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Thyrotoxicosis leads to loss of bone mass. Vitamin D is important to bone health. In this randomized, placebo-controlled trial, we showed that bone restoration did not improve when adding vitamin D supplementation to standard care of Graves' disease thyrotoxicosis. Bone density and microarchitecture improved markedly with treatment of thyrotoxicosis. PURPOSE: Vitamin D is important to skeletal health and ensuring a replete vitamin D status is recommended. In thyrotoxicosis, bone turnover is increased and bone mass density (BMD) reduced. We examined whether vitamin D supplementation improves bone recovery in thyrotoxicosis caused by Graves' disease (GD). METHODS: Using a double-blinded design, hyperthyroid patients with GD were randomized to vitamin D3 70 µg/day (2800 IU) or similar placebo as add-on to antithyroid drugs (ATD). At baseline and 9 months, we measured BMD and bone architecture using DXA and high resolution peripheral quantitative computerized tomography. Bone turnover markers (BTM) were measured at 3 months also. Effect of vitamin D versus placebo and the response to ATD treatment were analyzed using linear mixed modelling. RESULTS: Eighty-six GD patients were included (age 41 ± 14 years, 86% females). Compared to placebo, vitamin D3 did not improve BMD or microarchitecture. In response to ATD, BMD increased in the hip by 2% (95%CI: 1-4%). Cortical porosity decreased in tibia (- 7% [95%CI: - 12 to - 2%]) and radius [- 14% [95%CI: - 24 to - 3%]), and trabecular thickness increased (tibia (5% [95%CI: 2 - 9%]) and radius (4% [95%CI: 1-7%]). Changes in BTM, but not thyroid hormones, were associated with changes in BMD by DXA and with changes in the cortical compartment. CONCLUSION: In newly diagnosed GD, 9 months of high dose vitamin D3 supplementation does not offer benefit by improving skeletal health. Treatment of thyrotoxicosis is associated with the recovery of BMD and microarchitecture. GOV IDENTIFIER: NCT02384668.

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BACKGROUND: A variety of metrics are used to describe glycemic variation, some of which may be difficult to comprehend or require complex strategies for smoothing of the glucose curve. We aimed to describe a new metric named time with rapid change of glucose (TRC), which is presented as percentage of time, similar to time above range (TAR), time in range (TIR), and time below range (TBR). METHOD: We downloaded glucose data for 90 days from 159 persons with type 1 diabetes using the Abbott Freestyle Libre version 1. We defined TRC as the proportion of time (%) with an absolute rate of change of glucose > 1.5 mmol/L/15 minutes (1.8mg/dL/min) corresponding to a minimum rate of change for glucose in the 3.9-10.0 mmol/L (70-180 mg/dL) range within 1 hour. TRC is related to the other glucose variability metrics: CV within day (CVw) and mean amplitude of glycemic excursion (MAGE). RESULTS: The more than 1.27 million glucose rates were t-location scale distributed with SD 0.91 mmol/L/15 min (1.1 mg/dL/15 min). The median TRC was 6.9% (IQR 4.5%-9.5%). The proportion of TRC with positive slope was 3.9% (2.6%-5.3%) and significantly higher than the proportion with negative slope 2.8% (1.5%-4.4%) P < .001. TRC correlated with CVw and MAGE (Spearman's correlation coefficient .56 and .65, respectively, P < .001). CONCLUSION: TRC is proposed as an easily perceived metric to compare the performance of hybrid or fully automated closed-loop insulin delivery systems to obtain glucose homeostasis.

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OBJECTIVE: Some brachial cuffs for oscillometric blood pressure (BP) measurement are claimed to cover a wide range of upper-arm circumferences; however, their validation is rarely conducted. Our aim was to compare oscillometric BP measurements obtained with a universal cuff with those obtained with an appropriately sized cuff. METHODS: We utilised the Microlife B6 Connect monitor, conducting oscillometric BP measurements in a random sequence with both a universal cuff (recommended for arm circumferences from 22 to 42 cm) and an appropriately sized cuff (medium for circumference 22-32 cm and large for 32-42 cm). We included 91 individuals with an arm circumference of 22-32 cm and 64 individuals with an arm circumference of 32-42 cm. RESULTS: For arm circumferences > 32 cm, systolic and diastolic BP measured with the universal cuff was higher than that measured with the large cuff (systolic 6.4 mmHg, 95% confidence interval [CI]). 3.9-8.8, diastolic 2.4 mmHg, 95%CI, 1.2-3.7, p < 0.001 for both). Overestimation of BP with the universal cuff was statistically significant after correcting for the sequence of measurements. No statistical difference was found between the universal cuff and medium cuff for circumferences in the 22-32 cm range. The bladder size in the universal cuff matched the dimensions of the medium-sized cuff; however, the cuff was larger. CONCLUSION: Overestimation of BP measured with a universal cuff in persons with large arm circumferences is clinically important. It poses the risk of unnecessary initiation or intensification of antihypertensive medication in persons using the universal cuff.

