| 1. |
|
|
| 2. |
- Caspers, I. A., et al.
(författare)
-
Effect of preoperative chemotherapy on the histopathological classification of gastric cancer
- 2024
-
Ingår i: Gastric Cancer. - : Springer. - 1436-3291 .- 1436-3305. ; 27, s. 102-109
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In the era of individualized gastric cancer (GC) treatment, accurate determination of histological subtype becomes increasingly relevant. As yet, it is unclear whether preoperative chemotherapy may affect the histological subtype. The aim of this study was to assess concordance in histological subtype between pretreatment biopsies and surgical resection specimens before and after the introduction of perioperative treatment.Methods: Histological subtype was centrally determined in paired GC biopsies and surgical resection specimens of patients treated with either surgery alone (SA) in the Dutch D1/D2 study or with preoperative chemotherapy (CT) in the CRITICS trial. The histological subtype as determined in the resection specimen was considered the gold standard. Concordance rates and sensitivity and specificity of intestinal, diffuse, mixed, and "other" subtypes of GC were analyzed.Results: In total, 105 and 515 pairs of GC biopsies and resection specimens of patients treated in the SA and CT cohorts, respectively, were included. Overall concordance in the histological subtype was 72% in the SA and 74% in the CT cohort and substantially higher in the diffuse subtype (83% and 86%) compared to the intestinal (70% and 74%), mixed (21% and 33%) and "other" subtypes (54% and 54%). In the SA cohort, sensitivities and specificities were 0.88 and 0.71 in the intestinal, 0.67 and 0.93 in the diffuse, 0.20 and 0.98 in the mixed, and 0.50 and 0.93 in the "other" subtypes, respectively.Conclusion: Our results suggest that accurate determination of histological subtype on gastric cancer biopsies is suboptimal but that the impact of preoperative chemotherapy on histological subtype is negligible.
|
|
| 3. |
- Wang, Anqi, et al.
(författare)
-
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
-
Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
|
|
| 4. |
|
|
| 5. |
- Conti, David, V, et al.
(författare)
-
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Fountoulakis, K.N., et al.
(författare)
-
Modeling psychological function in patients with schizophrenia with the PANSS : An international multi-center study
- 2021
-
Ingår i: CNS Spectrums. - : Cambridge University Press. - 1092-8529 .- 2165-6509. ; 26:3, s. 290-298
-
Tidskriftsartikel (refereegranskat)abstract
- Background.The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.Methods.Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.Results.The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.Conclusions.The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
|
|
| 9. |
|
|
| 10. |
- Huynh-Le, MP, et al.
(författare)
-
Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1236-
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
|
|
| 11. |
|
|
| 12. |
- Lin, HY, et al.
(författare)
-
KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness
- 2021
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 9264-
-
Tidskriftsartikel (refereegranskat)abstract
- Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP–SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P < 3.5 × 10–9) and 3145 (P < 1 × 10–5) SNP–SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene–gene interactions were KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP–SNP interactions were supported by gene expression and protein–protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Brandao, A, et al.
(författare)
-
The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor
- 2020
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
-
Tidskriftsartikel (refereegranskat)abstract
- The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case–control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1–3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Gunton, L. M., et al.
(författare)
-
Annelids of the eastern Australian abyss collected by the 2017 RV 'Investigator' voyage
- 2021
-
Ingår i: Zookeys. - : Pensoft Publishers. - 1313-2989 .- 1313-2970. ; :1020, s. 1-198
-
Tidskriftsartikel (refereegranskat)abstract
- In Australia, the deep-water (bathyal and abyssal) benthic invertebrate fauna is poorly known in comparison with that of shallow (subtidal and shelf) habitats. Benthic fauna from the deep eastern Australian margin was sampled systematically for the first time during 2017 RV 'Investigator' voyage 'Sampling the Abyss'. Box core, Brenke sledge, and beam trawl samples were collected at one-degree intervals from Tasmania, 42 degrees S, to southern Queensland, 24 degrees S, from 900 to 4800 m depth. Annelids collected were identified by taxonomic experts on individual families around the world. A complete list of all identified species is presented, accompanied with brief morphological diagnoses, taxonomic remarks, and colour images. A total of more than 6000 annelid specimens consisting of 50 families (47 Polychaeta, one Echiura, two Sipuncula) and 214 species were recovered. Twenty-seven species were given valid names, 45 were assigned the qualifier cf., 87 the qualifier sp., and 55 species were considered new to science. Geographical ranges of 16 morphospecies extended along the eastern Australian margin to the Great Australian Bight, South Australia; however, these ranges need to be confirmed with genetic data. This work providing critical baseline biodiversity data on an important group of benthic invertebrates from a virtually unknown region of the world's ocean will act as a springboard for future taxonomic and biogeographic studies in the area.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Witjes, J. Alfred, et al.
