Making Sense of Our Working Lives: The concept of the career imagination

In 2001 foot and mouth hit and obviously devastated the business completely. So it’s a honeypot village and literally it was as though somebody had put a gate against it. It was incredible. There were no cars, the kids were just riding bikes up and down the road, playing football. I don’t know if you remember but Blair said, ‘keep out of the country’ and they did! Sometimes it feels as though I’ve not been in charge of my own destiny to some degree. You know, you always seem to be overtaken by a series of events that lead you somewhere (Sylvia, hotel owner, Cohen, 2014)) Jill was all excited about the possibility of getting a modem that would enable her to work from home! Commenting on the modem story nearly twenty years later, Jill observed that ‘any firm is a technology firm now. It’s probably the biggest cultural shift of the last century’ (Cohen, 2014: 78, 79),The notion of vocational public service has become passé through ‘managerialising’ and ‘targetising’ the service. What’s gone is the notion of voluntary effort and endeavour that went alongside what you were being paid for. There would have been no welfare rights service created in the 1980s if the people setting it up had just turned up at 9 o’clock and left at 5 o’clock. It came to be because people actually lived the creation. That’s impossible to achieve in an environment which is all about targets set from on high, and action plans on Excel spreadsheets (Pete, welfare rights officer, Cohen, Duberley & Smith, 2019).These quotes, taken from our own research (Cohen, 2014; Cohen, Duberley & Smith, 2018) vividly highlight the ongoing evolution of our working lives and careers. As we write this essay, in Autumn 2020, this change feels more dramatic and closer than ever, fuelled not only by well-rehearsed, long-term social, economic and technological transformation (Grimshaw, 2020), but also by the shock of the Covid 19 crisis and impending Brexit. For some commentators such on-going change offers the potential to forge ‘boundaryless’ (Tams & Arthur, 2010) and entrepreneurial careers (Liguori, Winkler, Vanevenhoven and Winkel and James, 2020): as the Uber pitch to potential drivers goes, ‘no shifts, no boss, no limits’ (Kessler, 2018: 12). For others, though, the picture is far bleaker (Snyder, 2016), with increased insecurity and a lack of stable foundations from which to develop a work identity (Petriglieri, Ashford, & Wrzesniewski, 2019: 158) and make sense of effort as part of a meaningful, ongoing project of forging a meaningful career (Tweedie, 2013)

Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

Background The autosomal-recessive cerebellar ataxias (ARCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders. The large number of ARCA genes leads to delay and difficulties obtaining an exact diagnosis in many patients and families. Ubiquinone (CoQ10) deficiency is one of the potentially treatable causes of ARCAs as some patients respond to CoQ10 supplementation. The AarF domain containing kinase 3 gene (ADCK3) is one of several genes associated with CoQ10 deficiency. ADCK3 encodes a mitochondrial protein which functions as an electron-transfer membrane protein complex in the mitochondrial respiratory chain (MRC). Methods We report two siblings from a consanguineous Pakistani family who presented with cerebellar ataxia and severe myoclonus from adolescence. Whole exome sequencing and biochemical assessment of fibroblasts were performed in the index patient. Results A novel homozygous frameshift mutation in ADCK3 (p.Ser616Leufs*114), was identified in both siblings. This frameshift mutation results in the loss of the stop codon, extending the coding protein by 81 amino acids. Significant CoQ10 deficiency and reduced MRC enzyme activities in the index patient's fibroblasts suggested that the mutant protein may reduce the efficiency of mitochondrial electron transfer. CoQ10 supplementation was initiated following these genetic and biochemical analyses. She gained substantial improvement in myoclonic movements, ataxic gait and dysarthric speech after treatment. Conclusion This study highlights the importance of diagnosing ADCK3 mutations and the potential benefit of treatment for patients. The identification of this new mutation broadens the phenotypic spectrum associated with ADCK3 mutations and provides further understanding of their pathogenic mechanism

Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

AbstractUnlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD

Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

The autosomal-recessive cerebellar ataxias (ARCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders. The large number of ARCA genes leads to delay and difficulties obtaining an exact diagnosis in many patients and families. Ubiquinone (CoQ10) deficiency is one of the potentially treatable causes of ARCAs as some patients respond to CoQ10 supplementation. The AarF domain containing kinase 3 gene (ADCK3) is one of several genes associated with CoQ10 deficiency. ADCK3 encodes a mitochondrial protein which functions as an electron-transfer membrane protein complex in the mitochondrial respiratory chain (MRC)

The Menopause Taboo at Work: Examining Women’s Embodied Experiences of Menopause in the UK Police Service

