Vitamin D, d-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study

© 2015.To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6. months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 21 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study.

New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols

A large number of optically active drugs and natural products contain α-functionalised ketones or simple derivatives thereof. Furthermore, chiral α-alkylated ketones are useful synthons and have found widespread use in total synthesis. The asymmetric alkylation of ketones represents one of the most powerful and longstanding procedures in organic chemistry. Surprisingly, however, only one effective methodology is available, and this involves the use of chiral auxiliaries. This is discussed in Chapter 1, which also provides a background of other key topics discussed throughout the thesis. Expanding on the existing methodology of chiral auxiliaries, Chapter 2 details the synthesis of a novel chiral auxiliary containing a pyrrolidine ring and its use in the asymmetric preparation of α-alkylated ketones with good enantioselectivity. The synthesis of racemic α-alkylated ketones as reference standards for GC chromatography is also reported in this chapter. Chapter 3 details a new approach to chiral α-alkylated ketones using an intermolecular chirality transfer methodology. This approach employs the use of simple non-chiral dimethylhydrazones and their asymmetric alkylation using the chiral diamine ligands, (+)- and (-)-sparteine. The methodology described represents the first example of an asymmetric alkylation of non-chiral azaenolates. Enantiomeric ratios up to 83 : 17 are observed. Chapter 4 introduces the first aldol-Tishchenko reaction of an imine derivative for the preparation of 1,3-aminoalcohol precursors. 1,3-Aminoalcohols can be synthesised via indirect routes involving various permutations of stepwise construction with asymmetric induction. Our approach offers an alternative highly diastereomeric route to the synthesis of this important moiety utilising N-tert-butanesulfinyl imines in an aldol-Tishchenko-type reaction. Chapter 5 details the experimental procedures for all of the above work. Chapter 6 discusses the results of a separate research project undertaken during this PhD. 2-alkyl-quinolin-4-ones and their N-substituted derivatives have several important biological functions such as the role of Pseudomonas quinolone signal (PQS) in quorum sensing. Herein, we report the synthesis of its biological precursor, 2-heptyl-4-hydroxy-quinoline (HHQ) and possible isosteres of PQS; the C-3 Cl, Br and I analogues. N-Methylation of the iodide was also feasible and the usefulness of this compound showcased in Pd-catalysed cross-coupling reactions, thus allowing access to a diverse set of biologically important molecules.

Calcium/Calmodulin-Dependent Protein Kinase II Serves as a Biochemical Integrator of Calcium Signals for the Induction of Synaptic Plasticity

Repetitive Ca2+ transients in dendritic spines induce various forms of synaptic plasticity by transmitting information encoded in their frequency and amplitude. CaMKII plays a critical role in decoding these Ca2+ signals to initiate long-lasting synaptic plasticity. However, the properties of CaMKII that mediate Ca2+ decoding in spines remain elusive. Here, I measured CaMKII activity in spines using fast-framing two-photon fluorescence lifetime imaging. Following each repetitive Ca2+ elevations, CaMKII activity increased in a stepwise manner. This signal integration, at the time scale of seconds, critically depended on Thr286 phosphorylation. In the absence of Thr286 phosphorylation, only by increasing the frequency of repetitive Ca2+ elevations could high peak CaMKII activity or plasticity be induced. In addition, I measured the association between CaMKII and Ca2+/CaM during spine plasticity induction. Unlike CaMKII activity, association of Ca2+/CaM to CaMKII plateaued at the first Ca2+ elevation event. This result indicated that integration of Ca2+ signals was initiated by the binding of Ca2+/CaM and amplified by the subsequent increases in Thr286-phosphorylated form of CaMKII. Together, these findings demonstrate that CaMKII functions as a leaky integrator of repetitive Ca2+ signals during the induction of synaptic plasticity, and that Thr286 phosphorylation is critical for defining the frequencies of such integration.

(Table S1) Diatom abundance according to ice cycles in ANDRILL AND1-1B drill core

The influence of Antarctica and the Southern Ocean on Late Pliocene global climate reconstructions has remained ambiguous due to a lack of well-dated Antarctic-proximal, paleoenvironmental records. Here we present ice sheet, sea-surface temperature, and sea ice reconstructions from the ANDRILL AND-1B sediment core recovered from beneath the Ross Ice Shelf. We provide evidence for a major expansion of an ice sheet in the Ross Sea that began at ~3.3 Ma, followed by a coastal sea surface temperature cooling of ~2.5°C, a stepwise expansion of sea ice, and polynya-style deep mixing in the Ross Sea between 3.3 and 2.5 Ma. The intensification of Antarctic cooling resulted in strengthened westerly winds and invigorated ocean circulation. The associated northward migration of Southern Ocean fronts has been linked with reduced Atlantic Meridional Overturning Circulation by restricting surface water connectivity between the ocean basins, with implications for heat transport to the high latitudes of the North Atlantic. While our results do not exclude low-latitude mechanisms as drivers for Pliocene cooling, they indicate an additional role played by southern high-latitude cooling during development of the bipolar world.

