| 1. |
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| 2. |
- Ingegnoli, Francesca, et al.
(författare)
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A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study
- 2015
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Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 102, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% Cl 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% Cl 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% Cl 0.34-3.56. Conclusion: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of sderoderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. (C) 2015 Elsevier Inc. All rights reserved.
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| 3. |
- Zaniew, Marcin, et al.
(författare)
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Long-term renal outcome in children with OCRL mutations : Retrospective analysis of a large international cohort
- 2018
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 33:1, s. 85-94
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Tidskriftsartikel (refereegranskat)abstract
- Background. Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated with mutations in the OCRL gene and characterized by progressive chronic kidney disease (CKD). Here, we aimed to investigate the long-term renal outcome and identify potential determinants of CKD and its progression in children with these tubulopathies. Methods. Retrospective analyses were conducted of clinical and genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype-phenotype analysis, we grouped mutations according to their type and localization. To investigate progression of CKD we used survival analysis by Kaplan-Meier method using stage 3 CKD as the end-point. Results. Median estimated glomerular filtration rate (eGFR) was lower in the LS group compared with DD2 (58.8 versus 87.4 mL/min/1.73 m2, P < 0.01). CKD stage II-V was found in 82% of patients, of these 58% and 28% had moderate-to-severe CKD in LS and DD2, respectively. Three patients (3%), all with LS, developed stage 5 of CKD. Survival analysis showed that LS was also associated with a faster CKD progression than DD2 (P < 0.01). On multivariate analysis, eGFR was dependent only on age (b0.46, P < 0.001). Localization, but not type of mutations, tended to correlate with eGFR. There was also no significant association between presence of nephrocalcinosis, hypercalciuria, proteinuria and number of adverse clinical events and CKD. Conclusions. CKD is commonly found in children with OCRL mutations. CKD progression was strongly related to the underlying diagnosis but did not associate with clinical parameters, such as nephrocalcinosis or proteinuria.
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| 4. |
- Baumeister, Sebastian E., et al.
(författare)
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Association between physical activity and risk of hepatobiliary cancers : A multinational cohort study
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 70:5, s. 885-892
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection).Results: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38–0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33–0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC.Conclusions: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity.Lay summary: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.
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| 5. |
- Costa, Raquel, et al.
(författare)
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Regional differences in the quality of maternal and neonatal care during the COVID-19 pandemic in Portugal : Results from the IMAgiNE EURO study
- 2022
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Ingår i: International Journal of Gynecology and Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 159:S1, s. 137-153
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth across Nomenclature of Territorial Units for Statistics 2 (NUTS-II) regions in Portugal during the COVID-19 pandemic. Methods: Women participating in the cross-sectional IMAgiNE EURO study who gave birth in Portugal from March 1, 2020, to October 28, 2021, completed a structured questionnaire with 40 key WHO standards-based quality measures. Four domains of QMNC were assessed: (1) provision of care; (2) experience of care; (3) availability of human and physical resources; and (4) reorganizational changes due to the COVID-19 pandemic. Frequencies for each quality measure within each QMNC domain were computed overall and by region. Results: Out of 1845 participants, one-third (33.7%) had a cesarean. Examples of high-quality care included: low frequencies of lack of early breastfeeding and rooming-in (8.0% and 7.7%, respectively) and informal payment (0.7%); adequate staff professionalism (94.6%); adequate room comfort and equipment (95.2%). However, substandard practices with large heterogeneity across regions were also reported. Among women who experienced labor, the percentage of instrumental vaginal births ranged from 22.3% in the Algarve to 33.5% in Center; among these, fundal pressure ranged from 34.8% in Lisbon to 66.7% in Center. Episiotomy was performed in 39.3% of noninstrumental vaginal births with variations between 31.8% in the North to 59.8% in Center. One in four women reported inadequate breastfeeding support (26.1%, ranging from 19.4% in Algarve to 31.5% in Lisbon). One in five reported no exclusive breastfeeding at discharge (22.1%; 19.5% in Lisbon to 28.2% in Algarve). Conclusion: Urgent actions are needed to harmonize QMNC and reduce inequities across regions in Portugal.
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| 6. |
- de la Ossa, Xenia, et al.
