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  • Membrane insertion and secretion of the Engrailed-2 (EN2) transcription factor by prostate cancer cells may induce antiviral activity in the stroma

    Punia, N.; Primon, Monika; Simpson, G.R.; Pandha, H.S.; Morgan, Richard (2019-03)
    Engrailed-2 (EN2) is a homeodomain-containing transcription factor that has roles in boundary formation and neural guidance in early development, but which is also expressed in a range of cancers. In addition to transcriptional regulation, it is secreted by cells and taken up by others through a mechanism that is yet to be fully elucidated. In this study, the distribution of EN2 protein in cells was evaluated using immunofluorescence with a set of antibodies raised against overlapping epitopes across the protein, and through the use of an EN2-GFP construct. MX2 expression in primary prostate tumors was evaluated using immunohistochemistry. We showed that EN2 protein is present in the cell membrane and within microvesicles that can be secreted from the cell and taken up by others. When taken up by normal cells from the stroma EN2 induces the expression of MX2 (MxB), a protein that has a key role in the innate immune response to viruses. Our findings indicate that EN2 secretion by tumors may be a means of preventing viral-mediated immune invasion of tissue immediately adjacent to the tumor.
  • Efficient simulations of the aqueous bio-interface of graphitic nanostructures with a polarisable model

    Hughes, Zak E.; Tomasio, S.M.; Walsh, T.R. (2014-05)
    To fully harness the enormous potential offered by interfaces between graphitic nanostructures and biomolecules, detailed connections between adsorbed conformations and adsorption behaviour are needed. To elucidate these links, a key approach, in partnership with experimental techniques, is molecular simulation. For this, a force-field (FF) that can appropriately capture the relevant physics and chemistry of these complex bio-interfaces, while allowing extensive conformational sampling, and also supporting inter-operability with known biological FFs, is a pivotal requirement. Here, we present and apply such a force-field, GRAPPA, designed to work with the CHARMM FF. GRAPPA is an efficiently implemented polarisable force-field, informed by extensive plane-wave DFT calculations using the revPBE-vdW-DF functional. GRAPPA adequately recovers the spatial and orientational structuring of the aqueous interface of graphene and carbon nanotubes, compared with more sophisticated approaches. We apply GRAPPA to determine the free energy of adsorption for a range of amino acids, identifying Trp, Tyr and Arg to have the strongest binding affinity and Asp to be a weak binder. The GRAPPA FF can be readily incorporated into mainstream simulation packages, and will enable large-scale polarisable biointerfacial simulations at graphitic interfaces, that will aid the development of biomolecule-mediated, solution-based graphene processing and self-assembly strategies.
  • Molecular mechanism of the synergistic effects of vitrification solutions on the stability of phospholipid bilayers

    Hughes, Zak E.; Mancera, R.L. (2014-06-17)
    The vitrification solutions used in the cryopreservation of biological samples aim to minimize the deleterious formation of ice by dehydrating cells and promoting the formation of the glassy state of water. They contain a mixture of different cryoprotective agents (CPAs) in water, typically polyhydroxylated alcohols and/or dimethyl sulfoxide (DMSO), which can damage cell membranes. Molecular dynamics simulations have been used to investigate the behavior of pure DPPC, pure DOPC, and mixed DOPC-β-sitosterol bilayers solvated in a vitrification solution containing glycerol, ethylene glycol, and DMSO at concentrations that approximate the widely used plant vitrification solution 2. As in the case of solutions containing a single CPA, the vitrification solution causes the bilayer to thin and become disordered, and pores form in the case of some bilayers. Importantly, the degree of thinning is, however, substantially reduced compared to solutions of DMSO containing the same total CPA concentration. The reduction in the damage done to the bilayers is a result of the ability of the polyhydroxylated species (especially glycerol) to form hydrogen bonds to the lipid and sterol molecules of the bilayer. A decrease in the amount of DMSO in the vitrification solution with a corresponding increase in the amount of glycerol or ethylene glycol diminishes further its damaging effect due to increased hydrogen bonding of the polyol species to the bilayer headgroups. These findings rationalize, to our knowledge for the first time, the synergistic effects of combining different CPAs, and form the basis for the optimization of vitrification solutions.
  • Comparative study of materials-binding peptide interactions with gold and silver surfaces and nanostructures: A thermodynamic basis for biological selectivity of inorganic materials

