Compact and evenly distributed k-mer binning for genomic sequences.

MOTIVATION: The processing of k-mers (subsequences of length k) is at the foundation of many sequence processing algorithms in bioinformatics, including k-mer counting for genome size estimation, genome assembly, and taxonomic classification for metagenomics. Minimizers-ordered m-mers where m < k-are often used to group k-mers into bins as a first step in such processing. However, minimizers are known to generate bins of very different sizes, which can pose challenges for distributed and parallel processing, as well as generally increase memory requirements. Furthermore, although various minimizer orderings have been proposed, their practical value for improving tool efficiency has not yet been fully explored. RESULTS: We present Discount, a distributed k-mer counting tool based on Apache Spark, which we use to investigate the behaviour of various minimizer orderings in practice when applied to metagenomics data. Using this tool, we then introduce the universal frequency ordering, a new combination of frequency-sampled minimizers and universal k-mer hitting sets, which yields both evenly distributed binning and small bin sizes. We show that this ordering allows Discount to perform distributed k-mer counting on a large dataset in as little as 1/8 of the memory of comparable approaches, making it the most efficient out-of-core distributed k-mer counting method available. AVAILABILITY AND IMPLEMENTATION: Discount is GPL licensed and available at https://github.com/jtnystrom/discount. The data underlying this article are available in the article and in its online supplementary material. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer.

Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n = 352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n = 199) with available RNA-seq data. We observed a large variation in macrophage density between cases and a strong correlation between CD68 and CD163, suggesting that the majority of TAMs present in NSCLC exhibit a protumor phenotype. Correlation to clinical data only showed a weak trend toward worse survival for patients with high macrophage infiltration. Interestingly, MARCO was expressed on a distinct subpopulation of TAMs, which tended to aggregate in close proximity to tumor cell nests. On the transcriptomic level, we found a positive association between MARCO gene expression and general immune response pathways including strong links to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules. Indeed, a higher macrophage infiltration was seen in tumors expressing PD-L1, and macrophages residing within tumor cell nests co-expressed MARCO and PD-L1. Thus, MARCO is a potential new immune target for anti-TAM treatment in a subset of NSCLC patients, possibly in combination with available immune checkpoint inhibitors.

Sex is a moderator of the association between NOS1AP sequence variants and QTc in two long QT syndrome founder populations: a pedigree-based measured genotype association analysis.

BACKGROUND: Sequence variants in the NOS1AP gene have repeatedly been reported to influence QTc, albeit with moderate effect sizes. In the long QT syndrome (LQTS), this may contribute to the substantial QTc variance seen among carriers of identical pathogenic sequence variants. Here we assess three non-coding NOS1AP sequence variants, chosen for their previously reported strong association with QTc in normal and LQTS populations, for association with QTc in two Swedish LQT1 founder populations. METHODS: This study included 312 individuals (58% females) from two LQT1 founder populations, whereof 227 genotype positive segregating either Y111C (n = 148) or R518* (n = 79) pathogenic sequence variants in the KCNQ1 gene, and 85 genotype negatives. All were genotyped for NOS1AP sequence variants rs12143842, rs16847548 and rs4657139, and tested for association with QTc length (effect size presented as mean difference between derived and wildtype, in ms), using a pedigree-based measured genotype association analysis. Mean QTc was obtained by repeated manual measurement (preferably in lead II) by one observer using coded 50 mm/s standard 12-lead ECGs. RESULTS: A substantial variance in mean QTc was seen in genotype positives 476 ± 36 ms (Y111C 483 ± 34 ms; R518* 462 ± 34 ms) and genotype negatives 433 ± 24 ms. Female sex was significantly associated with QTc prolongation in all genotype groups (p < 0.001). In a multivariable analysis including the entire study population and adjusted for KCNQ1 genotype, sex and age, NOS1AP sequence variants rs12143842 and rs16847548 (but not rs4657139) were significantly associated with QT prolongation, +18 ms (p = 0.0007) and +17 ms (p = 0.006), respectively. Significant sex-interactions were detected for both sequent variants (interaction term r = 0.892, p < 0.001 and r = 0.944, p < 0.001, respectively). Notably, across the genotype groups, when stratified by sex neither rs12143842 nor rs16847548 were significantly associated with QTc in females (both p = 0.16) while in males, a prolongation of +19 ms and +8 ms (p = 0.002 and p = 0.02) was seen in multivariable analysis, explaining up to 23% of QTc variance in all males. CONCLUSIONS: Sex was identified as a moderator of the association between NOS1AP sequence variants and QTc in two LQT1 founder populations. This finding may contribute to QTc sex differences and affect the usefulness of NOS1AP as a marker for clinical risk stratification in LQTS.

