Search

A selection of novel non-symmetric supramolecular liquid crystal dimers and trimers formed by hydrogen-bonding have been prepared and their phase behaviour characterised by polarised optical microscopy, X-ray diffraction and temperature-dependent Fourier-transform infrared spectroscopy. We mix the bent twist-bend nematogen 4-[6-(4&rsquo, cyanobiphenyl-4-yl) hexyloxy]-benzoic acid (CB6OBA) with a series of small stilbazole-based compounds 4-[(E)-2-(n-alkoxyphenyl)ethenyl]pyridines (nOS) of varying terminal chain length (n) to obtain the CB6OBA:nOS complexes. Complexes with n &le, 7 exhibit nematic and twist-bend nematic behaviour, followed on cooling by a smectic C phase for n = 4&ndash, 7, and finally, a hexatic-type smectic X phase for n = 3&ndash, 7. Mixtures with n = 8&ndash, 10 exhibit a smectic A phase below the conventional nematic phase, and on further cooling, a biaxial smectic Ab phase and the same hexatic-type SmX phase. Supramolecular trimers, CB6OBA:CB6OS and CB6OBA:1OB6OS, formed between CB6OBA and dimeric stilbazoles [(E)-2-(4-{[6-(4&rsquo, methoxy[1,1&rsquo, biphenyl]-4-yl)hexyl]oxy}phenyl)ethenyl]pyridine (1OB6OS) or 4-[(E)-4&rsquo, (6-{4-[(E)-2-(pyridin-4-yl)ethenyl]phenoxy}hexyl)[1,1&rsquo, biphenyl]-4- carbonitrile (CB6OS), exhibit nematic and twist-bend nematic phases, and are the first hydrogen-bonded trimers consisting of unlike donor and acceptor fragments to do so.

Why is there a need to innovate healthcare'? The basic reason stems from the sheer scale of the challenges now facing healthcare provision in the UK and across many other countries. The aim of this book is to interrogate past and current attempts to innovate in this arena and to draw-out the key lessons. Innovating Healthcare: The Role of Political, Managerial and Clinical Leadership presents the latest state of knowledge based on original data from a series of NIHR-funded research projects set in the context of a review of extensive secondary research. The book draws upon first-person verbatim accounts of change attempts made by doctors and other clinicians as well as upon research findings about the roles played by policy-makers and managers. The analysis draws upon theory and practice in leadership, innovation and institution-building. The mutually-reinforcing contributions of political, managerial and clinical leadership are at the core of the investigative narrative. This book will be of interest to students and researchers, clinicians and managers in the health and care sectors as well as policy-makers. While the focus in on healthcare, the book has wider relevance for students of management, leadership, innovation and organizational studies

The synthesis and characterisation of a range of non-symmetric liquid crystal dimers designed to exhibit the twist-bend nematic phase is reported. Beginning with 1-(4-cyanobiphenyl-4′-yloxy)-6-(4-cyanobiphenyl-4′-yl) hexane, each nitrile group is exchanged systematically for a methoxy group. The behaviour of these dimers is interpreted in terms of their bent shape being the predominant driving force for the formation of the twist-bend nematic phase, and the small differences between the twist-bend nematic–nematic transition temperatures are attributed to the differences between the interaction strength parameters of the mesogenic units. The 4-alkyloxyphenyl 4-[6-(4′-cyanobiphenyl-4-yl)hexyloxy]benzoates with ethyl, butyl, hexyl and octyl chains show the twist-bend nematic phase, whereas the corresponding 4-alkyloxyphenyl 4-[5-(4′-cyanobiphenyl-4-yloxy)pentyloxy]benzoates do not. This difference in behaviour is attributed to the more bent structure of the former. Increasing the terminal chain length initially decreases the twist-bend nematic–nematic transition temperature and this suggests that the chain disrupts the interactions between the mesogenic units. Subsequent increases in chain length have a smaller effect suggesting that the chain can be accommodated within an intercalated arrangement. The transitional behaviour of 1-(4-cyanobiphenyl-4′-yloxy)-6-(4-butyloxybiphenyl-4′-yl) hexane is compared to that of 1-(4-cyanobiphenyl-4′-yloxy)-6-(4-((S)-2-methyl)butyloxybiphenyl-4′-yl) hexane, and it is shown that chain branching strongly destabilises the twist-bend nematic phase. This is attributed to difficulties associated with packing the dimers.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. This paper examines how senior managers in a developing economy, Ethiopia, navigate between, and draw upon, the competing logics of ‘state’ and ‘market’ when seeking to explain their firm’s business strategies. This fault-line is especially critical in such contexts. The empirical work is based on qualitative analysis of interviews with 22 senior managers in matched-paired case studies drawn from a state-owned bank and private sector bank respectively, supplemented with secondary sources. The study reveals how top teams develop shared dominant logics which are patterned in a manner which reveals that the degree of ‘state-dependency’ was the critical variable and that the notion of the ‘market’ was a subsidiary variable. By extending management dominant logic literature into the literature on institutional logics, the study reveals the complementarity of these logics and their consequences for the strategic orientations of firms.

