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1.	Andersson, Bodil, et al. (författare) Gastrointestinal complications after cardiac surgery - improved risk stratification using a new scoring model. 2010 Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 10:3, s. 366-370 Tidskriftsartikel (refereegranskat)abstract Gastrointestinal (GI) complications are serious consequences of cardiac surgery. The aim of this study was to develop, evaluate and validate a new risk score model for GI complications after cardiac surgery. The risk score model, named gastrointestinal complication score (GICS), was developed using prospectively collected data from 5593 patients who underwent 5636 cardiac surgical procedures between 1996 and 2001. The model was validated on 1031 cardiac surgery patients between 2005 and 2006. The scoring system's ability to predict GI complications was estimated by receiver operating characteristic (ROC)-curves and Hosmer-Lemeshow test. Fifty GI complications were identified in 47 patients (0.8%) in the developmental data set and eight (0.8%) in the validation data set. The ROC area in the developmental data set was 0.81 with a good calibration estimated by Hosmer-Lemeshow test (p=0.89). In the validation data set, the area under the curve was 0.83. The estimated probability for the patient to develop a GI complication after cardiac surgery at a GICS >/=15 is >20% and at a GICS
2.	Andersson, Bodil, et al. (författare) Riskbedömning för gastrointestinal komplikation efter hjärtkirurgi 2007 Ingår i: Svensk kirurgi. - 0346-847X. ; , s. 65-65 Konferensbidrag (refereegranskat)
3.	Halvarsson, Peter, et al. (författare) Relationship between helminth infections and MHC class II supertype diversity in natural water voles (Arvicola amphibius) populations Annan publikation (övrigt vetenskapligt/konstnärligt)
4.	Harbst, Katja, et al. (författare) Molecular profiling reveals low- and high-grade forms of primary melanoma. 2012 Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1557-3265. ; 18:15, s. 4026-4036 Tidskriftsartikel (refereegranskat)abstract For primary melanomas, tumor thickness, mitotic rate, and ulceration are well-laid cornerstones of prognostication. However, a molecular exposition of melanoma aggressiveness is critically missing. We recently uncovered a four-class structure in metastatic melanoma, which predicts outcome and informs biology. This raises the possibility that a molecular structure exists even in the early stages of melanoma and that molecular determinants could underlie histophenotype and eventual patient outcome.We subjected 223 archival primary melanomas to a horizontally integrated analysis of RNA expression, oncogenic mutations at 238 lesions, histomorphometry, and survival data.Our previously described four-class structure that was elucidated in metastatic lesions was evident within the expression space of primary melanomas. Because these subclasses converged into two larger prognostic and phenotypic groups, we used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between "high" and "low" grade forms of the disease. The two-grade signature was subsequently applied to the primary melanomas. Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration (all P < 0.01), and poorer relapse-free (HR = 4.94; 95% CI, 2.84-8.59), and overall (HR = 3.66; 95% CI, 2.40-5.58) survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes. Importantly, the molecular-grade signature was validated in two external gene expression data sets.We provide evidence for a molecular organization within melanomas, which is preserved across all stages of disease.
5.	Holm, Karolina, et al. (författare) An integrated genomics analysis of epigenetic subtypes in human breast tumors links DNA methylation patterns to chromatin states in normal mammary cells. 2016 Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18:1 Tidskriftsartikel (refereegranskat)abstract Aberrant DNA methylation is frequently observed in breast cancer. However, the relationship between methylation patterns and the heterogeneity of breast cancer has not been comprehensively characterized.
6.	Höijer, Carl Johan, et al. (författare) Single chamber atrial pacing: A realistic option in sinus node disease: A long-term follow-up study of 213 patients 2007 Ingår i: PACE. - : Wiley. - 1540-8159. ; 30:6, s. 740-747 Tidskriftsartikel (refereegranskat)abstract Background: Despite several decades of experience with atrial pacing, many centers do not apply this mode to any greater extent, mainly because of concerns for the development of future atrioventricular (AV) block or atrial fibrillation. Recent studies have emphasized possible negative effects of right ventricular stimulation, even when AV-synchrony is preserved, and have thus given rise to renewed interest in single chamber atrial pacing for sinus node disease. Methods: This study presents the results of up to 19 years' follow-up of 213 patients with sinus node disease treated with atrial pacing with respect to survival and causes of death, development of atrial fibrillation and AV block, and total mode survival. Patients were divided into two groups: with or without associated atrial tachyarrhythmias at the time of implant. Results are given for all patients and for the two groups separately. Results: The mean follow-up time was 10.1 years. The survival of the entire group was lower after 10 years than that of an age and gender-matched general Swedish population. This was caused by patients with the brady-tachy syndrome (BT) having a significantly higher mortality rate than controls, whereas those with bradycardia only (B) had survival comparable to the general population. Permanent atrial fibrillation (AF) developed in 20% of patients and was significantly more common in patients with BT. The majority of patients with AF (78%) no longer needed any pacing, i.e., did not require ventricular stimulation due to slow ventricular rate. The annual incidence of high grade AV block was 1.8%. If patients with preexisting bundle branch block were excluded, the incidence was 1.6%. No fatal episode of AV block was seen. The overall mode survival at the end of follow-up was 75%, with 155 patients still with atrial pacemakers. Conclusion: Atrial pacing is a safe and reliable mode of pacing in patients with sinus node disease, even in the very long-term.
7.	Jönsson, Göran B, et al. (författare) High-resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization. 2007 Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:6, s. 543-558 Tidskriftsartikel (refereegranskat)abstract A BAC-array platform for comparative genomic hybridization was constructed from a library of 32,433 clones providing complete genome coverage, and evaluated by screening for DNA copy number changes in 10 breast cancer cell lines (BT474, MCF7, HCC1937, SK-BR-3, L56Br-C1, ZR-75-1, JIMTI, MDA-MB-231, MDA-MB-361, and HCC2218) and one cell line derived from fibrocystic disease of the breast (MCF10A). These were also characterized by gene expression analysis and found to represent all five recently described breast cancer subtypes using the '' intrinsic gene set '' and centroid correlation. Three cell lines, HCC 1937 and L56BrC1 derived from BRCA I mutation carriers and MDA-MB-23 1, were of basal-like subtype and characterized by a high frequency of low-level gains and losses of typical pattern, including limited deletions on Sq. Four estrogen receptor positive cell lines were of luminal A subtype and characterized by a different pattern of aberrations and high-level amplifications, including ERBB2 and other 17q amplicons in BT474 and MDA-MB-361. SK-BR-3 cells, characterized by a complex genome including ERBB2 amplification, massive high-level amplifications on 8q and a homozygous deletion of CDH1 at 16q22, had an expression signature closest to luminal B subtype. The effects of gene amplifications were verified by gene expression analysis to distinguish targeted genes from silent amplicon passengers. JIMT1, derived from an ERBB2 amplified trastuzumab resistant tumor, was of the ERBB2 subtype. Homozygous deletions included other known targets such as PTEN (HCC1937) and CDKN2A (MDA-MB-231, MCF10A), but also new candidate suppressor genes such as FUSSEL18 (HCC1937) and WDR11 (L56Br-C1) as well as regions without known genes. The tiling BAC-arrays constitute a powerful tool for high-resolution genomic profiling suitable for cancer research and clinical diagnostics.
8.	Nilsson, Johan, et al. (författare) Comparison of 19 pre-operative risk stratification models in open-heart surgery. 2006 Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 27:7, s. 867-874 Tidskriftsartikel (refereegranskat)
9.	Nilsson, Johan, et al. (författare) Early mortality in coronary bypass surgery: the EuroSCORE versus The Society of Thoracic Surgeons risk algorithm. 2004 Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 77:4, s. 1235-1240 Tidskriftsartikel (refereegranskat)
10.	Nilsson, Johan, et al. (författare) EuroSCORE predicts intensive care unit stay and costs of open heart surgery 2004 Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 78:5, s. 1528-1535 Tidskriftsartikel (refereegranskat)abstract Background. This study aimed to determine whether the preoperative risk stratification model EuroSCORE predicts the different components of resource utilization in open heart surgery. Methods. Data for all adult patients undergoing heart surgery at the University Hospital of Lund, Sweden, between 1999 and 2002 were prospectively collected. Costs were calculated for the surgery and intensive care and ward stay for each patient (excluding transplant cases and patients who died intraoperatively). Regression analysis was applied to evaluate the correlation between EuroSCCRE and costs. The predictive accuracy for prolonged postoperative intensive care unit (ICU) stay was assessed by the Hosmer-Lemeshow goodness-of-fit test. The discriminatory power was evaluated by calculating the areas under receiver operating characteristics curves. Results. The study included 3,404 patients. The mean cost for the surgery was $7,300, in the ICU $3,746, and in the ward $3,500. Total cost was significantly correlated with EuroSCORE, with a correlation coefficient of 0.47 (p < 0.0001); the correlation coefficient was 0.31 for the surgery cost, 0.46 for the ICU cost, and 0.11 for the ward cost. The Hosmer-Lemeshow p value for EuroSCORE prediction of more than 2 days' stay in the ICU was 0.40, indicating good accuracy. The area under the receiver operating characteristics curve was 0.78. The probability of an ICU stay exceeding 2 days was more than 50% at a EuroSCORE of 14 or more. Conclusions. In this single-institution study, the additive EuroSCORE algorithm could be used to predict ICU cost and also an ICU stay of more than 2 days after open heart surgery. (C) 2004 by The Society of Thoracic Surgeons.