Strain distribution in single, suspended germanium nanowires studied using nanofocused x-rays.

Within the quest for direct band-gap group IV materials, strain engineering in germanium is one promising route. We present a study of the strain distribution in single, suspended germanium nanowires using nanofocused synchrotron radiation. Evaluating the probed Bragg reflection for different illumination positions along the nanowire length results in corresponding strain components as well as the nanowire's tilting and bending. By using these findings we determined the complete strain state with the help of finite element modelling. The resulting information provides us with the possibility of evaluating the validity of the strain investigations following from Raman scattering experiments which are based on the assumption of purely uniaxial strain.

Toxygates: interactive toxicity analysis on a hybrid microarray and linked data platform.

MOTIVATION: In early stage drug development, it is desirable to assess the toxicity of compounds as quickly as possible. Biomarker genes can help predict whether a candidate drug will adversely affect a given individual, but they are often difficult to discover. In addition, the mechanism of toxicity of many drugs and common compounds is not yet well understood. The Japanese Toxicogenomics Project provides a large database of systematically collected microarray samples from rats (liver, kidney and primary hepatocytes) and human cells (primary hepatocytes) after exposure to 170 different compounds in different dosages and at different time intervals. However, until now, no intuitive user interface has been publically available, making it time consuming and difficult for individual researchers to explore the data. RESULTS: We present Toxygates, a user-friendly integrated analysis platform for this database. Toxygates combines a large microarray dataset with the ability to fetch semantic linked data, such as pathways, compound-protein interactions and orthologs, on demand. It can also perform pattern-based compound ranking with respect to the expression values of a set of relevant candidate genes. By using Toxygates, users can freely interrogate the transcriptome's response to particular compounds and conditions, which enables deep exploration of toxicity mechanisms.

Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families.

BACKGROUND: The R518X/KCNQ1 mutation is a common cause of autosomal recessive (Jervell and Lange Nielsen Syndrome- JLNS) and autosomal dominant long QT syndrome (LQTS) worldwide. In Sweden p.R518X accounts for the majority of JLNS cases and is the second most common cause of LQTS. Here we investigate the clinical phenotype and origin of Swedish carriers of the p.R518X mutation. METHODS: The study included 19 Swedish p.R518X index families, ascertained by molecular genetics methods (101 mutation-carriers, whereof 15 JLNS cases and 86 LQTS cases). In all families analyses included assessment of clinical data (symptoms, medications and manually measured electrocardiograms), genealogy (census records), haplotype (microsatellite markers) as well as assessment of mutation age and associated prevalence (ESTIAGE and DMLE computer software). RESULTS: Clinical phenotype ranged from expectedly severe in JLNS to surprisingly benign in LQTS (QTc 576 ± 61 ms vs. 462 ± 34 ms, cumulative incidence of (aborted) cardiac arrest 47% vs. 1%, annual non-medicated incidence rate (aborted) cardiac arrest 4% vs. 0.04%).A common northern origin was found for 1701/1929 ancestors born 1650-1950. Historical geographical clustering in the coastal area of the Pite River valley was shown. A shared haplotype spanning the KCNQ1 gene was seen in 17/19 families. Mutation age was estimated to 28 generations (95% CI 19;41). A high prevalence of Swedish p.R518X heterozygotes was suggested (~1:2000-4000). CONCLUSIONS: R518X/KCNQ1 occurs as a common founder mutation in Sweden and is associated with an unexpectedly benign phenotype in heterozygous carriers.

The effect and duration of prophylactic platelet transfusions before insertion of a central venous catheter in patients with bone marrow failure evaluated with point-of-care methods and flow cytometry.

