| 1. |
- Gaziano, Liam, et al.
(författare)
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Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19
- 2021
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Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 27:4
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19. Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.
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| 2. |
- Lossow, Stefan, et al.
(författare)
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A reassessment of the discrepancies in the annual variation of delta D-H2O in the tropical lower stratosphere between the MIPAS and ACE-FTS satellite data sets
- 2020
-
Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 13:1, s. 287-308
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Tidskriftsartikel (refereegranskat)abstract
- The annual variation of delta D in the tropical lower stratosphere is a critical indicator for the relative importance of different processes contributing to the transport of water vapour through the cold tropical tropopause region into the stratosphere. Distinct observational discrepancies of the delta D annual variation were visible in the works of Steinwagner et al. (2010) and Randel et al. (2012). Steinwagner et al. (2010) analysed MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) observations retrieved with the IMK/IAA (Institut fur Meteorologie und Klimaforschung in Karlsruhe, Germany, in collaboration with the Instituto de Astrofisica de Andalucia in Granada, Spain) processor, while Randel et al. (2012) focused on ACE-FTS (Atmospheric Chemistry Experiment Fourier Transform Spectrometer) observations. Here we reassess the discrepancies based on newer MIPAS (IMK/IAA) and ACE-FTS data sets, also showing for completeness results from SMR (Sub-Millimetre Radiometer) observations and a ECHAM/MESSy (European Centre for Medium-Range Weather Forecasts Hamburg and Modular Earth Sub-model System) Atmospheric Chemistry (EMAC) simulation (Eichinger et al., 2015b). Similar to the old analyses, the MIPAS data set yields a pronounced annual variation (maximum about 75 parts per thousand), while that derived from the ACE-FTS data set is rather weak (maximum about 25 parts per thousand). While all data sets exhibit the phase progression typical for the tape recorder, the annual maximum in the ACE-FTS data set precedes that in the MIPAS data set by 2 to 3 months. We critically consider several possible reasons for the observed discrepancies, focusing primarily on the MIPAS data set. We show that the delta D annual variation in the MIPAS data up to an altitude of 40 hPa is substantially impacted by a start altitude effect, i.e. dependency between the lowermost altitude where MIPAS retrievals are possible and retrieved data at higher altitudes. In itself this effect does not explain the differences with the ACE-FTS data. In addition, there is a mismatch in the vertical resolution of the MIPAS HDO and H2O data (being consistently better for HDO), which actually results in an artificial tape-recorder-like signal in delta D. Considering these MIPAS characteristics largely removes any discrepancies between the MIPAS and ACE-FTS data sets and shows that the MIPAS data are consistent with a delta D tape recorder signal with an amplitude of about 25 parts per thousand in the lowermost stratosphere.
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| 3. |
- Högberg, Cecilia, et al.
(författare)
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Diagnosing colorectal cancer in primary care : cohort study in Sweden of qualitative faecal immunochemical tests, haemoglobin levels, and platelet counts
- 2020
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Ingår i: British Journal of General Practice. - London : Royal College of General Practitioners. - 0960-1643 .- 1478-5242. ; 70:701, s. E843-E851
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Tidskriftsartikel (refereegranskat)abstract
- Background Colorectal cancer (CRC) diagnostics are challenging in primary care and reliable diagnostic aids are desired. Qualitative faecal immunochemical tests (FITs) have been used for suspected CRC in Sweden since the mid-2000s, but evidence regarding their effectiveness is scarce. Anaemia and thrombocytosis are both associated with CRC. Aim To evaluate the usefulness of qualitative FITs requested for symptomatic patients in primary care, atone and combined with findings of anaemia and thrombocytosis, in the diagnosis of CRC. Design and setting A population-based cohort study using electronic health records and data from the Swedish Cancer Register, covering five Swedish regions. Method Patients aged >= 18 years in the five regions who had provided FITs requested by primary care practitioners from 1 January 2015 to 31 December 2015 were identified. FIT and blood-count data were registered and all CRC diagnoses made within 2 years were retrieved. Diagnostic measurements were calculated. Results In total, 15 789 patients provided FITs (four different brands); of these patients, 304 were later diagnosed with CRC. Haemoglobin levels were available for 13 863 patients, and platelet counts for 10 973 patients. Calculated for the different FIT brands only, the sensitivities for CRC were 81.6%-100%; specificities 65.7%-79.5%: positive predictive values 4.7%-8.1%; and negative predictive values 99.5%-100%. Calculated for the finding of either a positive FIT or anaemia, the sensitivities increased to 88.9-100%. Adding thrombocytosis did not further increase the diagnostic performance. Conclusion Qualitative FITs requested in primary care seem to be useful as rule in tests for referral when CRC is suspected. A negative FIT and no anaemia indicate a low risk of CRC.
