Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377)

In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy-experienced children were randomized to 4 treatment arms that included different combinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (Nfv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanosine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance ((R)) mutations were assessed before study treatment (baseline) and at virologic failure. Zdv(R), ddI(R), and ddC(R) mutations were detected frequently at baseline but were not associated with virologic failure. Children with drug resistance mutations at baseline had greater reductions in virus load over time than did children who did not. Nvp(R) and 3TC(R) mutations were detected frequently at virologic failure, and Nvp(R) mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children who were maintained on their study regimen after virologic failure accumulated additional Nvp(R) and 3TC(R) mutations plus Rtv(R) and Nfv(R) mutations. However, Rtv(R) and Nfv(R) mutations were detected at unexpectedly low rates.

Selection and characterisation of two attenuated vaccine lines of Eimeria tenella in Australia

Objective To attenuate two strains of Eimeria tenella by selecting for precocious development and evaluate the strains in characterisation trials and by field evaluation, to choose one precocious line for incorporation into an Australian live coccidiosis vaccine for poultry. Design Two strains from non-commercial flocks were passaged through chickens while selecting for precocious development. Each strain was characterised for drug sensitivity, pathogenicity, protection against homologous and heterologous challenge, and oocyst output in replicated experiments in which the experimental unit was a cage of three birds. Oocyst output and/or body weight gain data collected over a 10 to 12 day period following final inoculation were measured. Feed conversion ratios were also calculated where possible. Results Fifteen passages resulted in prepatent periods reduced by 24 h for the Redlands strain (from 144 h to 120 h)and 23 h for the Darryl strain (from 139 h to 116 h). Characterisation trials demonstrated that each precocious line was significantly less pathogenic than its parent strain and each effectively induced immunity that protected chickens against challenge with both the parent strain and other virulent field strains. Both lines had oocyst outputs that, although significantly reduced relative to the parent strains, remained sufficiently high for commercial vaccine production, and both showed susceptibility to coccidiostats. Conclusion Two attenuated lines have been produced that exhibit the appropriate characteristics for use in an Australian live coccidiosis vaccine.

Structure of 2',3'-O-Isopropylidene-5'-O-tosyluridine, C19H22N 2Oas

M r = 438.45, trigonal, P32, a = b = 13.385 (4), c = 9.900 (5) A,, V = 1536.0 A 3, Z = 3, D x = 1.42, D m = 1.42 Mg m -3, 2(Cu Ka) = 1.5418 A,,g(CuKa) = .800mm -], T=290K, F(000)=690, R=6.0% for 1222 unique reflections with F o>_2o(Fo). This is the first 2',3'-O-isopropylidene pyrimidine nucleoside with the base in a syn orientation with respect to the ribose [Xcy= 116.0(7)°]. The ribose has a C(3')-endo conformation with the phase angle of pseudorotation P = 16.36 (2) °. The dioxolane ring assumes an envelope conformation with 0(2') displaced from the best four-atom plane by 0.50 (1) k. The crystal structure is possibly stabilized by a bifurcated hydrogen bond between N(3) and the 0(2) and 0(4) atoms of screw-related molecules.

A reply to a discussion by D.J. Cook of the paper a reaction product of lime and silica from rice husk asha star, open

Abstract is not available.

Comparative performance of Corymbia hybrids and parental species in subtropical Queensland and implications for breeding and deployment.

Eighty six full-sib Corymbia F1 hybrid families (crosses between C. torelliana and four spotted gum taxa: C. citriodora subsp. variegata, C. citriodora subsp. citriodora, C. henryi and C. maculata), were planted in six trials across six disparate sites in south-eastern Queensland to evaluate their productivity and determine their potential utility for plantation forestry. In each trial, the best-growing 20% of hybrid families grew significantly faster (P=0.05) than open-pollinated seedlots of the parent species Corymbia citriodora subsp. variegata, ranging from 107% to 181% and 127% to 287% of the height and diameter respectively. Relative performance of hybrid families growing on more than one site displayed consistency in ranking for growth across sites and analysis showed low genotype-by-environment interaction. Heritability estimates based on female and male parents across two sites at age six years for height and diameter at breast height, were high (0.62±0.28 to 0.64±0.35 and 0.31±0.21 to 0.69±0.37 respectively), and low to moderate (0.03±0.04 to 0.33±0.22) for stem straightness, branch size, incidence of ramicorns, and frost and disease resistance traits at ages one to three years. The proportion of dominance variance for height and diameter had reduced to zero by age six years. Based on these promising results, further breeding and pilot-scale family forestry and clonal forestry deployment is being undertaken. These results have also provided insights regarding the choice of a future hybrid breeding strategy.

