| 1. |
|
|
| 2. |
|
|
| 3. |
- Felton, Adam, et al.
(författare)
-
Forest biodiversity and ecosystem services from spruce-birch mixtures : The potential importance of tree spatial arrangement
- 2022
-
Ingår i: Environmental Challenges. - : Elsevier BV. - 2667-0100. ; 6
-
Forskningsöversikt (refereegranskat)abstract
- There is increasing empirical support for the biodiversity and ecosystem service (ES) benefits of mixed-species production forests. However, few studies control for the spatial arrangement of the trees within mixtures to determine the influence that clustering the tree species (patch scale mixtures), versus evenly dispersing them (intimate scale mixtures), may have for biodiversity and ES outcomes. To highlight the potential implications of altering tree spatial arrangement in mixtures, and the need to fill related knowledge gaps, here we provide a qualitative multi-disciplinary overview of ecological and socio-economic drivers with the potential to alter biodiversity, ecosystem services, and management-related outcomes from patch versus intimate scale mixtures. We focused our overview on even-aged mixtures of Norway spruce (Picea abies) and birch (Betula pendula or B. pubescens) in Sweden, which enabled us to contrast findings within a biogeographical and silvicultural setting. Specifically, we targeted implications for biodiversity (understory vascular plants, epiphytic lichens, saproxylic beetles, birds), biomass production, harvesting costs, management ease, recreation and aesthetics, cervid game, as well as abiotic and biotic risks (wind, fire, pathogens, pests, browsing damage). In the absence of direct empirical evidence, we primarily relied on expert inference from theory and relevant empirical studies sourced from the Fennoscandian region, and further afield if needed. Collectively these efforts allowed us to develop a number of informed hypotheses indicating that for spruce-birch mixtures in this region, patch scale mixtures may have the potential to favour the diversity of several forest dependant taxonomic groups, cervid game and reduce harvesting costs, whereas intimate mixtures may have the potential to reduce pathogen and pest damage, and likewise, potentially benefit production outcomes. Current knowledge was too limited, inconsistent or context dependant to even tentatively infer outcomes for fire risk, wind damage, browsing damage, management ease, recreational and aesthetic outcomes. We emphasize that our hypotheses require testing, but are sufficient to (1) highlight the likely importance of spatial-scale to biodiversity and ecosystem services outcomes in mixed-species production forests, (2) caution against generalization from mixture studies that lack scale considerations, and (3) motivate the targeted consideration of spatial grain in future mixture studies.
|
|
| 4. |
|
|
| 5. |
- Parnetti, L, et al.
(författare)
-
Changes in CSF acetyl- and butyrylcholinesterase activity after long-term treatment with AChE inhibitors in Alzheimer's disease.
- 2011
-
Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 124:2, s. 122-129
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives - To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs). Materials and methods - Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1-year treatment. Results - Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment. Conclusions - AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Agestam, E, et al.
(författare)
-
Productivity scenarios for the Asa Forest Park
- 2002
-
Ingår i: Developing principles and models for sustainable forestry in Sweden. - 1402009992 ; , s. 355-380
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 10. |
|
|
| 11. |
- Austeng, Dordi, et al.
(författare)
-
Incidence of and risk factors for neonatal morbidity after active perinatal care : extremely preterm infants study in Sweden (EXPRESS)
- 2010
-
Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:7, s. 978-992
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
|
|
| 12. |
- Backman, Sofia, et al.
(författare)
-
Swedish consensus reached on recording, interpretation and reporting of neonatal continuous simplified electroencephalography that is supported by amplitude-integrated trend analysis
- 2018
-
Ingår i: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 107:10, s. 1702-1709
-
Tidskriftsartikel (refereegranskat)abstract
- Continuous monitoring of electroencephalography (EEG), with a focus on amplitude-integrated EEG (aEEG), has been used in neonatal intensive care for decades. A number of systems have been suggested for describing and quantifying aEEG patterns. Extensive full-montage EEG monitoring is used in specialised intensive care units. The American Clinical Neurophysiology Society published recommendations for defining and reporting EEG findings in critically ill adults and infants. Swedish neonatologists and clinical neurophysiologists collaborated to optimise simplified neonatal continuous aEEG and EEG recordings based on these American documents. Conclusion: This paper describes the Swedish consensus document produced by those meetings.
|
|
| 13. |
- Baussan, E., et al.
(författare)
-
A very intense neutrino super beam experiment for leptonic CP violation discovery based on the European spallation source linac
- 2014
-
Ingår i: Nuclear Physics B. - : Elsevier BV. - 0550-3213 .- 1873-1562. ; 885, s. 127-149
-
Tidskriftsartikel (refereegranskat)abstract
- Very intense neutrino beams and large neutrino detectors will be needed in order to enable the discovery of CP violation in the leptonic sector. We propose to use the proton linac of the European Spoliation Source currently under construction in Lund, Sweden, to deliver, in parallel with the spoliation neutron production, a very intense, cost effective and high performance neutrino beam. The baseline program for the European Spoliation Source linac is that it will be fully operational at 5 MW average power by 2022, producing 2 GeV 2.86 ms long proton pulses at a rate of 14 Hz. Our proposal is to upgrade the linac to 10 MW average power and 28 Hz, producing 14 pulses/s for neutron production and 14 pulses/s for neutrino production. Furthermore, because of the high current required in the pulsed neutrino horn, the length of the pulses used for neutrino production needs to be compressed to a few mu s with the aid of an accumulator ring. A long baseline experiment using this Super Beam and a megaton underground Water Cherenkov detector located in existing mines 300-600 km from Lund will make it possible to discover leptonic CP violation at 5 sigma significance level in up to 50% of the leptonic Dirac CP-violating phase range. This experiment could also determine the neutrino mass hierarchy at a significance level of more than 3 sigma if this issue will not already have been settled by other experiments by then. The mass hierarchy performance could be increased by combining the neutrino beam results with those obtained from atmospheric neutrinos detected by the same large volume detector. This detector will also be used to measure the proton lifetime, detect cosmological neutrinos and neutrinos from supernova explosions. Results on the sensitivity to leptonic CP violation and the neutrino mass hierarchy are presented.
|
|
| 14. |
- Blennow, Jörgen, 1966, et al.
