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Abstract Background The dopamine transporter (DaT) PET ligand [18F]FE-PE2I is used to aid the diagnosis of Parkinson’s disease. After encountering four patients with a history of daily sertraline use, who all showed atypical findings on [18F]FE-PE2I PET, we suspected that the selective serotonin reuptake inhibitor (SSRI), sertraline, might interfere with the results and lead to globally reduced striatal [18F]FE-PE2I binding due to sertraline’s high affinity for DaT. Methods We rescanned the four patients with [18F]FE-PE2I PET after a 5-day sertraline pause. Sertraline plasma concentration was estimated based on body weight and dose, and specific binding ratios (SBR) in caudate nucleus, known to be more preserved in Parkinson’s, were used to estimate the effect on tracer binding. Comparison was made to a patient with [18F]FE-PE2I PET before and after a 7-day Modafinil pause. Results We found a significant effect of sertraline on caudate nucleus SBR (p = 0.029). The effect showed a linear dose-dependent relationship that corresponds to a reduction in SBR by 0.32 or 0.44 for a 75 kg male or a 65 kg female, respectively, taking a daily dose of 50 mg sertraline. Conclusion Sertraline is one of the most commonly used antidepressants and in contrast to other SSRI’s, sertraline show high affinity for DaT. We recommend that sertraline treatment is taken into account when patients are undergoing [18F]FE-PE2I PET especially in patients showing apparent globally reduced PE2I binding. If tolerable, pausing of the sertraline treatment should be considered, especially for doses above 50 mg/day.

BackgroundDiagnosis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is challenging and new tools are needed for early diagnosis as well as to understand the biochemical events that underlie the pathology in TB-IRIS.MethodsPlasma samples were obtained from participants from a randomized HIV/TB treatment strategy study (AIDS Clinical Trials Group [ACTG] A5221) with (n = 26) and without TB-IRIS (n = 22) for an untargeted metabolomics pilot study by liquid-chromatography mass spectrometry. The metabolic profile of these participants was compared at the study entry and as close to the diagnosis of TB-IRIS as possible (TB-IRIS window). Molecular features with p

Abstract Background Chronic low‐grade inflammation has been suggested as one of the key elements in the development of sarcopenia, but in contrast to disease‐related loss of muscle mass, the role of chronic low‐grade inflammation in age‐related (primary) sarcopenia is still not clear. The aim of this study was to investigate low‐grade inflammation in relation to age and the potential association between inflammatory biomarkers and body composition, muscle strength and physical performance in a healthy Danish cohort. Methods There were 1160 generally healthy men and women (range: 22–93 years) included. Appendicular lean mass (ALM) and visceral fat normalized to height (kg/m2) was assessed by dual‐energy X‐ray absorptiometry (iDXA, GE Lunar). Muscle strength and physical performance were evaluated by handgrip strength (HGS), 30 s sit‐to‐stand performance, and maximal gait speed (GS). Systemic levels of TNF‐α, IL‐6, IL‐1β, IL‐4, IL‐13, and IFN‐γ were measured using multiplex bead‐based immunoassays (Bio‐Rad). hsCRP was assessed using latex particle‐enhanced immunoturbidimetric assays (Roche Diagnostics). Results With age, ALM/h2, HGS, sit‐to‐stand performance and GS decreased, whereas visceral fat/h2 increased in both men and women (P

Abstract Background Whilst much attention is given to eliminating HIV mother-to-child transmission (MTCT), little has been done to ensure the same for hepatitis B virus (HBV) transmission. The introduction of HBV immunization at six weeks of age has reduced HBV horizontal transmission in South Africa. However, in order to eliminate HBV MTCT, further interventions are needed. The risk of hepatitis C virus (HCV) MTCT in HIV-infected (HIV+) African women is not yet well described. This study aimed to determine the rate of HBV and HCV vertical transmission in HIV-exposed infants in South Africa. Methods Serum samples from infants enrolled in an isoniazid prevention study (P1041) were screened for HBV and HCV serology markers; screening was performed on samples collected at approximately 60 weeks of age of the infants. HBV DNA was quantified in HBsAg positive samples and HBV strains characterized through gene sequencing. All HCV antibody samples with inconclusive results underwent molecular testing. Results Three of 821 infants were positive for both HBsAg and HBV DNA. All HBV strains belonged to HBV sub-genotype A1. The rtM204I mutation associated with lamivudine resistance was identified in one infant, a second infant harboured the double A1762T/G1764A BCP mutation. Phylogenetic analysis showed clustering between mother and infant viral genomic sequences. Twenty-one of 821 HIV-exposed infants tested had inconclusive HCV antibody results, none were HCV PCR positive. Conclusions This study suggests that HBV vertical transmission is likely to be occurring in HIV-exposed infants in South Africa.. A more robust strategy of HBV prevention, including birth dose vaccination, is required to eradicate HBV MTCT. HCV infection was not detected.