Argon analyses of volcanic rocks from the Japan Sea floor

Volcanic rocks recovered from the Japan Sea during ODP Legs 127 and 128 were analyzed by 40Ar-39Ar whole-rock stepwise-heating experiments. All three experiments on samples from Site 795 in the Japan Basin revealed disturbed age spectra, but they are consistent with crystallization ages of 15 to 25 Ma for the samples. At Site 797 in the Yamato Basin, three of the five samples showed plateau ages of 18-19 Ma. At Site 794 in the northern Yamato Basin, three of the five samples revealed concordant age spectra of 20-21 Ma. The radiometric age results are consistent with the estimated ages for the oldest sediments at Site 797 based on the biostratigraphy, but are significantly older than those of the oldest sediments at Site 794. However, the radiometric ages are concordant with previously inferred ages for the formation of the Japan Sea floor based on radiometric age data from dredged igneous rocks from the Japan Sea. The present results indicate that formation of the Japan Sea floor started at least 19-20 Ma ago and give more precise age constraints.

Sea-surface temperature and salinity reconstruction for sediment core GeoB5844-2

We present high-resolution paleoceanographic records of surface and deep water conditions within the northern Red Sea covering the last glacial maximum and termination I using alkenone paleothermometry, stable oxygen isotopes, and sediment compositional data. Paleoceanographic records in the restricted desert-surrounded northern Red Sea are strongly affected by the stepwise sea level rise and appear to record and amplify well-known millennial-scale climate events from the North Atlantic realm. During the last glacial maximum (LGM), sea surface temperatures were about 4°C cooler than the late Holocene. Pronounced coolings associated with Heinrich event 1 (~2°C below the LGM level) and the Younger Dryas imply strong atmospheric teleconnections to the North Atlantic. Owing to the restricted exchange with the Indian Ocean, Red Sea salinity is particularly sensitive to changes in global sea level. Paleosalinities exceeded 50 psu during the LGM. A pronounced freshening of the surface waters is associated with the meltwater peaks MWP1a and MWP1b owing to an increased surface-near inflow of "normal" saline water from the Indian Ocean. Vertical delta18O gradients are also increased during these phases, indicating stronger surface water stratification. The combined effect of deglacial changes in sea surface temperature and salinity on water column stratification initiated the formation of two sapropel layers, which were deposited under almost anoxic condition in a stagnant water body.

Dinoflagellate cyst counts of sediment core GIK23071-3

Marine sediments from the Vøring Plateau (Norwegian Sea) have been studied for their dinoflagellate cyst (dinocyst) and foraminiferal content in order to reconstruct sea-surface conditions in the eastern Norwegian Sea during Marine Isotope Stage (MIS) 5e. In combination with stable oxygen isotope and ice rafted detritus (IRD) data, the variations in foraminiferal and dinocyst assemblage composition reflect a stepwise transition from the final phase of deglaciation (Termination II) into typical interglacial conditions. This stepwise change is repeated subsequently during the cooling conditions of glacial inception towards MIS 5d. The interval studied is characterized by relatively high abundances of Bitectatodinium tepikiense, in comparison to present-day values in the area, indicating a larger seasonal temperature amplitude with enhanced surface water stratification during MIS 5e. The important occurrence of the warm-temperate dinocyst Spiniferites mirabilis s.l. concurrent with subpolar foraminifers Turborotalita quinqueloba, Globigerina bulloides, and Globigerinita glutinata reveals that most pronounced interglacial marine conditions prevailed in the area just prior to the transition towards MIS 5d. The late stratigraphic position of this phase in the interglacial is verified by comparison with dinocyst data from south of Iceland, manifesting its over-regional implication. Besides the good agreement in dinocyst and foraminiferal assemblage changes, the variations in and between both fossil assemblages also point to the existence of some significant surface water variability in the eastern Norwegian Sea during MIS 5e.

The Role of Enjoyment and Motivational Climate in Relation to the Personal Development of Team Sport Athletes

Sport has been identified as a context in which youth encounter positive and negative experiences. However, relatively little is known about the factors that lead to positive and negative personal development among sport participants. The purpose of this study was to investigate the role of enjoyment and motivational climate on positive and negative personal development of team sport participants. A sample of 510 athletes between the ages of 9 and 19 completed questionnaires on positive and negative personal development, enjoyment, and motivational climate. Stepwise multiple regression analyses examined the effects of enjoyment and motivational climate on the personal development of the athletes. Results demonstrated that positive experiences in sport were most strongly predicted by affiliation with peers, self-referenced competency, effort expenditure, and a task climate. Negative experiences were most strongly predicted by an ego climate and other-referenced competency. Results suggest that creating an environment that encourages peer affiliation and personal achievement can result in the positive personal development of youth sport participants.

