| 1. |
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| 2. |
- Bergvall, Anders, 1981, et al.
(författare)
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Basic Theory of Electron Transport Through Molecular Contacts
- 2016
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Ingår i: Handbook of Single-Molecule Electronics. - 9789814463393 ; , s. 31-78
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In this chapter, we will introduce a basic theoretical description of coherent electron transport through low-dimensional junctions and molecular devices. The description introduced is based on quantum transport theory using a tight-binding description of molecules and lead materials. We apply this theory in a few worked examples on junctions based on graphene and carbon nanotubes and on molecular-superconducting hybrid junctions.
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| 3. |
- Bergvall, Anders, 1981, et al.
(författare)
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Graphene nanogap for gate-tunable quantum-coherent single-molecule electronics
- 2011
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 84:15
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Tidskriftsartikel (refereegranskat)abstract
- We present atomistic calculations of quantum coherent electron transport through fulleropyrrolidine terminated molecules bridging a graphene nanogap. We predict that three difficult problems in molecular electronics with single molecules can be solved by utilizing graphene contacts: (1) a back gate modulating the Fermi level in the graphene leads facilitates control of the device conductance in a transistor effect with high on-off current ratio; (2) the size mismatch between leads and molecule is avoided, in contrast to the traditional metal contacts; (3) as a consequence, distinct features in charge flow patterns throughout the device are directly detectable by scanning techniques. We show that moderate graphene edge disorder is unimportant for the transistor function.
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| 4. |
- Bergvall, Anders, 1981, et al.
(författare)
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Influence of 0001 tilt grain boundaries on the destruction of the quantum Hall effect in graphene
- 2015
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 91:24
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Tidskriftsartikel (refereegranskat)abstract
- The half-integer quantum Hall effect (QHE) is often suppressed in graphene grown by chemical vapor deposition on metals. The reason behind the suppression is unclear, and we hypothesize that it might be connected to extended defects in the material. In this paper we present results for the quantum Hall effect in graphene with [0001] tilt grain boundaries connecting opposite sides of Hall bar devices. Such grain boundaries contain 5-7 ring complexes that host defect states that hybridize to form bands with varying degree of metallicity depending on grain-boundary defect density. In a magnetic field, edge states on opposite sides of the Hall bar can be connected by the defect states along the grain boundary. This destroys Hall resistance quantization and leads to nonzero longitudinal resistance. Anderson disorder can partly recover quantization, where current instead flows along returning paths along the grain boundary depending on defect density in the grain boundary and on disorder strength. Since grain sizes in graphene made by chemical vapor deposition are usually small, this may help explain why the quantum Hall effect is usually poorly developed in devices made of this material.
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| 5. |
- Bergvall, Anders, 1981, et al.
(författare)
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Spectral footprints of impurity scattering in graphene nanoribbons
- 2013
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 87:20
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Tidskriftsartikel (refereegranskat)abstract
- We report a detailed investigation of the interplay between size quantization and local scattering centers in graphene nanoribbons, as seen in the local density of states. The spectral signatures, obtained after Fourier transformation of the local density of states, include characteristic peaks that can be related to the transverse modes of the nanoribbon. In armchair ribbons, the Fourier transformed density of states of one of the two inequivalent sublattices takes a form similar to that of a quantum channel in a two-dimensional electron gas, modified according to the differences in band structure. After addition of the second sublattice contribution, a characteristic modulation of the pattern due to superposition is obtained, similar to what has been obtained in spectra due to single impurity scattering in large-area graphene. We present analytic results for the electron propagator in armchair nanoribbons in the Dirac approximation, including a single scattering center within a T-matrix formulation. For comparison, we have extended the investigation with numerics obtained with an atomistic recursive Green's function approach. The spectral signatures of the atomistic approach include the effects of trigonal warping. The impurity induced oscillations in the local density of states are not decaying at large distance in few-mode nanoribbons.
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| 6. |
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| 7. |
- Bergvall, Ida, 1975-, et al.
(författare)
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The Subject Language Use In Year 8 TIMSS-Test Questions : A Comparison Of Language Uses In Science And Mathematics
- 2018
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Ingår i: Network Sessions as ECER 2018.
