| 1. |
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| 2. |
- Jiao, Xiang, et al.
(författare)
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PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1
- 2017
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:61, s. 102769-102782
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Tidskriftsartikel (refereegranskat)abstract
- Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.
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| 3. |
- Rivano Eckerdal, Johanna, et al.
(författare)
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Ett vatten stiger i mina ögon
- 2021
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Ingår i: ETN : H2O - H2O. - 1653-1361. ; 10, s. 53-64
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- I denna text är fokus på Öresundsbron, en förbindelse över ett specifikt vatten som gett den sitt namn. Från att tidigare ha varit en trafikled för båtar blev det med förbindelsen, som även inkluderar en tunnel, möjligt att färdas mellan Danmark och Sverige med bil eller tåg. Jag vill förstå den ambivalens inför bron som framträder när den av skilda anledningar inte är farbar. Centralt är de starka känslor som då väcks. Läsaren inbjuds via de referenser till musikstycken som finns i texten att lyssna på dessa stycken under sin läsning. Min idé är att dessa konstnärliga uttryck i ord och ton ska förstärka textens innebörd och ge ytterligare en dimension till läsningen. Den röda, vindlande tråden jag följer är att sondera känslors konstruktiva kraft och potential.
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| 4. |
- Stenman, Sebastian, et al.
(författare)
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A deep learning-based algorithm for tall cell detection in papillary thyroid carcinoma
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:According to the World Health Organization, the tall cell variant (TCV) is an aggressive subtype of papillary thyroid carcinoma (PTC) comprising at least 30% epithelial cells two to three times as tall as they are wide. In practice, applying this definition is difficult causing substantial interobserver variability. We aimed to train a deep learning algorithm to detect and quantify the proportion of tall cells (TCs) in PTC.Methods: We trained the deep learning algorithm using supervised learning, testing it on an independent dataset, and further validating it on an independent set of 90 PTC samples from patients treated at the Hospital District of Helsinki and Uusimaa between 2003 and 2013. We compared the algorithm-based TC percentage to the independent scoring by a human investigator and how those scorings associated with disease outcomes. Additionally, we assessed the TC score in 71 local and distant tumor relapse samples from patients with aggressive disease.Results: In the test set, the deep learning algorithm detected TCs with a sensitivity of 93.7% and a specificity of 94.5%, whereas the sensitivity fell to 90.9% and specificity to 94.1% for non-TC areas. In the validation set, the deep learning algorithm TC scores correlated with a diminished relapse-free survival using cutoff points of 10% (p = 0.044), 20% (p < 0.01), and 30% (p = 0.036). The visually assessed TC score did not statistically significantly predict survival at any of the analyzed cutoff points. We observed no statistically significant difference in the TC score between primary tumors and relapse tumors determined by the deep learning algorithm or visually.Conclusions: We present a novel deep learning-based algorithm to detect tall cells, showing that a high deep learning-based TC score represents a statistically significant predictor of less favorable relapse-free survival in PTC.
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| 5. |
- Winberg, Johanna, et al.
(författare)
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Chimerism Resulting From Parthenogenetic Activation and Dispermic Fertilization
- 2010
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Ingår i: American Journal of Medical Genetics, Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 152A:9, s. 2277-2286
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Tidskriftsartikel (refereegranskat)abstract
- Whole-body human chimerism is the result of two zygotes giving rise to one individual, and is a rarely detected condition. We have studied the molecular background and discuss the likely mechanism for the chimerism in a patient with a 46,XX/47,XY,+14 karyotype and ambiguous genitalia, cryptorchidism, pigment anomalies, and normal psychomotor development. We have used karyotyping, interphase-FISH and array-CGH analysis as well as molecular analysis of polymorphic markers from 48 loci in order to define the origin and percentage of 47,XY,+14 cells in different tissues. Based on the findings of two paternal alleles and the detection of homozygous maternal alleles without evidence of crossing-over, and the fact that four alleles were never detected, our results indicate that the chimerism in our patient is the result of dispermic fertilization of a parthenogenetically activated oocyte. Our report underlines that cytogenetic findings suggesting mosaicism might actually indicate chimerism as an underlying mechanism in patients. It also highlights the difficulties in predicting the clinical outcome in patients with genetic aberrations in mosaic or chimeric form.
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| 6. |
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| 7. |
- Arkani, Samara, et al.
(författare)
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Evaluation of the ISL1 gene in the pathogenesis of bladder exstrophy in a Swedish cohort
- 2018
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Ingår i: Human genome variation. - : Springer Nature. - 2054-345X. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Bladder exstrophy is a congenital closure defect of the urinary bladder with a profound effect on morbidity. Although the malformation is usually sporadic, a genetic background is supported by an increased recurrence risk in relatives, higher concordance rates in monozygotic twins and several associated chromosomal aberrations. Recently, the ISL1 gene was presented as a candidate gene for bladder exstrophy and epispadias complex (BEEC) development in two different studies. In our study, we screened for genetic variants in the ISL1 gene in DNA from 125 Swedish patients using Sanger sequencing and array-CGH analysis. In addition, we evaluated ISL1 expression in RNA of human bladder during embryonic and fetal weeks 5–10 relative to that in lung tissue (week 9). In total, 21 single-nucleotide variants were identified, including a potentially novel missense variant, c.137C>G p.(Ala46Gly), substituting a conserved amino acid. This variant was inherited from an unaffected mother. No structural variants were identified. RNA sequencing revealed ISL1 mRNA expression during the critical time frame of human bladder development. In conclusion, we did not detect any known or likely pathogenic variants in the ISL1 gene in 125 Swedish BEEC patients, indicating that variation in the ISL1 gene is not a common genetic mechanism of BEEC development in the Swedish population.
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| 8. |
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| 9. |
- Berglund, Karin, 1967-, et al.
(författare)
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Engaged Sisters : studying the entrepreneurship and innovation support system from ‘within’
- 2013
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Konferensbidrag (refereegranskat)abstract
- Entrepreneurship and innovation support has grown into large institutions in a society that cherishes an enterprising culture. Individuals are encouraged to be entrepreneurial and innovative in general, and to start up their own companies in particular. To support individuals in their business creation processes, policy stresses the need of providing with measures. Together these measures comprise a support system, directed towards supporting new and established entrepreneurs. It has however been recognized that the entrepreneurship and innovation public support system is highly gendered, favoring men and male businesses, whilst programs targeting women put the onus on individual women to start and grow businesses. As well it has been recognized that the policy support system tends to exclude ‘othered’ groups rather than including them in enterprising activities. The subtext of entrepreneurship support points to how some people “are” entrepreneurs, whilst others need support in order to become more entrepreneurial. Hence, there is a need to change the support system of entrepreneurship and innovation since it tends to disempower rather than to empower ‘othered’ groups in society.“Sisters in Business” make up an organization of wo/men entrepreneurs who have joined forces to address this need. Their vision is that entrepreneurship should reflect the society at large. During the last year they have therefore taken several initiatives to make this happen and is today one of the support organizations in a medium sized Swedish town. In this paper three Sisters are working together with a researcher within this area. Together we have formed a group of “engaged sisters´”. In our dialogue the dichotomy between ‘practice’ and ‘theory’ have temporarily dissolved in favor of creating narratives, from episodes, experiences and the everyday life of sister´s, to illustrate how the support system works from ‘within’. This led us to questioning whether the ‘support system’ really is a support system, or something else? Furthermore, this insight made it apparent that there exists ‘other’ support system, tough concealed and silenced. Finally, suggestions are proposed for how ‘practitioners’ can work together with ‘academics’ to change the rules of the game.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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ETN:H2O
- 2021
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Falconer, Henrik, et al.
