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| 2. |
- Ludvigsson, Johnny, et al.
(författare)
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Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial
- 2011
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Ingår i: DIABETOLOGIA. - : Springer Science Business Media. - 0012-186X .- 1432-0428. ; 54:3, s. 634-640
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 mu g of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with andlt; 6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 +/- 0.032 nmol/l at day 1 and 0.215 +/- 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 +/- 0.039 and 0.184 +/- 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years. Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide. ClinicalTrials.gov NCT00435981 The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.
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| 3. |
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A Longitudinal Investigation Of Business Angel Relationship Risk Mitigation Strategies Within Investments - A Three-dimensional Approach
- 2015
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Proceedings (redaktörskap) (refereegranskat)abstract
- Business angel (BA) investing is associated with various types of risks, where relationship risk often is highlighted as being especially critical (Fiet, 1995). Three investor strategies for mitigating relationship risks associated with BA investing in young private firms can be traced in the literature: (i) indirect control through monitoring and rewarding/punishing entrepreneur behavior and output, (ii) direct control through active involvement, and (iii) relying on mutual trust (Van Osnabrugge and Robinson, 2000; Maxwell and Lévesque, 2011). While early research in the field adopted a rather static view on BA categorization (Coveney and Moore, 1998; Sørheim and Landström, 2001), more contemporary research shows that BAs change investment roles across investments (Avdeitchikova, 2008; Lahti, 2011). However, whether BAs behave differently regarding risk mitigation within investments is less explored. This explorative study contributes to the opening of the black box of how BAs may shift risk mitigation strategies over time within single investments.
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| 4. |
- Ahlund, Mikael, 1959-, et al.
(författare)
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Prerafaeliterna
- 2009
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Bok (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Ainegren, Mats, 1963-, et al.
(författare)
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A Study of Skin-Close Heat and Moisture with Different Types of Backpacks in Cycling
- 2020
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Ingår i: The 13th Conference of the International Sports Engineering Association. - Basel Switzerland : MDPI.
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Konferensbidrag (refereegranskat)abstract
- The aim of this project was to evaluate effects of backpacks with different design intended for use during cycling on skin-close temperature and relative humidity, oxygen uptake, heart rate and aerodynamic drag. Seven subjects took part in the study cycling on a mountain bike mounted on a “smart trainer” placed on a force plate in a wind tunnel. Three series of experiments were carried out: without backpack, with conventional backpack and with a backpack having innovative rear panel design. As hypothesized, the results showed that an innovatively designed backpack with the ducts deflecting part of the airflow towards some areas of the user’s back provided lower temperature and relative humidity for the microclimate compared to a conventional backpack without airflow channels. Further, reference tests without any backpack resulted in the lowest temperature and humidity. However, no differences were found between the three tests for oxygen uptake, heart rate and aerodynamic drag.
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| 6. |
- Bernesson, Sven, et al.
(författare)
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Glycerin från omförestring av vegetabiliska oljor som tillsatsmedel : praktiska försök med pelletering och eldning av några biobränslen
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- During transesterification of vegetable oils in particular, but also animal fats and used frying oils, glycerine is obtained as a by-product. It is important for transesterification economics that the glycerine by-product can be sold for the best possible price. In Sweden today, glycerine is often sold to biogas production for a few Swedish crowns per kilo. If other markets where glycerine replaces a more expensive product can be found, the willingness to pay for glycerine will increase. This project examined whether glycerine can be used as an additive in pelleting some biofuel types, and the value it would have in this use. The project investigated admixtures of appropriate amounts of glycerine of varying quality during pelleting of some types of fuel (straw, reed canary grass and pine wood). To determine how these affect pellet quality, the function of the pellet press, pellet storage properties, the risk of harmful emission levels of carbon monoxide (CO), nitrogen oxides (NOx), sulphur oxides (SO2) and aldehydes during incineration of the pellets, the risk of ash sintering and the risk of corrosive deposits in flue gas channels were examined. In addition, the commercial value of the glycerine when added to pellets was estimated. Pelleting trials were conducted using 1% and 5% admixtures of four types of glycerine in three types of fuel. Two of the glycerine products were alkaline, originating from alkaline transesterification of rapeseed oil, and two were acidic, originating from acid esterification/transesterification followed by alkaline transesterification, of rapeseed oil in one case and used frying oil in the other. The fuel types were pine wood, reed canary grass and straw. After pelleting, pellet durability, the amount of fine fraction and bulk density were measured. Chemical analyses were performed of glycerine types, fuel types and glycerine/fuel mixtures to evaluate ash melting behaviour and the risk of corrosion associated with alkali chlorides. Pellets from the trials were stored for 6 months, during which time moisture uptake and the incidence of mould were studied. After the storage experiments, pellet durability was measured again. Wherever possible, the experimental design was evaluated statistically using multivariate data analysis. About