Chemistry, manufacturing and controls strategies for using novel excipients in lipid nanoparticles.

Lipid nanoparticles (LNPs) for nucleic acid delivery often use novel lipids as functional excipients to modulate the biodistribution, pharmacokinetics, pharmacodynamics and efficacy of the nucleic acid. Novel excipients used in pharmaceutical products are subject to heightened regulatory scrutiny and often require data packages comparable to an active pharmaceutical ingredient. Although these regulatory requirements may help to ensure patient safety they also create economic and procedural barriers that can disincentivize innovation and delay clinical investigation.

Wavemeter calibration by frequency comb.

Upgrades to the vacuum wavelength calibration service at the National Institute of Standards and Technology are reported. The instrumentation centerpiece is an optical frequency comb stabilized to a GPS-disciplined oscillator, thereby providing direct traceability to the SI second. Historically, the service has covered lasers at the popular interferometry wavelengths red and green.

Conversion of a piston-cylinder dimensional dataset to the effective area of a mechanical pressure generator.

Recent developments in diameter metrology at NIST have improved the dimensional characterization of piston-cylinder assemblies (PCAs) to unprecedented precision. For the newest generation of PCAs, the standard uncertainty in the measurement of the outer diameter is 12 nm, while uncertainty in the measurement of the inner diameter is 14 nm. With a high-accuracy dimensional dataset in hand, the task of determining the pressure generated by a specific PCA is reduced to converting the diameter (and straightness and roundness) to an effective area (and distortion coefficient).

Expansivity of Fused Quartz Glass Measured Within 6 × 10 K.

A method is described to measure the thermal expansion coefficient of fused quartz glass. The measurement principle is to monitor the change in resonance frequency of a Fabry-Perot cavity as its temperature changes; the Fabry-Perot cavity is made from fused quartz glass. The standard uncertainty in the measurement was less than 0.

Energy Absorption of 3D Printed ABS and TPU Multimaterial Honeycomb Structures.

Advances in multimaterial 3D printing are enabling the construction of advantageous engineering structures that benefit from material synergies. Cellular structures, such as honeycombs, provide high-energy absorption to weight ratios that could benefit from multimaterial strategies to improve the safety and performance of engineered systems. In this study, we investigate the energy absorption for honeycombs with square and hexagonal unit cells constructed from acrylonitrile butadiene styrene (ABS) and thermoplastic polyurethane (TPU).

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19.

Importance: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.

Objective: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.

Design, Setting, And Participants: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection.

Impact of aluminum adjuvants on the stability of pneumococcal polysaccharide-protein conjugate vaccines.

Development of a vaccine drug product requires formulation optimization to ensure that the vaccine's effectiveness is preserved upon storage throughout the shelf-life of the product. Although aluminum adjuvants have been widely used in vaccine formulations to safely and effectively potentiate an immune response, careful attention must be directed towards ensuring that the type of aluminum adjuvant does not impact the stability of the antigenic composition. PCV15 is a polysaccharide-protein conjugate vaccine comprising the pneumococcal polysaccharide (PnPs) serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F), each individually conjugated to the protein carrier CRM197.

Grayanotoxin I variation across tissues and species of Rhododendron suggests pollinator-herbivore defence trade-offs.

Grayanotoxin I (GTX I) is a major toxin in leaves of Rhododendron species, where it provides a defence against insect and vertebrate herbivores. Surprisingly, it is also present in R. ponticum nectar, and this can hold important implications for plant-pollinator mutualisms.

Special Issue Editorial: Applications of 3D Printing for Polymers.

Polymer 3D printing is an emerging technology highly relevant in diverse industries, including medicine, electronics, and robotics [...

Evolutionarily inspired solutions to the crop pollination crisis.

The global decline in insect diversity threatens pollination services, potentially impacting crop production and food security. Here, we argue that this looming pollination crisis is generally approached from an ecological standpoint, and that consideration of evolutionary principles offers a novel perspective. First, we outline that wild plant species have overcome 'pollination crises' throughout evolutionary history, and show how associated principles can be applied to crop pollination.

Consumer Assessment of 3D-Printed Food Shape, Taste, and Fidelity Using Chocolate and Marzipan Materials.

Additive manufacturing enables the production of complex structures with emerging approaches showing great promise in the food industry for design customization. Three-dimensional food printing has benefits for providing personalized health and shape fabrication for consumers. Past studies have demonstrated positive consumer perceptions for 3D food printing, but there is still a need for consumer validation of the technology through consumption and rating of fabricated 3D-printed foods.

The Importance of Recency of Cancer Diagnosis in Patients Hospitalized with COVID-19-Glimpses from an EHR-based Study.

Multiple prior studies have shown an increased risk of severe disease and death from SARS-CoV-2 infection in patients with cancer. Nolan and colleagues conducted a multi-institution, electronic health record (EHR)-based study of adults hospitalized with COVID-19 delineating the difference in outcomes when stratified by current versus former cancer diagnosis and found that only a current diagnosis appears to confer an increased risk of severe COVID-19 and death.We review these findings in the context of other studies examining outcomes for individuals with cancer diagnoses and COVID-19.

Mechanics of 3D-Printed Polymer Lattices with Varied Design and Processing Strategies.

