Colloidal Assemblies of Oriented Maghemite Nanocrystals and their NMR Relaxometric Properties

Elevated-temperature polyol-based colloidal-chemistry approach allows for the development of size-tunable (50 and 86 nm) assemblies of maghemite iso-oriented nanocrystals, with enhanced magnetization. 1H-Nuclear Magnetic Resonance (NMR) relaxometric experiments show that the ferrimagnetic cluster-like colloidal entities exhibit a remarkable enhancement (4 to 5 times) in the transverse relaxivity, if compared to that of the superparamagnetic contrast agent Endorem, over an extended frequency range (1-60 MHz). The marked increase of the transverse relaxivity r2 at a clinical magnetic field strength (1.41 T), which is 405.1 and 508.3 mM-1 s-1 for small and large assemblies respectively, allows to relate the observed response to the raised intra-aggregate magnetic material volume fraction. Furthermore, cell tests with murine fibroblast culture medium confirmed the cell viability in presence of the clusters. We discuss the NMR dispersion profiles on the basis of relaxivity models to highlight the magneto-structural characteristics of the materials for improved T2-weighted magnetic resonance images.Comment: Includes supporting informatio

VisAge: Augmented reality for heritage

In this paper we describe the VisAge project, which explored how a community-based Augmented Reality (AR) system could be used to tell stories and cultural histories about urban environments. Our work focussed on two main themes - user engagement and immersiveness of the experience. To address the first theme, we developed an online portal where anybody could upload digital content and create their own stories using routes through a physical environment. To address the second theme, we developed a flexible, reconfigurable mobile platform to investigate different types and kinds of displays. The performance of the system was assessed in a series of workshops, which have provided insights to inform the development of future systems

Spatio-temporal patterns of recent and future climate extremes in the eastern Mediterranean and Middle East region

Recent and future changes in temperature and precipitation climate extremes are estimated using the Hadley Centre PRECIS ("Providing REgional Climates for Impacts Studies") climate model for the eastern Mediterranean and Middle East region. The area of interest is considered vulnerable to extreme climate events as there is evidence for a temperature rise while precipitation tends to decline, suggesting likely effects on vital socioeconomic sectors in the region. Observations have been obtained for the recent period (1961–1990) and used to evaluate the model output. The spatial distribution of recent temporal trends in temperature indicates strong increasing in minimum temperature over the eastern Balkan Peninsula, Turkey and the Arabian Peninsula. The rate of warming reaches 0.4–0.5 °C decade⁻¹ in a large part of the domain, while warming is expected to be strongest in summer (0.6–0.7 °C decade⁻¹) in the eastern Balkans and western Turkey. The trends in annual and summer maximum temperature are estimated at approximately 0.5 and 0.6 °C decade⁻¹ respectively. Recent estimates do not indicate statistically significant trends in precipitation except for individual sub-regions. Results indicate a future warming trend for the study area over the last 30 years of the 21st century. Trends are estimated to be positive and statistically significant in nearly the entire region. The annual trend patterns for both minimum and maximum temperature show warming rates of approximately 0.4–0.6 °C decade⁻¹, with pronounced warming over the Middle Eastern countries. Summer temperatures reveal a gradual warming (0.5–0.9 °C decade⁻¹) over much of the region. The model projects drying trends by 5–30% in annual precipitation towards the end of the 21st century, with the number of wet days decreasing at the rate of 10–30 days year⁻¹, while heavy precipitation is likely to decrease in the high-elevation areas by 15 days year⁻¹

Investigating the entire course of telithromycin binding to Escherichia coli ribosomes

Applying kinetics and footprinting analysis, we show that telithromycin, a ketolide antibiotic, binds to Escherichia coli ribosomes in a two-step process. During the first, rapidly equilibrated step, telithromycin binds to a low-affinity site (KT = 500 nM), in which the lactone ring is positioned at the upper portion of the peptide exit tunnel, while the alkyl–aryl side chain of the drug inserts a groove formed by nucleotides A789 and U790 of 23S rRNA. During the second step, telithromycin shifts slowly to a high-affinity site (KT* = 8.33 nM), in which the lactone ring remains essentially at the same position, while the side chain interacts with the base pair U2609:A752 and the extended loop of protein L22. Consistently, mutations perturbing either the base pair U2609:A752 or the L22-loop hinder shifting of telithromycin to the final position, without affecting the initial step of binding. In contrast, mutation Lys63Glu in protein L4 placed on the opposite side of the tunnel, exerts only a minor effect on telithromycin binding. Polyamines disfavor both sequential steps of binding. Our data correlate well with recent crystallographic data and rationalize the changes in the accessibility of ribosomes to telithromycin in response to ribosomal mutations and ionic changes

