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International audience; PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13–16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2–0.9) to 0.5 (95% CI, 0.3–1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8–1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

A unified expression for topological invariants has been proposed recently to describe the topological order in Dirac models belonging to any dimension and symmetry class. We uncover a correspondence between the curvature function that integrates to this unified topological invariant and the quantum metric that measures the distance between properly defined many-body Bloch states in momentum space. Based on this metric-curvature correspondence, a time-resolved and angle-resolved photoemission spectroscopy experiment is proposed to measure the violation of spectral sum rule caused by a pulse electric field to detect the quantum metric, from which the topological properties of the system may be extracted., Comment: 8 pages, 2 figures

ZUSAMMENFASSUNGDie Planung eines individuell optimalen Gefäßzuganges für die Hämodialyse beginnt frühzeitig vor Beginn der Nierenersatztherapie. Im Vordergrund steht die Chancenwahrung für ein – ggf. mehrschrittiges – Shuntkonzept, das Langlebigkeit mit dem individuellen Patientennutzen verknüpft. Die enge Abstimmung zwischen Shuntchirurgen und Nephrologen ist hierfür – optimalerweise in zertifizierten Shuntzentren – wesentliche Grundlage. Wir schlagen die Verbesserung der Versorgung durch die Etablierung eines Shuntteams aus Ärzten und Pflegekräften im Zentrum zur Verbesserung des Shuntmanagements durch Schulung und Nutzung neuer Techniken, wie die ultraschallgesteuerte Shuntpunktion und -überwachung (Survaillance), vor. Die Verbesserung der Schnittstelle zwischen Klinik und Praxis und die Etablierung eines Shuntregisters sind weitere Maßnahmen zur Optimierung der Gefäßzugangspraxis in den Nierenzentren. Die Motivation der Mitarbeiter für dieses Konzept ist Führungsaufgabe.

Topological phases of materials are characterized by topological invariants that are conventionally calculated by different means according to the dimension and symmetry class of the system. For topological materials described by Dirac models, we introduce a wrapping number as a unified approach to obtain the topological invariants in arbitrary dimensions and symmetry classes. Given a unit vector that parametrizes the momentum-dependence of the Dirac model, the wrapping number describes the degree of the map from the Brillouin zone torus to the sphere formed by the unit vector that we call Dirac sphere. This method is gauge-invariant and originates from the intrinsic features of the Dirac model, and moreover places all known topological invariants, such as Chern number, winding number, Pfaffian, etc, on equal footing., 10 pages, 2 figure

Background and Aims Only a subset of all patients on dialysis is eligible for kidney transplantation (KTx) due to the large variation of mortality risk. It has been shown that the burden of disease is increasing over the last years in patients at dialysis inception. Moreover, the number of available kidney grafts is decreasing, resulting in a prolonged time on the waiting list. In our study we describe the burden of disease and 3-year mortality in a sample of incident dialysis patients in Germany, stratified by KTx status, including trends over time. Method The QiN (Quality in Nephrology) dataset is a registry-based observational study in which >90% of all patients treated in dialysis centers of the non-profit kidney care provider KfH are enrolled. In our analyses we included all adult patients beginning dialysis treatment between 2008 and 2016. Primary outcome was 3-year all-cause death up until Dec 31, 2019. Patients were stratified by last available KTx- status: (a) KTx within 3 years, (b) on dialysis - on waiting list, (c) on dialysis - in evaluation for KTx, (d) on dialysis - KTx never planned, (e) on dialysis - KTx status missing. The burden of disease was assessed by the AROii score (Floege et al. 2015), a predictive model including patient characteristics, laboratory variables and dialysis parameters. Results Of a total of n=25987 incident patients analyzed, 3.2% underwent KTx within 3 years, 10.6% were listed for KTx, and 13.4% were in evaluation. In 49.5% KTx was never planned and in 23.3% KTx status was missing. These groups differed significantly in median AROii score, reflecting their burden of disease at dialysis inception: KTx never planned or missing (AROii score 10) as compared to KTx (AROii score 1), listed (AROii score 3) and in evaluation (AROii score 4) (p Similarly, 3-year observed mortality (n=8059 [31%]) differed widely across KTx strata (log rank p Conclusion About three quarters of patients started dialysis with a very high mortality risk and at least half of them were considered ineligible for KTx. Patients listed or in evaluation for KTx in Germany have become sicker over the last decade. With decreasing numbers of KTx in Germany the time on the waiting list is prolonged. Longer waiting times and the increasing burden of disease result in advanced risk at the time of transplantation.

