Interaction imaging with amplitude-dependence force spectroscopy

Knowledge of surface forces is the key to understanding a large number of processes in fields ranging from physics to material science and biology. The most common method to study surfaces is dynamic atomic force microscopy (AFM). Dynamic AFM has been enormously successful in imaging surface topography, even to atomic resolution, but the force between the AFM tip and the surface remains unknown during imaging. Here, we present a new approach that combines high accuracy force measurements and high resolution scanning. The method, called amplitude-dependence force spectroscopy (ADFS) is based on the amplitude-dependence of the cantilever's response near resonance and allows for separate determination of both conservative and dissipative tip-surface interactions. We use ADFS to quantitatively study and map the nano-mechanical interaction between the AFM tip and heterogeneous polymer surfaces. ADFS is compatible with commercial atomic force microscopes and we anticipate its wide-spread use in taking AFM toward quantitative microscopy

Use of information on disease diagnoses from databases for animal health economic, welfare and food safety purposes: strengths and limitations of recordings

Many animal health, welfare and food safety databases include data on clinical and test-based disease diagnoses. However, the circumstances and constraints for establishing the diagnoses vary considerably among databases. Therefore results based on different databases are difficult to compare and compilation of data in order to perform meta-analysis is almost impossible. Nevertheless, diagnostic information collected either routinely or in research projects is valuable in cross comparisons between databases, but there is a need for improved transparency and documentation of the data and the performance characteristics of tests used to establish diagnoses. The objective of this paper is to outline the circumstances and constraints for recording of disease diagnoses in different types of databases, and to discuss these in the context of disease diagnoses when using them for additional purposes, including research. Finally some limitations and recommendations for use of data and for recording of diagnostic information in the future are given. It is concluded that many research questions have such a specific objective that investigators need to collect their own data. However, there are also examples, where a minimal amount of extra information or continued validation could make sufficient improvement of secondary data to be used for other purposes. Regardless, researchers should always carefully evaluate the opportunities and constraints when they decide to use secondary data. If the data in the existing databases are not sufficiently valid, researchers may have to collect their own data, but improved recording of diagnostic data may improve the usefulness of secondary diagnostic data in the future

A phasing and imputation method for pedigreed populations that results in a single-stage genomic evaluation

<p>Abstract</p> <p>Background</p> <p>Efficient, robust, and accurate genotype imputation algorithms make large-scale application of genomic selection cost effective. An algorithm that imputes alleles or allele probabilities for all animals in the pedigree and for all genotyped single nucleotide polymorphisms (SNP) provides a framework to combine all pedigree, genomic, and phenotypic information into a single-stage genomic evaluation.</p> <p>Methods</p> <p>An algorithm was developed for imputation of genotypes in pedigreed populations that allows imputation for completely ungenotyped animals and for low-density genotyped animals, accommodates a wide variety of pedigree structures for genotyped animals, imputes unmapped SNP, and works for large datasets. The method involves simple phasing rules, long-range phasing and haplotype library imputation and segregation analysis.</p> <p>Results</p> <p>Imputation accuracy was high and computational cost was feasible for datasets with pedigrees of up to 25 000 animals. The resulting single-stage genomic evaluation increased the accuracy of estimated genomic breeding values compared to a scenario in which phenotypes on relatives that were not genotyped were ignored.</p> <p>Conclusions</p> <p>The developed imputation algorithm and software and the resulting single-stage genomic evaluation method provide powerful new ways to exploit imputation and to obtain more accurate genetic evaluations.</p

Patient dose reduction during voiding cystourethrography

Voiding cystourethrography (VCUG) is a commonly performed examination in a pediatric uroradiology practice. This article contains suggestions on how the radiation dose to a child from VCUG can be made ‘as low as reasonably achievable–(ALARA). The pediatric radiologist should consider the appropriateness of the clinical indication before performing VCUG and utilize radiation exposure techniques and parameters during VCUG to reduce radiation exposure to a child. The medical physicist and fluoroscope manufacturer can also work together to optimize a pulsed-fluoroscopy unit and further reduce the radiation exposure. Laboratory and clinical research is necessary to investigate methods that reduce radiation exposures during VCUG, and current research is presented here

oA novel nonparametric approach for estimating cut-offs in continuous risk indicators with application to diabetes epidemiology

