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| 2. |
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| 3. |
- Gilbert, F., et al.
(author)
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Sediment reworking by the burrowing polychaete Hediste diversicolor modulated by environmental and biological factors across the temperate North Atlantic. A tribute to Gaston Desrosiers
- 2021
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In: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981. ; 541
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Journal article (peer-reviewed)abstract
- Particle mixing and irrigation of the seabed by benthic fauna (bioturbation) have major impacts on ecosystem functions such as remineralization of organic matter and sediment-water exchange. As a tribute to Prof. Gaston Desrosiers by the Nereis Park association, eighteen laboratories carried out a collaborative experiment to acquire a global snapshot of particle reworking by the polychaete Hediste diversicolor at 16 sites surrounding the Northern Atlantic. Organisms and soft sediments were collected during May - July at different geographical locations and, using a common laboratory protocol, particulate fluorescent tracers (`luminophores') were used to quantify particle transport over a 10-day period. Particle mixing was quantified using the maximum penetration depth of tracers (MPD), particle diffusive coefficients (D-b), and non-local transport coefficients (r). Non-local coefficients (reflecting centimeter scale transport steps) ranged from 0.4 to 15 yr(-1), and were not correlated across sites with any measured biological (biomass, biovolume) or environmental parameters (temperature, grain size, organic matter). Maximum penetration depths (MPD) averaged similar to 10.7 cm (6.5-14.5 cm), and were similar to the global average bioturbation depth inferred from short-lived radiochemical tracers. MPD was also not correlated with measures of size (individual biomass), but increased with grain size and decreased with temperature. Bio-diffusion (D-b) correlated inversely with individual biomass (size) and directly with temperature over the environmental range (Q(10) similar to 1.7; 5-21 degrees C). The transport data were comparable in magnitude to rates reported for localized H. diversicolor populations of similar size, and confirmed some but not all correlations between sediment reworking and biological and environmental variables found in previous studies. The results imply that measures of particle reworking activities of a species from a single location can be generally extrapolated to different populations at similar conditions.
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| 4. |
- Wrobel, L., et al.
(author)
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Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Enhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for a number of neurodegenerative diseases, especially Huntington's disease and various spinocerebellar ataxias. Ideally, such approaches should preferentially clear the mutant/misfolded species, while having minimal impact on the stability of wild-type/normally-folded proteins. Furthermore, activation of both ubiquitin-proteasome and autophagy-lysosome routes may be advantageous, as this would allow effective clearance of both monomeric and oligomeric species, the latter which are inaccessible to the proteasome. Here we find that compounds that activate the D1 ATPase activity of VCP/p97 fulfill these requirements. Such effects are seen with small molecule VCP activators like SMER28, which activate autophagosome biogenesis by enhancing interactions of PI3K complex components to increase PI(3)P production, and also accelerate VCP-dependent proteasomal clearance of such substrates. Thus, this mode of VCP activation may be a very attractive target for many neurodegenerative diseases. Several neurodegenerative diseases are characterized by the aggregation of cytoplasmic proteins. Here, the authors demonstrate that the small molecule SMER28 activates VCP, which enhances both autophagic and proteasomal clearance of aggregate-prone proteins.
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| 5. |
- Dahlqvist, Johanna, 1979-, et al.
(author)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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In: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Journal article (peer-reviewed)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 6. |
- Hartman, E. A. R., et al.
(author)
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Decisions on antibiotic prescribing for suspected urinary tract infections in frail older adults: a qualitative study in four European countries
- 2022
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In: Age and ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 51:6
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Journal article (peer-reviewed)abstract
- Background a suspected urinary tract infection (UTI) is the most common reason to prescribe antibiotics in a frail older patient. Frequently, antibiotics are prescribed unnecessarily. To increase appropriate antibiotic use for UTIs through antibiotic stewardship interventions, we need to thoroughly understand the factors that contribute to these prescribing decisions. Objectives (1) to obtain insight into factors contributing to antibiotic prescribing for suspected UTIs in frail older adults. (2) To develop an overarching model integrating these factors to guide the development of antibiotic stewardship interventions for UTIs in frail older adults. Methods we conducted an exploratory qualitative study with 61 semi-structured interviews in older adult care settings in Poland, the Netherlands, Norway and Sweden. We interviewed physicians, nursing staff, patients and informal caregivers. Results participants described a chain of decisions by patients, caregivers and/or nursing staff preceding the ultimate decision to prescribe antibiotics by the physician. We identified five themes of influence: (1) the clinical situation and its complexity within the frail older patient, (2) diagnostic factors, such as asymptomatic bacteriuria, (3) knowledge (gaps) and attitude, (4) communication: interprofessional, and with patients and relatives and (5) context and organisation of care, including factors such as availability of antibiotics (over the counter), antibiotic stewardship efforts and factors concerning out-of-hours care. Conclusions decision-making on suspected UTIs in frail older adults is a complex, multifactorial process. Due to the diverse international setting and stakeholder variety, we were able to provide a comprehensive overview of factors to guide the development of antibiotic stewardship interventions.
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| 7. |
- Hartman, E. A. R., et al.
(author)
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Multifaceted antibiotic stewardship intervention using a participatory-action-research approach to improve antibiotic prescribing for urinary tract infections in frail elderly (ImpresU): study protocol for a European qualitative study followed by a pragmatic cluster randomised controlled trial
- 2021
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In: Bmj Open. - : BMJ. - 2044-6055. ; 11:10
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Journal article (peer-reviewed)abstract
- Introduction Almost 60% of antibiotics in frail elderly are prescribed for alleged urinary tract infections (UTIs). A substantial part of this comprises prescriptions in case of non-specific symptoms or asymptomatic bacteriuria, for which the latest guidelines promote restrictiveness with antibiotics. We aim to reduce inappropriate antibiotic use for UTIs through an antibiotic stewardship intervention (ASI) that encourages to prescribe according to these guidelines. To develop an effective ASI, we first need a better understanding of the complex decision-making process concerning suspected UTIs in frail elderly. Moreover, the implementation approach requires tailoring to the heterogeneous elderly care setting. Methods and analysis First, we conduct a qualitative study to explore factors contributing to antibiotic prescribing for UTIs in frail elderly, using semi-structured interviews with general practitioners, nursing staff, patients and informal caregivers. Next, we perform a pragmatic cluster randomised controlled trial in elderly care organisations. A multifaceted ASI is implemented in the intervention group; the control group receives care as usual. The ASI is centred around a decision tool that promotes restrictive antibiotic use, supported by a toolbox with educational materials. For the implementation, we use a modified participatory-action-research approach, guided by the results of the qualitative study. The primary outcome is the number of antibiotic prescriptions for suspected UTIs. We aim to recruit 34 clusters with in total 680 frail elderly residents >= 70 years. Data collection takes place during a 5-month baseline period and a 7-month follow-up period. Finally, we perform a process evaluation. The study has been delayed for 6 months due to COVID-19 and is expected to end in July 2021. Ethics and dissemination Ethical approvals and/or waivers were obtained from the ethical committees in Poland, the Netherlands, Norway and Sweden. The results will be disseminated through publication in peer-reviewed journals and conference presentations.
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| 8. |
- Leeksma, AC, et al.
