Vascular uptake on 18F-sodium fluoride positron emission tomography:precursor of vascular calcification?

Background: Microcalcifications cannot be identified with the present resolution of CT; however, 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) imaging has been proposed for non-invasive identification of microcalcification. The primary objective of this study was to assess whether 18F-NaF activity can assess the presence and predict the progression of CT detectable vascular calcification. Methods and Results: The data of two longitudinal studies in which patients received a 18F-NaF PET-CT at baseline and after 6 months or 1-year follow-up were used. The target to background ratio (TBR) was measured on PET at baseline and CT calcification was quantified in the femoral arteries at baseline and follow-up. 128 patients were included. A higher TBR at baseline was associated with higher calcification mass at baseline and calcification progression (β = 1.006 [1.005-1.007] and β = 1.002 [1.002-1.003] in the studies with 6 months and 1-year follow-up, respectively). In areas without calcification at baseline and where calcification developed at follow-up, the TBR was.11–.13 (P < .001) higher compared to areas where no calcification developed. Conclusion: The activity of 18F-NaF is related to the amount of calcification and calcification progression. In areas where calcification formation occurred, the TBR was slightly but significantly higher

Pre-launch calibration results of the TROPOMI payload on-board the Sentinel-5 Precursor satellite

The Sentinel-5 Precursor satellite was successfully launched on 13 October 2017, carrying the Tropospheric Monitoring Instrument (TROPOMI) as its single payload. TROPOMI is the next-generation atmospheric sounding instrument, continuing the successes of GOME, SCIAMACHY, OMI, and OMPS, with higher spatial resolution, improved sensitivity, and extended wavelength range. The instrument contains four spectrometers, divided over two modules sharing a common telescope, measuring the ultraviolet, visible, near-infrared, and shortwave infrared reflectance of the Earth. The imaging system enables daily global coverage using a push-broom configuration, with a spatial resolution as low as 7×3.5&thinsp;km2 in nadir from a Sun-synchronous orbit at 824&thinsp;km and an Equator crossing time of 13:30 local solar time. This article reports the pre-launch calibration status of the TROPOMI payload as derived from the on-ground calibration effort. Stringent requirements are imposed on the quality of on-ground calibration in order to match the high sensitivity of the instrument. A new methodology has been employed during the analysis of the obtained calibration measurements to ensure the consistency and validity of the calibration. This was achieved by using the production-grade Level 0 to 1b data processor in a closed-loop validation set-up. Using this approach the consistency between the calibration and the L1b product, as well as confidence in the obtained calibration result, could be established. This article introduces this novel calibration approach and describes all relevant calibrated instrument properties as they were derived before launch of the mission. For most of the relevant properties compliance with the calibration requirements could be established, including the knowledge of the instrument spectral and spatial response functions. Partial compliance was established for the straylight correction; especially the out-of-spectral-band correction for the near-infrared channel needs future validation. The absolute radiometric calibration of the radiance and irradiance responsivity is compliant with the high-level mission requirements, but not with the stricter calibration requirements as the available on-ground validation shows. The relative radiometric calibration of the Sun port was non-compliant. The non-compliant subjects will be addressed during the in-flight commissioning phase in the first 6 months following launch.</p

The Age of the 20 Meter Solo River Terrace, Java, Indonesia and the Survival of Homo erectus in Asia

Homo erectus was the first human lineage to disperse widely throughout the Old World, the only hominin in Asia through much of the Pleistocene, and was likely ancestral to H. sapiens. The demise of this taxon remains obscure because of uncertainties regarding the geological age of its youngest populations. In 1996, some of us co-published electron spin resonance (ESR) and uranium series (U-series) results indicating an age as young as 35–50 ka for the late H. erectus sites of Ngandong and Sambungmacan and the faunal site of Jigar (Indonesia). If correct, these ages favor an African origin for recent humans who would overlap with H. erectus in time and space. Here, we report 40Ar/39Ar incremental heating analyses and new ESR/U-series age estimates from the “20 m terrace" at Ngandong and Jigar. Both data sets are internally consistent and provide no evidence for reworking, yet they are inconsistent with one another. The 40Ar/39Ar analyses give an average age of 546±12 ka (sd±5 se) for both sites, the first reliable radiometric indications of a middle Pleistocene component for the terrace. Given the technical accuracy and consistency of the analyses, the argon ages represent either the actual age or the maximum age for the terrace and are significantly older than previous estimates. Most of the ESR/U-series results are older as well, but the oldest that meets all modeling criteria is 143 ka+20/−17. Most samples indicated leaching of uranium and likely represent either the actual or the minimum age of the terrace. Given known sources of error, the U-series results could be consistent with a middle Pleistocene age. However, the ESR and 40Ar/39Ar ages preclude one another. Regardless, the age of the sites and hominins is at least bracketed between these estimates and is older than currently accepted