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Konferensbidrag (refereegranskat)abstract
- In this study we want to make a contribution by making a comparison between the subject languages in mathematics and science based on linguistic theories about language and language function. Through this theoretical foundation in this present study we also have the opportunity to analyze the language function and thus we can also discuss the language's role in teaching. The aim of this study is to compare and thus gain more knowledge of grammatical features in subject language in science and mathematics and how these grammatical features are used to express meaning. To fulfil this purpose, science and mathematics items from Trends in International Mathematics and Science Study (TIMSS) 2011, grade eight, have been analysed from a functional perspective on language.Empirical studies that compare language use in different subjects are sparsely present (Österholm & Bergqvist, 2013) but there are studies pointing out that how language are used to express meaning varies between different school subjects (e.g. Fang & Schleppegrell, 2008; Schleppegrell, 2004). These linguistic differences have been highlighted as arguments for a more differentiated language-based teaching of subjects, leaning on disciplinary literacy (Shanahan & Shanahan, 2008). In order to conduct such a language-based teaching of subjects, an awareness of the different functions in the language used in various school subject is of great importance. One example of a comparative language study is the corpus study conducted by Ribeck (2015) where the language in Swedish teaching materials in science is analyzed, and compared with teaching materials in social science and with textbooks in mathematics. However, Ribeck does not make a direct analysis of mathematical subject language, her focus is rather on the language used in natural science compared to social science. There are also studies that focuses on the language use within subjects. Here it appears that the subject language is used differently and has different functions in different content areas within school mathematics (e.g. Bergvall, 2016) as well as within the different school science subjects, e.g. biology, physics, chemistry and earth science (e.g. Persson, 2016). This study draws on a social semiotic perspective and systemic functional linguistics (SFL) (Halliday & Matthiessen, 2004). A point of departure is the perspective that different registers of language are used in different social contexts, which in this study is defined as the two school subjects science and mathematics. Grounded in SFL and the three meta-functions ideational, interpersonal and textual function the meaning dimension model of analysis was developed in a previous research project (Bergvall et al., 2016; Persson et al., 2016). Four central meaning dimensions, packing, precision, personification and presentation, were condensed from previous research regarding academic language and language use in the school subjects science and mathematics. The meaning dimensions can be used as measures of how grammatical features are used in various types of texts in order to express meaning. Packing and precision are regarded as aspects of the ideational meta-function. Packing is a measure of the information density in a text and precision is a measure of how and to what extent the given information in the text is specified. Personification, as an aspect of the interpersonal meta-function, is a measure of how personal relations between the reader and the text are expressed. The last meaning dimension, presentation, concerns how the information is structured in the text and is regarded as an aspect of the textual meta-function. In the present study, the four meaning dimensions are used to describe and compare the language and its function in science and mathematics items in TIMSS 2011.MethodBy the use of a quantitative method all items in mathematics and science from the Swedish version of TIMSS 2011, grade eight were analyzed. This material consists of 197 items in science and 217 items in mathematics. The language in these items have been analyzed for word class, word length and number of words per items by a computer based automatic parsing. For this parsing Extensible Markup Language (XML) was used. Some other linguistic features, i.e. passive forms and subordinate clauses, were identified manually. Since the meaning dimensions are used as a base for the linguistic analysis, the results will possibly be generally applicable also for other European languages, although the analysis was conducted on the Swedish version of TIMSS items. Packing was measured by calculating the number of nouns and the number of long words (>6 characters). Precision in the items were provided by words such as adjectives, adverbs, participles and counting words specifying different attributes in the items. Personification was here measured by the number of personal pronouns and proper names and presentation