Foreword

The Journal, in partnership with the Law of the Sea Institute at the University of California, Berkeley, is therefore proud to present a symposium on Multilateralism in International Ocean Resources Law. The authors represented in this symposium delivered papers last year at a conference organized by the Institute at the Boalt Hall School of Law, UC-Berkeley; and those papers have been extensively revised for publication in this issue

Community-engaged primary care medical education

BACKGROUND: Community-engaged medical education (CEME) requires medical schools to partner with local communities to help address community priorities, whilst enhancing the learning experiences of students. Current literature on CEME has focused on evaluating its effects on students; however, there remains a gap in exploring whether CEME initiatives can have a sustainable impact for communities. APPROACH: The Community Action Project (CAP) at Imperial College London, is an eight-week, community-engaged, quality improvement project for Year 3 medical students. Students initially consult with clinicians, patients and wider community stakeholders to understand local needs and assets, and identify a health priority to address. They then work with relevant stakeholders to design, implement and evaluate a project to help address their identified priority. EVALUATION: All CAPs (n = 264) completed in the 2019-2021 academic years were evaluated for evidence of several key areas, including community engagement and sustainability. 91% of projects evidenced a needs analysis, 71% demonstrated patient involvement in their development, and 64% demonstrated sustainable impacts from their projects. Analysis revealed the topics frequently addressed, and the formats used by students. Two CAPs are described in more detail to demonstrate their community impact. IMPLICATIONS: The CAP demonstrates how the principles of CEME (meaningful community engagement and social accountability) can lead to sustainable benefits for local communities through purposeful collaboration with patients and local communities. Strengths, limitations and future directions are highlighted

Phenotypic Properties of Collagen in Dentinogenesis Imperfecta Associated with Osteogenesis Imperfecta

Introduction: Dentinogenesis imperfecta type 1 (OIDI) is considered a relatively rare genetic disorder (1:5000 to 1:45,000) associated with osteogenesis imperfecta. OIDI impacts the formation of collagen fibrils in dentin, leading to morphological and structural changes that affect the strength and appearance of teeth. However, there is still a lack of understanding regarding the nanoscale characterization of the disease, in terms of collagen ultrastructure and mechanical properties. Therefore, this research presents a qualitative and quantitative report into the phenotype and characterization of OIDI in dentin, by using a combination of imaging, nanomechanical approaches. Methods: For this study, 8 primary molars from OIDI patients and 8 primary control molars were collected, embedded in acrylic resin and cut into longitudinal sections. Sections were then demineralized in 37% phosphoric acid using a protocol developed in-house. Initial experiments demonstrated the effectiveness of the demineralization protocol, as the ATR-FTIR spectral fingerprints showed an increase in the amide bands together with a decrease in phosphate content. Structural and mechanical analyses were performed directly on both the mineralized and demineralized samples using a combination of scanning electron microscopy, atomic force microscopy, and Wallace indentation. Results: Mesoscale imaging showed alterations in dentinal tubule morphology in OIDI patients, with a reduced number of tubules and a decreased tubule diameter compared to healthy controls. Nanoscale collagen ultrastructure presented a similar D-banding periodicity between OIDI and controls. Reduced collagen fibrils diameter was also recorded for the OIDI group. The hardness of the (mineralized) control dentin was found to be significantly higher (p<0.05) than that of the OIDI (mineralized) dentine. Both the exposed peri- and intratubular dentinal collagen presented bimodal elastic behaviors (Young's moduli). The control samples presented a stiffening of the intratubular collagen when compared to the peritubular collagen. In case of the OIDI, this stiffening in the collagen between peri- and intratubular dentinal collagen was not observed and the exposed collagen presented overall a lower elasticity than the control samples. Conclusion: This study presents a systematic approach to the characterization of collagen structure and properties in OIDI as diagnosed in dentin. Structural markers for OIDI at the mesoscale and nanoscale were found and correlated with an observed lack of increased elastic moduli of the collagen fibrils in the intratubular OIDI dentin. These findings offer an explanation of how structural changes in the dentin could be responsible for the failure of some adhesive restorative materials as observed in patients affected by OIDI