BackgroundSome studies have shown an attenuated immune response in haemodialysis patients after vaccination. The present study examines the humoral response after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large population of haemodialysis patients from different outpatient dialysis centres.MethodsWe retrospectively assessed antibodies against SARS-CoV-2 spike protein and nucleocapsid protein (chemiluminescence immunoassays, Roche diagnostics) 3–6 weeks after the second mRNA vaccine dose in 179 maintenance haemodialysis and 70 non-dialysis patients (control cohort). Differences in anti-SARS-CoV-2 spike protein titers were statistically analysed with respect to patient-relevant factors, including age, gender, previous coronavirus disease 2019 (COVID-19) infection, systemic immunosuppressive therapy and time on dialysis.ResultsWe found a favourable, but profoundly lower SARS-CoV-2 spike protein antibody response in comparison with a non-dialysis cohort (median 253.5 versus 1756 U/mL, P ConclusionWe strongly argue in favour of regular antibody testing after COVID-19 vaccination in haemodialysis patients. Further studies should elucidate the utility of booster vaccinations to foster a stronger and persistent antibody response.

Background and Aims The risk of mortality varies considerably among end stage kidney disease patients. As the population ages, patients on renal replacement therapy are presenting with an increasing number of non-renal complications such as heart failure and, subsequently, an increased mortality risk. Thus, in recent years, patient care in dialysis units has become more complex. In this study we describe trends in baseline risk of mortality and 3-year mortality risk in a sample of incident dialysis patients in Germany. Method The QiN (Quality in Nephrology) dataset is a registry-based observational study in which >90% of all patients treated in dialysis centers of the non-profit kidney care provider KfH are enrolled. In our analyses we included all adult patients beginning hemodialysis (HD) or peritoneal dialysis (PD) treatment between 2008 and 2014 who were enrolled in QiN within 6 months after inception of dialysis. Primary outcome was all-cause death within 3 years. Cox models were censored for transplantation and loss to follow-up. Baseline risk of mortality was assessed by the AROii score (Floege et al. 2015), a predictive model including patient characteristics, laboratory variables and dialysis parameters. In this score higher values indicate greater mortality risk. Results A total of n=20369 patients were analyzed, HD n=18255 (89.6%), PD n=2114 (10.4%). Baseline mortality risk increased over time: AROii score for the 2008/09 incidence cohort was median 8.1 (interquartile range 4.4; 11.9), for the 2010/11 cohort 8.8 (5.0; 12.0) and for the 2012-14 cohort 9.0 (5.0; 12.0), p Conclusion Our results show that patients starting dialysis in Germany have become sicker over the last decade, as indicated by the AROii risk score. Simultaneously the observed risk of mortality decreased in recent years, indicating success of optimized medical treatment including dialysis therapy as well as non-nephrology medical care.

Background and Aims Recent studies demonstrate that US patients undergoing chronic dialysis treatment for end stage renal disease (ESRD) at for-profit facilities had a lower access to kidney transplantation than patients at non-profit facilities. However, even at non-profit facilities only around 20% of patients were placed on the kidney transplantation waiting list. At first glance, this number appears rather low, as kidney transplantation is the only way to curatively treat ESRD. We want to compare these figures with a recently performed survey in Germany. Method We analyzed the status of transplant evaluation in the largest non-profit facility in Germany, the Kuratorium für Dialyse und Nierentransplantation e.V. (kfh, www.kfh.de). In total, the transplant status was assessed in 16,705 patients. Results Out of these only 19.4% of patients (n=3241) are on the kidney transplant waiting list, comparable to recently performed US studies. The reason why patients are not waitlisted are multifaceted as seen in attached figure. Due to severe comorbidities about 50% are considered too sick to benefit from transplantation, in turn representing the complex and high multi-morbidity of patients with ESRD. On the other hand, approximately 10% of dialysis patients actively decline listing for renal transplantation at least at some point. Conclusion We conclude that further research is needed to identify and break the mechanisms behind the low likelihood for access to kidney transplantation waiting list. Distribution of patients with surveyed transplant status in the largest non-profit dialysis facility (kfh, www.kfh.de) in Germany