Biochemical effects of 3,5-diethoxycarbonyl-1, 4-dihydrocollidine in mouse liver

3,5-Diethoxycarbonyl-1,4-dihydrocollidine (DDC) is a porphyrinogenic agent and is a powerful inducer of δ-aminolaevulinate synthetase, the first and rate-limiting enzyme of the haem-biosynthetic pathway, in mouse liver. However, DDC strikingly inhibits mitochondrial as well as microsomal haem synthesis by depressing the activity of ferrochelatase in vivo. The drug on repeated administration to female mice has been found to elicit hypertrophic effects in the liver microsomes initially, but the effects observed at later stages denote either hyperplasia or increase in polyploidal cells. The microsomal protein concentration shows a striking decrease with repeated doses of the drug. The rate of microsomal protein synthesis in vivo as well as in vitro shows an increase with two injections of DDC but decreases considerably with repeated administration of the drug. The activities of NADPH-cytochrome creductase and ribonuclease are not affected in the liver microsomes of drug-treated animals when expressed per mg of microsomal protein. DDC has also been found to cause degradation of microsomal haem, which is primarily responsible for the decrease in cytochrome P-450 content. The drug also leads to a decrease in mitochondrial cytochrome c levels due to inhibition of haem synthesis and also due to degradation of mitochondrial haem at later stages. The biochemical effects of the drug are compared and discussed with those reported for allylisopropylacetamide and phenobarbital.

Integration of natural hazards, risk and climate change into spatial planning practices

Most countries of Europe, as well as many countries in other parts of the world, are experiencing an increased impact of natural hazards. It is often speculated, but not yet proven, that climate change might influence the frequency and magnitude of certain hydro-meteorological natural hazards. What has certainly been observed is a sharp increase in financial losses caused by natural hazards worldwide. Eventhough Europe appears to be a space that is not affected by natural hazards to such catastrophic extents as other parts of the world are, the damages experienced here are certainly increasing too. Natural hazards, climate change and, in particular, risks have therefore recently been put high on the political agenda of the EU. In the search for appropriate instruments for mitigating impacts of natural hazards and climate change, as well as risks, the integration of these factors into spatial planning practices is constantly receiving higher attention. The focus of most approaches lies on single hazards and climate change mitigation strategies. The current paradigm shift of climate change mitigation to adaptation is used as a basis to draw conclusions and recommendations on what concepts could be further incorporated into spatial planning practices. Especially multi-hazard approaches are discussed as an important approach that should be developed further. One focal point is the definition and applicability of the terms natural hazard, vulnerability and risk in spatial planning practices. Especially vulnerability and risk concepts are so many-fold and complicated that their application in spatial planning has to be analysed most carefully. The PhD thesis is based on six published articles that describe the results of European research projects, which have elaborated strategies and tools for integrated communication and assessment practices on natural hazards and climate change impacts. The papers describe approaches on local, regional and European level, both from theoretical and practical perspectives. Based on these, passed, current and future potential spatial planning applications are reviewed and discussed. In conclusion it is recommended to shift from single hazard assessments to multi-hazard approaches, integrating potential climate change impacts. Vulnerability concepts should play a stronger role than present, and adaptation to natural hazards and climate change should be more emphasized in relation to mitigation. It is outlined that the integration of risk concepts in planning is rather complicated and would need very careful assessment to ensure applicability. Future spatial planning practices should also consider to be more interdisciplinary, i.e. to integrate as many stakeholders and experts as possible to ensure the sustainability of investments.

