| 1. |
- Frederiksen, KS, et al.
(author)
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Corpus callosum tissue loss and development of motor and global cognitive impairment: the LADIS study
- 2011
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In: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 32:4, s. 279-286
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Journal article (peer-reviewed)abstract
- <i>Objective:</i> To examine the impact of corpus callosum (CC) tissue loss on the development of global cognitive and motor impairment in the elderly. <i>Methods:</i> This study was based on the Leukoaraiosis and Disability (LADIS) study. Assessment of cognitive and motor functions and magnetic resonance imaging (MRI) were done at baseline and at a 3-year follow-up in nondemented elderly subjects. <i>Results:</i> 328 of 639 LADIS subjects had MRIs at baseline and at the 3-year follow-up, which allowed for assessment of CC. Logistic regression revealed differential tissue loss rates in posterior CC in subjects converting to dementia, compared to nonconverters (p < 0.05). Anterior and posterior CC tissue loss was significantly correlated with self-perceived memory impairment in nonconverters (p < 0.05). CC tissue loss was also significantly associated with impaired single leg stance time (p < 0.01). <i>Conclusion:</i> The present longitudinal study on CC supports the role of callosal tissue loss in the development of global cognitive as well as motor impairment.
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| 3. |
- Teunissen, C, et al.
(author)
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Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis
- 2013
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:13, s. 1802-1809
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Journal article (peer-reviewed)abstract
- The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use of available resources. This will lead to improved quality of CSF biomarker research in MS and related disorders.
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| 5. |
- Beniczky, Sandor, et al.
(author)
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Source localization of rhythmic ictal EEG activity: A study of diagnostic accuracy following STARD criteria
- 2013
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In: Epilepsia. - : Wiley. - 0013-9580. ; 54:10, s. 1743-1752
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Journal article (peer-reviewed)abstract
- PurposeAlthough precise identification of the seizure-onset zone is an essential element of presurgical evaluation, source localization of ictal electroencephalography (EEG) signals has received little attention. The aim of our study was to estimate the accuracy of source localization of rhythmic ictal EEG activity using a distributed source model. MethodsSource localization of rhythmic ictal scalp EEG activity was performed in 42 consecutive cases fulfilling inclusion criteria. The study was designed according to recommendations for studies on diagnostic accuracy (STARD). The initial ictal EEG signals were selected using a standardized method, based on frequency analysis and voltage distribution of the ictal activity. A distributed source modellocal autoregressive average (LAURA)was used for the source localization. Sensitivity, specificity, and measurement of agreement (kappa) were determined based on the reference standardthe consensus conclusion of the multidisciplinary epilepsy surgery team. Predictive values were calculated from the surgical outcome of the operated patients. To estimate the clinical value of the ictal source analysis, we compared the likelihood ratios of concordant and discordant results. Source localization was performed blinded to the clinical data, and before the surgical decision. Key FindingsReference standard was available for 33 patients. The ictal source localization had a sensitivity of 70% and a specificity of 76%. The mean measurement of agreement (kappa) was 0.61, corresponding to substantial agreement (95% confidence interval (CI) 0.38-0.84). Twenty patients underwent resective surgery. The positive predictive value (PPV) for seizure freedom was 92% and the negative predictive value (NPV) was 43%. The likelihood ratio was nine times higher for the concordant results, as compared with the discordant ones. SignificanceSource localization of rhythmic ictal activity using a distributed source model (LAURA) for the ictal EEG signals selected with a standardized method is feasible in clinical practice and has a good diagnostic accuracy. Our findings encourage clinical neurophysiologists assessing ictal EEGs to include this method in their armamentarium.
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| 6. |
- Frederiksen, C., et al.
(author)
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Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer
- 2011
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 22:2, s. 369-375
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Journal article (peer-reviewed)abstract
- Background: The aim was to evaluate the association between plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) and serum carcinoembryonic antigen (CEA) levels and outcome in patients with metastatic colorectal cancer (mCRC) receiving XELOX (combination chemotherapy with capecitabine and oxaliplatin) as first-line treatment. Patients and methods: One hundred and twenty patients were included. Blood samples were collected before treatment and 3 weeks later before the next treatment cycle. Plasma TIMP-1 and serum CEA levels were correlated to treatment outcome. Results: No significant associations between baseline TIMP-1 or CEA levels and best response to treatment or progression-free survival (PFS) could be demonstrated. In contrast, high baseline plasma TIMP-1 levels were associated with poor overall survival (OS), P = 0.008, hazard ratio (HR) = 1.80 [95% confidence interval (CI): 1.17-2.78]. Furthermore, increase in TIMP-1 levels from baseline to immediately before the second cycle of chemotherapy had a significant negative effect on survival (P = 0.03, HR = 1.30, 95% CI: 1.02-1.65) while a decrease in TIMP-1 was significantly associated with a higher objective response rate (P = 0.03). Conclusions: Both high baseline and subsequent increase in TIMP-1 levels were associated with shorter OS in patients with mCRC receiving XELOX as first-line treatment, whereas baseline TIMP-1 levels were not associated with response or PFS following XELOX treatment.
