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In this community review report, we discuss applications and techniques for fast machine learning (ML) in science-the concept of integrating powerful ML methods into the real-time experimental data processing loop to accelerate scientific discovery. The material for the report builds on two workshops held by the Fast ML for Science community and covers three main areas: applications for fast ML across a number of scientific domains; techniques for training and implementing performant and resource-efficient ML algorithms; and computing architectures, platforms, and technologies for deploying these algorithms. We also present overlapping challenges across the multiple scientific domains where common solutions can be found. This community report is intended to give plenty of examples and inspiration for scientific discovery through integrated and accelerated ML solutions. This is followed by a high-level overview and organization of technical advances, including an abundance of pointers to source material, which can enable these breakthroughs., Competing Interests: MB was employed by the company Xilinx Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor EC is currently organizing a Research Topic with the authors JD, ML, and JN., (Copyright © 2022 Deiana, Tran, Agar, Blott, Di Guglielmo, Duarte, Harris, Hauck, Liu, Neubauer, Ngadiuba, Ogrenci-Memik, Pierini, Aarrestad, Bähr, Becker, Berthold, Bonventre, Müller Bravo, Diefenthaler, Dong, Fritzsche, Gholami, Govorkova, Guo, Hazelwood, Herwig, Khan, Kim, Klijnsma, Liu, Lo, Nguyen, Pezzullo, Rasoulinezhad, Rivera, Scholberg, Selig, Sen, Strukov, Tang, Thais, Unger, Vilalta, von Krosigk, Wang and Warburton.)

Vehicle-to-everything (V2X) communications enable real-time information exchange between vehicles and infrastructure, which extends the perception range of vehicles beyond the limits of on-board sensors and, thus, facilitating the realisation of cooperative, connected, and automated mobility (CCAM) services that will improve road safety and traffic efficiency. In the context of CCAM, the successful deployments of cooperative intelligent transport system (C-ITS) use cases, with the integration of advanced wireless communication technologies, are effectively leading to make transport safer and more efficient. However, the evaluation of multi-vendor and multi-protocol based CCAM service architectures can become challenging and complex. Additionally, conducting on-demand field trials of such architectures with real vehicles involved is prohibitively expensive and time-consuming. In order to overcome these obstacles, in this paper, we present the development of a standards-compliant experimental vehicular on-board unit (OBU) that supports the integration of multiple V2X protocols from different vendors to communicate with heterogeneous cloud-based services that are offered by several original equipment manufacturers (OEMs). We experimentally demonstrate the functionalities of the OBU in a real-world deployment of a cooperative collision avoidance service infrastructure that is based on edge and cloud servers. In addition, we measure end-to-end application-level latencies of multi-protocol supported V2X information flows to show the effectiveness of interoperability in V2X communications between different vehicle OEMs.

