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Background: Spinal Muscular Atrophy (SMA) is the most common neurodegenerative disease in childhood. New therapeutic interventions have been developed to interrupt rapid motor deterioration. The current standard of clinical evaluation for severely weak infants is the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), originally developed for SMA type 1. This test however, remains subjective and requires extensive training to be performed reliably. Objective: Proof of principle of the motion tracking method for capturing complex movement patterns in ten children with SMA. Methods: We have developed a system for tracking full-body motion in infants (KineMAT) using a commercially available, low-cost RGB-depth sensor. Ten patients with SMA (2–46 months of age; CHOP INTEND score 10–50) were recorded for 2 minutes during unperturbed spontaneous whole-body activity. Five predefined motion parameters representing 56 degrees of freedom of upper, lower extremities and trunk joints were correlated with CHOP INTEND scores using Pearson product momentum correlation (r). Test-retest analysis in two patients used descriptive statistics. Results: 4/5 preselected motion parameters highly correlated with CHOP INTEND: 1. Standard deviation of joint angles (r = 0.959, test-retest range 1.3–1.9%), 2. Standard deviation of joint position (r = 0.933, test-retest range 2.9%), 3. Absolute distance of hand/foot travelled (r = 0.937, test-retest range 6–10.5%), 4. Absolute distance of hand/foot travelled against gravity (r = 0.923; test-retest range 4.8–8.5%). Conclusions: Markerless whole-body motion capture using the KineMAT proved to objectively capture motor performance in infants and children with SMA across different severity and ages.

Avelumab; Cetuximab; Non–small cell lung cancer Avelumab; Cetuximab; Càncer de pulmó de cèl·lules no petites Avelumab; Cetuximab; Cáncer de pulmón de células no pequeñas Introduction We present the results of a phase 2a trial of first-line avelumab (anti–programmed death-ligand 1 antibody) plus cetuximab (anti–EGFR antibody) in patients with advanced squamous NSCLC. Methods Patients with recurrent or metastatic squamous NSCLC received avelumab 800 mg (d 1 and 8), cetuximab 250 mg/m2 (d 1) and 500 mg/m2 (d 8), cisplatin 75 mg/m2 (d 1), and gemcitabine 1250 mg/m2 (d 1 and 8) for four 3-week cycles, followed by avelumab 800 mg and cetuximab 500 mg/m2 every 2 weeks. The primary end point was the best overall response; the secondary end points were progression-free survival, duration of response, overall survival, and safety. Efficacy analyses were reported from an updated data cutoff. Results A total of 43 patients were enrolled. The median follow-up was 6.6 months for the primary analyses and 9.2 months for the efficacy analyses. In the efficacy analyses, 15 patients had a confirmed partial response (objective response rate, 34.9% [95% confidence interval: 21.0%–50.9%]), and the median duration of response was 7.1 months (95% confidence interval: 4.2–12.5 mo). The median progression-free survival and overall survival were 6.1 months and 10.0 months, respectively. In the safety analyses (primary analysis), 38 patients (88.4%) had a treatment-related adverse event, of whom 24 (55.8%) had a grade 3 or higher treatment-related adverse event. Conclusions The combination of avelumab + cetuximab and chemotherapy showed antitumor activity and tolerable safety; however, the ORR was not improved compared with those reported for current standards of care (NCT03717155). This study was sponsored by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945) as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany, and Pfizer. Employees of the sponsor are coauthors of this manuscript and contributed to the design, execution, interpretation of the analyses, writing the report, and the decision to submit the article for publication, along with other coauthors. We thank the patients and their families, the investigators, co-investigators, and study teams at each participating center and the healthcare business of Merck KGaA, Darmstadt, Germany. Medical writing support was provided by Abhijith Thippeswamy of ClinicalThinking and funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945) and Pfizer.

Servitization increases uncertainty and complexity in manufacturing firms by introducing dynamic interdependencies within and between organisations. This study proposes the conceptual lens of Complex Adaptive Systems (CAS) to frame manufacturers’ service delivery systems and a hybrid simulation approach to explore the dynamic interdependencies of their servitization journeys. The case of a boiler manufacturer transforming to a provider of Heat-as-a-Service (HaaS) is used to examine the dynamic interdependencies between the growth of a service business, digitalisation efforts and operational efficiency as well as the interaction between the emerging service- and existing product business. The findings indicate that the manufacturer will experience an initial ‘cost-shock’ which will significantly decline as service delivery optimises and diagnostic accuracy improves. The study contributes to the servitization literature by introducing CAS as a theoretical perspective and hybrid modelling as a practical approach to explore and reconcile the strategic and operational dimensions of servitization. Funding: European Union [721909]; UKs Engineering and Physical Science Research Council through the Digitally Enhanced Advanced Services NetworkPlus [EP/R044937/1]; EPSRC

Business models are becoming more inclined towards platforms, which allow inclusion of diverse participants to promote leveraged growth and modularity of offerings. Despite being closely linked, several aspects of platforms are often studied exclusively from their ecosystems, lacking integrative insights on the topic of platform ecosystems. Most studies are tunnel focussed on the technical aspects, failing to account for the social factors that play a critical role within platform firms. In addressing this gap, the study aims to review research on both social and technical aspects of platform ecosystems to account for the complex interdependencies stemming from platform-oriented actor interactions. The study extends beyond a typical literature review approach to also include a theoretically grounded, yet practically relevant framework of socio-technical systems to offer a holistic review of literature on how platform ecosystems function and sustain in competitive environments.

