| 1. |
- Walther, Charles, et al.
(författare)
-
Biphasic, Hyperdiploid Breast Tumors in Children: A Distinct Entity?
- 2012
-
Ingår i: Journal of Pediatric Hematology/Oncology. - 1536-3678.
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: The differentiation between a giant fibroadenoma and a phyllodes tumor can be a precarious diagnostic task. However, the distinction between the 2 lesions is important to make, especially since the latter can be malignant and consequently the prognoses differ. PROCEDURE:: We used various genetic approaches to study a breast tumor showing features of both entities in a 10-year-old girl with a congenital cerebral malformation and diabetes mellitus. RESULTS:: Cytogenetic analysis of cultured tumor cells from 3 different samples revealed a hyperdiploid karyotype: 50-54,XX,+5,+13,+17,+18,+19,+20,+21. High-resolution single nucleotide polymorphism array analysis not only confirmed the trisomies, but also revealed uniparental disomy (UPD) for chromosomes 10, 11, and 22. A consequence of UPD11 was a homozygous deletion in chromosome band 11p15 affecting the PARVA gene; this gene was hemizygously lost in constitutional DNA. Extended analysis of the family revealed that the deletion was inherited, but it did not segregate with breast tumors or congenital malformations. CONCLUSIONS:: Combined with the literature data, the findings in the present case strongly suggest that biphasic tumors with high hyperdiploid karyotypes constitute a distinct clinicomorphologic subgroup of benign breast tumors, being particularly common among young children.
|
|
| 2. |
- Westin, Johan, 1965, et al.
(författare)
-
Multiplex real-time PCR for detection of respiratory tract infections
- 2008
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 41:1, s. 53-56
-
Tidskriftsartikel (refereegranskat)abstract
- Background Broad diagnostics of respiratoryinfection by molecular assays has not yet won acceptance due to technical difficulties and high costs. Objectives To evaluate clinical applicability of multiplexreal-timePCR. Study design An assay targeting influenza virus A (IfA) and B (IfB), parainfluenza 1-3 (PIV), human metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RV), enterovirus (EV), adenovirus (AdV), human coronaviruses (229E, OC43, NL63), M. pneumoniae and Ch. pneumoniae was developed and run daily on consecutive clinical nasopharyngeal swab samples. Results An etiology was identified in 48% of the 954 samples, with IfA in 25%, RV in 20%, MPV in 10% and M. pneumoniae in 10% of the positive. By a rational procedure costs could be reduced and the customer price set relatively low (€33 per sample). Conclusion Streamlined testing and cost limitation is achievable and probably critical for implementation of a broad molecular diagnostics of respiratoryinfections.
|
|
| 3. |
- Ali Motamed, Mohammad, et al.
(författare)
-
Part-load thermal efficiency enhancement in gas turbine combined cycles by exhaust gas recirculation
- 2024
-
Ingår i: Applied Thermal Engineering. - 1359-4311. ; 244
-
Tidskriftsartikel (refereegranskat)abstract
- Gas turbine power plants are popular for offshore power generation due to high power density and their reliability. However, growing usage of renewable energies put gas turbines in a load following backup operation. These power plants suffer part-load efficiency losses when operating at less than full capacity, resulting in higher carbon dioxide (CO2) emission from natural gas combined cycles or higher consumption of carbon-free fuels in decarbonized gas turbines. In this article, a solution is proposed for enhancement of power plant part-load thermal efficiency based on exhaust gas recirculation in the gas turbine cycle. Recirculating exhaust gas into the gas turbine have been studied by several researchers and engineers due to its benefit for carbon-free combustion and carbon capture mechanisms. The proposed operation strategy is evaluated for single-spool and two-spool gas turbines operating jointly with a steam bottoming cycle harvesting the waste heat for further power production. In the suggested strategy, eliminating the necessity to cool down the recirculated gas resulted in less equipment footprint for the power plant which makes it more favorable for offshore applications. An in-house design and simulation tool is developed for evaluating gas turbines with modern gas recirculating systems and a flexibility in operation with carbon-free fuel mixtures. The enhancement in efficiency boost, emission reduction, and fuel consumption is quantified demonstrating the improvements with the proposed solution.
|
|
| 4. |
|
|
| 5. |
- Andersson, Kent, 1967-, et al.
(författare)
-
Introduktion till Operationsanalys : En antologi med essäer av studerande i militärteknik 2011
- 2012
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- I ämnesplanen definieras militärteknik som ”den vetenskap som beskriver och förklarar hur tekniken inverkar på militär verksamhet på alla nivåer, strategisk, operativ och taktisk, samt hur officersprofessionen påverkar och påverkas av tekniken.”[1] En militärteknikers uppgift brukar, utgående från definitionen, uttryckas som att beskriva och förklara den militära nyttan med tekniken. För att kunna göra detta behövs verktyg. Och många av dem kommer från den vetenskapliga disciplinen Operationsanalys.Syftet med den här antologin är att introducera studerande i militärteknik på Försvarshögskolan till två av de mest refererade boktitlarna i operationsanalys – Methods for conducting military operational analysis editerad av Andrew G. Loerch och Larry B. Rainey samt Military Operations Research, quantitative decision making av N.K. Jaiswal.Kapitlen utgörs av essäer skrivna av studerande på den högre stabsofficersutbildningen med teknisk inriktning, som examinationsuppgift i en fördjupningskurs. Essäerna är till del referat av kapitel i de två böckerna ovan, men kryddade med exempel satta i svenskt sammanhang och med de studerandes egen värdering av metodernas användbarhet.[1]Försvarshögskolan, Ämnesplan militärteknik, 2007.
|
|
| 6. |
- Berg, Tove, et al.
(författare)
-
Gene expression analysis of membrane transporters and drug-metabolizing enzymes in the lung of healthy and COPD subjects.