Background: Denys-Drash syndrome (DDS) is a rare disease caused by mutations in exons 8 and 9 of the WT1 gene. It is characterized by the association of early onset steroid-resistant nephrotic syndrome (SRNS), Wilms' tumour and, in some patients, intersex disorders, with increasing risk of gonadoblastoma. There are few published data concerning the long-term outcome of patients with DDS. The aim of this study was to report our experience., Methods: Data were collected from five children (three boys) with confirmed DDS diagnosed from 1996 to 2017. The mean follow-up of these patients was 16 years., Results: The patients presented with SRNS and diffuse mesangial sclerosis at renal biopsy. All patients were hypertensive and progressed to end-stage kidney disease, initiating dialysis at a mean age of 28 months. Three patients developed Wilms' tumour 9 months after the SRNS was identified, which was treated by nephrectomy and chemotherapy. All five patients received kidney transplantation. SRNS did not recur after transplantation in any of the patients and graft survival was similar to that of other kidney transplant recipients in our programme. All three boys had ambiguous genitalia and cryptorchidism but a confirmed male karyotype (46, XY). One girl presented with gonadal agenesis, whereas the other one had normal female ovarian tissue and external genitalia. Both girls had a female karyotype (46, XX). Gonadoblastoma was not observed at any case., Conclusions: Early DDS recognition in patients with SRNS is crucial due to its low prevalence, the specific treatment approach required and early detection of Wilms' tumour. Few data are available regarding long-term outcomes., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background and Objectives: The prognostic value of mesangial C4d deposits in IgA nephropathy has been analyzed in patients with reduced GFR but has not been analyzed in those with normal kidney function. The main objective of the study was to analyze the prognostic value of C4d deposits and association with response to treatment in patients with IgA nephropathy and normal GFR., Design, Setting, Participants, & Measurements: This retrospective cohort study included 190 patients with idiopathic IgA nephropathy diagnosed by kidney biopsy between 1988 and 2005. The patients had GFR≥80 ml/min per 1.73 m 2 at the time of diagnosis, and they had a paraffin-embedded kidney biopsy with eight glomeruli available., Results: In total, 170 (89%) and 20 (11%) patients were >18 and <18 years old, respectively; median (interquartile range) follow-up was 15 (12-22) years. Mesangial C4d deposit prevalence was 20% (38 of 190). At diagnosis, C4d-positive versus -negative patients had higher protein-to-creatinine ratio (median [interquartile range]: 1.94 g/g [0.9-3.1] versus 1.45 g/g [0.9-2.2]; P =0.04). During follow-up, C4d-positive patients showed a higher number of nephritic flares (median [range]: 1.4 [0-5] versus 0.9 [0-2]; P =0.04), had a higher protein-to-creatinine ratio (median [interquartile range]: 1.32 g/g [0.7-1.7] versus 0.89 g/g [0.1-1.3]; P <0.01), were more prone to receive repeated treatment with corticosteroids (45% versus 24%; P <0.01), and showed a larger reduction in eGFR (-1.6 versus -0.8 ml/min per 1.73 m 2 per year; P =0.04). Furthermore, the presence of mesangial C4d deposits was an independent predictor of long-term kidney survival., Conclusions: C4d deposits may be one of the earliest poor prognostic variables available for patients with idiopathic IgA nephropathy and normal kidney function at the time of diagnosis. However, Cd4 deposits alone are not associated with the response to angiotensin blockers or corticosteroid treatment., (Copyright © 2018 by the American Society of Nephrology.)

Introduction: Liver-kidney transplantation is a rare procedure in children, with just ten to 30 cases performed annually worldwide. The main indications are autosomal recessive polycystic liver-kidney disease and primary hyperoxaluria. This study aimed to report outcomes of liver-kidney transplantation in a cohort of pediatric patients., Methods: We retrospectively analyzed all pediatric liver-kidney transplantations performed in our center between September 2000 and August 2015. Patient data were obtained by reviewing inpatient and outpatient medical records and our transplant database., Results: A total of 14 liver-kidney transplants were performed during the study period, with a median patient age and weight at transplant of 144.4 months (131.0-147.7) and 27.3 kg (12.0-45.1), respectively. The indications for liver-kidney transplants were autosomal recessive polycystic liver-kidney disease (8/14), primary hyperoxaluria -1 (5/14), and idiopathic portal hypertension with end-stage renal disease (1/14). Median time on waiting list was 8.5 months (5.7-17.3). All but two liver-kidney transplants were performed simultaneously. Patients with primary hyperoxaluria-1 tended to present a delayed recovery of renal function compared with patients transplanted for other indications (62.5 vs 6.5 days, respectively, P 0.076). Patients with liver-kidney transplants tended to present a lower risk of acute kidney rejection than patients transplanted with an isolated kidney transplant (7.2% vs 32.7%, respectively; P < 0.07). Patient and graft survival at 1, 3, and 5 years were 100%, 91.7%, 91.7%, and 91.7%, 83.3%, 83.3%, respectively. No other grafts were lost., Conclusion: Long-term results of liver-kidney transplants in children are encouraging, being comparable with those obtained in isolated liver transplantation.

