Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene

Ankylosing spondylitis (AS) is polygenic with contributions from the immunologically relevant genes HLA-B27, ERAP1 and IL23R. A recent genome-wide association screen (GWAS) identified associations (P0.005) with the non-synonymous single-nucleotide polymorphisms (nsSNPs), rs4077515 and rs3812571, in caspase recruitment domain-containing protein 9 (CARD9) and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) on chromosome 9q that had previously been linked to AS. We replicated these associations in a study of 730 AS patients compared with 2879 historic disease controls (rs4077515 P0.0004, odds ratio (OR)1.2, 95% confidence interval (CI)1.1-1.4; rs3812571 P0.0003, OR1.2, 95% CI1.1-1.4). Meta-analysis revealed strong associations of both SNPs with AS, rs4077515 P0.000005, OR1.2, 95% CI1.1-1.3 and rs3812571 P0.000006, OR1.2, 95% CI1.1-1.3. We then typed 1604 AS cases and 1020 controls for 13 tagging SNPs; 6 showed at least nominal association, 5 of which were in CARD9. We imputed genotypes for 13 additional SNPs but none was more strongly associated with AS than the tagging SNPs. Finally, interrogation of an mRNA expression database revealed that the SNPs most strongly associated with AS (or in strong linkage disequilibrium) were those most associated with CARD9 expression. CARD9 is a plausible candidate for AS given its central role in the innate immune response.

Target acquired: Progress and promise of targeted therapeutics in the treatment of prostate cancer

Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient’s disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

Effect of ion nitriding on the microstructure and properties of Maraging steel (250 Grade)

In the present investigation, ion nitriding of Maraging steel (250 grade) has been carried out at three different temperatures i.e., at 435 degrees C, 450 degrees C and 465 degrees C for 10 h duration in order to achieve good wear resistance along with high strength required for the slat track component of aircraft. The microstructure of the base material and the nitrided layer was examined by optical and scanning electron microscope, and various phases present were determined by X-ray diffraction. Various properties, such as, hardness, case depth, tensile, impact, fatigue properties and corrosion resistance were investigated for both un-nitrided and ion-nitrided materials. It is observed that the microstructure of the core material remains unaltered and Fe4N is formed in the hardened surface layer after ion nitriding at all the three temperatures employed. Surface hardness increases substantially after ion nitriding. Surface hardness remains almost the same but case depth increases with the increase in ion nitriding temperature due to greater diffusivity at higher temperatures. Tensile strength, fatigue strength and corrosion resistance are improved but ductility and energy absorbed in impact test decrease on ion nitriding. These results are explained on the basis of microstructural observations. The properties obtained after ion nitriding at 450 degrees C for 10 h are found to be optimum when compared to the other two ion nitriding temperatures.

Growth and characterization of $SrBi_{2}Nb_{2}O_{9}$ thin films by pulsed-laser ablation

Polycrystalline films of SrBi2Nb2O9 were grown using pulsed-laser ablation. The ferroelectric properties were achieved by low-temperature deposition followed by a subsequent annealing process. The lower switching voltage was obtained by lowering the thickness, which did not affect the insulating nature of the films. The hysteresis results showed an excellent square-shaped loop with results (P-r=6 mu C/cm(2), E-c=100 kV/cm) in good agreement with earlier reports. The films also exhibited a dielectric constant of 250 and a dissipation factor of 0.02. The transport studies indicated an ohmic behavior, while higher voltages induced a bulk space charge.

3,3,6,6-Tetramethyl-9-phenyl-3,4,5,6-tetrahydro-9H-xanthene-1,8(2H,7H)-dione

In the title compound, C23H26O3, the three six-membered rings of the xanthene system are non-planar, having total puckering amplitudes, QT, of 0.443 (2), 0.202 (2) and 0.449 (2) Å. The central ring adopts a boat conformation and the outer rings adopt sofa conformations. The crystal structure is stabilized by van der Waals interactions.

