Single-Molecule Junctions Based on Nitrile-Terminated Biphenyls: A Promising New Anchoring Group

We present a combined experimental and theoretical study of the electronic transport through single-molecule junctions based on nitrile-terminated biphenyl derivatives. Using a scanning tunneling microscope-based break-junction technique, we show that the nitrile-terminated compounds give rise to well-defined peaks in the conductance histograms resulting from the high selectivity of the N-Au binding. Ab initio calculations have revealed that the transport takes place through the tail of the LUMO. Furthermore, we have found both theoretically and experimentally that the conductance of the molecular junctions is roughly proportional to the square of the cosine of the torsion angle between the two benzene rings of the biphenyl core, which demonstrates the robustness of this structure-conductance relationship.

Apparent diffusion coefficient in the aging mouse brain: a magnetic resonance imaging study

Novel magnetic resonance imaging sequences have and still continue to play an increasing role in neuroimaging and neuroscience. Among these techniques, diffusion-weighted imaging (DWI) has revolutionized the diagnosis and management of diseases such as stroke, neoplastic disease and inflammation. However, the effects of aging on diffusion are yet to be determined. To establish reference values for future experimental mouse studies we tested the hypothesis that absolute apparent diffusion coefficients (ADC) of the normal brain change with age. A total of 41 healthy mice were examined by T2-weighted imaging and DWI. For each animal ADC frequency histograms (i) of the whole brain were calculated on a voxel-by-voxel basis and region-of-interest (ROI) measurements (ii) performed and related to the animals' age. The mean entire brain ADC of mice <3 months was 0.715(+/-0.016) x 10(-3) mm2/s, no significant difference to mice aged 4 to 5 months (0.736(+/-0.040) x 10(-3) mm2/s) or animals older than 9 months 0.736(+/-0.020) x 10(-3) mm2/s. Mean whole brain ADCs showed a trend towards lower values with aging but both methods (i + ii) did not reveal a significant correlation with age. ROI measurements in predefined areas: 0.723(+/-0.057) x 10(-3) mm2/s in the parietal lobe, 0.659(+/-0.037) x 10(-3) mm2/s in the striatum and 0.679(+/-0.056) x 10(-3) mm2/s in the temporal lobe. With advancing age, we observed minimal diffusion changes in the whole mouse brain as well as in three ROIs by determination of ADCs. According to our data ADCs remain nearly constant during the aging process of the brain with a small but statistically non-significant trend towards a decreased diffusion in older animals.

Collapsed cone convolution and analytical anisotropic algorithm dose calculations compared to VMC++ Monte Carlo simulations in clinical cases

The purpose of this work was to study and quantify the differences in dose distributions computed with some of the newest dose calculation algorithms available in commercial planning systems. The study was done for clinical cases originally calculated with pencil beam convolution (PBC) where large density inhomogeneities were present. Three other dose algorithms were used: a pencil beam like algorithm, the anisotropic analytic algorithm (AAA), a convolution superposition algorithm, collapsed cone convolution (CCC), and a Monte Carlo program, voxel Monte Carlo (VMC++). The dose calculation algorithms were compared under static field irradiations at 6 MV and 15 MV using multileaf collimators and hard wedges where necessary. Five clinical cases were studied: three lung and two breast cases. We found that, in terms of accuracy, the CCC algorithm performed better overall than AAA compared to VMC++, but AAA remains an attractive option for routine use in the clinic due to its short computation times. Dose differences between the different algorithms and VMC++ for the median value of the planning target volume (PTV) were typically 0.4% (range: 0.0 to 1.4%) in the lung and -1.3% (range: -2.1 to -0.6%) in the breast for the few cases we analysed. As expected, PTV coverage and dose homogeneity turned out to be more critical in the lung than in the breast cases with respect to the accuracy of the dose calculation. This was observed in the dose volume histograms obtained from the Monte Carlo simulations.

Conversion of CT numbers into tissue parameters for Monte Carlo dose calculations: a multi-centre study

The conversion of computed tomography (CT) numbers into material composition and mass density data influences the accuracy of patient dose calculations in Monte Carlo treatment planning (MCTP). The aim of our work was to develop a CT conversion scheme by performing a stoichiometric CT calibration. Fourteen dosimetrically equivalent tissue subsets (bins), of which ten bone bins, were created. After validating the proposed CT conversion scheme on phantoms, it was compared to a conventional five bin scheme with only one bone bin. This resulted in dose distributions D(14) and D(5) for nine clinical patient cases in a European multi-centre study. The observed local relative differences in dose to medium were mostly smaller than 5%. The dose-volume histograms of both targets and organs at risk were comparable, although within bony structures D(14) was found to be slightly but systematically higher than D(5). Converting dose to medium to dose to water (D(14) to D(14wat) and D(5) to D(5wat)) resulted in larger local differences as D(5wat) became up to 10% higher than D(14wat). In conclusion, multiple bone bins need to be introduced when Monte Carlo (MC) calculations of patient dose distributions are converted to dose to water.

