Treatment of subclinical hyperthyroidism: Effect on body composition

Background: subclinical hyperthyroidism (SHT) is associated with harmful effects on cardiovascular system, bone metabolism and progression to clinical hyperthyroidism. Loss of weight is a common fact in patients with clinical hyperthyroidism and of particular relevance in elderly patients. Objective: to assess changes in body composition after radioiodine therapy for SHT due to toxic nodular goiter. Subjects and methods: prospective controlled cohort study. Patients with persistent SHT due to toxic nodular goiter were purposed to receive treatment with radioiodine (treatment group) or to delay treatment until the study was over (control group). All treated patients received 555 MBq of 131I. Body composition (lean mass, fat mass and bone mineral content) was determined by dual-energy X-ray absorptiometry (DEXA) at baseline and 12 months after. Results: twenty-nine patients were studied (age 69.5 ± 11.5; 75.9% women; BMI 27.1 ± 5.7 kg/m²; serum thyrotropin (TSH) 0.20 ± 0.21 µUI/mL; serum free thyroxine (T4) 1.01 ± 0.19 ng/dL), 17 belonging to the treatment group and 12 to the control group. Study groups were comparable, although there was a trend for the treatment group to have more fat mass. No longitudinal changes in body composition were noted in either group, except for a trend to gain fat mass. However, when individuals with age > 65 years were selected, only patients who received radioiodine therapy showed a significant increase in body weight (from 64.1 ± 10.0 to 66.9 ± 9.2 kg), BMI (from 27.3 ± 4.8 to 28.7 ± 4.5 kg/m²), fat mass (from 26.1 ± 8.5 to 27.8 ± 7.9 kg), lean mass (from 36.3 ± 0.4 to 37.4 ± 0.4 kg) and skeletal muscle mass index (SMI) (from 6.0 ± 0.6 to 6.3 ± 0.6 kg/m²). Conclusions: treatment of SHT has impact on body composition in subjects older than 65 years. Weight gain reflects increases in fat and, more interestingly, in lean mass

New considerations for PM, black carbon and particle number concentration for air quality monitoring across different European cities

In many large cities of Europe standard air quality limit values of particulate matter (PM) are exceeded. Emissions from road traffic and biomass burning are frequently reported to be the major causes. As a consequence of these exceedances a large number of air quality plans, most of them focusing on traffic emissions reductions, have been implemented in the last decade. In spite of this implementation, a number of cities did not record a decrease of PM levels. Thus, is the efficiency of air quality plans overestimated? Do the road traffic emissions contribute less than expected to ambient air PM levels in urban areas? Or do we need a more specific metric to evaluate the impact of the above emissions on the levels of urban aerosols? This study shows the results of the interpretation of the variability of levels of PM, Black Carbon (BC), aerosol number concentration (N) and a number of gaseous pollutants in seven selected urban areas covering road traffic, urban background, urban-industrial, and urban-shipping environments from southern, central and northern Europe. The results showed that variations of PM and N levels do not always reflect the variation of the impact of road traffic emissions on urban aerosols. However, BC levels vary proportionally with those of traffic related gaseous pollutants, such as CO, NO₂ and NO. Due to this high correlation, one may suppose that monitoring the levels of these gaseous pollutants would be enough to extrapolate exposure to traffic-derived BC levels. However, the BC/CO, BC/NO₂ and BC/NO ratios vary widely among the cities studied, as a function of distance to traffic emissions, vehicle fleet composition and the influence of other emission sources such as biomass burning. Thus, levels of BC should be measured at air quality monitoring sites. During morning traffic rush hours, a narrow variation in the N/BC ratio was evidenced, but a wide variation of this ratio was determined for the noon period. Although in central and northern Europe N and BC levels tend to vary simultaneously, not only during the traffic rush hours but also during the whole day, in urban background stations in southern Europe maximum N levels coinciding with minimum BC levels are recorded at midday in all seasons. These N maxima recorded in southern European urban background environments are attributed to midday nucleation episodes occurring when gaseous pollutants are diluted and maximum insolation and O₃ levels occur. The occurrence of SO₂ peaks may also contribute to the occurrence of midday nucleation bursts in specific industrial or shipping-influenced areas, although at several central European sites similar levels of SO₂ are recorded without yielding nucleation episodes. Accordingly, it is clearly evidenced that N variability in different European urban environments is not equally influenced by the same emission sources and atmospheric processes. We conclude that N variability does not always reflect the impact of road traffic on air quality, whereas BC is a more consistent tracer of such an influence. However, N should be measured since ultrafine particles (<100 nm) may have large impacts on human health. The combination of PM₁₀ and BC monitoring in urban areas potentially constitutes a useful approach for air quality monitoring. BC is mostly governed by vehicle exhaust emissions, while PM₁₀ concentrations at these sites are also governed by non-exhaust particulate emissions resuspended by traffic, by midday atmospheric dilution and by other nontraffic emissions

