A multi-center study: Intra-scan and inter-scan variability of diffusion spectrum imaging

The objective of this study was to investigate whether it is possible to pool together diffusion spectrum imaging data from four different scanners, located at three different sites. Two of the scanners had identical configuration whereas two did not. To measure the variability, we extracted three scalar maps (ADC, FA and GFA) from the DSI and utilized a region and a tract-based analysis. Additionally, a phantom study was performed to rule out some potential factors arising from the scanner performance in case some systematic bias occurred in the subject study. This work was split into three experiments: intra-scanner reproducibility, reproducibility with twin-scanner settings and reproducibility with other configurations. Overall for the intra-scanner and twin-scanner experiments, the region-based analysis coefficient of variation (CV) was in a range of 1%-4.2% and below 3% for almost every bundle for the tract-based analysis. The uncinate fasciculus showed the worst reproducibility, especially for FA and GFA values (CV 3.7-6%). For the GFA and FA maps, an ICC value of 0.7 and above is observed in almost all the regions/tracts. Looking at the last experiment, it was found that there is a very high similarity of the outcomes from the two scanners with identical setting. However, this was not the case for the two other imagers. Given the fact that the overall variation in our study is low for the imagers with identical settings, our findings support the feasibility of cross-site pooling of DSI data from identical scanners.

Intra-subject variability in attention-deficit hyperactivity disorder

BACKGROUND: This study is based on a comprehensive survey of the neuropsychological attention-deficit hyperactivity disorder (ADHD) literature and presents the first psychometric analyses of different parameters of intra-subject variability (ISV) in patients with ADHD compared to healthy controls, using the Continuous Performance Test, a Go-NoGo task, a Stop Signal Task, as well as N-back tasks. METHODS: Data of 57 patients with ADHD and 53 age- and gender-matched controls were available for statistical analysis. Different parameters were used to describe central tendency (arithmetic mean, median), dispersion (standard deviation, coefficient of variation, consecutive variance), and shape (skewness, excess) of reaction time distributions, as well as errors (commissions and omissions). RESULTS: Group comparisons revealed by far the strongest effect sizes for measures of dispersion, followed by measures of central tendency, and by commission errors. Statistical control of ISV reduced group differences in the other measures substantially. One (patients) or two (controls) principal components explained up to 67% of the inter-individual differences in intra-individual variability. CONCLUSIONS: Results suggest that, across a variety of neuropsychological tests, measures of ISV contribute best to group discrimination, with limited incremental validity of measures of central tendency and errors. Furthermore, increased ISV might be a unitary construct in ADHD.

Analysis of hand kinematics reveals inter-individual differences in intertemporal decision dynamics

During intertemporal decisions, the preference for smaller, sooner reward over larger-delayed rewards (temporal discounting, TD) exhibits substantial inter-subject variability; however, it is currently unclear what are the mechanisms underlying this apparently idiosyncratic behavior. To answer this question, here we recorded and analyzed mouse movement kinematics during intertemporal choices in a large sample of participants (N = 86). Results revealed a specific pattern of decision dynamics associated with the selection of “immediate” versus “delayed” response alternatives, which well discriminated between a “discounter” versus a “farsighted” behavior—thus representing a reliable behavioral marker of TD preferences. By fitting the Drift Diffusion Model to the data, we showed that differences between discounter and farsighted subjects could be explained in terms of different model parameterizations, corresponding to the use of different choice mechanisms in the two groups. While farsighted subjects were biased toward the “delayed” option, discounter subjects were not correspondingly biased toward the “immediate” option. Rather, as shown by the dynamics of evidence accumulation over time, their behavior was characterized by high choice uncertainty.

Quantitative multi-slice computed tomography assessment of the mitral valvular complex for transcatheter mitral valve interventions part 1: systematic measurement methodology and inter-observer variability

AIMS Transcatheter mitral valve replacement (TMVR) is an emerging technology with the potential to treat patients with severe mitral regurgitation at excessive risk for surgical mitral valve surgery. Multimodal imaging of the mitral valvular complex and surrounding structures will be an important component for patient selection for TMVR. Our aim was to describe and evaluate a systematic multi-slice computed tomography (MSCT) image analysis methodology that provides measurements relevant for transcatheter mitral valve replacement. METHODS AND RESULTS A systematic step-by-step measurement methodology is described for structures of the mitral valvular complex including: the mitral valve annulus, left ventricle, left atrium, papillary muscles and left ventricular outflow tract. To evaluate reproducibility, two observers applied this methodology to a retrospective series of 49 cardiac MSCT scans in patients with heart failure and significant mitral regurgitation. For each of 25 geometrical metrics, we evaluated inter-observer difference and intra-class correlation. The inter-observer difference was below 10% and the intra-class correlation was above 0.81 for measurements of critical importance in the sizing of TMVR devices: the mitral valve annulus diameters, area, perimeter, the inter-trigone distance, and the aorto-mitral angle. CONCLUSIONS MSCT can provide measurements that are important for patient selection and sizing of TMVR devices. These measurements have excellent inter-observer reproducibility in patients with functional mitral regurgitation.