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| 7. |
- Frederiksen, T., et al.
(author)
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Theory of action spectroscopy for single-molecule reactions induced by vibrational excitations with STM
- 2014
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 89:3, s. 035427-
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Journal article (peer-reviewed)abstract
- A theory of action spectroscopy, i.e., a reaction rate or yield as a function of bias voltage, is presented for single-molecule reactions induced by the inelastic tunneling current with a scanning tunneling microscope. A formula for the reaction yield is derived using the adsorbate resonance model, which provides a versatile tool to analyze vibrationally mediated reactions of single adsorbates on conductive surfaces. This allows us to determine the energy quantum of the excited vibrational mode, the effective broadening of the vibrational density of states (as described by Gaussian or Lorentzian functions), and a prefactor characterizing the elementary process behind the reaction. The underlying approximations are critically discussed. We point out that observation of reaction yields at both bias voltage polarities can provide additional insight into the adsorbate density of states near the Fermi level. As an example, we apply the theory to the case of flip motion of a hydroxyl dimer (OD)(2) on Cu(110) which was experimentally observed by Kumagai et al. [Phys. Rev. B 79, 035423 (2009)]. In combination with density functional theory calculations for the vibrational modes, the vibrational damping due to electron-hole pair generation, and the potential energy landscape for the flip motion, a detailed microscopic picture for the switching process is established. This picture reveals that the predominant mechanism is excitation of the OD stretch modes which couple anharmonically to the low-energy frustrated rotation mode.
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| 8. |
- Kolstad, Arne, et al.
(author)
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Nordic MCL-3 study : 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma
- 2014
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 123:19, s. 2953-2959
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Journal article (peer-reviewed)abstract
- The main objective of the MCL3 study was to improve outcome for patients not in CR before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. 160 consecutive, untreated stage II-IV MCL patients < 66 years received rituximab (R)- maxi-CHOP alternating with R-high-dose Ara-C (6 cycles total), followed by high-dose BEAM or BEAC and autologous stem cell transplantation 2005-2009. Zevalin (0.4 mCi/kg) was given to responders in only CRu/PR prior to high-dose therapy. The overall response rate (ORR) pre-transplant was 97%. After a median follow-up of 4.4 years the outcome did not differ from that of the historic control, the MCL2 trial with the same treatment except for Zevalin. Overall (OS), event free (EFS), and progression-free survival (PFS) at 4 years were 78, 62 and 71%, respectively. For patients in CRu/PR before transplant who received Zevalin duration of response was shorter than in the CR group. Inferior PFS, EFS- and OS were predicted by PET-positivity pre-transplant and detectable minimal residual disease (MRD) before and after transplant. In conclusion, a positive PET prior to transplant and MRD are strong predictors of outcome. Late intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant.
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| 9. |
- Lapenta, Giovanni, et al.
(author)
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SWIFF : Space weather integrated forecasting framework
- 2013
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In: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 3, s. A05-
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Journal article (peer-reviewed)abstract
- SWIFF is a project funded by the Seventh Framework Programme of the European Commission to study the mathematical-physics models that form the basis for space weather forecasting. The phenomena of space weather span a tremendous scale of densities and temperature with scales ranging 10 orders of magnitude in space and time. Additionally even in local regions there are concurrent processes developing at the electron, ion and global scales strongly interacting with each other. The fundamental challenge in modelling space weather is the need to address multiple physics and multiple scales. Here we present our approach to take existing expertise in fluid and kinetic models to produce an integrated mathematical approach and software infrastructure that allows fluid and kinetic processes to be modelled together. SWIFF aims also at using this new infrastructure to model specific coupled processes at the Solar Corona, in the interplanetary space and in the interaction at the Earth magnetosphere.
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| 10. |
- Ziemssen, Tjalf, et al.
(author)
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A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial
- 2014
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In: Journal of Neurology. - : Springer Verlag (Germany). - 0340-5354 .- 1432-1459. ; 261:11, s. 2101-2111
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Journal article (peer-reviewed)abstract
- Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p less than 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p less than 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.
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