A “Framework of Ideas” to Support an Action Research Study of ICT- Enabled Organisational Change in the Not-for-Profit Sector

This paper develops a theoretic framework which may be used to guide research into effective organisational change. The focus of our work is restricted to (i) ICT-mediated organisational change and (ii) change within a Non-Profit-Organisation (NPO) and, therefore, the framework of ideas presented here is focussed on a characteristic of NPOs: an unusually highly intrinsically motivated workforce. This focus has suggested that more than usual attention is paid to individual employees and the granularity of the underlying study for which this framework has been defined is set accordingly. The framework is, however, not necessarily restricted in its scope of application to such organisations, or to such organisational change. We encourage the use of the framework beyond the boundaries we have set for our project

Organisational Change in the Third Sector and Implications for Organisational Networks

This paper reports an action research study in which we explore the problems of organisational change within a large non-profit organisation – a so-called “third sector” – organisation. We focus on the mutual interaction of an organisational change initiative and the motivation of the workforce. We review the nature of the social service delivery sector, of which the focal organisation is a part, and develop, in the context of this study, an analogy with the class of systems described as organisational networks. We argue that the findings from this study may be expected to have application in organisational change within organisational networks, generally

Reconceptualising Motivation in Adoption and Acceptance Research: Back to Basics

In the adoption and acceptance of technology, the technology acceptance model (TAM) has been a dominant influence. TAM, however, simplifies and trivialises the concept of motivation, (a concept not well developed and used in the IS field) by failing to recognise the fundamental needs influencing behaviour. This, in turn, restricts its use to design and use interventions to enhance adoption and use within an ICT-enabled organisational change project. Given this, this paper will re-conceptualise the concept of motivation by exploring the inner or intrinsic motivation influencing behaviour and will indicate how this motivation underlies the TAM variables. Further, using the concept of participative management we will explore how various organisational interventions might be designed to enhance user motivation to adopt and use a new system. Finally, these interventions are applied to an ongoing action research study to improve the success of implementing a document management system within a non-profit organisation

Prkci Regulates Autophagy and Pancreatic Tumorigenesis in Mice

Protein kinase C iota (PKCι) functions as a bonafide human oncogene in lung and ovarian cancer and is required for Kras(G12D)-mediated lung cancer initiation and progression. PKCι expression is required for pancreatic cancer cell growth and maintenance of the transformed phenotype; however, nothing is known about the role of PKCι in pancreas development or pancreatic tumorigenesis. In this study, we investigated the effect of pancreas-specific ablation of PKCι expression on pancreatic cellular homeostasis, susceptibility to pancreatitis, and Kras(G12D)-mediated pancreatic cancer development. Knockout of pancreatic Prkci significantly increased pancreatic immune cell infiltration, acinar cell DNA damage, and apoptosis, but reduced sensitivity to caerulein-induced pancreatitis. Prkci-ablated pancreatic acinar cells exhibited P62 aggregation and a loss of autophagic vesicles. Loss of pancreatic Prkci promoted Kras(G12D)-mediated pancreatic intraepithelial neoplasia formation but blocked progression to adenocarcinoma, consistent with disruption of autophagy. Our results reveal a novel promotive role for PKCι in pancreatic epithelial cell autophagy and pancreatic cancer progression

Exploiting Adaptive Laboratory Evolution of Streptomyces clavuligerus for Antibiotic Discovery and Overproduction

Adaptation is normally viewed as the enemy of the antibiotic discovery and development process because adaptation among pathogens to antibiotic exposure leads to resistance. We present a method here that, in contrast, exploits the power of adaptation among antibiotic producers to accelerate the discovery of antibiotics. A competition-based adaptive laboratory evolution scheme is presented whereby an antibiotic-producing microorganism is competed against a target pathogen and serially passed over time until the producer evolves the ability to synthesize a chemical entity that inhibits growth of the pathogen. When multiple Streptomyces clavuligerus replicates were adaptively evolved against methicillin-resistant Staphylococcus aureus N315 in this manner, a strain emerged that acquired the ability to constitutively produce holomycin. In contrast, no holomycin could be detected from the unevolved wild-type strain. Moreover, genome re-sequencing revealed that the evolved strain had lost pSCL4, a large 1.8 Mbp plasmid, and acquired several single nucleotide polymorphisms in genes that have been shown to affect secondary metabolite biosynthesis. These results demonstrate that competition-based adaptive laboratory evolution can constitute a platform to create mutants that overproduce known antibiotics and possibly to discover new compounds as well

A Pilot Study Identifying Statin Nonadherence With Visit-to-Visit Variability of Low-Density Lipoprotein Cholesterol