Archaean crustal evolution in eastern Finland : New geochronological and geochemical constraints from the Kuhmo terrain and the Nurmes belt

This thesis summarises the results of four original papers concerning U-Pb geochronology and geochemical evolution of Archaean rocks from the Kuhmo terrain and the Nurmes belt, eastern Finland. The study area belongs to a typical Archaean granite-greenstone terrain, composed of metavolcanic and metasedimentary rocks in generally N-S trending greenstone belts as well as a granitoid-gneiss complex with intervening gneissic and migmatised supracrustal and plutonic rocks. U-Pb data on migmatite mesosomes indicate that the crust surrounding the Tipasjärvi-Kuhmo-Suomussalmi greenstone belt is of varying age. The oldest protolith detected for a migmatite mesosome from the granitoid-gneiss complex is 2.94 Ga, whereas the other dated migmatites protoliths have ages of 2.84 2.79 Ga. The latter protoliths are syngenetic with the majority of volcanic rocks in the adjacent Tipasjärvi-Kuhmo-Suomussalmi greenstone belt. This suggests that the genesis of some of the volcanic rocks within the greenstone belt and surrounding migmatite protoliths could be linked. Metamorphic zircon overgrowths with ages of 2.84 2.81 Ga were also obtained. The non-migmatised plutonic rocks in the Kuhmo terrain and in the Nurmes belt record secular geochemical evolution, typical of Archaean cratons. The studied tonalitic rocks have ages of 2.83 2.75 Ga and they have geochemical characteristics similar to low-Al and high-Al TTD (tonalite-trondhjemite-dacite). The granodiorites, diorites, and gabbros with high Mg/Fe and LILE-enriched characteristics were mostly emplaced between 2.74 2.70 Ga and they exhibit geochemical characteristics typical of Archaean sanukitoid suites. The latest identified plutonic episode took place at 2.70 2.68 Ga, when compositionally heterogeneous leucocratic granitoid rocks, with a variable crustal component, were emplaced. U-Pb data on migmatite leucosomes suggest that leucosome generation may have been coeval with this latest plutonic event. On the basis of available U-Pb and Sm-Nd isotopic data it appears that the plutonic rocks of the Kuhmo terrain and the Nurmes belt do not contain any significant input from Palaeoarchaean sources. A characteristic feature of the Nurmes belt is the presence of migmatised paragneisses, locally preserving primary edimentary structures, with sporadic amphibolite intercalations. U-Pb studies on zircons indicate that the precursors of the Nurmes paragneisses were graywackes that were deposited between 2.71 Ga and 2.69 Ga and that they had a prominent 2.75 2.70 Ga source. Nd isotopic and whole-rock geochemical data for the intercalated amphibolites imply MORB sources. U-Pb data on zircons from the plutonic rocks and paragneisses reveal that metamorphic zircon growth took place at 2.72 2.63 Ga. This was the last tectonothermal event related to cratonisation of the Archaean crust of eastern Finland.

Conformational effects in the hydrogenation of hemimellitic and cyclohex-1-ene-1,2,3-tricarboxylic acids

The three possible isomers of cyclohexane-1,2,3-tricarboxylic acid were synthesised and separated in order to study the regiospecificity and stereoselectivity of the α-C alkylation of their trimethyl esters. No definitive conclusions could be reached on this aspect for reasons which became apparent in the course of the work. However, the three independent methods adopted for the synthesis of the isomeric tricarboxylic acids have given dramatically different isomer compositions. The reasons are explored in this paper.

Effect of some "strong" excitants of central neurones on the uptake of L-glutamate and L-aspartate by synaptosomes

"Strong" excitants of central neurones such as β N-oxalyl L α,β-diaminopropionic acid (ODAP), N-methyl-D-aspartic acid (NMDA) and kainic acid (KA) were found to inhibit the high affinity uptake of glutamate and aspartate in synaptosomes isolated from young rat brain. The potency of these "strong" excitants as convulsants appear to parallel their ability to inhibit glutamate uptake by synaptosomes. The data suggest the possibility that the convulsive effect of these "strong" excitants could be mediated by glutamate/aspartate.

