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Abstract A Product-Service System (PSS) is an integrated combination of products and services. This Western concept embraces a service-led competitive strategy, environmental sustainability, and the basis to differentiate from competitors who simply offer lower priced products. This paper aims to report the state-of-the-art of PSS research by presenting a clinical review of literature currently available on this topic. The literature is classified and the major outcomes of each study are addressed and analysed. On this basis, this paper defines the PSS concept, reports on its origin and features, gives examples of applications along with potential benefits and barriers to adoption, summarizes available tools and methodologies, and identifies future research challenges.

Transcranial magnetic stimulation (TMS) is a non-invasive method used to investigate neurophysiological integrity of the human neuromotor system. We describe in detail, the methodology of a single pulse TMS protocol that was performed in a large cohort of people (n = 110) with multiple sclerosis (MS). The aim was to establish and validate a core-set of TMS variables that predicted typical MS clinical outcomes: walking speed, hand dexterity, fatigue, and cognitive processing speed. We provide a brief and simple methodological pipeline to examine excitatory and inhibitory corticospinal mechanisms in MS that map to clinical status. Delayed and longer ipsilateral silent period (a measure of transcallosal inhibition; the influence of one brain hemisphere’s activity over the other), longer cortical silent period (suggestive of greater corticospinal inhibition via GABA) and higher resting motor threshold (lower corticospinal excitability) most strongly related to clinical outcomes, especially when measured in the hemisphere corresponding to the weaker hand. Greater interhemispheric asymmetry (imbalance between hemispheres) correlated with poorer performance in the greatest number of clinical outcomes. We also show, not surprisingly, that TMS variables related more strongly to motor outcomes than non-motor outcomes. As it was validated in a large sample of patients with varying severities of central nervous system dysfunction, the protocol described herein can be used by investigators and clinicians alike to investigate the role of TMS as a biomarker in MS and other central nervous system disorders.

We have previously shown that supraspinal excitability is higher during arm cycling than a position- and intensity-matched tonic contraction. The present study sought to determine if short-interval intracortical inhibition (SICI) was present during arm cycling and if so, if the amount of SICI was different from an intensity-matched tonic contraction. SICI was assessed using conditioning stimuli (CS) of 70 and 90% of active motor threshold (AMT) and a test stimulus (TS) of 120% AMT at an interstimulus interval (ISI) of 2.5 ms. SICI was elicited in all participants; on average (i.e., cycling and tonic contraction grouped) test MEP amplitudes were reduced by 64.2% (p < 0.001) and 62.8% (p = 0.001) following conditioning stimuli of 70% and 90% AMT, respectively. There was no significant difference in extent of SICI between tasks (p = 0.360). These data represent the novel finding that SICI is present during arm cycling, a motor output partially mediated by spinal interneuronal networks. The amount of SICI, however, was not different from that during a position- and intensity-matched tonic contraction, suggesting that SICI is not likely a cortical mechanism contributing to higher supraspinal excitability during arm cycling compared to tonic contraction.

Purpose – The purpose of this paper is to explore the management of information flow for delivery reliability. It analyses how the integration strategies of traceability, transaction costs and vertical integration that shape integrated information flow are managed during delivery processes of firms. While delivery reliability contributes to firm competitiveness, information flow is central to firms interaction internally and externally to facilitate delivery. Design/methodology/approach – The paper applies an exploratory multiple-case study involving 21 delivery team members in three industrial technology-based firms. Informed by a multidisciplinary framework from literature, the study captures “what” and “how” existing firms manage information flow during delivery. Individual cases from the company were compared analysed to determine themes that drive delivery-related integrated information flow management. Findings – The paper finds that case firms prioritised understanding interaction logics, maintaining process timeliness, review-oriented streamlining and communication-oriented coordination. The study also finds that for delivery reliability in technology-based firms, the interplay of vertical integration, market relations and long term, voluntary relations, especially through the use of small, dedicated and highly skilled team, is required to effectively manage delivery-related integrated information flow. Originality/value – The major contribution of this paper is an exposition on practices for facilitating information flow integration. It also offers insights that suggest integrated information flow for delivery reliability could be enhanced through the use of customer-focused communication channels, context-driven documentations, multiple and alternate communication channels as well as intuitive and user-friendly documentation strategies.

Table 1 England Royal United Hospital Bath Birmingham Children's Hospital Birmingham Royal Alexandra Children's Hospital Brighton Bristol Royal Hospital for Children Bristol Frenchay Hospital Bristol Royal Derby Hospital Derby Royal Devon and Exeter Hospital Exeter Leicester Royal Infirmary Leicester Alder Hey Children's Hospital Liverpool Barts & The London London Chelsea & Westminster Hospital London Evelina Hospital London King's College Hospital London Lewisham Hospital London Royal Free Hospital London St George's Hospital London St Mary's Hospital London North Manchester General Hospital Manchester Royal Manchester Children's Hospital Manchester Nottingham Children's Hospital Nottingham Derriford Hospital Plymouth Queen Alexandra Hospital Portsmouth Salford Royal Hospital Salford Sheffield Children's Hospital Sheffield University Hospital Southampton Southampton Sunderland Royal Hospital Sunderland Ireland Cork University Hospital Cork Temple Street Children's University Hospital Dublin Our Lady's Children's Hospital, Crumlin Dublin Tallaght Children's Hospital, Tallaght Dublin Northern Ireland Royal Belfast Hospital for Sick Children Belfast Scotland Aberdeen Royal Infirmary Aberdeen Forth Valley Hospital Dumbarton Royal Hospital for Sick Children Edinburgh Royal Hospital for Sick Children (Yorkhill) Glasgow Crosshouse Hospital Kilmarnock Royal Alexandra Hospital Paisley Wales Children's Hospital for Wales Cardiff Morriston Hospital Swansea Individual membership is open to anyone with this vision including doctors, nurses and allied health professionals.

