Local Nature of Coset Models

The local algebras of the maximal Coset model C_max associated with a chiral conformal subtheory A\subset B are shown to coincide with the local relative commutants of A in B, provided A contains a stress energy tensor. Making the same assumption, the adjoint action of the unique inner-implementing representation U^A associated with A\subset B on the local observables in B is found to define net-endomorphisms of B. This property is exploited for constructing from B a conformally covariant holographic image in 1+1 dimensions which proves useful as a geometric picture for the joint inclusion A\vee C_max \subset B. Immediate applications to the analysis of current subalgebras are given and the relation to normal canonical tensor product subfactors is clarified. A natural converse of Borchers' theorem on half-sided translations is made accessible.Comment: 33 pages, no figures; typos, minor improvement

Electrolyte disorders

Electrolyte disorders can result in life-threatening complications. The kidneys are tasked with maintaining electrolyte homoeostasis, yet the low glomerular filtration rate of neonatal kidneys, tubular immaturity, and high extrarenal fluid losses contribute to increased occurrence of electrolyte disorders in neonates. Understanding the physiologic basis of renal electrolyte handling is crucial in identifying underlying causes and initiation of proper treatment. This article reviews key aspects of renal physiology, the diagnostic workup of disorders of plasma sodium and potassium, and the appropriate treatment, in addition to inherited disorders associated with neonatal electrolyte disturbances that illuminate the physiology of renal electrolyte handling

A Catalog of Absorption Lines in Eight HST/STIS E230M 1.0 < z < 1.7 Quasar Spectra

We have produced a catalog of line identifications and equivalent width measurements for all absorption features in eight ultraviolet echelle quasar spectra. These spectra were selected as having the highest signal-to-noise among the HST/STIS spectra obtained with the E230M grating. We identify 56 metal-line systems toward the eight quasars, and present plots of detected transitions, aligned in velocity-space. We found that about 1/4 - 1/3 of the features in the Lya forest region, redward of the incidence of the Lyb forest, are metal lines. High ionization transitions are common. We see both O VI and C IV in 88 - 90% of the metal-line systems for which the spectra cover the expected wavelength. Si III is seen in 58%, while low ionization absorption in C II, Si II, and/or Al II is detected in 50% of the systems for which they are covered. This catalog will facilitate future studies of the Lya forest and of metal-line systems of various types.Comment: 13 pages, 2 figures, submitted to Monthly Notices of the Royal Astronomical Society, a complete version with the appendix and all figures is available at http://www.astro.psu.edu/users/misawa/pub/Paper/qalcat.pdf.g

Quantification of FAM20A in human milk and identification of calcium metabolism proteins

BACKGROUND: FAM20A, a recently discovered protein, is thought to have a fundamental role in inhibiting ectopic calcification. Several studies have demonstrated that variants of FAM20A are causative for the rare autosomal recessive disorder, enamel-renal syndrome (ERS). ERS is characterized by defective mineralization of dental enamel and nephrocalcinosis suggesting that FAM20A is an extracellular matrix protein, dysfunction of which causes calcification of the secretory epithelial tissues. FAM20A is a low-abundant protein that is difficult to detect in biofluids such as blood, saliva, and urine. Thus, we speculated the abundance of FAM20A to be high in human milk, since the secretory epithelium of lactating mammary tissue is involved in the secretion of highly concentrated calcium. Therefore, the primary aim of this research is to describe the processes/methodology taken to quantify FAM20A in human milk and identify other proteins involved in calcium metabolism. METHOD: This study used mass spectrometry-driven quantitative proteomics: (1) to quantify FAM20A in human milk of three women and (2) to identify proteins associated with calcium regulation by bioinformatic analyses on whole and milk fat globule membrane fractions. RESULTS: Shotgun MS/MS driven proteomics identified FAM20A in whole milk, and subsequent analysis using targeted proteomics also successfully quantified FAM20A in all samples. Combination of sample preparation, fractionation, and LC-MS/MS proteomics analysis generated 136 proteins previously undiscovered in human milk; 21 of these appear to be associated with calcium metabolism. CONCLUSION: Using mass spectrometry-driven proteomics, we successfully quantified FAM20A from transitional to mature milk and obtained a list of proteins involved in calcium metabolism. Furthermore, we show the value of using a combination of both shotgun and targeted driven proteomics for the identification of this low abundant protein in human milk

HNF1B mutations are associated with a Gitelman-like tubulopathy that develops during childhood

Mutations in the transcription factor hepatocyte nuclear factor 1B (HNF1B) are the most common inherited cause of renal malformations, yet also associated with renal tubular dysfunction, most prominently magnesium wasting with hypomagnesemia. The presence of hypomagnesemia has been proposed to help select appropriate patients for genetic testing. Yet, in a large cohort, hypomagnesemia was discriminatory only in adult, but not in pediatric patients. We therefore investigated whether hypomagnesemia and other biochemical changes develop with age.This article is freely available via Open Access. Click on the Additional Link to access full-text

Long-term renal function in children with Wilms Tumour and constitutional WT1 pathogenic variant