(författare)
-
Active High Voltage Insulation
- 2002
-
Ingår i: Journal of Electrostatics. ; 55:2, s. 159-172
-
Tidskriftsartikel (refereegranskat)
|
|
| 15. |
- Blennow, Mats, et al.
(författare)
-
Fosterasfyxi
- 2008
-
Ingår i: Lärobok i obstetrik. Redaktörer: Marsal, Karel, Hagberg, Henrik, Westgren, Magnus. - : Studentlitteratur. - 9789144007311 ; , s. 235-242
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 16. |
|
|
| 17. |
- Blennow, Mats, et al.
(författare)
-
Omhändertagande av det asfyktiska barnet
- 2008
-
Ingår i: Lärobok i neonatologi. Redaktörer: Lagercrantz, H; Hellström-Vestas, L; Norrman, M. - : Studentlitteratur. - 9789144046433 ; , s. 57-76
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 18. |
|
|
| 19. |
- Dempsey, Tina, et al.
(författare)
-
Endotracheal intubation performance at a large obstetric hospital delivery room, Hanoi, Vietnam
- 2022
-
Ingår i: Resuscitation Plus. - : Elsevier. - 2666-5204. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Intrapartum-related events account for nearly 700,000 neonatal deaths globally yearly. Endotracheal intubation is a cornerstone in preventing many of these deaths, but it is a difficult skill to acquire. Previous studies have described intubation performances in high-income coun-tries, but data from low-and middle-income countries are lacking. We aimed to assess the performance of delivery room intubation in a lower middle -income country.Methods: This prospective observational study was conducted at the Phu San Hanoi Hospital, Vietnam, from September 2020 to January 2021. Video cameras were positioned above the resuscitation tables and data were extracted using adopted software (NeoTapAS). All neonates requiring positive pressure ventilation were included. Our main variables of interest were time to first intubation attempt, first intubation attempt duration, and successful first intubation attempt.Results: 18,107 neonates were born during the five months. Of these, 75 (0.4%) received positive pressure ventilation, and 36 (0.2%) required endotracheal intubation of whom 24 were captured on video. The median time to the first intubation attempt was 252 seconds (range 91-771 sec-onds), the median first attempt duration was 49 seconds (range 10-105 seconds), and the first attempt success rate was 75%.Conclusion: Incidences of positive pressure ventilation and endotracheal intubation were low in comparison to global estimates. Three out of four intubations were successful at the first attempt and the procedural duration was often longer than recommended. Future studies should focus on how to achieve and maintain intubation skills and could include considering alternative devices for airway management at birth.
|
|
| 20. |
- Dempsey, Tina, et al.
(författare)
-
Incidence of Intrapartum-Related Events at the Largest Obstetric Hospital in Hanoi, Vietnam : A Retrospective Study
- 2022
-
Ingår i: Children. - : MDPI AG. - 2227-9067. ; 9:3
-
Tidskriftsartikel (refereegranskat)abstract
- Every year, 2.4 million neonates die during their first month of life and even more suffer permanent injury. The main causes are intrapartum-related events, prematurity, and infection, with sub-Saharan Africa and southern Asia being the worst affected regions. With a focus on intrapartum-related events, we aimed to assess the neonatal demographic characteristics, clinical management, and outcomes among neonates born at the largest obstetric hospital in Hanoi, Vietnam. This was a retrospective cross-sectional study that included all the inborn neonates in November 2019, which was selected as a representative month. A total of 4554 neonates were born during the study period. Of these, 1.0% (n = 44) were stillbirths, 0.15% (n = 7) died in hospital, 0.61% (n = 28) received positive pressure ventilation at birth, and 0.15% (n = 7) were diagnosed with hypoxic ischemic encephalopathy. A total of 581 (13%) neonates were admitted to the neonatal unit, among which the most common diagnoses were prematurity (37%, n = 217) and infection (15%, n = 89). Except for the intrapartum-related events, our findings are consistent with the previously documented data on neonatal morbidity. The intrapartum-related events, however, were surprisingly low in number even in comparison to high-income countries. Research on the current clinical practice at Phu San Hanoi Hospital may bring further clarity to identify the success factors.
|
|
| 21. |
- Dsilna, Ann, et al.
(författare)
-
Continuous feeding promotes gastrointestinal tolerance and growth in very low birth weight infants
- 2005
-
Ingår i: Journal of Pediatrics. - : Elsevier BV. - 0022-3476 .- 1097-6833. ; 147:1, s. 43-49
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the effects of continuous versus intermittent feeding on gastrointestinal tolerance and growth in very low birth weight (VLBW) infants. STUDY DESIGN: In a randomized, controlled trial conducted at 3 neonatal units, 70 premature infants with a gestational age 24 to 29 weeks and birth weight < 1200 g were assigned to 1 of 3 feeding methods: continuous nasogastric feeding, intermittent nasogastric feeding, or intermittent orogastric feeding. Feeding was initiated within 30 hours of birth. Daily enteral and parenteral volumes, caloric and protein intakes, growth, enteral intolerance, and clinical complications were recorded. Cox regression analysis was used to determine primary outcome, the time to achieve full enteral feeding. RESULTS: The continuously fed infants achieved full enteral feeding significantly faster than the intermittently fed infants (hazard ratio [HR] = 1.86; 95% confidence interval [CI] = 1.07 to 3.22). In stratified analysis according to birth weight, the improvement was even more pronounced in the smallest infants, those with birth weight < or = 850 g (adjusted HR = 4.13; 95% CI = 1.48 to 11.53). Growth rate was significantly faster in the continuously fed infants ( P = .002). CONCLUSION: In VLBW infants, continuous feeding seems to be better than intermittent feeding with regard to gastrointestinal tolerance and growth.
|
|
| 22. |
- Edsbagge, Mikael, et al.
