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Publisher Copyright: © 2022 The Author. Published by American Chemical Society and Division of Chemical Education, Inc. In this action research study, I propose a guided inquiry alternative to the traditional physical chemistry laboratory module where the equilibrium constant of acetic acid is determined conductometrically. I complement the guided inquiry structure with a 360° feedback support framework for the preparation and assessment of a laboratory report. The new laboratory module showed great promise, improving both report marks and student experiences. Diligent training of teaching assistants, ample availability of formative feedback, and reservation of sufficient time for the guided inquiry activities were identified as key contributors for the success of the module.

Funding Information: We acknowledge all the participants and researchers of the 23 biobanks that have contributed to the GBMI. Biobank-specific acknowledgments are included in the Data S3 . We thank H. Huang, A.R. Martin, B.M. Neale, Y. Okada, K. Tsuo, J.C. Ulirsch, Y. Wang, and all the members of Finucane and Daly labs for their helpful feedback. M.K. was supported by a Nakajima Foundation Fellowship and the Masason Foundation . H.K.F. was funded by NIH grant DP5 OD024582 . Publisher Copyright: © 2022 The Author(s) Meta-analysis is pervasively used to combine multiple genome-wide association studies (GWASs). Fine-mapping of meta-analysis studies is typically performed as in a single-cohort study. Here, we first demonstrate that heterogeneity (e.g., of sample size, phenotyping, imputation) hurts calibration of meta-analysis fine-mapping. We propose a summary statistics-based quality-control (QC) method, suspicious loci analysis of meta-analysis summary statistics (SLALOM), that identifies suspicious loci for meta-analysis fine-mapping by detecting outliers in association statistics. We validate SLALOM in simulations and the GWAS Catalog. Applying SLALOM to 14 meta-analyses from the Global Biobank Meta-analysis Initiative (GBMI), we find that 67% of loci show suspicious patterns that call into question fine-mapping accuracy. These predicted suspicious loci are significantly depleted for having nonsynonymous variants as lead variant (2.7×; Fisher's exact p = 7.3 × 10−4). We find limited evidence of fine-mapping improvement in the GBMI meta-analyses compared with individual biobanks. We urge extreme caution when interpreting fine-mapping results from meta-analysis of heterogeneous cohorts.

Background: Prediction tools that combine polygenic risk scores with clinical factors provide a new opportunity for improved prediction and prevention of atherosclerotic cardiovascular disease, but the clinical utility of polygenic risk score has remained unclear. Methods: We collected a prospective cohort of 7342 individuals (64% women, mean age 56 years) and estimated their 10-year risk for atherosclerotic cardiovascular disease both by a traditional risk score and a composite score combining the effect of a polygenic risk score and clinical risk factors. We then tested how returning the personal risk information with an interactive web-tool impacted on the participants’ health behavior. Results: When reassessed after 1.5 years by a clinical visit and questionnaires, 20.8% of individuals at high (>10%) 10-year atherosclerotic cardiovascular disease risk had seen a doctor, 12.4% reported weight loss, 14.2% of smokers had quit smoking, and 15.4% had signed up for health coaching online. Altogether, 42.6% of persons at high risk had made one or more health behavioral changes versus 33.5% of persons at low/average risk such that higher baseline risk predicted a favorable change (OR [CI], 1.53 [1.37–1.72] for persons at high risk versus the rest, P P P =0.003) contributing independently. Conclusions: Web-based communication of personal atherosclerotic cardiovascular disease risk-data including polygenic risk to middle-aged persons motivates positive changes in health behavior and the propensity to seek care. It supports integration of genomic information into clinical risk calculators as a feasible approach to enhance disease prevention.

