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BACKGROUND CONTEXT: Idiopathic scoliosis is a spinal deformity affecting approximately 3% of otherwise healthy children or adolescents. The etiology is still largely unknown but has an important genetic component. Genome-wide association studies have identified a number of common genetic variants that are significantly associated with idiopathic scoliosis in Asian and Caucasian populations, rs11190870 close to the LBX1 gene being the most replicated finding.PURPOSE: The aim of the present study was to investigate the genetics of idiopathic scoliosis in a Scandinavian cohort by performing a candidate gene study of four variants previously shown to be associated with idiopathic scoliosis and exome sequencing of idiopathic scoliosis patients with a severe phenotype to identify possible novel scoliosis risk variants.STUDY DESIGN: This was a case control study.PATIENT SAMPLE: A total of 1,739 patients with idiopathic scoliosis and 1,812 controls were included.OUTCOME MEASURE: The outcome measure was idiopathic scoliosis.METHODS: The variants rs10510181, rs11190870, rs12946942, and rs6570507 were genotyped in 1,739 patients with idiopathic scoliosis and 1,812 controls. Exome sequencing was performed on pooled samples from 100 surgically treated idiopathic scoliosis patients. Novel or rare missense, nonsense, or splice site variants were selected for individual genotyping in the 1,739 cases and 1,812 controls. In addition, the 5'UTR, noncoding exon and promoter regions of LBX1, not covered by exome sequencing, were Sanger sequenced in the 100 pooled samples.RESULTS: Of the four candidate genes, an intergenic variant, rs11190870, downstream of the LBX1 gene, showed a highly significant association to idiopathic scoliosis in 1,739 cases and 1,812 controls (p=7.0×10(-18)). We identified 20 novel variants by exome sequencing after filtration and an initial genotyping validation. However, we could not verify any association to idiopathic scoliosis in the large cohort of 1,739 cases and 1,812 controls. We did not find any variants in the 5'UTR, noncoding exon and promoter regions of LBX1.CONCLUSIONS: Here, we confirm LBX1 as a susceptibility gene for idiopathic scoliosis in a Scandinavian population and report that we are unable to find evidence of other genes of similar or stronger effect.

The efficiency of immune-mediated clearance of cancer cells is hampered by immunosuppressive mediators in the malignant microenvironment, including NADPH oxidase–derived reactive oxygen species. We aimed at defining the effects of histamine, an inhibitor of the myeloid NADPH oxidase/NOX2, on the development of Ag-presenting dendritic cells (DCs) from myeloid precursors and the impact of these mechanisms for tumor growth. Histamine was found to promote the maturation of human DCs from monocytes by increasing the expression of HLA-DR and costimulatory molecules, which resulted in improved induction of Th cells with Th0 polarity. Experiments using wild-type and NOX2-deficient myelomonoblastic cells showed that histamine facilitated myeloid cell maturation only in cells capable of generating reactive oxygen species. Treatment of mice with histamine reduced the growth of murine EL-4 lymphomas in parallel with an increment of tumor-infiltrating DCs in NOX2-sufficient mice but not in NOX2-deficient (gp91phox−/−) mice. We propose that strategies to target the myeloid NADPH oxidase may facilitate the development of endogenous DCs in cancer.

This work discusses the practical limits imposed by magnetic saturation for the force density in low-speed permanent-magnet electric machines. The force density dependence on current density and slot depth is investigated with the aid of finite-element modeling. For saturation reasons, shallow slots are more favorable for achieving high force densities. However, for thermal reasons, deeper slots become favorable. Therefore, an optimum slot depth that maximizes the force density for each current density level exists. The maximum allowable slot depth range for four low-speed applications has been identified for a given maximum motor diameter.

This paper discusses two of the mechanisms that limit the attainable force density in slotted low-speed permanent-magnet (PM) electric machines. Most of the interest is focused on the force density limits imposed by heating of the windings and by stator reactance. The study is based on analytical models for the force and reactance calculations and a lumped parameter thermal model. It is found that in a machine with an indirectly cooled stator, it is difficult to achieve a force density greater than 100 kN/m/sup 2/ due to temperature limits. A high force density is achieved by using deep slots, which lead to high reactance. The high reactance severely increases the converter kilovolt-ampere requirement and total system cost. It is also shown that the cost caused by the high reactance will also limit the force density reached. In machines with one slot per pole per phase, the reactance limited the useful slot depth to approximately 200 mm. However, in machines having a greater number of slots per pole per phase the reactance becomes no longer an important limiting factor for the slot depth and force density.

