| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 3. |
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| 4. |
- Biancari, Fausto, et al.
(författare)
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Central versus Peripheral Postcardiotomy Veno-Arterial Extracorporeal Membrane Oxygenation : Systematic Review and Individual Patient Data Meta-Analysis
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:24
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Forskningsöversikt (refereegranskat)abstract
- Background: It is unclear whether peripheral arterial cannulation is superior to central arterial cannulation for postcardiotomy veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: A systematic review was conducted using PubMed, Scopus, and Google Scholar to identify studies on postcardiotomy VA-ECMO for the present individual patient data (IPD) meta-analysis. Analysis was performed according to the intention-to-treat principle. Results: The investigators of 10 studies agreed to participate in the present IPD meta-analysis. Overall, 1269 patients were included in the analysis. Crude rates of in-hospital mortality after central versus peripheral arterial cannulation for VA-ECMO were 70.7% vs. 63.7%, respectively (adjusted OR 1.38, 95% CI 1.08–1.75). Propensity score matching yielded 538 pairs of patients with balanced baseline characteristics and operative variables. Among these matched cohorts, central arterial cannulation VA-ECMO was associated with significantly higher in-hospital mortality compared to peripheral arterial cannulation VA-ECMO (64.5% vs. 70.8%, p = 0.027). These findings were confirmed by aggregate data meta-analysis, which showed that central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation (OR 1.35, 95% CI 1.04–1.76, I2 21%). Conclusions: Among patients requiring postcardiotomy VA-ECMO, central arterial cannulation was associated with an increased risk of in-hospital mortality compared to peripheral arterial cannulation. This increased risk is of limited magnitude, and further studies are needed to confirm the present findings and to identify the mechanisms underlying the potential beneficial effects of peripheral VA-ECMO.
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| 5. |
- Biancari, Fausto, et al.
(författare)
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Inter-institutional analysis of the outcome after postcardiotomy veno-arterial extracorporeal membrane oxygenation
- 2024
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Ingår i: International Journal of Artificial Organs. - 0391-3988 .- 1724-6040. ; 47:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Patients requiring postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) have a high risk of early mortality. In this analysis, we evaluated whether any interinstitutional difference exists in the results of postcardiotomy V-A-ECMO. Methods: Studies on postcardiotomy V-A-ECMO were identified through a systematic review for individual patient data (IPD) meta-analysis. Analysis of interinstitutional results was performed using direct standardization, estimation of observed/expected in-hospital mortality ratio and propensity score matching. Results: Systematic review of the literature yielded 31 studies. Data from 10 studies on 1269 patients treated at 25 hospitals were available for the present analysis. In-hospital mortality was 66.7%. The relative risk of in-hospital mortality was significantly higher in six hospitals. Observed versus expected in-hospital mortality ratio showed that four hospitals were outliers with significantly increased mortality rates, and one hospital had significantly lower in-hospital mortality rate. Participating hospitals were classified as underperforming and overperforming hospitals if their observed/expected in-hospital mortality was higher or lower than 1.0, respectively. Among 395 propensity score matched pairs, the overperforming hospitals had significantly lower in-hospital mortality (60.3% vs 71.4%, p = 0.001) than underperforming hospitals. Low annual volume of postcardiotomy V-A-ECMO tended to be predictive of poor outcome only when adjusted for patients’ risk profile. Conclusions: In-hospital mortality after postcardiotomy V-A-ECMO differed significantly between participating hospitals. These findings suggest that in many centers there is room for improvement of the results of postcardiotomy V-A-ECMO.
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| 6. |
- Birve, Anna, et al.