Complexes of lanthanide perchlorates with the open-chain pentadentate ligand n,n,$n^{'},n^{'}$-tetramethyl-3,6,9-trioxaundecane diamide

Complexes of lanthanide perchlorates with the ligand N,N,N,N-tetra-methyl-3,6,9-trioxaundecane diamide (TUD) of the composition Ln(TUD)2-(ClO4)3 (Ln triple bond; length as m-dash La, Nd, Ho, Er, Y) were isolated. Electrical conductivity values indicate that all the perchlorate groups are ionic. IR and nuclear magnetic resonance (1H and 13C) data prove that the ligand coordinates to the metal via the three ether oxygens and the two carbonyl oxygens. A probable coordination number of ten can be assigned for all the complexes.

MHD Flow of a 2nd Grade Fluid in an Orthogonal Rheometer

The magnetohydrodynamics (MHD) flow of a conducting, homogeneous incompressible Rivlin-Ericksen fluid of second grade contained between two infinite, parallel, insulated disks rotating with the same angular velocity about two noncoincident axes, under the application of a uniform transverse magnetic field, is investigated. This model represents the MHD flow of the fluid in the instrument called an orthogonal rheometer, except for the fact that in the rheometer the rotating plates are necessarily finite. An exact solution of the governing equations of motion is presented. The force components in the x and y directions on the disks are calculated. The effects of magnetic field and the viscoelastic parameter on the forces are discussed in detail.

Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children

Background Guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) around the world vary greatly. Most institutions recommend the use of heparin to prevent occlusion, however there is debate regarding the need for heparin and evidence to suggest 0.9% sodium chloride (normal saline) may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased cost. Objectives To assess the clinical effects (benefits and harms) of intermittent flushing of heparin versus normal saline to prevent occlusion in long term central venous catheters in infants and children. Search Methods The Cochrane Vascular Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (Issue 3, 2015). We also searched the reference lists of retrieved trials. Selection criteria Randomised controlled trials that compared the efficacy of normal saline with heparin to prevent occlusion of long term CVCs in infants and children aged up to 18 years of age were included. We excluded temporary CVCs and peripherally inserted central catheters (PICC). Data Collection and Analysis Two review authors independently assessed trial inclusion criteria, trial quality and extracted data. Rate ratios were calculated for two outcome measures - occlusion of the CVC and central line-associated blood stream infection. Other outcome measures included duration of catheter placement, inability to withdraw blood from the catheter, use of urokinase or recombinant tissue plasminogen, incidence of removal or re-insertion of the catheter, or both, and other CVC-related complications such as dislocation of CVCs, other CVC site infections and thrombosis. Main Results Three trials with a total of 245 participants were included in this review. The three trials directly compared the use of normal saline and heparin, however, between studies, all used different protocols for the standard and experimental arms with different concentrations of heparin and different frequency of flushes reported. In addition, not all studies reported on all outcomes. The quality of the evidence ranged from low to very low because there was no blinding, heterogeneity and inconsistency between studies was high and the confidence intervals were wide. CVC occlusion was assessed in all three trials (243 participants). We were able to pool the results of two trials for the outcomes of CVC occlusion and CVC-associated blood stream infection. The estimated rate ratio for CVC occlusion per 1000 catheter days between the normal saline and heparin group was 0.75 (95% CI 0.10 to 5.51, two studies, 229 participants, very low quality evidence). The estimated rate ratio for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37, two studies, 231 participants; low quality evidence). The duration of catheter placement was reported to be similar between the two study arms, in one study (203 participants). Authors' Conclusions The review found that there was not enough evidence to determine the effects of intermittent flushing of heparin versus normal saline to prevent occlusion in long term central venous catheters in infants and children. Ultimately, if this evidence were available, the development of evidenced-based clinical practice guidelines and consistency of practice would be facilitated.

Sustaining productivity of a Vertosol at Warra, Queensland, with fertilisers, no-tillage or legumes. 9. Production and nitrogen benefits from mixed grass and legume pastures in rotation with wheat