half the samples were incinerated and emissions of CO, NOx, SO2, particulate matter, acrolein and formaldehyde were measured. In addition, the average temperature and maximum temperature during incineration were measured and the amount of combustion residues and their content of unburned and sintered material were determined. Some ash samples from the combustion of glycerine/pine wood mixes were sent for chemical analysis. The admixture of glycerine in the fuel types generally resulted in pellets with lower durability, higher proportion of fines (fine fraction) and significantly lower bulk density. However, pellets with the same or slightly better durability and the same or lower proportion of fines were obtained by admixture of 1% acidic glycerine to the fuel types. The specific energy consumption for pelleting the fuels containing glycerine was generally lowered, which may have been due to the lubricating properties of the glycerine. The addition of glycerine in all cases resulted in a decrease in pellet bulk density. Reed canary grass had the best durability, least share of fines and highest bulk density, while straw usually had the worst durability, highest share of fines and lowest bulk density. During the storage experiments the pellets took up some water, but never to such a level that the storability was compromised. Pellets with glycerine took up more water, often an increasing amount with increasing glycerine content. Mould was not found in any pellets from any experiment. Durability deteriorated more frequently with higher glycerine content, and thus low durability in the pellets at the outset. The initial moisture content and thus the type of fuel were also of great importance for moisture absorption. Straw contained most moisture from the start and took up the most water. In addition, durability decreased most for straw during storage. During incineration, the main problem with an increasing admixture of glycerine in the fuels was an increasing amount of particles in the flue gas. Calculations of potassium (K) losses with the flue gases, based on analysis of fuels and their ash composition, suggested that this increased sharply with increasing admixture of glycerine. For example, incineration of pine wood with about 1% added glycerine increased the amount of K leaving with the flue gases to the level observed with straw incineration. There seemed to be a close link between the amount of particles in the flue gas and the amount of K released. It is therefore likely that addition of glycerine will cause problems with corrosive deposits in the flues for fuels that normally do not present such problems. However, with fuels that normally give rise to such problems, e.g. straw, it is likely that there will be little obvious difference. Glycerine (acid) containing sulphur can probably prevent particle release and thus lower the risk of corrosion associated with alkali chlorides in the flue gas. The emissions of acrolein and formaldehyde did not increase as might be expected in experiments with glycerine admixture. The levels of acrolein were below the detection limit, and the levels of formaldehyde were very low. Emissions of CO, NOx and SO2 varied widely between experiments in a more or less random way. However, CO emissions may have increased with lower pellet quality. Sulphur dioxide should be produced during incineration of pellets with high sulphur levels. Ash melting point declined in pine wood in particular on addition of glycerine, but also in reed canary grass. The ash melting point for straw was not affected at all by glycerine admixture. The reason why pine wood ash was more sensitive is that the amounts produced from pine are so small that properties of the glycerine ash can have an impact even at small admixture rates. The K content of reed canary grass is so low that very little glycerine with high K content is required before its properties start to become apparent. However, straw has a high initial content of an ash that is already high in K, so the K content of glycerine ash is les obvious even at rather high admixture rates. Calculations using key numbers showed that the ash melting point of reed canary grass in particular should be lowered by the admixture of glycerine, but also that of pine wood to a lesser degree, from an initially high level. Straw ash should scarcely be affected at all. High losses of K in the flue gases can suppress the problem of ash melting point depression in bottom ash. Some of the glycerine types initially had high contents of methanol. It is important that this can be removed, as it constitutes a fire hazard during pelleting and also during transport and handling of the glycerine. High methanol concentrations are also a human health risk, as methanol is toxic. The commercial value of the glycerine is at one of three different levels depending on how it functions when mixed in different fuels. A) If glycerine admixture degrades a good fuel such as wood in terms of the risk of acid deposits in the flue so much that it is similar to straw as a fuel, glycerine value has a negative value. B) On admixture of glycerine in a poor fuel, such as straw, the properties of the glycerine are not evident and its value based on the energy is therefore the same as for the pure fuel. This is currently approximately SEK 0.6-0.9/kg glycerine, which can be compared with the current price of SEK 1/kg for glycerine in biodigestion applications. These factors combined make it difficult to find a profitable use for glycerine as an additive in pelleting or when used as fuel. Glycerine would therefore not be of commercial interest for use in these applications. C) If the glycerine acts as an additive in very small amounts at pelleting, most likely as a lubricant, the value would then be about SEK 3/kg. However, only small amounts would be used in this application, probably just a few hundred tonnes per annum. The advice to the industry is that glycerine should not be used in pelleting as it probably does not work well for this application. If glycerine is incinerated, it should be co-fired with a poor fuel, so as not to impair the properties of the fuel. Glycerine is probably more profitable in applications other than fuel to produce heat. At low addition rates glycerine could probably act as a lubricant during pelleting of certain fuels. However, more research is required to determine whether glycerine can act as a lubricant along with some cheap binding agent in pelleting of fuels
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| 7. |
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| 8. |
- Borg, Farhana, Lektor, 1967-, et al.