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| 4. |
- Högberg, Cecilia, et al.
(författare)
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Qualitative faecal immunochemical tests (FITs) for diagnosing colorectal cancer in patients with histories of rectal bleeding in primary care : a cohort study
- 2020
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 35, s. 2035-2040
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Tidskriftsartikel (refereegranskat)abstract
- Background Rectal bleeding is considered an alarm symptom for colorectal cancer (CRC) but it is common and mostly caused by benign conditions. Qualitative faecal immunochemical tests (FITs) for occult blood have been used as diagnostic aids for many years in Sweden when CRC is suspected. The study aimed to evaluate the usefulness of FITs requested by primary care physicians for patients with and without histories of rectal bleeding, in the diagnosis of CRC. Methods Results of all FITs requested in primary care for symptomatic patients in the orebro region during 2015 were retrieved. Data on each patient's history of rectal bleeding was gathered from electronic health records. Patients diagnosed with CRC within 2 years were identified from the Swedish Cancer Register. The analysis focused on three-sample FITs, the customary FIT in Sweden. Results A total of 4232 patients provided three-sample FITs. Information about the presence/absence of rectal bleeding was available for 2027 patients, of which 59 were diagnosed with CRC. For 606 patients with the presence of rectal bleeding, the FIT showed sensitivity 96.2%, specificity 60.2%, positive predictive value 9.8% (95% CI 6.1-13.4) and negative predictive value 99.7% (95% CI 99.2-100) for CRC. For 1421 patients without rectal bleeding, the corresponding figures were 100%, 73.6%, 8.3% (95% CI 5.6-10.9) and 100% (95% CI 99.6-100). Conclusion The diagnostic performance of a qualitative three-sample FIT provided by symptomatic patients in primary care was similar for those with and without a history of rectal bleeding. FITs seem useful for prioritising patients also with rectal bleeding for further investigation.
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| 5. |
- Högberg, Cecilia, et al.
(författare)
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Use of faecal immunochemical tests common in patients with suspected colorectal cancer but unrelated to travel distance to secondary care : a population-based study from Swedish primary care
- 2022
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Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis Group. - 0281-3432 .- 1502-7724. ; 40:4, s. 459-465
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Tidskriftsartikel (refereegranskat)abstract
- Background Evidence is increasing for the use of faecal immunochemical tests (FITs) for occult blood as diagnostic tools when colorectal cancer can be suspected. FITs have been used for this purpose in Swedish primary care since around 2005 despite absence of supporting guidelines. To our knowledge, the extent of this use has not been studied. Objective To investigate the use of FITs as diagnostic tools, and if the use was related to patient age, sex and travel time from primary care to diagnostic facilities in secondary care. Design Population-based retrospective study using data from electronic health records. Setting and subjects Patients >= 18 years that provided FITs in primary care in five Swedish health care regions during 2015. Driving times from their primary care centres to secondary care were calculated. Main outcome measures The proportion of patients that provided FITs was calculated for each region, different age intervals and grouped driving times. Results 18,913 patients provided FITs. The proportion of listed patients in the five regions that provided FITs increased with age: 0.86-1.2% for ages <65 years, 3.6-4.1% for ages 65-79 years and 3.8-6.1% for ages >= 80 years. Differences between the regions were small. There was no overall correlation between the proportion of patients that provided FITs and driving time to secondary care. Conclusion FITs were used extensively in Swedish primary care with a higher use in older age groups. There was no tendency towards a higher use of FITs at primary care centres with longer driving times to secondary care.
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| 6. |
- Lind, Andreas, 1985-, et al.
(författare)
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Multi-Objective Optimization of an Assembly Layout Using Nature-Inspired Algorithms and a Digital Human Modeling Tool
- 2024
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Ingår i: IISE Transactions on Occupational Ergonomics and Human Factors. - : Taylor & Francis Group. - 2472-5838 .- 2472-5846.
