Isolated neurological presentations of mevalonate kinase deficiency

Mevalonate kinase (MK) deficiency is a rare autosomal recessive metabolic disorder caused by pathogenic variants in the MVK gene with a broad phenotypic spectrum including autoinflammation, developmental delay and ataxia. Typically, neurological symptoms are considered to be part of the severe end of the phenotypical spectrum and are reported to be in addition to the autoinflammatory symptoms. Here, we describe a patient with MK deficiency with severe neurological symptoms but without autoinflammation and we found several similar patients in the literature. Possibly, the non‐inflammatory phenotype is related to a specific genotype: the MVK p.(His20Pro)/p.(Ala334Thr) variant. There is probably an underdetection of the neurological MK deficient phenotype without inflammatory symptoms as clinicians may not test for MK deficiency when patients present with only neurological symptoms. In conclusion, although rare, neurological symptoms without hyperinflammation might be more common than expected in MK deficiency. It seems relevant to consider MK deficiency in patients with psychomotor delay and ataxia, even if there are no inflammatory symptoms

Continuous-action reinforcement learning for memory allocation in virtualized servers

In a virtualized computing server (node) with multiple Virtual Machines (VMs), it is necessary to dynamically allocate memory among the VMs. In many cases, this is done only considering the memory demand of each VM without having a node-wide view. There are many solutions for the dynamic memory allocation problem, some of which use machine learning in some form. This paper introduces CAVMem (Continuous-Action Algorithm for Virtualized Memory Management), a proof-of-concept mechanism for a decentralized dynamic memory allocation solution in virtualized nodes that applies a continuous-action reinforcement learning (RL) algorithm called Deep Deterministic Policy Gradient (DDPG). CAVMem with DDPG is compared with other RL algorithms such as Q-Learning (QL) and Deep Q-Learning (DQL) in an environment that models a virtualized node. In order to obtain linear scaling and be able to dynamically add and remove VMs, CAVMem has one agent per VM connected via a lightweight coordination mechanism. The agents learn how much memory to bid for or return, in a given state, so that each VM obtains a fair level of performance subject to the available memory resources. Our results show that CAVMem with DDPG performs better than QL and a static allocation case, but it is competitive with DQL. However, CAVMem incurs significant less training overheads than DQL, making the continuous-action approach a more cost-effective solution.This research is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 754337 (EuroEXA) and the European Union’s 7th Framework Programme under grant agreement number 610456 (Euroserver). It also received funding from the Spanish Ministry of Science and Technology (project TIN2015-65316-P), Generalitat de Catalunya (contract 2014-SGR-1272), and the Severo Ochoa Programme (SEV-2015-0493) of the Spanish Government.Peer ReviewedPostprint (author's final draft

Characterizing the kinetics of presepsin and associated inflammatory biomarkers in human endotoxemia

In this study, we describe the kinetics of a new potential inflammatory biomarker, presepsin, together with a panel of well-established biomarkers in a human endotoxemia study. We evaluated biomarker correlations and identified combinations that could hold valuable insights regarding the state of infection.Pharmacolog

Community health center efficiency: The role of grant revenue in health center efficiency

Abstract: Objective: To test the relationship between external environments, organizational characteristics, and technical efficiency in federally qualified health centers (FQHCs). We tested the relationship between grant revenue and technical efficiency in FQHCs. Principal Findings: Increased grant revenues did not increase the probability that a health center would be on the efficiency frontier. However, increased grant revenues had a negative association with technical efficiency for health centers that were not fully efficient. Data Conclusion: If all health centers were operating efficiently, anywhere from 39 to 45 million patient encounters could have been delivered instead of the actual total of 29 million in 2007. Policy makers should consider tying grant revenues to performance indicators, and future work is needed to understand the mechanisms through which diseconomies of scale are present in FQHCs

Intracranial bleeding due to vitamin K deficiency: advantages of using a pediatric intensive care registry

Item does not contain fulltextAIM: To determine the incidence of late intracranial vitamin K deficiency bleeding (VKDB) in The Netherlands using the Dutch Pediatric Intensive Care Evaluation (PICE) registry. METHODS: The PICE registry was used to identify all infants who were admitted to a Dutch pediatric intensive care unit (PICU) with intracranial bleeding between 1 January 2004 and 31 December 2007. Cases of confirmed late intracranial VKDB were used to calculate the incidence for each year. To estimate the completeness of ascertainment of the PICE registry, data from 2005 were compared with general surveillance data from that year. RESULTS: In the 4-year study period, 16/64 (25%) of the infants admitted with intracranial bleeding had late intracranial VKDB, resulting in an overall incidence of 2.1/100,000 live births (95% confidence interval 1.2-3.5). The single-year incidence varied markedly between 0.5 and 3.3 per 100,000 live births. All five ascertained cases in 2005 were identified using the PICE registry, while general surveillance identified only three. CONCLUSIONS: The PICE registry allows ongoing monitoring of the incidence of late intracranial VKDB and appears to be associated with a higher rate of completeness than general surveillance. We propose the use of pediatric intensive care registries to assess the efficacy of national vitamin K prophylactic regimens

In-Brace versus Out-of-Brace Protocol for Radiographic Follow-Up of Patients with Idiopathic Scoliosis:A Retrospective Study

The purpose of this retrospective study was to compare two standardized protocols for radiological follow-up (in-brace versus out-of-brace radiographs) to study the rate of curve progression over time in surgically treated idiopathic scoliosis (IS) patients after failed brace treatment. In-brace radiographs have the advantage that proper fit of the brace and in-brace correction can be evaluated. However, detection of progression might theoretically be more difficult. Fifty-one IS patients that underwent surgical treatment after failed brace treatment were included. For 25 patients, follow-up radiographs were taken in-brace. For the other 26 patients, brace treatment was temporarily stopped before out-of-brace follow-up radiographs were taken. Both groups showed significant curve progression compared to baseline after a mean follow-up period of 3.4 years. The protocol with in-brace radiographs was noninferior regarding curve progression rate over time. The estimated monthly Cobb angle progression based on the mixed-effect model was 0.5 degrees in both groups. No interaction effect was found for time, and patients' baseline Cobb angle (p = 0.98), and for time and patients' initial in-brace correction (p = 0.32). The results of this study indicate that with both in-brace and out-of-brace protocols for radiographic follow-up, a similar rate of curve progression can be expected over time in IS patients with failed brace treatment