Geology and Wine 12. New Zealand Terroir

New Zealand produces premium quality wines and its wine industry is growing rapidly. The winegrowing regions have growing degree-days that range from 900 in cool Central Otago and Canterbury, to more than 1600 in the warmest region in the country, Auckland. Average growing season temperatures for the same regions range from approximately 14.3°C to 17.6°C. Most trophy-winning red wines are grown in areas with a climate cooler than where similar wines are grown to high standard internationally. New Zealand vineyards are planted mainly on flat alluvium and aggradation gravels with slopes of less than 3°. Rapid growth is pushing new plantings onto adjacent hillsides that are underlain by greywacke, schist, and (less commonly) limestone. The expansion of the industry onto these different substrates will affect grape and wine characteristics and may lead to new styles of New Zealand ultra-premium wines. SOMMAIRE La Nouvelle-Zélande produit des vins de hautes qualités et son industrie vini-cole croît rapidement. Les degrésjours de croissance des régions vinicoles vont de 900 dans les régions fraîches d’Otago et de Canterbury, et dépasse 1 600 dans la région d’Auckland, la plus chaude du pays. Les températures de croissance moyenne pour ces mêmes régions vont de 14,3 °C à 17,6 °C. La plupart des vins rouges primés proviennent de régions au climat plus frais que leurs équivalents ailleurs dans le monde. Les vignes de Nouvelle-Zélande sont cultivées dans des sols alluvionnaires plats et des graviers d’aggradation au pendage de moins de 3°. La croissance rapide de l’industrie vinicole entraîne la plantation de vignes sur les sols des collines environnantes qui recouvrent des formations de grauwackes, de schistes argileux, et plus rarement de calcaires. L’expansion de l’industrie vinicole sur ces nouveaux substrats aura des répercussions sur les caractéristiques du raisin et du vin, ce qui pourrait donner de nouveaux styles de très grands vins de Nouvelle-Zélande

Some Comments on the Entropy-Based Criteria for Piping

This paper is an extension of previous work which characterises soil behaviours using the grading entropy diagram. The present work looks at the piping process in granular soils, by considering some new data from flood-protection dikes. The piping process is divided into three parts here: particle movement at the micro scale to segregate free water; sand boil development (which is the initiation of the pipe), and pipe growth. In the first part of the process, which occurs during the rising flood, the increase in shear stress along the dike base may cause segregation of water into micro pipes if the subsoil in the dike base is relatively loose. This occurs at the maximum dike base shear stress level (ratio of shear stress and strength) zone which is close to the toe. In the second part of the process, the shear strain increment causes a sudden, asymmetric slide and cracking of the dike leading to the localized excess pore pressure, liquefaction and the formation of a sand boil. In the third part of the process, the soil erosion initiated through the sand boil continues, and the pipe grows. The piping in the Hungarian dikes often occurs in a two-layer system; where the base layer is coarser with higher permeability and the cover layer is finer with lower permeability. The new data presented here show that the soils ejected from the sand boils are generally silty sands and sands, which are prone to both erosion (on the basis of the entropy criterion) and liquefaction. They originate from the cover layer which is basically identical to the soil used in the Dutch backward erosion experiments

Case Studies and Benchmark Examples for the Use of Grading Entropy in Geotechnics

The grading entropy concept can be adapted to the field of geotechnics, to establish criteria for phenomena such as particle packing, particle migration and filtering, through a quantified expression of the order/disorder in the grain size distribution, in terms of two entropy-based parameters. In this paper, the grading entropy theory is applied in some geotechnical case studies, which serve as benchmark examples to illustrate its application to the characterisation of piping, softening and dispersive soils, and to filtering problems in the context of a leachate collection system for a landfill site. Further, since unstable cohesive (dispersive) soils are generally improved by lime, the effect of lime addition is also considered, on the basis of some measurements and a further application of the grading entropy concept, which allows evolutions in the entropy of a soil to be considered as its grading is modified. The examples described support the hypothesis that the potential for soil erosion and particle migration can be reliably identified using grading entropy parameters derived from grading curve data, and applied through an established soil structure stability criteria and a filtering rule. It is shown that lime modification is not necessarily helpful in stabilizing against particle migration

