| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 4. |
- Abazov, V. M., et al.
(författare)
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The upgraded DO detector
- 2006
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
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Tidskriftsartikel (refereegranskat)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
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| 5. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 6. |
- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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| 7. |
- Kousathanas, A, et al.
(författare)
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Whole-genome sequencing reveals host factors underlying critical COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 607:7917, s. 97-
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Tidskriftsartikel (refereegranskat)abstract
- Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
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| 8. |
- Thomas, B., et al.
(författare)
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Global Cardiovascular and Renal Outcomes of Reduced GFR
- 2017
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 28:7, s. 2167-2179
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Tidskriftsartikel (refereegranskat)abstract
- The burden of premature death and health loss from ESRD is well described. Less is known regarding the burden of cardiovascular disease attributable to reduced GFR. We estimated the prevalence of reduced GFR categories 3, 4, and 5 (not on RRT) for 188 countries at six time points from 1990 to 2013. Relative risks of cardiovascular outcomes by three categories of reduced GFR were calculated by pooled random effects meta-analysis. Results are presented as deaths for outcomes of cardiovascular disease and ESRD and as disability-adjusted life years for outcomes of cardiovascular disease, GFR categories 3, 4, and 5, and ESRD. In 2013, reduced GFR was associated with 4% of deaths worldwide, or 2.2 million deaths (95% uncertainty interval [95% UI], 2.0 to 2.4 million). More than half of these attributable deaths were cardiovascular deaths (1.2 million; 95% UI, 1.1 to 1.4 million), whereas 0.96 million (95% UI, 0.81 to 1.0 million) were ESRD-related deaths. Compared with metabolic risk factors, reduced GFR ranked below high systolic BP, high body mass index, and high fasting plasma glucose, and similarly with high total cholesterol as a risk factor for disability-adjusted life years in both developed and developing world regions. In conclusion, by 2013, cardiovascular deaths attributed to reduced GFR outnumbered ESRD deaths throughout the world. Studies are needed to evaluate the benefit of early detection of CKD and treatment to decrease these deaths.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Baldi, R. D., et al.
(författare)
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LeMMINGs - I. The eMERLIN legacy survey of nearby galaxies. 1.5-GHz parsec-scale radio structures and cores
- 2018
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 476:3, s. 3478-3522
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Tidskriftsartikel (refereegranskat)abstract
- We present the first data release of high-resolution (≤0.2 arcsec) 1.5-GHz radio images of 103 nearby galaxies from the Palomar sample, observed with the eMERLIN array, as part of the LeMMINGs survey. This sample includes galaxies which are active (low-ionization nuclear emission-line regions [LINER] and Seyfert) and quiescent (H II galaxies and absorption line galaxies, ALGs), which are reclassified based upon revised emission-line diagrams.We detect radio emission ≳0.2 mJy for 47/103 galaxies (22/34 for LINERS, 4/4 for Seyferts, 16/51 for HII galaxies, and 5/14 for ALGs) with radio sizes typically of ≲100 pc. We identify the radio core position within the radio structures for 41 sources. Half of the sample shows jetted morphologies. The remaining half shows single radio cores or complex morphologies. LINERs show radio structures more core-brightened than Seyferts. Radio luminosities of the sample range from 1032to 1040erg s-1: LINERs and HII galaxies show the highest and lowest radio powers, respectively, while ALGs and Seyferts have intermediate luminosities. We find that radio core luminosities correlate with black hole (BH) mass down to ~107M⊙, but a break emerges at lower masses. Using [OIII] line luminosity as a proxy for the accretion luminosity, active nuclei and jetted HII galaxies follow an optical Fundamental Plane of BH activity, suggesting a common disc-jet relationship. In conclusion, LINER nuclei are the scaled-down version of FR I radio galaxies; Seyferts show less collimated jets; HII galaxies may host weak active BHs and/or nuclear star-forming cores; and recurrent BH activity may account for ALG properties.
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| 14. |
- Baldi, R. D., et al.
