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The podocyte injury, and consequent proteinuria, that characterize the pathology of idiopathic membranous nephropathy (IMN) is mediated by an autoimmune reaction against podocyte antigens. In particular, the activation of pathways leading to abundant renal deposits of complement is likely to involve the binding of mannose-binding lectin (MBL) to aberrant glycans on immunoglobulins. To obtain a landscape of circulatory IgG Fc glycosylation characterizing this disease, we conducted a systematic N-glycan profiling study of IgG1, 2, and 4 by mass spectrometry. The cohort included 57 IMN patients, a pathological control group with nephrotic syndrome (PN) (n = 20), and 88 healthy control subjects. The effect of sex and age was assessed in all groups and controlled by rigorous matching. Several IgG Fc glycan traits were found to be associated with IMN. Interestingly, among them, only IgG4-related results were specific for IMN and not for PN. Hypo-galactosylation of IgG4, already shown for IMN, was observed to occur in the absence of core fucose, in line with a probable increase of pro-inflammatory IgG. In addition, elevated levels of fucosylated IgG4, along with low levels of hybrid-type glycans, were detected. Some of these IgG4 alterations are likely to be more pronounced in high PLA2R (phospholipase A2 receptor) patients. IgG Fc glycosylation patterns associated with IMN warrant further studies of their role in disease mechanisms and may eventually enrich the diagnostic spectrum regarding patient stratification.

We examined the relationships between the dietary inflammatory index (DII®), dietary habits and cardiovascular risk factor profiles in people with type 2 diabetes mellitus (T2DM). Energy-adjusted DII (E-DII™) scores were calculated from a Food Frequency Questionnaire in 2568 T2DM patients from different parts of Italy. Analyses were conducted according to quartiles of sex-specific E-DII scores. Higher, more pro-inflammatory, (quartile 4) E-DII scores were associated with overall poor quality of the diet characterised by higher content of refined carbohydrates, added sugars, saturated fat and cholesterol and lower unsaturated fat, fibre and polyphenols compared to quartile 1. Higher E-DII scores also were associated with higher waist circumference (105.4 vs. 103.5 cm; p = 0.002), triglycerides (154.6 vs. 146.1 mg/dL; p = 0.005), diastolic blood pressure (80.05 vs. 78.6 mmHg; p = 0.04) and lower HDL-cholesterol (45.3 vs. 47.4 mg/dL; p = 0.04). In conclusion, E-DII is a potent marker of overall quality of the diet and is associated with an unfavourable cardiovascular risk factor profile.

While integrated photonics is a robust platform for quantum information processing, architectures for photonic quantum computing place stringent demands on high quality information carriers. Sources of single photons that are highly indistinguishable and pure, that are either near-deterministic or heralded with high efficiency, and that are suitable for mass-manufacture, have been elusive. Here, we demonstrate on-chip photon sources that simultaneously meet each of these requirements. Our photon sources are fabricated in silicon using mature processes, and exploit a dual-mode pump-delayed excitation scheme to engineer the emission of spectrally pure photon pairs through inter-modal spontaneous four-wave mixing in low-loss spiralled multi-mode waveguides. We simultaneously measure a spectral purity of 0.9904 ± 0.0006, a mutual indistinguishability of 0.987 ± 0.002, and >90% intrinsic heralding efficiency. We measure on-chip quantum interference with a visibility of 0.96 ± 0.02 between heralded photons from different sources., Suitability for large-scale quantum computation imposes severe requirements on single-photon sources in terms of purity, indistinguishability and heralding efficiency. Here, the authors boost all these figures of merit through a dual-mode pump-delayed four-wave mixing scheme in low-loss silicon waveguides.

Le politiche per la salute e sicurezza sul lavoro (SSL) sono raramente oggetto di valutazioni di efficacia. Le ragioni principali sono da ricondursi a problemi empirici e metodologici, alle fonti di dati disponibili, all'assenza di validi modelli. Quantificare l'impatto di interventi complessi esige infatti lo sviluppo di disegni valutativi complessi. L'articolo esplora uno studio di fattibilità per la valutazione dei bandi Isi, la misura di incentivazione che Inail (Istituto Nazionale per l'Assicurazione contro gli Infortuni sul Lavoro) rivolge alle piccole e medie imprese che investono in SSL: dal 2010 sono stati stanziati attraverso Isi oltre 2 miliardi di euro. Nell'articolo si evidenziano le criticità relative alla valutazione dei bandi Isi e si esplora la fattibilità di un disegno controfattuale. Si discutono inoltre strategie per mitigare i relativi rischi e rispondere alla domanda di ricerca "gli incentivi Isi aumentano la salute e la sicurezza sul lavoro?".

