Population Change and International and Internal Migration in Italy, 2002-2017: Ravenstein Revisited

In 1885, Ravenstein formulated his "laws" of migration, based on the experience of the British Isles. In a further 1889 paper, he extended his analysis as a tour d’horizon of migration and population changes in other nations, including Italy. Even if social and economic processes including globalisation and rising mobility have changed the world since then, Ravenstein's "laws" remain a point of reference today. Harnessing theoretical and methodological advances made since the 19th century, this paper describes and seeks to explain the role of international and internal migration in regional population change in Italy from 2002-2017. This paper provides the first geographically detailed migration analysis for the country's 611 Local Labour Market Areas (LLMAs), using register-based migration and population data. Our contribution focuses on several of Ravenstein's "laws" relating to gender (differences between men and women), natives and non-natives (differences between the Italian and the foreign population), distance migrated from origin to destination, and the role of the economy in shaping push and pull factors of migration. The results show that international migration is more prominent among men than women. In the case of internal moves, the rates of migration among men and women are similar, and internal migration is more prominent among the foreign than the native Italian population. Overall, international migration gains contribute substantially more to population change than internal migration gains and losses do. In Italy, the effects of persistent economic imbalances and of distance on migration patterns are not in line with Ravenstein's hypotheses: not all areas with high unemployment show an effect of dispersion, nor does distance always act as a deterrent to migration. The geographically detailed analysis presented here illustrates the temporal and spatial coexistence of diverse international and internal migration processes depending on local characteristics, as well as the importance of the economic or administrative centres as the driving force behind national patterns. Our results show that, even 130 years after their formulation, Ravenstein’s migration "laws" (more accurately called "hypotheses" today) are still a valuable starting point in assessing and understanding migration processes and their role in regional population change

Do the Fastest Open-Water Swimmers have A Higher Speed in Middle- and Long-Distance Pool Swimming Events?

Background: It has been shown that the fastest open-water swimmers (OW-swimmers) increase significantly the speed in the last split of the open-water events. The aim of the present work was to determine if the fastest OW-swimmers have a higher speed in the middle- and long-distance pool swimming events, and to develop a multivariate model that can predict the medalist group in the 10-km competition. Methods: A total of 484 athletes (252-males and 232-females) were included in the analysis. Swimmers were divided into four groups based on their finishing position in the competition. For each swimmer, the absolute best performance (PB) of 200, 400, 800 and 1500-meter in long course, the seasonal best performance (SPB) obtained before the open-water events and critical velocity (CV) were analyzed. Multivariate analysis of variance (MANOVA) was used to detect significant differences between groups and discriminant analysis was used to predict a grouping variable. Results: All the variables analyzed were significantly different between groups (p < 0.001). The first discriminant function correctly classified 50% of the overall female and male swimmers. Conclusion: Fastest OW-swimmers have a higher speed in middle- and long-distance pool swimming events. Further studies should include different anthropometric and physiological variables to increase the accuracy of classification

The impact of a 14-day altitude training camp on olympic-level open-water swimmers' sleep

Despite the common belief that sleep quality at altitude is poor, the scientific evidence to support this notion is still modest. Therefore, the purpose of the present study was to evaluate possible changes of actigraphy-based and subjective sleep parameters in a group of elite open-water swimmers during a 14-day altitude training camp (ATC) at 1500 m. The study subjects were five Olympic-level open-water swimmers (mean age: 25.0 ± 3.2 years; 3 females and 2 males). All subjects wore a wrist activity monitor and filled a sleep diary for 18 consecutive nights, 4 nights before and 14 nights during ATC. The data were then analyzed at four different time points: before ATC (PRE), the first two days of ATC (T1), and after one (T2) and two weeks of ATC (T3). Training load, assessed as the covered distance (km), session rating of perceived exertion (sRPE), and heart rate (HR), was monitored during the week before and the first and second week of ATC. No significant differences in objective and subjective scores of sleep quality were detected, whereas the sleep onset time (p = 0.018; η2p = 0.83, large) and sleep offset time (p &lt; 0.001; η2p = 0.95, large) significantly differed among PRE, T1, T2, and T3: elite athletes started to sleep and woke up ≃ 1 h earlier the first two days of ATC compared to PRE (sleep onset time: p = 0.049; sleep offset time: p = 0.016). Further, an increase in the training volume during the two weeks of the ATC was observed, with the most time spent in a low-intensity regime and an increase in time spent in a high-intensity regime compared to PRE. Sleep quality was not negatively influenced by a 14-day altitude training camp at 1500 m in a group of Olympic-level elite swimmers despite an increase in perceived exertion during training sessions. Nonetheless, early sleep onset and sleep offset times were observed for the first two nights of ATC: elite athletes started to sleep and woke up ≃ 1 h earlier compared to the baseline nights

Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukaemia

The most recent clinical trials on adult acute lymphoid leukaemia (ALL) have shown complete remission and disease-free survival (DFS) rates of 80-85% and 30-40%, respectively (Annino, et al, Durrant, et al, Kantarjian, et al, Larson, et al, Ribera, et al, Rowe). Intensified consolidation, particularly with high-dose methotrexate and high-dose cytarabine, may be one of the reasons for the improved outcome in recent series (Bassan and Hoelzer, Hoelzer and Gokbuget, Kebriaei and Larson). In addition, risk-adapted and subtype-oriented therapy may have contributed to this better outcome. However, the long term outcome of adult patients is still dismal, with approximately one third of the cases only being cured. At present, therapeutic options include conventional chemotherapy (CHT), high dose therapy with autologous and, especially, allogeneic stem cells transplantation (SCT) and, for certain subsets, such as BCR-ABL1+ ALL, specific targeted therapy (Piccaluga, et al). Although SCT has been used in adult ALL for more than 20 years, its role remains controversial as demonstrated by conflicting results in various studies. Previous casecontrolled studies did not show that allogeneic SCT (alloSCT) provided any advantage over CHT (Horowitz, et al, Zhang, et al) while in some studies there was an advantage, but restricted to young adults (Oh, et al). The number of controlled published or ongoing trials is remarkably small and some of them did not include both standard-risk and high-risk patients. Thus, it is difficult to draw definitive conclusions from their results. In fact, while some authors did not report any differences between alloSCT and chemotherapy or autologous SCT (ASCT)(Gupta, et al, Labar, et al), others only found differences favouring allogeneic SCT in standard risk (Goldstone, et al) or high-risk ALL patients (Sebban, et al, Thiebaut, et al, Thomas, et al). In this chapter, the Authors reviewed data concerning alloSCT in adult ALL and discuss current controversial and possible perspectives

Real-world evidence of brexucabtagene autoleucel for the treatment of relapsed or refractory mantle cell lymphoma

Treatment; Mantle cell lymphoma; RelapsedTractament; Limfoma de cèl·lules del mantell; RecaigudaTratamiento; Linfoma de células del manto; Recaíd

Mutational analysis of Peroxiredoxin IV: exclusion of a positional candidate for multinodular goitre

BACKGROUND: Multinodular goitre (MNG) is a common disorder characterised by an enlargement of the thyroid, occurring as a compensatory response to hormonogenesis impairment. The incidence of MNG is dependent on sex (female:male ratio 5:1) and several reports have documented a genetic basis for the disease. Last year we mapped a MNG locus to chromosome Xp22 in a region containing the peroxiredoxin IV (Prx-IV) gene. Since Prx-IV is involved in the removal of H(2)O(2) in thyroid cells, we hypothesize that mutations in Prx-IV gene are involved in pathogenesis of MNG. METHODS: Four individuals (2 affected, 2 unrelated unaffected) were sequenced using automated methods. All individuals were originated from the original three-generation Italian family described in previous studies. A Southern blot analysis using a Prx-IV full-length cDNA as a probe was performed in order to exclude genomic rearrangements and/or intronic mutations. In addition a RT-PCR of PRX-IV was performed in order to investigate expression alterations. RESULTS: No causative mutations were found. Two adjacent nucleotide substitutions were detected within introns 1 and 4. These changes were also detected in unaffected individuals, suggesting that they were innocuous polymorphisms. No gross genomic rearrangements and/or restriction fragment alterations were observed on Southern analysis. Finally, using RT-PCR from tissue-specific RNA, no differences of PRX-IV expression-levels were detected between affected and unaffected samples. CONCLUSIONS: Based on sequence and genomic analysis, Prx-IV is very unlikely to be the MNG2 gene