Reduced supplies of nitrogen (N) in many soils of southern Queensland that were cropped exhaustively with cereals over many decades have been the focus of much research to avoid declines in profitability and sustainability of farming systems. A 45-month period of mixed grass (purple pigeon grass, Setaria incrassata Stapf; Rhodes grass, Chloris gayana Kunth.) and legume (lucerne, Medicago sativa L.; annual medics, M. scutellata L. Mill. and M. truncatula Gaertn.) pasture was one of several options that were compared at a fertility-depleted Vertosol at Warra, southern Queensland, to improve grain yields or increase grain protein concentration of subsequent wheat crops. Objectives of the study were to measure the productivity of a mixed grass and legume pasture grown over 45 months (cut and removed over 36 months) and its effects on yield and protein concentrations of the following wheat crops. Pasture production (DM t/ha) and aboveground plant N yield (kg/ha) for grass, legume (including a small amount of weeds) and total components of pasture responded linearly to total rainfall over the duration of each of 3 pastures sown in 1986, 1987 and 1988. Averaged over the 3 pastures, each 100 mm of rainfall resulted in 0.52 t/ha of grass, 0.44 t/ha of legume and 0.97 t/ha of total pasture DM, there being little variation between the 3 pastures. Aboveground plant N yield of the 3 pastures ranged from 17.2 to 20.5 kg/ha per 100 mm rainfall. Aboveground legume N in response to total rainfall was similar (10.6 - 13.2 kg/ha. 100 mm rainfall) across the 3 pastures in spite of very different populations of legumes and grasses at establishment. Aboveground grass N yield was 5.2 - 7.0 kg/ha per 100mm rainfall. In most wheat crops following pasture, wheat yields were similar to that of unfertilised wheat except in 1990 and 1994, when grain yields were significantly higher but similar to that for continuous wheat fertilised with 75 kg N/ha. In contrast, grain protein concentrations of most wheat crops following pasture responded positively, being substantially higher than unfertilised wheat but similar to that of wheat fertilised with 75 kg N/ha. Grain protein averaged over all years of assay was increased by 25 - 40% compared with that of unfertilised wheat. Stored water supplies after pasture were < 134mm (< 55% of plant available water capacity); for most assay crops water storages were 67 - 110 mm, an equivalent wet soil depth of only 0.3 - 0.45 m. Thus, the crop assays of pasture benefits were limited by low water supply to wheat crops. Moreover, the severity of common root rot in wheat crop was not reduced by pasture - wheat rotation.

Assessing university students' prior knowledge

The aim of this dissertation was to explore how different types of prior knowledge influence student achievement and how different assessment methods influence the observed effect of prior knowledge. The project started by creating a model of prior knowledge which was tested in various science disciplines. Study I explored the contribution of different components of prior knowledge on student achievement in two different mathematics courses. The results showed that the procedural knowledge components which require higher-order cognitive skills predicted the final grades best and were also highly related to previous study success. The same pattern regarding the influence of prior knowledge was also seen in Study III which was a longitudinal study of the accumulation of prior knowledge in the context of pharmacy. The study analysed how prior knowledge from previous courses was related to student achievement in the target course. The results implied that students who possessed higher-level prior knowledge, that is, procedural knowledge, from previous courses also obtained higher grades in the more advanced target course. Study IV explored the impact of different types of prior knowledge on students’ readiness to drop out from the course, on the pace of completing the course and on the final grade. The study was conducted in the context of chemistry. The results revealed again that students who performed well in the procedural prior-knowledge tasks were also likely to complete the course in pre-scheduled time and get higher final grades. On the other hand, students whose performance was weak in the procedural prior-knowledge tasks were more likely to drop out or take a longer time to complete the course. Study II explored the issue of prior knowledge from another perspective. Study II aimed to analyse the interrelations between academic self-beliefs, prior knowledge and student achievement in the context of mathematics. The results revealed that prior knowledge was more predictive of student achievement than were other variables included in the study. Self-beliefs were also strongly related to student achievement, but the predictive power of prior knowledge overruled the influence of self-beliefs when they were included in the same model. There was also a strong correlation between academic self-beliefs and prior-knowledge performance. The results of all the four studies were consistent with each other indicating that the model of prior knowledge may be used as a potential tool for prior knowledge assessment. It is useful to make a distinction between different types of prior knowledge in assessment since the type of prior knowledge students possess appears to make a difference. The results implied that there indeed is variation between students’ prior knowledge and academic self-beliefs which influences student achievement. This should be taken into account in instruction.

