Project leadership: skills, behaviours, knowledge and values

This research has sought to draw out project leadership competences from the perspective of practising project leaders, aspiring project leaders, heads of profession, project sponsors and clients. The aim of this research report is to help focus, develop and refine our understanding of project leadership so we can support continued capability building for project professionals and their organisations. To compile this report, the authors Sarah Coleman and Professor Mike Bourne conducted in-depth interviews with 38 individuals across five multinational organisations (BAE Systems, IQVIA, Jacobs, Shell and Siemens). These organisations were chosen because of their reliance on complex projects for the delivery of strategy and performance, and the individuals for their substantial knowledge and experience of project delivery, and their range of perspectives. The interviewees held and had experience of a wide variety of roles, from the aspiring leaders delivering smaller projects to the most experienced project leaders (responsible for £1bn+ budget major, complex projects), heads of profession, project sponsors and clients. Together, these individuals have over 500 years of project experience

Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits

Deep brain stimulation (DBS) has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive compulsive disorder (OCD), which is characterized by recurrent unwanted thoughts or ideas (obsessions) and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions). Abnormal activity in cortico-striato-thalamo-cortical (CSTC) circuits including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), ventral striatum, and mediodorsal (MD) thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), ventral caudate nucleus, subthalamic nucleus (STN), and nucleus accumbens (NAc) have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level

Navigating the Health Seas : Experiences of accessing freely available PrEP on the National Health Service

This thesis presents three papers exploring different aspects of Pre-Exposure Prophylaxis (PrEP) in the United Kingdom. This includes a systematic scoping review on knowledge, perceptions, and attitudes towards PrEP; a qualitative study exploring experiences of accessing PrEP on the National Health Service (NHS) and a critical appraisal. Section one reports a systematic scoping review of UK-based literature, which aims to map various aspects of knowledge, perceptions, and attitudes towards PrEP. Forty-seven studies met the requirements for inclusion. Results present a diverse methodological landscape that is rapidly growing in scope. Knowledge and awareness of PrEP were variable across different populations. Underrepresentation in research and media campaigns continues to perpetuate bias towards gay, bisexual, and other men who have sex with men (GBMSM) as being the main proponents of PrEP. Lack of representation and poor awareness of PrEP candidacy impacted the acceptability of PrEP in several groups who experience inequitable PrEP uptake. Self-perceived HIV risk was highlighted as an important factor in PrEP uptake and adherence. Stigma towards PrEP was often associated with moralising views of sex and promiscuity. The empirical section of this project presents a reflexive thematic analysis (RTA) of eight individuals' experiences of accessing freely available PrEP on the National Health Service (NHS). Three main themes were derived from the data. (1) Choosing PrEP: risk analysis at every turn; (2) To be, is to be perceived: the importance of feeling seen, heard and cared for by services; and (3) Added benefits: lifting the weight of risk and freedom to explore pleasure. The final section offers a critical appraisal of the project as a whole including an overview of both papers, bringing together the results and suggesting clinical implications and future research. In keeping with reflexive qualitative methods, positionality, subjectivity and personal reflections will also be discussed

Drug Discovery Using Chemical Systems Biology: Repositioning the Safe Medicine Comtan to Treat Multi-Drug and Extensively Drug Resistant Tuberculosis

The rise of multi-drug resistant (MDR) and extensively drug resistant (XDR) tuberculosis around the world, including in industrialized nations, poses a great threat to human health and defines a need to develop new, effective and inexpensive anti-tubercular agents. Previously we developed a chemical systems biology approach to identify off-targets of major pharmaceuticals on a proteome-wide scale. In this paper we further demonstrate the value of this approach through the discovery that existing commercially available drugs, prescribed for the treatment of Parkinson's disease, have the potential to treat MDR and XDR tuberculosis. These drugs, entacapone and tolcapone, are predicted to bind to the enzyme InhA and directly inhibit substrate binding. The prediction is validated by in vitro and InhA kinetic assays using tablets of Comtan, whose active component is entacapone. The minimal inhibition concentration (MIC99) of entacapone for Mycobacterium tuberculosis (M.tuberculosis) is approximately 260.0 µM, well below the toxicity concentration determined by an in vitro cytotoxicity model using a human neuroblastoma cell line. Moreover, kinetic assays indicate that Comtan inhibits InhA activity by 47.0% at an entacapone concentration of approximately 80 µM. Thus the active component in Comtan represents a promising lead compound for developing a new class of anti-tubercular therapeutics with excellent safety profiles. More generally, the protocol described in this paper can be included in a drug discovery pipeline in an effort to discover novel drug leads with desired safety profiles, and therefore accelerate the development of new drugs

Quantifying Reproducibility in Computational Biology: The Case of the Tuberculosis Drugome

How easy is it to reproduce the results found in a typical computational biology paper? Either through experience or intuition the reader will already know that the answer is with difficulty or not at all. In this paper we attempt to quantify this difficulty by reproducing a previously published paper for different classes of users (ranging from users with little expertise to domain experts) and suggest ways in which the situation might be improved. Quantification is achieved by estimating the time required to reproduce each of the steps in the method described in the original paper and make them part of an explicit workflow that reproduces the original results. Reproducing the method took several months of effort, and required using new versions and new software that posed challenges to reconstructing and validating the results. The quantification leads to “reproducibility maps” that reveal that novice researchers would only be able to reproduce a few of the steps in the method, and that only expert researchers with advance knowledge of the domain would be able to reproduce the method in its entirety. The workflow itself is published as an online resource together with supporting software and data. The paper concludes with a brief discussion of the complexities of requiring reproducibility in terms of cost versus benefit, and a desiderata with our observations and guidelines for improving reproducibility. This has implications not only in reproducing the work of others from published papers, but reproducing work from one’s own laboratory