(författare)
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Almost contact structures on manifolds with a G(2) structure
- 2022
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Ingår i: Advances in Theoretical and Mathematical Physics. - : INT PRESS BOSTON, INC. - 1095-0761 .- 1095-0753. ; 26:1, s. 143-216
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Tidskriftsartikel (refereegranskat)abstract
- We review the construction of almost contact metric (three-) struc-tures, abbreviated ACM(3)S, on manifolds with a G2 structure. These are of interest for certain supersymmetric configurations in string and M-theory. We compute the torsion of the SU(3) struc-ture associated to an ACMS and apply these computations to het -erotic G2 systems and supersymmetry enhancement. We initiate the study of the space of ACM3Ss, which is an infinite dimensional space with a local product structure and interesting topological features. Tantalising links between ACM3Ss and associative and coassociative submanifolds are observed.
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| 7. |
- de la Ossa, Xenia, et al.
(författare)
-
Almost contact structures on manifolds with a G2 structure
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We review the construction of almost contact metric (three-) structures, abbreviated ACM(3)S, on manifolds with a G2 structure. These are of interest for certain supersymmetric configurations in string and M-theory. We compute the torsion of the SU(3) structure associated to an ACMS and apply these computations to heterotic G2 systems and supersymmetry enhancement. We initiate the study of the space of ACM3Ss, which is an infinite dimensional space with a local product structure and interesting topological features. Tantalising links between ACM3Ss and associative and coassociative submanifolds are observed.
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| 8. |
- de la Ossa, Xenia, et al.
(författare)
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Exploring SU(3) structure moduli spaces with integrable G(2) structures
- 2015
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Ingår i: Advances in Theoretical and Mathematical Physics. - 1095-0761 .- 1095-0753. ; 19:4, s. 837-903
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Tidskriftsartikel (refereegranskat)abstract
- We study the moduli space of SU(3) structure manifolds X that form the internal compact spaces in four-dimensional N = 1/2 domain wall solutions of heterotic supergravity with flux. Together with the direction perpendicular to the four-dimensional domain wall, X forms a non-compact 7-manifold Y with torsionful G(2) structure. We use this G(2) embedding to explore how X(t) varies along paths C(t) in the SU(3) structure moduli space. Our analysis includes the Bianchi identities which strongly constrain the flow. We show that requiring that the SU(3) structure torsion is preserved along the path leads to constraints on the G(2) torsion and the embedding of X in Y. Furthermore, we study flows along which the torsion classes of X go from zero to non-zero values. In particular, we present evidence that the flow of half-flat SU(3) structures may contain Calabi-Yau loci, in the presence of non-vanishing H-flux.
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| 9. |
- de la Ossa, Xenia, et al.
(författare)
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Infinitesimal moduli of G2 holonomy manifolds with instanton bundles
- 2016
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Ingår i: Journal of High Energy Physics (JHEP). - : SPRINGER. - 1126-6708 .- 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- We describe the infinitesimal moduli space of pairs (Y, V) where Y is a manifold with G(2) holonomy, and V is a vector bundle on Y with an instanton connection. These structures arise in connection to the moduli space of heterotic string compactifications on compact and non-compact seven dimensional spaces, e.g. domain walls. Employing the canonical G(2) cohomology developed by Reyes-Carrion and Fern\'andez and Ugarte, we show that the moduli space decomposes into the sum of the bundle moduli H-d(sic)A(1)(Y, End(V)) plus the moduli of the G(2) structure preserving the instanton condition. The latter piece is contained in H-d(sic)theta(1)(Y, TY), and is given by the kernel of a map F(sic) which generalises the concept of the Atiyah map for holomorphic bundles on complex manifolds to the case at hand. In fact, the map F(sic) is given in terms of the curvature of the bundle and maps H-d(sic)theta(1)(Y, TY) into H-d(sic)A(2) (Y, End(V)), and moreover can be used to define a cohomology on an extension bundle of TY by End(V). We comment further on the resemblance with the holomorphic Atiyah algebroid and connect the story to physics, in particular to heterotic compactifications on (Y,V) when alpha'=0.
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| 10. |
- de la Ossa, Xenia, et al.