We present traceable three-parameter extended Hückel equations for the activity coefficient of sodium chloride and for the osmotic coefficient of water in aqueous NaCl solutions from 273.15 to 373.15 K. In this temperature range, our equations seem to apply within experimental error to all thermodynamic data available for these solutions up to the molality of the saturated solution. Our previous studies (J. Chem. Eng. Data 2017, 62, 2617-2632 and 2019, 64, 16-33) showed that, from 273.15 to 373.15 K, two-parameter Hückel equations can successfully explain the literature results of electrochemical, isopiestic, and cryoscopic measurements at least up to a molality of 0.2 mol·kg-1. The model recommended in this study employs the values of our previous two-parameter model for the ion-size parameter in the original Debye-Hückel equation, B, and for the coefficient of the linear term with respect to the molality, b1. In addition, it includes a quadratic term with respect to the molality with the coefficient b2. Both b1 and b2 are quadratically dependent on temperature. With the introduction of b2, our model is able to explain the existing vapor pressure, electrochemical, and solubility data from 273.15 to 373.15 K up to the saturated solution. A comparison with the most important literature values for the activity and osmotic coefficients revealed that the agreement is always at least satisfactory, but is best for temperatures below 363 K. On the basis of these results, our activity and osmotic coefficients are the most reliable values for these thermodynamic quantities so far. We propose this is true also for the values from 363 to 373 K.

Physics letters / B 834, 137479 (2022). doi:10.1016/j.physletb.2022.137479, Published by North-Holland Publ., Amsterdam

Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies have thoroughly investigated their best practices in global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance in 9 different biobanks for 14 disease endpoints. Specifically, we constructed PRSs using pruning and thresholding (P + T) and PRS-continuous shrinkage (CS). For both methods, using a European-based linkage disequilibrium (LD) reference panel resulted in comparable or higher prediction accuracy compared with several other non-European-based panels. PRS-CS overall outperformed the classic P + T method, especially for endpoints with higher SNP-based heritability. Notably, prediction accuracy is heterogeneous across endpoints, biobanks, and ancestries, especially for asthma, which has known variation in disease prevalence across populations. Overall, we provide lessons for PRS construction, evaluation, and interpretation using GBMI resources and highlight the importance of best practices for PRS in the biobank-scale genomics era.

