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International comparisons of stillbirth allow assessment of variations in clinical practice to reduce mortality. Currently, such comparisons include only stillbirths from 28 or more completed weeks of gestational age, which underestimates the true burden of stillbirth. With increased registration of early stillbirths in high-income countries, we assessed the reliability of including stillbirths before 28 completed weeks in such comparisons. In this population-based study, we used national cohort data from 19 European countries participating in the Euro-Peristat project on livebirths and stillbirths from 22 completed weeks of gestation in 2004, 2010, and 2015. We excluded countries without national data for stillbirths by gestational age in these periods, or where data available were not comparable between 2004 and 2015. We also excluded those countries with fewer than 10 000 births per year because the proportion of stillbirths at 22 weeks to less than 28 weeks of gestation is small. We calculated pooled stillbirth rates using a random-effects model and changes in rates between 2004 and 2015 using risk ratios (RR) by gestational age and country. Stillbirths at 22 weeks to less than 28 weeks of gestation accounted for 32% of all stillbirths in 2015. The pooled stillbirth rate at 24 weeks to less than 28 weeks declined from 0·97 to 0·70 per 1000 births from 2004 to 2015, a reduction of 25% (RR 0·75, 95% CI 0·65–0·85). The pooled stillbirth rate at 22 weeks to less than 24 weeks of gestation in 2015 was 0·53 per 1000 births and did not significantly changed over time (RR 0·97, 95% CI 0·80–1·16) although changes varied widely between countries (RRs 0·62–2·09). Wide variation in the percentage of all births occurring at 22 weeks to less than 24 weeks of gestation suggest international differences in ascertainment. Present definitions used for international comparisons exclude a third of stillbirths. International consistency of reporting stillbirths at 24 weeks to less than 28 weeks suggests these deaths should be included in routinely reported comparisons. This addition would have a major impact, acknowledging the burden of perinatal death to families, and making international assessments more informative for clinical practice and policy. Ascertainment of fetal deaths at 22 weeks to less than 24 weeks should be stabilised so that all stillbirths from 22 completed weeks of gestation onwards can be reliably compared. EU Union under the framework of the Health Programme and the Bridge Health Project.

Background Despite concerns about worsening pregnancy outcomes resulting from healthcare restrictions, economic difficulties and increased stress during the COVID-19 pandemic, preterm birth (PTB) rates declined in some countries in 2020, while stillbirth rates appeared stable. Like other shocks, the pandemic may have exacerbated existing socioeconomic disparities in pregnancy, but this remains to be established. Our objective was to investigate changes in PTB and stillbirth by socioeconomic status (SES) in European countries. Methods The Euro-Peristat network implemented this study within the Population Health Information Research Infrastructure (PHIRI) project. A common data model was developed to collect aggregated tables from routine birth data for 2015–2020. SES was based on mother’s educational level or area-level deprivation/maternal occupation if education was unavailable and harmonized into low, medium and high SES. Country-specific relative risks (RRs) of PTB and stillbirth for March to December 2020, adjusted for linear trends from 2015 to 2019, by SES group were pooled using random effects meta-analysis. Results Twenty-one countries provided data on perinatal outcomes by SES. PTB declined by an average 4% in 2020 {pooled RR: 0.96 [95% confidence intervals (CIs): 0.94–0.97]} with similar estimates across all SES groups. Stillbirths rose by 5% [RR: 1.05 (95% CI: 0.99–1.10)], with increases of between 3 and 6% across the three SES groups, with overlapping confidence limits. Conclusions PTB decreases were similar regardless of SES group, while stillbirth rates rose without marked differences between groups.

Few studies have investigated international variations in the gestational age (GA) distribution of births. While preterm births (22-36 weeks GA) and early term births (37-38 weeks) are at greater risk of adverse health outcomes compared to full term births (39-40 weeks), it is not known if countries with high preterm birth rates also have high early term birth rates. We examined rate associations between preterm and early term births and mean term GA by mode of delivery onset. We used routine aggregate data on the GA distribution of singleton live births from up to 34 high-income countries/regions in 1996, 2000, 2004, 2008 and 2010 to study preterm and early term births overall and by spontaneous or indicated onset. Pearson correlation coefficients were adjusted for clustering in time trend analyses. Preterm and early term births ranged from 4.1% to 8.2% (median 5.5%) and 15.6% to 30.8% (median 22.2%) of live births in 2010, respectively. Countries with higher preterm birth rates in 2004-2010 had higher early term birth rates (r > 0.50, P < 0.01) and changes over time were strongly correlated overall (adjusted-r = 0.55, P < 0.01) and by mode of onset. Positive associations between preterm and early term birth rates suggest that common risk factors could underpin shifts in the GA distribution. Targeting modifiable population risk factors for delivery before 39 weeks GA may provide a useful preterm birth prevention paradigm.

