E-læring som pedagogisk virkemiddel for innlæring av anatomi, fysiologi og biokjemi i sykepleierutdanningen

Utgangspunktet for studien er at naturvitenskaplige fag, særlig anatomi, fysiologi og biokjemi (AFB), oppleves som vanskelig for sykepleierstudentene. Hensikten var å undersøke om læringsverktøyet e-læring, i form av nettester, kan være et effektivt virkemiddel til innlæring av og påvirke læringsutbyttet i AFB. Førsteårsstudentene i bachelorutdanningen i sykepleie ved Høgskolen i Akershus fikk et spørreskjema med 23 spørsmål som ble besvart anonymt. Resultatet av studentundersøkelsen viste at nettoppgavene ble mye brukt, og at studentene mente de ga et godt læringsutbytte. Nettoppgaver med umiddelbar feedback gir stor studentaktivitet og «time-on-task». Testene kan tette hullet mellom det studentene forventes å kunne og det de faktisk kan, og egner seg til faktafag som m å pugges og forstås. E-læring kan gi god hjelp til studenters strukturering av tid, læringsstrategier og selvregulering. Læringsutbyttet av nettester diskuteres i lys av nytten av umiddelbar feedback i et pedagogisk perspektiv

Evolving marketing strategies for Swiss ICT SMEs : a marketing strategy canvas in the light of digital transformation

It is crucial that small and medium sized businesses in the ICT sector adopt strategies to enable them to exploit, capitalise upon, and respond to the digital transformation. SMEs will need to undergo profound and continuous changes, developing more strategic focused marketing thinking and business models to enable or find new markets while attaining and retaining competitive advantage. SMEs have to fulfil the same marketing tasks as large companies, but under conditions characterised by smaller sales volumes and small market niches. The major difference for SMEs relates to the lower availability of resources, especially financial and human resources. This constraint makes it even more important to define an appropriate marketing strategy. SMEs need to adopt marketing strategies that build on their main advantages such as close proximity to customers, operational flexibility, flat hierarchies, short decision-making paths and rapid reaction times. The researcher addresses the research question: ‘How should Swiss SMEs in the ICT sector define their marketing strategy to benefit from digitalisation?’ by adopting a constructivist philosophy utilising a qualitative approach. Although this has been generally researched for large enterprises, SMEs with their specific characteristics should also be accounted for. A conceptual framework was formulated to inform the development of a marketing strategy for SMEs in the digital context. The research employed a mono methodological research design involving 14 case studies, conducted across businesses that have successfully transformed for the digital age. One marketing expert and two marketing agencies were additionally considered to strengthen the credibility and plausibility of the case studies. The findings indicate that changes in the market situation and the rapid evolution of various modern media channels require new levels of personalisation and targeted campaigns that drive engagement and brand loyalty. The study contributes to the existing theoretical body by arguing that the current view of marketing strategy in the digital era needs to be reformed to emphasise on the customer journey and to add data-driven elements to the mix using key digital marketing metrics. Further, the study suggests that ICT SMEs can improve customer experience and gain competitive advantage by designing new customer touchpoints through content. The study makes a practical contribution by proposing a marketing strategy canvas with eleven dimensions as a tool to help SMEs strategise digitisation and marketing strategy

Ras-induzierte Differenzierung nach Schädigung der DNA in Zellen der akuten myeloischen Leukämie