    Palafox-Hernandez, J.P.; Tang, Z.; Hughes, Zak E.; Li, Y.; Swihart, M.T.; Prasad, P.N.; Walsh, T.R.; Knecht, M.R. (2014-09)
    Controllable 3D assembly of multicomponent inorganic nanomaterials by precisely positioning two or more types of nanoparticles to modulate their interactions and achieve multifunctionality remains a major challenge. The diverse chemical and structural features of biomolecules can generate the compositionally specific organic/inorganic interactions needed to create such assemblies. Toward this aim, we studied the materials-specific binding of peptides selected based upon affinity for Ag (AgBP1 and AgBP2) and Au (AuBP1 and AuBP2) surfaces, combining experimental binding measurements, advanced molecular simulation, and nanomaterial synthesis. This reveals, for the first time, different modes of binding on the chemically similar Au and Ag surfaces. Molecular simulations showed flatter configurations on Au and a greater variety of 3D adsorbed conformations on Ag, reflecting primarily enthalpically driven binding on Au and entropically driven binding on Ag. This may arise from differences in the interfacial solvent structure. On Au, direct interaction of peptide residues with the metal surface is dominant, while on Ag, solvent-mediated interactions are more important. Experimentally, AgBP1 is found to be selective for Ag over Au, while the other sequences have strong and comparable affinities for both surfaces, despite differences in binding modes. Finally, we show for the first time the impact of these differences on peptide mediated synthesis of nanoparticles, leading to significant variation in particle morphology, size, and aggregation state. Because the degree of contact with the metal surface affects the peptide’s ability to cap the nanoparticles and thereby control growth and aggregation, the peptides with the least direct contact (AgBP1 and AgBP2 on Ag) produced relatively polydispersed and aggregated nanoparticles. Overall, we show that thermodynamically different binding modes at metallic interfaces can enable selective binding on very similar inorganic surfaces and can provide control over nanoparticle nucleation and growth. This supports the promise of bionanocombinatoric approaches that rely upon materials recognition.
  • Binding affinities of amino acid analogues at the charged aqueous titania interface: implications for titania-binding peptides

    Sultan, A.M.; Hughes, Zak E.; Walsh, T.R. (2014-11)
    Despite the extensive utilization of biomolecule-titania interfaces, biomolecular recognition and interactions at the aqueous titania interface remain far from being fully understood. Here, atomistic molecular dynamics simulations, in partnership with metadynamics, are used to calculate the free energy of adsorption of different amino acid side chain analogues at the negatively-charged aqueous rutile TiO2 (110) interface, under conditions corresponding with neutral pH. Our calculations predict that charged amino acid analogues have a relatively high affinity to the titania surface, with the arginine analogue predicted to be the strongest binder. Interactions between uncharged amino acid analogues and titania are found to be repulsive or weak at best. All of the residues that bound to the negatively-charged interface show a relatively stronger adsorption compared with the charge-neutral interface, including the negatively-charged analogue. Of the analogues that are found to bind to the titania surface, the rank ordering of the binding affinities is predicted to be "arginine" > "lysine" ≈ aspartic acid > "serine". This is the same ordering as was found previously for the charge-neutral aqueous titania interface. Our results show very good agreement with available experimental data and can provide a baseline for the interpretation of peptide-TiO2 adsorption data.
  • Structure of the electrical double layer at aqueous gold and silver interfaces for saline solutions

