| 1. |
- Bilén, Anna-Karin, et al.
(författare)
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Miljökvalitetsmålen 2016 : Årlig uppföljning av miljökvalitetsmålen
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I Blekinge bedöms inte något miljökvalitetsmål vara möjligt att nå till år 2020. För att kunna lämna över ett hållbart samhälle till nästa generation krävs förebyggande arbete, ef?????????????????r. Ambitionerna måste öka och miljöfrågorna prioriteras högre på den politiska agendan.De mål som rör biologisk mångfald och bevarande av kulturmiljö följer enneutral eller negativ trend. I odlingslandskapet leder färre lantbrukare ochbrist på betesdjur till igenväxning av hagmarker. Livsmiljöer försvinner och????????????????????????????????????????,främst möte insekter.För att god ekologisk status ska uppnås i vattendragen behövs ny vattenlagstiftning och mer resurser för tillsyn. I Blekinges kustvatten är övergödning ett stort miljöproblem och det krävs kraftfulla åtgärder för att minska näringsläckaget. Arbetet med vattenförsörjningsplaner behöver fortsätta för att trygga framtida dricksvattenförsörjning. De senaste årens fynd av PFAS i dricksvatten visar på vikten av att skydda vattentäkter, genomföra riskbedömningar och undersöka förekomst av föroreningar.Obalans mellan den tätbefolkade kusten och den glesbyggda landsbygden är en utmaning i länet. Byggandet vid kusten ställer krav på en hänsynsfull bebyggelseutveckling som tydligt beaktar miljökvalitetsmålen.Internationella överenskommelser om kemikalier och minskade utsläpp till luft och vatten är nödvändigt för att uppnå uppsatta mål. Dessutom behövs en omställning till ett samhälle som baseras på förnybar energi. För att skapa en hållbar framtid måste vi förändra vår livsstil och vår attityd till konsumtion. Lokala och regionala åtgärder såsom arbete för en giftfri förskola och minskade utsläpp av mikroplaster är steg i rätt riktning.Minskad biologisk mångfald påverkar tillsammans med klimatförändringar, övergödning och miljögifter många av de ekosystemtjänster som vi är beroende av för mänsklig välfärd och en hållbar samhällsutveckling. Det pågår insatser som förbättrar tillståndet i miljön, men det går för långsamt. Det krävs mer resurser och modiga politiska beslut för att möjliggöra en hållbar framtid, den framtid som vi är skyldiga våra barn!
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| 2. |
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| 3. |
- Brandén, Gunnar
(författare)
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Understanding Intergenerational Mobility : Inequality, Student Aid and Nature-Nurture Interactions
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Essay I: A body of evidence has emerged in the literature on intergenerational mobility documenting that unequal countries experience less social mobility: a relationship known as the Great Gatsby Curve. In this paper I estimate the Great Gatsby Curve within Sweden across 125 commuting zones and 20 cohorts, exploiting both cross-sectional and longitudinal variation. I find that children who were exposed to higher levels of inequality during childhood experienced less social mobility as adults, thereby confirming the existence of a Great Gatsby Curve in Sweden. I also present new evidence on the underlying mechanisms of the Great Gatsby Curve. By decomposing intergenerational mobility into separate transmission channels, I find that the Great Gatsby Curve is exclusively driven by the mediating effect that children's educational attainment and development of cognitive and non-cognitive skills has on the persistence of income across generations. Hence, the results suggest that adverse effects of inequality on mobility can be alleviated by policies that target children's educational attainment and development of cognitive and non-cognitive skills.