(författare)
-
Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not Correlate with CSF Volumes or CSF Production Rate.
- 2017
-
Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 58:3, s. 821-828
-
Tidskriftsartikel (refereegranskat)abstract
- Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively.To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals.CSF concentrations of Aβ42, P-tau, and T-tau, as well as a number of other AD-related CSF biomarkers were analyzed together with intracranial subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic resonance imaging volumetric measurements, and CSF production rate in 19 cognitively normal healthy subjects (mean age 70.6, SD 3.6 years).Negative correlations were seen between the concentrations of three CSF biomarkers (albumin ratio, Aβ38, and Aβ40), and ventricular CSF volume, but apart from this finding, no significant correlations were observed.These results speak against inter-individual variations in CSF volume and production rate as important confounds in the AD biomarker research field.
|
|
| 23. |
- Eriksson, Sandra, 1979-
(författare)
-
Direct Driven Generators for Vertical Axis Wind Turbines
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Wind power is a renewable energy source that is increasingly used all over the world. Most wind turbines have a horizontal axis of rotation but a few have a vertical axis of rotation. The concept presented in this thesis is a straight-bladed vertical axis wind turbine with a direct driven cable-wound permanent magnet synchronous generator. A comparison of the two different types of wind turbines, vertical axis wind turbines and horizontal axis wind turbines, have been performed considering several different aspects. However, the main focus in this thesis is on the generator. Several generators have been modelled with a combined field and circuit model, which has been solved by using the finite element method. A 12 kW generator has been designed, which has a high overall efficiency and a high overload capability. The generator has been constructed at the department and was tested in the laboratory before being mounted in a vertical axis wind turbine. Results from experiments correspond well with results from simulations. The generator has been tested for different loading conditions and the harmonic content of the voltage has been analysed. A 12 kW vertical axis wind turbine was completed and tests have been performed. The results are encouraging and further studies on the prototype will be performed in the future. The simulation method has been used to study electromagnetic losses in several generators. The comparison showed that the average losses should be considered when a variable speed generator for wind power is designed and it concluded that the design optimization process becomes a compromise between lowering the electromagnetic losses and having high overload capability. When constructing a wind turbine, it is important to consider vibrations in the structure. Torsional vibrations in the drive shaft connecting the turbine to the rotor of the generator have been studied. It is shown that a direct driven generator is to prefer over an induction generator with a gearbox when torsional vibrations are concerned. This thesis is based on eight papers all concerning vertical axis wind turbines with three of them focusing on the generator.
|
|
| 24. |
- Fatima, Tahzeeb, et al.
(författare)
-
Association between serum urate and CSF markers of Alzheimer's disease pathology in a population-based sample of 70-year-olds
- 2021
-
Ingår i: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. - : Wiley. - 2352-8729. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The relationship between urate and biomarkers for Alzheimer's disease (AD) pathophysiology has not been investigated. Methods: We examined whether serum concentration of urate was associated with cerebrospinal fluid biomarkers, amyloid beta (A beta)(42), A beta(40), phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), and A beta(42)/A beta(40) ratio, in cognitively unimpaired 70-year-old individuals from Gothenburg, Sweden. We also evaluated whether possible associations were modulated by the apolipoprotein E (APOE) epsilon 4 allele. Results: Serum urate was positively associated with A beta(42) in males (beta = 0.55 pg/mL, P = .04). There was a positive urate-APOE epsilon 4 interaction (1.24 pg/mL, P-interaction = .02) in relation to A beta(42) association. The positive urate and A beta(42) association strengthened in male APOE epsilon 4 carriers (beta = 1.28 pg/mL, P = .01). Discussion: The positive association between urate and A beta(42) in cognitively healthy men may suggest a protective effect of urate against deposition of amyloid protein in the brain parenchyma, and in the longer term, maybe against AD dementia.
|
|
| 25. |
- Fellman, Vineta, et al.
(författare)
-
One-year survival of extremely preterm infants after active perinatal care in Sweden.
- 2009
-
Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 301:21, s. 2225-33
-
Tidskriftsartikel (refereegranskat)abstract
- Up-to-date information on infant survival after extremely preterm birth is needed for assessing perinatal care services, clinical guidelines, and parental counseling.
|
|
| 26. |
|
|
| 27. |
- Gatenholm, Birgitta, 1986, et al.
(författare)
-
Peptidomic analysis of cartilage and subchondral bone in OA patients
- 2019
-
Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 49:5
-
Tidskriftsartikel (refereegranskat)abstract
- © 2019 Stichting European Society for Clinical Investigation Journal Foundation Background: The objective of this study was to develop a method for directly analysing osteochondral samples straight out of the operating room without cell culturing, thereby enabling identification of potential peptide biomarkers to better understand the mechanisms involved in the development of osteoarthritis and pain. Material and Methods: Osteochondral plugs from wounded and macroscopically nonwounded zones of the femur condyle were collected from six patients with manifest osteoarthritis (OA) undergoing total knee arthroplasty (TKA). The samples were demineralized and supernatant was collected and isotopically marked with Tandem Mass Tag (TMT) labelling and analysed using liquid chromatography coupled with tandem mass spectrometry LC-MS/MS. Results: Using peptidomics, 6292 endogenous peptides were identified. Five hundred sixty-six peptides (8 identified endogenous peptides) differed significantly (P-value 0.10) from wounded zones compared to nonwounded zones. Conclusion: This pilot study shows promising results for enabling peptidomic analysis of cartilage and bone straight out of the operating room. With further refinement, peptidomics can potentially become a diagnostic tool for OA, and improve the knowledge of disease progression and genesis of pain.
|
|
| 28. |
- Gillgren, T., et al.
