Frenet–Serret formula). During the single stance, the curvature showed a bell-shaped increment, lasting a few tenths of a millisecond, and peaking at 365–683 m−1 (radius of 2.7–1.4 mm, respectively), the higher the walking velocity. The CoM was redirected towards the swinging lower limb. The curvature increment was sustained by muscle-driven braking of the CoM. Smoother increments of curvature (peaking at approximately 37–150 m−1), further orienting the CoM towards the leading lower limb, were observed during the double stance. The peaks of the curvatures were symmetric between the two sides. The high curvature peaks during the single stance may represent an index of dynamic balance during walking. This index might be useful for both rehabilitation and sports training purposes.

Background: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed “non-drugable” progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. Methods: We conducted a study on “post-progression” (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), “switched therapies” or best supportive care only (BSC). Results: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35–0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33–0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68–1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52–1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). Conclusion: Our study confirmed that in clinical practice, in case of “non-druggable” disease progre

Background: The role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non-small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%. Patients and methods: We previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes. Results: A total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival. Conclusions: This study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting.

Background The association between obesity and outcomes in patients receiving programmed death-1/programmed death ligand-1 (PD-L1) checkpoint inhibitors has already been confirmed in pre-treated non-small cell lung cancer (NSCLC) patients, regardless of PD-L1 tumor expression. Methods We present the outcomes analysis according to baseline body mass index (BMI) and BMI variation in a large cohort of metastatic NSCLC patients with a PD-L1 expression ≥50%, receiving first line pembrolizumab. We also evaluated a control cohort of metastatic NSCLC patients treated with first line platinum-based chemotherapy. Normal weight was set as control group. Results 962 patients and 426 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Obese patients had a significantly higher objective response rate (ORR) (OR=1.61 (95% CI: 1.04-2.50)) in the pembrolizumab cohort, while overweight patients had a significantly lower ORR (OR=0.59 (95% CI: 0.37-0.92)) within the chemotherapy cohort. Obese patients had a significantly longer progression-free survival (PFS) (HR=0.61 (95% CI: 0.45-0.82)) in the pembrolizumab cohort. Conversely, they had a significantly shorter PFS in the chemotherapy cohort (HR=1.27 (95% CI: 1.01-1.60)). Obese patients had a significantly longer overall survival (OS) within the pembrolizumab cohort (HR=0.70 (95% CI: 0.49-0.99)), while no significant differences according to baseline BMI were found in the chemotherapy cohort. BMI variation significantly affected ORR, PFS and OS in both the pembrolizumab and the chemotherapy cohorts. Conclusions Baseline obesity is associated to significantly improved ORR, PFS and OS in metastatic NSCLC patients with a PD-L1 expression of ≥50%, receiving first line pembrolizumab, but not among patients treated with chemotherapy. BMI variation is also significantly related to clinical outcomes.

Background: Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%. Methods: We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50%. Results: One thousand and twenty-six consecutive patients were included. The objective response rate (ORR) was 44.5% (95% CI 40.2–49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p < 0.0001) and bone metastases (p = 0.0003) were confirmed to be independent predictors of a worse ORR. Former smokers (p = 0.0002), but not current smokers (p = 0.0532) were confirmed to have a significantly prolonged PFS compared to never smokers at multivariate analysis. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a worse PFS. Previous palliative RT was significantly related to a shortened OS (p = 0.0104), while previous non-palliative RT was significantly related to a prolonged OS (p = 0.0033). Former smokers (p = 0.0131), but not current smokers (p = 0.3433) were confirmed to have a significantly prolonged OS compared to never smokers. ECOG-PS (p < 0.0001), bone metastases (p < 0.0001) and liver metastases (p < 0.0001) were also confirmed to be independent predictors of a shortened OS. A PD-L1 expression of ≥ 90%, as assessed by recursive partitioning, was associated with significantly higher ORR (p = 0.0204), and longer and OS (p = 0.0346) at multivariable analysis. Conclusion: Pembrolizumab was effective in a large cohort of NSCLC patients treated outside of clinical trials. Questions regarding the effe

A common claim is that mafia families arrange marriages strategically to seal alliances, cement partnerships and enhance cohesion. However, this claim is mainly based on anecdotal evidence and limited case studies. In this paper, by relying on an original database of biographical and relational information on over 4,600 members, we carry out the first large-scale exploratory analysis of the network of interfamily marriages in ’Ndrangheta. Our analysis shows that this alliance network is polycentric, made up of cohesive subgroups centered around well-connected, powerful families, that occupy different positions in the network. The presence of patterns suggests that marriages in ’Ndrangheta are possibly the result of family strategies to explore and exploit their power and business. We discuss the implications of these findings for the study of marriages as an organizational instrument.