- 2014
-
Ingår i: Pharmacology research & perspectives. - : Wiley. - 2052-1707. ; 2:4, s. e00054-
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes for the first time the expression levels of genes encoding membrane transporters and drug-metabolizing enzymes in the lungs of ex-smoking patients with chronic obstructive pulmonary disease (COPD). Membrane transporters and drug-metabolizing enzymes are key determinants of drug uptake, metabolism, and elimination for systemically administered as well as inhaled drugs, with consequent influence on clinical efficacy and patient safety. In this study, while no difference in gene expression was found between healthy and COPD subjects, we identified a significant regional difference in mRNA expression of both membrane transporters and drug-metabolizing enzymes between central and peripheral tissue in both healthy and COPD subjects. The majority of the differentially expressed genes were higher expressed in the central airways such as the transporters SLC2A1 (GLUT1), SLC28A3 (CNT3), and SLC22A4 (OCTN1) and the drug-metabolizing enzymes GSTZ1, GSTO2, and CYP2F1. Together, this increased knowledge of local pharmacokinetics in diseased and normal lung may improve modeling of clinical outcomes of new chemical entities intended for inhalation therapy delivered to COPD patients. In addition, based on the similarities between COPD and healthy subjects regarding gene expression of membrane transporters and drug-metabolizing enzymes, our results suggest that clinical pharmacological studies in healthy volunteers could be a valid model of COPD patients regarding drug disposition of inhaled drugs in terms of drug metabolism and drug transporters.
|
|
| 7. |
- Csenki, Leonard, et al.
(författare)
-
Proof of principle of a generalized fuzzy Hough transform approach to peak alignment of one-dimensional 1H NMR data
- 2007
-
Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 389:3, s. 875-885
-
Tidskriftsartikel (refereegranskat)abstract
- In metabolic profiling, multivariate data analysis techniques are used to interpret one-dimensional (1D) 1H NMR data. Multivariate data analysis techniques require that peaks are characterised by the same variables in every spectrum. This location constraint is essential for correct comparison of the intensities of several NMR spectra. However, variations in physicochemical factors can cause the locations of the peaks to shift. The location prerequisite may thus not be met, and so, to solve this problem, alignment methods have been developed. However, current state-of-the-art algorithms for data alignment cannot resolve the inherent problems encountered when analysing NMR data of biological origin, because they are unable to align peaks when the spatial order of the peaks changes—a commonly occurring phenomenon. In this paper a new algorithm is proposed, based on the Hough transform operating on an image representation of the NMR dataset that is capable of correctly aligning peaks when existing methods fail. The proposed algorithm was compared with current state-of-the-art algorithms operating on a selected plasma dataset to demonstrate its potential. A urine dataset was also processed using the algorithm as a further demonstration. The method is capable of successfully aligning the plasma data but further development is needed to address more challenging applications, for example urine data.
|
|
| 8. |
- de Ståhl, Teresita Díaz, et al.
(författare)
-
Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array
- 2008
-
Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 29:3, s. 398-408
-
Tidskriftsartikel (refereegranskat)abstract
- To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.
|
|
| 9. |
- del Río, Miren, et al.
(författare)
-
Emerging stability of forest productivity by mixing two species buffers temperature destabilizing effect
- 2022
-
Ingår i: Journal of Applied Ecology. - : John Wiley & Sons. - 0021-8901 .- 1365-2664. ; 59:11, s. 2730-2741
-
Tidskriftsartikel (refereegranskat)abstract
- The increasing disturbances in monocultures around the world are testimony to their instability under global change. Many studies have claimed that temporal stability of productivity increases with species richness, although the ecological fundamentals have mainly been investigated through diversity experiments. To adequately manage forest ecosystems, it is necessary to have a comprehensive understanding of the effect of mixing species on the temporal stability of productivity and the way in which it is influenced by climate conditions across large geographical areas. Here, we used a unique dataset of 261 stands combining pure and two-species mixtures of four relevant tree species over a wide range of climate conditions in Europe to examine the effect of species mixing on the level and temporal stability of productivity. Structural equation modelling was employed to further explore the direct and indirect influence of climate, overyielding, species asynchrony and additive effect (i.e. temporal stability expected from the species growth in monospecific stands) on temporal stability in mixed forests. We showed that by adding only one tree species to monocultures, the level (overyielding: +6%) and stability (temporal stability: +12%) of stand growth increased significantly. We identified the key effect of temperature on destabilizing stand growth, which may be mitigated by mixing species. We further confirmed asynchrony as the main driver of temporal stability in mixed stands, through both the additive effect and species interactions, which modify between-species asynchrony in mixtures in comparison to monocultures. Synthesis and applications. This study highlights the emergent properties associated with mixing two species, which result in resource efficient and temporally stable production systems. We reveal the negative impact of mean temperature on temporal stability of forest productivity and how the stabilizing effect of mixing two species can counterbalance this impact. The overyielding and temporal stability of growth addressed in this paper are essential for ecosystem services closely linked with the level and rhythm of forest growth. Our results underline that mixing two species can be a realistic and effective nature-based climate solution, which could contribute towards meeting EU climate target policies.
|
|
| 10. |
|
|
| 11. |
- Hordoir, Robinson, et al.
(författare)
-
Nemo-Nordic 1.0 : a NEMO-based ocean model for the Baltic and North seas - research and operational applications
- 2019
-
Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 12:1, s. 363-386
-
Tidskriftsartikel (refereegranskat)abstract
- We present Nemo-Nordic, a Baltic and North Sea model based on the NEMO ocean engine. Surrounded by highly industrialized countries, the Baltic and North seas and their assets associated with shipping, fishing and tourism are vulnerable to anthropogenic pressure and climate change. Ocean models providing reliable forecasts and enabling climatic studies are important tools for the shipping infrastructure and to get a better understanding of the effects of climate change on the marine ecosystems. Nemo-Nordic is intended to be a tool for both short-term and long-term simulations and to be used for ocean forecasting as well as process and climatic studies. Here, the scientific and technical choices within Nemo-Nordic are introduced, and the reasons behind the design of the model and its domain and the inclusion of the two seas are explained. The model's ability to represent barotropic and baroclinic dynamics, as well as the vertical structure of the water column, is presented. Biases are shown and discussed. The short-term capabilities of the model are presented, especially its capabilities to represent sea level on an hourly timescale with a high degree of accuracy. We also show that the model can represent longer timescales, with a focus on the major Baltic inflows and the variability in deep-water salinity in the Baltic Sea.
|
|
| 12. |
|
|
| 13. |
- Jonsson, Magnus, 1979, et al.