(författare)
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LeMMINGs - II. The e-MERLIN legacy survey of nearby galaxies. The deepest radio view of the Palomar sample on parsec scale
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 500:4, s. 4749-4767
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Tidskriftsartikel (refereegranskat)abstract
- We present the second data release of high-resolution (≤0.2 arcsec) 1.5-GHz radio images of 177 nearby galaxies from the Palomar sample, observed with the e-MERLIN array, as part of the Legacy e-MERLIN Multi-band Imaging of Nearby Galaxies Sample (LeMMINGs) survey. Together with the 103 targets of the first LeMMINGs data release, this represents a complete sample of 280 local active (LINER and Seyfert) and inactive galaxies (H ii galaxies and absorption line galaxies, ALG). This large program is the deepest radio survey of the local Universe, ≳1017.6 W Hz-1, regardless of the host and nuclear type: we detect radio emission ≳0.25 mJy beam-1 for 125/280 galaxies (44.6 per cent) with sizes of typically ≲100 pc. Of those 125, 106 targets show a core which coincides within 1.2 arcsec with the optical nucleus. Although we observed mostly cores, around one third of the detected galaxies features jetted morphologies. The detected radio core luminosities of the sample range between ∼1034 and 1040 erg s-1. LINERs and Seyferts are the most luminous sources, whereas H ii galaxies are the least. LINERs show FR I-like core-brightened radio structures while Seyferts reveal the highest fraction of symmetric morphologies. The majority of H ii galaxies have single radio core or complex extended structures, which probably conceal a nuclear starburst and/or a weak active nucleus (seven of them show clear jets). ALGs, which are typically found in evolved ellipticals, although the least numerous, exhibit on average the most luminous radio structures, similar to LINERs.
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| 15. |
- Baldi, R. D., et al.
(författare)
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LeMMINGs III. The e-MERLIN legacy survey of the Palomar sample: Exploring the origin of nuclear radio emission in active and inactive galaxies through the [O iii] - Radio connection
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 508:2, s. 2019-2038
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Tidskriftsartikel (refereegranskat)abstract
- What determines the nuclear radio emission in local galaxies? To address this question, we combine optical [O iii] line emission, robust black hole (BH) mass estimates, and high-resolution e-MERLIN 1.5-GHz data, from the LeMMINGs survey, of a statistically complete sample of 280 nearby optically active (LINER and Seyfert) and inactive [H ii and absorption line galaxies (ALGs)] galaxies. Using [O iii] luminosity (L[O III]) as a proxy for the accretion power, local galaxies follow distinct sequences in the optical-radio planes of BH activity, which suggest different origins of the nuclear radio emission for the optical classes. The 1.5-GHz radio luminosity of their parsec-scale cores (Lcore) is found to scale with BH mass (MBH) and [O iii] luminosity. Below MBH ∼106.5 M⊙, stellar processes from non-jetted H ii galaxies dominate with Lcore ∝ MBH0.61 ± 0.33 and Lcore ∝ L[O III]0.79 ± 0.30. Above MBH ∼106.5 M⊙, accretion-driven processes dominate with Lcore ∝ MBH1.5-1.65 and Lcore ∝ L[O III]0.99-1.31 for active galaxies: radio-quiet/loud LINERs, Seyferts, and jetted H ii galaxies always display (although low) signatures of radio-emitting BH activity, with L1.5 GHz ≳ 1019.8 W Hz-1 and MBH ≳ 107 M⊙, on a broad range of Eddington-scaled accretion rates (m). Radio-quiet and radio-loud LINERs are powered by low-m discs launching sub-relativistic and relativistic jets, respectively. Low-power slow jets and disc/corona winds from moderately high to high-m discs account for the compact and edge-brightened jets of Seyferts, respectively. Jetted H ii galaxies may host weakly active BHs. Fuel-starved BHs and recurrent activity account for ALG properties. In conclusion, specific accretion-ejection states of active BHs determine the radio production and the optical classification of local active galaxies.
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| 16. |
- Rohracher, A., et al.
