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Massively parallel sequencing has markedly improved mendelian diagnostic rates. This study assessed the effects of custom alterations to a diagnostic genomic bioinformatic pipeline in response to clinical need and derived practice recommendations relative to diagnostic rates and efficiency. The Genomic Annotation and Interpretation Application (GAIA) bioinformatics pipeline was designed to detect panel, exome, and genome sample integrity and prioritize gene variants in mendelian disorders. Reanalysis of selected negative cases was performed after improvements to the pipeline. GAIA improvements and their effect on sensitivity are described, including addition of a PubMed search for gene-disease associations not in the Online Mendelian Inheritance of Man database, inclusion of a process for calling low-quality variants (known as QPatch), and gene symbol nomenclature consistency checking. The new pipeline increased the diagnostic rate and reduced staff costs, resulting in a saving of US$844.34 per additional diagnosis. Recommendations for genomic analysis pipeline requirements are summarized. Clinically responsive bioinformatics pipeline improvements increase diagnostic sensitivity and increase cost-effectiveness.

The range of diagnostic and therapeutic applications of needle arthroscopy (NA) continue to expand due to advances in image quality and resolution. Minimally invasive techniques can be augmented by the smaller camera size and reduced fluid use made possible by NA. Small-bore arthroscopy presents opportunities for use in smaller joints, such as the elbow, where applications of standard arthroscopic equipment may be limited by small anatomic spaces and fluid extravasation. In this Technical Note, we present our technique for NA-assisted treatment of terrible triad injuries, specifically in the setting of an intact radial head. The technique describes a stepwise approach to arthroscopically aided fixation of the coronoid process, followed by open reconstruction of the lateral collateral ligament complex., Technique Video Video 1 Details the described technique in a stepwise approach to arthroscopically aided fixation of the coronoid process, followed by open reconstruction of the lateral collateral ligament complex (Lateral decubitus position with left elbow with anterior medial viewing portal).

« Homme-orchestre de la chose imprimée », Jean Alessandrini a créé une œuvre variée, puisqu’il est à la fois dessinateur de caractères typographiques, illustrateur et écrivain, auteur de romans policiers et de littérature pour la jeunesse. Né le 3 août 1942 à Marseille, il étudie et travaille à Paris, avant de s’installer à Strasbourg dans les années 1990. Sa carrière est un véritable Who’s who des milieux de l’édition, du graphisme et de la typographie. Il rencontre l’affichiste Raymond Gid,...

The medial collateral ligament (MCL) is a major contributor to knee joint stability and is the most common ligament involved in knee injuries. When conservative management for high-grade MCL injuries fails, operative treatment is indicated. Various reconstruction techniques are described in the literature. The following report describes a reconstruction technique based on the modified Bosworth. We present a step-by-step technique for using autograft semitendinosus tendon as a double limb to reconstruct the MCL and if necessary, the posterior oblique ligament. The technique is versatile with respect to a spectrum of MCL injury patterns, isometric, incorporates techniques that are common to other knee reconstructions, and uses readily available autograft. It has been used extensively by the senior authors as an adjunct/augmentation to the repair of acute MCL injuries as well as in the reconstruction of chronic MCL laxity. The technique restores stability to rotation and valgus stress while maintaining the distal insertion of the semitendinosus intact.

Transgenerational immune priming is the process of increased resistance to infection in offspring due to parental pathogen exposure. Honey bees (Apis mellifera L. (Hymenoptera: Apidae)) are hosts to multiple pathogens, and this complex immune function could help protect against overwhelming infection. Honey bees have demonstrated transgenerational immune priming for the bacterial pathogen Paenibacillus larvae; however, evidence for viral transgenerational immune priming is lacking across insects in general. Here we test for the presence of transgenerational immune priming in honey bees with Deformed wing virus (DWV) by injecting pupae from DWV-exposed queens and measuring virus titer and immune gene expression. Our data suggest that there is evidence for viral transgenerational immune priming in honey bees, but it is highly context-dependent based on route of maternal exposure and potentially host genetics or epigenetic factors.

