| 1. |
- Werren, John H, et al.
(author)
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Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
- 2010
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
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Journal article (peer-reviewed)abstract
- We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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| 2. |
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| 3. |
- Abdallah, J, et al.
(author)
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Rapidity-alignment and p(T) compensation of particle pairs in hadronic Z(0) decays
- 2002
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 533:3-4, s. 243-252
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Journal article (peer-reviewed)abstract
- Observation is made of rapidity-alignment of K+K- and (p) over barp pairs which results from their asymmetric orientation in rapidity, with respect to the direction from primary quark to antiquark. The K+K- and (p) over barp data are consistent with predictions from the fragmentation string model. However, the (p) over barp data strongly disagree with the conventional implementation of the cluster model. The non-perturbative process of 'gluon splitting to diquarks' has to be incorporated into the cluster model for it to agree with the data. Local conservation of PT between particles nearby in rapidity (i.e., p(T) compensation) is analysed with respect to the thrust direction for pi(+)pi(-), K+K-, and (p) over barp pairs. In this case, the string model provides fair agreement with the data. The cluster model is incompatible with the data for all three particle pairs. The model with its central premiss of isotropically-decaying clusters predicts a p(T) correlation not seen in the data. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 4. |
- Abdallah, J, et al.
(author)
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Search for charged Higgs bosons in e(+)e(-) collisions root s=189-202 GeV
- 2002
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 525:1-2, s. 17-28
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Journal article (peer-reviewed)abstract
- A search for pair-produced charged Higgs bosons was performed in the high energy data collected by the DELPHI detector at LEP II at centre-of-mass energies from 189 GeV to 202 GeV. The three different final states, taunutaunu, c (s) over bar(c) over bars and c (s) over bar taunu were considered. New methods were applied to reject wrong hadronic jet pairings and for the tau identification, where a discriminator based on tau polarisation and polar angles was used. No excess of data compared to the expected Standard Model processes was observed and the existence of a charged Higgs boson with mass lower than 71.5 GeV/c(2) is excluded at the 95% confidence level. (C) 2002 Published by Elsevier Science B.V.
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| 5. |
- Abdallah, J, et al.
(author)
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Searches for neutral Higgs bosons in e(+)e(-), collisions from root s=191.6 to 201.7 GeV
- 2002
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 23:3, s. 409-435
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Journal article (peer-reviewed)abstract
- Neutral Higgs bosons of the Standard Model (SM) and the Minimal Supersymmetric Standard Model (MSSM) were searched for in the data collected in 1999 by the DELPHI experiment at centre-of-mass energies between 191.6 and 201.7 GeV with a total integrated luminosity of 228 pb(-1). These analyses, in combination with our results at lower energies, set 95% confidence level lower mass bounds on the Standard Model Higgs boson (107.3 GeV/c(2)) and on the lightest neutral scalar (85.9 GeV/c(2)) and neutral pseudoscalar (86.5 GeV/c(2)) Higgs bosons in representative scans of the MSSM parameter space. An extended scan of the MSSM parameter space was also performed to test the robustness of these limits.
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| 6. |
- Abreu, P, et al.
(author)
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b-tagging in DELPHI at LEP
- 2004
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 32:2, s. 185-208
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Journal article (peer-reviewed)abstract
- The standard method used for tagging b-hadrons in the DELPHI experiment at the CERN LEP Collider is discussed in detail. The main ingredient of b-tagging is the impact parameters of tracks, which relies mostly on the vertex detector. Additional information, such as the mass of particles associated to a secondary vertex, significantly improves the selection efficiency and the background suppression. The paper describes various discriminating variables used for the tagging and the procedure of their combination. In addition, applications of b-tagging to some physics analyses, which depend crucially on the performance and reliability of b-tagging, are described briefly.
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| 7. |
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| 8. |
- Eriksson, D, et al.
(author)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Journal article (peer-reviewed)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 9. |
- Fazey, Ioan, et al.
(author)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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In: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Journal article (peer-reviewed)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 10. |
- Hammar, Linus, et al.
(author)
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Studier på småfisk vid Lillgrund vindpark : Effektstudier under konstruktionsarbeten och anläggning av gravitationsfundament
- 2008
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Reports (other academic/artistic)abstract
- En betydande aspekt beträffande miljöpåverkan från havsbaserad vindkraft är potentiell störning av fisk under konstruktionsarbetet. För att förankra vindkraftverken i sjöbotten kan olika fundament användas. Många fundamentmodeller kräver pålningsarbeten och för dessa är det känt att fisk kan störas betydande över stora avstånd på grund av de höga ljudnivåer som uppstår vid anläggningsarbetet. En annan vanlig fundamentmodell är gravitationsfundament, där inget pålningsarbete behövs men däremot muddring och stenläggning. Till skillnad mot pålningsarbeten är det sedan tidigare inte känt huruvida gravitationsfundamentens muddring och stenläggning medför någon betydande påverkan på fisk i dess omgivning. Som en delstudie till den parallella Vindval-publikationen Miljömässig optimering av fundament för havsbaserad vindkraft har provtagningar av fiskförekomst utförts under anläggningen av gravitationsfundament vid Lillgrund vindpark. Provtagningarna, som utfördes med liten trål, omfattade endast småfisk – definierat som juvenil (ung) fisk samt småväxta fiskarter. Småfisk förväntas emellertid vara särskilt känslig mot den sedimentspridning som uppstår genom muddringsarbeten. Provtagningarna fördelades mellan tre fallstudier omfattande olika delar av konstruktionsarbetet; 1) långtidseffekter av muddring, 2) korttidseffekter av muddring, samt 3) direkteffekter av stenläggning. Studiens utförande baseras på den statistiska designen BACI (Before/After Control/Impact), där provtagningar utförs före och efter en förväntad påverkan, dels i det påverkade området och dels i ett opåverkat kontrollområde.Eftersom löst kalkrikt sediment i höga halter kan påverka syreupptaget hos småfisk kunde det teoretiskt sett förväntas att muddringsarbetet medfört en lokal reduktion av antal individer eller arter av fisk i närområdet. Resultatet visade dock inte några indikationer på att enskilda mudderverksamheter medfört några negativa trender i förekomsten av småfisk, varken 1 månad (fallstudie 1; närmsta avstånd 60 m) eller 1 dygn (fallstudie 2; närmsta avstånd 150 m) efter utförd muddring. En viktig slutsats är följaktligen att ingen småfisk, varken juveniler eller enskilda arter, uppvisade någon negativ trend 1 dygn efter muddringsverksamhet på ett avstånd av 150 m.Det buller som uppstår under stenläggningen kunde teoretiskt sett förväntas medföra en lokal reduktion av antal individer eller arter av fisk i närområdet. Resultatet under stenläggningen (fallstudie 3) visade för juvenil fisk en signifikant större minskning av antal arter i påverkansområdena (Lillgrund; c:a 60 och 200 m från det pågående anläggningsarbetet) jämfört med det opåverkade kontrollområdet. Beträffande adult (vuxen) småfisk visades att ökningen av antal individer och biomassa var signifikant mindre i påverkansområdena vid det pågående stenläggningsarbetet, jämfört med kontrollområdet. Detta överensstämmer med den multivariata analysen (MDS) där kontrollområdet skiljer sig från de båda påverkansområdena under efter-studien. Beaktansvärt är emellertid att ingen av analyserna antyder några skillnader mellan de två olika avstånden 60 och 200 m från stenläggningsarbetet, vilket pekar på att det enskilda stenläggningsarbetet inte är förklaringen till avvikelserna. Mer sannolikt är att konstruktionsarbetena vid Lillgrund som helhet, alternativt naturliga skillnader mellan Lillgrund och kontrollområdet, bidragit till de funna skillnaderna efter stenläggningen i fallstudie 3. De fiskarter som tydligast visade en större ökning i kontrollområdet är sjustrålig smörbult, storspigg, småspigg samt tångsnälla.
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| 11. |
- Horton, Tammy, et al.
(author)
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Improving nomenclatural consistency: a decade of experience in the World Register of Marine Species
- 2017
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In: European journal of taxonomy. - : Museum National D'Histoire Naturelle. - 2118-9773. ; 389, s. 1-24
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Journal article (peer-reviewed)abstract
- The World Register of Marine species (WoRMS) has been established for a decade. The early history of the database involved compilation of existing global and regional species registers. This aggregation, combined with changes to data types and the changing needs of WoRMS users, has resulted in an evolution of data-entry consistency over time. With the task of aggregating the accepted species names for all marine species approaching completion, our focus has shifted to improving the consistency and quality of data held while keeping pace with the addition of > 2000 new marine species described annually. This paper defines priorities and longer-term aims that promote standardisation within and interoperability among biodiversity databases, provides editors with further information on how to input nomenclatural data in a standardised way and clarifies for users of WoRMS how and why names are represented as they are. We 1) explain the categories of names included; 2) list standard reasons used to explain why a name is considered ‘unaccepted’ or ‘uncertain’; 3) present and explain the more difficult situations encountered; 4) describe categories of sources and notes linked to a taxon; and 5) recommend how type material, type locality and environmental information should be entered.
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| 12. |
- Kjaergaard, M., et al.
(author)
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Demonstration of Density Matrix Exponentiation Using a Superconducting Quantum Processor
- 2022
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In: Physical Review X. - 2160-3308. ; 12:1
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Journal article (peer-reviewed)abstract
- Quantum computers hold the potential to outperform classical supercomputers at certain tasks. To implement algorithms on a quantum computer, programmers use conventional computers and hardware to create a set of classical control signals that implement a desired quantum algorithm. However, feeding the quantum information forward requires an inefficient conversion: extraction of quantum information, conversion to classical control signals, and reinjection of those signals into the system to implement quantum operations. Here, we demonstrate a more natively quantum strategy to programming quantum computers. Our approach uses the density matrix exponentiation (DME) protocol, a general technique for using a quantum state to enact a quantum operation. It can be thought of as a subroutine with which programmers can turn multiple copies of a quantum state into instructions for next steps in a quantum algorithm.We implement DME using two qubits in a superconducting quantum processor. Our implementation relies on a high-fidelity two-qubit gate and a novel technique called quantum measurement emulation to approximately reset a known quantum state. These developments enable us to demonstrate the DME protocol for the first time on a small-scale quantum processor and benchmark its performance.While DME was originally proposed in the context of a specific quantum machine-learning algorithm, it may also represent a fundamentally different approach to quantum programming. It allows the possibility of encoding quantum algorithms directly into quantum states and executing those algorithms on other quantum states, enabling a new class of efficient quantum algorithms.
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| 13. |
- Langeveld, Egbert, et al.
(author)
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Att tolka derivator med hjälp av enheter
- 2023
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In: Nämnaren. - 0348-2723. ; 49:2, s. 47-53
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Journal article (pop. science, debate, etc.)abstract
- Författarna har i ett ULF-projekt om proportionalitet i matematiken vid Malmö universitet utformat ett arbetsmaterial för elever som läser gymnasiets kurser Matematik 3b och 3c. Elever som kan derivera mekaniskt kan genom att undersöka aktuella enheter - enhetsanalys/dimensionsanalys - få bättre förståelse för hur de ska tolka derivator i ett sammanhang.
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| 14. |
- Petersson, Jöran, et al.
(author)
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Teaching dimensional analysis in secondary school mathematics
- 2021
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In: Abstract book nofa8. - : Western Norway University of Applied Sciences.
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Conference paper (other academic/artistic)abstract
- AbstractIn its elementary form, the idea of dimensional analysis is to look at the unit of a magnitude, for example speed, and conclude that speed measured in m/s is a quotient having meters in the numerator and seconds in the denominator. However, despite dimensional analysis being a not un-common theme for research in mathematics education at tertiary level teaching, it seems in practice absent below that level. This is surprising since dimensional analysis is useful in mathematical problem solving involving proportionality. Even more so since, from halves and doubles in preschool to scalar multiplication in upper secondary school, proportionality permeates school mathematics and is well-researched (Lamon, 2007). Hence, the authors initiated a research project on how to teach dimensional analysis in school years 6-12. The novelty of this area made us choose didactical engineering (Artigue, 2015) as a theoretical framework suitable for developing the teaching of dimensional analysis. Accordingly, in a cycle of a priori and a posteriori analyses, the authors are developing an empirically based teaching model for dimensional analysis including the topic of constructing exercises for students. We present results from this on-going development project. ReferencesArtigue, M. (2015). Perspectives on Design Research: The Case of Didactical Engineering. In A. Bikner-Ahsbahs, C. Knipping, N. Presmeg. (Eds.). Approaches to Qualitative Research in Mathematics Education. Dordrecht: Springer.Lamon, S. J. (2007). Rational numbers and proportional reasoning: Towards a theoretical framework. In F.K. Lester (red) Second handbook of research on mathematics teaching and learning, vol 2 (pp. 629–668). Charlotte, NC: NCTM.
