Asiakkaan osallistaminen uuden ohjelmistopohjaisen palvelun kehittämisprosessiin:tapaus S-mobiili

Tiivistelmä. Tämän tutkimuksen keskeisenä sisältönä on tutkia asiakkaan osallistamista uuden ohjelmistopohjaisen palvelun kehittämisprosessiin. Palveluliiketoiminta on viime vuosikymmeninä kasvanut huomattavasti, kun perinteisten tuotteiden lisäksi organisaatiot tarjoavat asiakkailleen lisäarvoa myös palveluiden muodossa. Erityisesti digitaalisten palveluiden osuus on nousussa, joten niiden kehittämisprosessista tarvitaan lisää tietoa. Tutkimusaukko on rajattu asiakkaan osallistamisen merkitykseen uuden palvelun kehittämisprosessissa, koska asiakkaan osallistamista pidetään yleisesti yhtenä onnistuneen palvelunkehityksen avaintekijöistä. Tavoitteena on muodostaa havainnollistava kuvio niistä tekijöistä, joita palvelunkehittäjät ottavat huomioon osallistaessaan asiakkaita kehittämisprosessiin. Tutkimusmenetelmänä käytetään tapaustutkimusta, koska tavoitteena on ymmärtää tapauksen kautta tutkittavaa ilmiötä laajemmassa kontekstissa. Tutkimuksen tapaukseksi valikoitui mobiilisovellus: S-mobiili. S-mobiili on palvelu, jossa yhdistyvät S-ryhmän asiakasomistajien tärkeimmät hyödyt: bonukset, edut, toimipaikka-haku ja S-pankin mobiilipankki. Empiirinen aineisto kerättiin kolmella teemahaastattelulla. Haastateltavina toimivat S-pankin sähköisten kanavien päällikkö, SOK:n digitaalisen markkinoinnin päällikkö ja ulkoisen suunnittelutoimisto Ideanin ‖Head of Insight‖. Tutkimuksen keskeisiin tuloksiin lukeutuu ohjelmistopohjaisen uuden palvelun kehittämisprosessin etenemisen määrittäminen. Prosessi voidaan nähdä kolmivaiheisena, sisältäen ideageneroinnin, analysoinnin ja lanseerauksen. Prosessi ei ole vesiputousmainen, koska eri vaiheet etenevät rinnakkain. Asiakkaan osallistaminen korostuu erityisesti prosessin alkuvaiheessa, jolloin hahmotetaan loppuasiakkaiden ydinkokemus. Tämä tehdään osallistamalla asiakas käyttäjäraatiin, jossa keskustellaan asiakkaan kanssa ja havainnoidaan heidän käyttäytymistään. Asiakkaan rooli korostuu jälleen toisessa käyttäjäraadissa, joka järjestetään varmistavana pilotointina juuri ennen lanseerausta. Tällä varmistetaan uuden palvelun soveltuvuus markkinoille. Muita huomioon otettavia asioita asiakkaan osallistamisen suhteen ovat muun muassa palveluorganisaation itsenäisen palautejärjestelmän luominen ja asiakastyyppien erojen merkityksen ymmärtäminen. Tapaustutkimuksen luonteen mukaisesti tämän tutkimuksen tulokset eivät ole suoraan yleistettävissä kaikkeen palvelun kehitykseen. Tutkimus tarjoaa kuitenkin ohjelmistopohjaisen palvelun kehittämiseen selkeän mallin, jonka pohjalta yrityksen liikkeenjohto voi ennakoida tulevaa uuden palvelun kehittämisprosessia, ja asiakkaan osallistamista siihen

Влияние изменения тиреоидного статуса на активность центральной стресс-лимитирующей системы

ТИРЕОИДНЫЕ ГОРМОНЫЙОДСОДЕРЖАЩИЕ ТИРЕОИДНЫЕ ГОРМОНЫСТРЕСССТРЕСС-ЛИМИТИРУЮЩИЕ СИСТЕМЫТИРОКСИНГИПЕРТИРЕОЗГИПОТИРЕОЗЭКСПЕРИМЕНТЫ НА ЖИВОТНЫХБИОМЕДИЦИНСКИЕ ИССЛЕДОВАНИЯКРЫС

