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Digitalisation has provoked the rapid proliferation of changes in the operational landscape, thus requiring prompt decision making across end-to-end supply chains. Notwithstanding the fact that technology is the epicentre of digital transformation, more often than not, organisations fail to effectively adopt innovative applications, harness their full potential and realise growth and competitiveness. Therefore, this research argues that a unique strategy formulation process is required to embrace digitalisation in manufacturing supply chains. However, within the context of manufacturing networks, strategy formulation approaches are limited. To this end, this research adopts a case study approach to extract tacit knowledge across twelve multinational companies within the theoretical boundaries of corporate strategy development. Research findings and a theoretically derived framework demonstrate that there are three typologies of digital strategy development approaches for manufacturing supply chains, namely: (i) top-down; (ii) bottom-up; and (iii) mixed. Every identified typology is supplemented with three determinant criteria for digital supply chain strategy formulation, i.e., number of suppliers, market demand, and product types. Noteworthy, the aforementioned strategies are context-dependent. This research contributes to the Operations Management field by formulating a novel strategy development framework for digital supply chains. The proposed framework, synthesised via strategic management theoretical views and primary evidence, can provide a reference point as companies chart their current and future digital supply chain strategy state.

Thermal heat loading has become a burden on today’s naval ships. Expanding operations in hot climate zones, increasing use of high energy systems (for example weapons) and maintaining the cooling of electronics that require fine temperature control have all contributed to a higher cooling demand. Designing cooling plant for a range of operating climates and varying equipment loads is a challenge due to high peaks in the thermal load that occur for short durations of time. Specification of a traditional chilled water system to meet peak load demands will result in a system that is oversized for normal operating loads and is likely to be deemed impractical. The use of thermal storage tanks provides a potential solution to catering for these peak load demands. This consists of a tank filled with a medium that can be cooled so that it absorbs heat from the ships systems when cooling water is passed through the tank. The thermal storage medium can be used as a heat sink to smooth thermal load peaks and then be recharged during periods of lower demand. Various materials have shown potential for use as thermal storage mediums. This paper summarises the operational advantages and integration challenges of thermal storage tanks, focusing on the use of water and wax as storage mediums.Relative tank sizes, cooling capacities and system scheme design solutions are presented for a range of thermal storage tank solutions.

Summary Right ventricular (RV) function has prognostic value in acute, chronic and peri‐operative disease, although the complex RV contractile pattern makes rapid assessment difficult. Several two‐dimensional (2D) regional measures estimate RV function, however the optimal measure is not known. High‐resolution three‐dimensional (3D) cardiac magnetic resonance cine imaging was acquired in 300 healthy volunteers and a computational model of RV motion created. Points where regional function was significantly associated with global function were identified and a 2D, optimised single‐point marker (SPM‐O) of global function developed. This marker was prospectively compared with tricuspid annular plane systolic excursion (TAPSE), septum‐freewall displacement (SFD) and their fractional change (TAPSE‐F, SFD‐F) in a test cohort of 300 patients in the prediction of RV ejection fraction. RV ejection fraction was significantly associated with systolic function in a contiguous 7.3 cm2 patch of the basal RV freewall combining transverse (38%), longitudinal (35%) and circumferential (27%) contraction and coinciding with the four‐chamber view. In the test cohort, all single‐point surrogates correlated with RV ejection fraction (p < 0.010), but correlation (R) was higher for SPM‐O (R = 0.44, p < 0.001) than TAPSE (R = 0.24, p < 0.001) and SFD (R = 0.22, p < 0.001), and non‐significantly higher than TAPSE‐F (R = 0.40, p < 0.001) and SFD‐F (R = 0.43, p < 0.001). SPM‐O explained more of the observed variance in RV ejection fraction (19%) and predicted it more accurately than any other 2D marker (median error 2.8 ml vs 3.6 ml, p < 0.001). We conclude that systolic motion of the basal RV freewall predicts global function more accurately than other 2D estimators. However, no markers summarise 3D contractile patterns, limiting their predictive accuracy.

Background There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012. Methods A false positive diagnosis of COPD was considered when participants reported a doctor’s diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC < 0.7). Results Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of “chronic bronchitis” or “emphysema” (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication. Conclusions False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.