Background: There are still open questions with respect to the optimal dietary treatment in patients with type 2 diabetes (T2D) and coexisting non-alcoholic steatohepatitis (NASH). The aim of this study is to investigate, in patients with T2D, the association between NASH, dietary component intake, food groups and adherence to the Mediterranean diet. Methods: Cross-sectional analysis of 2026 people with T2D (1136 men and 890 women). The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. NASH was identified by the Index Of NASH (ION). Based on the cluster analysis two dietary patterns were identified: the NASH and the NO-NASH pattern. Results: The macronutrient composition of the diet was similar in the two patterns. However, the NASH pattern compared with the NO-NASH pattern was characterized by a significantly lower content of fibre (p < 0.001), β-carotene (p < 0.001), vitamin C (p < 0.001), vitamin E (p < 0.001), polyphenols (p = 0.026) and antioxidant capacity (p < 0.001). With regard to food consumption, the NASH pattern compared with NO-NASH pattern was characterized by higher intake of rice (p = 0.021), potatoes (p = 0.013), red (p = 0.004) and processed meat (p = 0.003), and a lower intake of wholegrain bread (p = 0.019), legumes and nuts (p = 0.049), vegetables (p = 0.047), fruits (p = 0.002), white meat (p = 0.001), fatty fish (p = 0.005), milk and yogurt (p < 0.001). Conclusions: NO-NASH dietary pattern was characterized by a food consumption close to the Mediterranean dietary model, resulting in a higher content of polyphenols, vitamins, and fibre. These finding highlight the potential for dietary components in the prevention/treatment of NASH in people with T2D.

Introduction Chest pain and its clinical manifestations are the most common reasons for presentation to the emergency department (ED). Given that the prevalence of chest pain due to acute myocardial infarction (AMI) in the ED is modest, clinicians should use cardiac troponins to safely and rapidly rule out AMI, avoiding the delayed release of low risk patients. The study aims to develop and validate an algorithm to early rule-out of non-ST elevation myocardial infarction (NSTEMI) in subjects admitted to the ED with symptoms of myocardial infarction. Methods High sensitivity cardiac Troponin T (hs-cTnT) serial measurements (baseline, T0; after 1 h, T1; after 3 h, T3) were used to develop and validate the algorithm, respectively, in 6403 and 773 consecutive admissions suggestive of AMI. Results Patients were classified as having or not having NSTEMI according to clinical assessment, diagnostic imaging, and serial measurements ofhs-cTnT; ROC curve analysis allowed to find changes in consecutive hs-cTnT associated with diagnostic sensitivity close to 100%. Only patients with hs-cTnTat T0 lower than 14 ng/L resultedto be eligible for the safe rule-out of NSTEMI. Conclusions Although some points remain to be improved, the results obtained indicate that algorithms for fast NSTEMI rule-out are feasible and safe.

Premesse: In una società che invecchia è sempre più importante per aziende, parti sociali e governi promuovere l’occupabilità sostenibile di tutti i lavoratori. Nella letteratura internazionale, la prima definizione di occupabilità sostenibile è stata proposta da Van der Klink et al.: “Per occupabilità sostenibile si intende quanto i lavoratori, durante tutta la loro vita lavorativa, possano raggiungere condizioni di opportunità reali in termini di ampliamento delle proprie capacità, beneficiandone personalmente e restituendo prestazioni di qualità alle realtà aziendali, ora e nel futuro, salvaguardando nel contempo il proprio benessere e la propria salute” (2015). Hazelzet et al., in un lavoro di revisione della letteratura e riprendendo la definizione di van der Klink et al., hanno individuato quattro componenti chiave o aspetti che rendono un lavoratore occupato in modo sostenibile: la salute (benessere, stile di vita, vitalità), la produttività (engagement, work ability), il lavoro di valore (motivazione, competenze, conoscenze) e la prospettiva di lungo periodo (2019). In Italia, tale costrutto è ancora poco conosciuto, così come agli albori sono gli studi che si propongono di sviluppare strumenti specifici con la finalità di monitorare l’occupabilità sostenibile dei lavoratori (uno di questi strumenti è il Il MAastricht Instrument for Sustainable Employability, MAISE-NL Houkes et al. 2020, MAISE-IT Picco et al. submitted). Obiettivi: Lo studio, in collaborazione tra il Dipartimento di Psicologia dell’Università di Milano-Bicocca e INAIL, si propone di identificare, sviluppare, sperimentare e valutare un modello di occupabilità sostenibile presso un campione di imprese e definire orientamenti per l’implementazione dell’occupabilità sostenibile presso le organizzazioni. In particolare, si svilupperà uno studio quali-quantitativo finalizzato a identificare e analizzare i fattori che determinano l’occupabilità sostenibile, sviluppare un questionario per la sua misurazione e definire orientamenti per innovare l’organizzazione promuovendo l’occupabilità sostenibile. Metodi: La prima fase dello studio prevede lo sviluppo di un nuovo strumento per la valutazione dell’occupabilità sostenibile, partendo dal questionario MAISE-IT (Picco et al. submitted), già presente in italiano, ma la cui prima validazione ha permesso di evidenziare diversi punti migliorabili. Una seconda fase prevederà il reclutamento di aziende in cui verrà sperimentato il processo di valutazione e intervento dell’occupabilità sostenibile. I lavoratori apparterranno ad un gruppo di aziende con un livello di scolarità sufficientemente elevato da comprendere gli obiettivi e i materiali utilizzati nella ricerca. A livello aziendale verranno distribuiti, all’interno di uno studio longitudinale, diversi strumenti quali-quantitativi che analizzeranno i funzionamenti aziendali e dei singoli lavoratori, l’occupabilità sostenibile attraverso la compilazione di un questionario specifico, i fattori individuali e organizzativi che promuovono l’occupabilità sostenibile. I questionari e in generale il processo di valutazione saranno proposti ad un ampio numero di lavoratori e manager e la raccolta dati avverrà online attraverso l’utilizzo di Qualtrics. Al fine di garantire un numero sufficiente di partecipanti allo studio in tutte le fasi di ricerca si ipotizza di invitare a partecipare un campione iniziale di almeno 700 partecipanti. Verrà quindi avviato un processo di analisi dell’organizzazione al fine di definire possibili azioni migliorative. Principali risultati: Sulla base delle premesse teoriche, un primo risultato che ci si aspetta di conseguire, nel lavoro, riguarda lo sviluppo di una nuova versione del MAISE-IT, o di un nuovo strumento che valuti l’occupabilità sostenibile. In particolare, ci si aspetta di verificare la validità di costrutto, la validità di criterio e l’attendibilità del nuovo strumento. Inoltre, ci si aspetta che tale strumento possa mettere in luce quali siano gli aspetti su cui le aziende italiane possono intervenire per migliorare l’occupabilità sostenibile. Successivamente si vogliono generare indicazioni operative per la promozione, a livello aziendale, dell’occupabilità sostenibile ed eventuali linee di intervento.

