Helping Business Schools Engage with Real Problems: The Contribution of Critical Realism and Systems Thinking

The world faces major problems, not least climate change and the financial crisis, and business schools have been criticised for their failure to help address these issues and, in the case of the financial meltdown, for being causally implicated in it. In this paper we begin by describing the extent of what has been called the rigour/relevance debate. We then diagnose the nature of the problem in terms of historical, structural and contextual mechanisms that initiated and now sustain an inability of business schools to engage with real-world issues. We then propose a combination of measures, which mutually reinforce each other, that are necessary to break into this vicious circle – critical realism as an underpinning philosophy that supports and embodies the next points; holism and transdisciplinarity; multimethodology (mixed-methods research); and a critical and ethical-committed stance. OR and management science have much to contribute in terms of both powerful analytical methods and problem structuring methods

What Makes AI ‘Intelligent’ and ‘Caring’?:Exploring Affect and Relationality Across Three Sites of Intelligence and Care

This research was funded in whole by the Wellcome Trust [Seed Award ‘AI and Health’ 213643/Z/18/Z]. For the purpose of Open Access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The authors would like to thank Dr Jane Hopton for inspiring discussions about AI and dimensions of intelligence, and three anonymous reviewers as well as the editor in chief Dr Timmemans at Social Science and Medicine for their very helpful and constructive feedback.Peer reviewedPublisher PD

Prepatterning in the Stem Cell Compartment

The mechanism by which an apparently uniform population of cells can generate a heterogeneous population of differentiated derivatives is a fundamental aspect of pluripotent and multipotent stem cell behaviour. One possibility is that the environment and the differentiation cues to which the cells are exposed are not uniform. An alternative, but not mutually exclusive possibility is that the observed heterogeneity arises from the stem cells themselves through the existence of different interconvertible substates that pre-exist before the cells commit to differentiate. We have tested this hypothesis in the case of apparently homogeneous pluripotent human embryonal carcinoma (EC) stem cells, which do not follow a uniform pattern of differentiation when exposed to retinoic acid. Instead, they produce differentiated progeny that include both neuronal and non-neural phenotypes. Our results suggest that pluripotent NTERA2 stem cells oscillate between functionally distinct substates that are primed to select distinct lineages when differentiation is induced

SETD2 loss-of-function promotes renal cancer branched evolution through replication stress and impaired DNA repair

The research leading to these results is supported by Cancer Research UK (XYG, RAB, EG, PM, PE, SG, C Santos, AJR, NM, PAB, AS and C Swanton), Breast Cancer Research Foundation (C Swanton and NK), Medical Research Council (ID: G0902275 to MG and C Santos; ID: G0701935/2 to AJR and C Swanton), the Danish Cancer Society (AMM, J Bartkova and J Bartek), the Lundbeck Foundation (R93-A8990 to J Bartek), the Ministry of the interior of the Czech Republic (grant VG20102014001 to MM and J Bartek), the National Program of Sustainability (grant LO1304 to MM and J Bartek), the Danish Council for Independent Research (grant DFF-1331-00262 to J Bartek), NIHR RMH/ICR Biomedical Research Centre for Cancer (JL), the EC Framework 7 (PREDICT 259303 to XYG, EG, PM, MG, TJ and C Swanton; DDResponse 259892 to J Bartek and J Bartkova and RESPONSIFY ID:259303 to C Swanton), UCL Overseas Research Scholarship (SG). C Swanton is also supported by the European Research Council, Rosetrees Trust and The Prostate Cancer Foundation. This research is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these groups were compared on the cognitive and physical health variables. Higher polygenic risk for AD, ALS, and FTD was associated with lower cognitive performance. Higher polygenic risk for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS. The results suggest some overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health

Therapeutic opportunities within the DNA damage response

The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study

Background: There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months. Methods: In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM. Results: Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51–70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06–13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, − 0.19 [− 0.28 to − 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty. Conclusions: At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning.Carol L. Hodgson, Alisa M. Higgins, Michael J. Bailey, Anne M. Mather, Lisa Beach, Rinaldo Bellomo, Bernie Bissett, Ianthe J. Boden, Scott Bradley, Aidan Burrell, D. James Cooper, Bentley J. Fulcher, Kimberley J. Haines, Jack Hopkins, Alice Y. M. Jones, Stuart Lane, Drew Lawrence, Lisa van der Lee, Jennifer Liacos, Natalie J. Linke, Lonni Marques Gomes, Marc Nickels, George Ntoumenopoulos, Paul S. Myles, Shane Patman, Michelle Paton, Gemma Pound, Sumeet Rai, Alana Rix, Thomas C. Rollinson, Janani Sivasuthan, Claire J. Tipping, Peter Thomas, Tony Trapani, Andrew A. Udy, Christina Whitehead, Isabelle T. Hodgson, Shannah Anderson, Ary Serpa Neto, and The COVID-Recovery Study Investigators and the ANZICS Clinical Trials Grou

Inductive Praxis and Management Research: Towards a Reflexive Framework

This paper examines how induction legitimately varies according to the impact of different knowledge constituting philosophical assumptions. As a result of its prevalence in qualitative management research, the paper focuses on grounded theory and uses this as a vehicle to explore the key parameters of the philosophical diversity articulated in judgements around neutrality, description and theorization. A reflexive framework of inductive praxis is offered as a heuristic device for interrogating the choices evidently at play in the variable constitution of inductive management research. We indicate how there are multiple modes of engagement, each of which is legitimate within its own philosophical commitments. This implies the need for a more tolerant pluralistic stance in the evaluation of qualitative management research

On the Dynamics of the Spontaneous Activity in Neuronal Networks

Most neuronal networks, even in the absence of external stimuli, produce spontaneous bursts of spikes separated by periods of reduced activity. The origin and functional role of these neuronal events are still unclear. The present work shows that the spontaneous activity of two very different networks, intact leech ganglia and dissociated cultures of rat hippocampal neurons, share several features. Indeed, in both networks: i) the inter-spike intervals distribution of the spontaneous firing of single neurons is either regular or periodic or bursting, with the fraction of bursting neurons depending on the network activity; ii) bursts of spontaneous spikes have the same broad distributions of size and duration; iii) the degree of correlated activity increases with the bin width, and the power spectrum of the network firing rate has a 1/f behavior at low frequencies, indicating the existence of long-range temporal correlations; iv) the activity of excitatory synaptic pathways mediated by NMDA receptors is necessary for the onset of the long-range correlations and for the presence of large bursts; v) blockage of inhibitory synaptic pathways mediated by GABA(A) receptors causes instead an increase in the correlation among neurons and leads to a burst distribution composed only of very small and very large bursts. These results suggest that the spontaneous electrical activity in neuronal networks with different architectures and functions can have very similar properties and common dynamics