Joint cluster reconstructions: Combining free-form lensing and X-rays

Galaxy clusters provide a multitude of observational data across wavelengths and their structure and morphology are of considerable interest in cosmology as well as astrophysics. We develop a framework that allows the combination of lensing and non-lensing observations in a free-form and mesh-free approach to infer the projected mass distribution of individual galaxy clusters. This method can be used to test common assumptions on the morphology of clusters in parametric models. We make use of the lensing reconstruction code SaWLens2 and expand its capabilities by incorporating an estimate of the projected gravitational potential based on X-ray data that are deprojected using the local Richardson-Lucy method and used to infer the Newtonian potential of the cluster and we discuss how potentially arising numerical artefacts can be treated. We demonstrate the feasibility of our method on a simplified mock NFW halo and on a cluster from a realistic hydrodynamical simulation and show how the combination of X-ray and weak lensing data can affect a free-form reconstruction, improving the accuracy in the central region in some cases by a factor of two.Comment: 14 pages, 19 figures, submitted to A&A; revised to match the accepted versio

Reconstructing phylogenetic level-1 networks from nondense binet and trinet sets

Binets and trinets are phylogenetic networks with two and three leaves, respectively. Here we consider the problem of deciding if there exists a binary level-1 phylogenetic network displaying a given set T of binary binets or trinets over a taxon set X, and constructing such a network whenever it exists. We show that this is NP-hard for trinets but polynomial-time solvable for binets. Moreover, we show that the problem is still polynomial-time solvable for inputs consisting of binets and trinets as long as the cycles in the trinets have size three. Finally, we present an O(3^{|X|} poly(|X|)) time algorithm for general sets of binets and trinets. The latter two algorithms generalise to instances containing level-1 networks with arbitrarily many leaves, and thus provide some of the first supernetwork algorithms for computing networks from a set of rooted 1 phylogenetic networks

Feasibility of cardiopulmonary exercise testing using a robotics-assisted tilt tabele in dependent-ambulatory stroke patients

BACKGROUND: We evaluated the feasibility of an augmented robotics-assisted tilt table (RATT) for incremental cardiopulmonary exercise testing (CPET) and exercise training in dependent-ambulatory stroke patients. METHODS: Stroke patients (Functional Ambulation Category ≤ 3) underwent familiarization, an incremental exercise test (IET) and a constant load test (CLT) on separate days. A RATT equipped with force sensors in the thigh cuffs, a work rate estimation algorithm and real-time visual feedback to guide the exercise work rate was used. Feasibility assessment considered technical feasibility, patient tolerability, and cardiopulmonary responsiveness. RESULTS: Eight patients (4 female) aged 58.3 ± 9.2 years (mean ± SD) were recruited and all completed the study. For IETs, peak oxygen uptake (V'O(2peak)), peak heart rate (HR(peak)) and peak work rate (WR(peak)) were 11.9 ± 4.0 ml/kg/min (45 % of predicted V'O(2max)), 117 ± 32 beats/min (72 % of predicted HR(max)) and 22.5 ± 13.0 W, respectively. Peak ratings of perceived exertion (RPE) were on the range "hard" to "very hard". All 8 patients reached their limit of functional capacity in terms of either their cardiopulmonary or neuromuscular performance. A ventilatory threshold (VT) was identified in 7 patients and a respiratory compensation point (RCP) in 6 patients: mean V'O(2) at VT and RCP was 8.9 and 10.7 ml/kg/min, respectively, which represent 75 % (VT) and 85 % (RCP) of mean V'O(2peak). Incremental CPET provided sufficient information to satisfy the responsiveness criteria and identification of key outcomes in all 8 patients. For CLTs, mean steady-state V'O(2) was 6.9 ml/kg/min (49 % of V'O(2) reserve), mean HR was 90 beats/min (56 % of HR(max)), RPEs were > 2, and all patients maintained the active work rate for 10 min: these values meet recommended intensity levels for bouts of training. CONCLUSIONS: The augmented RATT is deemed feasible for incremental cardiopulmonary exercise testing and exercise training in dependent-ambulatory stroke patients: the approach was found to be technically implementable, acceptable to the patients, and it showed substantial cardiopulmonary responsiveness. This work has clinical implications for patients with severe disability who otherwise are not able to be tested

Association of growth with neurodevelopment in extremely low gestational age infants: a population-based analysis.