(författare)
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Robot-assisted approach to cervical cancer (RACC) : an international multi-center, open-label randomized controlled trial
- 2019
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Ingår i: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 29:6, s. 1072-1076
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival.Primary Objective: To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy.Study Hypothesis: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes.Trial Design: Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden.Major Inclusion/Exclusion Criteria: Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years.Primary Endpoint: Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer.Sample Size: The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (alpha) of 5% and a power (1-beta) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients.Estimated Dates for Completing Accrual and Presenting Results: Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.
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| 15. |
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| 16. |
- Georgiopoulos, Charalampos, et al.
(författare)
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Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging
- 2024
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Ingår i: Journal of Neurosurgery. - 0022-3085. ; 140:3, s. 612-620
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Diffusion tensor imaging (DTI) along the perivascular space (ALPS) (DTI-ALPS)-by calculating the ALPS index, a ratio accentuating water diffusion in the perivascular space-has been proposed as a noninvasive, indirect MRI method for assessing glymphatic function. The main aim of this study was to investigate whether DTI-ALPS would reveal glymphatic dysfunction in idiopathic normal pressure hydrocephalus (iNPH) and whether the ALPS index was associated with disease severity. METHODS: Thirty iNPH patients (13 men; median age 77 years) and 27 healthy controls (10 men; median age 73 years) underwent MRI and clinical assessment with the Timed Up and Go test (TUG) and Mini-Mental State Examination (MMSE); only the patients were evaluated with the Hellström iNPH scale. MRI data were analyzed with the DTI-ALPS method and Radscale screening tool. RESULTS: iNPH patients showed significantly lower mean ALPS index scores compared with healthy controls (median [interquartile range] 1.09 [1.00-1.15] vs 1.49 [1.36-1.59], p < 0.001). Female healthy controls showed significantly higher ALPS index scores than males in both hemispheres (e.g., right hemisphere 1.62 [1.47-1.67] vs 1.33 [1.14-1.41], p = 0.001). This sex difference was not seen in iNPH patients. The authors found a moderate exponential correlation between mean ALPS index score and motor function as measured with time required to complete TUG (r = -0.644, p < 0.001), number of steps to complete TUG (r = -0.571, p < 0.001), 10-m walk time (r = -0.637, p < 0.001), and 10-m walk steps (r = -0.588, p < 0.001). The authors also found a positive linear correlation between mean ALPS index score and MMSE score (r = 0.416, p = 0.001). Simple linear regression showed a significant effect of diagnosis (B = -0.39, p < 0.001, R2 = 0.459), female sex (B = 0.232, p = 0.002, R2 = 0.157), and Evans index (B = -4.151, p < 0.001, R2 = 0.559) on ALPS index. Multiple linear regression, including diagnosis, sex, and Evans index score, showed a higher predictive value (R2 = 0.626) than analysis of each of these factors alone. CONCLUSIONS: The ALPS index, which was significantly decreased in iNPH patients, could serve as a marker of disease severity, both clinically and in terms of neuroimaging. However, it is important to consider the significant influence of biological sex and ventriculomegaly on the ALPS index, which raises the question of whether the ALPS index solely reflects glymphatic function or if it also encompasses other types of injury. Future studies are needed to address potential confounding factors and further validate the ALPS method.
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| 17. |
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| 18. |
- Guath, Mona, et al.
(författare)
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Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents
- 2023
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 436
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Tidskriftsartikel (refereegranskat)abstract
- Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.
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| 19. |
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| 20. |
- Hendry, Alexandra, et al.
(författare)
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Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits
- 2020
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Ingår i: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 50:11, s. 4085-4105
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Tidskriftsartikel (refereegranskat)abstract
- Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.
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| 21. |
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| 22. |
- Karlsson, Johanna, et al.
(författare)
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Uppmaningar uttryckta som hintar på lektioner i Idrott och hälsa
- 2022
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Ingår i: Idrott och språk – Språk i idrott : Nordisk nätverkskonferens vid Linnéuniversitetet den 12-13 januari 2022 - Nordisk nätverkskonferens vid Linnéuniversitetet den 12-13 januari 2022. - 9789189709393 - 9789189709409 ; , s. 61-82
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Konferensbidrag (refereegranskat)abstract
- This article spotlights the school subject Physical Education and Health (PEH) in Sweden and examines a teacher's use of requests to communicate with her students in order to convey the content of the subject. I focus on the variation in language use that occurs within requests and whether this variation is recipient-related depending on the recipient's language level in Swedish. The main focus in this article is on the occurence of requests that are expressed as hints, that is, requests where the content is expressed between the lines: Being in the way causes problems ≈ Move!Among the 88 hints analyzed in this study, 55 show some structural patterns, suggesting that there is a certain predictability among them. The analysis also shows that the teacher makes adjustments in relation to the recipients' language skills: students with a lower Swedish language level receive more hints with a predicable structure and fewer with an unpredictable one.
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| 23. |
- Korberg, Izabella Baranowska, et al.
(författare)
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WNT3 involvement in human bladder exstrophy and cloaca development in zebrafish
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5069-5078
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Tidskriftsartikel (refereegranskat)abstract
- Bladder exstrophy, a severe congenital urological malformation when a child is born with an open urinary bladder, is the most common form of bladder exstrophy-epispadias complex (BEEC) with an incidence of 1: 30,000 children of Caucasian descent. Recent studies suggest that WNT genes may contribute to the etiology of bladder exstrophy. Here, we evaluated WNT-pathway genes in 20 bladder exstrophy patients using massively parallel sequencing. In total 13 variants were identified in WNT3, WNT6, WNT7A, WNT8B, WNT10A, WNT11, WNT16, FZD5, LRP1 and LRP10 genes and predicted as potentially disease causing, of which seven variants were novel. One variant, identified in a patient with a de novo nonsynonymous substitution in WNT3 (p.Cys91Arg), was further evaluated in zebrafish. Knock down of wnt3 in zebrafish showed cloaca malformations, including disorganization of the cloaca epithelium and expansion of the cloaca lumen. Our study suggests that the function of the WNT3 p.Cys91Arg variant was altered, since RNA overexpression of mutant Wnt3 RNA does not result in embryonic lethality as seen with wild-type WNT3 mRNA. Finally, we also mutation screened the WNT3 gene further in 410 DNA samples from BEEC cases and identified one additional mutation c.638G> A (p.Gly213Asp), which was paternally inherited. In aggregate our data support the involvement of WNT-pathway genes in BEEC and suggest that WNT3 in itself is a rare cause of BEEC.