Steady state free precession magnetization transfer imaging

The formerly proposed concept for magnetization transfer imaging (MTI) using balanced steady-state free precession (SSFP) image acquisitions is in this work extended to nonbalanced protocols. This allows SSFP-based MTI of targets with high susceptibility variation (such as the musculoskeletal system), or at ultra-high magnetic fields (where balanced SSFP suffers from considerable off-resonance related image degradations). In the first part, SSFP-based MTI in human brain is analyzed based on magnetization transfer ratio (MTR) histograms. High correlations are observed among all different SSFP MTI protocols and thereby ensure proper conceptual extension to nonbalanced SSFP. The second part demonstrates SSFP-based MTI allowing fast acquisition of high resolution volumetric MTR data from human brain and cartilage at low (1.5T) to ultra-high (7.0T) magnetic fields.

Multi-parametric classification of Alzheimer's disease and mild cognitive impairment: the impact of quantitative magnetization transfer MR imaging

Multi-parametric and quantitative magnetic resonance imaging (MRI) techniques have come into the focus of interest, both as a research and diagnostic modality for the evaluation of patients suffering from mild cognitive decline and overt dementia. In this study we address the question, if disease related quantitative magnetization transfer effects (qMT) within the intra- and extracellular matrices of the hippocampus may aid in the differentiation between clinically diagnosed patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI) and healthy controls. We evaluated 22 patients with AD (n=12) and MCI (n=10) and 22 healthy elderly (n=12) and younger (n=10) controls with multi-parametric MRI. Neuropsychological testing was performed in patients and elderly controls (n=34). In order to quantify the qMT effects, the absorption spectrum was sampled at relevant off-resonance frequencies. The qMT-parameters were calculated according to a two-pool spin-bath model including the T1- and T2 relaxation parameters of the free pool, determined in separate experiments. Histograms (fixed bin-size) of the normalized qMT-parameter values (z-scores) within the anterior and posterior hippocampus (hippocampal head and body) were subjected to a fuzzy-c-means classification algorithm with downstreamed PCA projection. The within-cluster sums of point-to-centroid distances were used to examine the effects of qMT- and diffusion anisotropy parameters on the discrimination of healthy volunteers, patients with Alzheimer and MCIs. The qMT-parameters T2(r) (T2 of the restricted pool) and F (fractional pool size) differentiated between the three groups (control, MCI and AD) in the anterior hippocampus. In our cohort, the MT ratio, as proposed in previous reports, did not differentiate between MCI and AD or healthy controls and MCI, but between healthy controls and AD.

A case of EDTA-dependent pseudothrombocytopenia: simple recognition of an underdiagnosed and misleading phenomenon

1. BMC Clin Pathol. 2014 May 1;14:19. doi: 10.1186/1472-6890-14-19. eCollection 2014. A case of EDTA-dependent pseudothrombocytopenia: simple recognition of an underdiagnosed and misleading phenomenon. Nagler M, Keller P, Siegrist D, Alberio L. Author information: Department of Hematology and Central Hematology Laboratory, Inselspital University Hospital and University of Berne, CH-3010 Berne, Switzerland. BACKGROUND: EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is a common laboratory phenomenon with a prevalence ranging from 0.1-2% in hospitalized patients to 15-17% in outpatients evaluated for isolated thrombocytopenia. Despite its harmlessness, EDTA-PTCP frequently leads to time-consuming, costly and even invasive diagnostic investigations. EDTA-PTCP is often overlooked because blood smears are not evaluated visually in routine practice and histograms as well as warning flags of hematology analyzers are not interpreted correctly. Nonetheless, EDTA-PTCP may be diagnosed easily even by general practitioners without any experiences in blood film examinations. This is the first report illustrating the typical patterns of a platelet (PLT) and white blood cell (WBC) histograms of hematology analyzers. CASE PRESENTATION: A 37-year-old female patient of Caucasian origin was referred with suspected acute leukemia and the crew of the emergency unit arranged extensive investigations for work-up. However, examination of EDTA blood sample revealed atypical lymphocytes and an isolated thrombocytopenia together with typical patterns of WBC and PLT histograms: a serrated curve of the platelet histogram and a peculiar peak on the left side of the WBC histogram. EDTA-PTCP was confirmed by a normal platelet count when examining citrated blood. CONCLUSION: Awareness of typical PLT and WBC patterns may alert to the presence of EDTA-PTCP in routine laboratory practice helping to avoid unnecessary investigations and over-treatment. PMCID: PMC4012027 PMID: 24808761 [PubMed]

Respiratory-related leg movements and their relationship with periodic leg movements during sleep