(författare)
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Methodological and ethical issues when interviewing preschool children : Experiences from a study on sustainability in Sweden
- 2023
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Ingår i: 31st EECERA ANNUAL CONFERENCE. Children’s Curiosity, Agency and Participation: Challenges for Professional Action and Development. ; , s. 135-135
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Konferensbidrag (refereegranskat)abstract
- To contribute to the methodological and ethical discourse on children’sparticipation in research on complex issues, this case-study critically discusses experiences from a large-scale randomized interview study about preschool education for sustainability in Sweden. Young children’s ability to express their views has been subject to debate, resulting in them often being excluded asresearch participants. Hence, age-appropriate methodological approaches are needed to ensure their participation.This study draws from Josefsson and Wall’s(2020) concept of children’s “empowered inclusion” and Lundy’s (2007) model of voice, space, audience, and influence.Employing a qualitative case-studyapproach, methodological approaches and ethical considerations and experiences of a randomized study are scrutinized. A total of 403 children from 50 preschools were interviewed about sustainability using illustrations. An interview instrument was developed and pretested in two iterations. Data were analyzed thematically. The Swedish Ethical Review Authority did not raise any objection to the interview study. Consent to participate was collected from parents and children.They were informed that the children could withdraw at any time if they wanted. The findings demonstrate that research with young children can be undertaken in an ethically acceptable manner. The use of illustrations was helpful in creating a friendly environment and supporting children’s understanding of complex issues. Individual and pair interviews were effective while group interviews were problematic. Children’s attention dropped after 12-15 minutes. These findings suggest that preschool children can express their views on important matters under ethically acceptable and methodologically appropriate conditions.
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| 9. |
- Brundin, L., et al.
(författare)
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An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
- 2016
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
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| 10. |
- Bäck, Marcus, et al.
(författare)
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Novel potent macrocyclic inhibitors of the hepatitis C virus NS3 protease : use of cyclopentane and cyclopentene P2-motifs
- 2007
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 15:22, s. 7184-7202
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Tidskriftsartikel (refereegranskat)abstract
- Several highly potent novel HCV NS3 protease inhibitors have been developed from two inhibitor series containing either a P2 trisubstituted macrocyclic cyclopentane- or a P2 cyclopentene dicarboxylic acid moiety as surrogates for the widely used N-acyl-(4R)-hydroxyproline in the P2 position. These inhibitors were optimized for anti HCV activities through examination of different ring sizes in the macrocyclic systems and further by exploring the effect of P4 substituent removal on potency. The target molecules were synthesized from readily available starting materials, furnishing the inhibitor compounds in good overall yields. It was found that the 14-membered ring system was the most potent in these two series and that the corresponding 13-, 15-, and 16-membered macrocyclic rings delivered less potent inhibitors. Moreover, the corresponding P1 acylsulfonamides had superior potencies over the corresponding P1 carboxylic acids. It is noteworthy that it has been possible to develop highly potent HCV protease inhibitors that altogether lack the P4 substituent. Thus the most potent inhibitor described in this work, inhibitor 20, displays a Ki value of 0.41 nM and an EC50 value of 9 nM in the subgenomic HCV replicon cell model on genotype 1b. To the best of our knowledge this is the first example described in the literature of a HCV protease inhibitor displaying high potency in the replicon assay and lacking the P4 substituent, a finding which should facilitate the development of orally active small molecule inhibitors against the HCV protease.
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