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| 4. |
- Claesson Lingehall, Helena, 1965-
(författare)
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Delirium in older people after cardiac surgery : risk factors, dementia, patients’ experiences and assessments
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background:Delirium is common in older people undergoing cardiac surgery. Delirium is an acute or subacute neuro-psychiatric syndrome, characterized by a change in cognition, disturbances in consciousness; it fluctuates, develops over a short period of time and always has an underlying cause. It is associated with a disturbance in psychomotor activity, and is classified according to different clinical profiles such as hypoactive, hyperactive and mixed delirium. Delirium after cardiac surgery is not harmless, it increases the risk of complications such as prolonged stay in hospital, falls, reduced quality of life, reduced cognitive function and increased mortality.Aim:The overall aim of this thesis was to investigate postoperative delirium in older people undergoing cardiac surgery with Cardiopulmonary Bypass (CPB), focusing on risk factors, dementia and patients’ experiences; and to evaluate an assessment for screening delirium.Methods:This thesis compromises four studies. All participants (n=142) were scheduled for cardiac surgery with use of CPB at the Cardiothoracic Surgery Department, Heart Centre, Umeå University Hospital, Sweden, between February and October 2009. Six structured interviews were conducted preoperatively, day one and day four postoperatively, and in home visits, one, three and five years after surgery (2010, 2012 and 2014). The assessment scales used in Studies I, II and IV were: the Mini-Mental State Examination (MMSE) for cognition, the Organic Brain Syndrome Scale (OBS) for delirium, Geriatric Depression Scale 15 (GDS-15) for depression, Katz staircase with Activities of Daily Living (ADL) for participants’ functional status and the Numerical Rating Scale (NRS) for pain. During the hospital stay, nursing staff used the Swedish version of the Nursing Delirium Screening Scale (Nu-DESC) to assess delirium. Semi-structured interviews were also carried out (III) in the one-year follow up. Delirium, dementia and depression were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV TR).Results: Out of 142 participants 54.9% (78/142) developed delirium after cardiac surgery (I). Independent risk factors, predisposing and precipitating, associated with delirium were: age, diabetes, gastritis/peptic ulcer, volume load during operation, longer time on ventilator in intensive care, increased temperature and plasma sodium concentration in the intensive care unit. Out of 114 participants thirty (26.3%) developed dementia within the five years of follow-up. It was shown that a lower preoperative MMSE score and postoperative delirium were factors independently associated with development of dementia (II). One year after cardiac surgery, participants diagnosed with postoperative delirium described in detail feelings of extreme vulnerability and frailty. Despite this, the participants were grateful for the care they had received (III). Hypoactive was the most common symptom profile for delirium. The Swedish version of Nu-DESC showed high sensitivity in detecting hyperactive delirium, but low sensitivity in detecting hypoactive delirium (IV).Conclusion:Delirium was common among older patients undergoing cardiac surgery. Both predisposing and precipitating factors contributed to postoperative delirium. Preventive strategies should be considered in future randomized studies. It might also be suggested that cognitive function should be screened for preoperatively and patients who develop delirium should be followed up to enable early detection of symptoms of dementia. Whether prevention of postoperative delirium can reduce the risk of future dementia remains to be studied. To minimise unnecessary suffering, patients and next of kin should be informed about and prepared for the risk of delirium developing during hospitalization. The Swedish version of Nu-DESC should be combined with cognitive testing to improve detection of hypoactive delirium, but further research is needed. Healthcare professionals need knowledge concerning postoperative delirium in order to prevent, detect and treat delirium so as to avoid and relieve the suffering it might cause.
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| 5. |
- Claesson Lingehall, Helena, et al.
(författare)
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Preoperative Cognitive Performance and Postoperative Delirium Are independently Associated With Future Dementia in Older People Who Have Undergone Cardiac Surgery : A Longitudinal Cohort Study
- 2017
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 45:8, s. 1295-1303
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate if postoperative delirium was associated with the development of dementia within 5 years after cardiac surgery.Design: Longitudinal cohort study.Setting: Cardiothoracic Division, Umeå University Hospital, Sweden.Patients: Patients aged 70 years old or older (n = 114) scheduled for routine cardiac procedures with cardiopulmonary bypass without documented dementia were enrolled in 2009.Intervention: Structured assessments were performed preoperatively, 1 and 4 days after extubation, and 1, 3, and 5 years postoperatively.Measurements and Main Results: Patients were assessed comprehensively, including cognitive and physical function, coexisting medical conditions, demographic characteristics, and medications. Diagnoses of delirium, depression, and dementia were made according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. During the 5-year period, 30 of 114 participants (26.3%) developed dementia. Postoperative delirium had occurred in 87% of those who later developed dementia. A multivariable logistic regression model showed a lower preoperative Mini-Mental State Examination score (p < 0.001; odds ratio, 0.68; 95% CI, 0.54–0.84) and the occurrence of postoperative delirium (p = 0.002; odds ratio, 7.57; 95% CI, 2.15–26.65) were associated with dementia occurrence.Conclusions: Our findings suggest that older patients with reduced preoperative cognitive functions or who develop postoperative delirium are at risk of developing dementia within 5 years after cardiac surgery. Cognitive functions should be screened for preoperatively, those who develop postoperative delirium should be followed up to enable early detection of dementia symptoms, and management should be implemented.
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| 6. |
- Contreras, F.-Xabier, et al.
(författare)
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Molecular recognition of a single sphingolipid species by a protein's transmembrane domain
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 481:7382, s. 525-529
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Tidskriftsartikel (refereegranskat)abstract
- Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the headgroup and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.
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| 7. |
- Gustafsson, Mattias C U, et al.
(författare)
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Factor H Binds to the Hypervariable Region of Many Streptococcus pyogenes M Proteins but Does Not Promote Phagocytosis Resistance or Acute Virulence.