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| 24. |
- Kvarnung, Malin, et al.
(författare)
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Inherited mosaicism for the supernumerary marker chromosome in cat eye syndrome : Inter- and intra-individual variation and correlation to the phenotype
- 2012
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Ingår i: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 158A:5, s. 1111-1117
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Tidskriftsartikel (refereegranskat)abstract
- We have studied a family with repeated transmission of mosaicism for a supernumerary marker chromosome (SMC), giving rise to varying symptoms of the cat eye syndrome (CES) in the offspring. The frequency of the SMC was investigated using FISH with probes from the CES critical region on lymphocytes as well as buccal cells. The same probes were used to study the frequency of the SMC in spermatozoa from the father. The SMC was characterized in detail using array-CGH and was found to correspond to a symmetrical cat eye SMC type I, with two extra copies of the most proximal part of 22q11, not extending into the classical 22q11.2 deletion region. Mosaicism for the SMC was detected in 4 out of 7 family members, the father and all his three children. The degree of mosaicism varied greatly between individuals as well as between tissues, with twice as many cells with the SMC in epithelial cells compared to blood. The highest frequency (almost 50%) was found in spermatozoa from the father. There was a direct correlation between the degree of mosaicism and the symptoms, varying from no obvious symptoms to classical CES. The study confirms the occurrence of direct transmission of SMC-mosaicism in CES. The results indicate that examination of parental epithelial cells should be preferred compared to blood cells in order to exclude a recurrence risk in parents of a child with CES. Interphase FISH analysis of spermatozoa is the most sensitive method to exclude paternal germ line mosaicsm. (c) 2012 Wiley Periodicals, Inc.
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| 25. |
- Lindberg, Jonatan, et al.
(författare)
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En spark i baken för ett aktivare liv
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Efter årtionden av inaktivitet fick några patienter i 60-årsåldern fysisk aktivitet på recept (FaR). Vår studie pekar på att det var ett bra sätt att hjälpa dem att finna motivation och att ta ett första steg mot ett aktivare liv.
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| 26. |
- Lindh, Markus V., et al.
(författare)
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Disentangling seasonal bacterioplankton population dynamics by high-frequency sampling
- 2015
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Ingår i: Environmental Microbiology. - : Society for Applied Microbiology and John Wiley & Sons Ltd. - 1462-2912 .- 1462-2920. ; 17:7, s. 2459-2476
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Tidskriftsartikel (refereegranskat)abstract
- Multiyear comparisons of bacterioplankton succession reveal that environmental conditions drive community shifts with repeatable patterns between years. However, corresponding insight into bacterioplankton dynamics at a temporal resolution relevant for detailed examination of variation and characteristics of specific populations within years is essentially lacking. During 1 year, we collected 46 samples in the Baltic Sea for assessing bacterial community composition by 16S rRNA gene pyrosequencing (nearly twice weekly during productive season). Beta-diversity analysis showed distinct clustering of samples, attributable to seemingly synchronous temporal transitions among populations (populations defined by 97% 16S rRNA gene sequence identity). A wide spectrum of bacterioplankton dynamics was evident, where divergent temporal patterns resulted both from pronounced differences in relative abundance and presence/absence of populations. Rates of change in relative abundance calculated for individual populations ranged from 0.23 to 1.79 day(-1). Populations that were persistently dominant, transiently abundant or generally rare were found in several major bacterial groups, implying evolution has favoured a similar variety of life strategies within these groups. These findings suggest that high temporal resolution sampling allows constraining the timescales and frequencies at which distinct populations transition between being abundant or rare, thus potentially providing clues about physical, chemical or biological forcing on bacterioplankton community structure.
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| 27. |
- Lindh, Markus V., et al.
(författare)
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Metapopulation theory identifies biogeographical patterns among core and satellite marine bacteria scaling from tens to thousands of kilometers
- 2017
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Ingår i: Environmental Microbiology. - : Wiley-Blackwell. - 1462-2912 .- 1462-2920. ; 19:3, s. 1222-1236
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Tidskriftsartikel (refereegranskat)abstract
- Metapopulation theory developed in terrestrial ecology provides applicable frameworks for interpreting the role of local and regional processes in shaping species distribution patterns. Yet, empirical testing of metapopulation models on microbial communities is essentially lacking. We determined regional bacterioplankton dynamics from monthly transect sampling in the Baltic Sea Proper using 16S rRNA gene sequencing. A strong positive trend was found between local relative abundance and occupancy of populations. Notably, the occupancy-frequency distributions were significantly bimodal with a satellite mode of rare endemic populations and a core mode of abundant cosmopolitan populations (e.g. Synechococcus, SAR11 and SAR86 clade members). Temporal changes in population distributions supported several theoretical frameworks. Still, bimodality was found among bacterioplankton communities across the entire Baltic Sea, and was also frequent in globally distributed datasets. Datasets spanning waters with widely different physicochemical characteristics or environmental gradients typically lacked significant bimodal patterns. When such datasets were divided into subsets with coherent environmental conditions, bimodal patterns emerged, highlighting the importance of positive feedbacks between local abundance and occupancy within specific biomes. Thus, metapopulation theory applied to microbial biogeography can provide novel insights into the mechanisms governing shifts in biodiversity resulting from natural or anthropogenically induced changes in the environment.
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| 28. |
- Lindh, Markus V., et al.
(författare)
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Transplant experiments uncover Baltic Sea basin-specific responses in bacterioplankton community composition and metabolic activities
- 2015
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenically induced changes in precipitation are projected to generate increased river runoff to semi enclosed seas, increasing loads of terrestrial dissolved organic matter and decreasing salinity. To determine how bacterial community structure and functioning adjust to such changes, we designed microcosm transplant experiments with Baltic Proper (salinity 7.2) and Bothnian Sea (salinity 3.6) water. Baltic Proper bacteria generally reached higher abundances than Bothnian Sea bacteria in both Baltic Proper and Bothnian Sea water, indicating higher adaptability. Moreover, Baltic Proper bacteria growing in Bothnian Sea water consistently showed highest bacterial production and beta-glucosidase activity. These metabolic responses were accompanied by basin specific changes in bacterial community structure. For example, Baltic Proper Pseudomonas and Limnobacter populations increased markedly in relative abundance in Bothnian Sea water, indicating a replacement effect. In contrast, Roseobacter and Rheinheknera populations were stable or increased in abundance when challenged by either of the waters, indicating an adjustment effect. Transplants to Bothnian Sea water triggered the initial emergence of particular Burkholderiaceae populations, and transplants to Baltic Proper water triggered Alteromonadaceae populations. Notably, in the subsequent re transplant experiment, a priming effect resulted in further increases to dominance of these populations. Correlated changes in community composition and metabolic activity were observed only in the transplant experiment and only at relatively high phylogenetic resolution. This suggested an importance of successional progression for interpreting relationships between bacterial community composition and functioning. We infer that priming effects on bacterial community structure by natural episodic events or climate change induced forcing could translate into long-term changes in bacterial ecosystem process rates.