La letteratura moderna, in particolare nei capolavori, tra gli altri, di Manzoni, Camus, Steinbeck presi in considerazione nel presente volume, con la capacità di iscriversi nelle coscienze che è propria della grande narrativa, ha posto sotto gli occhi e dentro la mente del lettore le crudeli devastazioni della antica e perversa dinamica alla base della costruzione del capro espiatorio e dei riti sacrificali. Specie di quelli che rivestano le pratiche persecutorie col manto legittimo e rispettabile del diritto e del processo penale. Dinamica che in René Girard ha trovato uno dei suoi massimi diagnosti e di cui il libro invita a fare dolente ma salutare esperienza, calandosi negli abissi più oscuri dell’animo umano, non senza riemergerne con possibili prospettive di giustizia e antidoti culturali e regolativi idonei a portare alla luce, contrastare o almeno contenere la formidabile spinta alla ricerca di vittime su cui illusoriamente scaricare colpe e nodi irrisolti da individui, istituzioni e collettività. Nella Storia della colonna infame di Alessandro Manzoni, da cui non a caso si è tratta ispirazione per il titolo del volume, il meccanismo del capro espiatorio trova il suo unico punto di rottura nella figura di Gasparo Migliavacca che, come Cristo in Girard, rifiuta di espandere la furia sacrificale evitando ulteriori chiamate di correità. Senza il suo esempio – come si legge nel libro – l’uomo sarebbe costretto a negare la Provvidenza o ad accu¬sarla, cioè si troverebbe vincolato all’interno di un dualismo incapace di dare una risposta al problema dell’esistenza del male. [Risvolto di copertina]

This chapter introduces the reader to the origins, structure and main contents of the volume 'The shadow of the "columns of infamy". Literature and the ijustice of scapegoating' ['L'ombra delle "colonne infami". La letteratura e l'ingiustizia del capro espiatorio'].

La letteratura moderna, in particolare nei capolavori, tra gli altri, di Manzoni, Camus, Steinbeck presi in considerazione nel presente volume, con la capacità di iscriversi nelle coscienze che è propria della grande narrativa, ha posto sotto gli occhi e dentro la mente del lettore le crudeli devastazioni della antica e perversa dinamica alla base della costruzione del capro espiatorio e dei riti sacrificali. Specie di quelli che rivestano le pratiche persecutorie col manto legittimo e rispettabile del diritto e del processo penale. Dinamica che in René Girard ha trovato uno dei suoi massimi diagnosti e di cui il libro invita a fare dolente ma salutare esperienza, calandosi negli abissi più oscuri dell’animo umano, non senza riemergerne con possibili prospettive di giustizia e antidoti culturali e regolativi idonei a portare alla luce, contrastare o almeno contenere la formidabile spinta alla ricerca di vittime su cui illusoriamente scaricare colpe e nodi irrisolti da individui, istituzioni e collettività. Nella Storia della colonna infame di Alessandro Manzoni, da cui non a caso si è tratta ispirazione per il titolo del volume, il meccanismo del capro espiatorio trova il suo unico punto di rottura nella figura di Gasparo Migliavacca che, come Cristo in Girard, rifiuta di espandere la furia sacrificale evitando ulteriori chiamate di correità. Senza il suo esempio – come si legge nel libro – l’uomo sarebbe costretto a negare la Provvidenza o ad accu¬sarla, cioè si troverebbe vincolato all’interno di un dualismo incapace di dare una risposta al problema dell’esistenza del male. [Risvolto di copertina]