(författare)
-
Effects of short range forces on a three-terminal nanorelay
- 2003
-
Ingår i: Fullerenes vol. 13 -- Fullerenes and Nanotubes: The Building Blocks of Next Generation Nanodevices. - 1566773970 ; , s. 432-439
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We have performed a theoretical analysis of the operational characteristics of a carbon-nanotube-based three-terminal nanorelay. In the present study we focus on introducing short range forces into the model. We show is that these forces have a significant impact on the characteristics of the relay. We also investigate the nanorelay as a memory element, and conclude that this is a promising application.
|
|
| 14. |
- Jonsson, Magnus, 1979, et al.
(författare)
-
Effects of surface forces and phonon dissipation in a three-terminal nanorelay
- 2004
-
Ingår i: Journal of Apllied Physics. ; 96, s. 629-
-
Tidskriftsartikel (refereegranskat)abstract
- We have performed a theoretical analysis of the operational characteristics of a carbonnanotube-based three-terminal nanorelay. We show that short range and van der Waals forces have a significant impact on the characteristics of the relay and introduce design constraints. We also investigate the effects of dissipation due to phonon excitation in the drain contact, which changes the switching time scales of the system, decreasing the longest time scale by 2 orders of magnitude. We show that the nanorelay can be used as a memory element and investigate the dynamics and properties of such a device.
|
|
| 15. |
|
|
| 16. |
- Kristiansson, M., et al.
(författare)
-
Drones can be used to provide dispatch centres with on-site photos before arrival of EMS in time critical incidents
- 2024
-
Ingår i: Resuscitation. - 0300-9572 .- 1873-1570. ; , s. 110312-110312
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundDrones are able to deliver automated external defibrillators in cases of out-of-hospital cardiac arrest (OHCA) but can be deployed for other purposes. Our aim was to evaluate the feasibility of sending live photos to dispatch centres before arrival of other units during time-critical incidents.MethodsIn this retrospective observational study, the regional dispatch centre implemented a new service using five existing AED-drone systems covering an estimated 200 000 inhabitants in Sweden. Drones were deployed automatically over a 4-month study period (December 2022–April 2023) in emergency calls involving suspected OHCAs, traffic accidents and fires in buildings. Upon arrival at the scene, an overhead photo was taken and transmitted to the dispatch centre. Feasibility of providing photos in real time, and time delays intervals were examined.ResultsOverall, drones were deployed in 59/440 (13%) of all emergency calls: 26/59 (44%) of suspected OHCAs, 20/59 (34%) of traffic accidents, and 13/59 (22%) of fires in buildings.The main reasons for non-deployment were closed airspace and unfavourable weather conditions (68%). Drones arrived safely at the exact location in 58/59 cases (98%). Their overall median response time was 3:49 min, (IQR 3:18–4:26) vs. emergency medical services (EMS), 05:51 (IQR: 04:29–08:04) p-value for time difference between drone and EMS = 0,05. Drones arrived first on scene in 47/52 cases (90%) and the largest median time difference was found in suspected OHCAs 4:10 min, (IQR: 02:57–05:28). The time difference in the 5/52 (10%) cases when EMS arrived first the time difference was 5:18 min (IQR 2:19–7:38), p = NA. Photos were transmitted correctly in all 59 alerts. No adverse events occurred.ConclusionIn a newly implemented drone dispatch service, drones were dispatched to 13% of relevant EMS calls. When drones were dispatched, they arrived at scene earlier than EMS services in 90% of cases. Drones were able to relay photos to the dispatch centre in all cases.Although severely affected by closed airspace and weather conditions, this novel method may facilitate additional decision-making information during time-critical incidents.
|
|
| 17. |
- Lundgren, Moa, et al.
(författare)
-
Reasons for hospitalisation and cumulative mortality in people, 75 years or older, at high risk of hospital admission: a prospective study
- 2024
-
Ingår i: BMC Geriatrics. - : BMC. - 1471-2318. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background A small proportion of the older population accounts for a high proportion of healthcare use. For effective use of limited healthcare resources, it is important to identify the group with greatest needs. The aim of this study was to explore frequency and reason for hospitalisation and cumulative mortality, in an older population at predicted high risk of hospital admission, and to assess if a prediction model can be used to identify individuals with the greatest healthcare needs. Furthermore, discharge diagnoses were explored to investigate if they can be used as basis for specific interventions in the high-risk group. Methods All residents, 75 years or older, living in ostergotland, Sweden, on January 1st, 2017, were included. Healthcare data from 2016 was gathered and used by a validated prediction model to create risk scores for hospital admission. The population was then divided into groups by percentiles of risk. Using healthcare data from 2017-2018, two-year cumulative incidence of hospitalisation was analysed using Gray ' s test. Cumulative mortality was analysed with the Kaplan-Meier method and primary discharge diagnoses were analysed with standardised residuals. Results Forty thousand six hundred eighteen individuals were identified (mean age 82 years, 57.8% women). The cumulative incidence of hospitalisation increased with increasing risk of hospital admission (24% for percentiles < 60 to 66% for percentiles 95-100). The cumulative mortality also increased with increasing risk (7% for percentiles < 60 to 43% for percentiles 95-100). The most frequent primary discharge diagnoses for the population were heart diseases, respiratory infections, and hip injuries. The incidence was significantly higher for heart diseases and respiratory infections and significantly lower for hip injuries, for the population with the highest risk of hospital admission (percentiles 85-100). Conclusions Individuals 75 years or older, with high risk of hospital admission, were demonstrated to have considerable higher cumulative mortality as well as incidence of hospitalisation. The results support the use of the prediction model to direct resources towards individuals with highest risk scores, and thus, likely the greatest care needs. There were only small differences in discharge diagnoses between the risk groups, indicating that interventions to reduce hospitalisations should be personalised. Trial registration clinicaltrials.gov Identifier: NCT03180606, first posted 08/06/2017.
|
|
| 18. |
- Marcusson, Jan, et al.