BACKGROUND: Patients with bone marrow failure and severe thrombocytopenia are frequently given prophylactic platelet transfusion before interventions. The clinical effects of such transfusions, however, are poorly defined. We performed a prospective observational study on patients with bone marrow failure scheduled for prophylactic platelet transfusion before the insertion of a central venous catheter. The objectives were to evaluate the effect and duration of prophylactic platelet transfusions on central venous catheter insertion in thrombocytopenic patients with bone marrow failure. METHODS: Thirty-nine adult patients with bone marrow failure and platelet counts below 50 × 10/L were consecutively enrolled before prophylactic platelet transfusion for subclavian central venous catheter insertion. Blood samples were drawn from the patients before platelet transfusion, 1 hour, and 4 hours after completion of the transfusion. The coagulation profile was assessed by conventional hematological tests, thromboelastometry (ROTEM) assays (EXTEM and FIBTEM), multiple electrode aggregometry (Multiplate) assays including adenosine diphosphate, collagen, and thrombin receptor agonist peptide, and by flow cytometry for the platelet expression of P-selectin (CD62P) and activated glycoprotein IIb-IIIa (PAC-1). Bleeding complications were classified with a 5-grade scale, according to the Common Terminology Criteria for Adverse Events. RESULTS: Seventeen women and 22 men were included in the study. Platelet count was increased from 24 × 10/L (18-32) before to 42 × 10/L (31-50) 1 hour after transfusion (P < 0.0001) and was not significantly different 4 hours after transfusion (40 × 10/L (29-50), P = 0.047). Maximal clot firmness EXTEM was increased from 38 mm (32-45) before to 46 mm (41-52) 1 hour after transfusion (P < 0.0001) and did not change 4 hours after transfusion. Clotting time EXTEM was decreased from 58.5 seconds (50-78) beforehand to 53 seconds (45-61) 1 hour after transfusion (P = 0.0006) and was not significantly different 4 hours after transfusion (57 seconds (52-70, P = 0.025). FIBTEM results were all unchanged after transfusion. All Multiplate analyses were significantly increased after 1 hour and were not diminished 4 hours after transfusion. Four grade 1 bleeding episodes occurred, but no grade 2 to 5 bleeding could be detected. Flow cytometry analyses showed mixed results with no overall trend. CONCLUSIONS: Prophylactic platelet transfusions in thrombocytopenic patients with bone marrow failure improve hemostatic parameters on ROTEM and Multiplate by increasing the number of platelets, and not through enhancement of platelet function. Improved clotting parameters on ROTEM and platelet aggregation on Multiplate appear to persist between 1 and 4 hours after transfusion.

Importance of the infusion rate for the plasma expanding effect of 5% albumin, 6% HES 130/0.4, 4% gelatin, and 0.9% NaCl in the septic rat.

OBJECTIVES: To compare the plasma volume (PV) expanding effect of a fast infusion rate with that of a slow infusion rate of a fixed volume of 5% albumin, of the synthetic colloids, 6% hydroxyethyl starch 130/0.4 and 4% gelatin, and of 0.9% NaCl in a rat sepsis model and to compare the plasma-expanding effect among these fluids. DESIGN: Prospective, randomized animal study. SETTING: University hospital laboratory. SUBJECTS: One hundred and twelve adult male rats. INTERVENTIONS: Sepsis was induced by cecal ligation and incision followed by closure of the abdomen. After 3 hrs, an infusion of the PV expander under study was started at a volume of 12mL/kg for the colloids and of 48mL/kg for 0.9% NaCl, either for 15 mins or for 3 hrs. A control group underwent the same experimental procedure but no fluid was given. MEASUREMENTS AND MAIN RESULTS: Three hours after start of the infusion (end of experiment), the plasma-expanding effect was better with a slow than a fast infusion rate for the colloids, especially albumin, but the NaCl groups did not differ significantly from the control group. The PV for the control group was 28.7±3mL/kg. In the slow and the fast infusion groups, it was 38.9±4.3 and 32.6±4.2mL/kg for albumin (p < 0.001), 32.9±4.3 and 29.5±4.4mL/kg for hydroxyethyl starch 130/0.4 (p < 0.05), 31.8±3.9 and 28.2±4.1mL/kg for gelatin (p < 0.05), and 31.8±5.3 and 30.7±6.6mL/kg for NaCl (n.s), respectively. CONCLUSIONS: The study showed that the PV expansion by a colloid was greater when given at a slow than at a fast infusion rate, an effect more pronounced for albumin. This difference was not seen for NaCl. The PV-expanding effect was poor for NaCl and better for albumin than for the other colloids.

Patients with sepsis exhibit increased mitochondrial respiratory capacity in peripheral blood immune cells.