was measured by the presence of subordinate clauses and passive forms. In order to compensate for the varying length of different items, the number of the different linguistic features were divided by the number of words in the particular item. To enable the adding of different features, each feature is normalized by calculating its z-score. An index was then calculated for each meaning dimension based on the linguistic information on each item. From these indices a comparison between the language uses in the two subjects was possible. In the next step of the analysis each subject were separated into content domains: Algebra, Data & chance, Geometry and Numbers for mathematics items and Biology, Chemistry, Earth science and Physics for science items. This enabled variations of language use within the subjects also to be analyzed. The results were compiled in box-plots diagrams which visualized the distribution of the expressions of the four meaning dimensions in the various content domains.Expected OutcomesPreliminary results show that central traits of the academic language as measured by the four meaning dimensions are used in similar ways in both science and mathematics. The levels of packing, precision and presentation are fairly similar when looking at differences between the subjects. Personification shows the largest differences between the subjects, where mathematics as a whole makes more use of personal pronouns and proper names in the items. When separating the subjects into content domains, Statistics shows the highest level of personification. In this domain it can therefore be concluded that human participants are essential, thus emphasizing that this is a domain that this is an area of relevance for people in general or for the student him/herself. This can be interpreted as signaling the possibility to actively participate and interact in similar situations as described by the items context. On the other hand, in domains such as Algebra, Geometry and Earth science where the content is expressed with a low level of personification, the interpretation is that the content of these domains –at least as expressed in TIMSS items- are more separated from peoples’ everyday lives and thus the students’ own reality. Another result that emerges from the analysis relates to the meaning dimension presentation where we see that the written texts, especially in Algebra, but also in Geometry, Numbers and Earth science, mainly contains short sentences without subordinate clauses. In written academic language, subordinate clauses are a common tool for creating information flow and link different parts of the text (Fang, 2006; Schleppegrell, 2004; Veel, 1997). The lack of subordinate clauses in tasks in certain content areas of TIMSS indicates a subject-specific linguistic form that may require a familiarity with this specific form of language use.ReferencesBergvall, I. (2016). Bokstavligt, bildligt och symboliskt i skolans matematik – en studie om ämnesspråk i TIMSS. [Diss.] Uppsala: Acta Universitatis Upsaliensis. Bergvall, I., Wiksten Folkeryd, J., & Liberg, C. (2016). Linguistic features and their function in different mathematical content areas in TIMSS 2011. Nordic Studies in Mathematics Education, 21(2), 45-68. Fang, Z. (2006). The Language Demands of Science Reading in Middle School, International Journal of Science Education, 28(5) 491-520. Fang, Z., & Schleppegrell, M. J. (2008). Reading in secondary content areas: A language-based pedagogy. Ann Arbor: University of Michigan Press. Halliday, M. A. K., & Matthiessen, C. M. I. M. (2004). An introduction to functional grammar (3.th ed.). London: Arnold. Persson, Tomas (2016). De naturvetenskapliga ämnesspråken. De naturvetenskapliga uppgifterna i och elevers resultat från TIMSS 2011 år 8. [Diss.] Uppsala: Acta Universitatis Upsaliensis. Persson, T., af Geijerstam, Å., & Liberg, C. (2016). Features and functions of scientific language(s) in TIMSS 2011. Nordic Studies in Science Education, 12(2), 176-196. Ribeck, Judy (2015). Steg för steg. Naturvetenskapligt ämnesspråk som räknas. [Diss.] Data linguistica. No. 28, Institutionen för svenska språket, Göteborgs universitet. Shanahan, T., & Shanahan, C. (2008). Teaching disciplinary literacy to adolescents: Rethinking content-area literacy. Harvard Educational Review, 78(1), 40–59. Schleppegrell, M. J. (2004). The language of schooling; a functional linguistics perspective. London: Lawrence Erlbaum Associates. Veel, R. (1997). Learning How to Mean-Scientifically Speaking: Apprenticeship into Scientific Discourse in the Secondary School. In. Christie Frances & Jim R. Martin (Eds.), Genre and Institutions: Social Processes in the Workplace and School, s. 161-195. London: Cassell. Österholm, M. & Bergqvist, E. (2013). What is so special about mathematical texts? Analyses of common claims in research literature and of properties of textbooks. ZDM Mathematics education, 45(5) 751-763.
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| 8. |
- Bergvall, Tomas, et al.
