Health of singletons born after frozen embryo transfer until early adulthood : a Finnish register study

STUDY QUESTION Is the health of singletons born after frozen embryo transfer (FET) comparable to that of singletons born after fresh embryo transfer (ET) until early adulthood? SUMMARY ANSWER The health of singletons born after FET does not differ from that of singletons born after fresh ET. WHAT IS KNOWN ALREADY The differences in perinatal outcomes of children born after FET and fresh ET are well known. FET is associated with an increased risk of large-for-gestational-age but diminished risks of preterm birth (PTB), small-for-gestational-age and decreased perinatal mortality compared to fresh ET. However, knowledge on the long-term health after FET is scarce. STUDY DESIGN, SIZE, DURATION This retrospective register-based cohort study compares singletons born after FET (n = 1825) between the years 1995 and 2006 to those born after fresh ET (n = 2933) and natural conception (NC, n = 31 136) with a mean follow-up time of 18-20 years. PARTICIPANTS/MATERIALS, SETTING, METHODS Singletons born after FET were compared to those born after fresh ET and NC regarding the frequencies of diagnoses in the main ICD-10 chapters (International Statistical Classification of Diseases and Related Health Problems, 10th revision), the number of outpatient visits and hospital admissions, and mortality. Adjustments were made for PTB, maternal age, parity, socioeconomic status based on mother's occupation and offspring sex. The study combines data from the Finnish Medical Birth Register, the Finnish Care Register for Health Care (CRHC) and the Cause-of-Death Register at Statistics Finland. The Student's T-test was used for continuous variables, and the Chi-square test was used for categorical variables. Cox regression was used to estimate crude and adjusted hazard ratios (HRs and aHRs, respectively). A general linear model was used to compare the means of outpatient visits, hospital admissions and lengths of hospital stays per person. MAIN RESULTS AND THE ROLE OF CHANCE No significant differences between the FET and fresh ET groups were found in the frequency of diagnoses in any of the ICD-10 chapters or in the parameters describing the need for hospital care. However, compared to the NC group, higher proportions in the FET group had outpatient visits in the hospital (93.5% vs 92.2%, aHR 1.23, 95% CI 1.17, 1.30) or hospital admissions (48% vs 46.5%, aHR 1.28, 95% CI 1.19, 1.37). Compared to the NC group, the FET group had elevated adjusted risks of diagnoses of infectious and parasitic diseases (aHR 1.24; 95% CI 1.11, 1.38), neoplasms (aHR 1.68; 95% CI 1.48, 1.91), diseases of the eye and adnexa, the ear or mastoid process (aHR 1.11; 95% CI 1.01, 1.21), the respiratory system (aHR 1.15; 95% CI 1.06, 1.23), the digestive system (aHR 1.17; 95% CI 1.05, 1.32), the skin or subcutaneous tissue (aHR 1.28; 95% CI 1.14, 1.43) and the genitourinary system (aHR 1.27; 95% CI 1.11, 1.45), as well as congenital malformations or chromosomal abnormalities (aHR 1.31; 95% CI 1.14, 1.50) and symptoms, signs or abnormal clinical or laboratory findings (aHR 1.25, 95% CI 1.16, 1.34). LIMITATIONS, REASONS FOR CAUTION Only hospital-based inpatient and outpatient care is covered by the CRHC register, excluding milder cases diagnosed elsewhere. We were not able to study the effect of ART treatments and subfertility separately in our setting. In addition, although our cohort is reasonably sized, even larger cohorts would be needed to reliably study rare outcomes, such as cancer. WIDER IMPLICATIONS OF THE FINDINGS For many ICD-10 chapters, we present the first published data on the long-term outcome of singletons born after FET. The results on FET versus fresh ET are reassuring, whereas the results on FET versus NC warrant further investigation. STUDY FUNDING/COMPETING INTEREST(S) Finnish government research funding was obtained for this study. Funding was also obtained from the Finnish Medical Society Duodecim, the Paivikki and Sakari Sohlberg Foundation, Orion Research Foundation, Finnish Society of Obstetrics and Gynaecology (research grants to A.M.T.) and Finnish government research funding. The funding sources were not involved in the planning or execution of the study. The authors have no competing interests to declare.Peer reviewe