INTRODUCTION: In sepsis, mitochondria have been associated with both initial dysfunction and subsequent upregulation (biogenesis). However, the evolvement of mitochondrial function in sepsis over time is largely unknown, and we therefore investigated mitochondrial respiration in peripheral blood immune cells (PBICs) in sepsis patients during the first week after admission to the intensive care unit (ICU). METHODS: PBICs from 20 patients with severe sepsis or septic shock were analyzed with high-resolution respirometry 3 times after admission to the ICU (within 48 hours, days 3 to 4 and days 6 to 7). Mitochondrial DNA (mtDNA), cytochrome c (Cyt c), and citrate synthase (CS) were measured as indicators of cellular mitochondrial content. RESULTS: In intact PBICs with endogenous substrates, a gradual increase in cellular respiration reached 173% of controls after 1 week (P = 0.001). In permeabilized cells, respiration using substrates of complex I, II, and IV were significantly increased days 1 to 2, reaching 137%, 130%, and 173% of controls, respectively. In parallel, higher levels of CS activity, mtDNA, and Cyt c content in PBICs (211%, 243%, and 331% of controls for the respective indicators were found at days 6 to 7; P < 0.0001). No differences in respiratory capacities were noted between survivors and nonsurvivors at any of the time points measured. CONCLUSIONS: PBICs from patients with sepsis displayed higher mitochondrial respiratory capacities compared with controls, due to an increased mitochondrial content, as indicated by increased mitochondrial DNA, protein content, and enzyme activity. The results argue against mitochondrial respiratory dysfunction in this type of cells in sepsis.

Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis.

One extra chromosome copy (i.e., trisomy) is the most common type of chromosome aberration in cancer cells. The mechanisms behind the generation of trisomies in tumor cells are largely unknown, although it has been suggested that dysfunction of the spindle assembly checkpoint (SAC) leads to an accumulation of trisomies through failure to correctly segregate sister chromatids in successive cell divisions. By using Wilms tumor as a model for cancers with trisomies, we now show that trisomic cells can form even in the presence of a functional SAC through tripolar cell divisions in which sister chromatid separation proceeds in a regular fashion, but cytokinesis failure nevertheless leads to an asymmetrical segregation of chromosomes into two daughter cells. A model for the generation of trisomies by such asymmetrical cell division accurately predicted several features of clones having extra chromosomes in vivo, including the ratio between trisomies and tetrasomies and the observation that different trisomies found in the same tumor occupy identical proportions of cells and colocalize in tumor tissue. Our findings provide an experimentally validated model explaining how multiple trisomies can occur in tumor cells that still maintain accurate sister chromatid separation at metaphase-anaphase transition and thereby physiologically satisfy the SAC.

Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden.

AIMS: To explore the national prevalence, mutation spectrum, cardiac phenotype, and outcome of the uncommon Jervell and Lange-Nielsen syndrome (JLNS), associated with a high risk of sudden cardiac death. METHODS AND RESULTS: A national inventory of clinical JLNS cases was performed. Genotype and area of origin were ascertained in index families. Retrospective clinical data were collected from medical records and interviews. We identified 19 cases in 13 Swedish families. A JLNS prevalence >1:200 000 was revealed (five living cases <10 years of age). The mutation spectrum consisted of eight KCNQ1 mutations, whereof p.R518X in 12/24 alleles. Geographic clustering of four mutations (20/24 alleles) and similarities to Norway's mutation spectrum were seen. A high prevalence of heterozygotes was suggested. Three paediatric cases on ß-blockers since birth were as yet asymptomatic. Seven symptomatic cases had suffered an aborted cardiac arrest and four had died suddenly. QTc prolongation was significantly longer in symptomatic cases (mean 605 ± 62 vs. 518 ± 50 ms, P = 0.016). ß-Blockers reduced, but did not abolish, cardiac events in any previously symptomatic case. ß-Blocker type, dosage, and compliance probably affect outcome significantly. Implantable cardioverter-defibrillator therapy (ICD, n = 6) was associated with certain complications; however, no case of sudden death. CONCLUSION: Founder effects could explain 83% of the Swedish JLNS mutation spectrum and probably contribute to the high JLNS prevalence found in preadolescent Swedish children. Due to the severe cardiac phenotype in JLNS, the importance of stringent ß-blocker therapy and compliance, and consideration of ICD implantation in the case of therapy failure is stressed.

Unit cell structure of crystal polytypes in InAs and InSb nanowires.

The atomic distances in hexagonal polytypes of III-V compound semiconductors differ from the values expected from simply a change of the stacking sequence of (111) lattice planes. While these changes were difficult to quantify so far, we accurately determine the lattice parameters of zinc blende, wurtzite, and 4H polytypes for InAs and InSb nanowires, using X-ray diffraction and transmission electron microscopy. The results are compared to density functional theory calculations. Experiment and theory show that the occurrence of hexagonal bilayers tends to stretch the distances of atomic layers parallel to the c axis and to reduce the in-plane distances compared to those in zinc blende. The change of the lattice parameters scales linearly with the hexagonality of the polytype, defined as the fraction of bilayers with hexagonal character within one unit cell.

