A firm level perspective on migration: the role of extra-EU workers in Italian manufacturing

A production-theory approach to migration is adopted in this paper to address the role of migrant workers from extra-EU countries in Italian manufacturing firms. The adoption of flexible functional forms to model firm-level technology lets us directly derive different measures of elasticity from the coefficients of the estimated production and cost functions. The use of foreign labour is shown to affect the industry composition in favour of low skill intensive sectors and the estimated cross demand elasticities confirm the complementarity between migrant and native workers found in previous studies. However, the two labour inputs prove to be substitutes in terms of the Morishima elasticity of substitution: in general, firms tend to increase the foreign labour intensity of production in response to a decline in migrants’ wage, while the migrant to domestic labour ratio responds to changes in the domestic workers’ wage only for firms in low skill intensive sectors

Morpho-molecular traits of Indo-Pacific and Caribbean <i>Halofolliculina </i>ciliate infections

Coral diseases are emerging as a major threat to coral reefs worldwide, and although many of them have been described, knowledge on their epizootiology is still limited. This is the case of the Halofolliculina ciliate infections, recognized as the skeletal eroding band (SEB) and Caribbean ciliate infection (CCI), two diseases caused by ciliates belonging to the genus Halofolliculina (Class Heterotrichea). Despite their similar macroscopic appearance, the two diseases are considered different and their pathogens have been hypothesized to belong to different Halofolliculina species. In this work, we analysed the morphology and genetic diversity of Halofolliculina ciliates collected in the Caribbean Sea, Red Sea and Indo-Pacific Ocean. Our analyses showed a strong macroscopic similarity of the lesions and similar settlement patterns of the halofolliculinids from the collection localities. In particular, the unique erosion patterns typical of the SEB were observed also in the Caribbean corals. Fine-scale morphological and morphometric examinations revealed a common phenotype in all analysed ciliates, unequivocally identified as Halofolliculina corallasia. Phylogenetic analyses based on nuclear and mitochondrial (COI) molecular markers consistently found all samples as monophyletic. However, although the nuclear marker displayed an extremely low intra-specific diversity, consistent with the morphological recognition of a single species, the analyses based on COI showed a certain level of divergence between samples from different localities. Genetic distances between localities fall within the intra-specific range found in other heterotrich ciliates, but they may also suggest the presence of a H. corallasia species complex. In conclusion, the presented morpho-molecular characterization of Halofolliculina reveals strong similarities between the pathogens causing SEB and CCI and call for further detailed studies about the distinction of these two coral diseases

Correlation between B7-H4 and Survival of Non-Small-Cell Lung Cancer Patients Treated with Nivolumab

Reliable predictors of benefit from immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are still limited. We aimed to evaluate the association between the expression of selected molecules involved in immune response and clinical outcomes in NSCLC patients receiving nivolumab. In our study, the outcomes of 46 NSCLC patients treated with nivolumab in second or subsequent lines (Nivolumab Cohort) were compared with the expression of PD-L1, PD-L2, PD-1, B7-H3, and B7-H4 assessed by immunohistochemistry (IHC). Samples from 17 patients (37.0%) in the Nivolumab Cohort were positive for B7-H4 expression. At univariate analyses, only B7-H4 expression was associated with significantly decreased progression-free survival (PFS; 1.7 vs. 2.0 months; p = 0.026) and with a disadvantage in terms of overall survival (OS) close to statistical significance (4.4 vs. 9.8 months; p = 0.064). At multivariate analyses, B7-H4 expression was significantly associated with decreased PFS (hazard ratio (HR) = 2.28; p = 0.021) and OS (HR = 2.38; p = 0.022). Subsequently, B7-H4 expression was compared with clinical outcomes of 27 NSCLC patients receiving platinum-based chemotherapy (Chemotherapy Cohort), but no significant association was observed. Our results suggest a negative predictive role of B7-H4 in a population of NSCLC treated with immune checkpoint inhibitors, which deserves further research

Mannose as a biomarker of coronary artery disease: Angiographic evidence and clinical significance

Background High mannose has previously associated with insulin resistance and cardiovascular disease (CVD). Our objective is to establish whether mannose is associated with anatomical evidence of coronary artery disease (CAD). Methods Plasma mannose concentrations were measured by liquid chromatography/tandem mass spectrometry in a discovery cohort (n = 513) and a validation cohort (n = 221) of carefully phenotyped individuals. In both cohorts CAD was quantitated using state-of-the-art imaging techniques (coronary computed coronary tomography angiography (CCTA), invasive coronary angiography and optical coherence tomography). Information on subsequent CVD events/death was collected. Associations of mannose with angiographic variables and biomarkers were tested using univariate and multivariate regression models. Survival analysis was performed using the Kaplan-Meier estimator. Results Mannose was related to indices of CAD and features of plaque vulnerability. In the discovery cohort, mannose was a marker of quantity and quality of CCTA-proven CAD and subjects with a mannose level in the top quartile had a significantly higher risk of CVD events/death (p = 3.6e-5). In the validation cohort, mannose was significantly associated with fibrous cap thickness &lt; 65 \u3bcm (odds ratio = 1.32 per each 10 \u3bcmol/L mannose change [95% confidence interval, 1.05\u20131.65]) and was an independent predictor of death (hazard ratio for mannose 65vs &lt; 84.6 \u3bcmol/L: 4.0(95%CI, 1.4\u201311.3), p = 0.006)

Su alcuni punti nodali della questione ucraina (XIX-XXI secolo)

