Interface electronic states and boundary conditions for envelope functions

The envelope-function method with generalized boundary conditions is applied to the description of localized and resonant interface states. A complete set of phenomenological conditions which restrict the form of connection rules for envelope functions is derived using the Hermiticity and symmetry requirements. Empirical coefficients in the connection rules play role of material parameters which characterize an internal structure of every particular heterointerface. As an illustration we present the derivation of the most general connection rules for the one-band effective mass and 4-band Kane models. The conditions for the existence of Tamm-like localized interface states are established. It is shown that a nontrivial form of the connection rules can also result in the formation of resonant states. The most transparent manifestation of such states is the resonant tunneling through a single-barrier heterostructure.Comment: RevTeX4, 11 pages, 5 eps figures, submitted to Phys.Rev.

Comparison of advanced echocardiographic right ventricular functional parameters with cardiovascular magnetic resonance in adult congenital heart disease

AimsAdvanced transthoracic echocardiography (TTE) using volumetric and deformational indices provides detailed quantification of right ventricular (RV) function in adults with congenital heart disease (ACHD). Two-dimensional multi-plane echocardiography (2D-MPE) has demonstrated regional wall differences in RV longitudinal strain (LS). This study aims to evaluate the association of these parameters with cardiovascular magnetic resonance (CMR).Methods and resultsOne hundred stable ACHD patients with primarily affected RVs were included (age 50±5 years; 53% male). Conventional and advanced echocardiographic RV functional parameters were compared to CMR-derived RV function.Advanced echocardiographic RV functional parameters were measurable in approximately one-half of the study co-hort, whilst multi-wall LS assessment feasibility was lower. CMR RV ejection fraction (CMR-RVEF) was moderately correlated with deformational, area and volumetric parameters (RV global LS [lateral wall and septum], n=55: r=-0.62, p<0.001; RV wall average LS, n=34: r=-0.49, p=0.002; RV lateral wall LS, n=56: r=-0.45, p<0.001; fractional area change [FAC], n=67: r=0.48, p<0.001; 3D-RVEF, n=48: r=0.40, p=0.005). Conventional measurements such as TAPSE and RV S’ correlated poorly. RV global LS best identified CMR-RVEF <45% (AUC: 0.84, p<0.001: cut-off value -19%: sensitivity 100%, specificity 57%). RVEF and LS values were significantly higher when measured by CMR compared to TTE (mean difference RVEF: 5[-9 to 18]%; lateral (free) wall LS: -7[7 to -21]%; RV global LS: -6 [5 to -16]%) whilst there was no association between respective LS values.ConclusionIn ACHD patients, advanced echocardiographic RV functional parameters are moderately correlated with CMR-RVEF, although significant differences exist between indices measurable by both modalities

Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy

Background: In-depth phylogeographic analysis can reveal migration patterns relevant for public health planning. Here, as a model, we focused on the provenance, in the current Italian HCV subtype 1a epidemic, of the NS3 resistance-associated variant (RAV) Q80K, known to interfere with the action of NS3/4A protease inhibitor simeprevir. HCV1a migration patterns were analysed using Bayesian phylodynamic tools, capitalising on newly generated and publicly available time and geo-referenced NS3 encoding virus genetic sequence data. Results: Our results showed that both immigration and local circulation fuel the current Italian HCV1a epidemic. The United States and European continental lineages dominate import into Italy, with the latter taking the lead from the 1970s onwards. Since similar migration patterns were found for Q80K and other lineages, no clear differentiation of the risk for failing simeprevir can be made between patients based on their migration and travel history. Importantly, since HCV only occasionally recombines, these results are readily transferable to the genetic sequencing policy concerning NS5A RAVs. Conclusions: The patient migration and travel history cannot be used to target only part of the HCV1a infected population for drug resistance testing before start of antiviral therapy. Consequently, it may be cost-effective to expand genotyping efforts to all HCV1a infected patients eligible for simeprevir-based therapies. © 2017 The Author(s)

A new approach for interpreting Random Forest models and its application to the biology of ageing

This work uses the Random Forest (RF) classification algorithm to predict if a gene is over-expressed, under-expressed or has no change in expression with age in the brain. RFs have high predictive power, and RF models can be interpreted using a feature (variable) importance measure. However, current feature importance measures evaluate a feature as a whole (all feature values). We show that, for a popular type of biological data (Gene Ontology-based), usually only one value of a feature is particularly important for classification and the interpretation of the RF model. Hence, we propose a new algorithm for identifying the most important and most informative feature values in an RF model

A community resource for paired genomic and metabolomic data mining

Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite structures.Peer reviewe

Conceptualizing and measuring distance in international business research:Recurring questions and best practice guidelines

Distance is a central concept in international business research, yet there is debate about the construct as well as its operationalization. In this editorial, we address three of the most important recurring questions posed by authors, editors, and reviewers by examining the theory, methods, and data of distance research. We discuss (1) how to theorize on distance, and (2) what method and (3) what data to use when constructing a distance index. We develop practical recommendations grounded in theory, illustrating and supporting them by calculating cross-country distance indices for all available country pairs and two of the most used distance indices: cultural and institutional. We show that, whereas a specific method to calculate distance may matter to some extent, the choice for a specific cultural or institutional framework to measure cultural or institutional distance has a major impact on country-pair distances. Overall, this editorial highlights the importance of matching data and method to the theoretical argument.</p

Phase I studies of AZD1208, a proviral integration Moloney virus kinase inhibitor in solid and haematological cancers.

BACKGROUND:Proviral integration Moloney virus (PIM) kinases (PIM1, 2 and 3) are overexpressed in several tumour types and contribute to oncogenesis. AZD1208 is a potent ATP-competitive PIM kinase inhibitor investigated in patients with recurrent or refractory acute myeloid leukaemia (AML) or advanced solid tumours. METHODS:Two dose-escalation studies were performed to evaluate the safety and tolerability, and to define the maximum tolerated dose (MTD), of AZD1208 in AML and solid tumours. Secondary objectives were to evaluate the pharmacokinetics, pharmacodynamics (PD) and preliminary efficacy of AZD1208. RESULTS:Sixty-seven patients received treatment: 32 in the AML study over a 120-900 mg dose range, and 25 in the solid tumour study over a 120-800 mg dose range. Nearly all patients (98.5%) in both studies experienced adverse events, mostly gastrointestinal (92.5%). Dose-limiting toxicities included rash, fatigue and vomiting. AZD1208 was not tolerated at 900 mg, and the protocol-defined MTD was not confirmed. AZD1208 increased CYP3A4 activity after multiple dosing, resulting in increased drug clearance. There were no clinical responses; PD analysis showed biological activity of AZD1208. CONCLUSIONS:Despite the lack of single-agent clinical efficacy with AZD1208, PIM kinase inhibition may hold potential as an anticancer treatment, perhaps in combination with other agents

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe