| 1. |
- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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| 2. |
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| 3. |
- Barnes, DR, et al.
(författare)
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
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| 4. |
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| 5. |
- Hakkaart, C, et al.
(författare)
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Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
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| 6. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 7. |
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| 8. |
- Murray, Alison E., et al.
(författare)
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Roadmap for naming uncultivated Archaea and Bacteria
- 2020
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
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Tidskriftsartikel (refereegranskat)abstract
- The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
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| 9. |
- Binder, Zev A., et al.
(författare)
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Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development
- 2018
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 34:1, s. 163-177
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Tidskriftsartikel (refereegranskat)abstract
- We explored the clinical and pathological impact of epidermal growth factor receptor (EGFR) extracellular domain missense mutations. Retrospective assessment of 260 de novo glioblastoma patients revealed a significant reduction in overall survival of patients having tumors with EGFR mutations at alanine 289 (EGFR(A289D/T/V)). Quantitative multi-parametric magnetic resonance imaging analyses indicated increased tumor invasion for EGFR(A289D/T/V) mutants, corroborated in mice bearing intracranial tumors expressing EGFR(A289V) and dependent on ERK-mediated expression of matrix metalloproteinase-1. EGFR(A289V) tumor growth was attenuated with an antibody against a cryptic epitope, based on in silico simulation. The findings of this study indicate a highly invasive phenotype associated with the EGFR(A289V) mutation in glioblastoma, postulating EGFR(A289V) as a molecular marker for responsiveness to therapy with EGFR-targeting antibodies.
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| 10. |
- Hentschel, U, et al.
(författare)
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Defense mechanisms: Current approaches to research and measurement
- 2004
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Ingår i: Defense mechanisms: Theoretical, Research, and Clinical Perspectives. - 9780444512635 - 0444512632 ; , s. 3-41
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter highlights the general theme of the book, including definitions of defense mechanisms within various theoretical frames of reference. After a period of exclusion from mainstream clinical psychology the concept of defense has now returned to center stage.
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| 11. |
- Franke, A., et al.
(författare)
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Operationalizing Ocean Health : Toward Integrated Research on Ocean Health and Recovery to Achieve Ocean Sustainability
- 2020
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Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 2:6, s. 557-565
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Tidskriftsartikel (refereegranskat)abstract
- Protecting the ocean has become a major goal of international policy as human activities increasingly endanger the integrity of the ocean ecosystem, often summarized as “ocean health.” By and large, efforts to protect the ocean have failed because, among other things, (1) the underlying socio-ecological pathways have not been properly considered, and (2) the concept of ocean health has been ill defined. Collectively, this prevents an adequate societal response as to how ocean ecosystems and their vital functions for human societies can be protected and restored. We review the confusion surrounding the term “ocean health” and suggest an operational ocean-health framework in line with the concept of strong sustainability. Given the accelerating degeneration of marine ecosystems, the restoration of regional ocean health will be of increasing importance. Our advocated transdisciplinary and multi-actor framework can help to advance the implementation of more active measures to restore ocean health and safeguard human health and well-being.
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| 12. |
- Smith, Gudmund, et al.
(författare)
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Pereptgenetic identification of defense
- 2004
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Ingår i: Defense mechanisms: Theoretical, Research, and Clinical Perspectives. - 0444512632 - 9780444512635 ; , s. 129-147
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The chapter presents the Defence Mechanism Test (DMT), the Meta-Contrast Technique (MCT) and new innovations within the same family of percept-genetic methods.
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| 13. |
- Andersson, Staffan, et al.
(författare)
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Continuous and stepwise cystometry through suprapubic catheters : effect of infusion pattern and infusion rate on the cystometrogram of the normal human bladder
- 1989
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Ingår i: Clinical Physiology. - 0144-5979 .- 1365-2281. ; 9:1, s. 89-96
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Tidskriftsartikel (refereegranskat)abstract
- Continuous cystometry at two filling rates (50 and 100 ml min-1) and stepwise cystometry (successive rapid volume infusions followed by bladder wall relaxation) were performed in 12 healthy subjects. Suprapubic catheters were used for infusion and recording of perivesical and intravesical pressures. The continuous cystometrograms obtained at filling rates of 50 and 100 ml min-1, respectively, did not differ with respect to desire to void, transmural pressure increase or bladder capacity. Stepwise cystometry allowed the bladders to be filled to a slightly larger volume than during continuous cystometry, but with comparatively lower transmural pressures only at very large distension of the bladder. There was considerable inter-individual variation in transmural pressure at both continuous and stepwise cystometry. Stepwise cystometry did not appear to provide any important additional information about pressure-volume relationship in the normal human bladder than could be obtained at routine clinical cystometry
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| 14. |
- Andersson, Staffan, et al.
(författare)
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Wall mechanics of the rat bladder. II. Hydrodynamic studies in the frequency domain
- 1988
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 134:4, s. 463-466
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Tidskriftsartikel (refereegranskat)abstract
- The hydrodynamic properties of the urinary bladder in rat were examined by means of very small periodic changes in volume at different frequencies. The elastance increased with increasing frequency of volume changes, indicating the presence of viscoelastic elements. When the bladder was only moderately distended the influence of viscosity was minor. We consider that the rat bladder examined by this technique is an ideal experimental model for assessment of in vivo effects of pharmacological agents on bladder wall tonus. For example, cholinergic treatment showed a 100% increase in elastance and atropine inhibited this effect completely within 3 min.