(författare)
-
EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
- 2020
-
Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
|
|
| 30. |
- Alenius Dahlqvist, Jenny, 1972-, et al.
(författare)
-
Changes in Heart Rate and Heart Rate Variability During Surgical Stages to Completed Fontan Circulation
- 2021
-
Ingår i: Pediatric Cardiology. - : Springer Science and Business Media LLC. - 0172-0643 .- 1432-1971. ; 42:5, s. 1162-1169
-
Tidskriftsartikel (refereegranskat)abstract
- Arrhythmia is related to heart rate variability (HRV), which reflects the autonomic nervous regulation of the heart. We hypothesized that autonomic nervous ganglia, located at the junction of the superior vena cava's entrance to the heart, may be affected during the bidirectional Glenn procedure (BDG), resulting in reduced HRV. We aimed to investigate changes in heart rate and HRV in a cohort of children with univentricular heart defects, undergoing stepwise surgery towards total cavopulmonary connection (TCPC), and compare these results with healthy controls. Twenty four hours Holter-ECG recordings were obtained before BDG (n = 47), after BDG (n = 47), and after total cavopulmonary connection (TCPC) (n = 45) in patients and in 38 healthy controls. HRV was analyzed by spectral and Poincare methods. Age-related z scores were calculated and compared using linear mixed effects modeling. Total HRV was significantly lower in patients before BDG when compared to healthy controls. The mean heart rate was significantly reduced in patients after BDG compared to before BDG. Compared to healthy controls, patients operated with BDG had significantly reduced heart rate and reduced total HRV. Patients with TCPC showed reduced heart rate and HRV compared with healthy controls. In patients after TCPC, total HRV was decreased compared to before TCPC. Heart rate was reduced after BDG procedure, and further reductions of HRV were seen post-TCPC. Our results indicate that autonomic regulation of cardiac rhythm is affected both after BDG and again after TCPC. This may be reflected as, and contribute to, postoperative arrhythmic events.
|
|
| 31. |
- Almby, Kristina E., et al.
(författare)
-
Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia
- 2021
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277
-
Tidskriftsartikel (refereegranskat)abstract
- While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Caspers, Irene A., et al.
(författare)
-
The impact of sex on treatment and outcome in relation to histological subtype in patients with resectable gastric cancer : Results from the randomized CRITICS trial
- 2024
-
Ingår i: Journal of Surgical Oncology. - : John Wiley & Sons. - 0022-4790 .- 1096-9098. ; 129:4, s. 734-744
-
Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectiveThis study aims to investigate the impact of sex on outcome measures stratified by histological subtype in patients with resectable gastric cancer (GC).MethodsA post-hoc analysis of the CRITICS-trial, in which patients with resectable GC were treated with perioperative therapy, was performed. Histopathological characteristics and survival were evaluated for males and females stratified for histological subtype (intestinal/diffuse). Additionally, therapy-related toxicity and compliance were compared.ResultsData from 781 patients (523 males) were available for analyses. Female sex was associated with a distal tumor localization in intestinal (p = 0.014) and diffuse tumors (p < 0.001), and younger age in diffuse GC (p = 0.035). In diffuse GC, tumor-positive resection margins were also more common in females than males (21% vs. 10%; p = 0.020), specifically at the duodenal margin. During preoperative chemotherapy, severe toxicity occurred in 327 (63%) males and 184 (71%) females (p = 0.015). Notwithstanding this, relative dose intensities were not significantly different between sexes.ConclusionsPositive distal margin rates were higher in females with diffuse GC, predominantly at the duodenal site. Females also experience more toxicity, but this neither impacts dose intensities nor surgical resection rates. Clinicians should be aware of these different surgical outcomes when treating males and females with GC.
|
|
| 36. |
- Chakravarty, D, et al.
