| 1. |
- Palica, Katarzyna, 1992-, et al.
(författare)
-
Metallo-β-Lactamase Inhibitor Phosphonamidate Monoesters
- 2022
-
Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 7:5, s. 4550-4562
-
Tidskriftsartikel (refereegranskat)abstract
- Being the second leading cause of death and the leading cause of disability-adjusted life years worldwide, infectious diseases remain─contrary to earlier predictions─a major consideration for the public health of the 21st century. Resistance development of microbes to antimicrobial drugs constitutes a large part of this devastating problem. The most widely spread mechanism of bacterial resistance operates through the degradation of existing β-lactam antibiotics. Inhibition of metallo-β-lactamases is expected to allow the continued use of existing antibiotics, whose applicability is becoming ever more limited. Herein, we describe the synthesis, the metallo-β-lactamase inhibition activity, the cytotoxicity studies, and the NMR spectroscopic determination of the protein binding site of phosphonamidate monoesters. The expression of single- and double-labeled NDM-1 and its backbone NMR assignment are also disclosed, providing helpful information for future development of NDM-1 inhibitors. We show phosphonamidates to have the potential to become a new generation of antibiotic therapeutics to combat metallo-β-lactamase-resistant bacteria.
|
|
| 2. |
|
|
| 3. |
- Andersson, Ulf, 1985-, et al.
(författare)
-
Clinical Reasoning among Registered Nurses in Emergency Medical Services : A Case Study
- 2022
-
Ingår i: Journal of Cognitive Engineering and Decision Making. - : Sage Publications. - 1555-3434 .- 2169-5032. ; 16:3, s. 123-156
-
Tidskriftsartikel (refereegranskat)abstract
- In emergency medical services (EMS), the clinical reasoning (CR) of registered nurses (RNs) working in ambulance care plays an important role in providing care and treatment that is timely, accurate, appropriate and safe. However, limited existing knowledge about how CR is formed and influenced by the EMS mission hinders the development of service provision and decision support tools for RNs that would further enhance patient safety. To explore the nature of CR and influencing factors in this context, an inductive case study examined 34 observed patient-RN encounters in an EMS setting focusing on ambulance care. The results reveal a fragmented CR approach involving several parallel decision-making processes grounded in and led by patients' narratives. The findings indicate that RNs are not always aware of their own CR and associated influences until they actively reflect on the process, and additional research is needed to clarify this complex phenomenon.
|
|
| 4. |
- Andersson, Ulf, 1985-, et al.
(författare)
-
Organizational factors influencing clinical reasoning in a Swedish emergency medical service organization: An explorative qualitative case study
- 2023
-
Ingår i: Paramedicine. - : Sage Publications. - 2753-6386 .- 2753-6386.
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionClinical reasoning (CR) among healthcare professionals working in emergency medical services (EMS) who focus on ambulance care is a vital part of ensuring timely and safe patient care. The EMS environment continually fluctuates, so clinicians constantly need to adapt to new situations. Organizational support is described as important for CR, but overall, research on organizational influences for CR in an EMS context is lacking. An increased understanding of these influencing factors can assist in the development of EMS by strengthening CR among clinicians. Therefore, the purpose of this study was to investigate the organizational factors influencing EMS clinicians’ CR.MethodsUsing a qualitative single case study design, an EMS organization in southwestern Sweden was explored. Data were collected from participant observations of patient encounters, individual and group interviews with clinicians and organizational representatives, and organizational document audits. Data were analyzed using qualitative content analysis and triangulation of data sources.ResultsThe results revealed several organizational influencing factors. Collaboration and information sharing internally and externally were emphasized as essential components influencing CR. Additionally, the structure for the clinicians’ ‘room for action’ appeared confused and created uncertainties for CR related to decision mandates.ConclusionThe conclusion is that organizational factors do play an important role in clinicians’ CR. Moreover, the EMS community needs to develop suitable forums for discussing and developing these influencing factors across organizational hierarchies. Finally, clarification is needed on clinicians’ ‘room for action’ within their own organization but also with possible collaborators.
|
|
| 5. |
- Andersson, Ulf, 1985-, et al.
(författare)
-
Situation awareness in Sweden’s emergency medical services : a goal-directed task analysis
- 2023
-
Ingår i: Discover Health Systems. - 2731-7501. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- Situation awareness is knowing what is going on in the situation. Clinicians working in the emergency medical services (EMS) encounter numerous situations in various conditions, and to be able to provide efficient and patient safe care they need to understand what is going on and possible projections of the current situation. The design of this study encompassed a Goal-Directed Task analysis where situation awareness information requirements were mapped in relation to goals related to various aspects of the EMS mission. A group of 30 EMS subject matter experts were recruited and answered a web-based survey in three rounds related to what they though themselves or a colleague might need to achieve situation awareness related to the specific goals of various situations. The answers were analysed using content analysis and descriptive statistics. Answers reached consensus at a predetermined level of 75%. Those who reached consensus were entered into the final goal-directed task analysis protocol. The findings presented that EMS clinicians must rely on their own, or their colleagues prior experience or knowledge to achieve situation awareness. This suggests that individual expertise plays a crucial role in developing situation awareness. There also seems to be limited support for situation awareness from organizational guidelines. Furthermore, achieving situation awareness also involves collaborative efforts from the individuals involved in the situation. These findings could add to the foundation for further investigation in this area which could contribute to the development of strategies and tools to enhance situation awareness among EMS clinicians, ultimately improving patient care and safety.
|
|
| 6. |
- Palica, Katarzyna, 1992-, et al.