Ras-Proteine gehören zu einer Familie von Proto-Onkogenen, die für kleine GTPasen kodieren. Sie sind an vielen zellulären Prozessen wie Zellteilung, Apoptose und Differenzierung beteiligt. In 20-30% aller menschlichen Tumore weisen die RAS-Gene Punktmutationen auf, die das Protein in einen konstitutiv aktiven Zustand versetzen. Aus einer retrospektiven Studie von Patienten mit akuter myeloischer Leukämie (CALGB 8525) ist hervorgegangen, dass es eine Korrelation zwischen RAS-Status und Rezidivrate nach hochdosierter Cytarabin-Behandlung gibt. Patienten mit mutiertem RAS und Hochdosis-Cytarabin Behandlung, entwickelten signifikant weniger häufig Rezidive als Patienten mit wildtyp RAS oder Patienten, die mit Niedrigdosis-Cytarabin behandelt wurden. Somit geht aus der Studie hervor, dass die Expression eines Onkogens in Tumorzellen positive Auswirkungen auf die Behandlung mit Chemotherapeutika haben kann. Ausgehend von dieser Beobachtung sollte in dieser Arbeit der Effekt von onkogenem RAS in einem Zellsystem in vitro studiert und die molekularen Mechanismen aufgeklärt werden. Um onkogenes Ras in einem Zellsystem zu untersuchen, das als Model für akute myeloische Leukämie herangezogen werden kann, wurden hämatopoetische Zellen der Maus, die mit dem onkogenen Fusionsprotein MLL-ENL immortalisiert wurden, verwendet. Das Fusionsonkoprotein MLL-ENL kommt ausschließlich in Leukämien vor und die Zellen zeigen einen myeloischen Phänotyp. Diese Zellen wurden mit einem Kontrollvektor bzw. mit einem Vektor, der onkogenes RASV12 exprimiert, infiziert und auf die Behandlung mit Chemotherapeutika, insbesondere Cytarabin, untersucht. Die zytotoxische Wirkung von Cytarabin beruht darauf, dass die Substanz das Fortschreiten der Replikationsgabel behindert, woraufhin eine NASchadenssignalkaskade aktiviert wird, die nachfolgend Zellzyklusarrest oder Apoptose vermittelt. Cytarabin wirkt somit hauptsächlich auf Zellen, die sich in der Replikationsphase befinden. In Suspension wiesen die RAS-infizierten Zellen auf die Behandlung mit Cytarabin keinen Unterschied zu den Kontroll-Zellen hinsichtlich Zellzahl, Zellzyklus und Apoptose auf. Erfolgte die Kultivierung jedoch in semisolidem Medium, um die Klonogenität der Zellen zu untersuchen, zeigten die RAS-infizierten Zellen nach der Behandlung mit Cytarabin, Etoposid und Daunorubicin, eine starke Einschränkung in der Koloniebildung. Um die Ursache festzustellen, wodurch die klonogenen Zellen eliminiert werden, wurden die Zellen hinsichtlich Apoptose, Seneszenz und Differenzierung untersucht. Expressions- und Durchflusszytometrie-Analysen von Apoptosemarkern belegen, dass die Induktion von Apoptose in den RAS-infizierten Zellen niedriger war als in den Kontroll-Zellen und Apoptose damit nicht als Ursache für die eingeschränkte Klonogenität herangezogen werden kann. Aus der Literatur ist bekannt, dass die Infektion von primären Zellen mit onkogenem Ras eine DNA-Schadensantwort aktiviert, die einen seneszenten Phänotyp auslöst. Seneszente Zellen zeichnen sich durch eine erhöhte Expression von p53, p21Cip1 und des Ink4/Arf Locus (mit den Tumor Suppressoren p16Ink4a, p19Arf und p15Ink4b) aus. Zudem exprimieren seneszente Zellen das Enzym SA-β-Galaktosidase, dessen Aktivität in den Zellen sichtbar gemacht werden kann. Die Untersuchung der Kontrollproteine Chk1, H2A.x und ATM ergab, dass die DNASchadensantwort nur in den RAS-infizierten Zellen aktiviert war und diese durch Cytarabin weiter verstärkt wurde. Die Proteine p53, p21Cip1, p16Ink4a, p19Arf und p15Ink4b wurden in den RAS-infizierten Zellen stärker exprimiert als in den Kontroll-Zellen und durch Cytarabin teilweise weiter induziert (p53 und p21Cip1). Dagegen wurde das Enzym SA-β-Galaktosidase, sowohl in Kontroll-Zellen als auch in RAS-infizierten Zellen durch die Behandlung mit Cytarabin gleichermaßen aktiviert, was einen Hinweis darauf gibt, dass Cytarabin in Kontroll-Zellen Seneszenz auslösen kann. Die oben genannten Proteine sind auch in differenzierten Zellen stärker exprimiert. Ferner löst onkogenes Ras in hämatopoetischen Zellen Differenzierung aus, was im Übrigen auch für Cytarabin gezeigt wurde. Expressions- und Durchflusszytometrie-Analysen der Differenzierungsmarker ly6g (Gr1) und itgam (Mac1) zeigen, dass RAS-infizierte Zellen stärker differenziert waren als Kontroll-Zellen und die Behandlung mit Cytarabin die Differenzierung weiter verstärkte. Dies wurde auch anhand der Morphologie der Zellen bestätigt. Entscheidend für die Induktion der Differenzierung war dabei die Aktivierung der DNASchadenssignalkaskade, was durch die zusätzliche Behandlung der Zellen mit dem ATM/R-Inhibitor Koffein belegt werden konnte. Die Ergebnisse dieser Arbeit weisen darauf hin, dass konventionelle Zytostatika einen weiteren Mechanismus zur Tumorbekämpfung aktivieren können: Differenzierung. Differenzierung als therapeutischer Ansatz findet bereits in der Behandlung der akuten Promyelozyten Leukämie Anwendung. Die Induktion der Differenzierung könnte vor allem für Tumor-initiierende Zellen von größtem Interesse sein. Diese Krebsstammzellen werden durch herkömmliche Chemotherapeutika oft nicht vollständig eliminiert und können somit Ursache für Rezidive sein. Die Entwicklung von Substanzen, die die Differenzierung dieser Zellen aktivieren, wäre ein wichtiger Schritt der Resistenz vieler Tumorzellen gegenüber Chemotherapeutika entgegenzuwirken

