| 1. |
- Suzuki, Chikako, et al.
(author)
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Impact of the first tumor response at eight weeks on overall survival in metastatic breast cancer patients treated with first-line combination chemotherapy
- 2013
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In: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 30:1
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Journal article (peer-reviewed)abstract
- The aim of this was to determine whether the change of size observed at the first response evaluation after initiation of first-line combination chemotherapy correlates with overall survival (OS) in patients with metastatic breast cancer (MBC). The change in size of tumors derived from measurements according to Response Evaluation Criteria In Solid Tumors (RECIST) at the first evaluation on computed tomography (CT) was obtained from a multicenter, randomized phase III trial ("TEX trial," n = 287) comparing treatment with a combination of epirubicin and paclitaxel alone or with capecitabine (TEX). Cox regression and Kaplan-Meier analyses were performed to evaluate the correlations between the first change in tumor size, response according to RECIST and OS. Data from CT evaluations of 233 patients were available. Appearance of new lesions or progression of non-target lesions (new/non-target) indicated short OS by univariable regression analysis (HR 3.76, 95 % CI 1.90-7.42, p andlt; 0.001). A decrease by andgt;30 % at this early time point was prognostic favorable (HR 0.69, 95 % CI 0.49-0.98, p = 0.04) and not significantly less than the best overall response according to RECIST. After adjustment for previous adjuvant treatment and the treatment given within the frame of the randomized trial, OS was still significantly shorter in patients with new/non-target lesions after a median 8 weeks of treatment (HR 4.41, 95 % CI 2.74-7.11, p andlt; 0.001). Disease progression at the first evaluation correlates with OS in patients with MBC treated with first-line combination chemotherapy. The main reason for early disease progression was the appearance of new lesions or progression of non-target lesions. These patients had poor OS even though more lines of treatment were available. Thus, these factors should be focused on in the response evaluations besides tumor size changes.
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| 2. |
- Alajbeg, Ivan, et al.
(author)
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Intraoralelectrostimulator for xerostomia relief : along-term, multicenter, open-label, uncontrolled, clinical trial
- 2012
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In: Oral surgery, oral medicine, oral pathology and oral radiology. - : Elsevier. - 2212-4403 .- 2212-4411. ; 113:6, s. 773-781
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Journal article (peer-reviewed)abstract
- OBJECTIVE: A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. STUDY DESIGN: The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. RESULTS: Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the secondary outcomes resting whole salivary flow rate, xerostomia frequency, oral discomfort, and difficulties in speech, swallowing, and sleeping. No significant side effects were detected. CONCLUSIONS: The beneficial effects of a removable intraoral electrostimulating device were sustained for an 11-month period.
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| 3. |
- Alestig, Erik, 1973, et al.
(author)
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Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection
- 2011
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In: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 11
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Journal article (peer-reviewed)abstract
- Background: Patients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients. Methods: The core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor. Results: No association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860. Conclusions: The results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.
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| 4. |
- Andaloussi, Mounir, et al.
(author)
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Design, Synthesis, and X-ray Crystallographic Studies of alpha-Aryl Substituted Fosmidomycin Analogues as Inhibitors of Mycobacterium tuberculosis 1-Deoxy-D-xylulose 5-Phosphate Reductoisomerase
- 2011
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54:14, s. 4964-4976
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Journal article (peer-reviewed)abstract
- The natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR), but it lacks antibacterial activity probably because of poor uptake. alpha-Aryl substituted fosmidomycin analogues have more favorable physicochemical properties and are also more active in inhibiting malaria parasite growth. We have solved crystal structures of MtDXR in complex with 3,4-dichlorophenyl substituted fosmidomycin analogues; these show important differences compared to our previously described forsmidomycin-DXR complex. Our best inhibitor has an IC(50) = 0.15 mu M on MtDXR but still lacked activity in a mycobacterial growth assay (MIC > 32 mu g/mL). The combined results, however, provide insights into how DXR accommodates the new inhibitors and serve as an excellent starting point for the design of other novel and more potent inhibitors, particularly against pathogens where uptake is less of a problem, such as the malaria parasite.