What is the context?Clinical guidelines recommend individualisation of the size of the cuff used for blood pressure measurement according to the circumference of the upper arm.Many blood pressure monitors are sold with a single "universal" cuff claimed to cover a wide range of upper arm sizes.We compared blood pressure obtained with the Microlife B6 Connect monitor and a "universal" cuff with the results obtained with individual sized cuffs (medium size for arm circumference between 22 and 32 cm and large size for arm circumference between 32 and 42 cm).What is new?In persons with large upper arm circumference is the systolic blood pressure 6.4 mmHg higher and the diastolic blood pressure 2.4 mmHg higher with the universal cuff than with the individual-sized large cuff.What is the impact?The universal cuff overestimates blood pressure in persons with large arm circumference.

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The reactivity of Nbn+ (1 ≤ n ≤ 21) clusters with B2H6 is studied by using a self-developed multiple-ion laminar flow tube reactor combined with a triple quadrupole mass spectrometer (MIFT-TQMS). The Nbn+ clusters were generated by a magnetron sputtering source and reacted with the B2H6 gas under fully thermalized conditions in the downstream flow tube where the reaction time was accurately controlled and adjustable. The complete and partial dehydrogenation products NbnB1-4+ and NbnB1-4H1,2,4+ were detected, indicative of the removal of H2 and likely BHx moieties. Interestingly, these NbnB1-4+ and NbnB1-4H1,2,4+ products are limited to 3 ≤ n ≤ 6, suggesting that the small Nbn+ clusters are relatively more reactive than the larger Nbn>6+ clusters under the same conditions. By varying the B2H6 gas concentrations and the reactant doses introduced into the flow tube, and by changing the reaction time, we performed a detailed analysis of the reaction dynamics in combination with the DFT-calculated thermodynamics. It is demonstrated that the lack of cooperative active sites on the Nb1+ cations accounts for the weakened dehydrogenation efficiency. Nb2+ forms partial dehydrogenation products at a faster rate. In contrast, the Nbn>6+ clusters are subject to more flexible vibrational relaxation which disperse the energy gain of B2H6-adsorption and thus are unable to overcome the energy barriers for subsequent hydrogen atom transfer and H2 release.

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AIM: To estimate the proportion of persons with type 2 diabetes (T2DM) receiving intensive insulin treatment in the secondary healthcare who could be candidates for continuous glucose monitoring (CGM), based on different HbA1c criteria. For comparison, the results are also presented as proportion of persons with type 1 diabetes (T1DM) in the same region. PATIENTS AND METHODS: In the Central Denmark Region, we identified all persons with T1DM (n = 6179) and T2DM (n = 4315) who had a minimum of one contact to a diabetes outpatient clinic from September 2021 to September 2022. Insulin regimen and HbA1c measured after a minimum of 2 months with a stable insulin regimen were retrieved from the healthcare administrative electronic platform used in the region. RESULTS: The numbers of persons with T1DM and T2DM with HbA1c meeting the criteria were 5145 and 3090, respectively. The fraction of T2DM with basal-bolus insulin was 35.3%, and the fraction with basal-bolus insulin and HbA1c >53 (7%) mmol/mol or >58 (7.5%) mmol/mol was 20.5% and 16.6%, respectively. These proportions correspond to 19.4%, 14.4% and 11.7% of the persons with T1DM in the same geographical area. CONCLUSION: The proportion of persons with T2DM in secondary healthcare undergoing intensive insulin treatment who could be candidates for CGM corresponded to only a minor fraction of persons with T1DM in the same region, irrespective of any HbA1c criteria applied.

