Increasing the power of genome wide association studies in natural populations using repeated measures - evaluation and implementation

1. Genomewide association studies (GWAS) enable detailed dissections of the genetic basis for organisms' ability to adapt to a changing environment. In long-term studies of natural populations, individuals are often marked at one point in their life and then repeatedly recaptured. It is therefore essential that a method for GWAS includes the process of repeated sampling. In a GWAS, the effects of thousands of single-nucleotide polymorphisms (SNPs) need to be fitted and any model development is constrained by the computational requirements. A method is therefore required that can fit a highly hierarchical model and at the same time is computationally fast enough to be useful. 2. Our method fits fixed SNP effects in a linear mixed model that can include both random polygenic effects and permanent environmental effects. In this way, the model can correct for population structure and model repeated measures. The covariance structure of the linear mixed model is first estimated and subsequently used in a generalized least squares setting to fit the SNP effects. The method was evaluated in a simulation study based on observed genotypes from a long-term study of collared flycatchers in Sweden. 3. The method we present here was successful in estimating permanent environmental effects from simulated repeated measures data. Additionally, we found that especially for variable phenotypes having large variation between years, the repeated measurements model has a substantial increase in power compared to a model using average phenotypes as a response. 4. The method is available in the R package RepeatABEL. It increases the power in GWAS having repeated measures, especially for long-term studies of natural populations, and the R implementation is expected to facilitate modelling of longitudinal data for studies of both animal and human populations.Peer reviewe

Predictive response-relevant clustering of expression data provides insights into disease processes

This article describes and illustrates a novel method of microarray data analysis that couples model-based clustering and binary classification to form clusters of ;response-relevant' genes; that is, genes that are informative when discriminating between the different values of the response. Predictions are subsequently made using an appropriate statistical summary of each gene cluster, which we call the ;meta-covariate' representation of the cluster, in a probit regression model. We first illustrate this method by analysing a leukaemia expression dataset, before focusing closely on the meta-covariate analysis of a renal gene expression dataset in a rat model of salt-sensitive hypertension. We explore the biological insights provided by our analysis of these data. In particular, we identify a highly influential cluster of 13 genes-including three transcription factors (Arntl, Bhlhe41 and Npas2)-that is implicated as being protective against hypertension in response to increased dietary sodium. Functional and canonical pathway analysis of this cluster using Ingenuity Pathway Analysis implicated transcriptional activation and circadian rhythm signalling, respectively. Although we illustrate our method using only expression data, the method is applicable to any high-dimensional datasets

The Relationship between Zinc Intake and Serum/Plasma Zinc Concentration in Children: A Systematic Review and Dose-Response Meta-Analysis

Recommendations for zinc intake during childhood vary widely across Europe. The EURRECA project attempts to consolidate the basis for the definition of micronutrient requirements, taking into account relationships among intake, status and health outcomes, in order to harmonise these recommendations. Data on zinc intake and biomarkers of zinc status reported in randomised controlled trials (RCTs) can provide estimates of dose-response relationships which may be used for underpinning zinc reference values. This systematic review included all RCTs of apparently healthy children aged 1–17 years published by February 2010 which provided data on zinc intake and biomarkers of zinc status. An intake-status regression coefficient was calculated for each individual study and calculated the overall pooled and SE using random effects meta-analysis on a double log scale. The pooled dose-response relationship between zinc intake and zinc status indicated that a doubling of the zinc intake increased the serum/plasma zinc status by 9%. This evidence can be utilised, together with currently used balance studies and repletion/depletion studies, when setting zinc recommendations as a basis for nutrition policies

A szimbolizmus és az avantgarde kora az orosz művészeti kultúrában (kétnyelvű dokumentumgyűjtemény) = The age of symbolism and avant-garde in russian art (a bilingual textbook)

