Oxygen isotope ratios (18O/16O) of hemicellulose-derived sugar biomarkers in plants, soils and sediments as paleoclimate proxy II: insight from a climate transect study

The oxygen isotopic composition of precipitation (δ18Oprec) is well known to be a valuable (paleo-)climate proxy. Paleosols and sediments and hemicelluloses therein have the potential to serve as archives recording the isotopic composition of paleoprecipitation. In a companion paper (Zech et al., 2014) we investigated δ18Ohemicellulose values of plants grown under different climatic conditions in a climate chamber experiment. Here we present results of compound-specific δ18O analyses of arabinose, fucose and xylose extracted from modern topsoils (n = 56) along a large humid-arid climate transect in Argentina in order to answer the question whether hemicellulose biomarkers in soils reflect δ18Oprec. The results from the field replications indicate that the homogeneity of topsoils with regard to δ18Ohemicellulose is very high for most of the 20 sampling sites. Standard deviations for the field replications are 1.5‰, 2.2‰ and 1.7‰, for arabinose, fucose and xylose, respectively. Furthermore, all three hemicellulose biomarkers reveal systematic and similar trends along the climate gradient. However, the δ18Ohemicellulose values (mean of the three sugars) do not correlate positively with δ18Oprec (r = −0.54, p < 0.014, n = 20). By using a Péclet-modified Craig-Gordon (PMCG) model it can be shown that the δ18Ohemicellulose values correlate highly significantly with modeled δ18Oleaf water values (r = 0.81, p < 0.001, n = 20). This finding suggests that hemicellulose biomarkers in (paleo-)soils do not simply reflect δ18Oprec but rather δ18Oprec altered by evaporative 18O enrichment of leaf water due to evapotranspiration. According to the modeling results, evaporative 18O enrichment of leaf water is relatively low (∼10‰) in the humid northern part of the Argentinian transect and much higher (up to 19‰) in the arid middle and southern part of the transect. Model sensitivity tests corroborate that changes in relative air humidity exert a dominant control on evaporative 18O enrichment of leaf water and thus δ18Ohemicellulose, whereas the effect of temperature changes is of minor importance. While oxygen exchange and degradation effects seem to be negligible, further factors needing consideration when interpreting δ18Ohemicellulose values obtained from (paleo-)soils are evaporative 18O enrichment of soil water, seasonality effects, wind effects and in case of abundant stem/root-derived organic matter input a partial loss of the evaporative 18O enrichment of leaf water. Overall, our results prove that compound-specific δ18O analyses of hemicellulose biomarkers in soils and sediments are a promising tool for paleoclimate research. However, disentangling the two major factors influencing δ18Ohemicellulose, namely δ18Oprec and relative air humidity controlled evaporative 18O enrichment of leaf water, is challenging based on δ18O analyses alone.

Diffusion tensor imaging of the human kidney: Does image registration permit scanning without respiratory triggering?

PURPOSE To investigate if image registration of diffusion tensor imaging (DTI) allows omitting respiratory triggering for both transplanted and native kidneys MATERIALS AND METHODS: Nine kidney transplant recipients and eight healthy volunteers underwent renal DTI on a 3T scanner with and without respiratory triggering. DTI images were registered using a multimodal nonrigid registration algorithm. Apparent diffusion coefficient (ADC), the contribution of perfusion (FP ), and the fractional anisotropy (FA) were determined. Relative root mean square errors (RMSE) of the fitting and the standard deviations of the derived parameters within the regions of interest (SDROI ) were evaluated as quality criteria. RESULTS Registration significantly reduced RMSE in all DTI-derived parameters of triggered and nontriggered measurements in cortex and medulla of both transplanted and native kidneys (P < 0.05 for all). In addition, SDROI values were lower with registration for all 16 parameters in transplanted kidneys (14 of 16 SDROI values were significantly reduced, P < 0.04) and for 15 of 16 parameters in native kidneys (9 of 16 SDROI values were significantly reduced, P < 0.05). Comparing triggered versus nontriggered DTI in transplanted kidneys revealed no significant difference for RMSE (P > 0.14) and for SDROI (P > 0.13) of all parameters. In contrast, in native kidneys relative RMSE from triggered scans were significantly lower than those from nontriggered scans (P < 0.02), while SDROI was slightly higher in triggered compared to nontriggered measurements in 15 out of 16 comparisons (significantly for two, P < 0.05). CONCLUSION Registration improves the quality of DTI in native and transplanted kidneys. Diffusion parameters in renal allografts can be measured without respiratory triggering. In native kidneys, respiratory triggering appears advantageous. J. Magn. Reson. Imaging 2016.