To Modify or Not to Modify: Allele-Specific Effects of 3'UTR-KCNQ1 Single Nucleotide Polymorphisms on Clinical Phenotype in a Long QT 1 Founder Population Segregating a Dominant-Negative Mutation.

Background There are conflicting reports with regard to the allele-specific gene suppression effects of single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of the KCNQ1 gene in long QT syndrome type 1 (LQT1) populations. Here we assess the allele-specific effects of 3 previously published 3'UTR-KCNQ1's SNPs in a LQT1 founder population segregating a dominant-negative mutation. Methods and Results Bidirectional sequencing of the KCNQ1's 3'UTR was performed in the p.Y111C founder population (n=232, 147 genotype positive), with a minor allele frequency of 0.1 for SNP1 (rs2519184) and 0.6 for linked SNP2 (rs8234) and SNP3 (rs107980). Allelic phase was assessed in trios aided by haplotype data, revealing a high prevalence of derived SNP2/3 in cis with p.Y111C (89%). Allele-specific association analyses, corrected using a relatedness matrix, were performed between 3'UTR-KCNQ1 SNP genotypes and clinical phenotypes. SNP1 in trans was associated with a significantly higher proportion of symptomatic phenotype compared with no derived SNP1 allele in trans (58% versus 32%, corrected P=0.027). SNP2/3 in cis was associated with a significantly lower proportion of symptomatic phenotype compared with no derived SNP2/3 allele in cis (32% versus 69%, corrected P=0.010). Conclusions Allele-specific modifying effects on symptomatic phenotype of 3'UTR-KCNQ1 SNPs rs2519184, rs8234, and rs107980 were seen in a LQT1 founder population segregating a dominant-negative mutation. The high prevalence of suppressive 3'UTR-KCNQ1 SNPs segregating with the founder mutation could contribute to the previously documented low incidence of cardiac events in heterozygous carriers of the p.Y111C KCNQ1 mutation.

High-performance single nanowire tunnel diodes.

We demonstrate single nanowire tunnel diodes with room temperature peak current densities of up to 329 A/cm(2). Despite the large surface to volume ratio of the type-II InP-GaAs axial heterostructure nanowires, we measure peak to valley current ratios (PVCR) of up to 8.2 at room temperature and 27.6 at liquid helium temperature. These sub-100-nm-diameter structures are promising components for solar cells as well as electronic applications.

The Effects of Sub-Technique and Pole Length on Classic Roller Skiing Performance and Physiological Responses at Steep Uphill Inclination.

The aims of this study were to compare performance with physiological and perceptual responses on steep uphill inclines between double poling and diagonal stride and to investigate the effects of pole length when double poling. Eight male, competitive cross-country skiers (22 ± 1.1 yrs, peak oxygen uptake (VO2peak) in the diagonal stride: 69.4 ± 5.5 ml·kg-1·min-1) performed four identical tests, one in the diagonal stride, and three in double poling with different pole lengths (self-selected, self-selected -5 cm and self-selected +10 cm). Each test was conducted at a fixed speed (10 km/h), with inclination rising by 1%, starting with 7%, each until voluntary exhaustion. VO2peak, the heart rate, blood lactate concentration, and the rating of perceived exertion were determined for each pole length in each test. The peak heart rate (p < 0.001) and VO2peak (p = 0.004) were significantly higher in the diagonal stride test compared with double poling with all pole lengths. Time to exhaustion (TTE) differed significantly between all four conditions (all p < 0.001), with the following order from the shortest to the longest TTE: short poles, normal poles and long poles in double poling, and the diagonal stride. Consequently, a significantly higher slope inclination was reached (p < 0.001) using the diagonal stride (17%) than for double poling with long poles (14%), normal (13%) and short (13%) poles. The current study showed better performance and higher VO2peak in the diagonal stride compared to double poling in steep uphill terrain, demonstrating the superiority of the diagonal stride for uphill skiing. However, in double poling, skiers achieved improved performance due to greater skiing efficiency when using long poles, compared to normal and short poles.

Panomicon: A web-based environment for interactive, visual analysis of multi-omics data.