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| 29. |
- Lindstrand, Anna, et al.
(författare)
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From cytogenetics to cytogenomics : whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability
- 2019
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Ingår i: Genome Medicine. - : BMC. - 1756-994X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSince different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.MethodsWe analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n=68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n=156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.ResultsFirst, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850kb (min 500bp, max 155Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (>10kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data.Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively.ConclusionThe overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
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| 30. |
- Lundgren, Ewa, et al.
(författare)
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Primary hyperparathyroidism revisited in menopausal women with serum calcium in upper normal range at population-based screening 8 years ago
- 2002
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 26:8, s. 931-936
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. Population-based screening showed 2.1% prevalence of primaryhyperparathyroidism (pHPT) in postmenopausal women. Individualswith total serum (s)-calcium levels of 2.55 mmol/L or more at screeningwere diagnosed with pHPT when subsequent analysis supported inappropriatelyelevated intact parathormone (PTH) levels in relation to evennormal s-calcium levels. The arbitrary diagnostic criteria were validatedby parathyroidectomy. Herein we reinvestigated biochemical signs ofpHPT in women not diagnosed with pHPT due to s-calcium 2.50 to 2.54mmol/L (group A, n 160) at screening or due to appropriate PTH levelson two occasions after screening (group B, n 70). Altogether, 99 womenin group A and 47 in group B underwent reinvestigation 8.8 years afterscreening when they were 65 to 84 years old. The s-calcium levels averaged2.56 mmol/L and had increased in group A (mean 0.04 mmol/L) anddecreased in group B (mean 0.05 mmol/L). A total of 48 and 18 females(48%, 38%), respectively, met the previously validated criteria of pHPT.Altogether 21% of them were hypercalcemic (range 2.60 –3.12 mmol/L).Subgroup analysis showed that PTH had not increased with time (n 47)and that atherogenic blood lipids, but not glucose levels, were similar inpHPT patients and matched controls (n 37). Assuming the existence ofpHPT already at screening, the prevalence of pHPT could be adjusted to3.4%. Even the most liberal diagnostic criteria utilized at pHPT screeningseemed to underdiagnose the disease by inefficient cutoff limits for scalciumand PTH. Because one-fifth of the women with pHPT progressedto hypercalcemia, long-term follow-up is advocated for those with scalciumin the upper normal range.
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| 31. |
- Lundin, Douglas, et al.
(författare)
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A median voter model of health insurance with ex post moral hazard
- 2001
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- One of the main features of health insurance is moral hazard, as defined by Pauly (1968); people face incentives for excess utilization of medical care since they do not pay the full marginal cost for provision. To mitigate the moral hazard problem, a coinsurance can be included in the insurance contract. We analyze under what conditions there is a conflict between individuals on what coinsurance rate should be set with public health insurance, and we establish conditions for a median-voter equilibrium. Then we allow the public insurance to be supplemented with private insurance, and we establish conditions under which public provision will lead to larger aggregate spending than private provision does.
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| 32. |
- Lundin Frisk, Emrik, 1994, et al.
(författare)
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Improved assessments of subsurface projects: Systematic mapping of geosystem services and a review of their economic values
- 2024
-
Ingår i: Journal of Environmental Management. - 0301-4797 .- 1095-8630. ; 365
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Tidskriftsartikel (refereegranskat)abstract
- Awareness of the subsurface and its multitude of resources is generally low and decisions on access to subsurface resources are often guided by a ‘first come, first served principle’. Although not yet fully developed, the concept of geosystem services has been put forward to make subsurface resources more visible and acknowledged in decision-making. This study (1) illustrates a systematic mapping of effects on geosystem services using a process-oriented perspective in two conceptual case studies; (2) translates the mapped effects into costs and benefits items in a qualitative cost-benefit analysis (CBA) context; and (3) presents a systematic review of economic valuation studies of geosystem services to investigate the available support for a quantitative CBA. The findings suggest that systematic mapping of effects on multiple geosystem services can inform different types of assessment methods and decision-makers on trade-offs and provide a basis for well-informed and responsible decisions on subsurface use. Combining such mapping with a CBA can further strengthen decision support through indications of the net effects on human well-being. However, although economic valuation of non-market geosystem services is possible using established valuation methods, such studies are scarce in scientific literature. Thus, although a CBA can provide a basis for supporting decisions on subsurface use from a consequentialist perspective, full quantification of all effects may require great efforts, and it needs to be complemented with other methods to capture the full range of values the subsurface can provide. This study also highlights that depending on the context, supporting and regulating geosystem services can be either intermediate or final services. Therefore, if geosystem services are to be included in the abiotic extension of CICES, in which supporting services by definition are excluded, reclassification of the supporting geosystem services should be considered not to risk being overlooked in economic valuation and CBA.
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| 33. |
- Lundin, Johanna, et al.
(författare)
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22q11.2 microduplication in two patients with bladder exstrophy and hearing impairment
- 2010
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 53:2, s. 61-65
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Tidskriftsartikel (refereegranskat)abstract
- Bladder exstrophy is a congenital malformation of the bladder and urethra. The genetic basis of this malformation is unknown however it is well known that chromosomal aberrations can lead to defects in organ development. A few bladder exstrophy patients have been described to carry chromosomal aberrations. Chromosomal rearrangements of 22q11.2 are implicated in several genomic disorders i.e. DiGeorge/velocardiofacial- and cat-eye syndrome. Deletions within this chromosomal region are relatively common while duplications of 22q11.2 are much less frequently observed. An increasing number of reports of microduplications of this region describe a highly variable phenotype. We have performed array-CGH analysis of 36 Swedish bladder exstrophy patients. The analysis revealed a similar and approximately 3 Mb duplication, consistent with the recently described 22q11.2 microduplication syndrome, in two unrelated cases with bladder exstrophy and hearing impairment. This finding was confirmed by multiplex ligation-dependent probe amplification (MLPA) and FISH analysis. Subsequent MLPA analysis of this chromosomal region in 33 bladder exstrophy patients did not reveal any deletion/duplication within this region. MLPA analysis of 171 anonymous control individuals revealed one individual carrying this microduplication. This is the first report of 22q11.2 microduplication associated with bladder exstrophy and hearing impairment. Furthermore the finding of one carrier among a cohort of normal controls further highlights the variable phenotype linked to this microduplication syndrome.