The chapter analyses the \u201cUkrainian Question\u201d, through examples of old and new analyses on Ukrainian identity, starting from an essay written by the British historian A.J. Toynbee in 1916, when the result of the WW1 and the future of Ukraine was still uncertain. Toynbee\u2019s assumptions are compared with interpretations given by various authors from 19th up to 21st centuries, showing that the crux of the matter is still debated by conteporary analysts. In conclusion, it is expressed the hope that the new presidency could take significant steps in order to consolidate the Ukrainian sovereignity in a peaceful perspective of democratic development

A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes: a multicentre, observational cohort study

Background Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. Methods In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Dusseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. Findings The study included 7792 (58middot7%) men and 5492 (41middot3%) women. 10 906 (82middot1%) patients were White, and race was not reported for 2378 (17middot9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p<0middot0001 in both cohorts; DDX41 not available in the EuroMDS cohort vs p=0middot0062 in the IWG-PM cohort; IDH2 p<0middot0001 in EuroMDS vs p=0middot042 in IWG-PM; TET2 p=0middot031 vs p=0middot035; U2AF1 p=0middot033 vs p<0middot0001) and mutations in two genes were enriched in women (DNMT3A p<0middot0001 in EuroMDS vs p=0middot011 in IWG-PM; TP53 p=0middot030 vs p=0middot037). Additionally, sex biases were observed in co-mutational pathways of founding genomic lesions (splicing-related genes, predominantly in men, p<0middot0001 in both the EuroMDS and IWG-PM cohorts), in DNA methylation (predominantly in men, p=0middot046 in EuroMDS vs p<0middot0001 in IWG-PM), and TP53 mutational pathways (predominantly in women, p=0middot0073 in EuroMDS vs p<0middot0001 in IWG-PM). In the retrospective EuroMDS cohort, men had worse median overall survival (81middot3 months, 95% CI 70middot4-95middot0 in men vs 123middot5 months, 104middot5-127middot5 in women; hazard ratio [HR] 1middot40, 95% CI 1middot26-1middot52; p<0middot0001). This result was confirmed in the prospective validation cohorts (median overall survival was 54middot7 months, 95% CI 52middot4-59middot1 in men vs 74middot4 months, 69middot3-81middot2 in women; HR 1middot30, 95% CI 1middot23-1middot35; p<0middot0001 in the GEMSD MDS registry; 40middot0 months, 95% CI 33middot4-43middot7 in men vs 54middot2 months, 38middot6-63middot8 in women; HR 1middot23, 95% CI 1middot08-1middot36; p<0middot0001 in the Dusseldorf MDS registry). We developed new personalised prognostic tools that included sex information (the sex-informed prognostic scoring system and the sex-informed genomic scoring system). Sex maintained independent prognostic power in all prognostic systems; the highest performance was observed in the model that included both sex and genomic information. A five-to-five mapping between the IPSS-R and new score categories resulted in the re-stratification of 871 (43middot0%) of 2025 patients from the EuroMDS cohort and 1003 (42middot0%) of 2387 patients from the IWG-PM cohort by using the sex-informed prognostic scoring system, and of 1134 (56middot0%) patients from the EuroMDS cohort and 1265 (53middot0%) patients from the IWG-PM cohort by using the sex-informed genomic scoring system. We created a web portal that enables outcome predictions based on a sex-informed personalised approach. Interpretation Our results suggest that a sex-informed approach can improve the personalised decision making process in patients with myelodysplastic syndromes and should be considered in the design of clinical trials including low-risk patients. Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Effect of avalanche frequency on forest ecosystem services in a spruce–fir mountain forest

Mountain forests provide important ecosystem services, such as protection against natural hazards, carbon sequestration, and plant and animal biodiversity. Natural disturbances occurring in forests can alter the provision of ecosystem services to local and offsite communities, but their influence on multiple service tradeoffs has rarely been analyzed. Our aim is to analyze the effect of avalanche frequency on the provision of ecosystem services in a mountain forest in the Italian Alps. We sampled tree and understory vegetation, soil carbon, and intensity of the browsing damage at 10 plots at each of the following observation sites: (1) an active avalanche track (“recent disturbance”), (2) an area last disturbed in 1959 by avalanches (“old disturbance”), occupied now by a dense aspen forest, and (3) the regularly managed spruce–fir stand (“control”). We computed metrics of plant diversity (Shannon and evenness indices), aboveground and belowground carbon stocks, and a browsing index on regeneration and shrubs as a proxy for ungulate habitat. Finally, we assessed the ability of forests in each site to mitigate rockfall hazard. In our study, higher avalanche frequency was associated with lower carbon stock, higher species diversity, and lower protection against rockfall. Of all species found in the avalanche track, 54% were exclusive to that site. After 50 years, the post-disturbance stand provided a very high protection effect against rockfall, but was temporarily unsuitable for wild ungulate habitat, due to the high tree density and lack of open areas. Species richness and diversity were lower in older than in more recently disturbed sites, and not significantly different than the control stand. The control stand fulfilled the requirements for minimal protection against rockfall, but may lose its effectiveness in the near future due to senescence or disturbance-related mortality of canopy trees. Elucidating the tradeoffs between ecosystem services and disturbance frequency will support managers in planning management actions (e.g., avalanche protection measures), and assess tradeoffs between the need to mitigate risks in the most vulnerable areas and the opportunity to improve the provision of ecosystem services where some disturbance can be allowed to occur