| 1. |
- Ademuyiwa, Adesoji O., et al.
(author)
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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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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)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. |
- Andersson, Erik, et al.
(author)
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Cost-effectiveness of an internet-based booster program for patients with obsessive-compulsive disorder : Results from a randomized controlled trial
- 2015
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In: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier. - 2211-3649 .- 2211-3657. ; 4, s. 14-19
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Journal article (peer-reviewed)abstract
- Cognitive behavior therapy (CBT) is an effective treatment for OCD when delivered face-to-face, in group-format and also via the internet. However, despite overall large effect sizes, a considerable amount of the patients relapse. One intervention that has the potential to reduce these relapse rates is booster programs, but if booster program is a cost-effective method of preventing relapse is still unknown. We used health economical data from a recent randomized controlled trial, where patients who had undergone an internet-based CBT were randomly allocated to receive an additional booster program. Assessment points were 4-, 7-, 12- and 24-month. Health economical data were primarily analyzed using a societal perspective. Results showed that the booster program was effective in preventing relapse, and the cost of one avoided relapse was estimated to $1066-1489. Cost-effectiveness acceptability curves showed that the booster program had a 90% probability of being cost-effective given a willingness to pay of $1000-1050 the first year, but this figure grew considerably after two years ($2500-5500). We conclude that internet-based booster programs are probably a cost-effective alternative within one-year time frame and that more treatment may be needed to maintain adequate cost-effectiveness up to two years. (C) 2014 Elsevier Inc. All rights reserved.
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| 3. |
- Andersson, Erik, et al.
(author)
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d-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants A Randomized Clinical Trial
- 2015
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 72:7, s. 659-667
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Journal article (peer-reviewed)abstract
- IMPORTANCE It is unclear whether D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist that enhances fear extinction, can augment the effects of exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD). OBJECTIVES To examine whether DCS augments the effects of CBT for OCD and to explore (post hoc) whether concomitant antidepressant medication moderates the effects of DCS. DESIGN, SETTING, AND PARTICIPANTS A 12-week, double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4, 2012, and September 26, 2013. Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial. The main analysis was by intention-to-treat population. INTERVENTIONS All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo, administered 1 hour before each of 5 exposure and response prevention tasks. MAIN OUTCOMES AND MEASURES Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up. Remission was defined as a score of 12 or lower on the Y-BOCS. RESULTS In the primary intention-to-treat analyses, DCS did not augment the effects of CBT compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50] at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week 12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction with antidepressants (clinician-rated Y-BOCS, B = -1.08; Z = -2.79; P = .005). Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group, at both posttreatment and follow-up (clinician-rated Y-BOCS: t(62) = -3.00; P = .004; and t(61) = -3.49; P < .001, respectively). In the DCS group, a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up (60% [95% CI, 45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P = .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%] remission rate in both groups). CONCLUSIONS AND RELEVANCE The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction. Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD.
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| 4. |
- Andersson, Simon, 1980-
(author)
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Skälig misstanke
- 2016
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Doctoral thesis (other academic/artistic)abstract
- This doctoral dissertation studies the legal standard of proof called reasonable suspicion (skälig misstanke). This standard is central for criminal investigations as the majority of state criminal procedural actions (tvångsmedel) are tied to it, as well as the majority of a suspect’s rights. Despite the central role played by this standard, it has not to any significant extent been researched previously. What the standard entails cannot be seen from either the law or legislative history, and there are no published cases discussing it. As the meaning of the standard is not clear, there is much room for discretion in assessments as to whether the standard has been met. There consequently is a need to clarify what reasonable suspicion entails. What is required to fulfill the standard? How is reasonable suspicion to be assessed? These questions are answered in this dissertation.My investigation demonstrates that reasonable suspicion is a three-pronged standard:A requirement of preponderance of the evidenceReasonable suspicion entails a requirement of a preponderance of the evidence (sannolikhetsövervikt). This means, somewhat simplified, that it should be more probable that the suspect is guilty than