(författare)
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Restrictions of Heterotic G2 Structures and Instanton Connections
- 2017
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Ingår i: Proceedings, Nigel Hitchin’s 70th Birthday Conference. - Oxford : Oxford University Press. - 9780198802020
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Konferensbidrag (refereegranskat)abstract
- This note revisits recent results regarding the geometry and moduli of solutions of the heterotic string on manifolds Y with a G2 structure. In particular, such heterotic G2 systems can be rephrased in terms of a differential Dˇ acting on a complex Ωˇ∗(Y,Q), where Q=T∗Y⊕End(TY)⊕End(V), and Dˇ is an appropriate projection of an exterior covariant derivative D which satisfies an instanton condition. The infinitesimal moduli are further parametrized by the first cohomology H1Dˇ(Y,Q). We proceed to restrict this system to manifolds X with an SU(3) structure corresponding to supersymmetric compactifications to four-dimensional Minkowski space, often referred to as Strominger–Hull solutions. In doing so, we derive a new result: the Strominger-Hull system is equivalent to a particular holomorphic Yang–Mills covariant derivative on Q|X=T∗X⊕End(TX)⊕End(V).
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| 11. |
- de la Ossa, Xenia, et al.
(författare)
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Superpotential of three dimensional N=1 heterotic supergravity
- 2020
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Ingår i: Journal of High Energy Physics (JHEP). - : SPRINGER. - 1126-6708 .- 1029-8479. ; :1
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Tidskriftsartikel (refereegranskat)abstract
- We dimensionally reduce the ten dimensional heterotic supergravity action on spacetimes of the form M-(1,M- 2) x Y, where M-(1,M- 2) is three dimensional maximally symmetric Anti de Sitter or Minkowski space, and Y is a compact seven dimensional manifold with G(2) structure. In doing so, we derive the real superpotential functional of the corresponding three dimensional N = 1 theory. We confirm that extrema of this functional correspond to supersymmetric heterotic compacti:fications on manifolds of G(2) structure in the large volume, weak coupling limit to first order in a'. We make some comments on the role of the superpotential functional with respect to the coupled moduli problem of instanton bundles over G(2) manifolds.
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| 12. |
- de la Ossa, Xenia, et al.
(författare)
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The Infinitesimal Moduli Space of Heterotic G2 Systems
- 2018
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Ingår i: Communications in Mathematical Physics. - : Springer Science and Business Media LLC. - 0010-3616 .- 1432-0916. ; 360:2, s. 727-775
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Tidskriftsartikel (refereegranskat)abstract
- Heterotic string compactifications on integrable G(2) structure manifolds Y with instanton bundles (V, A), (TY, (theta) over tilde )yield supersymmetric three-dimensional vacua that are of interest in physics. In this paper, we define a covariant exterior derivative D and show that it is equivalent to a heterotic G(2) system encoding the geometry of the heterotic string compactifications. This operator D acts on a bundle Q = T*Y circle plus End (V) circle plus End (TY) and satisfies a nilpotency condition (sic)(2) = 0, for an appropriate projection of D. Furthermore, we determine the infinitesimal moduli space of these systems and show that it corresponds to the finite-dimensional cohomology group (sic)(1)((sic)) (Q). We comment on the similarities and differences of our result with Atiyah's well-known analysis of deformations of holmorphic vector bundles over complex manifolds. Our analysis leads to results that are of relevance to all orders in the alpha' expansion.
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| 13. |
- Drandić, Daniela, et al.
(författare)
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Women's perspectives on the quality of hospital maternal and newborn care around the time of childbirth during the COVID-19 pandemic : Results from the IMAgiNE EURO study in Slovenia, Croatia, Serbia, and Bosnia-Herzegovina
- 2022
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Ingår i: International Journal of Gynecology and Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 159:S1, s. 54-69
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the quality of maternal and newborn care (QMNC) in countries of the former Yugoslavia. Method: Women giving birth in a facility in Slovenia, Croatia, Serbia, and Bosnia-Herzegovina between March 1, 2020 and July 1, 2021 answered an online questionnaire including 40 WHO standards-based quality measures. Results: A total of 4817 women were included in the analysis. Significant differences were observed across countries. Among those experiencing labor, 47.4%–62.3% of women perceived a reduction in QMNC due to the COVID-19 pandemic, 40.1%–69.7% experienced difficulties in accessing routine antenatal care, 60.3%–98.1% were not allowed a companion of choice, 17.4%–39.2% reported that health workers were not always using personal protective equipment, and 21.2%–53.8% rated the number of health workers as insufficient. Episiotomy was performed in 30.9%–62.8% of spontaneous vaginal births. Additionally, 22.6%–55.9% of women received inadequate breastfeeding support, 21.5%–62.8% reported not being treated with dignity, 11.0%–30.5% suffered abuse, and 0.7%–26.5% made informal payments. Multivariate analyses confirmed significant differences among countries, with Slovenia showing the highest QMNC index, followed by Croatia, Bosnia-Herzegovina, and Serbia. Conclusion: Differences in QMNC among the countries of the former Yugoslavia during the COVID-19 pandemic were significant. Activities to promote high-quality, evidence-based, respectful care for all mothers and newborns are urgently needed. ClinicalTrials.gov Identifier: NCT04847336.