Background: Patients with programmed cell death-ligand 1 (PD-L1) ≥50% metastatic non-small cell lung cancer (mNSCLC) and ECOG performance status (PS) of 2 treated with first-line immunotherapy have heterogeneous clinical assessment and outcomes. Methods: To explore the role of immune-inflammatory surrogates by the validated lung immuno-oncology prognostic score (LIPS) score, including the neutrophil-to-lymphocyte ratio (NLR) and the pretreatment use of steroids, alongside other prognostic variables. A retrospective analysis of 128 patients with PS2 and PD-L1 ≥50% mNSCLC treated between April 2018 and September 2019 with first-line pembrolizumab in a real-world setting was performed. Results: With a median follow-up of 15.3 months, the 1-year overall survival (OS) and median progression-free survival (PFS) were 32.3% (95% CI: 30.9–33.9) and 3.3 months (95% CI: 1.8–4.7), respectively. The NLR, lactate dehydrogenase (LDH) and pretreatment steroids results were the only significant prognostic factors on the univariate analysis and independent prognostic factors by the multivariate analysis on both OS and PFS. The LIPS score, including the NLR and pretreatment steroids, identified 29 (23%) favourable-risk patients, with 0 factors, 1-year OS of 67.6% and median PFS of 8.2 months; 57 (45%) intermediate-risk patients, with 1 factor, 1-year OS 32.1% and median PFS 2.7 months; 42 (33%) poor-risk patients, with both factors, 1-year OS of 10.7% and median PFS of 1.2 months. Conclusions: The assessment of pre-existing imbalance of the host immune response by combined blood and clinical immune-inflammatory markers may represent a way to unravel the heterogeneous outcome and assessment of patients with mNSCLC and poor PS in the immune-oncology setting.

Few studies have investigated the kinematic aspects of the body centre of mass motion, that is, its three-dimensional path during strides and their changes with child development. This study aimed to describe the three-dimensional path of the centre of mass in children while walking in order to disentangle the effect of age from that of absolute forward speed and body size and to define preliminary pediatric normative values. The three-dimensional path of the centre of mass during walking was compared across healthy children 5-6- years (n = 6), 7-8 years (n = 6), 9-10 years (n = 5), and 11-13 years of age (n = 5) and healthy adults (23-48 years, n = 6). Participants walked on a force-sensing treadmill at various speeds, and height normalization of speed was conducted with the dimensionless Froude number. The total length and maximal lateral, vertical, and forward displacements of the centre of mass path were calculated from the ground reaction forces during complete strides and were scaled to the participant's height. The centre of mass path showed a curved figure-of-eight shape. Once adjusted for speed and participants' height, as age increased, there was a decrease in the three-dimensional parameters and in the lateral displacement, with values approaching those of adults. At each step, lateral redirection of the centre of mass requires brisk transient muscle power output. The base of support becomes relatively narrower with increasing age. Skilled shortening of the lateral displacement of the centre of mass may therefore decrease the risk of falling sideways. The three-dimensional path of the centre of mass may represent maturation of neural control of gait during growth.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially w

Background/Aim: Brain metastases are an additional challenge in patients with non-small-cell lung cancer (NSCLC) because most chemotherapy agents cannot cross the blood–brain barrier. Nivolumab has demonstrated efficacy in patients with advanced squamous NSCLC, but because patients with central nervous system (CNS) metastases are typically excluded from registration trials, ‘field-practice’ data are needed. Patients and Methods: Patients in the Italian cohort of the Expanded Access Program (EAP) who had CNS metastases at baseline were analyzed. Results: Thirty-seven patients with CNS metastases received a median of six doses of nivolumab. Three patients (8%) had grade 3-4 adverse events and one patient discontinued due to an adverse event. The objective response rate was 19%. Median overall survival was 5.8 (95% confidence interval=1.9-9.8) months and median progression-free survival was 4.9 (95% confidence interval=2.7-7.1) months. Conclusion: The safety and efficacy of nivolumab in patients with CNS metastases appear to be similar to those seen in the overall EAP cohort in Italy.

History serves to understand the present, to understand who we are and to plan the future. To achieve these goals, it is important to arouse emotions in children through the historical story. The challenge to deal with is to ensure that young people can identify with the many small stories that make up the "big" story. It is therefore essential to start from local history, from the environment in which the children live. In this way, through the analysis and comparison of sources, children will understand the reasons for their lifestyle and will be able to build their own cultural identity and feel part of the social and cultural context in which they live. From this perspective, it can be said that civic education is part of the teaching of history and must be practiced and practiced above all in the school environment.

Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking stat

To address systemic organizational problems with individual solutions is one of the main weaknesses of organizational and institutional processes of change. Recent scandals related to the Italian High Judicial Council (HJC) have shed light on deviant practices in the selection process of court presidents. In particular, the career system was mostly based on membership in specific organized groups within the judiciary, rather than on the professional value of candidates. This article, adopting an organizational perspective, focuses on the governance of the judiciary and on the functioning of the HJC in the selection process of court presidents. Our explanatory case study, based on many interviews to judges, public prosecutors, and experts of the Italian judicial system, aims at highlighting the «concrete system of action» (Crozier and Friedberg 1977) behind the HJC selection process of court presidents. To this end, the article proceeds as follow: 1) firstly, it describes the gap between the formal and real organization in judicial career management; 2) then, it identifies «good reasons» and systemic nodes that could explain the emergence of alternative models of governance, and 3) finally, it discusses problems related to organizational learning. In particular, the article explains why the reaction of the judicial system to the scandal has been functional for maintaining the status quo, rather than promoting real processes of organizational learning and change.

Walking on split-belt treadmills (each belt rotating at a different velocity) has inspired a growing number of researchers to study gait adaptation and rehabilitation. An overlooked peculiarity of this artificial form of gait is that the mean velocity adopted by the participant, considered as a whole system represented by the body Center of Mass, can be different from the mean velocity of the two belts. Twelve healthy adults (21-34 yrs) were requested to walk for 15 mins on a treadmill with belts rotating at 0.4 and 1.2 m sec-1, respectively (mean = 0.8 m sec-1). Each belt was supported by four 3-dimensional force sensors. For each participant, six strides were analyzed during the 1st and the 15th minute of the trial. The mean Center of Mass velocity was computed as the sum of the velocities of each belt weighted by the percentage of time during which the resulting forces, underlying the accelerations of the Center of Mass, originated from each belt. Across early and late observations, the median Center of Mass velocities were 0.72 and 0.67 m sec-1, respectively (P < 0.05). Therefore, the real velocity of the Center of Mass and its time course should be individually assessed when studying walking on split-belt treadmills.

The aim of the research was to analyse the practical and daily dimension of the work of the air traffic control officer (ATCO). The ATCO is an operator able to handle unexpected situations within a complex operating, technological and regulatory system while maintaining a high level of reliability and safety. In particular, the work of the ATCO is characterized by two crucial elements: (1) the accurate management of time variables (air traffic management requires the air traffic controller to take decisions and act in extremely restricted fractions of time) and (2) continuous coordination with various items of technology and with other workers (pilots, other ATCOs and other types of personnel employed at airports). This means that it is an activity that at the same time presupposes both individual skills and capabilities and also collective capabilities, aimed at building a common space of mutual understanding and agreement with regard to the interpretive schemes to be utilised in order to deal with the multiple scenarios that can arise in the field of air traffic management. The aims of the research were descriptive-analytical in nature: Describe the characteristics of the ATCO profession, highlighting the aspects of reliability, safety and management of unexpected events; Describe and analyse the cognitive and organizational complexity of the ATCO's work. The research also involved goals of a practical-improvement kind, encouraging greater awareness in terms of: the operators, with reference to the management of unexpected events, to the cognitive and organizational complexity of air traffic control activity, to the operational specificities associated with maintaining and increasing effectiveness, efficiency, reliability and safety in the management of air traffic; The identification of improvement criteria for the initial selection and training (both at the start and then ongoing) of staff dedicated to air traffic control; The complexity of the work of ATCOs in