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| 34. |
- Lundin, Johanna, et al.
(författare)
-
Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting LZTR1 as a candidate gene
- 2019
-
Ingår i: Molecular Genetics and Genomic Medicine. - : Wiley. - 2324-9269. ; 7:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The bladder exstrophy-epispadias complex (BEEC) is a congenital malformation of the bladder and urethra. The underlying causes of this malformation are still largely unknown; however, aside from environment, genetics is thought to play an essential role. The recurrent 22q11.2 microduplication is the most persistently detected genetic aberration found in BEEC cases. Methods: We performed array comparative genomic hybridization (array-CGH) analysis of 76 Swedish BEEC patients. Statistical analysis was performed on current dataset pooled with previously published data on the 22q11.2 microduplication in BEEC patients. We performed massive parallel sequencing (MPS) of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication followed by functional studies. Results: We identified three additional cases with the 22q11.2 microduplication. Pooling data from this study with previously published reports showed a statistically significant enrichment of the 22q11.2 microduplication in BEEC patients (2.61% in cases vs. 0.08% in controls; OR = 32.6; p = 8.7 × 10−4). MPS of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication identified a novel variant in LZTR1 (p.Ser698Phe) in one patient. Functional evaluation of the LZTR1 p.Ser698Phe variant in live NIH 3T3 cells showed that the concentration and cytoplasmic mobility differ between the Lztr1wt and Lztr1mut, indicating a potential functional effect of the LZTR1mut. Conclusion: Our study further emphasizes the involvement of the 22q11.2 region in BEEC development and highlights LZTR1 as a candidate gene underlying the urogenital malformation.
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| 35. |
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| 36. |
- Lundin, Lisa, et al.
(författare)
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The behavior of PCDD and PCDF during thermal treatment of waste incineration ash
- 2011
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 84:3, s. 305-310
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Tidskriftsartikel (refereegranskat)abstract
- The polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) content of three fly ash samples with different elemental compositions from different municipal waste incinerators were analyzed before and after thermal treatment at 300°C or 500°C. Gas phase emissions during the treatments were also collected and analyzed. Substantial reductions in the total PCCD/F content of the ashes were observed after treatment at 500°C, seemingly due to degradation rather than dechlorination. Treatment at 300°C resulted in an increase in the PCDD/F content of the three ashes. Initial concentration of PCDD/F in the untreated ashes did not reflect the outcome of the treatment at the different temperatures. In addition, the composition of the ash was found to influence the rate of decomposition and formation of PCDD and PCDF during thermal treatment; the results showed that Cu, Fe, Ca and S play important roles in these processes.
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| 37. |
- Mercke Odeberg, Johanna, et al.
(författare)
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A pharmacokinetic and pharmacodynamic study of desmopressin: evaluating sex differences and the effect of pre-treatment with piroxicam, and further validation of an indirect response model.
- 2004
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Ingår i: The Journal of pharmacy and pharmacology. - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 56:11, s. 1389-98
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Tidskriftsartikel (refereegranskat)abstract
- Desmopressin is a synthetic vasopressin analogue mainly used in treatment of diabetes insipidus and nocturia. Studies in rats have revealed a sex difference in the response to a vasopressin infusion, which was diminished after treatment with an NSAID. This study was performed in man to investigate the influence of sex and concomitant treatment of piroxicam on the pharmacokinetics and dynamics of desmopressin, and to validate a previously described indirect response model. Eight healthy males and eight healthy females participated in the trial, which was conducted in a pharmacokinetic (PK) part followed by a pharmacodynamic (PD) part. Desmopressin was administered intravenously as a single dose (PK = dose 2 microg, PD = dose 0.2 microg). Piroxicam was administered to achieve steady state. The pharmacokinetic parameters of desmopressin were estimated and calculated by means of two-compartmental analysis. In the dynamic part a study design based on an oral hydration model was used. Parameters for urine flow and urine osmolality were estimated. Individual estimates of the pharmacokinetic parameters served as input to the indirect response model that subsequently was fitted to urine osmolality data. The pharmacokinetics of desmopressin after a fixed bolus injection was neither influenced by piroxicam nor sex of the subject. The pharmacodynamics of desmopressin showed a sex difference where females exhibited a more pronounced antidiuretic effect than males, which was statistically significant when the effects were submaximal (>4.5 h after dose). The sex differences were diminished after pre-treatment with piroxicam, indicating a prostaglandin PGE(2)-mediated mechanism. The indirect response model was confirmed, although the modelling could not distinguish a sex difference, indicating a limitation of this model compared with traditional descriptive statistics.
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| 38. |
- Nazaryan-Petersen, Lusine, et al.
(författare)
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Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization
- 2018
-
Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 14:11
-
Tidskriftsartikel (refereegranskat)abstract
- Clustered copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) are often reported as germline chromothripsis. However, such cases might need further investigations by massive parallel whole genome sequencing (WGS) in order to accurately define the underlying complex rearrangement, predict the occurrence mechanisms and identify additional complexities. Here, we utilized WGS to delineate the rearrangement structure of 21 clustered CNV carriers first investigated by CMA and identified a total of 83 breakpoint junctions (BPJs). The rearrangements were further sub-classified depending on the patterns observed: I) Cases with only deletions (n = 8) often had additional structural rearrangements, such as insertions and inversions typical to chromothripsis; II) cases with only duplications (n = 7) or III) combinations of deletions and duplications (n = 6) demonstrated mostly interspersed duplications and BPJs enriched with microhomology. In two cases the rearrangement mutational signatures indicated both a breakage-fusion-bridge cycle process and haltered formation of a ring chromosome. Finally, we observed two cases with Alu- and LINE-mediated rearrangements as well as two unrelated individuals with seemingly identical clustered CNVs on 2p25.3, possibly a rare European founder rearrangement. In conclusion, through detailed characterization of the derivative chromosomes we show that multiple mechanisms are likely involved in the formation of clustered CNVs and add further evidence for chromoanagenesis mechanisms in both "simple" and highly complex chromosomal rearrangements. Finally, WGS characterization adds positional information, important for a correct clinical interpretation and deciphering mechanisms involved in the formation of these rearrangements.
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| 39. |
- Nyqvist, Johanna, et al.
(författare)
-
Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up
- 2016
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 118:2, s. 335-341
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. Material and methods: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, NO glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1 + 2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. Results: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. Conclusion: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.
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| 40. |
- Pejlare, Johanna, 1976, et al.
