| 1. |
- Ahlbeck Bergendahl, Ida, et al.
(författare)
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Fisk- och skaldjursbestånd i hav och sötvatten 2016 : Resursöversikt
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten omfattar 41 fiskarter uppdelade i olika bestånd, samt sju skal- och blötdjursarter.Nytt för årets upplaga är kapitlet om ekosystemtjänster. Avsnittet beskriver de fördelar människan får genom ekosystemen, till exempel hur fisk och skaldjur kommer till nytta för människan genom föda, rekreation och biologisk mångfald. Nytt för i år är också att rapportens diagram och figurer anpassats för läsare med defekt färgseende.Översikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
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| 2. |
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| 3. |
- Ahlbeck Bergendahl, Ida, et al.
(författare)
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Fisk- och skaldjursbestånd i hav och sötvatten 2017 : Resursöversikt
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten omfattar 41 fiskarter och sju skaldjursarter.Nytt för i år är att vi även beskriver fritidsfisket mer utförligt. Det fisket får allt större betydelse för utvecklingen av många av Sveriges bestånd av fisk- och skaldjur, till exempel sötvattens- och kustlevande arter som abborre, gädda, gös, lax, röding och öring, liksom marina arter som torsk och hummerÖversikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
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| 4. |
- Ayoun Alsoud, Rami, et al.
(författare)
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Combined quantitative tuberculosis biomarker model for time-to-positivity and colony forming unit to support tuberculosis drug development
- 2023
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers are quantifiable characteristics of biological processes. In Mycobacterium tuberculosis, common biomarkers used in clinical drug development are colony forming unit (CFU) and time-to-positivity (TTP) from sputum samples. This analysis aimed to develop a combined quantitative tuberculosis biomarker model for CFU and TTP biomarkers for assessing drug efficacy in early bactericidal activity studies. Daily CFU and TTP observations in 83 previously patients with uncomplicated pulmonary tuberculosis after 7 days of different rifampicin monotherapy treatments (10-40 mg/kg) from the HIGHRIF1 study were included in this analysis. The combined quantitative tuberculosis biomarker model employed the Multistate Tuberculosis Pharmacometric model linked to a rifampicin pharmacokinetic model in order to determine drug exposure-response relationships on three bacterial sub-states using both the CFU and TTP data simultaneously. CFU was predicted from the MTP model and TTP was predicted through a time-to-event approach from the TTP model, which was linked to the MTP model through the transfer of all bacterial sub-states in the MTP model to a one bacterial TTP model. The non-linear CFU-TTP relationship over time was well predicted by the final model. The combined quantitative tuberculosis biomarker model provides an efficient approach for assessing drug efficacy informed by both CFU and TTP data in early bactericidal activity studies and to describe the relationship between CFU and TTP over time.
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| 5. |
- Bengtsson, Andreas, 1991, et al.
(författare)
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Improved Success Probability with Greater Circuit Depth for the Quantum Approximate Optimization Algorithm
- 2020
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Ingår i: Physical Review Applied. - 2331-7019. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Present-day, noisy, small or intermediate-scale quantum processors-although far from fault tolerant-support the execution of heuristic quantum algorithms, which might enable a quantum advantage, for example, when applied to combinatorial optimization problems. On small-scale quantum processors, validations of such algorithms serve as important technology demonstrators. We implement the quantum approximate optimization algorithm on our hardware platform, consisting of two superconducting transmon qubits and one parametrically modulated coupler. We solve small instances of the NP (nondeterministic polynomial time)-complete exact-cover problem, with 96.6% success probability, by iterating the algorithm up to level two.
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| 6. |
- Berntsson, Tommy, et al.
(författare)
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Ambulanssjukvården måste bli jämlik
- 2013
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Ingår i: Helsingborgs Dagblad. - Helsingborg : Helsingborgs Dagblad. - 1103-9388. ; 2013-06-17
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Skiftande vårdkvalité hotar patientsäkerheten inom ambulanssjukvården. Nu måste regeringen och Socialstyrelsen skapa nationella riktlinjer, skriver Nätverket för utbildning av ambulanssjuksköterskor .
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| 7. |
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| 8. |
- Dawson, Andreas, et al.
(författare)
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Effects of Acute Experimental Stress on Pain Sensitivity and Cortisol Levels in Healthy Participants : A Randomized Crossover Pilot Study
- 2020
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Ingår i: Journal of oral & facial pain and headache. - : Quintessence publishing co inc. - 2333-0384. ; 34:3, s. 281-290
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate pain sensitivity in the masseter muscle and index finger in response to acute psychologic stress in healthy participants. Methods: Fifteen healthy women (23.7 +/- 2.3 years) participated in two randomized sessions: in the experimental stress session, the Paced Auditory Serial Addition Task (PASAT) was used to induce acute stress, and in the control session, a control task was performed. Salivary cortisol, perceived stress levels, electrical and pressure pain thresholds (PTs), and pain tolerance levels (PTLs) were measured at baseline and after each task. Mixed-model analysis was used to test for significant interaction effects between time and session. Results: An interaction effect between time and session occurred for perceived stress levels (P < .001); perceived stress was significantly higher after the experimental task than after the control task (P < .01). No interaction effects occurred for salivary cortisol levels, electrical PTs, or pressure PTLs. Although significant interactions did occur for electrical PTL (P < .05) and pressure PT (P < .001), the simple effects test could not identify significant differences between sessions at any time point. Conclusion: The PASAT evoked significant levels of perceived stress; however, pain sensitivity to mechanical or electrical stimuli was not significantly altered in response to the stress task, and the salivary cortisol levels were not altered in response to the PASAT. These results must be interpreted with caution, and more studies with larger study samples are needed to increase the clinical relevant understanding of the pain mechanisms and psychologic stress.