(författare)
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A novel SOD1 splice site mutation associated with familial ALS revealed by SOD activity analysis
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:21, s. 4201-4206
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Tidskriftsartikel (refereegranskat)abstract
- More than 145 mutations have been found in the gene CuZn-Superoxide dismutase (SOD1) in patients with amyotrophic lateral sclerosis (ALS). The vast majority are easily detected nucleotide mutations in the coding region. In a patient from a Swiss ALS family with half-normal erythrocyte SOD1 activity, exon flanking sequence analysis revealed a novel thymine to guanine mutation 7 bp upstream of exon 4 (c.240-7T>G). The results of splicing algorithm analyses were ambiguous, but five out of seven analysis tools suggested a potential novel splice site that would add six new base pairs to the mRNA. If translated, this mRNA would insert Ser and Ile between Glu78 and Arg79 in the SOD1 protein. In fibroblasts from the patient, the predicted mutant transcript and the mutant protein were both highly expressed, and despite the location of the insertion into the metal ion-binding loop IV, the SOD1 activity appeared high. In erythrocytes, which lack protein synthesis and are old compared with cultured fibroblasts, both SOD1 protein and enzymic activity was 50% of controls. Thus, the usage of the novel splice site is near 100%, and the mutant SOD1 shows the reduced stability typical of ALS-associated mutant SOD1s. The findings suggests that this novel intronic mutation is causing the disease and highlights the importance of wide exon-flanking sequencing and transcript analysis combined with erythrocyte SOD1 activity analysis in comprehensive search for SOD1 mutations in ALS. We find that there are potentially more SOD1 mutations than previously reported.
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| 7. |
- Borg, Markus, et al.
(författare)
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Adopting automated bug assignment in practice — a longitudinal case study at Ericsson
- 2024
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Ingår i: Empirical Software Engineering. - : Springer. - 1382-3256 .- 1573-7616. ; 29:5
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Tidskriftsartikel (refereegranskat)abstract
- [Context] The continuous inflow of bug reports is a considerable challenge in large development projects. Inspired by contemporary work on mining software repositories, we designed a prototype bug assignment solution based on machine learning in 2011-2016. The prototype evolved into an internal Ericsson product, TRR, in 2017-2018. TRR’s first bug assignment without human intervention happened in April 2019. [Objective] Our study evaluates the adoption of TRR within its industrial context at Ericsson, i.e., we provide lessons learned related to the productization of a research prototype within a company. Moreover, we investigate 1) how TRR performs in the field, 2) what value TRR provides to Ericsson, and 3) how TRR has influenced the ways of working. [Method] We conduct a preregistered industrial case study combining interviews with TRR stakeholders, minutes from sprint planning meetings, and bug-tracking data. The data analysis includes thematic analysis, descriptive statistics, and Bayesian causal analysis. [Results] TRR is now an incorporated part of the bug assignment process. Considering the abstraction levels of the telecommunications stack, high-level modules are more positive while low-level modules experienced some drawbacks. Most importantly, some bug reports directly reach low-level modules without first having passed through fundamental root-cause analysis steps at higher levels. On average, TRR automatically assigns 30% of the incoming bug reports with an accuracy of 75%. Auto-routed TRs are resolved around 21% faster within Ericsson, and TRR has saved highly seasoned engineers many hours of work. Indirect effects of adopting TRR include process improvements, process awareness, increased communication, and higher job satisfaction. [Conclusions] TRR has saved time at Ericsson, but the adoption of automated bug assignment was more intricate compared to similar endeavors reported from other companies. We primarily attribute the difference to the very large size of the organization and the complex products. Key facilitators in the successful adoption include a gradual introduction, product champions, and careful stakeholder analysis.
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| 8. |
- Borg, Markus, et al.
(författare)
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The More the Merrier: Leveraging on the Bug Inflow to Guide Software Maintenance
- 2015
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Ingår i: Tiny Transactions on Computer Science. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Issue management, a central part of software maintenance, requires much effort for complex software systems. The continuous inflow of issue reports makes it hard for developers to stay on top of the situation, and the threatening information overload makes activities such as duplicate management, Issue Assignment (IA), and Change Impact Analysis (CIA) tedious and error-prone. Still, most practitioners work with tools that act as little more than issue containers. Machine Learning encompasses approaches that identify patterns or make predictions based on empirical data. While humans have limited ability to work with big data, ML instead tends to improve the more training data that is available. Consequently, we argue that the challenge of information overload in issue management appears to be particularly suitable for ML-based tool support. While others have initially explored the area, we develop two ML-based tools, and evaluate them in proprietary software engineering contexts. We replicated [1] for five projects in two companies, and our automated IA obtains an accuracy matching the current manual processes. Thus, as our solution delivers instantaneous IA, an organization can potentially save considerable analysis effort. Moreover, for the most comprehensive of the five projects, we implemented automated CIA in the tool ImpRec [3]. We evaluated the tool in a longitudinal in situ study, i.e., deployment in two development teams in industry. Based on log analysis and complementary interviews using the QUPER model [2] for utility assessment, we conclude that ImpRec offered helpful support in the CIA task.
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| 9. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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