| 1. |
- Cheng, Min, et al.
(författare)
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Distinct and overlapping patterns of cytokine regulation of thymic and bone marrow-derived NK cell development.
- 2009
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Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 182:3, s. 1460-1468
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Tidskriftsartikel (refereegranskat)abstract
- Although bone marrow (BM) represents the main site for postnatal NK cell development, recently a distinct thymic-dependent NK cell pathway was identified. These studies were designed to investigate the role of cytokines in regulation of thymic NK cells and to compare with established regulatory pathways of BM-dependent NK cell compartment. The common cytokine receptor gamma-chain (Il2rg) essential for IL-15-induced signaling, and FMS-like tyrosine kinase 3 (FLT3) receptor ligand (Flt3l) were previously identified as important regulatory pathways of the BM NK cell compartment based on lack of function studies in mice, however their complementary action remains unknown. By investigating mice double-deficient in Il2rg and Flt3l (Flt3l(-/-) Il2rg(-/-)), we demonstrate that FLT3L is important for IL2Rg-independent maintenance of both immature BM as well as peripheral NK cells. In contrast to IL-7, which is dispensable for BM but important for thymic NK cells, IL-15 has a direct and important role in both thymic and BM NK cell compartments. Although thymic NK cells were not affected in Flt3l(-/-) mice, Flt3l(-/-)Il2rg(-/-) mice lacked detectable thymic NK cells, suggesting that FLT3L is also important for IL-2Rg-independent maintenance of thymic NK cells. Thus, IL-2Rg cytokines and FLT3L play complementary roles and are indispensable for homeostasis of both BM and thymic dependent NK cell development, suggesting that the cytokine pathways crucial for these two distinct NK cell pathways are largely overlapping.
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| 2. |
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| 3. |
- Brauner, Hanna, et al.
(författare)
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Distinct phenotype and function of NK cells in the pancreas of nonobese diabetic mice.
- 2010
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Ingår i: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 184:5, s. 2272-2280
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about target organ-infiltrating NK cells in type 1 diabetes and other autoimmune diseases. In this study, we identified NK cells with a unique phenotype in the pancreas of NOD mice. Pancreatic NK cells, localized to the endocrine and exocrine parts, were present before T cells during disease development and did not require T cells for their infiltration. Furthermore, NK cells, or NK cell precursors, from the spleen could traffic to the pancreas, where they displayed the pancreatic phenotype. Pancreatic NK cells from other mouse strains shared phenotypic characteristics with pancreatic NK cells from NOD mice, but displayed less surface killer cell lectin-like receptor G1, a marker for mature NK cells that have undergone proliferation, and also did not proliferate to the same extent. A subset of NOD mouse pancreatic NK cells produced IFN-gamma spontaneously, suggesting ongoing effector responses. However, most NOD mouse pancreatic NK cells were hyporesponsive compared with spleen NK cells, as reflected by diminished cytokine secretion and a lower capacity to degranulate. Interestingly, such hyporesponsiveness was not seen in pancreatic NK cells from the nonautoimmune strain C57BL/6, suggesting that this feature is not a general property of pancreatic NK cells. Based on our data, we propose that NK cells are sentinel cells in a normal pancreas. We further speculate that during inflammation, pancreatic NK cells initially mediate proinflammatory effector functions, potentially contributing to organ-specific autoimmunity, but later become hyporesponsive because of exhaustion or regulation.
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| 4. |
- Fahlman, Åsa, et al.