(författare)
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Programmering för en problembaserad undervisning i gymnasieskolan
- 2021
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Ingår i: Programmering i skolmatematiken - möjligheter och utmaningar. - Lund : Studentlitteratur. - 9789144143293 ; , s. 123-142
-
Bokkapitel (refereegranskat)abstract
- I det här kapitlet beskrivs ett fortbildningsprojekt vars syfte var att öka kunskapen om vilka möjligheter till lärande i matematik som programmering kan erbjuda i gymnasieskolan. I projektet fick gymnasieelever tillsammans med lärarstudenter och gymnasielärare ägna sig åt problemlösning med hjälp av programmering. Speciellt för detta projekt var att programmeringen gjordes i Mathematica, vars programmeringsspråk skiljer sig ganska mycket från de som vanligen används i grundskolan. Författarna menar att fokus vid programmering i matematikundervisning alltför ofta ligger på algoritmer, och argumenterar för att man i stället bör fokusera på programmering som skapande, där frågorna snarare handlar om vad som ska skapas, vad det skapade ska gestalta, och hur det bör vara strukturerat.
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| 41. |
- Rydja, Johanna, et al.
(författare)
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Evaluating the cerebrospinal fluid tap test with the Hellstrom iNPH scale for patients with idiopathic normal pressure hydrocephalus
- 2021
-
Ingår i: Fluids and Barriers of the CNS. - : BioMed Central. - 2045-8118. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The cerebrospinal fluid tap test (CSF TT) is used for selecting shunt surgery candidates among patients with idiopathic normal pressure hydrocephalus (iNPH). We aimed to evaluate the predictive value of the CSF TT, by using the Hellstrom iNPH scale for shunted iNPH patients with a standardized method. Methods One hundred and sixteen shunt-operated iNPH patients were retrospectively included in this study. The gait and balance domains in the iNPH scale were used as outcome measures for the CSF TT and the total iNPH scale score as the postoperative outcome. A positive response to CSF TT was defined as a change of >= 5 points in the gait domain and >= 16 points in the balance domain. Differences between CSF TT responders and non-responders, sensitivity, specificity, positive and negative predictive values, accuracy, and correlations between changes from baseline to post CSF TT and from baseline to the postoperative follow-up, were calculated. Results In the CSF TT there were 63.8% responders in the gait domain and correspondingly 44.3% in the balance domain. CSF TT responders had a significantly better postoperative outcome in the total scale score (gait P <= 0.001, balance P <= 0.012) and gait CSF TT responders improved more in gait (P <= 0.001) and balance CSF TT responders in balance (P <= 0.001). No differences between CSF TT gait or balance responders could be found in neuropsychological or urinary continence assessments postoperatively. The sensitivity and specificity of the CSF TT and the outcome of the total iNPH scale score postoperatively were 68.1% and 52.0% for gait and 47.8% and 68.0% for balance, respectively. Conclusions The CSF TT, with the Hellstrom iNPH scale as the outcome measure, has clear limitations in predicting postoperative results. The gait domain may be used to predict outcomes for gait, but the balance domain is too insensitive.
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| 42. |
- Rydja, Johanna, 1972-
(författare)
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Gait Characteristics, Physical Activity and Subjective Outcome after Shunt Surgery in Normal Pressure Hydrocephalus
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Idiopathic normal pressure hydrocephalus (iNPH) is a common but under-diagnosed disease among the elderly. The condition is characterised by gait disturbance, postural instability, cognitive decline and incontinence, caused by accumulated cerebrospinal fluid within the central nerve system. The treatment is a shunt insertion to divert excess fluid. Few studies have described the detailed gait in INPH, there is a lack of research about physical activity, and patient-reported outcomes after shunt surgery are sparsely described. The overall aim of this thesis was to increase the knowledge of the gait pattern, the level of physical activity, and to evaluate the effect of a physical exercise programme in iNPH. Another aim was to evaluate the patient’s self-experienced outcome after surgery. Methods and results, study I In total 127 patients were randomised to either a supervised 12-week high-intensity exercise programme or to standard care after shunt surgery. Evaluation was performed with the iNPH scale and goal attainment after the intervention and after six months. There was low compliance to the exercise programme and no differences between the groups could be detected according to the iNPH scale at any of the follow-ups. Patients with high attendance rate achieved their set goals to a higher extent than the control group at the post intervention follow-up. Methods and results, study II In total 109 patients from the population in study I, were evaluated with an actigraphy recording of physical activity variables for seven days before and three- and six months after shunt surgery. In addition, physical performance was evaluated with the 10-meter walk test, the 6-minute walk test and 30 s chair stand test. The patients walked faster with improved results on the walking tests postoperatively. Improvement in the 30 s chair stand test was interpreted as improved postural control. The physical activity intensity was not affected by surgery. The patients had very low energy expenditure and were to a large extent sedentary, before and after shunt surgery. The exercise intervention had no effect on physical activity or the physical performance tests. Methods and results, study III In total 47 patients were included to a gait analysis with an inertial sensor system. Additionally, the patients were assessed with the Timed Up and Go test and the iNPH scale, pre- and three months postoperatively and in relation with 42 older healthy individuals. The patients walked with shorter strides, decreased velocity, increased time in stance and with decreased joint angles, especially in the ankle joint. The gait pattern im-proved after shunt surgery, but outcome on all variables were still worse compared to the healthy individuals, except for step hight that was normalised. Shunt surgery had no effect on stride length variability. Methods and results, study IV In total 58 patients rated their experienced changes three months after shunt surgery. The subjective outcome was analysed in relation to objective clinical outcomes (the iNPH scale) and questionnaires regarding, sense of coherence, quality of life, anxiety and depression. Clinical outcome and the questionnaires were evaluated before and three months after shunt surgery and in relation to 42 older healthy individuals. The patients reported most frequently some degree of positive changes after surgery. The subjective outcomes in overall experience, gait and continence correlated moderately with the corresponding objective outcomes, but there were not correlations within the cognition and balance areas. Depression and quality of life improved after surgery, but the result was still lower than for healthy individuals. There was no correlation between the patients´ sense of coherence and the subjective outcome. Conclusion Shunt surgery contributes to improved walking patterns, improved physical functions, reduced signs of depression and increased quality of life, but patients with iNPH are still more affected than healthy elderly. The patients report most frequently positive changes, but not total recovery after shunt surgery. Despite improvements within several areas the physical activity level is very low, both before and after the shunt operation. A postoperative high-intensity physical training program had no additional effect, which is explained by the fact that few patients completed the program. Patients with iNPH probably need guidance to additional improvement and to increase physical activity through meaningful activities after shunt surgery. Further research is needed to evaluate interventions that address the specific iNPH impairments.
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| 43. |
- Rydja, Johanna, et al.
