There are research questions whose answers require record linkage of multiple databases that may be characterized by limited options for full data sharing. For this purpose, the Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI) consortium has supported the development of the ODISSEI Secure Supercomputer (OSSC) platform that allows researchers to link cohort data to data from Statistics Netherlands and run large-scale analyses in a high-performance computing (HPC) environment. Here, we report a successful record linkage genomewide association (GWA) study on expenditure for total health, mental health, primary and hospital care, and medication. Record linkage for genotype data from 16,726 participants from the Netherlands Twin Register (NTR) with data from Statistics Netherlands was accomplished in the secure OSSC platform, followed by gene-based tests and estimation of total and single nucleotide polymorphism (SNP)-based heritability. The total heritability of expenditure ranged between 29.4% (SE 0.8) and 37.5% (SE 0.8), but GWA analyses did not identify SNPs or genes that were genomewide significantly associated with health care expenditure. SNP-based heritability was between 0.0% (SE 3.5) and 5.4% (SE 4.0) and was different from zero for mental health care and primary care expenditure. We conclude that successfully linking genotype data to administrative health care expenditure data from Statistics Netherlands is feasible and demonstrates a series of analyses on health care expenditure. The OSSC platform offers secure possibilities for analyzing linked data in large scale and realizing sample sizes required for GWA studies, providing invaluable opportunities to answer many new research questions.

Irrigation according to reliable estimates of crop water requirements (CWR) is one of the key strategies to ensure long-term sustainability of irrigated agriculture. In southern Mediterranean regions, during the irrigation season, CWR is almost totally controlled by the potential evapotranspiration of the irrigated crop. An innovative system for forecasting crop potential evapotranspiration (ETp) has been implemented recently in the Campania region (southern Italy). The system produces ETp forecasts with a lead time of up to 5 days, by coupling the visible and near-infrared crop imagery with numerical weather prediction outputs of a limited area model. The forecasts are delivered to farmers with a simple and intuitive web app interface, which makes daily real-time ETp maps accessible from desktop computers, tablets and smartphones. Forecast performances were evaluated for maize fields of two farms in two irrigation seasons (2014–2015). The mean absolute bias of the forecasted ETp was <0.3 mm/day and the RMSE was <0.6 mm/day, both for lead times up to 5 days.

Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.

Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10, 000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10-8) for ND (rs964170 in ARHGAPlOon chromosome 4, p = 4.43 x 10”8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10-9), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10-9) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10-8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepre-sentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be requirec before the detailed causes of comorbidity between AC and ND are understood.

The purpose of the present study was to examine the ability of nicotinamide to prevent the appearance of neurobehavioral symptoms induced by 3-acetyl pyridine (3-AP) in rats. Nicotinamide in doses of 5,50 and 500 mg/kg was injected immediately after administration of 65 mg/kg 3-AP, and neurobehavioral measurements were made at 6, 12, 24, 48 and 72 hours after injections. The effects of 500 mg/kg nicotinamide injected at 3 and 6 hours after 3-AP treatment were also investigated. The results indicate that, starting at 50 mg/kg, nicotinamide can protect animals against most of the neurobehavioral effects of 3-AP. However, the muscular rigidity induced by 3-AP can only be reversed by 500 mg/kg nicotinamide, and the depressing influence of 3-AP on locomotor activity is not blocked by any of the doses of nicotinamide tested. In terms of time course, the protective action of 500 mg/kg is seen when injected 3, but not 6 hours after 3-AP.

We performed a double-blind cross-over study with amantadine hydrochloride in 12 patients with Friedreich's disease and 2 with autosomal dominant cerebellar ataxia. Patients were randomly assigned to a placebo-amantadine or amantadine-placebo sequence. The interval between the treatments was two weeks. Patients were graded according to a functional ataxia scoring scale and videotaped in basal conditions and 90 min after a single oral dose of 100 mg amantadine or placebo. Three evaluators independently scored the videotapes. Statistical analysis showed no significant effect of amantadine in Friedreich's disease.

The purpose of this experiment was to examine the effects of intraventricular injections of glutamate and aspartate on the gait of animals rendered ataxic by the administration of acrylamide. Contrary to their previously reported corrective Influence on ataxia induced by 3-acetyl pyridine, these amino acids did not modify the ataxic gait of acrylamide treated animals. This suggests that glutamate and aspartate can act in cerebellar but not in peripheral types of ataxia in animals.

We investigated the serum fatty acid profiles of cholesterol esters, phospholipids and triglycerides in 24 patients with Friedreich's disease and 16 patients with other forms of spinocerebellar degeneration. In 8 patients with Friedreich's disease we also analyzed the fatty acid profile of the lipoprotein fractions. We found no major differences in fatty acid profiles between ataxic patients and sex and age-matched controls; in particular there was no decrease of linoleic acid in Friedreich's disease. The level of linoleic acid in serum cholesterol esters decreased with increasing disability of patients.

The main purpose of this study was to examine the effects of intraventricular injections of glutamate and aspartate on the walking gait of rendered ataxic by the administration of 3-acetyl pyridine. Both amino acids significantly improved the walking gait of these animals. The effects of other substances known to have a stimulatory influence on locomotor activity in rats were also investigated. Amphetamine, apomorphine and thyrotropin releasing hormone (TRH) had no effect on the ataxic gait of 3-AP treated animals. Substance P significantly improved the gait of ataxic animals, but to a lesser extent than that seen with glutamate and aspartate.