On spin-rotation contribution to nuclear spin conversion in C_{3v}-symmetry molecules. Application to CH_3F

The symmetrized contribution of E-type spin-rotation interaction to conversion between spin modifications of E- and A_1-types in molecules with C_{3v}-symmetry is considered. Using the high-J descending of collisional broadening for accidental rotational resonances between these spin modifications, it was possible to co-ordinate the theoretical description of the conversion with (updated) experimental data for two carbon-substituted isotopes of fluoromethane. As a result, both E-type spin-rotation constants are obtained. They are roughly one and a half times more than the corresponding constants for (deutero)methane.Comment: 13 pages with single-spacing, REVTeX, no figures, accepted for publication in <J. Phys. B

PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal

Many acute and chronic anaemias, including haemolysis, sepsis and genetic bone marrow failure diseases such as Diamond–Blackfan anaemia, are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production. Treatment of these anaemias requires a drug that acts at an earlier stage of red cell formation and enhances the formation of Epo-sensitive CFU-E progenitors. Recently, we showed that glucocorticoids specifically stimulate self-renewal of an early erythroid progenitor, burst-forming unit erythroid (BFU-E), and increase the production of terminally differentiated erythroid cells. Here we show that activation of the peroxisome proliferator-activated receptor α (PPAR-α) by the PPAR-α agonists GW7647 and fenofibrate synergizes with the glucocorticoid receptor (GR) to promote BFU-E self-renewal. Over time these agonists greatly increase production of mature red blood cells in cultures of both mouse fetal liver BFU-Es and mobilized human adult CD34+ peripheral blood progenitors, with a new and effective culture system being used for the human cells that generates normal enucleated reticulocytes. Although Ppara−/− mice show no haematological difference from wild-type mice in both normal and phenylhydrazine (PHZ)-induced stress erythropoiesis, PPAR-α agonists facilitate recovery of wild-type but not Ppara−/− mice from PHZ-induced acute haemolytic anaemia. We also show that PPAR-α alleviates anaemia in a mouse model of chronic anaemia. Finally, both in control and corticosteroid-treated BFU-E cells, PPAR-α co-occupies many chromatin sites with GR; when activated by PPAR-α agonists, additional PPAR-α is recruited to GR-adjacent sites and presumably facilitates GR-dependent BFU-E self-renewal. Our discovery of the role of PPAR-α agonists in stimulating self-renewal of early erythroid progenitor cells suggests that the clinically tested PPAR-α agonists we used may improve the efficacy of corticosteroids in treating Epo-resistant anaemias.United States. Defense Advanced Research Projects Agency (Grant HR0011-14-2-0005)United States. Army Medical Research and Materiel Command (Grant W81WH-12-1-0449)National Heart, Lung, and Blood Institute (Grant 2 P01 HL032262-25

Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase

Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy

Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study

Publisher Copyright: © 2022 The Author(s)Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.Peer reviewe

Diablo/SMAC: A novel biomarker of pollutant exposure in European flounder (Platichthys flesus)

Diablo (or SMAC) is a protein released from mitochondria following apoptotic stimuli and inhibits the actions of Inhibitors of Apoptosis (IAP) proteins. IAPs regulate the activity of caspases and NFkB, the primary executioners of apoptosis and of inflammation respectively. Thus, Diablo is important for the regulation of cellular responses to damage. In Northern Europe, statutory governmental marine monitoring programs measure various biomarkers in flounder to indicate biological effects of pollutant exposure. More recently transcriptomic techniques have been applied in flounder to gain a more comprehensive understanding of pollutant effects, and to discover novel biomarkers. In most of these studies utilising flounder, Diablo was amongst the most highly increased transcripts identified. The aim of this study was to further examine piscine Diablo, at the gene level and mRNA level, after exposure to prototypical pollutants, and in flounder caught from polluted environments. The results show that two genes encoding Diablo exist in fish species, and in flounder one of these genes is increased in liver after exposure to polyaromatic hydrocarbons and polychlorinated biphenyls, and also in livers from fish living on contaminated estuarine sediments. Therefore, Diablo measurement has potential as a biomarker of pollutant exposure, and could indicate damaging effects of chemical contaminants