Nonadherence to cardiovascular medications such as statins is a common, important problem. Clinicians currently rely on intuition to identify medication nonadherence. The visit-to-visit variability (VVV) of low-density lipoprotein (LDL) cholesterol might represent an opportunity to identify statin nonadherence with greater accuracy. We examined the clinical and pharmacy data from 782 members of the Boston Medical Center Health Plan, seen at either the Boston Medical Center or its affiliated community health centers, who were taking statins and had ≥3 LDL cholesterol measurements from 2008 to 2011. The LDL cholesterol VVV (defined by the within-patient SD) was categorized into quintiles. Multivariate logistic regression models were generated with statin nonadherence (defined by the standard 80% pharmacy refill-based medication possession ratio threshold) as the dependent variable. The proportion of statin nonadherence increased across the quintiles of LDL cholesterol VVV (64.3%, 71.2%, 89.2%, 92.3%, 91.7%). Higher quintiles of LDL cholesterol VVV had a strong positive association with statin nonadherence, with an adjusted odds ratio of 3.4 (95% confidence interval 1.7 to 7.1) in the highest versus lowest quintile of LDL cholesterol VVV. The age- and gender-adjusted model had poor discrimination (C-statistic 0.62, 95% confidence interval 0.57 to 0.67), but the final adjusted model (age, gender, race, mean LDL cholesterol) demonstrated good discrimination (C-statistic 0.75, 95% confidence interval 0.71 to 0.79) between the adherent and nonadherent patients. In conclusion, the VVV of LDL cholesterol demonstrated a strong association with statin nonadherence in a clinic setting. Furthermore, a VVV of LDL cholesterol-based model had good discrimination characteristics for statin nonadherence. Research is needed to validate and generalize these findings to other populations and biomarkers

Dysregulation of regulatory CD56bright NK cells/T cells interactions in multiple sclerosis

Recent evidence has shown that CD56bright NK cells, a subset of NK cells abundant in lymph nodes, may have an immunoregulatory function. In multiple sclerosis (MS), expansion of CD56bright NK cells has been associated to successful response to different treatments and to remission of disease during pregnancy; how whether they exert immunoregulation in physiologic conditions and whether this is impaired in MS is not known. We dissected the immunoregulatory role of CD56bright NK cells function in healthy subjects (HS) and compared it with that of untreated MS subjects or patients with clinically isolated syndrome suggestive of MS (CIS). We found that CD56bright NK cells from HS acquire, upon inflammatory cues, the capability of suppressing autologous CD4+T cell proliferation through direct cytotoxicity requiring engagement of natural cytotoxicity receptors (NCRs) and secretion of granzyme B. CD56bright NK cells from patients with MS/CIS did not differ in frequency and share a similar phenotype but displayed a significantly lower ability to inhibit autologous T cell proliferation. This impairment was not related to deficient expression of NCRs or granzyme B by CD56bright NK cells, but to increased HLA-E expression on T cells from MS/CIS subjects, which could enhance the inhibitory effect mediated by NKG2A that is homogeneously expressed on CD56bright NK cells. The defect in controlling autologous T cells by CD56bright NK cells in MS/CIS might contribute to the excess of autoimmune response that is associated to disease development

A 2 R_⊕ Planet Orbiting the Bright Nearby K Dwarf Wolf 503

Since its launch in 2009, the Kepler telescope has found thousands of planets with radii between that of Earth and Neptune. Recent studies of the distribution of these planets have revealed a gap in the population near 1.5–2.0 R⊕, informally dividing these planets into "super-Earths" and "sub-Neptunes." The origin of this division is difficult to investigate directly because the majority of planets found by Kepler orbit distant, dim stars and are not amenable to radial velocity follow-up or transit spectroscopy, making bulk density and atmospheric measurements difficult. Here, we present the discovery and validation of a newly found 2.03^(+0.08)_(-0.07) R⊕ planet in direct proximity to the radius gap, orbiting the bright (J = 8.32 mag), nearby (D = 44.5 pc) high proper motion K3.5V star Wolf 503 (EPIC 212779563). We determine the possibility of a companion star and false positive detection to be extremely low using both archival images and high-contrast adaptive optics images from the Palomar observatory. The brightness of the host star makes Wolf 503b a prime target for prompt radial velocity follow-up, and with the small stellar radius (0.690 ± 0.025R⊙), it is also an excellent target for HST transit spectroscopy and detailed atmospheric characterization with JWST. With its measured radius near the gap in the planet radius and occurrence rate distribution, Wolf 503b offers a key opportunity to better understand the origin of this radius gap as well as the nature of the intriguing populations of "super-Earths" and "sub-Neptunes" as a whole

Sensitization in transplantation: Assessment of risk (STAR) 2019 Working Group Meeting Report.

The purpose of the STAR 2019 Working Group was to build on findings from the initial STAR report to further clarify the expectations, limitations, perceptions, and utility of alloimmune assays that are currently in use or in development for risk assessment in the setting of organ transplantation. The goal was to determine the precision and clinical feasibility/utility of such assays in evaluating both memory and primary alloimmune risks. The process included a critical review of biologically driven, state-of-the-art, clinical diagnostics literature by experts in the field and an open public forum in a face-to-face meeting to promote broader engagement of the American Society of Transplantation and American Society of Histocompatibility and Immunogenetics membership. This report summarizes the literature review and the workshop discussions. Specifically, it highlights (1) available assays to evaluate the attributes of HLA antibodies and their utility both as clinical diagnostics and as research tools to evaluate the effector mechanisms driving rejection; (2) potential assays to assess the presence of alloimmune T and B cell memory; and (3) progress in the development of HLA molecular mismatch computational scores as a potential prognostic biomarker for primary alloimmunity and its application in research trial design