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| 9. |
- de Man Lapidoth, Julia, et al.
(författare)
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Trends in renal function in Northern Sweden 1986-2014 : data from the seven cross-sectional surveys within the Northern Sweden MONICA study
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The prevalence of chronic kidney disease (CKD) is increasing globally, and CKD is closely related to cardiovascular disease (CVD). CKD and CVD share several risk factors (RF), such as diabetes, hypertension, obesity and smoking, and the prevalence of these RF has changed during the last decades, and we aimed to study the effect on renal function over time.Design: Repeated cross-sectional population-based studies.Setting: The two Northern counties (Norr- and Vasterbotten) in Sweden.Participants: Within the MONitoring Trends and Determinants of CArdiovascular Disease (MONICA) study, seven surveys were performed between 1986 and 2014, including participants aged 25-64 years (n=10 185).Interventions: None.Measures: Information on anthropometry, blood pressure and cardiovascular risk factors was collected. Creatinine and cystatin C were analysed in stored blood samples and the estimated glomerular filtration rate (eGFR) calculated using the creatinine-based Lund-Malmo revised and Chronic Kidney Disease Epidemiology Collaboration (eGFR(crea)) equations as well as the cystatin C-based Caucasian, Asian, Paediatric and Adult cohort (CAPA) equation (eGFR(cysC)). Renal function over time was analysed using univariable and multivariable linear regression models.Results: Renal function, both eGFR(crea) and eGFR(cysC), decreased over time (both p<0.001) and differed between counties and sexes. In a multivariable analysis, study year remained inversely associated with both eGFR(crea) and eGFR(cysC) (both p<0.001) after adjustment for classical cardiovascular RF.Conclusion: Renal function has deteriorated in Northern Sweden between 1986 and 2014.
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| 10. |
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| 11. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 12. |
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| 13. |
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| 14. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 15. |
- Otten, Julia, 1973-, et al.
(författare)
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A heterogeneous response of liver and skeletal muscle fat to the combination of a Paleolithic diet and exercise in obese individuals with type 2 diabetes : a randomised controlled trial
- 2018
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 61:7, s. 1548-1559
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: The aim of the study was to investigate ectopic fat deposition and insulin sensitivity, in a parallel single-blinded randomised controlled trial, comparing Paleolithic diet alone with the combination of Paleolithic diet and exercise in individuals with type 2 diabetes. Methods: Thirty-two individuals with type 2 diabetes with BMI 25-40 kg/m(2) and 30-70 years of age followed a Paleolithic diet ad libitum for 12 weeks. In addition, study participants were randomised by computer program to either supervised combined exercise training (PD-EX group) or standard care exercise recommendations (PD group). Staff performing examinations and assessing outcomes were blinded to group assignment. Thirteen participants were analysed in each group: hepatic and peripheral insulin sensitivity were measured using the hyperinsulinaemic-euglycaemic clamp technique combined with [6,6-H-2(2)]glucose infusion, and liver fat was assessed by proton magnetic resonance spectroscopy; both analyses were secondary endpoints. Intramyocellular lipid (IMCL) content was measured by magnetic resonance spectroscopy as a secondary analysis. All examinations were performed at Umca University Hospital, Umca, Sweden. Results: Both study groups showed a median body weight loss of 7 kg. Fat mass decreased by 5.7 kg in the PD group and by 6.5 kg in the PD-EX group. Maximum oxygen uptake increased in the PD-EX group only. Liver fat showed a consistent reduction (74% decrease) in the PD group, while the response in the PD-EX group was heterogeneous (p < 0.05 for the difference between groups). IMCL content of the soleus muscle decreased by 40% in the PD group and by 22% in the PD-EX group (p < 0.05 for the difference between groups). Both groups improved their peripheral and adipose tissue insulin sensitivity, but not their hepatic insulin sensitivity. Plasma fetuin-A decreased by 11% in the PD group (p < 0.05) and remained unchanged in the PD-EX group. Liver fat changes during the intervention were correlated with changes in fetuin-A (r(S) = 0.63, p < 0.01). Participants did not report any important adverse events caused by the intervention. Conclusions/interpretation: A Paleolithic diet reduced liver fat and IMCL content, while there was a tissue-specific heterogeneous response to added exercise training.
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| 16. |
- Otten, Julia, 1973-, et al.
(författare)
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Benefits of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control : a randomized controlled trial in individuals with type 2 diabetes
- 2017
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Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 33:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMeans to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed.MethodsThirty-two patients with type 2 diabetes (age 59 ± 8 years) followed a Paleolithic diet for 12 weeks. Participants were randomized to either standard care exercise recommendations (PD) or 1-h supervised exercise sessions (aerobic exercise and resistance training) three times per week (PD-EX).ResultsFor the within group analyses, fat mass decreased by 5.7 kg (IQR: −6.6, −4.1; p < 0.001) in the PD group and by 6.7 kg (−8.2, −5.3; p < 0.001) in the PD-EX group. Insulin sensitivity (HOMA-IR) improved by 45% in the PD (p < 0.001) and PD-EX (p < 0.001) groups. HbA1c decreased by 0.9% (−1.2, −0.6; p < 0.001) in the PD group and 1.1% (−1.7, −0.7; p < 0.01) in the PD-EX group. Leptin decreased by 62% (p < 0.001) in the PD group and 42% (p < 0.001) in the PD-EX group. Maximum oxygen uptake increased by 0.2 L/min (0.0, 0.3) in the PD-EX group, and remained unchanged in the PD group (p < 0.01 for the difference between intervention groups). Male participants decreased lean mass by 2.6 kg (−3.6, −1.3) in the PD group and by 1.2 kg (−1.3, 1.0) in the PD-EX group (p < 0.05 for the difference between intervention groups).ConclusionsA Paleolithic diet improves fat mass and metabolic balance including insulin sensitivity, glycemic control, and leptin in subjects with type 2 diabetes. Supervised exercise training may not enhance the effects on these outcomes, but preserves lean mass in men and increases cardiovascular fitness.