A kétnyelvű dokumentumgyűjteményben a tematikusan csoportosított anyagok a XIX-XX század fordulóját (a szimbolizmus és a szecesszió kora) és az 1910-20-as évek (a posztszimbolizmus és az avantgarde kora) időszakát követik végig. A bemutatott korszak nem csupán a festészeti kultúra virágkorát, a művészi módszerek kísérleti megújítását jelentette az orosz művészetben, hanem a művészi gyakorlat kritikai és elméleti reflexiójának, a művészetkritikai és művészetfilozófiai gondolkodásnak a virágkorát is. Ennek a korszaknak az átfogó bemutatása eddig még nem valósult meg a hazai művészettörténeti és szlavisztikai szakkutatásokban. A válogatás koncepcióját a kötet szaklektorai nemzetközi vonatkozásban is jelentősnek minősítették. Az eredeti szövegek magyar nyelvű fordítása az ELTE Orosz Irodalmi Doktori Programjának műhelyében készült. A kötetben szereplő szövegeket a doktori program tanárai és hallgatói fordították 500 oldal terjedelemben. A szövegeket mintegy 400 kép illusztráció kíséri. A dokumentumok közlését jegyzetapparátus és ajánló bibliográfia egészíti ki. A dokumentumgyűjtemény az egyetemi alapfokú és posztgraduális képzés területén hasznosítható a művészettörténet, az esztétika és a szlavisztika szakokon; a szélesebb olvasóközönség körében is népszerűsíthető. Mivel a kötet az eredeti orosz nyelvű forrásanyagot is tartalmazza, ezért nemzetközi érdeklődésre is számot tarthat. | Materials in the bilingual textbook are classified thematically in chronological order to follow the main trends of art criticism at the turn of the 19th and 20th centuries (the age of Symbolism and Art Nouveau) as well as in the 1910s and 1920s (the age of Post-Symbolism and Avant-Garde). The described period marked not only the golden age of painting culture, the experimental renewal of artistic principles, but also the golden age of the critical and theoretical thinking. An all-embracing presentation of this period has not been accomplished so far in special research into Art History and Slavonic studies in Hungary. The translation of primary texts into Hungarian and the elaboration on up-to-date and easy-to-understand special terminology was prepared as a result of teamwork in the workshop of the PhD Program in Russian Literature at the Eötvös Loránd University of Budapest. The texts in the book were translated by the Professors and Students of the PhD program. The documents are complemented by 400 pictures illustrating the main trends of the period, and are accompanied by an extensive scholarly apparatus and a selected bibliography. The bilingual textbook illustrated with pictures can be used first of all as a university reference book in graduate and postgraduate education in Art History, Aesthetics, and Slavonic Studies. Since the bilingual book also contains the primary source material in Russian, it will arouse international interest

Tuberculosis retreatment 'others' in comparison with classical retreatment cases; a retrospective cohort review.

BACKGROUND: Many of the countries in sub-Saharan Africa are still largely dependent on microscopy as the mainstay for diagnosis of tuberculosis (TB) including patients with previous history of TB treatment. The available guidance in management of TB retreatment cases is focused on bacteriologically confirmed TB retreatment cases leaving out those classified as retreatment 'others'. Retreatment 'others' refer to all TB cases who were previously treated but with unknown outcome of that previous treatment or who have returned to treatment with bacteriologically negative pulmonary or extra-pulmonary TB. This study was conducted in 11 regional referral hospitals (RRHs) serving high burden TB districts in Uganda to determine the profile and treatment success of TB retreatment 'others' in comparison with the classical retreatment cases. METHODS: A retrospective cohort review of routinely collected National TB and Leprosy Program (NTLP) facility data from 1 January to 31 December 2010. This study uses the term classical retreatment cases to refer to a combined group of bacteriologically confirmed relapse, return after failure and return after loss to follow-up cases as a distinct group from retreatment 'others'. Distribution of categorical characteristics were compared using Chi-squared test for difference between proportions. The log likelihood ratio test was used to assess the independent contribution of type of retreatment, human immunodeficiency virus (HIV) status, age group and sex to the models. RESULTS: Of the 6244 TB cases registered at the study sites, 733 (11.7%) were retreatment cases. Retreatment 'others' constituted 45.5% of retreatment cases. Co-infection with HIV was higher among retreatment 'others' (70.9%) than classical retreatment cases (53.5%). Treatment was successful in 410 (56.2%) retreatment cases. Retreatment 'others' were associated with reduced odds of success (AOR = 0.44, 95% CI 0.22,0.88) compared to classical cases. Lost to follow up was the commonest adverse outcome (38% of adverse outcomes) in all retreatment cases. Type of retreatment case, HIV status, and age were independently associated with treatment success. CONCLUSION: TB retreatment 'others' constitute a significant proportion of retreatment cases, with higher HIV prevalence and worse treatment success. There is need to review the diagnosis and management of retreatment 'others'

