New approaches to investigating the function of mycelial networks

Fungi play a key role in ecosystem nutrient cycles by scavenging, concentrating, translocating and redistributing nitrogen. To quantify and predict fungal nitrogen redistribution, and assess the importance of the integrity of fungal networks in soil for ecosystem function, we need better understanding of the structures and processes involved. Until recently nitrogen translocation has been experimentally intractable owing to the lack of a suitable radioisotope tracer for nitrogen, and the impossibility of observing nitrogen translocation in real time under realistic conditions. We have developed an imaging method for recording the magnitude and direction of amino acid flow through the whole mycelial network as it captures, assimilates and channels its carbon and nitrogen resources, while growing in realistically heterogeneous soil microcosms. Computer analysis and modeling, based on these digitized video records, can reveal patterns in transport that suggest experimentally testable hypotheses. Experimental approaches that we are developing include genomics and stable isotope NMR to investigate where in the system nitrogen compounds are being acquired and stored, and where they are mobilized for transport or broken down. The results are elucidating the interplay between environment, metabolism, and the development and function of transport networks as mycelium forages in soil. The highly adapted and selected foraging networks of fungi may illuminate fundamental principles applicable to other supply networks

Extreme managers, extreme workplaces: capitalism, organizations and corporate psychopaths

This paper reports on in-depth, qualitative research carried out in England in 2013 among five organizational directors and two senior managers who had worked with other senior directors or managers who were Corporate Psychopaths, as measured by a management psychopathy measure. The Corporate Psychopaths reported on in this research displayed remarkable consistency in their approach to management to the extent that they could be called “text book examples” of managerial psychopathy. They were seen as being organizational stars and as deserving of performance awards by those above them, while the Corporate Psychopaths simultaneously subjected those below them to extreme forms of behavior, including bullying, intimidation and coercion and also engaged in extreme forms of mismanagement; such as very poor levels of personnel management, directionless leadership, miss-management of resources and outright fraud

Generation of otic lineages from integration-free human-induced pluripotent stem cells reprogrammed by mRNAs

Damage to the sensory hair cells and the spiral ganglion neurons of the cochlea leads to deafness. Induced pluripotent stem cells (iPSCs) are a promising tool to regenerate the cells in the inner ear that have been affected by pathology or have been lost. To facilitate the clinical application of iPSCs, the reprogramming process should minimize the risk of introducing undesired genetic alterations while conferring the cells the capacity to differentiate into the desired cell type. Currently, reprogramming induced by synthetic mRNAs is considered to be one of the safest ways of inducing pluripotency, as the transgenes are transiently delivered into the cells without integrating into the genome. In this study, we explore the ability of integration-free human-induced pluripotent cell lines that were reprogrammed by mRNAs, to differentiate into otic progenitors and, subsequently, into hair cell and neuronal lineages. hiPSC lines were induced to differentiate by culturing them in the presence of fibroblast growth factors 3 and 10 (FGF3 and FGF10). Progenitors were identified by quantitative microscopy, based on the coexpression of otic markers PAX8, PAX2, FOXG1, and SOX2. Otic epithelial progenitors (OEPs) and otic neuroprogenitors (ONPs) were purified and allowed to differentiate further into hair cell-like cells and neurons. Lineages were characterised by immunocytochemistry and electrophysiology. Neuronal cells showed inward Na+ () currents and outward () and inward K+ () currents while hair cell-like cells had inward and outward delayed rectifier K+ currents, characteristic of developing hair cells. We conclude that human-induced pluripotent cell lines that have been reprogrammed using nonintegrating mRNAs are capable to differentiate into otic cell types

High-dose cyclosporin with etoposide--toxicity and pharmacokinetic interaction in children with solid tumours.

The tolerability, anti-tumour activity and pharmacokinetic interaction of high-dose intravenous cyclosporin combined with intravenous etoposide was evaluated in children. Eighteen patients with recurrent or refractory tumours, all of whom had previously received etoposide, were treated with a combination of high-dose cyclosporin and etoposide. In 13, cyclosporin was given as a continuous infusion (15 mg kg(-1) per 24 h for 60 h) and in five a short 3-hour infusion of 30 mg kg(-1) day(-1) on three consecutive days. Pharmacokinetic profiles of etoposide were determined with and without cyclosporin. Cyclosporin levels ranged from 1359 to 4835 ng ml(-1) and cyclosporin increased the median area under the concentration time for etoposide curve from 7.2 to 12.5 mg ml(-1) min. The major toxicity was acute with varying forms of hypersensitivity reactions. In four cases this was severe. Hyperbilirubinaemia was present in 25 of 32 courses but was of short duration. In 14 courses, creatinine and/or urea was elevated, but was also transient. Significant hypertension was seen in six courses. Four of 17 patients evaluable for response obtained a partial response and one showed stable disease. It is concluded that in children given the combination of high-dose cyclosporin and etoposide, the etoposide dose should be halved in order to achieve an area under the drug concentration-time curve similar to that with etoposide alone. A continuous infusion schedule of cyclosporin is better tolerated during the period of administration but is associated with similar hepatic and renal dysfunction to a short schedule. The 24% response rate in children who had previously received etoposide suggests that this may be an effective method of enhancing drug sensitivity and further phase II evaluation is justified