Infliximab treatment for steroid-refractory acute graft-versus-host disease

Background and Objectives. Tumor necrosis factor \u3b1 is one of the principal cytokines involved in the pathogenesis of acute graft-versus-host- disease (GVHD). Infliximab is an antibody to this cytokine. Design and Methods. We performed a retrospective analysis to evaluate the activity of infliximab in 32 patients with severe steroid-refractory acute GVHD. The patients received a median of 3 weekly courses of infliximab. The main organs involved in the patients were skin (n=2) liver (n=1), bowel (n=19), liver and bowel at the same stage (n=10). Results. Nineteen out 32 patients (59%) responded to infliximab with 6 (19%) complete and 13 (40%) partial responses. Age younger than 35 years, intestinal involvement and a longer time between hematopoietic stem cell transplantation and infliximab administration were factors predicting a favorable response. Infective episodes developed in 23/32 (72%) patients. All the 13 unresponsive patients died of GVHD shortly after infliximab. Thirteen of 19 responsive patients were alive at a median follow-up of 449 days (range 155-842) after infliximab, with no signs of chronic GVHD (n=5), limited (n=5) or extensive involvement (n=3). Six patients who responded subsequently died, one of chronic lung GVHD, the others of vascular complications or infections (2 fungal diseases). Interpretation and Conclusions. We conclude that infliximab is active in the treatment of severe steroid-refractory acute GVHD, particularly when the intestine is involved. Infections commonly followed its administration. The clinical activity of infliximab and the possibility that it increases the risk of infections are worth investigating in prospective trials

Does Cytokine-Release Syndrome Induced by CAR T-Cell Treatment Have an Impact on the Pharmacokinetics of Meropenem and Piperacillin/Tazobactam in Patients with Hematological Malignancies? Findings from an Observational Case-Control Study

Chimeric antigen receptor (CAR) T-cell therapy is a promising approach for some relapse/refractory hematological B-cell malignancies; however, in most patients, cytokine release syndrome (CRS) may occur. CRS is associated with acute kidney injury (AKI) that may affect the pharmacokinetics of some beta-lactams. The aim of this study was to assess whether the pharmacokinetics of meropenem and piperacillin may be affected by CAR T-cell treatment. The study included CAR T-cell treated patients (cases) and oncohematological patients (controls), who were administered 24-h continuous infusion (CI) meropenem or piperacillin/tazobactam, optimized by therapeutic drug monitoring, over a 2-year period. Patient data were retrospectively retrieved and matched on a 1:2 ratio. Beta-lactam clearance (CL) was calculated as CL = daily dose/infusion rate. A total of 38 cases (of whom 14 and 24 were treated with meropenem and piperacillin/tazobactam, respectively) was matched with 76 controls. CRS occurred in 85.7% (12/14) and 95.8% (23/24) of patients treated with meropenem and piperacillin/tazobactam, respectively. CRS-induced AKI was observed in only 1 patient. CL did not differ between cases and controls for both meropenem (11.1 vs. 11.7 L/h, p = 0.835) and piperacillin (14.0 vs. 10.4 L/h, p = 0.074). Our findings suggest that 24-h CI meropenem and piperacillin dosages should not be reduced a priori in CAR T-cell patients experiencing CRS