Long term effect of air pollution on incident hospital admissions: Results from the Italian Longitudinal Study within LIFE MED HISS project

Background: The LIFE MED HISS project aims at setting up a surveillance system on the long term effects of air pollution on health, using data from National Health Interview Surveys and other currently available sources of information in most European countries. Few studies assessed the long term effect of air pollution on hospital admissions in European cohorts. Objective: The objective of this paper is to estimate the long term effect of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) on first-ever (incident) cause-specific hospitalizations in Italy. Methods: We used data from the Italian Longitudinal Study (ILS), a cohort study based on the 1999–2000 National Health Interview Survey (NHIS), followed up for hospitalization (2001–2008) at individual level. The survey contains information on crucial potential confounders: occupational/educational/marital status, body mass index (BMI), smoking habit and physical activity. Annual mean exposure to PM2.5 and NO2 was assigned starting from simulated gridded data at spatial resolution of 4 × 4 km2 firstly integrated with data from monitoring stations and then up-scaled at municipality level. Statistical analyses were conducted using Cox proportional hazard models with robust variance estimator. Results: For each cause of hospitalization we estimated the hazard ratios (HRs) adjusted for confounders with 95% Confidence Interval (CI) related to a 10 μg/m3 increase in pollutants. For PM2.5 and NO2, respectively, we found positive associations for circulatory system diseases [1.05(1.03–1.06); 1.05(1.03–1.07)], myocardial infarction [1.15(1.12–1.18); 1.15(1.12–1.18)], lung cancer [1.18(1.10–1.26); 1.20(1.12–1.28)], kidney cancer [1.24(1.11–1.29); 1.20(1.07–1.33)], all cancers (but lung) [1.06(1.04–1.08); 1.06(1.04–1.08)] and Low Respiratory Tract Infections (LRTI) [1.07 (1.04–1.11); 1.05 (1.02–1.08)]. Discussion: Our results add new evidence on the effects of air pollution on first-ever (incident) hospitalizations, both in urban and rural areas. We demonstrated the feasibility of a low-cost monitoring system based on available data

Mystery Solved: The Identification of the Two Missing Romanov Children Using DNA Analysis

One of the greatest mysteries for most of the twentieth century was the fate of the Romanov family, the last Russian monarchy. Following the abdication of Tsar Nicholas II, he and his wife, Alexandra, and their five children were eventually exiled to the city of Yekaterinburg. The family, along with four loyal members of their staff, was held captive by members of the Ural Soviet. According to historical reports, in the early morning hours of July 17, 1918 the entire family along with four loyal members of their staff was executed by a firing squad. After a failed attempt to dispose of the remains in an abandoned mine shaft, the bodies were transported to an open field only a few kilometers from the mine shaft. Nine members of the group were buried in one mass grave while two of the children were buried in a separate grave. With the official discovery of the larger mass grave in 1991, and subsequent DNA testing to confirm the identities of the Tsar, the Tsarina, and three of their daughters – doubt persisted that these remains were in fact those of the Romanov family. In the summer of 2007, a group of amateur archeologists discovered a collection of remains from the second grave approximately 70 meters from the larger grave. We report forensic DNA testing on the remains discovered in 2007 using mitochondrial DNA (mtDNA), autosomal STR, and Y- STR testing. Combined with additional DNA testing of material from the 1991 grave, we have virtually irrefutable evidence that the two individuals recovered from the 2007 grave are the two missing children of the Romanov family: the Tsarevich Alexei and one of his sisters

Genotype–phenotype correlation in PRKN- associated Parkinson’s disease

Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson’s disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p < 0.05). Furthermore, variants located in the N-terminus of the protein, a region enriched with frameshift variants, were associated with an earlier age at onset. The phenotype of PRKN-PD was characterised by slow motor progression, preserved cognition, an excellent motor response to levodopa therapy and later development of motor complications compared to early-onset PD. Non-motor symptoms were however common in PRKN-PD. Our findings on the relationship between the type of variant in PRKN and the phenotype of the disease may have implications for both genetic counselling and the design of precision clinical trials

Genotype-phenotype correlation in PRKN-associated Parkinson's disease

Bi-allelic pathogenic variants in PRKN are the most common cause of autosomal recessive Parkinson's disease (PD). 647 patients with PRKN-PD were included in this international study. The pathogenic variants present were characterised and investigated for their effect on phenotype. Clinical features and progression of PRKN-PD was also assessed. Among 133 variants in index cases (n = 582), there were 58 (43.6%) structural variants, 34 (25.6%) missense, 20 (15%) frameshift, 10 splice site (7.5%%), 9 (6.8%) nonsense and 2 (1.5%) indels. The most frequent variant overall was an exon 3 deletion (n = 145, 12.3%), followed by the p.R275W substitution (n = 117, 10%). Exon3, RING0 protein domain and the ubiquitin-like protein domain were mutational hotspots with 31%, 35.4% and 31.7% of index cases presenting mutations in these regions respectively. The presence of a frameshift or structural variant was associated with a 3.4 ± 1.6 years or a 4.7 ± 1.6 years earlier age at onset of PRKN-PD respectively (p &lt; 0.05). Furthermore, variants located in the N-terminus of the protein, a region enriched with frameshift variants, were associated with an earlier age at onset. The phenotype of PRKN-PD was characterised by slow motor progression, preserved cognition, an excellent motor response to levodopa therapy and later development of motor complications compared to early-onset PD. Non-motor symptoms were however common in PRKN-PD. Our findings on the relationship between the type of variant in PRKN and the phenotype of the disease may have implications for both genetic counselling and the design of precision clinical trials

Health Impact Assessment of airport noise on people living nearby six Italian airports

BACKGROUND: aircraft noise has been associated with several health effects. Because of the great success of low-cost flights, small airports have been turned into international airports thus exposing nearby residents to an increase in noise levels and potential disturbances and health disorders. OBJECTIVE: to estimate the exposure levels and evaluate the health impact of aircraft noise on residents nearby six airports in Italy (Rome: Ciampino; Milan: Linate and Malpensa; Pisa; Turin; Venice) focusing on hypertension, acute myocardial infarction (AMI), annoyance and sleep disturbances. METHODS: residents in the local Municipalities considered at 31.12.2010 were included in the study and their addresses were geocoded. Aircraft noise exposure in 2011 was defined using the Integrated Noise Model linked to each participant s address. Lden (55dB were considered: 55,915 (76.3%) were exposed to 55-60 dB; 16,562 (22.6%) to 60-65 dB; 795 (1.2%) to 65-70 dB. Exposure to aircraft noise levels above 55 dB was estimated to be responsible each year of 4,607 (95%CI 0-9,923) additional cases of hypertension; 3.4 (95%CI 0-10.7) cases of AMI; 9,789 (95%CI 6,895-11,962) cases of annoyance; 5,084 (95%CI 1,894-10,509) cases of sleep disturbances. CONCLUSIONS: a significant impact of airport noise on the health of residents nearby six Italian airports was estimated. Epidemiological evaluation and noise mitigation measures should be introduced to protect the health of residents

Calorimetry for Lepton Collider Experiments – CALICE results and activities

The CALICE collaboration conducts calorimeter R&D for highly granular calorimeters, mainly for their application in detectors for a future lepton collider at the TeV scale. The activities ranges from generic R&D with small devices up to extensive beam tests with prototypes comprising up to several 100000 calorimeter cells. CALICE has validated the performance of particle flow algorithms with test beam data and delivers the proof of principle that highly granular calorimeters can be built, operated and understood. The successes achieved in the past years allows the step from prototypes to calorimeter systems for particle physics detectors to be addressed