We propose a simple clockwork model of flavor which successfully generates the Standard Model flavor hierarchies from random order-one couplings. With very few parameters we achieve distributions of models in excellent agreement with observation. We explain in some detail the interpretation of our mechanism as random localization of zero modes in theory space. The scale of the vectorlike fermions is mostly constrained by lepton flavor violation with secondary constraints arising from rare meson decays., 27 pages + appendices

ZusammenfassungDer Diabetes mellitus ist trotz besserer Blutzucker- und Blutdruckeinstellung nach wie vor die häufigste Grunderkrankung beim Auftreten einer terminalen Niereninsuffizienz. Sofern eine Nierentransplantation nicht möglich ist, sind Hämodialyse und Peritonealdialyse bei der diabetischen Dialysepopulation als gleichwertige Verfahren anzusehen. Dieser Artikel fasst aktuelle epidemiologische, diagnostische und therapeutische Aspekte von Diabetikern an Dialyse zusammen.

Patients with chronic kidney disease (CKD) on hemodialysis (HD) experience treatment-related immobility and physical deconditioning, which is responsible for an increased risk of frailty and a high burden of multi-morbidity. Exercise has been shown to counteract this vicious cycle; however, its effectiveness has only been investigated in small cohorts. Therefore, the objective of the Dialysis Training Therapy (DiaTT) trial will be to assess the effects of a 12-month intradialytic exercise program on physical functioning, frailty and health economics in a large cohort of HD patients in a real-world setting. DiaTT will be a prospective, cluster-randomized (1:1), controlled, multi-center, interventional clinical trial across 28 dialysis units, aiming at the recruitment of >1100 CKD patients on HD. The intervention group will receive 12 months’ intradialytic exercise (combined aerobic and resistance training), whereas the usual care group will not receive intervention. The primary endpoint will be a change on the sit-to-stand test (STS60) result between baseline and 12 months. Secondary endpoints will include physical functioning, frailty, quality of life, 3-point MACE, hospitalizations, survival, quality of HD, health literacy and health care costs. By including almost as many patients as previously investigated in smaller trials, DiaTT will be the largest randomized, controlled trial assessing frailty, quality of life and mortality in the field of nephrology.

Trainingstherapie an der Dialyse ist ein therapeutisches Modul, mit dem wesentliche Fortschritte bei der Behandlung von chronisch Nierenkranken gemacht werden konnen. Die Dosierung muss an die individuellen Moglichkeiten der Pa tienten angepasst und nach objektiven Testverfahren gesteuert werden, um die sportwissenschaftlich notwendigen Ergebnisse erzielen zu konnen. Das durch die gleichzeitig ablaufende Dialysebehandlung ermoglichte Monitoring fuhrt zu hoher Patientensicherheit und bewirkt eine hohe Adharenz der Patienten. Damit ist auch die Behandlung von Pa tienten mit multiplen und schweren Komorbiditaten und im fortgeschrittenen Alter moglich. Positive Effekte wurden, auch bei diesen Patienten, in einer Vielzahl von randomisierten Studien nachgewiesen und in rezenten Metaanalysen zusammengefasst. Sie betreffen den Erhalt oder die Wiederherstellung funktioneller Kapazitaten (wie z. B. Anfahrt ins Dialysezentrum, Sturzgefahr), die Verbesserung kardialer Dimensionen (v. a. Herzfrequenz-Variabilitat), eine verbesserte Elimination von Soluten an Dialyse (z. B. Phosphat, Harnstoff) und deutliche Verbesserungen verschiedener Komponenten der Lebensqualitat, insbesondere bzgl. Depressionen. Einer weitreichenden Anwendung bei Dialysepatienten stehen zurzeit verschiedene Hurden bei der Umsetzung und Kostenerstattung entgegen. Ein Modell konnte die gute Umsetzung und Integration in den Dialysealltag in mehreren Dialysezentren demonstrieren und wird deshalb inzwischen auch von einer ortlichen Krankenkasse in Sachsen und Thuringen mitfinanziert.

