| 1. |
- Montagnese, Sara, et al.
(författare)
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A pilot study of golexanolone, a new GABA-A receptor-modulating steroid antagonist, in patients with covert hepatic encephalopathy
- 2021
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:1, s. 98-107
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Golexanolone is a novel small molecule GABA-A receptor-modulating steroid antagonist under development for the treatment of cognitive and vigilance disorders caused by allosteric over-activation of GABA-A receptors by neurosteroids. It restored spatial learning and motor coordination in animal models of hepatic encephalopathy (HE) and mitigated the effects of intravenous allopregnanolone in healthy adults in a dose-dependent fashion. Herein, we report data on the safety, pharmacokinetics (PK) and efficacy of golexanolone in adult patients with cirrhosis.Methods: Following single/multiple ascending dose studies, adults with Child-Pugh A/B cirrhosis and abnormal continuous reaction time (CRT) on screening were randomized to 3 weeks’ dosing with golexanolone (10, 40 or 80 mg BID) or placebo. CRT, psychometric hepatic encephalopathy score (PHES), animal naming test (ANT), Epworth sleepiness scale (ESS) and electroencephalogram (mean dominant frequency [MDF]; delta+theta/alpha+beta ratio [DT/AB]) were obtained at baseline, 10, and 21 days.Results: Golexanolone exhibited satisfactory safety and PK. Baseline characteristics were similar between the 12 and 33 patients randomized to placebo or golexanolone, respectively. By prespecified analyses, golexanolone was associated with directionally favourable changes vs. placebo in ESS (p = 0.047), MDF (p = 0.142) and DT/AB (p = 0.021). All patients also showed directionally favourable changes in CRT, PHES and ANT, but with no statistical difference between golexanolone and placebo. Post hoc analyses taking into account the variability and improvement in CRT, PHES and ANT observed between screening and baseline suggested an efficacy signal by cognitive measures as well.Conclusion: Golexanolone was well tolerated and associated with improvement in cognitive performance. These results implicate GABA-A receptor-modulating neurosteroids in the pathogenesis of HE and support the therapeutic potential of golexanolone.Lay summary: Many patients with cirrhosis experience subtle but disabling cognitive problems, including sleepiness and poor attention span, that impair their ability to be gainfully employed or carry out activities of daily living. This pilot study tested the hypothesis that these problems with cognition, for which there is no approved treatment, might be improved by an experimental drug, golexanolone, designed to normalize the function of receptors which inhibit brain function. The results of this study suggest that golexanolone is well tolerated and may improve cognition, as reflected by measures of sleepiness, attention span and brain wave activity, paving the way for future larger studies of this promising experimental drug.Clinical trial registration number: EudraCT 2016-003651-30.
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| 2. |
- Backström, Fredrik, et al.
(författare)
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Surgical Needs at the End of the Battle of Mosul: Results from Mosul General Hospital
- 2020
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Ingår i: World Journal of Surgery. - : SPRINGER. - 0364-2313 .- 1432-2323.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim of the study was to analyze the surgical needs of patients seeking emergency care at the Mosul General Hospital in the final phase of the battle of Mosul in northern Iraq between an international military coalition and rebel forces. During the conflict, the International Red Committee of the Red Cross (ICRC) supported the hospital with staff and resources. Ceasefire in the conflict was declared at the end of July 2017. Methods Routinely collected hospital data from the ICRC-supported Mosul General Hospital from June 6, 2017, to October 1, 2017 were collected and analyzed retrospectively. All patients with weapon-related injuries as well as all patients with other types of injuries or acute surgical illness were included. Results Some 265 patients were admitted during the study period. Non-weapon-related conditions were more common than weapon-related (55.1%). The most common non-weapon-related condition was appendicitis followed by hernia and soft tissue wounds. Blast/fragment was the most frequent weapon-related injury mechanism followed by gunshot. The most commonly injured body regions were chest and abdomen. Children accounted for 35.3% of all weapon-related injuries. Patients presented at the hospital with weapon-related injuries more than 2 months after the official declaration of ceasefire. A majority of the non-weapon-related, as well as the weapon-related conditions, needed surgery (88.1% and 87.6%, respectively). Few postoperative complications were reported. Conclusions The number of children affected by the fighting seems to be higher in this cohort compared to previous reports. Even several months after the fighting officially ceased, patients with weapon-related injuries were presenting. Everyday illnesses or non-weapon-related injuries dominated. This finding underlines the importance of providing victims of conflicts with surgery for life-threatening conditions, whether weapon related or not.