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Svensson, Elin M., 1985-, et al.
(författare)
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The Potential for Treatment Shortening With Higher Rifampicin Doses : Relating Drug Exposure to Treatment Response in Patients With Pulmonary Tuberculosis
- 2018
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Ingår i: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 67:1, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- Background. Tuberculosis remains a huge public health problem and the prolonged treatment duration obstructs effective tuberculosis control. Higher rifampicin doses have been associated with better bactericidal activity, but optimal dosing is uncertain. This analysis aimed to characterize the relationship between rifampicin plasma exposure and treatment response over 6 months in a recent study investigating the potential for treatment shortening with high-dose rifampicin. Methods. Data were analyzed from 336 patients with pulmonary tuberculosis (97 with pharmacokinetic data) treated with rifampicin doses of 10, 20, or 35 mg/kg. The response measure was time to stable sputum culture conversion (TSCC). We derived individual exposure metrics with a previously developed population pharmacokinetic model of rifampicin. TSCC was modeled using a parametric time-to-event approach, and a sequential exposure-response analysis was performed. Results. Higher rifampicin exposures increased the probability of early culture conversion. No maximal limit of the effect was detected within the observed range. The expected proportion of patients with stable culture conversion on liquid medium at week 8 was predicted to increase from 39% (95% confidence interval, 37%-41%) to 55% (49%-61%), with the rifampicin area under the curve increasing from 20 to 175 mg/L.h (representative for 10 and 35 mg/kg, respectively). Other predictors of TSCC were baseline bacterial load, proportion of culture results unavailable, and substitution of ethambutol for either moxifloxacin or SQ109. Conclusions. Increasing rifampicin exposure shortened TSCC, and the effect did not plateau, indicating that doses >35 mg/kg could be yet more effective. Optimizing rifampicin dosage while preventing toxicity is a clinical priority.
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| 22. |
- Svensson, Madeleine, 1983-, et al.
(författare)
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The effect of reminders in a web-based intervention study
- 2012
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Ingår i: European Journal of Epidemiology. - Dordrecht : Springer Netherlands. - 0393-2990 .- 1573-7284. ; 27:5, s. 333-340
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge on effective strategies to encourage participation in epidemiological web-based research is scant. We studied the effects of reminders on overall participation. 3,876 employees were e-mailed a baseline web-based lifestyle questionnaire. Nine months later, a follow-up questionnaire was sent. To encourage study participation, 4–5 and 11 e-mail reminders were sent at baseline and follow-up, respectively. Additional reminders (media articles, flyers, SMS etc) were also administered. Reminders (e-mails + additional) were given in low (≤6 reminders), medium (7–9 reminders) or high amounts (>9 reminders). Participation was examined with respect to participant characteristics (i.e. age, sex, Body Mass Index, occupation), type/number of reminders, and time of participation. Most participants were males, 35–49 years, and field workers (non-office based). About 29 % responded before any e-mail reminder, following 26 and 45 % after 1 respective ≥ 2 e-mail reminders. Participant characteristics were not related to when the participants responded. The 4–5 e-mail reminders increased total response rate by 15 %, the eleven by 21 % (greatest increases in September). Those receiving medium amounts of reminders (reference) had the highest response rate (75 %), likewise office workers (54 %) compared to field workers (33 %). High amounts of reminders were particularly effective on office workers. The participants’ characteristics were not related to when they responded in this web-based study. Frequent reminders were effective on response rates, especially for those with high Internet availability. The highest increases in response rates were found in September. © The Author(s) 2012.
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| 23. |
- Svensson, Robin J., et al.
(författare)
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Greater Early Bactericidal Activity at Higher Rifampicin Doses Revealed by Modeling and Clinical Trial Simulations
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 218:6, s. 991-999
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Tidskriftsartikel (refereegranskat)abstract
- Background. The currently recommended rifampicin dose (10 mg/kg) for treating tuberculosis is suboptimal. The PanACEA HIGHRIF1 trial evaluated the pharmacokinetics and early bactericidal activity of rifampicin doses of up to 40 mg/kg. Conventional statistical analyses revealed no significant exposure-response relationship. Our objectives were to explore the exposure-response relationship for high-dose rifampicin by using pharmacokinetic-pharmacodynamic modeling and to predict the early bactericidal activity of 50 mg/kg rifampicin.Methods. Data included time to Mycobacterium tuberculosis positivity of liquid cultures of sputum specimens from 83 patients with tuberculosis who were treated with 10 mg/kg rifampicin (n = 8; reference arm) or 20, 25, 30, 35, or 40 mg/kg rifampicin (n = 15/arm) for 7 days. We used a semimechanistic time-to-event approach to model the time-to-positivity data. Rifampicin exposure and baseline time to culture positivity were explored as covariates.Results. The baseline time to culture positivity was a significant covariate on the predicted initial bacterial load, and rifampicin exposure was a significant covariate on the bacterial kill rate in sputum resulting in increased early bactericidal activity. The 90% prediction interval for the predicted median day 7 increase in time to positivity for 50 mg/kg rifampicin was 7.25-10.3 days.Conclusions. A significant exposure-response relationship was found between rifampicin exposure and early bactericidal activity. Clinical trial simulations showed greater early bactericidal activity for 50 mg/kg rifampicin.
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| 24. |
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| 25. |
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| 26. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 27. |
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| 28. |
- Abdelwahab, Mahmoud Tareq, et al.