Funding Information: The work of the contributing biobanks was supported by numerous grants from governmental and charitable bodies. Biobank-specific acknowledgments and more detailed acknowledgments are included in Data S2. Initiative management, S.B.C. J.C. N.J.C. M.J.D. E.E.K. A.R.M. B.M.N. Y.O. A.V.P. D.A.v.H. R.G.W. C.J.W. W.Z. and S.Z.; individual biobank analysis, A.B. Y.B. B.M.B. C.D.B. S.C. T.-T.C. K.C. S.M.D. M.D. G.H.d.B. Y.D. N.J.D. M.-J.F. Y.-C.A.F. S.F. V.L.F. L.G.F. E.R.G. T.R.G. D.H.G. C.R.G. G.G.-A. S.E.G. L.A.G. C.H. J.B.H. W.E.H. H.H. K.H. N.I. A.I. R.J. M. Kurki, J.K. N.K. E.E.K. J.T.K. M. Kanai, T.L. K.L. M.H.L. S.L. K.L. Y.-F.L. V.L.F. R.J.F.L. E.A.L.-M. A.R.-M. S.M.-G. R.M. R.E.M. H.C.M. A.R.M. Y.M. H.M. S.E.M. I.Y.M. B.M. S.M. K.N. S.N. M.A.N.-A. K.N. Y.O. P.P. A.L.-P. A.P. B.P. S.P. M.H.P. D.J.R. N.R. M.D.R. A.R. C.S. S.S. S.S.S. J.A.S. P.S. I.S. T.T. R.T. K.T. J.U. D.A.v.H. B.V. M.V. Y.V. J.M.V. R.G.W. Y.W. S.J.W. B.N.W. K.-H.H.W. M.Z. X.Z. and S.Z.; individual biobank management, N.A. A.A.T. K.M.A.-D. P.A. K.C.B. M. Boehnke, M. Boezen, C.D.B. A.C. Z.C. C.-Y.C. J.C. N.J.C. S.M.D. S.F. Y.-C.A.F. S.F. E.F. T.G. C.R.G. C.J.G. Y.G. H.H. K.A.H. K.H. S.I.I. N.M.J. N.K. E.E.K. J.T.K. C.L. M.H.L. M.T.M.L. L.L. K.L. Y.-F.L. R.J.F.L. J.L. S.M. Y.M. K.M. I.Y.M. Y.O. C.M.O. A.V.P. B.P. D.J.P. D.J.R. M.D.R. S.S. J.W.S. H.S. K.S. T.T. U.T. R.C.T. D.A.v.H. M.V. R.G.W. D.C.W. C.W. J.W. M.Z. X.Z. and S.Z.; study design and interpretation of results, A.B. M. Boehnke, M. Boezen, B.M.B. T.-T.C. C.-Y.C. M.J.D. G.D.S. N.J.D. S.F. M.-J.F. H.K.F. E.R.G. A.G. T.G. J.B.H. J.H. K.H. R.J. M.K. E.E.K. T.K. C.M.L. V.L.F. E.A.L.-M. A.R.M. S.N. B.M.N. C.M.O. J.J.P. B.P. N.R. H.R. J.A.S. I.S. K.T. D.A.v.H. R.G.W. Y.W. D.C.W. S.J.W. C.J.W. B.N.W. J.W. K.-H.H.W. M.Z. H.Z. J.Z. W.Z. X.Z. and S.Z.; drafted and edited the paper, A.B. M. Boehnke, M. Boezen, M.J.D. G.H.d.B. N.J.D. T.R.G. J.B.H. N.I. N.M.J. M.K. V.L.F. S.M. A.R.M. H.M. S.N. B.M.N. C.M.O. B.P. H.R. C.S. J.A.S. J.W.S. K.T. Y.W. D.C.W. C.J.W. K.-H.H.W. H.Z. J.Z. W.Z. and S.Z.; primary meta-analysis and quality control, M.J.D. H.K.F. M. Kanai, J.K. J.T.K. M. Kurki, M.M. B.M.N. C.J.W. K.-H.H.W. and W.Z.; drug discovery: S.N. T.K. K.-H.H.W. W.Z. and Y.O.; fine mapping, M. Kanai, W.Z. M.J.D. and H.K.F.; polygenic risk score, Y.W. S.N. E.A.L.-M. S.K. K.T. K.L. M. Kanai, W.Z. K.W. M.-J.F. L.B. P.A. P.D. V.L.F. R.M. Y.M. B.B. S.S. J.U. E.R.G. N.J.C. I.S. Y.O. A.R.M. and J.B.H.; proteome-wide Mendelian randomization, H.Z. H.R. A.B. G.H. G.D.S. B.M.B. W.Z. B.M.N. T.R.G. and J.Z.; transcriptome-wide association study, A.B. J.B.H. W.Z. J.Z. M. Kanai, B.P. E.R.G. and N.J.C.; asthma, K.T. W.Z. Y.W. M. Kanai, S.N. Y.O. B.M.N. M.J.D. and A.R.M.; heart failure, K.-H.H.W. N.J.D. B.N.W. I.S. S.E.G. J.B.H. N.J.C. M.P. R.J.F.L. M.J.D. B.M.N. W.Z. W.E.H. and C.J.W.; idiopathic pulmonary fibrosis, J.J.P. W.Z. M.J.D. J.T.K. N.J.C. and J.B.H.; primary open-angle glaucoma, V.L.F. A.B. W.Z. Y.W. K.L. M. Kanai, E.A.L.-M. P.S. R.T. X.Z. S.N. S.S. Y.O. N.I. S.M. H.S. I.S. C.W. A.R.M. E.R.G. N.M.J. N.J.C. and J.B.H.; stroke, I.S. K.-H.H.W. W.H. B.N.W. W.Z. J.E.H. A.P. B.B. A.H.S. M.E.G. R.G.W. K.H. C.K. S.Z. M.J.D. B.M.N. and C.J.W.; venous thromboembolism, B.N.W. I.S. K.-H.H.W. B.B. V.L.F. K.T. M.D. B.N. W.Z. J.A.S. and C.J.W. All authors reviewed the manuscript. M.J.D. is a founder of Maze Therapeutics. B.M.N. is a member of the scientific advisory board at Deep Genomics and a consultant for Camp4 Therapeutics, Takeda Pharmaceutical, and Biogen. The spouse of C.J.W. works at Regeneron Pharmaceuticals. C.-Y.C. is employed by Biogen. C.R.G. owns stock in 23andMe, Inc. T.R.G. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. E.E.K. has received speaker fees from Regeneron, Illumina, and 23andMe and is a member of the advisory board for Galateo Bio. R.E.M. has received speaker fees from Illumina and is a scientific advisor to the Epigenetic Clock Development Foundation. G.D.S. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. K.S. and U.T. are employed by deCODE Genetics/Amgen, Inc. J.Z. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. S.M. is a co-founder of and holds stock in Seonix Bio. Publisher Copyright: © 2022 Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)—a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.