Inter-hemispheric temperature variability over the past millennium

The Earth’s climate system is driven by a complex interplay of internal chaotic dynamics and natural and anthropogenic external forcing. Recent instrumental data have shown a remarkable degree of asynchronicity between Northern Hemisphere and Southern Hemisphere temperature fluctuations, thereby questioning the relative importance of internal versus external drivers of past as well as future climate variability1, 2, 3. However, large-scale temperature reconstructions for the past millennium have focused on the Northern Hemisphere4, 5, limiting empirical assessments of inter-hemispheric variability on multi-decadal to centennial timescales. Here, we introduce a new millennial ensemble reconstruction of annually resolved temperature variations for the Southern Hemisphere based on an unprecedented network of terrestrial and oceanic palaeoclimate proxy records. In conjunction with an independent Northern Hemisphere temperature reconstruction ensemble5, this record reveals an extended cold period (1594–1677) in both hemispheres but no globally coherent warm phase during the pre-industrial (1000–1850) era. The current (post-1974) warm phase is the only period of the past millennium where both hemispheres are likely to have experienced contemporaneous warm extremes. Our analysis of inter-hemispheric temperature variability in an ensemble of climate model simulations for the past millennium suggests that models tend to overemphasize Northern Hemisphere–Southern Hemisphere synchronicity by underestimating the role of internal ocean–atmosphere dynamics, particularly in the ocean-dominated Southern Hemisphere. Our results imply that climate system predictability on decadal to century timescales may be lower than expected based on assessments of external climate forcing and Northern Hemisphere temperature variations5, 6 alone.

Geometry-Aware Multiscale Image Registration via OBBTree-Based Polyaffine Log-Demons

Non-linear image registration is an important tool in many areas of image analysis. For instance, in morphometric studies of a population of brains, free-form deformations between images are analyzed to describe the structural anatomical variability. Such a simple deformation model is justified by the absence of an easy expressible prior about the shape changes. Applying the same algorithms used in brain imaging to orthopedic images might not be optimal due to the difference in the underlying prior on the inter-subject deformations. In particular, using an un-informed deformation prior often leads to local minima far from the expected solution. To improve robustness and promote anatomically meaningful deformations, we propose a locally affine and geometry-aware registration algorithm that automatically adapts to the data. We build upon the log-domain demons algorithm and introduce a new type of OBBTree-based regularization in the registration with a natural multiscale structure. The regularization model is composed of a hierarchy of locally affine transformations via their logarithms. Experiments on mandibles show improved accuracy and robustness when used to initialize the demons, and even similar performance by direct comparison to the demons, with a significantly lower degree of freedom. This closes the gap between polyaffine and non-rigid registration and opens new ways to statistically analyze the registration results.

Variability in pain response to a non-pharmacological intervention across repeated routine pain exposure in preterm infants: a feasibility study

AIM: To explore the variability in pain response in preterm infants across time who received sucrose during routine heel stick. METHOD: Single group, exploratory repeated measures design. SETTING: Two tertiary level neonatal intensive care units (NICU) in Switzerland. SUBJECTS: Nine preterm infants born between 28 2/7 and 31 4/7 weeks of gestation during their first 14 days of life. MEASUREMENTS: Pain was assessed by the Bernese Pain Scale for Neonates (BPSN), the Premature Infant Pain Profile (PIPP) and the Visual Analogue Scale (VAS). Salivary cortisol was analysed. RESULTS: 72-94% of the variability was within-subject variability, indicating inconsistency of pain responses across the 5 heel sticks. Interrater agreement was highest during heel sticks 1-3 and decreased during heel stick 4 and 5, indicating a possible alteration of pain patterns. No significant differences in the amount of cortisol could be detected before and after the heel sticks (p = 0.55), indicating no stress-induced peak after the painful intervention. However, a general gradual decrease of cortisol levels across time could be detected. CONCLUSION: A high variability in pain response among preterm neonates across time could be described. Consistency of cortisol levels before and after the heel sticks could indicate the effectiveness of sucrose across time.

Intra- and inter-individual variation of BIS-index and Entropy during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study

INTRODUCTION: We studied intra-individual and inter-individual variability of two online sedation monitors, BIS and Entropy, in volunteers under sedation. METHODS: Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS and Entropy (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered. RESULTS: Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy values showed greater variability than BIS(R) values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation. CONCLUSIONS: The large intra-individual and inter-individual variability of BIS and Entropy values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability. TRIAL REGISTRATION: clinicaltrials.gov Nr. NCT00641563.