Rifapentine is a potent antituberculosis drug currently in phase III trials. Bioavailability decreases with increasing dose, yet high daily exposures are likely needed to improve efficacy and shorten the tuberculosis treatment duration. Further, the limits of tolerability are poorly defined. The phase I multicenter trial in healthy adults described here investigated two strategies to increase rifapentine exposures: dividing the dose or giving the drug with a high-fat meal. In arm 1, rifapentine was administered at 10 mg/kg of body weight twice daily and 20 mg/kg once daily, each for 14 days, separated by a 28-day washout; the dosing sequence was randomized. In arm 2, 15 mg/kg rifapentine once daily was given with a high-fat versus a low-fat breakfast. Sampling for pharmacokinetic analysis was performed on days 1 and 14. Population pharmacokinetic analyses were performed. This trial was stopped early for poor tolerability and because of safety concerns. Of 44 subjects, 20 discontinued prematurely; 11 of these discontinued for protocol-defined toxicity (a grade 3 or higher adverse event or grade 2 or higher rifamycin hypersensitivity). Taking rifapentine with a high-fat meal increased the median steady-state area under the concentration-time curve from time zero to 24 h (AUC0-24ss) by 31% (relative standard error, 6%) compared to that obtained when the drug was taken with a low-fat breakfast. Dividing the dose increased exposures substantially (e.g., 38% with 1,500 mg/day). AUC0-24ss was uniformly higher in our study than in recent tuberculosis treatment trials, in which toxicity was rare. In conclusion, two strategies to increase rifapentine exposures, dividing the dose or giving it with a high-fat breakfast, successfully increased exposures, but toxicity was common in healthy adults. The limits of tolerability in patients with tuberculosis remain to be defined. (AIDS Clinical Trials Group study A5311 has been registered at ClinicalTrials.gov under registration no. NCT01574638.).

Abstract Background Despite no international consensus on the diagnostic criteria for sarcopenia, low lean mass, muscle strength, and physical function are important risk factors for disability, frailty, and mortality in older individuals, as well as in a wide range of patients with muscle loss. Here, we provide a population‐based reference material of total and regional lean body mass, muscle strength/power parameters, and physical function in a healthy cohort of Danish men and women across the lifespan. Methods Volunteers aged 20–93 years from the Copenhagen City Heart Study were invited to establish a Danish reference material (Copenhagen Sarcopenia Study) on lean mass characteristics [appendicular lean mass (ALM), iDXA, GE Lunar], muscle function [handgrip strength (HGS), Jamar dynamometer and leg extension power (LEP), Nottingham Power Rig], and physical function [30 s sit‐to‐stand test (STS), 10‐m maximal and habitual gait speed (GS)]. Results A total of 1305 participants [729 women (age: 56.4 ± 18.9 years, height: 1.66 ± 0.01 m, body mass index: 24.6 ± 4.3 kg/m2 and 576 men, age: 57.0 ± 17.5 years, height: 1.80 ± 0.07 m, body mass index: 26.0 ± 3.9 kg/m2] completed all measurements and were included in the present analysis. Lean mass characteristics (TLM, ALM, and ALM/h2) decreased with increasing age in both men and women (P < 0.001). Men demonstrated larger absolute and relative total ALM and higher HGS and LEP compared with women at all age intervals (P < 0.001). HGS and LEP decreased progressively with age in both men and women (P < 0.01); 30 s STS performance, habitual GS, and maximal GS decreased at an accellerated rate of decline with increasing age in both men and women (P < 0.001). Habitual GS was reduced in men and women aged ≥70 years, while maximal GS was reduced from the age of ≥60 years compared with young adults (P < 0.001). Regardless of sex, 30 s STS was reduced from the age of ≥50 years compared with the young reference group (P < 0.001) Conclusions While the power‐based measurements (LEP and 30 s STS) started to decline already at age +50 years, less power‐based parameters (GS and HGS) and lean mass characteristics (TLM, ALM, and ALM/h2) remained unaltered until after the age of +70 years. Notably, the cut‐off thresholds derived in the present study differed from earlier reference data, which underlines the importance of obtaining updated and local reference materials.