«Taushet er gull, men det hjulet som knirker mest får smøring»

Master in Business Administration (MBA) - Nord universitet 201

Anatomic site-specific patterns of gene copy number gains in skin, mucosal, and uveal melanomas detected by fluorescence in situ hybridization

To assess the differences between melanomas of different location and different etiology, 372 malignant melanomas were brought in a tissue microarray format. The collection included 23 acral and 118 non-acral skin melanomas, 9 mucosal melanomas, 100 uveal melanomas, and 122 melanoma metastases. Fluorescence in situ hybridization (FISH) was used to assess copy number changes of the cyclin D1 (CCND1), MDM2, c-myc (MYC), and HER2 genes. FISH analysis revealed distinct differences between melanomas from different locations. CCND1 amplifications were detected in skin melanomas from sites with chronic sun exposure (6 of 32 cases), acral melanomas (4 of 17 cases), and mucosal melanomas (one of ten cases) but not in uveal melanomas. High-level MDM2 amplifications were exclusively present in acral melanomas (2 of 19 cases). MYC copy number gains were detected in 32 of 71 uveal melanomas, five of eight mucosal melanomas, and 6 of 67 melanomas from sites with intermittent sun exposure but not in acral melanomas nor melanomas from sites with chronic sun exposure. Alterations of the MYC gene were associated with advanced tumor stage. There were no high-level HER2 amplifications. Site-specific genetic and epigenetic features may impact the response of melanomas to various anti-cancer drugs and should be considered in future studies on the molecular pathogenesis of malignant melanoma

Expression and amplification of therapeutic target genes in retinoblastoma

Purpose: We set out to evaluate alterations of the therapeutic target genes KIT (CD 117), EGFR, and HER-2 in human retinoblastoma. Methods: Ninety-five formalin-fixed, paraffin-embedded retinoblastomas were brought into a tissue microarray (TMA) format. Immunohistochemistry was performed to analyze the expression of CD117, EGFR, and HER-2. Fluorescence in situ hybridization (FISH) was utilized for detection of EGFR amplifications. Three tumors with strong CD117 positivity were sequenced for KIT exon 11 mutations. Results: Detectable CD117 expression was seen in 19% of all interpretable cases. Sequence analysis of the three tumors with the strongest CD117 expression revealed no mutations. EGFR was positive in 14% of all cases. No EGFR amplification was observed by FISH, however. All tumors were negative for HER-2 expression. Conclusions: Our data suggest that selected cases of retinoblastoma may be candidates for anti-EGFR and imatinib mesylate (STI571) therap

Partial Pressure of Arterial Oxygen in Healthy Adults at High Altitudes: A Systematic Review and Meta-Analysis

Importance: With increasing altitude, the partial pressure of inspired oxygen decreases and, consequently, the Pao$_{2}$ decreases. Even though this phenomenon is well known, the extent of the reduction as a function of altitude remains unknown. Objective: To calculate an effect size estimate for the decrease in Pao$_{2}$ with each kilometer of vertical gain among healthy unacclimatized adults and to identify factors associated with Pao$_{2}$ at high altitude (HA). Data Sources: A systematic search of PubMed and Embase was performed from database inception to April 11, 2023. Search terms included arterial blood gases and altitude. Study Selection: A total of 53 peer-reviewed prospective studies in healthy adults providing results of arterial blood gas analysis at low altitude (<1500 m) and within the first 3 days at the target altitude (≥1500 m) were analyzed. Data Extraction and Synthesis: Primary and secondary outcomes as well as study characteristics were extracted from the included studies, and individual participant data (IPD) were requested. Estimates were pooled using a random-effects DerSimonian-Laird model for the meta-analysis. Main Outcomes and Measures: Mean effect size estimates and 95% CIs for reduction in Pao$_{2}$ at HA and factors associated with Pao$_{2}$ at HA in healthy adults. Results: All of the 53 studies involving 777 adults (mean [SD] age, 36.2 [10.5] years; 510 men [65.6%]) reporting 115 group ascents to altitudes between 1524 m and 8730 m were included in the aggregated data analysis; 13 of those studies involving 305 individuals (mean [SD] age, 39.8 [13.6] years; 185 men [60.7%]) reporting 29 ascents were included in the IPD analysis. The estimated effect size of Pao$_{2}$ was −1.60 kPa (95% CI, −1.73 to −1.47 kPa) for each 1000 m of altitude gain (τ$^{2}$ = 0.14; I$^{2}$ = 86%). The Pao$_{2}$ estimation model based on IPD data revealed that target altitude (−1.53 kPa per 1000 m; 95% CI, −1.63 to −1.42 kPa per 1000 m), age (−0.01 kPa per year; 95% CI, −0.02 to −0.003 kPa per year), and time spent at an altitude of 1500 m or higher (0.16 kPa per day; 95% CI, 0.11-0.21 kPa per day) were significantly associated with Pao$_{2}$. Conclusions and Relevance: In this systematic review and meta-analysis, the mean decrease in Pao$_{2}$ was 1.60 kPa per 1000 m of vertical ascent. This effect size estimate may improve the understanding of physiological mechanisms, assist in the clinical interpretation of acute altitude illness in healthy individuals, and serve as a reference for physicians counseling patients with cardiorespiratory disease who are traveling to HA regions