Single photons for quantum computing should be pure, indistinguishable and available in a large amount on the same chip. By using pump-delayed intermodal spontaneous four wave mixing we demonstrated the first source of heralded single photons meeting all these requirements on a silicon chip.

Microring resonators made of materials with a zinc-blend or diamond lattice allow exploiting their 4-bar symmetry to achieve quasi-phase matching condition for second-order optical nonlinearities. However, fabrication tolerances impose severe limits on the quasi-phase matching condition, which in turn degrades the generation efficiency. Here, we present a method to mitigate these limitations. As an example, we studied the geometry and the pump wavelength conditions to induce the second-harmonic generation in silicon-based microrings with a second-order susceptibility &chi, zxy(2)&ne, 0. We found the best compromises between performances and experimental requirements, and we unveil a strategy to minimize the impacts of fabrication defects. The method can be easily transferred to other material systems.

Single photon sources by heralding time correlated photons are described. By intermodal four wave mixing (FWM) in a silicon photon circuit, we generate a herald photon at 1260 nm and the heralded one beyond 2 um, with a coincidence to accidental ratio larger than 50 and a single photon purity of 0.75. The discrete band intermodal phase matching does not require further filtering to improve the purity of the single photon. Moreover, the intermodal FWM exhibits high controllability of the signal/idler wavelengths, that can be generated far from the Raman and pump noise, with improved noise filtering.

BackgroundIn animal studies, perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters thyroid homoeostasis and thyroid hormone concentrations; epidemiologic evidence is limited.ObjectivesWe aimed to determine the association of prenatal exposure to TCDD with thyroid hormone concentrations in the Seveso Second Generation Study, a unique cohort of children born to TCDD-exposed women resulting from a 1976 chemical factory explosion in Seveso, Italy.MethodsWe included 570 children (288 female, 282 male) with complete follow-up data, including a fasting blood draw. Serum levels of total and free thyroxine (T4), free triiodothyronine (T3), and thyroid stimulating hormone (TSH) were measured using immunoassays. We defined prenatal TCDD exposure as: 1) maternal initial TCDD concentration measured in serum collected soon after the explosion and 2) maternal TCDD estimated at pregnancy.ResultsCompared to the lowest quartile (Q1), maternal initial serum TCDD was associated with lower free T3 (Q2: adj-β=-0.13, 95%CI -0.26, 0.00; Q3: adj-β=-0.22, 95%CI -0.35, -0.09; Q4: adj-β=-0.14, 95%CI -0.28, 0.00; p-trend=0.02). In participants with high thyroid antibody status, inverse associations between maternal initial serum TCDD and free T3 were significantly stronger than in participants with normal antibody status (p-interaction=0.02). We also observed a positive association between maternal initial serum TCDD and TSH concentrations in participants with high thyroid antibody status (Q2: adj-β=11.4%, 95%CI -25.2, 66.1; Q3: adj-β=49.0%, 95%CI 3.0, 115.5; Q4: adj-β=105.5, 95%CI 36.6, 209.2; p-trend&nbsp

We develop integrated spontaneous photon sources in silicon photonics simultaneously satisfying all requirements for large-scale photonic quantum computing: 0:9904 ± 0:0006 spectral purity, 0:985 ± 0:002 indistinguishability, > 90% heralding efficiency, and 0:96 ± 0:02 on-chip heralded quantum interference visibility.

