Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-Analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Molecular-Conformation of 1,3-Pyridylphenylureas by H-1 and C-13 NMR-study

1H and 13C NMR spectra are reported for several 1,3-pyridylphenyl ureas. Analysis of the spectra yielded the chemical shifts. The variations in the chemical shifts have been discussed in terms of the molecular conformations.

Microbiological status of piggery effluent from 13 piggeries in the south east Queensland region of Australia

Aims: To assist in the development of safe piggery effluent re-use guidelines by determining the level of selected pathogens and indicator organisms in the effluent ponds of 13 south-east Queensland piggeries. Methods and Results: The numbers of thermotolerant coliforms, Campylobacter jejuni/coli, Erysipelothrix rhusiopathiae, Escherichia coli, Salmonella and rotavirus were determined in 29 samples derived from the 13 piggeries. The study demonstrated that the 13 final effluent ponds contained an average of 1Æ2 · 105 colony-forming units (CFU) 100 ml)1 of thermotolerant coliforms and 1Æ03 · 105 CFU 100 ml)1 of E. coli. The Campylobacter level varied from none detectable (two of 13 piggeries) to a maximum of 930 most probable number (MPN) 100 ml)1 (two of 13 piggeries). Salmonella was detected in the final ponds of only four of the 13 piggeries and then only at a low level (highest level being 51 MPN 100 ml)1). No rotavirus and no Erysip. rhusiopathiae were detected. The average log10 reductions across the ponding systems to the final irrigation pond were 1Æ77 for thermotolerant coliforms, 1Æ71 for E. coli and 1Æ04 for Campylobacter. Conclusions: This study has provided a baseline knowledge on the levels of indicator organisms and selected pathogens in piggery effluent. Significance and Impact of the Study: The knowledge gained in this study will assist in the development of guidelines to ensure the safe and sustainable re-use of piggery effluent.

Studies of Phosphazenes. Part 13.' Thermal Rearrangement Reactions of Some Met hoxycyclo phosp hazenes

The methoxycyclophosphazenes [NP(OMe),], (n = 3-6) rearrange on heating to give oxocyclophosphazanes, [N(Me)PO(OMe)],. Isomeric products are formed when n = 4-6. The lH, ,lP, and 13C n.m.r. data for the starting materials and the products are presented. The ethoxy- and n-propoxy-derivatives N,P,( OR)* do not undergo the above rearrangement. The geminal derivatives N,P,R,(OMe), (R = Ph or NHBut) on heating yield both fully and partially rearranged products, namely dioxophosphaz-1 -enes and oxophosphazadienes, as shown by 270- MHz lH n.m.r. spectroscopy. The non-geminal derivative N,P,( NMe,),(OMe), gives only the fully rearranged product N,Me,P,(NMe,),O,(OMe), whose structure has been established from its lH and 31P n.m.r. spectra.

An evaluation of the apxIVA based PCR-REA method for differentiation of Actinobacillus pleuropneumoniae

A restriction analysis of PCR (PCR-REA) amplified apxIVA gene has been suggested as an alternative method for serotyping of Actinobacillus pleuropneumoniae by Jaglic et al. [Jaglic, Z., Svastova, P., Rychlik, I., Nedbalcova, K., Kucerova, Z., Pavlik, I., Bartos, M., 2004. Differentiation of Actinobacillus pleuropneumoniae by PCR-REA based on sequence variability of the apxIVA gene and by ribotyping. Vet. Microbiol. 103, 63-69]. The current study investigated whether this alternative method could distinguish between the reference strains of serovars 13-15 and the value of the method when applied to 47 field isolates representing serovars 1-3, 5, 7-9, 12 and 15 as well as non-typable isolates. The reference strains of serovars 13 and 14 had the same sized product after the apxIVA PCR, while the product for serovar 15 was of different size compared to all the other serovar reference strains. The CfoI digest profiles of the reference serovars 13 and 14 strains were different from each other and from all other serovars. The HpaII digest profiles of these two serovars were very similar to each other, but both were distinctively different from the other serovar profiles. The CfoI digest profile of serovar 15 strain was very similar to the serovars 3 and 12 strains except for two faint extra bands for serovar 15. The HpaII digest profiles of serovars 12 and 15 reference strains were identical. The PCR-REA method correctly recognized the serovar of 21 of 43 field isolates. It was concluded that the method was a useful additional tool to support, but could not replace, conventional serotyping.