Objective: To review our single-center experience in managing posttransplant lymphoceles in pediatric kidney recipients. Lymphoceles are well-known complications after pediatric kidney transplantation (KT). However, there is no standard treatment for lymphoceles, and the literature lacks consensus on which is the most appropriate approach., Materials and Methods: We reviewed our retrospective institutional database for recipients of pediatric KT performed between January 2000 and December 2015 who developed lymphoceles., Results: Out of the 176 patients who underwent KT, lymphoceles occurred in 9 (5.1%) patients. The mean age of recipients in this group was 12.8 years (standard deviation [SD] 4.8) (r: 1-17) and the mean body weight was 43.1 kg (SD 18.8) (r: 9.5-69). Mean lymphocele onset was 32.2 days (SD 23.4) (r: 11-85) post transplantation. Six patients presented with increased serum creatinine from the baseline, whereas 3 patients remained asymptomatic. Ultrasound was the primary diagnostic procedure in all patients. Lymphoceles resolved spontaneously in asymptomatic patients (n = 3), and thus these patients were not further treated. All symptomatic patients (n = 6) were treated: 2 underwent percutaneous catheter drainage and 4 underwent transcatheter sclerotherapy (TS). The main sclerosing agent used was povidone-iodine. In 3 patients, TS with povidone-iodine failed, and they underwent additional procedures: 2 underwent TS with polidocanol and 1 underwent open drainage. There was no graft loss in any of the patients, and no recurrence was documented during a follow-up period of mean 30.3 months (SD 15.6) (r: 7-57)., Conclusion: There is no gold-standard treatment for lymphoceles in children, and reports in the literature on the topic are scarce. Percutaneous catheter drainage with or without TS is safe and effective, although it can lengthen hospitalization and increase morbidity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Traditional studies on effects of outdoor pollution on asthma have been criticized for questionable statistical validity and inefficacy in exploring the effects of multiple air pollutants, alone and in combination. Association rule mining (ARM), a method easily interpretable and suitable for the analysis of the effects of multiple exposures, could be of use, but the traditional interest metrics of support and confidence need to be substituted with metrics that focus on risk variations caused by different exposures., Methods: We present an ARM-based methodology that produces rules associated with relevant odds ratios and limits the number of final rules even at very low support levels (0.5%), thanks to post-pruning criteria that limit rule redundancy and control for statistical significance. The methodology has been applied to a case-crossover study to explore the effects of multiple air pollutants on risk of asthma in pediatric subjects., Results: We identified 27 rules with interesting odds ratio among more than 10,000 having the required support. The only rule including only one chemical is exposure to ozone on the previous day of the reported asthma attack (OR=1.14). 26 combinatory rules highlight the limitations of air quality policies based on single pollutant thresholds and suggest that exposure to mixtures of chemicals is more harmful, with odds ratio as high as 1.54 (associated with the combination day0 SO 2 , day0 NO, day0 NO 2 , day1 PM)., Conclusions: The proposed method can be used to analyze risk variations caused by single and multiple exposures. The method is reliable and requires fewer assumptions on the data than parametric approaches. Rules including more than one pollutant highlight interactions that deserve further investigation, while helping to limit the search field., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Haemolytic uraemic syndrome (HUS) is a clinical entity defined as the triad of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). Different causes can induce the TMA process that characterizes HUS. In this document we consider atypical HUS (aHUS) a sub-type of HUS in which the TMA phenomena are the consequence of the endotelial damage in the microvasculature of the kidneys and other organs due to a disregulation of the activity of the complement system. In recent years, a variety of aHUs-related mutations have been identified in genes of the the complement system, which can explain approximately 60% of the aHUS cases, and a number of mutations and polymorphisms have been functionally characterized. These findings have stablished that aHUS is a consequence of the insufficient regulation of the activiation of the complement on cell surfaces, leading to endotelial damage mediated by C5 and the complement terminal pathway. Eculizumab is a monoclonal antibody that inhibits the activation of C5 and blocks the generation of the pro-inflammatory molecule C5a and the formation of the cell membrane attack complex. In prospective studies in patients with aHUS, the use of Eculizumab has shown a fast and sustained interruption of the TMA process and it has been associated with significative long-term improvements in renal function, the interruption of plasma therapy and important reductions in the need of dialysis. According to the existing literature and the accumulated clinical experience, the Spanish aHUS Group published a consensus document with recommendations for the treatment of aHUs (Nefrologia 2013;33[1]:27-45). In the current online version of this document, we update the aetiological classification of TMAs, the pathophysiology of aHUS, its differential diagnosis and its therapeutic management., (Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Software defined networking (SDN) and flexible grid optical transport technology are two key technologies that allow network operators to customize their infrastructure based on application requirements and therefore minimizing the extra capital and operational costs required for hosting new applications. In this paper, for the first time we report on design, implementation & demonstration of a novel OpenFlow based SDN unified control plane allowing seamless operation across heterogeneous state-of-the-art optical and packet transport domains. We verify and experimentally evaluate OpenFlow protocol extensions for flexible DWDM grid transport technology along with its integration with fixed DWDM grid and layer-2 packet switching.

