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| 4. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 5. |
- Mani, K, et al.
(författare)
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Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside preferentially inhibits growth of transformed cells
- 1998
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Ingår i: Cancer Research. - 0008-5472. ; 58:6, s. 104-1099
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Tidskriftsartikel (refereegranskat)abstract
- Xylose forms the direct carbohydrate-protein link in extra- or pericellular proteoglycans (PGs) that are substituted with either chondroitin sulfate (CS)/dermatan sulfate (DS) and/or heparan sulfate (HS). Cell surface PGs carrying HS are important regulators of cell growth. Xylose coupled to an aromatic compound can enter cells and initiate either CS/DS synthesis or both HS and CS/DS synthesis, depending on the nature of the aromatic adduct. Here, we show that 2-(6-hydroxynaphthyl)-O-beta-D-xylopyranoside, which can prime both types of glycan chains, inhibits growth of a set of normal and transformed cells. Transformed cells are preferentially inhibited, and at a concentration of 0.15-0.20 mM xyloside, transformed cells are totally growth arrested, whereas normal cells are only < or = 50% inhibited. No inhibition of growth is observed with the stereoisomeric 2-(6-hydroxynaphthyl)-O-beta-L-xylopyranoside, which does not prime glycosaminoglycan synthesis at all; with the nonhydroxylated 2-naphthyl-O-beta-D-xylopyranoside, which only primes CS/DS synthesis under these conditions; or with p-nitrophenyl-O-beta-D-xylopyranoside, which is known to prime only CS/DS synthesis. We conclude that growth inhibition is due to priming of HS and/or CS/DS synthesis, which may either lead to the formation of specific antiproliferative glycans or glycan fragments or to interference with endogenous PG synthesis and turnover.
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| 6. |
- Radhakrishnan, M, et al.
(författare)
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Effect of chromium variation on evolution of magnetic properties in laser direct energy additively processed CoCrxFeNi alloys
- 2023
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Ingår i: Scripta Materialia. - : Elsevier BV. - 1359-6462. ; 226
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Tidskriftsartikel (refereegranskat)abstract
- The soft magnetic behavior of laser directed energy deposited CoCrxFeNi (x = 0 - 24 at.% Cr) alloys has been investigated as a function of chromium content. The saturation magnetization of these CoCrxFeNi alloys monotonically decreased with increasing concentration of Cr, and exhibited paramagnetic behavior at room temperature for equiatomic CoCrFeNi alloy composition. Similarly, the Curie temperature (Tc) of the ferromagnetic CoFeNi alloy linearly decreased with Cr content, while the paramagnetic equiatomic alloy indicated a ferromagnetic transition temperature of 94 K. Interestingly, all the as-deposited alloys exhibited coercivity values less than 2 Oe irrespective of the Cr content. The results indicate that the magnetic behavior of the ferromagnetic CoFeNi alloy can be systematically tuned with addition of antiferromagnetic Cr, and the additive manufacturing route was successful in rapid processing alloys of any desired composition, in a high throughput manner, with negligible chemical variation. These findings are promising for the fabrication of components for applications demanding gradient magnetic coatings and alloys.
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| 7. |
- Varahabhatla, S. M., et al.
(författare)
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Influence of energy density on the microstructure, growth orientation, and anisotropy of magnetic properties in additively manufactured Fe-3.8wt%Si transformer steels
- 2023
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Ingår i: Materialia. - 2589-1529. ; 30
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Tidskriftsartikel (refereegranskat)abstract
- Fe-3.8wt%Si transformer steels were processed using two different additive manufacturing (AM) techniques, laser powder bed fusion (LPBF) and directed energy deposition (DED). While the LPBF processed samples exhibited a strong <001> orientation of the BCC grains along the build axis, the DED processed samples exhibited a randomized texture along the build axis. DED processed samples showed substantially coarser columnar grains as compared to their LPBF counterparts. The columnar grains exhibited a substantial number of low-angle sub-grain boundaries. All samples exhibited very good soft magnetic properties, with saturation magnetization (Ms) values ranging from 205 - 232 emu/gm, and coercivity (Hc) values ranging from 1.2 – 4.2 Oe. The Coercivity (Hc) values were significantly lower when the magnetic field was applied parallel to the build axis, as compared to being perpendicular, which can be rationalized based on the columnar nature of the grains, resulting in a higher number density of grain boundaries in case of the field applied perpendicular to the build axis.
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| 9. |
- Bernstein, W. Z., et al.