(författare)
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Perampanel in routine clinical use across Europe: Pooled, multicenter, observational data
- 2018
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Ingår i: Epilepsia. - : Wiley. - 0013-9580. ; 59:9, s. 1727-1739
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Tidskriftsartikel (refereegranskat)abstract
- Objective To pool observational data on the routine use of perampanel to obtain information on real‐world outcomes and data in populations typically underrepresented in clinical trials. Methods Individual‐level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1‐year retention rate, 1‐year seizure freedom rate (duration ≥6 months), and incidence of treatment‐emergent adverse events (TEAEs). In addition, relationships were explored with logistic regression analyses. Results The full analysis set comprised 2396 people: 95% had focal seizures; median epilepsy duration was 27 years; median number of concomitant antiepileptic drugs (AEDs) was 2; and median prior AEDs was 6. One‐year retention rate was 48% (1117/2332; 95% confidence interval [CI] 46‐50%), and 1‐year seizure‐free rate (≥6‐month duration) was 9.2% (74/803; 95% CI 7‐11%). Median treatment duration was 11.3 months (1832 patient‐years); median dose was 8 mg. In 388 individuals with available data at 3, 6, and 12 months, responder rates were 42%, 46%, and 39%, respectively. During the first year, TEAEs were reported in 68% of participants (1317/1497; 95% CI 66‐70%). Logistic regression found higher age at perampanel initiation was associated with higher seizure‐free rate, and higher number of prior AEDs with lower seizure‐free rate and lower rates of somatic TEAEs. In 135 individuals aged ≥65 years, 1‐year retention rate was 48% and seizure‐free rate was 28%. Significance Across a large, treatment‐resistant population, add‐on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure‐free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel.
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| 17. |
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| 18. |
- Shankar, K. V., et al.
(författare)
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Investigation of SiC particle size variation on the tribological properties of Cu-6Sn-SiC composite
- 2020
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Ingår i: Archives of Foundry Engineering. - 1897-3310 .- 2299-2944. ; 20:4, s. 133-138
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Tidskriftsartikel (refereegranskat)abstract
- Copper have always been an important material and incorporation of elements into copper for property enhancement. Bronze is a relevant cuprous alloy which is important for many industrial and automotive applications like bearings and machineries. The present research is directed towards the fabrication and tribological analysis of regular bronze (Cu-6Sn) and metal matrix composites reinforced with varying particle sized SiC ceramic reinforcement (30, 35 and 40 µm). The developed specimens were subjected to wear analysis according to ASTM standards, to identify the tribological properties utilizing a pin on disk tribometer. It was noted that the wear rates of developed MMC's phenomenally decremented with an increase in size of SiC particle reinforcement. Also, the test parameters were influential in altering the wear rates to notable margins. The standard scanning electron microscopy techniques aided in identifying the influence of adhesive wear on the specimen surface.
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| 19. |
- Shankar, K. V., et al.
(författare)
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Solutionising Temperature Influence on the Morphological and Mechanical Characteristics of Al–Si–Mg–Ni Hypoeutectic Alloys
- 2021
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Ingår i: Journal of The Institution of Engineers (India): Series D. - : Springer Nature. - 2250-2122 .- 2250-2130. ; 102:1, s. 131-148
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Tidskriftsartikel (refereegranskat)abstract
- The current work is focused to ascertain the impact on the mechanical and morphological characteristics of hypoeutectic alloy Al–Ni with a range of solution treatment temperatures. Al, Ni, Si, and Mg of necessary weight percentages were melted in a crucible (make–clay graphite) and were cast. The cast alloys were then solutionised for 8 h from 450 to 550 °C, quenched and was aged for 12 h at 170 °C. The fractography, intermediate phase and the elementary composition of alloy was determined. It was observed from the investigation that a rise in solutionising temperature caused grain refinement in the developed hypoeutectic alloys. A surge in the value of hardness was observed with respect to the rise in solutionising temperature. It was also noticed from the analysis that the value of tensile strength, yield strength, ductility and impact resistance of the hypoeutectic alloys enhanced with temperature rise from 480 to 510 °C and then declined from 510 to 550 °C.
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| 20. |
- Williams, D. R.A., et al.