(författare)
-
Association between Incidental Pelvic Inflammation and Aggressive Prostate Cancer
- 2022
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:11
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of pelvic inflammation on prostate cancer (PCa) biology and aggressive phenotype has never been studied. Our study objective was to evaluate the role of pelvic inflammation on PCa aggressiveness and its association with clinical outcomes in patients following radical prostatectomy (RP). This study has been conducted on a retrospective single-institutional consecutive cohort of 2278 patients who underwent robot-assisted laparoscopic prostatectomy (RALP) between 01/2013 and 10/2019. Data from 2085 patients were analyzed to study the association between pelvic inflammation and adverse pathology (AP), defined as Gleason Grade Group (GGG) > 2 and ≥ pT3 stage, at resection. In a subset of 1997 patients, the association between pelvic inflammation and biochemical recurrence (BCR) was studied. Alteration in tumor transcriptome and inflammatory markers in patients with and without pelvic inflammation were studied using microarray analysis, immunohistochemistry, and culture supernatants derived from inflamed sites used in functional assays. Changes in blood inflammatory markers in the study cohort were analyzed by O-link. In univariate analyses, pelvic inflammation emerged as a significant predictor of AP. Multivariate cox proportional-hazards regression analyses showed that high pelvic inflammation with pT3 stage and positive surgical margins significantly affected the time to BCR (p ≤ 0.05). PCa patients with high inflammation had elevated levels of pro-inflammatory cytokines in their tissues and in blood. Genes involved in epithelial-to-mesenchymal transition (EMT) and DNA damage response were upregulated in patients with pelvic inflammation. Attenuation of STAT and IL-6 signaling decreased tumor driving properties of conditioned medium from inflamed sites. Pelvic inflammation exacerbates the progression of prostate cancer and drives an aggressive phenotype.
|
|
| 37. |
- Cid Gomes, L., et al.
(författare)
-
Light-driven (cross-)dimerization of terpenes as a route to renewable C15-C30 crudes for fuel and lubricant oil applications
- 2023
-
Ingår i: Sustainable Energy & Fuels. - : Royal Society of Chemistry. - 2398-4902. ; 7:3, s. 868-882
-
Tidskriftsartikel (refereegranskat)abstract
- Non-fossil hydrocarbons are desirable for transport fuels and lubricant oils to reach a fossil carbon neutral economy. Herein, we show the production of such end-products from crude raw materials via the photosensitized dimerization of terpenes. Terpenes are hydrocarbons originating from renewable sources, such as forestry, industrial bio-waste and photosynthetically active microorganisms. Under irradiation at 365 nm, we observed high conversions of terpenes with conjugated diene segments into their dimers (e.g. 96.1 wt%, 12 h for α-phellandrene), and remarkable results were obtained using simulated and natural sunlight (90.8 wt% and 46.6 wt%, respectively, for α-phellandrene). We show that the lower reactivities of some isomeric monoterpenes could be overcome by a cross-photodimerization with α-phellandrene. We also utilized the cross-photodimerization approach to obtain C15 and C30 products, combining mixtures of isoprene, monoterpenes and sesquiterpenes. Hydrogenation of the terpene dimers gave materials with physical properties suitable as high energy density fuels and lubricant oils. Finally, our preliminary analysis based on recent literature points to the commercial viability of this route to produce fuels and lubricant oils, as well as to a potential for reduction of the environmental impact compared to fossil-based routes.
|
|
| 38. |
- Danielson, Mattias, et al.
(författare)
-
Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study
- 2020
-
Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 87:3, s. 370-382
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of >= 1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. Methods Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. Results Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). Interpretation Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Heinrichs, Jannica, et al.