Central America: Labor Reports and Child Labor Reports Pursuant to the Trade Act of 2002, Section 2102(c)(8)-(9)

[Excerpt] These comments are in response to the “Request for Information Concerning Labor Rights in Costa Rica, El Salvador, Guatemala, Honduras and Nicaragua and their Laws Governing Exploitative Child Labor” published at 68 Fed. Reg. 19580 (April 21, 2003). This Request for Information was issued pursuant to Section 2102(c)(8) and (9) of the Trade Act of 2002, Pub. L. 107-210, which requires the President, with respect to any proposed trade agreement, to submit to Congress a “meaningful labor rights report” and a “report describing the extent to which the country or countries that are parties to the agreement have in effect laws governing exploitative child labor.”

Idealähtöistä koulualgebraa : IDEAA-opetusmallin kehittäminen algebran opetukseen peruskoulun 7. luokalla

This research is based on the problems in secondary school algebra I have noticed in my own work as a teacher of mathematics. Algebra does not touch the pupil, it remains knowledge that is not used or tested. Furthermore the performance level in algebra is quite low. This study presents a model for 7th grade algebra instruction in order to make algebra more natural and useful to students. I refer to the instruction model as the Idea-based Algebra (IDEAA). The basic ideas of this IDEAA model are 1) to combine children's own informal mathematics with scientific mathematics ("math math") and 2) to structure algebra content as a "map of big ideas", not as a traditional sequence of powers, polynomials, equations, and word problems. This research project is a kind of design process or design research. As such, this project has three, intertwined goals: research, design and pedagogical practice. I also assume three roles. As a researcher, I want to learn about learning and school algebra, its problems and possibilities. As a designer, I use research in the intervention to develop a shared artefact, the instruction model. In addition, I want to improve the practice through intervention and research. A design research like this is quite challenging. Its goals and means are intertwined and change in the research process. Theory emerges from the inquiry; it is not given a priori. The aim to improve instruction is normative, as one should take into account what "good" means in school algebra. An important part of my study is to work out these paradigmatic questions. The result of the study is threefold. The main result is the instruction model designed in the study. The second result is the theory that is developed of the teaching, learning and algebra. The third result is knowledge of the design process. The instruction model (IDEAA) is connected to four main features of good algebra education: 1) the situationality of learning, 2) learning as knowledge building, in which natural language and intuitive thinking work as "intermediaries", 3) the emergence and diversity of algebra, and 4) the development of high performance skills at any stage of instruction.

Kasvilajien tunnistaminen, oppiminen ja opettaminen yleissivistävän koulutuksen näkökulmasta

The purpose of the research was to determine how well Finnish pupils and students of different ages recognize plant species, which variables explain recognition of plant species, what plants and nature mean to the subjects and how plant species identification should be taught in general education in Finland. The subjects were pupils from: every class level of the primary schools (grades 1 6); lower- secondary school (grades 7 9); high school (grades I II); university departments of teacher education and classroom teachers and teachers from university involved with environmental teaching and also experts from education and botany. A total of 883 people took part in the research. Both quantitative and qualitative research methods were used. The quantitative methods were: a) plant species recognition test, where 70 plant species photos were shown to subjects and b) an experiment in which three experimental groups had a plant recognition test on the nature trail and the three comparison groups were tested on recognition of the same species in classroom. The testing materials consisted of 31 real plants outdoors and 31 photos taken of these real plant species that were shown to pupils from fourth, fifth and sixth classes (grade levels) from primary school. The qualitative methods were a questionnaire administered to pupils from elementary school and high school and students from the department of teacher education, to teachers from university and interviews, where 3 5 pupils and students who recognized the plant species best or worst in the recognition test were selected to be interviewed. Furthermore, classroom teachers from primary school and experts were interviewed. The research results showed that on average plant species were recognized insufficiently on every level of education. There was also variation between answers from primary school to university teachers. However, species recognition skills improved from primary school to university teachers. Among other things, sex and place of residence explained species recognition skills, because girls and pupils from rural areas knew plant species statistically significantly better than boys or pupil from cities. Almost every pupil, student and all classroom teachers wanted to recognize plant species better. Many pupils mentioned that a motivating teaching method would be to go outdoors and investigate the plant species themselves. University teachers and experts also mentioned that the best and most efficient learning and teaching method for species recognition skills, is to practice in nature. We should teach plant species in nature, using many senses and teaching methods. Also new technology could be used in teaching species recognition skills. Keywords: plant species recognition, plant species education, general education