Label-free CARS microscopy reveals similar triacylglycerol acyl chain length and saturation in myocellular lipid droplets of athletes and individuals with type 2 diabetes

Aims/hypothesis: Intramyocellular lipid (IMCL) content associates with development of insulin resistance, albeit not in insulinsensitive endurance-trained athletes (trained). Qualitative and spatial differences in muscle lipid composition may underlie this so-called athlete’s paradox. Here we studied triacylglycerol (TAG) composition of individual myocellular lipid droplets (LDs) in trained individuals and individuals with type 2 diabetes mellitus.Methods: Trained (˙V O2max 71.0 \ub1 1.6 ml O2 [kg lean body mass (LBM)]−1 min−1), normoglycaemic (fasting glucose 5.1 \ub1 0.1 mmol/l) individuals and untrained (V O2max 36.8 \ub1 1.5 ml O2 [kg LBM]−1 min−1) individuals with type 2 diabetes (fasting glucose 7.4 \ub1 0.5 mmol/l), with similar IMCL content (3.5 \ub1 0.7% vs 2.5 \ub1 0.3%, p = 0.241), but at opposite ends of the insulin sensitivity spectrum(glucose infusion rate 93.8 \ub1 6.6 vs 25.7 \ub1 5.3 μmol [kg LBM]−1 min−1 for trained individuals and those with type 2 diabetes, respectively) were included from our database in the present study. We applied in situ label-free broadbandcoherent anti-Stokes Raman scattering (CARS) microscopy to sections from skeletal muscle biopsies to measure TAG acyl chain length and saturation of myocellular LDs. This approach uniquely permits examination of individual LDs in their native environment, in a fibre-type-specific manner, taking into account LD size and subcellular location.Results: Despite a significant difference in insulin sensitivity, we observed remarkably similar acyl chain length and saturation in trained and type 2 diabetic individuals (chain length: 18.12 \ub1 0.61 vs 18.36 \ub1 0.43 number of carbons; saturation: 0.37 \ub1 0.05 vs 0.38 \ub1 0.06 number of C=C bonds). Longer acyl chains or higher saturation (lower C=C number) could be detected in subpopulations of LDs, i.e. large LDs (chain length: 18.11 \ub1 0.48 vs 18.63 \ub1 0.57 carbon number) and subsarcolemmal LDs (saturation: 0.34 \ub1 0.02 vs 0.36 \ub1 0.04 C=C number), which are more abundant in individuals with type 2 diabetes.Conclusions/interpretation: In contrast to reports of profound differences in the lipid composition of lipids extracted from skeletal muscle from trained and type 2 diabetic individuals, our in situ, LD-specific approach detected only modest differences in TAGcomposition in LD subpopulations, which were dependent on LD size and subcellular location. If, and to what extent, these modest differences can impact insulin sensitivity remains to be elucidated

Covering problems in edge- and node-weighted graphs

This paper discusses the graph covering problem in which a set of edges in an edge- and node-weighted graph is chosen to satisfy some covering constraints while minimizing the sum of the weights. In this problem, because of the large integrality gap of a natural linear programming (LP) relaxation, LP rounding algorithms based on the relaxation yield poor performance. Here we propose a stronger LP relaxation for the graph covering problem. The proposed relaxation is applied to designing primal-dual algorithms for two fundamental graph covering problems: the prize-collecting edge dominating set problem and the multicut problem in trees. Our algorithms are an exact polynomial-time algorithm for the former problem, and a 2-approximation algorithm for the latter problem, respectively. These results match the currently known best results for purely edge-weighted graphs.Comment: To appear in SWAT 201