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| 5. |
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| 6. |
- Andersson, Axel G, et al.
(author)
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High Exposure to Perfluoroalkyl Substances and Antibody Responses to SARS-CoV-2 mRNA Vaccine-an Observational Study in Adults from Ronneby, Sweden.
- 2023
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In: Environmental health perspectives. - 1552-9924. ; 131:8
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Journal article (peer-reviewed)abstract
- Per- and polyfluoroalkyl substances (PFAS) are widely used, environmentally ubiquitous, and stable chemicals that have been associated with lower vaccine-induced antibody responses in children; however, data on adults are limited. The drinking water from one of the two waterworks in Ronneby, Sweden, was heavily contaminated for decades with PFAS from firefighting foams, primarily perfluorohexane sulfonic acid and perfluorooctanesulfonic acid (PFOS). Vaccination against SARS-CoV-2 offered a unique opportunity to investigate antibody responses to primary vaccination in adults who had been exposed to PFAS.Our objective was to evaluate associations between PFAS, across a wide range of exposure levels, and antibody responses in adults 5 wk and 6 months after a two-dose vaccination regime against SARS-CoV-2.Adults age 20-60 y from Ronneby (n=309, median PFOS serum level 47ng/mL, fifth to 95th percentile 4-213ng/mL) and a group with background exposure (n=47, median PFOS serum level 4ng/mL) received two doses of the Spikevax (Moderna) mRNA vaccine. The levels of seven PFAS were measured in serum before vaccination. Serum immunoglobulin G antibodies against the SARS-CoV-2 spike antigen (S-Abs) were measured before vaccination and at 5 wk (n=350) and 6 months (n=329) after the second vaccine dose. Linear regression analyses were fitted against current, historical, and prenatal exposure to PFAS, adjusting for sex, age, and smoking, excluding individuals with previous SARS-CoV-2-infection.PFAS exposure, regardless of how it was estimated, was not negatively associated with antibody levels 5 wk [current PFOS: -0.5% S-Abs/PFOS interquartile range (IQR); 95% confidence interval (CI): -8, 7] or 6 months (current PFOS: 3% S-Abs/PFOS IQR; 95% CI: -6, 12) after COVID-19 vaccination.Following a strict study protocol, rigorous study design, and few dropouts, we found no indication that PFAS exposure negatively affected antibody responses to COVID-19 mRNA vaccination for up to 6 months after vaccination. https://doi.org/10.1289/EHP11847.
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| 7. |
- Andersson, Kent, 1967-, et al.
(author)
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Introduktion till Operationsanalys : En antologi med essäer av studerande i militärteknik 2011
- 2012
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Other publication (other academic/artistic)abstract
- I ämnesplanen definieras militärteknik som ”den vetenskap som beskriver och förklarar hur tekniken inverkar på militär verksamhet på alla nivåer, strategisk, operativ och taktisk, samt hur officersprofessionen påverkar och påverkas av tekniken.”[1] En militärteknikers uppgift brukar, utgående från definitionen, uttryckas som att beskriva och förklara den militära nyttan med tekniken. För att kunna göra detta behövs verktyg. Och många av dem kommer från den vetenskapliga disciplinen Operationsanalys.Syftet med den här antologin är att introducera studerande i militärteknik på Försvarshögskolan till två av de mest refererade boktitlarna i operationsanalys – Methods for conducting military operational analysis editerad av Andrew G. Loerch och Larry B. Rainey samt Military Operations Research, quantitative decision making av N.K. Jaiswal.Kapitlen utgörs av essäer skrivna av studerande på den högre stabsofficersutbildningen med teknisk inriktning, som examinationsuppgift i en fördjupningskurs. Essäerna är till del referat av kapitel i de två böckerna ovan, men kryddade med exempel satta i svenskt sammanhang och med de studerandes egen värdering av metodernas användbarhet.[1]Försvarshögskolan, Ämnesplan militärteknik, 2007.