Heterogeneous results have been obtained in the relationship between serum uric acid (SUA) and target organ damage (TOD) in patients with hypertension. Clinic blood pressure, SUA, and cardiac, arterial (carotid and aortic), and renal TOD were assessed in 762 consecutive patients with hypertension. Hyperuricemia was defined as an SUA >7.0 in men and >6.0mg/dL in women. Men with hyperuricemia compared with those with normal SUA showed lower estimated glomerular filtration rates and E/A ratios and a higher prevalence of carotid plaques. Women with hyperuricemia showed lower estimated glomerular filtration rates and E/A ratios and a higher intima-media thickness. Except for pulse wave velocity, all TODs significantly correlated with SUA. However, at multivariate analysis, only estimated glomerular filtration rate was significantly determined by SUA. Our data provide evidence on the role of SUA in the development of TOD only in the case of renal alteration. It is likely that SUA may indirectly act on the other TODs through the increase in blood pressure and the decrease in glomerular filtration rate

Background/objectives In utero exposure to endocrine-disrupting compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may alter risk of obesity and related metabolic disease later in life. We examined the relationship of prenatal exposure to TCDD with obesity and metabolic syndrome (MetS) in children born to a unique cohort of TCDD-exposed women resulting from a 1976 explosion in Seveso, Italy. Subjects/methods In 2014, nearly 40 years after the explosion, we enrolled 611 post-explosion offspring, 2 to 39 years of age, in the Seveso Second Generation Study. In utero TCDD exposure was defined primarily as TCDD concentration measured in maternal serum collected soon after the explosion and alternately as TCDD estimated at pregnancy. We measured height, weight, waist circumference, body fat, blood pressure, and fasting blood levels of lipids and glucose, which were combined to assess body mass index (BMI) and MetS. Results Children (314 female, 297 male) averaged 23.6 (±6.0) years of age. Among the 431 children ≥18 years, a 10-fold increase in initial maternal TCDD concentration was inversely associated with BMI in daughters (adj-β = -0.99 kg/m2; 95% CI -1.86, -0.12), but not sons (adj-β = 0.41 kg/m2; 95% CI -0.35, 1.18) (p-int = 0.02). A similar relationship was found in the younger children (2-17 years); a 10-fold increase in initial maternal TCDD was inversely associated with BMI z-score (adj-β = -0.59 kg/m2; 95% CI -1.12, -0.06) among daughters, but not sons (adj-β = 0.04 kg/m2; 95% CI -0.34, 0.41) (p-int = 0.03). In contrast, in sons only, initial maternal TCDD was associated with increased risk for MetS (adj-RR = 2.09, 95% CI 1.09, 4.02). Results for TCDD estimated at pregnancy were comparable. Conclusions These results suggest prenatal TCDD exposure alters cardiometabolic endpoints in a sex-specific manner. In daughters, in utero TCDD is inversely associated with adiposity measures. In sons, in utero TCDD is associated with increased risk for MetS.

We design, fabricate and test an integrated silicon photonics chip for inter-modal four wave mixing, whose phase-matching relays on the modal dispersions of different waveguide modes. This phase-matching technique allows for tunable and broadband wavelength conversion and generation. We demonstrate that idler and signal photons can be generated with 800 nm spectral distance in between. We measure several inter-modal combinations, with up to the third order mode involvement. We demonstrate a maximum conversion efficiency of -12.4 dB from 1468.5 nm to 1641.1 nm with a bandwidth of 11 nm. We also prove the high and broadband tunability of the generated signal by scanning the pump wavelength when the signal wavelength is fixed. All these features make the inter-modal four wave mixing a viable solution for all optical processing in the near as well as in the mid infrared and for quantum applications.