(författare)
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Measurement of catestatin and vasostatin in wild boar Sus scrofa captured in a corral trap
- 2021
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Ingår i: BMC Research Notes. - : BioMed Central (BMC). - 1756-0500. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Our aim was to analyse the chromogranin A-derived peptides vasostatin and catestatin in serum from wild boar (Sus scrofa) captured in a corral trap. Acute capture-related stress quickly leads to a release of adrenalin and noradrenalin, but these hormones have a short half-life in blood and are difficult to measure. Chromogranin A (CgA), a glycoprotein which is co-released with noradrenalin and adrenalin, is relatively stable in circulation and the CgA-derived peptides catestatin and vasostatin have been measured in domestic species, but not yet in wildlife. Results Vasostatin and catestatin could be measured and the median (range) serum concentrations were 0.91 (0.54-2.86) and 0.65 (0.35-2.62) nmol/L, respectively. We conclude that the CgA-derived peptides vasostatin and catestatin can be measured in wild boar serum and may thus be useful as biomarkers of psychophysical stress.
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| 5. |
- Halvarsson, Peter, et al.
(författare)
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Parasitic strongyle nemabiome communities in wild ruminants in Sweden
- 2022
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Ingår i: Parasites and Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Wildlife hosts may serve as reservoirs for strongyles, which can be transmitted to domestic livestock. Therefore, studies evaluating nemabiome compositions in wildlife ruminants are of great use in assessing the possibility of transmission of important nematode pathogens to domestic sheep in Sweden.Methods: First, fecal samples were collected from roe deer (n = 125), fallow deer (n = 106), red deer (n = 18) and mouflon (n = 13) in south central Sweden during the hunting season in 2019. Second, after fecal examination samples were cultured and the larvae were harvested, followed by DNA extractions. Third, all samples were barcoded and processed for sequence analysis on the PacBio platform. Finally, bioinformatic sequence analysis was conducted with DADA2, while species diversity and richness, as well as interactions between the different hosts, were calculated and analyzed in R.Results: Nematode ITS2 sequences were found in 225 of 262 (86%) samples. In total, 31 taxa were identified, among which 26 (86%) to the species level. These were found in different combinations, among which 24 (77%) occurred in roe deer, 19 (61%) in fallow deer, 20 (65%) in red deer and 10 (32%) in mouflon. Five of the species found are known to be associated with livestock (Chabertia ovina, Haemonchus contortus, Oesophagostomum venulosum, Teladorsagia circumcincta and Trichostrongylus axei). However, in the present study the relative abundance and prevalence of most of these species were low. The most striking exception was T axei, which was relatively abundant in all wildlife hosts. Mostly a wide range of wildlife specific nematodes such as Ostertagia leptospicularis and Spiculopteragia spp. were identified including the invasive nematode Spiculopteragia houdemeri, which was found for the first time in red deer, fallow deer, and mouflon in Sweden. The difference in the number of shared species between mouflon and all cervids (n = 6) was less than among all three cervids (n= 8).Conclusion: In this study, we investigated the community structure of parasitic intestinal nematodes in four wildlife hosts, and we found that the majority of the parasite species identified were wildlife specific. We also found a new, potentially invasive species not reported before. After comparing the nemabiome of the wildlife hosts in this study with a previous study in sheep from the same geographical region, we conclude that the horizontal transmission potential appears to be relatively low. Still, cross-infections of nematodes between game and sheep cannot be completely ignored.
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| 6. |
- Haroun-Izquierdo, Alvaro, et al.
(författare)
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Adaptive single-KIR(+)NKG2C(+) NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia
- 2022
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Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 10:11, s. e005577-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNatural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR)(+)NKG2C(+) adaptive NK cells to maximize missing-self reactivity.MethodsWe developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline. We studied the adaptive state of the cell product (ADAPT-NK) by flow cytometry and mass cytometry as well as cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq). We investigated the functional responses of ADAPT-NK cells against a wide range of tumor target cell lines and primary AML samples using flow cytometry and IncuCyte as well as in a mouse model of AML.ResultsADAPT-NK cells were >90% pure with a homogeneous expression of a single self-HLA specific KIR and expanded a median of 470-fold. The ADAPT-NK cells largely retained their adaptive transcriptional signature with activation of effector programs without signs of exhaustion. ADAPT-NK cells showed high degranulation capacity and efficient killing of HLA-C/KIR mismatched tumor cell lines as well as primary leukemic blasts from AML patients. Finally, the expanded adaptive NK cells had preserved robust antibody-dependent cellular cytotoxicity potential and combination of ADAPT-NK cells with an anti-CD16/IL-15/anti-CD33 tri-specific engager led to near-complete killing of resistant CD45(dim) blast subtypes.ConclusionsThese preclinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population with full missing-self recognition capability.
