| 1. |
|
|
| 2. |
- Sartelli, Massimo, et al.
(författare)
-
Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
-
Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
-
Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
|
|
| 3. |
- Timmermann, C., et al.
(författare)
-
Neural correlates of the DMT experience assessed with multivariate EEG
- 2019
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity. Time-referenced and neurophenomenological analyses revealed close relationships between changes in various aspects of subjective experience and changes in brain activity. Importantly, the emergence of oscillatory activity within the delta and theta frequency bands was found to correlate with the peak of the experience - particularly its eyes-closed visual component. These findings highlight marked changes in oscillatory activity and signal diversity with DMT that parallel broad and specific components of the subjective experience, thus advancing our understanding of the neurobiological underpinnings of immersive states of consciousness.
|
|
| 4. |
- Begam, Nafisa, et al.
(författare)
-
Effects of temperature and ionic strength on the microscopic structure and dynamics of egg white gels
- 2023
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 158:7
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the thermal gelation of egg white proteins at different temperatures with varying salt concentrations using x-ray photon correlation spectroscopy in the geometry of ultra-small angle x-ray scattering. Temperature-dependent structural investigation suggests a faster network formation with increasing temperature, and the gel adopts a more compact network, which is inconsistent with the conventional understanding of thermal aggregation. The resulting gel network shows a fractal dimension δ, ranging from 1.5 to 2.2. The values of δ display a non-monotonic behavior with increasing amount of salt. The corresponding dynamics in the q range of 0.002–0.1 nm−1 is observable after major change of the gel structure. The extracted relaxation time exhibits a two-step power law growth in dynamics as a function of waiting time. In the first regime, the dynamics is associated with structural growth, whereas the second regime is associated with the aging of the gel, which is directly linked with its compactness, as quantified by the fractal dimension. The gel dynamics is characterized by a compressed exponential relaxation with a ballistic-type of motion. The addition of salt gradually makes the early stage dynamics faster. Both gelation kinetics and microscopic dynamics show that the activation energy barrier in the system systematically decreases with increasing salt concentration.
|
|
| 5. |
- Bölling, T, et al.
(författare)
-
Development of Curative Therapies for Ewing Sarcomas by Interdisciplinary Cooperative Groups in Europe.
- 2015
-
Ingår i: Klinische Pädiatrie. - : Georg Thieme Verlag KG. - 1439-3824 .- 0300-8630. ; 227:3, s. 108-115
-
Forskningsöversikt (refereegranskat)abstract
- Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.
|
|
| 6. |
- Eckernäs, Emma, 1992, et al.
(författare)
-
N,N-dimethyltryptamine affects electroencephalography response in a concentration-dependent manner-A pharmacokinetic/pharmacodynamic analysis
- 2023
-
Ingår i: Cpt-Pharmacometrics & Systems Pharmacology. - : Wiley. - 2163-8306. ; 12:4, s. 474-486
-
Tidskriftsartikel (refereegranskat)abstract
- N,N-dimethyltryptamine (DMT) is a psychedelic substance and is being used as a research tool in investigations of the neurobiology behind the human consciousness using different brain imaging techniques. The effects of psychedelics have commonly been studied using electroencephalography (EEG) and have been shown to produce suppression of alpha power and increase in signal diversity. However, the relationship between DMT exposure and its EEG effects has never been quantified. In this work, a population pharmacokinetic/pharmacodynamic analysis was performed investigating the relationship between DMT plasma concentrations and its EEG effects. Data were obtained from a clinical study where DMT was administered by intravenous bolus dose to 13 healthy subjects. The effects on alpha power, beta power, and Lempel-Ziv complexity were evaluated. DMT was shown to fully suppress alpha power. Beta power was only partially suppressed, whereas an increase in Lempel-Ziv complexity was observed. The relationship between plasma concentrations and effects were described using effect compartment models with sigmoidal maximum inhibitory response or maximum stimulatory response models. Values of the concentration needed to reach half of the maximum response (EC50,e) were estimated at 71, 137, and 54 nM for alpha, beta, and Lempel-Ziv complexity, respectively. A large amount of between-subject variability was associated with both beta power and Lempel-Ziv complexity with coefficients of variability of 75% and 77% for the corresponding EC50,e values, respectively. Alpha power appeared to be the most robust response, with a between-subject variability in EC50,e of 29%. Having a deeper understanding of these processes might prove beneficial in choosing appropriate doses and response biomarkers in the future clinical development of DMT.
|
|
| 7. |
- Eckernäs, Emma, 1992, et al.
