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High-resolution nano-focus X-ray fluorescence microscopy using hard X-rays at the European Synchrotron Radiation Facility (ESRF) IDB16 beamline detected endogenous barium, bromine, calcium, chlorine, copper, iron, manganese, potassium, phosphorus, rubidium, sulphur, selenium, strontium and zinc, at tissue, cellular and subcellular level in the outer retinal complex of light adapted, 3-week-old, male C57BL6 mice. Fresh snap-frozen (20 μm) cryosections dried at room temperature were scanned at 1 μm, 300 nm and 50 nm spatial resolution by incident X-ray photons from the synchrotron beam. Analysis of 2D maps and 3D surface plots by PyMCA and ImageJ revealed elevated zinc concentrations in the choriocapillaris (CC) (mean 45, range 28–77 ppm), retinal pigment epithelium (RPE) layer (mean 47, range 20–76 ppm), photoreceptor inner segments (RIS) ellipsoid zone, outer limiting membrane (OLM) (mean 32, range < 1–44 ppm) and outer nuclear layer (ONL) in between photoreceptor cell bodies. Mūller cells processes in ONL and their interdigitations in RIS ellipsoid zone seem to contain zinc in the cell membrane. Iron was found at elevated amounts in RIS myoid zone (mean 38, range 14–68 ppm), RPE layer (52, range 24–143 ppm), and choroid (60, range 36–172 ppm). Copper was also detected in the CC (4.3, range 1.9–9.7 ppm), RPE layer (4.5, range 1.6–20.8 ppm), and RIS myoid zone (4.9, range 1.25–10.2 ppm). Calcium was found with granular/punctate distribution in OLM (159, range 49–962 ppm), RIS myoid zone (245, range 36-1370 ppm), RPE layer (1134, range 257–2503 ppm), and CC (1101, range 323–2090 ppm). The metalloid selenium was present in the CC (1.8, range < 1-4.7 ppm] and across the RPE (basal, central, apical) (2.4, range < 1-8.5 ppm). High resolution maps of the interface photoreceptor outer segments (ROS) and the RPE apical side revealed selenium-rich spherical structures (appr. 1 μm diameter) (mean 5.6, range 2.2–8.1 ppm), associated with calcium (mean 1057, range 619–1755 ppm), phosphorus (9924, range 6118–15058 ppm), and manganese (0.7, < 1–24 ppm), surrounded by a zinc-containing layer. This study presents the first nanoprobe X-ray fluorescence microscopy image analysis of adult mouse light adapted outer retinal complex from the whole tissue to subcellular structures. The high spatial resolution (location) and high sensitivity (metal quantity) findings, together with the information on biometals available in the literature, allowed us to propose a schematic model of possible selenium biological processes and their role in physiological activities in the outer retinal complex. We hypothesise there is a dedicated selenium-rich spherical structure with the ability to cross RPE cell membranes (i.e. the outer blood retinal barrier) and with potential roles in certain biological function(s) (e.g. ROS phagocytosis by RPE cell microvilli, trans-RPE transport).

In the past several decades, polymeric microparticles (MPs) have emerged as viable solutions to address the limitations of standard pharmaceuticals and their corresponding delivery methods. While there are many preclinical studies that utilize polymeric MPs as a delivery vehicle, there are limited FDA-approved products. One potential barrier to the clinical translation of these technologies is a lack of understanding with regard to the manufacturing process, hindering batch scale-up. To address this knowledge gap, we sought to first identify critical processing parameters in the manufacturing process of blank (no therapeutic drug) and protein-loaded double-emulsion poly(lactic-co-glycolic) acid MPs through a quality by design approach. We then utilized the design of experiments as a tool to systematically investigate the impact of these parameters on critical quality attributes (e.g., size, surface morphology, release kinetics, inner occlusion size, etc.) of blank and protein-loaded MPs. Our results elucidate that some of the most significant CPPs impacting many CQAs of double-emulsion MPs are those within the primary or single-emulsion process (e.g., inner aqueous phase volume, solvent volume, etc.) and their interactions. Furthermore, our results indicate that microparticle internal structure (e.g., inner occlusion size, interconnectivity, etc.) can heavily influence protein release kinetics from double-emulsion MPs, suggesting it is a crucial CQA to understand. Altogether, this study identifies several important considerations in the manufacturing and characterization of double-emulsion MPs, potentially enhancing their translation.

