MIKE-SHE integrated groundwater and surface water model used to simulate scenario hydrology for input to DRIFT-ARID: the Mokolo River case study

A fully integrated, physically-based MIKE SHE/MIKE11 model was developed for the Mokolo River basin flow system to simulate key hydraulic and hydrologic indicator inputs to the Downstream Response to Imposed Flow Transformation for Arid Rivers (DRIFT-ARID) decision support system (DSS). The DRIFT-ARID tool is used in this study to define environmental water requirements (EWR) for non-perennial river flow systems in South Africa to facilitate ecosystembased management of water resources as required by the National Water Act (Act No. 36 of 1998). Fifty years of distributed daily climate data (1950 to 2000) were used to calibrate the model against decades of daily discharge data at various gauges, measurements of Mokolo Dam stage levels, and one-time groundwater level measurements at hundreds of wells throughout the basin. Though the calibrated model captures much of the seasonal and post-event stream discharge response characteristics, lack of sub-daily climate and stream discharge data limits the ability to calibrate the model to event-level system response (i.e. peak flows). In addition, lack of basic subsurface hydrogeologic characterisation and transient groundwater level data limits the ability to calibrate the groundwater flow model, and therefore baseflow response, to a high level. Despite these limitations, the calibrated model was used to simulate changes in hydrologic and hydraulic indicators at five study sites within the basin for five 50-year land-use change scenarios, including a present-day (with dam), natural conditions (no development/irrigation), and conversion of present-day irrigation to game farm, mine/city expansion, and a combination of the last two. Challenges and recommendations for simulating the range of non-perennial systems are presented.Keywords: hydrology, non-perennial, MIKE SHE, integrated surface and groundwater modellin

DRIFT-ARID: A method for assessing environmental water requirements (EWRs) for non-perennial rivers

Environmental water requirement (EWR) assessment methods, for ascertaining how much water should be retained in rivers to sustain ecological functioning and desired levels of biodiversity, have mostly been developed for perennial rivers. Despite non-perennial rivers comprising about 30–50% of the world’s freshwater systems, data on their hydrology, biota and ecological functioning are sparse. Current EWR assessments require hydrological and other data that may not be available for such rivers and some adaptation in the methods used seems necessary. DRIFT is an EWR method for perennial (or near-perennial) rivers that has been developed in South Africa over the past two decades and is now widely applied nationally and internationally. When applied to the semi-permanent Mokolo River, challenges particular to, or accentuated by, non-perennial rivers included the reliable simulation of hydrological data, the extent of acceptable extrapolation of data, difficulties in predicting surface-water connectivity along the river, and the location and resilience of pools, as well as whether it was possible to identify a reference (natural) condition. DRIFT-ARID, reported on here, is an adaptation of the DRIFT approach to begin addressing these and other issues. It consists of 11 phases containing 29 activities.Keywords: EWR, non-perennial, DRIFT, DS

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Accounting for Extreme Events in the Economic Assessment of Climate Change

Extreme events are one of the main channels through which climate and socio- economic systems interact. It is likely that climate change will modify their probability distributions and their consequences. The long-term growth models used in climate change assessments, however, cannot capture the effects of short-term shocks; they thus model extreme events in a very crude manner. To assess the importance of this limitation, a non-equilibrium dynamic model (NEDyM) is used to model the macroeconomic consequences of extreme events. Its conclusions are the following: (i) Dynamic processes multiply the extreme event direct costs by a factor 20; half of this increase comes from short-term processes; (ii) A possible modication of the extreme event distribution due to climate change can be responsible for significant GDP losses; (iii) The production losses caused by extreme events depend, with strong non-linearity, both on the changes in the extreme distribution and on the ability to fund the rehabilitation after each disaster. These conclusions illustrate that the economic assessment of climate change does not only depend on beliefs on climate change but also on beliefs on the economy. Moreover, they suggest that averaging short-term processes like extreme events over the five- or ten-year time step of a classical long-term growth model can lead to inaccurately low assessments of the climate change damages

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Plasma globotriaosylsphingosine in relation to phenotypes of Fabry disease