11.	Nilsson, Johan, et al. (författare) Risk factor identification and mortality prediction in cardiac surgery using artificial neural networks. 2006 Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 1097-685X .- 0022-5223. ; 132:1, s. 12-31 Tidskriftsartikel (refereegranskat)
12.	Nozohoor, Shahab, et al. (författare) Validation of a modified EuroSCORE risk stratification model for cardiac surgery: the Swedish experience. 2011 Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940. ; 40:1, s. 185-191 Tidskriftsartikel (refereegranskat)abstract Objective: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is used to identify patients at high risk for aortic valve replacement (AVR) in whom alternative procedures, such as trans-catheter aortic valve implantation (TAVI), may be appropriate. The aim of the present study was to calibrate and validate the EuroSCORE for different cardiac surgery procedures to improve patient selection for valve surgery. Methods: The study included 46516 patients undergoing open cardiac surgery during 2001-2007. A fivefold cross-validation technique was used to calibrate four different models. Model discrimination was determined by the area under the receiver operating characteristic (ROC) curve and model calibration by the Hosmer-Lemeshow (H-L) test. Results: The actual and predicted 30-day mortality was 3.2%. The discrimination (ROC area) of the calibrated 30-day mortality prediction models was 0.79 for coronary bypass surgery, 0.77 for mitral valve surgery (MVS), and 0.75 for miscellaneous procedures, compared with 0.78 (p=0.199), 0.74 (p=0.077), and 0.72 (p=0.001), respectively, for the original EuroSCORE. The discrimination for AVR was the same for the calibrated and the original EuroSCORE model (0.70). The H-L test gave a p-value of 0.104 for the calibrated and <0.001 for the original EuroSCORE model. Conclusions: A calibration of EuroSCORE resulted in an acceptable predictive capacity for 30-day mortality, and improved discrimination and calibration for MVS and miscellaneous procedures. However, the poor discriminatory for the AVR procedure suggests that the EuroSCORE may not be satisfying for assessing risk prior to TAVI and that more optimized risk stratification models may be needed.
13.	Persson, Helena, et al. (författare) Identification of new microRNAs in paired normal and tumor breast tissue suggests a dual role for the ERBB2/Her2 gene. 2011 Ingår i: Cancer Research. - 1538-7445. ; 71:1, s. 78-86 Tidskriftsartikel (refereegranskat)abstract To comprehensively characterize microRNA (miRNA) expression in breast cancer, we performed the first extensive next-generation sequencing expression analysis of this disease. We sequenced small RNA from tumors with paired samples of normal and tumor-adjacent breast tissue. Our results indicate that tumor identity is achieved mainly by variation in the expression levels of a common set of miRNAs rather than by tissue-specific expression. We also report 361 new, well-supported miRNA precursors. Nearly two-thirds of these new genes were detected in other human tissues and 49% of the miRNAs were found associated with Ago2 in MCF7 cells. Ten percent of the new miRNAs are located in regions with high-level genomic amplifications in breast cancer. A new miRNA is encoded within the ERBB2/Her2 gene and amplification of this gene leads to overexpression of the new miRNA, indicating that this potent oncogene and important clinical marker may have two different biological functions. In summary, our work substantially expands the number of known miRNAs and highlights the complexity of small RNA expression in breast cancer.
14.	Staaf, Johan, et al. (författare) Normalization of Illumina Infinium whole-genome SNP data improves copy number estimates and allelic intensity ratios 2008 Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 9, s. 409- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples. RESULTS: We demonstrate an asymmetry in the detection of the two alleles for each SNP, which deleteriously influences both allelic proportions and copy number estimates. The asymmetry is caused by a remaining bias between the two dyes used in the Infinium II assay after using the normalization method in Illumina's proprietary software (BeadStudio). We propose a quantile normalization strategy for correction of this dye bias. We tested the normalization strategy using 535 individual hybridizations from 10 data sets from the analysis of cancer genomes and normal blood samples generated on Illumina Infinium II 300 k version 1 and 2, 370 k and 550 k BeadChips. We show that the proposed normalization strategy successfully removes asymmetry in estimates of both allelic proportions and copy numbers. Additionally, the normalization strategy reduces the technical variation for copy number estimates while retaining the response to copy number alterations. CONCLUSION: The proposed normalization strategy represents a valuable tool that improves the quality of data obtained from Illumina Infinium arrays, in particular when used for LOH and copy number variation studies.
15.	Staaf, Johan, et al. (författare) Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays 2008 Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1465-6906 .- 1465-6914. ; 9:9 Tidskriftsartikel (refereegranskat)abstract We present a strategy for detection of loss-of-heterozygosity and allelic imbalance in cancer cells from whole genome single nucleotide polymorphism genotyping data. Using a dilution series of a tumor cell line mixed with its paired normal cell line and data generated on Affymetrix and Illumina platforms, including paired tumor-normal samples and tumors characterized by fluorescent in situ hybridization, we demonstrate a high sensitivity and specificity of the strategy for detecting both minute and gross allelic imbalances in heterogeneous tumor samples.
16.	Tranér, Johan Vindician, 1770-1835 (författare) Panyasis Halicarnassensis, symposiacus Græcorum poëta, quem ... præside mag. Johanne Tranér ... pro gradu philosophico p.p. Andreas Gustavus Höglund ... In audit. Gustav. die XXVIII maji MDCCCXXXIII h.p.m.s. 1833 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
17.	Tyden, Eva, et al. (författare) Deep amplicon sequencing of preselected isolates of Parascaris equorum in beta-tubulin codons associated with benzimidazole resistance in other nematodes 2014 Ingår i: Parasites & Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 7, s. 410- Tidskriftsartikel (refereegranskat)abstract Background: The development of anthelmintic resistance (AR) to macrocyclic lactones in the equine roundworm Parascaris equorum has resulted in benzimidazoles now being the most widely used substance to control Parascaris infections. However, over-reliance on one drug class is a risk factor for the development of AR. Consequently, benzimidazole resistance is widespread in several veterinary parasites, where it is associated with single nucleotide polymorphisms (SNPs) in drug targets encoded by the beta-tubulin genes. The importance of these SNPs varies between different parasitic nematodes, but it has been hypothesised that they occur, at low allele frequencies, even in unselected populations. This study investigated whether these SNPs exist in the P. equorum population and tested the hypothesis that BZ resistance can develop from pre-existing SNPs in codons 167, 198 and 200 of the beta-tubulin isotype 1 and 2 genes, reported to be associated with AR in strongylids. The efficacy of the oral paste formula fenbendazole on 11 farms in Sweden was also assessed. Methods: Two isotype-specific primer pairs were designed, one on either side of the codon 167 and one on either side of codons 198 and 200. A pool of 100 000 larvae was sequenced using deep amplicon sequencing by Illumina HiSeq. Faecal egg count reduction test was used to assess the efficacy of fenbendazole. Results: No SNPs were observed in codons 167, 198 or 200 of the beta-tubulin isotype 1 or 2 genes of P. equorum, even though 100 000 larvae were sequenced. Faecal egg count reduction testing of fenbendazole showed that this anthelmintic was still 100% effective, meaning that the likelihood of finding high allele frequency of SNPs associated with benzimidazoles resistance in P. equorum was low. Unexpectedly, the allele frequencies observed in single worms were comparable to those in pooled samples. Conclusions: We concluded that fenbendazole does not exert selection pressure on the beta-tubulin genes of isotypes 1 and 2 in P. equorum. The fact that no pre-existing SNPs were found in codons 167, 198 and 200 in P. equorum also illustrates the difficulties in generalising about AR mechanisms between different taxonomic groups of nematodes.