Accelerated Hydrolysis of Aspirin Using Alternating Magnetic Fields

The major problem of current drug-based therapy is selectivity. As in other areas of science, a combined approach might improve the situation decisively. The idea is to use the pro-drug principle together with an alternating magnetic field as physical stimulus, which can be applied in a spatially and temporarily controlled manner. As a proof of principle, the neutral hydrolysis of aspirin in physiological phosphate buffer of pH 7.5 at 40 °C was chosen. The sensor and actuator system is a commercially available gold nanoparticle (NP) suspension which is approved for animal usage, stable in high concentrations and reproducibly available. Applying the alternating magnetic field of a conventional NMR magnet system accelerated the hydrolysis of aspirin in solution

5′UTR Variants of Ribosomal Protein S19 Transcript Determine Translational Efficiency: Implications for Diamond-Blackfan Anemia and Tissue Variability

Background: Diamond-Blackfan anemia (DBA) is a lineage specific and congenital erythroblastopenia. The disease is associated with mutations in genes encoding ribosomal proteins resulting in perturbed ribosomal subunit biosynthesis. The RPS19 gene is mutated in approximately 25 % of DBA patients and a variety of coding mutations have been described, all presumably leading to haploinsufficiency. A subset of patients carries rare polymorphic sequence variants within the 59untranslated region (59UTR) of RPS19. The functional significance of these variants remains unclear. Methodology/Principal Findings: We analyzed the distribution of transcriptional start sites (TSS) for RPS19 mRNAs in testis and K562 cells. Twenty-nine novel RPS19 transcripts were identified with different 59UTR length. Quantification of expressed w.t. 59UTR variants revealed that a short 59UTR correlates with high levels of RPS19. The total levels of RPS19 transcripts showed a broad variation between tissues. We also expressed three polymorphic RPS19 59UTR variants identified in DBA patients. The sequence variants include two insertions (c.-147_-146insGCCA and c.-147_-146insAGCC) and one deletion (c.-144_-141delTTTC). The three 59UTR polymorphisms are associated with a 20–30 % reduction in RPS19 protein levels when compared to the wild-type (w.t.) 59UTR of corresponding length. Conclusions: The RPS19 gene uses a broad range of TSS and a short 59UTR is associated with increased levels of RPS19. Comparisons between tissues showed a broad variation in the total amount of RPS19 mRNA and in the distribution of TS

Altered translation of GATA1 in Diamond-Blackfan anemia

Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA)[superscript 1, 2], congenital asplenia[superscript 3] and T cell leukemia[superscript 4]. Yet, how mutations in genes encoding ubiquitously expressed proteins such as these result in cell-type– and tissue-specific defects remains unknown[superscript 5]. Here, we identify mutations in GATA1, encoding the critical hematopoietic transcription factor GATA-binding protein-1, that reduce levels of full-length GATA1 protein and cause DBA in rare instances. We show that ribosomal protein haploinsufficiency, the more common cause of DBA, can lead to decreased GATA1 mRNA translation, possibly resulting from a higher threshold for initiation of translation of this mRNA in comparison with other mRNAs. In primary hematopoietic cells from patients with mutations in RPS19, encoding ribosomal protein S19, the amplitude of a transcriptional signature of GATA1 target genes was globally and specifically reduced, indicating that the activity, but not the mRNA level, of GATA1 is decreased in patients with DBA associated with mutations affecting ribosomal proteins. Moreover, the defective hematopoiesis observed in patients with DBA associated with ribosomal protein haploinsufficiency could be partially overcome by increasing GATA1 protein levels. Our results provide a paradigm by which selective defects in translation due to mutations affecting ubiquitous ribosomal proteins can result in human disease.National Institutes of Health (U.S.) (Grant P01 HL32262)National Institutes of Health (U.S.) (Grant U54 HG003067-09