Radiation and breast cancer: a review of current evidence

This paper summarizes current knowledge on ionizing radiation-associated breast cancer in the context of established breast cancer risk factors, the radiation dose–response relationship, and modifiers of dose response, taking into account epidemiological studies and animal experiments. Available epidemiological data support a linear dose–response relationship down to doses as low as about 100 mSv. However, the magnitude of risk per unit dose depends strongly on when radiation exposure occurs: exposure before the age of 20 years carries the greatest risk. Other characteristics that may influence the magnitude of dose-specific risk include attained age (that is, age at observation for risk), age at first full-term birth, parity, and possibly a history of benign breast disease, exposure to radiation while pregnant, and genetic factors

Determinants of 18F-NaF uptake in femoral arteries in patients with type 2 diabetes mellitus

Background: The goal of this study was to investigate the potential determinants of 18F-NaF uptake in femoral arteries as a marker of arterial calcification in patients with type 2 diabetes and a history of arterial disease. Methods and Results: The study consisted of participants of a randomized controlled trial to investigate the effect of vitamin K2 (NCT02839044). In this prespecified analysis, subjects with type 2 diabetes and known arterial disease underwent full body 18F-NaF PET/CT. Target-to-background ratio (TBR) was calculated by dividing the mean SUVmax from both superficial femoral arteries by the SUVmean in the superior vena cava (SVC) and calcium mass was measured on CT. The association between 18F-NaF TBR and cardiovascular risk factors was investigated using uni- and multivariate linear regression corrected for age and sex. In total, 68 patients (mean age: 69 ± 8 years; male: 52) underwent 18F-NaF PET/CT. Higher CT calcium mass, total cholesterol, and HbA1c were associated with higher 18F-NaF TBR after adjusting. Conclusion: This study shows that several modifiable cardiovascular risk factors (total cholesterol, triglycerides, HbA1c) are associated with femoral 18F-NaF tracer uptake in patients with type 2 diabetes

Six months vitamin K treatment does not affect systemic arterial calcification or bone mineral density in diabetes mellitus 2

Purpose: Vitamin K-dependent proteins are involved in (patho)physiological calcification of the vasculature and the bones. Type 2 diabetes mellitus (DM2) is associated with increased arterial calcification and increased fractures. This study investigates the effect of 6 months vitamin K2 supplementation on systemic arterial calcification and bone mineral density (BMD) in DM2 patients with a history of cardiovascular disease (CVD). Methods: In this pre-specified, post hoc analysis of a double-blind, randomized, controlled clinical trial, patients with DM2 and CVD were randomized to a daily, oral dose of 360 µg vitamin K2 or placebo for 6 months. CT scans were made at baseline and follow-up. Arterial calcification mass was quantified in several large arterial beds and a total arterial calcification mass score was calculated. BMD was assessed in all non-fractured thoracic and lumbar vertebrae. Results: 68 participants were randomized, 35 to vitamin K2 (33 completed follow-up) and 33 to placebo (27 completed follow-up). The vitamin K group had higher arterial calcification mass at baseline [median (IQR): 1694 (812–3584) vs 1182 (235–2445)] for the total arterial calcification mass). Six months vitamin K supplementation did not reduce arterial calcification progression (β [95% CI]: − 0.02 [− 0.10; 0.06] for the total arterial calcification mass) or slow BMD decline (β [95% CI]: − 2.06 [− 11.26; 7.30] Hounsfield units for all vertebrae) when compared to placebo. Conclusion: Six months vitamin K supplementation did not halt progression of arterial calcification or decline of BMD in patients with DM2 and CVD. Future clinical trials may want to pre-select patients with very low vitamin K status and longer follow-up time might be warranted. This trial was registered at clinicaltrials.gov as NCT0283904

Six months vitamin K treatment does not affect systemic arterial calcification or bone mineral density in diabetes mellitus 2

