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| 2. |
- Nordquist, J, et al.
(författare)
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Case-based learning in surgery: lessons learned
- 2012
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Ingår i: World journal of surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 36:5, s. 945-955
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Stenstedt, K, et al.
(författare)
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CYP2W1 polymorphism: functional aspects and relation to risk for colorectal cancer
- 2013
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Ingår i: Pharmacogenomics. - : Future Medicine Ltd. - 1744-8042 .- 1462-2416. ; 14:13, s. 1615-1622
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study aims to investigate the possible association between the risk of colorectal cancer (CRC) and allelic variants of CYP2W1 and their functional properties. Materials & methods: The distribution of three different CYP2W1 alleles (CYP2W1*1, CYP2W1*2 and CYP2W1*6) in 1785 CRC patients and 1761 healthy blood donors was determined using the TaqMan® (Applied Biosystems, CA, USA) allelic discrimination assay or allele-specific amplification. Corresponding gene products (CYP2W1.1, CYP2W1.2 and CYP2W1.6) were expressed in human colon cancer SW480 cells and their activities towards two different substrates, the duocarmycin analogs ICT2706 and ICT2726, were monitored. Results: No significant differences in the distribution of CYP2W1*1, CYP2W1*2 and CYP2W1*6 alleles were found between CRC patients and controls. The CYP2W1.1, CYP2W1.2 and CYP2W1.6 variant enzymes were expressed at the similar levels in the transfected SW480 cells and had comparable kinetics in terms of the metabolism of the duocarmycin ICT2726, as well as in the bioactivation of ICT2706 into a cytotoxic product. Conclusion: These epidemiological data obtained from a large population of CRC patients and controls cannot confirm the previously suggested decreased risk for CRC among carriers of CYP2W1*2. On the molecular level, this conclusion is further supported by the similar catalytic characteristics of the CYP2W1.1, CYP2W1.2 and CYP2W1.6 variants of CYP2W1. Original submitted 19 March 2013; Revision submitted 15 July 2013
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| 6. |
- Wengström, Yvonne, 1959-, et al.
(författare)
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Symptom management for cancer patients via mobile phones
- 2013
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Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 49, s. S62-S62
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the front line in cancer care is to systematically integratepatient reported outcomes (PRO) in clinical practice. The development ofthis research program is based on The Participatory Care Model, and buildson how patients can be integrated in their care. The aim is to evaluate the effects of an interactive e-health solution for assessment of symptom burden, generating instant self-care advice and instant access to health care professionals.Methods: The hypothesis is that the intervention promotes safe and participatory care and thereby improves clinical management and health care costs. The experimental multicenter studies incorporate a mixedmethod approach. Ongoing studies include patients with pancreatic and prostate cancer using the mobile phone application in comparison to control groups in standard care. Outcomes are collected before and after treatment by questionnaires concerning capacity to understand, communicate health needs and promote healthy behaviors (health literacy), symptom burden and management and quality of life and from records and registers about disease progress and health care costs. Interviews concern participatory and meaningful care. Studies are ongoing for patients with prostate and pancreatic cancer and elderly populations living at home or in care homes.Results: By using technology patients are able to communicate symptoms and receive instant support while cared for on an outpatient basis and at the same time feel reassured that their condition is monitored by health care professionals facilitating safe and participatory care.
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| 9. |
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| 10. |
- Halanych, K. M., et al.
(författare)
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Phylogeography of the horse mussel Modiolus modiolus
- 2013
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Ingår i: Journal of the Marine Biological Association of the United Kingdom. - : Cambridge University Press (CUP). - 0025-3154 .- 1469-7769. ; 93:7, s. 1857-1869
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Tidskriftsartikel (refereegranskat)abstract
- Phylogeographic inferences concerning marine species are largely based on intertidal species. In high latitudes, intertidal species have been affected by ice coverage and ice scour, and therefore show northern range limitations during glaciations. In this study, we use the subtidal horse mussel (Modiolus modiolus) to investigate whether generalizations about genetic structure of high latititude intertidal species, specifically in the North Atlantic, are representative of other near shore taxa. We analysed genetic diversity, molecular variance, and geographical patterns of genetic relatedness using data from the mtDNA CO1 gene. Although we do find little to no haplotype structure in the North Atlantic, our results show that north-eastern Pacific individuals represent a different haplotype network with no haplotypes in common with Atlantic individuals. Thus, M. modiolus in the Pacific may represent an unrecognized species. Genetic diversity and population expansion times suggest a Pacific origin is most likely, with subsequent dispersal to the Atlantic. The lack of genetic structure in the Atlantic suggests that a rapid range expansion occurred less than 50 KYA, rather than a stepping stone mode of dispersal.