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The objective of this study was to assess the feasibility of the Arteriograph 24 device to measure 24-hour PWV and central systolic blood pressure (cSBP) in patients with type 2 diabetes (T2DM) and non-diabetic controls and compare daytime and nighttime characteristics in the two groups. Twenty-four-hour PWV and cSBP was measured in 58 patients with T2DM (mean age: 66 ±â€…9 years, 50% women, mean duration of T2DM: 7.8 ±â€…1.5 years) and 62 age- and sex-matched controls. Seventy percent of participants (71% T2DM patients and 69% controls) had sufficient readings to generate an acceptable 24-hour report (≥14 day and ≥7 night readings). Lower nocturnal than daytime PWV and cSBP were observed in both groups. Nocturnal PWV and cSBP dipping were attenuated in T2DM patients compared to controls (PWV: -0.3 ±â€…0.9 vs. -0.7 ±â€…0.9 m/s, P  = 0.04, cSBP: -8 ±â€…14 vs. -18 ±â€…18 mmHg, P  < 0.01). No group differences in PWV or cSBP were observed during daytime (T2D vs. controls, PWV: 9.2 ±â€…1.1 vs. 9.2 ±â€…1.3 m/s, P  = 0.99, cSBP: 133 ±â€…19 vs. 137 ±â€…25 mmHg, P  = 0.42) or nighttime (PWV: 8.9 ±â€…1.3 vs. 8.4 ±â€…1.3 m/s, P  = 0.14, cSBP 124 ±â€…20 vs. 118 ±â€…27 mmHg, P  = 0.26). The study findings indicate that the nocturnal dipping of PWV and cSBP is attenuated in T2DM patients. The significant number of missing measurements raises concerns regarding the clinical utility of the Arteriograph 24 device.

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Millisecond-delayed photodissociation of gas-phase Sn22- clusters stored in a Penning trap is investigated as a function of excitation energy. Sn15- is the only significant charged fragment, indicative of the break-off of neutral heptamers. Fits of the time-resolved fragmentation require a distribution of decay constants, caused by the finite width of the internal energy distribution of the cluster ensemble prior to photoexcitation. A lower limit for the dissociation energy for the loss of Sn7 is determined to be 2.1(1) eV, a factor of two above literature quantum chemical calculations.

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Despite the worldwide prevalence of multilingualism, the knowledge of the relationship between domain-general cognitive control and multilingual language control remains scant. Here we provide new insights into this issue by examining systematically how different components of inhibitory control (i.e., response inhibition and interference suppression) contribute to language control in multilingual populations with high L2 proficiency. To this end, 65 Tibetan-Chinese-English trilinguals highly proficient in L2 were recruited to complete three tasks: a picture-naming task measuring the performance of online trilingual speech production, and two nonlinguistic tasks, a go/no-go task and a Simon task, as proxies for measuring response inhibition and interference suppression abilities, respectively. Using mixed-effects modeling, we analyzed both the trilingual language switching/nonswitching performances and their correlations with these two components of inhibitory control. Our data revealed unexpected patterns of reversed language dominance effect and (a)symmetries in switch costs. Notably, interaction analysis revealed that while response inhibition was robustly engaged in trilingual language control, interference suppression did not appear to play a role. Taken together, our study suggests that, for trilingual speakers highly proficient in L2, the recruitment of different subprocesses of inhibitory control in lexical access was selective and was constrained to reactive and local-level language control. We conclude by discussing theoretical implications. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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The unimolecular fragmentation channels of highly excited small cationic carbon clusters have been measured with a time-of-flight mass spectrometer after photofragmentation. The dominant channel is loss of the neutral trimer, for all CN+N = 10-27 clusters except for N = 11, 12 which decay by monomer emission, and C25+ which shows competing loss of C2 and C3. The results permit to quantify the role of the rotational entropy in the competition between monomer and trimer decays with the help of energies calculated with density functional theory.

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We report a joint experimental and theoretical study on the reactivity of Agn+ clusters with H2S, D2O, and NH3. Complete dehydrogenation products are observed for Agn+ reacting with H2S, but no dehydrogenation products are found for D2O or NH3 under the same reaction condition. Theoretical calculations elucidate why Agn+ clusters show different reactivities with these inorganic hydrides. NH3 shows strong coordination with Agn+, but the dehydrogenation reactions are unfavorable; in contrast, the fragile H-S bonds and stable AgnS+ products facilitate the hydrogen evolution of H2S on Agn+. We fully analyzed the metal-ligand interactions of Agn+ clusters with three molecules and illustrated the reaction dynamics and charge-transfer interactions and altered the superatomic states during the formation of cluster sulfides. We expect this study to benefit the design of stable environmentally friendly desulfurization catalysts and also the understanding of the mechanism on ligand-protected metal clusters in wet chemistry.

