What’s new in lung ultrasound during the COVID-19 pandemic.

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Multicentre pilot study evaluation of lung ultrasound for the management of paediatric pneumonia in low-resource settings: a study protocol

Introduction: Pneumonia is the leading infectious cause of death among children under 5 years of age worldwide. However, pneumonia is challenging to diagnose. Lung ultrasound (LUS) is a promising diagnostic technology. Further evidence is needed to better understand the role of LUS as a tool for the diagnosis of childhood pneumonia in low-resource settings. Methods and analysis: This study aims to pilot LUS in Mozambique and Pakistan and to generate evidence regarding the use of LUS as a diagnostic tool for childhood pneumonia. Children with cough \u3c14 days with chest indrawing (n=230) and without chest indrawing (n=40) are enrolled. World Health Organization Integrated Management of Childhood Illness assessment is performed at enrolment, along with a chest radiograph and LUS examination. Respiratory and blood specimens are collected for viral and bacterial testing and biomarker assessment. Enrolled children are followed for 14 days (in person) and 30 days (phone call) post-enrolment with LUS examinations performed on Days 2, 6 and 14. Qualitative and quantitative data are also collected to assess feasibility, usability and acceptability of LUS among healthcare providers and caregivers. The primary outcome is LUS findings at enrolment with secondary outcomes including patient outcomes, repeat LUS findings, viral and bacterial test results, and patient status after 14 and 30 days of follow-up. Ethics and dissemination: This trial was approved by the Western Institutional Review Board as well as local ethics review committees at each site. We plan to disseminate study results in peer-reviewed journals and international conferences. Trial registration number: NCT03187067

Generation of induced pluripotent stem cell line, CSSi004-A (2962), from a patient diagnosed with Huntington's disease at the presymptomatic stage

Huntington's disease (HD) is an incurable, autosomal dominant, hereditary neurodegenerative disorder that typically manifests itself in midlife. This pathology is linked to the deregulation of multiple, as yet unknown, cellular processes starting before HD onset. A human iPS cell line was generated from skin fibroblasts of a subject at the presymptomatic life stage, carrying a polyglutamine expansion in HTT gene codifying Huntingtin protein. The iPSC line contained the expected CAG expansion, expressed the expected pluripotency markers, displayed in vivo differentiation potential to the three germ layers and had a normal karyotype

Towards Comprehensive Computational Representations of Arabic Multiword Expressions

A successful computational treatment of multiword expressions (MWEs) in natural languages leads to a robust NLP system which considers the long-standing problem of language ambiguity caused primarily by this complex linguistic phenomenon. The first step in addressing this challenge is building an extensive reliable MWEs language resource LR with comprehensive computational representations across all linguistic levels. This forms the cornerstone in understanding the heterogeneous linguistic behaviour of MWEs in their various manifestations. This paper presents a detailed framework for computational representations of Arabic MWEs (ArMWEs) across all linguistic levels based on the state-of-the-art lexical mark-up framework (LMF) with the necessary modifications to suit the distinctive properties of Modern Standard Arabic (MSA). This work forms part of a larger project that aims to develop a comprehensive computational lexicon of ArMWEs for NLP and language pedagogy LP (JOMAL project)

Performance of lung ultrasound in the diagnosis of pediatric pneumonia in Mozambique and Pakistan

Introduction: Improved pneumonia diagnostics are needed in low-resource settings (LRS); lung ultrasound (LUS) is a promising diagnostic technology for pneumonia. The objective was to compare LUS versus chest radiograph (CXR), and among LUS interpreters, to compare expert versus limited training with respect to interrater reliability.Methods: We conducted a prospective, observational study among children with World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) chest-indrawing pneumonia at two district hospitals in Mozambique and Pakistan, and assessed LUS and CXR examinations. The primary endpoint was interrater reliability between LUS and CXR interpreters for pneumonia diagnosis among children with WHO IMCI chest-indrawing pneumonia.Results: Interrater reliability was excellent for expert LUS interpreters, but poor to moderate for expert CXR interpreters and onsite LUS interpreters with limited training.Conclusions: Among children with WHO IMCI chest-indrawing pneumonia, expert interpreters may achieve substantially higher interrater reliability for LUS compared to CXR, and LUS showed potential as a preferred reference standard. For point-of-care LUS to be successfully implemented for the diagnosis and management of pneumonia in LRS, the clinical environment and amount of appropriate user training will need to be understood and addressed