Evaluation of high-definition and conventional oscillometric blood pressure measurement in anaesthetised dogs using ACVIM guidelines

OBJECTIVES: To evaluate high-definition and conventional oscillometry in comparison with direct blood pressure measurements in anaesthetised dogs. METHODS: Eight simultaneous readings for systolic, diastolic and mean pressure were obtained directly and with each of two devices in nine anaesthetised dogs. Measurement procedure and validation were based on the 2007 ACVIM guidelines. RESULTS: Sixty-three simultaneous readings were evaluated for each device and direct measurements. The mean differences (bias) to direct values were within 10 mmHg for both devices although bias for systolic and diastolic blood pressures was higher for Memodiagnostic. The standard deviations of differences (precision) were within 15 mmHg for Dinamap but exceeded for Memodiagnostic. Correlation coefficients were higher for Dinamap than Memodiagnostic but both failed to reach a correlation of 0.9. Over 50% of values lay within 10 mmHg of direct measures for both devices, but this percentage was greater for Dinamap than Memodiagnostic. Over 80% of values lay within 20 mmHg of direct measures for Dinamap but not for Memodiagnostic. CLINICAL SIGNIFICANCE: Both devices failed to meet ACVIM guideline validation. However, Dinamap only failed with regards to correlation. Memodiagnostic failed on several requirements, and based on poor correlation, accuracy and precision, this device cannot be currently recommended for dogs under anaesthesia.

A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders

BACKGROUND: The recurrent ~600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. OBJECTIVE: To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. METHODS: We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. RESULTS: When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. CONCLUSIONS: The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.

Neonatal macrocephaly: cerebral primitive neuroectodermal tumor or neuroblastoma as an infrequent cause--a case report and review of the literature

We report a male term newborn presenting with a congenital macrocephaly 3.5 standard deviations above the median, with a wide and tense anterior fontanel, splayed calvarial sutures, and muscular hypotonia. Antenatal head circumferences were repeatedly below the median. A postnatal head ultrasound showed a large right intracerebral mass with right lateral ventricle compression, right temporal horn dilation, and right frontal horn enlargement with lateral displacement. Additional imaging by computed tomography scan and magnetic resonance imaging was performed. A decompression was performed and histology, immunohistochemistry, and molecular biology supported the diagnosis of a primitive neuroectodermal tumor. A MYCN gene amplification assay remained negative. The incidence of neonatal brain tumors is between 1.4 and 4.1/100,000 live births. Their most common presentation is macrocephaly, hydrocephalus, stillbirth, or diagnosis by pre- or postnatal imaging. Although hydrocephaly and intra- or extracranial hemorrhage are the most frequent causes of congenital macrocephaly, this should be initially investigated by head ultrasound. A suspected malignancy will be confirmed by histopathology, immunohistochemistry, and molecular biology.

An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension

OBJECTIVES: To assess perioperative outcomes and blood pressure (BP) responses to an implantable carotid sinus baroreflex activating system being investigated for the treatment of resistant hypertension. METHODS: We report on the first seventeen patients enrolled in a multicenter study. Bilateral perivascular carotid sinus electrodes (CSL) and a pulse generator (IPG) are permanently implanted. Optimal placement of the CSL is determined by intraoperative BP responses to test activations. Acute BP responses were tested postoperatively and during the first four months of follow-up. RESULTS: Prior to implant, BP was 189.6+/-27.5/110.7+/-15.3 mmHg despite stable therapy (5.2+/-1.8 antihypertensive drugs). The mean procedure time was 202+/-43 minutes. No perioperative strokes or deaths occurred. System tests performed 1 or up to 3 days postoperatively resulted in significant (all p < or = 0.0001) mean maximum reduction, with standard deviations and 95% confidence limits for systolic BP, diastolic BP and heart rate of 28+/-22 (17, 39) mmHg, 16+/-11 (10, 22) mmHg and 8+/-4 (6, 11) BPM, respectively. Repeated testing during 3 months of therapeutic electrical activation demonstrated a durable response. CONCLUSIONS: These preliminary data suggest an acceptable safety of the procedure with a low rate of adverse events and support further clinical development of baroreflex activation as a new concept to treat resistant hypertension.