(författare)
-
Modulating rheo-kinetics of native starch films towards improved wet-strength
- 2011
-
Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 83:2, s. 383-391
-
Tidskriftsartikel (refereegranskat)abstract
- Starch directly functionalised in the plant by modulation of its biosynthesis by mutagenesis and transgene technology was exploited for its extended functionality beyond the normal variation In this study we investigated the theological and mechanical properties of films from such structurally highly different starch types derived from potato and cereal sources of normal and mutant and transgenic backgrounds A new improved technique was developed to permit the dynamic mechanical analysis of films in the presence of water It was found that the amylose content was decisive for the mechanical properties of the films - an increase in the amylose content resulted in both a higher stress and strain at break Interestingly there was no correlation between the speed of hydration and mechanical water resistance of the films Generally the films were clear and transparent even after wetting Transgenic potato starch with a low content of phosphate displayed an extraordinary combination of high robustness transparency mechanical strength and extensibility even in a wet condition The combination of optimal phosphate and amylose concentrations in this sample probably favoured hydration and amorphisation without compromising the inter-chain interactions of the polysaccharide network.
|
|
| 29. |
- Grønning, Rebecca, et al.
(författare)
-
Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus
- 2023
-
Ingår i: Fluids and Barriers of the CNS. - : BioMed Central (BMC). - 2045-8118. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes. Methods: In 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aβ38), Aβ40, Aβ42, amyloid beta 42/40 ratio (Aβ42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPβ, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin. Results: The neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365ng/L (IQR 186–544) vs 330 (205–456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R2 = 0.06, p = 0.047. The Aβ42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aβ ratio group (median 25, IQR 23–28) compared to the high subgroup (26, 24–29) (p = 0.028). The T-Tau x Aβ40/42 ratio and P-tau x Aβ40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response. Discussion: A higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome.
|
|
| 30. |
- Heinonen, Essi, et al.
(författare)
-
MAGDALENA : study protocol of a randomised, placebo-controlled trial on cognitive development at 2 years of age in children exposed to SSRI in utero
- 2018
-
Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 8:8
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Ten per cent of all pregnant women are depressed. Standard therapy of pregnant women with moderate depression is selective serotonin reuptakeinhibitors (SSRI). Observational studies on neurodevelopment after fetal SSRI exposure show conflicting results. Our primary objective is to compare the cognitive development in children exposed to sertraline and maternal depression with those exposed to maternal depression and placebo in utero. We hypothesise that there is a significant neurodevelopmental difference between the groups. As a secondary objective, we study the add-on effect of sertraline to internet-based cognitive behavioural therapy (ICBT) to treat moderate depression during pregnancy. Methods and analysis MAGDALENA is a randomised, placebo-controlled, double-blinded trial in Stockholm Healthcare Region with 2.3 million inhabitants. The women are recruited in weeks 9-21 of pregnancy either through Antenatal Health Clinics or through social media. They are to be diagnosed with moderate depression without ongoing antidepressive therapy or any serious comorbidity. The women in the intervention arm receive sertraline combined with a 12-week period of ICBT; the control arm is treated with placebo and ICBT. We assess the cognitive development in the offspring at the age of 2 years using Bayley Scales of Infant and Toddler Development, third edition (BSID-III). We aim at recruiting 200 women, 100 women in each treatment arm, to ensure statistical power to detect a clinically relevant difference between the groups. Ethics and dissemination This randomised trial will provide long-sought evidence about the effects of SSRI and maternal depression during pregnancy on the neurodevelopment in the offspring. The study is approved by the Regional Ethical Review Board at Karolinska Institutet in Stockholm and the Swedish Medical Products Agency. It is registered with the European Clinical Trials Database (EudraCT), Number: 2013-004444-31. Results will be disseminated at scientific conferences, published in peer-reviewed journals and made available to the public.
|
|
| 31. |
|
|
| 32. |
- Jakobsson, Joel, et al.
(författare)
-
Decreased cerebrospinal fluid secretogranin II concentrations in severe forms of bipolar disorder.
- 2013
-
Ingår i: Journal of psychiatry & neuroscience : JPN. - : CMA Joule Inc.. - 1488-2434 .- 1180-4882. ; 38:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Bipolar disorder is a common psychiatric mood disorder that is defined by recurrent episodes of abnormally elevated mood and depression. Progressive structural brain changes in individuals with bipolar disorder have been suggested to be associated with defects in the secretion of neurotrophic factors. We sought to assess how the regulated secretory pathway in the brain is affected in patients with bipolar disorder by measuring chromogranin B and secretogranin II, which are 2 cerebrospinal fluid (CSF) biological markers for this process. Methods: We measured the concentrations of chromogranin B (peptide 439-451) and secretogranin II (peptide 154-165) in the CSF of patients with well-defined bipolar disorder and healthy controls. The lifetime severity of bipolar disorder was rated using the Clinical Global Impression (CGI) scale. Results: We included 126 patients with bipolar disorder and 71 healthy controls in our analysis. Concentrations of secretogranin II were significantly lower in patients with bipolar disorder type I than in healthy controls. The reduction was most pronounced in patients with high CGI scores (i.e., severe disease). Limitations: The cross-sectional design of the current study limits the ability to pinpoint the causalities behind the observed associations. Conclusion: This study shows that the CSF marker secretogranin II has the potential to act as a biological marker for severe forms of bipolar disorder. Our findings indicate that patients with bipolar disorder possess defects in the regulatory secretory pathway, which may be of relevance to the progressive structural brain changes seen in those with severe forms of the disease.
|
|
| 33. |
- Jarvid, Markus, 1985, et al.