Background: Exposure to endocrine disrupting compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during susceptible developmental windows may alter risk of metabolic disease later in life. Animal studies of in utero and lactational TCDD exposure report associations with alterations in insulin sensitivity and energy homeostasis, but epidemiologic evidence is limited. We examined the relationship of prenatal TCDD exposure with markers of glucose homeostasis in the Seveso Second Generation study, a unique cohort of children born to TCDD-exposed women resulting from a 1976 explosion in Seveso, Italy. Methods: We included 426 children who were 18 years or older with complete follow-up data including a fasting blood draw. Insulin and glucose were measured and the updated homoeostatic model assessment was used to estimate insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B). Prenatal TCDD exposure was defined in two ways, as initial maternal serum TCDD concentration and TCDD estimated at pregnancy. Results: The children (222 female, 204 male) averaged 28.6 (±6.0) years. We found a 10-fold increase in TCDD estimated at pregnancy was inversely associated with insulin (adj-β = −1.24 μIU/mL, 95% confidence interval (CI): −2.38, −0.09) and HOMA2-B (adj-β = −10.2% decrease, 95% CI: −17.8, −1.9) among daughters, but not sons (insulin: adj-β = 0.57 μIU/mL, 95% CI: −0.84, 1.98, P for interaction = 0.04; and HOMA2-B: adj-β = 0.8% increase, 95% CI −10.7, 13.9, P for interaction = 0.11). Similar effect modification was observed for TCDD estimated at pregnancy and HOMA2-IR (P for interaction = 0.13). The models for initial maternal serum TCDD showed similar effect modification by child sex. The observed associations in daughters showed evidence of mediation by body mass index, which we have previously found to be associated with prenatal TCDD exposure in female offspring. Conclusion: These results suggest prenatal exposure to TCDD is associated with lower insulin resistance and beta compensation in female offspring, and show evidence of mediation by body mass index. Keywords: Dioxin, Glucose metabolism markers, 2,3,7,8-Tetrachlorodibenzo-p-dioxin, TCDD, Seveso, Insulin

Background Prenatal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure has been shown to alter sexual differentiation of the brain in animal models, impacting pubertal development, behavior, cortical dominance, and cognition. The effects of early life exposure to dioxin-like compounds on human neurodevelopment, however, are less clear and warrant further investigation. Methods The Seveso Women's Health Study (SWHS), initiated in 1996, is a well-characterized cohort of 981 Italian women who lived in proximity to an industrial accident in July 1976 that resulted in one of the highest residential TCDD exposures on record. In 2014–2016, we enrolled offspring born after the accident into the Seveso Second Generation Health Study. Children aged 7–17 years old (n = 161) completed a neuropsychological assessment spanning executive function and reverse learning (Wisconsin Card Sort), non-verbal intelligence (Raven's Progressive Matrices), attention and hyperactivity (Connor's Continuous Performance (CPT), and memory (Rey's Auditory Verbal Learning). We used multivariate regression with robust standard error estimates accounting for clustering of siblings to model the associations between these outcomes and prenatal exposure defined as TCDD measured in maternal serum collected soon after the explosion and estimated to pregnancy. Results The children (82 male, 79 female) averaged 13.1 (±2.9) years of age. Adjusting for covariates, a 10-fold increase in maternal serum TCDD was not adversely associated with reverse learning/set-shifting, memory, attention/impulsivity, or non-verbal intelligence. In sex-stratified models, prenatal TCDD was associated with more non-perseverative errors in boys but not in girls (pint = 0.04). TCDD was also associated with attention deficits on the CPT but only among children with the shortest breastfeeding histories. Conclusions While overall, there were no significant associations, the observed differential neurotoxic sensitivities to TCDD by sex and lactation history may warrant confirmation in future studies.

We generate correlated photons with 600 nm spectral distance via intermodal four wave mixing in silicon. We want to demonstrate on-silicon-chip heralded single photons, beyond 2 µm, without post spectral filtering.

L'Agenzia europea per la sicurezza e la salute sul lavoro (Eu-Osha) "Priorities for OSH research in Europe: 2013 - 2020" sottolinea come lo sviluppo, l'implementazione degli interventi di salute e sicurezza sul lavoro (SSL) a tutti i livelli, compresi i programmi, le politiche in materia di SSL e gli effetti conseguenti prodotti, non vengono valutati usando rigorosi criteri di ricerca basati sull'evidenza scientifica, riscontrando una mancanza di una ricerca-intervento di qualità in materia di SSL. Tra i programmi rientrano gli incentivi economici la cui erogazione è normata dal d.lgs. 81/2008, articolo 11 "Attività promozionali", che demanda a diversi soggetti pubblici l'erogazione di finanziamenti in favore di piccole, medie e micro imprese (PMI) per la realizzazione di progetti d'investimento in materia di salute e sicurezza sul lavoro. Il più importate intervento, per estensione dei beneficiari e per importi erogati, è quello dell'Inail che dal 2010 ad oggi ha finanziato progetti per circa 2 miliardi di euro e che va sotto il nome di "bandi ISI". Fino a oggi gli aspetti valutativi messi in atto da Inail, relativi ai finanziamenti, hanno prevalentemente riguardato i processi gestionali, il controllo delle prestazioni e la rendicontazione delle azioni intraprese e solo più recentemente è emersa la necessità, al fine di migliorarne l'efficacia, di valutare ex-post quali effetti gli interventi medesimi abbiano prodotto. L'Inail, pertanto, ha inteso programmare nel proprio Piano di attività della ricerca uno specifico studio che ha come obiettivi l'identificazione di modelli appropriati per la valutazione dell'impatto degli incentivi e, attraverso l'analisi degli esiti, l'evidenziazione dei punti di forza e di criticità degli interventi di sostegno economico alla PMI. Con il presente contributo, dopo un inquadramento dello strumento degli incentivi alle imprese nell'ambito complessivo delle politiche per la sicurezza e la salute sui luoghi di lavoro, si intende dunque presentare una panoramica ragionata dei principali aspetti teorici e metodologici da considerare nella valutazione delle politiche per la sicurezza sul lavoro. Tale inquadramento è fondamentale perché l'argomento è poco affrontato dalla letteratura, sia nazionale sia internazionale, e sono altresì poco diffusi gli studi su questo tema. In particolare, si rifletterà sui disegni valutativi più adeguati per rispondere alle domande valutative e sulle problematiche metodologiche che ne conseguono (es. validità interna ed esterna della valutazione, fattibilità di una valutazione basata solo su dati amministrativi), apportando anche alcuni primi riscontri concreti derivanti dall'indagine sulla valutazione dei Bandi ISI realizzata attraverso indagine sul campo e attualmente in corso.

Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol

The role of uric acid (UA) on the arterial stiffness progression has been evaluated only in three studies. Our aim was to evaluate its role as a possible determinant of the pulse wave velocity (PWV) progression over a 3.7 ± 0.5 years follow-up period in hypertensive patients. Specific sex analysis was done due to the well-known sex interaction with UA levels. We enrolled 422 consecutive hypertensive outpatients. At baseline anamnestic, blood pressure (BP) and laboratory data as well as PWV were assessed. PWV was performed again at follow-up examination. Hyperuricemia was defined as a UA > 6 mg/dL for women and > 7 mg/dL for men. Baseline age was 53.2 ± 13 years, 58% were males, systolic and diastolic BP (SBP/DBP) 141.7 ± 17.7/86.8 ± 10.8 mm Hg, UA 5.2 ± 1.4 mg/dL, and PWV 8.5 ± 1.9 m/s. At follow-up, despite better BP values (-8.5 ± 24.6 for SBP and -7.5 ± 15.4 for DBP), PWV increases to 9.1 ± 2.3 m/s (P

L'Agenzia europea per la sicurezza e la salute sul lavoro (Eu-Osha) "Priorities for OSH research in Europe: 2013 - 2020" sottolinea come lo sviluppo, l'implementazione degli interventi di salute e sicurezza sul lavoro (SSL) a tutti i livelli, compresi i programmi, le politiche in materia di SSL e gli effetti conseguenti prodotti, non vengono valutati usando rigorosi criteri di ricerca basati sull'evidenza scientifica, riscontrando una mancanza di una ricerca-intervento di qualità in materia di SSL. Tra i programmi rientrano gli incentivi economici la cui erogazione è normata dal d.lgs. 81/2008, articolo 11 "Attività promozionali", che demanda a diversi soggetti pubblici l'erogazione di finanziamenti in favore di piccole, medie e micro imprese (PMI) per la realizzazione di progetti d'investimento in materia di salute e sicurezza sul lavoro. Il più importate intervento, per estensione dei beneficiari e per importi erogati, è quello dell'Inail che dal 2010 ad oggi ha finanziato progetti per circa 2 miliardi di euro e che va sotto il nome di "Bandi Isi". Fino a oggi gli aspetti valutativi messi in atto da Inail, relativi ai finanziamenti, hanno prevalentemente riguardato i processi gestionali, il controllo delle prestazioni e la rendicontazione delle azioni intraprese e solo più recentemente è emersa la necessità, al fine di migliorarne l'efficacia, di valutare ex-post quali effetti gli interventi medesimi abbiano prodotto. L'Inail, pertanto, ha inteso programmare nel proprio Piano di attività della ricerca uno specifico studio che ha come obiettivi l'identificazione di modelli appropriati per la valutazione dell'impatto degli incentivi e, attraverso l'analisi degli esiti, l'evidenziazione dei punti di forza e di criticità degli interventi di sostegno economico alla PMI. Con il presente contributo, dopo un inquadramento dello strumento degli incentivi alle imprese nell'ambito complessivo delle politiche per la sicurezza e la salute sui luoghi di lavoro, si intende dunque presentare una panoramica ragionata dei principali aspetti teorici e metodologici da considerare nella valutazione delle politiche per la sicurezza sul lavoro. Tale inquadramento è fondamentale perché l'argomento è poco affrontato dalla letteratura, sia nazionale sia internazionale, e sono altresì poco diffusi gli studi su questo tema. In particolare, si rifletterà sui disegni valutativi più adeguati per rispondere alle domande valutative e sulle problematiche metodologiche che ne conseguono (es. validità interna ed esterna della valutazione, fattibilità di una valutazione basata solo su dati amministrativi), apportando anche alcuni primi riscontri concreti derivanti dall'indagine sulla valutazione dei Bandi Isi realizzata attraverso indagine sul campo e attualmente in corso.