(författare)
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vigiGrade : A Tool to Identify Well-Documented Individual Case Reports and Highlight Systematic Data Quality Issues
- 2014
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Ingår i: Drug Safety. - : Springer Science and Business Media LLC. - 0114-5916 .- 1179-1942. ; 37:1, s. 65-77
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Tidskriftsartikel (refereegranskat)abstract
- Individual case safety reports of suspected harm from medicines are fundamental to post-marketing surveillance. Their value is directly proportional to the amount of clinically relevant information they include. To improve the quality of the data, communication between stakeholders is essential and can be facilitated by a simple score and visualisation of the results. The objective of this study was to propose a measure of completeness and identify predictors of well-documented reports, globally. The Uppsala Monitoring Centre has developed the vigiGrade completeness score to measure the amount of clinically relevant information in structured format, without reflecting whether the information establishes causality between the drug and adverse event. The vigiGrade completeness score (C) starts at 1 for reports with information on time-to-onset, age, sex, indication, outcome, report type, dose, country, primary reporter and comments. For each missing dimension, a penalty is detracted which varies with clinical relevance. We classified reports with C > 0.8 as well-documented and identified all such reports in the WHO global individual case safety report database, VigiBase, from 2007 to January 2012. We utilised odds ratios with statistical shrinkage to identify subgroups with unexpectedly high proportions of well-documented reports. Altogether, 430,000 (13 %) of the studied reports achieved C > 0.8 in VigiBase. For VigiBase as a whole, the median completeness was 0.41 with an interquartile range of 0.26-0.63. Two out of three well-documented reports come from Europe, and two out of three from physicians. Among the countries with more than 1,000 reports in total, the highest rate of well-documented reports is 65 % in Italy. Tunisia, Spain, Portugal, Croatia and Denmark each have rates above 50 %, and another 20 countries have rates above 30 %. On the whole, 24 % of the reports from physicians are well-documented compared with only 4 % for consumers/non-health professionals. Notably, Denmark and Norway have more than 50 % well-documented reports from consumers/non-health professionals and higher rates than for physicians. The rate of well-documented reports for the E2B format is 11 % compared with 22 % for the older INTDIS (International Drug Information System) format. However, for E2B reports entered via the WHO programme's e-reporting system VigiFlow, the rate is 29 %. Overall, only one report in eight provides the desired level of information, but much higher proportions are observed for individual countries. Physicians and e-reporting tools also generate greater proportions of well-documented reports overall. Reports from consumers/non-health professionals in specific regions have excellent quality, which illustrates their potential for the future. vigiGrade has already provided valuable information by highlighting data quality issues both in Italy and the USA.
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| 9. |
- Caster, Ola, et al.
(författare)
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vigiRank for statistical signal detection in pharmacovigilance : First results from prospective real-world use
- 2017
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 26:8, s. 1006-1010
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: vigiRank is a data-driven predictive model for emerging safety signals. In addition to disproportionate reporting patterns, it also accounts for the completeness, recency, and geographic spread of individual case reporting, as well as the availability of case narratives. Previous retrospective analysis suggested that vigiRank performed better than disproportionality analysis alone. The purpose of the present analysis was to evaluate its prospective performance. Methods: The evaluation of vigiRank was based on real-world signal detection in VigiBase. In May 2014, vigiRank scores were computed for pairs of new drugs and WHO Adverse Reaction Terminology critical terms with at most 30 reports from at least 2 countries. Initial manual assessments were performed in order of descending score, selecting a subset of drug-adverse drug reaction pairs for in-depth expert assessment. The primary performance metric was the proportion of initial assessments that were decided signals during in-depth assessment. As comparator, the historical performance for disproportionality-guided signal detection in VigiBase was computed from a corresponding cohort of drug-adverse drug reaction pairs assessed between 2009 and 2013. During this period, the requirement for initial manual assessment was a positive lower endpoint of the 95% credibility interval of the Information Component measure of disproportionality, observed for the first time. Results: 194 initial assessments suggested by vigiRank's ordering eventually resulted in 6 (3.1%) signals. Disproportionality analysis yielded 19 signals from 1592 initial assessments (1.2%; P <.05). Conclusions: Combining multiple strength-of-evidence aspects as in vigiRank significantly outperformed disproportionality analysis alone in real-world pharmacovigilance signal detection, for VigiBase.
