| 1. |
- Fall, Tove, et al.
(författare)
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The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
- 2013
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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| 2. |
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| 3. |
- Elfineh, Lioudmila, et al.
(författare)
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Tyrosine phosphorylation profiling via in situ proximity ligation assay
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 14, s. 435-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tyrosine phosphorylation (pTyr) is an important cancer relevant posttranslational modification since it regulates protein activity and cellular localization. By controlling cell growth and differentiation it plays an important role in tumor development. This paper describes a novel approach for detection and visualization of a panel of pTyr proteins in tumors using in situ proximity ligation assay. Methods: K562 leukemia cells were treated with tyrosine kinase and/or phosphatase inhibitors to induce differences in pTyr levels and mimic cells with different malignant properties. Cells were then probed with one antibody against the pTyr modification and another probe against the detected protein, resulting in a detectable fluorescent signal once the probes were in proximity. Results: Total and protein specific pTyr levels on ABL, SHC, ERK2 and PI3K proteins were detected and samples of control and treated cells were distinguished at the pTyr level using this novel approach. Promising results were also detected for formalin fixed and paraffin embedded cells in the micro array format. Conclusions: This application of in situ proximity ligation assay is valuable in order to study the pTyr modification of a panel of proteins in large data sets to validate mass spectrometric data and to be combined with tissue microarrays. The approach offers new opportunities to reveal the pTyr signatures in cells of different malignant properties that can be used as biomarker of disease in the future.
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| 4. |
- Erhag, Thomas, 1970, et al.
(författare)
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Retroaktivitet i social trygghetsreglering
- 2013
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Ingår i: I Ketscher, K. Lilleholt, K. Smith, E & Syse, A (Red) Velferd og rettferd, Festskrift til Asbjörn Kjönstad 70 år. - Oslo : Gyldendal. - 9788205424432 ; , s. 139-153
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Eriksson, Anna, et al.
(författare)
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On-target titanium dioxide-based enrichment for characterization of phosphorylations in the Adenovirus pIIIa protein
- 2013
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1317:SI, s. 105-109
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Tidskriftsartikel (refereegranskat)abstract
- A recently developed titanium dioxide (TiO2) based on-target method for phosphopeptide enrichment and matrix assisted laser desorption-ionization mass spectrometry (MALDI MS) analysis was used to investigate phosphorylations in the Adenovirus type 2 structural protein pIIIa. Lysates of purified virus particles were separated on 1-D SDS-PAGE and the band for the pIIIa protein was excised for tryptic digestion into peptides that were enriched with the on-target method. The enrichment provided by the method clearly improved the detectability of phosphorylated peptides and the results show for the first time evidence for multi-phosphorylated peptides in pIIIa. Moreover, three novel phosphorylations were identified in the protein sequence, even though the precise positions could not be determined. These results illustrate the potential of the method for the characterization of novel phosphoproteomes in biological samples of medical relevance.
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| 6. |
- Gholami, Ali, et al.
(författare)
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Privacy Threat Modeling for Emerging BiobankClouds
- 2014
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Ingår i: Procedia Computer Science. - : Elsevier. ; 37, s. 489-496
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Konferensbidrag (refereegranskat)abstract
- There is an increased amount of data produced by next generation sequencing (NGS) machines which demand scalable storage and analysis of genomic data. In order to cope with this huge amount of information, many biobanks are interested in cloud computing capabilities such as on-demand elasticity of computing power and storage capacity. There are several security and privacy requirements mandated by personal data protection legislation which hinder biobanks from migrating big data generated by the NGS machines. This paper describes the privacy requirements of platform-as-service BiobankClouds according to the European Data Protection Directive (DPD). It identifies several key privacy threats which leave BiobankClouds vulnerable to an attack. This study benefits health-care application designers in the requirement elicitation cycle when building privacy-preserving BiobankCloud platforms.
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| 7. |
- Hemdan, Tammer, et al.
(författare)
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The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer
- 2014
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 111:6, s. 1180-1187
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Tidskriftsartikel (refereegranskat)abstract
- Background:The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target.Methods:Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA.Results:In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA.Conclusions:STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.
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| 8. |
- Kindström Dahlin, Moa, 1980-
(författare)
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Psykiatrirätt : Intressen, rättigheter och principer
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mentally-ill individuals today are seen as having the same right to self-determination as others. Despite this, involuntary psychiatric care is accepted with reference to the patient's own best interests and to a certain extent, the need for societal protection. The legal regulations with respect to involuntary mental health care lack comparable regulations with respect to physical care. This special treatment is motivated against the background of the ideas as to decision-making abilities of mentally-ill individuals as well as the risks for committing serious crimes.This doctoral dissertation provides a critical overview of Swedish mental health law from a rights perspective, with a focus both on The instrument of government (regeringsformen) as well as the European Convention on Human Rights (Europakonventionen). The overarching issue is how the legal system addresses those conflicts of interests arising with involuntary psychiatric care as between autonomy, care and societal protection. This ultimately concerns clarifying the patient’s legal status as having the ability to make decisions within psychiatric care.This doctoral dissertation highlights and problematizes the – partially diffuse – assumptions upon which the law rests. The overarching conclusion is that a strong stance needs to be taken by the legislator in order to clarify the fundamental principles underlying mental health law. Taking into consideration that this is a particularly vulnerable target group, and that this concerns extremely invasive measures, high requirements ought to be imposed on the legal regulations with respect to legality, objectivity, and proportionality.
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| 9. |
- Lind, Anna-Sara, 1977-, et al.
(författare)
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A New Proportionality Test for Fundamental Rights? : The Joined Cases C-92/09 and C-93/09 Volker und Markus Schecke GbR (C-92/09) and Hartmut Eifert (C-93/09) v. Land Hessen
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In the joined cases C-92/09 and C-93/09 Volker und Markus Schecke GbR (C-92/09) and Hartmut Eifert (C-93/09) v. Land Hessen Judgment of 9 November 2010, not yet published, the Court of Justice of the European Union (Court of Justice) was called upon to balance the right to respect of private life in general, and to the protection of personal data in particular, protected by Articles 7 and 8 of the Charter of Fundamental Rights of the European Union (the Charter), against the principle of transparency stated in Articles 1 and 10 of the Treaty on European Union (TEU) and in Article 15 of the Treaty on the Functioning of the European Union (TFEU). The Court of Justice approached this problem within the context of a reference for a preliminary ruling under Article 267 TFEU. This reference, however, took the form of an indirect challenge to certain EU law provisions that, in the view of the applicants, violated the right to respect of private life and of the protection of personal data. In this analysis the method of the Court of Justice when balancing diverging or even opposing interests protected by EU law will be scrutinised. The authors are critical of the Court’s reasoning, which they consider put too little weight on the fundamental interest of transparency in the case at hand. The analysis is structured as follows. First, in section 1, the arguments of the Applicants and the respondent State respectively will be summarised, followed by the main reasoning of the Court. In section 2, the question of how to balance fundamental rights and general interests will be analysed, taking as the point of departure the question of proportionality as described by the Court. The conclusions are presented in the final section 3.
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