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| 14. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 15. |
- Ivarsson, Lovisa, et al.
(författare)
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Changes in testing and incidence of Chlamydia trachomatis and Neisseria gonorrhoeae : the possible impact of the COVID-19 pandemic in the three Scandinavian countries
- 2022
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 52:9, s. 623-631
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study aimed to investigate what impact the COVID-19 pandemic and its associated restrictions had on Chlamydia trachomatis and Neisseria gonorrhoeae infections in Sweden, Denmark and Norway, countries with very different governmental strategies for handling this pandemic.Methods: Retrospective analysis of data collected via requests to Swedish regions and to health authorities in Denmark and Norway. The data were collected for the years 2018-2020 and the data from Sweden were more detailed.Results: When the pandemic restrictions were installed in 2020, the number of reported chlamydia cases decreased. The decline was most pronounced in Norway 10.8% (2019: n = 28,446; 2020: n = 25,444) while it was only 3.1% in Denmark (2019: n = 35,688; 2020: n = 34,689) and 4.3% in Sweden (2019: n = 34,726; 2020: n = 33,339). Nucleic acid amplifications tests for chlamydia decreased in Sweden (10%) and Norway (18%) in 2020 compared to 2019, while in Denmark a 21% decrease was noted in April 2020 but thereafter increased to a higher level than 2019. The number of reported gonorrhoea cases decreased in Sweden (17%) and in Norway (39%) in 2020 compared to 2019, while a 21% increase was noted in Denmark.Conclusions: Pandemic restrictions had an impact on the number of reported chlamydia infections in all three countries, but only temporarily and did not seem to be correlated to the restriction levels. The number of reported gonorrhoea infections in Sweden and Norway significantly decreased but not in Denmark. Pandemic restrictions appear to have had a limited effect on the spread of chlamydia and gonorrhoea.
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| 16. |
- Kerr White, John, et al.
(författare)
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A Synthetic Cyclized Antimicrobial Peptide with Potent Effects against Drug-Resistant Skin Pathogens
- 2023
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Ingår i: ACS - Infectious Diseases. - : American Chemical Society (ACS). - 2373-8227. ; 9:5, s. 1056-1063
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Tidskriftsartikel (refereegranskat)abstract
- Dermal infections requiring treatment are usually treated with conventional antibiotics, but the rise of bacterial resistance to first-line antibiotics warrants alternative therapeutics. Here, we report that a backbone-cyclized antimicrobial peptide, CD4-PP, designed from the human host defense peptide LL-37, has strong direct antibacterial effects on antibiotic sensitive as well as resistant-type strains and clinical isolates of common skin pathogens in the low (<2) μM range. In addition, it influences innate immunity in keratinocytes, and treatment with CD4-PP is able to clear bacterial infections in infected keratinocytes. Additionally, CD4-PP treatment significantly reduces the wound area in a lawn of keratinocytes infected with MRSA. In conclusion, CD4-PP has the potential to serve as a future drug treating wounds infected with antibiotic-resistant bacteria.
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| 17. |
- Key, Timothy J., et al.