Виявлення впливу конструкційно-технологічних параметрів газо-дуттьового вузла на розподіл потоків повітря в газогенераторі

The object of this study is the structural and technological parameters of the gas blower unit in the gasification chamber of a gas generator. The task to enable uniform distribution of air masses in the gas generator has been solved using the ANSYS Fluent software. The study is based on a simulation of the movement of air flows in the characteristic cross-sections of the gas generator, in particular the cross-section of the gasification chamber at the border of the oxidation and reduction zones. Seven structures of the gas blower unit were analyzed, the effectiveness of which was determined by the coefficient of variation. The most effective was the design whose value of the coefficient of variation is the smallest and equal to 93 %. At the same time, the total area of zones with no movement of air masses, that is, the absence of a gasification process, does not exceed 12 % of the total cross-sectional area of the gas generator. The speed of air masses at the boundary of the oxidation and reduction zones is aligned in the entire cross-section of the chamber and is V»4.5 m/s. The average value of the vertical component of the speed of air masses in the cross-section at the inlet to the recovery zone of the gasification chamber is V»0.6 m/s. Under such conditions, the production of synthesis gas of high calorific value with the absence of resins, acids, heavy hydrocarbons, and mechanical impurities is ensured. The correspondence of the simulation results with experimental data is confirmed by the coefficient of determination, which amounted to 0.87. The results reported here could be the basis of a modernized methodology for the study of aerodynamic, heat and mass exchange processes that occur during biomass gasification. This would make it possible to define the rational structural and technological parameters of gas generators and improve the efficiency of the gasification process as a whole.Об’єктом дослідження є конструкційно-технологічні параметри газо-дуттьового вузла камери газифікації газогенератора. Вирішено проблему забезпечення рівномірного розподілу повітряних мас в газогенераторі із застосуванням програми ANSYS Fluent. Дослідження засноване на імітаційному моделюванні руху потоків повітря в характеристичних перерізах газогенератора, зокрема в поперечному перерізі камери газифікації на межі зон окислення і відновлення. Проаналізовано сім конструкцій газо-дуттьового вузла, ефективність яких визначалася коефіцієнтом варіації. Найбільш ефективною виявилася конструкція, значення коефіцієнту варіації якої найменше і рівне 93 %. При цьому загальна площа зон з відсутністю руху повітряних мас, тобто відсутністю процесу газифікації, не перевищує 12 % від загальної площі перерізу газогенератора. Швидкість повітряних мас на межі зон окислення і відновлення вирівняна в усьому поперечному перерізі камери і складає V»4,5 м/с. Усереднене значення вертикальної складової швидкості повітряних мас у перерізі на вході в зону відновлення камери газифікації становить V»0,6 м/с. За таких умов забезпечується виробництво синтез-газу високої теплотворної здатності з відсутністю смол, кислот, важких вуглеводнів і механічних домішок. Відповідність результатів імітаційного моделювання експериментальним даним підтверджена коефіцієнтом детермінації, який склав 0,87. Отримані результати можуть бути покладені в основу осучасненої методології дослідження аеродинамічних, тепло і масообмінних процесів, які протікають під час газифікації біомаси. Це дозволить визначати раціональні конструкційно-технологічні параметри газогенераторів та підвищити ефективність процесу газифікації в цілом

DASH Swedish National Doctoral School in Digital Humanities: From Local Expertise to National Research Infrastructure

This paper presents the Swedish National Doctoral School in Digital Humanities: Data, Culture, and Society – Critical Perspectives (DASH) that is run in 2023–2027 by Uppsala University, Umeå University, Linnaeus University, and Gothenburg University. Though Swedish universities have established PhD courses, MA programmes and training in digital humanities previously, DASH is the first encompassing educational programme in digital humanities at the doctoral level. The present paper discusses the rationale behind the DASH doctoral school, its role in the landscape of Swedish humanities infrastructures, and provides insights from the first PhD courses and seminars. The focus of DASH is to equip PhD candidates in humanities and social sciences with knowledge and skills necessary to pursue high quality, innovative and critical research in digital humanities. DASH aims to provide knowledge in relation to digital research, its methods, tools, and critical perspectives, and to build and strengthen the networks among early career scholars. DASH facilitates access and use of the resources in the national infrastructures in the humanities, but also emerges as an element in the infrastructure by providing new resources and competences