(author)
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Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study
- 2021
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 106:1, s. 87-97
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Journal article (peer-reviewed)abstract
- Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence of a CK. Current knowledge on genomic arrays in CLL is based on outcomes of single center studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2293 arrays from 13 diagnostic laboratories according to established standards. CNAs were found outside regions captured by CLL FISH probes in 34% of patients, and several of them including gains of 8q, deletions of 9p and 18p (p<0.01) were linked to poor outcome after correction for multiple testing. Patients (n=972) could be divided in three distinct prognostic subgroups based on the number of CNAs. Only high genomic complexity (high-GC), defined as ≥5 CNAs emerged as an independent adverse prognosticator on multivariable analysis for time to first treatment (Hazard ratio: 2.15, 95% CI: 1.36-3.41; p=0.001) and overall survival (Hazard ratio: 2.54, 95% CI: 1.54-4.17; p<0.001; n=528). Lowering the size cutoff to 1 Mb in 647 patients did not significantly improve risk assessment. Genomic arrays detected more chromosomal abnormalities and performed at least as well in terms of risk stratification compared to simultaneous chromosome banding analysis as determined in 122 patients. Our findings highlight genomic array as an accurate tool for CLL risk stratification.
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| 9. |
- Lundtoft, Christian, et al.
(author)
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Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjogren's Syndrome
- 2022
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 74:11, s. 1842-1850
-
Journal article (peer-reviewed)abstract
- Objective Complete genetic deficiency of the complement component C2 is a strong risk factor for monogenic systemic lupus erythematosus (SLE), but whether heterozygous C2 deficiency adds to the risk of SLE or primary Sjogren's syndrome (SS) has not been studied systematically. This study was undertaken to investigate potential associations of heterozygous C2 deficiency and C4 copy number variation with clinical manifestations in patients with SLE and patients with primary SS. Methods The presence of the common 28-bp C2 deletion rs9332736 and C4 copy number variation was examined in Scandinavian patients who had received a diagnosis of SLE (n = 958) or primary SS (n = 911) and in 2,262 healthy controls through the use of DNA sequencing. The concentration of complement proteins in plasma and classical complement function were analyzed in a subgroup of SLE patients. Results Heterozygous C2 deficiency-when present in combination with a low C4A copy number-substantially increased the risk of SLE (odds ratio [OR] 10.2 [95% confidence interval (95% CI) 3.5-37.0]) and the risk of primary SS (OR 13.0 [95% CI 4.5-48.4]) when compared to individuals with 2 C4A copies and normal C2. For patients heterozygous for rs9332736 with 1 C4A copy, the median age at diagnosis was 7 years earlier in patients with SLE and 12 years earlier in patients with primary SS when compared to patients with normal C2. Reduced C2 levels in plasma (P = 2 x 10(-9)) and impaired function of the classical complement pathway (P = 0.03) were detected in SLE patients with heterozygous C2 deficiency. Finally, in a primary SS patient homozygous for C2 deficiency, we observed low levels of anti-Scl-70, which suggests a risk of developing systemic sclerosis or potential overlap between primary SS and other systemic autoimmune diseases. Conclusion We demonstrate that a genetic pattern involving partial deficiencies of C2 and C4A in the classical complement pathway is a strong risk factor for SLE and for primary SS. Our results emphasize the central role of the complement system in the pathogenesis of both SLE and primary SS.
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| 10. |
- Ahlström, Aisling, 1976, et al.
(author)
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A double-blind randomized controlled trial investigating a time-lapse algorithm for selecting Day 5 blastocysts for transfer
- 2022
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In: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:4, s. 708-717
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Journal article (peer-reviewed)abstract
- STUDY QUESTION Can use of a commercially available time-lapse algorithm for Day 5 blastocyst selection improve pregnancy rates compared with morphology alone? SUMMARY ANSWER The use of a time-lapse selection model to choose blastocysts for fresh single embryo transfer on Day 5 did not improve ongoing pregnancy rate compared to morphology alone. WHAT IS KNOWN ALREADY Evidence from time-lapse monitoring suggests correlations between timing of key developmental events and embryo viability. No good quality evidence exists to support improved pregnancy rates following time-lapse selection. STUDY DESIGN, SIZE, DURATION A prospective multicenter randomized controlled trial including 776 randomized patients was performed between 2018 and 2021. Patients with at least two good quality blastocysts on Day 5 were allocated by a computer randomization program in a proportion of 1:1 into either the control group, whereby single blastocysts were selected for transfer by morphology alone, or the intervention group whereby final selection was decided by a commercially available time-lapse model. The embryologists at the time of blastocyst morphological scoring were blinded to which study group the patients would be randomized, and the physician and patients were blind to which group they were allocated until after the primary outcome was known. The primary outcome was number of ongoing pregnancies in the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS From 10 Nordic IVF clinics, 776 patients with a minimum of two good quality blastocysts on Day 5 (D5) were randomized into one of the two study groups. A commercial time-lapse model decided the final selection of blastocysts for 387 patients in the intervention (time-lapse) group, and blastocysts with the highest morphological score were transferred for 389 patients in the control group. Only single embryo transfers in fresh cycles were performed. MAIN RESULTS AND THE ROLE OF CHANCE In the full analysis set, the ongoing pregnancy rate for the time-lapse group was 47.4% (175/369) and 48.1% (181/376) in the control group. No statistically significant difference was found between the two groups: mean difference -0.7% (95% CI -8.2, 6.7, P = 0.90). Pregnancy rate (60.2% versus 59.0%, mean difference 1.1%, 95% CI -6.2, 8.4, P = 0.81) and early pregnancy loss (21.2% versus 18.5%, mean difference 2.7%, 95% CI -5.2, 10.6, P = 0.55) were the same for the time-lapse and the control group. Subgroup analyses showed that patient and treatment characteristics did not significantly affect the commercial time-lapse model D5 performance. In the time-lapse group, the choice of best blastocyst changed on 42% of occasions (154/369, 95% CI 36.9, 47.2) after the algorithm was applied, and this rate was similar for most treatment clinics. LIMITATIONS, REASONS FOR CAUTION During 2020, the patient recruitment rate slowed down at participating clinics owing to coronavirus disease-19 restrictions, so the target sample size was not achieved as planned and it was decided to stop the trial prematurely. The study only investigated embryo selection at the blastocyst stage on D5 in fresh IVF transfer cycles. In addition, only blastocysts of good morphological quality were considered for transfer, limiting the number of embryos for selection in both groups: also, it could be argued that this manual preselection of blastocysts limits the theoretical selection power of time-lapse, as well as restricting the results mainly to a good prognosis patient group. Most patients were aimed for blastocyst stage transfer when a minimum of five zygotes were available for extended culture. Finally, the primary clinical outcome evaluated was pregnancy to only 6-8 weeks. WIDER IMPLICATIONS OF THE FINDINGS The study suggests that time-lapse selection with a commercially available time-lapse model does not increase chance of ongoing pregnancy after single blastocyst transfer on Day 5 compared to morphology alone. STUDY FUNDING/COMPETING INTEREST(S) The study was financed by a grant from the Swedish state under the ALF-agreement between the Swedish government and the county councils (ALFGBG-723141). Vitrolife supported the study with embryo culture dishes and culture media. During the study period, T.H. changed his employment from Livio AB to Vitrolife AB. All other authors have no conflicts of interests to disclose. DATE OF FIRST PATIENT'S ENROLMENT 11 June 2018.
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| 11. |
- Braganca, F. M. Serra, et al.
(author)
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Improving gait classification in horses by using inertial measurement unit (IMU) generated data and machine learning
- 2020
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- For centuries humans have been fascinated by the natural beauty of horses in motion and their different gaits. Gait classification (GC) is commonly performed through visual assessment and reliable, automated methods for real-time objective GC in horses are warranted. In this study, we used a full body network of wireless, high sampling-rate sensors combined with machine learning to fully automatically classify gait. Using data from 120 horses of four different domestic breeds, equipped with seven motion sensors, we included 7576 strides from eight different gaits. GC was trained using several machine-learning approaches, both from feature-extracted data and from raw sensor data. Our best GC model achieved 97% accuracy. Our technique facilitated accurate, GC that enables in-depth biomechanical studies and allows for highly accurate phenotyping of gait for genetic research and breeding. Our approach lends itself for potential use in other quadrupedal species without the need for developing gait/animal specific algorithms.