(författare)
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An open web-based repository for capturing manufacturing process information
- 2016
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Ingår i: ASME 2016 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference, IDETC/CIE 2016, Charlotte, United States, 21-24 August. ; 4
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Konferensbidrag (refereegranskat)abstract
- With recent progress in developing more effective models for representing manufacturing processes, this paper presents an approach towards an open web-based repository for storing manufacturing process information. The repository is envisioned to include several new use cases in the context of information use in smart manufacturing. This paper examines several key benefits through usage scenarios engaging existing engineering activities. Based on the scenarios, the desired characteristics of an open web-based repository are presented, namely that it will be (1) complementary to existing practices, (2) open and netcentric, (3) able to enforce model consistency, (4) modular (5) extensible, and (5) able to govern contributions. A repository will support and motivate the ubiquitous and extended use of standardized representations of unit manufacturing processes in order to promote consistency of performance assessments across industries and provide a tangible, data-driven perspective for analysis-related activities. Furthermore, the paper presents additional benefits and possible applications that could result from a shared manufacturing repository.
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| 12. |
- Mani, M., et al.
(författare)
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Standard Representations for Sustainability Characterization of Industrial Processes
- 2016
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Ingår i: Journal of Manufacturing Science and Engineering, Transactions of the ASME. - : ASME International. - 1087-1357 .- 1528-8935. ; 138:10
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Tidskriftsartikel (refereegranskat)abstract
- Sustainability assessments are dependent on accurate measures for energy, material, and other resources used by the processes involved in the life cycle of a product. Manufacturing accounts for about 1/5 of the energy consumption in the U.S. Minimizing energy and material consumption in this field has the promise of dramatically reducing our energy dependence. To this end, ASTM International [1] has formed both a committee on Sustainability (E60) and a Subcommittee on Sustainable Manufacturing (E60.13). This paper describes ASTM's new guide for characterizing the environmental aspects of manufacturing processes [2]. The guide defines a generic representation to support structured processes. Representations of multiple unit manufacturing processes (UMPs) can be linked together to support system-level analyses, such as simulation and evaluation of a series of manufacturing processes used in the manufacture and assembly of parts. The result is the ability to more accurately assess and improve the sustainability of production processes. Simulation is commonly used in manufacturing industries to assess individual process performance at a system level and to understand behaviors and interactions between processes. This paper explores the use of the concepts outlined in the standard with three use cases based on an industrial example in the pulp and paper industry. The intent of the use cases is to show the utility of the standard as a guideline for composing data to characterize manufacturing processes. The data, besides being useful for descriptive purposes, is used in a simulation model to assess sustainability of a manufacturing system.
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| 13. |
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| 14. |
- Rebouillat, Laurie, et al.
(författare)
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Understanding sustainability data through unit manufacturing process representations: a case study on stone production
- 2016
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Ingår i: Procedia CIRP. - : Elsevier BV. - 2212-8271. ; 57, s. 686-691
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Konferensbidrag (refereegranskat)abstract
- Efficiency of natural stone production processes in quarries directly affects the economic output and environmental performances, such as production lead times and energy consumptions. Knowledge on stone production processes is crucial in making responsible decisions in this business. Having a structured representation of information characterizing the stone production processes will support stakeholders in better assessing production resources in terms of sustainability and productivity. Value stream mapping can provide an overview and guidance for sustainability performance evaluation, but its application is limited. The challenges arise when trying to specifically map and relate sustainability data between processes e.g., variability in lead time and CO2 emissions. Manufacturing process characterization standards currently being developed by ASTM International manifest the potential to not only fill this gap but also to provide opportunities to characterize and compose manufacturing processes with relevant environmental information and description. This paper shows the application and lessons learned from deploying once such effort towards standardization.
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| 15. |
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| 16. |
- Aguggia, Julieta P., et al.