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| 3. |
- Bengtsson, Martin, et al.
(författare)
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Experimental method for verification of calculated Cs-137 content in nuclear fuel assemblies
- 2022
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Ingår i: Nuclear Technology. - : Informa UK Limited. - 0029-5450 .- 1943-7471. ; 208:2, s. 295-302
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Tidskriftsartikel (refereegranskat)abstract
- A method to determine the absolute activity of 137Cs in irradiated nuclear fuel is presented. Using a well-known point-like calibration source in combination with measurements of the gamma-ray intensity from the nuclear fuel and Monte Carlo calculations based on the nominal measurement geometry, the activity content can be determined without prior knowledge of the intrinsic detection efficiency of the gamma-ray detector. The presented method is tested using measurements of the 137Cs intensity from spent nuclear fuel of the pressurized water type at the central interim storage in Sweden. Using an assumption of homogeneous distribution of 137Cs throughout the fuel, we demonstrate a linear relationship between measured activity and the activity calculated by a state-of-the-art simulation code. For future studies, we suggest some factors that potentially can decrease the uncertainty in the correlation between measured and calculated activity.
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| 4. |
- Bäckström, Fredrik, et al.
(författare)
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Normal range and predictors of serum erythroferrone in infants
- 2023
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Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447. ; 94:3, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Background: Erythroferrone (ERFE) has been identified as a hepcidin-regulating hormone synthetized by erythroblasts correlating to the erythropoietic activity and the needs for iron substrate in bone marrow of adults. The present study aimed to assess the ERFE serum concentrations and its predictors in infants.Methods: ERFE was explored at 4 time points during the first year of life in 45 healthy, breastfed, normal birth weight (NBW) infants, and 136 marginally low birth weight infants (LBW, 2000–2500 g) receiving iron (N = 58) or placebo (N = 78) between 6 weeks and 6 months of age.Results: ERFE concentrations were low at birth, increasing gradually during the first year of life. In NBW infants, reference ranges (5th to 95th percentile) were at 6 weeks <0.005–0.99 ng/mL and at 12 months <0.005–33.7 ng/mL. ERFE was higher in LBW infants at 6 weeks but lower at 12 months compared to NBW and minimally affected by iron supplementation among LBW infants. Correlations of ERFE with erythropoietic and iron status markers were weak and inconsistent.Conclusions: The role of ERFE in the crosstalk of erythropoiesis and iron homeostasis remains unclear in infants and further studies on ERFE in infants and older children are warranted within the framework of the erythropoietin–ERFE–hepcidin axis.Impact: Normal range of erythroferrone in healthy infants is described for the first time. Erythroferrone in infants lacks correlation to iron status and markers of erythropoiesis. The findings indicate differences in infant regulation of iron homeostasis as compared to adults. The findings point to a need to study infant erythropoiesis separately from its adult counterpart. The findings may have clinical impact on management strategies of iron-loading anemia in infancy.
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| 5. |
- Bäckström, Martin, et al.
(författare)
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Five-factor personality inventories have a competence-related higher-order factor due to item phrasing
- 2020
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078.
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Tidskriftsartikel (refereegranskat)abstract
- This research examines whether the items of some of the most well-established five-factor inventories refer to competence. Results reveal that both experts and laymen can distinguish between items that refer to how competently a behavior is performed and items that do not (Study 1). Responses to items that refer to competence create a higher-order factor in the personality inventories (Study 2), and the variability in responses to competence-related items in personality self-ratings is best modeled as a general factor rather than as also tied to the specific Big Five factors (Studies 3 and 4). We suggest that a focused debate on what personality items should refer to is likely to have considerable positive consequences for both theory and measurement of personality.
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| 6. |
- Bäckström, Martin, et al.
(författare)
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Is the General Factor of Personality really related to frequency of agreeable, conscientious, emotionally stable, extraverted, and open behavior? : An experience sampling study
- 2021
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Ingår i: Journal of Individual Differences. - : Hogrefe Publishing Group. - 1614-0001 .- 2151-2299. ; 42:3, s. 148-155
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Tidskriftsartikel (refereegranskat)abstract
- Proponents of the general factor of personality have suggested that it is related to more instances of agreeable, conscientious, emotionally stable, extraverted, and open behavior. We tested this frequency hypothesis by relating the GFP from personality self-ratings to the number of instances of typical Big Five behaviors in real life. For a period of 18 consecutive days, 108 students provided responses to experience sampling items on their mobile phones. The items described concrete behaviors that were rated by experts of the Big Five as typical of either of the five traits and were phrased in a way that made them easy to interpret and respond to. The items were then validated in study 1 and it was found that the behavior correlated with Big Five ratings. In a second study, we tested the hypothesis that GFP is related to a higher frequency of GFP related behavior. The results provided little support for the frequency hypothesis and are more compatible with an interpretation of the GFP in terms of style rather than substance.