(författare)
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Consumption of Meat, Fish, Dairy Products, Eggs and Risk of Ischemic Heart Disease : A Prospective Study of 7198 Incident Cases Among 409,885 Participants in the Pan-European EPIC Cohort
- 2019
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 139:25, s. 2835-2845
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is uncertainty about the relevance of animal foods to the etiology of ischemic heart disease (IHD). We examined meat, fish, dairy products and eggs and risk for IHD in the pan-European EPIC cohort.METHODS: A prospective study of 409,885 men and women in nine European countries. Diet was assessed using validated questionnaires, calibrated using 24-hour recalls. Lipids and blood pressure were measured in a subsample. During 12.6 years mean follow up, 7198 participants had a myocardial infarction or died from IHD. The relationships of animal foods with risk were examined using Cox regression with adjustment for other animal foods and relevant covariates.RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI 1.06-1.33) for a 100 g/d increment in intake of red and processed meat, and this remained significant after excluding the first 4 years of follow-up (HR 1.25 [1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR 0.93 [0.89-0.98] per 100 g/d increment), cheese (HR 0.92 [0.86-0.98] per 30 g/d increment) and eggs (HR 0.93 [0.88-0.99] per 20 g/d increment); the associations with yogurt and eggs were attenuated and non-significant after excluding the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish or milk. In analyses modelling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese or eggs was associated with approximately 20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-HDL cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-HDL cholesterol.CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat, and inversely associated with consumption of yogurt, cheese and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-HDL cholesterol, and for red and processed meat with systolic blood pressure, which could mediate such effects.
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| 18. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 19. |
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| 20. |
- Lazzerini, Marzia, et al.
(författare)
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Quality of facility-based maternal and newborn care around the time of childbirth during the COVID-19 pandemic : online survey investigating maternal perspectives in 12 countries of the WHO European Region
- 2022
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Ingår i: The Lancet regional health. Europe. - : Elsevier BV. - 2666-7762. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multi-country studies assessing the quality of maternal and newborn care (QMNC) during the COVID-19 pandemic, as defined by WHO Standards, are lacking.Methods: Women who gave birth in 12 countries of the WHO European Region from March 1, 2020 - March 15, 2021 answered an online questionnaire, including 40 WHO Standard-based Quality Measures.Findings: 21,027 mothers were included in the analysis. Among those who experienced labour (N=18,063), 41·8% (26·1%- 63·5%) experienced difficulties in accessing antenatal care, 62% (12·6%-99·0%) were not allowed a companion of choice, 31·1% (16·5%-56·9%) received inadequate breastfeeding support, 34·4% (5·2%-64·8%) reported that health workers were not always using protective personal equipment, and 31·8% (17·8%-53·1%) rated the health workers' number as "insufficient". Episiotomy was performed in 20·1% (6·1%-66·0%) of spontaneous vaginal births and fundal pressure applied in 41·2% (11·5% -100%) of instrumental vaginal births. In addition, 23·9% women felt they were not treated with dignity (12·8%-59·8%), 12·5% (7·0%-23·4%) suffered abuse, and 2·4% (0·1%-26·2%) made informal payments. Most findings were significantly worse among women with prelabour caesarean birth (N=2,964). Multivariate analyses confirmed significant differences among countries, with Croatia, Romania, Serbia showing significant lower QMNC Indexes and Luxemburg showing a significantly higher QMNC Index than the total sample. Younger women and those with operative births also reported significantly lower QMNC Indexes.Interpretation: Mothers reports revealed large inequities in QMNC across countries of the WHO European Region. Quality improvement initiatives to reduce these inequities and promote evidence-based, patient-centred respectful care for all mothers and newborns during the COVID-19 pandemic and beyond are urgently needed.Funding: The study was financially supported by the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.Study registration: ClinicalTrials.gov Identifier: NCT04847336.
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| 21. |
- Malehmir, Alireza, 1977-, et al.