(författare)
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Growth hormone secretagogue receptor signaling in the supramammillary nucleus targets nitric oxide-producing neurons and controls recognition memory in mice
- 2022
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- Ghrelin is a stomach-derived hormone that acts via the growth hormone secretagogue receptor (GHSR). Recent evidence suggests that some of ghrelin's actions may be mediated via the supramammillary nucleus (SuM). Not only does ghrelin bind to cells within the mouse SuM, but ghrelin also activates SuM cells and intra-SuM ghrelin administration induces feeding in rats. In the current study, we aimed to further characterize ghrelin action in the SuM. We first investigated a mouse model expressing enhanced green fluorescent protein (eGFP) under the promoter of GHSR (GHSR-eGFP mice). We found that the SuM of GHSR-eGFP mice contains a significant amount of eGFP cells, some of which express neuronal nitric oxide synthase. Centrally-, but not systemically-, injected ghrelin reached the SuM, where it induced c-Fos expression. Furthermore, a 5-day 40% calorie restriction protocol, but not a 2-day fast, increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice, whereas c-Fos induction by calorie restriction was not observed in GHSR-deficient mice. Exposure of satiated mice to a binge-like eating protocol also increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice in a GHSR-dependent manner. Finally, intra-SuM-injected ghrelin did not acutely affect food intake, locomotor activity, behavioral arousal or spatial memory but increased recognition memory. Thus, we provide a compelling neuroanatomical characterization of GHSR SuM neurons and its behavioral implications in mice.
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| 17. |
- Ahmed, Ahfaz, et al.
(författare)
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Kinetic modelling and experimental study of small esters : Methyl acetate and ethyl acetate
- 2017
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Ingår i: 11th Asia-Pacific Conference on Combustion, ASPACC 2017. ; 2017-December
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Konferensbidrag (refereegranskat)abstract
- A detailed chemical kinetic mechanism comprising methyl acetate and ethyl acetate has been developed based on the previous work by Westbrook et al. [1]. The newly developed kinetic mechanism has been updated with new reaction rates from recent theoretical studies. To validate this model, shock tube experiments measuring ignition delay time have been conducted at 15 & 30 bar and equivalence ratio 0.5, 1.0 and 2.0. Another set of experiments measuring laminar burning velocity was also performed on a heat flux burner at atmospheric pressure over wide range of equivalence ratios [ ~ 0.7-1.4]. The new mechanism shows significant improvement in prediction of experimental data over earlier model across the range of experiments.In this study, a detailed chemical kinetic model for methyl and ethyl acetate (Fig. 1) has been developed. This model is advanced from the mechanism proposed for laminar premixed flames by Westbrook and coworkers in 2009 [1]. Acetates studied in this work are both high RON fuels with suitable physical and chemical properties [Table 1] to be considered as potential fuels in advanced gasoline engines [4]. Shock tube experiments measuring ignition delay time have been conducted at 15 & 30 bar and equivalence ratio 0.5, 1.0 and 2.0. Another set of experiments measuring laminar burning velocity have also been performed on a heat flux burner at atmospheric pressure over wide range of equivalence ratios. The model developed in this work shows good agreement with ignition data and laminar burning velocity data across the temperature and equivalence ratio range respectively.
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| 18. |
- Ahmed, Ahfaz, et al.
(författare)
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Small ester combustion chemistry : Computational kinetics and experimental study of methyl acetate and ethyl acetate
- 2019
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Ingår i: Proceedings of the Combustion Institute. - : Elsevier BV. - 1540-7489. ; 37:1, s. 419-428
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Tidskriftsartikel (refereegranskat)abstract
- Small esters represent an important class of high octane biofuels for advanced spark ignition engines. They qualify for stringent fuel screening standards and could be synthesized through various pathways. In this work, we performed a detailed investigation of the combustion of two small esters, MA (methyl acetate) and EA (ethyl acetate), including quantum chemistry calculations, experimental studies of combustion characteristics and kinetic model development. The quantum chemistry calculations were performed to obtain rates for H-atom abstraction reactions involved in the oxidation chemistry of these fuels. The series of experiments include: a shock tube study to measure ignition delays at 15 and 30 bar, 1000-1450 K and equivalence ratios of 0.5, 1.0 and 2.0; laminar burning velocity measurements in a heat flux burner over a range of equivalence ratios [0.7-1.4] at atmospheric pressure and temperatures of 298 and 338 K; and speciation measurements during oxidation in a jet-stirred reactor at 800-1100 K for MA and 650-1000 K for EA at equivalence ratios of 0.5, 1.0 and at atmospheric pressure. The developed chemical kinetic mechanism for MA and EA incorporates reaction rates and pathways from recent studies along with rates calculated in this work. The new mechanism shows generally good agreement in predicting experimental data across the broad range of experimental conditions. The experimental data, along with the developed kinetic model, provides a solid groundwork towards improving the understanding the combustion chemistry of smaller esters.
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| 19. |
- Apine, E., et al.