(författare)
-
Clinically useful prediction of hospital admissions in an older population
- 2020
-
Ingår i: BMC Geriatrics. - : BMC. - 1471-2318. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The healthcare for older adults is insufficient in many countries, not designed to meet their needs and is often described as disorganized and reactive. Prediction of older persons at risk of admission to hospital may be one important way for the future healthcare system to act proactively when meeting increasing needs for care. Therefore, we wanted to develop and test a clinically useful model for predicting hospital admissions of older persons based on routine healthcare data. Methods We used the healthcare data on 40,728 persons, 75-109 years of age to predict hospital in-ward care in a prospective cohort. Multivariable logistic regression was used to identify significant factors predictive of unplanned hospital admission. Model fitting was accomplished using forward selection. The accuracy of the prediction model was expressed as area under the receiver operating characteristic (ROC) curve, AUC. Results The prediction model consisting of 38 variables exhibited a good discriminative accuracy for unplanned hospital admissions over the following 12 months (AUC 0.69 [95% confidence interval, CI 0.68-0.70]) and was validated on external datasets. Clinically relevant proportions of predicted cases of 40 or 45% resulted in sensitivities of 62 and 66%, respectively. The corresponding positive predicted values (PPV) was 31 and 29%, respectively. Conclusion A prediction model based on routine administrative healthcare data from older persons can be used to find patients at risk of admission to hospital. Identifying the risk population can enable proactive intervention for older patients with as-yet unknown needs for healthcare.
|
|
| 19. |
- Marcusson, Jan, et al.
(författare)
-
Proactive healthcare for frail elderly persons : study protocol for a prospective controlled primary care intervention in Sweden
- 2019
-
Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:5
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction The provision of healthcare services is not dedicated to promoting maintenance of function and does not target frail older persons at high risk of the main causes of morbidity and mortality. The aim of this study is to evaluate the effects of a proactive medical and social intervention in comparison with conventional care on a group of persons aged 75 and older selected by statistical prediction.Methods and analysis In a pragmatic multicentre primary care setting (n=1600), a prediction model to find elderly (75+) persons at high risk of complex medical care or hospitalisation is used, followed by proactive medical and social care, in comparison with usual care. The study started in April 2017 with a run-in period until December 2017, followed by a 2-year continued intervention phase that will continue until the end of December 2019. The intervention includes several tools (multiprofessional team for rehabilitation, social support, medical care home visits and telephone support). Primary outcome measures are healthcare cost, number of hospital care episodes, hospital care days and mortality. Secondary outcome measures are number of outpatient visits, cost of social care and informal care, number of prescribed drugs, health-related quality of life, cost-effectiveness, sense of security, functional status and ability. We also study the care of elderly persons in a broader sense, by covering the perspectives of the patients, the professional staff and the management, and on a political level, by using semistructured interviews, qualitative methods and a questionnaire.Ethics and dissemination Approved by the regional ethical review board in Linköping (Dnr 2016/347-31). The results will be presented in scientific journals and scientific meetings during 2019–2022 and are planned to be used for the development of future care models.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Nord, Magnus, 1967-, et al.
(författare)
-
Cost-Effectiveness of Comprehensive Geriatric Assessment Adapted to Primary Care
- 2022
-
Ingår i: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 23:12, s. 2003-2009
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To estimate the cost-effectiveness of a pragmatic trial of comprehensive geriatric assessment adapted to primary care, compared with care as usual. Design Within-trial cost-effectiveness study of a prospective controlled multicenter trial. Setting and Participants Nineteen primary care practices in Sweden. The original trial included 1304 individuals aged ≥75 years at high risk of hospitalization selected using a prediction model. From the original trial, 369 individuals participated in the cost-effectiveness analysis, 185 in the intervention group and 184 in the control group. Mean age was 83.9 years and 57% of the participants were men. Methods We obtained health care costs from administrative registries. Community costs and health-related quality of life data were obtained from a questionnaire sent to participants. Health-related quality of life was measured using EQ-5D-3L and quality-adjusted life years were calculated. We analyzed all outcomes according to intention to treat, and adjusted them to age, gender, and risk score (risk of hospitalization in the next 12 months). The primary outcome was the incremental cost-effectiveness ratio associated with the intervention at follow-up after 24 months. Results The difference in total cost (incremental cost) between intervention and control groups was USD −11,275 (95% CI −407 to −22,142). The incremental effect in quality-adjusted life years was −0.05 (95% CI −0.17 to 0.08). In the cost-effectiveness plane that illustrates the uncertainty of the analysis, 77.9 of the observations were within the south-east quadrant, implying lower cost and greater effect in the intervention group. Conclusions and Implications The results suggests that a primary care comprehensive geriatric assessment intervention delivered to older adults at high risk of hospitalization is cost-effective at follow-up after 24 months. The use of a prediction model to select participants and an intervention with a low cost is promising but requires further study.
|
|
| 23. |
- Nord, Magnus, et al.
(författare)
-
Costs and effects of comprehensive geriatric assessment in primary care for older adults with high risk for hospitalisation
- 2021
-
Ingår i: BMC Geriatrics. - : BMC. - 1471-2318. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe healthcare system needs effective strategies to identify the most vulnerable group of older patients, assess their needs and plan their care proactively. To evaluate the effectiveness of comprehensive geriatric assessment (CGA) of older adults with a high risk of hospitalisation we conducted a prospective, pragmatic, matched-control multicentre trial at 19 primary care practices in Sweden.MethodsWe identified 1604 individuals aged 75years and older using a new, validated algorithm that calculates a risk score for hospitalisation from electronic medical records. After a nine-month run-in period for CGA in the intervention group, 74% of the available 646 participants had accepted and received CGA, and 662 participants remained in the control group. Participants at intervention practices were invited to CGA performed by a nurse together with a physician. The CGA was adapted to the primary care context. The participants thereafter received actions according to individual needs during a two-year follow-up period. Participants at control practices received care as usual. The primary outcome was hospital care days. Secondary outcomes were number of hospital care episodes, number of outpatient visits, health care costs and mortality. Outcomes were analysed according to intention to treat and adjusted for age, gender and risk score. We used generalised linear mixed models to compare the intervention group and control group regarding all outcomes.ResultsMean age was 83.2years, 51% of the 1308 participants were female. Relative risk reduction for hospital care days was -22% (-35% to -4%, p=0.02) during the two-year follow-up. Relative risk reduction for hospital care episodes was -17% (-30% to -2%, p=0.03). There were no significant differences in outpatient visits or mortality.Health care costs were significantly lower in the intervention group, adjusted mean difference was Euro - 4324 (Euro - 7962 to -686, p=0.02).Conclusions and relevanceOur findings indicate that CGA in primary care can reduce the need for hospital care days in a high-risk population of older adults. This could be of great importance in order to manage increasing prevalence of frailty and multimorbidity.Trial registrationclinicaltrials.gov Identifier: NCT03180606, first posted 08/06/2017.
