| 1. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 7. |
- Tobias, Deirdre K, et al.
(author)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Research review (peer-reviewed)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 9. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 10. |
- Mantzouki, Evanthia, et al.
(author)
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Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins
- 2018
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In: Toxins. - : MDPI. - 2072-6651. ; 10:4
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Journal article (peer-reviewed)abstract
- Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
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| 11. |
- Adam, J., et al.
(author)
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Fumarate Hydratase Deletion in Pancreatic beta Cells Leads to Progressive Diabetes
- 2017
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:13, s. 3135-3148
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Journal article (peer-reviewed)abstract
- We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic beta cells (Fh1 beta KO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1 alpha or Nrf2. Progressive hyperglycemia in Fh1bKO mice led to dysregulated metabolism in b cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca2+](i) elevation, and GSIS. Fh1 loss resulted in elevated intracellular fumarate, promoting succination of critical cysteines in GAPDH, GMPR, and PARK 7/DJ-1 and cytoplasmic acidification. Intracellular fumarate levels were increased in islets exposed to high glucose and in islets from human donors with type 2 diabetes (T2D). The impaired GSIS in islets from diabetic Fh1bKO mice was ameliorated after culture under normoglycemic conditions. These studies highlight the role of FH and dysregulated mitochondrial metabolism in T2D.
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| 12. |
- Donis, Daphne, et al.
(author)
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Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
- 2021
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In: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 66:12, s. 4314-4333
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Journal article (peer-reviewed)abstract
- To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L-1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 degrees C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature.
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| 13. |
- Berglund, Erik, et al.
(author)
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Clinical Significance of Alloantibodies in Hand Transplantation : A Multicenter Study
- 2019
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In: Transplantation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0041-1337 .- 1534-6080. ; 103:10, s. 2173-2182
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Journal article (peer-reviewed)abstract
- Background. Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. Methods. We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. Results. Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. Conclusions. While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.
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| 14. |
- Connelly, Sean, V, et al.
(author)
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Strong isolation by distance and evidence of population microstructure reflect ongoing Plasmodium falciparum transmission in Zanzibar
- 2024
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 12
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Journal article (peer-reviewed)abstract
- Background: The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission. Methods: To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018. Results: Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes. Conclusions: Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors.
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| 15. |
- Ozkan, M., et al.
(author)
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Early-Middle Jurassic metamorphic and non-metamorphic supra-subduction zone ophiolite fragments in a Late Cretaceous ophiolitic melange (northern Turkey): implications for long-lived and supra-subduction zone ophiolite formation
- 2022
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In: International Journal of Earth Sciences. - : Springer Science and Business Media LLC. - 1437-3254 .- 1437-3262. ; 111, s. 2391-2408
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Journal article (peer-reviewed)abstract
- The Late Cretaceous accretionary complexes along the Izmir-Ankara-Erzincan (IAE) Neo-Tethyan suture zone in northern Turkey record the subduction-accretion processes of the oceanic lithosphere ranging in age from the Late Triassic to the Late Cretaceous. These accretionary complexes contain fragments of Early and Middle Jurassic metamorphic and non-metamorphic ophiolites. Here, we report new geochemical and geochronological data from the metamorphic and non-metamorphic ophiolitic rocks, which are observed in the Tekelidag melange (northern Sivas) of the IAE suture zone. Geochemical characteristics of these rocks point to formation in a subduction-related tectonic setting. Igneous zircons from meta-plagiogranite injected into the meta-ophiolitic rocks yielded zircon U-Pb age of 188 +/- 4 Ma (2 sigma, Early Jurassic), and those from a non-metamorphic plagiogranite crosscutting the non-metamorphic ophiolitic rocks gave an age value of 168 +/- 2 Ma (2 sigma, Middle Jurassic). The igneous crystallization age of the non-metamorphic plagiogranite is identical with the metamorphic age of meta-ophiolitic rocks, which has been dated as Middle Jurassic (166.7 +/- 2 Ma, 2 sigma) by the Ar-40-Ar-39 method. These age data indicate that (i) the supra-subduction zone ophiolite formation lasted about 20 Ma, (ii) the supra-subduction zone ophiolite and the meta-ophiolitic rocks formed simultaneously in the Middle Jurassic, and (iii) the meta-ophiolitic rocks are remnants of the metamorphosed equivalents of the Early Jurassic supra-subduction zone oceanic crust. The supra-subduction zone ophiolite formation probably occurred over an extended period of time in the Jurassic Neo-Tethys.
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| 16. |
- Gokasar, I., et al.
