Localization of a gene for nonsyndromic renal hypodysplasia to chromosome 1p32-33.

Nonsyndromic defects in the urinary tract are the most common cause of end-stage renal failure in children and account for a significant proportion of adult nephropathy. The genetic basis of these disorders is not fully understood. We studied seven multiplex kindreds ascertained via an index case with a nonsyndromic solitary kidney or renal hypodysplasia. Systematic ultrasonographic screening revealed that many family members harbor malformations, such as solitary kidneys, hypodysplasia, or ureteric abnormalities (in a total of 29 affected individuals). A genomewide scan identified significant linkage to a 6.9-Mb segment on chromosome 1p32-33 under an autosomal dominant model with reduced penetrance (peak LOD score 3.5 at D1S2652 in the largest kindred). Altogether, three of the seven families showed positive LOD scores at this interval, demonstrating heterogeneity of the trait (peak HLOD 3.9, with 45% of families linked). The chromosome 1p32-33 interval contains 52 transcription units, and at least 23 of these are expressed at stage E12.5 in the murine ureteric bud and/or metanephric mesenchyme. These data show that autosomal dominant nonsyndromic renal hypodysplasia and associated urinary tract malformations are genetically heterogeneous and identify a locus for this common cause of human kidney failure

The Effect of Large Wood Accumulations With Rootwads on Local Geomorphic Changes

Large wood (LW) can be transported along a river during floods, increasing flood-associated hazards, particularly when it accumulates at river-spanning infrastructures such as bridges and weirs. While most flume studies have explored LW movement with simple wooden elements (dowels), only a few studies have used elements with more complex LW geometries, such as rootwads, under unsteady flow conditions. Quantitative assessment of interactions amongst more complex wood elements and river flow has rarely been attempted the effect of this additional complication has even been ignored, in both field and laboratory studies. In this study, flume experiments were conducted to assess the effect of rootwads on local scour and deposition in a flume with a mobile gravel-bed. The experiment was conducted under unsteady flow conditions, with a constricted segment of the reach, recreating conditions to wood accumulations and blockage. Results revealed that LW with rootwads tends to generate more stable accumulations than LW without rootwads, leading to the formation of more porous loosely packed accumulations. In this initial set of flume experiments, the patterns of scour were quite variable, but on average, the porous and stable LW accumulations with rootwads showed more spatially extensive disturbance of the bed. LW accumulations without rootwads led to the development of scour pits that reached the bottom of the flume more quickly than in the LW accumulations without rootwads. The mean accumulated bedload volumes were of similar magnitude overall, however, highlighting the many contingencies in the chain of processes between dam formation and resultant bed scour

Nowcasting industrial production using linear and non-linear models of electricity demand

This article proposes different modelling approaches which exploit electricity market data to nowcast industrial production. Our models include linear, mixed-data sampling (MIDAS), Markov-Switching (MS) and MS-MIDAS regressions. Comparisons against autoregressive approaches and other commonly used macroeconomic predictors show that electricity market data combined with an MS model significantly improve nowcasting performance, especially during turbulent economic states, such as those generated by the recent COVID-19 pandemic. The most promising results are provided by an MS model which identifies two volatility regimes. These results confirm that electricity market data provide timely and easy-to-access information for nowcasting macroeconomic variables, especially when it is most valuable, i.e. during times of crisis and uncertainty

Mutations in DSTYK and dominant urinary tract malformations.

ABSTRACT Introduction Congenital abnormalities of the kidney of the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and their etiology is poorly understood. Methods We performed genome-wide linkage analysis and whole-exome sequencing in a family with autosomal dominant congenital abnormalities of the kidney of the urinary tract (7 affected family members). We also performed sequence analysis in 311 unrelated patients, as well as histologic and functional studies. Results Linkage analysis identified five regions of the genome that were shared among all affected family members. Exome sequencing identified a single rare deleterious variant within these linkage intervals, a heterozygous splice-site mutation in dual serine/threonine and tyrosine protein kinase (DSTYK). This variant, which resulted in aberrant gene product splicing, was present in all affected family members. Additional independent DSTYK mutations, including nonsense and splice-site mutations, were detected among 7/311 unrelated patients. DSTYK is highly expressed in the maturing epithelia of all major organs, localizing to cell membranes. Knockdown in zebrafish resulted in multi-organ developmental defects, resembling loss of fibroblast growth factor (FGF) signaling. Consistent with this finding, DSTYK colocalizes with FGF receptors in the ureteric bud and metanephric mesenchyme. Finally, DSTYK knockdown in human embryonic kidney cells inhibited FGF-stimulated ERK-phosphorylation, the principal signal downstream of receptor tyrosine kinases. Conclusions We detected DSTYK mutations in 2.2% of patients with congenital abnormalities of the kidney and urinary tract whom we studied, suggesting that DSTYK is a major determinant of human urinary tract development, downstream of FGF signaling