The combination of freight transport and mobility—also known as cargo-hitching—is a form of delivery that has been implemented in various modes of transport. This concept is already widely used in Europe, Africa and North America in long-distance bus transport and ensures parcel delivery via the cargo compartment of long-distance buses. This paper aims to investigate the acceptance of cargo-hitching in long-distance bus transport in Germany. For this purpose, first the term cargo-hitching is defined, and an overview of cargo-hitching concepts in long-distance bus transport worldwide is given. In the following, the principles of attitudinal acceptance are explained. A modified version of the UTAUT2 model was used as the basis for an empirical study in the form of a quantitative online survey (n = 245). The results provide information about factors influencing acceptance as well as wishes and requirements of potential users. Parts of the UTAUT2 model were verified by regression analysis. It was shown that the variables’ habit, price value, hedonic motivation, performance expectancy and social influence predict the behavioural intention to use cargo-hitching in our sample significantly (p

Varroa mite-vectored viruses such as Deformed wing virus (DWV) are of great concern for honey bee health as they can cause disease in individuals and increase colony mortality. Two genotypes of DWV (A and B) are prevalent in the United States and may have differential virulence and pathogenicity. Honey bee genetic stocks bred to resist Varroa mites also exhibit differential infection responses to the Varroa mite-vectored viruses. The goal of this project was to determine if interactions between host genotype could influence the overall infection levels and dissemination of DWV within honey bees. To do this, we injected DWV isolated from symptomatic adult bees into mite-free, newly emerged adult bees from five genetic stocks with varying levels of resistance to Varroa mites. We measured DWV-A and DWV-B dissemination among tissues chosen based on relevance to general health outcomes for 10 days. Injury from sham injections did not increase DWV-A levels but did increase DWV-B infections. DWV injection increased both DWV-A and DWV-B levels over time with significant host stock interactions. While we did not observe any differences in viral dissemination among host stocks, we found differences in virus genotype dissemination to different body parts. DWV-A exhibited the highest initial levels in heads and legs while the highest initial levels of DWV-B were found in heads and abdomens. These interactions underscore the need to evaluate viral genotype and tissue specificity in conjunction with host genotype, particularly when the host has been selected for traits relative to virus-vector and virus resistance.

Change can affect employee work behavior and well-being in a variety of ways. The mediating and moderating factors that produce these effects, however, are not fully understood. This study examines the mediating role of uncertainty on affective commitment and organizational attractiveness and assesses whether psychological empowerment can mitigate the effects of change-related uncertainty. Survey data stems from 971 young German banking sector employees during a change period. Results reveal a negative relationship between change and affective commitment as well as between change and organizational attractiveness, with both relationships mediated by uncertainty. Furthermore, empowerment does not moderate this mediation for affective commitment but does for organizational attractiveness. Thus, there are fewer negative effects of uncertainty on organizational attractiveness when psychological empowerment is high. This has several implications for practice: uncertainty should be counteracted during change processes, for example, through transparent communication, and psychological empowerment should be promoted before and during change processes.

The middle glenohumeral ligament (MGHL) is well recognized as a primary stabilizer of the shoulder. Its role in shoulder pathologies such as adhesive capsulitis, subscapularis tendon tear, and glenohumeral arthritis is less understood. Biomechanically, the MGHL plays an important role in range of motion, specifically involving normal and pathologic external rotation in less than 45° of abduction. In this Technical Note, we present a technique for arthroscopic release of the MGHL in the setting of a stable shoulder with preoperative loss of external rotation and a patient at risk for postoperative restriction of external rotation., Technique Video Video 1 The technique is described in the setting of comprehensive arthroscopic management for glenohumeral arthritis, subscapularis tendon tear, and adhesive capsulitis. In each case, arthroscopic release of the MGHL is being performed in the setting of a stable shoulder. (MGHL, middle glenohumeral ligament.)

Stratified care for low back pain (LBP) has been shown to be clinically- and cost-effective in the UK, but its transferability to the German healthcare system is unknown. This study explores LBP patients’ perspectives regarding future implementation of stratified care, through in-depth interviews (n = 12). The STarT-Back-Tool was completed by participants prior to interviews. Interview data were analysed using Grounded Theory. The overarching theme identified from the data was ‘treatment-success’, with subthemes of ‘assessment and treatment planning’, ‘acceptance of the questionnaire’ and ‘contextual factors’. Patients identified the underlying cause of pain as being of great importance (whereas STarT-Back allocates treatment based on prognosis). The integration of the STarT-Back-Tool in consultations was considered helpful as long as it does not disrupt the therapeutic relationship, and was acceptable if tool results are handled confidentially. Results indicate that for patients to find STarT-Back acceptable, the shift from a focus on identifying a cause of pain and subsequent diagnosis, to prediction-orientated treatment planning, must be made clear. Patient ‘buy in’ is important for successful uptake of clinical interventions, and findings can help to inform future strategies for implementing STarT-Back in the Germany, as well as having potential implications for transferability to other similar healthcare systems.