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk

Risk Factors for Maternal Vitamin D Deficiency within the United Arab Emirates

Introduction: Vitamin D deficiency during pregnancy is a public health problem and it has been associated with negative pregnancy outcomes for both mothers and infants. Aim: To estimate the prevalence of vitamin D deficiency in pregnant women in the United Arab Emirates (UAE) and to identify the contribution of risk factors to the 25(OH)D levels. Methods: It is a cross-sectional study in which vitamin D levels of 1088 adult pregnant women were assessed. Information on vitamin D intake was available in a sub-sample of 266 women. Results: The mean serum 25(OH)D was 26.2 nmol/L (95% CI 25.2-27.1 range 5-129.1 nmol/L) with 69% of women being vitamin D deficient (<30 nmol/L). In the bivariate analysis, showed that no predictors could have been indicated as no values exceeded significance (p<0.2). Stepwise multiple linear regression analysis could not be applied to identify predictors of vitamin D levels as no values exceeded p=0.2. Conclusion: Due to the high prevalence of vitamin deficiency in UAE, there is an urge for interventions focusing on supplementation, fortification and diet diversity for preventing health consequences during a critical period of development.

Affect-Based Effects of Simulation Games on Learning

Empirical evidence has demonstrated the benefits of using simulation games in enhancing learning especially in terms of cognitive gains. This is to be expected as the dynamism and non-linearity of simulation games are more cognitively demanding. However, the other effects of simulation games, specifically in terms of learners’ emotions, have not been given much attention and are under-investigated. This study aims to demonstrate that simulation games stimulate positive emotions from learners that help to enhance learning. The study finds that the affect-based constructs of interest, engagement and appreciation are positively correlated to learning. A stepwise multiple regression analysis shows that a model involving interest and engagement are significantly associated with learning. The emotions of learners should be considered in the development of curriculum, and the delivery of learning and teaching as positive emotions enhances learning.

Socioeconomic Status and Health Behavior in Nepal

Thesis (Master's)--University of Washington, 2016-07

Practical calculations for uniform external pressure buckling in cylindrical shells with stepped walls

Metal cylindrical storage structures of significant size, such as silos and vertical-axis tanks, are almost always constructed from many short cylindrical shells of different thickness as the stress resultants on the wall progressively increase towards the base. The resulting increases in thickness are always made in step changes using metal sheets of uniform thickness because of the availability of such source materials. The result is a shell with a stepped wall with multiple discrete steps in thickness. Such shells are very susceptible to buckling under external pressure when empty or partially filled, but the buckling mode may involve only part of the shell height due to the changes in shell thickness. These changes must therefore be accounted for within the design process. A new method of determining the critical buckling resistance of such shells was recently developed, and although it has been shown to be valid, the methodology for its application in practical design has not been set out or shown. This paper therefore briefly describes the new method and demonstrates the manner in which it can be used to produce rapid, safe assessments of cylindrical shells with a wide range of patterns of wall thickness changes. The results are then suitable for direct introduction into such documents as the European standard on metal shells [1] and the ECCS Recommendations [2].

Motivação e satisfação à luz do modelo ASH: estudo de caso em indústria de alimentos