IntroductionPatients with end-stage kidney failure can be treated either by transplant or by dialysis, which can be administered as haemodialysis (HD) or peritoneal dialysis (PD). Although they are equivalent therapeutic options in terms of mortality, the percentage of patients in Germany treated with PD is currently very low (∼6%) compared with other countries. The aim of our study is to analyse the factors behind this percentage and their relevance to the choice of dialysis treatment in Germany. This includes analyses of regional disparities in the provision of care for dialysis patients as well as the evaluations of costs and the influence of reimbursement structures. This approach should provide further insights to explain the variation in the usage of PD and HD and will help to define starting points for future interventions.Methods and analysisA mixed-methods approach will be applied to several data sources, including administrative data (ambulatory physicians’ claim data, statutory health insurance claim data), quality assurance data from one of the largest German dialysis providers Kuratorium für Dialyse (KfH) and qualitative and quantitative survey data (patients, nephrologists and dialysis nurses). Qualitative data will be analysed content-analytically. Based on the quantitative data, multivariable analyses will be performed and, where possible, hierarchical models will be tested. This multidimensional approach will enable us to account for the different factors influencing the penetration of PD in Germany.Ethics and disseminationEthics approval (17-299) has been obtained from the Ethics Committee of the Medical Faculty of the University of Cologne on 25 April 2018. National and international dissemination will be accomplished by informing healthcare practitioners, patients and professional organisations and other stakeholders via conferences, scientific and non-scientific publications and seminars.Trial registration numberDRKS00012555; Pre-Results.

Patients with end-stage renal disease (ESRD) requiring hemodialysis are typically characterized by multimorbidity and increasingly by advanced age; however, there are few data on their geriatric needs. The aim of the study was to evaluate the clinical characteristics of a large cohort of incident patients in ambulatory hemodialysis units with a particular focus on those aged over 80 years in Germany. The electronic patient registry of the Board of Trustees (Kuratorium) for Dialysis and Kidney Transplantation (KfH) was searched for all patients who began hemodialysis in 1 of the 191 units between 2007 and 2013 and were 65 years and older. Patients were analyzed by age (65–79 years and ≥80 years) for clinical and biochemical characteristics, mortality, quality of life and hospitalizations. Of the 21,355 incident patients, a total of 13,872 (65%) were over 65 years old, with 9998 (46.8%) aged between 65 and 79 years and 3874 (18.1%) patients 80 years or older (oldest old). The spectrum of morbidity was comparable between the two age groups but there was a significantly higher prevalence of anemia, hypoalbuminemia and multimorbidity (>four comorbidities) in the older age group. Median survival was 4.5 years (1638 days) in the younger age group and 2.7 years (978 days) in the older group. Almost half of the patients experienced at least one episode of hospitalization during the first year but there were no significant differences between the age groups (45.9% in younger vs. 47% in older patients). In the older age group 463 (12%) patients survived more than 5 years after initiation of hemodialysis despite the presence of multiple risk factors for adverse clinical outcome. More than half of the chronic ambulatory hemodialysis patients were of advanced age and had a very high burden of multimorbidity. Nevertheless, a subgroup of ERSD patients over 80 years old survived at least 5 years on hemodialysis despite the presence of multiple risk factors for adverse clinical outcome. Identification of these patients as well as optimized care for frail hemodialysis patients will require application of geriatric assessment tools in addition to traditional parameters in nephrology. The development and validation of such tools should be the subject of further clinical studies.