(författare)
-
Evaluation of the Performance of Several Object Types for Electrical Treeing Experiments
- 2013
-
Ingår i: IEEE Transactions on Dielectrics and Electrical Insulation. - 1558-4135 .- 1070-9878. ; 20:5, s. 1712-1719
-
Tidskriftsartikel (refereegranskat)abstract
- A comparison of the efficiency of various types of object for studying the development of electrical trees in polymers is presented. Two types of newly developed wire-plane objects are investigated and compared with two versions of the traditionally used needle-needle objects. The two needle-needle objects are prepared according to ASTM standard and act as references, whereas the alternative objects rely on use of an ultra-thin tungsten wire (10 and 20 µm) in the test objects for providing the highly divergent electric stress. In one type of those object the wire extends from a semiconducting tab embedded in the tested material, while in the other type, the embedded wire is extended and connected externally by means of a copper tape. The comparison is made using cross linked polyethylene (XLPE) for the testing purposes. The wire type objects provide some promising advantages, including parallel formation of several electrical trees and an exposure of a larger material volume. Further advantages include the considerable simplification of both the manufacturing and the measuring procedures. Among the newly developed test objects, the one without the semiconducting tab is considered most advantageous as it allows for more accurate treeing initiation measurements at a lower voltage level. On the other hand the disadvantage is a formation of kinks on the wire that results from polyethylene shrink during sample preparation, which may yield some difficulties in correctly estimating the local field strength locally as well as straining the surrounding material. However the multitude of electric trees formed in each sample allows to easily discard the trees growing at such imperfections in following data analyses. Although finding a statistical method that makes good use of all the data poses a challenge, a suggested approach is presented.
|
|
| 34. |
- Jeppsson, Anna, et al.
(författare)
-
Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus
- 2016
-
Ingår i: Fluids and Barriers of the Cns. - : Springer Science and Business Media LLC. - 2045-8118. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with idiopathic normal pressure hydrocephalus (iNPH) have reduced cerebrospinal fluid (CSF) concentrations of amyloid-beta (A beta) and alpha- and beta-cleaved soluble forms of amyloid precursor protein (sAPP alpha and sAPP beta). The aims of this study were to examine if changes could also be seen in the CSF for secreted metabolites of APP-like protein 1 (APLP1) and to explore the prognostic value of amyloid-related CSF biomarkers, as well as markers of neuronal injury and astroglial activation, as regards to clinical outcome after shunt surgery. Methods: Twenty patients diagnosed with iNPH, 10 improved and 10 unchanged by shunt surgery, and 20 neurologically healthy controls were included. All patients were examined clinically prior to surgery and at 6-month follow-up after surgery using the iNPH scale. Lumbar puncture was performed pre-operatively. CSF samples were analyzed for neurofilament light (NFL), A beta isoforms A beta 38, A beta 40 and A beta 42, sAPP alpha, sAPP beta, APLP1 beta-derived peptides APL1 beta 25, APL1 beta 27 and APL1 beta 28 and YKL40 by immunochemical methods. Results: The concentrations of all soluble forms of APP, all A beta isoforms and APL1 beta 28 were lower, whilst APL1 beta 25 and APL1 beta 27 were higher in the CSF of iNPH patients compared to controls. There was no difference in biomarker concentrations between patients who improved after surgery and those who remained unchanged. Conclusions: The reduced CSF concentrations of A beta 38, A beta 40, A beta 42, sAPPa and sAPP beta suggest that APP expression could be downregulated in iNPH. In contrast, APLP1 concentration in the CSF seems relatively unchanged. The increase of APL1 beta 25 and APL1 beta 27 in combination with a slight decreased APL1 beta 28 could be caused by more available gamma-secretase due to reduced availability of its primary substrate, APP. The data did not support the use of these markers as indicators of shunt responsiveness.
|
|
| 35. |
- Jeppsson, Anna, et al.
(författare)
-
CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics
- 2019
-
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 90:10, s. 1117-1123
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer's disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. Methods: The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson's disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer's disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1). Results: Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers. Conclusions: The combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
|
|
| 36. |
- Jeppsson, Anna, et al.
(författare)
-
Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus
- 2023
-
Ingår i: Fluids and Barriers of the CNS. - 2045-8118. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Neurofilament light chain protein (NFL), a marker of neuronal axonal degeneration, is increased in cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). Assays for analysis of NFL in plasma are now widely available but plasma NFL has not been reported in iNPH patients. Our aim was to examine plasma NFL in iNPH patients and to evaluate the correlation between plasma and CSF levels, and whether NFL levels are associated with clinical symptoms and outcome after shunt surgery. Methods Fifty iNPH patients with median age 73 who had their symptoms assessed with the iNPH scale and plasma and CSF NFL sampled pre- and median 9 months post-operatively. CSF plasma was compared with 50 healthy controls (HC) matched for age and gender. Concentrations of NFL were determined in plasma using an in-house Simoa method and in CSF using a commercially available ELISA method. Results Plasma NFL was elevated in patients with iNPH compared to HC (iNPH: 45 (30-64) pg/mL; HC: 33 (26-50) (median; Q1-Q3), p = 0.029). Plasma and CSF NFL concentrations correlated in iNPH patients both pre- and postoperatively (r = 0.67 and 0.72, p < 0.001). We found only weak correlations between plasma or CSF NFL and clinical symptoms and no associations with outcome. A postoperative NFL increase was seen in CSF but not in plasma. Conclusions Plasma NFL is increased in iNPH patients and concentrations correlate with CSF NFL implying that plasma NFL can be used to assess evidence of axonal degeneration in iNPH. This finding opens a window for plasma samples to be used in future studies of other biomarkers in iNPH. NFL is probably not a very useful marker of symptomatology or for prediction of outcome in iNPH.
|
|
| 37. |
- Jeppsson, Anna, et al.
(författare)
-
Shared CSF Biomarker Profile in Idiopathic Normal Pressure Hydrocephalus and Subcortical Small Vessel Disease.