The etiology of idiopathic scoliosis remains unknown, but growth is a risk factor for progression. Growth pattern differs in children with and without scoliosis. Cartilage oligomeric matrix protein (COMP) may be associated with scoliosis and growth. We, therefore, studied COMP in children with and without idiopathic scoliosis.We included 105 children, with mean age 14.4 years (range 10-16), under observation or treatment for idiopathic scoliosis, and 103 children from an age-matched population-based cohort. COMP was measured in serum at the time of inclusion. Growth velocity was estimated from repeated height measurements. T tests, analysis of covariance or linear regression were used for statistical comparisons.COMP was mean (SD) 11 (5) units/liter (U/L) in children with scoliosis and 13 (5) U/L in the control cohort (p = 0.005, adjusted for sex and sampling time of the day). When patients and controls were analyzed together, high COMP was correlated with high growth velocity (β = 0.19, p = 0.003). When patients and controls were analyzed separately, COMP was correlated with growth velocity in children with scoliosis (β = 0.27, p = 0.007), but not in children without scoliosis (β = 0.02, p = 0.83) (all analyses adjusted for age, sex and sampling time). Low COMP was significantly correlated with large curve size in children with scoliosis (β = -0.29, p = 0.003), but not after adjustment for age, sex and sampling time (β = -0.16; p = 0.14).COMP was lower in children with idiopathic scoliosis than in a control cohort. In children with scoliosis, high COMP was modestly correlated with high growth velocity, but not with curve severity.

Study Design. Multi-center case-control studyObjective. To investigate the prevalence of back problems in adults with idiopathic scoliosis.Summary of Background Data. Information on the prevalence of back problems in adults with idiopathic scoliosis is scarce, especially in untreated individuals, males and individuals with an age at onset of the scoliosis of less than 10 years.Methods. 1069 individuals with idiopathic scoliosis and 158 individuals without scoliosis, all aged 20-65 years, answered a questionnaire on back problems. Individuals with scoliosis were diagnosed between ages 4 and 20 years and any treatment was terminated before age 20. Logistic regression or ANCOVA was used for group comparisons.Results. Mean (SD) age at the time of investigation in individuals with scoliosis (123 men and 946 women) was 41 (9) years, and in individuals without scoliosis (75 men and 83 women) 45 (13) years. 374 individuals with scoliosis were untreated, 451 had been brace treated and 244 surgically treated. The mean prevalence of back problems was 64% in the individuals with scoliosis and 29% in the individuals without scoliosis (p

A nucleic acid based optical biosensing strategy for the broad range detection of compounds with affinity for nucleic acids is described. The strategy attempts to use the chemical and structural information contained in the DNA helix as a sensing element per se . Detection is based on measuring changes in the fluorescence signal intensity of ToPro-3 complexed with nucleic acids. ToPro-3 is a cationic, planar aromatic fluorescent nucleic acid dye that binds to DNA by intercalation. The fluorescence of the dye is environment dependent and is greatly enhanced upon intercalation. ToPro-3 has a long excitation wavelength of 642 nm with emission occurring at 661 nm. At these wavelengths, spectral interference from organic compounds is dramatically reduced. The sensor is capable of detecting known intercalating and groove binding compounds over a broad range of binding affinities. Detection limits of 200, 20, 95 and 1 nM were obtained for EtBr, DAPI, PI and TOTO1, respectively. The ability of the assay to detect the known mutagens bisbenzidine, 1,2,4-benzenetriamine and proflavin, as well as of unknown compounds in natural product extracts was also investigated. Furthermore, the use of longer wavelengths allows the implementation of solid-state instrumentation which allows stable DC operation, reduces electronic noise and simplifies miniaturization, all of which increase portability. This scheme provides a flexible strategy for detecting compounds with affinity for DNA that can be used in a wide range of application areas. Approaches for expanding the informational content of the scheme are discussed.

This work is aimed at studying the profitability of Household Demand Side Management which is a Demand Response (DR) solution aiming at providing power margins to the non-automatic Balancing Market ...