Some Notes on Granular Mixtures with Finite, Discrete Fractal Distribution

Why fractal distribution is so frequent? It is true that fractal dimension is always less than 3? Why fractal dimension of 2.5 to 2.9 seems to be steady-state or stable? Why the fractal distributions are the limit distributions of the degradation path? Is there an ultimate distribution? It is shown that the finite fractal grain size distributions occurring in the nature are identical to the optimal grading curves of the grading entropy theory and, the fractal dimension n varies between-¥ and ¥. It is shown that the fractal dimensions 2.2-2.9 may be situated in the transitional stability zone, verifying the internal stability criterion of the grading entropy theory. Micro computed tomography (μCT) images and DEM (distinct element method) studies are presented to show the link between stable microstructure and internal stability. On the other hand, it is shown that the optimal grading curves are mean position grading curves that can be used to represent all possible grading curves

Effect of Apabetalone on Cardiovascular Events in Diabetes, CKD, and Recent Acute Coronary Syndrome: Results from the BETonMACE Randomized Controlled Trial

CKD and type 2 diabetes mellitus interact to increase the risk of major adverse cardiovascular events (i.e., cardiovascular death, nonfatal myocardial infarction, or stroke) and congestive heart failure. A maladaptive epigenetic response may be a cardiovascular risk driver and amenable to modification with apabetalone, a selective modulator of the bromodomain and extraterminal domain transcription system. We examined this question in a prespecified analysis of BETonMACE, a phase 3 trial.BETonMACE was an event-driven, randomized, double-blind, placebo-controlled trial comparing effects of apabetalone versus placebo on major adverse cardiovascular events and heart failure hospitalizations in 2425 participants with type 2 diabetes and a recent acute coronary syndrome, including 288 participants with CKD with eGFR <60 ml/min per 1.73 m2 at baseline. The primary end point in BETonMACE was the time to the first major adverse cardiovascular event, with a secondary end point of time to hospitalization for heart failure.Median follow-up was 27 months (interquartile range, 20-32 months). In participants with CKD, apabetalone compared with placebo was associated with fewer major adverse cardiovascular events (13 events in 124 patients [11%] versus 35 events in 164 patients [21%]; hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.96) and fewer heart failure-related hospitalizations (three hospitalizations in 124 patients [3%] versus 14 hospitalizations in 164 patients [9%]; hazard ratio, 0.48; 95% confidence interval, 0.26 to 0.86). In the non-CKD group, the corresponding hazard ratio values were 0.96 (95% confidence interval, 0.74 to 1.24) for major adverse cardiovascular events, and 0.76 (95% confidence interval, 0.46 to 1.27) for heart failure-related hospitalization. Interaction of CKD on treatment effect was P=0.03 for major adverse cardiovascular events, and P=0.12 for heart failure-related hospitalization. Participants with CKD showed similar numbers of adverse events, regardless of randomization to apabetalone or placebo (119 [73%] versus 88 [71%] patients), and there were fewer serious adverse events (29% versus 43%; P=0.02) in the apabetalone group.Apabetalone may reduce the incidence of major adverse cardiovascular events in patients with CKD and type 2 diabetes who have a high burden of cardiovascular disease

Novel Prognostic and Therapeutic Targets for Oral Squamous Cell Carcinoma

In oral squamous cell carcinoma (OSCC), metastasis to lymph nodes is associated with a 50% reduction in 5-year survival. To identify a metastatic gene set based on DNA copy number abnormalities (CNAs) of differentially expressed genes, we compared DNA and RNA of OSCC cells laser-microdissected from non-metastatic primary tumors (n = 17) with those from lymph node metastases (n = 20), using Affymetrix 250K Nsp single-nucleotide polymorphism (SNP) arrays and U133 Plus 2.0 arrays, respectively. With a false discovery rate (FDR)<5%, 1988 transcripts were found to be differentially expressed between primary and metastatic OSCC. Of these, 114 were found to have a significant correlation between DNA copy number and gene expression (FDR<0.01). Among these 114 correlated transcripts, the corresponding genomic regions of each of 95 transcripts had CNAs differences between primary and metastatic OSCC (FDR<0.01). Using an independent dataset of 133 patients, multivariable analysis showed that the OSCC-specific and overall mortality hazards ratio (HR) for patients carrying the 95-transcript signature were 4.75 (95% CI: 2.03-11.11) and 3.45 (95% CI: 1.84-6.50), respectively. To determine the degree by which these genes impact cell survival, we compared the growth of five OSCC cell lines before and after knockdown of over-amplified transcripts via a high-throughput siRNA-mediated screen. The expression-knockdown of 18 of the 26 genes tested showed a growth suppression ≥ 30% in at least one cell line (P<0.01). In particular, cell lines derived from late-stage OSCC were more sensitive to the knockdown of G3BP1 than cell lines derived from early-stage OSCC, and the growth suppression was likely caused by increase in apoptosis. Further investigation is warranted to examine the biological role of these genes in OSCC progression and their therapeutic potentials