Age modeling of young non-varved lake sediments: methods and limits. Examples from two lakes in Central Chile

High-resolution and highly precise age models for recent lake sediments (last 100–150 years) are essential for quantitative paleoclimate research. These are particularly important for sedimentological and geochemical proxies, where transfer functions cannot be established and calibration must be based upon the relation of sedimentary records to instrumental data. High-precision dating for the calibration period is most critical as it determines directly the quality of the calibration statistics. Here, as an example, we compare radionuclide age models obtained on two high-elevation glacial lakes in the Central Chilean Andes (Laguna Negra: 33°38′S/70°08′W, 2,680 m a.s.l. and Laguna El Ocho: 34°02′S/70°19′W, 3,250 m a.s.l.). We show the different numerical models that produce accurate age-depth chronologies based on 210Pb profiles, and we explain how to obtain reduced age-error bars at the bottom part of the profiles, i.e., typically around the end of the 19th century. In order to constrain the age models, we propose a method with five steps: (i) sampling at irregularly-spaced intervals for 226Ra, 210Pb and 137Cs depending on the stratigraphy and microfacies, (ii) a systematic comparison of numerical models for the calculation of 210Pb-based age models: constant flux constant sedimentation (CFCS), constant initial concentration (CIC), constant rate of supply (CRS) and sediment isotope tomography (SIT), (iii) numerical constraining of the CRS and SIT models with the 137Cs chronomarker of AD 1964 and, (iv) step-wise cross-validation with independent diagnostic environmental stratigraphic markers of known age (e.g., volcanic ash layer, historical flood and earthquakes). In both examples, we also use airborne pollutants such as spheroidal carbonaceous particles (reflecting the history of fossil fuel emissions), excess atmospheric Cu deposition (reflecting the production history of a large local Cu mine), and turbidites related to historical earthquakes. Our results show that the SIT model constrained with the 137Cs AD 1964 peak performs best over the entire chronological profile (last 100–150 years) and yields the smallest standard deviations for the sediment ages. Such precision is critical for the calibration statistics, and ultimately, for the quality of the quantitative paleoclimate reconstruction. The systematic comparison of CRS and SIT models also helps to validate the robustness of the chronologies in different sections of the profile. Although surprisingly poorly known and under-explored in paleolimnological research, the SIT model has a great potential in paleoclimatological reconstructions based on lake sediments

Saccadic eye movement changes in Parkinson's disease dementia and dementia with Lewy bodies.

Neurodegeneration in Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) affect cortical and subcortical networks involved in saccade generation. We therefore expected impairments in saccade performance in both disorders. In order to improve the pathophysiological understanding and to investigate the usefulness of saccades for differential diagnosis, saccades were tested in age- and education-matched patients with PDD (n = 20) and DLB (n = 20), Alzheimer's disease (n = 22) and Parkinson's disease (n = 24), and controls (n = 24). Reflexive (gap, overlap) and complex saccades (prediction, decision and antisaccade) were tested with electro-oculography. PDD and DLB patients had similar impairment in all tasks (P > 0.05, not significant). Compared with controls, they were impaired in both reflexive saccade execution (gap and overlap latencies, P < 0.0001; gains, P < 0.004) and complex saccade performance (target prediction, P < 0.0001; error decisions, P < 0.003; error antisaccades: P < 0.0001). Patients with Alzheimer's disease were only impaired in complex saccade performance (Alzheimer's disease versus controls, target prediction P < 0.001, error decisions P < 0.0001, error antisaccades P < 0.0001), but not reflexive saccade execution (for all, P > 0.05). Patients with Parkinson's disease had, compared with controls, similar complex saccade performance (for all, P > 0.05) and only minimal impairment in reflexive tasks, i.e. hypometric gain in the gap task (P = 0.04). Impaired saccade execution in reflexive tasks allowed discrimination between DLB versus Alzheimer's disease (sensitivity > or =60%, specificity > or =77%) and between PDD versus Parkinson's disease (sensitivity > or =60%, specificity > or =88%) when +/-1.5 standard deviations was used for group discrimination. We conclude that impairments in reflexive saccades may be helpful for differential diagnosis and are minimal when either cortical (Alzheimer's disease) or nigrostriatal neurodegeneration (Parkinson's disease) exists solely; however, they become prominent with combined cortical and subcortical neurodegeneration in PDD and DLB. The similarities in saccade performance in PDD and DLB underline the overlap between these conditions and underscore differences from Alzheimer's disease and Parkinson's disease.