In previous articles (Partanen et al. J. Chem. Eng. Data 2019, 64, 16-33 and Partanenet al. J. Chem. Eng. Data 2019, 64, 2519-2535), we presented traceable and transparent two-parameter Hückel equations (with parameters B and b1) for the activity coefficients of the salt and for the osmotic coefficients of water in aqueous KCl solutions in the temperature range of 273.15-383.15 K. The latter article is the first part (Part 1) of the calorimetric study. We showed in these articles that our equations for these solutions explain within experimental error the literature data on almost all thermodynamic quantities including the partial molar enthalpies at least up to a molality of 0.2 mol·kg-1 and up to 373 K. In this model, parameter B is regarded as a constant but parameter b1 has a quadratic temperature dependence. No calorimetric data were needed in the parameter estimation. In the second part (Part 2) of the calorimetric study, now, the results obtained for the heat capacity quantities of KCl (aq.) are considered. We show here that all heat capacity literature available for KCl solutions at least up to 0.5 mol·kg-1 is possible to explain within experimental error using exactly the same Hückel equations as those considered previously in our studies for dilute KCl solutions from 273 to 373 K. Because of the success of the used model, we supplement the existing thermodynamic tables with new values for the relative apparent and partial molar heat capacities for KCl solutions. It is likely that the new tables contain the most reliable values available for these heat capacity quantities.

openaire: EC/H2020/686053/EU//CritCat In this study, we looked at the hydrogen evolution reaction on Mg-, Mo-, Fe-, Co-, V-, and Cu-doped Ni3P2 and Ni3P2 + P terminated Ni2P surfaces. The DFT calculated hydrogen adsorption free energy was employed as a predictor of the materials' catalytic HER activity. Our results indicate that doping can substantially improve the catalytic activity of the Ni3P2 terminated surface. In contrast, the Ni3P2 + P terminated one seems to be catalytically active irrespective of the type of doping, including in the absence of doping. Based on our doping energy and adsorption free energy calculations, the most promising dopants are iron and cobalt, whereas copper is less likely to function well as a doping element.

According to the clinical criteria of ‘probable’ Alzheimer’s disease (AD), the diagnosis is supported by a normal pattern or nonspecific changes in the electroencephalogram (EEG) such as slow wave activity. EEG has been a traditional method in the diagnosis of dementia. Slight EEG alterations are common in normal elderly people after the age of 60 years. The main changes are slowing of the alpha rhythm, appearance of slow activity and a theta focus in left temporal region. However, the changes in EEG associated with aging are quite modest. EEG changes associated with AD consist of more slowing of the dominant occipital rhythm and more accentuation of theta and delta activity than is found in normal old people, but local slowing occurs rarely. When the EEG findings of AD patients at baseline, at the time the diagnosis was made, were compared to control values, there was a significant difference in all relative power values except beta power.

Excited states in the proton-unbound nucleus 151Lu have been established using γ-ray coincidence techniques. The lifetime of the first excited state above the proton-emitting ground state has been measured using the recoil-distance Doppler-shift method combined with recoil-decay tagging. The experimental level scheme and extracted lifetime have been compared with state-of-the-art theoretical calculations based upon a non-adiabatic deformed Woods–Saxon potential. This comparison suggests that the proton-emitting ground state in 151Lu is mildly oblate with a deformation β = − 0.11 − 0.05 + 0.02 and represents the best evidence to date for proton emission from an oblate nucleus.

Loss of heterozygosity (LOH) has been reported to cause false human leukocyte antigen (HLA) homozygous typing results in pre-transplant patients suffering from haematological malignancies, who in fact are HLA heterozygous. This poses a challenge for histocompatibility testing, as a stem cell graft from a genuinely HLA homozygous donor to a mistyped patient may lead to acute life-threatening graft-vs-host disease. LOH in the HLA region on chromosome 6 is known to be quite common in solid tumours, helping malignant cells to escape T-cell surveillance, but the incidence in haematological malignancies is less well known and the estimates vary. Here we report LOH in the HLA region of five patients with haematological malignancy. We found considerable differences in sensitivity between the three different HLA typing methods used in our laboratory: SSP was clearly the most sensitive method for detecting the lost haplotype, followed by rSSO, while SBT was the least sensitive technique. A subsequent, retrospective genotyping of 65 HLA homozygous haematological patients by SSP method showed no mistyped LOH cases in our laboratory in the past 10 years. The frequency of HLA homozygosity was found to be similar between haematological patients and control groups. It is important for an HLA laboratory to be aware of the differences in various HLA typing techniques' sensitivity for detecting an under-represented haplotype between HLA typing techniques when genotyping patients with haematological diseases. It is advisable for HLA laboratories to have at least two different methods with different sensitivities in their repertoire to be able to retype samples when a false homozygous result is suspected.

