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1.
  • Bin Kaderi, Mohamed Arifin, 1978- (författare)
  • Assessment of Novel Molecular Prognostic Markers in Chronic Lymphocytic Leukemia
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The clinical course of chronic lymphocytic leukemia (CLL) is highly heterogeneous, which has prompted<sup> </sup>the search for biomarkers that can predict prognosis in this disease. The IGHV gene mutation status and certain genomic aberrations have been identified as reliable prognostic markers of clinical outcome for this disorder. However, the search for more feasible prognostic markers in CLL is still being pursued. Recently, certain single nucleotide polymorphisms (SNPs) in the <em>GNAS1</em>, <em>BCL2</em> and <em>MDM2</em> genes and the RNA expression levels of the <em>LPL</em>, <em>ZAP70</em>, <em>TCL1, CLLU1 </em>and <em>MCL1</em> genes were suggested as novel prognostic markers in CLL.</p> <p>In papers I-III, we performed genotyping analyses of the <em>GNAS1</em> T393C, <em>BCL2</em> -938C&gt;A and <em>MDM2</em> SNP309 polymorphisms in 268-418 CLL patients and related the genotypes with clinical data. Association studies between the polymorphisms and established prognostic markers (i.e. IGHV mutation status, genomic aberrations, CD38 expression) were also performed. Our studies did not find any significant relationship between these SNPs with either clinical outcome or other known prognostic markers in CLL.</p> <p>In paper IV, we measured the RNA expression levels of <em>LPL</em>, <em>ZAP70</em>, <em>TCL1,</em> <em>CLLU1</em> and <em>MCL1</em> in 252 CLL cases and correlated these levels with clinical outcome. Here, we verified that high expression of all these RNA-based markers, except <em>MCL1</em>, were associated with an unfavourable prognosis. We also confirmed a close relationship between IGHV mutation status and the RNA-based markers, especially for <em>LPL</em> and <em>CLLU1</em> expression. Among the RNA-based markers, multivariate analysis revealed <em>LPL</em> expression as the strongest independent prognostic marker for overall survival and time to treatment. Furthermore, the RNA-based markers could add further prognostic information to established markers in subgroups of patients, with <em>LPL</em> expression status giving the most significant results.</p> <p>In summary, data from papers I-III could not verify the <em>GNAS1</em> T393C, <em>BCL2</em> -938C&gt;A and <em>MDM2 </em>SNP309 polymorphisms as prognostic markers in CLL. Future SNP markers must hence be confirmed in large, independent cohorts before being proposed as prognostic marker in CLL. In paper IV, we conclude that <em>LPL</em> expression appears to be the strongest among the RNA-based markers for CLL prognostication. Further efforts to standardize <em>LPL</em> quantification are required before it can be applied in the clinical laboratory to predict clinical outcome in this disease.<em></em></p>
2.
  • Ge, Chenjie, et al. (författare)
  • Enlarged Training Dataset by Pairwise GANs for Molecular-Based Brain Tumor Classification
  • 2020
  • Ingår i: IEEE Access. - 2169-3536. ; 8:1, s. 22560-22570
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper addresses issues of brain tumor subtype classification using Magnetic Resonance Images (MRIs) from different scanner modalities like T1 weighted, T1 weighted with contrast-enhanced, T2 weighted and FLAIR images. Currently most available glioma datasets are relatively moderate in size, and often accompanied with incomplete MRIs in different modalities. To tackle the commonly encountered problems of insufficiently large brain tumor datasets and incomplete modality of image for deep learning, we propose to add augmented brain MR images to enlarge the training dataset by employing a pairwise Generative Adversarial Network (GAN) model. The pairwise GAN is able to generate synthetic MRIs across different modalities. To achieve the patient-level diagnostic result, we propose a post-processing strategy to combine the slice-level glioma subtype classification results by majority voting. A two-stage course-to-fine training strategy is proposed to learn the glioma feature using GAN-augmented MRIs followed by real MRIs. To evaluate the effectiveness of the proposed scheme, experiments have been conducted on a brain tumor dataset for classifying glioma molecular subtypes: isocitrate dehydrogenase 1 (IDH1) mutation and IDH1 wild-type. Our results on the dataset have shown good performance (with test accuracy 88.82%). Comparisons with several state-of-the-art methods are also included.