Objective To assess self-reported executive dysfunction in young adult patients with persistent post-concussion symptoms (PCS) 2–6 months post-injury, and the association with self-reported Health-Related Quality of Life (HRQoL). Method This cross-sectional study carried out in a hospital setting was a secondary analysis of data from a separate randomized trial testing the effect of a novel intervention, “Get going After concussIoN ” (GAIN), for persistent PCS. Patients (18–30 years) were recruited from a clinical cohort of patients with a hospital diagnosis of concussion or referred by primary care physicians. Main measures were The Behaviour Rating Inventory of Executive Function—Adult Version providing two index scores, that is, the Metacognitive Index (MI) and the Behavioural Regulation Index (BRI), and the Quality of Life after Brain Injury—Overall Scale. Results Compared with normative data, patients had elevated scores (i.e., worse functioning) on both the MI and the BRI. In linear regression analysis, the MI score, but not the BRI score, was negatively associated with self-reported HRQoL (MI: slope = −.27, 95% confidence interval, CI [−.53, −.02], p = .03; BRI: slope = −.19, 95% CI [−.49, .13], p = .24), suggesting a positive association of subjective executive dysfunction and lower HRQoL. However, the association was attenuated after adjustment for self-reported psychological distress (MI: slope = −.09, 95% CI [−.34, .17], p = .51). Conclusion Self-reported executive dysfunction is common in young adult patients with persistent PCS, but not strongly associated with decreased HRQoL after adjusting for concurrent psychological distress.

PurposeThe purpose of this study is to investigate how the internet of things (IoT) contributes to manufacturers' advanced services development and delivery. To better understand the creation of these IoT contributions, the study adopts a socio-technical research perspective, which expands the scope of the investigation and integrates the technological, information and social factors that enable these IoT contributions.Design/methodology/approachA multiple-case research method was employed to investigate the IoT contribution scenarios of 15 manufacturers who offer advanced services and to examine their dependence on other non-IoT factors, using thematic analysis.FindingsThe analysis identified five advanced services value propositions, which are enabled by nine “IoT-enabled information systems (IS) artefacts” that specify the distinct interactions between the technological, information and social subsystems supporting the manufacturers' advanced services value propositions.Originality/valueThe study advances the servitisation research by demonstrating that IoT technology on its own is insufficient for the creation of the IoT contributions. It shows, instead, the need for close interactions with a diverse range of other factors, which are often not considered when developing an IoT strategy. The study also introduces the IS artefact notion as a unit of analysis that constitutes an alternative to the commonly adopted techno-centric perspective used to conceptualise IoT contributions. The study and its findings add to the development of a socio-technical perspective on the IoT in advanced services and thereby suggests a number of theoretical and practical implications.

Servitization describes a paradoxical and lengthy transformation process in the field of manufacturing, requiring manufacturers to move from competing on the basis of their products to competing on the basis of their services; yet the delivery of these services relies on the production of high-quality products. Such transformations may take several years, necessitating manufacturers to balance the competing demands of both the product and service businesses, as well as navigating their interdependency. In order to illuminate these competing demands, and understand their progression over the course of a manufacturer’s servitization journey, the present study conceptualises a processual perspective on the paradoxes inherent in servitization. The conceptualisation of the processual perspective integrates a servitization stage model with established paradox theory to depict the paradoxical tensions that servitization creates, while also demonstrating how, and when, these emerge. The conceptualisation is applied to longitudinal data from three case studies that reconstruct the manufacturers’ experiences from the point of the initial exploration of servitization to the implementation of their outcome-based service offering. The findings identify how learning, belonging, organising and performing paradoxical tensions emerge over time, and how they unfold and change depending on the objectives and activities of the manufacturers’ servitization stage.

The electron emission properties of a single-crystal nitrogen-doped diamond(001) photocathode inserted in a 10kV DC photoelectron gun are determined using a tunable (235-410nm) ultraviolet laser radiation source for photoemission from both the back nitrogen-doped substrate face and the front homo-epitaxially grown and undoped diamond crystal face. The measured spectral trends of the mean transverse energy (MTE) and quantum efficiency (QE) of the emitted electrons are both anomalous and non-monotonic, but are shown to be consistent with (i) the known physics of electron photoexcitation from the nitrogen substitution states into the conduction bands of diamond, (ii) the energy position and dispersion characteristics of the conduction bands of diamond in the (001) emission direction, (iii) the effective electron affinity of the crystal faces, (iv) the strong electron-(optical)phonon coupling in diamond, and (v) the associated hot electron transport dynamics under energy equipartition with the optical phonons. Notably, the observed hot electron emission is shown to be restricted parallel to the photocathode surface by the low transverse effective masses of the emitting band states - a transverse momentum filtering effect., Comment: 14 pages, 4 figures