Background: Diagnosis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is challenging and new tools are needed for early diagnosis as well as to understand the biochemical events that underlie the pathology in TB-IRIS. Methods: Plasma samples were obtained from participants from a randomized HIV/TB treatment strategy study (AIDS Clinical Trials Group [ACTG] A5221) with (n = 26) and without TB-IRIS (n = 22) for an untargeted metabolomics pilot study by liquid-chromatography mass spectrometry. The metabolic profile of these participants was compared at the study entry and as close to the diagnosis of TB-IRIS as possible (TB-IRIS window). Molecular features with p

Abstract Human studies have demonstrated that physiologically relevant changes in circulating glucagon‐like peptide‐1 (GLP‐1) elicit a rapid increase in renal sodium excretion when combined with expansion of the extracellular fluid volume. Other studies support the involvement of various gastrointestinal hormones, e.g., gastrin and cholecystokinin (CCK) in a gut‐kidney axis, responsible for a rapid‐acting feed‐forward natriuretic mechanism. This study was designed to investigate the hypothesis that the postprandial GLP‐1 plasma concentration is sensitive to the sodium content in the meal. Under fixed sodium intake for 4 days prior to each experimental day, 10 lean healthy male participants were examined twice in random order after a 12‐hr fasting period. Arterial blood samples were collected at 10–20‐min intervals for 140 min after 75 grams of oral glucose + 6 grams of oral sodium chloride (NaCl) load versus 75 grams of glucose alone. Twenty‐four‐hour baseline urinary sodium excretions were similar between study days. Arterial GLP‐1 levels increased during both oral glucose loads and were significantly higher at the 40–80 min period during glucose + NaCl compared to glucose alone. The postprandial arterial responses of CCK, gastrin, and glucose‐dependent insulinotropic polypeptide as well as glucose, insulin, and C‐peptide did not differ between the two study days. Arterial renin, aldosterone, and natriuretic peptides levels did not change within subjects or between study days. Angiotensin II levels were significantly lower at the time GLP‐1 was higher (60–80 min) during glucose + NaCl. Sodium intake in addition to a glucose load selectively amplifies the postprandial GLP‐1 plasma concentration. Thus, GLP‐1 may be part of an acute feed‐forward mechanism for natriuresis.

Currently, assessing physical activity (PA) and cardiorespiratory fitness in healthcare settings and supporting patients on their journey toward active living is not a standard of practice in the US, although significant progress is underway. This paper summarizes the foundational as well as supporting public policies necessary to make PA assessment, prescription, and referral a standard of care in the US healthcare system to support active living for all. Measure standardization and healthcare integration will be supported by digital health and public private partnerships, as well as payer strategies and quality and performance incentives. The policy and systems change effort, currently being led by the Physical Activity Alliance's "It's Time to Move" initiative, will improve patient care and the ability to monitor PA levels across the US population, filling in gaps in current national public health surveillance systems. Having patient data available will also allow for additional research that elucidates the relationship between PA and overall health and well-being. [ABSTRACT FROM AUTHOR]

We demonstrate a new image processing methodology for resolving gas bubbles travelling through liquid metal from dynamic neutron radiography images with an intrinsically low signal-to-noise ratio. Image pre-processing, denoising and bubble segmentation are described in detail, with practical recommendations. Experimental validation is presented—stationary and moving reference bodies with neutron-transparent cavities are radiographed with imaging conditions representative of the cases with bubbles in liquid metal. The new methods are applied to our experimental data from previous and recent imaging campaigns, and the performance of the methods proposed in this paper is compared against our previously achieved results. Significant improvements are observed as well as the capacity to reliably extract physically meaningful information from measurements performed under highly adverse imaging conditions. The showcased image processing solution and separate elements thereof are readily extendable beyond the present application, and have been made open-source.

The dynamics of water infiltration into soil have a strong influence on the subsequent distribution of air trapped inside pores. We present results of two infiltration experiments conducted on an artificially prepared sample under ponding and drip irrigation boundary conditions, with concurrent neutron imaging of the sample. A cylindrical sample was packed with two grades of sand and disks of fine porous ceramic in an axially symmetrical geometry. The configuration of the sample provided a number of interfaces between regions of higher and lower hydraulic conductivity. Infiltration was started in dry media. The bottom boundary condition was seepage face. Water was applied on the sample surface during the experiment with drip irrigation at a water application rate about one order of magnitude lower than the minimum flux reached during the ponding experiment. Despite this low application rate, ponding eventually occurred on the top of the sample due to an unexpectedly low infiltration rate. Neutron tomographic imaging revealed massive air entrapment in the coarse sand regions of the sample during slow infiltration under drip irrigation conditions. In contrast, during the ponded infiltration experiment, the air was mostly flushed out from the coarse sand regions by gravity-driven water flow due to greater hydraulic head. Neutron imaging showed that the capillary barrier effect, air entrapment, and entrapped air redistribution were responsible for the observed low infiltration capacity of the sample during the slow-infiltration-dominated drip irrigation experiment. It is reasonable to assume that similar phenomena can occur in natural soils having highly heterogeneous structures.

