What parathyroid hormone levels should we aim for in children with stage 5 chronic kidney disease; what is the evidence?

The bone disease that occurs as a result of chronic kidney disease (CKD) is not only debilitating but also linked to poor growth and cardiovascular disease. It is suspected that abnormal bone turnover is the main culprit for these poor outcomes. Plasma parathyroid hormone (PTH) levels are used as a surrogate marker of bone turnover, and there is a small number of studies in children that have attempted to identify the range of PTH levels that correlates with normal bone histology. It is clear that high PTH levels are associated with high bone turnover, although the range is wide. However, the ability of PTH levels to distinguish between low and normal bone turnover is less clear. This is an important issue, because current guidelines for calcium and phosphate management are based upon there being an “optimum” range for PTH. This editorial takes a critical look at the evidence upon which these recommendations are based

Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy

Background Nephronophthisis associated ciliopathies (NPHP-AC) comprise a group of autosomal recessive cystic kidney diseases that includes nephronophthisis (NPHP), Senior-Loken syndrome (SLS), Joubert syndrome (JBTS), and Meckel-Gruber syndrome (MKS). To date, causative mutations in NPHP-AC have been described for 18 different genes, rendering mutation analysis tedious and expensive. To overcome the broad genetic locus heterogeneity, a strategy of DNA pooling with consecutive massively parallel resequencing (MPR) was devised.Methods In 120 patients with severe NPHP-AC phenotypes, five pools of genomic DNA with 24 patients each were prepared which were used as templates in order to PCR amplify all 376 exons of 18 NPHP-AC genes (NPHP1, INVS, NPHP3, NPHP4, IQCB1, CEP290, GLIS2, RPGRIP1L, NEK8, TMEM67, INPP5E, TMEM216, AHI1, ARL13B, CC2D2A, TTC21B, MKS1, and XPNPEP3). PCR products were then subjected to MPR on an Illumina Genome-Analyser and mutations were subsequently assigned to their respective mutation carrier via CEL I endonuclease based heteroduplex screening and confirmed by Sanger sequencing.Results For proof of principle, DNA from patients with known mutations was used and detection of 22 out of 24 different alleles (92% sensitivity) was demonstrated. MPR led to the molecular diagnosis in 30/120 patients (25%) and 54 pathogenic mutations (27 novel) were identified in seven different NPHP-AC genes. Additionally, in 24 patients only single heterozygous variants of unknown significance were found.Conclusions The combined approach of DNA pooling followed by MPR strongly facilitates mutation analysis in broadly heterogeneous single gene disorders. The lack of mutations in 75% of patients in this cohort indicates further extensive heterogeneity in NPHP-AC

Ionospheric total electron content estimation using IONOLAB method [IONOLAB tekniǧi ile i̇yonosfer toplam elektron i̇çerigi kestirimi]

Ionosphere which is an important atmospheric layer for HF and satellite communications, can be investigated through Total Electron Content (TEC). Global Positioning System provides cost-effective means for TEC estimation. Regularized TEC estimation method (D-TEI) is developed to estimate high resolution, robust TEC values. The method combines measurements of GPS satellites above 10° elevation limit and estimates can be obtained with 30 s time resolution. In this paper, parameters that are used in D-TEI method such as ionospheric height, weighting function, and satellite receiver biases are studied. It is found that TEC estimation results of D-TEI method is almost independent of ionospheric height. Different weighting functions are tried and the weighting function that minimizes non-ionospheric effects is selected. By using satellite and receiver biases in the correct form consistent TEC estimation results are obtained with IGS analysis centers. In this paper, the method is improved to include phase measurements. Taking either pseudorange or phase measurements as input, high resolution, robust TEC estimates are obtained using D-TEI method

Gps/Tec Estimation With Ionolab Method

Total Electron Content (TEC) is a key variable to measure the ionospheric characteristics and disturbances. The Global Positioning System (GPS) can, be used for TEC estimation making use of the recorded signals at the GPS receiver. Reg-Est method that is developed by F.Arikan, C.B. Erol and O. Ankan can be used to estimate high resolution, robust TEC values combining GPS measurements of 30 s resolution obtained from the satellites which are above the 101 elevation limit. Using this method, it is possible to estimate TEC values for a whole day or a desired time period both for quiet and disturbed days of the ionosphere. Reg-Est provides robust TEC estimates for high-latitude, mid-latitude and equatorial stations. In this study, some important parameters of Reg-Est such as ionospheric thin shell height, weighting function and receiver-satellite biases are investigated. By incorporating the results of the investigation, Reg-Est algorithm is developed into IONOLAB method. Thin shell model height is an important parameter for Single Layer Ionosphere Model (SLIM). In this study, it is shown that IONOLAB provides reliable and robust TEC estimates independent of the choice of the maximum ionization height. Signals from the low elevation satellites are prone to multipath effects. In order to reduce the distortion due to multipath signals, the optimum weighting function is implemented in IONOLAB, minimizing the non-ionospheric noise effects. GPS receivers record both pseudorange and phase data of signals. IONOLAB can input absolute TEC computed from the pseudorange measurements or phase-corrected low-noise TEC. The TEC estimates for both of these inputs are in good accordance with each other. Thus, taking either pseoudorange or phase-corrected measurement data as input, high resolution, robust TEC estimates can be obtained from IONOLAB. Another important parameter for TEC estimation is satellite-receiver instrumental biases. The biases are the frequency dependent delays due to satellite and receiver hardware. In order to compute TEC, satellite and receiver biases should be removed from GPS measurements correctly. However, the proper procedure of how to include them in the TEC computation is generally vaguely defined. IONOLAB suggests a technique for inclusion of the hardware biases obtained from the web for TEC estimates that are consistent with the results from the IGS analysis centers.Wo

Total Electron Content Estimation With Reg-Est

Total Electron Content ( TEC) constitutes one of the key elements for observing the variable structure of the ionosphere. GPS provides a cost- effective alternative in TEC estimation through earth- based receivers. In this paper, one of the TEC estimation methods, namely Reg- Est, is investigated in detail in terms of its parameters and developed further to include improvements. Reg- Est estimates robust TEC using GPS measurements of 30 s time resolution. The method combines the vertical TEC computed from all the satellites in view over 10 degrees horizon limit in the least squares sense through the minimization of a cost function which also includes a high pass penalty filter. Optional weighting functions and sliding window median filters are added to enrich the processing and smoothing of the data. In this study, the input to the Reg- Est is enlarged to include phase- corrected TEC. The best way of including the instrumental biases is investigated and the algorithm is updated to include the biases in the slant TEC computation. The effect of the thin shell height of the ionosphere in Reg- Est estimates is studied. It is concluded that the Reg- Est algorithm is very robust to the choice of thin shell height. The best weighting function to reduce the multipath effects and to minimize the non- ionospheric noise is selected. The improved Reg- Est algorithm can be used for all latitudes and for both quite and disturbed days of the ionosphere. The Reg- Est TEC are in excellent accordance with the estimates from IGS analysis centers.Wo