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| 10. |
- Cavadino, Alana, et al.
(författare)
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Signal Detection in EUROmediCAT : Identification and Evaluation of Medication-Congenital Anomaly Associations and Use of VigiBase as a Complementary Source of Reference
- 2021
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Ingår i: Drug Safety. - : ADIS INT LTD. - 0114-5916 .- 1179-1942. ; 44:7, s. 765-785
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Knowledge on the safety of medication use during pregnancy is often sparse. Pregnant women are generally excluded from clinical trials, and there is a dependence on post-marketing surveillance to identify teratogenic medications. Aims This study aimed to identify signals of potentially teratogenic medications using EUROmediCAT registry data on medication exposure in pregnancies with a congenital anomaly, and to investigate the use of VigiBase reports of adverse events of medications in the evaluation of these signals. Methods Signals of medication-congenital anomaly associations were identified in EUROmediCAT (21,636 congenital anomaly cases with 32,619 medication exposures), then investigated in a subset of VigiBase (45,749 cases and 165,121 exposures), by reviewing statistical reporting patterns and VigiBase case reports. Evidence from the literature and quantitative and qualitative aspects of both datasets were considered before recommending signals as warranting further independent investigation. Results EUROmediCAT analysis identified 49 signals of medication-congenital anomaly associations. Incorporating investigation in VigiBase and the literature, these were categorised as follows: four non-specific medications; 11 likely due to maternal disease; 11 well-established teratogens; two reviewed in previous EUROmediCAT studies with limited additional evidence; and 13 with insufficient basis for recommending follow-up. Independent investigations are recommended for eight signals: pregnen (4) derivatives with limb reduction; nitrofuran derivatives with cleft palate and patent ductus arteriosus; salicylic acid and derivatives with atresia or stenosis of other parts of the small intestine and tetralogy of Fallot; carbamazepine with atrioventricular septal defect and severe congenital heart defect; and selective beta-2-adrenoreceptor agonists with posterior urethral valve and/or prune belly. Conclusion EUROmediCAT data should continue to be used for signal detection, accompanied by information from VigiBase and review of the existing literature to prioritise signals for further independent evaluation.
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| 11. |
- Low, Yen S., et al.
(författare)
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Cheminformatics-aided pharmacovigilance : application to Stevens-Johnson Syndrome
- 2016
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Ingår i: JAMIA Journal of the American Medical Informatics Association. - : Oxford University Press (OUP). - 1067-5027 .- 1527-974X. ; 23:5, s. 968-978
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Tidskriftsartikel (refereegranskat)abstract
- Objective Quantitative Structure-Activity Relationship (QSAR) models can predict adverse drug reactions (ADRs), and thus provide early warnings of potential hazards. Timely identification of potential safety concerns could protect patients and aid early diagnosis of ADRs among the exposed. Our objective was to determine whether global spontaneous reporting patterns might allow chemical substructures associated with Stevens-Johnson Syndrome (SJS) to be identified and utilized for ADR prediction by QSAR models. Materials and Methods Using a reference set of 364 drugs having positive or negative reporting correlations with SJS in the VigiBase global repository of individual case safety reports (Uppsala Monitoring Center, Uppsala, Sweden), chemical descriptors were computed from drug molecular structures. Random Forest and Support Vector Machines methods were used to develop QSAR models, which were validated by external 5-fold cross validation. Models were employed for virtual screening of DrugBank to predict SJS actives and inactives, which were corroborated using knowledge bases like VigiBase, ChemoText, and MicroMedex (Truven Health Analytics Inc, Ann Arbor, Michigan). Results We developed QSAR models that could accurately predict if drugs were associated with SJS (area under the curve of 75%-81%). Our 10 most active and inactive predictions were substantiated by SJS reports (or lack thereof) in the literature. Discussion Interpretation of QSAR models in terms of significant chemical descriptors suggested novel SJS structural alerts. Conclusions We have demonstrated that QSAR models can accurately identify SJS active and inactive drugs. Requiring chemical structures only, QSAR models provide effective computational means to flag potentially harmful drugs for subsequent targeted surveillance and pharmacoepidemiologic investigations.