- 2022
-
Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we examine similarities and differences between 52 patients with idiopathic normal pressure hydrocephalus (iNPH) and 17 patients with subcortical small vessel disease (SSVD), in comparison to 28 healthy controls (HCs) by a panel of cerebrospinal fluid (CSF) biomarkers.We analyzed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ isoforms -38, -40, and -42, neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), matrix metalloproteinases (MMP -1, -2, -3, -9, and -10), and tissue inhibitors of metalloproteinase 1 (TIMP1). Radiological signs of white matter damage were scored using the age-related white matter changes (ARWMC) scale.All amyloid fragments were reduced in iNPH and SSVD (p < 0.05), although more in iNPH than in SSVD in comparison to HC. iNPH and SSVD showed comparable elevations of NFL, MBP, and GFAP (p < 0.05). MMPs were similar in all three groups except for MMP-10, which was increased in iNPH and SSVD. Patients with iNPH had larger ventricles and fewer WMCs than patients with SSVD.The results indicate that patients with iNPH and SSVD share common features of subcortical neuronal degeneration, demyelination, and astroglial response. The reduction in all APP-derived proteins characterizing iNPH patients is also present, indicating that SSVD encompasses similar pathophysiological phenomena as iNPH.
|
|
| 38. |
- Jernås, Margareta, 1961, et al.
(författare)
-
MS risk genes are transcriptionally regulated in CSF leukocytes at relapse
- 2013
-
Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:4, s. 403-410
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infiltrating T-helper cells, cytotoxic T-cells, B-cells and monocytes are thought to mediate the damage to myelin, oligodendrocytes and axons in multiple sclerosis (MS), which results in progressive disability. OBJECTIVE: The objective of this paper is to explore gene expression profiles of leukocytes in the cerebrospinal fluid (CSF) compartment of MS patients during relapse. METHODS: Global gene expression was analyzed by DNA microarray analysis of cells in CSF from MS patients and controls, and verifications were performed with real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifty percent of the recently described risk genes for MS and 28% of non-risk genes were differently expressed in MS patients compared to controls (χ(2)-test, p=7.7 × 10(-5)). Genes involved in T- and NK-cell processes were up-regulated, and genes involved in processes targeting innate immunity or B-cells were down-regulated in MS. Increased expression of EDN1 and CXCL11 and decreased expression of HMOX1 was verified with real-time PCR and increased expression of CXCL13 was verified with ELISA in CSF. CONCLUSION: DNA microarray analysis is useful in identifying differently expressed genes in CSF leukocytes, which may be important in MS in vivo. Our findings suggest that many of the risk genes for MS are differently expressed in the disease-mediating leukocytes that penetrate the blood-brain barrier.
|
|
| 39. |
- Johansson, Anette, 1977, et al.
(författare)
-
A Versatile System for Electrical Treeing Tests under AC and DC Stress Using Wire Electrodes
- 2011
-
Ingår i: 8th International Conference on Insulated Power Cables, Jicable’11, 19 – 23 June 2011, Versailles - France.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- An alternative method to evaluate electrical treeing in solid dielectric materials is presented. Here the test sample utilises a wire electrode for creating the necessary high divergent electric field. This introduces a different preparation method and several of the disadvantages with the traditional needle sample can be avoided. Together with the test object a versatile test setup for both AC and DC measurements is illustrated. This alternative method has proven successful and an evaluation thereof as well as a comparative study between the two electrode systems is included.
|
|
| 40. |
- Johnson, Mats, 1956, et al.
(författare)
-
No neurochemical evidence of neuronal injury or glial activation in children with Pediatric Acute-onset Neuropsychiatric Syndrome: An explorative pilot study.
- 2021
-
Ingår i: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. - : Informa UK Limited. - 1814-1412. ; 22:10, s. 800-804
-
Tidskriftsartikel (refereegranskat)abstract
- Summary Objective: Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by an acute onset of obsessive compulsive disorder, combined with at least two other neuropsychiatric symptoms with acute onset. Diagnostic criteria also require that no specific medical etiology is identified. Although there are no verified etiological biomarkers, PANS is assumed to be a neuroinflammatory disorder with a possible autoimmune etiology. Neurochemical markers such as neurofilament light (NfL, a neuronal injury marker) and glial fibrillary acidic protein (GFAP, an astrocytic activation marker) have not been published for this patient group. Method: Blood samples from 17 children meeting diagnostic criteria for PANS, after assessment at a child neuropsychiatry clinic were analysed for serum concentrations of NfL and GFAP. Ten age-matched children without any neurological or psychiatric disorder served as a comparison group. Results: No difference was found in mean NfL and mean GFAP serum concentrations between children with PANS and controls. Conclusion: Neuronal injury and astrocyte activation do not seem to be a major event in PANS. The study group was small, and even if findings may be reassuring for parents and patients, they should be interpreted with caution and verified in larger cohort and possibly with other markers in both serum and CSF.
|
|
| 41. |
- Karrman, Kristina, et al.
(författare)
-
Clinical and cytogenetic features of a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias: rare T-cell receptor gene rearrangements are associated with poor outcome.