Background: Patients with LIS1-associated classic lissencephaly typically present with severe psychomotor retardation and drug resistant epilepsy within the first year. Aim: To analyze the epileptogenic phenotype and response to antiepileptic therapy in LIS1-associated classic lissencephaly. Method: Retrospective evaluation of 22 patients (8 months-24 years) with genetically and radiologically confirmed LIS1-associated classic lissencephaly in 16 study centers. Results: All patients in our cohort developed drug-resistant epilepsy. In 82% onset of seizures was noted within the first six months of life, most frequently with infantile spasms. Later in infancy the epileptogentic phenotype became more variable and included different forms of focal seizures as well generalized as tonic clonic seizures, with generalized tonic clonic seizures being the predominant type. Lamotrigine and valproate were rated most successful with good or partial response rates in 88-100% of the patients. Both were evaluated significantly better than levetiracetam (p < 0.05) and sulthiame (p < 0.01) in the neuropediatric assessment and better than levetiracetam, sulthiame (p < 0.05) and topiramate (p < 0.01) in the family survey. Phenobarbital and vigabatrin achieved good or partial response in 62-83% of the patients. Conclusion: Our findings suggest that patients with LIS1-associated lissencephaly might benefit most from lamotrigine, valproate, vigabatrin or phenobarbital. (c) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Background The aim of this study was to describe the experience of pediatric and young adult hemodialysis (HD) patients from a global cohort. Methods The Pediatric Investigation and Close Collaborative Consortium for Ongoing Life Outcomes for MONitoring Dialysis Outcomes (PICCOLO MONDO) study provided de-identified electronic information of 3244 patients, ages 0–30 years from 2000 to 2012 in four regions: Asia, Europe, North America and South America. The study sample was categorized into pediatric (≤18 years old) and young adult (19–30 years old) groups based on the age at dialysis initiation. Results For those with known end-stage renal disease etiology, glomerular disease was the most common diagnosis in children and young adults. Using Europe as a reference group, North America [odds ratio (OR) 2.69; CI 1.29, 5.63] and South America (OR 4.21; CI 2.32, 7.63) had the greatest mortality among young adults. North America also had higher rates of overweight, obesity, hypertension, cardiovascular disease, hospitalizations and secondary diabetes compared with all other regions. Initial catheter use was greater for North American (86.4% in pediatric patients and 75.2% in young adults) and South America (80.6% in pediatric patients and 75.9% in young adults). Catheter use at 1-year follow-up was most common in North American children (77.3%) and young adults (62.9%). Asia had the lowest rate of catheter use. For both age groups, dialysis adequacy (equilibrated Kt/V) ranged between 1.4 and 1.5. In Asia, patients in both age groups had significantly longer treatment times than in any other region. Conclusions The PICCOLO MONDO study has provided unique baseline and 1-year follow-up information on children and young adults receiving HD around the globe. This cohort has brought to light aspects of care in these age groups that warrant further investigation.

Paediatric dialysis patients still suffer from high morbidity rates. To improve this, quality assurance programs like the German QiNKid (Quality in Nephrology for Children)-Registry have been developed. In our study, the significance of underlying renal disease on a range of clinical and laboratory parameters impacting morbidity and mortality was analysed. Our aim was to evaluate whether or not disease-specific dialysis strategies should be considered in planning dialysis for a patient. Inclusion criteria were defined as follows: (1) CAKUT (congenital anomalies of the kidney and urinary tract) or glomerular disease patient, (2)

Programme zur Verbesserung der Qualitat der Dialysetherapie wurden Ende der 1990er- und Anfang der 2000er-Jahre in vielen Einrichtungen eingefuhrt und haben sich seither weit verbreitet. Ihr Ziel ist es sicherzustellen, dass alle Patienten die ihnen zugedachte optimale Therapie auch wirklich erhalten. Sie funktionieren am besten, wenn Qualitatsziele lokal vor dem Hintergrund der eigenen Gegebenheiten und der eigenen Patientenpopulation festgelegt werden. Eines der wichtigsten Elemente eines Qualitatsprogramms sind Daten und Informationen, die moglichst vergleichbar in den teilnehmenden Einrichtungen erfasst und ohne zusatzlichen Dokumentationsaufwand aus der elektronischen Patientenakte abgeleitet werden sollten. Das Programm „Qualitat in der Nephrologie“ (QiN) des Kuratoriums fur Dialyse und Nierentransplantation (KfH) macht es zusammen mit der QS-Richtlinie Dialyse moglich, eine sehr gleichformig hohe Qualitat in einem Grosteil aller Dialysezentren zu erreichen. Da QiN viele zusatzliche Indikatoren und Outcomes bereitstellt und ca. 20 % der Dialysepatienten in Deutschland erfasst, unterstutzt QiN nicht nur eine Vielzahl von lokalen Qualitatsinitiativen, sondern liefert auch Informationen zur Altersentwicklung, Mortalitat, Geschlechtsunterschieden und anderen populationsbezogenen Trends. Herausforderungen fur die Zukunft bestehen darin, die Qualitat der Dialysetherapie im Kontext schwerer Komorbiditaten, unterschiedlicher Prognosen und Patientenpraferenzen zu bewerten.