18.	Abé, Christoph, et al. (författare) Cytarabine dose intensification improves survival in older patients with secondary/high-risk acute myeloid leukemia in matched real-world versus clinical trial data 2024 Ingår i: Leukemia and Lymphoma. - 1042-8194 .- 1029-2403. Tidskriftsartikel (refereegranskat)abstract Since 1980’s, the established/standard treatment of acute myeloid leukemia (AML) is cytarabine infusion with anthracycline (7 + 3 regimen). We compared the 7 + 3 regimen in older secondary/high-risk AML patientsfrom a clinical trial with a matched population from the Swedish AML Registrytreated withan increased cytarabine dose in induction and consolidation as recommended in the Swedish National Guidelines since 2005. After successfulpropensity score matching, 104 patients per group were included. The primary outcome was overall survival (OS), and standard dosed patients had a median OS of 6.4 versus 10.7 months with increased dose intensity (hazard ratio:0.69, p = 0.012), with 5-year OS of 8.7% and 18.1%, andremission rates of 36% and 60%, respectively (p < 0.001). Median OS after allogeneic hematopoietic cell transplantation (in 27.9% per group) was 10.4 and 20.7 months, respectively. We conclude that the more intensive cytarabine schedule seems to provide improved outcomes inthe investigated AML patient group.
19.	Alvåsen, Karin, et al. (författare) A field survey on parasites and antibodies against selected pathogens in owned dogs in Lilongwe, Malawi 2016 Ingår i: Journal of the South African Veterinary Association / Tydkrif van die Suid-Afrikaanse Veterinere. - : Medpharm Publications. - 1019-9128. ; 87 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to screen for selected parasites and antibody levels against vector-borne pathogens in owned dogs in Lilongwe, Malawi. The study population consisted of 100 dogs; 80 participating in vaccination-spaying campaigns and 20 visiting a veterinary clinic as paying clients. All dogs went through a general physical examination including visual examination for signs of ectoparasites. A total of 100 blood samples were analysed using commercial snap tests and 40 faecal samples by egg flotation in saturated sodium chloride. The sampled dogs had a seroprevalence of 12% for Anaplasma spp., 22% for Ehrlichia spp., 4% for Dirofilaria immitis and 1% for Leishmania spp. Eggs from Ancylostoma spp. were found in 80% of the faecal samples, whereas eggs of Trichuris vulpis, Toxocara canis and Toxascaris leonina were only present in 3%, 8% and 13% of the samples, respectively. Ectoparasites such as Ctenocephalides sp., Trichodectes sp. and ticks were present on 98%, 25% and 11%, respectively, of the campaign dogs. Among client dogs, 35% had Ctenocephalides fleas, 10% had Trichodectes lice and none had ticks. Public education and prophylactic treatment could be used to improve the animal welfare of dogs; this would most likely also have positive impact on public health.
20.	Andersson, Anna, et al. (författare) Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status. 2007 Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 21:6, s. 1198-1203 Tidskriftsartikel (refereegranskat)abstract Gene expression analyses were performed on 121 consecutive childhood leukemias (87 B-lineage acute lymphoblastic leukemias (ALLs), 11 T-cell ALLs and 23 acute myeloid leukemias (AMLs)), investigated during an 8-year period at a single center. The supervised learning algorithm k-nearest neighbor was utilized to build gene expression predictors that could classify the ALLs/AMLs according to clinically important subtypes with high accuracy. Validation experiments in an independent data set verified the high prediction accuracies of our classifiers. B-lineage ALLs with uncharacteristic cytogenetic aberrations or with a normal karyotype displayed heterogeneous gene expression profiles, resulting in low prediction accuracies. Minimal residual disease status (MRD) in T-cell ALLs with a high (40.1%) MRD at day 29 could be classified with 100% accuracy already at the time of diagnosis. In pediatric leukemias with uncharacteristic cytogenetic aberrations or with a normal karyotype, unsupervised analysis identified two novel subgroups: one consisting mainly of cases remaining in complete remission (CR) and one containing a few patients in CR and all but one of the patients who relapsed. This study of a consecutive series of childhood leukemias confirms and extends further previous reports demonstrating that global gene expression profiling provides a valuable tool for genetic and clinical classification of childhood leukemias.
21.	Animal horror cinema : genre, history and criticism 2015 Proceedings (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract The first academic study of the genre of animal horror cinema is essential for cinema and animal studies scholars as well as for fans of horror film. It defines this popular sub-genre, outlines its history and studies recent films as well as cult classics from a variety of perspectives. A central idea in the book is that animal horror cinema mirrors socially entrenched fears of and attitudes toward animals. Thus, animal horror cinema reveals attitudes toward the fabric of social life, the fragility of the eco-system and a deep uncertainty about what makes humans different from animals. The book contains chapters by scholars with different national and disciplinary backgrounds, and therefore offers a wide range of interpretations on the significance of the animal in modern horror film.
22.	Ansari, David, et al. (författare) Analysis of the Influence of HLA-A Matching Relative to HLA-B and -DR Matching on Heart Transplant Outcomes 2015 Ingår i: Transplantation direct. - 2373-8731. ; 1:9 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: There are conflicting reports on the effect of donor-recipient HLA matching on outcomes in heart transplantation. The objective of this study was to investigate the effects of HLA-A matching relative to HLA-B and -DR matching on long-term survival in heart transplantation.METHODS: A total of 25 583 patients transplanted between 1988 and 2011 were identified from the International Society for Heart and Lung Transplantation registry. Transplants were divided into 2 donor-recipient matching groups: HLA-A-compatible (no HLA-A mismatches) and HLA-A-incompatible (1-2 HLA-A mismatches). Primary outcome was all-cause mortality. Secondary outcomes were graft failure-, cardiovascular-, infection-, or malignancy-related deaths.RESULTS: The risk of all-cause mortality 15 years after transplantation was higher for HLA-A-compatible (vs HLA-A-incompatible) grafts in patients who had HLA-B-, HLA-DR-, or HLA-B,DR-incompatible grafts (P = 0.027, P = 0.007, and P = 0.002, respectively) but not in HLA-B- and/or HLA-DR-compatible grafts. This was confirmed in multivariable Cox regression analysis where HLA-A compatibility (vs HLA-A incompatibility) was associated with higher mortality in transplants incompatible for HLA-DR or HLA-B and -DR (hazard ratio [HR], 1.59; 95% confidence interval [95% CI], 1.11-2.28; P = 0.012 and HR, 1.69; 95% CI, 1.17-2.43; P = 0.005, respectively). In multivariable analysis, the largest compromise in survival for HLA-A compatibility (vs HLA-incompatibility) was for chronic rejection in HLA-B- and -DR-incompatible grafts (HR, 1.91; 95% CI, 1.22-3.01; P = 0.005).CONCLUSIONS: Decreased long-term survival in heart transplantation was associated with HLA-A compatibility in HLA-B,DR-incompatible grafts.
23.	Ansari, Daniel, et al. (författare) CODUSA - Customize Optimal Donor Using Simulated Annealing In Heart Transplantation. 2013 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3:May,30 Tidskriftsartikel (refereegranskat)abstract In heart transplantation, selection of an optimal recipient-donor match has been constrained by the lack of individualized prediction models. Here we developed a customized donor-matching model (CODUSA) for patients requiring heart transplantations, by combining simulated annealing and artificial neural networks. Using this approach, by analyzing 59,698 adult heart transplant patients, we found that donor age matching was the variable most strongly associated with long-term survival. Female hearts were given to 21% of the women and 0% of the men, and recipients with blood group B received identical matched blood group in only 18% of best-case match compared with 73% for the original match. By optimizing the donor profile, the survival could be improved with 33 months. These findings strongly suggest that the CODUSA model can improve the ability to select optimal match and avoid worst-case match in the clinical setting. This is an important step towards personalized medicine.
24.	Ansari, David, et al. (författare) Comparison of Basiliximab and Anti-Thymocyte Globulin as Induction Therapy in Pediatric Heart Transplantation: A Survival Analysis. 2015 Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:1 Tidskriftsartikel (refereegranskat)abstract Basiliximab and anti-thymocyte globulin are widely used drugs for induction therapy after pediatric heart transplantation. The aim of this study was to determine whether any differences could be observed between basiliximab and anti-thymocyte globulin, with respect to long-term mortality, in a population of pediatric cardiac transplant recipients.