This paper presents a method to calculate the average efficiency from the turbine shaft to the grid in wind energy converters. The average efficiency of three 500 kW systems are compared. The systems are: a conventional grid-connected four-pole induction generator equipped with a gear, a variable-speed synchronous generator equipped with a gear and a frequency converter, and a directly driven variable-speed generator equipped with a frequency converter. In this paper it is shown that a variable-speed generator system can be almost as efficient as one for constant speed, although it has much higher losses at rated load. The increased turbine efficiency that variable speed leads to has not been included in this paper. It is also found that a directly driven generator can be more efficient than a conventional four-pole generator equipped with a gear.

To study family history in relation to curve severity, gender, age at diagnosis and treatment in idiopathic scoliosis.A self-assessment questionnaire on family history of scoliosis was administered to 1,463 untreated, brace or surgically treated idiopathic scoliosis patients.Out of the 1,463 patients, 51 % had one or more relatives with scoliosis. There was no significant difference between females and males, nor between juvenile and adolescent study participants in this respect (p = 0.939 and 0.110, respectively). There was a significant difference in maximum curve size between patients with one or more relatives with scoliosis (median 35°, interquartile range 25) and patients without any relative with scoliosis (median 32°, interquartile range 23) (p = 0.022). When stratifying patients according to treatment (observation, brace treatment or surgery), we found that it was more common to have a relative with scoliosis among the treated patients (p = 0.011). The OR for being treated was 1.32 (95% CI 1.06-1.64) when the patient had a relative with scoliosis, compared to not having.Larger curve sizes were found in patients with a family history of scoliosis than in the ones without. No relation between family history and gender or between family history and age at onset of idiopathic scoliosis was found. Although the presence of a family history of scoliosis may not be a strong prognostic risk factor, it indicates that these patients are at higher risk of developing a more severe curve.

This paper describes modeling steps to enable fast evaluation of performance and cost effectiveness of a plug-in hybrid electric vehicle. The paper also shows how convex optimization can be used to dimension the vehicle powertrain while simultaneously controlling the energy buffer power. The method allows for optimal control of powertrain components that are subject to thermal constraints. The studied vehicle is a city bus driven along a perfectly known bus line. The bus is equipped with an engine-generator unit and an energy buffer consisting of an ultracapacitor and a battery. The engine generator unit and the energy buffer are modeled with quadratic power losses and are sized for two different charging scenarios. In the first scenario the bus can charge for a couple of seconds while standing still at bus stops, and in the second scenario the bus can charge for a couple of minutes before starting the route. In both scenarios, the ultracapacitor temperature is kept below a certain limit.

BACKGROUND: Local pain at the site of an i.v. injection of propofol is a well-known problem, particularly in infants. This randomised investigator-blinded crossover study was designed to assess the effect of the i.v. bolus infusion rate on propofol-induced pain at the site of injection. METHODS: Thirty unpremedicated patients scheduled for ear-nose-throat or plastic surgery at Malmo University Hospital, Sweden, were given two consecutive 2.0 ml injections of propofol 10 mg/ml (Diprivan, AstraZeneca, Sweden/UK), at different infusion rates (0.2 or 1.0 ml/s), immediately before induction of general anesthesia. Half of the patients (n=15) received the first bolus of propofol over 2 s and the second bolus over 10 s, and the other half (n=15) had their injections in reversed order. After each injection, the patient was asked by an investigator to indicate pain intensity on a visual analog scale (VAS) and to report the times of the appearance, maximum point and disappearance of pain. The injections were given approximately 2 min apart. The investigators scoring pain intensity, as indicated by the patients on a 10-point numerical rate scale, were blinded to the order in which the injections were given, as were the patients themselves. RESULTS: There were no statistically significant differences in the incidence (both 86%) of intensity (median; 25th; 75th percentiles, in VAS units: 3.1; 1.0; 5.3 and 3.3; 1.4; 5.0, respectively) or duration (66+/-31 and 73+/-26 s, respectively) of pain between the faster (1.0 ml/s) and slower (0.2 ml/s) bolus infusion rates of propofol studied. CONCLUSIONS: We conclude that the i.v. bolus infusion rate of propofol does not influence drug-induced local pain on injection, at least not within the infusion rate interval studied. Therefore, adjusting i.v. injection speed does not seem to be a clinically useful tool for reducing the intensity or duration of propofol-induced pain at the site of administration.