(författare)
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LeMMINGs - IV. The X-ray properties of a statistically complete sample of the nuclei in active and inactive galaxies from the Palomar sample
- 2022
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 510:4, s. 4909-4928
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Tidskriftsartikel (refereegranskat)abstract
- All 280 of the statistically complete Palomar sample of nearby ( < 120 Mpc) galaxies δ> 20 ◦have been observed at 1.5 GHz as part of the LeMMINGs e -MERLIN le gac y surv e y. Here, we present Chandr a X-ray observations of the nuclei of 213 of these galaxies, including a statistically complete sub-set of 113 galaxies in the declination range 40 ◦<δ< 65 ◦. We observed galaxies of all optical spectral types, including 'active' galaxies [e.g. low-ionization nuclear emission line regions (LINERs) and Seyferts] and 'inactive' galaxies like H II galaxies and absorption line galaxies (ALG). The X-ray flux limit of our surv e y is 1.65 ×10 -14 erg s -1 cm -2 (0.3 -10 keV). We detect X-ray emission coincident within 2 arcsec of the nucleus in 150/213 galaxies, including 13/14 Seyferts, 68/77 LINERs, 13/22 ALGs and 56/100 H II galaxies, but cannot completely rule out contamination from non-AGN processes in sources with nuclear luminosities ≲ 10 39 erg s -1 . We construct an X-ray Luminosity function (XLF) and find that the local galaxy XLF, when including all active galactic nucleus (AGN) types, can be represented as a single power law of slope -0.54 ±0.06. The Eddington ratio of the Seyferts is usually 2 -4 decades higher than that of the LINERs, ALGs, and H II galaxies, which are mostly detected with Eddington ratios ≲ 10 -3 . Using [ O III ] line measurements and black hole masses from the literature, we show that LINERs, H II galaxies and ALGs follow similar correlations to low luminosities, suggesting that some 'inactive' galaxies may harbour AGN.
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| 21. |
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| 22. |
- Shankar, Suma P., et al.
(författare)
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A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder
- 2022
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Ingår i: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 24:7, s. 1567-1582
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs). Methods: Molecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) was created for a DPH5 p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate–ribosylation assays in DPH5-knockout human and yeast cells and in silico modeling were performed for the identified DPH5 potential pathogenic variants. Results: DPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate–ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2. Conclusion: We provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.
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| 23. |
- Cellini, Andrea, 1991, et al.
(författare)
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Directed ultrafast conformational changes accompany electron transfer in a photolyase as resolved by serial crystallography.
- 2024
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Ingår i: Nature chemistry. - : Springer Nature. - 1755-4349 .- 1755-4330.
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Tidskriftsartikel (refereegranskat)abstract
- Charge-transfer reactions in proteins are important for life, such as in photolyases which repair DNA, but the role of structural dynamics remains unclear. Here, using femtosecond X-ray crystallography, we report the structural changes that take place while electrons transfer along a chain of four conserved tryptophans in the Drosophila melanogaster (6-4) photolyase. At femto- and picosecond delays, photoreduction of the flavin by the first tryptophan causes directed structural responses at a key asparagine, at a conserved salt bridge, and by rearrangements of nearby water molecules. We detect charge-induced structural changes close to the second tryptophan from 1 ps to 20 ps, identifying a nearby methionine as an active participant in the redox chain, and from 20 ps around the fourth tryptophan. The photolyase undergoes highly directed and carefully timed adaptations of its structure. This questions the validity of the linear solvent response approximation in Marcus theory and indicates that evolution has optimized fast protein fluctuations for optimal charge transfer.
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| 24. |
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| 25. |
- Coresh, Josef, et al.
(författare)
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Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality
- 2014
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:24, s. 2518-2531
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event.OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
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| 26. |
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| 27. |
- Eby, F. J., et al.
(författare)
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Influence of Solutionising Time on the Dendrite Morphology and Mechanical Behaviour of Al-Si-Mg-Ni Hypoeutectic Alloy
- 2021
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Ingår i: Silicon. - : Springer Nature. - 1876-990X .- 1876-9918.
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Tidskriftsartikel (refereegranskat)abstract
- The existing work deals with the development of Al-Si-Mg-Ni hypoeutectic alloys and to investigate the impact of solutionising time on their morphology and how these alloys behave mechanically. Al, Si, Mg, Ni of required weight percentages were melted into a clay graphite crucible and the mixture was poured into a permanent mould from which cast rods of ø32 mm ×156 mm in length were obtained. The cast rods were solutionised at 538 °C for 2, 4, 6, 8 and 10 h, respectively. Further, the alloys were then quenched into 30 °C water and subsequently aged at 155 °C for 12 h. It is perceived from the investigation that, as the solutionising time increases, a refinement in the grain of the developed alloy occurs and the hardness and tensile properties were seen increasing. Moreover, ductility was found to be low for the alloy solutionised at 10 h as compared to the LM25 alloy. The scanning electron images of the fractured surface revealed that the increase of solutionising time from 2 to 10 h led to a much smaller extent of the observance of dimples on the fractograph. Furthermore, the fractured surface of the alloy solutionised for 10 h depicted the presence of micro-voids, which confirms the ceasing of ductile behaviour because of longer solutionising time.