Environmental conditions and host plant origin override endophyte effects on invertebrate communities

v2011okpka pka ks

How Do Software Startups Pivot? Empirical Results from a Multiple Case Study

In order to handle intense time pressure and survive in dynamic market, software startups have to make crucial decisions constantly on whether to change directions or stay on chosen courses, or in the terms of Lean Startup, to pivot or to persevere. The existing research and knowledge on software startup pivots are very limited. In this study, we focused on understanding the pivoting processes of software startups, and identified the triggering factors and pivot types. To achieve this, we employed a multiple case study approach, and analyzed the data obtained from four software startups. The initial findings show that different software startups make different types of pivots related to business and technology during their product development life cycle. The pivots are triggered by various factors including negative customer feedback.Comment: Conference publication, International Conference on Software Business (ICSOB'16), Sloveni

'It's almost like taking the sales out of selling'-Towards a conceptualization of value-based selling in business markets

While the creation of superior customer value is regarded as fundamental to a firm's long-term survival and growth, little is known about the effective implementation of a firm's value orientation at sales force level. As the sales force plays a pivotal role in implementing marketing strategies, this study adopts a discovery oriented approach and conceptualizes value-based selling as an effective sales approach in business markets. Based on in-depth interviews with sales managers in a variety of industries, we identify and portray three salient dimensions of value-based selling, namely (1) understanding the customer's business model, (2) crafting the value proposition, and (3) communicating customer value. The selling behavior entails a mutual orientation and focuses on the value-in-use potential of the offering for the customer's business profits. We argue that value-based selling is a unique concept that differs from the established selling approaches and propose a conceptual model linking value-based selling to performance outcomes. To further advance our knowledge about the effective implementation of a firm's value orientation, we identify future research avenues embracing qualitative and quantitative research methodologies. (C) 2011 Elsevier Inc. All rights reserved

How sales strategy translates into performance: The role of salesperson customer orientation and value-based selling

The role of selling has become increasingly analytical and it is a central topic on senior management&#39;s agenda in business markets. Still, sales strategy remains an under-researched topic in the business-to-business marketing domain. Very little is known about how to implement it effectively or about the mechanisms of how sales strategy affects performance, despite its apparent importance for firm success. Drawing on a large-scale sample of 816 salespeople and directors from 30 sales organizations, and employing multilevel structural equation modeling, this study sheds light on the chain of effects that transforms sales strategy as an organizational variable into selling performance captured on the individual salesperson level. The findings demonstrate that a firm&#39;s sales strategy is related to market performance and affects salesperson selling performance both directly and indirectly. Further, the results show that each sales strategy dimension affects salesperson performance in a unique way. Of the three dimensions of sales strategy studied, only segmentation directly impacts salesperson selling performance. Prioritization and selling models impact salesperson performance indirectly, via their impact on customer orientation and value-based selling. These results lead to actionable implications for the effective implementation of sales strategy in business markets. (C) 2015 Elsevier Inc. All rights reserved.</p

Changing and pivoting the business model in software startups

In a company, its business strategy and business model undergo changes throughout its life. These changes can be induced or forced externally or they can result from a deliberate strategy to improve the business performance and to achieve success. Certain changes can lead to a major change in the business model of the company (i.e., a pivot). Such change or innovation in the business model can occur in various of its dimensions. According to Osterwalder and Pigneur, there are four epicenters of change and innovation to be taken into consideration. In this manuscript, fifteen Portuguese software startups were studied using essentially semi-structured interviews to gather the information. The data was processed with a software application for qualitative data analysis. The main results are related to a dynamic process of evolution and change of the business model in software startups. In particular, we have identified that the changes in the business elements that support the production of the value proposition (left-hand side of the Business Model Canvas) affect the elements that explain the strategy of delivering the value proposition to customers (right-hand side of the Business Model Canvas).This work was supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT Fundação para a Ciência e a Tecnologia within the Project Scope: UID/CEC/00319/2013