25.	Ansari, David, et al. (författare) Induction with anti-thymocyte globulin in heart transplantation is associated with better long-term survival compared with basiliximab. 2015 Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 34:10, s. 1283-1291 Tidskriftsartikel (refereegranskat)abstract The use of induction therapy may reduce the risk of acute rejection after heart transplantation. This study assessed the association between basiliximab (BAS) vs anti-thymocyte globulin (ATG) induction and long-term survival after heart transplantation.
26.	Areskog, Marlene, et al. (författare) A controlled study on gastrointestinal nematodes from two Swedish cattle farms showing field evidence of ivermectin resistance 2014 Ingår i: Parasites and Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 7 Tidskriftsartikel (refereegranskat)abstract Background: Anthelmintic resistance (AR) is an increasing problem for the ruminant livestock sector worldwide. However, the extent of the problem is still relatively unknown, especially for parasitic nematodes of cattle. The effect of ivermectin (IVM) (Ivomec inj.(R), Merial) was investigated in Swedish isolates of gastrointestinal nematode (GIN) populations showing signs of AR in the field to further characterise the AR status by a range of in vivo and in vitro methods.Methods: Three groups, each of 11 calves, were infected with an equal mixture of third stage larvae (L3) of Cooperia oncophora and Ostertagia ostertagi. Group A was inoculated with an IVM-susceptible laboratory isolate and groups B and C with isolates originating from 'resistant' cattle farms. Faecal egg counts (FEC) were monitored from 0 to 45 days post infection (d.p.i.), and L3 were harvested continuously for larval migration inhibition testing (LMIT) and species-specific PCR (ITS2). At 31 d.p.i., one calf from each group was necropsied and adult worms were recovered pre-treatment. At 35 d.p.i., calves from all groups were injected with IVM at the recommended dose (0.2 mg/kg bodyweight). At 45 d.p.i., another two animals from each group were sacrificed and established gastrointestinal worms were collected and counted.Results: A few animals in all three groups were still excreting eggs (50-150 per g faeces) 10 days post IVM injection. However, there was no significant difference in the FEC reductions in groups A (95%; 95% CI 81-99), B (98%; 92-100) and C (99%; 97-100) between 35 and 44 d.p.i. Furthermore, LMIT showed no significant difference between the three groups. Approximately 100 adult O. ostertagi were found in the abomasum of one calf (group B), whereas low to moderate numbers (400-12 200) of C. oncophora remained in the small intestine of the calves in all three groups at 45 d.p.i. PCR on L3 harvested from faecal samples up to 10 days post treatment showed a ratio of 100% C. oncophora in the calves inoculated with isolates A and B, whereas C also had 8% O. ostertagi.Conclusions: Overall, this experiment showed that the animals were successfully treated according to the Faecal egg count reduction test (FECRT) standard (>= 95% reduction). However, several adult worms of the dose-limiting species C. oncophora demonstrably survived the IVM treatment.
27.	Areskog, Marlene, et al. (författare) Behovsanpassad användning av pour-on-preparat innehållande makrocykliska laktoner hos nötkreatur under svenska fältförhållanden 2011 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
28.	Areskog, Marlene, et al. (författare) Dexamethasone treatment interferes with the pharmacokinetics of ivermectin in young cattle 2012 Ingår i: Veterinary Parasitology. - : Elsevier BV. - 0304-4017 .- 1873-2550. ; 190, s. 482-488 Tidskriftsartikel (refereegranskat)abstract An experiment was carried out to study the possible interaction between dexamethasone (DXM) treatment and the efficacy of ivermectin (IVM) treatment in young cattle. Two groups, each of seven calves, were experimentally inoculated with an equal mixture containing 15,000 third stage larvae of Cooperia oncophora and Ostertagia ostertagi each, and with no history of being resistant to any anthelmintics. However, in this study C. oncophora was unexpectedly classified as IVM-resistant according to the outcome from the faecal egg count reduction test (FECRT). Blood parameters and faecal egg counts (FEC) were monitored from 0 to 35 days post infection (d.p.i.). The calves in one group received intramuscular injections of short and long-term acting DXM at 22 and 24 d.p.i., respectively. The other group remained as a control. Three days post patency (24 d.p.i.) both groups were injected subcutaneously with IVM (Merial) at the recommended dose (0.2 mg/kg). A significant difference (p < 0.001) in FEC patterns was observed between groups. Although both groups still excreted eggs (100-200 eggs per gram faeces) 11 days post anthelmintic treatment, the control group had a significantly higher reduction between 23 and 35 d.p.i. (p = 0.025). After 35 days, four animals per group were euthanized, and worms in the gastrointestinal tract were counted. No O. ostertagi were found in the abomasums, but low to high numbers (800-6200) of C. oncophora remained in the small intestines in both groups. Overall, these findings indicated that there was an interaction between the efficacy of IVM and DXM treatment. As significantly lower plasma levels of IVM were observed in the DXM group, we conclude that the impaired efficacy of ivermectin was most likely due to the altered pharmacokinetics. (C) 2012 Elsevier B.V. All rights reserved.
29.	Areskog, Marlene, et al. (författare) Limited efficacy of pour-on anthelmintic treatment of cattle under Swedish field conditions 2013 Ingår i: International Journal for Parasitology: Drugs and Drug Resistance. - : Elsevier BV. - 2211-3207. ; 3, s. 129-134 Tidskriftsartikel (refereegranskat)abstract A study on the effect of topical macrocyclic lactones (ML) against gastrointestinal nematodes (GIN) in Swedish first season grazing cattle (FSG) was performed during the grazing seasons of 2009 and 2010. Herds were recruited through farming press and both dairy and beef cattle farms were invited. A questionnaire revealed that 64% of participating farmers dewormed their animals in previous years, and of these 76% used topical formulations with ML. Four to six weeks after turnout, 107 (2009) and 64 (2010) farmers sent in individual faecal samples from 6-10 FSG. Faecal egg counts (FEC) were determined by the FECPAK (R)-method in 2009 and the McMaster-method in 2010, when also larvae were cultured. Average FEC of >= 100 eggs per gram faeces (EPG) was seen in 39% of the herds in 2009 and 42% in 2010 and with arithmetic means of 258 +/- 110 and 252 +/- 350 EPG, respectively. Interestingly, FSG in dairy and beef herds had similar mean FEC. In herds with mean FEC of >= 100 EPG, farmers dewormed all FSG in the tested grazing group with ivermectin (IVM) or doramectin (DOR) pour-on. In 2009, 33 (31%), and in 2010, 26 (40%) of the herds were retested 7-16 days post treatment. Mean reduction was 89% and 88%, respectively, and in only 12 (36%) and 10 (38%) herds it was >= 95%. Beef herds had mean reductions similar to those of the dairy herds. No significant difference (P = 0.66) in reduction was seen between the groups treated with three different pour-on formulations, nor was there any correlation between the previous year's usage of anthelmintics and the efficacy. Larvae from post-treatment cultures analysed in 2010 with a species-specific ITS2 qPCR showed that Cooperia oncophora was the predominant species after deworming. Four (15%) groups also harboured surviving Ostertagia ostertagi post treatment. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
30.	Areskog, Marlene, et al. (författare) Limited efficacy of pour-on anthelmintics for cattle under Swedish field conditions 2012 Ingår i: NJF Report. - 1653-2015. ; 8, s. 49-50 Annan publikation (övrigt vetenskapligt/konstnärligt)abstract It is commonly believed that deworming against gastrointestinal nematodes in cattle works well in Sweden. Globally, anthelmintic resistance is a well-known threat, due to years of excessive use of anthelmintics leading to genetic selection of resistant worms. However, other explanations to treatment failure may be present. A North European study published 2009 showed that the treatment effect, evaluated with a so called "faecal egg count reduction test" (FECRT) in herds on pasture, was lower than expected (Demeler et al 2009, Veterinary parasitology, 144. 74-80). As an attempt to further investigate the situation in Sweden, we investigated the effect of ivermectin (Ivomec pour-on®, Noromectin pour-on ®) and doramectin (Dectomax pour-on®) on the two most important parasitic gastrointestinal nematodes (Cooperia oncophora and Ostertagia ostertagi) in Swedish cattle herds. The study was performed during the grazing season of 2010 and herds were recruited through advertisement in the farming press. Both dairy and beef cattle herds were included, and when the farmers requisitioned sample material they answered a questionnaire about their herd management. Four to six weeks after cattle turnout, 64 farmers sent in individual fecal samples collected from fresh dung pats from six first season grazers (FSG) for egg counts and larval cultures. In herds with a mean EPG (eggs per gram faeces) of ≥100, advice was given to apply anthelmintic treatment with either ivermectin or doramectin pour-on to all FSG in the tested grazing group. The animals were dewormed by the farmers in accordance with the manufacturer's dosage recommendations. Faecal egg counts conducted 7 to 14 days post turnout (McMaster-method, sensitivity ≥ 20 EPG) revealed a mean of 119 EPG (min <20, max 1247) before treatment. Among the tested herds, 27 (42%) had an EPG higher than 100 EPG and the arithmetic mean was 248 EPG. Dairy herds (n=11) and beef herds (n=16) had a similar mean egg count of 283 EPG and 227 EPG respectively. In total, 26 herds were retested 7-14 days post treatment. The mean reduction was 87% (min 50%, max 100%) and 10 herds had a mean reduction of ≥ 95 %. Maximal reduction (100%), was seen in only eight herds. Beef herds had a mean reduction of 84%, which was slightly lower than the 92% reduction in the dairy herds. No significant difference (P=0.664) was seen between the groups treated with Ivomec pour-on® (n=8), Noromectin pour-on® (n=10) or Dectomax pour-on® (n=8). Larvae from post-treatment cultures were saved to determine the predominant surviving species using a species-specific ITS2 real time PCR. C. oncophora was the predominant species but five groups showed strong positive results for O. ostertagi, while the other 21 groups were weakly positive. Overall, this study showed that the efficacy of avermectin pour-on formulations was inadequate according to the FECRT standard (≥ 95% reduction). Only 42% of the herds had ≥100 EPG, which supports the concept of targeted selected treatments rather than blanket treatment without conducting diagnosis. This study also indicates that beef herds should consider parasite control in the beginning of the grazing period to a greater extent than is done in Sweden today. The dose limiting species C. oncophora was, in most cases, the survivor following anthelmintic treatment. However, it cannot be excluded that this may also reflect the development of resistance or altered pharmacodynamics towards avermectin compounds, especially on the few farms where the more pathogen O. ostertagi survived. Complementary laboratory investigations including pharmacokinetic studies of drug administration and uptake might further explain the poor efficacy under field conditions.