Background Although hydromethylthionine is a potent tau aggregation inhibitor, no difference was found in either of two Phase III trials in mild to moderate Alzheimer's disease (AD) comparing doses in the range 150-250 mg/day with 8 mg/day intended as a control. Objective To determine how drug exposure is related to treatment response. Methods A sensitive plasma assay for the drug was used in a population pharmacokinetic analysis of samples from 1,162 of the 1,686 patients who participated in either of the Phase III trials with available samples and efficacy outcome data. Results There are steep concentration-response relationships for steady state plasma levels in the range 0.3-0.8 ng/ml at the 8 mg/day dose. Using a threshold based on the lower limit of quantitation of the assay on Day 1, there are highly significant differences in cognitive decline and brain atrophy in patients with above threshold plasma levels, both for monotherapy and add-on therapy, but with effect sizes reduced by half as add-on. Plasma concentrations in the range 4-21 ng/ml produced by the high doses are not associated with any additional benefit. Conclusions Hydromethylthionine has pharmacological activity on brain structure and function at the 8 mg/day dose as monotherapy or as add-on to symptomatic treatments. This combined with a plateau at higher doses is consistent with the lack of dose-response seen in the Phase III trials. Treatment benefit is predicted to be maximal at 16 mg/day as monotherapy. A placebo-controlled trial in mild/moderate AD is now ongoing to confirm efficacy at this dose.

The most important inter­molecular inter­actions in the two indole derivatives described here are N—H⋯π bonds, which lead to chains in one case and inversion dimers in the other; C—H⋯π inter­actions appear to reinforce the N—H⋯π bonds in each case., We describe the syntheses and crystal structures of two indole derivatives, namely 6-isopropyl-3-(2-nitro-1-phenyl­eth­yl)-1H-indole, C19H20N2O2, (I), and 2-(4-meth­oxy­phen­yl)-3-(2-nitro-1-phenyl­eth­yl)-1H-indole, C23H20N2O3, (II); the latter crystallizes with two mol­ecules (A and B) with similar conformations (r.m.s. overlay fit = 0.139 Å) in the asymmetric unit. Despite the presence of O atoms as potential acceptors for classical hydrogen bonds, the dominant inter­molecular inter­action in each crystal is an N—H⋯π bond, which generates chains in (I) and A+A and B+B inversion dimers in (II). A different aromatic ring acts as the acceptor in each case. The packing is consolidated by C—H⋯π inter­actions in each case but aromatic π–π stacking inter­actions are absent.

