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Two published cosmogenic radionuclide (CRN) 26Al/10Be burial age calculation methods developed to correct for post-depositional production of nuclides in settings with low sediment overburden are compared. The advantages and limitations of simple (ISO; [1], [2]) and inverse modelling (INV, [3]) isochrons are investigated.The studied dataset originates from the gravel of a Danube terrace in the Central Vienna Basin (Austria) [4]., where two horizons (5.5 m and at 11.8 m subsurface depth) were sampled. Each sample set contained 6 quartz or quartzite cobbles.The advantage of ISO is that it is uninfluenced by changes in sample depth over time. However, the initial 26Al/10Be ratio is fixed and no pre- and post-burial denudation rates can be calculated. In addition to age, INV models source and sink denudation rates, but assumes constant depth over burial time.For correct application of ISO and INV outliers, must be excluded. The robustness of both methods is tested by systematically including or excluding data points (bootstrapping) to estimate the dependence of numerical ages on sample selection either in the field, or during outlier identification.For outlier identification the traditional method of data exclusion of points above or below the isochron line is used. In addition, a new way is introduced here: the post-burial production is calculated using the modelled burial age and denudation rate and compared to the measured inventories of 10Be and 26Al. If the fraction of post-burial production is equal or higher compared to the measured inventory and its ratio is considerably different for the two isotopes from the same sample, the datapoint is invalid.In addition, the influence of each sample on the modelled burial age, tested by bootsrapping, is used to exclude samples with a large effect on the age.The resulting ages at both levels using ISO and INV agree within errors with ISO being systematically slightly younger. The importance of outlier removal is stressed by the fact that inclusion of all samples results in a considerably older age of the stratigraphically higher level compared to the underlying one. When outliers are excluded, burial ages of the two sampled horizons overlap within uncertainty, suggesting one single deposition event for the whole sediment package.Interestingly, when the entire dataset is merged, both methods provide similar ages regardless of the outliers being excluded or kept in. This demonstrates that a larger sample number increases the robustness of a dataset considerably and decreases the sensitivity of either method to potential outliers.In summary, both ISO and INV are robust ways of CRN burial age determination, provided that model presumptions are not violated and outliers are excluded or the sample number large enough to overprint the influence of outliers.Funding: NKFIH FK124807; OMAA 90ou17; OMAA 98ou17. References[1] Balco, G., Rovey, C.W., 2008. American Journal of Science 308(10), 1083-1114.[2] Erlanger, E.D., et al., 2012. Geology 40(11), 1019-1022.[3] Pappu, S. et al., 2011. Science, 331(6024), 1596-1599.[4] Ruszkiczay-Rüdiger, Zs. et al., 2021. Journal of Radioanalytical and Nuclear Chemistry, 329(3), 1523-1536.

Satellite-based maps of glacial landforms reveal that the mountain landscapes of northeast Eurasia contain over one million km2 of glaciated terrain. Previous work has speculated on the existence of large ice masses during the Last Glacial Maximum (LGM) and the preceding cold phases, but the lack of age constraints means that little is known about the timing of past glaciations across this vast region.With an aim to gain a better understanding of the glacial history of this region, we collected samples for cosmogenic 10Be exposure dating of boulder erratics and moraines in the mountains of eastern Siberia. Here, we present the first results from two sites, both within the Chersky Range: (1) Malyk Sen, which contains a succession of three end moraines in a foreland setting; and (2) Ust-Nera, which features boulder erratics and glacial bedrock pavement exposed in a previously glaciated valley. At Malyk Sen, the relative positions and corresponding ages of the three moraines indicate progressive contraction of maximum glacier extent since termination of the Marine Isotope Stage (MIS) 6, with the innermost moraine dated to the LGM. Our preliminary results from Ust-Nera suggest exposure ages from glacially-transported boulders and bedrock pavement that are significantly older than the LGM. Both sites indicate limited extents of mountain glaciation during the LGM in eastern Siberia. And while the glacial chronology of our study does not extend beyond MIS 6, mapping of the surrounding areas indicates that even more expansive glaciers existed further back in time.Our findings confirm the trend of successively smaller glacial extent maxima’s in continental Eurasia towards the LGM, with at least one ice advance during MIS 5-3 larger than the LGM advance. This trend could to be linked to extreme continental settings such as in Eurasia and westernmost America, as it contrasts with larger parts of the Northern Hemisphere glaciations where Late Pleistocene maxima were reached during LGM.

