Conventional versus ultrasound treat to target: no difference in magnetic resonance imaging inflammation or joint damage over 2 years in early rheumatoid arthritis

Objective. To investigate whether an ultrasound-guided treat-to-target strategy for early RA would lead to reduced MRI inflammation or less structural damage progression compared with a conventional treat-to-target strategy.Methods. A total of 230 DMARD-naive early RA patients were randomized to an ultrasound tight control strategy targeting DAS <1.6, no swollen joints and no power Doppler signal in any joint or a conventional strategy targeting DAS <1.6 and no swollen joints. Patients in both arms were treated according to the same DMARD escalation strategy. MRI of the dominant hand was performed at six time points over 2 years and scored according to the OMERACT RA MRI scoring system. A total of 218 patients had baseline and one or more follow-up MRIs and were included in the analysis. The mean MRI score change from baseline to each follow-up and the 2 year risk for erosive progression were compared between arms.Results. MRI bone marrow oedema, synovitis and tenosynovitis improved over the first year and was sustained during the second year of follow-up, with no statistically significant differences between the ultrasound and the conventional arms at any time point. The 2 year risk for progression of MRI erosions was similar in both treatment arms: ultrasound arm 39%, conventional arm 33% [relative risk 1.16 (95% CI 0.81, 1.66), P = 0.40].Conclusion. Incorporating ultrasound information in treatment decisions did not lead to reduced MRI inflammation or less structural damage compared with a conventional treatment strategy. The findings support that systematic use of ultrasound does not provide a benefit in the follow-up of patients with early RA.Pathophysiology and treatment of rheumatic disease

The mandible and dentition of Borealestes serendipitus (Docodonta) from the Middle Jurassic of Skye, Scotland

The Middle Jurassic docodont Borealestes serendipitus was the first Mesozoic mammal found in Scotland over 40 years ago. Its affinities and morphology have remained poorly understood. Although multiple dentary fragments and isolated teeth have been recovered from Scotland and England, they have not yet been described in sufficient detail. We report new, more complete specimens collected during recent field work on Skye, Scotland, combined with previously collected material. This includes upper and lower dentition and an almost complete right dentary. We present an updated description and diagnosis of the genus Borealestes, based on high-resolution micro-computed tomography (micro-CT) and synchrotron scans. We identify seven key features that distinguish Borealestes from other docodonts, including a pronounced a–c crest, absence of the a–g crest on cusp a, an anterior fovea at the buccolingual midpoint of the upper molar, and the convergence of the Meckel’s groove with the ventral margin of the mandible. We also present a revised diagnosis for the second species, B. mussettae. Our phylogenetic analysis supports a clade formed by Borealestes, Haldanodon, Docofossor, and Docodon. Ontogenetic variation in the mandibular morphology of Borealestes is similar to that seen in Docodon and Haldanodon, with the delayed emergence of the ultimate lower molar, the shift of the last molar to the front of the coronoid process, and a posterior shift of the Meckel’s sulcus in successively older individuals. This supports a distinctive growth pattern in the clade including Borealestes and Docodon, one that may be present in Docodonta as a whole

Statistical support for the hypothesis of developmental constraint in marsupial skull evolution.

Background: In contrast to placental neonates, in which all cranial bones are ossified, marsupial young have only the bones of the oral region and the exoccipital ossified at birth, in order to facilitate suckling at an early stage of development. In this study, we investigated whether this heterochronic shift in the timing of cranial ossification constrains cranial disparity in marsupials relative to placentals. Methods: We collected three-dimensional (3D) landmark data about the crania of a wide range of extant placentals and marsupials, and from six fossil metatherians (the clade including extant marsupials and their stem relatives), using a laser scanner and a 3D digitizer. Principal components analysis and delta variance tests were used to investigate the distribution and disparity of cranial morphology between different landmark sets (optimizing either number of landmarks or number of taxa) of the whole skull and of individual developmental or functional regions (neurocranium, viscerocranium, oral region) for extant placentals and marsupials. Marsupial and placental data was also compared based on shared ecological aspects including diet, habitat, and time of peak activity. Results: We found that the extant marsupial taxa investigated here occupy a much smaller area of morphospace than the placental taxa, with a significantly (P<0.01) smaller overall variance. Inclusion of fossil taxa did not significantly increase the variance of metatherian cranial shape. Fossil forms generally plotted close to or within the realm of their extant marsupial relatives. When the disparities of cranial regions were investigated separately, significant differences between placentals and marsupials were seen for the viscerocranial and oral regions, but not for the neurocranial region. Conclusion: These results support the hypothesis of developmental constraint limiting the evolution of the marsupial skull, and further suggest that the marsupial viscerocranium as a whole, rather than just the early-ossifying oral region, is developmentally constrained

Morphology of the petrosal and stapes of Borealestes (Mammaliaformes, Docodonta) from the Middle Jurassic of Skye, Scotland

We describe, in unprecedented detail, the petros-als and stapes of the docodont Borealestes from the Middle Jurassic of Scotland, using high resolution lCT and phase- contrast synchrotron imaging. We describe the inner ear endocast and the vascularized interior structure of the pet-rosal, and provide the first endocranial view of a docodontan petrosal. Our study confirms some similarities in petrosal and stapedial morphology with the better known Haldan-odon of the Late Jurassic of Portugal, including: (1) the degree of curvature of the cochlea; (2) multiple features related to the highly pneumatized paroccipital region; (3) the shape of lateral trough, the fossa of the M. tensor tym-pani, and the ridge on the promontorium; (4) the round shape of the fenestra vestibuli; and (5) overall morphology of the stapes. But Borealestes differs from Haldanodon in having a bony ridge that separates the tympanic opening of the prootic canal, the secondary facial foramen and the hia-tus Fallopii, from the fenestra vestibuli. We identify two new vascular structures: the anterior and posterior trans-cochlear sinuses, which traverse the pars cochlearis around the cochlear nerve (VIII). These trans-cochlear sinuses have not been observed in previous docodont specimens, and could be an autapomorphy of Borealestes, or apomorphic for this clade. We also establish the anatomical relationship of the circum-promontorium plexus to the inner endocast. The high quality of our scans has made these structures visible for the first time

Paths to Innovation in Supply Chains: The Landscape of Future Research

This chapter presents a Strategic Research and Innovation Agenda for supply chain and it is the result of an intensive work jointly performed involving a wide network of stakeholders from discrete manufacturing, process industry and logistics sector to put forward a vision to strengthen European Supply Chains for the next decade. The work is based on matching visions from literature and from experts with several iterations between desk research and workshops, focus groups and interviews. The result is a detailed analysis of the supply chain strategies identified as most relevant for the next years and definition of the related research and innovation topics as future developments and steps for the full implementation of the strategies, thus proposing innovative and cutting-edge actions to be implemented based on technological development and organisational change