(författare)
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Sparse 3D reflection seismic survey for deep-targeting iron oxide deposits and their host rocks, Ludvika Mines, Sweden
- 2021
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Ingår i: Solid Earth. - : Copernicus Publications. - 1869-9510 .- 1869-9529. ; 12:2, s. 483-502
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Tidskriftsartikel (refereegranskat)abstract
- Many metallic mineral deposits have sufficient physical property contrasts, particularly density, to be detectable using seismic methods. These deposits are sometimes significant for our society and economic growth and can help to accelerate the energy transition towards decarbonization. However, their exploration at depth requires high-resolution and sensitive methods. Following a series of 2D seismic trials, a sparse, narrow source-receiver azimuth, 3D seismic survey was conducted in the Blotberget mine, in central Sweden, covering an area of approximately 6 km(2) for deep-targeting iron oxide deposits and their host rock structures. The survey benefited from a collaborative work by putting together 1266 seismic recorders and a 32 t vibrator, generating 1056 shot points in a fixed geometry setup. Shots were fired at every 10 m where possible, and receivers were placed at every 10-20 m. Notable quality data were acquired despite the area being dominated by swampy places as well as by built-up roads and historical tailings The data processing had to overcome these challenges for the static corrections and strong surface waves in particular. A tailored for hardrock setting and processing workflow was developed for handling such a dataset, where the use of mixed 2D and 3D refraction static corrections was relevant. The resulting seismic volume is rich in terms of reflectivity, with clear southeast-dipping reflections originating from the iron oxide deposits extending vertically and laterally at least 300 m beyond what was known from available boreholes. As a result, we estimate potential additional resources from the 3D reflection seismic experiment on the order of 10 Mt to be worth drilling for detailed assessments. The mineralization is crosscut by at least two major sets of northwest-dipping reflections interpreted to dominantly be normal faults and to be responsible for much of the lowland in the Blotberget area. Moreover, these post-mineralization faults likely control the current 3D geometry of the deposits. Curved and submerged reflections interpreted from folds or later intrusions are also observed, showing the geological complexity of the study area. The seismic survey also delineates the near-surface expression of a historical tailing as a by-product of refraction static corrections, demonstrating why 3D seismic data are so valuable for both mineral exploration and mine planning applications.
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| 22. |
- Pumpure, Elizabete, et al.
(författare)
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Womenʼs perspectives on the quality of maternal and newborn care in childbirth during the COVID-19 pandemic in Latvia : Results from the IMAgiNE EURO study on 40 WHO standards-based quality measures
- 2022
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Ingår i: International Journal of Gynecology and Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 159:S1, s. 97-112
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth during the COVID-19 pandemic in Latvia, comparing the years 2020 and 2021, among women who went into labor or had a prelabor cesarean. Methods: Women giving birth in healthcare facilities in Latvia from March 1, 2020, to October 28, 2021, answered an online questionnaire including 40 WHO standards-based quality measures. Descriptive and multivariate quantile regression analyses were performed to compare QMNC in 2020 and 2021. Results: 2079 women were included in the analysis: 1860 women who went into labor (group 1) and 219 with prelabor cesarean (group 2). Among group 1, 66.4% (n = 99/149) of women received fundal pressure in an instrumental vaginal birth, 43.5% (n = 810) lacked involvement in choices, 17.4% (n = 317) reported suffering abuse, 32.7% (n = 609) reported inadequate breastfeeding support while 5.2% (n = 96) lack of early breastfeeding. A significant reduction in QMNC due to the COVID-19 pandemic was reported by 29.5% (n = 219) and 25.0% (n = 270) of respondents in 2020 and 2021, respectively (P = 0.045). Multivariate analyses highlighted a significantly lower QMNC index for 2020 compared with 2021 (P < 0.001). Conclusion: This first study investigating QMNC in Latvia showed significant gaps in QMNC perceived by respondents, with slightly better results in 2021. Appropriate healthcare strategies to improve health care for women and newborns in Latvia are required. ClinicalTrials.gov Identifier:NCT04847336.
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| 23. |
- Ward, Heather A., et al.
(författare)
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Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
- 2019
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 8:73, s. 1122-1132
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 416,746 individuals from 10 countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident lung cancer (n = 3731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1489 matched controls for whom serum cotinine was available. Results: Haem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00–1.07), and in the highest versus lowest quintile (HR 1.16, 95% CI 1.02–1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case–control subset. Conclusions: Greater haem iron intake may be modestly associated with lung cancer risk.
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| 24. |
- Wilkinson, John L., et al.
(författare)
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Pharmaceutical pollution of the world's rivers
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:8
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Tidskriftsartikel (refereegranskat)abstract
- Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.
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| 25. |
- Wozniak, Magdalena B., et al.
(författare)
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Alcohol consumption and the risk of renal cancers in the European prospective investigation into cancer and nutrition (EPIC)
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:8, s. 1953-1966
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n=931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), 0.91 (0.63-1.30), respectively, (p(trend)=0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer. What's new? Previous studies have indicated that environmental or lifestyle factors may be involved in the etiology of renal cancer, and that moderate alcohol consumption may reduce the risk of this type of cancer. In this very large European study (nearly 500,000 subjects), the authors found that, indeed, total alcohol consumption was inversely associated with renal cancer overall (for all subsites combined), and also with cancers of the renal parenchyma.
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