    Hughes, Zak E.; Walsh, T.R. (2014-12-15)
    We report the structure of the electrical double layer, determined from molecular dynamics simulations, for a range of saline solutions (NaCl, KCl, MgCl2 and CaCl2) at both 0.16 and 0.60 mol kg(-1) on different facets of the gold and silver aqueous interfaces. We consider the Au/Ag(111), native Au/Ag(100) and reconstructed Au(100)(5×1) facets. For a given combination of metallic surface and facet, some variations in density profile are apparent across the different cations in solution, with the corresponding chloride counterion profiles remaining broadly invariant. All density profiles at the higher concentration are predicted to be very similar to their low-concentration counterparts. We find that each electrolyte responds differently to the different metallic surface and facets, particularly those of the divalent metal ions. Our findings reveal marked differences in density profiles between facets for a given metallic interface for both Mg(2+) and Ca(2+), with Na(+) and K(+) showing much less distinction. Mg(2+) was the only ion for which we find evidence of materials-dependent differences in interfacial solution structuring between the Ag and Au.
  • BMPRII deficiency impairs apoptosis via the BMPRII-ALK1-BclX-mediated pathway in pulmonary arterial hypertension (PAH)

    Chowdhury, H.M.; Sharmin, N.; Yuzbasioglu Baran, M.; Long, L.; Morrell, N.W.; Trembath, R.C.; Nasim, Md. Talat (2019)
    Pulmonary Arterial Hypertension (PAH) is a devastating cardiovascular disorder characterised by the remodelling of pre-capillary pulmonary arteries. The vascular remodelling observed in PAH patients results from excessive proliferation and apoptosis resistance of pulmonary arterial smooth muscle (PASMCs) and endothelial cells (PAECs). We have previously demonstrated that mutations in the type II receptor for bone morphogenetic protein (BMPRII) underlie the majority of the familial and inherited forms of the disease. We have further demonstrated that BMPRII deficiency promotes excessive proliferation and attenuates apoptosis in PASMCs, but the underlying mechanisms remain unclear. The major objective of this study is to investigate how BMPRII deficiency impairs apoptosis in PAH. Using multidisciplinary approaches, we demonstrate that deficiency in the expression of BMPRII impairs apoptosis by modulating the alternative splicing of the apoptotic regulator, Bcl-x (B-cell lymphoma X) transcripts: a finding observed in circulating leukocytes and lungs of PAH subjects, hypoxia-induced PAH rat lungs as well as in PASMCs and PAECs. BMPRII deficiency elicits cell specific effects: promoting the expression of Bcl-xL transcripts in PASMCs whilst inhibiting it in ECs, thus exerting differential apoptotic effects in these cells. The pro-survival effect of BMPRII receptor is mediated through the activin receptor like kinase 1 (ALK1) but not the ALK3 receptor. Finally, we show that BMPRII interacts with the ALK1 receptor and pathogenic mutations in the BMPR2 gene abolish this interaction. Taken together, dysfunctional BMPRII responsiveness impairs apoptosis via the BMPRII-ALK1-Bcl-xL pathway in PAH. We suggest Bcl-xL as a potential biomarker and druggable target.
  • Uptake of oral anticoagulants for stroke prevention in patients with atrial fibrillation in a single Clinical Commissioning Group in England without restrictions to their use