The mol­ecular conformations of three highly substituted cyclo­penta­[c]furans appear to correlate strongly with different intra­molecular O—H⋯O and C—H⋯O inter­actions., The crystal structures of three cyclo­penta­[c]furans with various substituents at the 4-, 5- and 6-positions of the ring system are reported, namely, (±)-(3aR,4S,5S,6aS)-4-methyl-5-phenyl­hexa­hydro-1H-cyclo­penta­[c]furan-4,5-diol, C14H18O3, (I), (±)-(3aR,4S,5S,6aS)-4-benz­yloxy-4-methyl-5-phenyl­hexa­hydro-1H-cyclo­penta­[c]furan-5-ol, C21H24O3, (II), and (±)-(1aR,1bS,4aR,5S,5aR)-5-benz­yloxy-5-methyl-5a-phenyl­hexa­hydro-2H-oxireno[2′,3′:3,4]cyclopenta­[1,2-c]furan, C21H22O3, (III). The dominant inter­action in (I) and (II) is an O—H⋯O hydrogen bond across the bicyclic 5,5-ring system between the non-functionalized hy­droxy group and the tetra­hydro­furan O atom, which appears to influence the envelope conformations of the fused five-membered rings, whereas in (III), the rings have different conformations. A weak intra­molecular C—H⋯O inter­action appears to influence the degree of tilt of the phenyl ring attached to the 5-position and is different in (I) compared to (II) and (III).

BackgroundClinical commissioning groups (CCGs) were established in England in 2013 to encourage GPs to exert greater influence over the processes of service improvement and redesign in the NHS. Little is known about the extent and the ways in which GPs have assumed these leadership roles.AimTo explore the nature of clinical leadership of GPs in CCGs, and to examine the enablers and barriers to implementing a policy of clinical leadership in the NHS.Design and settingA qualitative multi-case study approach in six localities across England. The case studies were purposefully sampled to represent different geographical localities and population demographics, and for their commitment to redesigning specified clinical or service areas.MethodData were collected from the case study CCGs and their partner organisations using a review of relevant documents, semi-structured individual or group interviews, and observations of key meetings. The data were analysed thematically and informed by relevant theories.ResultsGPs prefer a collaborative style of leadership that may be unlikely to produce rapid or radical change. Leadership activities are required at all levels in the system from strategy to frontline delivery, and the leadership behaviours of GPs who are not titular leaders are as important as formal leadership roles. A new alliance is emerging between clinicians and managers that draws on their different skillsets and creates new common interests. The uncertain policy environment in the English NHS is impacting on the willingness and the focus of GP leaders.ConclusionGPs are making an important contribution as leaders of health service improvement and redesign but there are significant professional and political barriers to them optimising a leadership role.

Given the repeated failure of amyloid-based approaches in Alzheimer's disease, there is increasing interest in tau-based therapeutics. Although methylthioninium (MT) treatment was found to be beneficial in tau transgenic models, the brain concentrations required to inhibit tau aggregation in vivo are unknown. The comparative efficacy of methylthioninium chloride (MTC) and leucomethylthioninium salts (LMTX; 5-75 mg/kg; oral administration for 3-8 weeks) was assessed in two novel transgenic tau mouse lines. Behavioural (spatial water maze, RotaRod motor performance) and histopathological (tau load per brain region) proxies were applied. Both MTC and LMTX dose-dependently rescued the learning impairment and restored behavioural flexibility in a spatial problem-solving water maze task in Line 1 (minimum effective dose: 35 mg MT/kg for MTC, 9 mg MT/kg for LMTX) and corrected motor learning in Line 66 (effective doses: 4 mg MT/kg). Simultaneously, both drugs reduced the number of tau-reactive neurons, particularly in the hippocampus and entorhinal cortex in Line 1 and in a more widespread manner in Line 66. MT levels in the brain followed a sigmoidal concentration-response relationship over a 10-fold range (0.13-1.38 μmol/l). These data establish that diaminophenothiazine compounds, like MT, can reverse both spatial and motor learning deficits and reduce the underlying tau pathology, and therefore offer the potential for treatment of tauopathies.

The phase behaviour of equimolar mixtures of 6-(4'-cyanobiphenyl-4-yl)hexyloxybenzoic acid (CB6OBA) with either 1-(4-butylazobenzene-4'-oxy)-5-(4-oxypyridine)pentane (BuABO5OPyr) or 1-(4-butylazobenzene-4'-oxy)-6-(4-oxypyridine)hexane (BuABO6OPyr) is reported. CB6OBA shows a monotropic twist-bend nematic phase and an enantiotropic nematic phase whereas the two pyridyl-based components do not exhibit liquid crystallinity. Both equimolar mixtures (CB6OBA/BuABOnOPyr) show enantiotropic nematic phases. The nematic-isotropic transition temperature and associated entropy change are higher for the CB6OBA/BuABO6OPyr mixture than for the CB6OBA/BuABO5OPyr mixture. This may be accounted for in terms of the average shapes of the hydrogen-bonded 1:1 complexes formed between the two differing components in the mixtures. However, Fourier transform infrared spectroscopy reveals that this complex is not formed quantitatively, but instead a complex mixture exists over the complete temperature range studied, involving the 1:1 complex, both cyclic and open acid dimers, free acid and hence, free BuABOnOPyr molecules.

