| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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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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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 3. |
- Abrahamsson, Per, 1985, et al.
(författare)
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Analysis of mesoscale effects in high-shear granulation through a computational fluid dynamics–population balance coupled compartment model
- 2018
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Ingår i: Particuology. - : Elsevier BV. - 2210-4291 .- 1674-2001. ; 36, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for mesoscale resolution and coupling between flow-field information and the evolution of particle properties in high-shear granulation. We have developed a modelling framework that compartmentalizes the high-shear granulation process based on relevant process parameters in time and space. The model comprises a coupled-flow-field and population-balance solver and is used to resolve and analyze the effects of mesoscales on the evolution of particle properties. A Diosna high-shear mixer was modelled with microcrystalline cellulose powder as the granulation material. An analysis of the flow-field solution and compartmentalization allows for a resolution of the stress and collision peak at the impeller blades. Different compartmentalizations showed the importance of resolving the impeller region, for aggregating systems and systems with breakage. An independent study investigated the time evolution of the flow field by changing the particle properties in three discrete steps that represent powder mixing, the initial granulation stage mixing and the late stage granular mixing. The results of the temporal resolution study show clear changes in collision behavior, especially from powder to granular mixing, which indicates the importance of resolving mesoscale phenomena in time and space.
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| 4. |
- Nguyen, Duy, 1986, et al.
(författare)
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A study of the redistribution of fines between carriers in adhesive particle mixing using image analysis with coloured tracers
- 2016
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Ingår i: Powder Technology. - : Elsevier BV. - 1873-328X .- 0032-5910. ; 299, s. 71-76
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the dynamics and kinetics of mixing mechanisms, i.e. random mixing, de-agglomeration, adhesion, and redistribution, is critical in order to achieve a structure of interest in adhesive particle mixing. In this work, the redistribution of fines between carrier particles, one of the key mechanisms in establishing a homogeneous mixture, was investigated. Coloured carriers (tracers) and image analysis utilizing CIELCH colour space are used as a tool to assess the dynamics of such a mechanism via the evolution of the colour of blends. It is found that, in a high shear mixer, redistribution quickly reaches a pseudo-steady state within a time scale that is of the same order of magnitude as that of random mixing. Considering all the governing mechanisms necessary to achieve an adhesive mixture, it is concluded that the de-agglomeration of fine-particle agglomerates is the rate-limiting step. This work also demonstrates that the redistribution of fines is influenced by the structure of fines on carrier surfaces resulting from processing conditions. This finding supports the fact that beside material properties, blending conditions, e.g. mixing speed and time, are crucial as regards the structure of adhesive mixtures for inhalation. (C) 2016 Elsevier B.V. All rights reserved.
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| 5. |
- Nguyen, Duy, 1986, et al.
(författare)
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The exchange of fines between carriers in adhesive particle mixing: A study using DEM simulation
- 2016
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Ingår i: Powder Technology. - : Elsevier BV. - 1873-328X .- 0032-5910. ; 288, s. 266-278
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Tidskriftsartikel (refereegranskat)abstract
- This study employs DEM simulations to investigate the transfer of fine particles between carrier particles, which is one of the important mechanisms governing adhesive particle mixing. Single collisions between a carrier coated with fines and a non-coated carrier were simulated, in which the interaction between particles was modelled using the JKR theory. Detailed post-impact analysis was carried out to characterise the transfer mechanism and the effects of interface energy between particles, impact velocity and impact angle on the transfer process. It was found that fines are transferred between carriers and are restructured with different patterns according to the relative magnitude of the kinetic energy and the interface energies of particles, both between fines and between fine-carrier. The impact angle, which is closely related to mixer type, has a significant influence on the transfer of fines when the kinetic energy is able to be dissipated into adhesive bonds between fines (which strength is characterised by the corresponding interface energy). The correlation of the particle properties (e.g. interface energies), the processing parameters (e.g. the impact velocity), and the type of mixer (e.g. the impact angle) in characterising the transfer mechanism is established.
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| 6. |
- Sandström, Per, et al.
(författare)
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ALPPS Improves Resectability Compared with Conventional Two-stage Hepatectomy in Patients with Advanced Colorectal Liver Metastasis : Results from a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial)
- 2018
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Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 267:5, s. 833-840
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). Background: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. Methods: A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome - RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. Results: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien-Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. Conclusion: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.
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| 7. |
- Tamadondar, Mohammadreza, 1989, et al.
(författare)
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Numerical modeling of adhesive particle mixing
- 2017
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Ingår i: AICHE Journal. - : Wiley. - 1547-5905 .- 0001-1541. ; 63:7, s. 2599-2609
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Tidskriftsartikel (refereegranskat)abstract
- The discrete element method is used to investigate adhesive particle mixing in a system that includes large carrier particles and fine particle agglomerates in a Couette mixer. The simulation starts with 200 carriers and 10 agglomerates with 1000 fine particles each. During mixing, the agglomerates are broken, fractions adhere to the carriers, and there is continuous redistribution of fines between carriers. The focus is to obtain information on the quantity and quality of fine particles adhered to carriers by postprocessing the simulation data. Variation in the structure of agglomerates due to shearing is studied over mixing time. Findings indicate that major fraction of fine particles are dispersed evenly onto the surface of carriers and the rest are in form of free debris. A time-dependent index is introduced to predict the degree of mixing. Finally, the adhesion force between carriers and coated layers is observed to have a peak at 1 nN.
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| 8. |
- Tamadondar, Mohammadreza, 1989, et al.
(författare)
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The influence of particle interfacial energies and mixing energy on the mixture quality of the dry-coating process
- 2018
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Ingår i: Powder Technology. - : Elsevier BV. - 1873-328X .- 0032-5910. ; 338, s. 313-324
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the effect of particle interface energies and mixing energy input on the macroscopic behavior of the dry-coating process by using the discrete element method (DEM). It is observed that the quality of the coating process is governed by two dimensionless numbers: the Stokes number St (mixing energy/strength of agglomerates) and the reduced intermixing coefficient Λ (cohesion /adhesion strength). Three unfavorable and one favorable process regimes were identified, and represented in a regime map as a function of St and Λ. For low St and Λ carriers are lumped and random mixing is fairly poor. For low St and high Λ the agglomerates are merged together and remain intact. At high St, the fine-carrier adhesion breaks and creates abundance of debris. Between these regions process conditions are favorable as is supported by experimental evidences. Results of this study can be used to establish guidelines for efficient operation of the dry-coating process in a high-shear mixer.
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| 9. |
- van der Laan, Sander W., et al.
(författare)
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Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study
- 2016
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 68:9, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.
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