(författare)
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Comparative analysis of the intestinal bacterial communities in mud crab Scylla serrata in South India
- 2021
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Ingår i: Microbiologyopen. - : Wiley. - 2045-8827. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the functions of the crustacean gut microbiome, but environmental parameters and habitat are known to affect the composition of the intestinal microbiome, which may in turn affect the physiological status of the host. The mud crab Scylla serrata is an economically important species, and is wild-caught, and farmed across the Indo-Pacific region. In this study, we compared the composition of the gut microbiome (in terms of gut microbial species richness and abundance) of S. serrata collected from wild sites, and farms, from the east and west coast of India, and also tested the effects of the environment on the composition. The water temperature had a statistically significant effect on gut microbiome composition, with microbial biodiversity decreasing with increasing water temperature. This could have negative effects on both wild and farmed mud crabs under future climate change conditions, although further research into the effects of temperature on gut microbiomes is required. By comparison, salinity, crab mass and carapace width, geographical location as well as whether they were farmed or wild-caught crabs did not have a significant impact on gut microbiome composition. The results indicate that farming does not significantly alter the composition of the gut microbiome when compared to wild-caught crabs.
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| 20. |
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| 21. |
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| 22. |
- Gan, M., et al.
(författare)
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Calibration of indoor UWB sub-band divided ray tracing using multiobjective simulated annealing
- 2014
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Ingår i: 2014 IEEE International Conference on Communications, ICC 2014. - 9781479920037 ; , s. 4844-4849
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Konferensbidrag (refereegranskat)abstract
- Sub-band divided ray tracing (RT) has been widely used to reproduce as reliably as possible the ultra-wideband (UWB) radio wave propagation channel in realistic indoor environments. However, its accuracy is strictly limited by the available description of the environment. Moreover, its computational complexity scales with the number of selected subbands and the number of propagation paths. In the present work, our RT tool considers not only deterministic propagation paths but also diffuse scattering components. Based on a low-complexity sub-band divided RT implementation, we propose a calibration method for indoor UWB sub-band divided RT. The method estimates the optimal material parameters, including the dielectric parameters and the scattering parameters, using channel measurements and multiobjective simulated annealing (MOSA). This calibration can improve the accuracy of sub-band divided RT in terms of the power delay profile (PDP) and the root mean square (RMS) delay spread for all test locations including those not considered by the calibration. A measurement campaign is used to verify the calibration technique. © 2014 IEEE.
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| 23. |
- Gan, M., et al.
(författare)
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Low-Complexity Sub-band Divided Ray Tracing for UWB Indoor Channels
- 2014
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Ingår i: IEEE Wireless Communications and Networking Conference, WCNC. - 1525-3511.
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Konferensbidrag (refereegranskat)abstract
- Ray tracing has been extensively used to simulateindoor channel characteristics. For an ultra-wideband system,the channel characteristics vary significantly over the entirebandwidth. To cope with this, sub-band divided RT has beenproposed by dividing the frequency of interest into multiplesubbands and superposing the RT results at the individual centerfrequency of each subband. Thus, the computational complexityis directly proportional to the number of subbands. In this paper,we propose a mathematical method to significantly reduce thecomputational complexity of the sub-band divided RT, making italmost independent of the number of subbands. It is important tonote that, based on our approach, not only the determination ofthe rays reaching a give location is made only once, but also theelectromagnetic calculation of the received signal is not neededto perform repeatedly. The accuracy of low-complexity sub-band divided RT algorithm is verified through a measurementcampaign.
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| 24. |
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| 25. |
- Heindel, Jerrold J., et al.
(författare)
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NIEHS/FDA CLARITY-BPA research program update
- 2015
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 58, s. 33-44
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Forskningsöversikt (refereegranskat)abstract
- Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program.
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| 26. |
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| 27. |
- Kuzniar, Marek K., et al.