Haemolytic uraemic syndrome (HUS) is a clinical entity defined as the triad of nonimmune haemolytic anaemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by systemic thrombotic microangiopathy (TMA). Atypical HUS (aHUS) is a sub-type of HUS in which the TMA phenomena are the consequence of decreased regulation of the alternative complement pathway on cell surfaces due to a genetic cause. aHUS is an extremely rare disease that, despite the administration of standard treatment with plasma therapy, often progresses to terminal chronic renal failure with a high associated rate of mortality. In recent years, research has established the key role that the complement system plays in the induction of endothelial damage in patients with aHUS, through the characterisation of multiple mutations and polymorphisms in the genes that code for certain complement factors. Eculizumab is a monoclonal antibody that inhibits the terminal fraction of the complement protein, blocking the formation of a cell membrane attack complex. In prospective studies in patients with aHUS, administering eculizumab produces a rapid and sustained interruption in the TMA process, with significant improvements in long-term renal function and an important decrease in the need for dialysis or plasma therapy. In this document, we review and bring up to date the important aspects of this disease, with special emphasis on how recent advancements in diagnostic and therapeutic processes can modify the treatment of patients with aHUS.

We present a Resource Broker with a Virtual Network Topology Manager (VNTM) which dynamically deploys virtual GMPLS-controlled WSON networks. Virtual Optical links are constructed by grouping established optical connections which are managed by the VNTM. We evaluate the performance of the Resource Broker in the ADRENALINE testbed.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare genetic disorder caused by chronic uncontrolled complement activation., Case-Diagnosis/treatment: We present a 4-year-old girl with aHUS who had multiple severe clinical manifestations of thrombotic microangiopathy (TMA) including acute kidney injury, dilated cardiomyopathy, and cardiorespiratory arrest. She was managed with intensive plasma exchange and hemodialysis, which could not halt the progression of TMA. The initial single dose of eculizumab only temporarily improved the clinical symptoms of TMA. Sustained improvement of renal, hematological, and cardiac values were only achieved upon institution of chronic treatment with eculizumab. During long-term treatment with eculizumab (>2.5 years), she has had no further clinical manifestations of TMA, and required neither plasma exchange nor hemodialysis., Conclusion: Chronic eculizumab treatment was associated with control of complement-mediated TMA and sustained long-term improvement in renal and cardiac function.