Effective implementation of relationship orientation in new product launches

The critical role of relationships in business performance is widely recognized in the business marketing literature. However, to date, the prevailing new product launch research has concentrated on firms&#39; general customer and competitor focus on predicting launch performance, and mainly applied a product centered or marketing mix perspective on considering effective strategic and tactical launch activities. Consequently, there is only scant knowledge on the relevance of a relational perspective when launching new products. The study contributes to this gap by examining the impact of firms&#39; relationship orientation on launch performance and the key activities through which it is transformed into performance in the new product launch context. A set of hypotheses is developed and tested with data collected from 109 new product launches in pharmaceutical companies. The results show that sales force management and relationship leveraging mediate relationship orientation&#39;s impact on launch performance through complexly intertwined relationships. From a theoretical perspective, this study highlights the role of the relational perspective in new product launch and fosters our understanding on how relationship-focused culture is effectively implemented in practice. From a managerial perspective, the results offer insights on how firms can effectively enhance the successful commercialization of new products through relationship-oriented sales and marketing activities.</p

BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for body mass index

Background Obesity is a heritable complex phenotype that can increase the risk of age-related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various "epigenetic clocks." Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely correlates with mortality. Objectives We aimed to assess the cross-sectional association of body mass index (BMI) with age acceleration in twins to limit confounding by genetics and shared environment. Methods and results Participants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twin pairs, and DNAm was measured using the Illumina 450K array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p-value = 6.1 x 10(-12)) per one-unit BMI increase. Additionally, heavier twins in a BMI-discordant MZ twin pair (Delta BMI >3 kg/m(2)) had an epigenetic age 5.2 months older than their lighter cotwin (p-value = 0.0074). We also found a positive association between log (homeostatic model assessment of insulin resistance) and age acceleration, confirmed by a meta-analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p-value = 4.1 x 10(-25)) from adjusted models. Conclusion We identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance.Peer reviewe

Epigenome-450K-wide methylation signatures of active cigarette smoking : The Young Finns Study

Smoking as a major risk factor for morbidity affects numerous regulatory systems of the human body including DNA methylation. Most of the previous studies with genome-wide methylation data are based on conventional association analysis and earliest threshold-based gene set analysis that lacks sensitivity to be able to reveal all the relevant effects of smoking. The aim of the present study was to investigate the impact of active smoking on DNA methylation at three biological levels: 5'-C-phosphate-G-3' (CpG) sites, genes and functionally related genes (gene sets). Gene set analysis was done with mGSZ, a modern threshold-free method previously developed by us that utilizes all the genes in the experiment and their differential methylation scores. Application of such method in DNA methylation study is novel. Epigenome-wide methylation levels were profiled from Young Finns Study (YFS) participants' whole blood from 2011 follow-up using Illumina Infinium Hu-manMethylation450 BeadChips. We identified three novel smoking related CpG sites and replicated 57 of the previously identified ones. We found that smoking is associated with hypomethylation in shore (genomic regions 0-2 kilobases from CpG island). We identified smoking related methylation changes in 13 gene sets with false discovery rate (FDR)Peer reviewe

Genome-wide association study of nocturnal blood pressure dipping in hypertensive patients

Abstract Background Reduced nocturnal fall (non-dipping) of blood pressure (BP) is a predictor of cardiovascular target organ damage. No genome-wide association studies (GWAS) on BP dipping have been previously reported. Methods To study genetic variation affecting BP dipping, we conducted a GWAS in Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 204) using the mean night-to-day BP ratio from up to four ambulatory BP recordings conducted on placebo. Associations with P < 1 × 10− 5 were further tested in two independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 183) and Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 180). We also tested the genome-wide significant single nucleotide polymorphism (SNP) for association with left ventricular hypertrophy in GENRES. Results In GENRES GWAS, rs4905794 near BCL11B achieved genome-wide significance (β = − 4.8%, P = 9.6 × 10− 9 for systolic and β = − 4.3%, P = 2.2 × 10− 6 for diastolic night-to-day BP ratio). Seven additional SNPs in five loci had P values < 1 × 10− 5. The association of rs4905794 did not significantly replicate, even though in DYNAMIC the effect was in the same direction (β = − 0.8%, P = 0.4 for systolic and β = − 1.6%, P = 0.13 for diastolic night-to-day BP ratio). In GENRES, the associations remained significant even during administration of four different antihypertensive drugs. In separate analysis in GENRES, rs4905794 was associated with echocardiographic left ventricular mass (β = − 7.6 g/m2, P = 0.02). Conclusions rs4905794 near BCL11B showed evidence for association with nocturnal BP dipping. It also associated with left ventricular mass in GENRES. Combined with earlier data, our results provide support to the idea that BCL11B could play a role in cardiovascular pathophysiology