Transcriptome and glycome profiling of human hematopoietic CD133+ and CD34+ cells

New blood cells are continuously provided by self-renewing multipotent hematopoietic stem cells (HSC). The capacity of HSCs to regenerate the hematopoietic system is utilized in the treatment of patients with hematological malignancies. HSCs can be enriched using an antibody-based recognition of CD34 or CD133 glycoproteins on the cell surface. The CD133+ and CD34+ cells may have partly different roles in hematopoiesis. Furthermore, each cell has a glycome typical for that cell type. Knowledge of HSC glycobiology can be used to design therapeutic cells with improved cell proliferation or homing properties. The present studies characterize the global gene expression profile of human cord blood-derived CD133+ and CD34+ cells, and demonstrate the differences between CD133+ and CD34+ cell populations that may have an impact in transplantation when CD133+ and CD34+ selected cells are used. In addition, these studies unravel the glycome profile of primitive hematopoietic cells and reveal the transcriptional regulation of N-glycan biosynthesis in CD133+ and CD34+ cells. The gene expression profile of CD133+ cells represents 690 differentially expressed transcripts between CD133+ cells and CD133- cells. CD34+ cells have 620 transcripts differentially expressed when compared to CD34- cells. The integrated CD133+/CD34+ cell gene expression profiles proffer novel transcripts to specify HSCs. Furthermore, the differences between the gene expression profiles of CD133+ and CD34+ cells indicate differences in the transcriptional regulation of CD133+ and CD34+ cells. CD133+ cells express a lower number of hematopoietic lineage differentiation marker genes than CD34+ cells. The expression profiles suggest a more primitive nature of CD133+ cells. Moreover, CD133+ cells have characteristic glycome that differ from the glycome of CD133- cells. High mannose-type and biantennary complex-type N-glycans are enriched in CD133+ cells. N-glycosylation-related gene expression pattern of CD133+ cells identify the key genes regulating the CD133+ cell-specific glycosylation including the overexpression of MGAT2 and underexpression of MGAT4. The putative role of MAN1C1 in the increase of unprocessed high mannose-type N-glycans in CD133+ cells is also discussed. These studies provide new information on the characteristics of HSCs. Improved understanding of HSC biology can be used to design therapeutic cells with improved cell proliferation and homing properties. As a result, HSC engineering could further their clinical use.

Measuring the expressed emotion in Chinese family caregivers of persons with dementia: Validation of a Chinese version of the Family Attitude Scale

- Background Expressed emotion (EE) captures the affective quality of the relationship between family caregivers and their care recipients and is known to increase the risk of poor health outcomes for caregiving dyads. Little is known about expressed emotion in the context of caregiving for persons with dementia, especially in non-Western cultures. The Family Attitude Scale (FAS) is a psychometrically sound self-reporting measure for EE. Its use in the examination of caregiving for patients with dementia has not yet been explored. - Objectives This study was performed to examine the psychometric properties of the Chinese version of the FAS (FAS-C) in Chinese caregivers of relatives with dementia, and its validity in predicting severe depressive symptoms among the caregivers. - Methods The FAS was translated into Chinese using Brislin's model. Two expert panels evaluated the semantic equivalence and content validity of this Chinese version (FAS-C), respectively. A total of 123 Chinese primary caregivers of relatives with dementia were recruited from three elderly community care centers in Hong Kong. The FAS-C was administered with the Chinese versions of the 5-item Mental Health Inventory (MHI-5), the Zarit Burden Interview (ZBI) and the Revised Memory and Behavioral Problem Checklist (RMBPC). - Results The FAS-C had excellent semantic equivalence with the original version and a content validity index of 0.92. Exploratory factor analysis identified a three-factor structure for the FAS-C (hostile acts, criticism and distancing). Cronbach's alpha of the FAS-C was 0.92. Pearson's correlation indicated that there were significant associations between a higher score on the FAS-C and greater caregiver burden (r = 0.66, p < 0.001), poorer mental health of the caregivers (r = −0.65, p < 0.001) and a higher level of dementia-related symptoms (frequency of symptoms: r = 0.45, p < 0.001; symptom disturbance: r = 0.51, p < 0.001), which serves to suggest its construct validity. For detecting severe depressive symptoms of the family caregivers, the receiving operating characteristics (ROC) curve had an area under curve of 0.78 (95% confidence interval (CI) = 0.69–0.87, p < 0.0001). The optimal cut-off score was >47 with a sensitivity of 0.720 (95% CI = 0.506–0.879) and specificity of 0.742 (95% CI = 0.643–0.826). - Conclusions The FAS-C is a reliable and valid measure to assess the affective quality of the relationship between Chinese caregivers and their relatives with dementia. It also has acceptable predictability in identifying family caregivers with severe depressive symptoms.