(författare)
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Clofazimine pharmacokinetics in patients with TB : dosing implications
- 2020
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 75:11, s. 3269-3277
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clofazimine is in widespread use as a key component of drug-resistant TB regimens, but the recommended dose is not evidence based. Pharmacokinetic data from relevant patient populations are needed to inform dose optimization. Objectives: To determine clofazimine exposure, evaluate covariate effects on variability, and simulate exposures for different dosing strategies in South African TB patients. Patients and methods: Clinical and pharmacokinetic data were obtained from participants with pulmonary TB enrolled in two studies with intensive and sparse sampling for up to 6 months. Plasma concentrations were measured by LC-MS/MS and interpreted with non-Linear mixed-effects modelling. Body size descriptors and other potential covariates were tested on pharmacokinetic parameters. We simulated different dosing regimens to safely shorten time to average daily concentration above a putative target concentration of 0.25 mg/L. Results: We analysed 1570 clofazimine concentrations from 139 participants; 79 (57%) had drug-resistant TB and 54 (39%) were HIV infected. Clofazimine pharmacokinetics were well characterized by a three-compartment model. Clearance was 11.5 L/h and peripheral volume 10500 L for a typical participant. Lower plasma exposures were observed in women during the first few months of treatment, explained by higher body fat fraction. Model-based simulations estimated that a Loading dose of 200 mg daily for 2 weeks would achieve average daily concentrations above a target efficacy concentration 37 days earlier in a typical TB participant. Conclusions: Clofazimine was widely distributed with a Long elimination half-Life. Disposition was strongly influenced by body fat content, with potential dosing implications for women with TB.
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| 29. |
- Abdelwahab, Mahmoud Tareq, et al.
(författare)
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Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis
- 2021
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:7
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Tidskriftsartikel (refereegranskat)abstract
- Clofazimine is classified as a WHO group B drug for the treatment of rifampin-resistant tuberculosis. QT prolongation, which is associated with fatal cardiac arrhythmias, is caused by several antitubercular drugs, including clofazimine, but there are no data quantifying the effect of clofazimine concentration on QT prolongation. Our objective was to describe the effect of clofazimine exposure on QT prolongation. Fifteen adults drug-susceptible tuberculosis patients received clofazimine monotherapy as 300mg daily for 3 days, followed by 100mg daily in one arm of a 2-week, multiarm early bactericidal activity trial in South Africa. Pretreatment Fridericia-corrected QT (QTcF) (105 patients, 524 electrocardiograms [ECGs]) and QTcFs from the clofazimine monotherapy arm matched with clofazimine plasma concentrations (199 ECGs) were interpreted with a nonlinear mixed-effects model. Clofazimine was associated with significant QT prolongation described by a maximum effect (Emax) function. We predicted clofazimine exposures using 100-mg daily doses and 2 weeks of loading with 200 and 300mg daily, respectively. The expected proportions of patients with QTcF change from baseline above 30 ms (DQTcF. 30) were 2.52%, 11.6%, and 23.0% for 100-, 200-, and 300-mg daily doses, respectively. At steady state, the expected proportion with Delta QTcF of >30 ms was 23.7% and with absolute QTcF of >450 ms was 3.42% for all simulated regimens. The use of loading doses of 200 and 300mg is not predicted to expose patients to an increased risk of QT prolongation, compared with the current standard treatment, and is, therefore, an alternative option for more quickly achieving therapeutic concentrations.
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| 30. |
- Abulfathi, Ahmed Aliyu, et al.
(författare)
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Clinical Pharmacokinetics and Pharmacodynamics of Rifampicin in Human Tuberculosis
- 2019
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Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 58:9, s. 1103-1129
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Forskningsöversikt (refereegranskat)abstract
- The introduction of rifampicin (rifampin) into tuberculosis (TB) treatment five decades ago was critical for shortening the treatment duration for patients with pulmonary TB to 6months when combined with pyrazinamide in the first 2months. Resistance or hypersensitivity to rifampicin effectively condemns a patient to prolonged, less effective, more toxic, and expensive regimens. Because of cost and fears of toxicity, rifampicin was introduced at an oral daily dose of 600mg (8-12mg/kg body weight). At this dose, clinical trials in 1970s found cure rates of >= 95% and relapse rates of < 5%. However, recent papers report lower cure rates that might be the consequence of increased emergence of resistance. Several lines of evidence suggest that higher rifampicin doses, if tolerated and safe, could shorten treatment duration even further. We conducted a narrative review of rifampicin pharmacokinetics and pharmacodynamics in adults across a range of doses and highlight variables that influence its pharmacokinetics/pharmacodynamics. Rifampicin exposure has considerable inter- and intra-individual variability that could be reduced by administration during fasting. Several factors including malnutrition, HIV infection, diabetes mellitus, dose size, pharmacogenetic polymorphisms, hepatic cirrhosis, and substandard medicinal products alter rifampicin exposure and/or efficacy. Renal impairment has no influence on rifampicin pharmacokinetics when dosed at 600mg. Rifampicin maximum (peak) concentration (C-max) > 8.2 mu g/mL is an independent predictor of sterilizing activity and therapeutic drug monitoring at 2, 4, and 6h post-dose may aid in optimizing dosing to achieve the recommended rifampicin concentration of >= 8 mu g/mL. A higher rifampicin C-max is required for severe forms TB such as TB meningitis, with C-max >= 22 mu g/mL and area under the concentration-time curve (AUC) from time zero to 6h (AUC(6)) >= 70 mu g.h/mL associated with reduced mortality. More studies are needed to confirm whether doses achieving exposures higher than the current standard dosage could translate into faster sputum conversion, higher cure rates, lower relapse rates, and less mortality. It is encouraging that daily rifampicin doses up to 35mg/kg were found to be safe and well-tolerated over a period of 12weeks. High-dose rifampicin should thus be considered in future studies when constructing potentially shorter regimens. The studies should be adequately powered to determine treatment outcomes and should include surrogate markers of efficacy such as C-max/MIC (minimum inhibitory concentration) and AUC/MIC.