|
|
| 24. |
- Nord, Magnus, 1967-
(författare)
-
Proactive Primary Care for Older Adults at High Risk of Hospital Admission
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Demographic change is leading to a higher proportion of older adults in most parts of the world. A minority of older adults have poor health, but this group has high care needs due to frailty and/or multimorbidity. Guidelines for the management of frailty emphasise early detection of frailty and recommend comprehensive care approaches in primary care, but the evidence for these interventions is low. To provide effective and individualised care, the health system needs to identify these patients and develop proactive interventions to improve quality of life and avoid treatments that are of no benefit to the individual. The aim of this thesis was to study the effects of a proactive primary care working model in which vulnerable older adults were identified and received individually tailored care, using an adaptation of comprehensive geriatric assessment (CGA). Methods: A pragmatic controlled trial was conducted in 19 primary care practices in Sweden from 2017 to 2020. A predictive model, using electronic medical records to assess the risk of hospital admission, selected participants at high risk. Participants in the intervention practices were offered a comprehensive geriatric assessment in their primary care practice and subsequent follow-up by a team consisting of a nurse and the patient's doctor. A new CGA tool - PASTEL (Primary care ASsessment Tool for Elders) was used for assessment and care planning. The primary outcome for the intervention was hospital care days and secondary outcomes were hospital care episodes, mortality, outpatient visits, healthcare costs and cost-effectiveness. The outcomes were adjusted for age, sex and risk score and ana-lysed according to intention-to-treat. The predictive model was validated, and performance was assessed using the C-statistic. Focus group interviews were conducted to explore primary care nurses' and doctors' experiences with the new tool PASTEL. Results: 1304 older adults were included in the trial. The mean age was 82.2 years, 51% were female. During the follow-up period of 24 months, the relative risk reduction of hospital care days in the intervention group was - 22% (CI 95% = -35% to - 4%, p = 0.02) compared with usual care. There was no significant difference in mortality and outpatient visits. The reduction in healthcare costs was - € 4324 (- € 7962 to - € 686, p = 0.02). The intervention was cost-effective compared with usual care, mainly due to lower costs.The predictive model had an AUC of 0.69 (CI 0.68- 0.70). Primary care staff considered PASTEL valuable and feasible in the primary care context.In conclusion, the results of this thesis indicate that vulnerable older adults at risk of hospitalisation can be identified by a predictive model. Proactive intervention with a comprehensive geriatric assessment adapted to pri-mary care can reduce the need for hospital care. Future studies in similar contexts are needed to determine whether these results are generalisable.
|
|
| 25. |
- Nord, Magnus
(författare)
-
Regulation and function of the Clara cell secretory protein
- 1997
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Clara cell secretory protein (CCSP; also known as Polychlorinated Biphenyl-binding protein (PCB-BP) or Uteroglobin) is specifically produced and secreted into the distal airway lumen by the non-ciliated Clara cell. It is a low molecular weight homodimeric protein and binds certain metabolites of PCBs as well as progestins and calcium. Yet, the physiological function of CCSP has not been established. The aims of this thesis have been to use the CCSP gene and its regulation as a model to study mechanisms of lung development and cellular differentiation and to elucidate the physiological function of CCSP with the aid of structure/function-analyses and targeted gene inactivation in intact animals, the latter also to define its role in PCB-bioaccumulation. Initially, the expression of CCSP during fetal development of rat lung was studied. The protein appears at day 19 of gestation and is preceeded by one day by its mRNA. Levels were increased 2-3 fold by glucocorticoids. To investigate the mechanisms behind the differentiation-dependent CCSP expression, we turned to isolated rat Clara cells. These cells proliferate and dedifferentiate in primary culture and levels of CCSP decrease concommitantly. Proximal elements in the CCSP-promoter exhibited a cell-specific activity in primary lung cells and further analysis demonstrated the importance of a C/EBP-related transcription factor interacting with proximal elements to regulate CCSP-expression. These studies establish CCSP as a useful differentiation marker and suggest a role for C/EBP in the differentiation of the terminal airways. To investigate the molecular basis behind CCSPs calcium-binding, we applied a hydrophobic contrast function to the three-dimensional structure of CCSP. One metal binding site per monomer was found and site directed mutagenesis confirmed that the identified region is a functional calcium-binding site. Prompted by the similarity of this site to the calcium-binding sites in annexins that mediate binding to phospholipids, we could show CCSP binding to phospholipids in a calcium-dependent manner. This suggests that one function of calcium-binding is to associate the protein to phospholipid bilayers. Finally, in an attempt to elucidate the physiological function of CCSP we generated CCSP deficient mice by targeted gene "knock-out". These mice do not accumulate methyl-sulfonyl metabolites of PCBs in lung as wild type mice do. Moreover, they show specific ultrastructural changes within the secretory apparatus of the Clara cells, including a total absence of secretory granules and reduced amounts of rough endoplasmic reticulum. These results establish CCSP as a determinant of PCB bio-accumulation and suggests a role for the protein in the secretory pathway of the Clara cell.
|
|
| 26. |
- Nord, Magnus, et al.
(författare)
-
Staff experiences of a new tool for comprehensive geriatric assessment in primary care (PASTEL): a focus group study Primary care staff experiences of geriatric assessment
- 2020
-
Ingår i: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724. ; 38:2, s. 132-145
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Comprehensive geriatric assessment (CGA) is recommended for the management of frailty. Little is known about professionals experiences of CGA; therefore we wanted to investigate the experiences of staff in primary care using a new CGA tool: the Primary care Assessment Tool for Elderly (PASTEL). Design: Focus group interviews. Manifest qualitative content analysis. Setting: Nine primary health care centres in Sweden that participated in a CGA intervention. These centres represent urban as well as rural areas. Subjects: Nine nurses, five GPs and one pharmacist were divided into three focus groups. Main outcome measures: Participants experiences of conducting CGA with PASTEL. Results: The analysis resulted in four main categories. A valuable tool for selected patients: The participants considered the assessment tool to be feasible and valuable. They stated that having enough time for the assessment interview was essential but views about the ideal patient for assessment were divided. Creating conditions for dialogue: The process of adapting the assessment to the individual and create conditions for dialogue was recognised as important. Managing in-depth conversations: In-depth conversations turned out to be an important component of the assessment. Patients were eager to share their stories, but talking about the future or the end of life was demanding. The winding road of actions and teamwork: PASTEL was regarded as a good preparation tool for care planning and a means of support for identifying appropriate actions to manage frailty but there were challenges to implement these actions and to obtain good teamwork. Conclusion: The participants reported that PASTEL, a tool for CGA, gave a holistic picture of the older person and was helpful in care planning.
|
|
| 27. |
- Olaison, Anna, 1974-, et al.