BACKGROUND: 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is proposed to interfere with fetal growth via altered activity of the aryl hydrocarbon receptor (protein: AHR; gene: AHR) pathway which regulates diverse biological and developmental processes including xenobiotic metabolism. Genetic variation in AHR is an important driver of susceptibility to low birthweight in children exposed to prenatal smoking, but less is known about these genetic interactions with TCDD, AHR’s most potent xenobiotic ligand. METHODS: The Seveso Women’s Health Study (SWHS), initiated in 1996, is a cohort of 981 Italian women exposed to TCDD from an industrial explosion in July 1976. We measured TCDD concentrations in maternal serum collected close to the time of the accident. In 2008 and 2014, we followed up the SWHS cohort and collected data on birth outcomes of SWHS women with post-accident pregnancies. We genotyped 19 single nucleotide polymorphisms (SNPs) in AHR among the 574 SWHS mothers. RESULTS: Among 901 singleton births, neither SNPs nor TCDD exposure alone were significantly associated with birthweight. However, we found six individual SNPs in AHR which adversely modified the association between maternal TCDD and birthweight, implicating gene-environment interaction. We saw an even stronger susceptibility to TCDD due to interaction when we examined the joint contribution of these SNPs in a risk allele score. These SNPs were all located in noncoding regions of AHR, particularly in proximity to the promoter. CONCLUSIONS: This is the first study to demonstrate that genetic variation across the maternal AHR gene may shape fetal susceptibilities to TCDD exposure.

On-chip heralded single photon sources are of key importance in the development of chip-scale devices exploiting the quantum properties of light. Single photon states can be produced as single photons heralded from correlated photon pairs generated through spontaneous four wave mixing. On-chip heralded single photon sources based on spontaneous four wave mixing have been already demonstrated. However, the heralded and herald photons are usually generated with wavelengths very close to the pump one, limiting the pump rejection efficiency and the application to the mid infrared. Moreover, the common sources of heralded photons based on spontaneous four wave mixing require spectral post filtering to achieve high purity, limiting the brightness and the integration of these sources. A solution to these problems can be provided by intermodal four wave mixing. In this work, we demonstrate the generation of photon pairs through intermodal four wave mixing in silicon waveguides, measuring the coincidences between the idler at 1.281 μm and the signal at 1.952 μm. We then discuss the application of intermodal four wave mixing to on-chip heralded single photon sources.

Silicon photonics is currently moving towards the Mid Infrared (MIR), which attracts plenty of emerging technologies, from integrated spectroscopy to quantum communications. However, the development of MIR-photonics is hindered by the lack of efficient detectors and light sources. A possible solution could be an integrated system able to link the MIR with the near infrared, where detectors and light sources have been already developed for telecommunications. Because of this, the possibility to perform broad and tunable wavelength conversion and generation is of great interest. In particular, the generation and conversion can be accomplished by means of Four Wave Mixing (FWM), a nonlinear optical process in which two input pump photons are converted into signal and idler photons of different frequency. Crucial for efficient FWM is the phase matching condition, which determines the spectral position of the maximum efficiency of the process. In order to achieve large spectral translation between signal and idler, we propose to use Intermodal FWM (IMFWM), which exploits the dispersion of the higher order waveguide modes to achieve the phase matching condition. In IMFWM, the pump, signal and idler propagate on different waveguide modes. With respect to common phase matching techniques, IMFWM does not require anomalous GVD, resulting in an easier handling of the phase matching condition. Moreover, due to the sensitivity of the higher order mode dispersion with the waveguide geometry, the spectral position of the intermodal phase matching can be easily tuned by engineering the waveguide cross-section, achieving also large detunings from the pump wavelength. Another advantage is the high tolerance to the fabrication defects, related to the large widths of the multimode waveguides used. In our work, we report the first experimental demonstration of spontaneous and stimulated on-chip IMFWM using Silicon-On-Insulator (SOI) channel multimode waveguides. We used a pulsed pump laser at 1550 nm with 10 MHz repetition rate and 40 ps pulse width. The excitation of the higher order modes is attained by displacing horizontally the input tapered lensed fiber with respect to the center of the waveguide facet. We investigated an intermodal combination involving the pump injected on both the first and second order modes, the signal on the second order mode and the idler on the first order mode, with transverse electric polarization. We used a 3.8-um-wide waveguide, of 1.5 cm length, to perform a spectral conversion of 140 nm with -21 dB efficiency. With the same waveguide, we measured -85 dB between the pump and the spontaneously generated idler. The coupled peak pump power was about 2 W. We then measured the spectral position of the idler as a function of the waveguide width, achieving a maximum wavelength detuning between the idler and the signal wavelengths of 861 nm in a 2-um-wide waveguide, corresponding to the generation of 1231 nm idler and 2092 nm signal. IMFWM enables effective and viable wavelength conversion and generation. It also promotes the development of emerging technologies, like mode division multiplexing and modal quantum interference, whose working principle relies on the higher order waveguide modes.

Background/Aim: In animal studies, maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with decreased fertility in offspring. The Seveso Women’s Health Study (SWHS) of wom...