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| 15. |
- Rosenberg, Guillermo Sanchez, et al.
(author)
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ChatGPT-4 generates orthopedic discharge documents faster than humans maintaining comparable quality : a pilot study of 6 cases
- 2024
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In: Acta Orthopaedica. - : Medical Journals Sweden. - 1745-3674 .- 1745-3682. ; 95, s. 152-156
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Journal article (peer-reviewed)abstract
- Background and purpose - Large language models like ChatGPT-4 have emerged. They hold the potential to reduce the administrative burden by generating everyday clinical documents, thus allowing the physician to spend more time with the patient. We aimed to assess both the quality and efficiency of discharge documents generated by ChatGPT-4 in comparison with those produced by physicians.Patients and methods - To emulate real -world situations, the health records of 6 fictional orthopedic cases were created. Discharge documents for each case were generated by a junior attending orthopedic surgeon and an advanced orthopedic resident. ChatGPT-4 was then prompted to generate the discharge documents using the same health record information. The quality assessment was performed by an expert panel (n = 15) blinded to the source of the documents. As secondary outcome, the time required to generate the documents was compared, logging the duration of the creation of the discharge documents by the physician and by ChatGPT-4.Results - Overall, both ChatGPT-4 and physiciangenerated notes were comparable in quality. Notably, ChatGPT-4 generated discharge documents 10 times faster than the traditional method. 4 events of hallucinations were found in the ChatGPT-4-generated content, compared with 6 events in the human/physician produced notes.Conclusion - ChatGPT-4 creates orthopedic discharge notes faster than physicians, with comparable quality. This shows it has great potential for making these documents more efficient in orthopedic care. ChatGPT-4 has the potential to significantly reduce the administrative burden on healthcare professionals.
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| 16. |
- Sandling, Johanna K., et al.
(author)
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Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing
- 2021
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80:1, s. 109-117
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Journal article (peer-reviewed)abstract
- Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE. Methods: We undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS). Results: We identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes. Conclusions: Our results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.
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| 17. |
- Sehouli, Jalid, et al.
(author)
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Catumaxomab with and without prednisolone premedication for the treatment of malignant ascites due to epithelial cancer: results of the randomised phase IIIb CASIMAS study
- 2014
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In: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 31:8, s. 76-
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Journal article (peer-reviewed)abstract
- This two-arm, randomised, multicentre, open-label, phase IIIb study investigated the safety and efficacy of a 3-h catumaxomab infusion with/without prednisolone premedication to reduce catumaxomab-related adverse events. Patients with malignant ascites due to epithelial cancer received four 3-h intraperitoneal catumaxomab infusions with/without intravenous prednisolone (25 mg) premedication before each infusion. The primary safety endpoint was a composite safety score calculated from the incidence and intensity of the most frequent catumaxomab-related adverse events (pyrexia, nausea, vomiting and abdominal pain). Puncture-free survival (PuFS) was a co-primary endpoint. Time to next puncture (TTPu) and overall survival (OS) were secondary endpoints. Prednisolone premedication did not result in a significant reduction in the main catumaxomab-related adverse events. The mean composite safety score was comparable in both arms (catumaxomab plus prednisolone, 4.1; catumaxomab, 3.8; p = 0.383). Median PuFS (30 vs. 37 days) and TTPu (78 vs. 102 days) were shorter in the catumaxomab plus prednisolone arm than in the catumaxomab arm, but the differences were not statistically significant (p = 0.402 and 0.599, respectively). Median OS was longer in the catumaxomab plus prednisolone arm than in the catumaxomab arm (124 vs. 86 days), but the difference was not statistically significant (p = 0.186). The superiority of catumaxomab plus prednisolone versus catumaxomab alone could not be proven for the primary endpoint. Prednisolone did not result in a significant reduction in the main catumaxomab-related adverse events. The study confirms the safety and efficacy of catumaxomab administered as four 3-h intraperitoneal infusions for the treatment of malignant ascites.