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| 11. |
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| 12. |
- Johnsson, A., et al.
(författare)
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A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer : the Nordic ACT Trial
- 2013
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 24:9, s. 2335-2341
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Tidskriftsartikel (refereegranskat)abstract
- Background: The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC). Patients and methods: Patients with untreated mCRC received doublet chemotherapy + bevacizumab during 18 weeks and those without tumor progression were eligible for randomization to bevacizumab + erlotinib (arm A) or bevacizumab alone (arm B), until progression or unacceptable toxic effect. Results: Of the 249 patients enrolled, 80 started maintenance treatment in arm A and 79 in arm B. The rate of any grade 3/4 toxic effect was 53% in arm A and 13% in arm B. Median PFS was 5.7 months in arm A and 4.2 months in arm B (HR = 0.79; 95% confidence interval 0.55-1.12; P = 0.19). Overall survival (OS) from start of induction chemotherapy was 26.7 months in the randomized population, with no difference between the two arms. Conclusions: The addition of erlotinib to bevacizumab as maintenance treatment after first-line chemotherapy in mCRC did not improve PFS significantly. On-going clinical and translational studies focus on identifying subgroups of patients that may benefit from erlotinib in the maintenance setting.
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| 13. |
- Kajihara, H., et al.
(författare)
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Taxonomic Identity of a Tetrodotoxin-Accumulating Ribbon-worm Cephalothrix simula (Nemertea: Palaeonemertea): A Species Artificially Introduced from the Pacific to Europe
- 2013
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Ingår i: Zoological Science. - : Zoological Society of Japan. - 0289-0003. ; 30:11, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- We compared the anatomy of the holotype of the palaeonemertean Cephalothrix simula (Iwata, 1952) with that of the holotypes of Cephalothrix hongkongiensis Sundberg, Gibson and Olsson, 2003 and Cephalothrix fasciculus (Iwata, 1952), as well as additional specimens from Fukue (type locality of C. simula) and Hiroshima, Japan. While there was no major morphological discordance between these specimens, we found discrepancies between the actual morphology and some statements in the original description of C. simula with respect to supposedly species-specific characters. Our observation indicates that these three species cannot be discriminated by the anatomical characters so far used to distinguish congeners. For objectivity of scientific names, topogenetypes of the mitochondrial cytochrome c oxidase subunit I (COI) sequences are designated for C. simula, C. hongkongiensis, and C. fasciculus. Analysis of COI sequence showed that the Hiroshima population can be identified as C. simula, which has been found in previous studies from Trieste, Italy, and also from both the Mediterranean and Atlantic coasts of the Iberian Peninsula, indicating an artificial introduction via (1) ballast water, (2) ship-fouling communities, or (3) the commercially cultured oyster Crassostrea gigas (Thunberg, 1793) brought from Japan to France in 1970s. Cephalothrix simula is known to be toxic, as it contains large amounts of tetrodotoxin (TTX). We report here that the grass puffer Takifugu niphobles (Jordan and Snyder, 1901)-also known to contain TTX-consumes C. simula. We suggest that the puffer may be able to accumulate TTX by eating C. simula.
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| 20. |
- Nimeskern, L., et al.
(författare)
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Mechanical evaluation of bacterial nanocellulose as an implant material for ear cartilage replacement
- 2013
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Ingår i: Journal of the Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161 .- 1878-0180. ; 22, s. 12-21
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial nanocellulose (BNC) is a novel non-degradable biocompatible material that promotes chondrocyte adhesion and proliferation. In this work, its potential use in ear cartilage tissue engineering (TE) is investigated. Firstly, the mechanical properties of native ear cartilage are measured in order to set a preliminary benchmark for ear cartilage replacement materials. Secondly, the capacity of BNC to match these requirements is assessed. Finally, a biofabrication process to produce patient-specific BNC auricular implants is demonstrated.BNC samples (n=78) with varying cellulose content (2.5-15%) were compared using stress-relaxation indentation with human ear cartilage (n=17, from 4 males, aged 49-93 years old). Additionally, an auricle from a volunteer was scanned using a 3T MRI with a spoiled gradient-echo sequence. A negative ear mold was produced from the MRI data in order to investigate if an ear-shaped BNC prototype could be produced from this mold.The results show that the instantaneous modulus E-in, equilibrium modulus E-eq, and maximum stress sigma(max) of the BNC samples are correlated to effective cellulose content. Despite significantly different relaxation kinetics, the E-in, E-eq and sigma(max),, of BNC at 14% effective cellulose content reached values equivalent to ear cartilage (for E-eq, BNC: 2.4+/-0.4 MPa and ear cartilage: 3.3+/-1.3 MPa). Additionally, this work shows that BNC can be fabricated into patient-specific auricular shapes. In conclusion, BNC has the capability to reach mechanical properties of relevance for ear cartilage replacement, and can be produced in patient-specific ear shapes.
