Estimating the burden of disease attributable to iron deficiency anaemia in South Africa in 2000

OBJECTIVES To estimate the extent of iron deficiency anaemia (IDA) among children aged 0 - 4 years and pregnant women aged 15 - 49 years, and the burden of disease attributed to IDA in South Africa in 2000. DESIGN The comparative risk assessment (CRA) methodology of the World Health Organization (WHO) was followed using local prevalence and burden estimates. IDA prevalence came from re-analysis of the South African Vitamin A Consultative Group study in the case of the children, and from a pooled estimate from several studies in the case of the pregnant women (haemoglobin level < 11 g/dl and ferritin level < 12 microg/l). Monte Carlo simulation-modelling was used for the uncertainty analysis. SETTING South Africa. SUBJECTS Children under 5 years and pregnant women 15 - 49 years. OUTCOME MEASURES Direct sequelae of IDA, maternal and perinatal deaths and disability-adjusted life years (DALYs) from mild mental disability related to IDA. Results. It is estimated that 5.1% of children and 9 - 12% of pregnant women had IDA and that about 7.3% of perinatal deaths and 4.9% of maternal deaths were attributed to IDA in 2000. Overall, about 174,976 (95% uncertainty interval 150,344 - 203,961) healthy years of life lost (YLLs), or between 0.9% and 1.3% of all DALYs in South Africa in 2000, were attributable to IDA. CONCLUSIONS This first study in South Africa to quantify the burden from IDA suggests that it is a less serious public health problem in South Africa than in many other developing countries. Nevertheless, this burden is preventable, and the study highlights the need to disseminate the food-based dietary guidelines formulated by the National Department of Health to people who need them and to monitor the impact of the food fortification programme.

Common genetic variants influence human subcortical brain structures

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08×10 -33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Combining meta- and mega-analytic approaches for multi-site diffusion imaging based genetic studies: From the enigma-DTI working group

Meta-analyses estimate a statistical effect size for a test or an analysis by combining results from multiple studies without necessarily having access to each individual study's raw data. Multi-site meta-analysis is crucial for imaging genetics, as single sites rarely have a sample size large enough to pick up effects of single genetic variants associated with brain measures. However, if raw data can be shared, combining data in a "mega-analysis" is thought to improve power and precision in estimating global effects. As part of an ENIGMA-DTI investigation, we use fractional anisotropy (FA) maps from 5 studies (total N=2, 203 subjects, aged 9-85) to estimate heritability. We combine the studies through meta-and mega-analyses as well as a mixture of the two - combining some cohorts with mega-analysis and meta-analyzing the results with those of the remaining sites. A combination of mega-and meta-approaches may boost power compared to meta-analysis alone.

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.

Identification of common variants associated with human hippocampal and intracranial volumes

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10 -16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7).

The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Schizophrenia Genetic Variants are not Associated with Intelligence

Background Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence. Method IQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls. Results Although significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p = 0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R 2 = 0.055, p = 2.1 × 10 -7) and with IQ in the entire sample (R 2 = 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status. Conclusions Our data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk. © Cambridge University Press 2013.

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.

Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10 -11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9).

Kalleuksia isänmaalle : Eliel Aspelin-Haapkylä taiteen keräilijänä ja taidehistorioitsijana

Treasures of a Patriot Eliel Aspelin-Haapkylä as an art collector and art historian Treasures of a Patriot is a study of Eliel Aspelin-Haapkylä (1847 - 1917), professor of aesthetics and modern literature, as an art collector and art historian. The study combines the biographical perspective, art history as a discipline in the 19th-century Finland, and Aspelin-Haapkylä s art historical scholarship. My intention was to answer to questions such as what kind of an art collector an academic art historian was, why he collected art and cultural-historical objects and what the purpose of his collecting was. Aspelin-Haapkylä was an ideal choice for the main character because the ideologies of the era, culture, art and European ideas, especially German ideas about museums, are intertwined in his life. In addition, the ideas of the Fennomen can be found in his ideological background. Together with his wife, Ida Aspelin-Haapkylä, he bequeathed a rich donation to the National Museum of Finland, and a wideranging archive concerning the collection, his writings, and letters to the Finnish Literature Society. I have highlighted the materials from the archives related both to the collection and art history, especially the letters between Aspelin-Haapkylä and artists, fellow members of academia, his spouse and relatives. The content and the structure of the research are divided into seven main chapters. First, I discuss Susan M. Pearce s theory of collecting and the history of collecting. I also introduce some other art historians who were private collectors. The late 19th-century Fennomen and other nationalists who were active in cultural life and the arts, are introduced in the second chapter. In the third I deal with Aspelin-Haapkylä s collection of European art combined with his writings, his early published works, studies and many trips to Europe. The fourth and the fifth chapters are dedicated to those Finnish artists who he wrote biographies of, and the artists of his own era whom he supported. The sixth chapter discusses institutions and channels of influence and power through which the initiative to found the National Museum of Finland, his action in the Antell Delegation and co-operation with the art merchant Henryk Bukowski, rise up to the fore. Finally, I process the last will and the fate of the collection from 1917 until 1932. As an appendix, I have included a report and reconstruction of the art collection. The catalogue is based on the words in Aspelin-Haapkylä s the so-called blue notebooks, which I have completed with additions from other sources.