We describe in this paper the experimental procedure, the data treatment and the quantification of the black body correction: an experimental approach to compensate for scattering and systematic biases in quantitative neutron imaging based on experimental data. The correction algorithm is based on two steps; estimation of the scattering component and correction using an enhanced normalization formula. The method incorporates correction terms into the image normalization procedure, which usually only includes open beam and dark current images (open beam correction). Our aim is to show its efficiency and reproducibility: we detail the data treatment procedures and quantitatively investigate the effect of the correction. Its implementation is included within the open source CT reconstruction software MuhRec. The performance of the proposed algorithm is demonstrated using simulated and experimental CT datasets acquired at the ICON and NEUTRA beamlines at the Paul Scherrer Institut.

Just after the start into the new millennium the concept for combined neutron and X-ray imaging was introduced by extending the standard configuration of the thermal neutron imaging NEUTRA instrument with a complementary 320 kV X-ray tube setup. Using essentially the same detector configuration for both neutron and X-ray imaging enables a pixel-wise (in radiography) and a voxel-wise (in tomography) correlation and combination of attenuation data. The optimal use and analyses of such complementary data sets depend on the specific investigation and research question and range from a combinatory interpretation of separately analyzed images to full data fusion approaches. Here, several examples from more than a decade of bimodal neutron and X-ray imaging at NEUTRA at PSI shall be reviewed.

This paper presents an empirical method by Kang et al. recently proposed for correcting two-dimensional neutron radiography for water quantification in soil. The method was tested on data from neutron imaging of the water infiltration in a soil sample. The raw data were affected by neutron scattering and by beam hardening artefacts. Two strategies for identifying the correction parameters are proposed in this paper. The method has been further developed for the case of three-dimensional neutron tomography. In a related experiment, neutron imaging is used to record ponded-infiltration experiments in two artificial soil samples. Radiograms, i.e., two-dimensional projections of the sample, were acquired during infiltration. A calculation was made of the amount of water and its distribution within the radiograms, in the form of two-dimensional water thickness maps. Tomograms were reconstructed from the corrected and uncorrected water thickness maps to obtain the 3D spatial distribution of the water content within the sample. Without the correction, the beam hardening and the scattering effects overestimated the water content values close to the perimeter of the sample, and at the same time underestimated the values close to the centre of the sample. The total water content of the entire sample was the same in both cases. The empirical correction method presented in this study is a relatively accurate, rapid and simple way to obtain the quantitatively determined water content from two-dimensional and three-dimensional neutron images. However, an independent method for measuring the total water volume in the sample is needed in order to identify the correction parameters.

Abstract Background Very few studies have investigated the determinants of circulating 25-hydroxyvitamin D (25[OH]D) in young adults (18–25 years old) using a set of variables that include lifestyle, sociodemographic, and anthropometric data. Our aim was to investigate the association between these variables and vitamin D status in a sample of untreated young adults. Methods A total of 738 young adults were enrolled in a (June cross-sectional study 2012 to May 2014) and were recruited from educational institutions in the Copenhagen area. For multivariate logistic regression subjects was categorized based on 25[OH]D in serum into; vitamin D sufficiency (S-25[OH]D > 50 nmol/L), vitamin D insufficiency (25 nmol/L ≤ S-25[OH]D ≤ 50 nmol/L), vitamin D deficiency (S-25[OH]D

This article explores the phenomenon of character migration in one of Alice Munro’s early works, Lives of Girls and Women from 1971. Munro vitally maintains the typical structure of the modern Anglo-American short story, with its tendency toward condensation and building toward its ending, as well as the form’s thematic principle of the epiphany concept. But she also allows her characters to live beyond each individual story, showing how they survive their climactic epiphanies and incorporate them into the larger narrative of their lives. In so doing, Munro challenges the usual distinction between the novel and the short story, illuminating what each genre is uniquely equipped to perform in terms of the presentation of character, while also suggesting the limits inherent in each.

Purpose: To investigate, longitudinally, whether increases in markers of inflammation (CRP, sICAM-1) and endothelial dysfunction (sICAM-1, sVCAM-1) are associated with and precede the increase in pulse pressure (PP) in individuals with type-1 diabetes (DM1). Methods: Inception cohort of 277 DM1 patients (114 women; mean age at diagnosis: 27.5±13.8 yrs) who were consecutively admitted, upon diagnosis, between Sep’79–Aug’84 to an outpatient diabetic clinic (Gentofte, Denmark). Throughout a follow-up period of >20 yrs, patients’ PP, other risk factors, and CRP, sICAM-1 and sVCAM-1 were measured repeatedly (at 3–4 months intervals). Associations were analysed with generalized estimating equations (GEEs) and adjusted for sex, age at diagnosis, smoking, anti-hypertensive treatment and MAP. Results: PP increased by 0.53 mmHg/yr, CRP by 0.033mg/L/yr, sICAM-1 by 1.8 ng/ml/yr and sVCAM-1 by 1.8 ng/ml/yr over the 20-yr longitudinal period (all p

Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p