7,479 research outputs found
Systems thinking research - principles and methodologies to grapple with complex real world problems
Shaking Stakeholders to Leverage a Firm’s Unique Capacity in Issue Networks
Firms are often seen to react to stakeholder pressure. However, if one changes the unit of analysis to a social or environmental issue, a firm emerges as a key influencer in mobilizing and connecting other stakeholders. For a variety of reasons, including the firm’s raison d’etre of creating value, a firm may be a critical leader or lynchpin in a movement, especially where it bridges gaps in a previously disconnected network. Two previously underappreciated aspects of stakeholder ties are highlighted in this paper. First, the firm can be seen as shaking otherwise latent stakeholders out of complacency, inasmuch as a firm informs and stimulates concerns, emotions, and actions among stakeholders in relation to a particular issue. Second, the firm can be seen as shaking-up the connections between stakeholders, catalyzing new contacts and relationships within an issue network
Shake Your Stakeholder: Firms Leading Engagement to Cocreate Sustainable Value
© The Author(s) 2017. While most extant scholarship has focused on how stakeholders influence firms, we propose that firms play a critical role in “shaking” stakeholders. Shaking stakeholders means to proactively initiate cooperation with those affected by a firm to alter awareness, behavior, and networks so as to catalyze change in society and the marketplace to reward cocreated innovations in core operations of the firm that improve social and environmental impacts. Two previously underappreciated aspects of stakeholder relations are highlighted. First, the firm can be the entity that leads engagement that shakes stakeholders out of complacency. Second, firms can catalyze collaborative relationships to cocreate sustainable value that is shared with stakeholders. We offer several cases to illustrate this strategy. While stakeholder shaking may be useful in any business environment, global ecological crises, societal problems, and governance failures heighten the need for firms to take action to bring about profound and systemic changes
African trypanosomiasis in travelers returning to the United Kingdom.
Two returning safari tourists with African trypanosomiasis were admitted to the Hospital for Tropical Diseases, London, in a 3-day period, compared with six cases in the previous 14 years. We describe the clinical features, diagnosis, and problems encountered in accessing appropriate therapy, and discuss the potential for emergence of this disease in increasingly adventurous international travelers
Modeling of arylamide helix mimetics in the p53 peptide binding site of hDM2 suggests parallel and anti-parallel conformations are both stable.
The design of novel α-helix mimetic inhibitors of protein-protein interactions is of interest to pharmaceuticals and chemical genetics researchers as these inhibitors provide a chemical scaffold presenting side chains in the same geometry as an α-helix. This conformational arrangement allows the design of high affinity inhibitors mimicking known peptide sequences binding specific protein substrates. We show that GAFF and AutoDock potentials do not properly capture the conformational preferences of α-helix mimetics based on arylamide oligomers and identify alternate parameters matching solution NMR data and suitable for molecular dynamics simulation of arylamide compounds. Results from both docking and molecular dynamics simulations are consistent with the arylamides binding in the p53 peptide binding pocket. Simulations of arylamides in the p53 binding pocket of hDM2 are consistent with binding, exhibiting similar structural dynamics in the pocket as simulations of known hDM2 binders Nutlin-2 and a benzodiazepinedione compound. Arylamide conformations converge towards the same region of the binding pocket on the 20 ns time scale, and most, though not all dihedrals in the binding pocket are well sampled on this timescale. We show that there are two putative classes of binding modes for arylamide compounds supported equally by the modeling evidence. In the first, the arylamide compound lies parallel to the observed p53 helix. In the second class, not previously identified or proposed, the arylamide compound lies anti-parallel to the p53 helix
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B1 resonance in coupled πω, πφ scattering from lattice QCD
We present the first lattice QCD calculation of coupled and
scattering, incorporating coupled and -wave in
. Finite-volume spectra in three volumes are determined via a
variational analysis of matrices of two-point correlation functions, computed
using large bases of operators resembling single-meson, two-meson and
three-meson structures, with the light-quark mass corresponding to a pion mass
of MeV. Utilizing the relationship between the discrete
spectrum of finite-volume energies and infinite-volume scattering amplitudes,
we find a narrow axial-vector resonance (), the analogue of the
meson, with mass MeV and width
MeV. The resonance is found to couple dominantly to -wave , with
a much-suppressed coupling to -wave , and a negligible coupling
to consistent with the `OZI rule'. No resonant behavior is observed
in , indicating the absence of a putative low-mass analogue of
the claimed in . In order to minimally present the contents
of a unitary three-channel scattering matrix, we introduce an -channel
generalization of the traditional two-channel Stapp parameterization
The revision partial knee classification system: understanding the causative pathology and magnitude of further surgery following partial knee arthroplasty.
