Fungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity

Although gut bacterial dysbiosis is recognized as a regulator of beta-cell autoimmunity, no data is available on fungal dysbiosis in the children at the risk of type 1 diabetes (T1D). We hypothesized that the co-occurrence of fungal and bacterial dysbiosis contributes to the intestinal inflammation and autoimmune destruction of insulin-producing beta-cells in T1D. Fecal and blood samples were collected from 26 children tested positive for at least one diabetes-associated autoantibody (IAA, GADA, IA-2A or ICA) and matched autoantibody-negative children with HLA-conferred susceptibility to T1D (matched for HLA-DQB1 haplotype, age, gender and early childhood nutrition). Bacterial 16S and fungal ITS2 sequencing, and analyses of the markers of intestinal inflammation, namely fecal human beta-defensin-2 (HBD2), calprotectin and secretory total IgA, were performed. Anti-Saccharomyces cerevisiae antibodies (ASCA) and circulating cytokines, IFNG, IL-17 and IL-22, were studied. After these analyses, the children were followed for development of clinical T1D (median 8 years and 8 months). Nine autoantibody positive children were diagnosed with T1D, whereas none of the autoantibody negative children developed T1D during the follow-up. Fungal dysbiosis, characterized by high abundance of fecal Saccharomyces and Candida, was found in the progressors, i.e., children with beta-cell autoimmunity who during the follow-up progressed to clinical T1D. These children showed also bacterial dysbiosis, i.e., increased Bacteroidales and Clostridiales ratio, which was, however, found also in the non-progressors, and is thus a common nominator in the children with beta-cell autoimmunity. Furthermore, the progressors showed markers of intestinal inflammation detected as increased levels of fecal HBD2 and ASCA IgG to fungal antigens. We conclude that the fungal and bacterial dysbiosis, and intestinal inflammation are associated with the development of T1D in children with beta-cell autoimmunity

Breast cancer in neurofibromatosis type 1 : overrepresentation of unfavourable prognostic factors

Background: An increased breast cancer incidence and poor survival have been reported for women with neurofibromatosis 1 (NF1). To explain the poor survival, we aimed to link the histopathology and clinical characteristics of NF1-associated breast cancers. Methods: The Finnish Cancer Registry and the Finnish NF Registry were cross-referenced to identify the NF1 patients with breast cancer. Archival NF1 breast cancer specimens were retrieved for histopathological typing and compared with matched controls. Results: A total of 32 breast cancers were diagnosed in 1404 NF1 patients during the follow-up. Women with NF1 had an estimated lifetime risk of 18.0% for breast cancer, and this is nearly two-fold compared with that of the general Finnish female population (9.74%). The 26 successfully retrieved archival NF1 breast tumours were more often associated with unfavourable prognostic factors, such as oestrogen and progesterone receptor negativity and HER2 amplification. However, survival was worse in the NF1 group (P = 0.053) even when compared with the control group matched for age, diagnosis year, gender and oestrogen receptor status. Scrutiny of The Cancer Genome Atlas data set showed that NF1 mutations and deletions were associated with similar characteristics in the breast cancers of the general population. Conclusions: These results emphasise the role of the NF1 gene in the pathogenesis of breast cancer and a need for active follow-up for breast cancer in women with NF1.Peer reviewe

Metabolic Regulation in Progression to Autoimmune Diabetes

Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes

Improving product development process through verification and validation

Abstract The workload of Verification and Validation (V&V) has increased constantly in the high technology industries. The changes in the business environment, with fast time-to-market and demands to decrease research and development costs, have increased the importance of efficient product creation process, including V&V. The significance of the V&V related know-how and testing is increasing in the high tech business environment. As a consequence, companies in the ICT sector have pressures for improving product development process and verification and validation activities. The main motive for this research arises from the fact that the research has been scarce on verification and validation from product development process perspective. This study approaches the above mentioned goal from four perspectives: current challenges and success factors, V&V maturity in different NPD phases, benchmarking automotive sector, and shifting the emphasis of NPD efforts. This dissertation is qualitative in nature and is based on interviewing experienced industrial managers, reflecting their views against scientific literature. The researcher has analysed the obtained material and made conclusions. The main implications of this doctoral dissertation can be concluded as a visible need to shift the emphasis of V&V activities to early NPD. These activities should be viewed and managed over the entire NPD process. There is a need for companies to understand the V&V maturity in different NPD phases and develop activities based on this understanding. Verification and validation activities must be seen as an integral element for successful NPD. Benchmarking other sectors may enable identifying development potential for NPD process. The automotive sector being a mature sector, has developed practices for successfully handling requirements during NPD. The role of V&V is different in different NPD phases. Set-based type V&V can provide required understanding during early product development. In addition, developing parallel technological alternatives and platforms during early NPD also support shifting the emphasis towards earlier development phases