(author)
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MSND : Modified Standard Normal Deviate Incident Detection Algorithm for Connected Autonomous and Human-Driven Vehicles in Mixed Traffic
- 2022
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In: IEEE transactions on intelligent transportation systems (Print). - : Institute of Electrical and Electronics Engineers Inc.. - 1524-9050 .- 1558-0016. ; , s. 1-10
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Journal article (peer-reviewed)abstract
- Advances in IoT and IoV technology have made connected autonomous vehicles (CAVs) data sources. Using CAVs as data sources and in incident management algorithms can create faster, more reliable, and more effective algorithms. This paper proposes a modified standard normal deviation (MSND) incident detection algorithm that uses CAVs as data sources and considers multiple traffic parameters. MSND is utilized in conjunction with two other incident detection algorithms, Standard Normal Deviation (SNS) and California (CAL), in a method of incident management known as Variable Speed Limits (VSL). SUMO Traffic Simulation Software is used to evaluate the effectiveness of the proposed method. A 10.4-kilometer road network is developed. Numerous scenarios are simulated on this road network, with variables including traffic demand, autonomous vehicle penetration rate, incident location, incident length, and incident lane. On the effectiveness metrics of detection rate, false alarm rate, and mean time to detect, simulation results demonstrate that the proposed method outperforms the SND and California methods. In terms of detection rate, the MSND algorithm performs the best, with a 12.27% improvement over the SND algorithm and a 21.99% improvement over the California method. After integrating all incident detection algorithms with the VSL traffic management method and simulating each combination, it was determined that the MSND-VSL integration reduced average density in the critical region by 19.73 percent, followed by SND-VSL with a 13.94 percent reduction and CAL-VSL with a 9.9 percent reduction. IEEE
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| 17. |
- Guidi, H., et al.
(author)
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Autonomous maintenance of advanced process control : Application to an industrial depropanizer
- 2014
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In: Fuels and Petrochemicals Division 2014 - Core Programming Area at the 2014 AIChE Spring Meeting and 10th Global Congress on Process Safety. - : AIChE. - 9781634390736 ; , s. 923-932
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Conference paper (peer-reviewed)abstract
- Although Model Predictive Control (MPC) has been widely accepted as a main technology for Advanced Process Control (APC) due to its ability of operating the system closely to the constraints, proper maintenance of MPC systems is still a challenge. Based on this observation, this research aims to develop an automated support strategy for the autonomous maintenance of MPC. In this work, re-tuning and re-identification components of the automated support strategy are considered as corrective action to retain the performance of the system after a change in the plant dynamics causes performance degradation. An industrial FT-depropanizer is used to test the implementation of these components. Results successfully show that an automated unified framework approach to MPC maintenance can successfully be used in further securing the economic leverage of MPC in industry.
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| 18. |
- Karamavus, Y., et al.
(author)
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Design of a new optic probe for diffuse reflectance spectroscopy
- 2015
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Conference paper (peer-reviewed)abstract
- Diffuse reflectance spectroscopy is a non-invasive spectroscopic technique for studying the optical properties of a biological tissue and hence can be used to detect chromophore concentration from the skin tissue. Here, a novel optical probe is presented to utilize diffuse reflectance spectroscopy. The proposed device contains an optical head that is easier to manufacture, more compact and more affordable than the existing fiber probes. This optical head consists of 19 fiber cables. The outer 12 fiber cables are used to expose the skin surface with a white light produced by a LED. And the reflected light emerging from the various layers of the tissue is collected by the inner 7 fiber cables, which is coupled to a spectrometer.
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| 19. |
- Keilwagen, J., et al.
(author)
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Separating the wheat from the chaff - a strategy to utilize plant genetic resources from ex situ genebanks
- 2014
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4
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Journal article (peer-reviewed)abstract
- The need for higher yielding and better-adapted crop plants for feeding the world's rapidly growing population has raised the question of how to systematically utilize large genebank collections with their wide range of largely untouched genetic diversity. Phenotypic data that has been recorded for decades during various rounds of seed multiplication provides a rich source of information. Their usefulness has remained limited though, due to various biases induced by conservation management over time or changing environmental conditions. Here, we present a powerful procedure that permits an unbiased trait-based selection of plant samples based on such phenotypic data. Applying this technique to the wheat collection of one of the largest genebanks worldwide, we identified groups of plant samples displaying contrasting phenotypes for selected traits. As a proof of concept for our discovery pipeline, we resequenced the entire major but conserved flowering time locus Ppd-D1 in just a few such selected wheat samples - and nearly doubled the number of hitherto known alleles.
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