Mapping Patent Classifications: Portfolio and Statistical Analysis, and the Comparison of Strengths and Weaknesses

The Cooperative Patent Classifications (CPC) jointly developed by the European and US Patent Offices provide a new basis for mapping and portfolio analysis. This update provides an occasion for rethinking the parameter choices. The new maps are significantly different from previous ones, although this may not always be obvious on visual inspection. Since these maps are statistical constructs based on index terms, their quality--as different from utility--can only be controlled discursively. We provide nested maps online and a routine for portfolio overlays and further statistical analysis. We add a new tool for "difference maps" which is illustrated by comparing the portfolios of patents granted to Novartis and MSD in 2016.Comment: Scientometrics 112(3) (2017) 1573-1591; http://link.springer.com/article/10.1007/s11192-017-2449-

A patient with Melorheostosis manifesting with features similar to tricho-dento-osseous syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>A case of melorheostosis in association with tricho-dento-osseous (TDO) syndrome has been encountered.</p> <p>Case presentation</p> <p>The clinical and the radiographic manifestations of melorheostosis have been encountered in a 41-year-old man. Mutations in the 13 exons and flanking intronic regions of the LEMD3-gene have not been detected. His phenotypic features were consistent but not completely diagnostic for tricho-dento-osseous syndrome (TDO). We report what might be a novel syndromic association.</p> <p>Conclusion</p> <p>Melorheostosis has not previously been reported to be a part of TDO and an extensive review of the literature suggests that the constellation of hair, tooth and bone abnormalities found in our patient either represents an unusual variant of tricho-dento-osseous syndrome or a new syndrome.</p

The impact of genetic relationship information on genomic breeding values in German Holstein cattle

<p>Abstract</p> <p>Background</p> <p>The impact of additive-genetic relationships captured by single nucleotide polymorphisms (SNPs) on the accuracy of genomic breeding values (GEBVs) has been demonstrated, but recent studies on data obtained from Holstein populations have ignored this fact. However, this impact and the accuracy of GEBVs due to linkage disequilibrium (LD), which is fairly persistent over generations, must be known to implement future breeding programs.</p> <p>Materials and methods</p> <p>The data set used to investigate these questions consisted of 3,863 German Holstein bulls genotyped for 54,001 SNPs, their pedigree and daughter yield deviations for milk yield, fat yield, protein yield and somatic cell score. A cross-validation methodology was applied, where the maximum additive-genetic relationship (<it>a</it>_<it>max</it>) between bulls in training and validation was controlled. GEBVs were estimated by a Bayesian model averaging approach (BayesB) and an animal model using the genomic relationship matrix (G-BLUP). The accuracy of GEBVs due to LD was estimated by a regression approach using accuracy of GEBVs and accuracy of pedigree-based BLUP-EBVs.</p> <p>Results</p> <p>Accuracy of GEBVs obtained by both BayesB and G-BLUP decreased with decreasing <it>a</it>_{<it>max </it>}for all traits analyzed. The decay of accuracy tended to be larger for G-BLUP and with smaller training size. Differences between BayesB and G-BLUP became evident for the accuracy due to LD, where BayesB clearly outperformed G-BLUP with increasing training size.</p> <p>Conclusions</p> <p>GEBV accuracy of current selection candidates varies due to different additive-genetic relationships relative to the training data. Accuracy of future candidates can be lower than reported in previous studies because information from close relatives will not be available when selection on GEBVs is applied. A Bayesian model averaging approach exploits LD information considerably better than G-BLUP and thus is the most promising method. Cross-validations should account for family structure in the data to allow for long-lasting genomic based breeding plans in animal and plant breeding.</p

The role of species charisma in biological invasions

Commonly used in the literature to refer to the "attractiveness", "appeal", or "beauty" of a species, charisma can be defined as a set of characteristics - and the perception thereof - that affect people's attitudes and behaviors toward a species. It is a highly relevant concept for invasion science, with implications across all stages of the invasion process. However, the concept of invasive alien species (IAS) charisma has not yet been systematically investigated. We discuss this concept in detail, provide a set of recommendations for further research, and highlight management implications. We review how charisma affects the processes associated with biological invasions andIASmanagement, including species introductions and spread, media portrayals, public perceptions of species management, research attention, and active public involvement in research and management. Explicit consideration ofIAScharisma is critical for understanding the factors that shape people's attitudes toward particular species, planning management measures and strategies, and implementing a combination of education programs, awareness raising, and public involvement campaigns.Peer reviewe

Impacts of both reference population size and inclusion of a residual polygenic effect on the accuracy of genomic prediction

<p>Abstract</p> <p>Background</p> <p>The purpose of this work was to study the impact of both the size of genomic reference populations and the inclusion of a residual polygenic effect on dairy cattle genetic evaluations enhanced with genomic information.</p> <p>Methods</p> <p>Direct genomic values were estimated for German Holstein cattle with a genomic BLUP model including a residual polygenic effect. A total of 17,429 genotyped Holstein bulls were evaluated using the phenotypes of 44 traits. The Interbull genomic validation test was implemented to investigate how the inclusion of a residual polygenic effect impacted genomic estimated breeding values.</p> <p>Results</p> <p>As the number of reference bulls increased, both the variance of the estimates of single nucleotide polymorphism effects and the reliability of the direct genomic values of selection candidates increased. Fitting a residual polygenic effect in the model resulted in less biased genome-enhanced breeding values and decreased the correlation between direct genomic values and estimated breeding values of sires in the reference population.</p> <p>Conclusions</p> <p>Genetic evaluation of dairy cattle enhanced with genomic information is highly effective in increasing reliability, as well as using large genomic reference populations. We found that fitting a residual polygenic effect reduced the bias in genome-enhanced breeding values, decreased the correlation between direct genomic values and sire's estimated breeding values and made genome-enhanced breeding values more consistent in mean and variance as is the case for pedigree-based estimated breeding values.</p