Alzheimer's disease is characterised by the self-assembly of tau and amyloid I² proteins into oligomers and fibrils. Tau protein assembles into paired helical filaments (PHFs) that constitute the neurofibrillary tangles observed in neuronal cell bodies in individuals with Alzheimer's disease. The mechanism of initiation of tau assembly into {PHFs} is not well understood. Here we report that a truncated 95-amino acid tau fragment (corresponding to residues 297-391 of full-length tau) assembles into PHF-like fibrils in vitro without the need for other additives to initiate or template the process. Using electron microscopy, circular dichroism and X-ray fibre diffraction, we have characterised the structure of the fibrils formed from truncated tau for the first time. To explore the contribution of disulphide formation to fibril formation, we have compared the assembly of tau(297-391) under reduced and non-reducing conditions and for truncated tau carrying a {C322A} substitution. We show that disulphide bond formation inhibits assembly and that the {C322A} variant rapidly forms long and highly ordered PHFs.

Chiral symmetry breaking in soft matter is a hot topic of current research. Recently, such a phenomenon was found in a fluidic phase showing orientational order of molecules—the nematic phase; although built of achiral molecules, the phase can exhibit structural chirality—average molecular direction follows a short-pitch helix. Here, we report a series of achiral asymmetric dimers with an odd number of atoms in the spacer, which form twisted structures in nematic as well as in lamellar phases. The tight pitch heliconical nematic (NTB) phase and heliconical tilted smectic C (SmCTB) phase are formed. The formation of a variety of helical structures is accompanied by a gradual freezing of molecular rotation. In the lowest temperature smectic phase, HexI, the twist is expressed through the formation of hierarchical structure: nanoscale helices and mesoscopic helical filaments. The short-pitch helical structure in the smectic phases is confirmed by resonant X-ray measurements., Systems that form chiral structures from achiral molecules are not common. Here, the authors synthesise a compound consisting of asymmetric and achiral bent-shaped mesogens, which exhibit a variety of liquid crystal phases including one in which chiral structures form from achiral constituent molecules.

A cholesteric liquid crystal (CLC) formed by chiral molecules represents a self-assembled one-dimensionally periodic helical structure with pitch p p in the submicrometer and micrometer range. Because of the spatial periodicity of the dielectric permittivity, a CLC doped with a fluorescent dye and pumped optically is capable of mirrorless lasing. An attractive feature of a CLC laser is that the pitch p p and thus the wavelength of lasing λ ¯ λ¯ can be tuned, for example, by chemical composition. However, the most desired mode to tune the laser, by an electric field, has so far been elusive. Here we present the realization of an electrically tunable laser with λ ¯ λ¯ spanning an extraordinarily broad range (>100 nm) of the visible spectrum. The effect is achieved by using an electric-field-induced oblique helicoidal (OH) state in which the molecules form an acute angle with the helicoidal axis rather than align perpendicularly to it as in a field-free CLC. The principal advantage of the electrically controlled CLCOH laser is that the electric field is applied parallel to the helical axis and thus changes the pitch but preserves the single-harmonic structure. The preserved single-harmonic structure ensures efficiency of lasing in the entire tunable range of emission. The broad tuning range of CLCOH lasers, coupled with their microscopic size and narrow line widths, may enable new applications in areas such as diagnostics, sensing, microscopy, displays, and holography.