31.	Areskog, Marlene, et al. (författare) PGP expression in Cooperia oncophora before and after ivermectin selection 2013 Ingår i: Parasitology Research. - : Springer Science and Business Media LLC. - 0932-0113 .- 1432-1955. ; 112, s. 3005-3012 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to investigate genetic selection and P-glycoprotein (PGP) expression in three different isolates of Cooperia oncophora before treatment and after ivermectin (IVM) injection. Adult parasites were recovered from nine calves experimentally infected with the isolates represented by one IVM susceptible laboratory isolate, and two field isolates showing signs of phenotypic macrocyclic lactone resilience according to the faecal egg count reduction test. Five males and five females per isolate were examined both pre- and post-IVM treatment giving a total of 60 worms. A sequence from C. oncophora (Con-pgp) was identified, showing 83% similarity to Pgp-9 of Caenorhabditis elegans. Primers specific to putative Con-pgp-9 mRNA were designed, generating a 153-bp PCR product. Total RNA was prepared from all worms, and Con-pgp-9 expression was measured by quantitative real-time reverse transcription PCR. Our results showed that mean PGP concentrations were four to five times higher in female as compared to male worms. No significant differences in gene expression between experimental groups pre- and post-IVM selection were detected. However, PGP gene expression tended to be increased by IVM treatment in male worms (p = 0.091), with 70% higher mean expression in treated than in untreated male worms. Amplified fragment length polymorphism analysis did not demonstrate any bottleneck effect within the different isolates post-treatment. The total mean gene diversity values were 0.158 and 0.153 before and after treatment, respectively. Inbreeding coefficient in subpopulations compared to total population F ST was 0.0112, suggesting no genetic differentiation between or within the investigated isolates in relation to treatment. In conclusion, comparison of Con-pgp-9 expression showed no significant difference before and after treatment, but some tendency towards increasing expression in male worms.
32.	Areskog, Marlene, et al. (författare) Pgp-expression in Ivermectin Selected GI Nematodes of Cattle 2011 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
33.	Arifin, Maria Immaculata, et al. (författare) Comparison of molecular and conventional methods for the diagnosis of Fasciola hepatica infection in the field 2016 Ingår i: Veterinary Parasitology. - : Elsevier BV. - 0304-4017 .- 1873-2550. ; 232, s. 8-11 Tidskriftsartikel (refereegranskat)abstract The liver fluke, Fasciola hepatica, is one of the major parasite threats to livestock industries world-wide. In sheep and cattle, F. hepatica infection is commonly diagnosed using a range of methods. Aside from conventional coprological and serological diagnostic methods, there are also several molecular methods available based on the detection of liver fluke DNA in faeces. In this study, the outcomes of faecal egg count (FEC), serology and coproantigen ELISA (cELISA) were compared with the performance of polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) in diagnosis of F. hepatica from naturally infected cattle and sheep. A total of 64 individual faecal and serum samples were collected from four sheep and beef cattle herds with previous histories of F. hepatica infection. FEC and coproantigen levels were measured in faecal samples and anti-F.hepatica antibody levels were measured in serum samples. DNA samples isolated from faeces were examined both by PCR and LAMP, targeting the internal transcribed spacer 2 (ITS2) region of the F. hepatica genome. Results showed that F. hepatica eggs were present in 28 animals, while coproantigen and specific anti-F. hepatica antibodies were detected in 36 and 53 animals, respectively. Only 3 and 6 samples were positive by PCR and LAMP, respectively. To calculate method specificity and sensitivity, a combination of FEC and cELISA was selected as the composite reference standard (CRS). When compared to the CRS, PCR had a sensitivity of 10.7% and specificity of 100%, whereas LAMP had a sensitivity and specificity of 17.9% and 97.2%, respectively. PCR and LAMP in this field study were highly specific, but both had poor sensitivity compared with FEC and cELISA. Potential reasons for PCR and LAMP failure were inadequate amounts of amplifiable F. hepatica DNA, possibly due to the choice of DNA extraction procedure, amount of faecal material processed, as well as different faeces consistency and composition between different animal species. (C) 2016 Elsevier B.V. All rights reserved.
34.	Armuand, Gabriela M., et al. (författare) Sex differences in fertility-related information received by young adult cancer survivors 2012 Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:17, s. 2147-2153 Tidskriftsartikel (refereegranskat)abstract PURPOSE: The aim was to investigate male and female cancer survivors' perception of fertility-related information and use of fertility preservation (FP) in connection with cancer treatment during reproductive age.METHODS: The study sample consisted of cancer survivors diagnosed from 2003 to 2007 identified in population-based registers in Sweden. Inclusion criteria included survivors who were age 18 to 45 years at diagnosis and had lymphoma, acute leukemia, testicular cancer, ovarian cancer, or female breast cancer treated with chemotherapy. Of 810 eligible participants, 484 survivors (60% response rate) completed a postal questionnaire.RESULTS: The majority of male participants reported having received information about treatment impact on fertility (80%) and FP (68%), and more than half of the men banked frozen sperm (54%). Among women, less than half (48%) reported that they received information about treatment impact on fertility, and 14% reported that they received information about FP. Only seven women (2%) underwent FP. Predictors for receiving information about treatment impact on fertility were a pretreatment desire to have children (odds ratio [OR], 3.5), male sex (OR, 3.2), and being ≤ 35 years of age at diagnosis (OR, 2.0). Predictors for receiving information about FP included male sex (OR, 14.4), age ≤ 35 at diagnosis (OR, 5.1), and having no children at diagnosis (OR, 2.5).CONCLUSION: Our results show marked sex differences regarding the receipt of fertility-related information and use of FP. There is an urgent need to develop fertility-related information adapted to female patients with cancer to improve their opportunities to participate in informed decisions regarding their treatment and future reproductive ability.