STUDY OBJECTIVES: To describe the time structure of leg movements (LM) in obstructive sleep apnea (OSA) syndrome, in order to advance understanding of their clinical significance. LOCATION: Sleep Research Centre, Oasi Institute (IRCCS), Troina, Italy. SETTING: Sleep laboratory. PATIENTS: Eighty-four patients (16 females, 68 males, mean age 55.1 y, range 29-74 y). METHODS: Respiratory-related leg movements (RRLM) and those unrelated to respiratory events (NRLM) were examined within diagnostic polysomnograms alone and together for their distributions within the sleep period and for their periodicity. MEASUREMENTS AND RESULTS: Patients with OSA and RRLM exhibited more periodic leg movements in sleep (PLMS), particularly in NREM sleep. A gradual decrease in number of NRLM across the sleep period was observed in patients with RRLM. This pattern was less clear for RRLM. Frequency histograms of intermovement intervals of all LMs in patients with RRLM showed a prominent first peak at 4 sec, and a second peak at approximately 24 sec coincident with that of PLMS occurring in the absence of OSA. A third peak of lowest amplitude was the broadest with a maximum at approximately 42 sec. In patients lacking RRLM, NRLM were evident with a single peak at 2-4 sec. A stepwise linear regression analysis showed that, after controlling for a diagnosis of restless legs syndrome and apnea-hypopnea index, PLMS remained significantly associated with RRLM. CONCLUSION: The time structure of leg movements occurring in conjunction with respiratory events exhibit features of periodic leg movements in sleep occurring alone, only with a different and longer period. This brings into question the validity, both biologic and clinical, of scoring conventions with their a priori exclusion from consideration as periodic leg movements in sleep.

Determination of genetic transferrin variants in human serum by high-resolution capillary zone electrophoresis(†)

High-resolution capillary zone electrophoresis in the routine arena with stringent quality assurance is employed for the determination of carbohydrate-deficient transferrin in human serum. The assay comprises mixing of human serum with a Fe(III) -containing solution prior to analysis of the iron-saturated mixture in a dynamically double-coated capillary using a commercial buffer at alkaline pH. In contrast to other assays, it provides sufficient resolution for proper recognition of genetic transferrin variants. Analysis of 7290 patient sera revealed 166 isoform patterns that could be assigned to genetic variants, namely, 109 BC, 53 CD, one BD and three CC variants. Several subtypes of transferrin D can be distinguished as they have large enough differences in pI values. Subtypes of transferrin C and B cannot be resolved. However, analysis of the detection time ratios of tetrasialo isoforms of transferrin BC and transferrin CD variants revealed multimodal frequency histograms, indicating the presence of subtypes of transferrin C, B and D. The data gathered over 11 years demonstrate the robustness of the high-resolution capillary zone electrophoresis assay. This is the first account of a capillary zone electrophoresis based carbohydrate-deficient transferrin assay with a broad overview on transferrin isoform patterns associated with genetic transferrin variants.

Evaluation of aeolian dust records obtained from Polar Ice Cores

When an ice core sample is analysed for its aeolian dust content, it is melted and the particles detected are suspended in water. Consequently, dust measurement techniques employed in the ice core community differ from those used for in-situ studies of airborne dust. Methods commonly used to classify insolubles suspended in a liquid are either based on the particles’ interaction with light or on the detection of resistive pulses by means of Coulter counting. Data sets obtained with Coulter counters are widely accepted as references and other techniques are judged against their ability to reproduce these. Unfortunately, optically acquired ice core dust records were found to differ. By analyzing two sections of the NEEM dust record, two different evaluation procedures are discussed before a third protocol is proposed. It is found that relative changes in the archived dust load can be reproduced, while the simultaneous attainment of absolute concentrations or changes in the grain size frequency histograms in high resolution remains difficult.

Creating LaTeX documents from within Stata using texdoc

At least since Thomas Piketty's best-selling "Capital in the Twenty-First Century" (2014, Cambridge, MA: The Belknap Press), percentile shares have become a popular approach for analyzing distributional inequalities. In their work on the development of top incomes, Piketty and collaborators typically report top-percentage shares, using varying percentages as thresholds (top 10%, top 1%, top 0.1%, etc.). However, analysis of percentile shares at other positions in the distribution may also be of interest. In this paper I present a new Stata command called pshare that estimates percentile shares from individual-level data and displays the results using histograms or stacked bar charts.

Improved VMAT planning for head and neck tumors with an advanced optimization algorithm

OBJECTIVE In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS For the phase 1 plans (PD=54Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95%=97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.

Assessing inequality using percentile shares

At least since Thomas Piketty's best-selling \Capital in the Twenty- First Century" (2014, Cambridge, MA: The Belknap Press), percentile shares have become a popular approach for analyzing distributional inequalities. In their work on the development of top incomes, Piketty and collaborators typically report top- percentage shares, using varying percentages as thresholds (top 10%, top 1%, top 0.1%, etc.). However, analysis of percentile shares at other positions in the distri- bution may also be of interest. In this paper I present a new Stata command called pshare that estimates percentile shares from individual-level data and displays the results using histograms or stacked bar charts.

Assessing inequality using percentile shares

At least since Thomas Piketty's best-selling "Capital in the Twenty-First Century" (2014, Cambridge, MA: The Belknap Press), percentile shares have become a popular approach for analyzing distributional inequalities. In their work on the development of top incomes, Piketty and collaborators typically report top-percentage shares, using varying percentages as thresholds (top 10%, top 1%, top 0.1%, etc.). However, analysis of percentile shares at other positions in the distribution may also be of interest. In this paper I present a new Stata command called -pshare- that estimates percentile shares from individual-level data and displays the results using histograms or stacked bar charts.