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| 12. |
- Bremme, K, et al.
(author)
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The presence of lupus nephritis additionally increases the risk of preeclampsia among pregnant women with systemic lupus erythematosus
- 2021
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In: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 30:7, s. 1031-1038
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Journal article (peer-reviewed)abstract
- Pregnant women with systematic lupus erythematosus (SLE) have an increased risk of obstetric complications, such as preeclampsia and premature births. Previous studies have suggested that renal involvement could further increase the risk for adverse obstetric outcomes. Aims: The aim of this study was to compare the obstetric outcomes in a Swedish cohort of patients with SLE with and without lupus nephritis (LN). Patients and methods The study was conducted as a retrospective observational study on 103 women with SLE, who gave birth at the Karolinska University Hospital between the years 2000-2017. Thirty-five women had previous or active LN and 68 women had non-renal lupus. Data was collected from digital medical records. The outcomes that were analysed included infants born small for gestational age (SGA), premature birth, preeclampsia, SLE- or nephritis flare and caesarean section. Results Women with LN, both with previous and with renal flare during pregnancy suffered from pre-eclampsia more often compared to women with non-renal lupus (25.7% vs 2.9%, p = 0.001) and this complication was associated with premature birth (p = 0.021) and caesarean section (p = 0.035). Conclusions Lupus nephritis is a significant risk factor for adverse obstetric outcomes in women with SLE, including preeclampsia. Those patients could benefit from more frequent antenatal controls and more vigorous follow-up.
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| 13. |
- Carmont, Michael R, 1972, et al.
(author)
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Musculotendinous ruptures of the achilles tendon had greater heel-rise height index compared with mid-substance rupture with non-operative management: A retrospective cohort study
- 2024
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In: Journal of ISAKOS. - 2059-7754 .- 2059-7762.
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Journal article (peer-reviewed)abstract
- Introduction: Achilles tendon ruptures (ATRs) may occur at varying locations with ruptures at the mid-substance (MS) of the tendon most common, followed tears at the musculotendinous (MT) junction. There is scant literature about the outcome of MT ATR. This study compared the outcome of patients with a MT ATR with patients following a MS ATR. Methods: The diagnostic features and clinical outcome of 37 patients with a MT ATR were compared with a cohort of 19 patients with a MS ATR. Patients in both groups were managed non-operatively and received the same rehabilitation protocol with weight-bearing rehabilitation in protective functional brace. Results: From February 2009 to August 2023, 556 patients presented with an ATR. Of these, 37 (6.7 %) patients were diagnosed with a MT tear. At final follow-up, at 12 months following injury, the MT group reported an Achilles tendon total rupture score (ATRS) of mean (standard deviation (SD)) of 83.6 (3.5) (95 % confidence interval (CI) 81.8, 85.4) and median (inter-quartile range (IQR)) ATRS of 86 points (78–95.5) and the MS group mean (SD) of 80.3 (8.5) (95%CI) 76.1, 80.5) and median (IQR) of 87 points (59–95) (p = 0.673). Functional evaluation, however, revealed statistically significant differences in mean (SD) heel-rise height index MT group 79 % (25) (95%CI 65.9, 92.1) and MS group 59 % (13) (95%CI 51.9, 67.1) (p = 0.019). In the MT rupture group, there were considerably less complications than the MS rupture group. Conclusions: When managed non-operatively, with only a 6 weeks period of brace protection, patients have little limitation although have some residual reduction of single heel-rise at the one-year following MT ATR. Level of evidence: IV.
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| 14. |
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| 15. |
- Faustini, F, et al.
(author)
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Rituximab in Systemic Lupus Erythematosus: Transient Effects on Autoimmunity Associated Lymphocyte Phenotypes and Implications for Immunogenicity
- 2022
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In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 826152-
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Journal article (peer-reviewed)abstract
- B cell abnormalities are common in systemic lupus erythematosus (SLE), and include expansion of double negative (DN) and age-associated-like B cells (ABC-like). We aimed to investigate rituximab (RTX) effects on DN and ABC-like B-cell subsets and, when possible, also secondary effects on T cells. Fifteen SLE patients, fulfilling the ACR 1982 criteria, starting RTX and followed longitudinally up to two years, were analyzed for B- and T- lymphocyte subsets using multicolor flow cytometry. DN were defined as IgD-CD27- and ABC-like as CD11c+CD21- within the DN gate. Additional phenotyping was performed adding CXCR5 in the B-cell panel. Cellular changes were further analyzed in the context of the generation of anti-drug antibodies (ADA) against RTX and clinical information. The SLE patients were mainly females (86.6%), of median age 36.7 (29.8-49.4) years and disease duration of 6.1 (1.6-11.8) years. Within the DN subset, ABC-like (IgD-CD27-CD11c+CD21-) B cell frequency reduced from baseline median level of 20.4% to 11.3% (p=0.03), at early follow-up. The DN B cells were further subdivided based on CXCR5 expression. Significant shifts were observed at the early follow-up in the DN2 sub-cluster (CD11c+CXCR5-), which reduced significantly (-15.4 percentage points, p=0.02) and in the recently described DN3 (CD11c-CXCR5-) which increased (+13 percentage points, p=0.03). SLE patients treated with RTX are at high risk of developing ADA. In our cohort, the presence of ADA at 6 months was associated with lower frequencies of DN cells and to a more pronounced expansion of plasmablasts at early follow-up. The frequency of follicular helper T cells (TFH, CD4+PD-1+CXCR5+) and of peripheral helper T cells (TPH, CD4+PD-1+CXCR5-) did not change after RTX. A sub-cluster of PD-1highCD4+ T cells showed a significant decrease at later follow-up compared to early follow-up (p=0.0039). It is well appreciated that RTX transiently influences B cells. Here, we extend these observations to cell phenotypes which are believed to directly contribute to autoimmunity in SLE. We show early transient effects of RTX on ABC-like memory B cells, later effects on PD-1high CD4+ cells, and possible implications for RTX immunogenicity. Further insight in such effects and their monitoring may be of clinical relevance.
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| 16. |
- Faustini, F, et al.