Pohjoisen biotalous:näkökulmia ja mahdollisuuksia Pohjois-Suomessa

Abstract This edited publication consists of four reports written as a part of BICON project that clarified the state and potential of Bioeconomy in Northern Finland. The whole formed by the individual reports constitute an extensive view over bioeconomy and its potential in the northern Finland. There is no single, wide-adopted definition of what bioeconomy is. However, as the theme represents a new economic platform, it is well recognised and has a social and political support. The strategies of nations and industries regarding bioeconomy have appeared in abundance in recent years. Almost without exception, these strategies are relying on existing industrial and national foundations. Bioeconomy has potential in Northern Finland. Especially biomass utilisation and refinement has long tradition in forestry and natural products. However, new ways to boost nascent bioeconomy are called for. One option is Biopark -concept as introduced by BusinessOulu. Also the policy directions should be clear enough for the investments to take place. Otherwise multiple risks can be envisaged by investors and make them reluctant to take action. The bioeconomy, as we can see it today, is still de facto by and largely built around traditional products and industries. Forest and wood industries and agriculture serve as good examples. In Northern Finland, there are well more than 100 companies the core business of which is relying on forest bio-mass. These companies employ around 4000 people. As to other sectors, the numbers are smaller, but by no means insignificant in relative respect. The growth of bioeconomy is highly dependent on investments and development carried out by these companies. Berries and fungi are one potential area with less volume but regarded as promising niche segment. The industry around these natural products comprises mostly micro-sized companies, so subsidies in the r&d are essential if growth is truly sought. Basic research is performed in number of Finnish universities and institutes, but the scaling-up of research into marketable end products with significant commercial market value requires more effective collaboration. “Northern quality” could be one of immaterial brands that could be utilised further. Organic products and processes continue to be a consumer-driven trend.Tiivistelmä Biotalous Pohjois-Suomen alueella on biotaloustoiminnan tilaa ja kehityspotentiaalia kartoittaneen (BICON) -projektin osaraporteista koostettu kokonaisuus. Osaraporttien muodostama kokonaisuus muodostaa kattavan katsauksen biotalouteen ja sen antamiin mahdollisuuksiin Pohjois-Suomessa. Biotaloudelle ei voida esittää yksikäsitteistä määritelmää, mutta se on teemana tunnistettu uudeksi talouden osa-alueeksi, jolle on olemassa sosiaalinen, taloudellinen ja poliittinenkin tilaus. Eri maiden ja teollisten sektoreiden biotalousstrategiat, joita on viime vuosina laadittu runsaasti, nojautuvat lähes poikkeuksetta teollisiin strategioihin ja olemassa oleviin perinteisiin vahvuuksiin kussakin maassa ja kullakin toimialalla. Pohjois-Suomessa biomassan käytölle on lupaavat mahdollisuudet. Eräänä konkreettisena askeleena voisi olla BusinessOulun esittelemä Biopark -konsepti. Jotta investointeihin kuitenkin oltaisiin valmiita, tulee poliittisten linjausten olla riittävän selkeitä, jotta niihin sisältyvät riskit ovat joltisenkin hallinnassa. Käytännössä Pohjois-Suomen alueen biotalous nojaa vielä vahvasti olemassa oleviin perinteisiin tuotteisiin ja yrityksiin. Näistä hyvinä esimerkkeinä ovat metsäbiomassan alkutuotanto, maatalous ja viljakasvien jatkojalostus. Metsäbiomassaa jalostavia yrityksiä on Pohjois-Suomessa reilusti yli 100 ja työpaikkoja muutamia tuhansia. Muissa biotalouden osa-alueissa määrät ovat pienempiä mutta eivät suinkaan merkityksettömiä. Alueellisen biotalouden kasvu on paljolti kiinni yritysten panostuksista ja niitä tukevasta tutkimuksesta ja kehittämisestä. Marjat ja sienet ovat eräs biotalouden potentiaalinen kehittämisalue. Alan yritykset ovat pääasiassa mikroyrityksiä, joten tuotekehitykseen tarvittaisiin selkeä yhteiskunnan tuki. Perustutkimusta tehdään kuitenkin useassa suomalaisessa yliopistossa ja tutkimuslaitoksessa, mutta potentiaalinen mittakaavaistaminen kaupallisiksi tuotteiksi ja jalosteiksi vaatii tutkijoiden ja yritysten välistä yhteistyötä. ”Pohjoinen laatu” voisi olla eräs merkittävä kaupallistettava brändi, sillä puhtaus ja luonnonmukaisuus ovat eräs kulutustrendi, joka voimistunee jatkossakin