Developing a broader understanding of children and young people's experiences of long-term attempts of weight management may provide insight into both enablers and barriers to successful weight loss maintenance. This review aims to explore children and young people's perceptions of long-term attempts of weight management. Six databases were searched for qualitative studies describing young participants (25 years, previously or currently above a healthy weight) experiences of weight management for6 months following intentional weight loss. A thematic synthesis was undertaken. Themes were interpreted using the Socio-ecological Model. Factors supporting attempts to maintain weight loss included having clear motivation for change; developing personal skills to manage the challenges of change; family support/dynamics that encourage healthy lifestyles; and health-promoting cultures in schools/workplaces, communities, and the broader living environment. Conversely, ambivalence, difficulty coping with changes, peer pressure, challenging family dynamics, limited professional support, and unhealthy living environments were barriers to maintaining behavior change. These facilitators and barriers at each level of the Socio-ecological Model informed a model of weight loss maintenance for children and young people. Supporting children, young people, and families to develop the skills to manage the individual, social, and environmental challenges that shape attempts of long-term weight management will help to support their ability to manage their weight long term.

Massively parallel sequencing has markedly improved mendelian diagnostic rates. This study assessed the effects of custom alterations to a diagnostic genomic bioinformatic pipeline in response to clinical need and derived practice recommendations relative to diagnostic rates and efficiency. The Genomic Annotation and Interpretation Application (GAIA) bioinformatics pipeline was designed to detect panel, exome, and genome sample integrity and prioritize gene variants in mendelian disorders. Reanalysis of selected negative cases was performed after improvements to the pipeline. GAIA improvements and their effect on sensitivity are described, including addition of a PubMed search for gene-disease associations not in the Online Mendelian Inheritance of Man database, inclusion of a process for calling low-quality variants (known as QPatch), and gene symbol nomenclature consistency checking. The new pipeline increased the diagnostic rate and reduced staff costs, resulting in a saving of US$844.34 per additional diagnosis. Recommendations for genomic analysis pipeline requirements are summarized. Clinically responsive bioinformatics pipeline improvements increase diagnostic sensitivity and increase cost-effectiveness.

Olivine is an important mineral phase in naturally cooled basaltic rocks. The texture and composition of olivine are strictly related to the interplay between the degree of magma undercooling and crystal growth rate. Crystals formed at low undercoolings and growth rates generally show polyhedral-hopper textures and quite homogeneous compositions, while skeletal-dendritic textures and evident crystal zonations occur at high undercoolings and growth rates. In this context, we have performed equilibrium and disequilibrium (i.e., cooling rate) experiments to better understand, by a comparatively approach, the effects of crystallization kinetics on the incorporation of major and trace cations in olivine lattice. The experiments were carried out in a 1 atm vertical tube CO-CO2 gas-mixing furnace to perform experiment at atmospheric pressure and oxygen fugacity of QFM-2 using a basaltic glass (i.e., OIB) as starting materials. The equilibrium experiment was performed at 1175 °C. These target temperatures were kept constant for 240 h and then quenched. Conversely, the disequilibrium experiments were performed at the superliquidus temperature of 1250, and 1300 °C, which was kept constant for 2 h before cooling. The final target temperatures of 1150 (undercooling -ΔT = 50 °C), and 1175 °C (-ΔT = 25 °C) were attained by applying cooling rates of 2 °C/h, 20 °C/h, and 60 °C/h. Then the experimental charges were quenched. Results show that the olivine texture shifts from euhedral (i.e., equilibrium) to anhedral (i.e., disequilibrium) under the effect of cooling rate and rapid crystal growth. In equilibrium experiments, the composition of olivine is homogeneous and non chemical gradients are found in the melt next to the crystal surface. In contrast, a diffusive boundary layer develops in the melt surrounding the olivine crystals growing rapidly under the effect of cooling rate and degree of undercooling. The compositional gradient in the melt increases with increasing cooling rate and undercooling, causing the diffusive boundary layer to expand towards the far field melt. Because of the effects of crystallization kinetics, skeletal-dendritic olivines incorporates higher proportions of major and trace elements that are generally incompatible within their crystal lattice under equilibrium conditions.