Aims We sought to identify metabolic pathways associated with right ventricular (RV) adaptation to pulmonary hypertension (PH). We evaluated candidate metabolites, previously associated with survival in pulmonary arterial hypertension, and used automated image segmentation and parametric mapping to model their relationship to adverse patterns of remodelling and wall stress. Methods and results In 312 PH subjects (47.1% female, mean age 60.8 ± 15.9 years), of which 182 (50.5% female, mean age 58.6 ± 16.8 years) had metabolomics, we modelled the relationship between the RV phenotype, haemodynamic state, and metabolite levels. Atlas-based segmentation and co-registration of cardiac magnetic resonance imaging was used to create a quantitative 3D model of RV geometry and function—including maps of regional wall stress. Increasing mean pulmonary artery pressure was associated with hypertrophy of the basal free wall (β = 0.29) and reduced relative wall thickness (β = −0.38), indicative of eccentric remodelling. Wall stress was an independent predictor of all-cause mortality (hazard ratio = 1.27, P = 0.04). Six metabolites were significantly associated with elevated wall stress (β = 0.28–0.34) including increased levels of tRNA-specific modified nucleosides and fatty acid acylcarnitines, and decreased levels (β = −0.40) of sulfated androgen. Conclusion Using computational image phenotyping, we identify metabolic profiles, reporting on energy metabolism and cellular stress-response, which are associated with adaptive RV mechanisms to PH.

Right ventricular (RV) function has prognostic value in acute, chronic and peri‐operative disease, although the complex RV contractile pattern makes rapid assessment difficult. Several two‐dimensional (2D) regional measures estimate RV function, however the optimal measure is not known. High‐resolution three‐dimensional (3D) cardiac magnetic resonance cine imaging was acquired in 300 healthy volunteers and a computational model of RV motion created. Points where regional function was significantly associated with global function were identified and a 2D, optimised single‐point marker (SPM‐O) of global function developed. This marker was prospectively compared with tricuspid annular plane systolic excursion (TAPSE), septum‐freewall displacement (SFD) and their fractional change (TAPSE‐F, SFD‐F) in a test cohort of 300 patients in the prediction of RV ejection fraction. RV ejection fraction was significantly associated with systolic function in a contiguous 7.3 cm2 patch of the basal RV freewall combining transverse (38%), longitudinal (35%) and circumferential (27%) contraction and coinciding with the four‐chamber view. In the test cohort, all single‐point surrogates correlated with RV ejection fraction (p < 0.010), but correlation (R) was higher for SPM‐O (R = 0.44, p < 0.001) than TAPSE (R = 0.24, p < 0.001) and SFD (R = 0.22, p < 0.001), and non‐significantly higher than TAPSE‐F (R = 0.40, p < 0.001) and SFD‐F (R = 0.43, p < 0.001). SPM‐O explained more of the observed variance in RV ejection fraction (19%) and predicted it more accurately than any other 2D marker (median error 2.8 ml vs 3.6 ml, p < 0.001). We conclude that systolic motion of the basal RV freewall predicts global function more accurately than other 2D estimators. However, no markers summarise 3D contractile patterns, limiting their predictive accuracy.

Purpose: To measure right ventricular (RV) trabecular complexity by its fractal dimension (FD) in healthy subjects and patients with pulmonary hypertension (PH) and assess its relationship to hemodynamic and functional parameters, and future cardiovascular events. Materials and methods: This retrospective study used data acquired from May 2004 to October 2013 for 256 patients with newly-diagnosed PH that underwent cardiac magnetic resonance (CMR) imaging, right heart catheterization and six-minute walk distance testing with a median follow-up of 4.0 years. 256 healthy controls underwent CMR only. Biventricular FD, volumes and function were assessed on short-axis cine images. Reproducibility was assessed by intraclass correlation coefficient, correlation between variables was assessed by Pearson’s correlation test, and mortality prediction compared by univariable and multivariable Cox regression analysis. Results: RV-FD reproducibility had an intraclass correlation coefficient of 0.97 (95% confidence interval [CI]: 0.96, 0.98). RV-FD was higher in PH patients than healthy subjects (median 1.310, inter-quartile range [IQR] 1.281-1.341 vs 1.264, 1.242-1.295, P

Background: Evaluation of left ventricular non-compaction (LVNC) is an increasingly common indication for cardiac magnetic resonance imaging (MRI). Fractal dimension (FD) is a unitless measure of geometrical complexity which can be used to quantify LV trabeculation. FD is increased in LVNC, but there have been few studies on FD in normal subjects. The aim of the study was to establish reference ranges for FD in a healthy population, and identify covariates which are associated with FD. Methods: MRI was performed in 1,913 volunteers without hypertension, diabetes, or heart disease (1055 female, 858 male; median age 40, range 19-82). FD was derived from LV short-axis images, using a custom MATLAB box-counting algorithm. The maximal FD in the apical half of the LV was used for all analyses, as previously described. Results: Normal ranges (2.5-97.5th percentile) for female and male subjects were 1.154 - 1.367 and 1.179 - 1.392, respectively. FD was significantly correlated with age, gender, ethnicity, body surface area (BSA), activity score, and systolic blood pressure. In multivariable analysis, FD was independently correlated with increased age (β 0.11, p