(författare)
-
Physical Capacity and Activity in Patients With Idiopathic Normal Pressure Hydrocephalus
- 2022
-
Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Most patients with idiopathic normal pressure hydrocephalus (iNPH) improve gait after surgery. However, knowledge on physical capacity and activity after shunt surgery is limited. One of the aims of this study was to evaluate the effect of shunt surgery in patients with iNPH on short-distance walking, functional exercise capacity, functional strength, and variables of activity and sleep, 3 and 6 months postoperatively. Another aim was to evaluate the effect of a physical exercise program. Additionally, we studied how changes in short-distance walking were correlated with functional exercise capacity and voluntary walking.& nbsp;Methods: In total, 127 patients were consecutively included and randomized to the exercise group (n = 62) or the control group (n = 65). Participants in the exercise group underwent the supervision of a 12-week exercise program. All patients were assessed before surgery, at 3 and 6 months postoperatively with the 10-m walk test (10MWT), the 6-min walk test (6MWT), 30-s chair stand test (30sCST), and with the actigraphic recordings of activity variables measured for a total of 24 h/day for at least 3 days.& nbsp;Results: All patients improved at 3 months postoperatively in the 10MWT (p < 0.001), 6MWT (p < 0.001), and 30sCST (p < 0.001). These results were maintained after 6 months. Actigraphic recordings for voluntary walking (steps per minute) were improved and nighttime sleep (%) increased after 6 months (p = 0.01, p = 0.04). There were no significant differences between the exercise group and the control group, except for the postoperative change in the proportion of daytime sleep after 3 months, which was slightly more reduced compared to baseline in the exercise group (p = 0.04). Changes after 3 months in the 10MWT and 6MWT were moderately correlated (rho= -0.49, p = 0.01) whereas the correlation between the 10MWT and voluntary walking was weak (rho = -0.34, p = 0.01).& nbsp;Conclusion: Shunt surgery improved short-distance walking, functional exercise capacity, functional strength, and voluntary walking. An exercise program did not affect these outcomes. Short-distance walking was weakly correlated with voluntary walking, indicating improved physical capacity does not directly translate to increased physical activity. Further research should address how interventions should be tailored to promote physical activity after shunt surgery.
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| 44. |
- Rydja, Johanna, et al.
(författare)
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Physical exercise and goal attainment after shunt surgery in idiopathic normal pressure hydrocephalus: a randomised clinical trial
- 2021
-
Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Rehabilitation in iNPH is suggested to be an important factor to improve patients'functions but there are lack of clinical trials evaluating the effect of rehabilitation interventions after shunt surgery in iNPH. The objective of this study was to evaluate the effect of a physical exercise programme and goal attainment for patients with idiopathic normal pressure hydrocephalus (iNPH) after surgery compared to a control group. Methods: This was a dual centre randomised controlled trial with assessor blinding, intention-to-treat (ITT) and per protocol (PP) analysis. Individuals diagnosed with iNPH scheduled to undergo shunt surgery at the Linkoping University Hospital in Linkoping and Sahlgrenska University Hospital in Gothenburg, Sweden were consecutively eligible for inclusion. Inclusion was conducted between January 2016 and June 2018. The patients were randomised 1:1 using sequentially numbered sealed envelopes to receive either written exercise information (control group) or written information and an additional supervised high-intensity, functional exercise programme (HIFE) executed twice weekly over 12 weeks (exercise group). Preoperatively, the patients set individual goals. The primary outcome was change from baseline in the total iNPH scale score at the post-intervention follow-up. Secondary outcomes were goal attainment, and change in the separate scores of gait, balance, neuropsychology and continence and in the total score after 6 months. Results: In total, 127 participants were randomised to the exercise group (n = 62) and to the control group (n=65). In the ITT population (exercise group, n =50; control group, n=59), there were no between-group differences in the primary outcome, but the attrition rate in the exercise group was high. The exercise group improved more than the control group in the balance domain scores after 6 months. Post-intervention, the PP exercise population achieved their set goals to a greater extent than the controls. Conclusions: An additional effect of the 12-week HIFE-programme on the overall improvement according to the iNPH-scale after shunt surgery in iNPH was not shown. This could be due to high attrition rate. However, the longterm effect on balance and higher goal achievement indicate beneficial influences of supervised physical exercise.
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| 45. |
- Shu, Rui, et al.
(författare)
-
Multicomponent TixNbCrAl nitride films deposited by dc and high-power impulse magnetron sputtering
- 2021
-
Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 426
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Tidskriftsartikel (refereegranskat)abstract
- Multicomponent TixNbCrAl nitride films were deposited on Si(100) substrates by reactive direct current magnetron sputtering (dcMS) and high power impulse magnetron sputtering (HiPIMS) in the absence of substrate heating and bias. Three single Ti, Nb, and Cr50Al50 targets were either driven by three de or three HiPIMS power supplies. The Ti content in the films was varied by tuning the power applied to the Ti target. The composition was determined by ion beam analysis. The nitrogen content is nearly stoichiometric (48-50 at.%) in the HiPIMS series, while the dcMS are understoichiometric (39-45 at.%). The crystal structure, stress and density of the studied film were investigated by X-ray techniques and the microstructure was examined by scanning electron microscopy. All the Ti-containing films for both series exhibit an fcc NaCl-type phase structure. In particular, the dcMS series shows a (111) preferred orientation, resulting in a faceted surface morphology compared to a dense and smooth microstructure of the HiPIMS films. The compressive stress of the HiPIMS series (> 2.0 GPa) is significantly larger than the values of the dcMS series (<0.5 GPa). Nanoindentation measurements show a maximum hardness of 29.9 GPa and Young's modulus of 304 GPa were obtained in the HiPIMS series. The results may promote HiPIMS techniques for the synthesis of complex multicomponent films for the application aspect to protective and hard coatings.
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| 46. |
- Smedler, Erik, et al.
(författare)
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Cerebrospinal fluid and serum protein markers in autism: A co-twin study.
- 2021
-
Ingår i: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 158:3, s. 798-806
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Tidskriftsartikel (refereegranskat)abstract
- No robust biomarkers have yet been identified for autism spectrum disorder (ASD) or autistic traits. Familial factors likely influence biomarkers such as protein concentrations. Comparing twins with ASD or high autistic traits to the less affected co-twin allows estimating the impact of familial confounding. We measured 203 proteins in cerebrospinal fluid (n=86) and serum (n=127) in twins (mean age 14.2years, 44.9% females) enriched for ASD and other neurodevelopmental conditions. Autistic traits were assessed by using the parent-report version of the Social Responsiveness Scale-2. In cerebrospinal fluid, autistic traits correlated negatively with three proteins and positively with one. In serum, autistic traits correlated positively with 15 and negatively with one. Also in serum, six were positively-and one negatively-associated with ASD. A pathway analysis of these proteins revealed immune system enrichment. In within twin pair analyses, autistic traits were associated with serum B-cell activating factor (BAFF) only, whereas Cystatin B (CSTB) remained significantly associated with ASD. These associations did not remain significant when only considering monozygotic twins. For the remainder, the within-pair analysis indicated familial confounding, including shared environment and genes, influencing both autism and protein levels. Our findings indicate proteins involved in immunity as putative biomarkers of autistic traits and ASD with partial genetic confounding. Although some results are in line with previous studies in general, further studies are needed for replication.