Purpose The purpose of this paper is to present proposed solutions and interventions to some of the major barriers to providing adequate access to healthcare in Kenya. Specific business models are proposed to improve access to quality healthcare in low- and middle-income countries. Finally, strategies are developed for the retail clinic concept (RCC). Design/methodology/approach Google Scholar, PubMed and EBSCOhost were among the databases used to collect articles relevant to the purpose in Kenya. Various governmental and news articles were collected from Google searches. Relevant business models from other sectors were considered for potential application to healthcare and the retail clinic concept. Findings After a review of current methodologies and approaches to business and franchising models in various settings, the most relevant models are proposed as solutions to improving quality healthcare in Kenya through the RCC. For example, authors reviewed physician recruitment strategies, insurance plans and community engagement. The paper is informed by existing literature and reports as well as key informants. Research limitations/implications This paper lacks primary data collection within Kenya and is limited to a brief scoping review of literature. The findings provide effective strategies for various business and franchising models in healthcare. Originality/value The assembling of relevant information specific to Kenya and potential business models provides effective means of improving health delivery through business and franchising, focusing on innovative approaches and models that have proven effective in other settings.

Sarah Lang outlines the vaccines travellers require for going abroad in what is an ever-evolving area of practice

In order to elucidate the kinetic partitioning of cations between olivine and basalt, we performed undercooling (−ΔT) and cooling rate (CR) experiments at atmospheric pressure and QFM-2 buffer. Starting from the superliquidus temperature of 1250 °C, a Hawaiian tholeiitic basalt was cooled at the rates of 4 (CR4), 20 (CR20), and 60 (CR60) °C/h to the final target temperatures of 1175 °C (−ΔT = 35 °C; −ΔT35) and 1125 °C (−ΔT = 85 °C; −ΔT85). Results show that polyhedral olivine morphologies are obtained at -ΔT35, whereas strong disequilibrium skeletal and/or dendritic textures form at -ΔT85. The amount of forsterite in olivine decreases from to 85% to 78% with increasing both -ΔT and CR. A diffusive boundary layer also develops in the melt next to the olivine surface and its composition becomes progressively enriched in Ca, owing to its incompatible behavior with the lattice site. Residual melts are progressively depleted in silica and enriched in alkali from CR4 to CR60, but silica-rich melts are observed with increasing -ΔT. In terms of Fe2+-Mg exchange, olivines obtained at -ΔT35 are always in equilibrium with the diffusive boundary layer, comprising both the interface melt next to the olivine surface and the far-field melt where all chemical gradients cease. At -ΔT85, however, the Fe2+-Mg exchange indicates two distinct equilibration stages between olivine core and far-field melt, and between olivine rim and interface melt. Partition coefficients (Kd) of Mg, Fe, Mn, Ca, and Cr calculated at the olivine-melt interface preferentially change as a function of -ΔT rather than CR. From -ΔT35 to -ΔT85, KdMg, KdFe, KdMn, and KdCr remarkably increase, whereas the opposite applies to KdCa. Through the application of equilibrium partitioning models, we found that Mg, Fe, Mn, and Ca are incorporated into the olivine lattice site at near-equilibrium proportions. This generally good agreement with modeling data demonstrates that diffusive mass transport of cations in our experiments occurred under the conditions of local equilibrium at the olivine surface. In contrast, marked deviations from the expected equilibrium are found for KCr in response to the major influence of crystal field stabilization energy on cation incorporation.