Microfluidic devices have several applications in different fields, such as chemistry, medicine and biotechnology. Many research activities are currently investigating the manufacturing of integrated microfluidic devices on a mass-production scale with relatively low costs. This is especially important for applications where disposable devices are used for medical analysis. Micromoulding of thermoplastic polymers is a developing process with great potential for producing low-cost microfluidic devices. Among different micromoulding techniques, micro-injection moulding is one of the most promising processes suitable for manufacturing polymeric disposable microfluidic devices. This review paper aims at presenting the main significant developments that have been achieved in different aspects of micro-injection moulding of microfluidic devices. Aspects covered include device design, machine capabilities, mould manufacturing, material selection and process parameters. Problems, challenges and potential areas for research are highlighted.

Polybrominated diphenyl ether (PBDE) congeners are constituents of flame retardants, and there is growing concern regarding their persistence, bioaccumulation, and toxicity. We collected breast milk samples between late 2001 and early 2003 from 54 U.K.-resident mothers. Of these, 27 originated from southeast England (London), and the other 27 originated from northwest England (Lancaster). Analysis of milk-fat extracts by gas chromatography-mass spectrometry was performed to determine the levels of 15 PBDE congeners, 15 polychlorinated biphenyl (PCB) congeners, and other selected chlorinated compounds. PCB and organochlorine (OC) levels in southeast samples were consistently higher, and significant differences (p < 0.05) were observed. ΣPBDE levels ranged from 0.3 to 69 ng/g lipid (geometric mean, 6.6 ng/g), and PBDE-47 was the most abundant congener. ΣPCB levels ranged from 26 to 530 ng/g lipid (geometric mean, 150 ng/g) and were composed mainly of PCB-153 (26%), PCB-138 (20%), and PCB-180 (13%). OC levels for 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its metabolites (ΣDDX) ranged from 24 to 2,300 ng/g lipid (geometric mean, 160 ng/g); hexachlorobenzene ranged from nondetectable levels to 180 ng/g lipid (geometric mean, 17 ng/g); and Σhexachlorocyclohexane levels ranged from 1.2 to 1,500 ng/g lipid (geometric mean, 16 ng/g). Using nuclear magnetic resonance-based metabonomics, samples (n = 7) containing the highest contaminant levels were compared with samples (n = 7) containing the lowest levels. Excellent separation along the first principal component implied that the chemical constituents of the two groups were significantly different. Although reasons for such differences remain obscure, lifestyle factors associated with a more heterogeneous London cohort could be responsible. Identifying primary routes of contaminant exposures and their biologic effects is of great importance.

This is the first study to examine corticospinal excitability (CSE) to antagonistic muscle groups during arm cycling. Transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of the corticospinal tract were used to assess changes in supraspinal and spinal excitability, respectively. TMS induced motor evoked potentials (MEPs) and TMES induced cervicomedullary evoked potentials (CMEPs) were recorded from the biceps and triceps brachii at two positions, mid-elbow flexion and extension, while cycling at 5% and 15% of peak power output. While phase-dependent modulation of MEP and CMEP amplitudes occurred in the biceps brachii, there was no difference between flexion and extension for MEP amplitudes in the triceps brachii and CMEP amplitudes were higher during flexion than extension. Furthermore, MEP amplitudes in both biceps and triceps brachii increased with increased workload. CMEP amplitudes increased with higher workloads in the triceps brachii, but not biceps brachii, though the pattern of change in CMEPs was similar to MEPs. Differences between changes in CSE between the biceps and triceps brachii suggest that these antagonistic muscles may be under different neural control during arm cycling. Putative mechanisms are discussed.

We present a case of primary antiphospholipid syndrome (APS), initially diagnosed as acute rheumatic fever, resulting in severe mitral valve incompetence. This case raises questions of the specificity of the Jones diagnostic criteria for rheumatic fever in a population where it is infrequently encountered. There are similarities in clinical, pathological and echocardiographic presentations between rheumatic fever and APS, in addition to common immunological mechanisms. Our case highlights the possibility that rather than rheumatic fever being primarily responsible for her recurrent attacks of chorea and arthritis, the streptococcal infections in our patient occurred either in the setting of underlying antiphospholipid antibodies (‘second hit’ phenomenon), or may have triggered the development of pathogenic antibodies (molecular mimicry), subsequently leading to the clinical evolution of APS. During the three decades of our patient and her recurrent problems, there has been an evolving knowledge of the mechanisms of APS and rheumatic fever, allowing us to extend our understanding beyond symptoms and syndromes, to a better realization of the underlying immunological relationship between the two.

A product–service system (PSS) is a combination of products and services to create value for both customers and manufacturers. Modelling a PSS based on function orientation offers a useful way to distinguish system inputs and outputs with regards to how data are consumed and information is used, i.e. information flow. This article presents a review of diagrammatic information flow tools, which are designed to describe a system through its functions. The origin, concept and applications of these tools are investigated, followed by an analysis of information flow modelling with regards to key PSS properties. A case study of selection laser melting technology implemented as PSS will then be used to show the application of information flow modelling for PSS design. A discussion based on the usefulness of the tools in modelling the key elements of PSS and possible future research directions are also presented.