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| 31. |
- Abulfathi, Ahmed A., et al.
(författare)
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Probability of mycobactericidal activity of para-aminosalicylic acid with novel dosing regimens
- 2020
-
Ingår i: European Journal of Clinical Pharmacology. - : Springer Nature. - 0031-6970 .- 1432-1041. ; 76:11, s. 1557-1565
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Para-aminosalicylic acid (PAS) is currently one of the add-on group C medicines recommended by the World Health Organization for multidrug-resistant tuberculosis treatment. At the recommended doses (8-12 g per day in two to three divided doses) of the widely available slow-release PAS formulation, studies suggest PAS exposures are lower than those reached with older PAS salt formulations and do not generate bactericidal activity. Understanding the PASER dose-exposure-response relationship is crucial for dose optimization. The objective of our study was to establish a representative population pharmacokinetics model for PASER and evaluate the probability of bactericidal and bacteriostatic target attainment with different dosing regimens.Methods To this end, we validated and optimized a previously published population pharmacokinetic model on an extended dataset. The probability of target attainment was evaluated for once-daily doses of 12 g, 14 g, 16 g and 20 g PASER. Results The final optimized model included the addition of variability in bioavailability and allometric scaling with body weight on disposition parameters. Peak PAS concentrations over minimum inhibitory concentration of 100, which is required for bactericidal activity are achieved in 53%, 65%, 72% and 84% of patients administered 12, 14, 16 and 20 g once-daily PASER, respectively, when MIC is 1 mg/L. For the typical individual, the exposure remained above 1 mg/L for >= 98% of the dosing interval in all the evaluated PASER regimens.Conclusion The pharmacokinetic/pharmacodynamic parameters linked to bactericidal activity should be determined for 14 g, 16 g and 20 g once-daily doses of PASER.
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| 32. |
- Abulfathi, Ahmed A., et al.
(författare)
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The pharmacokinetics of para-aminosalicylic acid and its relationship to efficacy and intolerance
- 2020
-
Ingår i: British Journal of Clinical Pharmacology. - : WILEY. - 0306-5251 .- 1365-2125. ; 86:11, s. 2123-2132
-
Forskningsöversikt (refereegranskat)abstract
- Following its introduction as an antituberculosis agent close to 75 years ago, the use of para-aminosalicylic acid (PAS) has been limited by gastrointestinal intolerance and multiple formulations were produced in attempts to reduce its occurrence. More recently, an enteric-coated, granular, slow-release PAS formulation (PASER) was introduced and is now in wide-spread use for the treatment of drug-resistant tuberculosis. The current PASER dosing regimen is based on recommendations derived from older studies using a variety of different PAS formulations and relegate PAS to a role as an exclusively bacteriostatic agent. However, there is ample evidence that if sufficiently high serum concentrations are reached, PAS can be bactericidal and that intolerance following once daily dosing, that aids the achievement of such concentrations, is no worse than that following intermittent daily dosing. In particular, prevention of resistance to companion drugs appears to be dependent on the size of the single dose, and hence the peak concentrations, and not on maintaining serum levels consistently above minimum inhibitory concentration. We present a narrative review of the development of PAS formulations, dosing practices, and published data regarding pharmacokinetics and pharmacodynamics and the relationship of PAS dosage to intolerance and efficacy. Our conclusions suggests that we are at present not using PAS to its maximum ability to contribute to regimen efficacy and protect companion drugs.
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| 33. |
- Abulfathi, Ahmed A., et al.
(författare)
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The Population Pharmacokinetics of Meropenem in Adult Patients With Rifampicin-Sensitive Pulmonary Tuberculosis
- 2021
-
Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Meropenem is being investigated for repurposing as an anti-tuberculosis drug. This study aimed to develop a meropenem population pharmacokinetics model in patients with pulmonary tuberculosis and identify covariates explaining inter-individual variability.Methods: Patients were randomized to one of four treatment groups: meropenem 2 g three times daily plus oral rifampicin 20 mg/kg once daily, meropenem 2 g three times daily, meropenem 1 g three times daily, and meropenem 3 g once daily. Meropenem was administered by intravenous infusion over 0.5-1 h. All patients also received oral amoxicillin/clavulanate together with each meropenem dose, and treatments continued daily for 14 days. Intensive plasma pharmacokinetics sampling over 8 h was conducted on the 14th day of the study. Nonlinear mixed-effects modeling was used for data analysis. The best model was chosen based on likelihood metrics, goodness-of-fit plots, and parsimony. Covariates were tested stepwise.Results: A total of 404 concentration measurements from 49 patients were included in the analysis. A two-compartment model parameterized with clearance (CL), inter-compartmental clearance (Q), and central (V1) and peripheral (V2) volumes of distribution fitted the data well. Typical values of CL, Q, V1, and V2 were 11.8 L/h, 3.26 L/h, 14.2 L, and 3.12 L, respectively. The relative standard errors of the parameter estimates ranged from 3.8 to 35.4%. The covariate relations included in the final model were creatinine clearance on CL and allometric scaling with body weight on all disposition parameters. An effect of age on CL as previously reported could not be identified.Conclusion: A two-compartment model described meropenem population pharmacokinetics in patients with pulmonary tuberculosis well. Covariates found to improve model fit were creatinine clearance and body weight but not rifampicin treatment. The final model will be used for an integrated pharmacokinetics/pharmacodynamics analysis linking meropenem exposure to early bactericidal activity.
