| 1. |
- Cederqvist, L, et al.
(författare)
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Improved Temperature and Depth Control During FSW of Copper Canisters Using Feedforward Compensation
- 2016
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Ingår i: Friction Stir Welding and Processing VIII. - Hoboken, NJ, USA : John Wiley & Sons, Inc.. - 9781119082491 ; , s. 69-76
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Konferensbidrag (refereegranskat)abstract
- The welding procedure to seal copper canisters requires variable power input throughout the 45 minute long weld cycle to keep the probe temperature within the process window. By using a cascaded loop that determines the power input requirement, the controller will not be dependent on repeatability in the necessary power input between weld cycles, and the lag time in the probe temperature measurement will not be critical. Due to fast-changing thermal boundary conditions during the downward sequence, a feedforward to the power input was designed to further improve controller performance. In addition to the cascade controller adjusting the tool rotation rate, a depth controller is adjusting the axial force to control the shoulder depth. The purpose is to eliminate flash due to excessive shoulder depth and to control the position of the probe tip, which influeces the size and shape of the hook defect produced. Controlling depth is challenging for several reasons, including deflection in the welding machine and thermal expansion of the weld material, and also results in cross-coupling between axial force and spindle torque. The cross-coupling was handled by another feedforward compensator that adjusts the tool rotation rate based on the commanded axial force. The implemented controllers and feedforward compensators have been evaluated over several welds with good results, where the depth is kept within ±0.1mm when the tool reaches the joint line sequence and the probe temperature is held within ±5°C during full circumferential welds compared to a process window of ±60°C.
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| 2. |
- Galon, Jerome, et al.
(författare)
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Cancer classification using the Immunoscore : a worldwide task force
- 2012
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 10, s. 205-
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Forskningsöversikt (refereegranskat)abstract
- Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the ` Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
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| 3. |
- Galon, Jerome, et al.
(författare)
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Towards the introduction of the 'Immunoscore' in the classification of malignant tumours
- 2014
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Ingår i: Journal of Pathology. - : Wiley-Blackwell. - 0022-3417 .- 1096-9896. ; 232:2, s. 199-209
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Forskningsöversikt (refereegranskat)abstract
- The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
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| 4. |
- Kijima, Tsunetaka, et al.
(författare)
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Patient satisfaction and loyalty in Japanese primary care : a cross-sectional study
- 2021
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study aimed to explore associations between various elements of primary care, patient satisfaction, and loyalty. Methods: This cross-sectional study used a modified version of the Primary Care Assessment Tool (PCAT), which was adapted for Japan. We distributed the PCAT questionnaire to patients aged 20 years or older at five rural primary care centres in Japan. We confirmed the validity and reliability of the measure for our study. Next, we examined which elements of primary care were related to patient satisfaction and loyalty using Spearman’s correlation and structural equation modelling. Results: Of 220 eligible patients, 206 participated in this study. We developed nine component scales: first contact (regular access), first contact (urgent access), longitudinality, coordination, comprehensiveness (variety of care), comprehensiveness (risk prevention), comprehensiveness (health promotion), family-centeredness, and community orientation. Longitudinality and first contact (urgent access) were related with patient satisfaction. Longitudinality, first contact (regular access), and family-centeredness were related to patient loyalty. In the structural equation modelling analysis, two variables were significantly related to loyalty, namely a combined variable including longitudinality and first contact (regular access), along with family-centeredness. Conclusions: While a patient satisfaction model could not be distilled from the data, longitudinality, first contact (urgent access), and family-centeredness were identified as important elements for the cultivation of patient loyalty. This implies that primary care providers need to develop a deep understanding of patients’ contexts and concerns and pay attention to their level of access to cultivate greater patient loyalty.
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| 5. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 6. |
- Ryu, Tsuguru, et al.