Fabry disease (FD), a lysosomal storage disorder caused by α-galactosidase A (GLA) gene variants, has a heterogeneous phenotype. GLA variants can lead to classical FD, an attenuated non-classical phenotype, or no disease at all. This study investigates the value of plasma globotriaosylsphingosine (lysoGb3) to distinguish between these groups. This is of particular importance in the diagnosis of individuals with a GLA variant and an uncertain diagnosis of FD, lacking characteristic features of classical FD. Subjects with GLA variants were grouped as classical, non-classical, uncertain or no FD, using strict phenotypical, biochemical and histological criteria. Plasma lysoGb3 was assessed by LC/MS/MS (normal ≤ 0.6 nmol/L). 154 subjects were grouped into classical (38 males (M), 66 females (F)), non-classical (13 M, 14 F), uncertain (5M, 9 F) or no FD (6M, 3F). All subjects with a classical phenotype had elevated lysoGb3 values (M: range 45-150, F: 1.5-41.5). LysoGb3 values in patients with a non-classical phenotype (M: 1.3-35.7, F: 0.5-2.0) were different from healthy controls (M: p <0.01, F: p <0.05), but females overlapped with controls. In the no-FD group, lysoGb3 was normal. LysoGb3 is a reliable diagnostic tool to discern classical FD from subjects without FD. This study suggests that the same applies to patients with a non-classical phenotype. LysoGb3 values of female patients overlap with controls. Consequently, in uncertain cases, increased lysoGb3 values are very suggestive for FD, but normal values cannot exclude FD. Confirmation in larger cohorts and data on the specificity of small lysoGb3 increases are necessar

DRIFT-ARID: Application of a method for environmental water requirements (EWRs) in a non-perennial river (Mokolo River) in South Africa

Methods developed to determine the amount of water required (EWR) to sustain ecosystem services in non-perennial rivers need a different approach to those used in perennial rivers. Current EWR methods were mostly developed for use in perennial rivers. Non-perennial rivers differ from perennial ones in terms of variability in flow, periods of no-flow and related habitat availability. A DRIFT-ARID method (an adaptation of the Downstream Response to Imposed Flow Transformation (DRIFT) method) was developed, tested and adjusted, using the semi-permanent Mokolo River. Field data from five study sites was collected from April to May 2010 by a multidisciplinary team. The results were used in a DRIFT-ARID Decision Support System (DSS) to determine the impact of five chosen development scenarios in the Mokolo River Catchment. An integrated groundwater–surface water MIKE-SHE hydrological model was used to simulate the hydrology of the chosen scenarios. Specific non-perennial river indicators such as onset of dry phase were identified and included in the DRIFT-ARID DSS. DRIFT-ARID has the potential to be used in non-perennial rivers and, once set up, can provide results for future scenarios. The method now needs to be tested on other non-perennial river types, especially episodic rivers where data are scarce or non-existent.Keywords: DRIFT-ARID, non-perennial, EWR, flow method, Mokolo Rive

Plasma and urinary levels of dermatan sulfate and heparan sulfate derived disaccharides after long-term enzyme replacement therapy (ERT) in MPS I: correlation with the timing of ERT and with total urinary excretion of glycosaminoglycans

Mucopolysaccharidosis type I (MPS I) results in a defective breakdown of the glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate, which leads to a progressive disease. Enzyme replacement therapy (ERT) results in clearance of these GAGs from a range of tissues and can significantly ameliorate several symptoms. The biochemical efficacy of ERT is generally assessed by the determination of the total urinary excretion of GAGs. However, this has limitations. We studied the concentrations of heparan sulfate and dermatan sulfate derived disaccharides (HS and DS, respectively) in the plasma and urine of seven patients and compared these levels with total urinary GAGs (uGAGs) levels. Plasma and urine samples were collected at different time points relative to the weekly ERT for three non-consecutive weeks in seven MPS I patients who had been treated with ERT for at least 2.5 years. Heparan and dermatan sulfate in plasma and urine were enzymatically digested into disaccharides, and HS and DS levels were determined by HPLC-MS/MS analysis. uGAGs were measured by the DMB test. The levels of HS and DS were markedly decreased compared with the levels before the initiation of ERT. However, the concentrations of DS in plasma and of both HS and DS in urine remained significantly elevated in all studied patients, while in six patients the level of total uGAGs had normalized. The concentrations of plasma and urinary HS during the weekly ERT followed a U-shaped curve. However, the effect size is small. The concentrations of plasma and urinary DS and uGAGs appeared to be in a steady state. HS and DS are sensitive biomarkers for monitoring the biochemical treatment efficacy of ERT and remain elevated despite long-term treatment. This finding may be related to the labeled dose or antibody status of the patient. The timing of the sample collection is not relevant, at least at the current dose of 100 IU/kg/weekl