Background: The number of patients receiving renal replacement therapy (RRT) increases annually and worldwide. Differences in the RRT incidence, prevalence, and modality vary between regions and countries for reasons yet to be clarified. Aims: Gain a better understanding of the association between hemodialysis (HD)-related variables and general population global health indicators. Methods: The present study included prevalent HD patients from 27 countries/regions from the monitoring dialysis outcomes (MONDO) database from 2006-2011. Global population health indicators were obtained from the 2014 World Health Organization report and the Human Development Index from the Human Development Report Office 2014. The Spearman rank test was used to assess the correlations between population social economic indicators and HD variables. Results: A total of 84,796 prevalent HD patients were included. Their mean age was 63 (country mean 52-71), and 60% were males (country mean 52-85%). Significant correlations were found between HD demographic clusters and population education, wealth, mortality, and health indicators. The cluster of nutrition and inflammation variables were also highly correlated with population mortality, wealth, and health indicators. Finally, cardiovascular, fluid management, and dialysis adequacy clusters were associated with education, wealth, and health care resource indicators. Conclusion: We identified socioeconomic indicators that were correlated with dialysis variables. This hypothesis-generating study may be helpful in the analysis of how global health indicators may interfere with access to HD, treatment provision, dialytic treatment characteristics, and outcomes.

Background/Aim: The neutrophil-to-lymphocyte ratio (NLR), defined as the neutrophil count divided by lymphocyte count, is an inexpensive and readily available parameter, which may serve as a surrogate for inflammation markers, such as C-reactive protein (CRP). The aim of this study was to determine the utility of NLR in the prediction of elevated CRP levels in hemodialysis (HD) patients. Methods: We analyzed 43,272 HD patients from 2 distinct cohorts within the Monitoring Dialysis Outcomes research collaboration in whom contemporaneous measurements of neutrophil and lymphocyte counts, serum albumin and CRP levels were available. Logistic regression was used to determine the relationship of trichotomized NLR (5.0) and albumin levels (4.0 g/dl) with elevated CRP levels (>10.0, >20.0 and >30.0 mg/l). Congruence of the prediction models was examined by comparing the regression parameters and by cross-validating each regression equation within the other cohort. Results: We found that NLR >5.0 vs. 10.0 mg/l. Stepwise increase in odds ratio for CRP >10.0 mg/l was observed with the combination of high NLR and low albumin levels (NLR >5.0 and albumin Conclusion: This study suggests that NLR could serve as a potential surrogate marker for CRP. Our results may add to diagnostic abilities in settings where CRP is not measured routinely in HD patients. NLR is easy to integrate into daily practice and may be used as a marker of systemic inflammation.

Background/Aims: Dialysis providers frequently collect detailed longitudinal and standardized patient data, providing valuable registries of routine care. However, even large organizations are restricted to certain regions, limiting their ability to separate effects of local practice from the pathophysiology shared by most dialysis patients. To overcome this limitation, the MONDO (MONitoring Dialysis Outcomes) research consortium has created a platform for the joint analysis of data from almost 200,000 dialysis patients worldwide. Methods: We examined design and operation of MONDO as well as its methodology with respect to patient inclusion, descriptive data and other study parameters. Results: MONDO partners contribute primary databases of anonymized patient data and collaboratively analyze populations across national and regional boundaries. To that end, datasets from different electronic health record systems are converted into a uniform structure. Patients are enrolled without systematic exclusions into open cohorts representing the diversity of patients. A large number of patient level treatment and outcome data is recorded frequently and can be analyzed with little delay. Detailed variable definitions are used to determine if a parameter can be studied in a subset or all databases. Conclusion: MONDO has created a large repository of validated dialysis data, expanding the opportunities for outcome studies in dialysis patients. The density of longitudinal information facilitates in particular trend analysis. Limitations include the paucity of uniform definitions and standards regarding descriptive information (e.g. comorbidities), which limits the identification of patient subsets. Through its global outreach, depth, breadth and size, MONDO advances the observational study of dialysis patients and care.