Aim and Method: The aim of this study was to describe the clinical characteristics and outcome of pandemic influenza A H1N1/2009 (pH1N1) infection, in a retrospective cohort of pediatric patients with kidney and/or liver transplant and confirmed pH1N1 infection from June to December 2009, diagnosed in 2 Spanish teaching hospitals., Results: Forty-nine patients were included. Pneumonia was diagnosed in 4 patients (8.2%), and 3 of them required respiratory support. There were no related deaths., Conclusion: Antiviral treatment within 48 h was associated with a lower likelihood of pneumonia (0/38, 0%) than treatment started after 48 h (4/11, 36.3%) (P < 0.01)., (© 2012 John Wiley & Sons A/S.)

Background: Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D3 (1,25(OH)2D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the PHEX gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies., Methods: Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the PHEX gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test., Results: Mutations in the PHEX gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)2D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013)., Conclusions: PHEX gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious PHEX mutations had lower TRP and 1,25(OH)2D levels suggesting that the PHEX type of mutation might predict the XLHR phenotype severity.

Background: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that frequently does not respond to treatment and progresses to kidney failure. FSGS can be of either genetic origin, caused by mutations in slit diaphragm proteins, such as podocin, or idiopathic origin of unknown cause., Study Design: Case series., Setting & Participants: Children with FSGS (aged 3-18 years); 15 with idiopathic and 11 with genetic forms of FSGS., Predictor: Genetic versus idiopathic forms., Outcomes & Measurements: Differentially expressed proteins in the plasma proteome, detected using 2-dimensional electrophoresis and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Western blot, and liquid chromatography electron spray ionization tandem mass spectrometry for fragmentation and identification of the peptides., Results: We found 3 very low-molecular-mass (9.2, 6.9, and 4.7 kDa; isoelectric point, 5.7) spots that were present in pooled samples from patients with genetic FSGS, but missing in patients with idiopathic FSGS and healthy individuals. Spots were identified using mass spectrometry as fragments of albumin, 2 of them apparently containing peptides from both C- and N-terminal parts of the whole protein. Proteomic analyses were carried out on all genetic patients individually; of these, 10 of 11 patients had > or =1 albumin fragment detected in the pool. We did not find an evident relationship between type of mutation or clinical status of patients and albumin fragments observed., Limitations: Very low-molecular-weight albumin fragments also can be produced by other diseases., Conclusions: We describe for the first time the presence of very low-molecular-mass albumin fragments in plasma of patients with FSGS with podocyte protein mutations that are absent in patients with idiopathic FSGS or healthy individuals. Additional studies are necessary to determine whether these fragments could be potential biomarkers to distinguish between genetic and idiopathic forms of FSGS.

Background: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown., Methods: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information., Results: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family., Conclusions: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Reduction of delayed graft function (DGF) is critical to the success of renal transplantation. We report graft outcomes with antithymocyte globulin (ATG) induction compared with using interleukin-2 receptor antagonist basiliximab (IL-2RA). Twelve pediatric patients received a pediatric deceased donor kidney. We treated them with ATG (group A, ATG; n = 6) or IL-2RA (group B, n = 6). DGF was observed in 0 cases (group A) and in 6 cases (group B), which showed a mean of 7 +/- 3 days (P < .001). In group A, lymphopenia occurred routinely resolving after 3-6 months, none with serious infection. The incidence of opportunistic infections was 0% in both groups. One-year patient and graft survivals were 100% in both groups. ATG induction significantly reduced the incidence of delayed graft function. Both induction treatments led to a good patient and graft survival.

