13 research outputs found
Incentivizing the Dynamic Workforce: Learning Contracts in the Gig-Economy
In principal-agent models, a principal offers a contract to an agent to
perform a certain task. The agent exerts a level of effort that maximizes her
utility. The principal is oblivious to the agent's chosen level of effort, and
conditions her wage only on possible outcomes. In this work, we consider a
model in which the principal is unaware of the agent's utility and action
space. She sequentially offers contracts to identical agents, and observes the
resulting outcomes. We present an algorithm for learning the optimal contract
under mild assumptions. We bound the number of samples needed for the principal
obtain a contract that is within of her optimal net profit for every
Enzyme replacement therapy in Hurler syndrome after failure of hematopoietic transplant
The most severe form of Mucopolysaccharosidosis type I (MPS-I), Hurler syndrome, presents with progressive respiratory, cardiac and musculoskeletal symptoms and cognitive deterioration.
Treatment includes enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT).
We describe the case of an 8-year old boy with MPS-I, homozygous for W402X, treated at 10 months of age with HSCT and after failure of the transplant, with ERT during 2 years showing good results, including a positive neuropsychological development
Spanish multicenter study: hyperammonemia not associated with inborn errors of metabolism in children
Introduction: The hyperammonemic encephalopathy induced by causes different from inborn errors of metabolism is a relatively uncommon but severe complication.Objectives: To study the characteristics of a secondary hyperammonemia episode to discern the triggering causes to get to the diagnosis, and the development in the therapeutic intervention.Methods: A multicenter retrospective study of children with hyperammonemia unrelated to inborn errors of metabolism, conducted in Spanish hospitals.Results: Nineteen patients were selected; hyperammonemia developed in infants under one year old in 47% of them, being diagnosed mostly with two or more symptoms. The most common clinical finding was an altered consciousness level similar to that of intoxication symptoms, followed by seizures. These clinical symptoms were present in 14 patients, with one of them or both. Twelve of the 19 patients were in treatment with more than two antiepileptic drugs routinely. All children were treated with protein restriction (n: 10), scavengers (n: 10) and/or carglumic acid (n: 12) for the treatment of hyperammonemia.Conclusions: This study suggests that secondary hyperammonemia could be underdiagnosed because it is only detected when severe symptoms appear. Risk seems to be higher in those patients receiving antiepileptic drugs or those critically ill with a restricted diet or incremented metabolism. The response to specific treatment is adequate but should be established earlier to avoid neurological sequelae of this entity
Fabry disease in the Spanish population: observational study with detection of 77 patients
Abstract Background Fabry disease is a multisystemic lysosomal storage disorder caused by the impairment of α-galactosidase A. The incidence of this rare disease is underestimated due to delayed diagnosis. Moreover, the management of the identified subjects is often complicated by the detection of variants of unclear diagnostic interpretation, usually identified in screening studies. We performed an observational study based on biochemical and genetic analysis of 805 dried blood spot samples from patients with clinical symptoms or family history of this pathology, which were collected from 109 Spanish hospitals, all over the country. Results We identified 77 new diagnosed patients with mutations related to classical Fabry disease, as well as 2 subjects with c.374A > T; p.His125Leu, a possible new mutation that need to be confirmed. Additionally, we detected 8 subjects carrying genetic variants possibly linked to late onset Fabry disease (p.Arg118Cys and p.Ala143Thr), 4 cases with polymorphism p.Asp313Tyr and 36 individuals with single nucleotide polymorphisms in intronic regions of GLA. Five of the identified mutations (c.431delG; c.1182delA; c.374A > T; c.932 T > C; c.125 T > A; c.778G > A), which were associated with a classical phenotype have not been previously described. Moreover 3 subjects presenting complex haplotypes made up by the association of intronic variants presented impaired levels of GLA transcripts and Gb3 deposits in skin biopsy. Conclusions Enzymatic screening for Fabry Disease in risk population (2 or more clinical manifestations or family history of the disease) helped to identify undiagnosed patients and unravel the impairment of GLA expression in some subjects with complex haplotypes
Unusual Heart Involvement of Wegener’s Granulomatosis and Literature Review
A female patient, 60 years of age, was presented to our hospital with chest pain and monomorphic ventricular tachycardia (VT). She was transferred to the Coronary Care Unit and amiodarone perfusion restored basal rhythm in atrial fibrillation. She has not sign of heart failure. A transtoracic echocardiogram (TTE) was performed and an one mitral mass was found at atrioventricular junction with displacement of the posterior mitral leaflet A transesophageal echocardiogram (TEE) demonstrated a mass at atrioventricular junction level with severe mitral regurgitation. Cardiac Magnetic Resonance (CMR) confirmed the mass and anterolateral papillary muscle was thickening and hypertrophied with hyperenhancement consistent with fibrosis. Moreover, T2-weighted imaging demonstrated hyperintense mass with respect to the surrounding myocardium in relation of inflammatory mass. She had saddle nose by destruction of the septum, bilateral hearing loss, sinusitis and scleritis and renal involvement as well. This patient was diagnosed of Wegener's Granulomatosis (WG) and she was treated with methylprednisolone during 3 days, continued with prednisolone and cyclophosphamide. An 8 days later echocardiogram did not find the mass. However, the patient developed symptomatology of heart failure and in the context of severe mitral regurgitation, mitral valve replacement was decided in multi-disciplinary Cardiology-Cardiothoracic meeting.
Complex I deficiency, due to NDUFAF4 mutations, causes severe mitochondrial dysfunction and is associated to early death and dysmorphia
Consensus guideline for the diagnosis and management of mannose phosphate isomerase-congenital disorder of glycosylation (MPI-CDG)
Mannose phosphate isomerase-congenital disorder of glycosylation (MPI-CDG) deficiency is a rare subtype of congenital disorders of protein N-glycosylation. It is characterised by deficiency of MPI caused by pathogenic variants in MPI gene. The manifestation of MPI-CDG is different from other CDGs as the patients suffer dominantly from gastrointestinal and hepatic involvement whereas they usually do not present intellectual disability or neurological impairment. It is also one of the few treatable subtypes of CDGs with proven effect of oral mannose. This article covers a complex review of the literature and recommendations for the management of MPI-CDG with an emphasis on the clinical aspect of the disease. A team of international experts elaborated summaries and recommendations for diagnostics, differential diagnosis, management, and treatment of each system/organ involvement based on evidence-based data and experts' opinions. Those guidelines also reveal more questions about MPI-CDG which need to be further studied.status: Published onlin
Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice
BackgroundHepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data.MethodsVia questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications.ResultsEarly treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400Â ÂżM) and NTBC-levels in the therapeutic range (20Âż40Â ÂżM). Side effects of NTBC are mild and often transient.Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood).ConclusionBased on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations
Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice.
Background: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data