Young, gifted and spiritual -The case of Finnish sixth-grade pupils

The aim of this study was to explore the spirituality of Finnish academically gifted 12 13-year old pre-adolescents (N = 101). Their spirituality was investigated through the following three questions: (1) What is their relationship to religion? (2) How do they perceive transcendence? and (3) How does their search for meaning integrate into their lives? A total of 60 girls and 41 boys participated in the study. They attend a special school, Helsingin Suomalainen yhteiskoulu, in Helsinki, Finland. The school includes classes from grade 3 to upper secondary school and has an entrance test. This study is part of a research project called Actualizing Finnish Giftedness which is funded by the Finnish Academy between 2000 2007 and is led by Professor Tirri. The research project is based on Gardner s Multiple Intelligences theory (Gardner 1993) and on Hay s (1998) work on spirituality. The data in this study was gathered in 2003 and 2004. It includes both qualitative and quantitative material. The emphasis is on data gathered with interviews. The mixed method approach was used as the methodological framework for connecting the qualitative content analysis, phenomenological approach and the quantitative tests of this study. The results of the sub-studies are reported in full in the four original articles. First, the articles show that the pupils connect religion mainly with Christian institutions and do not consider religion and spirituality to overlap. Second, the articles show that the pupils believe in God and the interference of God in their lives and they think that reality includes a spiritual dimension. Third, the pupils had four kinds of existentially significant interests: personal, transcendental, cosmic and ethical. Cosmic interests were especially highlighted in the article concerning boys as nature and science were reported to be integral sources for their existential thinking. In addition, perceptions on God seemed to be connected to the individual s perception on the meaning of life. In RE, spiritual development has been a constant topic of interest since the late eighties. Likewise, recently in gifted education there have been discussions concerning spiritual intelligence (Gardner 1999) and spirituality of the gifted (Kerr & Cohn 2001). Based on the empirical results of the study, this study concludes that education wishing to promote spiritual development should aim at being existentially relevant to the pupils and use their existential search as an integrative framework for their individual talents and skills.

Koulutuksellisen syrjäytymisriskin ennustettavuus yhteishakuvalintojen kautta tarkasteltuna : koulupudokkuusriskin yhteys oppilaan kognitiiviseen kompetenssiin, koulumenestykseen sekä itseä ja vanhempia koskeviin uskomuksiin

The objective of this study was to find factors that could predict educational dropout. Dropout risk was assessed against pupil’s cognitive competence, success in school, and personal beliefs regarding self and parents, while taking into account the pupil’s background and gender. Based on earlier research, an assumption was made that a pupil’s gender, success in school, and parent’s education would be related with dropping out. This study is part of a project funded by the Academy of Finland and led by Professor Jarkko Hautamäki. The project aims to use longitudinal study to assess the development of pupils’ skills in learning to learn. The target group of this study consisted all Finnish speaking ninth graders of a municipality in Southern Finland. There were in total 1534 pupils, of which 809 were girls and 725 boys. The assessment of learning to learn skills was performed about ninth graders in spring 2004. “Opiopi” test material was used in the assessment, consisting of cognitive tests and questions measuring beliefs. At the same time, pupils’ background information was collected together with their self-reported average grade of all school subjects. During spring 2009, the pupils’ joint application data from years 2004 and 2005 was collected from the Finnish joint application registers. The data were analyzed using quantitative methods assisted by the SPSS for Windows computer software. Analysis was conducted through statistical indices, differences in grade averages, multilevel model, multivariate analysis of variance, and logistic regression analysis. Based on earlier research, dropouts were defined as pupils that had not been admitted to or had not applied to second degree education under the joint application system. Using this definition, 157 students in the target group were classified as dropouts (10 % of the target group): 88 girls and 69 boys. The study showed that the school does not affect the drop-out risk but the school class explains 7,5 % of variation in dropout risk. Among girls, dropping out is predicted by a poor average grade, a lack of beliefs supporting learning, and an unrealistic primary choice in joint application system compared to one’s success in school. Among boys, a poor average grade, unrealistic choices in joint application system, and the belief of parent’s low appreciation of education were related to dropout risk. Keywords educational exclusion, school dropout, success in school, comprehensive school, learning to learn