It has long been known that the female sex is associated with a better clinical outcome in chronic renal diseases. Although many experimental, clinical, and epidemiological studies in adults have attempted to explain the difference in disease progression between females and males, a definitive understanding of the underlying mechanisms is still lacking. Hormone-modulating therapies are being increasingly used for various indications (such as post-menopausal hormone replacement, estrogen- or androgen-receptor antagonists for cancer therapy). Therefore, a deeper knowledge of the interaction between sexual hormones and progression of kidney disease is important, as hormone-modulating therapy for non-renal indication may influence both kidney structure and function. In addition, specific modulation of the sexual hormone system, such as the use of selective estrogen receptor modulators, may represent a therapeutic option for patients with renal diseases. Although conclusive data on this topic in the pediatric population are still lacking, the aim of this review is to familiarize pediatric nephrologists with gender-specific differences in renal physiology, pathophysiology, and the progression of kidney diseases. Experimental models that analyze the effects of sexual hormones on renal structure and function are discussed. It is hoped that this review will stimulate researchers to focus on pediatric studies that will provide a deeper insight into the interaction of gender hormones and the kidney both before and during puberty.

For a 5D Standard Model propagating in an AdS background with an IR localized Higgs, compatibility of bulk KK gauge modes with EWPT yields a phenomenologically unappealing KK spectrum (m > 12.5 TeV) and leads to a "little hierarchy problem". For a bulk Higgs the solution to the hierarchy problem reduces the previous bound only by sqrt(3). As a way out, models with an enhanced bulk gauge symmetry SU(2)_R x U(1)_(B-L) were proposed. In this note we describe a much simpler (5D Standard) Model, where introduction of an enlarged gauge symmetry is no longer required. It is based on a warped gravitational background which departs from AdS at the IR brane and a bulk propagating Higgs. The model is consistent with EWPT for a range of KK masses within the LHC reach.

We analyze a scenario where the right-handed neutrinos make part of a strongly coupled conformal field theory and acquire an anomalous dimension \gamma1/2 giving rise to an inverse see-saw mechanism. In this case light sterile neutrinos do appear and neutrino oscillation experiments are able to probe our model., Comment: 11 pages, 4 figures. v2: Discussion of the lepton number violating case corrected; References added

TRPP2, also known as polycystin-2, is a calcium permeable nonselective cation channel that is mutated in autosomal dominant polycystic kidney disease but has also been implicated in the regulation of cardiac development, renal tubular differentiation, and left-to-right (L-R) axis determination. For obtaining further insight into how TRPP2 exerts tissue-specific functions, this study took advantage of PACS-dependent trafficking of TRPP2 in zebrafish larvae. PACS proteins recognize an acidic cluster within the carboxy-terminal domain of TRPP2 that undergoes phosphorylation and mediate retrieval of TRPP2 to the Golgi and endoplasmic reticulum (ER). The interaction of human TRPP2 with PACS proteins can be inhibited by a Ser812Ala mutation (TRPP2(S812A)), thereby allowing TRPP2 to reach other subcellular compartments, and enhanced by a Ser812Asp mutation (TRPP2(S812D)), thereby trapping TRPP2 in the ER. It was found that the TRPP2(S812A) mutant rescued cyst formation of TRPP2-deficient zebrafish larvae to the same degree as wild-type TRPP2, whereas the TRPP2(S812D) mutant was significantly more effective in normalizing the distorted body axis of TRPP2-deficient fish. Surprisingly, the TRPP2(S812D) mutant rescued the abnormalities of L-R asymmetry more effectively than either wild-type or TRPP2(S812A), suggesting that the ER localization of TRPP2 plays an important role in the development of normal L-R asymmetry. Taken together, these findings support the hypothesis that TRPP2 assumes distinct subcellular localizations to exert tissue-specific functions.

The radial excitation of the global symmetry-breaking vacuum in composite Higgs models, called the "global Higgs", has been recently a focus of investigation. In this paper we study the prospects for detecting this composite scalar at the 13 TeV LHC. We compute the global Higgs production rates and estimate the discovery potential of a global Higgs decaying into top quark pairs and into Higgs and electroweak gauge bosons with subsequent hadronic decays. The global Higgs may also decay into fermion resonances such as top partners, providing a new window into compositeness. We show that top partner jets can be effectively unresolved in some regions of the parameter space. Such "boosted top partner" signatures would deserve the development of dedicated substructure analyses., Comment: 27 pages, 7 figures. v2: Comments added. Matches JHEP version