New considerations for PM, Black Carbon and particle number concentration for air quality monitoring across different European cities

In many large cities of Europe standard air quality limit values of particulate matter (PM) are exceeded. Emissions from road traffic and biomass burning are frequently reported to be the major causes. As a consequence of these exceedances a large number of air quality plans, most of them focusing on traffic emissions reductions, have been implemented in the last decade. In spite of this implementation, a number of cities did not record a decrease of PM levels. Thus, is the efficiency of air quality plans overestimated? Do the road traffic emissions contribute less than expected to ambient air PM levels in urban areas? Or do we need a more specific metric to evaluate the impact of the above emissions on the levels of urban aerosols? This study shows the results of the interpretation of the 2009 variability of levels of PM, Black Carbon (BC), aerosol number concentration (N) and a number of gaseous pollutants in seven selected urban areas covering road traffic, urban background, urban-industrial, and urban-shipping environments from southern, central and northern Europe. The results showed that variations of PM and N levels do not always reflect the variation of the impact of road traffic emissions on urban aerosols. However, BC levels vary proportionally with those of traffic related gaseous pollutants, such as CO, NO2 and NO. Due to this high correlation, one may suppose that monitoring the levels of these gaseous pollutants would be enough to extrapolate exposure to traffic-derived BC levels. However, the BC/CO, BC/NO2 and BC/NO ratios vary widely among the cities studied, as a function of distance to traffic emissions, vehicle fleet composition and the influence of other emission sources such as biomass burning. Thus, levels of BC should be measured at air quality monitoring sites. During morning traffic rush hours, a narrow variation in the N/BC ratio was evidenced, but a wide variation of this ratio was determined for the noon period. Although in central and northern Europe N and BC levels tend to vary simultaneously, not only during the traffic rush hours but also during the whole day, in urban background stations in southern Europe maximum N levels coinciding with minimum BC levels are recorded at midday in all seasons. These N maxima recorded in southern European urban background environments are attributed to midday nucleation episodes occurring when gaseous pollutants are diluted and maximum insolation and O3 levels occur. The occurrence of SO2 peaks may also contribute to the occurrence of midday nucleation bursts in specific industrial or shipping-influenced areas, although at several central European sites similar levels of SO2 are recorded without yielding nucleation episodes. Accordingly, it is clearly evidenced that N variability in different European urban environments is not equally influenced by the same emission sources and atmospheric processes. We conclude that N variability does not always reflect the impact of road traffic on air quality, whereas BC is a more consistent tracer of such an influence. However, N should be measured since ultrafine particles (<100 nm) may have large impacts on human health. The combination of PM10 and BC monitoring in urban areas potentially constitutes a useful approach for air quality monitoring. BC is mostly governed by vehicle exhaust emissions, while PM10 concentrations at these sites are also governed by non-exhaust particulate emissions resuspended by traffic, by midday atmospheric dilution and by other non-traffic emissions