The possibility to perform broad wavelength generation and conversion is of great interest in classical and quantum optics. With the introduction of integrated nonlinear silicon photonics, these tasks have been made even more viable thanks to the combination of the high nonlinear refractive index of silicon with the high confinement provided by the photonic waveguides. Exploiting this platform, several solutions for wavelength conversion have been investigated, for both optical processing [1] and applications in the Mid Infrared (MIR) [2]. The possibility to perform broad and controllable wavelength generation can be exploited also for creating integrated sources of quantum states of light based on single photons [3] or correlated photon pairs [4]. Both the generation and conversion can be accomplished by means of Four Wave Mixing (FWM). FWM is a nonlinear optical process in which two pump photons at frequency are converted into signal and idler photons at frequencies and ω/ respectively (with ω I /ω S ). In the particular case of wavelength conversion, FWM is stimulated by a seed wave at the same wavelength of the signal (idler) that will be converted to the wavelength of the idler (signal). FWM has to satisfy the energy conservation, according to which the relation ω P + ω P = ω S + ω I holds, and its efficiency is ruled by the phase matching condition. This latter condition is related to the phase mismatch among the waves involved in the FWM process, that is evaluated as Δk = k p + k p −k S −k I , where k P , k S , k I are the wavevectors for the pump, the signal and the idler, respectively. When Δk = 0, the phase matching condition is fulfilled and the efficiency of FWM is maximized. What is important for wavelength generation and conversion is the spectral position of the phase matching condition, which determines the wavelength at which the maximum efficiency of the conversion or generation process is achieved. Because of this, techniques for the control of the phase matching condition have been developed, focusing on the possibility to tailor the Group Velocity Dispersion (GVD) through a proper engineering of the waveguide geometry [5]. While these techniques consider only the first order waveguide mode, here we propose to exploit the higher order modes propagating inside a multimode waveguide. The dispersion of the higher order modes can be used to tune the spectral position of the phase matching condition for the FWM process, achieving controllable and large spectral translation in both Stimulated Four Wave Mixing (sFWM) and Spontaneous Four Wave Mixing (SFWM).

Objectives This study aimed to identify patient characteristics associated with low urinary creatinine in morning spot urine and investigate its association with clinical outcome. Background Twenty-four-hour creatinine excretion is an established marker of muscle mass in heart failure and other populations. Spot urine creatinine might be an easy obtainable, cheap marker of muscle wasting and prognosis in heart failure (HF) patients.Methods Spot urine creatinine concentration was measured in 2130 patients included in the GISSI-HF trial. We evaluated the prognostic value of urinary creatinine and its relation with clinical variables.Results Median spot urinary creatinine was 0.80 (IQR 0.50-1.10) g/L. Lower spot urinary creatinine was associated with older age, smaller height and weight, higher NYHA class, worse renal function and more frequent spironolactone and diuretic use (all P Conclusion Lower urinary creatinine, measured in morning spot urine in patients with chronic HF, is associated with worse renal function, smaller body size, more severe HF and is independently associated with an increased risk of all -cause death and HF hospitalization.

Aims: As promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the need for a precise characterization and comparability of the Lp(a)-associated cardiovascular risk is increasing. Therefore, we aimed to evaluate the distribution of Lp(a) concentrations across the European population, to characterize the association with cardiovascular outcomes and to provide high comparability of the Lp(a)-associated cardiovascular risk by use of centrally determined Lp(a) concentrations. Methods and results: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 56 804 participants from 7 prospective population-based cohorts across Europe with a maximum follow-up of 24 years. All Lp(a) measurements were performed in the central BiomarCaRE laboratory (Biokit Quantia Lp(a)-Test; Abbott Diagnostics). The three endpoints considered were incident major coronary events (MCE), incident cardiovascular disease (CVD) events, and total mortality. We found lower Lp(a) levels in Northern European cohorts (median 4.9 mg/dL) compared to central (median 7.9 mg/dL) and Southern European cohorts (10.9 mg/dL) (Jonckheere-Terpstra test P&thinsp

Chest pain is one of the most frequent reasons for presentation to the emergency department (ED), although the estimated prevalence of AMI (acute myocardial infarction) in the ED is about 4%. One criterion for diagnosis of AMI is the demonstration of a rise and/or fall in cardiac troponins, but time is needed for this to happen. Thus, the use of an additional ‘early marker’ of cardiac injury may aid to exclude AMI rapidly. The aim of the study was to evaluate the possibility of excluding AMI with the determination of heart-type fatty acid-binding protein (H-FABP) on baseline samples of patients referring to the ED for chest pain. 26 AMI patients and 41 non-AMI comparisons were included in the study. Both H-FABP and high sensitivity cardiac troponin T (hs-cTnT) were measured in baseline samples from these subjects. H-FABP had a negative predictive value of 100%, thus indicating the possibility of its usage in a rule-out strategy for AMI in ED for patients presenting with chest pain.