(author)
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RITUXIMAB THERAPY IN SYSTEMIC LUPUS ERYTHEMATOSUS - TRANSIENT EFFECTS ON AGE ASSOCIATED B-CELLS
- 2021
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 203-204
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Conference paper (other academic/artistic)abstract
- Immune system’s abnormalities in SLE involve several subsets of the B-cell compartment, including double negative B-cells (DN) and CD11c+CD21- B cells (also referred to as ABC-age associated B cells), which are expanded in the disease. ABC cells are also known to interact with T helper cells, T follicular and peripheral helper cells (1). Rituximab, a chimeric anti- CD20 antibody, depleting B cells, is commonly used off-label as treatment for SLE patients, especially in lupus nephritis. Little is known on the impact of B-cell depletion on such B-cell subsets and on B-T-cell interactions.Objectives:to investigate the effects of rituximab (RTX) on the frequencies of double negative B-cell subsets and CD11c+CD21- ABC cells and as well as T follicular helper (TFH, CXCR5+ PD-1+) and T peripheral helper (TPH, PD-1high) CD4+ T-cell subsets.Methods:15 SLE patients, starting RTX and followed longitudinally up to two years, were analyzed for lymphocyte subsets using multicolor flow cytometry. Cryopreserved PBMC were thawed and stained at the same time together with one buffy coat. Around 1 x 106 PBMC for each panel were labeled and further stained with fluorescent antibodies for B and T-cell markers. For the B-cell panel, PBMC were stained with anti-CD3, CD14, CD16, CD19, IgD, CD27, CD38, CD11c, CD21 and in some samples with anti-CXCR5 antibodies. For the T-cell panel, PBMC were labeled with anti-CD16, CD14, CD19 and CD3, CD4, CD8, PD-1, CCR7, CXCR5, CD45RA antibodies. All patients fulfilled the ACR 1982 classification criteria for SLE. Cellular changes were analyzed in the context of clinical information.Results:in the present cohort, the SLE patients were mainly female (86.6%) and of median age of 36.7 (29.8-49.4) with a disease duration of 6.1(1.6-11.8) years, and active disease with SLEDAI-2K at baseline 12.0 (8.0-16.0). The frequency of age-associated B cells (ABCs; CD27-IgD-CD11c+ CD21-) decreased by 13% (p=0.03) in the first two to four months after rituximab start, while globally the DN (IgD-CD27-) B cells transiently increased by around 3% (p=0.15) at the first follow-up. This increase could not be attributed to the DN1 (CXCR5+CD11c-) or DN2 (CXCR5-CD11c+) subsets but to the CD11c-CXCR5- DN (DN3) B cells (increase= 6.7%, p=0.03). In parallel, T effector cells (CCR7- CD45RA+) and TEMRA (CD45RA+ CCR7-) frequencies increased after first follow up in both CD4+ and CD8+ T cells. The frequency of TFH (CXCR5+ PD-1+) cells did not change after rituximab, however a decrease of PD-1high CD4+ cells was observed in most patients, although not significant, after 2-4 month of treatment. In most patients the frequency of PD-1high CD4+ cells either reduce or stay the same after RTX treatment (reduction= 0.53, p=0.28). After 11-15 months of RTX treatment the frequency of PD-1high CD4+ T cell reduces by a -0.5% in comparison to 2-4 months (p=0.039). The SLEDAI at baseline did not correlate with the frequency of PD-1high CD4+ T cells (r=0.03, p=0.9).Conclusion:the importance of T cell - B cell interactions in SLE pathogenesis was recently strengthened by the identification of the lymphocyte subsets TFH/TPH and ABCs respectively. Here, in the context of rituximab treated SLE, we could detect a reduction in the frequencies of both ABCs and PD-1high T cells after treatment with rituximab, while the DN3 and effector memory T cells frequencies increased. Our data suggests that anti-CD20 mediated B-cell depletion affects both B-cell and T-cell subsets frequencies, and that monitoring these specific cell subsets may be clinically relevant.References:[1]Bocharnikov AV, Keegan J, Wacleche VS, Cao Y, Fonseka CY, Wang G, et al. PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. JCI insight. 2019;4(20)Disclosure of Interests:Francesca Faustini Speakers bureau: More than two years ago and not in relation to any aspect of the present research, Natalie Sippl: None declared, Ragnhild Stålesen: None declared, Karine Chemin: None declared, Iva Gunnarsson: None declared, Vivianne Malmström: None declared.
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| 17. |
- Gkekas, Ioannis, et al.
(author)
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Mismatch repair status predicts survival after adjuvant treatment in stage II colon cancer patients.
- 2020
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In: Journal of Surgical Oncology. - : John Wiley & Sons. - 0022-4790 .- 1096-9098. ; 121:2, s. 392-401
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: Stage II colon cancer is primarily a surgical disease. Only a still not well-defined subset of patients may benefit from postoperative adjuvant chemotherapy. The relationship between adjuvant chemotherapy and survival after relapse is furthermore still not definitely explored in this group of patients. A number of reports suggest some association between defective mismatch repair (dMMR) and colorectal cancer stage II prognosis, but due to contradictory results from existing studies, the exact predictive role is still not fully understood.METHODS: Retrospective multicenter study including 451 stage II colon cancer patients. The proficiency or deficiency of mismatch repair was tested using immunohistochemistry and analyzed in relationship to two survival outcomes: overall survival (OS) and postrelapse survival.RESULTS: Patients with dMMR (20.4%) derived no OS benefit from adjuvant chemotherapy (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.47-2.38; P = .897). Patients with proficient mismatch repair (pMMR) tumors receiving adjuvant chemotherapy had the significantly better OS in comparison to those not receiving chemotherapy (HR, 0.54; 95% CI, 0.35-0.82; P = .004). This relationship remained significant in multivariable analysis (HR, 0.42; 95% CI, 0.22-0.78; P = .007). Patients with pMMR relapsing after adjuvant treatment lived significantly longer than those relapsing without previous adjuvant treatment (HR, 0.55; 95% CI, 0.32-0.96; P = .033) and this result remained significant in the multivariable model (HR, 0.49; 95% CI, 0.26-0.93; P = .030).CONCLUSION: In stage II CC patients, adjuvant chemotherapy improves therapeutic outcomes only in patients with pMMR tumors. Survival after relapse in patients having received adjuvant chemotherapy is significantly longer for patients with pMMR. No survival benefit from adjuvant chemotherapy was seen among patients with dMMR tumors.
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| 18. |
- Golding, Michael A., et al.
(author)
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The burden of food allergy on children and teens : A systematic review
- 2022
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In: Pediatric Allergy and Immunology. - : John Wiley & Sons. - 0905-6157 .- 1399-3038. ; 33:3
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Research review (peer-reviewed)abstract
- Background Over the last two decades, researchers have placed increasing attention on understanding how food allergy affects the health-related quality of life (HRQL) and psychosocial well-being of children and teens. In response, a number of reviews have been published that aim at synthesizing the literature. However, many of these papers focus narrowly on HRQL or suffer from methodological limitations.Method The current review aims to fill this gap by providing a comprehensive overview of the burden of pediatric food allergy by synthesizing the quantitative and qualitative literature.Results Findings from the present review provide evidence of reduced HRQL among children and teens with food allergy, particularly older children and those with more severe manifestations of the condition. In comparison to HRQL, the link between food allergy and psychosocial functioning is less clear; however, some evidence can be cited linking food allergy to greater levels of psychological distress. Qualitative evidence suggests that the burden of pediatric food allergy largely stems from worries surrounding exposures outside of the home and the social consequences of the condition. The current review also highlights several gaps in the literature, including a paucity of longitudinal research, research focused on predictors of psychological distress among children and teens with food allergy as well as a dearth of studies comparing rates of bullying in food-allergic and non-food-allergic samples.Conclusion More emphasis should be placed on not only alleviating the social and psychological consequences of food allergy, but also on identifying and assisting those most acutely burdened by the condition.
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| 19. |
- Gunnarsson, Adrian, 1990, et al.
(author)
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Discrete-Ordinates Modelling of the Radiative Heat Transfer in a Pilot-Scale Rotary Kiln
- 2020
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In: Energies. - : MDPI AG. - 1996-1073 .- 1996-1073. ; 13:9
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Journal article (peer-reviewed)abstract
- This paper presents work focused on the development, evaluation and use of a 3D model for investigation of the radiative heat transfer in rotary kilns. The model applies a discrete-ordinates method to solve the radiative transfer equation considering emission, absorption and scattering of radiation by gas species and particles for cylindrical and semi-cylindrical enclosures. Modelling input data on temperature, particle distribution and gas composition in the radial, axial and angular directions are experimentally gathered in a down-scaled version of a rotary kiln. The model is tested in its capability to predict the radiative intensity and heat flux to the inner wall of the furnace and good agreement was found when compared to measurements. Including the conductive heat transfer through the furnace wall, the model also satisfactorily predicts the intermediate wall temperature. The work also includes a first study on the effect of the incident radiative heat flux to the different surfaces while adding a cold bed material. With further development of the model, it can be used to study the heat transfer in full-scale rotary kilns.
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| 20. |
- Gunnarsson, Adrian, 1990, et al.