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Tidskriftsartikel (refereegranskat)abstract
- OCCUPATIONAL APPLICATIONSIn the context of Industry 5.0, our study advances manufacturing factory layout planning by integrating multi-objective optimization with nature-inspired algorithms and a digital human modeling tool. This approach aims to overcome the limitations of traditional planning methods, which often rely on engineers’ expertise and inputs from various functions in a company, leading to slow processes and risk of human errors. By focusing the multi-objective optimization on three primary targets, our methodology promotes objective and efficient layout planning, simultaneously considering worker well-being and system performance efficiency. Illustrated through a pedal car assembly station layout case, we demonstrate how layout planning can transition into a transparent, cross-disciplinary, and automated activity. This methodology provides multi-objective decision support, showcasing a significant step forward in manufacturing factory layout design practices.TECHNICAL ABSTRACTRationale: Integrating multi-objective optimization in manufacturing layout planning addresses simultaneous considerations of productivity, worker well-being, and space efficiency, moving beyond traditional, expert-reliant methods that often overlook critical design aspects. Leveraging nature-inspired algorithms and a digital human modeling tool, this study advances a holistic, automated design process in line with Industry 5.0. Purpose: This research demonstrates an innovative approach to manufacturing layout optimization that simultaneously considers worker well-being and system performance. Utilizing the Non-dominated Sorting Genetic Algorithm II (NSGA-II) and Particle Swarm Optimization (PSO) alongside a Digital Human Modeling (DHM) tool, the study proposes layouts that equally prioritize ergonomic factors, productivity, and area utilization. Methods: Through a pedal car assembly station case, the study illustrates the transition of layout planning into a transparent, cross-disciplinary, and automated process. This method offers objective decision support, balancing diverse objectives concurrently. Results: The optimization results obtained from the NSGA-II and PSO algorithms represent feasible non-dominated solutions of layout proposals, with the NSGA-II algorithm finding a solution superior in all objectives compared to the expert engineer-designed start solution for the layout. This demonstrates the presented method’s capacity to refine layout planning practices significantly. Conclusions: The study validates the effectiveness of combining multi-objective optimization with digital human modeling in manufacturing layout planning, aligning with Industry 5.0’s emphasis on human-centric processes. It proves that operational efficiency and worker well-being can be simultaneously considered and presents future potential manufacturing design advancements. This approach underscores the necessity of multi-objective consideration for optimal layout achievement, marking a progressive step in meeting modern manufacturing’s complex demands.
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| 7. |
- Lossow, Stefan, 1977, et al.
(författare)
-
A reassessment of the discrepancies in the annual variation of δD-H2O in the tropical lower stratosphere between the MIPAS and ACE-FTS satellite data sets
- 2020
-
Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 13:1, s. 287-308
-
Tidskriftsartikel (refereegranskat)abstract
- The annual variation of δD in the tropical lower stratosphere is a critical indicator for the relative importance of different processes contributing to the transport of water vapour through the cold tropical tropopause region into the stratosphere. Distinct observational discrepancies of the δD annual variation were visible in the works of Steinwagner et al. (2010) and Randel et al. (2012). Steinwagner et al. (2010) analysed MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) observations retrieved with the IMK/IAA (Institut für Meteorologie und Klimaforschung in Karlsruhe, Germany, in collaboration with the Instituto de Astrofísica de Andalucía in Granada, Spain) processor, while Randel et al. (2012) focused on ACE-FTS (Atmospheric Chemistry Experiment Fourier Transform Spectrometer) observations. Here we reassess the discrepancies based on newer MIPAS (IMK/IAA) and ACE-FTS data sets, also showing for completeness results from SMR (Sub-Millimetre Radiometer) observations and a ECHAM/MESSy (European Centre for Medium-Range Weather Forecasts Hamburg and Modular Earth Submodel System) Atmospheric Chemistry (EMAC) simulation (Eichinger et al., 2015b). Similar to the old analyses, the MIPAS data set yields a pronounced annual variation (maximum about 75 ‰), while that derived from the ACE-FTS data set is rather weak (maximum about 25 ‰). While all data sets exhibit the phase progression typical for the tape recorder, the annual maximum in the ACE-FTS data set precedes that in the MIPAS data set by 2 to 3 months. We critically consider several possible reasons for the observed discrepancies, focusing primarily on the MIPAS data set. We show that the δD annual variation in the MIPAS data up to an altitude of 40 hPa is substantially impacted by a “start altitude effect”, i.e. dependency between the lowermost altitude where MIPAS retrievals are possible and retrieved data at higher altitudes. In itself this effect does not explain the differences with the ACE-FTS data. In addition, there is a mismatch in the vertical resolution of the MIPAS HDO and H2O data (being consistently better for HDO), which actually results in an artificial tape-recorder-like signal in δD. Considering these MIPAS characteristics largely removes any discrepancies between the MIPAS and ACE-FTS data sets and shows that the MIPAS data are consistent with a δD tape recorder signal with an amplitude of about 25 ‰ in the lowermost stratosphere.
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