CHALLENGES FOR PROJECT MANAGEMENT IN THE 21ST CENTURY

Challenges could be observed as opportunities for success. The growth of project management body of knowledge and the advancement of project managers’ capabilities in dealing with resources are crucial to the successful delivery of projects. As the main objective of this paper is to overview the key challenges for project managers in the current century to help the Future Built Environment, a systematic literature review analysis on PM features was conducted by evaluating over 256 published research papers under the Project Management topic during the past 15 years (2003–2018). As result of this exploration, the research highlighted 18 main challenges and over 125 parameters related to challenges in projects from the extant literature. The management of uncertainty and dealing with different challenges are necessary conditions for effective project management. Sources of challenges are wide ranging and have fundamental effects on projects and the project management body of knowledge. These challenges are not limited to specific industries, and include scope management, information technology, team dynamics, customers’ satisfaction, lean management, communication, innovation and quality. Common project management body of knowledge does not address many of the listed sources of challenges, particularly in ‘soft’ project management skills where flexibility and tolerance of PMs are necessary. The findings of this review paper help scholars to put their attempts on key challenges in managing projects effectively. Such attempts need to entail project managers’ capabilities as well as the organization maturities including some aspects of organisation culture and learning

Oxidation of tertiary amine-derivatized surfaces to control protein adhesion

Selective oxidation of omega-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them. Efficient preparation of both secondary and tertiary linker amides as judged by X-ray photoelectron spectroscopy (XPS) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance (QCM) sensors using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl hexafluorophosphate methanaminium uronium (HATU). Oxidation with hydrogen peroxide was similarly assessed, and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM. Tertiary amine-functionalized sensors adsorbed multilayers of aggregated lysozyme, whereas tertiary amine N-oxides and triethylene glycol-terminated monolayers are consistent with small protein aggregates. The surface containing a dimethylamine N-oxide headgroup and ethyl secondary amide linker showed the largest difference in adsorption of both proteins. Oxidation of tertiary amine decorated surfaces therefore holds the potential for selective deposition of proteins and cells through masking and other patterning techniques

Evaluation of a library of FDA-approved drugs for their ability to potentiate antibiotics against multidrug resistant Gram-negative pathogens

The Prestwick library was screened for antibacterial activity or 'antibiotic-resistance breaking' (ARB) potential against four species of Gram-negative pathogens. Discounting known antibacterials, the screen identified very few ARB hits, which were strain/drug specific. These ARB hits included antimetabolites (zidovudine, floxuridine, didanosine, gemcitabine), anthracyclines (daunorubicin, mitoxantrone, epirubicin) and psychoactive drugs (gabapentin, fluspirilene, oxethazaine). This suggests that there are few approved drugs which could be directly repositioned as adjunct-antibacterials and these will need robust testing to validate efficacy. [Abstract copyright: © Crown copyright 2019.

Dynamic friction force in a carbon peapod oscillator

We investigate a new generation of fullerene nano-oscillators: a single-walled carbon nanotube with one buckyball inside with an operating frequency in the tens-of-gigahertz range. A quantitative characterization of energy dissipation channels in the peapod pair has been performed via molecular dynamics simulation. Edge effects are found to the dominant cause of dynamic friction in the carbon-peapod oscillators. A comparative study on energy dissipation also reveals significant impact of temperature and impulse velocity on the frictional force.Comment: 17 pages, 3 fig., 1 tabl

To Push or To Pull? In a Post-COVID World, Supporting and Incentivizing Antimicrobial Drug Development Must Become a Governmental Priority

This is the final version. Available on open access from the American Chemical Society via the DOI in this recorddata availability: This study did not generate any new data. The data on COVID-19 deaths used in the publication are publicly available at https://www.worldometers.info/coronavirus/ (access date 15th December 2020).The COVID-19 pandemic has refocused attention worldwide on the dangers of infectious diseases, in terms of both global health and the effects on the world economy. Even in high income countries, health systems have been found wanting in dealing with the new infectious agent. However, the even greater long-term danger of antimicrobial resistance in pathogenic bacteria and fungi is still under-appreciated, especially among the general public. Although antimicrobial drug development faces significant scientific challenges, the gravest challenge at the moment appears to be economic, where the lack of a viable market has led to a collapse in drug development pipelines. There is therefore a critical need for governments across the world to further incentivize the development of antimicrobials. Most incentive strategies over the past decade have focused on so-called “push” incentives that bridge the costs of antimicrobial research and development, but these have been insufficient for reviving the pipeline. In this Perspective, we analyze the current incentive strategies in place for antimicrobial drug development, and focus on “pull” incentives, which instead aim to improve revenue generation and thereby resolve the antimicrobial market failure challenge. We further analyze these incentives in a broader “One Health” context and stress the importance of developing and enforcing strict protocols to ensure appropriate manufacturing practices and responsible use. Our analysis reiterates the importance of international cooperation, coordination across antimicrobial research, and sustained funding in tackling this significant global challenge. A failure to invest wisely and continuously to incentivize antimicrobial pipelines will have catastrophic consequences for global health and wellbeing in the years to come.Wellcome TrustGCRF One Health Poultry HubMedical Research Council (MRC