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| 12. |
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| 13. |
- Norén, G. Niklas, et al.
(författare)
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Empirical Performance of the Calibrated Self-Controlled Cohort Analysis Within Temporal Pattern Discovery : Lessons for Developing a Risk Identification and Analysis System
- 2013
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Ingår i: Drug Safety. - : Springer Science and Business Media LLC. - 0114-5916 .- 1179-1942. ; 36, s. s107-S121
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Tidskriftsartikel (refereegranskat)abstract
- Background Observational healthcare data offer the potential to identify adverse drug reactions that may be missed by spontaneous reporting. The self-controlled cohort analysis within the Temporal Pattern Discovery framework compares the observed-to-expected ratio of medical outcomes during post-exposure surveillance periods with those during a set of distinct pre-exposure control periods in the same patients. It utilizes an external control group to account for systematic differences between the different time periods, thus combining within- and between-patient confounder adjustment in a single measure. Objectives To evaluate the performance of the calibrated self-controlled cohort analysis within Temporal Pattern Discovery as a tool for risk identification in observational healthcare data. Research Design Different implementations of the calibrated self-controlled cohort analysis were applied to 399 drug-outcome pairs (165 positive and 234 negative test cases across 4 health outcomes of interest) in 5 real observational databases (four with administrative claims and one with electronic health records). Measures Performance was evaluated on real data through sensitivity/specificity, the area under receiver operator characteristics curve (AUC), and bias. Results The calibrated self-controlled cohort analysis achieved good predictive accuracy across the outcomes and databases under study. The optimal design based on this reference set uses a 360 days surveillance period and a single control period 180 days prior to new prescriptions. It achieved an average AUC of 0.75 and AUC >0.70 in all but one scenario. A design with three separate control periods performed better for the electronic health records database and for acute renal failure across all data sets. The estimates for negative test cases were generally unbiased, but a minor negative bias of up to 0.2 on the RR-scale was observed with the configurations using multiple control periods, for acute liver injury and upper gastrointestinal bleeding. Conclusions The calibrated self-controlled cohort analysis within Temporal Pattern Discovery shows promise as a tool for risk identification; it performs well at discriminating positive from negative test cases. The optimal parameter configuration may vary with the data set and medical outcome of interest.
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| 14. |
- Romania, P., et al.
(författare)
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Identification of a Genetic Variation in ERAP1 Aminopeptidase that Prevents Human Cytomegalovirus miR-UL112-5p-Mediated Immunoevasion
- 2017
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:4, s. 846-853
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we demonstrate that HCMV miR-UL112-5p targets ERAP1, thereby inhibiting the processing and presentation of the HCMV pp65495-503 peptide to specific CTLs. In addition, we show that the rs17481334 G variant, naturally occurring in the ERAP1 30 UTR, preserves ERAP1 from miR-UL1125p-mediated degradation. Specifically, HCMV miRUL112-5p binds the 30 UTR of ERAP1 A variant, but not the 30 UTR of ERAP1 G variant, and, accordingly, ERAP1 expression is reduced both at RNA and protein levels only in human fibroblasts homozygous for the A variant. Consistently, HCMV-infected GG fibroblasts were more efficient in trimming viral antigens and being lysed by HCMV-peptide-specific CTLs. Notably, a significantly decreased HCMV seropositivity was detected among GG individuals suffering from multiple sclerosis, a disease model in which HCMV is negatively associated with adultonset disorder. Overall, our results identify a resistance mechanism to HCMV miR-UL112-5p-based immune evasion strategy with potential implications for individual susceptibility to infection and other diseases.
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| 15. |
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| 16. |
- Sayyab, Shumaila, et al.
