Molecular diagnostic yield of exome sequencing in patients with congenital hydrocephalus: A systematic review and meta-analysis

IMPORTANCE: Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH). OBJECTIVE: To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH. DATA SOURCES: PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, ventriculomegaly, cerebral ventriculomegaly, primary ventriculomegaly, fetal ventriculomegaly, prenatal ventriculomegaly, molecular analysis, genetic cause, genetic etiology, genetic testing, exome sequencing, whole exome sequencing, genome sequencing, microarray, microarray analysis, and copy number variants. STUDY SELECTION: Eligible studies included those with at least 10 probands with the defining feature of CH and/or severe cerebral ventriculomegaly that had undergone ES. Studies with fewer than 10 probands, studies of mild or moderate ventriculomegaly, and studies using genetic tests other than ES were excluded. A full-text review of 68 studies was conducted by 2 reviewers. Discrepancies were resolved by consensus. DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guidelines were used by 2 reviewers to extract data. Data were synthesized using a random-effects model of single proportions. Data analysis occurred in April 2023. MAIN OUTCOMES AND MEASURES: The primary outcome was pooled diagnostic yield. Additional diagnostic yields were estimated for specific subgroups on the basis of clinical features, syndromic presentation, and parental consanguinity. For each outcome, a 95% CI and estimate of interstudy heterogeneity (I2 statistic) was reported. RESULTS: From 498 deduplicated and screened records, 9 studies with a total of 538 CH probands were selected for final inclusion. The overall diagnostic yield was 37.9% (95% CI, 20.0%-57.4%; I2 = 90.1). The yield was lower for isolated and/or nonsyndromic cases (21.3%; 95% CI, 12.8%-31.0%; I2 = 55.7). The yield was higher for probands with reported consanguinity (76.3%; 95% CI, 65.1%-86.1%; I2 = 0) than those without (16.2%; 95% CI, 12.2%-20.5%; I2 = 0). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of the diagnostic yield of ES in CH, the diagnostic yield was concordant with that of previous recommendations for other neurodevelopmental disorders, suggesting that ES should also be recommended as a routine diagnostic adjunct for patients with CH

Aesthetic resin onlay restorations: 'rationale and methods'

Resin composite restorations have gained increasing popularity over the past two decades. This has been largely driven by a patient-orientated demand for the use of aesthetic restorative materials. It has occurred concomitantly with an improvement in the mechanical properties of available materials, and advances in our knowledge of resin bonding. Onlay restorations are advocated for a plethora of clinical applications. This paper considers the role of adhesive onlay restorations fabricated in resin composite in contemporary restorative practice, including the presentation of two case reports. Clinical Relevance: This case report describes a minimally invasive, aesthetic solution to provide cuspal coverage by means of either a direct or indirect resin composite onlay restoration, respectively

Effect of multiple technologies on minimizing the residual stresses in additive manufacturing

International audienceAdditive Manufacturing (AM) is rapidly becoming the directing technology for manufacturing components in many industries, including automotive, aerospace, medical, etc. Wire-arc additive manufacturing (WAAM) technology with a higher rate of deposition is becoming prominent technology in AM. Wire-based additive manufacturing involves high heat input for melting the wire for deposition. While the component builds up in multiple layers, it involves various heating and cooling cycles, causing non-homogenous thermal loads. Due to repeated cycles, residual stresses get trapped inside the parts and lead to various defects such as cracks, deformation, warpage, the reduced life cycle of the components, etc. It is required to reduce the residual stresses to minimize the defects. This paper talks about the effect of multiple technologies such as pre-heating and compressive loading by hammering to minimize the residual stresses. Pre-heating the substrate (over which deposition takes place) will decrease the thermal gradient and thus, reduce the residual stress. Since tensile residual stresses are generated during the wire-based cladding process, which is to be nullified by applying compressive loading, a pneumatic-based setup developed in-house for imparting the compressive residual stresses was used to minimize the tensile residual stresses. In this work, four different samples were prepared; 1) as-deposited (without pre-heating and hammering), 2) deposition followed by hammering, 3) preheating then deposition, 4) Pre-heating followed by deposition and then hammering to measure the residual stress through the X-ray diffraction method. It was found that pre-heating and hammering individually minimize the residual stresses, and the combined effect has shown much reduction in tensile residual stress

Effect of multiple technologies on minimizing the residual stresses in additive manufacturing

International audienceAdditive Manufacturing (AM) is rapidly becoming the directing technology for manufacturing components in many industries, including automotive, aerospace, medical, etc. Wire-arc additive manufacturing (WAAM) technology with a higher rate of deposition is becoming prominent technology in AM. Wire-based additive manufacturing involves high heat input for melting the wire for deposition. While the component builds up in multiple layers, it involves various heating and cooling cycles, causing non-homogenous thermal loads. Due to repeated cycles, residual stresses get trapped inside the parts and lead to various defects such as cracks, deformation, warpage, the reduced life cycle of the components, etc. It is required to reduce the residual stresses to minimize the defects. This paper talks about the effect of multiple technologies such as pre-heating and compressive loading by hammering to minimize the residual stresses. Pre-heating the substrate (over which deposition takes place) will decrease the thermal gradient and thus, reduce the residual stress. Since tensile residual stresses are generated during the wire-based cladding process, which is to be nullified by applying compressive loading, a pneumatic-based setup developed in-house for imparting the compressive residual stresses was used to minimize the tensile residual stresses. In this work, four different samples were prepared; 1) as-deposited (without pre-heating and hammering), 2) deposition followed by hammering, 3) preheating then deposition, 4) Pre-heating followed by deposition and then hammering to measure the residual stress through the X-ray diffraction method. It was found that pre-heating and hammering individually minimize the residual stresses, and the combined effect has shown much reduction in tensile residual stress