To assess the association between postnatal growth and neurodevelopment at the age of 2 years in extremely low gestational age newborns (ELGAN, < 28 weeks' gestation). Retrospective population-based cohort study including all live born ELGAN in 2006-2012 in Switzerland. Growth parameters (weight, length, head circumference, body mass index) were assessed at birth, at hospital discharge home, and 2-year follow-up (FU2). Unadjusted and adjusted regression models assessed associations between growth (birth to hospital discharge and birth to FU2) and neurodevelopment at FU2. A total of 1244 infants (mean GA 26.5 ± 1.0 weeks, birth weight 853 ± 189 g) survived to hospital discharge and were included in the analyses. FU2 was documented for 1049 (84.3%) infants. The mean (± SD) mental and a psychomotor development index at 2FU were 88.9 (± 18.0) and 86.9 (± 17.7), respectively. Moderate or severe neurodevelopmental impairment was documented in 23.2% of patients. Changes of z-scores between birth and discharge and between birth and FU2 for weight were - 1.06 (± 0.85) and - 0.140 (± 1.15), for length - 1.36 (± 1.34), and - 0.40 (± 1.33), for head circumference - 0.61 (± 1.04) and - 0.76 (± 1.32) as well as for BMI 0.22 (± 3.36) and - 0.006 (± 1.45). Unadjusted and adjusted analyses showed that none of the four growth parameters was significantly associated with any of the three outcome parameters of neurodevelopment. This was consistent for both time intervals. CONCLUSION In the present population-based cohort of ELGAN, neither growth between birth and hospital discharge nor between birth and FU2 were significantly associated with neurodevelopment at age of 2 years. WHAT IS KNOWN • Studies assessing the association between growth and neurodevelopment in extremely low gestational age newborns (28 weeks' gestation) show conflicting results. WHAT IS NEW • Neither growth between birth and hospital discharge nor between birth and corrected age of 2 years were significantly associated with neurodevelopment at age of 2 years. • The role of postnatal growth as a predictor of neurodevelopmental outcome during infancy might be smaller than previously assumed

Association of growth with neurodevelopment in extremely low gestational age infants: a population-based analysis

To assess the association between postnatal growth and neurodevelopment at the age of 2 years in extremely low gestational age newborns (ELGAN, < 28 weeks' gestation). Retrospective population-based cohort study including all live born ELGAN in 2006-2012 in Switzerland. Growth parameters (weight, length, head circumference, body mass index) were assessed at birth, at hospital discharge home, and 2-year follow-up (FU2). Unadjusted and adjusted regression models assessed associations between growth (birth to hospital discharge and birth to FU2) and neurodevelopment at FU2. A total of 1244 infants (mean GA 26.5 ± 1.0 weeks, birth weight 853 ± 189 g) survived to hospital discharge and were included in the analyses. FU2 was documented for 1049 (84.3%) infants. The mean (± SD) mental and a psychomotor development index at 2FU were 88.9 (± 18.0) and 86.9 (± 17.7), respectively. Moderate or severe neurodevelopmental impairment was documented in 23.2% of patients. Changes of z-scores between birth and discharge and between birth and FU2 for weight were - 1.06 (± 0.85) and - 0.140 (± 1.15), for length - 1.36 (± 1.34), and - 0.40 (± 1.33), for head circumference - 0.61 (± 1.04) and - 0.76 (± 1.32) as well as for BMI 0.22 (± 3.36) and - 0.006 (± 1.45). Unadjusted and adjusted analyses showed that none of the four growth parameters was significantly associated with any of the three outcome parameters of neurodevelopment. This was consistent for both time intervals. CONCLUSION In the present population-based cohort of ELGAN, neither growth between birth and hospital discharge nor between birth and FU2 were significantly associated with neurodevelopment at age of 2 years. WHAT IS KNOWN • Studies assessing the association between growth and neurodevelopment in extremely low gestational age newborns (28 weeks' gestation) show conflicting results. WHAT IS NEW • Neither growth between birth and hospital discharge nor between birth and corrected age of 2 years were significantly associated with neurodevelopment at age of 2 years. • The role of postnatal growth as a predictor of neurodevelopmental outcome during infancy might be smaller than previously assumed

Biallelic KIF24 Variants Are Responsible for a Spectrum of Skeletal Disorders Ranging From Lethal Skeletal Ciliopathy to Severe Acromesomelic Dysplasia