An Approach to Autonomizing Legacy Systems

Adding adaptation capabilities to existing distributed systems is a major concern. The question addressed here is how to retrofit existing systems with self-healing, adaptation and/or self management capabilities. The problem is obviously intensified for 'systems of systems' composed of components, whether new or legacy, that may have been developed by different vendors, mixing and matching COTS and 'open source' components. This system composition model is expected to be increasingly common in high performance computing. The usual approach is to train technicians to understand the complexities of these components and their connections, including performance tuning parameters, so that they can then manually monitor and reconfigure the system as needed. We envision instead attaching a 'standard' feedback loop infrastructure to existing distributed systems for the purposes of continual monitoring and dynamically adapting their activities and performance. (This approach can also be applied to 'new' systems, as an alternative to 'building in' adaptation facilities, but we do not address that here.) Our proposed infrastructure consists of multiple layers with the objectives of probing, measuring and reporting of activity and state within the execution of the legacy system among its components and connectors; gauging, analysis and interpretation of the reported events; and possible feedback to focus the probes and gauges to drill deeper, or when necessary - direct but automatic reconfiguration of the running system

Quantitative nanohistological investigation of scleroderma: An atomic force microscopy-based approach to disease characterization

Scleroderma (or systemic sclerosis, SSc) is a disease caused by excess crosslinking of collagen. The skin stiffens and becomes painful, while internally, organ function can be compromised by the less elastic collagen. Diagnosis of SSc is often only possible in advanced cases by which treatment time is limited. A more detailed analysis of SSc may provide better future treatment options and information of disease progression. Recently, the histological stain picrosirius red showing collagen register has been combined with atomic force microscopy (AFM) to study SSc. Skin from healthy individuals and SSc patients was biopsied, stained and studied using AFM. By investigating the crosslinking of collagen at a smaller hierarchical stage, the effects of SSc were more pronounced. Changes in morphology and Young’s elastic modulus were observed and quantified; giving rise to a novel technique, we have termed “quantitative nanohistology”. An increase in nanoscale stiffness in the collagen for SSc compared with healthy individuals was seen by a significant increase in the Young’s modulus profile for the collagen. These markers of stiffer collagen in SSc are similar to the symptoms experienced by patients, giving additional hope that in the future, nanohistology using AFM can be readily applied as a clinical tool, providing detailed information of the state of collagen

A cross-discipline approach to healthcare needs

With rapid advancements in technology and growing demand for better healthcare, hospitals are struggling to find a balance between providing the best possible care and maintaining a responsible budget. This issue is especially evident in small hospitals lacking resources and infrastructure to keep up with modern technology. The Engineering for Modern Healthcare Creative Inquiry is a collaboration between Industrial Engineering and Bioengineering students. Our goal is to help small hospitals to develop efficient, cost-effective solutions to their needs. Currently, we are working with hospitals in South Carolina and Virginia to explore these solutions. We are interviewing clinicians, nurses, and other staff members to better understand current practices and identify improvement opportunities. Our initial focus will be on inventory management and sterile processing. Utilizing both departments\u27 expertise, we will develop a comprehensive solution to this complicated need

Patient-reported outcome measure for children and young people with amelogenesis imperfecta

Background: Amelogenesis imperfecta (AI) is a genetic enamel defect that can affect both the primary and permanent dentition. It has a range of clinical phenotypes, and children and young people often present with challenging oral health needs. Patient-reported outcome measures (PROMs) can identify key patient concerns. Methods: This was a multi-centre service evaluation across several specialist paediatric dentistry services in the UK. A PROM questionnaire was created with clinician and patient input, through peer review with the national AI Clinical Excellence Network, as well as piloting the PROM with ten children and young people with AI. The final PROM questionnaire was distributed to all patients with AI attending each unit between January and March 2020. Results: Sixty children and young people (aged 5-17 years) across four specialist units participated, with 72% reporting that they 'often' or 'sometimes' experienced pain or sensitivity and 76% reporting that they 'often' or 'sometimes' felt unhappy with the way their teeth look. Of the patients who were post-treatment, 81% indicated that they were happy with their teeth, compared to just 41% of patients who were mid-treatment and 33% of patients who were pre-treatment. Conclusion: Children and young people with AI experience a range of issues related to their function and psychosocial wellbeing. This simple PROM demonstrates the range of issues this group of patients face, and could be used to monitor an individual's progress to ensure that treatment is planned to address the patient's individual concerns and needs