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| 7. |
- Hordoir, Robinson, et al.
(författare)
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Nemo-Nordic 1.0 : a NEMO-based ocean model for the Baltic and North seas - research and operational applications
- 2019
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 12:1, s. 363-386
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Tidskriftsartikel (refereegranskat)abstract
- We present Nemo-Nordic, a Baltic and North Sea model based on the NEMO ocean engine. Surrounded by highly industrialized countries, the Baltic and North seas and their assets associated with shipping, fishing and tourism are vulnerable to anthropogenic pressure and climate change. Ocean models providing reliable forecasts and enabling climatic studies are important tools for the shipping infrastructure and to get a better understanding of the effects of climate change on the marine ecosystems. Nemo-Nordic is intended to be a tool for both short-term and long-term simulations and to be used for ocean forecasting as well as process and climatic studies. Here, the scientific and technical choices within Nemo-Nordic are introduced, and the reasons behind the design of the model and its domain and the inclusion of the two seas are explained. The model's ability to represent barotropic and baroclinic dynamics, as well as the vertical structure of the water column, is presented. Biases are shown and discussed. The short-term capabilities of the model are presented, especially its capabilities to represent sea level on an hourly timescale with a high degree of accuracy. We also show that the model can represent longer timescales, with a focus on the major Baltic inflows and the variability in deep-water salinity in the Baltic Sea.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Ingvar, Åsa, et al.
(författare)
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Immunosuppressive treatment after solid organ transplantation and risk of post-transplant cutaneous squamous cell carcinoma
- 2010
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 25:8, s. 2764-2771
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The risk of cutaneous squamous cell carcinoma (CSCC) is found to be substantially increased after organ transplantation. The association with specific immunosuppressive regimens has been previously investigated, but results are not concordant. We aimed to clarify the relationship between separate immunosuppressive drugs, drug load, timing and risk of post-transplant CSCC. METHODS: A population-based nested case-control study was performed in the Swedish organ transplantation cohort (n = 5931). All patients who developed CSCC during the follow-up (1970-97) were eligible as cases (n = 207). Controls (n = 189) were randomly selected from the cohort and individually matched to the cases on follow-up time, age at and calendar period of transplantation. Exposure information was collected through extensive and standardized review of medical records. RESULTS: The median time to CSCC was 6.7 years. Post-transplant azathioprine (Aza) treatment considerably increased the risk of CSCC during all time periods analysed, and the risk augmented with increasing dose and duration. Patients who after the entire follow-up period had received a high accumulated dose of Aza had an 8.8-fold increased risk of CSCC in multivariate analysis (P < 0.0001), compared to patients never treated with Aza. Additionally, a high accumulated dose of corticosteroids during the same period conferred a 3.9-fold elevated risk of CSCC (P = 0.09), compared to the lowest accumulated dose of corticosteroids. Cyclosporine treatment was not associated with the risk of CSCC post-transplantation. CONCLUSIONS: This study provides evidence that Aza treatment, but not cyclosporine treatment, is strongly associated with post-transplant CSCC risk. The results suggest that the risk of CSCC after organ transplantation is not only an effect of the immunosuppressive load per se.
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| 12. |
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| 13. |
- Lindsjö, Johan, et al.