Forecasting energy commodity prices: a large global dataset sparse approach

This paper focuses on forecasting quarterly energy prices of commodities, such as oil, gas and coal, using the Global VAR dataset proposed by Mohaddes and Raissi (2018). This dataset includes a number of potentially informative quarterly macroeconomic variables for the 33 largest economies, overall accounting for more than 80% of the global GDP. To deal with the information on this large database, we apply a dynamic factor model based on a penalized maximum likelihood approach that allows to shrink parameters to zero and to estimate sparse factor loadings. The estimated latent factors show considerable sparsity and heterogeneity in the selected loadings across variables. When the model is extended to predict energy commodity prices up to four periods ahead, results indicate larger predictability relative to the benchmark random walk model for 1-quarter ahead for all energy commodities. In our application, the largest improvement in terms of prediction accuracy is observed when predicting gas prices from 1 to 4 quarters ahead

Brief communication: The curious case of the large wood-laden flow event in the Pocuro stream (Chile)

Large wood transported during extreme flood events can represent a relevant additional source of hazards that should be taken into account in mountain environments. However, direct observations and monitoring of large-wood transport during floods are difficult and scarce. Here we present a video of a flood characterised by multiple phases of large-wood transport, including an initial phase of wood-laden flow rarely described in the literature. Estimations of flow velocity and transported wood volume provide a good opportunity to develop models of large-wood-congested transport

Tracking log displacement during floods in the Tagliamento River using RFID and GPS tracker devices

Large pieces of in-channel wood can exert an important role on the ecological and morphological properties of gravel-bed rivers. On the other side, when transported during flood events, large wood can become a source of risk for sensitive structures such as bridges. However, wood displacement and velocity in river systems are still poorly understood, especially in large gravel-bed rivers. This study focuses on log transport in a valley reach of Tagliamento River (Italy). Log displacement during flood events of different magnitudes recorded from June 2010 to October 2011 has been analysed thanks to the installation of 113 radio frequency identification (RFID) tags and 42 GPS tracker devices in logs of different dimensions. Recovery rates of logs equipped with RFID and GPS trackers were about 43% and 42%, respectively. The GPS devices allowed us to analyse in details the log displacement and transport overtime, indicating a higher log entrainment during rising limb of hydrographs. The threshold for the entrainment of logs from low bars is around 40% of bankfull water stage. No clear relationship was found between the peak of flood and log displacement length and velocity. However, log displacement length and velocity appear significantly correlated to the ratio between the peak of flow and the water stage exceeding the flow duration curve for 25% of time (i.e. the ratio hmax/h25 ratio). Log deposition was observed to occur at the peak flow, and logs transported during ordinary events are preferably deposited on low bars. This study reveals the potentials of GPS tracker devices to monitor the entrainment and movements of logs in large gravel-bed rivers during floods. These observations could be useful for better planning of river management practices and strategies involving the use of large wood pieces and could help for calibrating wood budgets at the reach scale

Characteristics of the colorectal cancers diagnosed in the early 2000s in Italy. Figures from the IMPATTO study on colorectal cancer screening

The impact of organized screening programmes on colorectal cancer (CRC) can be observed at a population level only several years after the implementation of screening. We compared CRC characteristics by diagnostic modality (screen-detected, non-screen-detected) as an early outcome to monitor screening programme effectiveness. Data on CRCs diagnosed in Italy from 2000 to 2008 were collected by several cancer registries. Linkage with screening datasets made it possible to divide the cases by geographic area, implementation of screening, and modality of diagnosis (screen-detected, non-screen-detected).We compared the main characteristics of the different subgroups of CRCs through multivariate logistic regression models. The study included 23,668 CRCs diagnosed in subjects aged 50-69 years, of which 11.9%were screendetected (N=2,806), all from the North-Centre of Italy. Among screen-detected CRCs, we observed a higher proportion of males, of cases in the distal colon, and a higher mean age of the patients. Compared with pre-screening cases, screen-detected CRCs showed a better distribution by stage at diagnosis (OR for stage III or IV: 0.40, 95%CI: 0.36-0.44) and grading (OR for poorly differentiated CRCs was 0.86, 95%CI: 0.75-1.00). Screen-detected CRCs have more favourable prognostic characteristics than non-screen-detected cases. A renewed effort to implement screening programmes throughout the entire country is recommended

Characterization of wood-laden flows in rivers

Inorganic sediment is not the only solid‐fraction component of river flows; flows may also carry significant amounts of large organic material (i.e., large wood), but the characteristics of these wood‐laden flows (WLF) are not well understood yet. With the aim to shed light on these relatively unexamined phenomena, we collected home videos showing natural flows with wood as the main solid component. Analyses of these videos as well as the watersheds and streams where the videos were recorded allowed us to define for the first time WLF, describe the main characteristics of these flows and broaden the definition of wood transport regimes (adding a new regime called here hypercongested wood transport). According to our results, WLF may occur repeatedly, in a large range of catchment sizes, generally in steep, highly confined single thread channels in mountain areas. WLF are typically highly unsteady and the log motion is non‐uniform, as described for other inorganic sediment‐laden flows (e.g., debris flows). The conceptual integration of wood into our understanding of flow phenomena is illustrated by a novel classification defining the transition from clear water to hypercongested, wood and sediment‐laden flows, according to the composition of the mixture (sediment, wood, and water). We define the relevant metrics for the quantification and modelling of WLF, including an exhaustive discussion of different modelling approaches (i.e., Voellmy, Bingham and Manning) and provide a first attempt to simulate WLF. We draw attention to WLF phenomena to encourage further field, theoretical, and experimental investigations that may contribute to a better understanding of flows river basins, leading to more accurate predictions, and better hazard mitigation and management strategies