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| 34. |
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| 35. |
- Ahlberg, Erik, et al.
(författare)
-
"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 36. |
- Ahlinder, Jon, et al.
(författare)
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Increased knowledge of Francisella genus diversity highlights the benefits of optimised DNA-based assays
- 2012
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Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 12, s. 220-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent advances in sequencing technologies offer promising tools for generating large numbers of genomes, larger typing databases and improved mapping of environmental bacterial diversity. However, DNA-based methods for the detection of Francisella were developed with limited knowledge about genetic diversity. This, together with the high sequence identity between several Francisella species, means there is a high risk of false identification and detection of the highly virulent pathogen Francisella tularensis. Moreover, phylogenetic reconstructions using single or limited numbers of marker sequences often result in incorrect tree topologies and inferred evolutionary distances. The recent growth in publicly accessible whole-genome sequences now allows evaluation of published genetic markers to determine optimal combinations of markers that minimise both time and laboratory costs. Results: In the present study, we evaluated 38 previously published DNA markers and the corresponding PCR primers against 42 genomes representing the currently known diversity of the genus Francisella. The results highlight that PCR assays for Francisella tularensis are often complicated by low specificity, resulting in a high probability of false positives. A method to select a set of one to seven markers for obtaining optimal phylogenetic resolution or diagnostic accuracy is presented. Conclusions: Current multiple-locus sequence-typing systems and detection assays of Francisella, could be improved by redesigning some of the primers and reselecting typing markers. The use of only a few optimally selected sequence-typing markers allows construction of phylogenetic topologies with almost the same accuracy as topologies based on whole-genome sequences.
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| 37. |
- Aidoukovitch, Alexandra, et al.
(författare)
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Strontium chloride promotes cell proliferation in a human osteoblast cell line
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Strontium ranelate (SrRan) is the active component of drugs currently used for reducing the risk of fractures in patients suffering from osteoporosis. Despite extensive use, the underlying mechanisms of action of Sr2+ are not fully understood. In the present study, we assess the impact of SrCl2 on human osteoblast activity and proliferation. Cultures of the human osteoblast-like cell line MG63 were treated for 72 h in presence of 0.1 mM, 1 mM, 5 mM and 10 mM SrCl2 or vehicle, used in control groups. Cells were counted manually using a Bürker chamber. Total protein content was determined by colorimetric analysis performed by a microplate reader using Bio-Rad protein assay. Alkaline phosphatase (ALP) activity was determined enzymatically and normalized to total protein content in each sample. Cell viability was assessed using the MTT assay. Treatment with 5 mM SrCl2 for 72 h enhanced total MG63 cell protein content by 37% compared to controls (p<0.01). A lower concentration (0.1 mM) of SrCl2 had no effect on total protein. Incubation with 5 mM SrCl2 for 72 h increased MG63 cell number by 38% compared to controls (p<0.001). The SrCl2-induced increase in cell number was associated with enhanced (+14% compared to controls, p<0.05) cell viability. Treatment with a higher concentration (10 mM) of SrCl2 enhanced cell number similar to 5 mM SrCl2 (+54% compared to controls, p<0.05). Treatment with 0.1 or 5 mM SrCl2 for 72 h had no effect (p>0.05) on MG63 cell ALP activity, while 1 mM SrCl2 reduced ALP activity as well as total protein content by about 25% compared to controls (p<0.05). The current results demonstrate that treatment with SrCl2 for 72 h, at concentrations higher than 1 mM promotes cell proliferation in human osteoblast-like cells, suggesting that Sr2+ may enhance bone formation through this mechanism.
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| 38. |
- Alsterholm, Mikael, 1977, et al.
(författare)
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Establishment and utility of SwedAD : a nationwide Swedish registry for patients with atopic dermatitis receiving systemic pharmacotherapy
- 2023
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 103
-
Tidskriftsartikel (refereegranskat)abstract
- SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.
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| 39. |
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| 40. |
- Andersson, Henrik, et al.
(författare)
-
Ethics education to support ethical competence learning in healthcare : an integrative systematic review
- 2022
-
Ingår i: BMC Medical Ethics. - : BioMed Central. - 1472-6939. ; 23
-
Forskningsöversikt (refereegranskat)abstract
- Background: Ethical problems in everyday healthcare work emerge for many reasons and constitute threats to ethi- cal values. If these threats are not managed appropriately, there is a risk that the patient may be inflicted with moral harm or injury, while healthcare professionals are at risk of feeling moral distress. Therefore, it is essential to support the learning and development of ethical competencies among healthcare professionals and students. The aim of this study was to explore the available literature regarding ethics education that promotes ethical competence learning for healthcare professionals and students undergoing training in healthcare professions.Methods: In this integrative systematic review, literature was searched within the PubMed, CINAHL, and PsycInfo databases using the search terms ‘health personnel’, ‘students’, ‘ethics’, ‘moral’, ‘simulation’, and ‘teaching’. In total, 40 arti- cles were selected for review. These articles included professionals from various healthcare professions and students who trained in these professions as subjects. The articles described participation in various forms of ethics education. Data were extracted and synthesised using thematic analysis.Results: The review identified the need for support to make ethical competence learning possible, which in the long run was considered to promote the ability to manage ethical problems. Ethical competence learning was found to be helpful to healthcare professionals and students in drawing attention to ethical problems that they were not previ- ously aware of. Dealing with ethical problems is primarily about reasoning about what is right and in the patient’s best interests, along with making decisions about what needs to be done in a specific situation.Conclusions: The review identified different designs and course content for ethics education to support ethical competence learning. The findings could be used to develop healthcare professionals’ and students’ readiness and capabilities to recognise as well as to respond appropriately to ethically problematic work situations.