Litteraturundervisning och ämnessyn i modersmål och litteratur: En kvalitativ undersökning bland 13 modersmålslärare inom den grundläggande utbildningen (åk 7–9)

I denna avhandling undersöker jag hur modersmålslärare inom den grundläggande utbildningen (åk 7–9) undervisar i litteratur. De frågor jag ställer mig är: Hur förverkligar lärarna sin litteraturundervisning i praktiken, hur förhåller de sig till den nya läroplanen i ämnet, Grunderna för läroplanen för den grundläggande utbildningen 2004, samt med vilken ämnes-, litteratur- och kunskapssyn utgår de från i sin undervisning? Undersökningsresultatet analyseras utifrån läroplan och utifrån en läsarorienterad, sociokulturell och funktionell litteratursyn och litteraturpedagogik. Undersökningen är kvalitativ och riktar sig i form av ett frågeformulär till alla modersmålslärare i högstadierna i huvudstadsregionen. Tretton lärare deltar slutligen och åtta av dessa svar uppföljs genom en tematisk intervju. Undersökningen sker våren 2005. Forskningsresultatet visar på att flera av lärarna till stor del bygger upp sin undervisning utifrån färdiga uppgifter och koncept och att undervisningen styrs av metoden, av frågan hur. Dessa lärares undervisning sker således inte utgående från en enhetlig ämnes-, litteratur- och kunskapssyn, utan ämnessynen varierar beroende på uppgift. Recensionen är den arbetsuppgift som är vanligast bland lärarna, även om flera lärare ställer sig tveksamma till den. Övriga uppgifter som förekommer bland flera lärare är uppgiftskoncept kring klassiker och litterära samtal inför klass. Tematisk litteraturundervisning används även av flera lärare, liksom Netlibris, som innebär att två klasser från olika skolor över nätet diskuterar en skönlitterär text. Både Netlibris och tematisk litteraturundervisning är metoder som lärarna förhåller sig positiva till och ser pedagogiska fördelar med. Den tematiska undervisningen sker emellertid ofta i form av koncept som återkommer i samma form år efter år. Två lärare strävar dock efter att arbeta utifrån en enhetlig ämnessyn – den erfarenhetspedagogiska. Dessa lärare använder sig av färre koncept i sin undervisning. De bygger snarare upp sin undervisning utifrån frågan varför än hur, vilket innebär att de i högre grad har möjlighet att beakta elevernas intressen och behov i utformandet av undervisningen. Detta syns bland annat i valet av böcker och teman. En av dessa lärare använder sig även av portfölj- och loggboksmetodik och låter, i enlighet med läroplanen, eleverna själva vara med och utvärdera undervisningen och den egna utvecklingen. Lärarna verkar överlag förhålla sig mera positiva till de uppgifter som bygger på dialog och som tar fasta på läsaren i läsprocessen. Trots att lärarna betonar dialogens betydelse i litteraturundervisningen, bygger undervisningen ändå ofta, och i flera fall helt och hållet, på uppgifter som saknar dialog. En av orsakerna till detta kan vara att gamla koncept, trots nya uppgifter, lever kvar i undervisningen. Att lärarna framhåller de uppgifter som utgår från läsning av gemensamma texter och som tar fasta på en läsarorienterad och sociokulturell litteratursyn, visar dock på att de nya uppgifterna håller på att omkullkasta de gamla; lärarnas litteraturundervisning befinner sig således i förändring. Samtliga lärare förhåller sig positiva till litteraturundervisning och framhåller att litteraturen sedan deras egen skoltid fått en mera framträdande roll i undervisningen. De påpekar också att modersmålsundervisningen idag är mindre färdighetsinriktad och går mot en ökad dialog.

Aircraft pursuit-evasion problems with variable speeds

Aircraft pursuit-evasion encounters in a plane with variable speeds are analysed as a differential game. An engagement-dependent coordinate system confers open-loop optimality on the game. Each aircraft's optimal motion can be represented by extremel trajectory maps which are independent of role, adversary and capture radius. These maps are used in two different ways to construct the feedback solution. Some examples are given to illustrate these features. The paper draws on earlier results and surveys several existing papers on the subject.

