What influences the speed of prototyping? An empirical investigation of twenty software startups

It is essential for startups to quickly experiment business ideas by building tangible prototypes and collecting user feedback on them. As prototyping is an inevitable part of learning for early stage software startups, how fast startups can learn depends on how fast they can prototype. Despite of the importance, there is a lack of research about prototyping in software startups. In this study, we aimed at understanding what are factors influencing different types of prototyping activities. We conducted a multiple case study on twenty European software startups. The results are two folds, firstly we propose a prototype-centric learning model in early stage software startups. Secondly, we identify factors occur as barriers but also facilitators for prototyping in early stage software startups. The factors are grouped into (1) artifacts, (2) team competence, (3) collaboration, (4) customer and (5) process dimensions. To speed up a startups progress at the early stage, it is important to incorporate the learning objective into a well-defined collaborative approach of prototypingComment: This is the author's version of the work. Copyright owner's version can be accessed at doi.org/10.1007/978-3-319-57633-6_2, XP2017, Cologne, German

Beneficial impact of levosimendan in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials

INTRODUCTION: The incidence of Acute Kidney Injury is nowadays high in critically ill patients. Its etiology is multifactorial and a primary role is played by low cardiac output syndrome. Everything targeted to normalize cardiac output should increase the renal perfusion and abolish the secondary vasoconstriction. Levosimendan is a calcium sensitizer drug with inotropic properties that improves cardiac output and seems to increase renal blood flow. The aim of this meta-analysis was to evaluate the role of levosimendan in critically ill patients with or at risk of Acute Kidney Injury. METHODS: We performed a meta-analysis of randomized controlled trials searching for trials that compared levosimendan with any comparator. The endpoints were the number of patients receiving Renal Replacement Therapy after randomization and the number of patients developing Acute Kidney Injury. RESULTS: Final analysis included 33 trials and 3,879 patients (2,024 levosimendan and 1,855 control). The overall analysis showed that the use of levosimendan was associated with a significant reduction in the risk of Renal Replacement Therapy (17 of 492 [3.5%] in the levosimendan group versus 37 of 427 [8.7%] in the control group, relative risk =0.52 [0.32 to 0.86], p for effect =0.01) and of Acute Kidney Injury (114 of 1,598 [7.1%] in the levosimendan group versus 143 of 1,529 [9.4%] in the control arm, relative risk =0.79 [0.63 to 0.99], p for effect =0.048). CONCLUSIONS: This meta-analysis suggests that the use of levosimendan is associated with a significant reduction of Renal Replacement Therapy in critically ill patients

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

"We're all the same here"—Investigating the rehabilitative climate of a re-rolled sexual offender prison: a qualitative longitudinal study

Understanding how individuals with sexual convictions experience prison and its environment is important because such experiences can impact on rehabilitation outcomes. This is the first qualitative longitudinal investigation that explores the experiences of prisoners in a prison exclusively for individuals with sexual convictions over time. The purpose of this research was to explore the rehabilitative and therapeutic climate of a recently re-rolled prison (a general prison turned into a prison only for individuals who have sexually offended) at two time points (T1 at reroll and T2 a year later). The study focuses on prisoners perspectives of the purpose of the prison, experience of prison life, relationships in the prison, and the prison regime over time. Twenty interviews were conducted across the time points and revealed two main superordinate themes “‘Being’ in a prison for individuals with sexual convictions” and “obstructions to change". This research adds to the emerging body of knowledge surrounding the importance of the wider prison environment on the rehabilitation of individuals with sexual convictions and on the benefits and risks of co-locating men who have committed sexual offences in the same prison site. It also has implications wider than rehabilitation of those convicted of sexual offences and has insights for the types of environment and prisoner-staff relationships that are conducive to rehabilitation

What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review

Background Epidemiological studies indicate that gene–environment interactions play a role in atopic dermatitis (AD). Objectives To review the evidence for gene–environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations. Methods A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis. Results Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG–environment interactions in six of the studies (P-value for interaction ≤ 005), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions. Conclusions Evidence on FLG–environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment

Non-invasive fetal genotyping for maternal alleles with droplet digital PCR: A comparative study of analytical approaches

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.OBJECTIVES: To develop a flexible droplet digital PCR (ddPCR) workflow to perform non-invasive prenatal diagnosis via relative mutation dosage (RMD) for maternal pathogenic variants with a range of inheritance patterns, and to compare the accuracy of multiple analytical approaches. METHODS: Cell free DNA (cfDNA) was tested from 124 archived maternal plasma samples: 88 cases for sickle cell disease and 36 for rare Mendelian conditions. Three analytical methods were compared: sequential probability ratio testing (SPRT), Bayesian and z-score analyses. RESULTS: The SPRT, Bayesian and z-score analyses performed similarly well with correct prediction rates of 96%, 97% and 98%, respectively. However, there were high rates of inconclusive results for each cohort, particularly for z-score analysis which was 31% overall. Two samples were incorrectly classified by all three analytical methods; a false negative result predicted for a fetus affected with sickle cell disease and a false positive result predicting the presence of an X-linked IDS variant in an unaffected fetus. CONCLUSIONS: ddPCR can be applied to RMD for diverse conditions and inheritance patterns, but all methods carry a small risk of erroneous results. Further evaluation is required both to reduce the rate of inconclusive results and explore discordant results in more detail.National Institute for Health and Care Research (NIHR

What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.

BACKGROUND: Epidemiological studies indicate that gene-environment interactions play a role in atopic dermatitis (AD). OBJECTIVES: To review the evidence for gene-environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations. METHODS: A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis. RESULTS: Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG-environment interactions in six of the studies (P-value for interaction ≤ 0·05), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions. CONCLUSIONS: Evidence on FLG-environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411