3.
  • Friberg, Örjan, et al. (författare)
  • Incidence, microbiological findings, and clinical presentation of sternal wound infections after cardiac surgery with and without local gentamicin prophylaxis
  • 2007
  • Ingår i: European Journal of Clinical Microbiology and Infectious Diseases. - Berlin : Springer. - 0934-9723 .- 1435-4373. ; 26:2, s. 91-97
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Sternal wound infection (SWI) is a serious complication after cardiac surgery. In a previous randomized controlled trial, the addition of local collagen-gentamicin in the sternal wound before wound closure was found to significantly reduce the incidence of postoperative wound infections compared with the routine intravenous prophylaxis of isoxazolyl-penicillin only. The aims of the present study were to analyse the microbiological findings of the SWIs from the previous trial as well as to correlate these findings with the clinical presentation of SWI. Differences in clinical presentation of SWIs, depending on the causative agent, could be identified. Most infections had a late, insidious onset, and the majority of these were caused by staphylococci, predominantly coagulase-negative staphylococci. The clinically most fulminant infections were caused by gram-negative bacteria and presented early after surgery. Local administration of gentamicin reduced the incidence of SWIs caused by all major, clinically important bacterial species. Propionibacterium acnes was identified as a possible cause of SWI and may be linked to instability in the sternal fixation. There was no indication of an increase in the occurrence of gentamicin-resistant bacterial isolates in the treatment group. Furthermore, the addition of local collagen-gentamicin reduced the incidence of SWIs caused by methicillin-resistant coagulase-negative staphylococci. This technique warrants further evaluation as an alternative to prophylactic vancomycin in settings with a high prevalence of methicillin-resistant Staphylococcus aureus.</p>
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4.
  • Toschke, Audré M., et al. (författare)
  • Paternal smoking is associated with a decreased prevalence of type 1 diabetes mellitus among offspring in two national British birth cohort studies (NCDS and BCS70)
  • 2007
  • Ingår i: Journal of Perinatal Medicine. - Berlin : Walter de Gruyter. - 0300-5577 .- 1619-3997. ; 35:1, s. 43-7
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>AB Aims: An association between paternal age and type 1 diabetes (IDDM) among their offspring was recently reported as well as transgenerational responses in humans. This paper aims to assess the association of markers for prenatal exposures with IDDM. Methods: We analysed data from two birth cohorts in Great Britain on 5214 cohort members from the National Child Development Study (NCDS) and 6068 members of the 1970 British Birth Cohort Study (BCS70) with full information on IDDM and explanatory variables using multivariate logistic regression. Results: IDDM prevalence was 0.7% (95% CI 0.5-1.0%; n = 38) in the NCDS and 0.4% (95% CI 0.3-0.6%; n = 27) in the BCS70 cohort. Paternal age was not associated with IDDM possibly due to lack of sample power. Unex-pectedly, a lowered prevalence of IDDM was observed among offspring of smoking fathers in both cohorts, with a combined odds ratio of 0.44 (95% CI 0.25-0.75). This association could not be explained by maternal smoking prior to, during or after pregnancy, number of siblings, parental social class, maternal and paternal age, or cohort. Maternal smoking in pregnancy did not alter the IDDM prevalence among offspring. Conclusions: This unexpected finding may be explained by germ-line mutations or other mechanisms associated with paternal smoking. This phenomenon should be investigated and these results should not be used as a justification for smoking. Paternal exposures may be important in determining IDDM risk.</p>
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5.