(författare)
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Endovascular treatment of chronic aortic dissection with fenestrated and branched stent grafts
- 2021
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Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 73:5, s. 1573-1582.e1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Chronic aortic dissection with aneurysm development that includes the aortic arch and/or thoracoabdominal aorta (TAAA) is traditionally treated with open or hybrid surgery. Total endovascular treatment with fenestrated and branched aortic repair (F/B-EVAR) has recently been introduced as a less invasive alternative. The aim was to report the short- and midterm outcomes from a single tertiary vascular center.METHODS: All patients with chronic aortic dissection treated with F/B-EVAR from 2010 to 2019 at Uppsala University Hospital were identified. Perioperative and postoperative parameters were analyzed, with focus on short- (<30 days) and midterm survival, complication, and reintervention rates.RESULTS: F/B-EVAR was performed on 26 patients (median age, 63 years; range, 33-87 years; 18 men; median aortic diameter, 70 mm; range, 50-98 mm); with a median follow-up of 23 months (range, 0.5-118.0 months). One patient underwent both arch and TAAA repair. Overall, 13 arch repairs (arch group) after type A (n = 8) and type B (n = 5) dissection (all elective) were performed, and 14 TAAA repairs (TAAA group) after type A (n = 5) and type B (n = 9) dissection (one rupture). A total of 72 aortic branches were targeted (22 arch, 50 TAAA). Short-term technical success was achieved in 24 of 27 procedures (89%). Failures were related to one intraoperative retrograde type A dissection (RTAD) requiring open conversion (arch group), one persistent type IC endoleak on completion angiography (arch group), and one persistent type III endoleak (TAAA group). Mortality was 4% (n = 1) at 30 days and related to a second RTAD that occurred after discharge and was found on autopsy. Both RTADs occurred in patients with chronic type B dissection undergoing fenestrated arch repair. Paraplegia occurred in three cases (two arch, one TAAA) (11%), none permanent, and stroke in three cases (one arch, one TAAA) (11%); one was permanent. In the midterm, endoleaks were detected in 12 patients (44%); persistent false lumen flow (n = 3), type IB (n = 1), type IC (n = 3), type II (n = 7), and type IIIC (n = 2). The 3-year survival (Kaplan-Meier) of the arch repair was 75% and for the TAAA, 93%. Freedom from reintervention at 3 years were 100% for arch repairs and 48% for TAAA. In patients with a follow-up of more than 6 months (n = 23), all had stable or decreased aortic diameters and complete false lumen thrombosis at the level of stent graft was present in 65% (n = 15).CONCLUSIONS: Endovascular treatment of postdissection aneurysms is feasible, with acceptable short-term and midterm outcomes. RTAD after fenestrated and branched endovascular arch repair warrants caution when performed on patients with native ascending aortas, and reinterventions are frequent in TAAA repair.
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| 28. |
- Mansoori, Nasim, et al.
(författare)
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Serum Folic Acid and RFC A80G Polymorphism in Alzheimers Disease and Vascular Dementia
- 2014
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Ingår i: American Journal of Alzheimer’s Disease and Other Dementia. - : SAGE Publications (UK and US). - 1533-3175 .- 1938-2731. ; 29:1, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- Low level of vitamin B12 and folic acid has been reported to play an important role in the pathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). Serum folic acid and vitamin B12 were assayed in 80 AD and 50 VaD cases and in 120 healthy controls. The reduced folate carrier (RFC1) gene, rs1051266, which encodes the RFC 1, protein was analyzed for polymorphism by polymerase chain reaction-restriction fragment length polymorphism. It was observed that the patients having folic acid <8.45 ng/mL had 2.4 (95% confidence interval [CI]: 1.4-4.5) times higher odds of having AD and 2.1 (95% CI: 1.1-4.2) times higher odds of having VaD than patients having folic acid ≥8.45 ng/mL. Serum vitamin B12 level did not show any such statistically significant effect in altering the odds. No direct association was found between variant (G) allele or genotype of rs1051266 with AD and VaD cases. On serum folate level no association was observed with gene polymorphism.
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| 29. |
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| 30. |
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| 31. |
- Muroyama, A., et al.
(författare)
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Simulation and analysis for sustainability in manufacturing processes
- 2011
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Ingår i: ASME 2011 International Design Engineering Technical Conferences and Computers and Information in Engineering Conference, IDETC/CIE 2011. - 9780791854792 ; 2:Parts A and B, s. 935-941
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Konferensbidrag (refereegranskat)abstract
- "Sustainability" has become a ubiquitous term in almost every field, especially in engineering design and manufacturing. Recently, an increased awareness of environmental problems and resource depletion has led to an emphasis on environmentally friendly practices. This is especially true in the manufacturing industry where energy consumption and the amount of waste generated can be high. This requires proactive tools to be developed to carefully analyze the cause-effect of current manufacturing practices and to investigate alternative practices. One such approach to sustainable manufacturing is the combined use of Discrete Event Simulation (DES) and Life Cycle Assessment (LCA) to analyze the utilization and processing of manufacturing resources in a factory setting. On an economic aspect such method can significantly reduce the financial and environmental costs by evaluating the system performance before its construction or use. This project considers what-if scenarios in a simplified golf ball factory, using as close to real-world data as possible, to demonstrate DES and LCA's ability to facilitate decision-making and optimize the manufacturing process. Plastic injection molding, an energy-intensive step in the golf ball manufacturing process, is the focus of the DES model. AutoMod, a 3-D modeling software, was used to build the DES model and AutoStat was used to run the trials and analyze the data. By varying the input parameters such as type and number of injection molding machines and material used, the simulation model can output data indicating the most productive and energy efficient methods. On a more detailed level, the simulations can provide valuable information on bottlenecks or imbalances in the system. Correcting these can allow the factory to be both "greener" and more cost-effective.
