Studying bone mineral density in young people: The complexity of choosing a pQCT reference database

BACKGROUND: Many chronic illnesses affect bone health, and commonly lead to mineralization abnormalities in young people. As cortical and trabecular bone may be differentially affected in certain diseases, an imaging technique that allows for detailed study of the bone structure is required. Peripheral quantitative computed tomography (pQCT) overcomes the limitations of dual energy X-ray absorptiometry (DXA) and is perhaps more widely available for use in research than bone biopsy. However, in contrast to DXA, where there are large reference datasets, this is not the case for pQCT. METHODS: Fifty-five children and young adults aged 7 to 30 years had the non-dominant tibia scanned at the 3% & 4% sites for trabecular bone mineral density and the 38% site for cortical bone mineral density and bone mineral content. Image acquisition and analysis was undertaken according to the protocols of two of the largest reference datasets for tibial pQCT. The Z-scores generated were compared to examine the differences between protocols and the differences from the expected median of zero in a healthy population. RESULTS: The trabecular bone mineral density Z-scores generated by the two protocols were similar. The same was true for cortical mineral content Z-scores at the 38% site. Cortical bone mineral density was significantly different between protocols and likely affected by differences in the ethnicity of our cohort compared to the reference datasets. Only one reference dataset extended from childhood to young adulthood. Only trabecular bone mineral density, periosteal and endosteal circumference Z-scores from one methodology were not significantly biased when tested for deviation of the median from zero. CONCLUSIONS: pQCT is a useful tool for studying trabecular and cortical compartments separately but, there are variations in pQCT scanning protocols, analysis methodology, and a paucity of reference data. Reference datasets may not be generalizable to local study populations, even when analysed using identical analysis protocols

Planetary parameters, XUV environments and mass-loss rates for nearby gaseous planets with X-ray detected host-stars

We leverage Gaia DR2 parallactic distances to deliver new or revised estimates of planetary parameters and X-ray irradiation for a distance-limited ($\lesssim 100$ pc) sample of 27 gaseous planets (from super-Earths to hot Jupiters) with publicly available Chandra and/or XMM observations, for which we carry out a homogeneous data reduction. For 20 planets with X-ray detected host stars we make use of the photoionization hydrodynamics code ATES to derive updated atmospheric mass outflow rates. The newly derived masses/radii are not consistent with the $\verb|exoplanet.eu|$ values for five systems; HD 149026b and WASP-38, for mass; and Au Mic b, HAT-P-20 and HAT-P-2 for radii. Notably, the lower mass implies a (Saturn-like) density of $0.86\pm 0.09$ g cm$^{-3}$) for HD 149026 b. This independent estimate is consistent with the lowest values reported in the literature. Separately, we report on the X-ray detection of GJ 9827, HD 219134 and LHS 1140 for the first time. The inferred stellar X-ray luminosity of LHS 1140 ($1.34^{+0.19}_{-0.21} \times 10^{26}$ erg sec$^{-1}$) implies that LHS 1140 b is the least irradiated transiting super-Earth known to orbit within the habitable zone of a nearby M-dwarf.Comment: 15 pages, 6 figures; accepted for publication in Ap

CP Violation Results from B Decays at BaBar

In the present paper we review recent experimental results from the BaBar experiment concerning the measurement of the CKM angles. A particular highlight is given to the novel independent determination of the angle alpha from B0 -> a_1(1260)+/- pi -/+ and to the recent full-luminosity updates of several angle gamma measurements.Comment: 8 pages, contributed to the Proceedings of DISCRETE2010 Conferenc

Naturally Occurring Stable Calcium Isotope Ratios in Body Compartments Provide a Novel Biomarker of Bone Mineral Balance in Children and Young Adults