- 2009
-
Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 48:9, s. 795-805
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical characteristics and cytogenetic aberrations were ascertained and reviewed in a population-based consecutive series of 285 pediatric T-cell acute lymphoblastic leukemias (T-ALLs) diagnosed between 1992 and 2006 in the Nordic countries. Informative karyotypic results were obtained in 249 (87%) cases, of which 119 (48%) were cytogenetically abnormal. Most (62%) of the aberrant T-ALLs were pseudodiploid. Structural changes were more common than numerical ones; 86% displayed at least one structural abnormality and 41% at least one numerical anomaly. The most frequent abnormalities were T-cell receptor (TCR) gene rearrangements (20%) [TCR;11p13 (10%), TCR;10q24 (3%), TCR;other (8%)], del(9p) (17%), +8 (14%), del(6q) (12%), and 11q23 rearrangements (6%). The TCR;other group comprised the rare rearrangements t(X;14)(p11;q11), t(X;7)(q22;q34), t(1;14)(p32;q11), ins(14;5)(q11;q?q?), inv(7)(p15q34), t(8;14)(q24;q11), t(7;11)(q34;p15), and t(12;14)(p13;q11). The clinical characteristics of this Nordic patient cohort agreed well with previous larger series, with a median age of 9.0 years, male predominance (male/female ratio 3.1), median white blood cell (WBC) count of 66.5 x 10(9)/l, and a high incidence of mediastinal mass and central nervous system involvement (59% and 9.5%, respectively). These features did not differ significantly among the various genetic subgroups. 5-year event-free survival (EFS) and overall survival for all patients were 0.61 (+/-0.03) and 0.67 (+/-0.03), respectively. In a multivariate analysis, two factors affected negatively the EFS, namely a WBC count of > or =200 x 10(9)/l (P < 0.001) and the presence of rare TCR rearrangements (P = 0.001). In conclusion, in this large series of childhood T-ALLs from the Nordic countries, the cytogenetic findings were not associated with risk of therapy failure with the exception of the TCR;other group. However, further prospective and collaborative investigations of this genetically heterogeneous entity are needed to confirm these results.
|
|
| 42. |
- Kokkonen Nassef, Sari, et al.
(författare)
-
Experiences of parents whose school-aged children were treated with therapeutic hypothermia as newborns : A focus group study
- 2023
-
Ingår i: Nursing Open. - : John Wiley & Sons. - 2054-1058. ; 10:11, s. 7411-7421
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To describe parents' past and present experiences of their newborn infant's therapeutic hypothermia (TH) treatment after perinatal asphyxia 10-13 years after the event.Background: Newborn infants are treated with TH following perinatal asphyxia to improve neurodevelopmental outcomes.Design: A qualitative descriptive design using focus groups (FGs).Methods: Twenty one parents to 15 newborn infants treated with TH between 2007 and 2009 participated in five FGs. The FGs were transcribed verbatim and analysed using framework approach. The SRQR checklist was followed for study reporting.Results: Two main categories were identified: hardships and reliefs during TH treatment and struggles of everyday life. Both categories include three subcategories, the first: (1) concern and gratitude for the unrecognized treatment, (2) insufficiency of information and proposed participation and (3) NICU nurses instilled security and hope. The second with subcategories: (1) unprocessed experiences of the TH treatment, (2) later challenges at school and (3) existential and psychological challenges in everyday life.Conclusion: TH of their newborns affected the parents psychologically not only during the treatment, but lasted months and years later. Information and communication with health care professionals and school management were inefficient and inadequate. The parents' concerns could be prevented by an improved identification and understanding of the problems and the needs of the infants and their families before discharge.Relevance for Clinical Practice: Through more personalized and efficient preparation and communication by the nursing staff before discharge, many of the parents' worries and problems could be reduced. Check-up of parents' needs of psychosocial support before and after discharge and offering counselling should become routine. Also, nurses at Well-Baby Clinics and in school health care should receive knowledge about TH treatment and the challenges the children and the parents experience.Patient or Public Contribution: Participation of parents was limited to the data provided through interviews.
|
|
| 43. |
- Kruczyk, Marcin, et al.
(författare)
-
Monte Carlo feature selection and rule-based models to predict Alzheimer's disease in mild cognitive impairment.
- 2012
-
Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 119:7, s. 821-31
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of the present study was to evaluate a Monte Carlo feature selection (MCFS) and rough set Rosetta pipeline for generating rule-based models as a tool for comprehensive risk estimates for future Alzheimer's disease (AD) in individual patients with mild cognitive impairment (MCI). Risk estimates were generated on the basis of age, gender, Mini-Mental State Examination scores, apolipoprotein E (APOE) genotype and the cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phospho-tau(181) (P-tau) and the 42 amino acid form of amyloid β (Aβ42) in two sets of longitudinally followed MCI patients (n=217 in total). The predictive model was created in Rosetta, evaluated with the standard tenfold cross-validation approach and tested on an external set. Features were ranked and selected by the MCFS algorithm. Using the combined pipeline of MCFS and Rosetta, it was possible to predict AD among patients with MCI with an area under the receiver operating characteristics curve of 0.92. Risk estimates were produced for the individual patients and showed good correlation with actual diagnosis in cross validation, and on an external dataset from a new study. Analysis of the importance of attributes showed that the biochemical CSF markers contributed the most to the predictions, and that added value was gained by combining several biochemical markers. Despite a correlation with the biochemical markers, the genetic marker APOE ε4 did not contribute to the predictive power of the model.
|
|
| 44. |
|
|
| 45. |
- Kuchinskaya, Ekaterina, et al.
(författare)
-
Array-CGH reveals hidden gene dose changes in children with acute lymphoblastic leukaemia and a normal or failed karyotype by G-banding
- 2008
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 140:5, s. 572-577
-
Tidskriftsartikel (refereegranskat)abstract
- A tiling path 33K BAC array was used to study 28 children with acute lymphoblastic leukaemia (ALL) who had normal or failed G-banded karyotypes. Twenty-two patients (79%) had a total of 135 copy number alterations (CNA) (69 gains and 66 losses); most of these patients showed CNA that were below the resolution of G-banding. Molecular cytogenetic and array comparative genomic hybridization results enabled the division of B-precursor ALL patients into five groups: high hyperdiploidy, intrachromosomal amplification of 21q, ETV6/RUNX1 rearrangement, others and no CNA. Apart from a shared deletion of 9p21.3, T-ALL patients had additional small CNA, with no region in common.
|
|
| 46. |
- Kuchinskaya, E, et al.