(author)
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Full-scale 3D-modelling of the radiative heat transfer in rotary kilns with a present bed material
- 2020
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In: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310. ; 147
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Journal article (peer-reviewed)abstract
- This work discusses the development and use of a detailed 3D radiative heat transfer model of a rotary kiln with a present bed material, used for iron ore pelletizing. A discrete ordinates method is used to solve the radiative heat transfer equation with radiative properties calculated using a weighted-sum-of-grey-gases (WSGG) model for gases and Mie and Rayleigh theory for particles including fuel, ash and soot. Measurement data gathered from a pilot-scale test furnace, comprising temperature, gas composition and particle concentration, is used in combination with temperature data and operation parameters gathered from a conventional rotary kiln to model a full-scale rotary kiln with a present bed material. The modelled cases have a thermal input of about 37 MWth and in addition to radiative heat transfer, conductive heat transfer within, as well as between, the bed and wall material are included in the model along with convective heat transfer from the gas and heat release from exothermic reactions in the bed. The model also considers the rotational wall and includes a simplified mixing model of the bed material as well as heat losses from the outside wall of the rotary kiln due to radiation and convection. For two different flames, one coal and one oil flame, surface temperatures are calculated on the inside and outside of the rotary kiln and compared to measurements. The model appears to predict the inner wall and bed surface temperatures well with errors less than 11%. The total heat transfer to the present bed material was also studied revealing that more than 80% originated from the radiative heat transfer within the furnace.
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| 21. |
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| 22. |
- Gunnarsson, Ronny K, 1955, et al.
(author)
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Best management of patients with an acute sore throat - a critical analysis of current evidence and a consensus of experts from different countries and traditions
- 2023
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In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 55:6, s. 384-395
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Journal article (peer-reviewed)abstract
- BackgroundThere is a very large body of publications discussing the management of patients with an acute sore throat. Advocates for a restrictive antibiotic policy and advocates for a more liberal use of antibiotics emphasise different and valid arguments and to date have not been able to unite in a consensus. Contradicting guidelines based on the same body of knowledge is not logical, may cause confusion and cause unwanted variation in clinical management.MethodsIn multiple video meetings and email correspondence from March to November 2022 and finally in a workshop at the annual meeting for the North American Primary Care Group in November 2022, experts from different countries representing different traditions agreed on how the current evidence should be interpreted.ResultsThis critical analysis identifies that the problem can be resolved by introducing a new triage scheme considering both the acute risk for suppurative complications and sepsis as well as the long-term risk of developing rheumatic fever.ConclusionsThe new triage scheme may solve the long-standing problem of advocating for a restrictive use of antibiotics while also satisfying concerns that critically ill patients might be missed with severe consequences. We acknowledge that the perspective of this problem is vastly different between high- and low-income countries. Furthermore, we discuss the new trend which allows nurses and pharmacists to independently manage these patients and the increased need for safety netting required for such management.
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| 23. |
- Harbin, N. J., et al.
(author)
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Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis
- 2021
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In: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 39:4, s. 527-532
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Journal article (peer-reviewed)abstract
- Objective Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of >= 30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. Design Secondary analysis of randomized controlled trial data. Setting Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016-2018. Subjects A total of 277 ILI patients aged one year or older and symptom duration of <= 72 h. Main outcome measures Capillary blood CRP concentration at baseline, and ILI recovery time defined as having 'returned to usual daily activity' with residual symptoms minimally interfering. Results At baseline, 20% (55/277) had CRP concentrations >= 30mg/L (range 0-210). CRP concentration >= 30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50-1.3; p = 0.33). Interaction analysis of CRP concentration >= 30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37-1.3; p = 0.23). Conclusion There was no association between CRP concentration of >= 30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.
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| 24. |
- Hartman, Esther A R, et al.
(author)
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Effect of a multifaceted antibiotic stewardship intervention to improve antibiotic prescribing for suspected urinary tract infections in frail older adults (ImpresU): pragmatic cluster randomised controlled trial in four European countries.
- 2023
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In: BMJ (Clinical research ed.). - : BMJ. - 0959-535X .- 1756-1833. ; 380
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Journal article (peer-reviewed)abstract
- To evaluate whether antibiotic prescribing for suspected urinary tract infections in frail older adults can be reduced through a multifaceted antibiotic stewardship intervention.Pragmatic, parallel, cluster randomised controlled trial, with a five month baseline period and a seven month follow-up period.38 clusters consisting of one or more general practices (n=43) and older adult care organisations (n=43) in Poland, the Netherlands, Norway, and Sweden, from September 2019 to June 2021.1041 frail older adults aged 70 or older (Poland 325, the Netherlands 233, Norway 276, Sweden 207), contributing 411 person years to the follow-up period.Healthcare professionals received a multifaceted antibiotic stewardship intervention consisting of a decision tool for appropriate antibiotic use, supported by a toolbox with educational materials. A participatory-action-research approach was used for implementation, with sessions for education, evaluation, and local tailoring of the intervention. The control group provided care as usual.The primary outcome was the number of antibiotic prescriptions for suspected urinary tract infections per person year. Secondary outcomes included the incidence of complications, all cause hospital referrals, all cause hospital admissions, all cause mortality within 21 days after suspected urinary tract infections, and all cause mortality.The numbers of antibiotic prescriptions for suspected urinary tract infections in the follow-up period were 54 prescriptions in 202 person years (0.27 per person year) in the intervention group and 121 prescriptions in 209 person years (0.58 per person year) in the usual care group. Participants in the intervention group had a lower rate of receiving an antibiotic prescription for a suspected urinary tract infection compared with participants in the usual care group, with a rate ratio of 0.42 (95% confidence interval 0.26 to 0.68). No differences between intervention and control group were observed in the incidence of complications (<0.01 v 0.05 per person year), hospital referrals (<0.01 v 0.05), admissions to hospital (0.01 v 0.05), and mortality (0 v 0.01) within 21 days after suspected urinary tract infections, nor in all cause mortality (0.26 v 0.26).Implementation of a multifaceted antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infections in frail older adults.ClinicalTrials.gov NCT03970356.
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| 25. |
- Jonasdottir, A. D., et al.
(author)
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Pentraxin-3-a potential biomarker in ANCA-associated vasculitis
- 2023
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In: Scandinavian Journal of Rheumatology. - : Taylor & Francis Ltd. - 0300-9742 .- 1502-7732. ; 52:3, s. 293-301
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Journal article (peer-reviewed)abstract
- Objective The aim of this study was to investigate pentraxin-3 (PTX3) as a potential biomarker of inflammatory activity in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at baseline and 6 month follow-up in a longitudinal cohort. Method Plasma PTX3 levels were measured in 79 newly diagnosed or relapsing AAV patients at baseline and 6 month follow-up, and in 23 healthy controls. Urinary PTX3 levels were measured in 34 of the patients. C-reactive protein (CRP), creatinine, and albuminuria were measured and the cumulative glucocorticoid dose at inclusion was calculated. The Birmingham Vasculitis Activity Score (BVAS) was assessed at baseline and follow-up. Results Plasma PTX3 levels were significantly higher at baseline than at 6 months (2.85 vs 1.23 ng/mL, p < 0.001). Plasma and urinary PTX3 levels correlated with BVAS at baseline (rho = 0.45, p < 0.001, and rho = 0.49, p = 0.008, respectively). A significant correlation between both plasma and urinary PTX3 levels and estimated glomerular filtration rate and albuminuria was found. However, there was no correlation between plasma and urinary PTX3 levels. At baseline, plasma and urinary PTX3 levels were significantly higher in patients with kidney involvement. PTX3 levels did not correlate with CRP, nor was there a correlation between CRP levels and BVAS at baseline. Conclusion Plasma and urinary PTX3 seem to reflect disease activity in AAV better than the commonly used CRP. PTX3 may have a potential role as a biomarker in monitoring disease activity in AAV patients, particularly in patients with kidney involvement.