Clinically non-functioning pituitary adenomas account for about one-third of pituitary tumors. The majority of them are pathologically classified as gonadotropinomas or null-cell adenomas without hormonal expression. The rest represent silent corticotroph adenomas and plurihormonal tumors. Conservative therapy with dopamine agonists is effective in some cases only depending on the expression of dopamine 2 receptors (D2R). The aim of this study was to quantitatively estimate D2R expression in clinically non-functioning pituitary adenomas and correlate the results with adenoma type according to pathological classification. Out of the 87 adenomas investigated, 63 expressed gonadotropins, 7 were silent corticotroph adenomas, 7 were plurihormonal tumors, and only 6 did not express any pituitary hormone on immunohistochemical investigation. With the use of the reverse transcriptase PCR technique, D2R mRNA was expressed in all adenomas with very heterogeneous quantity. The expression was very low in corticotroph adenomas (relative median quantity after normalization to housekeeping gene 0.01) and lower in plurihormonal tumors (median 0.4) than in gonadotroph (median 1.3) and null-cell adenomas (median 1.9). The difference between corticotroph adenomas and plurihormonal tumors in comparison with other pathological types was statistically significant. The expression of D2R did not depend on the presence or absence of gonadotropins. We conclude that D2R expression is very low in corticotroph adenomas and significantly lower in plurihormonal tumors. The positivity of gonadotropins does not predict the D2R quantity.

Sox2 is one of the transcription factors responsible for the maintenance of stem cell phenotype. It has been implicated as a marker of stem cells in normal pituitaries and pituitary neuroendocrine tumours. To explore the clinical significance of Sox2 expression in histological sections, we performed immunohistochemical detection of Sox2 in 113 pituitary neuroendocrine tumours from 109 patients with acromegaly. In 11 tumours, we performed double immunostaining for Sox2, annexin A1 and S100 protein. Tumours were characterised using the WHO classification system. Proliferative activity and invasion were assessed. The amount of immunoreactive cells was evaluated and correlated with tumour size and biochemical features (levels of IGF1, GH, prolactin, βTSH). Sox2+ cells were identified in 35/38 normal pituitaries adjacent to the tumours. In 36 tumours (33%), ≥ 1% of the cells expressed Sox2, in 24 cases (22%), Sox2+ cells comprised < 1% and 49 cases (45%) were negative. We found no significant differences between Sox2+ and Sox2− groups with respect to the age, initial levels of GH, IGF1, prolactin, βTSH, tumour size, invasion, proliferative activity or histological features. We observed a positive correlation between Sox2+ cell count and βTSH immunoreactive cells (r = 0.459, p < 0.001) that was further verified by multivariate analysis. Using double stain, the majority of Sox2+ cells coexpressed annexin A1 (average 89%) and S100 protein (average 76.2%) and showed morphological features of folliculo-stellate cells. Sox2+ cells are thus commonly present in growth hormone–producing tumours and normal pituitaries, and their amount does not have any prognostic significance. Most of these cells represent a subpopulation of folliculo-stellate cells, pointing out to their role as a possible stem cell population.

BackgroundStillbirth and neonatal mortality rates declined in Europe between 2004 and 2010. We hypothesised that declines might be greater for countries with higher mortality in 2004 and disproportionally affect very preterm infants at highest risk.MethodsData about live births, stillbirths and neonatal deaths by gestational age (GA) were collected using a common protocol by the Euro-Peristat project in 2004 and 2010. We analysed stillbirths at ≥28 weeks GA in 22 countries and live births ≥24 weeks GA for neonatal mortality in 18 countries. Per cent changes over time were assessed by calculating risk ratios (RR) for stillbirth, neonatal mortality and preterm birth rates in 2010 vs 2004. We used meta-analysis techniques to derive pooled RR using random-effects models overall, by GA subgroups and by mortality level in 2004.ResultsBetween 2004 and 2010, stillbirths declined by 17% (95% CI 10% to 23%), with a range from 1% to 39% by country. Neonatal mortality declined by 29% (95% CI 23% to 35%) with a range from 9% to 67%. Preterm birth rates did not change: 0% (95% CI −3% to 3%). Mortality declines were of a similar magnitude at all GA; mortality levels in 2004 were not associated with RRs.ConclusionsStillbirths and neonatal deaths declined at all gestational ages in countries with both high and low levels of mortality in 2004. These results raise questions about how low-mortality countries achieve continued declines and highlight the importance of improving care across the GA spectrum.