Background/aim: Alport syndrome is a hereditary glomerulonephritis, X-linked in 85% of the cases. This form is associated with mutations in the COL4A5 gene which encodes the alpha5 chain of type IV collagen. We have performed the mutational analysis of the COL4A5 gene in a Spanish family with X-linked Alport syndrome., Methods: We have analyzed three polymorphic markers close to the gene to confirm the X chromosome linkage. By means of the PCR technique, we have screened the 51 exons of the gene., Results: The segregation of the alleles from the analyzed markers was in agreement with the X linkage. Direct sequencing of PCR-amplified products has shown a CCT-to-CTT change in exon 25, resulting in substitution of a proline for a leucine at position 619 of the polypeptide chain (nucleotide 2058)., Conclusions: Although proline is considered a nonconserved amino acid, it is essential, upon hydroxylation, in the maintenance of a stable alpha chain triple-helix collagen. Furthermore, the change cosegregates with the disease in all affected members of the family, not being present in 80 control chromosomes. This represents a new mutation in the COL4A5 gene found in the Spanish population., (Copyright 2002 S. Karger AG, Basel)

Fifty five patients with Schöelein-Henoch nephropathy were reviewed. These patients were divided into five groups according to the clinical picture initially presented: 1. Hematuria with proteinuria. 2. Hematuria with nephrotic syndrome. 3. Isolated hematuria. 4. Hematuria, nephrotic syndrome and renal failure. 5. Proteinuria. From a histopathological point of view, they were classified into six groups according to ISKDC criteria. A strong correlation was found between clinical presentation and histological lesion. The worst prognosis corresponded to patients with nephrotic syndrome and renal failure, whose biopsy revealed more than 75% of glomeruli with epithelial crescents.

Clinical and radiological studies of seven patients with autosomic recessive malignant osteopetrosis are presented. Diagnosis was established before the age of 3 months in six cases and at 7 months in one. In all cases the presenting signs were pallor and hepatosplenomegaly with associated neurological involvement in five. All patients had normocytic normochromic anemia, leucopenia and thrombocytopenia with features of extramedullary hematopoiesis. Radiological studies revealed increase in the density of bones with "mask" appearance of facial bones and diminished size of optic foramina. Long bones showed absence of normal trabeculae and anomalies in modeling with methaphiseal bands and "bone within bone" images. There was hypocalcemia and hypophosphatemia with slight increases in alkaline phosphatase; parathormone was normal. Clinical course was characterized by progressive pancytopenia, recurrent infections and neurological deterioration with convulsions, nistagmus and optic atrophy. Five out of the seven patients died after a median of 3 months, due to infections or haemorrhage. The patient diagnosed at 7 months of age presented bilateral optic atrophy and moderate anemia; no other complications appeared after 2 year follow-up. Histological findings included substitution of bone marrow by chondro-osseous tissue; focal obsteoblastic and osteoclastic activity in calcified cartilage, and myeloid metaplasia in liver, spleen, lymph nodes and kidneys. The lesions are in agreement with the concept of a defect in bone formation-resorbtion balance; dysfunction of both osteoclasts and osteocytes is implicated in the pathogenesis. Unlike experimental disease, osteopetrosis in man is probably an heterogeneous disease and appropriate therapy should be individualized. Nevertheless, at present, the only favorable results have been obtained with bone-marrow transplantation.

Authors describe initial characteristics, clinical course and response to treatment of 13 children, aged from eight months to nine years, with acquired aplastic anaemia. Six of the children had been exposed to products with potential bone-marrow toxicity: chloranphenicol (1), pirazolones (3) and insecticides (2). Pancytopenia was severe in twelve and moderate in one. Five patients with severe aplastic anaemia were given antilymphocytic (2) or antithymocytic (3) (ATG) gammaglobulins; two of those treated with ATG responded after two and five months respectively and there was no response in the other three. Twelve patients were given androgen treatment (oxymetholone or nandrolone decanoate): four, two of whom previously had received ATG, followed a favorable course. None of the severe initial pancytopenic patients responded to androgen single agent treatment. No marrow transplant was performed in any of the children. Eight of the thirteen patients died one to 37 months after onset (median, 6 months) and five (38%) are alive after 21 months to 10 years, corresponding to two patients with moderate and three with severe initial pancytopenia. Importance of an appropriate supportive treatment during initial stages of the disease and the probable efficacy or immunosupressive treatment in certain patients must be underlined.