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| 21. |
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| 22. |
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| 23. |
- Nystedt, Björn, et al.
(författare)
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The Norway spruce genome sequence and conifer genome evolution
- 2013
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 497:7451, s. 579-584
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Tidskriftsartikel (refereegranskat)abstract
- Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
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| 24. |
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| 25. |
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| 26. |
- Patel, S., et al.
(författare)
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Acoustic markers of emotions based on voice physiology
- 2010
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Ingår i: Proceedings of the International Conference on Speech Prosody. - : International Speech Communications Association. - 9780000000002
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Konferensbidrag (refereegranskat)abstract
- Acoustic models of emotions may benefit from considering the underlying voice production mechanism. This study sought to describe emotional expressions according to physiological variations measured from the inverse-filtered glottal waveform in addition to standard parameter extraction. An acoustic analysis was performed on a subset of the /a/ vowels within the GEMEP database (10 speakers, 5 emotions). of the 12 acoustic features computed, repeated measures ANOVA showed significant main effects for 11 parameters. Subsequent principal components analysis revealed the three components that explain acoustic variations due to emotion, including “tension” (CQ, H1-H2, MFDR, LTAS) “perturbation” (jitter, shimmer, HNR), and “voicing” (fundamental frequency).
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| 27. |
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| 29. |
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| 30. |
- Rodriguez, K., et al.
(författare)
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Electrospun nanofibrous cellulose scaffolds with controlled microarchitecture
- 2014
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 100, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- Introducing porosity in electrospun scaffolds is critical to improve cell penetration and nutrient diffusion for tissue engineering. Nanofibrous cellulose scaffolds were prepared by electrospinning cellulose acetate (CA) followed by saponification to regenerate cellulose. Using a computer-assisted design approach, scaffolds underwent laser ablation resulting in pores with diameters between 50 and 300 mu m. without damaging or modifying the surrounding scaffold area. A new mineralization method was employed in conjunction with microablation using commercial phosphate buffered saline (PBS) to soak carboxymethylcellulose surface-modified electrospun scaffolds. The resulting crystals within the scaffold on the interior of the pore had a calcium to phosphate ratio of 1.56, similar to hydroxyapatite. It was observed that porosity of the cellulose scaffolds enhanced osteoblast cell attachment at the edge of the pores, while mineralization enhanced overall cell density.
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| 35. |
- Sundberg, Johan, et al.
(författare)
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Interdependencies among voice source parameters in emotional speech
- 2011
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Ingår i: IEEE Transactions on Affective Computing. - 1949-3045. ; 2:3, s. 162-174
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Tidskriftsartikel (refereegranskat)abstract
- Emotions have strong effects on the voice production mechanisms and consequently on voice characteristics. The magnitude of these effects, measured using voice source parameters, and the interdependencies among parameters have not been examined. To better understand these relationships, voice characteristics were analyzed in 10 actors' productions of a sustained/a/vowel in five emotions. Twelve acoustic parameters were studied and grouped according to their physiological backgrounds, three related to subglottal pressure, five related to the transglottal airflow waveform derived from inverse filtering the audio signal, and four related to vocal fold vibration. Each emotion appeared to possess a specific combination of acoustic parameters reflecting a specific mixture of physiologic voice control parameters. Features related to subglottal pressure showed strong within-group and between-group correlations, demonstrating the importance of accounting for vocal loudness in voice analyses. Multiple discriminant analysis revealed that a parameter selection that was based, in a principled fashion, on production processes could yield rather satisfactory discrimination outcomes (87.1 percent based on 12 parameters and 78 percent based on three parameters). The results of this study suggest that systems to automatically detect emotions use a hypothesis-driven approach to selecting parameters that directly reflect the physiological parameters underlying voice and speech production.
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| 36. |
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| 37. |
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| 38. |
- Sundberg, K., et al.