Infants from multiple pregnancies have higher rates of preterm birth, stillbirth and neonatal death and differences in multiple birth rates (MBR) exist between countries. We aimed to describe differences in MBR in Europe and to investigate the impact of these differences on adverse perinatal outcomes at a population level. We used national aggregate birth data on multiple pregnancies, maternal age, gestational age (GA), stillbirth and neonatal death collected in the Euro-Peristat project (29 countries in 2010, N = 5 074 643 births). We also used European Society of Human Reproduction and Embryology (ESHRE) data on assisted conception and single embryo transfer (SET). The impact of MBR on outcomes was studied using meta-analysis techniques with random-effects models to derive pooled risk ratios (pRR) overall and for four groups of country defined by their MBR. We computed population attributable risks (PAR) for these groups. In 2010, the average MBR was 16.8 per 1000 women giving birth, ranging from 9.1 (Romania) to 26.5 (Cyprus). Compared to singletons, multiples had a nine-fold increased risk (pRR 9.4, 95% Cl 9.1-9.8) of preterm birth (<37 weeks GA), an almost 12-fold increased risk (pRR 11.7, 95% CI 11.0-12.4) of very preterm birth (<32 weeks GA). Pooled RR were 2.4 (95% Cl 1.5-3.6) for fetal mortality at or after 28 weeks GA and 7.0 (95% Cl 6.1-8.0) for neonatal mortality. PAR of neonatal death and very preterm birth were higher in countries with high MBR compared to low MBR (17.1% (95% CI 13.8-20.2) versus 9.8% (95% Cl 9.6-11.0) for neonatal death and 29.6% (96% CI 28.5-30.6) versus 17.5% (95% CI 15.7-18.3) for very preterm births, respectively). Wide variations in MBR and their impact on population outcomes imply that efforts by countries to reduce MBR could improve perinatal outcomes, enabling better long-term child health.

The superior question of this paper is how startups and spin-offs can be supported, and one major goal of this work is to give an overview of existing support mechanisms for new ventures. Through the research of affected stakeholders in the technology transfer process, the characteristics of incubation instruments and the development of the Venture Incubation Canvas, it provides an applied knowledge base for decision makers. The reader should get a picture about how different mechanisms help start-ups in various phases of their venture life cycle and have the necessary tools to create a robust and fruitful incubation business model from the beginning on. The abstract information, principles and the use of the model should be applicable in a general way for different projects and innovation (eco) systems. Since the paper aims at being used in projects in the area of R&D networks, it is important to provide knowledge about the process of transferring technologies into the economy and cast a light on the affected stakeholders. Moreover, a literature review about the different dimensions that are used to define start-up support programs is carried out and existing support mechanisms and best practice examples in the global market are examined. Finally, a practical model is introduced in order to simplify the set-up of an incubation mechanism.

Innovation is one of the main topics pushing economic activities today. The procedure to integrate innovation processes, which need a complex research and development (R & D) environment, is a challenge for enterprises to handle by themselves. As a result, innovation networks are one strategic solution for enterprises and other R & D related organizations and institutes, in order to successfully found and integrate innovation processes within their organization. Followed by further challenges regarding the management of innovation networks, the need of specific innovation network management knowledge and skills become a key competence. The following paper gives a state of the art overview of network management frameworks found in the relevant literature. The particular focus of this Paper lies on the management of innovation networks. The (Innovation) network management frameworks (INMF) of different authors were assembled in various literature research processes. Due to the small amount of INMFs discussed in pertinent literature, general network management frameworks that are applicable to examine innovation networks are identified as relevant as well. All frameworks were selected by their capability of presenting precise understanding about management of innovation networks. Further, the paper analyses all identified management frameworks in order to evaluate the competence of each framework implicating its specific characteristics. The analysis contains a description of all as relevant identified frameworks and elaborates their weaknesses and strengths while taking different innovation and enterprise environments into account. The evaluation process was developed for the specific needs of innovation network management and their individual partners. The conclusion of the paper provides a state of the art compilation and analysis of INMFs. The paper also points out the particular lack of research in this field and gives impulses to develop further ideas and specific INMFs.

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1‐5, dopamine D2 receptor, E‐cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E‐cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E‐cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E‐cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.