Exploring the views of UK regional primary care practitioners on the use and role of screening tools for learning disabilities in their services

BackgroundPeople with learning disabilities are at increased risk of physical health conditions and mortality compared to the general population. Initiatives to address these health inequalities include the introduction of learning disability registers, through which people with learning disabilities can be identified and offered annual health checks and reasonable adjustments in their healthcare provision. A barrier to offering such initiatives to people with learning disabilities is that practitioners/providers may be unaware of the presence of a learning disability, and people who meet criteria may not be entered onto general practice learning disability registers. Screening tools can be used to help identify people with learning disabilities in order that they can be offered appropriate health services and reasonable adjustments. This study aimed to explore the awareness and views of UK primary care staff about the existence and role of screening tools for learning disability in their services.Materials and MethodsA qualitative approach was used; semi-structured online interviews were conducted with a purposive sample of primary care staff recruited via a regional professional network of primary care practitioners. Five general practitioners and one nurse practitioner, representing five primary care practices in the North-East of England participated. Interview transcripts were analysed using thematic analysis.FindingsTwo themes and associated sub-themes were identified. Within Theme 1 (‘I haven’t had anything much to do with them’) two subthemes related to never using screening tools and reasons why screening tools were not routinely used. Theme 2 (‘I think they’re great that they exist’) comprised two subthemes that explored the benefits of screening tools, for example for those practitioners less experienced with people with learning disabilities, and also explored potential reluctance to use them.ConclusionsThe study found that most practitioners had some knowledge of screening tools and the general consensus was that they are beneficial. However, the tendency of participants was not to use screening tools in a consistent and/or systematic way, instead relying on informal approaches or other services for identifying the presence of learning disabilities. The study findings highlight the need for changes in practice to support primary care staff to access and systematically use evidence-based effective and efficient screening tools for learning disability

The Iowa Homemaker vol.10, no.3

Iowa State “Mans” the Kitchen by Helen Melton, page 1 At Home in Nippon by Sarah Field, page 2 And Rush That Order, Please! by Bessie Hammer, page 3 Luncheon – Mile High by Mildred Ghrist Day, page 3 Gotta Job? by Julia Bourne, page 4 “P’s” and “Q’s” in China Selection by Ida M. Shilling, page 5 4-H Club by Helen Melton, page 6 State Association by Marcia E. Turner, page 8 Child Health May Day by Anafred Stephenson, page 10 Editorial, page 11 Alumnae News by Dorothy B. Anderson, page 1

Dexamethasone Administration During Definitive Radiation and Temozolomide Renders a Poor Prognosis in a Retrospective Analysis of Newly Diagnosed Glioblastoma Patients

BACKGROUND: Dexamethasone (DXM) is commonly used in the management of cerebral edema in patients diagnosed with glioblastoma multiforme (GBM). Bevacizumab (BEV) is FDA-approved for the progression or recurrence of GBM but has not been shown to improve survival when given for newly diagnosed patients concurrently with radiation (RT) and temozolomide (TMZ). Both DXM and BEV reduce cerebral edema, however, DXM has been shown to induce cytokine cascades which could interfere with cytotoxic therapy. We investigated whether DXM would reduce survival of GBM patients in the setting of concurrent TMZ and BEV administration. METHODS: We reviewed the treatment of all 73 patients with GBM who received definitive therapy at our institution from 2005 to 2013 with RT (60 Gy) delivered with concurrent daily TMZ (75 mg/m2). Of these, 34 patients also were treated with concurrent BEV (10 mg/kg every two weeks). Patients received adjuvant therapy (TMZ or TMZ/Bev) until either progression, discontinuation due to toxicity, or 12 months after radiation completion. All patients who had GBM progression with TMZ were offered BEV for salvage therapy, with 19 (56 %) receiving BEV. RESULTS: With a median follow-up of 15.6 months, 67 (91.8 %) patients were deceased. The OS for the entire cohort was 15.9 months, while the PFS was 7.7 months. The extent of resection was a prognostic indicator for OS (p  = .0044). The median survival following gross tumor resection (GTR) was 22.5 months, subtotal resection (STR) was 14.9 months, and biopsy was 12.1 months. The addition of BEV to TMZ with RT was borderline significantly associated with increased PFS (9.4 vs. 5.1 months, p = 0.0574) although was not significantly associated with OS (18.1 vs. 15.3 months respectively, p  = 0.3064). In patients receiving TMZ, DXM use concurrent with RT was a poor prognostic indicator of both OS (12.7 vs. 22.6 months, p = 0.003) and PFS (3.6 vs. 8.4 months, p p = 0.4818). On multivariable analysis, DXM use predicted an unfavorable OS hazard ratio (HR) = 1.72, p = 0.045). CONCLUSIONS: Our results with TMZ, BEV, and RT are similar to previous studies in terms of PFS and OS. DXM use during RT with concurrent TMZ correlated with reduced OS and PFS unless BEV was administered