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INTRODUCTION: A total of 10% of older individuals harbour adrenal incidentalomas and need dedicated adrenal CT to exclude malignancy and biochemical evaluation. These investigations tax medical resources, and diagnostic delay may cause anxiety for the patient. We implemented a no-need-to-see pathway (NNTS) in which low-risk patients only attend the clinic if adrenal CT or hormonal evaluation is abnormal. METHODS: We investigated the impact of a NNTS pathway on the share of patients not requiring an attendance consultation, time to malignancy and hormonal clarification, and time to end of investigation. We prospectively registered adrenal incidentaloma cases (n = 347) and compared them with historical controls (n = 103). RESULTS: All controls attended the clinic. A total of 63% of cases entered and 84% completed the NNTS pathway without seeing an endocrinologist; 53% of consultations were avoided. Time-to-event analysis revealed a shorter time to clarification of malignancy (28 days; 95% confidence interval (CI): 24-30 days versus 64 days; 95% CI: 47-117 days) and hormonal status (43 days; 95% CI: 38-48 days versus 56 days; 95% CI: 47-68 days) and a shorter time to end of pathway (47 days; 95% CI: 42-55 days versus 112 days; 95% CI: 84-131 days) in cases than controls (p ≤ 0.01). CONCLUSION: We demonstrated that NNTS pathways may be an efficient way of handling the increased burden of incidental radiological findings, avoiding 53% of attendance consultations and achieving a shorter time to end of pathway. FUNDING: Supported by a grant from Regional Hospital Central Denmark, Denmark. The study was approved by the institutional review boards of all participating hospitals. TRIAL REGISTRATION: Not relevant.

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Fullerenes are lowest energy structures for gas phase all-carbon particles for a range of sizes, but graphite remains the lowest energy allotrope of bulk carbon. This implies that the lowest energy structure changes nature from fullerenes to graphite or graphene at some size and therefore, in turn, implies a limit on the size of free fullerenes as ground state structures. We calculate this largest stable single shell fullerene to be of size N = 1 × 104, using the AIREBO effective potential. Above this size fullerene onions are more stable, with an energy per atom that approaches graphite structures. Onions and graphite have very similar ground state energies, raising the intriguing possibility that fullerene onions could be the lowest free energy states of large carbon particles in some temperature range.

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AIMS: The aim was to investigate rebound hypoglycemic and hyperglycemic events, and describe their relation to other glycemic metrics. METHODS: Data from intermittently scanned continuous glucose monitoring were downloaded for 90 days for 159 persons with type 1 diabetes. A hypoglycemic event was defined as glucose <3.9 mmol/l for at least two 15-minute periods. Rebound hypoglycemia (Rhypo) was a hypoglycemic event preceded by glucose >10.0 mmol/l within 120 minutes and rebound hyperglycemia (Rhyper) was hypoglycemia followed by glucose >10.0 mmol/l within 120 minutes. RESULTS: A total of 10 977 hypoglycemic events were identified of which 3232 (29%) were Rhypo and 3653 (33%) were Rhyper, corresponding to a median frequency of 10.1, 2.5, and 3.0 events per person/14 days. For 1267 (12%) of the cases, Rhypo and Rhyper coexisted. The mean peak glucose was 13.0 ± 1.6 mmol/l before Rhypo; 12.8 ± 1.1 mmol/l in Rhyper. The frequency of Rhyper was significantly (P < .001) correlated with Rhypo (Spearman's rho 0.84), glucose coefficient of variation (0.78), and time below range (0.69) but not with time above range (0.12, P = .13). CONCLUSIONS: The strong correlation between Rhyper and Rhypo suggests an individual behavioral characteristic toward intensive correction of glucose excursions.

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Objective: Treatment options in Graves' disease (GD) are limited and do not target the underlying autoimmunity, and relapse rates following a course of antithyroid drug (ATD) reach 50%. Previous research has shown promising results for a role of vitamin D in GD. We aimed to investigate whether vitamin D reduces failure to enter and sustain remission in patients with GD treated with ATD. Design: A multicenter, double-blinded, randomized placebo-controlled trial comparing vitamin D 70 mcg once daily (2800 IU) or placebo. The intervention was given first as add-on to ATD treatment, maximally 24 months, and then for 12 months after ATD cessation. Inclusion period was from 2015 to 2017 and study completion by December 2020. Patients included were adults with a first-time diagnosis of GD treated with ATD. Exclusion criteria included pregnancy and glucocorticoid treatment. The primary endpoint was failure to enter and sustain remission defined as relapse of hyperthyroidism within 12 months after ATD cessation, inability to stop ATD within 24 months, or radioiodine treatment or thyroidectomy. Two hundred seventy-eight patients were included in the study, and 4 patients withdrew consent. No adverse effects were found. Results: Participants were aged 44 ± 14 years at enrollment and 79% were female. The risk of failure to enter and sustain remission was 42% [95% confidence interval (CI) 33-50%] in the vitamin D group and 32% [CI 24-40%] in the placebo group corresponding to a relative risk of 1.30 [CI 0.95-1.78]. Conclusions: Vitamin D supplementation did not improve the treatment of GD in patients with normal or insufficient vitamin D status. Thus, supplementation with high-dose vitamin D cannot be recommended for GD. Study registration: ClinicalTrials.gov NCT02384668.