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| 41. |
- Andersson, Jan, et al.
(författare)
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Utslagen fiskrekrytering och sviktande fiskbestånd i Kalmar läns kustvatten
- 2000
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Undersökningar gjorda 1994-1997 i ett antal områden i Kalmarsund visade minskande bestånd av främst gädda och abborre samt en låg årsyngelproduktion vid jämförelse med tidigare studier. Observationerna stöddes av rapporter från fiskare och allmänhet och uppfattades så allvarliga, att ett tvåårigt forskningsprojekt beslutades genomföras för att dels dokumentera skadornas karaktär och geografiska utbredning, dels analyserade bakomliggande orsakerna. Projektet, som pågick under 1998-1999, omfattade ett flertal områden efter Kalmarsunds fastlandskust, ett område öster om Öland, samt några referensområden norr om sundet och ett söder därom. Inventerande provfisken och årsyngelundersökningar gjordes för att kartlägga fisksamhällets sammansättning och rekryteringen till de vuxna bestånden. Trålningar genomfördes under abborrens kläckningsperiod för att mäta tätheten av fisklarver samt undersöka deras överlevnad och tillväxt. I samband med detta gjordes insamlingar av djurplankton för att kartlägga larvernas födounderlag. Fält- och laboratorieexperiment genomfördes för att studera romutveckling, kläckning och larvöverlevnad hos gädda och abborre. Som stöd vid tolkningarna av resultaten inhämtades vattenkemiska data från den samordnade kustvattenkontrollen i Kalmar län.Tätheten av främst vuxen abborre men även gädda var mycket låg i området mellan Emån och Revsudden i sundets mitt och andelen gamla fiskar var stor. Även längre ner mot länsgränsen fanns tecken på att bestånden var negativt påverkade. På lokalen vid östra Öland var tätheterna likaså mycket låga. Inventeringen av årsyngel gav en ännu mer negativ bild. Bara ett fåtal yngel av abborre och gädda fångades i hela Kalmarsundsområdet. Även yngel av karpfiskar,strömming och stubbar förekom i lågatätheter. Något påverkade alltså fiskrekryteringen så negativt, att även de vuxna bestånden av flertalet arter reducerats. Det strandnära yngel- och småfisksamhället dominerades av spiggar, vilka förekom i högre tätheter än i referensområdena. Resultaten från de lokaler som besökts vid upprepade tillfällen visade att skadorna förvärrats med tiden.Vattenkemiska data visade, att högsalt- eller ammoniumhalt knappast kunde vara en tänkbar förklaring till den uteblivna rekryteringen. Ammoniumhalterna når inte skadliga nivåer i rekryteringsområdena, och salthalten har minskat i stället för ökat i kustområdet under de senaste 10 åren. Såväl fält- som laboratorieexperimenten gav resultat som talar emot en toxisk påverkan på föräldrafiskar eller ägg och larver. Befruktningsgrad, kläckning och larvöverlevnad vartill synes normala. Undersökning av snäckor från de områden där kläckningsförsök och rekryteringsstudier genomfördes, visade att det åtminstone detta år inte förekom larver eller cerkarier ögonsugmasken Diplostomum sp. under den känsliga period då fisklarver kan dödas av parasitangrepp. Eutrofiering har förts fram som en tänkbar orsak till den sviktande fiskrekryteringen. Närsaltsdata visar att området är övergött, och en förändrad kväve/fosforkvot antyder att primärproduktionen blivit alltmer kvävebegränsad under produktionsperioden senare år.Eutrofieringen yttrar sig som en ökning av primärproduktionen. Halterna klorofyll-a har tenderat att öka i de kustnära vattnen och bedöms som höga enligt Naturvårdsverkets bedömningsgrunder för miljökvalitet, Kust och Hav (1999). Under de senaste 4-5 åren har halterna emellertid sjunkit, vilket kan kopplas till ökat siktdjup. Utvecklingen indikerar att en större del av primärproduktionen under senare år sker i det bentiska växtsamhället. Denna utveckling ses inte i referensområdena. Även om en rik bottenvegetation normalt är positivt för fisk, kan alltför kraftig algpåväxt ha flera negativa effekter, t ex att leksubstraten försämras. En förskjutning av produktionen från pelagiska mikroalger till det bentiska systemet kan också innebära att fiskens födotillgång påverkas. Analyserna av zooplanktonproven visade tydliga avvikelser jämfört med referensmaterialen, såväl vad avser artsammansättning som täthet, och indikerar att födounderlaget försämrats för pelagiska fisklarver, t ex abborre, strömming och stubbar.Utsläppen från Mönsterås Bruk har också ansetts utgöra en möjlig förklaring. Om skadorna på fisk beror på eutrofiering, kan effekterna av brukets utsläpp ses som ett bidrag bland andra till den antropogena belastningen i området. Risken för att toxiska eller hormonellt störande ämnen i avloppsvattnet påverkat fisken måste enligt resultaten från fält och laboratorieexperimenten bedömas vara liten.Kalmarsund hyser landets tätaste skarvkolonier. Teoretiska beräkningar, baserat på uppskattningar av skarvbeståndets storlek, visar att dess konsumtion skulle kunna uppgå till den totala produktionen av stationär fisk i området vilket kan vara en viktig förklaring till de minskande tätheterna. Det finns dock observationer som talar mot skarven som den enda bakomliggande faktorn. Årsyngel utnyttjas normalt inte som föda av skarvarna, och rekryteringen försämrades inte bara för de stationära arterna abborre och gädda, utan även för stubbar och sillar vars vuxna bestånd inte påverkas lika starkt av skarv. Modellsimuleringar visar dock, att i dagens situation kan skarvpredationen effektivt motverka att bestånden återhämtar sig när, förhoppningsvis, rekryteringen åter börjar bli normal.