innocent. The hypothesis underlying the reasonable suspicion of alleged guilt (gärningshypotesen) should be more probable than all other plausible hypotheses combined.A requirement of individualizationThe evidence must be sufficiently individualized in order to reach the level of reasonable suspicion. The requirement of individualization is in place to prevent that persons are suspected on the basis of group membership. The same is true with respect to persons belonging to groups where the probability of crime is generally high. In such situations, there must be a concrete circumstance pointing to just that person committing a certain crime. It can be, however, circumstances having very low evidentiary value. Group membership can still be of significance with respect to the suspect, but reasonable suspicion cannot be solely based on group membership. A generally applicable concept as to that distinguishing the general from the individual cannot however be articulated. All evidentiary evaluations are in some form based on generalizations. Consequently, the issue of whether the evidence is sufficiently individualized must be assessed from case to case. The main premise is that suspicion cannot be solely based on group belonging. This is a legal-political requirement. Legal-political aspects consequently must also be taken into consideration when evaluating evidence.A requirement of robustnessEven in cases where the evidence is evaluated so that a preponderance of the evidence exists and is sufficiently individualized, the evidence still needs to be sufficiently robust. Robustness is a measure of whether good grounds exist for the conclusion. It is not a question of how ”strong” the evidence is, but rather how thoroughly the situation has been investigated. Somewhat simplified, it is a question of ”how much” evidence exists rather than the strength of the individual pieces of evidence. This requirement of robustness varies depending upon time in that it is very low at the commencement of an investigation, but as time goes by, higher requirements are placed as to the ”completeness” of the investigation.
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| 5. |
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| 6. |
- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 7. |
- Satizabal, Claudia L., et al.
(author)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Journal article (peer-reviewed)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 8. |
- Alexander, Michelle, et al.
(author)
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Mitogenomic analysis of a 50-generation chicken pedigree reveals a rapid rate of mitochondrial evolution and evidence for paternal mtDNA inheritance
- 2015
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In: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 11:10
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Journal article (peer-reviewed)abstract
- Mitochondrial genomes represent a valuable source of data for evolutionary research, but studies of their short-term evolution have typically been limited to invertebrates, humans and laboratory organisms. Here we present a detailed study of 12 mitochondrial genomes that span a total of 385 transmissions in a well-documented 50-generation pedigree in which two lineages of chickens were selected for low and high juvenile body weight. These data allowed us to test the hypothesis of time-dependent evolutionary rates and the assumption of strict maternal mitochondrial transmission, and to investigate the role of mitochondrial mutations in determining phenotype. The identification of a non-synonymous mutation in ND4L and a synonymous mutation in CYTB, both novel mutations in Gallus, allowed us to estimate a molecular rate of 3.13 x 10(-7) mutations/site/year (95% confidence interval 3.75 x 10(-8)-1.12 x 10(-6)). This is substantially higher than avian rate estimates based upon fossil calibrations. Ascertaining which of the two novel mutations was present in an additional 49 individuals also revealed an instance of paternal inheritance of mtDNA. Lastly, an association analysis demonstrated that neither of the point mutations was strongly associated with the phenotypic differences between the two selection lines. Together, these observations reveal the highly dynamic nature of mitochondrial evolution over short time periods.
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| 9. |
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| 10. |
- Andersson, Anders, et al.
(author)
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Parameterization procedure of a powertrain model for a driving simulator
- 2016
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In: Advances in Transportation Studies. - : Aracne editrice. - 1824-5463. ; 1, s. 99-112
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Journal article (peer-reviewed)abstract
- The automotive industry is facing a major challenge to reduce environmental impacts. As a consequence, the increasing diversity of powertrain configurations put a demand on testing and evaluation procedures. One of the key tools for this purpose is simulators. In this paper a powertrain model and a procedure for parameterizing it, using chassis dynamometers and a developed pedal robot are presented. The parameterizing procedure uses the on-board diagnostics of the car and does not require any additional invasive sensors.Thus, the developed powertrain model and parameterization procedure provide a rapid non- invasive way of modelling powertrains of test cars. The parameterizing procedure has been used to model a front wheel drive Golf V with a 1.4L multi-fuel engine and a manual gearbox. The achieved results show a good match between simulation results and test data. The powertrain model has also been tested in real-time in a driving simulator.
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