Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke—A Prospective Observational Study

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4-8.5 and OR 5.7, 95% CI: 2.5-12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1-3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality

Serendipitous meta-transcriptomics : the fungal community of Norway Spruce (Picea abies)

After performing de novo transcript assembly of >1 billion RNA-Sequencing reads obtained from 22 samples of different Norway spruce (Picea abies) tissues that were not surface sterilized, we found that assembled sequences captured a mix of plant, lichen, and fungal transcripts. The latter were likely expressed by endophytic and epiphytic symbionts, indicating that these organisms were present, alive, and metabolically active. Here, we show that these serendipitously sequenced transcripts need not be considered merely as contamination, as is common, but that they provide insight into the plant’s phyllosphere. Notably, we could classify these transcripts as originating predominantly fromDothideomycetes and Leotiomycetes species, with functional annotation of gene families indicating active growth and metabolism, with particular regards to glucose intake and processing, as well as gene regulation.S1 Fig. Samples collected from Norway spruce. For each sample a brief description and sample ID are shown below a representative image of the associated plant tissue, while the sampling date is shown above.S2 Fig. Bioinformatics workflow of RNA data processing. We assembled reads from all samples into a single assembly (left column), computed Tau scores, GC content, and mapped the transcripts to the genome as well as to the Uniref90 protein database. For enriching for fungal transcripts (right column), we applied GC content and expression breadth filters to the reads and assembly respectively, clustered sequences by similarity, and performed functional annotation as well as phylogenetic analyses.S3 Fig. Putative taxonomic characterization of transcripts via protein alignments. Bar plot showing the number of transcripts by taxonomy (super)kingdoms. Parent summarises taxons hierarchically higher than the represented (super)kingdoms, NA summarises transcripts with no sequence similarity in the UniRef90 database. The number of transcripts is indicated at the top of every bar.S4 Fig. Taxonomic class and phylum of the fungal transcripts. (a) Number of transcripts per fungal phylum. The phylum are sorted by abundance top to bottom with Ascomycota (n = 81,181) and Basidiomycota (n = 4,839) being the most represented; the remaining phyla varying from n = 11 to n = 2. (b) A graph of the taxonomic hierarchy from species to phylum of the fungal transcripts, showing the broad species diversity of the largest clusters: Ascomycota (bottom) and Basidiomycota (top). (c) Similar to (a) for the fungal classes, with the Eurotiomycetes and Dothideomycetes classes being over-represented among the fungal transcripts. (d) Similar to (b) for the fungal classes (n = 24).S5 Fig. Characterisation of transcripts lacking taxonomic assignment by their GMAP alignments to the P. abies genome. (a) Boxplot of the tau scores for the no taxon transcripts split based on their GMAP alignments to the P. abies genome. The tau score ranges from 1 for complete specificity to 0 for equal expression in all samples. The transcripts having a GMAP alignment in the genome (99% of the GMAP hits cover 80% of the transcripts with at least a 90% identity) show a wide tau score distribution indicative of the presence of ubiquitously expressed transcripts as well as that of more tissue-specific transcripts. The transcripts having no GMAP alignment show a distribution typical of only tissue-specific expression (mean tau score of 0.98). (b) Percentage GC density distribution of the no taxon transcripts split based on their GMAP alignments to the P. abies genome. Transcripts having a GMAP alignment to the genome present a GC distribution typical of the P. abies transcripts. The transcripts without a GMAP alignment show a distribution enriched for higher percentage GC, similar to that of fungi. The shoulder observed under the peak of transcripts with GMAP alignments may indicate transcripts where the assembly contained gaps or created chimeras. (c) Scatterplot of log2 FPKM expression values vs. the percentage GC content for the transcripts with a GMAP alignment. Colouring indicates density, which is shaded from yellow (high) to blue (low). The expression of transcripts with a GMAP alignment resembles that of the Embryophita phylum. (d) Scatterplot of log2 FPKM expression values vs. the percentage GC content for transcripts with a GMAP alignment. Colouring as in (c). The expression of transcripts with no GMAP alignment resembled that of the fungal kingdom.S6 Fig. Phylogeny built on four nuclear genes. Shown are maximum-likelihood phylogenies based on fungal nucleotide sequences assembled from the spruce samples in context of known sequences, with highest sequence similarity to: (a) phosphoenolpyruvate carboxykinase; (b) NADP-dependent medium chain alcohol dehydrogenase; (c) beta lactamase; and (d) unspecific lipid transporter. Only branch with support values > 0.9 are shown. While clusters with more representative sequences yield better branch support (a, b), placement of clusters with fewer sequences is less certain (c, d). However, in all cases, at least one sequence is grouped with Dothideomycetes, and for (a,b) with Leotiomycetes.S1 Table. Sample IDs, description, and ENA submission IDs. Correspondence between the sample IDs as described in Nystedt et al., (2013), this manuscript and the ENA are shown in columns one to three. The fourth column contains a succinct description of the samples, refer to Nystedt et al., (2013) for full details.http://www.plosone.orgam201