Revealing the profound influence of diapause on gene expression: Insights from the annual transcriptome of the copepod Calanus finmarchicus

Annual rhythms are observed in living organisms with numerous ecological implications. In the zooplanktonic copepod Calanus finmarchicus, such rhythms are crucial regarding its phenology, body lipid accumulation, and global carbon storage. Climate change drives annual biological rhythms out of phase with the prevailing environmental conditions with yet unknown but potentially catastrophic consequences. However, the molecular dynamics underlying phenology are still poorly described. In a rhythmic analysis of C. finmarchicus annual gene expression, results reveal that more than 90% of the transcriptome shows significant annual rhythms, with abrupt and dramatic upheaval between the active and diapause life cycle states. This work explores the implication of the circadian clock in the annual timing, which may control epigenetic mechanisms to profoundly modulate gene expression in response to calendar time. Results also suggest an increased light sensitivity during diapause that would ensure the photoperiodic entrainment of the endogenous annual clock

Charge Dynamics of a CuO Thin Film on Picosecond to Microsecond Timescales Revealed by Transient Absorption Spectroscopy

Understanding the mechanism of charge dynamics in photocatalysts is the key to design and optimize more efficient materials for renewable energy applications. In this study, the charge dynamics of a CuO thin film are unraveled via transient absorption spectroscopy (TAS) on the picosecond to microsecond timescale for three different excitation energies, i.e., above, near, and below the band gap, to explore the role of incoherent broadband light sources. The shape of the ps-TAS spectra changes with the delay time, while that of the ns-TAS spectra is invariant for all the excitation energies. Regardless of the excitations, three time constants, τ1 ∼ 0.34–0.59 ps, τ2 ∼ 162–175 ns, and τ3 ∼ 2.5–3.3 μs, are resolved, indicating the dominating charge dynamics at very different timescales. Based on these observations, the UV–vis absorption spectrum, and previous findings in the literature, a compelling transition energy diagram is proposed. Two conduction bands and two defect (deep and shallow) states dominate the initial photo-induced electron transitions, and a sub-valence band energy state is involved in the subsequent transient absorption. By solving the rate equations for the pump-induced population dynamics and implementing the assumed Lorentzian absorption spectral shape between two energy states, the TAS spectra are modeled which capture the main spectral and time-dependent features for t > 1 ps. By further considering the contributions from free-electron absorption during very early delay times, the modeled spectra reproduce the experimental spectra very well over the entire time range and under different excitation conditions

Sequence analysis and high-throughput immunhistochemical profiling of KIT (CD 117) expression in uveal melanoma using tissue microarrays

We aimed to immunohistochemically examine the expression of KIT (CD 117) in human posterior uveal melanoma and to analyze KIT-positive tumors for gene mutations. Brought into a tissue microarray (TMA) format were 101 formalin-fixed, paraffin-embedded posterior uveal melanomas. Immunhistochemistry was performed using the polyclonal anti-CD117 antibody from Dako (A4502). In ten selected KIT-positive tumors, exons 2, 8, 9, 11, 13 and 17 were sequenced. Of the 101 cases, 89 (88%) could be evaluated on the TMAs. Immunohistochemistry for CD 117 was weakly positive in 5 cases (6%), moderately positive in 10 cases (12%) and strongly positive in 57 cases (69%). No KIT mutations were detected in the analyzed exons. In conclusion, human posterior uveal melanoma frequently expresses CD117 at high levels. Although KIT mutations could not be found, it appears justified to investigate the utility of imatinib mesylate in the treatment of these patient