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6.
  • Ruiz, Jonatan R., et al. (författare)
  • High cardiovascular fitness is associated with low metabolic risk score in children : the European Youth Heart Study
  • 2007
  • Ingår i: Pediatric Research. - Baltimore, Md : Williams and Wilkins Co. - 0031-3998 .- 1530-0447. ; 61:3, s. 350-355
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The aim of the present study was to examine the associations of cardiovascular fitness (CVF) with a clustering of metabolic risk factors in children, and to examine whether there is a CVF level associated with a low metabolic risk. CVF was estimated by a maximal ergometer bike test on 873 randomly selected children from Sweden and Estonia. Additional measured outcomes included fasting insulin, glucose, triglycerides, HDLC, blood pressure, and the sum of five skinfolds. A metabolic risk score was computed as the mean of the standardized outcomes scores. A risk score &lt;75th percentile was considered to indicate a low metabolic risk. CVF was negatively associated with clustering of metabolic risk factors in children. Receiver operating characteristic curve analysis showed a significant discriminatory accuracy of CVF in identifying the low/high metabolic risk in girls and boys (p &lt; 0.001). The CVF level for a low metabolic risk was 37.0 and 42.1 mL/kg/min in girls and boys, respectively. These levels are similar to the health-related threshold values of CVF suggested by worldwide recognized organizations. In conclusion, the results suggest a hypothetical CVF level for having a low metabolic risk, which should be further tested in longitudinal and/or intervention studies. Abbreviations: AUC, area under the curve CVF, cardiovascular fitness ROC, receiver operating characteristic</p>
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7.
  • Westius, Anders, et al. (författare)
  • View of life in persons with dementia
  • 2009
  • Ingår i: Dementia. - London : Sage. - 1471-3012 .- 1741-2684. ; 8:4, s. 481-499
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objective: To study the view of life in dementia. The view of life of an individual is defined as a conception of reality, a central system of values and a basic emotional attitude.Method: Interviews with persons (N = 21) with mild to moderate dementia of the Alzheimer’s type. The interview data were interpreted with a phenomenological hermeneutical method.Results: Despite their cognitive deterioration it was possible to understand the view of life of the participants in the frame of their life story. Their view of life seemed to guide them towards selecting mainly emotionally powerful and value-oriented memories. No exceptional characteristics that could be traced to their dementia disease were found in the participants’ views of life. Conclusions: The view of life of the participants with mild to moderate dementia was vital for their life story and was not erased by dementia.Implications: In order to respect people with dementia as persons, caregivers should strive for gaining some knowledge of their view of life.</p>
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8.
  • Westius, Anders, et al. (författare)
  • Views of life and sense of identity in people with Alzheimer's disease
  • 2010
  • Ingår i: Ageing & Society. - Cambridge, United Kingdom : Cambridge university press. - 0144-686X .- 1469-1779. ; 30:7, s. 1257-1278
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Making it possible for people with Alzheimer's disease to retain a sense of identity during the process of the disease poses a great challenge to care-givers, professionals and family carers. The aim of this study is to elucidate the role of the view of life of people with Alzheimer's in framing their sense of identity. Is their view of life a vital aspect of their sense of identity? ‘View of life’ was interpreted as a vital aspect of sense of identity, understood as the individual's beliefs about their life history and about the attributes that characterised them. Twenty-one people with mild to moderate stages of Alzheimer's disease were interviewed about their life story. The narratives were interpreted using a phenomenological hermeneutic method. By telling their life story, the participants also narrated their view of life, <em>i.e</em>. their conception of reality, their central system of values and their basic emotional attitudes. By their own accounts, the origins of the narrators' central values and basic emotional attitudes were established in early life. They also expressed a sense of meaningfulness and continuity when looking back on their lives. The findings suggest that for a care-giver or confidant, having knowledge of a person with dementia's view of life is valuable when seeking to confirm that person's sense of identity.</p>
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9.