On the breakdown of the most probable distribution for mayer clusters

We present an analysis of the breakdown of the most probable approximation to the Mayer cluster size distribution for clusters of size comparable to the size of the system. This failure is illustrated by considering an ideal Bose gas for which exact volume dependent reducible cluster integrals are available.

Hydrogen- 1 and Carbon- 13 Magnetic Resonance Studies of Nonactin-Calcium Complex

For an understanding of the cation selectivity and general binding characteristics of macrotetralide antibiotic nonactin (NA) with ions of different sizes and charges, the nature of binding of divalent cation, Ca2+, to NA and conformation of the NA-Ca2+ complex have been studied by use of 270-MHz proton nuclear magnetic resonance ('H NMR) and carbon-13 nuclear magnetic resonance (13C NMR). The calcium ion induced significantly large changes in chemical shifts for H7, H2, H3, and H5 protons of NA and relatively small changes for H18 and H2' protons. Changes in I3C chemical shift were quite large for carbonyl carbon, C,; it is noteworthy that in the NA-K+ complex, H2 and H2' protons practically do not show any change during complexation and carbonyl carbon shows a much smaller chemical shift change.

Theoretical investigations of the two-bond proton-carbon-13 coupling constants. Angular variations of the couplings involving carboxyl carbon

A formulation has been developed using perturbation theory to evaluate the π-contribution to the nuclear spin coupling constants involving nuclei at least one of which is an unsaturated center. This fromulation accounts for the π-contribution in terms of the core polarization and one-center exchange at the π-center. The formulation developed together with the Dirac vector model and Penney-Dirac bond-order formalisms was employed to calculate the geminal (two-bond) proton coupling constants of carboxyl carbons in α-disubstituted acetic acids. The calculated coupling constants were found to have an orientational dependence. The results of the calculation are in good agreement with the experimental values.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 x 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-kappaB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

Type 1 and type 2 diabetes among young adults in Finland : Incidence and perinatal exposures

This study aimed to examine the incidence of young adult-onset T1DM and T2DM among Finns, and to explore the possible risk factors for young adult-onset T1DM and T2DM that occur during the perinatal period and childhood. In the studies I-II, the incidence of diabetes was examined among 15-39-year-old Finns during the years 1992-2001. Information on the new diagnoses of diabetes was collected from four sources: standardized national reports filled in by diabetes nurses, the Hospital Discharge Register, the Drug Reimbursement Register, and the Drug Prescription Register. The type of diabetes was assigned using information obtained from these four data sources. The incidence of T1DM was 18 per 100,000/year, and there was a clear male predominance in the incidence of T1DM. The incidence of T1DM increased on average 3.9% per year during 1992-2001. The incidence of T2DM was 13 per 100,000/year, and it displayed an increase of 4.3% per year. In the studies III-V, the effects of perinatal exposures and childhood growth on the risk for young adult-onset T1DM and T2DM were explored in a case-control setting. Individuals diagnosed with T1DM (n=1,388) and T2DM (n=1,121) during the period 1992-1996 were chosen as the diabetes cases for the study, and two controls were chosen for each case from the National Population Register. Data on the study subjects parents and siblings was obtained from the National Population Register. The study subjects original birth records and child welfare clinic records were traced nationwide. The risk for young adult-onset T2DM was the lowest among the offspring of mothers aged about 30 years, whereas the risk for T2DM increased towards younger and older maternal ages. Birth orders second to fourth were found protective of T2DM. In addition, the risk for T2DM was observed to decrease with increasing birth weight until 4.2 kg, after which the risk began to increase. A high body mass index (BMI) at the BMI rebound between ages 3-11 years substantially increased the risk for T2DM, and the excess weight gain in individuals diagnosed with T2DM began in early childhood. Maternal age, birth order, or body size at birth had no effect on the risk for young adult-onset T1DM. Instead, individuals with T1DM were observed to have a higher maximum BMI before the age of 3 than their control subjects. In conclusion, the increasing trend in the development of both T1DM and T2DM among young Finnish adults is alarming. The high risk for T1DM among the Finnish population extends to at least 40 years of age, and at least 200-300 young Finnish adults are diagnosed with T2DM every year. Growth during the fetal period and childhood notably affects the risk for T2DM. T2DM prevention should also target childhood obesity. Rapid growth during the first years of life may be a risk factor for late-onset T1DM.