Cosmic-Ray Anisotropies in Right Ascension Measured by the Pierre Auger Observatory

We present measurements of the large-scale cosmic-ray (CR) anisotropies in R.A., using data collected by the surface detector array of the Pierre Auger Observatory over more than 14 yr. We determine the equatorial dipole component, through a Fourier analysis in R.A. that includes weights for each event so as to account for the main detector-induced systematic effects. For the energies at which the trigger efficiency of the array is small, the east-west method is employed. Besides using the data from the array with detectors separated by 1500 m, we also include data from the smaller but denser subarray of detectors with 750 m separation, which allows us to extend the analysis down to ∼0.03 EeV. The most significant equatorial dipole amplitude obtained is that in the cumulative bin above 8 EeV, %, which is inconsistent with isotropy at the 6σ level. In the bins below 8 EeV, we obtain 99% CL upper bounds on d ⊥ at the level of 1%-3%. At energies below 1 EeV, even though the amplitudes are not significant, the phases determined in most of the bins are not far from the R.A. of the Galactic center, at GC =-94°, suggesting a predominantly Galactic origin for anisotropies at these energies. The reconstructed dipole phases in the energy bins above 4 EeV point instead to R.A. that are almost opposite to the Galactic center one, indicative of an extragalactic CR origin

Hughes Abdominal Repair Trial (HART) – Abdominal wall closure techniques to reduce the incidence of incisional hernias: study protocol for a randomised controlled trial

Background Incisional hernias are common complications of midline closure following abdominal surgery and cause significant morbidity, impaired quality of life and increased health care costs. The ‘Hughes Repair’ combines a standard mass closure with a series of horizontal and two vertical mattress sutures within a single suture. This theoretically distributes the load along the incision length as well as across it. There is evidence to suggest that this technique is as effective as mesh repair for the operative management of incisional hernias; however, no trials have compared the Hughes Repair with standard mass closure for the prevention of incisional hernia formation following a midline incision. Methods/design This is a 1:1 randomised controlled trial comparing two suture techniques for the closure of the midline abdominal wound following surgery for colorectal cancer. Full ethical approval has been gained (Wales REC 3, MREC 12/WA/0374). Eight hundred patients will be randomised from approximately 20 general surgical units within the United Kingdom. Patients undergoing open or laparoscopic (more than a 5-cm midline incision) surgery for colorectal cancer, elective or emergency, are eligible. Patients under the age of 18 years, those having mesh inserted or undergoing musculofascial flap closure of the perineal defect in abdominoperineal wound closure, and those unable to give informed consent will be excluded. Patients will be randomised intraoperatively to either the Hughes Repair or standard mass closure. The primary outcome measure is the incidence of incisional hernias at 1 year as assessed by standardised clinical examination. The secondary outcomes include quality of life patient-reported outcome measures, cost-utility analysis, incidence of complete abdominal wound dehiscence and C-POSSUM scores. The incidence of incisional hernia at 1 year, assessed by computerised tomography, will form a tertiary outcome. Discussion A feasibility phase has been completed. The results of the study will be used to inform current and future practice and potentially reduce the risk of incisional hernia formation following midline incisions

Repurposing Vandetanib plus Everolimus for the Treatment of ACVR1-Mutant Diffuse Intrinsic Pontine Glioma.