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| 7. |
- Bäckström, Martin, et al.
(författare)
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Socially desirable responding in experience sampling : Consequences for personality research
- 2021
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Ingår i: Journal of Individual Differences. - : Hogrefe Publishing Group. - 1614-0001 .- 2151-2299. ; 42:4, s. 157-166
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Tidskriftsartikel (refereegranskat)abstract
- Experience sampling often makes use of items that are similar to personality questionnaire items. Arguably, this opens up for item-popularity effects, where some respondents react to the items' level of evaluative phrasing, causing a separate factor. Gauging the risk of item popularity effects in experience sampling is important since the multifactorial aspect of the responses to the items may cause spurious correlations. We investigate this in one original study and two existing datasets. The results reveal that evaluativeness in experience sampling items creates the same type of problems as in self-rating inventories. We conclude that personality researchers need to be aware that the experience sampling method is not vaccinated against socially desirable responding, and that careful phrasing of items promotes purer personality measures. This allows for more optimal testing of theoretical models of personality, as the fit between data and model will not concern variance in socially desirable responding but in the relevant constructs.
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| 8. |
- Bäckström, Martin, et al.
(författare)
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The NB5I: A full-scale Big-Five inventory with evaluatively neutralized items
- 2023
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Ingår i: European Journal of Psychological Assessment. - : Hogrefe Publishing Group. - 2151-2426 .- 1015-5759. ; 39:2, s. 132-140
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Tidskriftsartikel (refereegranskat)abstract
- Personality is usually measured by means of self-ratings. Despite some drawbacks, the method is here to stay, and improving on it, particularly regarding social desirability, is essential. One way to do this is evaluative neutralization, that is, to rephrase items such that it is less obvious to the respondent what would be a desirable response. We present a 120-item evaluatively neutralized five-factor inventory and compare it to the IPIP-NEO (Goldberg et al., 2006). Psychometric analyses revealed that the new inventory has high factor homogeneity, relatively independent facets with acceptable homogeneity and normally distributed ratings, and relatively evaluatively neutral ratings (as indicated by the level of item popularity). In sum, this new inventory captures the same personality variance as other five-factor inventories but with less influence from individual differences in evaluative responding, resulting in less correlation between factors and a factor structure more in line with the simple structure model than many other five-factor inventories. Evaluatively neutralized inventories should be particularly useful when the factor structure is central to the research question and focuses on discriminant validity, such as identifying theoretically valid relationships between personality traits and other concepts.
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| 9. |
- Bäckström, Martin, et al.
(författare)
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The properties and utility of less evaluative personality scales: Reduction of social desirability; increase of construct and discriminant validity.
- 2020
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 11, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Evaluative neutralization implies rephrasing items such that it is less clear to the respondent what would be a desirable response in the given population. The current research compares evaluatively neutralized scales measuring the FFM model with standard counterparts. Study 1 reveals that evaluatively neutralized scales are less influenced by social desirability. Study 2 estimates higher-order factor models for neutralized vs. standard five-factor scales. In contrast to standard inventories, there was little support for higher-order factors for neutralized scales. Study 3 demonstrates the convergent and discriminant validity for the neutralized scales, e.g., by less inflated correlations to external measures. It is argued that evaluatively neutralized inventories help researchers come to grips with social desirability in personality measurement, and are particularly useful when the factor structure is central to the research question and there is a focus on discriminant validity.
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| 10. |
- Bäckström, Martin, et al.
(författare)
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Why forced-choice and Likert items provide the same information on personality, including social desirability
- 2024
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Ingår i: Educational and Psychological Measurement. - 1552-3888. ; 84:3, s. 549-576
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Tidskriftsartikel (refereegranskat)abstract
- Forced-choice response format is often considered superior to standard Likert format for controlling social desirability in personality inventories. We performed simulations and found that the trait information based on the two formats converges when the number of items is high and forced-choice items are mixed with regard to positively and negatively keyed items. Given that forced-choice items extract the same personality information as Likert items do, including socially desirable responding, other means are needed to counteract social desirability. We propose using evaluatively neutralized items in personality measurement, since they can counteract social desirability regardless of response format.
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