Background Increasing access to essential respiratory medicines and influenza vaccination has been a priority for over three decades. Their use remains low in low- and middle-income countries (LMICs), where little is known about factors influencing use, or about the use of influenza vaccination for preventing respiratory exacerbations. Methods We estimated rates of regular use of bronchodilators, inhaled corticosteroids and influenza vaccine, and predictors for use among 19 000 adults in 23 high-income countries (HICs) and LMIC sites. Results Bronchodilators, inhaled corticosteroids and influenza vaccine were used significantly more in HICs than in LMICs, after adjusting for similar clinical needs. Although they are used more commonly by people with symptomatic or severe respiratory disease, the gap between HICs and LMICs is not explained by the prevalence of chronic obstructive pulmonary disease or doctor-diagnosed asthma. Site-specific factors are likely to influence use differently. The gross national income per capita for the country is a strong predictor for use of these treatments, suggesting that economics influence under-treatment. Conclusion We still need a better understanding of determinants for the low use of essential respiratory medicines and influenza vaccine in low-income settings. Identifying and addressing these more systematically could improve the access and use of effective treatments.

In a premedication study involving 135 children, aged 1 - 10 years, four regimens were investigated: (I) no premedication; (il) oral trimeprazine tartrate 2 mg/kg, methadone 0,1 mg/kg, droperidol 0,15 mg/kg (TMD); (iil) intramuscular midazolam . (Dormicum; Roche) 0,15 mg/kg; and (iv) oral midazolam 0,45 mg/kg. All premedications were given 60 'minutes before a standard halothane anaesthetic. No impairment of cardiovascular stability occurred but after premedication the mean oxygen saturation decreased by 1,6% and 1,1%, respectively, in the intramuscular midazolam and TMDgroups. Overall, children under 5 years of age behaved less satisfactorily in the holding room and at induction, than those over 5 years (P < 0,01). Midazolam, intramuscularty and orally, produced more satisfactory behaviour than the other two regimens (P< 0,05) and, combined with a 70% more rapid recovery than the TMD regimen (P < 0,05), suggests that oral midazolam is a more effective paediatric premedication agent than placebo orTMD.

Incorporation of prior knowledge about organ shape and location is key to improve performance of image analysis approaches. In particular, priors can be useful in cases where images are corrupted and contain artefacts due to limitations in image acquisition. The highly constrained nature of anatomical objects can be well captured with learning based techniques. However, in most recent and promising techniques such as CNN based segmentation it is not obvious how to incorporate such prior knowledge. State-of-the-art methods operate as pixel-wise classifiers where the training objectives do not incorporate the structure and inter-dependencies of the output. To overcome this limitation, we propose a generic training strategy that incorporates anatomical prior knowledge into CNNs through a new regularisation model, which is trained end-to-end. The new framework encourages models to follow the global anatomical properties of the underlying anatomy (e.g. shape, label structure) via learned non-linear representations of the shape. We show that the proposed approach can be easily adapted to different analysis tasks (e.g. image enhancement, segmentation) and improve the prediction accuracy of the state-of-the-art models. The applicability of our approach is shown on multi-modal cardiac datasets and public benchmarks. Additionally, we demonstrate how the learned deep models of 3D shapes can be interpreted and used as biomarkers for classification of cardiac pathologies., Comment: Published in IEEE Transactions on Medical Imaging (Aug 2017)

The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge. To address this, we collected coordinated Patch-seq and whole brain morphology data sets of excitatory neurons in mouse visual cortex. From the Patch-seq data, we defined 16 integrated morpho-electric-transcriptomic (MET)-types; in parallel, we reconstructed the complete morphologies of 300 neurons. We unified the two data sets with a multi-step classifier, to integrate cell type assignments and interrogate cross-modality relationships. We find that transcriptomic variations within and across MET-types correspond with morphological and electrophysiological phenotypes. In addition, this variation, along with the anatomical location of the cell, can be used to predict the projection targets of individual neurons. We also shed new light on infragranular cell types and circuits, including cell-type-specific, interhemispheric projections. With this approach, we establish a comprehensive, integrated taxonomy of excitatory neuron types in mouse visual cortex and create a system for integrated, high-dimensional cell type classification that can be extended to the whole brain and potentially across species.