(författare)
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Approval of Restraining and Killing Trap Models in Sweden, and Suggested Improvements Through Behavioural and Physiological Evaluation
- 2022
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Ingår i: Mammal Trapping : Wildlife Management, Animal Welfare & International Standards. - 9780980959826 ; , s. 49-68
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Bokkapitel (refereegranskat)abstract
- Trapping wildlife in Sweden is considered as hunting and is regulated by legislation from the Swedish Environmental Protection Agency. Any trap model used to trap wildlife in Sweden must be approved according to Regulation NFS 2013:13. The basis of the evaluation is to ensure that both killing and restraining traps do not cause unnecessary suffering. Animal welfare, as well as handler safety, are considered. The test protocol also evaluates selectivity, and bycatch is one criterion that can lead to non-approval. Over 30 trap models have been evaluated since the Regulation was implemented in 2013. Over 150 models had been approved previously, without a protocol guided by legislation. Here we summarize our experience from some trap evaluations in the context of future improvements of the animal welfare aspects when testing traps with the present Regulation. We are concerned about the inability of killing traps to cause immediate unconsciousness so that approved trap types cause unnecessary suffering. The present assessment of restraining traps is based on evaluation of lesions noted at necropsy of trapped test animals. Also, the trapping event is to be video-recorded. We suggest that inclusion of requirements such as behavioural studies, measurements of physiological parameters, and more species-specific trapping protocols in the Regulations could improve the animal welfare assessment of traps. The 3Rs need more consideration. Re-evaluation of trap models approved prior to the present Regulation is required as the current standards are higher.
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| 14. |
- Luu, Thuy T., et al.
(författare)
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FOXO1 and FOXO3 Cooperatively Regulate Innate Lymphoid Cell Development
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells via gene regulation of IL-15R beta (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment.
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| 15. |
- Sjödahl, Gottfrid, et al.
(författare)
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Different Responses to Neoadjuvant Chemotherapy in Urothelial Carcinoma Molecular Subtypes
- 2022
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 81:5, s. 523-532
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy.OBJECTIVE: To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy.DESIGN, SETTING, AND PARTICIPANTS: Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining. A cohort treated with radical cystectomy alone and public data sets were used for comparison and external validation.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Complete pathological response in the cystectomy specimen (ypT0N0) and survival were compared in predefined molecular subtypes. Differential gene expression and chemotherapy response were explored beyond molecular subtypes.RESULTS AND LIMITATIONS: Patients with genomically unstable (GU) and urothelial-like (Uro) tumors had higher proportions of complete pathological response (16/31 [52%] and 17/54 [31%]), versus five out of 24 (21%) with the basal/squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Molecular subtype was independently associated with improved survival for patients with GU tumors (hazard ratio [HR] 0.29, 95% confidence interval [CI]: 0.11-0.79) and UroC tumors (HR 0.37, 95% CI: 0.14-0.94) compared with Ba/Sq tumors, adjusting for clinical stage. In addition, expression of the gene coding for osteopontin (SPP1) showed a subtype-dependent effect on chemotherapy response.CONCLUSIONS: Urothelial cancer of the luminal-like (GU and Uro) subtypes is more responsive to cisplatin-based neoadjuvant chemotherapy. A second-generation of subtype-specific biomarkers, for example, SPP1, may be a way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC.PATIENT SUMMARY: This study shows that tumor classification by gene expression profiling and molecular subtyping can identify patients who are more likely to benefit from chemotherapy before radical cystectomy for muscle-invasive bladder cancer. Together with other markers for response, molecular subtypes could have a role in selective administration of such chemotherapy.
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| 16. |
- Sjödahl, Gottfrid, et al.
(författare)
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Different Responses to Neoadjuvant Chemotherapy in Urothelial Carcinoma Molecular Subtypes.