Somatic mutations in ACVR1 are found in a quarter of children with diffuse intrinsic pontine glioma (DIPG), but there are no ACVR1 inhibitors licensed for the disease. Using an artificial intelligence-based platform to search for approved compounds for ACVR1-mutant DIPG, the combination of vandetanib and everolimus was identified as a possible therapeutic approach. Vandetanib, an inhibitor of VEGFR/RET/EGFR, was found to target ACVR1 (K d = 150 nmol/L) and reduce DIPG cell viability in vitro but has limited ability to cross the blood-brain barrier. In addition to mTOR, everolimus inhibited ABCG2 (BCRP) and ABCB1 (P-gp) transporters and was synergistic in DIPG cells when combined with vandetanib in vitro. This combination was well tolerated in vivo and significantly extended survival and reduced tumor burden in an orthotopic ACVR1-mutant patient-derived DIPG xenograft model. Four patients with ACVR1-mutant DIPG were treated with vandetanib plus an mTOR inhibitor, informing the dosing and toxicity profile of this combination for future clinical studies. SIGNIFICANCE: Twenty-five percent of patients with the incurable brainstem tumor DIPG harbor somatic activating mutations in ACVR1, but there are no approved drugs targeting the receptor. Using artificial intelligence, we identify and validate, both experimentally and clinically, the novel combination of vandetanib and everolimus in these children based on both signaling and pharmacokinetic synergies.This article is highlighted in the In This Issue feature, p. 275

The observation of lightning-related events with the Surface Detector of the Pierre Auger Observatory

The Pierre Auger Observatory, designed to detect ultra-high energy cosmic rays, can be a valid instrument at the ground to study phenomena related to the atmospheric electricity. The fluorescence detector is a powerful instrument to observe ELVES thanks to its excellent time resolution, while peculiar events with a large number of triggered stations have been recorded by the surface detector. The characteristic signal of these events lasts more than 10 mu s, about two orders of magnitude more than the duration of a signal produced by a cosmic muon. Moreover, each of these events has at least one station with a signal dominated by a high-frequency noise that could be related with a lightning-induced signal. Stations with a long-lasting signal are arranged in a disk shape. There are "big" events characterized by a radius of about 6 km and few "small" events with a radius of about 2-3 km. The signal, generated by a source very close to the ground, first reaches the innermost stations and then spreads outwards. In the "big" events, a lack of signal in some of the central stations was observed. Further studies and checks are in progress to understand the origin of the lack of signal and what mechanisms occurring during the lightning evolution may provide for electric fields capable of generating and accelerating particles that can produce Cherenkov light in the stations of the surface detector

Analysis of ELVES at the Pierre Auger Observatory

In the last six years, the Fluorescence Detector (FD) of the Auger Observatory has been exploited for the study of transient luminous events occuring high above thunderstorms at large distances (250 to more than 1000 km) from the Observatory. The first ELVES candidate was discovered during a night shift in 2005, and further studies based on auxiliary subtriggers allowed to modify the third level trigger of the observatory in order to acquire them with reasonable efficiency. This report aims to briefly review the studies underway on the &gt;4000 ELVES triggers harvested in the years 2013-18 by the Observatory

Aerosol Optical Depth from MODIS satellite data above the Pierre Auger Observatory

Aerosol optical depth can be retrieved from measurements performed by Moderate Resolution Imaging Spectroradiometer (MODIS) satellite instrument. The MODIS satellite system includes two polar satellites, Terra and Aqua. Each of them flies over the Pierre Auger Observatory once a day, providing two measurements of aerosols per day and covering the whole area of the Observatory. MODIS aerosol data products have been generated by three dedicated algorithms over bright and dark land and over ocean surface. We choose the Deep Blue algorithm data to investigate the distribution of aerosols over the Observatory, as this algorithm is the most appropriate one for semi-arid land of the Pierre Auger Observatory. This data algorithm allows us to obtain aerosol optical depth values for the investigated region, and to build cloud-free aerosol maps with a horizontal resolution 0.1 degrees x0.1 degrees. Since a sufficient number of measurements was obtained only for Loma Amarilla and Coihueco fluorescence detector (FD) sites of the Pierre Auger Observatory, a more detailed analysis of aerosol distributions is provided for these sites. Aerosols over these FD sites are generally distributed in a similar way each year, but some anomalies are also observed. These anomalies in aerosol distributions appear mainly due to some transient events, such as volcanic ash clouds, fires etc. We conclude that the Deep Blue MODIS algorithm provides more realistic aerosol optical depth values than other available algorithms