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| 26. |
- Kevat, Priya M., et al.
(author)
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Adherence rates and risk factors for suboptimal adherence to secondary prophylaxis for rheumatic fever
- 2021
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In: Journal of Paediatrics and Child Health. - : Wiley. - 1034-4810 .- 1440-1754. ; 57:3, s. 419-424
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Journal article (peer-reviewed)abstract
- © 2020 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians). Aim: Secondary prophylaxis with 3–4 weekly benzathine penicillin G injections is necessary to prevent disease morbidity and cardiac mortality in patients with acute rheumatic fever (ARF) and rheumatic heart disease (RHD). This study aimed to determine secondary prophylaxis adherence rates in the Far North Queensland paediatric population and to identify factors contributing to suboptimal adherence. Methods: A retrospective analysis of data recorded in the online RHD register for Queensland, Australia, was performed for a 10-year study period. The proportion of benzathine penicillin G injections delivered within intervals of ≤28 days and ≤35 days was measured. A multi-level mixed model logistic regression assessed the influence of age, gender, ethnicity, suburb, Accessibility and Remoteness Index of Australia class, number of people per dwelling, Index of Relative Socio-economic Advantage and Disadvantage, Index of Education and Occupation, year of inclusion on an ARF/RHD register and individual effect. Results: The study included 277 children and analysis of 7374 injections. No children received ≥80% of recommended injections within a 28-day interval. Four percent received ≥50% of injections within ≤28 days and 46% received ≥50% of injections at an extended interval of ≤35 days. Increasing age was associated with reduced delivery of injections within 35 days. Increasing year of inclusion was associated with improved delivery within 28 days. The random effect of individual patients was significantly associated with adherence. Conclusions: Improved timely delivery of secondary prophylaxis for ARF and RHD is needed as current adherence is very low. Interventions should focus on factors specific to each individual child or family unit.
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| 27. |
- Kumar, R, et al.
(author)
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AUTOREACTIVE CD4+T CELLS AND THEIR TCR REPERTOIRE IN PR3-ANCA ASSOCIATED VASCULITIS
- 2021
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 1-1
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Conference paper (other academic/artistic)abstract
- ANCA-associated vasculitis (AAV) with proteinase 3 (PR3) ANCA is genetically associated with HLA-DP [1], is often relapsing in nature, and has a predisposition for kidneys, lungs and ear-nose-throat involvement [2]. Despite the presence of PR3+ANCA, indicating CD4+T-cell help in the disease, the knowledge about autoreactive CD4+T cells is scarce. Activated T cells have been shown at site of inflammation [3] and involvement of proinflammatory cytokines in circulation is also reported [4, 5].Objectives:Identification of autoreactive T cells may help to identify the drivers of the immune responses and chronicity. We therefore aimed to investigate PR3-specific CD4+T-cell responses in peripheral blood of AAV patients with a focus on both phenotype and T-cell receptor (TCR) repertoires.Methods:The study included sixty-six patients: 26 with active PR3 autoantibody+ AAV, 21 with inactive but PR3+ AAV and 19 with inactive PR3- AAV. In-vitro cultures with PR3 protein were established to assess antigen-specific cytokine responses in a 3-color fluorospot assay. Deep immunophenotyping was performed by flow cytometry. Antigen-responsive CD4+ T cells were isolated and single cell TCRαβ sequences were generated and analyzed from PR3+ AAV patients (n=5) using a previously published protocol [6].Results:PBMCs from AAV patients demonstrated an HLA-DP associated cytokine responses to PR3 stimulation including IFN-γ and IL-10, but not IL-17A. This T-cell autoreactivity was found to be confined to a highly differentiated CD4+ T cell population characterized by perforin and GPR56 expression, implicating a cytotoxic feature of the response. Active disease involved a reduction in expression of several markers associated with cytotoxicity amongst the CD4+GPR56+ T cells. Their frequency was also negatively associated with the doses of prednisolone. A similar phenotype was shared with T cells activated by human cytomegalovirus (HCMV) peptides in the same patient cohort. Single cell sequencing of paired alpha beta T-cell receptors (TCRs) revealed different patterns of gene usage between PR3 and HCMV reactive T cells. Moreover, we could identify shared (public) PR3-reactive T-cell clones between different HLA-DPB1*04:01+ patients.Conclusion:PR3 is an autoantigen which provokes ANCA responses in AAV patients. Our study identified PR3-reactive CD4+ T cells at the level of their phenotype and TCR repertoire. The autoreactive CD4+ T cells, present in both active and inactive disease, implicate chronic antigen exposure and the persistence of long-lived T-cell clones. The presence of public autoreactive clones between HLA-DPB1*04:01+ patients suggests an active role for these cells in pathogenesis of AAV and validates the link with predisposed genotype.References:[1]Lyons PA, Rayner TF, Trivedi S, Holle JU, Watts RA, Jayne DR, et al. Genetically distinct subsets within ANCA-associated vasculitis. New England Journal of Medicine. 2012; 367(3):214-223.[2]Kumar Sharma R, Lövström B, Gunnarsson I, Malmström V. Proteinase 3 autoreactivity in Anti-Neutrophil Cytoplasmic Antibody-associated vasculitis–immunological versus clinical features. Scandinavian Journal of Immunology. 2020:e12958.[3]Wilde B, Thewissen M, Damoiseaux J, van Paassen P, Witzke O, Tervaert JWCJAr, et al. T cells in ANCA-associated vasculitis: what can we learn from lesional versus circulating T cells? 2010; 12(1):204.[4]Hoffmann JC, Patschan D, Dihazi H, Müller C, Schwarze K, Henze E, et al. Cytokine profiling in anti neutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional cohort study. Rheumatology international. 2019; 39(11):1907-1917.[5]Berti A, Warner R, Johnson K, Cornec D, Schroeder D, Kabat B, et al. Circulating Cytokine Profiles and ANCA Specificity in Patients with ANCA-Associated Vasculitis. Arthritis & rheumatology (Hoboken, NJ). 2018; 70(7):1114.[6]Han A, Glanville J, Hansmann L, Davis MM. Linking T-cell receptor sequence to functional phenotype at the single-cell level. Nature biotechnology. 2014; 32(7):684-692.Disclosure of Interests:None declared
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| 29. |
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| 31. |
- Malik, R., et al.
(author)
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Factors associated with breast cancer awareness and breast self-examination in Fiji and Kashmir India - a cross-sectional study
- 2020
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20
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Journal article (peer-reviewed)abstract
- BackgroundIn low-income countries breast cancer awareness (BCA) is essential to reduce the proportion of advanced stage presentations of breast cancer. There is a lack of studies using multivariable techniques to explore factors related to BCA in low-income countries. The objective of this study was to identify to what extent women in Fiji and Kashmir, India have BCA and practice breast self-examination (BSE) as well as factors associated with BCA and BSE.MethodsA survey of women aged >= 18years was conducted in Fiji and Kashmir, India to assess BCA and rates of BSE. Comparison between Fiji and Kashmir was done using student's t-test for continuous data and chi-square for binary data. Factors associated with BCA and BSE were analysed using a multivariable logistic regression for Fiji and Kashmir separately.ResultsData were collected from 399 and 1982 women in Kashmir and Fiji, respectively. Of 1968 women in Fiji 57% were deemed to have an acceptable BCA compared to only 7.3% of 395 women in Kashmir. Having some education was associated with having BCA with an odds ratio of 4.7 (1.7-13) in Fiji and 10 (1.7-59) in Kashmir. Of 1976 women in Fiji 40% had tertiary education while 40% of 392 women in Kashmir had no education at all. The marital status was similar in both samples (n=1973 and 395) with 68-69% being married and 21-26% being single. The lack of female doctors or nurses with whom to discuss issues, was perceived as a problem in both countries.ConclusionsThe key finding is an association between having any level of education and BCA. This correlation was much stronger than for a family history of breast cancer and BCA. Hence, general education to illiterate women may reduce the proportion of women in low-income countries presenting with advanced-stage breast cancer.