Majority of hip fractures occur in individuals with bone mineral density (BMD) in non-osteoporotic range. This suggests that factors other than BMD are associated with increased fracture risk in these individuals. The aim of this study was to investigate the combined ability of radiograph-based trabecular and geometrical parameters to discriminate cervical hip fractures from controls in individuals with non-osteoporotic BMD. A total of 39 postmenopausal females with non-pathologic cervical hip fracture were recruited to the study. Nineteen of the fracture patients (48.7%) had non-osteoporotic BMD and they constituted the fracture group. The control group consisted of 35 BMD-matched non-osteoporotic females. Several geometrical and trabecular parameters were extracted from plain pelvic radiographs, and their combined ability to discriminate fracture patients from controls was studied using a receiver operating characteristics (ROC) analysis. Significant differences in several radiograph-based geometrical and trabecular parameters were found between the fracture patients and controls, whereas no statistically significant difference in BMD was observed (p = 0.92) between the groups. Area under the ROC curve was 0.993 (95% CI 0.977–1.008) for the combined multiple regression model, which included both trabecular and geometrical parameters as explanatory factors. Here, the sensitivity of 100% was achieved with the specificity of 94%. In a cross-validation of the model, 94.4% of the fracture patients, and 94.1% of the controls were classified correctly. The combination of radiograph-based trabecular and geometrical parameters was able to discriminate the cervical hip fracture cases from controls with similar BMD, showing that the method can provide additional information on bone structure and fracture risk beyond BMD.

This study describes the structure, process, and impact of a comprehensive sixteen-month safety enhancement program among stevedores at the Port of Havana, Cuba. Our objective was to reduce occupational injury risk and improve safety conditions by enhancing hazard knowledge and identification as well as improving safety behavior. The target group for the training program consisted of 185 male stevedores in one port terminal. A comparison group of 105 male stevedores was included from another terminal where the program was not implemented. Other personnel were included in the program. The training covered a number of safety procedures and used various training methods. As contrasted with the comparison group, injury incidence decreased in the intervention group, accompanied by significant improvements in safety knowledge and behavior and injury hazard identification. The practices of the program led to safety enhancements in the port and are being considered for adoption in other ports in Cuba.

A 57-year-old man with neuromyotonia and normocalcemic tetany as probable paraneoplastic symptoms of small-cell lung cancer was examined neurophysiologically. In EMG, spontaneous action potential generation was demonstrated in peripheral motor axons. There were also time-locked high-frequency discharges after some voluntarily activated motor unit potentials. After electrical stimulation of motor axons, the M-re-sponse as well as spinal F-response or H-reflex was often followed by a sequence of oscillating potentials which could last several hundred msec. There was no evident peripheral polyneuropathy. Tetany subsided when carbamazepine therapy was started. The only striking abnormality in extensive laboratory studies was an increase in the plasma noradrenaline value.

Gamma rays from excited states feeding a proton-emitting isomeric-state in 151Lu have been observed for the first time. Comparison with state-of-the-art nonadiabatic quasiparticle calculations indicates an oblately deformed, 3/2+ proton-emitting state with a quadrupole deformation of β2 = −0.11. The calculations suggest an increase in quadrupole deformation, to β2 = −0.18, with increasing spin which is understood in terms of the mixing of Nilsson states at the Fermi surface. It is also shown that the proton decay half-life is consistent with that from a 3/2+ state with a quadrupole deformation of β2 = −0.12. peerReviewed

The Latin American and Caribbean region is witnessing the emergence of discussion on workplace health promotion (WHP). The authors propose WHP as an equitable collective action targeting primarily work hazards and their determinants. It has its economic-political "macro" level and a downstream "micro" level. On the macro level, neoliberalism, privatization, and deregulation threaten equitable health and labor issues. Effective labor and health legislation and a fair degree of social redistribution of resources support WHP. Micro-scale WHP is important for contextual reasons and social diffusion, and can literally save lives. Worker involvement, free association of workers, public health affiliation, the precautionary principle, sensitization and training, employer responsibility for healthy working conditions, coalitions between workers and health professionals, and preference for reduction of direct work hazards over modification of personal lifestyles are basic tenets of WHP.