Background The association between obesity and outcomes in patients receiving programmed death-1/ programmed death ligand-1 (PD-L1) checkpoint inhibitors has already been confirmed in pre-treated non-small cell lung cancer (NSCLC) patients, regardless of PD-L1 tumor expression. Methods We present the outcomes analysis according to baseline body mass index (BMI) and BMI variation in a large cohort of metastatic NSCLC patients with a PD-L1 expression ≥50%, receiving first line pembrolizumab. We also evaluated a control cohort of metastatic NSCLC patients treated with first line platinum-based chemotherapy. Normal weight was set as control group. Results 962 patients and 426 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Obese patients had a significantly higher objective response rate (ORR) (OR=1.61 (95% CI: 1.04– 2.50)) in the pembrolizumab cohort, while overweight patients had a significantly lower ORR (OR=0.59 (95% CI: 0.37–0.92)) within the chemotherapy cohort. Obese patients had a significantly longer progression-free survival (PFS) (HR=0.61 (95% CI: 0.45–0.82)) in the pembrolizumab cohort. Conversely, they had a significantly shorter PFS in the chemotherapy cohort (HR=1.27 (95% CI: 1.01–1.60)). Obese patients had a significantly longer overall survival (OS) within the pembrolizumab cohort (HR=0.70 (95% CI: 0.49–0.99)), while no significant differences according to baseline BMI were found in the chemotherapy cohort. BMI variation significantly affected ORR, PFS and OS in both the pembrolizumab and the chemotherapy cohorts. Conclusions Baseline obesity is associated to significantly improved ORR, PFS and OS in metastatic NSCLC patients with a PD-L1 expression of ≥50%, receiving first line pembrolizumab, but not among patients treated with chemotherapy. BMI variation is also significantly related to clinical outcomes.

Come funzionano le mafie? Come reclutano le persone, come conducono i loro affari, come risolvono i conflitti e come ricorrono alla violenza? Perché elaborano un sistema così complesso di rituali, regole e codici di condotta? In che cosa si differenziano tra loro, e perché alcune mafie commettono molti più omicidi di altre? Il libro mette a confronto sette organizzazioni mafiose: tre italiane (Cosa Nostra siciliana, Camorra, ’Ndrangheta), Cosa Nostra americana, Yakuza giapponese, Triadi cinesi e Mafia russa, illustrandone l’architettura e ponendo in relazione i diversi modelli organizzativi adottati con i diversi usi della violenza. Sono inoltre discussi i dilemmi che queste organizzazioni devono affrontare per sopravvivere – le tensioni tra segretezza e consenso, legami di sangue e capacità criminali, accentramento e decentramento –, nella convinzione che comprendere la logica organizzativa delle mafie è indispensabile per poterle combattere efficacemente. Infine, si analizzano i principali cambiamenti nei comportamenti e nelle strategie delle mafie italiane, l’espansione in nuovi territori e il ruolo sempre più rilevante dei soggetti contigui esterni.

Italian mafias—Cosa Nostra, Camorra, and ‘Ndrangheta—are long-lived, resilient organizations that have evolved to adapt to environmental changes. They have different organizationalmodels.While CosaNostra (in the past) and ‘Ndrangheta are characterized by a unitary, vertical structure and higher-level coordination bodies, Camorra has a plurality of organizational models; the majority of clansmaintain a structure that is fluid, polycentric, and conflictual. In general, mafias with a vertical organizational order have greater control over conflict, and greater capacity to resist state power.The ‘Ndrangheta has become the richest and most powerful of the three, replacing Cosa Nostra in international drug trafficking. It is able to reproduce its organizational structures and business model in new territories in Italy and elsewhere. In contrast, owing to unprecedented law enforcement efforts in recent decades, Cosa Nostra is weaker, down but not out. Camorra continues to be the most violent mafia, committing more homicides than the other two combined.Consistentwith their adaptive capacity, mafias in new areas of expansion are treated as novel agents that can provide extralegal services and business opportunities. They are sought out by entrepreneurs, white-collar professionals, and local politicians to solve problems such as debt collection, labor unrest, and disputes with suppliers.