- 2022
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Ingår i: European urology. - : Elsevier. - 1873-7560 .- 0302-2838. ; 81:5, s. 523-532
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Tidskriftsartikel (refereegranskat)abstract
- For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy.To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy.Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining. A cohort treated with radical cystectomy alone and public data sets were used for comparison and external validation.Complete pathological response in the cystectomy specimen (ypT0N0) and survival were compared in predefined molecular subtypes. Differential gene expression and chemotherapy response were explored beyond molecular subtypes.Patients with genomically unstable (GU) and urothelial-like (Uro) tumors had higher proportions of complete pathological response (16/31 [52%] and 17/54 [31%]), versus five out of 24 (21%) with the basal/squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Molecular subtype was independently associated with improved survival for patients with GU tumors (hazard ratio [HR] 0.29, 95% confidence interval [CI]: 0.11-0.79) and UroC tumors (HR 0.37, 95% CI: 0.14-0.94) compared with Ba/Sq tumors, adjusting for clinical stage. In addition, expression of the gene coding for osteopontin (SPP1) showed a subtype-dependent effect on chemotherapy response.Urothelial cancer of the luminal-like (GU and Uro) subtypes is more responsive to cisplatin-based neoadjuvant chemotherapy. A second-generation of subtype-specific biomarkers, for example, SPP1, may be a way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC.This study shows that tumor classification by gene expression profiling and molecular subtyping can identify patients who are more likely to benefit from chemotherapy before radical cystectomy for muscle-invasive bladder cancer. Together with other markers for response, molecular subtypes could have a role in selective administration of such chemotherapy.
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| 17. |
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| 18. |
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| 19. |
- Strömqvist, Johan, et al.
(författare)
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A modified FCCS procedure applied to Ly49A-MHC class Icis-interaction studies in cell membranes
- 2011
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Ingår i: Biophysical Journal. - : Elsevier. - 0006-3495 .- 1542-0086. ; 101:5, s. 1257-1269
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Tidskriftsartikel (refereegranskat)abstract
- The activity of natural killer (NK) cells is regulated by a fine-tuned balance between activating and inhibitory receptors. Dual-color fluorescence cross-correlation spectroscopy (FCCS) was used to directly demonstrate a so-called cis-interaction between a member of the inhibitory NK cell receptor family Ly49 (Ly49A), and its ligand, the major histocompatibility complex (MHC) class I, within the plasma membrane of the same cell. By a refined FCCS model, calibrated by positive and negative control experiments on cells from the same lymphoid cell line, concentrations and diffusion coefficients of free and interacting proteins could be determined on a collection of cells. Using the intrinsic intercellular variation of their expression levels for titration, it was found that the fraction of Ly49A receptors bound in cis increase with increasing amounts of MHC class I ligand. This increase shows a tendency to be more abrupt than for a diffusion limited three dimensional bimolecular reaction, which most likely reflects the two-dimensional confinement of the reaction. For the Ly49A- MHC class I interaction it indicates that within a critical concentration range the local concentration level of MHC class I can provide a distinct regulation mechanism of the NK cell activity.
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| 20. |
- Thorvaldson, Lina, et al.
(författare)
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Impact of plastic adhesion in vitro on analysis of Th1 and Th2 cytokines and immune cell distribution from mice with multiple low-dose streptozotocin-induced diabetes
- 2005
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 307:1-2, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- Cytokines produced by Th1 or Th2 cells have been postulated to be important in the development of type 1 diabetes in humans and animal models, such as murine multiple low-dose streptozotocin (MLDSTZ)-induced diabetes. The aim of this study was to investigate cytokine production with or without in vitro depletion of plastic adherent cells from spleens isolated after MLDSTZ treatment. Spleen cells were prepared on day 14 from MLDSTZ- and saline-treated mice and divided into two fractions. One cell fraction was depleted of adherent cells by plastic adherence and the other was not. Both cell fractions were analysed by FACS for the distribution of immune cells. In other experiments, the cells were cultured for 48 h with concanavalin A stimulation. Supernatant samples were analysed by ELISA for TNFalpha, IFNgamma and IL-10 production. Either before or after the 48-h culture cytokine mRNA expression was determined by RT-PCR. Plastic adhesion decreased the macrophage numbers by approximately 30% and CD4(+)CD25(+) cells by about 60%. This was accompanied by increased medium levels of TNFalpha, IFNgamma and IL-10, which suggest that either CD4(+)CD25(+) cells, macrophages, or both, down-regulate production of both Th1 and certain Th2 cytokines. Depletion of adherent cells also decreased IL-4 mRNA amounts. MLDSTZ treatment increased the production of Th1 cytokines mainly at the protein level, and IL-10 mainly at the mRNA level. This indicates a sustained increase in Th1 production after MLDSTZ treatment and an increase in IL-10 that might reflect an attempt to counteract the MLDSTZ-induced immune damage. Plastic adhesion during cell preparation may affect the relative distribution of certain immune cells.