In a retrospective survey of 46 conservatively treated patients with obstetric brachial plexus palsy (OBPP) the following conclusions were reached. An immediate examination of the neurological status of the neonate root by root is essential for proper analysis of the course of the recovery. Mild cases with C5-C6 root injury (Erb's palsy) have a good outcome and may be treated conservatively. Intermediate cases with C5-C7 root injury with additional drop hand require close observation as early as age 3 weeks when the first electromyographic (EMG) examination is indicated. The second EMG should be performed at age 11-12 weeks. If the function of the brachial biceps muscle is lacking at age approximately 12 weeks (3 months), microsurgical intervention should be considered; such intervention definitely is required at age 5 months if the paresis in the brachial biceps muscle has not recovered. Severe cases with C5-C8 or C5-Th1 root injuries with flaccid abducted arm, wrist drop, claw hand, and possibly head tilt to the contralateral side and Horner's sign should be operated on primarily at age 1-2 months.

We prove that every compact C1-submanifold of Rn, with or without boundary, has the bilipschitz extension property in Rn.

Homozygosity for a nonsense mutation in the fucosyltransferase 2 (FUT2) gene (rs601338GA) leads to the absence of ABH blood groups (FUT2 non-secretor status) in body fluids. As the secretor status has been shown to be a major determinant for the gut microbial spectrum, assumed to be important in the gut immune homeostasis, we studied the association of rs601338-FUT2 with celiac disease (CelD) and inflammatory bowel disease (IBD) in the Finnish population. Rs601338 was genotyped in CelD (n = 909), dermatitis herpetiformis (DH) (n = 116), ulcerative colitis (UC) (n = 496) and Crohn's disease (CD) (n = 280) patients and healthy controls (n = 2738). CelD showed significant genotypic [P = 0.0074, odds ratio (OR): 1.28] and recessive (P = 0.015, OR: 1.28) association with the rs601338-AA genotype. This was also found in the combined CelD+DH dataset (genotype association: P = 0.0060, OR: 1.28; recessive association: P 0.011, OR: 1.28). The A allele of rs601338 showed nominal association with dominant protection from UC (P = 0.044, OR: 0.82) and UC+CD (P = 0.035, OR: 0.84). The frequency of non-secretors (rs601338-GG) in controls, CelD, DH, UC and CD datasets was 14.7%, 18%, 18.1%, 14.3% and 16.1%, respectively. No association was evident in the DH or CD datasets alone. In conclusion, FUT2 non-secretor status is associated with CelD susceptibility and FUT2 secretor status may also play a role in IBD in the Finnish population.

Graft-versus-host disease (GvHD) is a major complication in hematopoietic stem cell transplantation (HSCT). The immune response against gut microbes is thought to be an important factor in the beginning of GvHD. Toll-like receptors (TLR) recognize molecular structures of microbes and viruses and play central part in the innate immunity. We studied whether genetic variation in the TLR1, TLR2, TLR4, TLR5, TLR6 and TLR10 genes confers susceptibility to GvHD in 305 human leucocyte antigen-identical sibling donor HSCT's performed in a single Finnish centre. The results showed that the genetic markers rs4833079 (P = 0.035) in TLR1, rs4837656 (P = 0.032) and rs17582214 (P = 0.029) in TLR4, rs10737416 (P = 0.048) in TLR5, rs6531656 (P = 0.035) in TLR6, and rs337629 (P = 0.005) in TLR10 were associated with the occurrence of acute GvHD. Interestingly, two markers in the TLR5 gene, rs2800230 (P = 0.010) and rs2800237 (P = 0.017), were associated with chronic GvHD. These results indicate that many genes of the TLR system are involved in the overall genetic risk for GvHD and emphasize the role of innate immunity in GvHD.