(författare)
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Feasibility and acceptability of an interactive mobile phone application for early detection of patient reported symptom distress in prostate cancer
- 2013
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 49, s. S280-S280
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: For immediate and continuous dialogue between patients and caregivers new approaches in modern technology are encouraged today. In cooperation with a Swedish health management company, we developed an interactive mobile phone application for the assessment of symptom distress, evidence-based self-care advice and an alerting function of severe symptoms with instant access to professionals in real time. By using this technique patients can communicate symptoms with instant support while cared for out-side hospital but at the same time reassured that their condition is monitored by the professionals. The objective of this study was to evaluate the feasibility and acceptability of the application for patients with prostate cancer during radiotherapy and for the involved health care staff.Material and Methods: Evidence-based symptoms and related selfcareadvices were implemented in the application after literature review and interviews with patients and health care professionals. Nine patients diagnosed with prostate cancer undergoing radiotherapy treatment were recruited to test the application for two weeks. The patients reported in the electronic symptom questionnaire daily. After the two weeks they were interviewed about their experience. Nurses directly involved in the care and treatment of the participating patients were interviewed at the end of study.Results: Overall, patients and nurses reported positive experiences of using the mobile phone system. The patients considered the application helpful and easy to use although there were some suggestions for further development of the electronic questionnaire. Most of the patients had read the self-care advice and found them useful. The alerting system was activated in several cases; the nurses found it useful to identify and manage problematic symptoms early and the patients felt safe and well cared for. Some of the nurses considered the monitoring system time-consuming and made suggestions for improvement.Conclusions: Both patients and nurses could see the potential for using the mobile application in clinical practice. The system enables the involvement of the patients and the alerts showed problematic symptoms promoting timely interventions. The results support further development and testing of the system in full-scale.
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| 39. |
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| 40. |
- Sundberg, Kay K., et al.
(författare)
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Long-term survivors of childhood cancer report quality of life and health status in parity with a comparison group
- 2010
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 19, s. 78-78
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is a need for more knowledge about how survivors of childhood cancer perceive their lives and what influence current health status has on their quality of life. The purpose was to describe this among a group of long-term survivors and among a comparison group. PROCEDURE: Telephone interviews were performed with a cohort of 246 long-term survivors and 296 randomly selected from the general population using the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW). The participants nominated the areas they considered to be most important in life and rated the current status of each area on a seven-point category scale. An overall individual index score was calculated as a measure of quality of life. Self-reported health status was assessed using the Short Form Health Survey (SF-36). RESULTS: Long-term survivors rated their overall quality of life and self-reported health status almost in parity with the comparison group. In both groups, family life, relations to other people, work and career, interests and leisure activities were the areas most frequently reported to influence quality of life. The survivors only differed from the comparison group on one of eight SF-36 scales reflecting problems with daily activities owing to physical health. CONCLUSIONS: Health status was not shown to have a major impact on overall quality of life, indicating that health and quality of life should be evaluated distinctively as different constructs. This should be taken in consideration in clinical care of children with childhood cancer and long-term survivors.
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| 41. |
- Sundberg, Kay K., et al.
(författare)
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Self-reported quality of life in long-term survivors of childhood lymphoblastic malignancy treated with hematopoietic stem cell transplantation versus conventional therapy
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:8, s. 1382-1387
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic health conditions are known to be both abundant and severe after pediatric hematopoietic stem cell transplantation (SCT). The present objective was to investigate the impact of disease and treatment on individual QoL and health-related quality of life (HRQoL) in long-term survivors of childhood lymphoblastic malignancy treated with conventional therapy versus SCT. Procedure Survivors of lymphoblastic malignancy treated with (n=18) or without (n=52) SCT were recruited a median follow-up time of 18 and 14 years, respectively. The indication for SCT was relapsed disease in 17 of 18 cases. Autologous stem cells were used in 15 cases. Total body irradiation (TBI) was included in the conditioning regimen for all SCT patients. A cross-sectional study was conducted using two validated instruments: SEIQoL-DW (individual QoL) and SF-36 (HRQoL). Content analysis was used to analyze SEIQoL-DW and an overall QoL index score was calculated. Two multiple linear regression analyses were performed to detect factors influencing outcomes. Results Poorer ratings of overall QoL and more negative consequences related to physical dysfunctions were shown in the SCT group. The findings indicate that being unemployed or on sick leave are associated with a decline in HRQoL and individual QoL rather than SCT, cranial radiation therapy, present age, or sex. Conclusion In this small sample of long-term survivors of SCT, QoL seems reasonably good and similar to that of those having received conventional therapy. However, managing an employment must be acknowledged as an important part of life that has a great impact on QoL.
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| 42. |
- Sundberg, Kay K., et al.