A compact and portable deposition chamber to study nanoparticles in air-exposed tissue

BACKGROUND Epidemiological studies show that elevated levels of particulate matter in ambient air are highly correlated with respiratory and cardiovascular diseases. Atmospheric particles originate from a large number of sources and have a highly complex and variable composition. An assessment of their potential health risks and the identification of the most toxic particle sources would require a large number of investigations. Due to ethical and economic reasons, it is desirable to reduce the number of in vivo studies and to develop suitable in vitro systems for the investigation of cell-particle interactions. METHODS We present the design of a new particle deposition chamber in which aerosol particles are deposited onto cell cultures out of a continuous air flow. The chamber allows for a simultaneous exposure of 12 cell cultures. RESULTS Physiological conditions within the deposition chamber can be sustained constantly at 36-37°C and 90-95% relative humidity. Particle deposition within the chamber and especially on the cell cultures was determined in detail, showing that during a deposition time of 2 hr 8.4% (24% relative standard deviation) of particles with a mean diameter of 50 nm [mass median diameter of 100 nm (geometric standard deviation 1.7)] are deposited on the cell cultures, which is equal to 24-34% of all charged particles. The average well-to-well variability of particles deposited simultaneously in the 12 cell cultures during an experiment is 15.6% (24.7% relative standard deviation). CONCLUSIONS This particle deposition chamber is a new in vitro system to investigate realistic cell-particle interactions at physiological conditions, minimizing stress on the cell cultures other than from deposited particles. A detailed knowledge of particle deposition characteristics on the cell cultures allows evaluating reliable dose-response relationships. The compact and portable design of the deposition chamber allows for measurements at any particle sources of interest.

Comparative effects of Teriparatide and Risedronate in glucocorticoid‐induced osteoporosis in men: 18‐month results of the EuroGIOPs trial

Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T-score ≤ –1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L1–L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high-resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate.

Disentangling human tolerance and resistance against HIV.

In ecology, "disease tolerance" is defined as an evolutionary strategy of hosts against pathogens, characterized by reduced or absent pathogenesis despite high pathogen load. To our knowledge, tolerance has to date not been quantified and disentangled from host resistance to disease in any clinically relevant human infection. Using data from the Swiss HIV Cohort Study, we investigated if there is variation in tolerance to HIV in humans and if this variation is associated with polymorphisms in the human genome. In particular, we tested for associations between tolerance and alleles of the Human Leukocyte Antigen (HLA) genes, the CC chemokine receptor 5 (CCR5), the age at which individuals were infected, and their sex. We found that HLA-B alleles associated with better HIV control do not confer tolerance. The slower disease progression associated with these alleles can be fully attributed to the extent of viral load reduction in carriers. However, we observed that tolerance significantly varies across HLA-B genotypes with a relative standard deviation of 34%. Furthermore, we found that HLA-B homozygotes are less tolerant than heterozygotes. Lastly, tolerance was observed to decrease with age, resulting in a 1.7-fold difference in disease progression between 20 and 60-y-old individuals with the same viral load. Thus, disease tolerance is a feature of infection with HIV, and the identification of the mechanisms involved may pave the way to a better understanding of pathogenesis.

An investigation into the mechanical and aesthetic properties of new generation coated nickel-titanium wires in the as-received state and after clinical use.