Multi-omics analyses, combining transcriptomics, genomics, proteomics, and so on, have led to important insights in many areas of biology and medicine. To support these analyses, software that can handle the difficulties associated with multi-omics datasets is crucial. Here, we describe Panomicon, a web-based, interactive analysis environment for multi-omics data. Building on Toxygates, a tool previously created to study single-omics data that features interactive clustering, heatmaps, and user data uploads, Panomicon introduces improvements for the storage and handling of additional omics types, as well as tools for the generation and visualization of interaction networks between different types of omics data. Panomicon is a new type of environment for the collaborative study of multi-omics data, both for users uploading data to our server and for groups wishing to host their own deployment of Panomicon. We demonstrate Panomicon's capabilities by revisiting a microRNA-mRNA interaction networks study in a non-small cell lung cancer dataset.

Comparison of the plasma volume-expanding effects of 6% dextran 70, 5% albumin, and 6% HES 130/0.4 after hemorrhage in the guinea pig.

BACKGROUND: We still lack comparing data of the plasma volume (PV)-expanding effect of the most commonly used colloids including dextran 70. This study compares the PV-expanding effects of 6% dextran 70, 5% albumin, and 6% hydroxyethylstarch (HES) 130/0.4 after a standardized hemorrhage. METHODS: The prospective and randomized study on 33 anesthetized adult male guinea pigs involved three groups (n = 11 each); the dextran group, the albumin group, and the HES group. The left carotis artery was cannulated for blood pressure measurements and blood samples, and the right jugular vein was cannulated for infusions. After hemorrhage of 20 mL/kg for 8 minutes, the animals were transfused with 20 mL/kg of the colloid for 10 minutes. PV was determined with a I-albumin tracer dilution technique at baseline and 3 hours after the colloid infusion. The PV just after hemorrhage was calculated as the baseline value minus bled PV. Blood gases were measured at baseline, after hemorrhage, just after the colloid infusion and at the end of the experiment. RESULTS: The increase in PV 3 hours after the colloid infusion, including the 20 mL infused, was 36.3 mL/kg +/- 2.3 mL/kg in the dextran group, 26.4 mL/kg +/- 4.7 mL/kg in the albumin group, and 17.6 mL/kg +/- 3.5 mL/kg in the HES group. At the end of the experiment, hematocrit was lower in the dextran group than in the albumin and the HES groups. Urine production was higher in the HES group than in the dextran and the albumin groups. CONCLUSION: After hemorrhage, the PV-expanding capacity of 6% dextran 70 was better than that of 5% albumin, which was in turn better than that of HES 130/0.4 given in equal volumes.

"A call for a clear assignment" - A focus group study of the ambulance service in Sweden, as experienced by present and former employees.

AIM: The aim was to explore the ambulance service as experienced by present and former employees. BACKGROUND: Over the last decade, the number of ambulance assignments has increased annually by about 10%, and as many as 50% of all ambulance assignments are considered non-urgent. This raises questions about which assignments the Ambulance Service (AS) is supposed to deal with. DESIGN/METHOD: Data were collected from three focus group interviews with a total of 18 present and former employees of the Swedish AS. An inductive qualitative analysis method developed by Krueger was chosen. RESULTS: Five themes emerged in the analysis: "Poor guidance for practice", "An unclear assignment", "Being a gate keeper", "From saving lives to self-care" and "Working in no man's land", which together constitute the AS. CONCLUSION: Present and former employees of the AS in Sweden describe their mission as unclear and recognize the lack of consensus and a clearly developed mission statement. Furthermore, expectations and training mainly focus on emergency response, which is contrary to the reality of the ambulance clinicians' everyday work.

Stiffness and strength of cranioplastic implant systems in comparison to cranial bone.

PURPOSE: The aim of this study was to evaluate skull replacement options after decompressive craniectomy by systematically investigating which combination of geometrical properties and material selection would result in a mechanical response comparable in stiffness to that of native skull bone and a strength as high or higher than the same. MATERIALS AND METHODS: The study was conducted using a Finite Element Model of the top part of a human skull. Native skull bone, autografts and commercial implants made of PEEK, solid titanium, two titanium meshes and a titanium-ceramic composite were modeled under a set load to evaluate deformation and maximum stress. RESULTS: The computational result showed a large variation of the strength and effective stiffness of the autografts and implants. The stiffness of native bone varied by a factor of 20 and the strength by a factor of eight. The implants span the entire span of the native skull, both in stiffness and strength. CONCLUSION: All the investigated implant materials had a potential for having the same effective stiffness as the native skull bone. All the materials also had the potential to be as strong as the native bone. To match inherent properties, the best choice of material and thickness is thus patient specific, depending on the quality of the patient's native bone.