OBJECTIVES: The Transdiagnostic Self-injury Interview (TSI) is a new measure that assesses the onset, frequency, methods, and severity of non-suicidal self-injury. The aims were to demonstrate the feasibility of a TSI validation study, and to investigate TSI's criterion validity, clinical correlates, and interrater reliability.MATERIALS AND METHODS: Recruiting sites were psychiatric in- and outpatient units. Feasibility targets included number of participants completing the study, TSI completion time, total participation time, participants experiencing exacerbation of symptoms, along with other targets. Criterion validity was evaluated using the Deliberate Self-Harm Inventory (DSHI). Clinical correlates were examined with the Columbia-Suicide Severity Rating Scale (C-SSRS), the Personal and Social Performance Scale, the Affective Lability Scale-18, and the Brief Trauma Questionnaire. Interrater reliability was evaluated with video recordings and written material.RESULTS: Fifty participants were included. The majority were women (76%) and had a mean age of 31.3 years (SD: 10.4). Schizophrenia (44%) and schizoaffective disorder (18%) were the most prevalent diagnoses. TSI took an average 9.3 min to complete and the total participation time was on average less than one hour. One participant experienced an exacerbation of self-injury ideation (without the need of intervention). A significant correlation was found between TSI and DSHI ( r: 0.94, p-value: < 0.001). TSI was correlated to C-SSRS ideation intensity and ideation frequency but not suicidal attempts. TSI was not significantly correlated to other measures. Interrater reliabilities were statistically significant. CONCLUSIONS: The results support the feasibility of a TSI validation study, which is needed to validate TSI in different settings and across diagnoses.

INTRODUCTION: Malnutrition and disturbed sense of smell and taste frequently occur in patients treated with chronic haemodialysis. The common denominator between chemosensation and nutrition may be food preferences. Our aim was to investigate smell and taste function as well as food preferences among haemodialysis patients and compare the results with those of age-matched controls.METHODS: An observational case-control study was conducted on 29 patients on chronic haemodialysis and 39 age-matched healthy controls. Chemosensory function was evaluated using validated gustatory and olfactory tests. Food preferences were recorded using a questionnaire of 63 items including a five-point Likert scale of familiarity, liking and frequency.RESULTS: Chemosensory function was significantly poorer among patients than among controls. Patients had significantly lower familiarity and frequency of consumptions of all food categories than controls and they also had significantly lower liking of vegetables, fruits and starches.CONCLUSIONS: Implementation of the provided knowledge about haemodialysis patients' smell and taste function including their food preferences are suggested, such as enhancement of odorant intensity, use of taste amplification, cooking habits and exposure to more varied food items. Assessments of food preferences and chemosensory function prior to determination of individual dietary schedules are therefore recommended.FUNDING: The authors did not receive any financial support for the research or drafting of this article. The authors declare that they have no financial interests to report.TRIAL REGISTRATION: Danish Ethical Committee project number: M-2018-188-18.