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| 42. |
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| 43. |
- Andersson Lassila, Andreas, et al.
(författare)
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Numerical evaluation of cutting strategies for thin-walled parts
- 2024
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Static form errors due to in-process deflections is a major concern in flank milling of thin-walled parts. To increase both productivity and part geometric accuracy, there is a need to predict and control these form errors. In this work, a modelling framework for prediction of the cutting force-induced form errors, or thickness errors, during flank milling of a thin-walled workpiece is proposed. The modelled workpiece geometry is continuously updated to account for material removal and the reduced stiffness matrix is calculated for nodes in the engagement zone. The proposed modelling framework is able to predict the resulting thickness errors for a thin-walled plate which is cut on both sides. Several cutting strategies and cut patterns using constant z-level finishing are studied. The modelling framework is used to investigate the effect of different cut patterns, machining allowance, cutting tools and cutting parameters on the resulting thickness errors. The framework is experimentally validated for various cutting sequences and cutting parameters. The predicted thickness errors closely correspond to the experimental results. It is shown from numerical evaluations that the selection of an appropriate cut pattern is crucial in order to reduce the thickness error. Furthermore, it is shown that an increased machining allowance gives a decreased thickness error for thin-walled plates.
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| 44. |
- Andersson, My, et al.
(författare)
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Optogenetic control of human neurons in organotypic brain cultures
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies.
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| 45. |
- Andersson, Tobias, et al.
(författare)
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3D-Simulation of Heat Flow in Indexable Drilling
- 2023
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Ingår i: Key Engineering Materials. - : Scientific.Net. - 1013-9826 .- 1662-9795. ; 955, s. 53-62
-
Tidskriftsartikel (refereegranskat)abstract
- In machining, the heat flow into the workpiece during the cutting process is often a major concern. The temperature rise can lead to substantial residual stresses or elastic in-process deformations which may result in the dimensional tolerance requirements being violated. In the present study a modelling strategy is developed for determination of the heat load during indexable drilling. The heat load on the workpiece is determined from 3D thermomechanical Coupled Eulerian Lagrangian analyses of orthogonal turning for various chip thicknesses and cutting speeds. The determined heat load is then transferred to a 3D transient heat transfer analysis of the indexable drilling process for the determination of the temperature field. Thereby, this modelling technique avoids the complex cutting process that is performed in real cutting simulations and thereby reducing the computational complexity of the problem considerably. The simulated temperatures are compared with experimentally measured temperatures and some conclusions are drawn regarding the modelling approach.
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| 46. |
- Andersson, Tobias, et al.
(författare)
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Modelling and simulation of heat flow in indexable insert drilling
- 2024
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Ingår i: The International Journal of Advanced Manufacturing Technology. - : Springer Nature. - 0268-3768 .- 1433-3015. ; 131:9-10, s. 5177-5192
-
Tidskriftsartikel (refereegranskat)abstract
- In machining, the heat generated during the process deforms the components and the final shape might not meet specified tolerances. There is therefore a need for a compensation strategy which requires knowledge of the workpiece temperature field and the associated thermal distortions. In this work, a methodology is presented for the determination of the heat load for indexable insert drilling of AISI 4140. Compared to previous research, this work has introduced a varying heat load. The heat load is extracted from thermo-mechanical finite element simulations for different nominal chip thicknesses and cutting speeds using the coupled Eulerian-Lagrangian formulation of an orthogonal turning process. The heat load is then transferred to a simplified 2D axisymmetric heat transfer model where the in-process temperature field in the workpiece is predicted. To verify the methodology, the predicted temperatures are compared to the experimentally measured temperatures for various feed rates. It is found that the model is capable of predicting the workpiece temperatures reasonably well. However, the methodology needs to be further explored to validate its applicability.
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| 47. |
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| 48. |
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| 49. |
- Arion, Tiberiu, et al.
(författare)
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New insight into the Auger decay process in O-2: The coincidence perspective
- 2012
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 185:8-9, s. 234-243
-
Tidskriftsartikel (refereegranskat)abstract
- Photoelectron-Auger electron coincidence spectroscopy is a powerful tool for the investigation of Auger decay processes with different core-ionized intermediate states. In this paper we describe an investigation into the Auger decay of the O-2 molecule, with the purpose of bringing new insight into the dynamics of the core hole decay mechanism. Using a novel experimental approach to measuring such coincidence spectra we report the highest resolution Auger spectrum of O-2 recorded hitherto. In our approach, we have combined the advantages of these coincidence spectra with the high resolution and excellent signal-to-noise ratios of non-coincident Auger spectra and a state-of-the-art fit analysis. In this way we have derived information about the potential energy curves of the final states W-3 Delta(u), B-3 Pi(g), and B' (3)Sigma(-)(u) and concluded that the corresponding Auger transitions are formed to a large part by strongly overlapping vibrational progressions. The present findings are compared to earlier results reported in the literature confirming some theoretical predictions. (C) 2012 Elsevier B.V. All rights reserved.
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| 50. |
- Auer, Gunther, et al.
(författare)
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CELTIC CP5-026 WINNER+, D1.5 Intermediate Report on System Aspect of Advanced RRM
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The deliverable describes the second set of best innovations proposed in the framework of the WP1 on system aspect of advanced Radio Resource Management (RRM) approved by the System Group. These concepts consist of promising innovative techniques and include an initial evaluation of the performance and benefits as far as already available. A brief description of each technique together with the relevant state of the art is provided.Moreover, first considerations about the requirements on the system, especially regarding measurements, signalling, architecture and protocols are described. The last set of innovations will be ready for the final deliverable of proof of concept evaluation.
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