    Medlinskiene, Kristina; Fay, M.; Petty, Duncan R. (2019)
    Background and Objective In England, the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fbrillation has been slow and varied across diferent Clinical Commissioning Groups (CCGs). This study aimed to profle the prescribing of oral anticoagulants for stroke prevention in patients with atrial fbrillation over 3 years in a CCG without restrictions to DOACs use to understand more about organisational and/or individual barriers to the early uptake of DOACs. Methods Data were collected from nine general practices between 1 April 2012 and 31 March 2015 of patients who were initiated on the oral anticoagulant therapy. Data were analysed descriptively and with independent Student’s t test and Chi square test to explore if there was an association between type of oral anticoagulant initiated and sex, age, type of prescriber and prior aspirin use. Results The early uptake of DOACs signifcantly increased over the study period (p<0.0001; medium size efect φc=0.372). There was no statistically signifcant diference between sex or age and type of oral anticoagulant initiated. Primary-care prescribers were responsible for initiating the majority of oral anticoagulants (71%; N=257) and driving the use of DOACs (72%, N=71). Patients switched from aspirin to an oral anticoagulant were more likely to be initiated on warfarin than a DOAC. Conclusions The early use of DOACs, in a CCG without restrictions to their use, was embraced by primary-care prescribers in this particular CCG.
  • Prophylaxis pharmacotherapy to prevent the onset of post traumatic brain injury depression: a systematic review

    Clay, F.; Hicks, A.; Zaman, Hadar; Ponsford, J.; Batty, R.; Perry, L.; Hopwood, M.J. (2019)
    Background: Depression is a common psychiatric problem following traumatic brain injury (TBI) with reported prevalence rates of 30-77% in the first year post-TBI. Given the negative influence of post-TBI depression on cognition, interpersonal, social, physical and occupational functioning; early initiation of pharmacotherapy to prevent post-TBI depression has been considered. This systematic review will synthesize the available evidence from published studies on the effectiveness and harms of pharmacotherapy for the secondary prevention of post-TBI depression. Method: Studies published before November 2017 were reviewed. Six databases were searched, with additional searching of key additional documents. Studies meeting inclusion criteria were evaluated for methodological quality. Results: Six articles addressing five studies met inclusion criteria. Study designs included three randomised controlled trials (RCT), two retrospective cohorts and one case-control. Prophylactic pharmacotherapy included antidepressants, beta-blockers and statins. In one RCT, the number-needed-to-treat with sertraline to prevent one case of depression post-TBI at 24 weeks was 5.9 (95%CI: 3.1-71.1). Prescribing beta-blockers prior to TBI reduced the depression risk regardless of the specific brain trauma. TBI patients with pre-existing hyperlipidemia not treated with statins had an increased depression risk compared to those without hyperlipidemia. Conclusion: Early initiation of sertraline prophylaxis in nondepressed TBI patients shows promise to reduce the odds of post-TBI depression developing. However, in the absence of rigorous study of tolerability, existing data are insufficient to recommend sertraline prophylaxis. Optimal timing and treatment duration with identification of patients most likely to benefit from prophylaxis require further consideration. Dedicated prospective studies assessing the effects of beta-blockers and statins on post-TBI depression are required.
  • Highly-branched poly(N-isopropyl acrylamide) functionalised with pendant Nile red and chain end vancomycin for the detection of Gram-positive bacteria

    Swift, Thomas; Katsikogianni, Maria G.; Hoskins, Richard; Teratarantorn, P.; Douglas, I.; MacNeil, S.; Rimmer, Stephen (2019-03-15)
    This study shows how highly branched poly(N-isopropyl acrylamide) (HB-PNIPAM) with a chain pendant solvatochromic dye (Nile red) could provide a fluorescence signal, as end groups bind to bacteria and chain segments become desolvated, indicating the presence of bacteria. Vancomycin was attached to chain ends of HB-PNIPAM or as pendant groups on linear polymers each containing Nile red. Location of the dye was varied between placement in the core of the branched polymer coil or the outer domains. Both calorimetric and fluorescence data showed that branched polymers responded to binding of both the peptide target (D-Ala-D-Aa) and bacteria in a different manner than analogous linear polymers; binding and response was more extensive in the branched variant. The fluorescence data showed that only segments located in the outer domains of branched polymers responded to binding of Gram-positive bacteria with little response when linear analogous polymer or branched polymer with the dye in the inner core was exposed to Staphylococcus aureus.
  • A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals

    Helfer, Gisela; Barrett, P.; Morgan, P.J. (2019-03)
    Animals have evolved diverse seasonal variations in physiology and reproduction to accommodate yearly changes in environmental and climatic conditions. These changes in physiology are initiated by changes in photoperiod (daylength) and are mediated through melatonin, which relays photoperiodic information to the pars tuberalis of the pituitary gland. Melatonin drives thyroid‐stimulating hormone transcription and synthesis in the pars tuberalis, which, in turn, regulates thyroid hormone and retinoic acid synthesis in the tanycytes lining the third ventricle of the hypothalamus. Seasonal variation in central thyroid hormone signalling is conserved among photoperiodic animals. Despite this, different species adopt divergent phenotypes to cope with the same seasonal changes. A common response amongst different species is increased hypothalamic cell proliferation/neurogenesis in short photoperiod. That cell proliferation/neurogenesis may be important for seasonal timing is based on (i) the neurogenic potential of tanycytes; (ii) the fact that they are the locus of striking seasonal morphological changes; and (iii) the similarities to mechanisms involved in de novo neurogenesis of energy balance neurones. We propose that a decrease in hypothalamic thyroid hormone and retinoic acid signalling initiates localised neurodegeneration and apoptosis, which leads to a reduction in appetite and body weight. Neurodegeneration induces compensatory cell proliferation from the neurogenic niche in tanycytes and new cells are born under short photoperiod. Because these cells have the potential to differentiate into a number of different neuronal phenotypes, this could provide a mechanistic basis to explain the seasonal regulation of energy balance, as well as reproduction. This cycle can be achieved without changes in thyroid hormone/retinoic acid and explains recent data obtained from seasonal animals held in natural conditions. However, thyroid/retinoic acid signalling is required to synchronise the cycles of apoptosis, proliferation and differentiation. Thus, hypothalamic neurogenesis provides a framework to explain diverse photoperiodic responses.
  • Pharmacist educational interventions for cancer pain management: a systematic review and meta-analysis

    Edwards, Zoe; Ziegler, L.; Craigs, C.; Blenkinsopp, Alison; Bennett, M.I. (2019)
    Educational interventions by pharmacists for patients with cancer pain aim to improve pain management, but little is known about the different components of interventions and their effectiveness. Our aim was to assess the benefit of pharmacist delivered educational interventions for patients with cancer pain. A systematic review and meta‐analysis of experimental trials testing pharmacist delivered educational interventions for cancer pain was carried out to identify the components of interventions and effectiveness at improving pain‐related outcomes for patients with cancer. A literature review was conducted in EMBASE, MEDLINE, CINAHL, PsycINFO, ASSIA, Web of Science and CENTRAL from inception until January 2018 searching for educational interventions involving a pharmacist for patients with cancer pain. Four studies were included involving 944 patients. Meta‐analysis was carried out where possible. Meta‐analysis of three of the four studies found that mean pain intensity in the intervention group was reduced by 0.76 on a 0–10 scale (95% confidence interval), although only two of the studies used validated measures of pain. Improvements in knowledge, side effects and patient satisfaction were seen although with less reliable measures. Pharmacist educational interventions for patients with cancer pain have been found to show promise in reducing pain intensity. Studies were few and of varying quality. Further, good quality studies should be carried out in this area and these should be comprehensively reported. Trials measuring patient self‐efficacy and patient satisfaction are needed before the impact of the pharmacist delivered interventions on these outcomes can be established.
  • A muscle mimetic polyelectrolyte–nanoclay organic–inorganic hybrid hydrogel: its self-healing, shape-memory and actuation properties