BACKGROUND AND AIMS Non-invasive methods for assessing bone metabolism have been lacking in chronic kidney disease (CKD), and the effects of different treatments on bone metabolism are mostly unknown. However, fluorine-18 labeled sodium fluoride (18F-NaF) PET/CT scanning can assess bone turnover as skeletal plasma clearance of tracer (Ki) and bone volume/tissue volume (BV/TV) in CKD. In a randomized crossover study, we aimed to compare the 8-week treatment effects of a non-calcium-based phosphate binder, sucroferric oxyhydroxide (SO), with 8 weeks of treatment with a calcium-based phosphate binder, calcium carbonate (CC), on bone turnover and BV/TV. METHOD Whole body 18F-NaF PET/CT scans were performed at the end of the CC and SO treatment periods in each participant. Ki was determined by the single-point Patlak method with semi-population input functions. A recently established CKD-MDB population residual curve was applied. Estimation of BV/TV was made by CT-derived Hounsfield units (HU) in specified volumes of interest. Paired t-tests were used or non-parametric tests (Wilcoxon signed-ranks test) when data were not normally distributed. Statistical analyses were performed using SPSS 20. RESULTS Ki assessed by the 18F-NaF scan was not significantly different at the lumbar spine (CC: 0.030 ± 0.014 mL min–1 mL–1; SO: 0.031 ± 0.014 mL min–1 mL–1; P = .75) or any other site after short-term treatment with SO or CC. However, HU was significantly higher after CC treatment. CONCLUSION 18F-NaF PET/CT is a practical tool with which to evaluate bone metabolism in CKD. Short-term SO treatment did not affect Ki (turnover) differently than CC treatment, but BV/TV (volume) was significantly lower after SO treatment than after CC treatment.

BACKGROUND AND AIMS High blood pressure (BP) is an essential contributor to the risk of cardiovascular disease (CVD) and death. Hence, diagnosing and treating patients with high BP is paramount if the number of cardiovascular related death should be reduced. High nocturnal BP and blunting of normal nocturnal BP decrease have stronger correlation to the risk of CVD than high day time BP. Lowering nocturnal BP is assumed to reduce the risk of CVD. Patients with treatment resistant hypertension (TRH) represent a subgroup of hypertensive patients characterized by lack of BP control despite antihypertensive treatment. These patients are at particular risk of CVD and target organ damage. Patients with TRH are more likely to experience BP increase as a response to sodium loading than other individuals. Lifestyle modification is an important treatment angle in hypertensive patients. It is, in particular, central to reduce sodium intake, as high sodium intake increases the risk of TRH. Thus, in this study we aimed to analyse if self-performed dietary sodium restriction could be implemented in patients with TRH. Moreover, we aimed to analyse the effect of this attempted restriction on nocturnal BP and 24 h BP, on plasma levels of BNP and nitric oxide, and on body water content. METHOD Patients with TRH from 20 to 70 years with normal renal function were invited for participation in this cross-over interventional study. Patients were screened with 24 h ambulatory BP monitoring initiated after observed intake of usual antihypertensive medication, and they were included if 24 h systolic BP/diastolic BP ≥ 130/80 mmHg. Study participation included two periods of 14 days; a standard period with usual diet and an interventional period with instructed dietary sodium restriction and handed-out sodium-reduced bread. For both periods, all antihypertensive medication was dosed and handed out and ingested in the morning. At the end of each period, patients were examined with 24 h BP monitoring, 24 h urine collection (sodium excretion), blood samples (nitric oxide and BNP) and bioimpedance measurement (body water content). RESULTS Baseline characteristics of the fifteen included patients are shown in Table 1. Eleven of the patients were male. Patients had been treated for hypertension for a mean of 12.5 (7) years and excreted a mean of 11.2 grams of salt at baseline [192 (86) mmol sodium]. All patients but one reduced sodium excretion at follow up. Table 2 shows the effect of sodium restriction on BP, nitric oxide, BNP and body water content. Sodium excretion was reduced to 91 mmol/24 h, which equals 5.3 g of salt. BP (24 h, day and nocturnal) decreased significantly as well as body water content and plasma levels of BNP. These changes were, however, not correlated. Plasma levels of nitric oxide increased, but it was not related to the changes in BP. Nocturnal fraction of 24 h sodium excretion increased after sodium restriction; however, this was not correlated to changes in nocturnal BP. Renal function and urinary potassium excretion both remained unchanged. Four patients experienced side effects; three reported newly onset dizziness at follow-up; two of them had 24 h BP reduction > 10 mmHg systolic. One patient had increased creatinine and potassium at follow-up. CONCLUSION In a population of 15 treatment resistant hypertensive patients, we demonstrated that self-performed dietary sodium restriction could be implemented. Urinary sodium excretion was reduced significantly to 5.3 g/24 h. Nocturnal BP was reduced significantly; dipping status was, however, unchanged. Increased plasma levels of nitric oxide may be evidence of improved endothelial function. Hence, by the local vasodilating effect, NO may be one of the involved mechanisms in BP decrease following a sodium restriction. Reduced extracellular water content and BNP may be other explainable effects of BP reduction after inducing sodium restriction.

Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high‐risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high‐risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24‐hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0–170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8–7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m 2 (95% CI, 36.6–45.6). In 96 patients with available 3‐month follow‐up data, mean 24‐hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4–23.8; P< 0.001), the defined daily dose of antihypertensive medication was reduced by 52% (95% CI, 41%–62%; P 2 (95% CI, 4.5–11.1; P Conclusions In this prospective cohort study, we observed a reduction in blood pressure and antihypertensive medication, an increase in estimated glomerular filtration rate, and a decrease in new hospital admissions attributable to heart failure/sudden pulmonary edema after renal artery stenting. Registration URL: https://clinicaltrials.gov . Identifier: NCT02770066.

Background: Medical students in Denmark undertake a demanding 6-year course which is generally during a critical age for the development of psychiatric disorder and harmful substance or alcohol use behaviours. Previous literature has highlighted significant rates of distress in Danish students. Aims: We surveyed medical students in Denmark to better understand wellbeing, psychiatric morbidity, sources of stress, substance and alcohol use, psychological distress and burnout. Methods: Medical students were invited to participate in a single survey via email and social media which was completed through an online form, available for a 6-month period. The survey used a mixture of pre-defined answer options alongside free-text responses. Embedded within the survey were standardised and reliable specific instruments related to alcohol use (the CAGE questionnaire), overall psychological wellbeing and burnout. Results: There were 647 respondents, with a quite even year-group distribution, representing just over 16% of total number of students attending medical school in Denmark. Prior to medical school 35% had visited a professional regarding their mental health. While at medical school 16% reported a diagnosis of a mental health condition. 83% reported significant stress from study. Around 7 in 10 met case criteria using instruments designed to test for minor psychiatric morbidity and burnout. 13% tested CAGE positive, whilst 4% reported concerns from themselves or others about their substance use. Conclusions: Our study demonstrates high levels of psychiatric morbidity and worrying levels of burnout in this population. The striking 13% CAGE positive rate suggests this demographic is at risk of harm from alcohol. Our results suggest a high level of need to support this population – with further study required to demonstrate which interventions would be of most benefit for this population in light of our findings.

Background and Hypothesis In patients with schizophrenia spectrum disorder (SSD), the lifetime prevalence of self-harm (SH) and non-suicidal self-injury (NSSI) is currently uncertain. The primary aim of this review was to provide a synthesis of the existing literature concerning the prevalence of SH/NSSI in individuals with SSD, and individuals at clinical high risk of psychosis (CHR-P). Secondary aims were to investigate methods, severity, and functions of self-injurious behavior in these populations. Study Design Studies quantifying the prevalence of SH/NSSI in individuals with SSD or at CHR-P were included in this review. MEDLINE, EMBASE, and PsycInfo were searched for eligible studies June 10, 2022 and systematically screened by two independent reviewers. Risk of bias was assessed using the Joana Briggs Institute Critical Appraisal Checklist for Prevalence Studies by two independent reviewers. A meta-analysis of the lifetime prevalence of SH/NSSI was conducted using generalized linear mixed model with the logit transformation. Study Results Thirty-two studies were included in this review (n = 15 440), 4 of which included individuals at CHR-P (n = 397). The meta-analysis showed a pooled lifetime prevalence of SH of 31.0% (95% CI: 22.1%; 41.6%) in individuals with SSD (n = 2822) and 39.7% (95% CI: 17.5%; 70.0%) in individuals at CHR-P (n = 397). These estimates should be interpreted with caution due to substantial heterogeneity. Cutting was the most frequent method of SH/NSSI and SH command hallucinations may be an overlooked cause of self-injurious behavior in these patients. Conclusions Self-injurious behavior is a highly prevalent, and possibly overlooked concern, in individuals with SSD and at CHR-P.