Purpose: Vitamin K-dependent proteins are involved in (patho)physiological calcification of the vasculature and the bones. Type 2 diabetes mellitus (DM2) is associated with increased arterial calcification and increased fractures. This study investigates the effect of 6 months vitamin K2 supplementation on systemic arterial calcification and bone mineral density (BMD) in DM2 patients with a history of cardiovascular disease (CVD). Methods: In this pre-specified, post hoc analysis of a double-blind, randomized, controlled clinical trial, patients with DM2 and CVD were randomized to a daily, oral dose of 360 µg vitamin K2 or placebo for 6 months. CT scans were made at baseline and follow-up. Arterial calcification mass was quantified in several large arterial beds and a total arterial calcification mass score was calculated. BMD was assessed in all non-fractured thoracic and lumbar vertebrae. Results: 68 participants were randomized, 35 to vitamin K2 (33 completed follow-up) and 33 to placebo (27 completed follow-up). The vitamin K group had higher arterial calcification mass at baseline [median (IQR): 1694 (812–3584) vs 1182 (235–2445)] for the total arterial calcification mass). Six months vitamin K supplementation did not reduce arterial calcification progression (β [95% CI]: − 0.02 [− 0.10; 0.06] for the total arterial calcification mass) or slow BMD decline (β [95% CI]: − 2.06 [− 11.26; 7.30] Hounsfield units for all vertebrae) when compared to placebo. Conclusion: Six months vitamin K supplementation did not halt progression of arterial calcification or decline of BMD in patients with DM2 and CVD. Future clinical trials may want to pre-select patients with very low vitamin K status and longer follow-up time might be warranted. This trial was registered at clinicaltrials.gov as NCT0283904

An elevated ankle-brachial index is not a valid proxy for peripheral medial arterial calcification

Background and aims: The ankle brachial index (ABI) is often used as a proxy for medial arterial calcification (MAC) in studies investigating MAC as a cardiovascular risk factor, but evidence supporting this hypothesis is sparse. This study aims to investigate the use of an elevated ABI as proxy for MAC, as visualized with computed tomography (CT). Methods: Cross-sectional data of 718 participants with, or at risk of cardiovascular disease was used. The ABI was calculated using cutoffs >1.4 and > 1.3. The presence of MAC was assessed in the crural and femoral arteries by CT imaging. Modified Poisson regression was used to assess the association between an elevated ABI and the presence of MAC, and test characteristics were calculated. Results: MAC was found in 25.0% of participants. An ABI >1.4 was found in 8.7% of participants, of whom 45.2% had MAC. An elevated ABI was significantly associated with the presence of MAC (RR 1.74, CI: 1.26–2.40). However, poor positive specific agreement (23.3%, CI: 13.9–34.3), sensitivity (15.7%, CI: 10.4–21.1) and positive predictive value (45.2%, CI: 32.8–57.5) were found. Despite good specificity (93.6%, CI: 91.6–95.7) the area under the receiving operator curve remained poor (54.7%, CI: 51.8–57.6). Negative specific agreement (84.5%, CI: 81.4–87.0) and negative predictive value (77.0%, CI: 73.7–80.2) were acceptable. Conclusions: An elevated ABI is insufficient to serve as a true diagnostic proxy for MAC. Studies that have drawn conclusions on the association between MAC and cardiovascular disease, solely based on the ABI, are likely to underestimate the found effects

Vascular uptake on 18F-sodium fluoride positron emission tomography: precursor of vascular calcification?

Background: Microcalcifications cannot be identified with the present resolution of CT; however, 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) imaging has been proposed for non-invasive identification of microcalcification. The primary objective of this study was to assess whether 18F-NaF activity can assess the presence and predict the progression of CT detectable vascular calcification. Methods and Results: The data of two longitudinal studies in which patients received a 18F-NaF PET-CT at baseline and after 6 months or 1-year follow-up were used. The target to background ratio (TBR) was measured on PET at baseline and CT calcification was quantified in the femoral arteries at baseline and follow-up. 128 patients were included. A higher TBR at baseline was associated with higher calcification mass at baseline and calcification progression (β = 1.006 [1.005-1.007] and β = 1.002 [1.002-1.003] in the studies with 6 months and 1-year follow-up, respectively). In areas without calcification at baseline and where calcification developed at follow-up, the TBR was.11–.13 (P < .001) higher compared to areas where no calcification developed. Conclusion: The activity of 18F-NaF is related to the amount of calcification and calcification progression. In areas where calcification formation occurred, the TBR was slightly but significantly higher