Occupational exposure to organic dust and risk of lymphoma subtypes in the EPILYMPH case-control study

Objectives: This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods: We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case–control study, conducted in six European countries in 1998–2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results: We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01–4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00–4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95–4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions: Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma

52 Genetic Loci Influencing Myocardial Mass.

BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

AGILE detection of a rapid γ-ray flare from the blazar PKS 1510-089 during the GASP-WEBT monitoring

We report the detection by the AGILE satellite of a rapid gamma-ray flare from the powerful gamma-ray quasar PKS 1510-089, during a pointing centered on the Galactic Center region from 1 March to 30 March 2008. This source has been continuosly monitored in the radio-to-optical bands by the GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT). Moreover, the gamma-ray flaring episode triggered three ToO observations by the Swift satellite in three consecutive days, starting from 20 March 2008. In the period 1-16 March 2008, AGILE detected gamma-ray emission from PKS 1510-089 at a significance level of 6.2-sigma with an average flux over the entire period of (84 +/- 17) x 10^{-8} photons cm^{-2} s^{-1} for photon energies above 100 MeV. After a predefined satellite re-pointing, between 17 and 21 March 2008, AGILE detected the source at a significance level of 7.3-sigma, with an average flux (E > 100 MeV) of (134 +/- 29) x 10^{-8} photons cm^{-2} s^{-1} and a peak level of (281 +/- 68) x 10^{-8} photons cm^{-2} s^{-1} with daily integration. During the observing period January-April 2008, the source also showed an intense and variable optical activity, with several flaring episodes and a significant increase of the flux was observed at millimetric frequencies. Moreover, in the X-ray band the Swift/XRT observations seem to show an harder-when-brighter behaviour of the source spectrum. The spectral energy distribution of mid-March 2008 is modelled with a homogeneous one-zone synchrotron self Compton emission plus contributions from inverse Compton scattering of external photons from both the accretion disc and the broad line region. Indeed, some features in the optical-UV spectrum seem to indicate the presence of Seyfert-like components, such as the little blue bump and the big blue bump

AGILE detection of extreme γ -ray activity from the blazar PKS 1510-089 during March 2009: Multifrequency analysis

We report on the extreme gamma-ray activity from the FSRQ PKS 1510-089 observed by AGILE in March 2009. In the same period a radio-to-optical monitoring of the source was provided by the GASP-WEBT and REM. Moreover, several Swift ToO observations were triggered, adding important information on the source behaviour from optical/UV to hard X-rays. We paid particular attention to the calibration of the Swift/UVOT data to make it suitable to the blazars spectra. Simultaneous observations from radio to gamma rays allowed us to study in detail the correlation among the emission variability at different frequencies and to investigate the mechanisms at work. In the period 9-30 March 2009, AGILE detected an average gamma-ray flux of (311+/-21)x10^-8 ph cm^-2 s^-1 for E>100 MeV, and a peak level of (702+/-131)x10^-8 ph cm^-2 s^-1 on daily integration. The gamma-ray activity occurred during a period of increasing activity from near-IR to UV, with a flaring episode detected on 26-27 March 2009, suggesting that a single mechanism is responsible for the flux enhancement observed from near-IR to UV. By contrast, Swift/XRT observations seem to show no clear correlation of the X-ray fluxes with the optical and gamma-ray ones. However, the X-ray observations show a harder photon index (1.3-1.6) with respect to most FSRQs and a hint of harder-when-brighter behaviour, indicating the possible presence of a second emission component at soft X-ray energies. Moreover, the broad band spectrum from radio-to-UV confirmed the evidence of thermal features in the optical/UV spectrum of PKS 1510-089 also during high gamma-ray state. On the other hand, during 25-26 March 2009 a flat spectrum in the optical/UV energy band was observed, suggesting an important contribution of the synchrotron emission in this part of the spectrum during the brightest gamma-ray flare, therefore a significant shift of the synchrotron peak

Multiwavelength observations of 3C 454.3. III. Eighteen months of agile monitoring of the "crazy diamond"