To estimate the heritability of scoliosis in the Swedish Twin Registry. Self-reported data on scoliosis from 64,578 twins in the Swedish Twin Registry were analysed. Prevalence, pair- and probandwise concordances and tetrachoric correlations in mono- and dizygotic same-sex twins were calculated. The relative importance of genetic variance, i.e. the heritability, and unique and shared environmental variance was estimated using structural equation modelling in Mx software. In addition, all twins in the twin registry were matched against the Swedish Inpatient Register on the primary diagnosis idiopathic scoliosis. The prevalence of scoliosis was 4%. Pair- and probandwise concordance was 0.11/0.17 for mono- and 0.04/0.08 for same-sex dizygotic twins. The tetrachoric correlation (95% CI) was 0.41 (0.33–0.49) in mono- and 0.18 (0.09–0.29) in dizygotic twins. The most favourable model in the Mx analyses estimated the additive genetic effects (95% CI) to 0.38 (0.18–0.46) and the unique environmental effects to 0.62 (0.54–0.70). Shared environmental effects were not significant. The pairwise/probandwise concordance for idiopathic scoliosis in the Swedish Inpatient Register was 0.08/0.15 for monozygotic and zero/zero for same-sex dizygotic twins. Using self-reported data on scoliosis from the Swedish Twin Registry, we estimate that 38% of the variance in the liability to develop scoliosis is due to additive genetic effects and 62% to unique environmental effects. This is the first study of sufficient size to make heritability estimates of scoliosis.

BACKGROUND: Propofol, a popular intravenous (iv) anaesthetic induction agent for brief cases or day surgery, is associated with smooth induction, pleasant sleep, rapid recovery and little postoperative nausea. A major disadvantage is pain at the site of injection. The aim of the present study was to examine the influence of simultaneous iv infusion of carrier fluid on propofol-induced local pain. METHODS: Thirty patients, scheduled for ear-nose-throat or plastic surgery under general anaesthesia, were randomly allocated into two groups. Each patient had two 2 ml iv bolus injections of propofol given at two minutes' interval. In group I (n=15) the first bolus injection was given with no iv carrier fluid and the second one given with a 10 ml iv carrier fluid infused over 10 s. Correspondingly, the patients in group II (n=15) had their first injection with and their second one without the iv carrier fluid. Following each injection of propofol the patients were asked by a blinded investigator to score their pain on a 10-point visual analogue scale, and to report the appearance, maximum and disappearance of pain. After the second assessment of pain, general anaesthesia was induced with more propofol. RESULTS: Pain intensity at the site of propofol injection was found not to be influenced by simultaneous iv infusion of carrier fluid. CONCLUSION: It seems, from the results obtained here, that simultaneous iv infusion of carrier fluid has no particular effect on local pain following iv administration of propofol. (Less)

Bakgrunden visar att en hjärtinfarkt kan påverkar hela människans syn på livet. Hjärtsjukdomar påverkas både av människans genetiska arvsmassa samt av varje individs livsstil. En hjärtinfarkt kan innebära en akut livskris både för patienterna och för deras närstående. De drabbas ofta av oro, ångest och osäkerhet, som ofta är ett resultat av patienternas livsstil, och deras tankar om att insjukna igen senare i framtiden. Dagens korta vårdtid kan innebära att patienterna har svårt att ta emot all information som ges. Syftet var att belysa om den information som sjuksköterskan ger till patienter med hjärtinfarkt under vårdtiden kan påverka deras inställning till livsstilsförändringar. Metoden som valdes var en systematisk litteraturstudie där resultatet är hämtat från åtta stycken kvalitativa artiklar respektive två kvantitativa artiklar som svarade mot arbetets syfte. Artiklarna analyserades utifrån Granheim & Lundman (2004) beskrivningsmodell av kvalitativ innehållsanalys. Resultatet visade att många patienter upplever osäkerhet och rädsla samt att de känner sig oförberedda när hemgången börjar närma sig. Patienterna tycker det är svårt att fortsätta med livsstilsförändringarna i hemmiljön på grund av okunskap och minskad motivation, vilket leder till att de nöjer sig med den medicinska behandlingen. Patienterna efterfrågar även individuellt anpassad information om medicinsk behandling, faktorer som kan förändra deras livsstil. Slutsatsen tyder på att all information mellan sjuksköterskan och patienterna bör ske mer individuellt och att livsstilsförändringar bör prioriteras mer. Patienterna får inte bara lita till den medicinska behandlingen. Författarna tycker att återbesök och samarbete mellan primärvården och sjukhusvården bör ingå som en del av vårdandets yttersta mål.