The synthesis and characterisation of the nonsymmetric liquid crystal dimer, 1-(4-cyanobiphenyl-4'-yloxy)-6-(4-cyanobiphenyl-4'-yl)hexane (CB6OCB) is reported. An enantiotropic nematic (N)-twist-bend nematic (NTB) phase transition is observed at 109 °C and a nematic-isotropic phase transition at 153 °C. The NTB phase assignment has been confirmed using polarised light microscopy, freeze fracture transmission electron microscopy (FFTEM), (2)H-NMR spectroscopy, and X-ray diffraction. The effective molecular length in both the NTB and N phases indicates a locally intercalated arrangement of the molecules, and the helicoidal pitch length in the NTB phase is estimated to be 8.9 nm. The surface anchoring properties of CB6OCB on a number of aligning layers is reported. A Landau model is applied to describe high-resolution heat capacity measurements in the vicinity of the NTB-N phase transition. Both the theory and heat capacity measurements agree with a very weak first-order phase transition. A complementary extended molecular field theory was found to be in suggestive accord with the (2)H-NMR studies of CB6OCB-d2, and those already known for CB7CB-d4. These include the reduced transition temperature, TNTBN/TNI, the order parameter of the mesogenic arms in the N phase close to the NTB-N transition, and the order parameter with respect to the helix axis which is related to the conical angle for the NTB phase.

The dominant political-economic narrative of our time is that, under conditions of global competition with low-wage economies able to undercut even efficient western firms, the only viable and sustainable route to competitiveness is to trade on high value-added goods and services and that these in turn require enhanced skills and knowledge. This kind of analysis finds echo and sustenance in the management literature concerning 'knowledge'. For example, in a much-cited observation, Stewart (1997) claims that knowledge is 'the most important factor in economic life. It is the chief ingredient of what we buy and sell, the raw material with which we work. Intellectual capital - not natural resources, machinery or even financial capital - has become the one indispensable asset of corporations'. While this kind of analysis sets the agenda in management theory and policy circles, there is less certainty at the level of business practice. At firm level there is rather more evidence of multiple strategies - many of which do not depend upon upskilling. This may help explain why the take-up and demand for training provision, which is on offer, often falls short of the supply. However, the nature of the knowledge identified by those politicians and commentators who stress the importance of knowledge in the context of the global knowledge economy requires attention. In these analyses and exhortations, knowledge is defined as a factor of production - as a resource to be used in the design and production of goods and services. And so indeed it is. But it is more than this: it is also a key factor in the decision-making and capacity of senior managers, which impinges significantly on how they respond (or even recognise) the competitive pressures their businesses face. The behaviour of senior managers with regard tohow (and if) they respond to the opportunities and challenges of the knowlege economy raises a distinct and important set of issues pertaining to a different but crucially important type of knowledge - the knowledge required and the kinds of knowledge currently held at top levels (Storey and Salaman, 2005). Building on a series of research projects and a number of board level consultancy assignments, our analysis suggests that exhortation has only limited effects. The critical point of focus for us is the mental models constructed and used by individual members of top teams and by these teams collectively. However much directors may concur with the general rhetoric at one level, when it comes to practical business - their practical busines - they can remain deeply sceptical and resistant. In this paper, we explore and illustrate these points drawing upon detailed case evidence.

PurposeIn the light of public concern and of strong policy emphasis on quality and safety in the nursing care of patients in hospital settings, this paper aims to focus on the factors affecting the adoption of innovative quality assurance technologies.Design/methodology/approachTwo sets of complementary literature were mined for key themes. Next, new empirical insights were sought. Data gathering was conducted in three phases. The first involved contact with NHS Technology Hubs and other institutions which had insights into leading centres in quality assurance technologies. The second phase was a series of telephone interviews with lead nurses in those hospitals which were identified in the first phase as comprising the leading centres. The third phase comprised a series of face to face interviews with innovators and adopters of healthcare quality assurance technologies in five hospital trusts.FindingsThere were three main sets of findings. First, despite the strong policy push and the templates established at national level, there were significant variations in the nature and robustness of the quality assurance toolkits that were developed, adapted and adopted. Second, in most of the adopting cases there were important obstacles to the full adoption of the toolkits that were designed. Third, the extent and nature of the ambition of the developers varied dramatically – some wished to see their work impacting widely across the health service; others had a number of different reasons for wanting to restrict the impact of their work.Originality/valueThe general concerns about front‐line care and the various inquiries into care quality failures emphasise the need for improved and consistent care quality assurance methodologies and practice. The technology adoption literature gives only partial insight into the nature of the challenges; this paper offers specific insights into the factors inhibiting the full adoption of quality assurance technologies in ward‐based care.