Skeletal dysplasias comprise a large spectrum of mostly monogenic disorders affecting bone growth, patterning, and homeostasis, and ranging in severity from lethal to mild phenotypes. This study aimed to underpin the genetic cause of skeletal dysplasia in three unrelated families with variable skeletal manifestations. The six affected individuals from three families had severe short stature with extreme shortening of forelimbs, short long-bones, and metatarsals, and brachydactyly (family 1); mild short stature, platyspondyly, and metaphyseal irregularities (family 2); or a prenatally lethal skeletal dysplasia with kidney features suggestive of a ciliopathy (family 3). Genetic studies by whole genome, whole exome, and ciliome panel sequencing identified in all affected individuals biallelic missense variants in KIF24, which encodes a kinesin family member controlling ciliogenesis. In families 1 and 3, with the more severe phenotype, the affected subjects harbored homozygous variants (c.1457A>G; p.(Ile486Val) and c.1565A>G; p.(Asn522Ser), respectively) in the motor domain which plays a crucial role in KIF24 function. In family 2, compound heterozygous variants (c.1697C>T; p.(Ser566Phe)/c.1811C>T; p.(Thr604Met)) were found C-terminal to the motor domain, in agreement with a genotype-phenotype correlation. In vitro experiments performed on amnioblasts of one affected fetus from family 3 showed that primary cilia assembly was severely impaired, and that cytokinesis was also affected. In conclusion, our study describes novel forms of skeletal dysplasia associated with biallelic variants in KIF24. To our knowledge this is the first report implicating KIF24 variants as the cause of a skeletal dysplasia, thereby extending the genetic heterogeneity and the phenotypic spectrum of rare bone disorders and underscoring the wide range of monogenetic skeletal ciliopathies. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).Peer reviewe

NovelRPL13Variants and Variable Clinical Expressivity in a Human Ribosomopathy With Spondyloepimetaphyseal Dysplasia

Spondyloepimetaphyseal dysplasias (SEMDs) are a heterogeneous group of disorders with variable growth failure and skeletal impairments affecting the spine and long bone epiphyses and metaphyses. Here we report on four unrelated families with SEMD in which we identified two monoallelic missense variants and one monoallelic splice site variant inRPL13, encoding the ribosomal protein eL13. In two out of four families, we observed autosomal dominant inheritance with incomplete penetrance and variable clinical expressivity; the phenotypes of the mutation-positive subjects ranged from normal height with or without hip dysplasia to severe SEMD with severe short stature and marked skeletal dysplasia.In vitrostudies on patient-derived dermal fibroblasts harboringRPL13missense mutations demonstrated normal eL13 expression, with proper subcellular localization but reduced colocalization with eL28 (p<0.001). Cellular functional defects in fibroblasts from mutation-positive subjects indicated a significant increase in the ratio of 60S subunits to 80S ribosomes (p= 0.007) and attenuated global translation (p= 0.017). In line with the human phenotype, ourrpl13mutant zebrafish model, generated by CRISPR-Cas9 editing, showed cartilage deformities at embryonic and juvenile stages. These findings extend the genetic spectrum ofRPL13mutations causing this novel human ribosomopathy with variable skeletal features. Our study underscores for the first time incomplete penetrance and broad phenotypic variability in SEMD-RPL13 type and confirms impaired ribosomal function. Furthermore, the newly generatedrpl13mutant zebrafish model corroborates the role of eL13 in skeletogenesis. (c) 2020 The Authors.Journal of Bone and Mineral Researchpublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..Peer reviewe

A Survey of Combinatorial Methods for Phylogenetic Networks

The evolutionary history of a set of species is usually described by a rooted phylogenetic tree. Although it is generally undisputed that bifurcating speciation events and descent with modifications are major forces of evolution, there is a growing belief that reticulate events also have a role to play. Phylogenetic networks provide an alternative to phylogenetic trees and may be more suitable for data sets where evolution involves significant amounts of reticulate events, such as hybridization, horizontal gene transfer, or recombination. In this article, we give an introduction to the topic of phylogenetic networks, very briefly describing the fundamental concepts and summarizing some of the most important combinatorial methods that are available for their computation

Development and Validation of an Internationally-Standardized, High-Resolution Capillary Gel-Based Electrophoresis PCR-Ribotyping Protocol for Clostridium difficile

PCR-ribotyping has been adopted in many laboratories as the method of choice for C. difficile typing and surveillance. However, issues with the conventional agarose gel-based technique, including inter-laboratory variation and interpretation of banding patterns have impeded progress. The method has recently been adapted to incorporate high-resolution capillary gel-based electrophoresis (CE-ribotyping), so improving discrimination, accuracy and reproducibility. However, reports to date have all represented single-centre studies and inter-laboratory variability has not been formally measured or assessed. Here, we achieved in a multi-centre setting a high level of reproducibility, accuracy and portability associated with a consensus CE-ribotyping protocol. Local databases were built at four participating laboratories using a distributed set of 70 known PCR-ribotypes. A panel of 50 isolates and 60 electronic profiles (blinded and randomized) were distributed to each testing centre for PCR-ribotype identification based on local databases generated using the standard set of 70 PCR-ribotypes, and the performance of the consensus protocol assessed. A maximum standard deviation of only ±3.8bp was recorded in individual fragment sizes, and PCR-ribotypes from 98.2% of anonymised strains were successfully discriminated across four ribotyping centres spanning Europe and North America (98.8% after analysing discrepancies). Consensus CE-ribotyping increases comparability of typing data between centres and thereby facilitates the rapid and accurate transfer of standardized typing data to support future national and international C. difficile surveillance programs