For sediment-burial dating with a cosmogenic nuclide pair, the isochron burial method performs well provided that the sediment source has undergone (1) steady erosion and (2) continuous exposure to cosmic rays. These conditions exert important limitations on applications of the method. And yet, in mountainous fluvial and glacial landscapes, it is commonly found that the source area has experienced landsliding or glacial quarrying (i.e., non-steady erosion), and/or intermittent sediment storage or burial beneath glaciers (i.e., discontinuous exposure). As well as breaching the assumptions of the isochron method, such processes tend to yield low nuclide concentrations in the sample, which further limits its workability.Here we present a more flexible method that accommodates complex, non-steady pre-burial erosion and exposure histories: conditions that exclude the isochron burial method. P-PINI (Particle Pathway Inversion of Nuclide Inventories) is a Monte Carlo-based inversion model that employs a source-to-sink approach for estimating the depositional age of fluvial and glaciogenic sediments. This method has been successfully applied to the Deckenschotter in the northern Alpine foreland (see Knudsen et al. 2020, Earth & Planetary Science Letters 549, 116491). As with the isochron burial method, P-PINI exploits an ensemble of paired nuclide (e.g., 10Be-26Al) concentrations measured in different samples from the same depth in a sedimentary sequence. But unlike the isochron method, P-PINI applies a stochastic approach to simulate a wide range of possible pre-depositional exposure and erosion histories for each individual sample. These different pre-burial histories (unique to each sample) are then integrated with the constraint that all samples share a common burial history at the sink. Where cosmogenic nuclide data (or other chronometric data, e.g., OSL) are available for multiple sites, Bayesian inference modelling can impose a priori relative age constraints, or estimates on the maximum duration of sediment storage.In this presentation, we extend P-PINI to explore how sediment storage and reworking (i.e., a range of burial depths and durations) between source and sink affects burial age estimates. Significant intermediate storage is characteristic of large river systems, such as the Danube River. Using cosmogenic 10Be-26Al concentrations measured in fluvial gravels at Gänserndorf and Schlosshof, two terraces along the Danube River in the Vienna Basin (Braumann et al., 2019. Quat. Int. 509. 87-102), we examine how the burial ages at these two sites are a function of the pre-burial history experienced by the samples.