Are perinatal measures associated with a dolescent mental health? A retrospective e xploration with original data from psychiatric c ohorts

Background Perinatal markers of prenatal development are associated with offspring psychiatric symptoms. However, there is little research investigating the specificity of perinatal markers for the development of specific disorders. This study aimed to explore if perinatal markers are specifically associated with adolescent substance use disorder (SUDs). Methods Adolescent participants from two study centers, one for SUD patients (n = 196) and one for general psychopathology (n = 307), were recruited for participation. Since the SUD participants presented with a number of comorbid disorders, we performed a 1-on-1 matching procedure, based on age, gender, and specific pattern of comorbid disorders. This procedure resulted in n = 51 participants from each group. From all participants and their mothers we recorded perinatal markers (mode of birth, weeks of completed pregnancy, birth weight, Apgar score after 5 min) as well as intelligence quotient (IQ). The SUD sample additionally filled out the Youth Safe Report (YSR) as well as the PQ-16 and the DUDIT. We aimed to distinguish the two groups (SUD sample vs. general psychiatric sample) based on the perinatal variables via a logistic regression analysis. Additionally, linear regressions were performed for the total group and the subgroups to assess the relationship between perinatal variables and IQ, YSR, DUDIT and PQ-16. Results The perinatal variables were not able to predict group membership (X2 [4] = 4.77, p = .312, Cox & Snell R² = 0.053). Odds ratios indicated a small increase in probability to belonging to the general psychiatric sample instead of the SUD sample if birth was completed via C-section. After Bonferroni-correction, the linear regression models showed no relation between perinatal markers and IQ (p = .60, R² = 0.068), YSR (p = .09, R² = 0.121), DUDIT (p = .65, R² = 0.020), and PQ-16 (p = .73, R² =0.021)

OPTIMIZATION OF NO-TILL TECHNOLOGY ELEMENTS FOR WINTER WHEAT GROWING IN DRY CONDITIONS

Improvement of the technology for the cultivation of winter wheat in the arid zone of the Stavropol Territory based on the optimization and renewal of the varietal base of winter wheat grown using the No-Till technology. The work was carried out in 2019–2020 in the arid zone of the Stavropol Territory. In the experiment to study the assessment of varieties of winter wheat grown according to the predecessors of peas and sunflower, we studied 15 varieties. The economic variant, variety Yuka, was used as a control one. The total size of the experimental plot is 1.9 hectares. The yield of the predecessor peas was 23.92-39.44 q/ha, depending on the variety. The highest-yielding variety turned out to be Tanya (39.44 q/ha), which is 12.6% higher than the economic variant Yuka (35.04 q/ha). An increase of 4.8-7.1% in relation to the economic variant Yuka was given by the varieties Aksinya and Volny Don. All studied varieties showed a fairly high degree of resistance to the development of pathogens. The highest prevalence rate and intensity of development of pyrenophorosis in winter wheat plants sown after peas was noted in the Alekseich variety – 67% prevalence and 0.63% intensity, and the lowest in the Aist variety – 22% and 0.33%, respectively. The highest prevalence and development rate of pyrenophorosis in winter wheat plants sown after sunflower was observed in the Krasa Dona variety – 47% prevalence and 0.63% intensity, and the lowest in the Niva Stavropolya variety – 21% and 0.33%, respectively

Safe vs. Fair: A formidable trade-off in tackling climate change

Global warming requires a response characterized by forward-looking management of atmospheric carbon and respect for ethical principles. Both safety and fairness must be pursued, and there are severe trade-offs as these are intertwined by the limited headroom for additional atmospheric CO2 emissions. This paper provides a simple numerical mapping at the aggregated level of developed vs. developing countries in which safety and fairness are formulated in terms of cumulative emissions and cumulative per capita emissions respectively. It becomes evident that safety and fairness cannot be achieved simultaneously for strict definitions of both. The paper further posits potential global trading in future cumulative emissions budgets in a world where financial transactions compensate for physical emissions: the safe vs. fair tradeoff is less severe but remains formidable. Finally, we explore very large deployment of engineered carbon sinks and show that roughly 1,000 Gt CO2 of cumulative negative emissions over the century are required to have a significant effect, a remarkable scale of deployment. We also identify the unexplored issue of how such sinks might be treated in sub-global carbon accounting