(författare)
-
Exploring the tribochemical wear and material transfer caused by Cu15Zn alloys on shearing tools
- 2024
-
Ingår i: Wear. - : Elsevier. - 0043-1648 .- 1873-2577. ; 542
-
Tidskriftsartikel (refereegranskat)abstract
- Cemented carbide tools are extensively used in the zipper industry, including shearing of a pre-formed Cu15Zn wire into individual zipper elements. Although the work material is significantly softer than the tool, wear is the life limiting factor for the tools and is considered to be of tribochemical nature. So far it has not been explained, however, it is known that the wear rate of uncoated, as well as CrC and CrN coated, cemented carbide increases dramatically when Zn is omitted from the Cu alloy. In this paper, worn tool surfaces, including any transferred material, were studied to investigate the tribochemical wear mechanism in detail. Material transfer occurred onto all tool surfaces. Cu and Zn were separated on the sub-micron scale, and preferential transfer of one of the constituents was observed. This is reflected in the outermost surface of the sheared element, which shows a homogeneous composition elsewhere. Oxidation was observed of all tool surfaces, which indicates elements of oxidative wear. Further, any Zn transferred to the tool surfaces was oxidized. Thus, it is suggested that the presence of Zn reduces the oxygen available and consequently reduces the oxidation rate of the tool surfaces, leading to the protective effect previously observed. © 2024 The Authors
|
|
| 45. |
- Heinrichs, Jannica, et al.
(författare)
-
Wear of cemented carbide forging dies used in zipper production
- 2022
-
Ingår i: Wear. - : Elsevier. - 0043-1648 .- 1873-2577. ; 492-493
-
Tidskriftsartikel (refereegranskat)abstract
- Cemented carbide tools are commonly used in both cutting and forging processes associated to zipper produc-tion. In production, the tools experience many millions of repeated contacts, hence they must be very durable to keep the wear at acceptable levels. Although the zipper elements in this investigation are made in a relatively soft CuZn alloy, the wear becomes significant and the tool life a production limiting factor. The wear process is to a large extent unknown. To increase the understanding, forging dies used for an increasing number of forgings in actual production, have been studied in detail. Initially the Co binder is preferentially worn off, and transferred CuZn partly fills the cavities. Interestingly, the repeating forging contacts lead to modification of the composition of the transferred material, which partly separates into Cu rich and Zn rich parts, where the Zn rich parts show a high presence of oxygen. During the life span of the tool, represented by the controlled use of forging tools to different percentages of their estimated life, the WC grains are gradually worn into faceted shapes. The most severely worn region of the forging dies develops an increasing surface roughness, which act to shape a corre-sponding pattern on the zipper elements.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Jones, Daniel O.B., et al.
(författare)
-
Environment, ecology, and potential effectiveness of an area protected from deep-sea mining (Clarion Clipperton Zone, abyssal Pacific)
- 2021
-
Ingår i: Progress in Oceanography. - : Elsevier BV. - 0079-6611. ; 197:September-October 2021
-
Tidskriftsartikel (refereegranskat)abstract
- To protect the range of habitats, species, and ecosystem functions in the Clarion Clipperton Zone (CCZ), a region of interest for deep-sea polymetallic nodule mining in the Pacific, nine Areas of Particular Environmental Interest (APEIs) have been designated by the International Seabed Authority (ISA). The APEIs are remote, rarely visited and poorly understood. Here we present and synthesise all available observations made at APEI-6, the most north eastern APEI in the network, and assess its representativity of mining contract areas in the eastern CCZ. The two studied regions of APEI-6 have a variable morphology, typical of the CCZ, with hills, plains and occasional seamounts. The seafloor is predominantly covered by fine-grained sediments, and includes small but abundant polymetallic nodules, as well as exposed bedrock. The oceanographic parameters investigated appear broadly similar across the region although some differences in deep-water mass separation were evident between APEI-6 and some contract areas. Sediment biogeochemistry is broadly similar across the area in the parameters investigated, except for oxygen penetration depth, which reached >2 m at the study sites within APEI-6, deeper than that found at UK1 and GSR contract areas. The ecology of study sites in APEI-6 differs from that reported from UK1 and TOML-D contract areas, with differences in community composition of microbes, macrofauna, xenophyophores and metazoan megafauna. Some species were shared between areas although connectivity appears limited. We show that, from the available information, APEI-6 is partially representative of the exploration areas to the south yet is distinctly different in several key characteristics. As a result, additional APEIs may be warranted and caution may need to be taken in relying on the APEI network alone for conservation, with other management activities required to help mitigate the impacts of mining in the CCZ.
|
|
| 49. |
|
|
| 50. |
|
|