Syndromic Forms of Hyperinsulinaemic Hypoglycaemia A 15-year follow-up Study

OBJECTIVE: Hyperinsulinaemic hypoglycaemia (HH) is one of the commonest causes of hypoglycaemia in children. The molecular basis includes defects in pathways that regulate insulin release. Syndromic conditions like Beckwith-Wiedemann (BWS), Kabuki (KS) and Turner (TS) are known to be associated with a higher risk for HH. This systematic review of children with HH referred to a tertiary centre aims at estimating the frequency of a syndromic/multisystem condition to help address stratification of genetic analysis in infants with HH. METHODS: We performed a retrospective study of 69 patients with syndromic features and hypoglycaemia in a specialist centre from 2004 to 2018. RESULTS: Biochemical investigations confirmed HH in all the cases and several genetic diagnoses were established. Responsiveness to medications and the final outcome following medical treatment or surgery were studied. CONCLUSIONS: This study highlights the association of HH with a wide spectrum of syndromic diagnoses and that children with features suggestive of HH-associated syndromes should be monitored for hypoglycaemia. If hypoglycaemia is documented, they should also be screened for possible HH. Our data indicate that most syndromic forms of HH are diazoxide-responsive and that HH resolves over time; however a significant percentage continues to require medications years after the onset of the disease. Early diagnosis of hyperinsulinism and initiation of treatment is important for preventing hypoglycaemic brain injury and intellectual disability

Assembly-mediated Interplay of Dipolar Interactions and Surface Spin Disorder in Colloidal Maghemite Nanoclusters

Controlled assembly of single-crystal, colloidal maghemite nanoparticles is facilitated via a high-temperature polyol-based pathway. Structural characterization shows that size-tunable nanoclusters of 50 and 86 nm diameters (D), with high dispersibility in aqueous media, are composed of $\sim$ 13 nm (d) crystallographically oriented nanoparticles. The interaction effects are examined against the increasing volume fraction, $\phi$, of the inorganic magnetic phase that goes from individual colloidal nanoparticles ($\phi$= 0.47) to clusters ($\phi$= 0.72). The frozen-liquid dispersions of the latter exhibit weak ferrimagnetic behavior at 300 K. Comparative Mossbauer spectroscopic studies imply that intra-cluster interactions come into play. A new insight emerges from the clusters temperature-dependent ac susceptibility that displays two maxima in $\chi$''(T), with strong frequency dispersion. Scaling-law analysis, together with the observed memory effects suggest that a superspin glass state settles-in at T$_{B}$ $\sim$ 160-200 K, while at lower-temperatures, surface spin-glass freezing is established at T$_{f}$ $\sim$40- 70 K. In such nanoparticle-assembled systems, with increased $\phi$, Monte Carlo simulations corroborate the role of the inter-particle dipolar interactions and that of the constituent nanoparticles surface spin disorder in the emerging spin-glass dynamics

Requirements and validation of a prototype learning health system for clinical diagnosis

Introduction Diagnostic error is a major threat to patient safety in the context of family practice. The patient safety implications are severe for both patient and clinician. Traditional approaches to diagnostic decision support have lacked broad acceptance for a number of well-documented reasons: poor integration with electronic health records and clinician workflow, static evidence that lacks transparency and trust, and use of proprietary technical standards hindering wider interoperability. The learning health system (LHS) provides a suitable infrastructure for development of a new breed of learning decision support tools. These tools exploit the potential for appropriate use of the growing volumes of aggregated sources of electronic health records. Methods We describe the experiences of the TRANSFoRm project developing a diagnostic decision support infrastructure consistent with the wider goals of the LHS. We describe an architecture that is model driven, service oriented, constructed using open standards, and supports evidence derived from electronic sources of patient data. We describe the architecture and implementation of 2 critical aspects for a successful LHS: the model representation and translation of clinical evidence into effective practice and the generation of curated clinical evidence that can be used to populate those models, thus closing the LHS loop. Results/Conclusions Six core design requirements for implementing a diagnostic LHS are identified and successfully implemented as part of this research work. A number of significant technical and policy challenges are identified for the LHS community to consider, and these are discussed in the context of evaluating this work: medico-legal responsibility for generated diagnostic evidence, developing trust in the LHS (particularly important from the perspective of decision support), and constraints imposed by clinical terminologies on evidence generation

Mediated Spatial Narratives: Experiencing Archival Material and Shared Memories in Urban Space

In this paper we report on studies we conducted focusing on the use of Augmented Reality to annotate real sites with relevant archival content. This is an interdisciplinary study of novel interactive technologies and supportive platforms such as geolocation-navigation and contextual digital augmentation of archival material in public spaces. We involved community volunteers, experts and public in a participatory heritage initiative. We designed an experience that supported a multi-platform participation, via an online geo-tagging portal and a mixed reality navigational experience. In an iterative design process we explored the use and preference of mobile devices, the controlled design of digital content anchored to real sites and the use of AR to support urban narratives. We did this by conducting a series of user walkthroughs with recruited participants and workshops with local experts related to the case studies. In this paper we argue on the importance of situating urban experience of digital archives and stories in the actual locations of the events they represent as to better support immersion, enhance place experience and reinforce situated learning. Our work contributes to the design of hybrid spatialities and experiences in urban space that relate to local memory and culture