BACKGROUND/OBJECTIVES The purpose of this study was to compare the mechanical, structural, and aesthetic properties of two types of aesthetic coated nickel-titanium (NiTi) wires compared with comparable regular NiTi wires in the as-received state and after clinical use. MATERIALS/METHODS Sixty one subjects were randomly assigned to four groups (N = 61), two groups of coated wires and two groups of comparable, non-coated controls (n = 15/group). The period in the mouth ranged from 4 to 12 weeks after insertion. In total, 121 wires (61 retrieved and 60 as-received) were used in the study. The percentages of coating retention and loss were extrapolated from scans. A brief survey of five questions with three choices was given to all patients. Differential scanning calorimetry (DSC) and three-point bending tests were done on as-received and used wires. RESULTS The surface characterization by the percentage of resin remaining indicated that most wires in both test groups lost a significant amount of coating. A patient survey indicated that this was a noticeable feature for patients. DSC analysis of the wires indicated that the metallurgical properties of the coated wires were not similar to the uncoated wires in the as-received condition. Three-point bending results indicate a wide variation in test results with large standard deviations among all the groups. LIMITATIONS The extent of coating loss requires investigating, as do the biological properties of the detached coating. CONCLUSIONS Both wires lost a significant amount of aesthetic coating after varying periods in the mouth. The metallurgical testing of these findings may indicate that these wires perform differently in the mouth.

Image registration for triggered and non-triggered DTI of the human kidney: Reduced variability of diffusion parameter estimation

BACKGROUND: To investigate if non-rigid image-registration reduces motion artifacts in triggered and non-triggered diffusion tensor imaging (DTI) of native kidneys. A secondary aim was to determine, if improvements through registration allow for omitting respiratory-triggering. METHODS: Twenty volunteers underwent coronal DTI of the kidneys with nine b-values (10-700 s/mm2 ) at 3 Tesla. Image-registration was performed using a multimodal nonrigid registration algorithm. Data processing yielded the apparent diffusion coefficient (ADC), the contribution of perfusion (FP ), and the fractional anisotropy (FA). For comparison of the data stability, the root mean square error (RMSE) of the fitting and the standard deviations within the regions of interest (SDROI ) were evaluated. RESULTS: RMSEs decreased significantly after registration for triggered and also for non-triggered scans (P < 0.05). SDROI for ADC, FA, and FP were significantly lower after registration in both medulla and cortex of triggered scans (P < 0.01). Similarly the SDROI of FA and FP decreased significantly in non-triggered scans after registration (P < 0.05). RMSEs were significantly lower in triggered than in non-triggered scans, both with and without registration (P < 0.05). CONCLUSION: Respiratory motion correction by registration of individual echo-planar images leads to clearly reduced signal variations in renal DTI for both triggered and particularly non-triggered scans. Secondarily, the results suggest that respiratory-triggering still seems advantageous.J. Magn. Reson. Imaging 2014. (c) 2014 Wiley Periodicals, Inc.

The applicability of using different energy levels in CT imaging for differentiation or identification of dental restorative materials.

PURPOSE The goal of this study was to investigate whether different computed tomography (CT) energy levels could supply additional information for the differentiation of dental materials for forensic investigations. METHODS Nine different commonly used restorative dental materials were investigated in this study. A total of 75 human third molars were filled with the restorative dental materials and then scanned using the forensic reference phantom in singlesource mode. The mean Hounsfield unit values and standard deviations (SDs) of each material were calculated at 120, 80 and 140 kVp. RESULTS Most of the dental materials could be differentiated at 120 kVp. We found that greater X-ray density of a material resulted in higher SDs and that the material volume could influence the measurements. CONCLUSION Differentiation of dental materials in CT was possible in many cases using single-energy CT scans at 120 kVp. Because of the number of dental restorative materials available and scanner and scan parameter dependence, as well as the CT imaging artifacts, the identification (in contrast to differentiation) was problematic.

Observation of an Excited B±c Meson State with the ATLAS Detector

A search for excited states of the B ± c meson is performed using 4.9  fb −1 of 7 TeV and 19.2  fb −1 of 8 TeV pp collision data collected by the ATLAS experiment at the LHC. A new state is observed through its hadronic transition to the ground state, with the latter detected in the decay B ± c →J/ψπ ± . The state appears in the m(B ± c π + π − )−m(B ± c )−2m(π ± ) mass difference distribution with a significance of 5.2 standard deviations. The mass of the observed state is 6842±4±5  MeV , where the first error is statistical and the second is systematic. The mass and decay of this state are consistent with expectations for the second S -wave state of the B ± c meson, B ± c (2S) .