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Learning outcomes This case study aims to ensure that, students should be able to recognise the behaviours that influence the in-member out-member categorisation that transpires in the workplace, both from the leader’s perspective and that of the followers; determine and understand the relevance of forming interpersonal relationships in the workplace and that interpersonal relationships create fundamentally positive or negative work experiences and impact on career opportunities in the workplace; gain an understanding of the internal bias and subjective comfort that leaders must actively overcome to establish an environment in which the entire team becomes in-group members; and be able to assess the contextual variables that contribute to the negative or positive aggravation of the leader–member exchange. Case overview/synopsis It was 16 October 2014, and Nonkululeko Gobodo, Executive Chair of accounting firm SizweNtsalubaGobodo, was looking to her younger sister, Notemba Dlova, for emotional support, as she sought to address an important issue that was on the agenda of the firm’s board of directors’ meeting the following day. Tensions between her and Victor Sekese, Chief Executive Officer of the firm, were mounting, and a number of the directors were unhappy with the status quo. “How do you think I should address the issue?” she asked Dlova. Both sisters knew that at stake was Gobodo’s future at the firm she had battled so hard to build up in the face of racial and gender stereotypes. Complexity academic level The case study is appropriate for use in a range of postgraduate courses aimed at Master’s in Management and Master of Business Administration (MBA)-level students. It is also suitable for use in postgraduate diplomas in business and executive education short courses. Supplementary materials Teaching notes are available for educators only. Subject code CSS 6: Human Resource Management.

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Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an “intrinsic” spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management.Significance:Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion–positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related video: https://vimeo.com/438254885See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890

Summary Background Marked variation exists in the use of genomic data in tumour diagnosis, and optimal integration with conventional diagnostic technology remains uncertain despite several studies reporting improved diagnostic accuracy, selection for targeted treatments, and stratification for trials. Our aim was to assess the added value of molecular profiling in routine clinical practice and the impact on conventional and experimental treatments. Methods This population-based study assessed the diagnostic and clinical use of DNA methylation-based profiling in childhood CNS tumours using two large national cohorts in the UK. In the diagnostic cohort—which included routinely diagnosed CNS tumours between Sept 1, 2016, and Sept 1, 2018—we assessed how the methylation profile altered or refined diagnosis in routine clinical practice and estimated how this would affect standard patient management. For the archival cohort of diagnostically difficult cases, we established how many cases could be solved using modern standard pathology, how many could only be solved using the methylation profile, and how many remained unsolvable. Findings Of 484 patients younger than 20 years with CNS tumours, 306 had DNA methylation arrays requested by the neuropathologist and were included in the diagnostic cohort. Molecular profiling added a unique contribution to clinical diagnosis in 107 (35%; 95% CI 30–40) of 306 cases in routine diagnostic practice—providing additional molecular subtyping data in 99 cases, amended the final diagnosis in five cases, and making potentially significant predictions in three cases. We estimated that it could change conventional management in 11 (4%; 95% CI 2–6) of 306 patients. Among 195 historically difficult-to-diagnose tumours in the archival cohort, 99 (51%) could be diagnosed using standard methods, with the addition of methylation profiling solving a further 34 (17%) cases. The remaining 62 (32%) cases were unresolved despite specialist pathology and methylation profiling. Interpretation Together, these data provide estimates of the impact that could be expected from routine implementation of genomic profiling into clinical practice, and indicate limitations where additional techniques will be required. We conclude that DNA methylation arrays are a useful diagnostic adjunct for childhood CNS tumours. Funding The Brain Tumour Charity, Children with Cancer UK, Great Ormond Street Hospital Children's Charity, Olivia Hodson Cancer Fund, Cancer Research UK, and the National Institute of Health Research.