Objectives Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. Materials and methods This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015. Information regarding molecular profiling and treatment choices were collected. Description of patients’ outcome included overall survival (OS), progression-free survival in first (PFS1) and second-line (PFS2). Results and conclusion Among 1787 patients enrolled, 1388 (78%) performed at least one molecular analysis during the history of disease: 76% were tested for EGFR, 53% for ALK, 27% for KRAS, 16% for ROS1, 14% for BRAF, 5% for HER2, 4% for MET and 1% for FGFR. The remaining 399 patients (22.3%) did not receive any molecular test. Among patients receiving at least one molecular analysis, 583 (42%) presented a molecular alteration. Considering EGFR mutated and/or ALK rearranged patients (402), for which target agents were routinely reimbursed at time of study in Italy, the 86% received a personalized treatment as first and/or second line: the 90% (286) of EGFR mutants received an EGFR tyrosine kinase inhibitor, mostly gefitinib (41.1%) or afatinib (36.4%) while 74% (62) of ALK translocated patients received an ALK inhibitor, mostly crizotinib (64%). Median OS was 9.34 months (95% CI 8.62–10.0), median PFS1 was 4.61 months (95%CI 4.31–4.84) and median PFS2 was 2.76 months (95%CI 2.57–3.19). In the Italian clinical practice, routine molecular assessment was largely applied in NSCLC patients, according to national guidelines, but a low level of ALK test was reached. Most of EGFR mutants an ALK rearranged patients received a personalized treatment a

How do mafias work? How do they recruit people, control members, conduct legal and illegal business, and use violence? And why do they establish such a complex mix of rituals, rules and codes of conduct? Why do some commit many more murders than others? This book makes sense of mafias as organizations. Through the collation of historical accounts, official data, investigative sources, and interviews, it studies seven mafias around the world: in addition to the three Italian mafias, it studies the American Cosa Nostra, Japanese Jakuza, Chinese Triads, and Russian mafia. The book identifies the organizational architecture that characterizes these criminal groups, and relates different organizational models to the use of violence. Furthermore, it advances a theory of mafia rules, showing how rules perform specific functions in the criminal organization. Finally, it discusses major organizational dilemmas that mafias have to deal with, such as the trade-off between maintaining secrecy and pursuing their business efficiently, whether to use or contain violence, and whether to recruit on the bases of kinship or skills, and it shows how both organizational structure and rules help strike a balance between these alternative needs. Taken together, this book provides a new way of thinking about mafias that can also be extended to other form of organized crime (gangs, terrorist organizations, etc.). Beyond its scientific importance, the book has also practical implications: Understanding the physiology and organizational logic of mafias is an indispensable step in order to confront them.

Objectives: Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to investigate the efficacy of the somatostatine analogue lanreotide in maintenance for SCLC patients after response to standard treatment. Materials and Methods: A multicenter, randomized, phase 3 trial was conducted in SCLC expressing somatostatine receptors at baseline Octreoscan, responding after platinum-based chemotherapy with/without radiotherapy. Patients were randomized 1:1 to receive maintenance lanreotide 120 mg subcutaneously every 28 days, up to 1 year or progression versus observation. Randomization was stratified according to stage (limited/extended, LD/ED). The primary end-point was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. Results: Seventy-one patients were randomly assigned (39 to lanreotide, 32 to observation) in 9 Italian institutions. Median PFS was 3.6 (95% CI 3.2–3.9) with lanreotide versus 2.3 months (95% CI 1.7–2.9) with observation (HR 1.51, 95% CI 0.90–2.50; P = 0.11). Stage was an independent predictor for PFS (HR 3.14, 95% CI 1.77–5.57; P < 0.0001). Median PFS was 7.0 (95% CI <1-13.5) with lanreotide versus 3.8 months (95% CI <1-8.6) with observation in LD (P = 0.21), and 3.0 (95% CI 2.2–3.8) versus 2.2 (95% 1.7–2.7) in ED (P = 0.19). Median OS was 9.5 (95% CI 4.8–14.3) with lanreotide versus 4.7 months (95% CI <1-16.6) with observation (P = 0.47). Treatment-related adverse events occurred in 28% of patients with lanreotide (grade 3 in two patients). Conclusion: Although survival outcomes were not significantly prolonged with lanreotide as a maintenance in SCLC expressing somatostatin receptors after response to standard treatment, lanreotide showed a slight PFS benefit in LD SCLC deserving further investigations.