(författare)
-
‘Do you have a future when you are 93?’ Frail older person’s perceptions about the future and end of life – a qualitative interview study in primary care
- 2022
-
Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis Group. - 0281-3432 .- 1502-7724. ; 40:4, s. 417-425
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore frail older persons’ perceptions of the future and the end of life.Design: Qualitative content analysis of individual semi-structured interviews.Setting: Nine primary health care centres in both small and middle-sized municipalities in Sweden that participated in the intervention project Proactive healthcare for frail elderly persons.Subjects/Patients: The study includes 20 older persons (eight women and 12 men, aged 76–93 years).Main outcome measures: Frail older persons’ perceptions of the future and end of life.Results: The analysis uncovered two main categories: Dealing with the future and Approaching the end of life. Dealing with the future includes two subcategories: Plans and reflections and Distrust and delay. Approaching the end of life includes three subcategories: Practical issues, Worries and realism, and Keeping it away.Conclusion: This study highlights the diverse ways older people perceive future and the end of life. The results make it possible to further understand the complex phenomenon of frail older persons’ perceptions on the future and the end of life.
|
|
| 28. |
- Pan, Gang, et al.
(författare)
-
PATZ1 down-regulates FADS1 by binding to rs174557 and is opposed by SP1/SREBP1c
- 2017
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 45:5, s. 2408-2422
-
Tidskriftsartikel (refereegranskat)abstract
- The FADS1 and FADS2 genes in the FADS cluster encode the rate-limiting enzymes in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs). Genetic variation in this region has been associated with a large number of diseases and traits many of them correlated to differences in metabolism of PUFAs. However, the causative variants leading to these associations have not been identified. Here we find that the multiallelic rs174557 located in an AluYe5 element in intron 1 of FADS1 is functional and lies within a PATZ1 binding site. The derived allele of rs174557, which is the common variant in most populations, diminishes binding of PATZ1, a transcription factor conferring allele-specific downregulation of FADS1 The PATZ1 binding site overlaps with a SP1 site. The competitive binding between the suppressive PATZ1 and the activating complex of SP1 and SREBP1c determines the enhancer activity of this region, which regulates expression of FADS1.
|
|
| 29. |
- Parada, L A, et al.
(författare)
-
Cytogenetics of hepatoblastoma: further characterization of 1q rearrangements by fluorescence in situ hybridization: an international collaborative study
- 2000
-
Ingår i: Medical and Pediatric Oncology. - 1096-911X. ; 34:3, s. 165-170
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hepatoblastoma (HBT) is the most common hepatic neoplasm in children. This notwithstanding, little is known about pathogenetic factors, such as genetic abnormalities, of importance for the development and progression of this tumor type. To date, only 33 cytogenetically abnormal HBT have been published, and trisomies for chromosomes 2 and 20 have been shown to be the most frequent aberrations. Recently, unbalanced translocations involving proximal 1q have been described in several HBT, suggesting that a pathogenetically important gene maps to 1q. PROCEDURE: Six primary and one recurrent HBT were cytogenetically analyzed after short-term tissue culture. In addition, fluorescence in situ hybridization (FISH) studies, using locus-specific probes, were performed on three of these pediatric HBT as well as on one previously reported adult HBT. RESULTS: Total or partial trisomy 8, gain of chromosome 20, and structural rearrangements of chromosome 1 were detected in three HBT, and overrepresentation of chromosome 2 material was found in two HBT. The adjacent chromosome bands 1q12 and 1q21 were involved in three translocations, t(1;2), t(1;4), and t(1;11), which were all unbalanced and resulted in gain of 1q material. The previously reported adult HBT displayed 1q deletions with breakpoints at 1q12-21. FISH analyses of the 1q rearrangements revealed that all breakpoints were within the heterochromatic region. CONCLUSIONS: These findings provide further support for the importance of trisomies 2, 8, and 20 and rearrangements of 1q in the development of HBT. Furthermore, the consistent localization of breakpoints within the heterochromatic segment of chromosome 1 suggests that the important pathogenetic consequence of 1q abnormalities is the resulting genomic imbalance rather than a specific gene rearrangement.
|
|
| 30. |
- Pretzsch, Hans, et al.
(författare)
-
With increasing site quality asymmetric competition and mortality reduces Scots pine (Pinus sylvestris L.) stand structuring across Europe
- 2022
-
Ingår i: Forest Ecology and Management. - : Elsevier. - 0378-1127 .- 1872-7042. ; 520
-
Tidskriftsartikel (refereegranskat)abstract
- Heterogeneity of structure can increase mechanical stability, stress resistance and resilience, biodiversity and many other functions and services of forest stands. That is why many silvicultural measures aim at enhancing structural diversity. However, the effectiveness and potential of structuring may depend on the site conditions. Here, we revealed how the stand structure is determined by site quality and results from site-dependent partitioning of growth and mortality among the trees. We based our study on 90 mature, even-aged, fully stocked monocultures of Scots pine (Pinus sylvestris L.) sampled in 21 countries along a productivity gradient across Europe. A mini-simulation study further analyzed the site-dependency of the interplay between growth and mortality and the resulting stand structure. The overarching hypothesis was that the stand structure changes with site quality and results from the site-dependent asymmetry of competition and mortality.First, we show that Scots pine stands structure across Europe become more homogeneous with increasing site quality. The coefficient of variation and Gini coefficient of stem diameter and tree height continuously decreased, whereas Stand Density Index and stand basal area increased with site index.Second, we reveal a site-dependency of the growth distribution among the trees and the mortality. With increasing site index, the asymmetry of both competition and growth distribution increased and suggested, at first glance, an increase in stand heterogeneity. However, with increasing site index, mortality eliminates mainly small instead of all-sized trees, cancels the size variation and reduces the structural heterogeneity.Third, we modelled the site-dependent interplay between growth partitioning and mortality. By scenario runs for different site conditions, we can show how the site-dependent structure at the stand level emerges from the asymmetric competition and mortality at the tree level and how the interplay changes with increasing site quality across Europe.Our most interesting finding was that the growth partitioning became more asymmetric and structuring with increasing site quality, but that the mortality eliminated predominantly small trees, reduced their size variation and thus reversed the impact of site quality on the structure. Finally, the reverse effects of mode of growth partitioning and mortality on the stand structure resulted in the highest size variation on poor sites and decreased structural heterogeneity with increasing site quality. Since our results indicate where heterogeneous structures need silviculture interventions and where they emerge naturally, we conclude that these findings may improve system understanding and modelling and guide forest management aiming at structurally rich forests.