Numerous policy papers and academic contributions across a range of countries emphasize the importance of clinical leadership in health services. This is seen as especially vital at a time of simultaneous resource constraints and rising demand. Most of the literature in this topic area concerns itself with conceptual clarification of types of leadership and with delineation of requisite competences. But other work on leadership has emphasized the importance of attending to practice in concrete situations in order to identify the dynamics at play and the nature of the challenges. The purpose of this article is to contribute to this latter task by drawing upon a set of data which reveals crucial aspects of the problems facing potential clinical leaders of service redesign. This paper reports on the nature and extent of the challenges as identified by clinicians of different types as well as managers and commissioners.

By studying gene expression changes over time in a cohort of trauma patients, Keyur Desai and colleagues identify genes and pathways strongly associated with longer-term complications, which could lead to improved outcome prediction in the first 80 hours after injury., Background Trauma is the number one killer of individuals 1–44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition. Methods and Findings We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40–80 h window post-injury. Conclusions The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions. Trial Registration ClinicalTrials.gov NCT00257231 Please see later in the article for the Editors' Summary, Editors' Summary Background Trauma—a serious injury to the body caused by violence or by an accident—is a major global health problem. Every year, events that include traffic collisions, falls, blows, and fires cause injuries that kill more than 5 million people (9% of annual global deaths). Road traffic accidents alone are responsible for 1.3 million deaths a year and, if current trends continue, will be the fifth leading cause of death worldwide by 2030. Moreover, in many countries, including the US, trauma is the number one killer of individuals aged 1–44 y. Trauma can kill people rapidly through loss of blood or serious physical damage to internal organs, but it can also lead to localized infections and to sepsis, an infection of the bloodstream that is characterized by an amplified, body-wide (systemic) inflammatory response. Inflammation—redness, pain, and swelling—is an immune system response that normally provides protection against infections, but systemic inflammation can result in multiple organ failure (MOF) and death. Why Was This Study Done? Inflammatory complications of trauma are responsible for more than half of late trauma deaths, but at present it is impossible to predict which patients with major injuries will recover and which will spiral down into MOF and death, because the biological processes that underlie post-injury inflammatory complications are poorly understood. If the changes in gene expression (the process that converts the information encoded in genes into functional proteins) that accompany systemic inflammation could be elucidated, it might be possible to improve the diagnosis of MOF and to develop better treatments for post-trauma inflammatory complications. In this prospective, longitudinal clinical genomics study (part of the Inflammation and Host Response to Injury multi-disciplinary research program [IHRI]), the researchers developed an approach to associate early within-patient gene expression changes with later clinical outcomes. A prospective study is one in which patients with a specific condition are enrolled and then followed to see how various factors affect their outcomes; a longitudinal study analyzes multiple samples taken at different times from individual patients; a clinical genomics study investigates how genes and gene expression affect clinical outcomes. What Did the Researchers Do and Find? The researchers followed 168 patients for up to 28 d after they experienced blunt-force trauma (injuries caused when the human body hits or is hit by a large object such as a car). Using a molecular biology tool called a DNA microarray, they determined gene expression patterns in leukocytes (a type of immune system cell) isolated from multiple blood samples collected from each patient during the first few days after injury. Using clinical information collected by trained nurses, they organized the patients into five outcome categories based on a measure of MOF known as the Marshall score. Finally, they developed a statistical method (an analysis framework) to associate the early changes in gene expression with clinical outcomes. A quarter of the patients' genes showed early expression changes that were associated with longer-term post-injury inflammatory complications. Among the associations revealed by this analysis, down-regulation (reduced expression) of MHC-class II genes (which encode proteins involved in antigen presentation, the process by which molecules from foreign invaders are presented to immune cells to initiate an immune response) and up-regulation of genes encoding components of the p38 MAPK signaling pathway (which helps to drive inflammatory responses) between 40 and 80 h post-injury were particularly strongly associated with longer-term post-injury complications and provided the strongest discrimination between patient outcomes. What Do These Findings Mean? The statistical approach used in this study to link the early changes in gene expression that occur after trauma to clinical outcomes provides a detailed picture of genome-wide gene expression responses to trauma. These findings could help scientists understand why some patients develop inflammatory complications of trauma while others do not, and they could help to identify those patients most at risk of developing complications. They could also help to identify targets for therapy, although further studies are needed to confirm and extend these findings. Importantly, the quantitative approach developed by the researchers for analyzing associations between within-patient gene changes over time and clinical outcomes should provide more robust predictions of outcomes than single measurements of gene expression and could be applicable to genomic studies of other rapidly progressing clinical conditions. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001093. More details about the Inflammation and Host Response to Injury research program are available; the program's website includes a link to an article that explains how genomics can be used to understand the inflammatory complications of trauma The World Health Organization provides information on injuries and on violence and injury prevention (in several languages) The US National Institutes of Health has a factsheet on burns and traumatic injury in the USA The US Centers for Disease Control and Prevention has information on injury and violence prevention and control MedlinePlus provides links to further resources on injuries