Psychopathic leadership a case study of a corporate psychopath CEO

This longitudinal case study reports on a charity in the UK which gained a new CEO who was reported by two middle managers who worked in the charity, to embody (respectively) all or most of the ten characteristics within a measure of corporate psychopathy. The leadership of this CEO with a high corporate psychopathy score was reported to be so poor that the organisation was described as being one without leadership and as a lost organisation with no direction. This paper outlines the resultant characteristics of the ensuing aimlessness and lack of drive of the organisation involved. Comparisons are made to a previous CEO in the same organisation, who was reportedly an authentic, effective and transformational leader. Outcomes under the CEO with a high corporate psychopathy score were related to bullying, staff withdrawal and turnover as effective employees stayed away from and/or left the organisation. Outcomes also included a marked organisational decline in terms of revenue, employee commitment, creativity and organisational innovativeness. The paper makes a contribution to both leadership and to corporate psychopathy research as it appears to be the first reported study of a CEO with a high corporate psychopathy score

Space and patchiness affects diversity–function relationships in fungal decay communities

The space in which organisms live determines health and physicality, shaping the way in which they interact with their peers. Space, therefore, is critically important for species diversity and the function performed by individuals within mixed communities. The biotic and abiotic factors defined by the space that organisms occupy are ecologically significant and the difficulty in quantifying space-defined parameters within complex systems limits the study of ecological processes. Here, we overcome this problem using a tractable system whereby spatial heterogeneity in interacting fungal wood decay communities demonstrates that scale and patchiness of territory directly influence coexistence dynamics. Spatial arrangement in 2- and 3-dimensions resulted in measurable metabolic differences that provide evidence of a clear biological response to changing landscape architecture. This is of vital importance to microbial systems in all ecosystems globally, as our results demonstrate that community function is driven by the effects of spatial dynamics

Political brand image: an investigation into the operationalisation of the external orientation of David Cameron’s Conservative brand

This paper seeks to address the limited understanding of how to operationalise the external brand image of a political brand. More specifically, this research critically assesses the transfer potential of the six variables of brand image by Bosch, Venter, Han and Boshoff to deconstruct the UK Conservative Party brand from the perspective of young people aged 18–24 years during the 2010 UK General Election campaign. This research demonstrates the applicability of the six variables otherwise known as the ‘brand image framework’ to the political environment. However, the application of the brand image framework in its original conceptualisation proved problematic. Many of the brand image variables were clarified, rearticulated and simplified to address the political context. This refined conceptualisation provided an in-depth understanding of how to investigate the political brand image of David Cameron’s Conservative Party. This study addresses the paucity of research that operationalises external brand image and provides practitioners and academics within and beyond the context of political branding a mechanism to understand the external orientation of brands. This research may also be used by political and non-political brands as a basis to explore external brand image and compare its consistency with internal brand identity

Saturable metabolism of continuous high-dose ifosfamide with Mesna and GM-CSF: A pharmacokinetic study in advanced sarcoma patients

Background: The aim of this study was to assess the pharmacology, toxicity and activity of high-dose ifosfamide/mesna ± GM-CSF administered by a five-day continuous infusion at a total ifosfamide dose of 12-18 g/m2 in adult patients with advanced sarcomas. Patients and methods: Between January 1991 and October 1992 32 patients with advanced or metastatic sarcoma were entered the study. Twenty-seven patients were pretreated including twenty-three with prior ifosfamide at less than 8 g/m2 total dose/cycle. In 25 patients (27 cycles) extensive pharmacokinetic analyses were performed. Results: The area under the plasma concentration-time curve (AUC) for ifosfamide increased linearly with dose while the AUC's of the metabolites measured in plasma by thin-layer chromatography did not increase with dose, particularly that of the active metabolite isophosphoramide mustard. Furthermore the AUC of the inactive carboxymetabolite did not increase with dose. Interpatient variability of pharmacokinetic parameters was high. Dose-limiting toxicity was myelosup-pression at 18 g/m2 total dose with grade 4 neutropenia in five of six patients and grade 4 thrombocytopenia in four of six patients. Therefore the maximum tolerated dose was considered to be 18 g/m2 total dose. There was one CR and eleven PR in twenty-nine evaluable patients (overall response rate 41%). Conclusion: Both the activation and inactivation pathways of ifosfamide are non-linear and saturable at high-doses although the pharmacokinetics of the parent drug itself are dose linear. Ifosfamide doses greater than 14-16 g/m2 per cycle appear to result in a relative decrease of the active metabolite isophosphoramide mustard. These data suggest a dose-dependent saturation or even inhibition of ifosfamide metabolism by increasing high dose ifosfamide and suggest the need for further metabolic studie

The impact of a supplementary medication review and counselling service within the oncology outpatient setting

The impact on the care of breast cancer patients, of a pharmacy technician-led medication review and counselling clinic, provided in an outpatient setting, was investigated using a controlled randomised study. Compared to the controls, clinic patients showed a significantly improved level of understanding of their chemotherapy support medication (95% CI for difference in mean knowledge rating scores=2.165–2.826, P<0.001) and a significant reduction in the median number of support items required (two compared to five in the control, P<0.001). This resulted in a significant reduction in mean medication expenditure per patient (£26.70 vs £10.20, 95% CI for the mean difference in cost £6.72–£26.26, P<0.001). The clinic was also associated with significant reductions in chemotherapy delays (P<0.001) and dose reductions due to side effects (P=0.003). Other benefits from the clinic were a reduction in pharmacy dispensing time and a highly significant reduction in pharmacy time spent resolving post-clinic prescription queries (P<0.001). Taking into account the initial technician training cost, the scheme represented an annual saving to the Trust of over £15 000. The clinic serves as a model for those wishing to improve outpatient services to breast cancer patients