|
|
| 31. |
|
|
| 32. |
- Rytter, Lars, et al.
(författare)
-
Availability of Biomass for Energy Purposes in Nordic and Baltic Countries : Land Areas and Biomass Amounts
- 2015
-
Ingår i: Baltic Forestry. - Kėdainiai : Lietuvos Misku Institutas. - 1392-1355 .- 2029-9230. ; 21:2, s. 375-390
-
Forskningsöversikt (refereegranskat)abstract
- This review compiles information on the current state of the forests and analyses the potential of forest fuels for energy purposes in Denmark, Finland, Norway, Sweden, Estonia and Latvia. In these countries the forest area is 61 mill. ha, corresponding to 52% of the land areas, which is high in a European perspective where 38% of the land area is forest (EU-27). Although some forest areas are protected, 75-92% of the area can still be used for wood production. Further, substantial agriculture land areas may also be available for production of biomass for energy. Coniferous species dominate the forests in Finland, Norway and Sweden, while a more even distribution of conifers and deciduous species is found in Denmark, Estonia and Latvia. The total growing stock is around 7,400 mill. m(3) and the annual increment is estimated to about 275 mill. m(3) yr(-1) Annual growth currently exceeds annual harvest, leading to the conclusion that some of the difference may be used for energy purposes in the near future. The current potential for forest fuel resources was estimated to 230-410 TWh yr(-1) (830-1,480 PJ yr(-1)) for the countries included and forest fuels will thus be of utmost importance for the future energy supply in the area. A changing climate with larger standing volumes may affect the future growth positively and increase the potential harvest levels. Estimates from Finland, Sweden and Norway show an average growth increase of over 30% by the end of the century and substantially higher for specific regions. Wood is extensively used for energy purposes and the forests hold a large potential for increasing the production of renewable energy. The potential may be further increased in the future with increased fertilization, extended breeding for enhanced biomass production, larger cultivation areas and changes of tree species and management systems.
|
|
| 33. |
- Sadek, Christine M., et al.
(författare)
-
Characterization of human thioredoxin-like 2. A novel microtubule-binding thioredoxin expressed predominantly in the cilia of lung airway epithelium and spermatid manchette and axoneme
- 2003
-
Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 278:15, s. 13133-13142
-
Tidskriftsartikel (refereegranskat)abstract
- We describe here the cloning and characterization of a novel member of the thioredoxin family, thioredoxin-like protein 2 (Txl-2). The Txl-2 open reading frame codes for a protein of 330 amino acids consisting of two distinct domains: an N-terminal domain typical of thioredoxins and a C-terminal domain belonging to the nucleoside-diphosphate kinase family, separated by a small interface domain. The Txl-2 gene spans approximately 28 kb, is organized into 11 exons, and maps at locus 3q22.3-q23. A splicing variant lacking exon 5 (Delta 5Txl-2) has also been isolated. By quantitative real time PCR we demonstrate that Txl-2 mRNA is ubiquitously expressed, with testis and lung having the highest levels of expression. Unexpectedly, light and electron microscopy analyses show that the protein is associated with microtubular structures such as lung airway epithelium cilia and the manchette and axoneme of spermatids. Using in vitro translated proteins, we demonstrate that full-length Txl-2 weakly associates with microtubules. In contrast, Delta 5Txl-2 specifically binds with very high affinity brain microtubule preparations containing microtubule-binding proteins. Importantly, Delta 5Txl-2 also binds to pure microtubules, proving that it possesses intrinsic microtubule binding capability. Taken together, Delta 5Txl-2 is the first thioredoxin reported to bind microtubules and might therefore be a novel regulator of microtubule physiology.
|
|
| 34. |
- Sanfridsson, J, et al.
(författare)
-
Drone delivery of an automated external defibrillator - a mixed method simulation study of bystander experience.
- 2019
-
Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 27:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Out-of-hospital cardiac arrest (OHCA) affects some 275,000 individuals in Europe each year. Time from collapse to defibrillation is essential for survival. As emergency medical services (EMS) response times in Sweden have increased, novel methods are needed to facilitate early treatment. Unmanned aerial vehicles (i.e. drones) have potential to deliver automated external defibrillators (AED). The aim of this simulation study was to explore bystanders' experience of a simulated OHCA-situation where a drone delivers an AED and how the situation is affected by having one or two bystanders onsite.METHODS: This explorative simulation study used a mixed methodology describing bystanders' experiences of retrieving an AED delivered by a drone in simulated OHCA situations. Totally eight participants were divided in two groups of bystanders a) alone or b) in pairs and performed CPR on a manikin for 5 minutes after which an AED was delivered by a drone at 50 m from the location. Qualitative data from observations, interviews of participants and video recordings were analysed using content analysis alongside descriptive data on time delays during bystander interaction.RESULTS: Three categories of bystander experiences emerged: 1) technique and preparedness, 2) support through conversation with the dispatcher, and 3) aid and decision-making. The main finding was that retrieval of an AED as delivered by a drone was experienced as safe and feasible for bystanders. None of the participants hesitated to retrieve the AED; instead they experienced it positive, helpful and felt relief upon AED-drone arrival and were able to retrieve and attach the AED to a manikin. Interacting with the AED-drone was perceived as less difficult than performing CPR or handling their own mobile phone during T-CPR. Single bystander simulation introduced a significant hands-off interval when retrieving the AED, a period lasting 94 s (range 75 s-110 s) with one participant compared to 0 s with two participants.CONCLUSION: The study shows that it made good sense for bystanders to interact with a drone in this simulated suspected OHCA. Bystanders experienced delivery of AED as safe and feasible. This has potential implications, and further studies on bystanders' experiences in real cases of OHCA in which a drone delivers an AED are therefore necessary.
|
|
| 35. |
- Sax, Åsa, et al.