The purpose of this paper is to use sensemaking and learning theory to gain insight into how senior Ethiopian managers are coming to terms with radically different political and economic forces. These theories have developed in mature Western contexts and a further purpose is to test their applicability in an African context. The methods employed were detailed data gathering in five cases using semi-structured interviews and documentary analysis. The research found that senior managers in the five enterprises constructed very different sense-making patterns about the business environment and about appropriate business strategies depending on the degree of market or state dependency which they perceived. The analysis also reveals how these actors reflected upon the implications of their sense-making for their own and their organizations' future learning and capability development.

PurposeTo explore senior managers’ knowledge and thinking about strategy and organisational capabilities, and developments of both during a time of transition.Design/methodology/approachInterpretive case research based on semi‐structured interviews with 44 senior managers in a number of business organisations in Ethiopia supplemented by secondary sources.FindingsSenior managers had a narrow and contingent knowledge of, and interaction with, the external environment. The notion of “strategy” was problematical for them. Managers’ knowing of their environment and organisational aspects were differentiated, context specific and subject to changes and reinterpretations depending on shifting roles, responsibilities and changing contexts.Research limitations/implicationsThis research sheds light on how assumptions about the often “taken‐for‐grantedness” of the strategic “manageability” of change by senior managers may be exaggerated. This was revealed, at one extreme, in this research but it may extend also into other situations in varying degrees. In this and other ways the study of senior Ethiopian managers could be used as a way to reflect back upon conventional thinking about strategizing in other contexts.Practical implicationsThe research can help managers gain insight into how their everyday ways of knowing and seeing are unnecessarily limited and constrained.Originality/valueWork in business knowledge is just commencing and hence its continuity would further both scholars’ and practitioners’ understanding of the knowledge work of managers in varied contexts and environments.

This paper presents a critique of the normative, buyer–supplier literature and in addition suggests that the more empirically based literature needs to expand its scope of attention beyond its traditional confines. Four main deficiencies are identified within much of the existing buyer–supplier literature. Firstly, collaborative buyer–supplier theories fail to discriminate sufficiently between individual and firm-level buyer–supplier decision-making. Secondly, the stage models of relationship development are challenged. Thirdly, the interdependencies between buyer–supplier relations and other, competing organisational priorities are highlighted. Fourthly, we question the monolithic constructs of organisational ‘commitment’ and ‘trust’ underpinning much existing relationship-marketing literature.\ud \ud Examples are presented of collaborative buyer–supplier practice drawn from multi-sector case study research of customer-responsive supply chains. We argue that, even in exemplary circumstances, collaborative relationship practices are susceptible to failure due to wider organisational and behavioural issues.\ud \ud We conclude that researchers and management practitioners need to pay more attention to these issues if sustainable benefits derived from advances in buyer–supplier understanding are to be realised.