// Sarah Lang 1 , Hauke Busch 2, 3 , Melanie Boerries 3, 4 , Tilman Brummer 3, 4, 5 , Sylvia Timme 6 , Silke Lassmann 4, 5, 6 , Klaus Aktories 1 and Gudula Schmidt 1 1 Institute for Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany 2 Lubeck Institute of Experimental Dermatology, Institute for Cardiogenetics, University of Lubeck, Lubeck, Germany 3 Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, Freiburg, Germany 4 German Cancer Consortium (DKTK), Freiburg, Germany, German Cancer Research Center (DKFZ), Heidelberg, Germany 5 Center for Biological Signalling Studies (BIOSS), University of Freiburg, Freiburg, Germany 6 Institute for Surgical Pathology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany Correspondence to: Gudula Schmidt, email: Gudula.Schmidt@pharmakol.uni-freiburg.de Keywords: Rho GTPase, invasion, cyclooxygenase, breast cancer Received: June 14, 2017 Accepted: August 26, 2017 Published: September 16, 2017 ABSTRACT Rho GTPases are regulators of many cellular functions and are often dysregulated in cancer. However, the precise role of Rho proteins for tumor development is not well understood. In breast cancer, overexpression of RhoC is linked with poor prognosis. Here, we aim to compare the function of RhoC and its homolog family member RhoA in breast cancer progression. We established stable breast epithelial cell lines with inducible expression of RhoA and RhoC, respectively. Moreover, we made use of Rho-activating bacterial toxins (Cytotoxic Necrotizing Factors) to stimulate the endogenous pool of Rho GTPases in benign breast epithelial cells and simultaneously knocked down specific Rho proteins. Whereas activation of Rho GTPases was sufficient to induce an invasive phenotype in three-dimensional culture systems, overexpression of RhoA or RhoC were not. However, RhoC but not RhoA was required for invasion, whereas RhoA and RhoC equally regulated proliferation. We further identified downstream target genes of RhoC involved in invasion and identified PTGS2 (COX-2) being preferentially upregulated by RhoC. Consistently, the COX-2 inhibitor Celecoxib blocked the invasive phenotype induced by the Rho-activating toxins.

Multiple studies have shown that genomic testing has a high diagnostic yield and an impact on clinical management for patients with suspected genetic conditions. Therefore, there has been a push worldwide to apply rapid genomic sequencing in critically ill neonatal and pediatric patients. The goal of this study was to investigate the practicality of applying ultrarapid genomic testing for critically ill neonatal and pediatric patients with suspected monogenic conditions in Australia. The study recruited a total of 108 patients prospectively from March 2018 to February 2019, and data were collected until May 2019. Of the 12 hospitals that acted as collaborating sites, 5 were women's hospitals, 3 women's and children's hospitals, and 4 children's hospitals. Eligible patients included those who were admitted to a neonatal or pediatric intensive care unit (NICU or PICU) and were referred to clinical genetics for a possible monogenic condition. Chromosomal microarray was a requirement before enrollment if there was a suspected chromosomal condition. Chromosomal microarrays were performed concurrently with ultrarapid exome sequencing when the probability of a positive result on microarray was low. Additionally, rapid mitochondrial genome sequencing was performed alongside ultrarapid exome sequencing if a mitochondrial condition was suspected. When possible, ultrarapid exome sequencing was performed in both parents as well as the child (trio). The primary outcome of this study measured the time from the last sample received to the ultrarapid exome sequencing report finalized. Other outcomes measured were the diagnostic yield, change in clinical management after the report was finalized, number of reports returned before hospital discharge, and time from admission to the report being finalized. Of the 108 patients enrolled, the median age was 28 days, with a range of 0 days to 17 years. Overall, 34% were female, 57% were NICU admissions, 33% were PICU admissions, and 9% were from other hospital wards. The mean time it took from the last sample received to the report being issued was 3.3 days (95% confidence interval [CI], 3.2-3.5 days). The mean time from hospital admission to the sequencing report being finalized was 17.5 days (95% CI, 14.6-21.1 days). The mean time from hospital admission to clinical genetics referral was 8.1 days (95% CI, 6.0-10.8 days). Overall, 94% of reports were issued within the goal of 5 calendar days, and 56 molecular diagnoses were made for 55 patients (51%). Among the 62 patients in the NICU, 35 had a clear molecular diagnosis from ultrarapid exome sequencing (56%), whereas in the 36 PICU patients, 17 had a clear molecular diagnosis (47%), and in the 10 patients from other hospital wards, 3 had a clear molecular diagnosis (30%). After the ultrarapid exome sequencing report was finalized, clinical management changed for 48 of the 108 patients enrolled (44%). Overall, the ultrarapid sequencing reports that revealed a clear molecular diagnosis were regarded as “very useful” or “useful” by referring providers in 52 of 55 cases (95%) and “neutral” in 3 of 55 cases (5%). Negative reports were regarded as “very useful” or “useful” in 31 of 53 cases (58%), “neutral” in 20 of 53 cases, and “not useful” in 2 of 53 cases (4%). Altogether, this study demonstrates the utility of ultrarapid exome sequencing in critically ill pediatric patients with a suspected monogenic condition in Australia. Refereed/Peer-reviewed