We review electroweak symmetry breaking in supersymmetric models with a compact fifth dimension, the interval. We show how boundary conditions for hypermultiplets can be obtained dynamically by brane mass terms and present formulae for the spectrum in the presence of general bulk mass matrices. After giving a brief overview on the literature of models, we describe in detail a recently proposed model that at energies below the compactification scale reduces to the MSSM with a very peculiar superpartner spectrum., Comment: 14 pages, invited brief review for Mod. Phys. Lett. A

We classify the complete set of dimension-5 operators relevant for the resonant production of a singlet of spin 0 or 2 linearly coupled to the Standard Model (SM). We compute the decay width of such states as a function of the effective couplings, and provide the matching to various well-motivated New Physics scenarios. We then investigate the possibility that one of these neutral resonances be at the origin of the excess in diboson production recently reported by the ATLAS collaboration. We perform a shape analysis of the excess under full consideration of the systematic uncertainties to extract the width $\Gamma_{\rm tot}$ of the hypothetical resonance, finding it to be in the range 26 GeV $, Comment: 31 pages

We present a simple microscopic realization of a pseudo-Nambu-Goldstone (pNGB) boson Higgs scenario arising from the breaking of $SO(5) \rightarrow SO(4)$. The Higgs constituents are explicitly identified as well as the interactions responsible for forming the bound state and breaking the electroweak symmetry. This outcome follows from the presence of four-fermion interactions with a super-critical coupling, and uses the Nambu-Jona-Lasinio mechanism to break the global $SO(5)$ symmetry. The Higgs potential is found to be insensitive to high energy scales due to the existence of an approximate infrared fixed point. The appearance of vector resonances is described and the correspondence with other proposals in the literature established. The model described here is significantly simpler than other recent ultraviolet completions of pNGB scenarios. The observed Higgs mass can be accommodated, and agreement with electroweak precision tests achieved in certain regions of parameter space. There are also new vector-like fermions, some of which may lie within reach of the LHC. In addition, we predict a heavy standard model singlet scalar in the multi-TeV range. The amount of fine-tuning required in the model is studied. Finally, we show that such a scheme can be completed in the ultraviolet by a renormalizable theory., 32 pages plus appendices, 7 figures - reference added

To describe Vitamin D (VitD) status and prevalence of cancer in a large cohort of ambulatory hemodialysis patients in Germany.In a registry study adult patients starting dialysis between 2006 and 2012 were analyzed for VitD blood levels and International classification of diseases (ICD)-10 cancer diagnoses.Almost one third (32.7%) of patients initiating dialysis, had VitD levels12.5 ng/ml and 79.7% had levels30 ng/ml (n=8,377). Average VitD at dialysis initiation increased from 18.0 to 23.2 ng/ml between 2006 and 2012. Prevalence of cancer in this cohort was 22.1% with genital, renal and gastro-intestinal cancers being most common. Cancer frequencies were similar in patients with high and low vitamin D levels.Most chronic hemodialysis patients were vitamin D-deficient in spite of concurrent vitamin D supplementation. The burden of cancer was high in these patients. Future studies should address the role of vitamin D treatment on the course and progression of cancer in chronic kidney disease (CKD) patients.

We discuss the discovery potential of light-by-light scattering at the Large Hadron Collider (LHC), induced by the Standard Model (SM) and by new exotic charged particles. Our simulation relies on intact proton detection in the planned forward detectors of CMS and ATLAS. The full four-photon amplitudes generated by any electrically charged particles of spins $1/2$ and $1$, including the SM processes involving loops of leptons, quarks and $W$ bosons are implemented in the Forward Physics Monte Carlo generator. Our method provides model-independent bounds on massive charged particles, only parametrized by the spin, mass and "effective charge" $Q_{\rm eff}$ of the new particle. We find that a new charged vector (fermion) with $Q_{\rm eff}=4$ can be discovered up to $m=640~\rm GeV$ ($m=300~\rm GeV$) with an integrated luminosity of $300~\rm fb^{-1}$ at the LHC. We also discuss the sensitivities to neutral particles such as a strongly-interacting heavy dilaton and warped Kaluza-Klein gravitons, whose effects could be discovered for masses in the multi-TeV range., 27 pages, 11 figures. Updated/final figures and some typo corrected