(författare)
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Sense of coherence and need for support among long-term survivors of childhood cancer
- 2012
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Ingår i: Cancer Nursing. - : Lippincott Williams & Wilkins. - 0162-220X .- 1538-9804. ; 35:4, s. E43-E49
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The concept of sense of coherence (SOC) may be applied to explain individuals' resources for dealing with the stressors confronted in daily life. Little is known about what impact cancer in childhood may have on the development of SOC.OBJECTIVE: The objectives of this study were to compare SOC between long-term survivors of childhood cancer and a comparison group and to explore the need for current support among the survivors and the association between need for support and SOC.METHODS: Data were collected from 224 long-term survivors aged 18 to 37 years using the 13-item SOC scale and interviews. A matched comparison group (n = 283) randomly selected from the general population was included.RESULTS: There was no significant difference in the mean SOC score between the survivors and the comparison group. Twenty percent of the survivors reported a need for support, a need significantly predicted by a low SOC, as well as surgery and/or radiation treatment often in combination with chemotherapy.CONCLUSIONS: Long-term survivors of childhood cancer seem to have resources to cope with stressful situations in life to the same degree as people in general. Survivors with fewer resources to cope and those having received a more intense treatment were more likely to be in need of support.IMPLICATIONS FOR PRACTICE: The concept of SOC in nursing practice may be helpful to identify and discuss an individual's resources and impediments to health to better understand the need for support among survivors of childhood cancer.
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| 43. |
- Sundberg, Kay K., et al.
(författare)
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Sexual function and experience among long-term survivors of childhood cancer
- 2011
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 47:3, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The objective was to compare sexual function, sexual experience and quality of partner relationship by gender in a cohort of long-term survivors of childhood cancer with a sample from the general population. METHODS: A 30-item self-reported postal questionnaire was completed by a cohort of 224 (64%) long-term survivors of childhood cancer and 283 (51%) randomly selected persons from the general population. RESULTS: Male survivors more often reported periods of low sexual interest (p=0.019), more frequently reported low sexual satisfaction (p=0.015), less frequently reported feeling sexually attractive (p=0.020) and reported a lower total number of sexual partners (p=0.031) than males in the comparison group did. Males diagnosed with a central nervous system (CNS) tumour more frequently reported sexual arousal problems (p=0.003), low sexual satisfaction (p=0.021) and total number of sexual partners (p=0.012) than did males with other diagnoses. There were no statistically significant differences regarding sexual function between the female survivors and the females in the comparison group. CONCLUSION: : The results indicate that cancer disease and treatment have more impact on sexual function of male survivors than on the sexual function of female survivors. Amongst the survivors, males diagnosed with CNS tumours were shown to be the most vulnerable group. Assessment of sexual function is recommended to be included in regular follow-ups after childhood cancer.
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| 44. |
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| 45. |
- Sundberg, K, et al.
(författare)
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The Swedish duty hour enigma
- 2014
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Ingår i: BMC medical education. - 1472-6920. ; 1414 Suppl 1, s. S6-
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Tidskriftsartikel (refereegranskat)
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| 46. |
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| 47. |
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| 48. |
- Timmons, James A., et al.
(författare)
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Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans
- 2010
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 108:6, s. 1487-1496
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Tidskriftsartikel (refereegranskat)abstract
- Timmons JA, Knudsen S, Rankinen T, Koch LG, Sarzynski M, Jensen T, Keller P, Scheele C, Vollaard NB, Nielsen S, Akerstrom T, MacDougald OA, Jansson E, Greenhaff PL, Tarnopolsky MA, van Loon LJ, Pedersen BK, Sundberg CJ, Wahlestedt C, Britton SL, Bouchard C. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 108: 1487-1496, 2010. First published February 4, 2010; doi:10.1152/japplphysiol.01295.2009.-A low maximal oxygen consumption ((V) over dotO(2max)) is a strong risk factor for premature mortality. Supervised endurance exercise training increases (V) over dotO(2max) with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts (V) over dotO(2max) training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous (V) over dotO(2max) response. Two independent preintervention RNA expression data sets were generated (n = 41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in (V) over dotO(2max) (""predictor"" genes). The HERITAGE Family Study (n = 473) was used for genotyping. We discovered a 29-RNA signature that predicted (V) over dotO(2max) training response on a continuous scale; these genes contained similar to 6 new single-nucleotide polymorphisms associated with gains in (V) over dotO(2max) in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., ""reciprocal"" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in (V) over dotO(2max), corresponding to similar to 50% of the estimated genetic variance for (V) over dotO(2max). In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. (V) over dotO(2max) responses to endurance training can be predicted by measuring a similar to 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.
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| 49. |
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