35.	Arvidsson Segerkvist, Katarina, et al. (författare) Automatic weighing as an animal health monitoring tool on pasture 2020 Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413 .- 1878-0490. ; 240 Tidskriftsartikel (refereegranskat)abstract This project aimed to evaluate a novel method for monitoring the health of grazing cattle. The method studied in this paper is based on an unmanned, automatic precision weighing system that can be used on pasture, and which will alarm farmers when animals show abnormal weight gain curves. The project focused primarily on the detection of pasture-borne nematode parasite infections, which clearly reduce the weight gain of calves, but the method could be further developed to include other diseases that impair animal performance. The early detection of nematode infections would both improve animal welfare and minimize the use of anthelmintics. This study included a total of 63 first season grazing steers born from dairy cows that were allocated to one of two permanent semi-natural pasture enclosures for 20 weeks. Both enclosures had two identical scales except that one scale was powered with line current and one scale was equipped with solar panels. The automatic weighing stations were situated in close proximity to a source of water, salt and minerals so that animals would voluntarily pass through them on a regular basis. LiveStock Planner (R) software was used to identify usable data. The number of usable recordings per animal throughout the grazing season varied from 547 to 2677 amongst the four weighing stations, with an average of five usable recordings per animal obtained each week. The herds were guided to the weighing area on a daily basis during the first eight weeks of the grazing period to ensure that the steers received enough water. After this period, manual observations were used to verify that all animals entered the watering area without problems. The findings showed that the weighing technique worked well; hence, the developed method demonstrates great potential as an automatic supervision tool for grazing cattle. However, even though the summer of 2016 was quite dry, there was still water available in ditches and puddles. Accordingly, water alone was not a strong enough motivation to get cattle to pass through the weighing station into the watering area. Hence, in grazing areas with natural water sources, a reward more attractive than the water, salt and minerals used in this study is needed to ensure frequent voluntary passage of cattle through the scales.
36.	B-Movie Gothic : International Perspectives 2018 Samlingsverk (redaktörskap) (refereegranskat)abstract Following the Second World War, low-budget B-movies that explored and exploited Gothic narratives and aesthetics became a significant cinematic expression of social and cultural anxieties. Influencing new trends in European, Asian and African filmmaking, these films carried on the tradition established by the Gothic novel, and yet they remain part of a largely neglected subject. B-Movie Gothic: International Perspectives examines the influence of Gothic B-movies on the cinematic traditions of the United States, Britain, Scandinavia, Spain, Turkey, Japan, Hong Kong and India, highlighting their transgressive, transnational and provocative nature. It shows how B-movie Gothic is a relentlessly creative form, filled with political tensions and moving from shocking conservatism to profound social critique.
37.	Bahnan, Wael, et al. (författare) Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2 2022 Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12 Tidskriftsartikel (refereegranskat)abstract Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
38.	Baltrusis, Paulius, et al. (författare) Assessment of the F200Y mutation frequency in the beta tubulin gene of Haemonchus contortus following the exposure to a discriminating concentration of thiabendazole in the egg hatch test 2020 Ingår i: Experimental Parasitology. - : Elsevier BV. - 0014-4894 .- 1090-2449. ; 217 Tidskriftsartikel (refereegranskat)abstract The ruminant livestock production sector is under threat due to the infections with gastrointestinal nematode parasites and the subsequent development of anthelmintic resistance. One of most common and pathogenic species in small ruminants is Haemonchus contortus. The ability to control the infections with this and other gastrointestinal nematodes relies heavily on the use of anthelmintic drugs. Although resistance to all major classes of anthelmintics has been shown in H. contortus, the precise mechanism of resistance acquisition is only known for benzimidazoles. F200Y (TAC) is a common point mutation in the isotype 1 beta tubulin gene which is associated with an effective increase in the resistance towards benzimidazole drugs. Here, we show the utility of using this mutation as a marker in a droplet digital PCR assay to track how two H. contortus laboratory strains, characterized by different resistance levels, change with respect to this mutation, when subjected to increasing concentrations of thiabendazole. Additionally, we wanted to investigate whether exposure to a discriminating dose of thiabendazole in the egg hatch test resulted in the death of all H. contortus eggs with a susceptible genotype. We found the MHco5 strain to maintain an overall higher frequency of the F200Y mutation (80-100%) over all drug concentrations, whilst a steady, gradual increase from around 30%-60% was observed in the case of the MHco4 strain. This is further supported by the dose-response curves, displaying a much higher tolerance of the MHco5 strain (LD50 = 0.38 mu g/ml) in comparison to the MHco4 strain (LD50 = 0.07 mu g/ml) to the effects of thiabendazole. All things considered, we show that the F200Y mutation is still a viable and reliable marker for the detection and surveillance of benzimidazole drug resistance in H. contortus in Europe.
39.	Baltrusis, Paulius, et al. (författare) Digital PCR: modern solution to parasite diagnostics and population trait genetics 2023 Ingår i: Parasites and Vectors. - 1756-3305. ; 16 Forskningsöversikt (refereegranskat)abstract The use of polymerase chain reaction (PCR)-based diagnostic approaches has steadily increased in the field of parasitology in recent decades. The most recent large-scale technological modification of the PCR formula, also known as third-generation PCR, came in the form of digital PCR (dPCR). Currently, the most common form of dPCR on the market is digital droplet PCR (ddPCR). Unlike quantitative real-time PCR (qPCR), the digital format allows for highly sensitive, absolute quantification of nucleic acid targets and does not require external standards to be included in the developed assays. Dividing each sample into thousands of compartments and using statistical models also eliminates the need for technical replicates. With unprecedented sensitivity and enforcement of binary endpoint reactions, ddPCR not only allows the use of tiny sample volumes (especially important when working with limited amounts of DNA) but also minimises the impact of variations in amplification efficiency and the presence of inhibitors. As ddPCR is characterised by excellent features such as high throughput, sensitivity and robust quantification, it is widely used as a diagnostic tool in clinical microbiology. Due to recent advances, both the theoretical background and the practical, current applications related to the quantification of nucleic acids of eukaryotic parasites need to be updated. In this review, we present the basics of this technology (particularly useful for new users) and consolidate recent advances in the field with a focus on applications to the study of helminths and protozoan parasites.
40.	Baltrusis, Paulius, et al. (författare) Estimation of the impact of three different bioinformatic pipelines on sheep nemabiome analysis 2022 Ingår i: Parasites and Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: Next-generation sequencing (NGS) has provided an alternative strategy to study the composition of nematode communities with increased resolution and sensitivity. However, the handling and processing of gigabytes worth of amplicon sequence data produced by an NGS platform is still a major hurdle, limiting the use and adoption of faster and more convenient analysis software.Methods: In total 32 paired, fecal samples from Swedish sheep flocks were cultured and the larvae subsequently harvested subjected to internal transcribed spacer 2 (ITS2) amplicon sequencing using the PacBio platform. Samples were analyzed with three different bioinformatic pipelines, i.e. the DADA2, Mothur and SCATA pipelines, to determine species composition and richness.Results: For the the major species tested in this study (Haemonchus contortus, Teladorsagia circumcinta and Trichostrongylus colubriformis) neither relative abundances nor species diversity differed significantly between the three pipelines, effectively showing that all three analysis pipelines, although different in their approaches, yield nearly identical outcomes. In addition, the samples analyzed here had especially high frequencies of H. contortus (90-95% across the three pipelines) both before and after sample treatment, followed by T. circumcinta (3.5-4%). This shows that H. contortus is the parasite of primary importance in contemporary Swedish sheep farms struggling with anthelmintic resistance. Finally, although on average a significant reduction in egg counts was achieved post-treatment, no significant shifts in major species relative frequencies occurred, indicating highly rigid community structures at sheep farms where anthelmintic resistance has been reported.Conclusions: The findings presented here further contribute to the development and application of NGS technology to study nemabiome compositions in sheep, in addition to expanding our understanding about the most recent changes in parasite species abundances from Swedish sheep farms struggling with anthelmintic resistance.