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| 32. |
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| 33. |
- Nijs, Jo, et al.
(författare)
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Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine
- 2021
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Ingår i: Lancet Rheumatology. - : Elsevier BV. - 2665-9913. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- Chronic pain is a leading cause of disability globally and associated with enormous health-care costs. The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists. Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy. Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain. Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment. Central sensitisation predicts poor treatment outcomes in multiple patient populations. The available evidence supports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice. These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step. With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain
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| 34. |
- Olsson, Karl Wilhelm, 1985-, et al.
(författare)
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Outcomes after endovascular aortic intervention in patients with connective tissue disease
- 2023
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Ingår i: JAMA Surgery. - : American Medical Association (AMA). - 2168-6254 .- 2168-6262. ; 158:8, s. 832-839
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Endovascular treatment is not recommended for aortic pathologies in patients with connective tissue diseases (CTDs) other than in redo operations and as bridging procedures in emergencies. However, recent developments in endovascular technology may challenge this dogma.Objective: To assess the midterm outcomes of endovascular aortic repair in patients with CTD.Design, Setting, and Participants: For this descriptive retrospective study, data on demographics, interventions, and short-term and midterm outcomes were collected from 18 aortic centers in Europe, Asia, North America, and New Zealand. Patients with CTD who had undergone endovascular aortic repair from 2005 to 2020 were included. Data were analyzed from December 2021 to November 2022.Exposure: All principal endovascular aortic repairs, including redo surgery and complex repairs of the aortic arch and visceral aorta.Main Outcomes and Measures: Short-term and midterm survival, rates of secondary procedures, and conversion to open repair.Results: In total, 171 patients were included: 142 with Marfan syndrome, 17 with Loeys-Dietz syndrome, and 12 with vascular Ehlers-Danlos syndrome (vEDS). Median (IQR) age was 49.9 years (37.9-59.0), and 107 patients (62.6%) were male. One hundred fifty-two (88.9%) were treated for aortic dissections and 19 (11.1%) for degenerative aneurysms. One hundred thirty-six patients (79.5%) had undergone open aortic surgery before the index endovascular repair. In 74 patients (43.3%), arch and/or visceral branches were included in the repair. Primary technical success was achieved in 168 patients (98.2%), and 30-day mortality was 2.9% (5 patients). Survival at 1 and 5 years was 96.2% and 80.6% for Marfan syndrome, 93.8% and 85.2% for Loeys-Dietz syndrome, and 75.0% and 43.8% for vEDS, respectively. After a median (IQR) follow-up of 4.7 years (1.9-9.2), 91 patients (53.2%) had undergone secondary procedures, of which 14 (8.2%) were open conversions.Conclusions and Relevance: This study found that endovascular aortic interventions, including redo procedures and complex repairs of the aortic arch and visceral aorta, in patients with CTD had a high rate of early technical success, low perioperative mortality, and a midterm survival rate comparable with reports of open aortic surgery in patients with CTD. The rate of secondary procedures was high, but few patients required conversion to open repair. Improvements in devices and techniques, as well as ongoing follow-up, may result in endovascular treatment for patients with CTD being included in guideline recommendations.
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| 35. |
- Ottesen, Anett H., et al.