Bayesian modeling of recombination events in bacterial populations

Background: We consider the discovery of recombinant segments jointly with their origins within multilocus DNA sequences from bacteria representing heterogeneous populations of fairly closely related species. The currently available methods for recombination detection capable of probabilistic characterization of uncertainty have a limited applicability in practice as the number of strains in a data set increases. Results: We introduce a Bayesian spatial structural model representing the continuum of origins over sites within the observed sequences, including a probabilistic characterization of uncertainty related to the origin of any particular site. To enable a statistically accurate and practically feasible approach to the analysis of large-scale data sets representing a single genus, we have developed a novel software tool (BRAT, Bayesian Recombination Tracker) implementing the model and the corresponding learning algorithm, which is capable of identifying the posterior optimal structure and to estimate the marginal posterior probabilities of putative origins over the sites. Conclusion: A multitude of challenging simulation scenarios and an analysis of real data from seven housekeeping genes of 120 strains of genus Burkholderia are used to illustrate the possibilities offered by our approach. The software is freely available for download at URL http://web.abo.fi/fak/ mnf//mate/jc/software/brat.html

Structural studies suggest aggregation as one of the modes of action for teixobactin

Teixobactin is a new promising antibiotic that targets cell wall biosynthesis by binding to lipid II and has no detectable resistance thanks to its unique but yet not fully understood mechanism of operation. To aid in the structure-based design of teixobactin analogues with improved pharmacological properties, we present a 3D structure of native teixobactin in membrane mimetics and characterise its binding to lipid II through a combination of solution NMR and fast (90 kHz) magic angle spinning solid state NMR. In NMR titrations, we observe a pattern strongly suggesting interactions between the backbone of the C-terminal “cage” and the pyrophosphate moiety in lipid II. We find that the N-terminal part of teixobactin does not only act as a membrane anchor, as previously thought, but is actively involved in binding. Moreover, teixobactin forms a well-structured and specific complex with lipid II, where the N-terminal part of teixobactin assumes a b conformation that is highly prone to aggregation, which likely contributes to the antibiotic's high bactericidal efficiency. Overall, our study provides several new clues to teixobactin's modes of action

The European Photon Imaging Camera on XMM-Newton: The MOS Cameras

The EPIC focal plane imaging spectrometers on XMM-Newton use CCDs to record the images and spectra of celestial X-ray sources focused by the three X-ray mirrors. There is one camera at the focus of each mirror; two of the cameras contain seven MOS CCDs, while the third uses twelve PN CCDs, defining a circular field of view of 30 arcmin diameter in each case. The CCDs were specially developed for EPIC, and combine high quality imaging with spectral resolution close to the Fano limit. A filter wheel carrying three kinds of X-ray transparent light blocking filter, a fully closed, and a fully open position, is fitted to each EPIC instrument. The CCDs are cooled passively and are under full closed loop thermal control. A radio-active source is fitted for internal calibration. Data are processed on-board to save telemetry by removing cosmic ray tracks, and generating X-ray event files; a variety of different instrument modes are available to increase the dynamic range of the instrument and to enable fast timing. The instruments were calibrated using laboratory X-ray beams, and synchrotron generated monochromatic X-ray beams before launch; in-orbit calibration makes use of a variety of celestial X-ray targets. The current calibration is better than 10% over the entire energy range of 0.2 to 10 keV. All three instruments survived launch and are performing nominally in orbit. In particular full field-of-view coverage is available, all electronic modes work, and the energy resolution is close to pre-launch values. Radiation damage is well within pre-launch predictions and does not yet impact on the energy resolution. The scientific results from EPIC amply fulfil pre-launch expectations.Comment: 9 pages, 11 figures, accepted for publication in the A&A Special Issue on XMM-Newto

Toxic metal enrichment and boating intensity: sediment records of antifoulant copper in shallow lakes of eastern England

Tributyltin (TBT), an aqueous biocide derived from antifouling paint pollution, is known to have impacted coastal marine ecosystems, and has been reported in the sediment of the Norfolk and Suffolk Broads, a network of rivers and shallow lakes in eastern England. In the marine environment, the 1987 TBT ban has resulted in expanded use of alternative biocides, raising the question of whether these products too have impacted the Broads ecosystem and freshwaters in general. Here we examine the lake sediment record in the Norfolk and Suffolk Broads for contamination by copper (Cu) (as an active biocide agent) and zinc (Zn) (as a component of booster biocides), to assess their occurrence and potential for causing environmental harm in freshwater ecosystems. We find that, after the introduction of leisure boating, there is a statistically significant difference in Cu enrichment between heavily and lightly boated sites, while no such difference exists prior to this time. At the heavily boated sites the onset of Cu enrichment coincides with a period of rapid increase in leisure boating. Such enrichment is maintained to the present day, with some evidence of continued increase. We conclude that Cu-based antifouling has measurably contaminated lakes exposed to boating, at concentrations high enough to cause ecological harm. Similar findings can be expected at other boated freshwater ecosystems elsewhere in the world

Why do GPs with a special interest in headache investigate headache presentations with neuroradiology and what do they find?

The general practitioner with a special interest in headache offers an important contribution to the management of headache in primary care where the majority of presentations take place. A number of guidelines have been developed for neuroradiological investigation of headache, but their clinical utility and relevance is not known. Fourteen general practitioners with a special interest in headache recorded consecutive headache consultations over a 3-month period, whether patients were investigated with neuroradiology and if so the reason for investigation and outcome. Reason for investigation was compared to the guidelines published for the use in primary care. 895 patients were seen, of whom 270 (30.1%) were investigated. 47% of indications were outside the guidance framework used, the most common reason for investigation being reassurance. Of those investigated, 5.6% showed positive findings but only 1.9% of findings were felt to be of clinical significance. General practitioners with a special interest investigated with neuroradiology a greater level than general practitioners, but less than neurologists. However, yields of significant findings are broadly comparative across all groups. This report confirms other studies that suggest that even when there is a high level of clinical suspicion, yields of significant findings are very low