Lung ultrasound patterns in paediatric pneumonia in Mozambique and Pakistan

Objective: Improved pneumonia diagnostics are needed, particularly in resource-constrained settings. Lung ultrasound (LUS) is a promising point-of-care imaging technology for diagnosing pneumonia. The objective was to explore LUS patterns associated with paediatric pneumonia.Methods: We conducted a prospective, observational study among children aged 2 to 23 months with World Health Organization Integrated Management of Childhood Illness chest-indrawing pneumonia and among children without fast breathing, chest indrawing or fever (no pneumonia cohort) at two district hospitals in Mozambique and Pakistan. We assessed LUS and chest radiograph (CXR) examinations, and viral and bacterial nasopharyngeal carriage, and performed a secondary analysis of LUS patterns.Results: LUS demonstrated a range of distinctive patterns that differed between children with and without pneumonia and between children in Mozambique versus Pakistan. The presence of LUS consolidation or interstitial patterns was more common in children with chest-indrawing pneumonia than in those without pneumonia. Consolidations were also more common among those with only bacterial but no viral carriage detected (50.0%) than among those with both (13.0%) and those with only virus detected (8.3%; p=0.03). LUS showed high interrater reliability among expert LUS interpreters for overall determination of pneumonia (κ=0.915), consolidation (κ=0.915) and interstitial patterns (κ=0.901), but interrater reliability between LUS and CXR for detecting consolidations was poor (κ=0.159, Pakistan) to fair (κ=0.453, Mozambique).Discussion: Pattern recognition was discordant between LUS and CXR imaging modalities. Further research is needed to define and standardise LUS patterns associated with paediatric pneumonia and to evaluate the potential value of LUS as a reference standard

Generation of induced pluripotent stem cell line, CSSi002-A (2851), from a patient with juvenile Huntington Disease

Abstract Huntington Disease (HD) is an autosomal dominant disorder characterized by motor, cognitive and behavioral features caused by a CAG expansion in the HTT gene beyond 35 repeats. The juvenile form (JHD) may begin before the age of 20 years and is associated with expanded alleles as long as 60 or more CAG repeats. In this study, induced pluripotent stem cells were generated from skin fibroblasts of a 8-year-old child carrying a large size mutation of 84 CAG repeats in the HTT gene. HD appeared at age 3 with mixed psychiatric (i.e. autistic spectrum disorder) and motor (i.e. dystonia) manifestations

Generation of the induced pluripotent stem cell line CSSi006-A (3681) from a patient affected by advanced-stage Juvenile Onset Huntington's Disease

Abstract Juvenile Onset Huntington's Disease (JOHD) is a rare variant of HD withage of onset ≤20 years, accounting for 3–10% of all HD patients. The rarity occurrence of JOHD cases, who severely progress towards mental and physical disability with atypical clinical manifestations compared to classical HD, are responsible of general lack of knowledge about this variant. We obtained a fully reprogrammed iPS cell line from fibroblasts of a JOHD patient carrying 65 CAG repeats and age at onset at age 15. At the biopsy time, the patient showed an advanced stage after 10 years of disease

Feasibility, usability and acceptability of paediatric lung ultrasound among healthcare providers and caregivers for the diagnosis of childhood pneumonia in resource-constrained settings: A qualitative study

Objectives: Paediatric pneumonia burden and mortality are highest in low-income and middle-income countries (LMIC). Paediatric lung ultrasound (LUS) has emerged as a promising diagnostic tool for pneumonia in LMIC. Despite a growing evidence base for LUS use in paediatric pneumonia diagnosis, little is known about its potential for successful implementation in LMIC. Our objectives were to evaluate the feasibility, usability and acceptability of LUS in the diagnosis of paediatric pneumonia.Design: Prospective qualitative study using semistructured interviews SETTING: Two referral hospitals in Mozambique and Pakistan PARTICIPANTS: A total of 21 healthcare providers (HCPs) and 20 caregivers were enrolled.Results: HCPs highlighted themes of limited resource availability for the feasibility of LUS implementation, including perceived high cost of equipment, maintenance demands, time constraints and limited trained staff. HCPs emphasised the importance of policymaker support and caregiver acceptance for long-term success. HCP perspectives of usability highlighted ease of use and integration into existing workflow. HCPs and caregivers had positive attitudes towards LUS with few exceptions. Both HCPs and caregivers emphasised the potential for rapid, improved diagnosis of paediatric respiratory conditions using LUS.Conclusions: This was the first study to evaluate HCP and caregiver perspectives of paediatric LUS through qualitative analysis. Critical components impacting feasibility, usability and acceptability of LUS for paediatric pneumonia diagnosis in LMIC were identified for initial deployment. Future research should explore LUS sustainability, with a particular focus on quality control, device maintenance and functionality and adoption of the new technology within the health system. This study highlights the need to engage both users and recipients of new technology early in order to adapt future interventions to the local context for successful implementation.Trial registration number: NCT03187067

Generation of induced pluripotent stem cell line CSSi008-A (4698) from a patient affected by advanced stage of Dentato-Rubral-Pallidoluysian atrophy (DRPLA)

Abstract Dentato-Rubral-pallidoluysian atrophy (DRPLA) is a rare autosomal, dominant, progressive neurodegenerative disease that causes involuntary movements, mental and emotional problems. DRPLA is caused by a mutation in the ATN1 gene that encodes for an abnormal polyglutamine stretch in the atrophin-1 protein. DRPLA is most common in the Japanese population, where it has an estimated incidence of 2 to 7 per million people. This condition has also been seen in families from North America and Europe. We obtained a reprogrammed iPSC line from a Caucasian patient with a juvenile onset of the disease, carrying 64 CAG repeat expansion in the ATN1 gene