Tytöt, pojat ja sukupuolinen häirintä

In this research I ask what is interpreted as sex-based harassment by 15-16-year old girls and boys. By sex-based harassment I refer to one-sided, unwanted attention that is based on gender and that makes the target feel embarrassed, frightened, hurt or angry. My focus is not on the most overt cases of harassment but rather on everyday encounters. While young people differentiate between harassing and non-harassing attention, at the same time they define, assign value to and construct differences and power relations on the basis of gender, age and ethnicity, for example. My main data consists of essays (N 104, 54 girls, 54 boys) and thematic interviews (N 14; 20 girls, 3 boys) of ninth graders of a secondary school in Helsinki. In the essays and interviews, students construe the border between pleasant and unpleasant, tolerable and intolerable attention as clear in principle, but, they suggest that in practice this border is ambivalent, negotiable and contextual. The interpretations of incidents are justified by referring to features of the target, the scene or the perpetrator. Targets of harassment are most often construed as being girls who are characterized as thin-skinned, but at the same time they are expected to be understanding toward any sex-based attention they may get, particularly when it is not physical. On the other hand, girls are regarded as equal and even active participants in incidents of harassment. Such statements include considerations of how girls either reject or invite particular kinds of attention by their actions and outward appearance. Forms of harassment, ways of understanding it as well as overcoming it vary according to spatial context. By situating incidents in different spaces and places, young people contrast their experiences with ordinary and predictable non-harassment that takes place e.g. in discos and unusual and unexpected harassment that takes place e.g. in the city streets in the daytime. The behaviour of boys harassing a girls is naturalized by appealing to young masculinity and the childishness but also strong sexual drive which is seen as characteristic of teenage boys. On the other hand, sex-based harassment is racialized and pathologized in ways that separate the phenomenon from young, Finnish, normal masculinity. Both the material experiences of the young people and the definitions of the parties involved in harassing incidents are gendered. Girls encounter and deal with sexualized commenting and unwanted approaches much more often and in a more intensive way than boys. Furthermore, there is a vast cultural repertoire of acceptable accounts that can be mobilised in order to excuse male harassers, to critically evaluate the appearance or action of the female targets and to divide the responsibility between the female target and the male perpetrator.

Reversible double insertion of aryl isocyanates into the Ti-O bond of titanium(IV) isopropoxide

The insertion of phenyl isocyanate into titanium isopropoxide leads to the formation of a dimeric complex [Ti(O ' Pr)(2)(mu-O ' Pr){C6H5N(O ' Pr)CO}](2) (1) which has been structurally characterized. Reaction of titanium isopropoxide with two and more than 2 equiv. of phenyl isocyanate is complicated by competitive, reversible insertion between the titanium carbamate and titanium isopropoxide. The ligand formed by insertion of phenyl isocyanate into the titanium carbamate has been structurally characterized in its protonated form C6H5N{C(O ' Pr)O}C(O)N(H)C6H5 (3aH). Insertion into the carbamate is kinetically favored whereas insertion into isopropoxide gives the thermodynamically favored product. (c) 2004 Elsevier B.V. All rights reserved.