(författare)
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Secretoneurin Is an Endogenous Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor That Attenuates Ca2+-Dependent Arrhythmia
- 2019
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 1941-3149 .- 1941-3084. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Circulating SN (secretoneurin) concentrations are increased in patients with myocardial dysfunction and predict poor outcome. Because SN inhibits CaMKII delta (Ca2+/calmodulin-dependent protein kinase II delta) activity, we hypothesized that upregulation of SN in patients protects against cardiomyocyte mechanisms of arrhythmia. METHODS: Circulating levels of SN and other biomarkers were assessed in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT; n=8) and in resuscitated patients after ventricular arrhythmia-induced cardiac arrest (n=155). In vivo effects of SN were investigated in CPVT mice (RyR2 [ryanodine receptor 2]-R2474S) using adeno-associated virus-9-induced overexpression. Interactions between SN and CaMKII delta were mapped using pull-down experiments, mutagenesis, ELISA, and structural homology modeling. Ex vivo actions were tested in Langendorff hearts and effects on Ca2+ homeostasis examined by fluorescence (fluo-4) and patchclamp recordings in isolated cardiomyocytes. RESULTS: SN levels were elevated in patients with CPVT and following ventricular arrhythmia-induced cardiac arrest. In contrast to NT-proBNP (N-terminal proB- type natriuretic peptide) and hs-TnT (high-sensitivity troponin T), circulating SN levels declined after resuscitation, as the risk of a new arrhythmia waned. Myocardial pro-SN expression was also increased in CPVT mice, and further adeno-associated virus-9-induced overexpression of SN attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies mapped SN binding to the substrate binding site in the catalytic region of CaMKII delta. Accordingly, SN attenuated isoproterenol induced autophosphorylation of Thr287-CaMKII delta in Langendorff hearts and inhibited CaMKII delta-dependent RyR phosphorylation. In line with CaMKII delta and RyR inhibition, SN treatment decreased Ca2+ spark frequency and dimensions in cardiomyocytes during isoproterenol challenge, and reduced the incidence of Ca2+ waves, delayed afterdepolarizations, and spontaneous action potentials. SN treatment also lowered the incidence of early afterdepolarizations during isoproterenol; an effect paralleled by reduced magnitude of L-type Ca2+ current. CONCLUSIONS: SN production is upregulated in conditions with cardiomyocyte Ca2+ dysregulation and offers compensatory protection against cardiomyocyte mechanisms of arrhythmia, which may underlie its putative use as a biomarker in at-risk patients.
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| 36. |
- Sonesson, B, et al.
(författare)
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Outcome After Ruptured AAA Repair in Octo- and Nonagenarians in Sweden 1994-2014.
- 2017
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 53:5, s. 656-662
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To report the outcome after ruptured abdominal aortic aneurysm (rAAA) repair in octo- and nonagenarians from the Swedish Vascular Registry 1994-2014.MATERIAL AND METHODS: 2335 intact AAA (iAAA) and 1538 rAAA were identified in patients aged 80 years and older. Crude, long-term, and relative survival data were analysed using the Kaplan-Meier method. Crude survival was calculated including all deaths. Long-term survival was analysed excluding AAA repair related mortality, defined as death within 90 days of surgery. Relative survival was assessed by comparing the observed long-term survival after AAA repair with the expected survival of a Swedish population adjusted for age, gender, and operation year. Differences were compared using log-rank tests. The multivariate Cox model was used for adjusting for confounding factors between open repair (OR) and endovascular aneurysm repair (EVAR).RESULTS: Crude survival after rAAA repair was 30 days (55%), 90 days (50%), 1 year (45%), 5 years (26%), and 10 years (9%). Long-term survival was 1 year (90%), 5 years (53%), and 10 years (18%). When individuals with rAAA were categorized into males and females, crude and long-term survival showed no significant differences (p = .204 and p = .134). When rAAA patients were categorized into age groups (80-84 years, 85-89 years, 90+) crude survival diminished with increasing age, but long-term survival was not (p = .009 and p = .368). Compared with the general population, rAAA patients showed only a minor decrease in relative survival. Crude survival after rAAA was better for EVAR compared with OR (p = .007), hazard ratio 1.3 (95% CI 1.1-1.6, p < .012).CONCLUSIONS: There is a high (50%) peri-operative mortality after surgery for rAAA in octo- and nonagenarians, with no significant differences between the sexes and worse survival with increasing age. However, if a patient has survived the initial 90 days, long-term survival in this very old cohort is surprisingly good at more than 50% after 5 years, only slightly less than the general population.
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| 37. |
- Sorelius, Karl, et al.
(författare)
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The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting
- 2022
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Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 78, s. 112-122
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. Results: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P =.051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. Conclusion: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.
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| 38. |
- Starzmann, K., et al.
(författare)
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Validity must be discussed
- 2019
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Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis. - 0281-3432 .- 1502-7724. ; 37:3, s. 388-389
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 39. |
- Svee, Andreas, et al.
