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

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

Deglaciation of Fennoscandia

To provide a new reconstruction of the deglaciation of the Fennoscandian Ice Sheet, in the form of calendar-year time-slices, which are particularly useful for ice sheet modelling, we have compiled and synthesized published geomorphological data for eskers, ice-marginal formations, lineations, marginal meltwater channels, striae, ice-dammed lakes, and geochronological data from radiocarbon, varve, optically-stimulated luminescence, and cosmogenic nuclide dating. This 25 is summarized as a deglaciation map of the Fennoscandian Ice Sheet with isochrons marking every 1000 years between 22 and 13 cal kyr BP and every hundred years between 11.6 and final ice decay after 9.7 cal kyr BP. Deglaciation patterns vary across the Fennoscandian Ice Sheet domain, reflecting differences in climatic and geomorphic settings as well as ice sheet basal thermal conditions and terrestrial versus marine margins. For example, the ice sheet margin in the high-precipitation coastal setting of the western sector responded sensitively to climatic variations leaving a detailed record of prominent moraines and ice-marginal deposits in many fjords and coastal valleys. Retreat rates across the southern sector differed between slow retreat of the terrestrial margin in western and southern Sweden and rapid retreat of the calving ice margin in the Baltic Basin. Our reconstruction is consistent with much of the published research. However, the synthesis of a large amount of existing and new data support refined reconstructions in some areas. For example, we locate the LGM extent of the ice sheet in northwestern Russia further east than previously suggested and conclude that it occurred at a later time than the rest of the ice sheet, at around 17-15 cal kyr BP, and propose a slightly different chronology of moraine formation over southern Sweden based on improved correlations of moraine segments using new LiDAR data and tying the timing of moraine formation to Greenland ice core cold stages. Retreat rates vary by as much as an order of magnitude in different sectors of the ice sheet, with the lowest rates on the high-elevation and maritime Norwegian margin. Retreat rates compared to the climatic information provided by the Greenland ice core record show a general correspondence between retreat rate and climatic forcing, although a close match between retreat rate and climate is unlikely because of other controls, such as topography and marine versus terrestrial margins. Overall, the time slice reconstructions of Fennoscandian Ice Sheet deglaciation from 22 to 9.7 cal kyr BP provide an important dataset for understanding the contexts that underpin spatial and temporal patterns in retreat of the Fennoscandian Ice Sheet, and are an important resource for testing and refining ice sheet models

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

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

IFN-α with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia

In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-alpha is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-alpha in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCR beta sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8(+) recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-alpha reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-alpha had costimulatory effects on TCR signaling. Our work supports the combination of IFN-alpha with TKI therapy, as IFN-alpha broadens the immune repertoire and restores immunological function.Peer reviewe