Refractory dispersion promotes conduction disturbance and arrhythmias in a Scn5a+/− mouse model

Accentuated right ventricular (RV) gradients in action potential duration (APD) have been implicated in the arrhythmogenicity observed in Brugada syndrome in studies assuming that ventricular effective refractory periods (VERPs) vary in concert with APDs. The present experiments use a genetically modified mouse model to explore spatial heterogeneities in VERP that in turn might affect conduction velocity, thereby causing arrhythmias. Activation latencies, APDs and VERPs recorded during programmed S1S2 protocols were compared in RV and left ventricular (LV) epicardia and endocardia of Langendorff-perfused wild-type (WT) and Scn5a+/− hearts. Scn5a+/− and WT hearts showed similar patterns of shorter VERPs in RV than LV epicardia, and in epicardia than endocardia. However, Scn5a+/− hearts showed longer VERPs, despite shorter APD90s, than WT in all regions examined. The pro- and anti-arrhythmic agents flecainide and quinidine increased regional VERPs despite respectively decreasing and increasing the corresponding APD90s particularly in Scn5a+/− RV epicardia. In contrast, Scn5a+/− hearts showed greater VERP gradients between neighbouring regions, particularly RV transmural gradients, than WT (9.1 ± 1.1 vs. 5.7 ± 0.5 ms, p < 0.05, n = 12). Flecainide increased (to 21 ± 0.9 ms, p < 0.05, n = 6) but quinidine decreased (to 4.5 ± 0.5 ms, p < 0.05, n = 6) these gradients, particularly across the Scn5a+/− RV. Finally, Scn5a+/− hearts showed greater conduction slowing than WT following S2 stimuli, particularly with flecainide administration. Rather than arrhythmogenesis resulting from increased transmural repolarization gradients in an early, phase 2, reentrant excitation mechanism, the present findings implicate RV VERP gradients in potential reentrant mechanisms involving impulse conduction slowed by partial refractoriness

Comparative Lipidomics of Azole Sensitive and Resistant Clinical Isolates of Candida albicans Reveals Unexpected Diversity in Molecular Lipid Imprints

Although transcriptome and proteome approaches have been applied to determine the regulatory circuitry behind multidrug resistance (MDR) in Candida, its lipidome remains poorly characterized. Lipids do acclimatize to the development of MDR in Candida, but exactly how the acclimatization is achieved is poorly understood. In the present study, we have used a high-throughput mass spectrometry-based shotgun approach and analyzed the lipidome of genetically matched clinical azole-sensitive (AS) and -resistant (AR) isolates of C. albicans. By comparing the lipid profiling of matched isolates, we have identified major classes of lipids and determined more than 200 individual molecular lipid species among these major classes. The lipidome analysis has been statistically validated by principal component analysis. Although each AR isolate was similar with regard to displaying a high MIC to drugs, they had a distinct lipid imprint. There were some significant commonalities in the lipid profiles of these pairs, including molecular lipid species ranging from monounsaturated to polyunsaturated fatty acid-containing phosphoglycerides. Consistent fluctuation in phosphatidyl serine, mannosylinositolphosphorylceramides, and sterol esters levels indicated their compensatory role in maintaining lipid homeostasis among most AR isolates. Notably, overexpression of either CaCdr1p or CaMdr1p efflux pump proteins led to a different lipidomic response among AR isolates. This study clearly establishes the versatility of lipid metabolism in handling azole stress among various matched AR isolates. This comprehensive lipidomic approach will serve as a resource for assessing strategies aimed at disrupting the functions of Candida lipids, particularly the functional interactions between lipids and MDR determinants

Modelling human visual navigation using multi-view scene reconstruction

It is often assumed that humans generate a 3D reconstruction of the environment, either in egocentric or world-based coordinates, but the steps involved are unknown. Here, we propose two reconstruction-based models, evaluated using data from two tasks in immersive virtual reality. We model the observer’s prediction of landmark location based on standard photogrammetric methods and then combine location predictions to compute likelihood maps of navigation behaviour. In one model, each scene point is treated independently in the reconstruction; in the other, the pertinent variable is the spatial relationship between pairs of points. Participants viewed a simple environment from one location, were transported (virtually) to another part of the scene and were asked to navigate back. Error distributions varied substantially with changes in scene layout; we compared these directly with the likelihood maps to quantify the success of the models. We also measured error distributions when participants manipulated the location of a landmark to match the preceding interval, providing a direct test of the landmark-location stage of the navigation models. Models such as this, which start with scenes and end with a probabilistic prediction of behaviour, are likely to be increasingly useful for understanding 3D vision

Predictive value of coronary calcifications for future cardiac events in asymptomatic patients with diabetes mellitus: A prospective study in 716 patients over 8 years

<p>Abstract</p> <p>Background</p> <p>To establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus.</p> <p>Methods</p> <p>We included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2 ± 15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1 ± 1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined.</p> <p>Results</p> <p>During the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475 ± 208) was significantly higher compared to those without cardiac events (236 ± 199, p < 0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p < 0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p < 0.01.</p> <p>Conclusion</p> <p>By determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.</p