(författare)
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Survival and risk of breast cancer recurrence after breast reconstruction with deep inferior epigastric perforator flap
- 2018
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 105:11, s. 1446-1453
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women who undergo autologous breast reconstruction have been reported to have an increased risk of breast cancer recurrence compared with those who have mastectomy alone. It has been suggested that more extensive surgery possibly activates dormant micrometastases. The aim of this study was to evaluate whether delayed unilateral deep inferior epigastric perforator (DIEP) flap reconstruction after mastectomy increases the risk of breast cancer recurrence or affects mortality among women previously treated for breast cancer. Methods: This was a matched retrospective cohort study including women with a previous unilateral invasive breast cancer who received a delayed DIEP flap breast reconstruction and a control cohort of individually matched women with unilateral breast cancer who underwent mastectomy but no autologous breast reconstruction. Matching criteria comprised: year of diagnosis (+/–3 years), age at diagnosis (+/–5 years), type of cancer and demographic region. The primary endpoints were local recurrence or distant metastasis, and overall mortality was a secondary endpoint. Absolute risk of recurrent disease and mortality was analysed, and relative risks were estimated using Cox proportional hazards analysis. Results: There were 225 women in the DIEP cohort and 450 in the no-DIEP cohort. The median follow-up time was 125 months. There was no difference in absolute risk of recurrence between the cohorts. The hazard ratio for breast cancer recurrence in DIEP versus no-DIEP cohorts was 0·76 (95 per cent c.i. 0·47 to 1·21). Conclusion: There is no increased risk in breast cancer recurrence after delayed DIEP flap reconstruction compared with mastectomy alone.
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| 40. |
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| 41. |
- Wilson, L. F. L., et al.
(författare)
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The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:3314
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-d-glucuronosyl and N-acetyl-α-d-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)—each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3’s GT47 domain to transfer β-d-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism.
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| 42. |
- Winters, Z E, et al.
(författare)
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International validation of the European Organisation for Research and Treatment of Cancer QLQ-BRECON23 quality-of-life questionnaire for women undergoing breast reconstruction.
- 2018
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 105, s. 209-222
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim was to carry out phase 4 international field-testing of the European Organisation for Research and Treatment of Cancer (EORTC) breast reconstruction (BRECON) module. The primary objective was finalization of its scale structure. Secondary objectives were evaluation of its reliability, validity, responsiveness, acceptability and interpretability in patients with breast cancer undergoing mastectomy and reconstruction.METHODS: The EORTC module development guidelines were followed. Patients were recruited from 28 centres in seven countries. A prospective cohort completed the QLQ-BRECON15 before mastectomy and the QLQ-BRECON24 at 4-8 months after reconstruction. The cross-sectional cohort completed the QLQ-BRECON24 at 1-5 years after reconstruction, and repeated this 2-8 weeks later (test-retest reliability). All participants completed debriefing questionnaires.RESULTS: A total of 438 patients were recruited, 234 in the prospective cohort and 204 in the cross-sectional cohort. A total of 414 reconstructions were immediate, with a comparable number of implants (176) and donor-site flaps (166). Control groups comprised patients who underwent two-stage implant procedures (72, 75 per cent) or delayed reconstruction (24, 25 per cent). Psychometric scale validity was supported by moderate to high item-own scale and item-total correlations (over 0·5). Questionnaire validity was confirmed by good scale-to-sample targeting, and computable scale scores exceeding 50 per cent, except nipple cosmesis (over 40 per cent). In known-group comparisons, QLQ-BRECON24 scales and items differentiated between patient groups defined by clinical criteria, such as type and timing of reconstruction, postmastectomy radiotherapy and surgical complications, with moderate effect sizes. Prospectively, sexuality and surgical side-effects scales showed significant responsiveness over time (P < 0·001). Scale reliability was supported by high Cronbach's α coefficients (over 0·7) and test-retest (intraclass correlation more than 0·8). One item (finding a well fitting bra) was excluded based on high floor/ceiling effects, poor test-retest and weak correlations in factor analysis (below 0·3), thus generating the QLQ-BRECON23 questionnaire.CONCLUSION: The QLQ-BRECON23 is an internationally validated tool to be used alongside the EORTC QLQ-C30 (cancer) and QLQ-BR23 (breast cancer) questionnaires for evaluating quality of life and satisfaction after breast reconstruction.
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| 43. |
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| 44. |
- Yang, J, et al.
(författare)
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Guidelines and definitions for research on epithelial-mesenchymal transition
- 2020
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Ingår i: Nature reviews. Molecular cell biology. - : Springer Science and Business Media LLC. - 1471-0080 .- 1471-0072. ; 21:6, s. 341-352
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial–mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by ‘the EMT International Association’ (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.
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