  • Johansson, Per, et al. (författare)
  • Reduced cerebrospinal fluid concentration of interleukin-12/23 subunit p40 in patients with cognitive impairment.
  • 2017
  • Ingår i: PloS one. - 1932-6203. ; 12:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The role of inflammation in Alzheimer’s disease (AD) and other cognitive disorders is unclear. In a well-defined mono-center population, we measured cytokines and chemokines in paired serum and cerebrospinal fluid (CSF) samples. Methods Consecutive patients with AD (n = 30), stable mild cognitive impairment (SMCI, n = 11), other dementias (n = 11), and healthy controls (n = 18) were included. None of the subjects was treated with glucocorticoids, cholinesterase inhibitors, or non-steroidal anti-inflammatory drugs. Serum and CSF concentrations of interleukin-6 (IL-6), IL-8, IL-12/23 p40, IL-15, IL-16, vascular endothelial growth factor-A (VEGF-A), and three chemokines were measured using a multiplex panel. Results After correction for multiple comparisons, only CSF IL-12/23 p40 concentration differed significantly between the total patient group (n = 52) and controls (n = 18; p = 0.002). Further analyses showed that CSF IL-12/23 p40 concentration was decreased in all patient subgroups (AD, other dementias, and SMCI) compared to healthy controls (p < 0.01, p < 0.05, and p < 0.05, respectively). In the total study population (n = 70), CSF IL-12/23 p40 concentrations correlated positively with CSF concentrations of β-amyloid1-42 (Aβ1–42) and phosphorylated tau protein (P-tau) whereas in AD patients (n = 30), CSF IL-12/23 p40 only correlated positively with CSF P-Tau (r = 0.46, p = 0.01). Conclusions Most cytokines and chemokines were similar in patients and controls, but CSF IL-12/23 subunit p40 concentration was decreased in patients with cognitive impairment, and correlated with markers of AD disease status. Further studies are needed to evaluate the role of CSF IL-12/23 p40 in other dementias and SMCI.
10.
  • Stattin, Pär, et al. (författare)
  • Surveillance and deferred treatment for localized prostate cancer : Population based study in the National Prostate Cancer Register of Sweden
  • 2008
  • Ingår i: Journal of Urology. - Baltimore : Williams and Wilkins. - 0022-5347 .- 1527-3792. ; 180:6, s. 2423-2430
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>PURPOSE: To what extent active surveillance and deferred treatment for localized risk prostate cancer are used is unclear. We assessed the use of surveillance and of deferred treatment in a population based, nationwide cohort in Sweden.</p> <p>MATERIALS AND METHODS: In the National Prostate Cancer Register of Sweden, with a 98% coverage vs the compulsory Swedish Cancer Registry, we identified 8,304 incident cases of prostate cancer in 1997 to 2002 with age younger than 70 years, clinical local stage T1 or 2, N0 or Nx, M0 or Mx and serum prostate specific antigen less than 20 ng/ml. Data were extracted from medical charts for 7,782 of these men (94%) at a median of 4 years after diagnosis.</p> <p>RESULTS: Primary treatment was surveillance for 2,065 men (26%), radical prostatectomy for 3,722 (48%), radiotherapy for 1,632 (21%) and hormonal treatment for 363 (5%). Men on surveillance had lower local tumor stage, grade and prostate specific antigen, and were older than those who received active primary treatment (p &lt;0.001). After a median surveillance of 4 years 711 men (34%) on surveillance had received deferred treatment, which was radical prostatectomy for 279 (39%), radiotherapy for 212 (30%) and hormonal treatment for 220 (30%).</p> <p>CONCLUSIONS: Surveillance was a common treatment for patients younger than 70 years with localized prostate cancer in Sweden in 1997 to 2002, 26% of men with localized prostate cancer started surveillance and after a median followup of 4 years, 66% of these men remained on surveillance.</p>
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