Problem A recognised gap exists between current and recommended practices in the provision of lifestyle advice and weight management support for women across preconception and pregnancy care. Background Preconception and pregnancy are critical stages for promoting healthy maternal lifestyles and obesity prevention. Co-design is a novel approach with the potential to strengthen existing models of care to facilitate the implementation of clinical practice guidelines promoting preconception and pregnancy health, especially in relation to preconception weight management and preventing excessive gestational weight gain. Aim and methods The aims of this discussion paper are to (i) define co-design in the context of preconception and pregnancy care, (ii) outline key considerations when planning co-design initiatives and (iii) describe co-design opportunities in preconception and pregnancy care for promoting women’s health and obesity prevention. Discussion While several definitions of co-design exist, one critical element is the meaningful involvement of all key stakeholders. In this discussion, we specifically identified the involvement of women and expanding the role of practice nurses in primary care may assist to overcome barriers to the provision of healthy lifestyle advice and support for women during preconception. Co-designing pregnancy care will involve input from women, nurses, midwives, obstetricians, allied health and administration and management staff. Additional attention is required to co-design care for women considered most at-risk. Conclusion There is potential to enhance current provision of preconception and pregnancy care using co-design. Nursing and midwifery professions are active across both preconception and pregnancy and therefore, they have an important role to play.

Background Intermittent energy restriction (IER) has shown early success in adolescents with obesity, however efficacy trials are needed. This study aims to determine if IER results in lower body mass index (BMI) z-score after 52 weeks in metabolically unhealthy adolescents with obesity compared with continuous energy restriction (CER). Methods/design This is a prospective, randomised, multi-centre trial conducted in tertiary care settings, with three phases: jumpstart (weeks 0–4); intensive intervention (weeks 5–16); continued intervention and/or maintenance (weeks 17–52). During the jumpstart phase, all participants follow a very low energy diet (∼800 kcal/3350 kJ/day), then transition to their allocated intervention: IER or CER. IER involves three energy-restricted days/week, consuming one-third of daily energy requirements (∼600−700 kcal/2500−2950 kJ/day), and four days/week of a healthy meal plan. The CER, which is current standard care, has individually tailored energy prescription based on age and sex (13–14 years, 1430−1670 kcal/6000−7000 kJ/day; 15–17 years, 1670−1900 kcal/7000−8000 kJ/day). The study will recruit 186 (93 per arm) treatment-seeking adolescents aged 13–17 years with obesity and at least one metabolic co-morbidity. The primary outcome is change in BMI z-score at 52 weeks. Secondary outcomes are changes at 4, 16 and 52 weeks in: body composition; diet quality, food choices and food patterns; cardio-metabolic risk factors; physical activity and sedentary behaviour; sleep and psycho-behavioural measures. Discussion This study challenges existing clinical paradigms that CER is the only method for weight management in metabolically unhealthy adolescents. If successful, IER may offer an alternate medical nutrition therapy approach for those seeking treatment in tertiary settings. Clinical trial registration number ACTRN12617001630303.

IMPORTANCE: Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems.OBJECTIVE: To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system.DESIGN, SETTING, AND PARTICIPANTS: Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination,distributed leadership, and collective learning was used to facilitate adoption.EXPOSURES Ultra-rapid exome sequencing.MAIN OUTCOMES AND MEASURES: The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge RESULTS: The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The meantime from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI,3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing–based copy number analysis, use of international databases to identify novel gene–disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%)without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients(11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%).CONCLUSIONS AND RELEVANCE: This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings. Refereed/Peer-reviewed