AIMS: Joint registries classify all further arthroplasty procedures to a knee with an existing partial arthroplasty as revision surgery, regardless of the actual procedure performed. Relatively minor procedures, including bearing exchanges, are classified in the same way as major operations requiring augments and stems. A new classification system is proposed to acknowledge and describe the detail of these procedures, which has implications for risk, recovery, and health economics. METHODS: Classification categories were proposed by a surgical consensus group, then ranked by patients, according to perceived invasiveness and implications for recovery. In round one, 26 revision cases were classified by the consensus group. Results were tested for inter-rater reliability. In round two, four additional cases were added for clarity. Round three repeated the survey one month later, subject to inter- and intrarater reliability testing. In round four, five additional expert partial knee arthroplasty surgeons were asked to classify the 30 cases according to the proposed revision partial knee classification (RPKC) system. RESULTS: Four classes were proposed: PR1, where no bone-implant interfaces are affected; PR2, where surgery does not include conversion to total knee arthroplasty, for example, a second partial arthroplasty to a native compartment; PR3, when a standard primary total knee prosthesis is used; and PR4 when revision components are necessary. Round one resulted in 92% inter-rater agreement (Kendall's W 0.97; p < 0.005), rising to 93% in round two (Kendall's W 0.98; p < 0.001). Round three demonstrated 97% agreement (Kendall's W 0.98; p < 0.001), with high intra-rater reliability (interclass correlation coefficient (ICC) 0.99; 95% confidence interval 0.98 to 0.99). Round four resulted in 80% agreement (Kendall's W 0.92; p < 0.001). CONCLUSION: The RPKC system accounts for all procedures which may be appropriate following partial knee arthroplasty. It has been shown to be reliable, repeatable and pragmatic. The implications for patient care and health economics are discussed. Cite this article: Bone Jt Open 2021;2(8):638-645
Decays of an exotic 1-+ hybrid meson resonance in QCD
We present the first determination of the hadronic decays of the lightest
exotic resonance in lattice QCD. Working with SU(3) flavor
symmetry, where the up, down and strange quark masses approximately match the
physical strange-quark mass giving MeV, we compute
finite-volume spectra on six lattice volumes which constrain a scattering
system featuring eight coupled channels. Analytically continuing the scattering
amplitudes into the complex energy plane, we find a pole singularity
corresponding to a narrow resonance which shows relatively weak coupling to the
open pseudoscalar--pseudoscalar, vector--pseudoscalar and vector--vector decay
channels, but large couplings to at least one kinematically-closed
axial-vector--pseudoscalar channel. Attempting a simple extrapolation of the
couplings to physical light-quark mass suggests a broad resonance
decaying dominantly through the mode with much smaller decays into
, , and . A large total width is
potentially in agreement with the experimental candidate state,
observed in , , which we suggest may be heavily suppressed
decay channels
'Big Data' informed drug development: a case for acceptability
Data, which help inform various stages of drug product development, are increasingly being collected using newer, more novel platforms, such as mobile applications, and analysed computationally as much larger 'Big Data' data sets, revealing patterns relating to human behaviour and interactions. Medicine acceptability gauges the ability and willingness of patients to take their dosage forms. It has become a crucial human component of drug product design. Vouching for the age appropriateness of medicinal products, acceptability related data are now expected by regulatory bodies. Shifting from traditional paper-based to electronic data-gathering platforms will allow the pharmaceutical industry to collect real-world, real-time, clinically relevant data, capable of informing current and future drug product development, reducing time and cost, and setting foundations for patient-centric drug product design
The addition of granulocyte macrophage colony stimulating factor (GM-CSF) to juvenile systemic lupus erythematosus serum can reduce abnormal neutrophil apoptosis
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