Land‐use change from cropland to orchard leads to high nitrate accumulation in the soils of a small catchment

Land‐use change from cereals to fruit orchards usually results in a high nutrient surplus in soil. The excessive accumulation of nitrogen (N) in soil, mainly as nitrate, leached from the root zone may serve as a long‐term source of surface or groundwater pollution. The N balances and nitrate accumulation in the soil profiles of cereal fields and kiwifruit orchards in the Yujiahe catchment, Shaanxi, China, were compared. Excessive N fertilisation resulted in an excessive N surplus (1,133 kg N ha−1 yr−1) in orchards (8‐times higher than that in cereal fields). More than 77.5% of nitrate in the soil profile (0–400 cm) of the orchards was below a soil depth of 100 cm. The average accumulated nitrate within a profile 0–400 cm of orchards was 3,288 kg N ha−1, which was 16‐fold higher than that of cereal fields. The accumulated nitrate in soil profiles on the downslope (5,959 kg N ha−1) was approximately 2 times higher than that of the upslope in the same sloping orchards. The accumulated nitrate in soil profiles at the lowland zone of the catchment was higher than that of the upland zone. Excessive nitrate moves not only vertically downwards to deeper soil depth but also laterally into lower elevations at both field and catchment scales. The total stored nitrate in the upper soil profile of 400 cm in the catchment was 464.8 Mg N, whereas 94.8% (440.8 Mg N) was in orchards. Thus, changing land use from cereal crops to orchards leads to a high nitrate accumulation in the catchment

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Relationship between Trendelenburg tilt and internal jugular vein diameter

Objectives: To evaluate the relationship between Trendelenburg tilt and internal jugular vein (IJV) diameter, and to examine any cumulative effects of tilt on the IJV diameter. Methods: Using a tilt table, healthy volunteers were randomised to Trendelenburg tilts of 10°, 15°, 20°, 25°, and 30°. Ultrasound was used to measure and record the lateral diameter of the right IJV at the level of the cricoid cartilage. Following each reading the table was returned to the supine position. Balanced randomisation was used to assess cumulative tilt effects. Results: A total of 20 healthy volunteers were recruited (10 men, 10 women). Mean supine IJV diameter was 13.5 mm (95% CI 12.8 to 14.1) and was significantly greater at 10° (15.5 mm, 95% CI 14.9 to 16.1). There was no significant difference between 10° and greater angles of tilt. The effect of the previous angle of tilt did not prove to be statistically significant. Conclusion: Increasing the degree of Trendelenburg tilt increases the lateral diameter of the IJV. Even a 10° tilt is effective. The cumulative effect of tilt (that is, the effect of the previous angle) is not significant. Ultrasound guided cannulation is ideal, but in its absence Trendelenburg tilt will increase IJV diameter and improve the chance of successful cannulation. While 25° achieved optimum distension, this may not be practical and may be detrimental (for example, risk of raised intracranial pressure)