This article contributes to the growing body of knowledge about gendered ageing at work through an examination of the embodied experiences of women undergoing menopause transition in the UK police service. Drawing on 1197 survey responses, providing both quantitative and qualitative data gathered across three police forces in 2017–18, the findings highlight the importance of a material-discursive approach that considers contextual influences on women’s bodily experiences. The article evidences gendered ageism and the penalty suffered by women whose ageing bodies fail to comply with an ideal worker norm. It makes an important contribution both to theorising embodiment, drawing in age as well as gender discourses, and to promoting a material-discursive approach that recognises the materiality of the body while also offering the potential for agency, reflection and resistance

Pathogenic p62/SQSTM1 mutations impair energy metabolism through limitation of mitochondrial substrates

Abnormal mitochondrial function has been found in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Mutations in the p62 gene (also known as SQSTM1) which encodes the p62 protein have been reported in both disorders supporting the idea of an ALS/FTD continuum. In this work the role of p62 in energy metabolism was studied in fibroblasts from FTD patients carrying two independent pathogenic mutations in the p62 gene, and in a p62-knock-down (p62 KD) human dopaminergic neuroblastoma cell line (SH-SY5Y). We found that p62 deficiency is associated with inhibited complex I mitochondrial respiration due to lack of NADH for the electron transport chain. This deficiency was also associated with increased levels of NADPH reflecting a higher activation of pentose phosphate pathway as this is accompanied with higher cytosolic reduced glutathione (GSH) levels. Complex I inhibition resulted in lower mitochondrial membrane potential and higher cytosolic ROS production. Pharmacological activation of transcription factor Nrf2 increased mitochondrial NADH levels and restored mitochondrial membrane potential in p62-deficient cells. Our results suggest that the phenotype is caused by a loss-of-function effect, because similar alterations were found both in the mutant fibroblasts and the p62 KD model. These findings highlight the implication of energy metabolism in pathophysiological events associated with p62 deficiency

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Gene Therapy Corrects Mitochondrial Dysfunction in Hematopoietic Progenitor Cells and Fibroblasts from Coq9R239X Mice

This study has been submitted to the patent's offices at the "University of Granada" and "Fundación Progreso y Salud". Please note that the results of this manuscript have been submitted to patent protection (application number P201630630; title: “Uses of Coenzyme Q biosynthetic proteins”; date:05/16/2016).Recent clinical trials have shown that in vivo and ex vivo gene therapy strategies can be an option for the treatment of several neurological disorders. Both strategies require efficient and safe vectors to 1) deliver the therapeutic gene directly into the CNS or 2) to genetically modify stem cells that will be used as Trojan horses for the systemic delivery of the therapeutic protein. A group of target diseases for these therapeutic strategies are mitochondrial encephalopathies due to mutations in nuclear DNA genes. In this study, we have developed a lentiviral vector (CCoq9WP) able to overexpress Coq9 mRNA and COQ9 protein in mouse embryonic fibroblasts (MEFs) and hematopoietic progenitor cells (HPCs) from Coq9R239X mice, an animal model of mitochondrial encephalopathy due to primary Coenzyme Q (CoQ) deficiency. Ectopic over-expression of Coq9 in both cell types restored the CoQ biosynthetic pathway and mitochondrial function, improving the fitness of the transduced cells. These results show the potential of the CCoq9WP lentiviral vector as a tool for gene therapy to treat mitochondrial encephalopathies.This work was supported by grants from Ministerio de Economía y Competitividad (Spain) and the European Regional Development Fund (ERDF) from the European Union, to LCL through the research grants SAF2013-47761-R and SAF2015-65786-R; by Fondo de Investigaciones Sanitarias ISCIII (Spain) and the European Regional Development Fund (ERDF) from the European Union through the research grants PI12/01097 and ISCIII Red de Terapia Celular TerCel RD12/0019/0006 to FM; by the Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía-FEDER/Fondo de Cohesion Europeo (FSE) de Andalucía through the research grants P10-CTS-6133 to LCL; P09-CTS-04532, PI-57069, PI-0001/2009 and PAIDI-Bio-326 to F.M.; PI-0160/2012 to KB and PI-0407/2012 to MC; by the NIH through the research P01HD080642 to LCL and by the foundation “todos somos raros, todos somos únicos” to LCL. LCL is supported by the ‘Ramón y Cajal’ National Programme, Ministerio de Economía y Competitividad, Spain (RYC-2011-07643)

Career Resourcing and the Process of Professional Emergence

We theorize a career resourcing process that explains how individuals can create a new profession. Using historical archives, we trace the emergence of health services research as a new research profession through the career actions of early practitioners. We find that career resourcing can lead to the institutionalization of a new profession by: 1) a process of accretion, where people pursuing fulfilling careers generate resources that contribute to institutionalization, or 2) institutional work to deliberately build the professional community and infrastructure. We contribute to research on institutional change by specifying career actions that can lead to the institutionalization of a new profession, and by developing theory that accounts for the motivations and the means of individuals to act in ways that result in the institutionalization of a new profession