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| 47. |
- Soderhall, Cilla, et al.
(författare)
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A Case with Bladder Exstrophy and Unbalanced X Chromosome Rearrangement
- 2014
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Ingår i: European Journal of Pediatric Surgery. - : Georg Thieme Verlag KG. - 1439-359X .- 0939-7248. ; 24:4, s. 353-359
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Bladder exstrophy is a rare congenital malformation of the bladder and is believed to be a complex disorder with genetic and environmental background. We describe a young adult female with an isolated bladder exstrophy and with an X chromosome aberration. Patients and Methods Karyotyping identified an X chromosome rearrangement that was further characterized with array comparative genomic hybridization (CGH) and confirmed by multiplex ligation-dependent probe amplification and fluorescence in situ hybridization (FISH) analysis. Results The identified X chromosome rearrangement in our index patient consists of a gain of chromosomal material in region Xq26.3-> qter and loss in region Xp22.12->pter. This aberration was also carried by her mother and sister, none with bladder exstrophy. All three have a disproportionate short stature, as expected due to the deletion of one of the copies of the SHOX gene on Xp22.3. X-inactivation studies revealed a complete skewed inactivation pattern in carriers. Crossover events in the maternal germline furthermore resulted in different genetic material on the rearranged X chromosome between the index patient and her sister. Conclusion Our findings suggest an X-linked genetic risk factor for bladder exstrophy.
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| 48. |
- Stenman, Sebastian, et al.
(författare)
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Antibody Supervised Training of a Deep Learning Based Algorithm for Leukocyte Segmentation in Papillary Thyroid Carcinoma
- 2021
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Ingår i: IEEE journal of biomedical and health informatics. - : Institute of Electrical and Electronics Engineers (IEEE). - 2168-2194 .- 2168-2208. ; 25:2, s. 422-428
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Tidskriftsartikel (refereegranskat)abstract
- The quantity of leukocytes in papillary thyroid carcinoma (PTC) potentially have prognostic and treatment predictive value. Here, we propose a novel method for training a convolutional neural network (CNN) algorithm for segmenting leukocytes in PTCs. Tissue samples from two retrospective PTC cohort were obtained and representative tissue slides from twelve patients were stained with hematoxylin and eosin (HE) and digitized. Then, the HE slides were destained and restained immunohistochemically (IHC) with antibodies to the pan-leukocyte anti CD45 antigen and scanned again. The two stain-pairs of all representative tissue slides were registered, and image tiles of regions of interests were exported. The image tiles were processed and the 3,3'-diaminobenzidine (DAB) stained areas representing anti CD45 expression were turned into binary masks. These binary masks were applied as annotations on the HE image tiles and used in the training of a CNN algorithm. Ten whole slide images (WSIs) were used for training using a five-fold cross-validation and the remaining two slides were used as an independent test set for the trained model. For visual evaluation, the algorithm was run on all twelve WSIs, and in total 238,144 tiles sized 500 x 500 pixels were analyzed. The trained CNN algorithm had an intersection over union of 0.82 for detection of leukocytes in the HE image tiles when comparing the prediction masks to the ground truth anti CD45 mask. We conclude that this method for generating antibody supervised annotations using the destain-restain IHC guided annotations resulted in high accuracy segmentations of leukocytes in HE tissue images.
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| 49. |
- Sundström, Nina, et al.
(författare)
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The timed up and go test in idiopathic normal pressure hydrocephalus : a Nationwide Study of 1300 patients
- 2022
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Ingår i: Fluids and Barriers of the CNS. - London, United Kingdom : BioMed Central. - 2045-8118. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to describe the outcome measure timed up and go (TUG) in a large, nationwide cohort of patients with idiopathic normal pressure hydrocephalus (iNPH) pre- and post-operatively. Furthermore, to compare the TUG test to the 10-m walk test (10MWT), the iNPH scale, the modified Rankin scale (mRS) and the Mini Mental State Examination (MMSE), which are commonly applied in clinical assessment of iNPH.Methods: Patients with iNPH (n = 1300), registered in the Swedish Hydrocephalus Quality Registry (SHQR), were included. All data were retrieved from the SHQR except the 10MWT, which was collected from patient medical records. Clinical scales were examined pre- and 3 months post-operatively. Data were dichotomised by sex, age, and preoperative TUG time.Results: Preoperative TUG values were 19.0 [14.0–26.0] s (median [IQR]) and 23 [18–30] steps. Post-operatively, significant improvements to 14.0 [11.0–20.0] s and 19 [15–25] steps were seen. TUG time and steps were higher in women compared to men (p < 0.001) but there was no sex difference in improvement rate. Worse preoperative TUG and younger age favoured improvement. TUG was highly correlated to the 10MWT, but correlations of post-operative changes were only low to moderate between all scales (r = 0.22–0.61).Conclusions: This study establishes the distribution of TUG in iNPH patients and shows that the test captures important clinical features that improve after surgery independent of sex and in all age groups, confirming the clinical value of the TUG test. TUG performance is associated with performance on the 10MWT pre- and post-operatively. However, the weak correlations in post-operative change to the 10MWT and other established outcome measures indicate an additional value of TUG when assessing the effects of shunt surgery.
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| 50. |
- Thelaus, Johanna, et al.
(författare)
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Network Experiences from a Cross-Sector Biosafety Level-3 Laboratory Collaboration : A Swedish Forum for Biopreparedness Diagnostics
- 2017
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Ingår i: Health Security. - : Mary Ann Liebert. - 2326-5094 .- 2326-5108. ; 15:4, s. 384-391
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Forum for Biopreparedness Diagnostics (FBD) is a network that fosters collaboration among the 4 agencies with responsibility for the laboratory diagnostics of high-consequence pathogens, covering animal health and feed safety, food safety, public health and biodefense, and security. The aim of the network is to strengthen capabilities and capacities for diagnostics at the national biosafety level-3 (BSL-3) laboratories to improve Sweden's biopreparedness, in line with recommendations from the EU and WHO. Since forming in 2007, the FBD network has contributed to the harmonization of diagnostic methods, equipment, quality assurance protocols, and biosafety practices among the national BSL-3 laboratories. Lessons learned from the network include: (1) conducting joint projects with activities such as method development and validation, ring trials, exercises, and audits has helped to build trust and improve communication among participating agencies; (2) rotating the presidency of the network steering committee has fostered trust and commitment from all agencies involved; and (3) planning for the implementation of project outcomes is important to maintain gained competencies in the agencies over time. Contacts have now been established with national agencies of the other Nordic countries, with an aim to expanding the collaboration, broadening the network, finding synergies in new areas, strengthening the ability to share resources, and consolidating long-term financing in the context of harmonized European biopreparedness.
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