41.	Baltrusis, Paulius, et al. (författare) Exploring benzimidazole resistance in Haemonchus contortus by next generation sequencing and droplet digital PCR 2018 Ingår i: International Journal for Parasitology: Drugs and Drug Resistance. - : Elsevier BV. - 2211-3207. ; 8, s. 411-419 Tidskriftsartikel (refereegranskat)abstract Anthelmintic resistance in gastrointestinal nematode (GIN) parasites of grazing ruminants is on the rise in countries across the world. Haemonchus contortus is one of most frequently encountered drug-resistant GINs in small ruminants. This blood-sucking abomasal nematode contributes to massive treatment costs and poses a serious threat to farm animal health. To prevent the establishment of resistant strains of this parasite, up-to-date molecular techniques need to be proposed which would allow for quick, cheap and accurate identification of individuals infected with resistant worms. The effort has been made in the previous decade, with the development of the pyrosequencing method to detect resistance-predicting alleles. Here we propose a novel droplet digital PCR (ddPCR) assay for rapid and precise identification of H. contortus strains as being resistant or susceptible to benzimidazole drugs based on the presence or absence of the most common resistance-conferring mutation F200Y (T (A) under barG) in the beta tubulin isotype 1 gene. The newly developed ddPCR assay was first optimized and validated utilizing DNA templates from single-worm samples, which were previously sequenced using the next generation PacBio RSII Sequencing (NGS) platform. Subsequent NGS results for faecal larval cultures were then used as a reference to compare the obtained values for fractional abundances of the resistance-determining mutant allele between ddPCR and NGS techniques in each sample. Both methods managed to produce highly similar results and ddPCR proved to be a reliable tool which, when utilized at full capacity, can be used to create a powerful mutation detection and quantification assay.
42.	Baltrusis, Paulius, et al. (författare) Genome-wide analysis of the response to ivermectin treatment by a Swedish field population of Haemonchus contortus 2022 Ingår i: International Journal for Parasitology: Drugs and Drug Resistance. - : Elsevier BV. - 2211-3207. ; 18, s. 12-19 Tidskriftsartikel (refereegranskat)abstract Haemonchus contortus is a pathogenic gastrointestinal nematode of small ruminants and, in part due to its capacity to develop resistance to drugs, contributes to significant losses in the animal production sector worldwide. Despite decades of research, comparatively little is known about the specific mechanism(s) driving resistance to drugs such as ivermectin in this species. Here we describe a genome-wide approach to detect evidence of selection by ivermectin treatment in a field population of H. contortus from Sweden, using parasites sampled from the same animals before and seven days after ivermectin exposure followed by whole-genome sequencing. Despite an 89% reduction in parasites recovered after treatment measured by the fecal egg count reduction test, the surviving population was highly genetically similar to the population before treatment, suggesting that resistance has likely evolved over time and that resistance alleles are present on diverse haplotypes. Pairwise gene and SNP frequency comparisons indicated the highest degree of differentiation was found at the terminal end of chromosome 4, whereas the most striking difference in nucleotide diversity was observed in a region on chromosome 5 previously reported to harbor a major quantitative trait locus involved in ivermectin resistance. These data provide novel insight into the genome-wide effect of ivermectin selection in a field population as well as confirm the importance of the previously established quantitative trait locus in the development of resistance to ivermectin.
43.	Baltrusis, Paulius, et al. (författare) Molecular detection of two major gastrointestinal parasite genera in cattle using a novel droplet digital PCR approach 2019 Ingår i: Parasitology Research. - : Springer Science and Business Media LLC. - 0932-0113 .- 1432-1955. ; 118, s. 2901-2907 Tidskriftsartikel (refereegranskat)abstract Cooperia sp. and Ostertagia sp. are two cosmopolitan parasitic nematodes often found in mixed gastrointestinal infections in cattle across temperate regions. In light of the recent increase in the emergence of anthelmintic resistance in these and other nematodes derived from cattle around the globe, and their negative impact on animal health and productivity, novel molecular assays need to be put forth in order to facilitate the monitoring of parasite burden in infected herds, using pasture and/or fecal samples. Here, we describe a novel droplet digital PCR platform-based concept for precise identification and quantification of the two most abundant and important parasite genera in grazing western European cattle. By exploiting a single nucleotide difference in the two parasites' ITS2 sequence regions, we have developed two specific hydrolysis probes labeled with FAM (TM) or HEX (TM) fluorophores, which can not only distinguish between the DNA sequences of the two, but also quantify them in mixed DNA samples. A third, newly developed universal probe was also tested along the genus-specific probes to provide a robust and accurate reference. It was evident that the universal probe displayed congruent results to those obtained by the genus-specific probes when used with DNA from both parasites in a single sample. All in all, the results of our assay suggest that this novel protocol could be used to distinguish and quantify cattle parasites belonging to the two most important genera (i.e., Cooperia and Ostertagia) in a single mixed DNA sample.
44.	Baltrusis, Paulius, et al. (författare) The presence and relative frequency detection of the levamisole-resistance-associated S168T substitution in hco-acr-8 in Haemonchus contortus 2023 Ingår i: International Journal for Parasitology: Drugs and Drug Resistance. - : Elsevier BV. - 2211-3207. ; 21, s. 91-95 Tidskriftsartikel (refereegranskat)abstract Parasitic sheep nematodes, among which Haemonchus contortus is often considered to be the most clinically important, exact a significant toll on the animals, not least because of their capacity to evolve drug resistance. Despite decades of research, our understanding of the mechanism of resistance to compounds such as levamisole is fairly limited, which therefore constrains our ability to develop sensitive and efficient molecular diagnostic tools for rapid and accurate resistance detection in field settings. Herein, we investigated the presence and frequency of the newly reported, levamisole-resistance-associated, mutation, yielding a S168T substitution in exon 4 of hco-acr-8, in six different phenotypically described isolates (three susceptible and three resistant), three Swedish field isolates and eight larvae culture samples, the latter two of which originated on farms where le-vamisole showed complete parasite elimination. For this purpose, we created both an allele-specific and droplet digital PCR approaches and found the mutated allele to be present only in the Kokstad isolate, whereas the other five as well as both the Swedish isolates and larvae cultures displayed only the non-mutated, serine-encoding, allele. While the finding of only the non-mutated allele in the phenotypically susceptible and Swedish isolate and larvae culture samples seemed sensible, we speculate that for the other two phenotypically resistant isolates, different (perhaps secondary) variants are responsible for conferring the resistance to levamisole phenotype, given the polygenic nature of levamisole resistance. All in all, despite the limited number of samples tested here, the mutation causing the S168T substitution in hco-acr-8 represents a plausible levamisole resistance-associated variant in, at least, some isolates of H. contortus.
45.	Baltrusis, Paulius, et al. (författare) Using droplet digital PCR for the detection of hco-acr-8b levamisole resistance marker in H. contortus 2021 Ingår i: International Journal for Parasitology: Drugs and Drug Resistance. - : Elsevier BV. - 2211-3207. ; 15, s. 168-176 Tidskriftsartikel (refereegranskat)abstract The nematode Haemonchus contortus is one of the most prevalent and pathogenic parasites in small ruminants. Although usually controlled using anthelmintics, the development of drug resistance by the parasite has become a major issue in livestock production. While the molecular detection of benzimidazole resistance in H. contortus is well developed, the molecular tools and protocols are far less advanced for the detection of levamisole resistance. The hco-acr-8 gene encodes a critical acetylcholine susceptible subunit that confers levamisole-sensitivity to the receptor. Here, we report the development of a droplet digital PCR assay as a molecular tool to detect a 63 bp deletion in the hco-acr-8 that has been previously associated with levamisole resistance. Sanger sequencing of single adult H. contortus yielded 56 high-quality consensus sequences surrounding the region containing the deletion. Based on the sequencing data, new primers and probes were designed and validated with a novel droplet digital PCR assay for the quantification of the deletion containing "resistant" allele in genomic DNA samples. Single adult worms from six phenotypically described isolates (n = 60) and from two Swedish sheep farms (n = 30) where levamisole was effective were tested. Even though a significant difference in genotype frequencies between the resistant and susceptible reference isolates was found (p = 0.01), the homozygous "resistant" genotype was observed to be abundantly present in both the susceptible isolates as well as in some Swedish H. contortus samples. Furthermore, field larval culture samples, collected pre- (n = 7) and post- (n = 6) levamisole treatment on seven Swedish sheep farms where levamisole was fully efficacious according to Fecal Egg Count Reduction Test results, were tested to evaluate the frequency of the "resistant" allele in each. Frequencies of the deletion ranged from 35 to 80% in the pre-treatment samples, whereas no amplifiable H. contortus genomic DNA was detected in the post-treatment samples. Together, these data reveal relatively high frequencies of the 63 bp deletion in the hco-acr-8 both on individual H. contortus and field larval culture scales, and cast doubt on the utility of the deletion in the hco-acr-8 as a molecular marker for levamisole resistance detection on sheep farms.