Emerging polymer 3D-printing technologies are enabling the design and fabrication of mechanically efficient lattice structures with intricate microscale structures. During fabrication, manufacturing inconsistencies can affect mechanical efficiency, thereby driving a need to investigate how design and processing strategies influence outcomes. Here, mechanical testing is conducted for 3D-printed lattice structures while altering topology, relative density, and exposure time per layer using digital light processing (DLP).

Efficacy and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19: A Phase 2 Randomized Clinical Trial.

Importance: The morbidity and mortality associated with COVID-19 remain high despite advances in standard of care therapy, and the role of anti-inflammatory agents that inhibit the interleukin 6/JAK2 pathway is still being elucidated.

Objective: To evaluate the efficacy and safety of the oral JAK2/IRAK1 inhibitor pacritinib vs placebo in the treatment of adults with severe COVID-19.

Design, Setting, And Participants: This phase 2, double-blind, placebo-controlled, randomized clinical trial enrolled hospitalized adult patients with severe COVID-19 at 21 centers across the US between June 2020 and February 2021, with approximately 1.

IgD multiple myeloma: biology, diagnosis, and treatment.

IgD multiple myeloma is uncommon. Patients generally present at a younger age and have shorter progression free and overall survivals (OSs). Its rarity has inhibited development of a specific risk stratification system or informed best treatment protocols.

Vincristine Sulfate Liposome Injection with Bendamustine and Rituximab as First-Line Therapy for B-Cell Lymphomas: A Phase I Study.

Background: We conducted an investigator-initiated, phase I trial of vincristine sulfate liposomal injection (VSLI) in combination with bendamustine and rituximab (BR) for indolent B-cell (BCL) or mantle cell lymphoma.

Methods: Participants received 6 cycles of standard BR with VSLI at patient-specific dose determined by the Escalation with Overdose Control (EWOC) model targeting 33% probability of dose-limiting toxicity (DLT). Maximum tolerated dose (MTD) was the primary endpoint; secondary endpoints included rates of adverse events (AEs), overall response rate (ORR), and complete response (CR).

Beekeeping Livelihood Development in Nepal: Value-Added Opportunities and Professional Support Needs.

Beekeeping contributes to poverty reduction in many developing countries, and in addition, provides pollination services for sustainable crop production. In Nepal, management practices associated with beekeeping are poorly characterized, and so the potential for this sector to further contribute to livelihood development remains unclear. This study sought to examine and identify factors associated with production efficiency and financial profitability of beekeeping with the aim of enhancing economic gains for Nepali beekeepers.

Pollinator selection against toxic nectar as a key facilitator of a plant invasion.

Plant compounds associated with herbivore defence occur widely in floral nectar and can impact pollinator health. We showed previously that nectar contains grayanotoxin I (GTX I) at concentrations that are lethal or sublethal to honeybees and a solitary bee in the plant's non-native range in Ireland. Here we further examined this conflict and tested the hypotheses that nectar GTX I is subject to negative pollinator-mediated selection in the non-native range, but that phenotypic linkage between GTX I levels in nectar and leaves acts as a constraint on independent evolution.

Management of proximal metaphyseal curvilinear tibial fractures in 25 skeletally immature dogs (2009 to 2020).

Objectives: To describe the occurrence, management and outcome of proximal metaphyseal curvilinear tibial fractures in skeletally immature dogs.

Materials And Methods: A multi-centre retrospective review was conducted, searching for skeletally immature dogs presenting with proximal metaphyseal curvilinear tibial fractures between January 2009 and September 2020. Signalment, fracture description and case management data were retrieved.

Pollinators and herbivores interactively shape selection on strawberry defence and attraction.

Tripartite interactions between plants, herbivores, and pollinators hold fitness consequences for most angiosperms. However, little is known on how plants evolve in response-and in particular what the net selective outcomes are for traits of shared relevance to pollinators and herbivores. In this study, we manipulated herbivory ("presence" and "absence" treatments) and pollination ("open" and "hand pollination" treatments) in a full factorial common-garden experiment with woodland strawberry ( L.

Impact of Early Palliative Care on End-of-Life Outcomes in Hematologic Malignancies.

Patients with hematologic malignancies (HMs) receive more disease directed care at the end of life (EOL) and often die in the hospital. The impact of early palliative care (PC) consultation on EOL quality outcomes in HMs has not been well described. In 2017 we embedded a PC specialist within our inpatient malignant hematology team at our hospital in Providence, Rhode Island to facilitate the use of early PC.

Releasing Operating Room Nursing Time to Care through the Reduction of Surgical Case Preparation Time: A Lean Six Sigma Pilot Study.

Healthcare systems internationally are working under increasing demand to use finite resources with greater efficiency. The drive for efficiency utilises process improvement methodologies such as Lean Six Sigma. This study outlines a pilot Lean Six Sigma intervention designed to release nursing time to care within a peri-operative environment; this was achieved by collaborating with stakeholders to redesign the process for laparoscopic hernia surgical case preparation (set up) material.

Simulated tissue growth in tetragonal lattices with mechanical stiffness tuned for bone tissue engineering.

Bone tissue engineering approaches have recently begun considering 3D printed lattices as viable scaffold solutions due to their highly tunable geometries and mechanical efficiency. However, scaffold design remains challenging due to the numerous biological and mechanical trade-offs related to lattice geometry. Here, we investigate novel tetragonal unit cell designs by independently adjusting unit cell height and width to find scaffolds with improved tissue growth while maintaining suitable scaffold mechanical properties for bone tissue engineering.