    Banerjee, S.L.; Swift, Thomas; Hoskins, Richard; Rimmer, Stephen; Singha, N.K. (2019)
    Here in, we describe a non-covalent (ionic interlocking and hydrogen bonding) strategy of self-healing in a covalently crosslinked organic-inorganic hybrid 15 nanocomposite hydrogel, with special emphasize on it's improved mechanical stability. The hydrogel was prepared via in-situ free radical polymerization of sodium acrylate (SA) and successive crosslinking in the presence of poly(2-(methacryloyloxy)ethyl trimethyl ammonium chloride) (PMTAC) grafted cationically armed starch and organically modified montmorillonite (OMMT). This hydrogel shows stimuli triggered self-healing following damage in both neutral and acidic solutions (pH=7.4 and pH=1.2). This was elucidated by tensile strength and rheological analyses of the hydrogel segments joined at their fractured points. Interestingly this hydrogel can show water based shape memory effects. It was observed that the ultimate tensile strength (UTS) of the self-healed hydrogel at pH = 7.4 was comparable to extensor digitorum longus (EDL) muscle of the New Zealand white rabbit. The as synthesized self-healable hydrogel was found to be non-cytotoxic against NIH 3T3 fibroblast cells.
  • How do we avoid the ‘ever decreasing circles syndrome’ in service improvement?

    Manzoor, A.; Breen, Liz; Marques, Iuri; Edwards, Zoe (2018-09)
  • Description of Potential Energy Surfaces of Molecules using FFLUX Machine Learning Models

    Hughes, Zak E.; Thacker, J.C.R.; Wilson, A.L.; Popelier, P.L.A. (2019)
    A new type of model, FFLUX, to describe the interaction between atoms has been developed as an alternative to traditional force fields. FFLUX models are constructed from applying the kriging machine learning method to the topological energy partitioning method, Interacting Quantum Atoms (IQA). The effect of varying parameters in the construction of the FFLUX models is analyzed, with the most dominant effects found to be the structure of the molecule and the number of conformations used to build the model. Using these models the optimization of a variety of small organic molecules is performed, with sub kJ mol-1 accuracy in the energy of the optimized molecules. The FFLUX models are also evaluated in terms of their performance in describing the potential energy surfaces (PESs) associated with specific degrees of freedoms within molecules. While the accurate description of PESs presents greater challenges than individual minima, FFLUX models are able to achieve errors of <2.5 kJ mol-1 across the full C-C-C-C dihedral PES of n-butane, indicating the future possibilities of the technique.
  • Development and evaluation of nanoemulsion and microsuspension formulations of curcuminoids for lung delivery with a novel approach to understanding the aerosol performance of nanoparticles

    Al Ayoub, Yuosef; Gopalan, Rajendran C.; Najafzadeh, Mojgan; Mohammad, Mohammad A.; Anderson, Diana; Paradkar, Anant R.; Assi, Khaled H. (2019-02-25)
    Extensive research has demonstrated the potential effectiveness of curcumin against various diseases, including asthma and cancers. However, few studies have used liquid-based vehicles in the preparation of curcumin formulations. Therefore, the current study proposed the use of nanoemulsion and microsuspension formulations to prepare nebulised curcuminoid for lung delivery. Furthermore, this work expressed a new approach to understanding the aerosol performance of nanoparticles compared to microsuspension formulations. The genotoxicity of the formulations was also assessed. Curcuminoid nanoemulsion formulations were prepared in three concentrations (100, 250 and 500 µg/ml) using limonene and oleic acid as oil phases, while microsuspension solutions were prepared by suspending curcuminoid particles in isotonic solution (saline solution) of 0.02% Tween 80. The average fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of the nebulised microsuspension formulations ranged from 26% and 7.1 µm to 40% and 5.7 µm, for 1000 µg/ml and 100 µg/ml respectively. In a comparison of the low and high drug concentrations of the nebulised nanoemulsion, the average FPF and MMAD of the nebulised nanoemulsion formulations prepared with limonene oil ranged from 50% and 4.6 µm to 45% and 5.6 µm, respectively; whereas the FPF and MMAD of the nebulised nanoemulsion prepared with oleic acid oil ranged from 46% and 4.9 µm to 44% and 5.6 µm, respectively. The aerosol performance of the microsuspension formulations were concentration dependent, while the nanoemulsion formulations did not appear to be dependent on the curcuminoids concentration. The performance and genotoxicity results of the formulations suggest the suitability of these preparations for further inhalation studies in animals.
  • An assessment of supply chain vulnerabilities to dynamic disruptions in the pharmaceutical supply chain