<p>Abstract</p> <p>Background</p> <p>Epidemiological and clinical studies, often including anthropometric measures, have established obesity as a major risk factor for the development of type 2 diabetes. Appropriate cut-off values for anthropometric parameters are necessary for prediction or decision purposes. The cut-off corresponding to the Youden-Index is often applied in epidemiology and biomedical literature for dichotomizing a continuous risk indicator.</p> <p>Methods</p> <p>Using data from a representative large multistage longitudinal epidemiological study in a primary care setting in Germany, this paper explores a novel approach for estimating optimal cut-offs of anthropomorphic parameters for predicting type 2 diabetes based on a discontinuity of a regression function in a nonparametric regression framework.</p> <p>Results</p> <p>The resulting cut-off corresponded to values obtained by the Youden Index (maximum of the sum of sensitivity and specificity, minus one), often considered the optimal cut-off in epidemiological and biomedical research. The nonparametric regression based estimator was compared to results obtained by the established methods of the Receiver Operating Characteristic plot in various simulation scenarios and based on bias and root mean square error, yielded excellent finite sample properties.</p> <p>Conclusion</p> <p>It is thus recommended that this nonparametric regression approach be considered as valuable alternative when a continuous indicator has to be dichotomized at the Youden Index for prediction or decision purposes.</p

Assigning Backbone NMR Resonances for Full Length Tau Isoforms: Efficient Compromise between Manual Assignments and Reduced Dimensionality

Tau protein is the longest disordered protein for which nearly complete backbone NMR resonance assignments have been reported. Full-length tau protein was initially assigned using a laborious combination of bootstrapping assignments from shorter tau fragments and conventional triple resonance NMR experiments. Subsequently it was reported that assignments of comparable quality could be obtained in a fully automated fashion from data obtained using reduced dimensionality NMR (RDNMR) experiments employing a large number of indirect dimensions. Although the latter strategy offers many advantages, it presents some difficulties if manual intervention, confirmation, or correction of the assignments is desirable, as may often be the case for long disordered and degenerate polypeptide sequences. Here we demonstrate that nearly complete backbone resonance assignments for full-length tau isoforms can be obtained without resorting either to bootstrapping from smaller fragments or to very high dimensionality experiments and automation. Instead, a set of RDNMR triple resonance experiments of modest dimensionality lend themselves readily to efficient and unambiguous manual assignments. An analysis of the backbone chemical shifts obtained in this fashion indicates several regions in full length tau with a notable propensity for helical or strand-like structure that are in good agreement with previous observations

Season of birth and handedness in Serbian high school students

<p>Abstract</p> <p>Background</p> <p>Although behavioural dominance of the right hand in humans is likely to be under genetic control, departures from this population norm, i.e. left- or non-right-handedness, are believed to be influenced by environmental factors. Among many such environmental factors including, for example, low birth weight, testosterone level, and maternal age at birth, season of birth has occasionally been investigated. The overall empirical evidence for the season of birth effect is mixed.</p> <p>Methods</p> <p>We have investigated the effect of season of birth in an epidemiologically robust sample of randomly selected young people (n = 977), all born in the same year. A Kolmogorov-Smirnov type statistical test was used to determine season of birth.</p> <p>Results</p> <p>Neither the right-handed nor the non-right-handed groups demonstrated birth asymmetry relative to the normal population birth distribution. There was no between-group difference in the seasonal distribution of birth when comparing the right-handed to the non-right-handed groups.</p> <p>Conclusion</p> <p>The present study failed to provide support for a season of birth effect on atypical lateralisation of handedness in humans.</p

Applying the ALARA concept to the evaluation of vesicoureteric reflux

The voiding cystourethrogram (VCUG) is a widely used study to define lower urinary tract anatomy and to diagnose vesicoureteric reflux (VUR) in children. We examine the technical advances in the VCUG and other examinations for reflux that have reduced radiation exposure of children, and we give recommendations for the use of imaging studies in four groups of children: (1) children with urinary tract infection, (2) siblings of patients with VUR, (3) infants with antenatal hydronephrosis (ANH), and (4) children with a solitary functioning kidney. By performing examinations with little to no radiation, carefully selecting only the children who need imaging studies and judiciously timing follow-up examinations, we can reduce the radiation exposure of children being studied for reflux