Neste estudo, foram examinadas as relações existentes entre a motivação e a satisfação do trabalhador no espaço laboral. O estudo empírico foi conduzido em uma única etapa, por meio da qual buscou-se conhecer as dimensões latentes identificadas e, a partir das dimensões validadas, buscou-se estabelecer relações com características motivacionais, como antecedentes, e satisfação pelo trabalho realizado, como conseqüência do atendimento das necessidades manifestadas pelo trabalhador. Foram entrevistados 38 (trinta e oito) funcionários da empresa Água Mineral Cristalina, incluindo-se os que ocupam cargos de chefia. Como instrumento de coleta de dados, foi utilizada parte do complexo da Auditoria do Sistema Humano ASH, criado por Quijano (1999), que se trata de um modelo de pesquisa na área de Psicologia Social, incluindo a Administração de Recursos Humanos, que analisa os processos psicológicos e psicossociais nas organizações. Para esta pesquisa, foram utilizados dois formulários sugeridos pelo autor citado, (anexos 01 e 02). O primeiro denomina-se condições para a motivação , com 15 (quinze) questões do tipo likert. O segundo, "trabalho bem feito e satisfação de necessidades", tem 22 (vinte e duas) questões, também do tipo likert. O instrumento foi respondido por colaboradores, independente da posição hierárquica, em aproximadamente 10 (dez) a 15 (quinze) minutos. A aplicação foi realizada diretamente pelo pesquisador nas unidades de produção e de administração da empresa. Por meio de modelagem de equações estruturais, foi estabelecido um modelo de relações causais entre as dimensões latentes relacionadas à motivação e o desempenho do empregado quando tem satisfeitas as suas necessidades. Quanto ao tratamento dos dados, este ocorreu de forma quantitativa. Quanto à análise, aconteceu após os dados terem sido tratados. Nesta pesquisa, os dados foram analisados por meio de estatísticas descritivas, atualizando-se os recursos de softwares específicos como Statistic ou SPSS Statistic Package for Social Sciences. Usou-se a técnica de Análise de Regressão, na qual foi utilizado o método STEPWISE que inclui na equação de explicação de uma variável dependente somente aquelas que auxiliam ou incrementam sua explicação. Como variáveis dependentes, foram utilizadas as variáveis do formulário "trabalho bem feito e satisfação de necessidades" e como variável independe as variáveis do questionário "condições para motivação". Sob o ponto de vista prático, este estudo mostrou que um determinado conjunto de características motivacionais influi positivamente na satisfação do trabalhador, que poderá realizar um trabalho bem feito; do lado teórico, a pesquisa verificou explicitamente a hipótese de que os aspectos motivacionais contribuem para que o empregado, sentindo-se satisfeito, desempenhe melhor as atribuições que lhe são conferidas

Variación fenotípica y correlación de rendimiento con características morfo-agronómicas en una población de maíz (Zea mays L.) variedad NB-6 en la época de primera, Sábana Grande, Managua, 2014.

Con el objetivo de describir variación fenotípica y correlación de rendimiento con características morfo-agronómicas en una población de maíz (zea mays L.) variedad NB-6 en la época de primera, Sábana Grande, Managua, 2014, se estableció un ensayo en la Finca Santa Rosa Sabana Grande, Managua propiedad de la Universidad Nacional Agraria. La muestra consistió en 93 individuos para caracteres del tallo y hoja, diámetro del tallo (DiamT), altura de la mazorca (AltM), número de hojas (Nho), longitud de la hoja (LonHo), ancho de la hoja (AncHo), altura de la planta (AltP), y 393 individuos para rasgos asociados al rendimiento, longitud de la mazorca (LM), diámetro de la mazorca (DM), número de hilera por mazorca (NH), granos por hilera (GH), peso de granos de la mazorca (PGMAZ), peso de 100 granos (P100G) y peso de la mazorca (PMAZ). El análisis de los datos consistió en estadísticos descriptivos: media, desviación estándar, coeficiente de variación, valores máximos y mínimos, así como correlaciones entre variables morfológicas, correlaciones entre variables asociadas al rendimiento. Finalmente mediante regresión paso a paso (stepwise) se determinaron parámetros de estimación del rendimiento en grano a través de las variables PMAZ y GH. La media y desviación estándar para los caracteres evaluados fueron, 2.21±0.21 AltP, 1.14±0.17 AltM, 94.71±8.18 LonHo, 14.33±1.17 Nho,10.51±0.92 AncHo, 22.81±2.53 DiamT, 16.56±1.83 LM,48.22±3.48 DM, 14.39±1.83 NH, 33.85±4.74 GH, 183.65±40.15 PMAZ, 153.20±33.39 PGMAZ, 34.38±6.08 P100G. El coeficiente de variación mostró valores entre 14.88 y 8.13 % para los caracteres de tallo y hoja correspondientes a AltP y Nho respectivamente. Hubo correlación positiva y significativa AltP con AltM y LonHo (0.74, 036) y DiamT y AncHo (0.39). Para los caracteres relacionados al rendimiento el coeficiente de variación mostró valores entre 21.86 y 7.21 correspondiente a PMAZ y PGMAIZ. Se encontró correlación positiva y significativa para la mayoría de variables del rendimiento exceptuando DM con NH que fue significativa y negativa y LM y NH que no mostraron correlación. El PGMAZ mostró correlaciones positivas y significativas, el resto de variables asociadas al rendimiento con valores que oscilaron entre 0.95 y 0.19 la de mayor correlación fue el PMAZ. El peso de la mazorca contribuyó mas (R2 0.99) al ajuste del modelo de estimación seguido por el número de granos por hilera, para la ecuación final: Yij = 0.7705X1 + 0.3470X2, que puede ser utilizada en selección fenotípica inicial.