BACKGROUND: Wilms tumour (WT) survivors, especially patients with associated syndromes or genitourinary anomalies due to constitutional WT1 pathogenic variant, have increased risk of kidney failure. We describe the long-term kidney function in children with WT and WT1 pathogenic variant to inform the surgical strategy and oncological management of such complex children. METHODS: Retrospective analysis of patients with WT and constitutional WT1 pathogenic variant treated at a single centre between 1993 and 2016, reviewing genotype, phenotype, tumour histology, laterality, treatment, patient survival, and kidney outcome. RESULTS: We identified 25 patients (60% male, median age at diagnosis 14 months, range 4–74 months) with WT1 deletion (4), missense (2), nonsense (8), frameshift (7), or splice site (4) pathogenic variant. Thirteen (52%) had bilateral disease, 3 (12%) had WT-aniridia, 1 had incomplete Denys-Drash syndrome, 11 (44%) had genitourinary malformation, and 10 (40%) had no phenotypic anomalies. Patient survival was 100% and 3 patients were in remission after relapse at median follow-up of 9 years. Seven patients (28%) commenced chronic dialysis of which 3 were after bilateral nephrectomies. The overall kidney survival for this cohort as mean time to start of dialysis was 13.38 years (95% CI: 10.3–16.4), where 7 patients experienced kidney failure at a median of 5.6 years. All of these 7 patients were subsequently transplanted. In addition, 2 patients have stage III and stage IV chronic kidney disease and 12 patients have albuminuria and/or treatment with ACE inhibitors. Four patients (3 frameshift; 1 WT1 deletion) had normal blood pressure and kidney function without proteinuria at follow-up from 1.5 to 12 years. CONCLUSIONS: Despite the known high risk of kidney disease in patients with WT and constitutional WT1 pathogenic variant, nearly two-thirds of patients had sustained native kidney function, suggesting that nephron-sparing surgery (NSS) should be attempted when possible without compromising oncological risk. Larger international studies are needed for accurate assessment of WT1genotype-kidney function phenotype correlation

Genetic, Pathophysiological and Clinical Aspects of Nephrocalcinosis

Nephrocalcinosis describes the ectopic deposition of calcium salts in the kidney parenchyma. Nephrocalcinosis can result from a number of acquired causes, but also an even greater number of genetic diseases, predominantly renal, but also extra-renal. Here we provide a review of the genetic causes of nephrocalcinosis, along with putative mechanisms, illustrated by human and animal data

The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains

We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2 contribute to selectivity, and most mutations, including mutation of residues in the triplets GYG and GFG in P1 and P2, made channels nonselective. We interpret the effects of these—and of other mutations—in terms of the way the pore is likely to be stabilised structurally. We show also that residues in the outer pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of selectivity (e.g. I94S, G95A) were associated with slowing of the response of channels to depolarisation. More important physiologically, pH sensitivity is also lost or altered by such mutations. Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter

Short course daily prednisolone therapy during an upper respiratory tract infection in children with relapsing steroid-sensitive nephrotic syndrome (PREDNOS 2):protocol for a randomised controlled trial

BACKGROUND: Relapses of childhood steroid-sensitive nephrotic syndrome (SSNS) are treated with a 4- to 8-week course of high-dose oral prednisolone, which may be associated with significant adverse effects. There is a clear association between upper respiratory tract infection (URTI) and relapse development. Previous studies in developing nations have suggested that introducing a 5- to 7-day course of daily prednisolone during an URTI may prevent a relapse developing and the need for a treatment course of high-dose prednisolone. The aim of PREDNOS 2 is to evaluate the effectiveness of a 6-day course of daily prednisolone therapy during an URTI in reducing the development of a subsequent relapse in a developed nation.METHODS/DESIGN: The subjects will be 300 children with relapsing SSNS (≥2 relapses in preceding year), who will be randomised to receive either a 6-day course of daily prednisolone or no change to their current therapy (with the use of placebo to double blind) each time they develop an URTI over 12 months. A strict definition for URTI will be used. Subjects will be reviewed at 3, 6, 9 and 12 months to capture data regarding relapse history, ongoing therapy and adverse effect profile, including behavioural problems and quality of life. A formal health economic analysis will also be performed. The primary end point of the study will be the incidence of URTI-related relapse (3 days of Albustix +++) following the first infection during the 12-month follow-up period. DNA and RNA samples will be collected to identify a potential genetic cause for the disease. Subjects will be recruited from over 100 UK centres with the assistance of the Medicines for Children Research Network. PREDNOS 2 is funded by the National Institute for Health Research Health Technology Assessment Programme (11/129/261).DISCUSSION: We propose that PREDNOS 2 will be a pivotal study that will inform the future standard of care for children with SSNS. If it is possible to reduce the disease relapse rate effectively and safely, this will reduce the morbidity and cost associated with drug treatment, notwithstanding hospital admission and parental absence from employment.TRIAL REGISTRATION: Current Controlled Trials (ISRCTN10900733).</p