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| 32. |
- Proletov, Ian, et al.
(författare)
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Primary and secondary glomerulonephritides 1.
- 2014
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
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Tidskriftsartikel (refereegranskat)
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| 33. |
- Puglisi, A., et al.
(författare)
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KURVS: the outer rotation curve shapes and dark matter fractions of z ∼1.5 star-forming galaxies
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 524:2, s. 2814-2835
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Tidskriftsartikel (refereegranskat)abstract
- We present first results from the KMOS Ultra-deep Rotation Velocity Survey (KURVS), aimed at studying the outer rotation curves shape and dark matter content of 22 star-forming galaxies at z ∼1.5. These galaxies represent 'typical' star-forming discs at z ∼1.5, being located within the star-forming main sequence and stellar mass-size relation with stellar masses 9.5 ≤ log(M*/M⊙) ≤ 11.5. We use the spatially resolved H α emission to extract individual rotation curves out to 4 times the effective radius, on average, or ∼10-15 kpc. Most rotation curves are flat or rising between three and six disc scale radii. Only three objects with dispersion-dominated dynamics (vrot/σ0 ∼0.2) have declining outer rotation curves at more than 5σ significance. After accounting for seeing and pressure support, the nine rotation-dominated discs with vrot/σ0 ≥ 1.5 have average dark matter fractions of at the effective radius, similar to local discs. Together with previous observations of star-forming galaxies at cosmic noon, our measurements suggest a trend of declining dark matter fraction with increasing stellar mass and stellar mass surface density at the effective radius. Measurements of simulated EAGLE galaxies are in quantitative agreement with observations up to log, and overpredict the dark matter fraction of galaxies with higher mass surface densities by a factor of ∼3. We conclude that the dynamics of typical rotationally-supported discs at z ∼1.5 is dominated by dark matter from effective radius scales, in broad agreement with cosmological models. The tension with observations at high stellar mass surface density suggests that the prescriptions for baryonic processes occurring in the most massive galaxies (such as bulge growth and quenching) need to be reassessed.
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| 34. |
- Shankar, A., et al.
(författare)
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Estimation of viscosity for blast furnace type slags
- 2007
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Ingår i: Ironmaking & steelmaking. - : Informa UK Limited. - 0301-9233 .- 1743-2812. ; 34:6, s. 477-481
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Tidskriftsartikel (refereegranskat)abstract
- A viscosity model based on a new definition of basicity has been proposed for blast furnace type slags. Conceptually, this definition of basicity is close to Bell's definition of basicity as used for modelling of sulphide capacity of blast furnace type slags. The model developed in the present work is applicable for wide range of alumina, magnesia and titania containing blast furnace slags, while most of the models available in the literature are mainly applicable for a limited range of slag composition. Viscosity estimation by this model is close to the experimental value for all types of blast furnace slags. This model is based on the chemical composition of slag and is applicable for slags above liquidus temperature.
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| 36. |
- Smith, Emily R, et al.
(författare)
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Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality : a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries.