Genetic Incorporation of Human Metallothionein into the Adenovirus Protein IX for Non-Invasive SPECT Imaging

As the limits of existing treatments for cancer are recognized, clearly novel therapies must be considered for successful treatment; cancer therapy using adenovirus vectors is a promising strategy. However tracking the biodistribution of adenovirus vectors in vivo is limited to invasive procedures such as biopsies, which are error prone, non-quantitative, and do not give a full representation of the pharmacokinetics involved. Current non-invasive imaging strategies using reporter gene expression have been applied to analyze adenoviral vectors. The major drawback to approaches that tag viruses with reporter genes is that these systems require initial viral infection and subsequent cellular expression of a reporter gene to allow non-invasive imaging. As an alternative to conventional vector detection techniques, we developed a specific genetic labeling system whereby an adenoviral vector incorporates a fusion between capsid protein IX and human metallothionein. Our study herein clearly demonstrates our ability to rescue viable adenoviral particles that display functional metallothionein (MT) as a component of their capsid surface. We demonstrate the feasibility of 99mTc binding in vitro to the pIX-MT fusion on the capsid of adenovirus virions using a simple transchelation reaction. SPECT imaging of a mouse after administration of a 99mTc-radiolabeled virus showed clear localization of radioactivity to the liver. This result strongly supports imaging using pIX-MT, visualizing the normal biodistribution of Ad primarily to the liver upon injection into mice. The ability we have developed to view real-time biodistribution in their physiological milieu represents a significant tool to study adenovirus biology in vivo

Pharmacogenomics of GLP-1 receptor agonists: a genome-wide analysis of observational data and large randomised controlled trials

Background: In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making. We therefore aimed to identify genetic variants associated with glycaemic response to GLP-1 receptor agonist treatment. Methods: In this genome-wide analysis we included adults (aged ≥18 years) with type 2 diabetes treated with GLP-1 receptor agonists with baseline HbA1c of 7% or more (53 mmol/mol) from four prospective observational cohorts (DIRECT, PRIBA, PROMASTER, and GoDARTS) and two randomised clinical trials (HARMONY phase 3 and AWARD). The primary endpoint was HbA1c reduction at 6 months after starting GLP-1 receptor agonists. We evaluated variants in GLP1R, then did a genome-wide association study and gene-based burden tests. Findings: 4571 adults were included in our analysis, of these, 3339 (73%) were White European, 449 (10%) Hispanic, 312 (7%) American Indian or Alaskan Native, and 471 (10%) were other, and around 2140 (47%) of the participants were women. Variation in HbA1c reduction with GLP-1 receptor agonists treatment was associated with rs6923761G→A (Gly168Ser) in the GLP1R (0·08% [95% CI 0·04–0·12] or 0·9 mmol/mol lower reduction in HbA1c per serine, p=6·0 × 10−5) and low frequency variants in ARRB1 (optimal sequence kernel association test p=6·7 × 10−8), largely driven by rs140226575G→A (Thr370Met; 0·25% [SE 0·06] or 2·7 mmol/mol [SE 0·7] greater HbA1c reduction per methionine, p=5·2 × 10−6). A similar effect size for the ARRB1 Thr370Met was seen in Hispanic and American Indian or Alaska Native populations who have a higher frequency of this variant (6–11%) than in White European populations. Combining these two genes identified 4% of the population who had a 30% greater reduction in HbA1c than the 9% of the population with the worse response. Interpretation: This genome-wide pharmacogenomic study of GLP-1 receptor agonists provides novel biological and clinical insights. Clinically, when genotype is routinely available at the point of prescribing, individuals with ARRB1 variants might benefit from earlier initiation of GLP-1 receptor agonists. Funding: Innovative Medicines Initiative and the Wellcome Trus

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course