Background/Objectives: Controlled release systems, such as polymeric microparticles (MPs), have emerged as a promising solution to extend the bioavailability and reduce dosing frequency for biologic drugs; however, the formulation of these systems to encapsulate highly sensitive, hydrophilic biologic drugs within hydrophobic polymers remains a nontrivial task. Although scalable manufacturing and FDA approval of single emulsion processes encapsulating small molecules has been achieved, scaling more complex double emulsion processes to encapsulate hydrophilic biologics remains more challenging. Methods: Here, we demonstrate that two hydrophilic, low-molecular-weight, recombinant chemokines, CCL22 and CCL2, can be encapsulated in poly(lactic-co-glycolic acid) (PLGA) MPs using a single emulsion method where the proteins are dissolved in an organic solvent during formulation. Results: As expected, we observed some differences in release kinetics from single emulsion MPs compared to double emulsion MPs, which traditionally have been used to encapsulate proteins. Single emulsion MPs exhibited a substantially reduced initial burst. Importantly, protein released from single emulsion CCL22-MPs also retained biological activity, as determined by a cell-based functional assay. Decreasing particle size or changing the polymer end group from PLGA-COOH to PLGA-OH increased the initial burst from single emulsion MPs, demonstrating tunability of release kinetics for protein-loaded, single emulsion MPs. Finally, to improve scalability and enable more precise control over MP formulations, the single emulsion process was adapted to a microfluidic, continuous manufacturing system, and the resulting MPs were evaluated similarly. Conclusions: Altogether, this study demonstrates the feasibility of using a single emulsion encapsulation method for at least some protein biologics.

By issuing its decision in Dobbs v. Jackson Women's Health, the U.S. Supreme Court changed the operative meaning of federal constitutional law: On June 23, 2023, the Fourteenth Amendment Due Process Clause protected the right to an abortion; the next day, it did not. But is it possible that Dobbs also changed the meaning of state constitutional law? Curiously, the answer in some circumstances may be yes. That is because many state courts have incorporated U.S. Supreme Court interpretations of federal constitutional provisions, like the Due Process Clause, into the meaning of analogous state constitutional provisions, in what is often referred to as the \"lockstep \" method of state constitutional interpretation.

This paper considers a decentralized and autonomous wireless network of low SWaP (size, weight, and power) fixed-wing UAVs (unmanned aerial vehicles) used for remote exploration and monitoring of targets in an inaccessible area lacking communication infrastructure. Here, the UAVs collaborate to find target(s) and use routing protocols to forward the sensed data of target(s) to an aerial base station (BS) in real-time through multihop communication, which can then transmit the data to a control center. However, the unpredictability of target locations and the highly dynamic nature of autonomous, decentralized UAV networks result in frequent route breaks or traffic disruptions. Traditional routing schemes cannot quickly adapt to dynamic UAV networks and can incur large control overhead and delays. In addition, their performance suffers from poor network connectivity in sparse networks with multiple objectives (exploration and monitoring of targets), which results in frequent route unavailability. To address these challenges, we propose two routing schemes: Pipe routing and TC-Pipe routing. Pipe routing is a mobility-, congestion-, and energy-aware scheme that discovers routes to the BS on-demand and proactively switches to alternate high-quality routes within a limited region around the routes (referred to as the “pipe”) when needed. TC-Pipe routing extends this approach by incorporating a decentralized topology control mechanism to help maintain robust connectivity in the pipe region around the routes, resulting in improved route stability and availability. The proposed schemes adopt a novel approach by integrating the topology control with routing protocol and mobility model, and rely only on local information in a distributed manner. Comprehensive evaluations under diverse network and traffic conditions—including UAV density and speed, number of targets, and fault tolerance—show that the proposed schemes improve throughput by reducing flow interruptions and packet drops caused by mobility, congestion, and node failures. At the same time, the impact on coverage performance (measured in terms of coverage and coverage fairness) is minimal, even with multiple targets. Additionally, the performance of both schemes degrades gracefully as the percentage of UAV failures in the network increases. Compared to schemes that use dedicated UAVs as relay nodes to establish a route to the BS when the UAV density is low, Pipe and TC-Pipe routing offer better coverage and connectivity trade-offs, with the TC-Pipe providing the best trade-off.