- 2017
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Ingår i: The Lancet Global Health. - 2214-109X. ; 5:11, s. e1090-e1100
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Micronutrient deficiencies are common among women in low-income and middle-income countries. Data from randomised trials suggest that maternal multiple micronutrient supplementation decreases the risk of low birthweight and potentially improves other infant health outcomes. However, heterogeneity across studies suggests influence from effect modifiers. We aimed to identify individual-level modifiers of the effect of multiple micronutrient supplements on stillbirth, birth outcomes, and infant mortality in low-income and middle-income countries.METHODS: This two-stage meta-analysis of individual patient included data from 17 randomised controlled trials done in 14 low-income and middle-income countries, which compared multiple micronutrient supplements containing iron-folic acid versus iron-folic acid alone in 112 953 pregnant women. We generated study-specific estimates and pooled subgroup estimates using fixed-effects models and assessed heterogeneity between subgroups with the χ(2) test for heterogeneity. We did sensitivity analyses using random-effects models, stratifying by iron-folic acid dose, and exploring individual study effect.FINDINGS: Multiple micronutrient supplements containing iron-folic acid provided significantly greater reductions in neonatal mortality for female neonates compared with male neonates than did iron-folic acid supplementation alone (RR 0·85, 95% CI 0·75-0·96 vs 1·06, 0·95-1·17; p value for interaction 0·007). Multiple micronutrient supplements resulted in greater reductions in low birthweight (RR 0·81, 95% CI 0·74-0·89; p value for interaction 0·049), small-for-gestational-age births (0·92, 0·87-0·97; p=0·03), and 6-month mortality (0·71, 0·60-0·86; p=0·04) in anaemic pregnant women (haemoglobin <110g/L) as compared with non-anaemic pregnant women. Multiple micronutrient supplements also had a greater effect on preterm births among underweight pregnant women (BMI <18·5 kg/m(2); RR 0·84, 95% CI 0·78-0·91; p=0·01). Initiation of multiple micronutrient supplements before 20 weeks gestation provided greater reductions in preterm birth (RR 0·89, 95% CI 0·85-0·93; p=0·03). Generally, the survival and birth outcome effects of multiple micronutrient supplementation were greater with high adherence (≥95%) to supplementation. Multiple micronutrient supplements did not significantly increase the risk of stillbirth or neonatal, 6-month, or infant mortality, neither overall or in any of the 26 examined subgroups.INTERPRETATION: Antenatal multiple micronutrient supplements improved survival for female neonates and provided greater birth-outcome benefits for infants born to undernourished and anaemic pregnant women. Early initiation in pregnancy and high adherence to multiple micronutrient supplements also provided greater overall benefits. Studies should now aim to elucidate the mechanisms accounting for differences in the effect of antenatal multiple micronutrient supplements on infant health by maternal nutrition status and sex.
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| 37. |
- Upadhayaya, Ram Shankar, et al.
(författare)
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Synthesis and antimycobacterial activity of prodrugs of indeno[2,1-c]quinoline derivatives
- 2011
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 46:4, s. 1306-1324
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Tidskriftsartikel (refereegranskat)abstract
- Recently we have reported anti-TB properties of a new class of conformationally-constrained indeno[2,1-c]quinolines, which are although considerably active (MIC 0.39-0.78 mu g/mL) suffered from intense solubility problems. We thought of improving their bioavailability by prodrugs approach. Accordingly esters of the "Lead" indeno[2,1-c]quinolines 1,15 and 27 derivatives were synthesized and their prodrug nature at the physiological pH were confirmed. Prodrugs were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv by MABA assay to show that they have 2- to 4-fold improved anti-TB activities, increased aqueous solubility and superior selectivity index over their respective parent compounds. MIC of these prodrugs was in the range of <0.20-6.0 mu g/mL and in general, no cytotoxicity was observed in VERO cells.
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| 40. |
- Venugopalan, Shankar R., et al.
(författare)
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Novel expression and transcriptional regulation of FoxJ1 during oro-facial morphogenesis
- 2008
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 17:23, s. 3643-3654
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Tidskriftsartikel (refereegranskat)abstract
- Axenfeld-Rieger syndrome (ARS) patients with PITX2 point mutations exhibit a wide range of clinical features including mild craniofacial dysmorphism and dental anomalies. Identifying new PITX2 targets and transcriptional mechanisms are important to understand the molecular basis of these anomalies. Chromatin immunoprecipitation assays demonstrate PITX2 binding to the FoxJ1 promoter and PITX2C transgenic mouse fibroblasts and PITX2-transfected cells have increased endogenous FoxJ1 expression. FoxJ1 is expressed at embryonic day 14.5 (E14.5) in early tooth germs, then down-regulated from E15.5-E17.5 and re-expressed in the inner enamel epithelium, oral epithelium, tongue epithelium, sub-mandibular salivary gland and hair follicles during E18.5 and neonate day 1. FoxJ1 and Pitx2 exhibit overlapping expression patterns in the dental and oral epithelium. PITX2 activates the FoxJ1 promoter and, Lef-1 and beta-catenin interact with PITX2 to synergistically regulate the FoxJ1 promoter. FoxJ1 physically interacts with the PITX2 homeodomain to synergistically regulate FoxJ1, providing a positive feedback mechanism for FoxJ1 expression. Furthermore, FoxJ1, PITX2, Lef-1 and beta-catenin act in concert to activate the FoxJ1 promoter. The PITX2 T68P ARS mutant protein physically interacts with FoxJ1; however, it cannot activate the FoxJ1 promoter. These data indicate a mechanism for the activity of the ARS mutant proteins in specific cell types and provides a basis for craniofacial/ tooth anomalies observed in these patients. These data reveal novel transcriptional mechanisms of FoxJ1 and demonstrate a new role of FoxJ1 in oro-facial morphogenesis.