(författare)
-
Optimized infusion rates for N,N-dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework
- 2023
-
Ingår i: Cpt-Pharmacometrics & Systems Pharmacology. - 2163-8306. ; 12:10, s. 1398-1410
-
Tidskriftsartikel (refereegranskat)abstract
- N,N-dimethyltryptamine (DMT) is a psychedelic compound that is being studied as a therapeutic option in various psychiatric disorders. Due to its short half-life, continuous infusion of DMT has been proposed to extend the psychedelic experience and potential therapeutic effects. The primary aim of this work was to design an infusion protocol for DMT based on a desired level of psychedelic intensity using population pharmacokinetic/pharmacodynamic modeling. As a secondary aim, the impact of choosing a continuous variable or a bounded integer pharmacokinetic/pharmacodynamic model to inform such an infusion protocol was investigated. A previously published continuous variable model and two newly developed bounded integer models were used to assess optimal doses for achieving a target response. Simulations were performed to identify an optimal combination of a bolus dose and an infusion rate. Based on the simulations, optimal doses to achieve intensity ratings between 7 and 9 (possible range = 0-10) were a bolus dose of 16 mg DMT fumarate followed by an infusion rate of 1.4 mg/min based on the continuous variable model and 14 mg with 1.2 mg/min for the two bounded integer models. However, the proportion within target was low (<53%) for all models, indicating that individual dose adjustments would be necessary. Furthermore, some differences between the models were observed. The bounded integer models generally predicted lower proportions within a target of 7-9 with higher proportions exceeding target compared with the continuous variable model. However, results varied depending on target response with the major differences observed at the boundaries of the scale.
|
|
| 8. |
- Eckernäs, Emma, 1992, et al.
(författare)
-
Population pharmacokinetic/pharmacodynamic modeling of the psychedelic experience induced by N,N-dimethyltryptamine - Implications for dose considerations
- 2022
-
Ingår i: Cts-Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 15:12, s. 2928-2937
-
Tidskriftsartikel (refereegranskat)abstract
- N,N-dimethyltryptamine (DMT) is a psychedelic compound that is believed to have potential as a therapeutic option in several psychiatric disorders. The number of clinical investigations with DMT is increasing. However, very little is known about the pharmacokinetic properties of DMT as well as any relationship between its exposure and effects. This study aimed to characterize population pharmacokinetics of DMT as well as the relationship between DMT plasma concentrations and its psychedelic effects as measured through subjective intensity ratings. Data were obtained from 13 healthy subjects after intravenous administration of DMT. The data were analyzed using nonlinear mixed-effects modeling in NONMEM. DMT plasma concentrations were described by a two-compartment model with first-order elimination leading to formation of the major metabolite indole 3-acetic acid. The relationship between plasma concentrations and psychedelic intensity was described by an effect site compartment model with a sigmoid maximum effect (E-max) response. DMT clearance was estimated at 26 L/min, a high value indicating elimination of DMT to be independent of blood flow. Higher concentrations of DMT were associated with a more intense experience with the concentration of DMT at the effect site required to produce half of the maximum response estimated at 95 nM. The maximum achievable intensity rating was 10 and the simulated median maximum rating was zero, 2, 4, 8, and 9 after doses of 1, 4, 7, 14, and 20 mg, respectively. The model can be useful in predicting suitable doses for clinical investigations of DMT based on the desired intensity of the subjective experience.
|
|
| 9. |
- Eshmvminov, D., et al.
(författare)
-
FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review
- 2023
-
Ingår i: Annals of Surgical Oncology. - 1068-9265. ; 30:7, s. 4417-4428
-
Forskningsöversikt (refereegranskat)abstract
- BackgroundPancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.MethodsWe performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.ResultsA total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.ConclusionsIn patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.
|
|
| 10. |
- Gossmann, Toni I., et al.
(författare)
-
Ice-Age Climate Adaptations Trap the Alpine Marmot in a State of Low Genetic Diversity
- 2019
-
Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 29:10, s. 1712-1720.e7
-
Tidskriftsartikel (refereegranskat)abstract
- © 2019 The Author(s) Some species responded successfully to prehistoric changes in climate [1, 2], while others failed to adapt and became extinct [3]. The factors that determine successful climate adaptation remain poorly understood. We constructed a reference genome and studied physiological adaptations in the Alpine marmot (Marmota marmota), a large ground-dwelling squirrel exquisitely adapted to the “ice-age” climate of the Pleistocene steppe [4, 5]. Since the disappearance of this habitat, the rodent persists in large numbers in the high-altitude Alpine meadow [6, 7]. Genome and metabolome showed evidence of adaptation consistent with cold climate, affecting white adipose tissue. Conversely, however, we found that the Alpine marmot has levels of genetic variation that are among the lowest for mammals, such that deleterious mutations are less effectively purged. Our data rule out typical explanations for low diversity, such as high levels of consanguineous mating, or a very recent bottleneck. Instead, ancient demographic reconstruction revealed that genetic diversity was lost during the climate shifts of the Pleistocene and has not recovered, despite the current high population size. We attribute this slow recovery to the marmot's adaptive life history. The case of the Alpine marmot reveals a complicated relationship between climatic changes, genetic diversity, and conservation status. It shows that species of extremely low genetic diversity can be very successful and persist over thousands of years, but also that climate-adapted life history can trap a species in a persistent state of low genetic diversity. Despite being highly abundant and well adapted, Gossmann et al. report that the Alpine marmot is among the least genetically diverse animal species. The low diversity is found to be the consequence of consecutive, climate-related events, including long-term extreme niche adaptation, that also greatly retarded the recovery of its genetic diversity.
|
|