Mafias have been expanding outside their original homelands for several decades, penetrating both legal and illegal markets. Existing literature has explored the push and pull factors that underpin the movement and successful transplantation of mafia organizations, but less attention has been devoted to specify the mechanisms through which penetration takes place - especially in legal markets - and to empirically ground these mechanisms through a mixed-method approach. Starting with these premises, the article has two objectives. First, it explores the link between the type of legal markets and the presence of mafia activities in a given territory, focusing empirically on the Northern Italian region of Lombardy. Through quantitative analysis conducted at the municipal level in Lombardy, the article shows that mafias' activities in a territory tend to be correlated with the presence of relatively large markets in the construction, transport, and bars and restaurants economic sectors. Second, the article introduces a framework to describe the «services» that mafia organizations provide to entrepreneurs. Starting from the concept of «protection» (the basic service provided by mafias), three key activities are identified: business development, the ability to limit market competition, and extra-legal enforcement and resolution of controversies. It also shows empirically - through qualitative analysis based on judicial material emerging from investigations conducted in Lombardy over more than a decade - how these three types of services function in practice. The article finally suggests directions for advancing research on the topic and to analyse more thoroughly the impact of organized crime on market functioning.

L’articolo analizza l’uso (e l’abuso) del concetto di gray zone in varie discipline e in particolare nello studio delle mafie. Dopo avere chiarito in chiave sociologica il concetto di gray zone proposto da Primo Levi, l’articolo evidenzia come il crescente uso di tale concetto si allontani dal senso originario. Nello studio delle mafie la gray zone identifica uno spazio di confine fra legale e illegale in cui prendono forma rapporti di scambio e di collusione tra mafiosi, white collars e altri attori economici e politici. Come l’articolo mostrerà, c’è ben poca gray zone in questo: i white collars sono attratti dai vantaggi economici e professionali derivanti dalla collaborazione con le mafie che a loro volta traggono vantaggi dalla loro expertise e capacità di intermediazione. L’articolo propone, infine, un approccio analitico all’analisi dei meccanismi che portano alla collaborazione dei white collars con le mafie.

Homicides of politicians, prosecutors and judges perpetrated by mafiosi often make the media headlines, but are rarely considered in the social sciences. In the 1980s and the early 1990s, mafia wars in Italy took a heavy toll on anti-mafia judges, law enforcement officers, and politicians. The intrinsic relevance of the topic is increased by mafias and organised crime extending their reach beyond traditional strongholds and borders in recent decades. This makes it even more important to understand why and when organised crime groups directly challenge political and judicial authority (and/or other high-profile targets such as trade unionists and journalists). This chapter focuses on the three most prominent mafia groups currently operating in Italy – i.e., Cosa Nostra, the Camorra and the ’Ndrangheta – and investigates the rationale(s) underpinning their use of high-profile homicides. The chapter critically reviews the major theories that can explain the use of violence in organised crime, focusing on four dimensions: (a) criminal groups’ organisational features, (b) the type of markets penetrated by mafia groups, (c) the structure of political opportunities, and (d) law enforcement strategies. It is based on the empirical analysis of an original dataset of mafia homicides carried out since the late 19th century in Italy.

White collars and mafias. The dangerous relations in the economy of Northern Italy Relations with external individuals define organizations as much as their internal structures and members. Individuals formally external to the organizational structure can play a major role, especially within criminal organizations. In the mafias, members’ low human capital is balanced with their ability to cooperate with individuals who have specific professional skills, such as accountants, police officers, and politicians. Drawing information on almost 40 recent investigations on mafia networks in Northern Italy, this paper analyses the profile and activities of the professionals involved in mafias’ illicit business. All 60 identified professionals acted as either knowledge brokers (i.e. connecting mafiosi with the individuals needed to pursue their illicit goals), knowledge providers (i.e. providing mafiosi with the technical skills necessary for certain criminal activities), or both. These white collars are particularly crucial in the settlement of mafias outside of their territories of origin. Knowledge brokers and providers indeed reduce the cost of information for the mafias, which in turn allows them to proliferate in new territories. The paper concludes by underlying how mafias’ relations with external actors should be incorporated in the study of mafia organizations

In this paper, we consider a perturbation of the Ricci solitons equation proposed in [J.-P. Bourguignon, Ricci curvature and Einstein metrics, in Global Differential Geometry and Global Analysis, Lecture Notes in Mathematics, Vol. 838 (Springer, Berlin, 1981), pp. 42-63] and studied in [H.-D. Cao, Geometry of Ricci solitons, Chinese Ann. Math. Ser. B 27(2) (2006) 121-142] and we classify noncompact gradient shrinkers with bounded non-negative sectional curvature.