46.	Baltrusis, Paulius, et al. (författare) Utilization of droplet digital PCR to survey resistance associated polymorphisms in the beta tubulin gene of Haemonchus contortus in sheep flocks in Sweden 2020 Ingår i: Veterinary Parasitology. - : Elsevier BV. - 0304-4017 .- 1873-2550. ; 288 Tidskriftsartikel (refereegranskat)abstract Infections with gastrointestinal nematodes (GINs) in small ruminants are becoming increasingly harder to treat due to the development of anthelmintic resistance. Across Swedish sheep farms, Haemonchus contortus is one of the more persistent and pathogenic species encountered. Benzimidazole drugs, such as albendazole, are still widely used to control the GIN burden in small ruminants. However, the decline in efficacy of this drug has been observed across the country. In this study, we aimed to continue to investigate the presence of single nucleotide polymorphisms in the beta tubulin gene associated with benzimidazole drug resistance in H. contortus. This was carried out for sheep flocks from 67 farms around Sweden by screening for the two most commonly encountered SNPs at codons 167 and 200 in the isotype 1 beta tubulin gene utilizing the droplet digital PCR technology. We first established a good agreement (Lin's concordance correlation coefficient = 0.987) between the previously widely used pyrosequencing assay for the detection of the SNP at codon 200 (otherwise known as mutation F200Y) and our assay, as well as developed and validated primer-probe pairs for the detection of the mutation at codon 167 (mutation F167Y) in the beta tubulin gene of H. contortus. We then screened 174 pooled larval culture samples, collected either pre- or post-treatment, for the frequencies of the mutations F167Y and F200Y. Not only did we find the latter to be present at much higher frequencies, but the overall levels of this resistance conferring mutation have stayed stable throughout the years 2014-2019 at an average value of 88.5 +/- 20.3% in the pre-treatment samples across the tested farms (p = 0.61, Kruskal-Wallis test). Furthermore, after establishing a mixed model and fitting our data, we found a significant (p < 0.01) difference in the average frequency of the mutation F200Y between paired, pre- and post-treatment with albendazole, samples. Although the frequency difference in samples treated with albendazole was relatively minor (88.5% in pre- and 95.6% in post-treatment), no significant (p = 0.15) change in F200Y mutation frequency was observed between the samples from the flocks treated with ivermectin (90.8% and 92.6 %, respectively).
47.	Bastami, Salumeh, 1967- (författare) Practical and clinical use of opioids 2013 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Pain is a common symptom of a number of conditions including cancer and one of the most frequent reasons for seeking healthcare. Acute and chronic pain result in considerable discomfort with a detrimental impact on the quality of life. Opioids are the mainstay of pain management for many patients with severe pain. Opioids are, unfortunately, also commonly abused drugs, and are well-represented in forensic toxicology investigations.Side effects related to the central nervous system are the major reasons fordiscontinuation of opioid treatment. In this thesis, we tested the hypothesis that local analgesic treatment by opioids, without the usual opioid-related side effects, could be a potential alternative to systemic opioid treatment. We examined the analgesic effect of topically applied morphine in a randomized, double blind, cross over study in patients with painful leg ulcers. Significant reduction of pain was obtained after application of both morphine and placebo gel. Morphine reduced pain more than placebo but the difference was not statistically significant. However, morphine could reduce pain considerably more than placebo in those cases where VAS (Visual analog scale) was higher initially.Another issue with opioid therapy is the substantial individual variability in response to opioids including morphine and tramadol. We investigated the significance of UGT2B7, CYP2D6, OPRM1 and ABCB1 polymorphisms for pharmacokinetic and pharmacodynamic properties of morphine and tramadol. We showed that genetic variants in CYP2D6 and UGT2B7 have an important role in the metabolism of tramadol and morphine respectively. While the role of SNPs in ABCB1 remained unclear, genetic variants in OPRM1 gene were correlated with the required dose of morphine. Taken together, these findings suggest that genotypes should be taken into consideration when interpreting clinical pharmacology and forensic toxicology results.Opioids, besides their analgesic properties, have other pharmacological effects including effects on immune system. We evaluated potential differences between commonly used opiates with regard to their effect on the immune system. We found an inhibition of cytokine release, in the order of potency as follows: tramadol > ketobemidone >morphine >fentanyl. All opioids with the exception of fentanyl were capable of inhibiting production of mRNAs for TNF-alpha and IL-8. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of opioids and to improve opioid treatment strategies in patients with cancer.Here, we have found that individual genotype matters and affects the individual response. Further research is warranted to tailor individualized treatment. Personalized medicine has increased in importance and will hopefully in the near future become standard procedure to improve and predict the outcome of treatment by opioids.
48.	Bélteky, Johan, et al. (författare) Epigenetics and early domestication: differences in hypothalamic DNA methylation between red junglefowl divergently selected for high or low fear of humans 2018 Ingår i: Genetics Selection Evolution. - : BIOMED CENTRAL LTD. - 0999-193X .- 1297-9686. ; 50 Tidskriftsartikel (refereegranskat)abstract Background: Domestication of animals leads to large phenotypic alterations within a short evolutionary time-period. Such alterations are caused by genomic variations, yet the prevalence of modified traits is higher than expected if they were caused only by classical genetics and mutations. Epigenetic mechanisms may also be important in driving domesticated phenotypes such as behavior traits. Gene expression can be modulated epigenetically by mechanisms such as DNA methylation, resulting in modifications that are not only variable and susceptible to environmental stimuli, but also sometimes transgenerationally stable. To study such mechanisms in early domestication, we used as model two selected lines of red junglefowl (ancestors of modern chickens) that were bred for either high or low fear of humans over five generations, and investigated differences in hypothalamic DNA methylation between the two populations. Results: Twenty-two 1-kb windows were differentially methylated between the two selected lines at p amp;lt; 0.05 after false discovery rate correction. The annotated functions of the genes within these windows indicated epigenetic regulation of metabolic and signaling pathways, which agrees with the changes in gene expression that were previously reported for the same tissue and animals. Conclusions: Our results show that selection for an important domestication-related behavioral trait such as tameness can cause divergent epigenetic patterns within only five generations, and that these changes could have an important role in chicken domestication.
49.	Benedetti, Rosaria, et al. (författare) Inhibition of histone demethylases LSD1 and UTX regulates ERα signaling in breast cancer 2019 Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:12 Tidskriftsartikel (refereegranskat)abstract In breast cancer, Lysine-specific demethylase-1 (LSD1) and other lysine demethylases (KDMs), such as Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), are co-expressed and co-localize with estrogen receptors (ERs), suggesting the potential use of hybrid (epi)molecules to target histone methylation and therefore regulate/redirect hormone receptor signaling. Here, we report on the biological activity of a dual-KDM inhibitor (MC3324), obtained by coupling the chemical properties of tranylcypromine, a known LSD1 inhibitor, with the 2OG competitive moiety developed for JmjC inhibition. MC3324 displays unique features not exhibited by the single moieties and well-characterized mono-pharmacological inhibitors. Inhibiting LSD1 and UTX, MC3324 induces significant growth arrest and apoptosis in hormone-responsive breast cancer model accompanied by a robust increase in H3K4me2 and H3K27me3. MC3324 down-regulates ERα in breast cancer at both transcriptional and non-transcriptional levels, mimicking the action of a selective endocrine receptor disruptor. MC3324 alters the histone methylation of ERα-regulated promoters, thereby affecting the transcription of genes involved in cell surveillance, hormone response, and death. MC3324 reduces cell proliferation in ex vivo breast cancers, as well as in breast models with acquired resistance to endocrine therapies. Similarly, MC3324 displays tumor-selective potential in vivo, in both xenograft mice and chicken embryo models, with no toxicity and good oral efficacy. This epigenetic multi-target approach is effective and may overcome potential mechanism(s) of resistance in breast cancer.
50.	Bergenfeldt, Henrik, et al. (författare) ABO-Identical Blood Group Matching Has No Survival Benefit for AB Heart Transplant Recipients. 2015 Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 99:3, s. 762-769 Tidskriftsartikel (refereegranskat)abstract Although identical blood group matching is preferred, it is uncertain if this results in improved survival and, if so, how large the survival benefits are. Earlier studies have yielded conflicting results and are mostly based on single-center cohorts with few long-term results. Recipients with blood group AB are of particular interest regarding nonidentical blood group matching because they may receive organs from all blood groups. We wanted to test the hypothesis that ABO-identical matching results in superior survival in recipients with blood group AB.

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