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| 41. |
- Abbassi, Fariba, et al.
(författare)
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Novel Benchmark Values for Redo Liver Transplantation Does the Outcome Justify the Effort?
- 2022
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 276:5, s. 860-867
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To define benchmark cutoffs for redo liver transplantation (redo-LT). Background: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT. Methods: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score <= 25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers. Results: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI (R) at 1-year of <= 72, and in-hospital and 1-year mortality rates of <= 13% and <= 15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redoLT benchmarks. Conclusion: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
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| 43. |
- Alcock, S, et al.
(författare)
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Early diagnosis of mortality using admission CT perfusion in severe traumatic brain injury patients (ACT-TBI): protocol for a prospective cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:6, s. e047305-
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Tidskriftsartikel (refereegranskat)abstract
- Severe traumatic brain injury (TBI) is a catastrophic neurological condition with significant economic burden. Early in-hospital mortality (<48 hours) with severe TBI is estimated at 50%. Several clinical examinations exist to determine brain death; however, most are difficult to elicit in the acute setting in patients with severe TBI. Having a definitive assessment tool would help predict early in-hospital mortality in this population. CT perfusion (CTP) has shown promise diagnosing early in-hospital mortality in patients with severe TBI and other populations. The purpose of this study is to validate admission CTP features of brain death relative to the clinical examination outcome for characterizing early in-hospital mortality in patients with severe TBI.Methods and analysisThe Early Diagnosis of Mortality using Admission CT Perfusion in Severe Traumatic Brain Injury Patients study, is a prospective cohort study in patients with severe TBI funded by a grant from the Canadian Institute of Health Research. Adults aged 18 or older, with evidence of a severe TBI (Glasgow Coma Scale score ≤8 before initial resuscitation) and, on mechanical ventilation at the time of imaging are eligible. Patients will undergo CTP at the time of first imaging on their hospital admission. Admission CTP compares with the reference standard of an accepted bedside clinical assessment for brainstem function. Deferred consent will be used. The primary outcome is a binary outcome of mortality (dead) or survival (not dead) in the first 48 hours of admission. The planned sample size for achieving a sensitivity of 75% and a specificity of 95% with a CI of ±5% is 200 patients.Ethics and disseminationThis study has been approved by the University of Manitoba Health Research Ethics Board. The findings from our study will be disseminated through peer-reviewed journals and presentations at local rounds, national and international conferences. The public will be informed through forums at the end of the study.Trial registration numberNCT04318665
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| 48. |
- Azoulay, E., et al.
(författare)
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International variation in the management of severe COVID-19 patients
- 2020
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1466-609X .- 1364-8535. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background There is little evidence to support the management of severe COVID-19 patients. Methods To document this variation in practices, we performed an online survey (April 30-May 25, 2020) on behalf of the European Society of Intensive Care Medicine (ESICM). A case vignette was sent to ESICM members. Questions investigated practices for a previously healthy 39-year-old patient presenting with severe hypoxemia from COVID-19 infection. Results A total of 1132 ICU specialists (response rate 20%) from 85 countries (12 regions) responded to the survey. The survey provides information on the heterogeneity in patient's management, more particularly regarding the timing of ICU admission, the first line oxygenation strategy, optimization of management, and ventilatory settings in case of refractory hypoxemia. Practices related to antibacterial, antiviral, and anti-inflammatory therapies are also investigated. Conclusions There are important practice variations in the management of severe COVID-19 patients, including differences at regional and individual levels. Large outcome studies based on multinational registries are warranted.
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