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| 32. |
- Manoj, B. R., et al.
(author)
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MOVING OBJECT CLASSIFICATION WITH A SUB-6 GHZ MASSIVE MIMO ARRAY USING REAL DATA
- 2021
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In: 2021 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH AND SIGNAL PROCESSING (ICASSP 2021). - : IEEE. - 2379-190X .- 1520-6149. - 9781728176055 - 9781728176062 ; , s. 8133-8137
-
Conference paper (peer-reviewed)abstract
- Classification between different activities in an indoor environment using wireless signals is an emerging technology for various applications, including intrusion detection, patient care, and smart home. Researchers have shown different methods to classify activities and their potential benefits by utilizing WiFi signals. In this paper, we analyze classification of moving objects by employing machine learning on real data from a massive multi-input-multi-output (MIMO) system in an indoor environment. We conduct measurements for different activities in both line-of-sight and non line-of-sight scenarios with a massive MIMO testbed operating at 3.7 GHz. We propose algorithms to exploit amplitude and phase-based features classification task. For the considered setup, we benchmark the classification performance and show that we can achieve up to 98% accuracy using real massive MIMO data, even with a small number of experiments. Furthermore, we demonstrate the gain in performance results with a massive MIMO system as compared with that of a limited number of antennas such as in WiFi devices.
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| 34. |
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| 35. |
- Nilsson, Niklas, et al.
(author)
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Endoscopically assisted reconstruction of chronic Achilles tendon ruptures and re-ruptures using a semitendinosus autograft is a viable alternative to pre-existing techniques.
- 2022
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In: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 30:7, s. 2477-2484
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Journal article (peer-reviewed)abstract
- Achilles tendon ruptures are termed chronic after a delay in treatment for more than 4weeks. The literature advocates surgical treatment with reconstruction to regain ankle push-off strength. The preferred technique is, however, still unknown and is often individualized. This study aims to present the technique and clinical outcome of an endoscopically assisted free semitendinosus reconstruction of chronic Achilles tendon rupture and Achilles tendon re-ruptures with delayed representation. It is hypothesized that the presented technique is a viable and safe alternative for distal Achilles tendon ruptures and ruptures with large tendon gaps.Twenty-two patients (13 males and 9 females) with a median (range) age of 64 (34-73) treated surgically with endoscopically assisted Achilles tendon reconstruction using a semitendinosus autograft were included. The patients were evaluated at 12months post-operatively for Achilles tendon Total Rupture Score (ATRS), calf circumference, Achilles Tendon Resting Angle (ATRA), heel-rise height and repetitions together with tendon length determined by ultrasonography, concentric heel-rise power and heel-rise work.The patients reported a median (range) ATRS of 76 (45-99) out of 100. The median (range) ATRA on the injured side was 60° (49°-75°) compared with 49.5° (40-61°), p<0.001, on the non-injured side. Eighteen out of 22 patients were able to perform a single-leg heel-rise on the non-injured side. Sixteen patients out of those 18 (89%) were also able to perform a single heel-rise on the injured side. They did, however, perform significantly lower number of repetitions compared with the non-injured side with a median (range) heel-rise repetitions of 11 (2-22) compared with 26 (2-27), (p<0.001), and a median (range) heel-rise height of 5.5cm (1.0-11.0cm) compared with 9.0cm (5.0-11.5cm), (p<0.001). The median calf circumference was 1.5cm smaller on the injured side, 37.5cm compared with 39cm, when medians were compared. The median (range) tendon length of the injured side was 24.8cm (20-28.2cm) compared with 22cm (18.4-24.2cm), (p<0.001), on the non-injured side.The study shows that endoscopically assisted reconstruction using a semitendinosus graft to treat chronic Achilles tendon ruptures and re-ruptures with delayed representation produces a satisfactory outcome. The technique can restore heel-rise height in patients with more distal ruptures or large tendon defects and is therefore a viable technique for Achilles tendon reconstruction.IV.
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| 36. |
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| 37. |
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| 38. |
- Petersson, M., et al.
(author)
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Patient-Reported Symptom Severity in a Nationwide Myasthenia Gravis Cohort Cross-sectional Analysis of the Swedish GEMG Study
- 2021
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In: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 97:14
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Journal article (peer-reviewed)abstract
- Background and Objectives To describe myasthenia gravis activities of daily living (MG-ADL) in relation to clinical characteristics in a large Swedish nationwide cohort. Methods In a cross-sectional prevalence cohort study, the Genes and Environment in Myasthenia Gravis study, performed from November 2018 through August 2019, patients with myasthenia gravis (MG) were invited to submit an extensive 106-item life environment questionnaire, including the MG-ADL score. Patients were classified into early-onset MG (EOMG, <50 years), late-onset MG (LOMG, >= 50 years), or thymoma-associated MG (TAMG). Comparisons of disease-specific characteristics were made between subgroups, sexes, and different MG-ADL scores. Results A total of 1,077 patients were included, yielding a 74% response rate: 505 (47%) were classified as EOMG, 520 (48%) LOMG, and 45 (4%) TAMG. Mean age at inclusion was 64.3 years (SD 15.7) and mean disease duration was 14.6 years (SD 14.0). Complete MG-ADL scores (n = 1,035) ranged from 0p to 18p, where 26% reported a score of 0p. Higher MG-ADL scores were associated with female sex, obesity, and diagnostic delay (odds ratio [OR] 1.62, 1.72, and 1.69; p(adj) = 0.017, 0.013, and 0.008) and inversely correlated with high educational attainment (OR 0.59; p(adj) = 0.02), but not with age at inclusion, disease subtype, or disease duration. Almost half of the population (47%) reported MG-ADL >= 3p, corresponding to an unsatisfactory symptom state. Discussion In this nationwide study, comprising more than 40% of the prevalent MG population in Sweden, almost half of the patients reported current disease symptoms associated with an unsatisfactory symptom state, indicating the need for improved treatment options.
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| 39. |
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| 40. |
- Rasmusson, Lina M., et al.
(author)
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Effects of temperature and hypoxia on respiration, photorespiration, and photosynthesis of seagrass leaves from contrasting temperature regimes
- 2020
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In: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 77:6
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Journal article (peer-reviewed)abstract
- In near-future climate change scenarios, elevated ocean temperatures with higher and more frequent peaks are anticipated than at present. Moreover, increased eutrophication and higher primary and secondary productivity will affect the oxygen levels of shallow-water coastal ecosystems, creating hypoxic conditions that can be experienced regularly, especially in dense vegetated systems. These climate-related events may impose detrimental effects on the primary productivity of seagrass. To evaluate such effects, this study combined gas exchange measurements with pulse amplitude-modulated fluorometry to assess the impact of short-time exposure to a range of water temperatures at ambient and low-oxygen levels on mitochondrial respiration, chlorophyll fluorescence (based on the Fv/F0 ratio), photosynthetic oxygen evolution, and photorespiration in leaf segments of the temperate seagrass Zostera marina and the tropical seagrass Thalassia hemprichii. We found that mitochondrial respiration in both Z. marina and T. hemprichii increased with higher temperatures up to 40°C and that low O2 caused significantly reduced respiration rates, particularly in T. hemprichii. Elevated water temperature had a clear negative effect on the Fv/F0 of both seagrass species, indicating damage or inactivation of the photosynthetic apparatus, even when light is not present. Moreover, damage to the photosynthetic apparatus was observed as an effect of elevated temperature combined with low O2 during darkness, resulting in subsequent lower photosynthesis in light. Photorespiration was present, but not promoted by increased temperature alone and will thus not further contribute to productivity losses during warmer events (when not carbon limited). This study demonstrates the negative impact of hypoxic stress and elevated temperatures on seagrass productivity, which may influence the overall health of seagrass plants as well as oxygen and carbon fluxes of shallow-water coastal ecosystems in warmer climate scenarios.