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| 21. |
- Zeleke Aklilu, Abenezer, et al.
(författare)
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A pound for information or a penny for cure : Farmers' economic decisions on testing and treatment of livestock diseases
- 2024
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Ingår i: Australian Journal of Agricultural and Resource Economics. - : John Wiley & Sons. - 1364-985X .- 1467-8489. ; 68:2, s. 460-482
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Tidskriftsartikel (refereegranskat)abstract
- Livestock productivity and profitability are threatened by livestock diseases. In this study, we examine farmers' revealed preferences for testing and treating gastrointestinal parasites in sheep in Sweden, taking into account the sequential structure of these decisions. We control for preventive measures, as well as the potential impact of wildlife–livestock disease transmission on farmers' decisions. A zero-inflated ordered probit model is used to estimate the determinants of farmers' decisions, and we cross-validate the robustness of the results to alternative model assumptions. Results from the regressions are used to calculate the consequences of these choices for farmers' profits. The results show that treatment decisions are informed by faecal testing, while both testing and treatment are influenced by the grazing practices, the size of the operation and access to information. Contrary to expectations from the conceptual framework, preventive management practices are positively correlated with treatment. Farmers take multiple risk factors into account when deciding on testing, but we do not find that the same factors affect the outcome of treatment. The economic impacts are small and suggest that treatment without prior testing is more profitable for the farmer than informed treatment. If widespread treatment increases drug resistance, this could motivate policies that encourage testing.
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| 22. |
- Zhao, Jingcheng, et al.
(författare)
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Frequent platelet donation is associated with lymphopenia and risk of infections : A nationwide cohort study
- 2021
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Ingår i: Transfusion. - : John Wiley & Sons. - 0041-1132 .- 1537-2995. ; 61:2, s. 464-473
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, plateletpheresis donations using a widely used leukoreduction system (LRS) chamber have been associated with T-cell lymphopenia. However, clinical health consequences of plateletpheresis-associated lymphopenia are still unknown.Study Design and Methods: A nationwide cohort study using the SCANDAT3-S database was conducted with all platelet- and plasmapheresis donors in Sweden between 1996 and 2017. A Cox proportional hazards model, using donations as time-dependent exposures, was used to assess the risk of infections associated with plateletpheresis donations using an LRS chamber.Results: A total of 74 408 apheresis donors were included. Among donors with the same donation frequency, plateletpheresis donors using an LRS chamber were at an increased risk of immunosuppression-related infections and common bacterial infections in a dose-dependent manner. While very frequent donors and infections were rare in absolute terms resulting in wide confidence intervals (CIs), the increased risk was significant starting at one-third or less of the allowed donation frequency in a 10-year exposure window, with hazard ratios reaching 10 or more. No plateletpheresis donors that used an LRS chamber experienced a Pneumocystis jirovecii, aspergillus, disseminated mycobacterial, or cryptococcal infection. In a subcohort (n = 42), donations with LRS were associated with low CD4+ T-cell counts (Pearson's R = -0.41; 95% CI, - 0.63 to -0.12).Conclusion: Frequent plateletpheresis donation using an LRS chamber was associated with CD4+ T-cell lymphopenia and an increased risk of infections. These findings suggest a need to monitor T-lymphocyte counts in frequent platelet donors and to conduct future investigations of long-term donor health and for regulators to consider steps to mitigate lymphodepletion in donors.
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