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| 18. |
- Solaki, Maria, et al.
(author)
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Comprehensive variant spectrum of the CNGA3 gene in patients affected by achromatopsia
- 2022
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In: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:7, s. 832-858
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Journal article (peer-reviewed)abstract
- Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by impaired color discrimination, low visual acuity, photosensitivity, and nystagmus. To date, six genes have been associated with ACHM (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6), the majority of these being implicated in the cone phototransduction cascade. CNGA3 encodes the CNGA3 subunit of the cyclic nucleotide-gated ion channel in cone photoreceptors and is one of the major disease-associated genes for ACHM. Herein, we provide a comprehensive overview of the CNGA3 variant spectrum in a cohort of 1060 genetically confirmed ACHM patients, 385 (36.3%) of these carrying “likely disease-causing” variants in CNGA3. Compiling our own genetic data with those reported in the literature and in public databases, we further extend the CNGA3 variant spectrum to a total of 316 variants, 244 of which we interpreted as “likely disease-causing” according to ACMG/AMP criteria. We report 48 novel “likely disease-causing” variants, 24 of which are missense substitutions underlining the predominant role of this mutation class in the CNGA3 variant spectrum. In addition, we provide extensive in silico analyses and summarize reported functional data of previously analyzed missense, nonsense and splicing variants to further advance the pathogenicity assessment of the identified variants.
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| 19. |
- Stevens, Kristen N, et al.
(author)
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19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
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Journal article (peer-reviewed)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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| 20. |
- Tibbelin, Julius, et al.
(author)
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1,4-Disilacyclohexa-2,5-diene : a molecular building block that allows for remarkably strong neutral cyclic cross-hyperconjugation
- 2014
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In: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520. ; 5:1, s. 360-371
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Journal article (peer-reviewed)abstract
- 2,3,5,6-Tetraethyl-1,4-disilacyclohexa-2,5-dienes with either four chloro (1a), methyl (1b), or trimethylsilyl (TMS) (1c) substituents at the two silicon atoms were examined in an effort to design rigid compounds with strong neutral cross-hyperconjugation between pi- and sigma-bonded molecular segments arranged into a cycle. Remarkable variations in the lowest electronic excitation energies, lowest ionization energies, and the first oxidation potentials were observed upon change of substituents, as determined by gas phase ultraviolet (UV) absorption spectroscopy, ultraviolet photoelectron spectroscopy (UPS), and cyclic voltammetry. A particularly strong neutral cyclic cross-hyperconjugation was observed in 1c. Its lowest electron binding energy (7.1 eV) is distinctly different from that of 1b (8.5 eV). Molecular orbital analysis reveals a stronger interaction between filled pi(C=C) and pi(SiR2) group orbitals in 1c than in 1a and 1b. The energy shift in the highest occupied molecular orbital is also reflected in the first oxidation potentials as observed in the cyclic voltammograms of the respective compounds (1.47, 0.88, and 0.46 V for 1a, 1b and 1c, respectively). Furthermore, 1,4-disilacyclohexadiene 1c absorbs strongly at 273 nm (4.55 eV), whereas 1a and 1b have no symmetry allowed excitations above 215 nm (below 5.77 eV). Thus, suitably substituted 1,4-disilacyclohexa-2,5-dienes could represent novel building blocks for the design of larger cross-hyperconjugated molecules as alternatives to traditional purely cross-p-conjugated analogues, and could allow for design of molecules with properties that are not accessible to those that are exclusively pi-conjugated.
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| 21. |
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| 22. |
- Willeit, Peter, et al.
(author)
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Natriuretic peptides and integrated risk assessment for cardiovascular disease : an individual-participant-data meta-analysis
- 2016
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In: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 4:10, s. 840-849
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Journal article (peer-reviewed)abstract
- Background: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. Methods: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7.5%, and >= 7.5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. Findings: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1.76 (95% CI 1.56-1.98) for the combination of coronary heart disease and stroke and 2.00 (1.77-2.26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0.012 (0.010-0.014) and a net reclassification improvement of 0.027 (0.019-0.036) for the combination of coronary heart disease and stroke and a C-index increase of 0.019 (0.016-0.022) and a net reclassification improvement of 0.028 (0.019-0.038) for the combination of coronary heart disease, stroke, and heart failure. Interpretation: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.
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