Fraser syndrome is a recessive, multisystem disorder presenting with cryptophthalmos, syndactyly and renal defects 1 , 2 and associated with loss-of-function mutations of the extracellular matrix protein FRAS1. Fras1 mutant mice have a blebbed phenotype characterized by intrauterine epithelial fragility generating serous and, later, hemorrhagic blisters. The myelencephalic blebs ( my ) strain has a similar phenotype. We mapped my to Frem2 , a gene related to Fras1 and Frem1 , and showed that a Frem2 gene-trap mutation was allelic to my . Expression of Frem2 in adult kidneys correlated with cyst formation in my homozygotes, indicating that the gene is required for maintaining the differentiated state of renal epithelia. Two individuals with Fraser syndrome were homozygous with respect to the same missense mutation of FREM2 , confirming genetic heterogeneity. This is the only missense mutation reported in any blebbing mutant or individual with Fraser syndrome, suggesting that calcium binding in the CALXβ-cadherin motif is important for normal functioning of FREM2 .

•Non-routine samples are sent frequently when infection is suspected.•Blood cultures and PCR results are always checked and acted on.•Is there value to sending other microbiological samples? Current Medical team concerns•High number of swabs sent•Limited value of these with low pickup rate of positive cultures•High resultant cost implication•Identify all patients on Neonatal unit and TC over defined period of time (June-October 2022)•Review all samples (non-routine)•What was requested•When was result available (number of days)•Was it reviewedPatients and methods•Retrospective review of BADGER•Drug charts reviewed to identify if treatment receivedResults•Time period: 4 months (June – October 2022)•108 non-routine microbiological specimens sent (not including Blood culture, MRSA, COVID samples) including: eye swab, skin swab, urine, faeces, NPANumber of days until final result available•n=108•Range 1–28 days for result to be issuedPositive results•Number of positive results (any) = 33•Number of positive cultures where treatment indicated = 12•Number of positive cultures receiving appropriate treatment = 4•Number of positive cultures where treatment indicated but not received = 8Eye swabs•9 samples grew an organism•None were considered significant•Mixed flora (7/9), Enterobacter (2/9)•None treated•All resolvedPerianal skin swabs•12/31 positive swabs•8 positive for yeast species (4 mixed flora)•0 received treatment•2 received topical antifungals from GP following dischargeResults Discussion•We send a high number of non-routine microbiology specimens•Eye and nappy area swabs account for half of all samples sent•44% of all samples sent have never been reviewed.•There were no significant eye swab cultures•There were 19 perianal skin swabs sent•12 positive for microorganisms•8 positive for candida species•0 received appropriate treatment prior to discharge•There is a delay to obtaining some results (especially fungal) >10 daysConclusion•There is limited value to sending the majority of microbiology samples which we currently send•Eye swabs do not add any value to clinical management•Treat clinically if suspicion of Neisseria gonorrhoea or chlamydia and send confirmatory swab ONLY if high level of suspicion•No need to treat non-injected crusty eyes•If perianal excoriation is suggestive clinically of candida infection (typical satellite lesions) then should be treated with topical +/- oral antifungals (as is the case in primary care), rather than delay while waiting for a result

The School Librarians' Network (SLN) has been running since July 1998. An incredible 20 years. I never imagined, when I set it as part of my research for a Masters in Education designed for school librarians at Christchurch Canterbury, tutored by Sharon Markless, that it would still be going strong 20 years on. I had been working in schools since 1981 and was very aware of how isolated one can feel, being neither a teacher nor a member of the administration staff. I had come across the American listserv LM_NET and was struck by the support and information that was being shared there. While much larger than a UK list could ever hope to be, it was a clear illustration of the benefits that could be derived from communicating with others in school libraries.

This book takes a strategic approach to the leadership of school libraries and will inspire and enable school librarians to think creatively about their work and the community in which they operate. The Innovative School Librarian raises important questions about the functions of the school librarian and sets out to encourage the reader to re-examine their own professional values, assumptions and practices. This has led to the inclusion of a new chapter on using evidence, a large number of new vignettes to illustrate responses to challenges as well as a significant re-structuring of other chapters. Written by current leaders in the field, each chapter addresses the practical issues facing school librarians. This new edition has been fully updated In the light of curriculum revisions, resource changes, developments in the use and integration of technology and new routes into the profession. Key topics covered include: • the librarian's philosophy and professional identity • bridging the gap between different visions for the school library • identifying and understanding our community • making a positive response to change • keeping inspired and inspiring others • integrating the library into teaching and learning. This is an essential, thought-provoking book for all school librarians, practitioners in schools library services, and students of librarianship. It has plenty to interest school leadership, headteachers, educational thinkers, public library managers and local government officers.