(författare)
-
Children and adults with acute lymphoblastic leukaemia have similar gene expression profiles
- 2005
-
Ingår i: European Journal of Haematology. - Oxford : Blackwell Publishing. - 0902-4441 .- 1600-0609. ; 74:6, s. 466-480
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare the gene expression pattern in children and adults with acute lymphoblastic leukaemia (ALL) in order to improve our understanding of the difference in disease biology and prognosis.METHODS: The gene expression profiles in diagnostic samples from 29 children and 15 adults with ALL were analysed using the oligonucleotide chip Hu95ver2a, produced by Affymetrix.RESULTS: Unsupervised hierarchical cluster analysis revealed that, in spite of differences in outcome, patients clustered irrespective of age, first by T-cell or B-precursor immunophenotype, and second by cytogenetic changes within the B-precursor group. The expression pattern analysis allowed the reclassification of some samples into the proper cytogenetic group. We also showed that separate clustering of samples with the BCR/ABL translocation could be explained by different breakpoint regions in the BCR. No significant difference in gene expression was observed between samples with and without CDKN2A deletion within the B-precursor group. Analysis of different age groups revealed a similarity in expression profiles when infants with the MLL translocation and adults over 40 yr of age were compared irrespective of karyotype.CONCLUSIONS: In spite of the difference in clinical outcome, the gene expression pattern in children and adults with ALL is very similar and is primarily dependent on immunophenotype and cytogenetic aberrations. However, when age groups are compared, the expression patterns of infants and adults over 40 show a remarkable similarity.
|
|
| 47. |
- Kuchinskaya, Ekaterina, et al.
(författare)
-
Interphase fluorescent in situ hybridization deletion analysis of the 9p21 region and prognosis in childhood acute lymphoblastic leukaemia (ALL) : results from a prospective analysis of 519 Nordic patients treated according to the NOPHO-ALL 2000 protocol
- 2011
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 152:5, s. 615-622
-
Tidskriftsartikel (refereegranskat)abstract
- Interphase fluorescent in situ hybridization (FISH) was applied on diagnostic BM smears from 519 children with acute lymphoblastic leukaemia (ALL) in order to establish the frequency and prognostic importance of 9p21 deletion in children enrolled in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) - 2000 treatment protocol. Among the patients, 452 were diagnosed with B-cell precursor (BCP)-ALL and 66 with T-ALL. A higher incidence of 9p21 deletions was found in T-ALL (38%) compared to BCP-ALL (15·7%). Homozygous deletions were found in 19·7% of T-ALL and 4·0% of BCP-ALL; hemizygous deletions were found in 18·2% and 11·7% respectively. In our series, 9p21 deletions were detected in all age groups with a steady rise in the frequency with age. There was no significant difference in outcome between cases with or without 9p21 deletion or between cases with hemi- or homozygous deletions of 9p21. In conclusion, in this large series of childhood ALL deletion of 9p21 was not associated with worse prognosis. However, interphase FISH deletion analysis of 9p21 could be used as a first step to detect unfavourable subtle cytogenetic aberrations such as the dic(9;20) rearrangement.
|
|
| 48. |
- Lukkarinen, H., et al.
(författare)
-
Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients
- 2022
-
Ingår i: Fluids and Barriers of the Cns. - : Springer Science and Business Media LLC. - 2045-8118. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzheimer’s disease (AD)-related amyloid β (Aβ) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients. Methods: Mini Mental State Examination (MMSE) scores and gait velocity were evaluated pre- and postoperatively in cohorts of 65 Finnish (FIN) and 82 Swedish (SWE) iNPH patients. Lumbar CSF samples were obtained prior to shunt surgery and analysed for soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ); amyloid-β isoforms of 42, 40 and 38 (Aβ42, Aβ40, Aβ38); total tau (T-tau); phosphorylated tau (P-tau181); neurofilament light (NfL) and monocyte chemoattractant protein 1 (MCP1). Results: Preoperative patient characteristics showed no significant differences between patients in the FIN and SWE cohorts. Patients in both cohorts had significantly improved gait velocity after shunt surgery (p < 0.0001). Low CSF T-tau and absence of apolipoprotein E ε4 predicted over 20% gait improvement postoperatively (p = 0.043 and p = 0.008). Preoperative CSF T-tau, P-tau181 and NfL correlated negatively with MMSE scores both pre- (p < 0.01) and post-surgery (p < 0.01). Furthermore, T-tau, NfL and Aβ42 correlated with MMSE outcomes (p < 0.05). Low preoperative CSF P-tau181 (p = 0.001) and T-tau with NfL (p < 0.001 and p = 0.049) best predicted pre- and postoperative MMSE scores greater than or equal to 26. Conclusions: CSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery. © 2022, The Author(s).
|
|
| 49. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Cerebrospinal fluid concentrations of peptides derived from chromogranin B and secretogranin II are decreased in multiple sclerosis
- 2007
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 103:5, s. 1932-1939
-
Tidskriftsartikel (refereegranskat)abstract
- Novel biomarkers for multiple sclerosis (MS) could improve diagnosis and provide clues to pathogenesis. In this study surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to analyze protein expression in CSF from 46 MS patients, 46 healthy siblings to the patients, and 50 unrelated healthy controls. Twenty-four proteins in the mass range 2–10 kDa were expressed at significantly different levels (p < 0.01) in a robust manner when comparing the three groups. Identities of three proteins were determined using biochemical purification followed by tandem mass spectrometric analysis. Immunoprecipitation experiments confirmed the identities for two peptides derived from chromogranin B (m/z 6252) and from secretogranin II (m/z 3679). These peptides were all decreased in MS when compared with siblings or controls. Radioimmunoassays specific for each peptide confirmed these differences. The lowered concentrations did not correlate to the axonal damage marker neurofilament light protein and may thus reflect functional changes rather than neurodegeneration. Further studies will investigate the involvement of these peptides in MS pathogenesis.
|
|
| 50. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain
- 2010
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 20:4, s. 1039-1048
-
Tidskriftsartikel (refereegranskat)abstract
- Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50), and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sA beta PP and A beta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons.
|
|