RationaleSevere acute paediatric asthma may require treatment escalation beyond systemic corticosteroids, inhaled bronchodilators and low-flow oxygen. Current large asthma datasets report parenteral therapy only.ObjectivesTo identify the use and type of escalation of treatment in children presenting to hospital with acute severe asthma.MethodsRetrospective cohort study of children with an emergency department diagnosis of asthma or wheeze at 18 Australian and New Zealand hospitals. The main outcomes were use and type of escalation treatment (defined as any of intensive care unit admission, nebulised magnesium, respiratory support or parenteral bronchodilator treatment) and hospital length of stay (LOS).Measurements and main resultsOf 14 029 children (median age 3 (IQR 1–3) years; 62.9% male), 1020 (7.3%, 95% CI 6.9% to 7.7%) had treatment escalation. Children with treatment escalation had a longer LOS (44.2 hours, IQR 27.3–63.2 hours) than children without escalation 6.7 hours, IQR 3.5–16.3 hours; pConclusionsOverall, 7.3% children with acute severe asthma received some form of escalated treatment, with 4.2% receiving parenteral bronchodilators and 4.3% respiratory support. There is wide variation treatment escalation.

When addressing the quality of life in cities, it must be remembered that 86% of households in the UK live in suburban environments. Yet the Commission for Architecture and the Built Environment's national audit states that some 82% of housing is of poor or average quality. To understand this dysfunctional relationship it is necessary to explore how suburbs are created, nurtured and packaged, and the gaps between aspiration and the actuality on the ground. Barriers are continually encountered in trying to evolve new models of suburban living. The patterns for today's suburbs were set 150 years ago. The current results are often dormitories based on a series of myths and Victorian images, supported by a powerful but unimaginative industry that reflects the contradictions between consumer choice, values, procurement, design and invisible constraints. It is hoped this paper could help to start a debate on the quality of life desired in future suburbs. This is not just about policies and practice, or breaking the hold of the volume builder; it is perhaps also because there is currently no value system that reflects what is wanted from suburbs.

BACKGROUND Current guidelines recommend chromosomal microarray (CMA) testing as a first line etiologic investigation for developmental disorders such as intellectual disability or autism spectrum disorder (ASD). How often a copy number variation (CNV) is found, a definitive etiologic diagnosis is made and a change in clinical management occurs has not been well studied in a community setting. OBJECTIVES The study objective was to examine the real world use of CMA testing in a developmental paediatric setting: the prevalence of positive results and management decisions. DESIGN/METHODS This was a retrospective, descriptive study. The charts of 170 children seen by a single developmental paediatrician in a small city over a 7 year period (2010 - 2017) were reviewed. Referrals were received from both urban and rural communities. Information regarding reason for referral, clinical diagnosis, requests for CMA testing, test results and subsequent management decisions were extracted. The patient age ranged from 1 to 18 years (average 5.1 years). Children were referred for a wide variety of developmental and behavioural problems. Developmental delay, disruptive behavior, possible autism spectrum disorder or speech delay were the most common reasons for referral. Children were considered for CMA testing according to published guidelines. The most common clinical diagnoses in referred children were attention deficit hyperactivity disorder (ADHD), ASD and global developmental delay (GDD). Clinical management decisons were obtained from the medical chart and included follow-up visits. RESULTS CMA testing was recommended for 78 children, of which 65 had CMA testing completed (83%). Of these, 15 (23%) had an abnormal result and 6 (9%) were deemed pathogenic. The most common finding was a CNV at 2p16.3 in 2 children (3%). Of the children with pathogenic CNVs, 3 (50%) had more than one CNV. One child had a previously diagnosed trisomy X. One child with normal CMA had further testing, and a genetic diagnosis of atypical Rett Syndrome was made. The primary management decisions based on the CMA test results included parent education, genetic counselling and prognosis clarification. CONCLUSION In a developmental paediatrics setting, the use of CMA testing for first-line etiologic assessment in children with developmental disorders obtains positive results in close to 10% of tested children. This is similar to previously published results. Approximately 1/6 tested children had results of uncertain significance which require further study over time.

Acquired hypothyroidism is more common in children with Down syndrome than in other children. In children without Down syndrome, acquired hypothyroidism is rare before age 3 years and is not reported to occur frequently until adolescence. 1 Previous reports of hypothyroidism in children with Down syndrome have described onset at a similar age. Postneonatal-onset hypothyroidism in the very young children with Down syndrome described herein has not previously been reported, to our knowledge. At the Child and Parent Resource Institute in London, Ontario, we have a multidisciplinary outpatient developmental program for children with Down syndrome. At the time of this writing, we had approximately 120 children aged between 6 weeks and 17 years in the program. Patient Reports. Patient 1. This 6½-month-old female infant was born at 37 weeks' gestation to a 39-year-old mother who had a distant family history of thyroid disease. The mother and father were third cousins.