- 2013
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Many pathogens express a surface protein that binds the human complement regulator factor H (FH), as first described for Streptococcus pyogenes and the antiphagocytic M6 protein. It is commonly assumed that FH recruited to an M protein enhances virulence by protecting the bacteria against complement deposition and phagocytosis, but the role of FH-binding in S. pyogenes pathogenesis has remained unclear and controversial. Here, we studied seven purified M proteins for ability to bind FH and found that FH binds to the M5, M6 and M18 proteins but not the M1, M3, M4 and M22 proteins. Extensive immunochemical analysis indicated that FH binds solely to the hypervariable region (HVR) of an M protein, suggesting that selection has favored the ability of certain HVRs to bind FH. These FH-binding HVRs could be studied as isolated polypeptides that retain ability to bind FH, implying that an FH-binding HVR represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed new light on the HVR of M proteins, they suggest that FH-binding may affect S. pyogenes virulence by mechanisms not assessed in currently used model systems.
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| 8. |
- Hellstrom-Lindahl, Ewa, et al.
(författare)
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In vitro binding of [H-3]PIB to human amyloid deposits of different types
- 2014
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Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 21:1, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Systemic amyloidosis is caused by extracellular deposition of insoluble fibrillar proteins arranged in beta-pleated sheets. [C-11] PIB has been used in PET studies to assess A beta deposition in brain of patients with Alzheimer's disease (AD). The possibility to visualize other types of amyloid deposits with [C-11] PIB would be of potential clinical importance in early diagnosis and for following therapeutic effects. In the present study, we evaluated in vitro binding of [3 H] PIB to tissues containing transthyretin (ATTR), immunoglobulin light-chain (AL), amyloid protein A (AA) and Ab amyloid. We found significantly higher binding of [H-3] PIB in tissue from systemic amyloidoses than in control tissue, i.e. 4.7 times higher (p<0.05). [H-3] PIB showed the highest affinity to cortex of AD brain (IC50 = 3.84 nM), while IC50 values were much higher for ATTR, AA and AL type of amyloidosis and large variations in affinity were observed even within tissues having the same type of amyloidosis. Extraction with guanidine-HCl, which disrupts the beta-sheet structure, decreased the protein levels and, concomitantly, the binding of [H-3] PIB in all four types of amyloidoses.
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| 9. |
- Lannergård, Jonas, et al.
(författare)
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Sequence variability is correlated with weak immunogenicity in Streptococcus pyogenes M protein.
- 2015
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Ingår i: MicrobiologyOpen. - : Wiley. - 2045-8827. ; 4:5, s. 774-789
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Tidskriftsartikel (refereegranskat)abstract
- The M protein of Streptococcus pyogenes, a major bacterial virulence factor, has an amino-terminal hypervariable region (HVR) that is a target for type-specific protective antibodies. Intriguingly, the HVR elicits a weak antibody response, indicating that it escapes host immunity by two mechanisms, sequence variability and weak immunogenicity. However, the properties influencing the immunogenicity of regions in an M protein remain poorly understood. Here, we studied the antibody response to different regions of the classical M1 and M5 proteins, in which not only the HVR but also the adjacent fibrinogen-binding B repeat region exhibits extensive sequence divergence. Analysis of antisera from S. pyogenes-infected patients, infected mice, and immunized mice showed that both the HVR and the B repeat region elicited weak antibody responses, while the conserved carboxy-terminal part was immunodominant. Thus, we identified a correlation between sequence variability and weak immunogenicity for M protein regions. A potential explanation for the weak immunogenicity was provided by the demonstration that protease digestion selectively eliminated the HVR-B part from whole M protein-expressing bacteria. These data support a coherent model, in which the entire variable HVR-B part evades antibody attack, not only by sequence variability but also by weak immunogenicity resulting from protease attack.
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| 10. |
- Lannergård, Jonas, et al.
(författare)
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The Hypervariable Region of Streptococcus pyogenes M Protein Escapes Antibody Attack by Antigenic Variation and Weak Immunogenicity.
- 2011
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1934-6069 .- 1931-3128. ; 10:2, s. 147-157
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Tidskriftsartikel (refereegranskat)abstract
- Sequence variation of antigenic proteins allows pathogens to evade antibody attack. The variable protein commonly includes a hypervariable region (HVR), which represents a key target for antibodies and is therefore predicted to be immunodominant. To understand the mechanism(s) of antibody evasion, we analyzed the clinically important HVR-containing M proteins of the human pathogen Streptococcus pyogenes. Antibodies elicited by M proteins were directed almost exclusively against the C-terminal part and not against the N-terminal HVR. Similar results were obtained for mice and humans with invasive S. pyogenes infection. Nevertheless, only anti-HVR antibodies protected efficiently against infection, as shown by passive immunizations. The HVR fused to an unrelated protein elicited no antibodies, implying that it is inherently weakly immunogenic. These data indicate that the M protein HVR evades antibody attack not only through antigenic variation but also by weak immunogenicity, a paradoxical observation that may apply to other HVR-containing proteins.
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