Exploring the benefits of service productisation:support for business processes

Abstract Purpose: The study aims to explore the benefits of service productisation to provide further understanding on the productisation concept as support for business processes and service management. The concept has been deficiently discussed regardless of the potential significance to the whole formed by service products, business processes, information technology (IT), people and data. Design/methodology/approach: In the study, the exploratory empirical evidence is presented from 16 cases, 4 of which are from companies that are globally well-known. Findings: The key findings of the paper include an overview of the benefits of service productisation and the relation to service offering, service processes and related resources. The concept links to the management of the whole formed by service products, business processes, IT, people and data. The noted benefits seem to be applicable to productisation of different service types, whilst some service characteristics may affect the specific emphasis. Research limitations/implications: The limitations involve using secondary data, which, however, makes the cases less biased regarding the aims. Primary data are required to gain further insights into the phenomena and the identified benefits. Practical implications: The findings provide support for issues that are commonly discussed by practitioners on a concept that is less studied by the scientific literature. Practitioners can work towards organisational efficiency and effectiveness by understanding the benefits of productisation. Understanding service productisation can support the effective management of business processes and work towards prosperity in the service business. Originality/value: The study is the first one to analyse the benefits of service productisation by exploring the issue through multiple cases and attempting to identify aspects for further attention by the academic community

Establishing an automated brand index based on opinion mining:analysis of printed and social media

Abstract This article analyses the potential of using opinion mining based on big data to calculate a brand index to reflect brand image in the media. The study is realised as a combination of analysing previous literature and applying a media monitoring tool to analyse editorial publications and social media to gain brand-related media sentiment. The potential of opinion mining and the use of vast amounts of data are demonstrated. The results indicate that sentiment analysis based on big data has potential for automating the calculation of brand indices. It seems that big data can be used to compare brands and the nature of their media visibility. Marketing research and the analytics domain can benefit from big data and their related meaningful applications

The first wave impact of COVID-19 pandemic on the Nasdaq Helsinki stock exchange:weak signal detection with managerial implications

Abstract The global pandemic caused by the coronavirus disease (COVID-19) came mostlyas a surprise and had a major effect on the global economy. This type of major events that canbring societies to nearly a total standstill are difficult to predict but have a significant impacton business activities. Nevertheless, weak signals might be possible to detect beforehand toenable preparation for the impact, both globally and locally. This study analyses the impact ofthe first wave of the COVID-19 pandemic on the Nasdaq Helsinki stock exchange by utilisinglarge-scale media analytics. This entails gaining data through media monitoring over the entireduration of the pandemic by applying black-box algorithms and advanced analytics on realcases. The data analysis is carried out to understand the impact of a such global event ingeneral, while aiming to learn from the potential weak signals to enable future marketintelligence to prepare for similar events. A social media firestorm scale, similar to the Richterscale for earthquakes or Sapphir-Simpson scale for hurricanes, is utilised to support theanalysis and assist in explaining the phenomenon. The results indicate that pandemics andtheir impact on markets can be studied as a subset of a media firestorms that produce a sharkfintype of pattern in analytics. The findings indicate that early signals from such events arepossible to detect by means of media monitoring, and that the stock exchange behaviour isaffected. The implications include highlighting the importance of weak signal detection fromabundant data to have the possibility to instigate preventive actions and prepare for such eventsto avoid maximum negative business impact. The early reaction to this type of events requiresa very streamlined connection between market intelligence and different business activities

Opinion mining approach to study media-image of energy production:implications to public acceptance and market deployment

Abstract The nature of media image, through either traditional or social media, may have an influence on public acceptance of energy technologies. The potential impact on decision-making can make media image a factor for technology market deployment, similar to technical, legal, and economic factors. Public acceptance tends to be shaped by how technologies are presented in the media. This study compares and analyses the media image of various power production technologies. Editorial and social media are analysed by using the M-Adaptive tool for media monitoring to obtain the media sentiment. The analysis is rather broad, including three million social media platforms and various news outlets in many regions and covering an enormous number of data points, from which this study has selected over 250,000 for further analysis with the help of artificial intelligence. The results indicate that public sentiment towards power production technologies varies among different technologies, and between editorial publications and social media. Editorial content is usually constructed by using news frames, whereas social media includes more emotional content from single users. A potential chain from media image to energy technology market deployment is suggested. The findings support the notion of social media having an increasing role in shaping public opinion, which may need to be acknowledged to a larger extent

Improving strategic decision making with big data-based media analysis:the case of coal power

Abstract Big-data based methods are developed to aid corporate decision-making. This study utilises big-data based global media-analysis to clarify the role of coal-power related media-image in company decision-making. Opinion mining by a specific software tool for media-analysis and monitoring is utilised. The analysis bases on the notion that the media-image of company products — or specific technologies — may impact corporate investment and divestment decisions in the energy sector. The assumption is that coal-power related media-image may cause corporate brandimage pressures. The findings indicate that the general media-sentiment towards coal-power is negative, possibly influencing corporate decisions. The large negative media-sentiment towards coal-power may override the benefits of developing cleaner coal-power and related technologies such as carbon capture and storage and utilisation. The negative media-sentiment towards coal-power may mitigate the more positive image of related less-known technologies. Evidence is provided on the media-impact of coal-power related divestment decisions and potential impacts on decision making