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| 8. |
- Annerstedt, Claes, 1953, et al.
(author)
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Research-able through Problem-Based Learning
- 2010
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In: Journal of the Scholarship of Teaching and Learning. - 1527-9316. ; 10:2, s. 107-127
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Journal article (peer-reviewed)abstract
- This research project describes an attempt to move towards a more student centered and participatory approach on learning through problem-based storyboards (themes/scenarios) and a unique opportunity for students to have an academic cross-cultural exchange. The purpose of the study was to analyze students' conceptions of this approach on learning through storyboards, experiential learning and the evolution of assessment methods that reflect and further student capabilities. While student satisfaction with the aims of the course was high and technology facilitated a unique cross-cultural opportunity, the challenges of maintaining reliable technology and matching student expectations proved challenging. Despite critical comments, the overwhelming outcome was positive. (Contains 3 figures and 6 footnotes.)
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| 9. |
- Borne, Kurtis D., et al.
(author)
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Ultrafast electronic relaxation pathways of the molecular photoswitch quadricyclane
- 2024
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In: NATURE CHEMISTRY. - 1755-4330 .- 1755-4349. ; 16, s. 499-505
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Journal article (peer-reviewed)abstract
- The light-induced ultrafast switching between molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Prior work observed signatures of ultrafast molecular dynamics in both isomers upon ultraviolet excitation but could not follow the electronic relaxation all the way back to the ground state experimentally. Here we study the electronic relaxation of quadricyclane after exciting in the ultraviolet (201 nanometres) using time-resolved gas-phase extreme ultraviolet photoelectron spectroscopy combined with non-adiabatic molecular dynamics simulations. We identify two competing pathways by which electronically excited quadricyclane molecules relax to the electronic ground state. The fast pathway (<100 femtoseconds) is distinguished by effective coupling to valence electronic states, while the slow pathway involves initial motions across Rydberg states and takes several hundred femtoseconds. Both pathways facilitate interconversion between the two isomers, albeit on different timescales, and we predict that the branching ratio of norbornadiene/quadricyclane products immediately after returning to the electronic ground state is approximately 3:2.
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| 10. |
- Broström, Anders, et al.
(author)
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Worldwide estimation of restless legs syndrome : a systematic review and meta-analysis of prevalence in the general adult population
- 2023
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In: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 32:3
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Research review (peer-reviewed)abstract
- This systematic review, meta-analysis and meta-regression assessed the prevalence of restless legs syndrome (RLS) in the general adult population. Studies identified in Scopus, PubMed, Web of Science, and PsycInfo between January 2000 and February 2022 were included if they used a case–control or cross-sectional design and reported data regarding the prevalence of RLS. The protocol was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022300709). A total of 97 studies including 483,079 participants from 33 different countries met the eligibility criteria. The Newcastle Ottawa Scale was used to evaluate the methodological quality, and the fill-and-trim method was used to correct probable publication bias, while the jack-knife method was performed to assess small study effect. The corrected overall pooled prevalence of RLS was 3% (95% confidence interval [CI] 1.4%–3.8%). The pooled prevalence of RLS syndrome was affected by methodological quality (no data from non-respondents in the included studies), gender (higher among women), study design (lower prevalence in case–control versus cohort and cross-sectional studies). The figures for corrected pooled prevalence among men, women, alcohol consumers and smokers were 2.8% (95% CI 2%–3.7%); 4.7% (95% CI 3.2%–6.3%); 1.4% (95% CI 0%–4.2%); and 2.7% (95% CI 0%–5.3%), respectively. The prevalence among male and female participants was lower in community-based versus non-community-based studies. Moreover, the prevalence was higher in developed versus developing countries and among elders versus adults. In conclusion, RLS is a common disorder in the general adult population, with a higher prevalence in women; however, prevalence data are affected by study design and quality.
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