    Yaroson, Emilia V.; Sharief, Karam; Shah, Awn; Breen, Liz (2018-09)
    Objective: The adverse impact of supply chain disruptions on the operational performance of supply chains have been suggested to emanate from its existing vulnerabilities. However, empirical studies regarding this proposition remain limited. This study provides empirical evidence of vulnerabilities in the face of dynamic disruptions in the pharmaceutical supply chain. This is geared at developing resilience strategies capable of curbing these forms of disruptions. Research Approach: In seeking to achieve the objective of this study, the mixed method research design in a longitudinal framework was adopted. It involved a two-step procedure where the study began by conducting semi-structured interviews with the downstream stakeholders of the pharmaceutical supply chain. Here the sampling method adopted was both purposive and snowballing. Data collected from this process was analysed using thematic analysis where key variables were coded for further analysis. Findings from the interviews were employed to construct close ended questionnaires. The questionnaires were administered online, approximately nine months after the first data collection process ended and analysed using various statistical techniques. Findings: The themes that emerged from the first phase of the data generation process were classified into five main pillars which include: supply chain characteristics, regulatory framework (schemas), imbalance of market power, managerial decisions and supply chain structures. These themes were further confirmed by the findings from the survey. The study finds that imbalance of market power generates negative welfare such as time consumption and stress on the downstream stakeholders of the pharmaceutical supply chain. In the same vein, dependence on suppliers and consumers in designing the supply chain exacerbates the impact of a dynamic disruption. The findings from the survey complement these pillars by identifying other vulnerabilities: price manipulation, inadequate policies, inefficient manufacturing processes as well as available training in handling these vulnerabilities. Originality/Value: By providing empirical evidence of the vulnerabilities within the pharmaceutical supply chain in the face of a dynamic disruption, this study extends operations management literature by highlighting vulnerability benchmarks against which resilience strategies can be employed in dynamic disruptive scenarios. The innovative aspect of this research is the ability to identify the vulnerabilities peculiar to the pharmaceutical supply chain which is required in order to successfully develop strategies that are resilient to dynamic disruptions. Research Impact: This study extends existing debates on supply chain vulnerabilities as well as supply chain disruptions. Practical Impact: This study contributes to practical managerial decisions, as the identifications of vulnerabilities to dynamic disruptions will aid pharmaceutical and or operations managers in assessing supplier selection and design.
  • Identifying reverse exchange practices: a comparative study of laundry logistics in public hospitals (Thailand)

    Bandoophanit, T.; Breen, Liz (2018-09-07)
    The effective reverse exchange of healthcare products such as laundry within a hospital environment can support the health system, for achieving the highest goal: ‘to provide regular and timely supply of clean linen to the satisfaction of patients and staff’ (Srikar et al., 2015, p. 593). Previous studies by Bandoophanit et al. (2015, 2017) assert there are constant shortages of linen availability in many Thai public hospitals which can undermine the efficacy of laundry management and quality of medical treatment. This study investigates the practices, culture, and operational performance of three large-sized public hospitals (700-2,000 beds) located in Thailand reflecting on the application of Reverse Exchanges (R/E) theory. This study contributes to the Thai healthcare agenda, a core mission of which is to “Develop the health system with quality, efficiency and equality; with participation of the people, communities and all sectors for good health of all Thai people in order to achieve a good and sustainable society following the King’s Sufficiency Economy philosophy” (Ministry of Public Health, 2018).

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