Analyses of pig genomes provide insight into porcine demography and evolution

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model

New Product Development in a Medical Device Context : Managing Projects of different Novelty

Healthcare is a topic that matters since it aims to ensure better well-being for people. An important and essential part of health care is medical devices since it has the potential to increase the quality of life for people with a health problem. Among the suppliers of innovation, the medical device industry is a dynamic field providing thousands of products to the market every year with the aim to enhance people's lives. However, there are many actors that influences the medical device development such as regulations that ensures that medical devices follow a specific procedure during development, at the same time buyers and end-users need to be integrated throughout the medical device design, this results in challenges during medical device development. This thesis focuses on new product development (NPD) and investigates how projects are managed in a medical device context. Furthermore, the thesis elaborates projects of different novelty and the influence from the characteristic of complexity. This is done with a single-case study of a case company that develop and market medical devices. The empirical findings shows that the main challenges are in the area of clinical studies and product development, furthermore, managing NPD projects in a medical device context deals with specialized knowledge that is dispersed among a group of actors which can influence the development of the medical device no matter the novelty. It was found that the difference between the studied projects was minor in terms of complexity. Though, it was noticed that the project of radical novelty had more interaction with the end-user, which can relate to uncertainty in the function of the product, as a consequence from being completely new product. As a result from the findings, the implication is that the projects can not be treated and managed similarly as a result from uncertainty, thus, it depends on the integration of actors, consequently, influencing time of development and resources. This thesis contributes to the community of companies operating in a medical device context where there is minor focus on complexity in projects, it was found that it might be beneficial to make distinctions in complexity characteristics when identifying challenges and addressing NPD projects in a medical device context.

Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study

Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD) and conduct disorder (CD). The aims of this study were to identify gender-specific associations between the behavioural problems–ODD/CD-like problems–and the neurodevelopmental disorders–attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD)–and to investigate underlying genetic effects.Methods. 17,220 twins aged 9 or 12 were screened using the Autism–Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting.Results. Social interaction problems (one of the ASD subdomains) was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%–62% of the variance in behavioural problems, except in CD-like problems in girls (26%). Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls.Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD

Serendipitous meta-transcriptomics: the fungal community of Norway Spruce (Picea abies)

After performing de novo transcript assembly of >1 billion RNA-Sequencing reads obtained from 22 samples of different Norway spruce (Picea abies) tissues that were not surface sterilized, we found that assembled sequences captured a mix of plant, lichen, and fungal transcripts. The latter were likely expressed by endophytic and epiphytic symbionts, indicating that these organisms were present, alive, and metabolically active. Here, we show that these serendipitously sequenced transcripts need not be considered merely as contamination, as is common, but that they provide insight into the plant's phyllosphere. Notably, we could classify these transcripts as originating predominantly from Dothideomycetes and Leotiomycetes species, with functional annotation of gene families indicating active growth and metabolism, with particular regards to glucose intake and processing, as well as gene regulation

Circulating neurofilament light in ischemic stroke: temporal profile and outcome prediction

Background and purpose: Neurofilament light chain (NfL) is a marker of neuroaxonal damage. We aimed to study associations between serum NfL (sNfL) concentrations at different time points after ischemic stroke and outcomes. Methods: We prospectively included ischemic stroke cases (n = 595, mean age 59\ua0years, 64% males) and assessed outcomes by both the modified Rankin Scale (mRS) and the NIH stroke scale (NIHSS) at 3\ua0months and by mRS at 2\ua0years. In a subsample, long-term (7-year) outcomes were also assessed by both mRS and NIHSS. We used the ultrasensitive single-molecule array assay to measure sNfL in the acute phase (range 1–14, median 4\ua0days), after 3\ua0months and 7\ua0years in cases and once in controls (n = 595). Results: Acute-phase sNfL increased by the time to blood-draw and highest concentrations were observed at 3\ua0months post-stroke. High sNfL associated to stroke severity and poor outcomes, and both associations were strongest for 3-month sNfL. After adjusting for age, previous stroke, stroke severity, and day of blood draw, 3-month sNfL was significantly associated to both outcomes at all time points (p < 0.01 throughout). For all main etiological subtypes, both acute phase and 3-month sNfL were significantly higher than in controls, but the dynamics of sNfL differed by stroke subtype. Conclusions: The results from this study inform on sNfL in ischemic stroke and subtypes over time, and show that sNfL predicts short- and long-term neurological and functional outcomes. Our findings suggest a potential utility of sNfL in ischemic stroke outcome prediction