We report on 18 months of multiwavelength observations of the blazar 3C 454.3 (Crazy Diamond) carried out in the period 2007 July-2009 January. In particular, we show the results of the AGILE campaigns which took place on 2008 May-June, 2008 July-August, and 2008 October-2009 January. During the 2008 May-2009 January period, the source average flux was highly variable, with a clear fading trend toward the end of the period, from an average γ-ray flux F E>100 MeV ≳ 200 × 10-8photonscm -2s-1 in 2008 May-June, to F E>100 MeV 80 × 10-8photonscm-2s-1 in 2008 October-2009 January. The average γ-ray spectrum between 100 MeV and 1 GeV can be fit by a simple power law, showing a moderate softening (from ΓGRID ∼ 2.0 to ΓGRID ∼ 2.2) toward the end of the observing campaign. Only 3σ upper limits can be derived in the 20-60 keV energy band with Super-AGILE, because the source was considerably off-axis during the whole time period. In 2007 July-August and 2008 May-June, 3C 454.3 was monitored by Rossi X-ray Timing Explorer (RXTE). The RXTE/Proportional Counter Array (PCA) light curve in the 3-20 keV energy band shows variability correlated with the γ-ray one. The RXTE/PCA average flux during the two time periods is F 3-20 keV = 8.4 × 10-11ergcm-2s -1, and F 3-20 keV = 4.5 × 10 -11ergcm-2s-1, respectively, while the spectrum (a power law with photon index ΓPCA = 1.65 0.02) does not show any significant variability. Consistent results are obtained with the analysis of the RXTE/High-Energy X-Ray Timing Experiment quasi-simultaneous data. We also carried out simultaneous Swift observations during all AGILE campaigns. Swift/XRT detected 3C 454.3 with an observed flux in the 2-10 keV energy band in the range (0.9-7.5) × 10-11ergcm-2s-1 and a photon index in the range ΓXRT = 1.33-2.04. In the 15-150 keV energy band, when detected, the source has an average flux of about 5mCrab. GASP-WEBT monitored 3C 454.3 during the whole 2007-2008 period in the radio, millimeter, near-IR, and optical bands. The observations show an extremely variable behavior at all frequencies, with flux peaks almost simultaneous with those at higher energies. A correlation analysis between the optical and the γ-ray fluxes shows that the γ-optical correlation occurs with a time lag of τ = -0.4+0.6-0.8 days, consistent with previous findings for this source. An analysis of 15 GHz and 43 GHz VLBI core radio flux observations in the period 2007 July-2009 February shows an increasing trend of the core radio flux, anti-correlated with the higher frequency data, allowing us to derive the value of the source magnetic field. Finally, the modeling of the broadband spectral energy distributions for the still unpublished data, and the behavior of the long-term light curves in different energy bands, allow us to compare the jet properties during different emission states, and to study the geometrical properties of the jet on a time-span longer than one year. © 2010. The American Astronomical Society. All rights reserved

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Peer reviewe

Serum free thyroxine levels are positively associated with arterial stiffness in the SardiNIA study

OBJECTIVE: Thyroid dysfunction may accelerate atherosclerosis. Aortic pulse wave velocity is an early index of arterial stiffness and an important risk factor for cardiovascular disease, and might therefore be linked to changes in thyroid activity. We investigated the relationship between thyroid function and carotid-femoral pulse wave velocity, as an index of arterial stiffness. DESIGN: Cross-sectional cohort study. PATIENTS: Participants from the SardiNIA study. Those being treated for thyroid diseases were excluded, yielding a sample of 5,875 ages 14-102. MEASUREMENTS: Clinical parameters, blood tests including serum TSH and serum FT4, and carotid-femoral pulse wave velocity were measured. RESULTS: After adjusting for confounders, a direct and linear association between FT4 and pulse wave velocity was shown (multiple regression analysis). The model containing age, mean blood pressure, body mass index, heart rate, FT4, hypertension, diabetes and dyslipidaemia accounted for 55% of the variation in pulse wave velocity. CONCLUSIONS: Like several other known risk factors, serum FT4 levels are associated with carotid-femoral pulse wave velocity, suggesting that high FT4 levels have a detrimental effect on aortic stiffness and may contribute to aging process of the vascular system. This finding may help to understand the pathogenesis of cardiovascular disease and contribute to improve prevention therapy