International audience; The Ebro Basin constitutes the central part of the southern foreland of the Pyrenees. It was endorheic during the Cenozoic and accumulated sediments. By the end of the Miocene, erosion and river incision reconnected the basin to the Mediterranean Sea, establishing a post-opening drainage network. Those rivers left terraces that we study in this work. We first synthesize previous works on river terraces that are widely dispersed in the basin. We provide new age constraints, up to 3 Ma, obtained thanks to cosmogenic nuclides using both profile and burial methods. We derive a unified fluvial terrace chronology and a homogenized map of the highest terraces over the entire Ebro Basin. The dated terraces labeled A, B, C, D, and E are dated to 2.8±0.7 Ma, 1.15±0.15 Ma, 850±70 ka, 650±130 ka, and 400±120 ka, respectively. The chronology proposed here is similar to other sequences of river terraces dated in the Iberian Peninsula, around the Pyrenees, and elsewhere in Europe. The oldest terraces (A, B, C) are extensive, indicating they form a mobile fluvial network while from D to present, the network was stable and entrenched by 100 to 200 m-deep valleys. The transition from mobile to a fixed fluvial network is likely to have occurred during the Middle Pleistocene Transition (MPT, between 0.7 and 1.3 Ma), when long-period/high-intensity climate fluctuations were established in Europe. We estimate that between 2.8-1.15 Ma and present, the incision rates have tripled.; Le bassin de l’Ebre constitue le centre du piémont sud-pyrénéen. Il a été endorhéique et a accumulé une épaisseur importante de sédiments au cours du Cénozoique. Vers la fin du Miocène, l'érosion et l'incision fluviale ont reconnecté le bassin à la mer Méditerranée, en établissant un nouveau réseau de drainage. Les rivières constituant ce réseau ont laissé des terrasses que nous étudions dans le cadre de ce travail. Nous faisons d'abord une synthèse des travaux antérieurs sur les terrasses fluviales, qui sont largement dispersées dans le bassin. Ensuite, nous fournissons de nouvelles contraintes d'âge, jusqu'à 3 Ma, obtenues grâce aux nucléides cosmogéniques utilisant à la fois des méthodes de profil d’exposition et d'enfouissement. Enfin, nous en déduisons une chronologie unifiée des terrasses fluviales et une carte homogénéisée des terrasses les plus hautes sur l'ensemble du bassin de l'Ebre. Les terrasses, que nous notons A, B, C, D et E, sont datées respectivement de 2,8±0,7 Ma, 1,15±0,15 Ma, 850±70 ka, 650±130 ka et 400±120 ka. La chronologie proposée ici est similaire à d'autres séquences de terrasses fluviales datées dans la péninsule ibérique, autour des Pyrénées, et ailleurs en Europe. Les terrasses les plus anciennes (A, B, C) sont étendues, ce qui témoignent d’un réseau fluvial mobile alors que depuis la formation des terrasses D jusqu’à aujourd'hui, le réseau était stable et canalisé le long de vallées de 100 à 200 m de profondeur. Le passage d'un réseau fluvial mobile à un réseau fluvial fixe s'est probablement produit pendant la transition du Pléistocène moyen (entre 0,7 et 1,3 Ma), lorsque des fluctuations climatiques de longue période et de forte intensité ont été établies, comme l'ont déjà proposé Gibbard et Lewin (2009) pour les rivières européennes. Nous estimons qu'entre 2,8 et 1,15 Ma et la période actuelle, les taux d'incision ont triplé.

Additional file 1. Appendix: 82Rb-phantom studies for determination of recovery-coefficients.

A set of four outwash terraces in the northern Alpine Foreland motivated Penck and Brückner's classical scheme of four great Alpine ice ages: Günz, Mindel, Riss, and Würm. While it is now established that the Würm corresponds to marine isotope stages (MIS) 5d–2 (∼117–14 ka) and the Riss type locality to MIS 6 (∼191–130 ka), there is no consensus regarding the age of the older glaciations. The two oldest terraces, known as Höhere Deckenschotter (HDS) and Tiefere Deckenschotter (TDS) in Switzerland and neighbouring Germany, contain interbedded tills that directly indicate the first arrival of glaciers into the northern Alpine Foreland. Here, we set out to constrain the timing of the HDS, which signal the first major glaciations in the Alps. To achieve this goal, we devised a new burial-dating model tailored to glaciogenic sediments: P-PINI (Particle Pathway Inversion of Nuclide Inventories). The method applies a source-to-sink framework to a cosmogenic 10Be-26Al inversion model accounting for variable cosmic-ray exposure and non-steady erosion. Taking published 10Be-26Al data from five HDS sites (Feusi, Tromsberg, Siglistorf, Irchel Steig, and Irchel Hütz) and one TDS site (Iberig), we obtain age distributions (±1σ) that are especially well constrained for Feusi (0.93 ± 0.13 Ma), Iberig (0.93 ± 0.17 Ma), and Tromsberg (0.88 ± 0.14 Ma), less well-constrained for Irchel Steig (0.69 ± 0.25 Ma) and Siglistorf (0.94 ± 0.27 Ma), and very poorly constrained for Irchel Hütz (1.39 ± 0.56 Ma). Consistent with the morphostratigraphy, which dictates that the TDS postdates the HDS, we implemented a Bayesian modelling framework, yielding an age of 0.69 ± 0.12 Ma for Iberig (TDS) and a combined age of 0.95 ± 0.07 Ma for the HDS sites. Based on the P-PINI burial ages as well as the combined, Bayesian burial age, we propose an age around 1.0–0.9 Ma for the onset of the large Alpine glaciations that triggered the accumulation of the HDS outwash sediments. This roughly accords with the first long glaciation of the Pleistocene (MIS 24–22), identified as a step-change to colder climate and larger glaciations towards the end of the Middle Pleistocene Transition. While our results challenge previously reported ages of ∼2 Ma or more for the HDS in Switzerland, they corroborate evidence from the southern Alpine retroforeland and provide quantitative support for the early hypothesis by G.J. Kukla, who ascribed the oldest glacial deposits in the northern Alpine Foreland to around MIS 22. Finally, we suggest that the source-to-sink approach of P-PINI offers a viable alternative to the established isochron burial-dating method in cases involving non-steady exposure and erosion.