(författare)
-
α-Aminophosphonate inhibitors of metallo-β-lactamases NDM-1 and VIM-2
- 2023
-
Ingår i: RSC Medicinal Chemistry. - : Royal Society of Chemistry. - 2632-8682. ; 14:11, s. 2277-2300
-
Tidskriftsartikel (refereegranskat)abstract
- The upswing of antibiotic resistance is an escalating threat to human health. Resistance mediated by bacterial metallo-β-lactamases is of particular concern as these enzymes degrade β-lactams, our most frequently prescribed class of antibiotics. Inhibition of metallo-β-lactamases could allow the continued use of existing β-lactam antibiotics, such as penicillins, cephalosporins and carbapenems, whose applicability is becoming ever more limited. The design, synthesis, and NDM-1, VIM-2, and GIM-1 inhibitory activities (IC50 4.1–506 μM) of a series of novel non-cytotoxic α-aminophosphonate-based inhibitor candidates are presented herein. We disclose the solution NMR spectroscopic and computational investigation of their NDM-1 and VIM-2 binding sites and binding modes. Whereas the binding modes of the inhibitors are similar, VIM-2 showed a somewhat higher conformational flexibility, and complexed a larger number of inhibitor candidates in more varying binding modes than NDM-1. Phosphonate-type inhibitors may be potential candidates for development into therapeutics to combat metallo-β-lactamase resistant bacteria.
|
|
| 7. |
|
|
| 8. |
- Lundin, Samuel B, 1970, et al.
(författare)
-
A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein
- 2023
-
Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe COVID-19 pandemic illustrates the need for serology diagnostics with improved accuracy. While conventional serology based on recognition of entire proteins or subunits thereof has made significant contribution to the antibody assessment space, it often suffers from sub-optimal specificity. Epitope-based, high-precision, serology assays hold potential to capture the high specificity and diversity of the immune system, hence circumventing the cross-reactivity with closely related microbial antigens. MethodsWe herein report mapping of linear IgG and IgA antibody epitopes of the SARS-CoV-2 Spike (S) protein in samples from SARS-CoV-2 exposed individuals along with certified SARS-CoV-2 verification plasma samples using peptide arrays. ResultsWe identified 21 distinct linear epitopes. Importantly, we showed that pre-pandemic serum samples contain IgG antibodies reacting to the majority of protein S epitopes, most likely as a result of prior infection with seasonal coronaviruses. Only 4 of the identified SARS-CoV-2 protein S linear epitopes were specific for SARS-CoV-2 infection. These epitopes are located at positions 278-298 and 550-586, just proximal and distal to the RBD, as well as at position 1134-1156 in the HR2 subdomain and at 1248-1271 in the C-terminal subdomain of protein S. To substantiate the applicability of our findings, we tested three of the high-accuracy protein S epitopes in a Luminex assay, using a certified validation plasma sample set from SARS-CoV-2 infected individuals. The Luminex results were well aligned with the peptide array results, and correlated very well with in-house and commercial immune assays for RBD, S1 and S1/S2 domains of protein S. ConclusionWe present a comprehensive mapping of linear B-cell epitopes of SARS-CoV-2 protein S, that identifies peptides suitable for a precision serology assay devoid of cross-reactivity. These results have implications for development of highly specific serology test for exposure to SARS-CoV-2 and other members of the coronaviridae family, as well as for rapid development of serology tests for future emerging pandemic threats.
|
|
| 9. |
|
|
| 10. |
- Ahonen-Jonnarth, Ulla, et al.
(författare)
-
How do people aggregate value? An experiment with relative importance of criteria and relative goodness of alternatives as inputs
- 2022
-
Ingår i: Journal of Multi-Criteria Decision Analysis. - : Wiley. - 1057-9214 .- 1099-1360. ; 29:3-4, s. 259-273
-
Tidskriftsartikel (refereegranskat)abstract
- The concept of importance of criteria is used as a central element in several decision making contexts, specifically in value aggregation, e.g. as an input to decision support tools. For example, in the analytic hierarchy process (AHP) decision makers are asked to estimate how much more important one criterion is than another. However, it is not clear how people understand aggregation models based on importance of criteria in decision making situations. The purpose of this descriptive study is to investigate if people find an aggregation model in simple value aggregation tasks which remind of the way AHP elicits the input. Further, the purpose is to investigate if people's tendency to find a model depends on their cognitive abilities. In an exploratory laboratory experiment, participants assessed which of two alternatives is the best, based on information about the importance of two criteria and how good the two alternatives are compared to each other with respect to these criteria. The results confirm that people are willing to use importance of criteria and goodness of alternatives as input in value aggregations and show three main models for aggregation. More participants with higher numeracy applied a clear model compared to those with lower numeracy. None of the identified models was one of AHP's models but one of them reminded of one of the ways input can be aggregated in the AHP. The three models identified in the experiment are based on lexicographic order, multiplication and a combination of multiplication and addition. How the results could be used in a prescriptive context is discussed in the paper.
|
|
