ALIXE: a phase-combination tool for fragment-based molecular replacement.

Fragment-based molecular replacement exploits the use of very accurate yet incomplete search models. In the case of the ARCIMBOLDO programs, consistent phase sets produced from the placement and refinement of fragments with Phaser can be combined in order to increase their signal before proceeding to the step of density modification and autotracing with SHELXE. The program ALIXE compares multiple phase sets, evaluating mean phase differences to determine their common origin, and subsequently produces sets of combined phases that group consistent solutions. In this work, its use on different scenarios of very partial molecular-replacement solutions and its performance after the development of a much-optimized set of algorithms are described. The program is available both standalone and integrated within the ARCIMBOLDO programs. ALIXE has been analysed to identify its rate-limiting steps while exploring the best parameterization to improve its performance and make this software efficient enough to work on modest hardware. The algorithm has been parallelized and redesigned to meet the typical landscape of solutions. Analysis of pairwise correlation between the phase sets has also been explored to test whether this would provide additional insight. ALIXE can be used to exhaustively analyse all partial solutions produced or to complement those already selected for expansion, and also to reduce the number of redundant solutions, which is particularly relevant to the case of coiled coils, or to combine partial solutions from different programs. In each case parallelization and optimization to provide speedup makes its use amenable to typical hardware found in crystallography. ARCIMBOLDO_BORGES and ARCIMBOLDO_SHREDDER now call on ALIXE by default

ALIXE: a phase-combination tool for fragment-based molecular replacement.

Fragment-based molecular replacement exploits the use of very accurate yet incomplete search models. In the case of the ARCIMBOLDO programs, consistent phase sets produced from the placement and refinement of fragments with Phaser can be combined in order to increase their signal before proceeding to the step of density modification and autotracing with SHELXE. The program ALIXE compares multiple phase sets, evaluating mean phase differences to determine their common origin, and subsequently produces sets of combined phases that group consistent solutions. In this work, its use on different scenarios of very partial molecular-replacement solutions and its performance after the development of a much-optimized set of algorithms are described. The program is available both standalone and integrated within the ARCIMBOLDO programs. ALIXE has been analysed to identify its rate-limiting steps while exploring the best parameterization to improve its performance and make this software efficient enough to work on modest hardware. The algorithm has been parallelized and redesigned to meet the typical landscape of solutions. Analysis of pairwise correlation between the phase sets has also been explored to test whether this would provide additional insight. ALIXE can be used to exhaustively analyse all partial solutions produced or to complement those already selected for expansion, and also to reduce the number of redundant solutions, which is particularly relevant to the case of coiled coils, or to combine partial solutions from different programs. In each case parallelization and optimization to provide speedup makes its use amenable to typical hardware found in crystallography. ARCIMBOLDO_BORGES and ARCIMBOLDO_SHREDDER now call on ALIXE by default

Serum Beta-D-Glucan in the Diagnosis of Invasive Fungal Disease in Neonates, Children and Adolescents: A Critical Analysis of Current Data

β-D-glucan (BDG) is a cell wall component of many pathogenic fungi. The detection of BDG as an assay is clinically broadly used as a diagnostic tool. However, the current data on BDG in paediatrics are limited, prompting specific considerations about when BDG can be used in neonates and children. We aimed to analyse the available data for the use of serum BDG in neonates and immunocompromised children and adolescents; as well as to understand the extent and characteristics of the use of BDG in children in Europe

Cerebrospinal Fluid System Infection in Children with Cancer: A Retrospective Analysis over 14 Years in a Major European Pediatric Cancer Center

Infection of a cerebrospinal fluid system is a serious medical complication. We performed a retrospective monocentric analysis on temporary and permanent cerebrospinal fluid devices in children with and without cancer, covering a period of over 14 years. Between 2004 and 2017, 275 children with a cerebrospinal fluid system were seen at our institution. Thirty-eight children suffered from 51 microbiologically proven infectious episodes of the cerebrospinal fluid system (12 children with cancer and 26 children without cancer). Independently of the cerebrospinal fluid system used, the incidence of infection did not significantly differ between children with and without cancer and was the highest in children younger than one year. Infection occurred earlier in external ventricular drain (EVD) than ventriculoperitoneal (VP) shunt, and in EVD significantly earlier in children with cancer compared with patients without cancer. The pathogens isolated were mainly Gram-positive bacteria, in particular Staphylococcus spp., which should be taken into account for empirical antimicrobial therapy