Serum calcium (Ca), bone biomarkers, and radiological imaging do not allow accurate evaluation of bone mineral balance (BMB), a key determinant of bone mineral density (BMD) and fracture risk. We studied naturally occurring stable (non‐radioactive) Ca isotopes in different body pools as a potential biomarker of BMB. {42}^Ca and {44}^Ca are absorbed from our diet and sequestered into different body compartments following kinetic principles of isotope fractionation; isotopically light {42}^Ca is preferentially incorporated into bone, whereas heavier {44}^Ca preferentially remains in blood and is excreted in urine and feces. Their ratio (δ^{44/42}Ca) n serum and urine increases during bone formation and decreases with bone resorption. In 117 healthy participants, we measured Ca isotopes, biomarkers, and BMD by dual‐energy X‐ray absorptiometry (DXA) and tibial peripheral quantitative CT (pQCT). {44}^Ca and 42Ca were measured by multi‐collector ionization‐coupled plasma mass‐spectrometry in serum, urine, and feces. The relationship between bone Ca gain and loss was calculated using a compartment model. δ^{44/42}Ca_{serum} and δ^{44/42}Ca_{urine} were higher in children (n = 66, median age 13 years) compared with adults (n = 51, median age 28 years; p < 0.0001 and p = 0.008, respectively). δ^{44/42}Ca_{serum} increased with height in boys (p < 0.001, R^{2} = 0.65) and was greatest at Tanner stage 4. δ^{44/42}Ca_{serum} correlated positively with biomarkers of bone formation (25‐hydroxyvitaminD [p < 0.0001, R^{2} = 0.37] and alkaline phosphatase [p = 0.009, R^{2} = 0.18]) and negatively with bone resorption marker parathyroid hormone (PTH; p = 0.03, R^{2} = 0.13). δ^{44/42}Ca_{serum} strongly positively correlated with tibial cortical BMD Z‐score (n = 62; p < 0.001, R^{2} = 0.39) but not DXA. Independent predictors of tibial cortical BMD Z‐score were δ^{44/42}Ca_{serum} (p = 0.004, β = 0.37), 25‐hydroxyvitaminD (p = 0.04, β = 0.19) and PTH (p = 0.03, β = −0.13), together predicting 76% of variability. In conclusion, naturally occurring Ca isotope ratios in different body compartments may provide a novel, non‐invasive method of assessing bone mineralization. Defining an accurate biomarker of BMB could form the basis of future studies investigating Ca dynamics in disease states and the impact of treatments that affect bone homeostasis

Routine serum biomarkers, but not dual-energy X-ray absorptiometry, correlate with cortical bone mineral density in children and young adults with chronic kidney disease

BACKGROUND: Biomarkers and dual-energy X-ray absorptiometry (DXA) are thought to be poor predictors of bone mineral density (BMD). The Kidney Disease: Improving Global Outcomes guidelines suggest using DXA if the results will affect patient management, but this has not been studied in children or young adults in whom bone mineral accretion continues to 30 years of age. We studied the clinical utility of DXA and serum biomarkers against tibial cortical BMD (CortBMD) measured by peripheral quantitative computed tomography, expressed as Z-score CortBMD, which predicts fracture risk. METHODS: This was a cross-sectional multicentre study in 26 patients with CKD4 and 5 and 77 on dialysis. RESULTS: Significant bone pain that hindered activities of daily living was present in 58%, and 10% had at least one low-trauma fracture. CortBMD and cortical mineral content Z-scores were lower in dialysis compared with CKD patients (P = 0.004 and P = 0.02). DXA BMD hip and lumbar spine Z-scores did not correlate with CortBMD or biomarkers. CortBMD was negatively associated with parathyroid hormone (PTH; r = -0.44, P < 0.0001) and alkaline phosphatase (ALP; r = -0.22, P = 0.03) and positively with calcium (Ca; r = 0.33, P = 0.001). At PTH <3 times upper limit of normal, none of the patients had a CortBMD below -2 SD (odds ratio 95% confidence interval 7.331 to infinity). On multivariable linear regression PTH (β = -0.43 , P < 0.0001), ALP (β = -0.36, P < 0.0001) and Ca (β = 0.21, P = 0.005) together predicted 57% of variability in CortBMD. DXA measures did not improve this model. CONCLUSIONS: Taken together, routinely used biomarkers, PTH, ALP and Ca, but not DXA, are moderate predictors of cortical BMD. DXA is not clinically useful and should not be routinely performed in children and young adults with CKD 4-5D

