| 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. |
- Andersson, David A., et al.
(författare)
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TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Delta(9)-tetrahydrocannabiorcol
- 2011
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- TRPA1 is a unique sensor of noxious stimuli and, hence, a potential drug target for analgesics. Here we show that the antinociceptive effects of spinal and systemic administration of acetaminophen (paracetamol) are lost in Trpa1(-/-) mice. The electrophilic metabolites N-acetyl-p-benzoquinoneimine and p-benzoquinone, but not acetaminophen itself, activate mouse and human TRPA1. These metabolites also activate native TRPA1 and, as a consequence, reduce voltage-gated calcium and sodium currents in primary sensory neurons. The N-acetyl-p-benzoquinoneimine metabolite l-cysteinyl-S-acetaminophen was detected in the mouse spinal cord after systemic acetaminophen administration. In the hot-plate test, intrathecal administration of N-acetyl-p-benzoquinoneimine, p-benzoquinone and the electrophilic TRPA1 activator cinnamaldehyde produced antinociception that was lost in Trpa1(-/-) mice. Intrathecal injection of a non-electrophilic cannabinoid, Delta(9)-tetrahydrocannabiorcol, also produced TRPA1-dependent antinociception in this test. Our study provides a molecular mechanism for the antinociceptive effect of acetaminophen and discloses spinal TRPA1 activation as a potential pharmacological strategy to alleviate pain.
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| 3. |
- Andersson, Erik, et al.
(författare)
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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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Ingår i: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier. - 2211-3649 .- 2211-3657. ; 4, s. 14-19
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Andersson, Erik, et al.
(författare)
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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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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 72:7, s. 659-667
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Andersson, Gerhard, et al.
(författare)
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Free choice of treatment content, support on demand and supervision in internet-delivered CBT for adults with depression : A randomized factorial design trial
- 2023
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Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 162
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Tidskriftsartikel (refereegranskat)abstract
- Even if much is known regarding the effects of internet-delivered cognitive behaviour therapy (ICBT) for depression there are several topics that have not been studied. In this factorial design trial with 197 participants we investigated if clients in ICBT could select treatment modules themselves based on a selection of 15 tailored treatment modules developed for use in ICBT for depression. We contrasted this against clinician-tailored module selection. We also investigated if support on demand (initiated by the client) could work as well as scheduled support. Finally, we tested if clients that were mentioned in supervision would improve more than clients not mentioned (with the exception of acute cases). The treatment period lasted for 10 weeks, and we measured effects at post-treatment and two-year follow-up. Measures of depression and secondary outcomes were collected at pre-treatment, post-treatment and two-year follow-up. Overall, within-group effects were large across con-ditions (e.g., d = 1.73 on the BDI-II). We also found a small but significant difference in favour of self-tailored treatment over clinician-tailored (d = 0.26). Within-group effects for the secondary measures were all moderate to large including a test of knowledge about CBT. The other two contrasts "support on demand" and "supervision" yielded mostly non-significant differences, with the exception of a larger dropout rate in the support on demand condition. There were few negative effects (2.2%). Effects were largely maintained at a two-year follow-up. We conclude that clients can choose treatment modules and that support on demand may work. The role of su-pervision is not yet clear as advice can be transferred across clients.
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| 6. |
- Andersson, Niklas, et al.
(författare)
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Methodology for fast development of digital solutions in integrated continuous downstream processing
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Ingår i: Biotechnology and Bioengineering. - 0006-3592.
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Tidskriftsartikel (refereegranskat)abstract
- The methodology for production of biologics is going through a paradigm shift from batch-wise operation to continuous production. Lot of efforts are focused on integration, intensification, and continuous operation for decreased foot-print, material, equipment, and increased productivity and product quality. These integrated continuous processes with on-line analytics become complex processes, which requires automation, monitoring, and control of the operation, even unmanned or remote, which means bioprocesses with high level of automation or even autonomous capabilities. The development of these digital solutions becomes an important part of the process development and needs to be assessed early in the development chain. This work discusses a platform that allows fast development, advanced studies, and validation of digital solutions for integrated continuous downstream processes. It uses an open, flexible, and extendable real-time supervisory controller, called Orbit, developed in Python. Orbit makes it possible to communicate with a set of different physical setups and on the same time perform real-time execution. Integrated continuous processing often implies parallel operation of several setups and network of Orbit controllers makes it possible to synchronize complex process system. Data handling, storage, and analysis are important properties for handling heterogeneous and asynchronous data generated in complex downstream systems. Digital twin applications, such as advanced model-based and plant-wide monitoring and control, are exemplified using computational extensions in Orbit, exploiting data and models. Examples of novel digital solutions in integrated downstream processes are automatic operation parameter optimization, Kalman filter monitoring, and model-based batch-to-batch control.
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| 7. |
- Andersson, Simon, 1980-
(författare)
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Skälig misstanke
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 8. |
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| 9. |
- Dima, Danai, et al.
(författare)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 10. |
- Dorozynska, Karolina, et al.
(författare)
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Snapshot multicolor fluorescence imaging using double multiplexing of excitation and emission on a single detector
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence-based multispectral imaging of rapidly moving or dynamic samples requires both fast two-dimensional data acquisition as well as sufficient spectral sensitivity for species separation. As the number of fluorophores in the experiment increases, meeting both these requirements becomes technically challenging. Although several solutions for fast imaging of multiple fluorophores exist, they all have one main restriction; they rely solely on spectrally resolving either the excitation- or the emission characteristics of the fluorophores. This inability directly limits how many fluorophores existing methods can simultaneously distinguish. Here we present a snapshot multispectral imaging approach that not only senses the excitation and emission characteristics of the probed fluorophores but also all cross term combinations of excitation and emission. To the best of the authors’ knowledge, this is the only snapshot multispectral imaging method that has this ability, allowing us to even sense and differentiate between light of equal wavelengths emitted from the same fluorescing species but where the signal components stem from different excitation sources. The current implementation of the technique allows us to simultaneously gather 24 different spectral images on a single detector, from which we demonstrate the ability to visualize and distinguish up to nine fluorophores within the visible wavelength range.
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