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The later stages of cooling of molecules and clusters in the interstellar medium are dominated by emission of vibrational infrared radiation. With the development of cryogenic storage it has become possible to experimentally study these processes. Recent storage ring results demonstrate that intramolecular vibrational redistribution takes place within the cooling process, and an harmonic cascade model has been used to interpret the data. Here we analyze this model and show that the energy distributions and the photon emission rates develop into near-universal functions that can be characterized with only a few parameters, irrespective of the precise vibrational spectra and oscillator strengths of the systems. We show that the photon emission rate and emitted power vary linearly with total excitation energy with a small offset. The time developments of ensemble internal energy distributions are calculated with respect to their first two moments. The excitation energy decreases exponentially with a rate constant which is the average of all k1→0 Einstein coefficients, and the time development of the variance is also calculated.

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The conversion of ethane into value-added chemicals under ambient conditions has attracted much attention but the mechanisms remain not fully understood. Here we report a study on the reaction of ethane with thermalized Nbn + clusters based on a multiple-ion laminar flow tube reactor combined with a triple quadrupole mass spectrometer (MIFT-TQMS). It is found that ethane reacts with Nbn + clusters to form both products of dehydrogenation and methane-removal (odd-carbon products). Combined with density functional theory (DFT) calculations, we studied the reaction mechanisms of the C-C bond activation and C-H bond cleavage on the Nbn + clusters. It is unveiled that hydrogen atom transfer (HAT) initiates the reaction process, giving rise to the formation of Nb-C bonds and an elongated C-C distance in the HNbn + CH2 CH3 motif. Subsequent reactions allow for C-C bond activation and a competitive HAT process which is associated with CH4 removal or H2 release, resulting in the production of the observed carbides.

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The geometric structures and reaction dynamics of clusters of carbon fullerene molecules are reviewed. The topics on structure cover the elementary building blocks, the interatomic and intermolecular potentials, and the geometric structures of the aggregates. The dynamics part describes the time development after excitation with laser light, in bimolecular collisions, and in collisions with high energy atomic ions. These reactions produce singly or multiply charged clusters, fragmented or intact fullerene monomers, and fusion products. The duration of the interaction time and the transferred energy are found to play determining roles for the nature of the products. Short interaction times and high energy excitation favor intramolecular reactions on excited potential energy surfaces, producing fused products, often with a strong release of the combined excess energy and heat of fusion. Clusters excited at low energies tend to disintegrate into intact fullerene molecules.

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BACKGROUND: The indication for treatment of type 1 diabetes(T1D) with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin has been withdrawn in Europe likely because of concern for diabetic ketoacidosis (DKA). We calculated the incidence of DKA in people with T1D treated with SGLT2i in Denmark. METHODS: Clinical data from adults with T1D in Denmark were collected from nine outpatient clinics. Electronic health records made the search for DKA accurate. RESULTS: From a population of 10.500 we observed 134 people treated with SGLT2i over a total period of 222 patient-years. Of those 72% were female, mean age (SD) was 51.4 (13.6) years and median duration of treatment (median, IQR) with an SGLT2i were 12.0 (6.0-29.0) months. The incidence of DKA was zero%. CONCLUSION: In 134 people with T1D treated with SGLT2i we found that none of the participants developed DKA during the treatment.

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INTRODUCTION: The aim of the study was to assess the variation of glucose time in range (TIR) for persons with type 1 diabetes who perform intermittently scanned continuous glucose monitoring (isCGM). METHODS: Glucose data for 8 weeks were analysed for 166 persons. TIR was calculated over four consecutive 2 weeks periods. Sixty-one of the persons had two downloads with an interval of >3 months. RESULTS: A total of 140 individuals (84%) used multiple daily injection, and 26 (16%) used continuous insulin infusion. The within-individual standard deviation (SD) for TIR was 6.3% corresponding to 95% limits of agreement for the difference between two TIR values of ±17.6%. Mean TIR calculated from the first and last 2 weeks was 52.2 ± 17.1% and 53.7 ± 16.4%, respectively (difference 1.5%, SD of the difference 10.4%, p = .07). For persons with two downloads separated by months, the SD of the difference in TIR was 12.6%. CONCLUSIONS: The 95% limit of agreement for TIR is vast for persons using isCGM. It is difficult to draw firm conclusions regarding systematic differences when individual TIR from 2 weeks are compared. This may not be valid for users of insulin pumps with closed-loop insulin delivery.

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