(författare)
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Whole-Genome Sequencing of a Canine Family Trio Reveals a FAM83G Variant Associated with Hereditary Footpad Hyperkeratosis
- 2016
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Ingår i: G3. - : Oxford University Press (OUP). - 2160-1836. ; 6, s. 521-527
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Tidskriftsartikel (refereegranskat)abstract
- Over 250 Mendelian traits and disorders, caused by rare alleles have been mapped in the canine genome. Although each disease is rare in the dog as a species, they are collectively common and have major impact on canine health. With SNP-based genotyping arrays, genome-wide association studies (GWAS) have proven to be a powerful method to map the genomic region of interest when 10-20 cases and 10-20 controls are available. However, to identify the genetic variant in associated regions, fine-mapping and targeted resequencing is required. Here we present a new approach using whole-genome sequencing (WGS) of a family trio without prior GWAS. As a proof-ofconcept, we chose an autosomal recessive disease known as hereditary footpad hyperkeratosis (HFH) in Kromfohrländer dogs. To our knowledge, this is the first time this family trio WGS-approach has been used successfully to identify a genetic variant that perfectly segregates with a canine disorder. The sequencing of three Kromfohrländer dogs from a family trio (an affected offspring and both its healthy parents) resulted in an average genome coverage of 9.2X per individual. After applying stringent filtering criteria for candidate causative coding variants, 527 single nucleotide variants (SNVs) and 15 indels were found to be homozygous in the affected offspring and heterozygous in the parents. Using the computer software packages ANNOVAR and SIFT to functionally annotate coding sequence differences, and to predict their functional effect, resulted in seven candidate variants located in six different genes. Of these, only FAM83G:c155G. C (p.R52P) was found to be concordant in eight additional cases, and 16 healthy Kromfohrländer dogs.
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| 17. |
- Star, Kristina, 1963-, et al.
(författare)
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Paediatric safety signals identified in VigiBase : Methods and results from Uppsala Monitoring Centre
- 2019
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Ingår i: Pharmacoepidemiology and Drug Safety. - : WILEY. - 1053-8569 .- 1099-1557. ; 28:5, s. 680-689
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study is to uncover previously unrecognised risks of medicines in paediatric pharmacovigilance reports and thereby advance a safer use of medicines in paediatrics. Methods: Individual case safety reports (ICSRs) with ages less than 18 years were retrieved from VigiBase, the World Health Organization (WHO) global database of ICSRs, in September 2014. The reports were grouped according to the following age spans: 0 to 27 days; 28 days to 23 months; 2 to 11 years; and 12 to 17 years. vigiRank, a data-driven predictive model for emerging safety signals, was used to prioritise the list of drug events by age groups. The list was manually assessed, and potential signals were identified to undergo in-depth assessment to determine whether a signal should be communicated. Results: A total of 472 drug-event pairs by paediatric age groups were the subject of an initial manual assessment. Twenty-seven drug events from the two older age groups were classified as potential signals. An in-depth assessment resulted in eight signals, of which one concerned harm in connection with off-label use of dextromethorphan and another with accidental overdose of olanzapine by young children, and the remaining signals referred to potentially new causal associations for atomoxetine (two signals), temozolamide, deferasirox, levetiracetam, and desloratadine that could be relevant also for adults. Conclusions: Clinically relevant signals were uncovered in VigiBase by using vigiRank applied to paediatric age groups. Further refinement of the methodology is needed to identify signals in reports with ages under 2 years and to capture signals specific to the paediatric population as a risk group.
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| 18. |
- Tesch, J., et al.
(författare)
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Impurity scattering and size quantization effects in a single graphene nanoflake
- 2017
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 95:7
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Tidskriftsartikel (refereegranskat)abstract
- By using Fourier-transform scanning tunneling spectroscopy we measure the interference patterns produced by the impurity scattering of confined Dirac quasiparticles in epitaxial graphene nanoflakes. Upon comparison of the experimental results with tight-binding calculations of realistic model flakes, we show that the characteristic features observed in the Fourier-transformed local density of states are related to scattering between different transverse modes (subbands) of a graphene nanoflake and allow direct insight into the gapped electronic spectrum of graphene. We also observe a strong reduction of quasiparticle lifetime which is attributed to the interaction with the underlying substrate. In addition, we show that the distribution of the on-site energies at flower defects leads to an effectively broken pseudospin selection rule, where intravalley backscattering is allowed.
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