"Det utspridda kärret; överallt och växande form" : Eva Wichmans novell "Kärret" som en prosamodernistisk berättelse om kvinnligt skapande

I min avhandling diskuterar jag om och hur man kan läsa Eva Wichmans novell "Kärret" (ur Molnet såg mig, 1942) som en prosamodernistisk berättelse om ett kvinnligt subjekt, och om kvinnligtskapande. Jag vill mot en prosamodernistisk bakgrund visa min tolkning med en stilistisk och entematisk analys. I min inledning markerar jag att forskare har haft svårt att avgöra vad Eva Wichman egentligen vill säga med "Kärret". De flesta definierar "Kärret" som en fabel, en moralisk berättelse. I min tolkning betonar jag att novellen kan läsas som en prosamodernistisk fabel om det kvinnliga skapandet. Eva Wichman har i många av sina verk beskrivit en kvinnlig konstnärs svårigheter i massamhället och den manliga världen. Jag anser därför att denna tolkning inte är långsökt då det gäller en naturallegori som "Kärret". Jag redovisar kort för bakgrunden till prosamodernismen; definierar stilistiska grundbegrepp i lyrikoch prosa samt diskuterar med hjälp av Peter Luthersson och Gunilla Domellöf hur den modernistiska individualiteten konstituerar sig i förhållande till samhället ochmoderniseringsprocessen. Jag tar fasta på den kvinnliga författarens skapandeprocess och poängterar, med hjälp av bl.a. Dominique Head och Domellöf, att det kvinnliga skapandet ofta är svårt att erhålla i ett traditionellt manligt samhälle. Head, Domellöf och Rachel Blau DuPlessis menar att det modernistiska skapandet hos kvinnor i stor grad sker med hjälp av stilistiska brott och luckor. I synnerhet förhållandet mellan metafor och metonymi utgör en viktig metod för den kvinnliga modernisten. I mitt tredje kapitel analyserar jag "Kärret" stilistiskt. Modernismen i "Kärret" går ut sammanställa motsatser och sinnesanalogier. Jag tar upp det lyriska och metaforiska i "Kärret"; upprepningar,parallellismer, rytm och dynamik, samt förhållandet mellan metaforer och metonymier utgående från en artikel av David Lodge. Jag demonstrerar i stilanalysen hur Eva Wichman bygger upp ett cykliskt mytiskt berättande. Detta cirkelberättande kan, enligt Domellöf, ses som en kvinnlig utmaning mot det traditionella manliga berättandet. Förhållandet mellan metaforer och metonymier spelar en stor roll också i min tematiska analys. Jag läser kärret i novellen som en symbol för ett kvinnlig subjekt. Kärret är uppbyggt av motsatser. Dessamotsatser kan ses som metaforer i min tolkning av kärret som kvinnligt subjekt. Motsatsparen yta/djup läser jag som den medvetna respektive undermedvetna nivån i det kvinnliga subjektet. Djupet, den undermedvetna nivån, analyserar jag delvis med hjälp av Julia Kristevas begrepp abjektet. Metaforerna spegel/öga ser jag som subjekt/objekt och manligt/kvinnligt i förhållande till det kvinnliga subjektet. Med hjälp av abjektet, omnipotens/känslighet, rörelse/statis samt liv/död visar jag hur Eva Wichman beskriver det konstnärliga skapandet, och den konstnärliga alieneringen i kontrast till det förtryckandet massamhället. Här baserar jag mig på Lutherssons resonemang om den modernistiska individualiteten. På så sätt drar jag slutsatsen att kärret som kvinnligt subjekt kan läsas som ett kvinnligt författarjag. "Kärret" är en berättelse om kvinnlig skaparkraft, om ett kvinnligt subjekt som skapar och verkar isamhället. Eva Wichman gestaltar det kvinnliga berättandet både tematiskt och språkligt. Därför är "Kärret" enligt mig inte en pessimistisk berättelse om ett "säkert nederlag" som många påstår, utan en storslagen fabel om ett modernistiskt subjekt i process. Nyckelord: Eva Wichman, Molnet såg mig, prosamodernism, kvinnligt subjekt, abjekt, metafor, metonymi

Meeting of the Joint Distribution Committee and the Executive Committee of the American Jewish Relief Committee 1918 in New York

Reproduction of a painting of a meeting of the Joint Distribution Committee (representing the American Jewish Relief Committee, the Central Rellief Committee and the People's Relief Committee) and the Executive Committee of the American Jewish Relief Committee, with chairman Felix Warburg, secretary Albert Lucas, stenographer Mrs. F. Friedman, executive director Boris Bogen, comptroller Harriet Lowenstein, associate treasurer Paul Baerwald and treasurer Arthur Lehman; Office of Mr. Felix M. Warburg, 52 William Street, New York

Liederkranz trip to Hundseck Portraits Groups

Liederkranzausflug nach Hundseck; Standing l-r; Sidi Ullmann, Ehepaar, Alfred und Toni Hirschland, Willi Ullmann, Lisel Suess, Lene Hesse-Sinzheimer, Julius Suess, ?, Hermann Boehm, Eugen Hirsch, Dr. Carl Kahn, Frau von Michael Rothschild (Ella?), Max Sinzheimer, Grete Hirschland and Alfred Liebmann ; Seated l-r: Adele Boehm, Michael Rothschild, rosel Suess, Louis Kahn (Junior), Ehepaar Dr. Gustav Hecht, Paula Hirsch and Marianne Kahn

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.