Stratification of responders towards eculizumab using a structural epitope mapping strategy

The complement component 5 (C5)-binding antibody eculizumab is used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). As recently reported there is a need for a precise classification of eculizumab responsive patients to allow for a safe and cost-effective treatment. To allow for such stratification, knowledge of the precise binding site of the drug on its target is crucial. Using a structural epitope mapping strategy based on bacterial surface display, flow cytometric sorting and validation via haemolytic activity testing, we identified six residues essential for binding of eculizumab to C5. This epitope co-localizes with the contact area recently identified by crystallography and includes positions in C5 mutated in non-responders. The identified epitope also includes residue W917, which is unique for human C5 and explains the observed lack of cross-reactivity for eculizumab with other primates. We could demonstrate that Ornithodorus moubata complement inhibitor (OmCI), in contrast to eculizumab, maintained anti-haemolytic function for mutations in any of the six epitope residues, thus representing a possible alternative treatment for patients non-responsive to eculizumab. The method for stratification of patients described here allows for precision medicine and should be applicable to several other diseases and therapeutics

Program Leadership from a Nordic Perspective - Program Leaders' Power to Influence Their Program

Поточний інформаційний список містить перелік статей про Сумський державний університет з періодичних видань, які надійшли до бібліотеки за лютий

Uptake of atrial fibrillation screening aiming at stroke prevention: geo-mapping of target population and non-participation

Background: In a screening study for silent atrial fibrillation (AF), which is a frequent source of cardiac emboli with ischemic stroke, the proportion of non-participants was considerable and their clinical profile differed from the participants' profile. We intended to geo-map the target population and non-participation in an attempt to understand factors related to screening uptake and, thereby, obtain useful information needed to intervene for improved uptake. Method: In the municipality of Halmstad, Sweden, all residents born in 1934-1935 were invited to the screening study during April 2010 to February 2012. The total study group included 848 participants and 367 non-participants from 12 parishes. Geo-maps displaying participation, along with target-population-based geo-maps displaying proportion of immigrants and ischemic stroke incidence, were used. Results: Smoothed non-participation ratios (SmNPR) varied from 0.81 to 1.24 across different parishes (SmNRP = 1 corresponds to the expected participation based on the total study group). Among high risk individuals, the geographical variation was more pronounced (SmNPR range 0.75-1.51). Two parishes with higher share of immigrants and elevated population-based ischemic stroke incidence showed markedly lower participation, particularly among high-risk individuals. Conclusion: AF screening uptake varied evidently between parishes, particularly among high-risk individuals. Geo-mapping of target population and non-participation yielded useful information needed to intervene for improved screening uptake

Nation Brand Management, en fallstudie av Sverige och Tyskland

Purpose: The aim of this paper is to compare the Nation Branding initiatives of Sweden and Germany in order to identify important factors while navigating their Nation Brand. A framework has been developed on the basis of existing theory which has been tested on the objects of the case study. The purpose was to demonstrate possible empirical correlations not described by the theory. Finally the paper provides an analysis of the deduced theoretical framework which subsequently has been developed and expanded with the new theoretical aspects. Methodology: The paper presents the output of qualitative case study research of the Nation Branding initiatives of Sweden and Germany. An abductive approach was used whereby a deduced framework has been used which subsequently has been expanded through induction. Empirical foundation The empirical material consists of semi-structured interviews with persons from the respective initiatives and specialists in the field of Nation Branding, as well as information from the websites of the initiatives. Results The paper has contributed with the addition of three further factors: the learning organization, structure and multipliers which complement the existing theory

Time-dynamic effects on the global temperature when harvesting logging residues for bioenergy

The climate mitigation potential of using logging residues (tree tops and branches) for bioenergy has been debated. In this study, a time-dependent life cycle assessment (LCA) was performed using a single-stand perspective. Three forest stands located in different Swedish climate zones were studied in order to assess the global temperature change when using logging residues for producing district heating. These systems were compared with two fossil reference systems in which the logging residues were assumed to remain in the forest to decompose over time, while coal or natural gas was used for energy. The results showed that replacing coal with logging residues gave a direct climate benefit from a single-stand perspective, while replacing natural gas gave a delayed climate benefit of around 8-12 years depending on climate zone. A sensitivity analysis showed that the time was strongly dependent on the assumptions for extraction and combustion of natural gas. The LCA showed that from a single-stand perspective, harvesting logging residues for bioenergy in the south of Sweden would give the highest temperature change mitigation potential per energy unit. However, the differences between the three climate zones studied per energy unit were relatively small. On a hectare basis, the southern forest stand would generate more biomass compared to the central and northern locations, which thereby could replace more fossil fuel and give larger climate benefits

Plasma proteomics of biomarkers for inflammation or cancer cannot predict relapse in chronic myeloid leukaemia patients stopping tyrosine kinase inhibitor therapy

Several studies have now shown that chronic myeloid leukaemia (CML) patients in deep molecular remission may discontinue tyrosine kinase inhibitor (TKI) treatment with a treatment free remission (TFR) rate of approximately 40-60 %. Some factors influencing the possibility of TFR have been described but better tools are needed for individual prediction of long-term TFR. Herein, two multiplex panels were utilised to analyse a total of 162 different plasma proteins from 56 patients included in the TKI stopping trial EURO-SKI (Saussele a al., 2018). The purpose was to identify possible plasma protein markers for prediction of successful TKI discontinuation and to evaluate effects of TKI discontinuation on plasma protein profiles. No protein biomarkers sampled before TKI discontinuation could separate relapse cases from non-relapse cases but some plasma proteins differed between patients who relapsed and those who remained in TFR when followed over time after TKI cessation. In conclusion, the plasma protein markers in this study could not predict relapse after TKI discontinuation but may be of use to understand the mechanisms involved in maintenance of TFR.Peer reviewe

Correction:Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib – interim results from the DAstop2 trial (Leukemia, (2024), 10.1038/s41375-024-02145-6)

Correction to: Leukemiahttps://doi.org/10.1038/s41375-024-02145-6 published online 26 January 2024 The information provided in the Figure III legend states: “TFR probability at 6, 12 and 24 months was 62, 55 and 42%respectively”, the figure should have appeared as shown below: “TFR probability at 6, 12 and 24 months was 61, 56 and 46%, respectively”.</p