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| 41. |
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| 44. |
- Stervik, Louise, 1993, et al.
(author)
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Analysis of early respiratory-related mortality after radiation therapy of non-small-cell lung cancer : feasibility of automatic data extraction for dose–response studies
- 2020
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In: Acta Oncologica. - 0284-186X. ; 59:6, s. 628-635
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Journal article (peer-reviewed)abstract
- Purpose: To examine the feasibility of automatic data extraction from clinical radiation therapy (RT) databases at four hospitals to investigate the impact of mean lung dose (MLD) and age on the risk of early respiratory-related death and early overall death for patients treated with RT for non-small-cell lung cancer (NSCLC). Material and methods: We included adult patients with NSCLC receiving curatively intended RT between 2002 and 2017 at four hospitals. A script was developed to automatically extract RT-related data. The cause of death for patients deceased within 180 days of the start of RT was retrospectively assessed. Using logistic regression, the risks of respiratory-related death and of overall death within 90 and 180 days were investigated using MLD and age as variables. Results: Altogether, 1785 patients were included in the analysis of early overall mortality and 1655 of early respiratory-related mortality. The respiratory-related mortalities within 90 and 180 days were 0.9% (15/1655) and 3.6% (60/1655). The overall mortalities within 90 and 180 days were 2.5% (45/1785) and 10.6% (190/1785). Higher MLD and older age were associated with an increased risk of respiratory-related death within 180 days and overall death within 90 and 180 days (all p<.05). For example, the risk of respiratory-related death within 180 days and their 95% confidence interval for patients aged 65 and 75 years with MLDs of 20 Gy was according to our logistic model 3.8% (2.6–5.0%) and 7.7% (5.5–10%), respectively. Conclusions: Automatic data extraction was successfully used to pool data from four hospitals. MLD and age were associated with the risk of respiratory-related death within 180 days of the start of RT and with overall death within 90 and 180 days. A model quantifying the risk of respiratory-related death within 180 days was formulated.
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| 45. |
- Svenningsson, A., et al.
(author)
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Safety and efficacy of rituximab versus dimethyl fumarate in patients with relapsing-remitting multiple sclerosis or clinically isolated syndrome in Sweden: a rater-blinded, phase 3, randomised controlled trial
- 2022
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In: Lancet Neurology. - : Elsevier BV. - 1474-4422. ; 21:8, s. 693-703
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Journal article (peer-reviewed)abstract
- Background B-cell depleting therapies are highly efficacious in relapsing-remitting multiple sclerosis but one such therapy, rituximab, is not approved for multiple sclerosis and no phase 3 trial data are available. We therefore examined the safety and efficacy of rituximab compared with dimethyl fumarate in patients with relapsing-remitting multiple sclerosis to obtain data that might allow inclusion of rituximab in treatment guidelines. Methods RIFUND-MS was a multicentre, rater-blinded, active-comparator, phase 3, randomised controlled trial done at 17 Swedish university and community hospitals. Key inclusion criteria for participants were: age 18-50 years; relapsing-remitting multiple sclerosis or clinically isolated syndrome according to prevailing McDonald criteria; 10 years or less since diagnosis; untreated or only exposed to interferons or glatiramer acetate; and with clinical or neuroradiological disease activity in the past year. Patients were automatically randomly assigned (1:1) by the treating physician using a randomisation module in the Swedish multiple sclerosis registry, without stratification, to oral dimethyl fumarate 240 mg twice daily or to intravenous rituximab 1000 mg followed by 500 mg every 6 months. Relapse evaluation, Expanded Disability Status Scale rating, and assessment of MRI scans were done by examining physicians and radiologists masked to treatment allocation. The primary outcome was the proportion of patients with at least one relapse (defined as subacute onset of new or worsening neurological symptoms compatible with multiple sclerosis with a duration of more than 24 h and preceded by at least 30 days of clinical stability), assessed in an intention-to-treat analysis using log-binomial regression with robust standard errors. This trial is registered at ClinicalTrials.gov, NCT02746744. Findings Between July 1, 2016, and Dec 18, 2018, 322 patients were screened for eligibility, 200 of whom were randomly assigned to a treatment group (100 assigned to rituximab and 100 assigned to dimethyl fumarate). The last patient completed 24-month follow-up on April 21, 2021. 98 patients in the rituximab group and 97 patients in the dimethyl fumarate group were eligible for the primary outcome analysis. Three (3%) patients in the rituximab group and 16 (16%) patients in the dimethyl fumarate group had a protocol-defined relapse during the trial, corresponding to a risk ratio of 0.19 (95% CI 0.06-0.62; p=0.0060). Infusion reactions (105 events [40.9 per 100 patient-years]) in the rituximab group and gastrointestinal reactions (65 events [47.4 per 100 patient-years]) and flush (65 events [47.4 per 100 patient-years]) in the dimethyl fumarate group were the most prevalent adverse events. There were no safety concerns. Interpretation RIFUND-MS provides evidence that rituximab given as 1000 mg followed by 500 mg every 6 months is superior to dimethyl fumarate in preventing relapses over 24 months in patients with early relapsing-remitting multiple sclerosis. Health economic and long-term safety studies of rituximab in patients with multiple sclerosis are needed.
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| 47. |
- Walhelm, Tomas, et al.
(author)
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Clinical Experience of Proteasome Inhibitor Bortezomib Regarding Efficacy and Safety in Severe Systemic Lupus Erythematosus: A Nationwide Study
- 2021
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Journal article (peer-reviewed)abstract
- As treatment options in advanced systematic lupus erythematosus (SLE) are limited, there is an urgent need for new and effective therapeutic alternatives for selected cases with severe disease. Bortezomib (BTZ) is a specific, reversible, inhibitor of the 20S subunit of the proteasome. Herein, we report clinical experience regarding efficacy and safety from all patients receiving BTZ as therapy for SLE in Sweden during the years 2014-2020. 8 females and 4 males were included with a mean disease duration at BTZ initiation of 8.8 years (range 0.7-20 years). Renal involvement was the main target for BTZ. Reduction of global disease activity was recorded by decreasing SLEDAI-2K scores over time and remained significantly reduced at the 6-month (p=0.007) and the 12-month (p=0.008) follow-up visits. From BTZ initiation, complement protein 3 (C3) levels increased significantly after the 2(nd) treatment cycle (p=0.05), the 6-month (p=0.03) and the 12-month (p=0.04) follow-up visits. The urine albumin/creatinine ratio declined over time and reached significance at the 6-month (p=0.008) and the 12-month follow-up visits (p=0.004). Seroconversion of anti-dsDNA (27%), anti-C1q (50%) and anti-Sm (67%) was observed. 6 of 12 patients experienced at least one side-effect during follow-up, whereof the most common adverse events were infections. Safety parameters (C-reactive protein, blood cell counts) mainly remained stable over time. To conclude, we report favorable therapeutic effects of BTZ used in combination with corticosteroids in a majority of patients with severe SLE manifestations irresponsive to conventional immunosuppressive agents. Reduction of proteinuria was observed over time as well as seroconversion of some autoantibody specificities. In most patients, tolerance was acceptable but mild adverse events was not uncommon. Special attention should be paid to infections and hypogammaglobinemia.
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