Variation in Glycemic Outcomes in Focal Forms of Congenital Hyperinsulinism - The UK Perspective

Context: In focal congenital hyperinsulinism (CHI), localized clonal expansion of pancreatic β-cells causes excess insulin secretion and severe hypoglycemia. Surgery is curative, but not all lesions are amenable to surgery. Objective: We describe surgical and nonsurgical outcomes of focal CHI in a national cohort. Methods: Patients with focal CHI were retrospectively reviewed at 2 specialist centers, 2003-2018. Results: Of 59 patients with focal CHI, 57 had heterozygous mutations in ABCC8/KCNJ11 (51 paternally inherited, 6 de novo). Fluorine-18 L-3,4 dihydroxyphenylalanine positron emission tomography computed tomography scan identified focal lesions in 51 patients. In 5 patients, imaging was inconclusive; the diagnosis was established by frozen section histopathology in 3 patients, a lesion was not identified in 1 patient, and 1 declined surgery. Most patients (n = 56) were unresponsive to diazoxide, of whom 33 were unresponsive or partially responsive to somatostatin receptor analog (SSRA) therapy. Fifty-five patients underwent surgery: 40 had immediate resolution of CHI, 10 had persistent hypoglycemia and a focus was not identified on biopsy in 5. In the 10 patients with persistent hypoglycemia, 7 underwent further surgery with resolution in 4 and ongoing hypoglycemia requiring SSRA in 3. Nine (15% of cohort) patients (1 complex surgical access; 4 biopsy negative; 4 declined surgery) were managed conservatively; medication was discontinued in 8 children at a median (range) age 2.4 (1.5-7.7) years and 1 remains on SSRA at 16 years with improved fasting tolerance and reduction in SSRA dose. Conclusion: Despite a unifying genetic basis of disease, we report inherent heterogeneity in focal CHI patients impacting outcomes of both surgical and medical management

Search for 14.4 keV solar axions from M1 transition of Fe-57 with CUORE crystals

We report the results of a search for axions from the 14.4 keV M1 transition from Fe-57 in the core of the sun using the axio-electric effect in TeO2 bolometers. The detectors are 5x5x5 cm3 crystals operated at about 10 mK in a facility used to test bolometers for the CUORE experiment at the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 43.65 kg d of data was made using a newly developed low energy trigger which was optimized to reduce the detectors energy threshold. An upper limit of 0.63 c kg-1 d-1 was established at 95% C.L.. From this value, a lower bound at 95% C.L. was placed on the Peccei-Quinn energy scale of fa >= 0.76 10**6 GeV for a value of S=0.55 for the flavor-singlet axial vector matrix element. Bounds are given for the interval 0.15 < S < 0.55.Comment: 14 pages, 6 figures, submitted to JCA

First array of enriched Zn82^{82}Se bolometers to search for double beta decay

The R&D activity performed during the last years proved the potential of ZnSe scintillating bolometers to the search for neutrino-less double beta decay, motivating the realization of the first large-mass experiment based on this technology: CUPID-0. The isotopic enrichment in $^{82}$Se, the Zn$^{82}$Se crystals growth, as well as the light detectors production have been accomplished, and the experiment is now in construction at Laboratori Nazionali del Gran Sasso (Italy). In this paper we present the results obtained testing the first three Zn$^{82}$Se crystals operated as scintillating bolometers, and we prove that their performance in terms of energy resolution, background rejection capability and intrinsic radio-purity complies with the requirements of CUPID-0