(författare)
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HIGH-CONTRAST IMAGING OF INTERMEDIATE-MASS GIANTS WITH LONG-TERM RADIAL VELOCITY TRENDS
- 2016
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 825:2
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Tidskriftsartikel (refereegranskat)abstract
- A radial velocity (RV) survey for intermediate-mass giants has been in operation for over a decade at Okayama Astrophysical Observatory (OAO). The OAO survey has revealed that some giants show long-term linear RV accelerations (RV trends), indicating the presence of outer companions. Direct-imaging observations can help clarify what objects generate these RV trends. We present the results of high-contrast imaging observations of six intermediate-mass giants with long-term RV trends using the Subaru Telescope and HiCIAO camera. We detected co-moving companions to gamma Hya B (0.61(-0.14)(+0.12)M(circle dot)), HD 5608 B (0.10 +/- 0.01M(circle dot)), and HD 109272 B (0.28 +/- 0.06M(circle dot)). For the remaining targets (iota Dra, 18 Del, and HD 14067), we exclude companions more massive than 30-60 M-Jup at projected separations of 1 ''-7 ''. We examine whether these directly imaged companions or unidentified long-period companions can account for the RV trends observed around the six giants. We find that the Kozai mechanism can explain the high eccentricity of the inner planets iota Dra b, HD 5608 b, and HD 14067 b.
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| 7. |
- Tanaka, Tomoyuki, et al.
(författare)
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Foxf2 represses bone formation via Wnt2b/β-catenin signaling.
- 2022
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Ingår i: Experimental & molecular medicine. - : Springer Science and Business Media LLC. - 2092-6413. ; 54, s. 753-64
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Tidskriftsartikel (refereegranskat)abstract
- Differentiation of mesenchymal stem cells (MSCs) into osteoblasts is a critical process for proper skeletal development and acquisition/maintenance of bone mass. However, since this regulatory mechanism has not yet been fully elucidated, the treatment of severe osteoporosis and fractures is a challenge. Here, through a comprehensive analysis of gene expression during the differentiation of MSCs into osteoblasts, we show that the forkhead transcription factor Foxf2 is a crucial regulator of this process. Foxf2 expression transiently increased during MSC osteoblastic differentiation. Overexpression of Foxf2 in MSCs inhibited osteoblastic differentiation, and conversely, knockdown of Foxf2 expression promoted this process. Osteoprogenitor-specific Foxf2 knockout mice developed a high bone mass phenotype due to increased bone formation. RNA-seq analysis and molecular experiments revealed that Foxf2 regulation of bone formation is mediated by Wnt2b. Knockdown of Foxf2 in mouse femurs enhanced bone regeneration in vivo. FOXF2 expression was correlated with hip bone mineral density in postmenopausal women with low bone mass. Finally, inhibition of FOXF2 promoted osteoblastic differentiation of human MSCs. This study uncovers a critical role of Foxf2 in the differentiation of MSCs into osteoblasts and provides insight into the pathogenesis associated with bone-related diseases such as osteoporosis and nonunion after fracture.
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| 8. |
- Tanaka, Tomoyuki, et al.
(författare)
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Regulation of osteoblast to osteocyte differentiation by cyclin-dependent kinase-1
- 2023
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Ingår i: Advanced biology. - 2701-0198. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Osteocytes have recently been identified as a new regulator of bone remodeling, but the detailed mechanism of their differentiation from osteoblasts remains unclear. The purpose of this study is to identify cell cycle regulators involved in the differentiation of osteoblasts into osteocytes and determine their physiological significance. The study uses IDG-SW3 cells as a model for the differentiation from osteoblasts to osteocytes. Among the major cyclin-dependent kinases (Cdks), Cdk1 is most abundantly expressed in IDG-SW3 cells, and its expression is down-regulated during differentiation into osteocytes. Inhibition of CDK1 activity reduces IDG-SW3 cell proliferation and differentiation into osteocytes. Osteocyte and Osteoblast-specific Cdk1 knockout in mice (Dmp1-Cdk1 KO ) results in trabecular bone loss. Pthlh expression increases during differentiation, but inhibiting CDK1 activity reduces Pthlh expression. Parathyroid hormone-related protein concentration is reduced in the bone marrow of Dmp1-Cdk1 KO mice. Four weeks of Parathyroid hormone administration partially recovers the trabecular bone loss in Dmp1-Cdk1 KO mice. These results demonstrate that Cdk1 plays an essential role in the differentiation from osteoblast to osteocyte and the acquisition and maintenance of bone mass. The findings contribute to a better understanding of the mechanisms of bone mass regulation and can help develop efficient therapeutic strategies for osteoporosis treatment.
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| 9. |
- Yasuda, Kazuki, et al.
(författare)
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Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:9, s. 1092-1097
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest P value (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.
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