(författare)
-
Trustful conversations: a qualitative interview study on older patients experiences of the intervention Proactive healthcare in a Swedish primary care setting
- 2023
-
Ingår i: Primary Health Care Research and Development. - : CAMBRIDGE UNIV PRESS. - 1463-4236 .- 1477-1128. ; 24
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore older patients experiences of the intervention Proactive healthcare for frail elderly persons. Background: Previous research has indicated that continuity and good access to primary care can improve satisfaction in older people seeking care. However, little is known about the older patients experiences in taking part of interventions aiming to enhance the care. Methods: Individual interviews were conducted with 24 older patients who participated in the intervention Proactive healthcare for frail elderly persons, selected from nine Swedish primary care centres. Interviews were analysed using qualitative content analysis. Findings: Older patients experiences of the intervention involved five manifest categories: Ways of naming the elder care team, covering the older patients lack of understanding regarding their connection to the team, and the need for clarity on this and on how the specialised care provided differed from conventional care; Availability, indicating how older patients associated easy access and a direct telephone number with a team nurse available at certain times with a sense of security; The importance of relations, covering how patients appreciated continuity in their personal and professional conversations with staff; A feeling of safety and trust, stressing the value of older persons attach to being given enough time, to be listened to and being recognised as people; and Finiteness of life, which refers to the difficulty of having end-of-life conversations and the need for experienced staff with personal knowledge of the patients. The latent theme Trustful conversations was created to give a deeper meaning to the content of the categories.Trustful conversations, created through good personal knowledge of patients and continuity of contact, engender a feeling of safety in older patients. Using elder care teams could result in a better quality of care, with increased satisfaction and feelings of security among patients, and a reduction in healthcare needs.
|
|
| 36. |
- Tsakonas, Georgios, et al.
(författare)
-
An immune gene expression signature distinguishes central nervous system metastases from primary tumours in non-small-cell lung cancer
- 2020
-
Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 132, s. 24-34
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Dissemination of non-small-cell lung cancer (NSCLC) in the central nervous system is a frequent and challenging clinical problem. Systemic or local therapies rarely prolong survival and have modest activity regarding local control. Alterations in gene expression in brain metastasis versus primary tumour may increase aggressiveness and impair therapeutic efforts.Methods: We identified 25 patients with surgically removed NSCLC brain metastases in two different patient cohorts. For 13 of these patients, primary tumour samples were available. Gene expression analysis using the nCounter (R) PanCancer Immune Profiling gene expression panel (nanoString technologies Inc.) was performed in brain metastases and primary tumour samples. Identification of differentially expressed genes was conducted on normalized data using the nSolver analysis software.Results: We compared gene expression patterns in brain metastases with primary tumours. Brain metastasis samples displayed a distinct clustering pattern compared to primary tumour samples with a statistically significant downregulation of genes related to immune response and immune cell activation. Results from KEGG term analysis on differentially expressed genes revealed a concomitant enrichment of multiple KEGG terms associated with the immune system. We identified a 12-gene immune signature that clearly separated brain metastases from primary tumours.Conclusions: We identified a unique gene downregulation pattern in brain metastases compared with primary tumours. This finding may explain the lower intracranial efficacy of systemic therapy, especially immunotherapy, in brain metastasis of patients with NSCLC.
|
|
| 37. |
- Tsakonas, Georgios, et al.
(författare)
-
Matched Analyses of Brain Metastases versus Primary Non-Small Cell Lung Cancer Reveal a Unique microRNA Signature
- 2023
-
Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Distant spreading of tumor cells to the central nervous system in non-small cell lung cancer (NSCLC) occurs frequently and poses major clinical issues due to limited treatment options. RNAs displaying differential expression in brain metastasis versus primary NSCLC may explain distant tumor growth and may potentially be used as therapeutic targets. In this study, we conducted systematic microRNA expression profiling from tissue biopsies of primary NSCLC and brain metastases from 25 patients. RNA analysis was performed using the nCounter Human v3 miRNA Expression Assay, NanoString technologies, followed by differential expression analysis and in silico target gene pathway analysis. We uncovered a panel of 11 microRNAs with differential expression and excellent diagnostic performance in brain metastasis versus primary NSCLC. Five microRNAs were upregulated in brain metastasis (miR-129-2-3p, miR-124-3p, miR-219a-2-3p, miR-219a-5p, and miR-9-5p) and six microRNAs were downregulated in brain metastasis (miR-142-3p, miR-150-5p, miR-199b-5p, miR-199a-3p, miR-199b-5p, and miR-199a-5p). The differentially expressed microRNAs were predicted to converge on distinct target gene networks originating from five to twelve core target genes. In conclusion, we uncovered a unique microRNA profile linked to two target gene networks. Our results highlight the potential of specific microRNAs as biomarkers for brain metastasis in NSCLC and indicate plausible mechanistic connections.
|
|
| 38. |
- Viefers, Susanne, 1970, et al.
(författare)
-
ELECTROMECHANICAL NANOTUBE TUNNELING DEVICE COMPRISING SOURCE, DRAIN AND GATE
- 2011
-
Patent (övrigt vetenskapligt/konstnärligt)abstract
- The present invention relates to a nanotube device (100) comprising a nanotube with a longitudinal and a lateral extension, a structure for supporting at least a first part of the nanotube, and first means for exerting a force upon the nanotube in a first direction defined by its lateral extension. At least a second part of the nanotube protrudes beyond the support of said structure, so that when said force exceeds a certain level, the second part of the nanotube will flex in the direction of its lateral extension, and thereby close a first electrical circuit. Suitably, the first means for exerting said force upon the nanotube is an electrical means, the force being created by applying a voltage to the means. The device allows for quantum mechanics tunnel effects, both at a source and at a drain electrode.
|
|
| 39. |
|
|
| 40. |
|
|