BackgroundMethods for assessing bone metabolism which can replace the gold standard bone biopsy are sorely needed in the clinical setting in patients with chronic kidney disease - mineral and bone disorder (CKD-MBD). The aim of the present study was implementation, validation and comparison of non-invasive dynamic and static whole-body (WB) [18F]NaF PET/CT scan methods to replace invasive bone biopsy, used for quantitative analysis of bone clearance in CKD-MBD patients.MethodsSeventeen patients with CKD-MBD underwent a 60-minute dynamic scan followed by a 30-minute static WB scan. Tracer kinetics in four thoracic vertebrae were analyzed using non-linear regression with the Hawkins model and two different Patlak-analysis methods using image-derived arterial input functions obtained from the left myocardial ventricle and the thoracic aorta. For future use in WB PET/CT scans, we validated the use of a semi-population input function. The resulting kinetic parameters (Ki, K1, k2, k3, k4, V0) were compared between the different methods of analysis using the various derived input functions.ResultsDynamic kinetic results from both standard and single-point Patlak analyses correlate well with non-linear regression analysis, but Ki results using Patlak analysis are generally lower for all tested input functions compared to regression analysis. Single-point Patlak analysis on WB scans correlates well with standard Patlak analysis on dynamic scans but show 13-21% higher Ki-values. ConclusionsOur results show good correlation between dynamic and static analysis of skeletal plasma clearance but different Ki-values depending on the analysis method and choice of input function used. Thus, WB [18F]NaF PET/CT scans can be applied in future studies, but the results should not be compared uncritically with results obtained using non-linear regression analysis.

BACKGROUND: Treatment with thyroid hormones is occasionally used in the management of treatment-resistant depression. However, the evidence supporting this treatment is not fully established. The aim of this study was to systematically review the literature on the effect of adjunctive thyroid hormone in the management of treatment-resistant unipolar depression and to provide a pooled estimate of its efficacy.METHODS: The study is registered with PROSPERO (reg. no. CRD42018108088) and followed the PRISMA guidelines. Searches were carried out on June 24th , 2019 in PubMed, EMBASE, and PsycINFO. Each record was screened independently by at least two reviewers. In instances of discrepancies, consensus was reached upon discussion. Pooled efficacy estimates were calculated based on response rates (decrease of ≥50% on the primary outcome measure) using random effect statistics.RESULTS: The search yielded 1355 records. Based on the screening of these records, we identified 10 studies that met the inclusion criteria (total number of patients = 663). The comparison of response to thyroid hormones versus placebo resulted in an odds ratio of 1.56 (95%CI: 0.50-4.84). Similarly, the comparison of response to thyroid hormones versus lithium resulted in an odds ratio of 1.91 (95%CI: 0.85-4.26). Thus, adjunctive therapy with thyroid hormones was not superior to placebo or lithium in the management of treatment-resistant unipolar depression.CONCLUSION: According to this review and meta-analysis, there is not sufficient evidence to support the use of adjunctive thyroid hormones for treatment-resistant unipolar depression.