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| 15. |
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Defense mechanisms: Theoretical, Research, and Clinical Perspectives
- 2004
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Contains 27 chapters on defense mechanisms with authors from 10 countries, 6 of them from Lund. The coverage is comprehensive including theories of psychological defense, methods to describe defense empirically, studies of defense in various clinical groups, etc. The book can be used, in its entirety or in parts, as a text for students in clinical psychology.
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| 16. |
- Rosenhahn, Erik, et al.
(författare)
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Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications
- 2022
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Ingår i: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 109:8, s. 1421-1435
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Tidskriftsartikel (refereegranskat)abstract
- PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy, and progressive microcephaly. Further common clinical findings included muscular hyper- and hypotonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, ventriculomegaly, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM domain region that is essential for protein-protein interaction. For further insight into the effects of PPFIBP1 loss of function, we performed automated behavioral phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model, which revealed defects in spontaneous and light-induced behavior and confirmed resistance to the acetylcholinesterase inhibitor aldicarb, suggesting a defect in the neuronal presynaptic zone. In conclusion, we establish bi-allelic loss-of-function variants in PPFIBP1 as a cause of an autosomal recessive severe neurodevelopmental disorder with early-onset epilepsy, microcephaly, and periventricular calcifications.
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| 17. |
- Rydén, Olof, et al.
(författare)
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In Defense of Obesity
- 2004
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Ingår i: Defense mechanisms: Theoretical, research, and clinical perspectives (Advances in psychology; 136). - 0166-4115. - 0444512632 ; , s. 557-579
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Previous research suggests that an inclination to eat in response to unlabeled anxiety and a strong dependence on environmental stimuli are more common in overweight individuals than in normal-weight controls. In particular, individuals who habitually use food and eating in order to alleviate painful feelings have to face these feelings when dieting, unless they can be neutralised by psychological defences. In a series of studies we investigated 1) psychological features in obese patients before and after surgical or dietary treatment and, 2) psychological correlates of differential weight loss after treatment. We expected that certain psychological features—immature psychological defence, depression, anxiety and impulsivity/—would be more common among obese than among normal-weight individuals and tend to be linked with treatment failure. Since the obese individual with immature or ineffective defences cannot readily neutralise painful feelings which he/she is liable to experience during food deprivation, s/he is left dependent on somatic or behavioural reac¬tions, or is prone to experience depressive affects as a protection against anxiety. Hence, success or failure after treatment for obesity should be predictable on the basis of the maturity of the individual’s defences
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| 18. |
- Tempelaars, Coen, et al.
(författare)
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Real-time priority processing on the Cell platform
- 2011
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Ingår i: Digest of Technical Papers - IEEE International Conference on Consumer Electronics. - 9781424487127 ; , s. 157-158
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Konferensbidrag (refereegranskat)abstract
- Flexible signal processing on programmable platforms are increasingly important for consumer electronic applications. Scalable video algorithms (SVAs) using the novel principle of priority processing guarantee real-time performance on programmable platforms, even with limited resources. Dynamic resource allocation is required to maximize the overall output quality of independent, competing priority processing algorithms that are executed on a shared platform. In this paper we describe the mapping of a priority processing application on the Cell/B.E. platform. We compare the performance of different implementations for dynamic-resource-allocation mechanisms, and show that priority processing achieves real-time performance.
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| 19. |
- van den Heuvel, Martijn, et al.
(författare)
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Dynamic resource allocation for real-time priority processing applications
- 2010
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Ingår i: IEEE transactions on consumer electronics. - 0098-3063 .- 1558-4127. ; 56:2, s. 879-887
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Tidskriftsartikel (refereegranskat)abstract
- Flexible signal processing on programmable platforms are increasingly important for consumer electronic applications and others. Scalable video algorithms (SVAs) using novel priority processing can guarantee real-time performance on programmable platforms even with limited resources. Dynamic resource allocation is required to maximize the overall output quality of independent, competing priority processing algorithms that are executed on a shared platform. In this paper, we describe basic mechanisms for dynamic resource allocation and compare the performance of different implementations on a general purpose platform.
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| 20. |
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| 21. |
- van Kaam, Anton H., et al.
(författare)
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Modes and strategies for providing conventional mechanical ventilation in neonates
- 2021
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Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447. ; 90:5, s. 957-962
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Forskningsöversikt (refereegranskat)abstract
- Neonatal respiratory failure is a common and serious clinical problem which in a considerable proportion of infants requires invasive mechanical ventilation. The basic goal of mechanical ventilation is to restore lung function while limiting ventilator-induced lung injury, which is considered an important risk factor in the development of bronchopulmonary dysplasia (BPD). Over the last decades, new conventional mechanical ventilation (CMV) modalities have been introduced in clinical practice, aiming to assist clinicians in providing lung protective ventilation strategies. These modalities use more sophisticated techniques to improve patient-ventilator interaction and transfer control of ventilation from the operator to the patient. Knowledge on how these new modalities work and how they interact with lung physiology is essential for optimal and safe use. In this review, we will discuss some important basic lung physiological aspects for applying CMV, the basic principles of the old and new CMV modalities, and the evidence to support their use in daily clinical practice.
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| 22. |
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