Synoptic drivers of 400 years of summer temperature and precipitation variability on Mt. Olympus, Greece

The Mediterranean region has been identified as a global warming hotspot, where future climate impacts are expected to have significant consequences on societal and ecosystem well-being. To put ongoing trends of summer climate into the context of past natural variability, we reconstructed climate from maximum latewood density (MXD) measurements of Pinus heldreichii (1521–2010) and latewood width (LWW) of Pinus nigra (1617–2010) on Mt. Olympus, Greece. Previous research in the northeastern Mediterranean has primarily focused on inter-annual variability, omitting any low-frequency trends. The present study utilizes methods capable of retaining climatically driven long-term behavior of tree growth. The LWW chronology corresponds closely to early summer moisture variability (May–July, r = 0.65, p < 0.001, 1950–2010), whereas the MXD-chronology relates mainly to late summer warmth (July–September, r = 0.64, p < 0.001; 1899–2010). The chronologies show opposing patterns of decadal variability over the twentieth century (r = −0.68, p < 0.001) and confirm the importance of the summer North Atlantic Oscillation (sNAO) for summer climate in the northeastern Mediterranean, with positive sNAO phases inducing cold anomalies and enhanced cloudiness and precipitation. The combined reconstructions document the late twentieth—early twenty-first century warming and drying trend, but indicate generally drier early summer and cooler late summer conditions in the period ~1700–1900 CE. Our findings suggest a potential decoupling between twentieth century atmospheric circulation patterns and pre-industrial climate variability. Furthermore, the range of natural climate variability stretches beyond summer moisture availabilityobserved in recent decades and thus lends credibility to the significant drying trends projected for this region in current Earth System Model simulations.

Evaluation of renal allograft function early after transplantation with diffusion-weighted MR imaging

To determine the inter-patient variability of apparent diffusion coefficients (ADC) and concurrent micro-circulation contributions from diffusion-weighted MR imaging (DW-MRI) in renal allografts early after transplantation, and to obtain initial information on whether these measures are altered in histologically proven acute allograft rejection (AR).

Pharmacogenetics and forensic toxicology

Large inter-individual variability in drug response and toxicity, as well as in drug concentrations after application of the same dosage, can be of genetic, physiological, pathophysiological, or environmental origin. Absorption, distribution and metabolism of a drug and interactions with its target often are determined by genetic differences. Pharmacokinetic and pharmacodynamic variations can appear at the level of drug metabolizing enzymes (e.g., the cytochrome P450 system), drug transporters, drug targets or other biomarker genes. Pharmacogenetics or toxicogenetics can therefore be relevant in forensic toxicology. This review presents relevant aspects together with some examples from daily routines.

Investigation of different apple cultivars by high resolution magic angle spinning NMR. A feasibility study

(1)H HR-MAS NMR spectroscopy was applied to apple tissue samples deriving from 3 different cultivars. The NMR data were statistically evaluated by analysis of variance (ANOVA), principal component analysis (PCA), and partial least-squares-discriminant analysis (PLS-DA). The intra-apple variability of the compounds was found to be significantly lower than the inter-apple variability within one cultivar. A clear separation of the three different apple cultivars could be obtained by multivariate analysis. Direct comparison of the NMR spectra obtained from apple tissue (with HR-MAS) and juice (with liquid-state HR NMR) showed distinct differences in some metabolites, which are probably due to changes induced by juice preparation. This preliminary study demonstrates the feasibility of (1)H HR-MAS NMR in combination with multivariate analysis as a tool for future chemometric studies applied to intact fruit tissues, e.g. for investigating compositional changes due to physiological disorders, specific growth or storage conditions.

Clinical application and reliability of a post abdominal surgery pain assessment scale (PASPAS) in horses

The aim of this study was to refine a multi-dimensional scale based on physiological and behavioural parameters, known as the post abdominal surgery pain assessment scale (PASPAS), to quantify pain after laparotomy in horses. After a short introduction, eight observers used the scale to assess eight horses at multiple time points after laparotomy. In addition, a single observer was used to test the correlation of each parameter with the total pain index in 34 patients, and the effect of general anaesthesia on PASPAS was investigated in a control group of eight horses. Inter-observer variability was low (coefficient of variation 0.3), which indicated good reliability of PASPAS. The correlation of individual parameters with the total pain index differed between parameters. PASPAS, which was not influenced by general anaesthesia, was a useful tool to evaluate pain in horses after abdominal surgery and may also be useful to investigate analgesic protocols or for teaching purposes.